bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for siderophore‐dependent iron acquisition in group B streptococcus
Authors: Clancy Anne , Loar Jesse W. , Speziali Craig D. , Oberg Michael , Heinrichs David E. , Rubens Craig E.
Published: December 2005

Mutagenesis of group B streptococcus (GBS) with TnphoZ, a transposon designed to identify secreted protein genes, identified the gene homologues fhuD and fhuG. The encoded proteins participate in siderophore (hydroxamate)‐dependent iron(III) transport in other bacterial species. Sequence analysis of the genome determined that fhuD and fhuG are members of a polycistronic operon comprised of four genes, fhuCDBG, that encode a putative ATPase, cell surface receptor and two transmembrane proteins respectively. We hypothesized that FhuD was a siderophore receptor. Western analysis of cell extracts localized FhuD to the bacterial cell membrane. Fluorescence quenching experiments determined that purified FhuD bound hydroxamate‐type siderophores. FhuD displayed highest affinity for iron(III)‐desferroxamine, with a KD (µM) = 0.05, identical to that described for FhuD2 from Staphylococcus aureus. The role of Fhu in siderophore‐iron transport was also characterized. A fhu mutant, ACFhu1, was equally sensitive to the iron‐dependent antibiotic streptonigrin as the wild‐type strain, suggesting that ACFhu1 was not reduced for intracellular iron concentrations in the absence of exogenous siderophore. However, ACFhu1 transported significantly less siderophore‐bound iron in 55Fe accumulation assays. These data provide the first evidence of siderophore‐mediated iron acquisition by GBS.
Heterocyst differentiation and pattern formation in cyanobacteria: a chorus of signals
Authors: Zhang Cheng‐Cai , Laurent Sophie , Sakr Samer , Peng Ling , Bédu Sylvie
Published: December 2005

Heterocyst differentiation in filamentous cyanobacteria provides an excellent prokaryotic model for studying multicellular behaviour and pattern formation. In Anabaena sp. strain PCC 7120, for example, 5–10% of the cells along each filament are induced, when deprived of combined nitrogen, to differentiate into heterocysts. Heterocysts are specialized in the fixation of N2 under oxic conditions and are semi‐regularly spaced among vegetative cells. This developmental programme leads to spatial separation of oxygen‐sensitive nitrogen fixation (by heterocysts) and oxygen‐producing photosynthesis (by vegetative cells). The interdependence between these two cell types ensures filament growth under conditions of combined‐nitrogen limitation. Multiple signals have recently been identified as necessary for the initiation of heterocyst differentiation, the formation of the heterocyst pattern and pattern maintenance. The Krebs cycle metabolite 2‐oxoglutarate (2‐OG) serves as a signal of nitrogen deprivation. Accumulation of a non‐metabolizable analogue of 2‐OG triggers the complex developmental process of heterocyst differentiation. Once heterocyst development has been initiated, interactions among the various components involved in heterocyst differentiation determine the developmental fate of each cell. The free calcium concentration is crucial to heterocyst differentiation. Lateral diffusion of the PatS peptide or a derivative of it from a developing cell may inhibit the differentiation of neighbouring cells. HetR, a protease showing DNA‐binding activity, is crucial to heterocyst differentiation and appears to be the central processor of various early signals involved in the developmental process. How the various signalling pathways are integrated and used to control heterocyst differentiation processes is a challenging question that still remains to be elucidated.
Brain–gut connections in functional GI disorders: anatomic and physiologic relationships
Authors: Jones M. P. , Dilley J. B. , Drossman D. , Crowell M. D.
Published: December 2005

Abstract  Understanding the neural regulation of gut function and sensation makes it easier to understand the interrelatedness of emotionality, symptom‐attentive behavior or hypervigilance, gut function and pain. The gut and the brain are highly integrated and communicate in a bidirectional fashion largely through the ANS and HPA axis. Within the CNS, the locus of gut control is chiefly within the limbic system, a region of the mammalian brain responsible for both the internal and external homeostasis of the organism. The limbic system also plays a central role in emotionality, which is a nonverbal system that facilitates survival and threat avoidance, social interaction and learning. The generation of emotion and associated physiologic changes are the work of the limbic system and, from a neuroanatomic perspective, the ‘mind‐body interaction’ may largely arise in this region. Finally, the limbic system is also involved in the ‘top down’ modulation of visceral pain transmission as well as visceral perception. A better understanding of the interactions of the CNS, ENS and enteric immune system will significantly improve our understanding of ‘functional’ disorders and allow for a more pathophysiologic definition of categories of patients currently lumped under the broad umbrella of FGID.
Heat sensitivity of photosynthetic electron transport varies during the day due to changes in sugars and osmotic potential
Authors: HÜVE KATJA , BICHELE IRINA , TOBIAS MARI , NIINEMETS ÜLO
Published: December 2005

In water‐stressed leaves, accumulation of neutral osmotica enhances the heat tolerance of photosynthetic electron transport. There are large diurnal and day‐to‐day changes in leaf sugar content because of variations in net photosynthetic production, respiration and retranslocation. To test the hypothesis that diurnal and day‐to‐day variations in leaf sugar content and osmotic potential significantly modify the responses to temperature of photosynthetic electron transport rate, we studied chlorophyll fluorescence rise temperatures (i.e. critical temperatures at break‐points in fluorescence versus temperature response curves, corresponding to enhanced damage of PSII centers and detachment of pigment‐binding complexes) in the dark at a background of weak far‐red light (TFR) and under actinic light (TL), and responses of foliar photosynthetic electron transport rate to temperature using gas‐exchange and chlorophyll fluorescence techniques in the temperate tree Populus tremula L. Sucrose and sorbitol feeding experiments demonstrated strong increases of fluorescence rise temperatures TFR and TL with decreasing leaf osmotic potential and increasing internal sugar concentration. Similar TFR and TL changes were observed in response to natural variation in leaf sugar concentration throughout the day. Increases in leaf sugar concentration led to an overall down‐regulation of the rate of photosynthetic electron transport (J), but increases in the optimum temperature (Topt) of J. For the entire dataset, Topt varied from 33.8 °C to 43 °C due to natural variation in sugars and from 33.8 °C to 52.6 °C in the sugar feeding experiments, underscoring the importance of sugars in modifying the response of J to temperature. However, the correlations between the sugar concentration and fluorescence rise temperature varied between the days. This variation in fluorescence rise temperature was best explained by the average temperature of the preceding 5 or 6 days. In addition, there was a significant year‐to‐year variation in heat sensitivity of photosynthetic electron transport that was associated with year‐to‐year differences in endogenous sugar content. Our data demonstrate a diurnal variation in leaf heat tolerance due to changes in sugar concentration, but they also show that this short‐term modification in heat tolerance is superimposed by long‐term changes in heat resistance driven by average temperature of preceding days.
Long‐term acclimatization of hydraulic properties, xylem conduit size, wall strength and cavitation resistance inPhaseolus vulgarisin response to different environmental effects
Authors: HOLSTE ELLEN K. , JERKE MEGAN J. , MATZNER STEVEN L.
Published: December 2005

Phaseolus vulgarisgrown under various environmental conditions was used to assess long‐term acclimatization of xylem structural characteristics and hydraulic properties. Conduit diameter tended to be reduced and ‘wood’ density (of ‘woody’ stems) increased under low moisture (‘dry’), increased soil porosity (‘porous soil’) and low phosphorus (‘low P’) treatments. Dry and low P had the largest percentage of small vessels. Dry, low light (‘shade’) and porous soil treatments decreasedP50(50% loss in conductivity) by 0.15–0.25 MPa (greater cavitation resistance) compared with ‘controls’. By contrast, low P increasedP50by 0.30 MPa (less cavitation resistance) compared with porous soil (the control for low P). Changes in cavitation resistance were independent of conduit diameter. By contrast, changes in cavitation resistance were correlated with wood density for the control, dry and porous soil treatments, but did not appear to be a function of wood density for the shade and low P treatments. In a separate experiment comparing control and porous soil plants, stem hydraulic conductivity (kh), specific conductivity (ks), leaf specific conductivity (LSC), total pot water loss, plant biomass and leaf area were all greater for control plants compared to porous soil plants. Porous soil plants, however, demonstrated higher midday stomatal conductance to water vapour (gs), apparently because they experienced proportionally less midday xylem cavitation.
Senescence‐specific regulation of catalases in Arabidopsis thaliana (L.) Heynh
Authors: ZIMMERMANN PETRA , HEINLEIN CHRISTINA , ORENDI GABRIELE , ZENTGRAF ULRIKE
Published: December 2005

Oxygen free radicals are thought to play an essential role in senescence, especially those derived from peroxisomes. Therefore, the activities of different isoforms of the peroxisomal hydrogen peroxide (H2O2)‐scavenging enzyme catalase (CAT) were analysed during senescence of Arabidopsis. CAT2 activity decreased with bolting time parallel with cytosolic ascorbate peroxidase 1 (APX1) activity before loss of chlorophyll could be measured. At the same time point, the H2O2 content increased. Subsequently, the stress‐inducible CAT3 isoform was activated and APX1 activity was recovered, accompanied by a decline of the H2O2 content. In very late stages, low activities of the seed‐specific CAT1 became detectable in leaves, but H2O2 increased again. Further analyses of CAT expression by promoter : β‐glucuronidase (GUS) fusions in transgenic plants revealed a vasculature‐specific CAT3 expression, whereas CAT2 expression turned out to be specific for photosynthetic active tissues. CAT2 expression is down‐regulated during leaf senescence, while CAT3 expression is induced with age and corresponds to an accumulation of H2O2 in the vascular bundles. CAT2 down‐regulation on the transcriptional level appears as the initial step in creating the H2O2 peak during bolting time, while the decrease in APX1 activity might only be a secondary and amplifying effect.
Immunomodulation in Type 1 Diabetes by NBI‐6024, an Altered Peptide Ligand of the Insulin B(9−23) Epitope
Authors: Alleva D. G. , Maki R. A. , Putnam A. L. , Robinson J. M. , Kipnes M. S. , Dandona P. , Marks J. B. , Simmons D. L. , Greenbaum C. J. , Jimenez R. G. , Conlon P. J. , Gottlieb P. A.
Published: December 2005

NBI‐6024 is an altered peptide ligand (APL) corresponding to the 9–23 amino acid region of the insulin B chain (B(9−23)), an epitope recognized by inflammatory interferon‐γ‐producing T helper (Th)1 lymphocytes in type 1 diabetic patients. Immunomodulatory effects of NBI‐6024 administration in recent‐onset diabetic patients in a phase I clinical trial (NBI‐6024‐0003) were measured in peripheral blood mononuclear cells using the enzyme‐linked immunosorbent spot assay. Analysis of the mean magnitude of cytokine responses to B(9−23) and NBI‐6024 for each cohort showed significant increases in interleukin‐5 responses (a Th2 regulatory phenotype) in cohorts that received APL relative to those receiving placebo. A responder analysis showed that Th1 responses to B(9−23) and NBI‐6024 were observed almost exclusively in the placebo‐treated diabetic population but not in nondiabetic control subjects and that APL administration (five biweekly subcutaneous injections) significantly and dose‐dependently reduced the percentage of patients with these Th1 responses. The results of this phase I clinical study strongly suggest that NBI‐6024 treatment shifted the Th1 pathogenic responses in recent‐onset type 1 diabetic patients to a protective Th2 regulatory phenotype. The significance of these findings on the clinical outcome of disease is currently under investigation in a phase II multidose study.
Phylogenetic relationships and evolution of cleaning behaviour in the family Labridae
Authors: Arnal C. , Verneau O. , Desdevises Y.
Published: December 2005

The family Labridae contains numerous fishes known to act as cleaners in the wild. Previous studies suggested that a small body size and specific colour patterns may be prerequisites for cleaning. We investigated whether cleaning behaviour is linked to particular fish phenotypes. We first present a phylogeny based on partial 12S rRNA gene sequences of 32 wrasses sampled from different localities in the Indo-Pacific and Atlantic oceans, and in the Mediterranean Sea. Secondly, descriptive data (fish body size, fish body shape and fish body colour patterns) were analyzed in a phylogenetic context using comparative methods. We found no relationship between fish cleaning behaviour and fish body size and shape, but instead a correlation between cleaning behaviour and the presence of a dark lateral stripe within wrasses. Our results suggest that the evolution of cleaning depends upon the presence of a dark median lateral stripe on the fish body surface.
Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis
Authors: LAY CHII‐SHYAN , TSAI YANG‐TE , LEE FA‐YAUH , LAI YI‐LIANG , YU CHENG‐JU , CHEN CHIH‐BIN , PENG CHENG‐YUAN
Published: December 2005

Background and Aim: To compare the efficacy and safety of endoscopic variceal ligation (EVL) with propranolol in prophylaxis on the rate of first esophageal variceal bleeding in patients with cirrhosis.

Methods: A prospective, randomized trial was conducted in 100 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end‐points of the study were bleeding and death.

Results: Life‐table curves showed that prophylactic EVL and propranolol were similarly effective for primary prophylaxis of variceal bleeding (11/50 [22%]vs12/50 [24%];P = 0.68) and overall mortality (14/50 [28%]vs12/50 [24%];P = 0.49). The 2‐year cumulative bleeding rate was 18% (9/50) in the EVL group and 16% (8/50) in the propranolol group. The 2‐year cumulative mortality rate was 28% (14/50) in the EVL group and 24% (12/50) in the propranolol group. Comparison of Kaplan‐Meier estimates of the time to death of both groups showed no significant difference in mortality in both groups (P = 0.86). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. In the propranolol group, the mean daily dosage of the drug was 68.2 ± 32.8 mg, which was sufficient to reduce the pulse rate by 25%. 20% of patients withdrew from propranolol treatment due to adverse events.

Conclusions: Prophylaxis EVL is as effective and as safe as treatment with propranolol in decreasing the incidence of first variceal bleeding and death in cirrhotic patients with high‐risk esophageal varices.
Measurement of parenchymal function and bile duct flow in primary sclerosing cholangitis using dynamic 99mTc‐HIDA SPECT
Authors: JONAS EDUARD , NÄSLUND ERIK , FREEDMAN JACOB , BEFRITS RAGNAR , BLOMQVIST LENNART , SIÖSTEEN ANNA‐KARIN , JACOBSSON HANS , HULTCRANTZ ROLF
Published: December 2005

Background and Aim:  Primary sclerosing cholangitis is a chronic cholestatic disease characterized by obliterative fibrosis of intrahepatic and/or extrahepatic bile ducts. The unpredictable clinical course of the disease can be relentless, leading to premature death in a large percentage of patients. Prognostic index formulas, the revised Mayo model being the most frequently used, have been developed to predict clinical course and prognosis. The aim of this study was to investigate the potential value of dynamic 99mTc‐HIDA SPECT in patients with primary sclerosing cholangitis by correlating scintigraphic results with cholangiographic and biochemical findings and prognostic scoring systems used in clinical practice.

Methods:  In 18 patients with primary sclerosing cholangitis, segmental parenchymal and bile duct functions were measured using dynamic 99mTc‐HIDA SPECT. Quantitative scintigraphic results were compared to cholangiographic findings, as graded by a biliary classification system, the Child–Pugh score and revised Mayo prognostic score, as well as the individual biochemical parameters included in the scoring systems.

Results:  In individual segments, scintigraphic quantitative parameters indicative of bile flow showed a statistically significant correlation with the state of the bile‐flow path for the respective segments as assessed by the biliary classification system. The revised Mayo score correlated with the scintigraphic quantitative parameters indicative of parenchymal function and bile flow as calculated for the whole liver.

Conclusions:  Dynamic 99mTc‐HIDA SPECT, capable of assessing different aspects of liver function for the total liver, as well as for individual segments, has potential value in the management of patients with primary sclerosing cholangitis.
Providing guidelines and education is not enough: an audit of gentamicin use at The Royal Melbourne Hospital
Authors: Leong C. L. , Buising K. , Richards M. , Robertson M. , Street A.
Published: December 2005

Background: Aminoglycoside antibiotics are commonly prescribed for the treatment of Gram‐negative infections. Appropriate dosing and therapeutic monitoring of aminoglycosides are important because these agents have a narrow therapeutic index.

Aim: To audit gentamicin use at our hospital, focusing on selection of the initial dose and therapeutic monitoring practices, and to compare the results against recommendations in the existing hospital aminoglycoside guidelines, which had recently been promoted to doctors.

Methods: This audit included all inpatients receiving gentamicin at The Royal Melbourne Hospital from 1 February to 12 March 2004. The principal researcher checked the drug charts of all inpatients to identify those receiving gentamicin and collected data from the medical records and the pathology database. Doses were considered ‘concordant’ if the dose given was within the recommended dosing range ±20 mg.

Results: A total of 132 courses of gentamicin was included in the study. Gentamicin was prescribed for prophylaxis in 31.1% of courses. Thirty‐six per cent of patients prescribed gentamicin were more than 65 years of age. Eighty‐two per cent of the gentamicin used therapeutically was given as a single daily dose. Sixty‐six per cent of gentamicin initial dosing was not in accordance with existing hospital guidelines. Seventy‐seven per cent of gentamicin courses requiring therapeutic drug monitoring received such monitoring; however, in only 8.8% of these was the monitoring conducted according to guidelines.

Conclusion: Aminoglycoside prescribing practices at our hospital are suboptimal, despite ready access to prescribing guidelines. Provision of a guideline and education sessions with doctors do not necessarily lead to widespread adoption of recommended practices. We suggest that changes to hospital systems related to prescribing and monitoring of aminoglycosides are required.
Epidemiology of the functional gastrointestinal disorders diagnosed according to Rome II criteria: an Australian population‐based study
Authors: Boyce P. M. , Talley N. J. , Burke C. , Koloski N. A.
Published: December 2005

Background: Population‐based studies of the prevalence of all functional gastrointestinal disorders (FGID) using the Rome II criteria are lacking. It is also not certain whether subjects who meet the Rome II criteria for an FGID are different in terms of demographic and psychological characteristics from those subjects meeting exclusively the more restrictive Rome I criteria.

Aim: To determine whether using the more restrictive Rome I criteria would result in a more biologically determined group of FGID than when the Rome II is applied.

Methods: Subjects included individuals aged 18 years and older (n = 1225) from the Penrith population who were initially surveyed with the Penrith District Health Survey in 1997. Subjects were sent a self‐report questionnaire that contained items on gastrointestinal symptoms applying the Rome II criteria. Subjects were also assessed on psychological and personality factors and on physical and mental functioning.

Results: A total of 36.1% (n = 275) of respondents was diagnosed with an FGID according to Rome II criteria. The five most prevalent FGID were functional heartburn (10.4%), irritable bowel syndrome (8.9%), functional incontinence (7.6%), proctalgia fugax (6.5%) and functional chest pain (5.1%). Subjects meeting Rome II only criteria for FGID scored significantly higher on measures of psychological caseness and emotionality than Rome I only subjects, and these were independently associated with meeting Rome I only versus Rome II only criteria for FGID.

Conclusion: The Rome II criteria FGID are common and do not appear to identify a vastly different group of FGID sufferers compared with the earlier Rome I criteria.
Deep Brain Stimulation for Neuropathic Cephalalgia
Authors: Green AL , Owen SLF , Davies P , Moir L , Aziz TZ
Published: December 2005

The aim of this study was to determine the efficacy of deep brain stimulation (DBS) in the treatment of various types of intractable head and facial pains. Seven patients underwent the insertion of DBS electrodes into the periventricular/periaqueductal grey region and/or the ventroposteromedial nucleus of the thalamus. We have shown statistically significant improvement in pain scores (visual analogue and McGill's) as well as health-related quality of life (SF-36v2) following surgery. There is wide variability in patient outcomes but, overall, DBS can be an effective treatment. Our results are compared with the published literature and electrode position for effective analgesia is discussed.
Secretion of brain‐derived neurotrophic factor from PC12 cells in response to oxidative stress requires autocrine dopamine signaling
Authors: Wang Hong , Yuan Guoxiang , Prabhakar Nanduri R. , Boswell Mark , Katz David M.
Published: December 2005

Expression of brain‐derived neurotrophic factor (BDNF) is sensitive to changes in oxygen availability, suggesting that BDNF may be involved in adaptive responses to oxidative stress. However, it is unknown whether or not oxidative stress actually increases availability of BDNF by stimulating BDNF secretion. To approach this issue we examined BDNF release from PC12 cells, a well‐established model of neurosecretion, in response to hypoxic stimuli. BDNF secretion from neuronally differentiated PC12 cells was strongly stimulated by exposure to intermittent hypoxia (IH). This response was inhibited by N‐acetyl‐l‐cysteine, a potent scavenger of reactive oxygen species (ROS) and mimicked by exogenous ROS. IH‐induced BDNF release requires activation of tetrodotoxin sensitive Na+ channels and Ca2+ influx through N‐ and L‐type channels, as well as mobilization of internal Ca2+ stores. These results demonstrate that oxidative stress can stimulate BDNF release and that underlying mechanisms are similar to those previously described for activity‐dependent BDNF secretion from neurons. Surprisingly, we also found that IH‐induced secretion of BDNF was blocked by dopamine D2 receptor antagonists or by inhibition of dopamine synthesis with α‐methyl‐p‐tyrosine. These data indicate that oxidative stress can stimulate BDNF release through an autocrine or paracrine loop that requires dopamine receptor activation.
Cyclosporine monitoring in renal transplant recipients with induction therapy: C2 levels in patients monitored on C0
Authors: Loichot Cécile , Bentue‐Ferrer Danièle , Bernard Nicole , Bonardet Andrée , Boulieu Roselyne , Kergueris Marie‐France , Paintaud Gilles , Peytavin Gilles , Simon Nicolas , Marquet Pierre ,   the therapeutic drug monitoring group of the French Pharmacological Society
Published: December 2005

The aim of this retrospective study was to compare the cyclosporine C2 blood levels in renal transplant recipients with induction therapy, monitored on C0 levels during the early and long‐term post‐transplantation periods in different French transplantation centres, to the target values recommended by the International Consensus on Neoral® and used in the Mo2art study. A retrospective study was conducted by the therapeutic drug monitoring (TDM) committee of the French Pharmacological Society. Cyclosporine C0 and C2 concentrations from 168 renal transplant recipients were collected at different post‐transplantation periods by six TDM laboratories of transplantation centres from April 2001 to April 2002. Cyclosporine blood levels were determined by fluorescence polarization immunoassay (mFPIA, AxSYM, Abbott) or enzyme immunoassay (EMIT, Dade Behring). Most patients had C0 values in the recommended target ranges, with C2 levels below the targets used in the Mo2art study or proposed by the International Consensus Conference, both during the early and long‐term post‐transplantation periods. Sixty‐eight per cent of patients had C2 below 1500 μg/L ± 20% in the first 2 months post‐transplantation and 55% had C2 below 800 μg/L ± 20% in the late post‐transplantation period (>1 year). Cyclosporine dose should be increased by 40% on average during the first week post‐transplantation period and by 50% during the maintenance period to achieve the C2 targets. In France, most renal transplant recipients receiving induction agents monitored on C0 had C2 levels below the targets recommended by the International Consensus Conference. In clinical practice, the optimal therapeutic windows for CsA monitoring based on C2 needs to be more precisely defined, both during the early and long‐term post‐transplantation periods in renal transplant recipients receiving induction agents.
Adenosine receptors: promising targets for the development of novel therapeutics and diagnostics for asthma
Authors: Russo Cristina , Arcidiacono Giuseppe , Polosa Riccardo
Published: December 2005

Interest in the role of adenosine in asthma has escalated considerably since the early observation of its powerful bronchoconstrictor effects in asthmatic but not normal airways. A growing body of evidence has emerged in support of a proinflammatory and immunomodulatory role for the purine nucleoside adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma. The fact that adenosine enhances mast cell allergen‐dependent activation, that elevated levels of adenosine are present in chronically inflamed airways, and that adenosine given by inhalation cause dose‐dependent bronchoconstriction in subjects with asthma emphasizes the importance of adenosine in the initiation, persistence and progression of these common inflammatory disorders of the airways. These distinctive features of adenosine have been recently exploited in the clinical and research setting to identify innovative diagnostic applications for asthma. In addition, because adenosine exerts its multiple biological activities by interacting with four adenosine receptor subtypes, selective activation or blockade of these receptors may lead to the development of novel therapies for asthma.
Clinical and prognostic role of plasma coagulation factor XIII activity for bleeding disorders and 6‐year survival in patients with chronic liver disease
Authors: Tacke Frank , Fiedler Kai , von Depka Mario , Luedde Tom , Hecker Hartmut , Manns Michael P. , Ganser Arnold , Trautwein Christian
Published: December 2005

Abstract: Background/Aims: Alterations of plasma coagulation factor XIII may contribute to bleeding disorders in patients with liver cirrhosis. As standard clotting tests such as prothrombin time or activated thromboplastin time (aPTT) cannot detect factor XIII deficiency, this may often be overlooked in clinical practice. We aimed to define factor XIII's clinical and prognostic role in chronic liver disease.

Patients and methods: Factor XIII activities were assessed among various other parameters in 111 patients with chronic liver diseases during evaluation for liver transplantation in a prospective study.

Results: Unlike coagulation factors II, V or VII, factor XIII activity was maintained in the majority of patients with liver cirrhosis. However, although rarely, factor XIII deficiencies (<50%) occurred, especially in Child C cirrhosis. Factor XIII levels correlated with liver's biosynthetic capacity (cholinesterase activity, albumin, total protein) as well as with platelet count, global coagulation tests and other single coagulation factors. Patients reporting a current systemic bleeding tendency at study entry had significantly reduced factor XIII. In a 6‐year follow‐up, patients with factor XIII <50% had a significantly increased risk of severe upper gastrointestinal bleed, and reduced factor XIII (<50%, 50–75% vs. normal) was associated with increased mortality.

Conclusions: Factor XIII deficiency is rare in patients with liver cirrhosis, but is associated with a clinical bleeding tendency and an unfavorable prognosis for future hemorrhages and survival.
Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease
Authors: Palekar Nicole A. , Naus Rhonda , Larson Steven P. , Ward John , Harrison Stephen A.
Published: December 2005

Abstract: Nonalcoholic fatty liver disease (NAFLD) encompasses both simple steatosis and nonalcoholic steatohepatitis (NASH). Differentiation of these two entities requires histopathologic evaluation. The aim of this study was to establish a reliable diagnostic model for differentiating steatosis from steatohepatitis utilizing both clinical characteristics and a panel of biochemical markers of lipid peroxidation and fibrosis. Eighty subjects with biopsy proven NAFLD were enrolled, 39 with simple steatosis and 41 with histopathologic evidence of NASH. Demographic and laboratory data to include serologic testing for 8‐epi‐PGF2α, transforming growth factor‐β (TGF‐β), adiponectin, and hyaluronic acid (HA) were obtained and compared between the two groups. There were significant differences between the two groups with respect to age (P=0.004), female gender (P=0.024), aspartate aminotransferase (AST) (P=0.028), body mass index (BMI) (P=0.003), fasting insulin (0.018), AST/alanine aminotransferase (ALT) ratio (AAR) (P=0.017), quantitative insulin sensitivity check index (QUICKI) (P=0.002), and HA (P=0.029). A composite index for distinguishing steatosis from NASH was calculated by summing the risk factors of age ≥50 years, female gender, AST≥45 IU/l, BMI ≥30 mg/kg2, AAR≥0.80, and HA≥55 mcg/l, and its accuracy was determined by receiver operating characteristic (ROC) analysis to be 0.763 (95% CI: 0.650–0.876). The presence of three or more risk factors had a sensitivity, specificity, PPV, and NPV of 73.7%, 65.7%, 68.2%, and 71.4%, respectively. In addition, HA at a cutoff of 45.3 mcg/l was a good predictor of advanced fibrosis. In conclusion, we propose a noninvasive screening model for distinguishing simple steatosis from NASH. Identifying patients at risk for NASH will allow clinicians to more accurately determine who may benefit from liver biopsy.
Intraspecific and interspecific competition for larval nests of the caddisflies Stenopsyche marmorata and Stenopsyche sauteri
Authors: FUNAKOSHI Shintaro
Published: December 2005

Two closely related species of the trichopteran genus Stenopsyche–S. marmorata and S. sauteri– are both widely distributed in Japan, and their larvae often co‐occur in stony stream beds. The larvae make nests by spinning nets in spaces between stones. In this study, I examined the effects of the intruder–resident relationship, bodyweight difference, and species combination on contest outcome in laboratory experiments. In S. marmorata, bodyweight was revealed to be a better predictor of winning a contest than was residency. In S. sauteri, however, there was a prior‐resident effect in the contests, and takeover occurred in a few cases when the intruders were larger than the residents. The duration of agonistic behavior increased as the bodyweight differences between the fighting individuals decreased. In heterospecific contests, outcomes were generally asymmetric: the larvae of S. marmorata (the larger species) rarely intruded into the nest of S. sauteri, while they, in most cases, protected their own nests from intrusion by S. sauteri larvae. In conclusion, the resident wins in both forms of competition when either S. marmorata or S. sauteri is an intruder.
Study of the genetics of female sex pheromone production and male behavioral response in a moth, Ostrinia orientalis
Authors: FU Xiaoyan , TATSUKI Sadahiro , HOSIZAKI Sugihiko , ISHIKAWA Yukio
Published: December 2005

Inheritance patterns of female sex pheromone production and male behavioral response were studied in Ostrinia orientalis. Results showed that the production of the female sex pheromone in O. orientalis was mainly controlled by a single autosomal factor, while the male behavioral response was controlled by a sex‐linked major gene.
Morphological features and molecular phylogeny of Placochela Rübsaamen (Diptera: Cecidomyiidae) with implications for taxonomy and host specificity
Authors: TOKUDA Makoto , HARRIS Keith M. , YUKAWA Junichi
Published: December 2005

Morphological studies, combined with phylogenetic analysis based on partial nucleotide sequencing of the mitochondrial DNA cytochrome oxidase subunit I region, were used to elucidate the taxonomic status of the genus Placochela Rübsaamen within the tribe Asphondyliini and of two included species. Placochela is confirmed as a distinct genus, separated from Schizomyia Kieffer morphologically and phylogenetically, but its two European species are not separable and are therefore synonymized. Illustrated descriptions of adults and larvae of Placochela nigripes (Löw) on two of its known hosts, Sambucus nigra Linnaeus and Ligustrum vulgare Linnaeus, are provided. Polyphagy has been recorded in the subtribe Asphondyliina, but this is the first record of such polyphagy in the subtribe Schizomyiina.
Detection of West Nile virus in the Mexican blood supply
Authors: Sánchez‐Guerrero Sergio A. , Romero‐Estrella Sagrario , Rodríguez‐Ruiz Antonio , Infante‐Ramírez Lilia , Gómez Angélica , Villanueva‐Vidales Eduardo , García‐Torres Martha , Domínguez Ana MA. , Vázquez Jaime A. , Calderón Eva D. , Valiente‐Banuet Leopoldo , Linnen Jeffrey M. , Broulik Amy , Harel William , Marín y López Rafael A.
Published: December 2005

BACKGROUND: West Nile virus (WNV) is the etiologic agent of an emerging disease in the Western Hemisphere that can be transmitted to humans by blood transfusion. WNV first appeared in the United States in 1999, in Canada in 2001, and in Mexico in 2002. The aim of this nationwide study was to determine the prevalence of WNV in blood donors in Mexico as a first step in preventing its transfusion‐associated transmission.

STUDY DESIGN AND METHODS: In July and August 2004, a total of 3856 fresh plasma specimens collected from each state's center for blood transfusion in 29 of 31 Mexican states were screened with an investigational WNV assay (Procleix,® Gen‐Probe Inc. and Chiron Corp.), a nucleic acid test based on transcription‐mediated amplification (TMA). Reactive specimens were confirmed with a second TMA‐based test, the alternative WNV assay (Gen‐Probe), and with WNV capture enzyme‐linked immunosorbent assays (ELISAs) for detection of immunoglobulin M (IgM) and IgG antibodies. In addition, 3714 frozen plasma samples collected in 2002 and 2003 were similarly tested.

RESULTS: One of 3856 fresh samples from an asymptomatic donor from Chihuahua was reactive by both TMA‐based tests and IgM ELISA, suggesting a recently acquired infection. The observed percentage of viremic donors blood donors was 0.03 percent. Results from frozen samples were not included in the prevalence calculation and none were TMA‐reactive for WNV.

CONCLUSIONS: WNV is present in the Mexican blood supply and measures should be taken to reduce the risk of transfusion transmission.
Red blood cells intended for transfusion: quality criteria revisited
Authors: Högman Claes F. , Meryman Harold T.
Published: December 2005

Great variation exists with respect to viability and function of fresh and stored red blood cells (RBCs) as well as of the contents of RBC hemoglobin (Hb) in individual units. Improved technology is available for the preparation as well as the storage of RBCs. The authors raise the question whether it may be time to revise current standards for RBC units. The establishment of a standard unit of blood based on Hb content should be a high‐priority goal. It is recommended that a standard RBC unit should contain 50 g of Hb. Major organizations concerned with the collection and distribution of blood components should agree on the criteria for a standard unit of RBCs based on Hb content and for the collection of double units. Manufacturers of blood collection equipment should provide suitable technology for collecting a standard unit with defined contents of RBC Hb. Efforts should be directed at the design of storage solutions acceptable for transfusion that maximize the maintenance of both RBC viability and function during storage. The ideal storage protocol would require sterile, high‐pH solutions containing both glucose and electrolytes.
Prospective investigations of the prodromal state of schizophrenia: assessment instruments
Authors: Olsen K. A. , Rosenbaum B.
Published: December 2005

Objective:  To review assessment instruments used for detection of prodromal or at‐risk mental states, and discuss their role in current research.

Method:  A systematic electronic literature search was conducted and supplemented by a manual search. All relevant scales were selected for the purpose of the review.

Results:  Six interviews and four screening instruments were found. Two main traditions are prevailing: the Attenuated Positive Symptoms approach and the Basic Symptoms approach. Reports of psychometric properties of the interviews are preliminary.

Conclusion:  The instruments detect individuals with an increased risk of psychosis in clinical populations, but predictive validity and measures of reliability is insufficiently evaluated. Studies including instruments from both traditions should be conducted, in order to obtain an empirical basis of hypothesized relations between instruments. Instruments elucidating phenomenological aspects of anomalies in self‐experience may contribute with valuable data on the pre‐onset phase of psychosis.
Patients with schizophrenia treated with aripiprazole, a multicentre naturalistic study
Authors: Christensen A. F. , Poulsen J. , Nielsen C. T. , Bork B. , Christensen A. , Christensen M.
Published: December 2005

Objective:  The purpose was to carry out a naturalistic study on efficacy, safety and tolerability of aripiprazole during treatment of schizophrenia. Fifty‐one patients with an ICD‐10 diagnosis of schizophrenia and partial responders to prior antipsychotic medication were offered treatment with aripiprazole as monotherapy or in combination their prior medication. Inclusion criteria were lack of therapeutic effect or adverse events on former antipsychotic treatment.

Method:  Six‐month open multicentre naturalistic study with prospective assessments including Body Mass Index (BMI), Clinical Global Impression – Severity (CGI‐S), Clinical Global Impression – Improvment, Global Assessment of Functioning Scale (GAF) and adverse events.

Results:  A statistically significant improvement in the different measures of psychopathology and global functioning (CGI‐S reduction 34.7%; GAF improvement 14%) was shown in combination with a statistically significant reduction in BMI of 2.9%. Nine patients (17.6%) did not complete the 6‐month treatment.

Conclusion:  In an open multicentre naturalistic study, aripiprazole showed to improve the severity of psychotic symptoms and the global level of functioning. However, many of the patients (47%) were also given another antipsychotic drug at the same time. Also, high compliance and few side effects were reported. However, because of the study design, the results must be interpreted conservatively.
Long‐term remission in HIV‐negative patients with multicentric Castleman's disease using rituximab
Authors: Ide Makoto , Kawachi Yasunori , Izumi Yoichiro , Kasagi Kanji , Ogino Tetsuro
Published: December 2005

Abstract:  Multicentric Castleman's disease (MCD) is an indolent lymphoproliferative disorder. The pathogenesis of MCD has not been established, and its treatment remains uncertain. Several authors have described the relationship of human herpes virus type 8 (HHV‐8) to MCD in human immunodeficiency virus (HIV)‐positive patients. Recently, anti‐CD20 monoclonal antibody (rituximab) is increasingly being used to treat HIV‐positive MCD; although it is uncertain whether rituximab is effective for HIV‐negative patients with MCD. To explore the benefit of rituximab for HIV‐negative patients with MCD, we describe the clinical and biologic course in three HIV‐negative patients with MCD, and examined the relationship of HHV‐8 infection to HIV‐negative MCD. Their polymerase chain reaction analyses for the HHV‐8 sequence in peripheral blood were negative, and there was no relationship between HHV‐8 infection and symptoms of HIV‐negative MCD. Two of three patients (66%) achieved a near complete remission with no clinical symptoms due to MCD with a follow‐up of 16–40 months after rituximab administration. One of the three patients presented no clinical remission of MCD after rituximab administration, although a significant decrease of inflammatory parameters was observed. These findings suggest that rituximab treatment may be an appropriate first‐line therapy for HIV‐negative MCD.
A LUMBOSACRAL TRANSITIONAL VERTEBRA IN THE DOG PREDISPOSES TO CAUDA EQUINA SYNDROME
Authors: FLÜCKIGER MARK A. , DAMUR‐DJURIC NATASCHA , HÄSSIG MICHAEL , MORGAN JOE P. , STEFFEN FRANK
Published: December 2005

The association between the occurrence of a lumbosacral transitional vertebra (LTV) and the cauda equina syndrome (CES) in dogs was investigated. In 4000 control dogs without signs of CES, 3.5% had an LTV, while in 92 dogs with CES, 16.3% had an LTV. The lesion causing CES always occurred between the last true lumbar vertebra and the LTV. Dogs with an LTV were eight times more likely to develop CES than dogs without an LTV. German Shepherd dogs were eight times more likely to develop CES compared with other breeds. Male dogs were twice as likely to develop CES than females. Dogs with an LTV develop CES 1–2 years earlier than dogs without an LTV.
MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF ASCENDING HEMORRHAGIC MYELOMALACIA IN A DOG
Authors: PLATT SIMON R. , MCCONNELL J. FRASER , BESTBIER MARK
Published: December 2005

A 4‐year‐old neutered female terrier‐cross was evaluated for an acute onset of paraplegia. Utilizing magnetic resonance (MR) imaging, the cause of the neurologic deficits was determined to be a lumbar intervertebral disc extrusion. The MR study additionally demonstrated parenchymal hyperintensity on T2‐weighted images and similarly located diffuse hypointensity on gradient echo images, cranial and caudal to the compressive extradural lesion. Hemorrhagic myelomalacia was suspected based on these MR characteristics, which was subsequently confirmed surgically and histopathologically.
Inhibition of aryl acid adenylation domains involved in bacterial siderophore synthesis
Authors: Miethke Marcus , Bisseret Philippe , Beckering Carsten L. , Vignard David , Eustache Jacques , Marahiel Mohamed A.
Published: December 2005

Aryl acid adenylation domains are the initial enzymes for aryl‐capping of catecholic siderophores in a plethora of microorganisms. In order to overcome the problem of iron acquisition in host organisms, siderophore biosynthesis is decisive for virulence development in numerous important human and animal pathogens. Recently, it was shown that growth of Mycobacterium tuberculosis and Yersinia pestis can be inhibited in an iron‐dependent manner using the arylic acyl adenylate analogue 5′‐O‐[N‐(salicyl)‐sulfamoyl] adenosine that acts on the salicylate activating domains, MbtA and YbtE [Ferreras JA, Ryu JS, Di Lello F, Tan DS, Quadri LEN (2005) Nat Chem Biol1, 29–32]. The present study explores the behaviour of the 2,3‐dihydroxybenzoate activating domain DhbE (bacillibactin synthesis) and compares it to that of YbtE (yersiniabactin synthesis) upon enzymatic inhibition using a set of newly synthesized aryl sulfamoyl adenosine derivatives. The obtained results underline the highly specific mode of inhibition for both aryl acid activating domains in accordance with their natively accepted aryl moiety. These findings are discussed regarding the structure–function based aspect of aryl substrate binding to the DhbE and YbtE active sites.
Renal endothelin system and excretory function in Wistar–Kyoto and Long–Evans rats
Authors: Girchev R. , Bäcker A. , Markova P. , Kramer H. J.
Published: December 2005

Aim:  The role of the kidney endothelin system in the renal regulation of fluid and electrolyte excretion was investigated in Wistar–Kyoto (WKY) and Long–Evans (LE) rats in which we found previously marked differences in the renal excretory responses to endothelin A receptor blockade.

Methods:  The selective endothelin A and B receptor antagonists BQ‐123 (16.4 nmol kg−1 min−1) and BQ‐788 (25 nmol kg−1 min−1) were infused i.v. for 50 min in conscious chronically instrumented WKY and LE rats and their renal function and renal endothelin system were studied.

Results:  Without effects on glomerular filtration rate or renal blood flow, BQ‐123 and BQ‐788 decreased by more than 50% (P < 0.01) both urine flow rate and electrolyte excretion in WKY rats but only urine flow rate (P < 0.05) in LE rats. Endothelin‐1 content, preproET‐1/GPDH mRNA ratio, Bmax and Kd of total endothelin receptors in renal cortex did not differ between the two strains. In contrast, plasma endothelin‐1 concentration (0.58 ± 0.04 vs. 1.05 ± 0.01 femtomol mL−1; P < 0.01), renal papillary ET‐1 concentration (68 ± 5 vs. 478 ± 62 fmol mg−1 protein; P < 0.01) and preproET‐1/GPDH mRNA ratio (0.65 ± 0.09 vs. 0.88 ± 0.05; P < 0.05) as well as total endothelin receptor number in renal papilla (Bmax 5.3 ± 0.4 vs. and 9.0 ± 1.2 pmol mg−1 protein; P < 0.05) were markedly lower in LE than in WKY rats. In vitro studies showed that in both strains ETB receptors on renal cortical membranes amounted between 65% and 67% and on papillary membranes between 85% and 88%.

Conclusion:  The present data show that the selective ETA or ETB receptor blockade differentially affects tubular water and salt handling, which becomes apparent in conditions of low renal papillary endothelin receptor number and tissue endothelin‐1 concentration.