bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Role of Enhanced Cytokinemia and Plasma Inhibitor on the Decreased Activity of Plasma ADAMTS13 in Patients With Alcoholic Hepatitis: Relationship to Endotoxemia
Authors: Ishikawa Masatoshi , Uemura Masahito , Matsuyama Tomomi , Matsumoto Masanori , Ishizashi Hiromichi , Kato Seiji , Morioka Chie , Fujimoto Masao , Kojima Hideyuki , Yoshiji Hitoshi , Tsujimoto Tatsuhiro , Takimura Chikara , Fujimura Yoshihiro , Fukui Hiroshi 
Published: December 2008

Background:  Deficiency of ADAMTS13 (adisintegrin‐like and metalloproteinase with thrombospondin type‐1 motifs 13) results in an increase in unusually large von Willebrand factor multimer (UL‐VWFM) of the plasma and finally causes microcirculatory disturbance. Our previous study demonstrated that the imbalance of increased UL‐VWFM over decreased ADAMTS13 activity may contribute to the development of multiorgan failure in patients with alcoholic hepatitis (AH). The aim of this study was to explore the potential mechanism to reduce the activity of plasma ADAMTS13.Methods:  Plasma cytokine levels including interleukin (IL)‐6, IL‐8, and tumor necrosis factor‐α (TNF‐α), plasma endotoxin concentration, and the plasma inhibitor against ADAMTS13 were determined together with ADAMTS13 activity, VWF antigen (VWF:Ag), and UL‐VWFM in 24 patients with AH and 5 patients with severe alcoholic hepatitis (SAH).Results:  The concentrations of IL‐6, IL‐8, and TNF‐α on admission were significantly higher in patients with SAH than in those with AH and controls. The ADAMTS13 activity concomitantly decreased, and the VWF:Ag progressively elevated with increasing concentrations of these cytokines from normal range to over 100 pg/ml. Plasma endotoxin concentration was markedly higher in patients with SAH (mean 52.3 pg/ml) and AH (21.7 pg/ml) than in controls (7.9 pg/ml). The endotoxin concentration inversely correlated with ADAMTS13 activity and was higher in patients with UL‐VWFM than those without. The inhibitor was detected in 4 patients with SAH (0.9 to 2.1 BU/ml) and 6 patients with AH (0.5 to 1.6 BU/ml). Patients with the inhibitor showed lower functional liver capacity, higher endotoxin concentration, and marked inflammatory signs than those without. At the recovery stage, the ADAMTS13 activity increased to normal range, the VWF:Ag decreased, and the UL‐VWFM disappeared with the decrease in the concentrations of cytokines and endotoxin, and the disappearance of the inhibitor.Conclusion:  Decreased ADAMTS13 activity and increased VWF:Ag could be induced not only by pro‐inflammatory cytokinemia, but also by its inhibitor, both of which may be closely related to enhanced endotoxemia in patients with AH and SAH.
Exogenous IL‐15 in Combination With IL‐15Rα Rescues Natural Killer Cells From Apoptosis Induced by Chronic Alcohol Consumption
Authors: Zhang Hui , Meadows Gary G. 
Published: December 2008

Background:  Chronic alcohol consumption reduces the percentage and number of peripheral natural killer (NK) cells in mice and in humans. The underlying mechanism for these changes is only partly known. We recently found that chronic alcohol consumption inhibits NK cell release from the bone marrow (BM) and that this is associated with a decrease in splenic NK cells. The number of peripheral NK cells is tightly controlled by homeostatic proliferation. It is not known whether this mechanism is initiated in response to the reduction in splenic NK cells, or if so, why the steady state levels of NK cells are not restored.Methods:  To examine this mechanism, female C57BL/6 mice were given 20% w/v alcohol in the drinking water for 3 months. NK cell proliferation and apoptosis were determined before and after treatment with IL‐15 alone or combined with its alpha receptor.Results:  Chronic alcohol consumption invoked homeostatic proliferation of splenic NK cells in an attempt to return NK cells to normal levels; however, this did not happen due to enhanced apoptosis of NK cells relative to proliferation. Chronic alcohol consumption decreased IL‐15 producing cells in the spleen but not in the BM. The numbers of NK cells in the alcohol‐consuming mice returned to normal levels in the spleen and were higher than normal in the BM after 2 daily injections of IL‐15; however, the enhanced rate of apoptosis due to alcohol consumption was not decreased in the spleen or BM. Combined IL‐15 and IL‐15Rα treatment decreased apoptosis of NK cells from alcohol‐consuming mice to levels similar to untreated water‐drinking mice and greatly increased the percentage and number of NK cells in both the spleen and BM.Conclusion:  Chronic alcohol consumption causes a self‐unrecoverable loss of NK cells in the spleen by compromising NK cell release from the BM and enhancing splenic NK cell apoptosis that can be reversed with IL‐15/IL‐15Rα treatment.
Sensitivity and Tolerance to the Hypnotic and Ataxic Effects of Ethanol in Adolescent and Adult C57BL/6J and DBA/2J Mice
Authors: Linsenbardt David N. , Moore Eileen M. , Gross Carly D. , Goldfarb Karen J. , Blackman Laverne C. , Boehm II Stephen L. 
Published: December 2008

Background:  There is considerable research examining differences in adolescent and adult sensitivity and tolerance to ethanol related behavioral phenotypes. However, the available published data has almost exclusively assessed these behaviors in outbred rats. The present study was conducted using the alcohol preferring inbred mouse strain C57BL/6J (B6) and the alcohol nonpreferring inbred mouse strain DBA/2J (D2) to determine if differences in the sedative and ataxic effects of ethanol exist between adolescents and adults, and to determine whether there are any genetic influences involved therein.Methods:  Adolescent and adult mice of each sex and genotype were given intraperitoneal (i.p.) injections of ethanol (1.5, 1.75, or 4.0 g/kg) or saline and assessed for the loss of righting reflex (LORR) or hind footslips on the balance beam apparatus. These animals were then tested for the development of tolerance to these behaviors on subsequent days.Results:  Despite evident pharmacokinetic differences, D2 adolescents were found to be relatively less sensitive to ethanol’s hypnotic actions than their adult D2 counterparts. Adolescent and adult B6 animals did not differ. Furthermore, although adult animals appeared to develop significantly greater degrees of tolerance to ethanol‐induced hypnosis compared with adolescents, these effects were likely in part related to differences in ethanol absorption/metabolism across time. Taking into account pharmacokinetic differences and the overall poor performance of male adults, adolescent animals were found to be equally if not more sensitive to the motor incoordinating (ataxic) effects of ethanol. Overall, tolerance to these effects varied by age and genotype but appeared to be related to changes in ethanol pharmacokinetics rather than strict behavioral sensitivity.Conclusion:  The current work suggests that adolescent B6 and D2 inbred mice exhibit ontogenetic differences in sensitivity to ethanol’s hypnotic and ataxic effects. Importantly, in some cases age differences emerge as a function of differential ethanol pharmacokinetics. These results extend the current literature examining this critical developmental period in mice and illustrate the benefits of comparing ethanol related developmental differences in different genetic mouse populations.
Global–Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior‐DTI Association Study
Authors: Müller‐Oehring Eva M. , Schulte Tilman , Fama Rosemary , Pfefferbaum Adolf , Sullivan Edith V. 
Published: December 2008

Background: Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global–local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism‐related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes.Methods: A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age‐matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure.Results: Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits.Conclusion: Global–local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference‐callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.
Neuronal migration disorders: clinical, neuroradiologic and genetics aspects
Authors: Spalice Alberto , Parisi Pasquale , Nicita Francesco , Pizzardi Giorgia , Del Balzo Francesca , Iannetti Paola 
Published: December 2008

AbstractDisorders of neuronal migration are a heterogeneous group of disorders of nervous system development.One of the most frequent disorders is lissencephaly, characterized by a paucity of normal gyri and sulci resulting in a ‘smooth brain’. There are two pathologic subtypes: classical and cobblestone. Six different genes could be responsible for this entity (LIS1, DCX, TUBA1A, VLDLR, ARX, RELN), although co‐delection of YWHAE gene with LIS1 could result in Miller–Dieker Syndrome.Heterotopia is defined as a cluster of normal neurons in abnormal locations, and divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Genetically, heterotopia is related to Filamin A (FLNA) or ADP‐ribosylation factor guanine exchange factor 2 (ARFGEF2) genes mutations.Polymicrogyria is described as an augmentation of small circonvolutions separated by shallow enlarged sulci; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria results in a clinical syndrome manifested by mild mental retardation, epilepsy and pseudobulbar palsy. Gene mutations linked to this disorder are SRPX2, PAX6, TBR2, KIAA1279, RAB3GAP1 and COL18A1.Schizencephaly, consisting in a cleft of cerebral hemisphere connecting extra‐axial subaracnoid spaces and ventricles, is another important disorder of neuronal migration whose clinical characteristics are extremely variable. EMX2 gene could be implicated in its genesis.Focal cortical dysplasia is characterized by three different types of altered cortical laminations, and represents one of most severe cause of epilepsy in children. TSC1 gene could play a role in its etiology.Conclusion: This review reports the main clinical, genetical and neuroradiological aspects of these disorders. It is hoped that accumulating data of the development mechanisms underlying the expanded network formation in the brain will lead to the development of therapeutic options for neuronal migration disorders.
Intravitreal bevacizumab (Avastin®) for neovascular age‐related macular degeneration in treatment‐naive patients
Authors: Pedersen Karen Bjerg , Sjølie Anne Katrin , Møller Flemming 
Published: December 2008

Abstract.Purpose:  To report the effects of intravitreal bevacizumab (Avastin®) in treatment‐naive patients with exudative age‐related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity.Methods:  A prospective, uncontrolled, pilot study of 26 eyes of 26 patients, all previously treatment‐naive to photodynamic therapy, argon laser or anti‐vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3 months and 6 months after the first injection. Re‐treatment was given on an ‘as needed’ basis.Results:  Twenty‐four eyes of 24 patients completed 6 months of follow‐up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P < 0.01) and to 61 letters at 6 weeks (P < 0.01). No significant improvement in VA from baseline was found after 3 and 6 months. Patients with pigment epithelial detachment (PED) had a significantly worse outcome in VA at 6 months. Contrast sensitivity improved from baseline to 3 or 6 months, but this improvement was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow‐up examinations (P < 0.01).Conclusion:  Mean ETDRS VA improved significantly after 1 and 6 weeks; thereafter, it remained stable throughout the study period. Macular thickness improved significantly at all time points. The results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment‐naive ARMD patients.
Concordant Proficiency in Measurement of T-Cell Immunity in Human Immunodeficiency Virus Vaccine Clinical Trials by Peripheral Blood Mononuclear Cell and Enzyme-Linked Immunospot Assays in Laboratories from Three Continents
Authors: Boaz Mark J. , Hayes Peter , Tarragona Tony , Seamons Laura , Cooper Andrew , Birungi Josephine , Kitandwe Paul , Semaganda Aloysius , Kaleebu Pontiano , Stevens Gwynneth , Anzala Omu , Farah Bashir , Ogola Simon , Indangasi Jackton , Mhlanga Patrick , Van Eeden Melanie , Thakar Madhuri , Pujari Ashwini , Mishra Shadri , Goonetilleke Nilu , Moore Stephen , Mahmoud Abdul , Sathyamoorthy Pattabiraman , Mahalingam Jayashri , Narayanan Paranji R. , Ramanathan Vadakkuppattu D. , Cox Josephine H. , Dally Len , Gill Dilbinder K. , Gilmour Jill 
Published: December 2008

ABSTRACT
The gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay is used routinely to evaluate the potency of human immunodeficiency virus (HIV) vaccine candidates and other vaccine candidates. In order to compare candidates and pool data from multiple trial laboratories, validated standardized methods must be applied across laboratories. Proficiency panels are a key part of a comprehensive quality assurance program to monitor inter- and intralaboratory performance, as well as assay performance, over time. Seven International AIDS Vaccine Initiative-sponsored trial sites participated in the proficiency panels described in this study. At each laboratory, two operators independently processed identical sample sets consisting of frozen peripheral blood mononuclear cell (PBMC) samples from different donors by using four blind stimuli. PBMC recovery and viability after overnight resting and the IFN-γ ELISPOT assay performance were assessed. All sites demonstrated good performance in PBMC thawing and resting, with a median recovery of 78% and median viability of 95%. The laboratories were able to detect similar antigen-specific T-cell responses, ranging from 50 to >3,000 spot-forming cells per million PBMC. An approximate range of a half log in results from operators within or across sites was seen in comparisons of antigen-specific responses. Consistently low background responses were seen in all laboratories. The results of these proficiency panels demonstrate the ability of seven laboratories, located across three continents, to process PBMC samples and to rank volunteers with differential magnitudes of IFN-γ ELISPOT responses. These findings also illustrate the ability to standardize the IFN-γ ELISPOT assay across multiple laboratories when common training methods, reagents such as fetal calf serum, and standard operating procedures are adopted. These results are encouraging for laboratories that are using cell-based immunology assays to test HIV vaccines and other vaccines.
Protection against AsiaticTaenia soliumInduced by a Recombinant 45W-4B Protein
Authors: Luo Xuenong , Zheng Yadong , Hou Junling , Zhang Shaohua , Cai Xuepeng 
Published: December 2008

ABSTRACTTaenia soliumis a great threat not only to human health but also to the pig-raising industry. Oncospheral stage-specific 45W proteins are good candidates for the development of anticysticercosis vaccines. In this study, a recombinant 45W-4B protein was highly produced and used for vaccination. Two animal trials resulted in a significant reduction in parasite burden induced by the definite protein against AsiaticT. solium, up to 97.0% and 98.4%, respectively. These provide informative results for the development of effective 45W-4B vaccines against cysticercosis caused by both Chinese and MexicanT. soliumisolates and even by other isolates.
Fourteen Years of Severe Arthralgia in a Man without Gastrointestinal Symptoms: Atypical Whipple's Disease
Authors: Mancini Fabiola , Sbaragli Serena , Colivicchi Gilberto , Cassone Antonio , Ciervo Alessandra 
Published: December 2008

ABSTRACT

We report here the case of Whipple's disease in a 60-year-old man with severe arthralgia and systemic disorders but without gastrointestinal manifestations. The patient had different clinical diagnoses over a period of 14 years. We identified
Tropheryma whipplei
by real-time PCR. Molecular typing was also performed by sequencing the 16S-23S rRNA intergenic spacer region and domain III of the 23S rRNA gene.
Association of High
Orientia tsutsugamushi
DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus
Authors: Sonthayanon Piengchan , Chierakul Wirongrong , Wuthiekanun Vanaporn , Phimda Kriangsak , Pukrittayakamee Sasithon , Day Nicholas P. , Peacock Sharon J. 
Published: December 2008

ABSTRACT

Orientia tsutsugamushi
, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region. The severity of infection ranges from mild features to multiorgan failure and death. The aim of this prospective study was to define the
O. tsutsugamushi
loads in the blood samples of patients with scrub typhus on the day of hospital admission and to determine whether this was associated with disease severity. Quantitation was performed using a real-time PCR assay targeting the 16S rRNA gene of
O. tsutsugamushi
. A total of 155 patients with a confirmed diagnosis of scrub typhus had a median (interquartile range [IQR], range)
O. tsutsugamushi
DNA load in blood of 13 (0 to 334, 0 to 310,253) copies/ml. This included 74 patients who had undetectable bacterial loads. An analysis of bacterial load versus clinical features for all 155 patents demonstrated that duration of illness (
P
< 0.001), presence of eschar (
P
= 0.004), and concentrations of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (
P
< 0.001 for all three) were positively correlated with bacterial load. Patients who died had a significantly higher bacterial load than those who survived (mean [standard deviation] values: 17,154 [12.7] versus 281 [5.2] copies/ml;
P
< 0.001). This study has demonstrated a relationship between bacterial load and disease severity in adults with scrub typhus.
Mutational Analysis of a Conserved Glutamic Acid Required for Self-Catalyzed Cross-Linking of Bacteriophage HK97 Capsids
Authors: Dierkes Lindsay E. , Peebles Craig L. , Firek Brian A. , Hendrix Roger W. , Duda Robert L. 
Published: December 2008

ABSTRACT
The capsid of bacteriophage HK97 is stabilized by ∼400 covalent cross-links between subunits which form without any action by external enzymes or cofactors. Cross-linking only occurs in fully assembled particles after large-scale structural changes bring together side chains from three subunits at each cross-linking site. Isopeptide cross-links form between asparagine and lysine side chains on two subunits. The carboxylate of glutamic acid 363 (E363) from a third subunit is found ∼2.4 Å from the isopeptide bond in the partly hydrophobic pocket that contains the cross-link. It was previously reported without supporting data that changing E363 to alanine abolishes cross-linking, suggesting that E363 plays a role in cross-linking. This alanine mutant and six additional substitutions for E363 were fully characterized and the proheads produced by the mutants were tested for their ability to cross-link under a variety of conditions. Aspartic acid and histidine substitutions supported cross-linking to a significant extent, while alanine, asparagine, glutamine, and tyrosine did not, suggesting that residue 363 acts as a proton acceptor during cross-linking. These results support a chemical mechanism, not yet fully tested, that incorporates this suggestion, as well as features of the structure at the cross-link site. The chemically identical isopeptide bonds recently documented in bacterial pili have a strikingly similar chemical geometry at their cross-linking sites, suggesting a common chemical mechanism with the phage protein, but the completely different structures and folds of the two proteins argues that the phage capsid and bacterial pilus proteins have achieved shared cross-linking chemistry by convergent evolution.
Severe Acute Respiratory Syndrome Coronavirus Protein 6 Is Required for Optimal Replication
Authors: Zhao Jincun , Falcón Ana , Zhou Haixia , Netland Jason , Enjuanes Luis , Pérez Breña Pilar , Perlman Stanley 
Published: December 2008

ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes several accessory proteins of unknown function. One of these proteins, protein 6 (p6), which is encoded by ORF6, enhances virus replication when introduced into a heterologous murine coronavirus (mouse hepatitis virus [MHV]) but is not essential for optimal SARS-CoV replication after infection at a relatively high multiplicity of infection (MOI). Here, we reconcile these apparently conflicting results by showing that p6 enhances SARS-CoV replication to nearly the same extent as when expressed in the context of MHV if cells are infected at a low MOI and accelerates disease in mice transgenic for the human SARS-CoV receptor.