bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: the diagnosis and management of alcoholic hepatitis
Authors: COHEN S. M. , AHN J. 
Published: March 2009

SummaryBackground  Alcoholic hepatitis is a severe, cholestatic liver disease occurring in patients with alcohol abuse. Mortality is substantial; however, therapies may improve clinical outcomes.Aim  To provide an updated review of the epidemiology, diagnosis, staging and treatment of alcoholic hepatitis.Methods  A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed.Results  Severe alcoholic hepatitis occurs in a small fraction of patients who abuse alcohol. The 28‐day mortality ranges from 30% to 50% in most series. Diagnosis is generally based on clinical features, with a limited role for liver biopsy. Beneficial treatment options include alcohol abstinence and nutritional therapy. Despite variable results in clinical trials, corticosteroids and pentoxifylline appear to provide moderate survival benefit. Anti‐tumour necrosis factor agents and antioxidants have not proven beneficial, and should be limited to clinical trials. Liver transplant is not a frequent option given the active or recent alcohol use.Conclusions  Severe alcoholic hepatitis is a clinically‐diagnosed condition associated with significant mortality. Alcohol abstinence and nutritional therapy have been associated with improved clinical parameters and should be considered in all patients. Corticosteroid therapy and pentoxifylline therapy appear to show moderate survival benefit and should be considered as first‐line therapeutic agents.
Review article: adherence to medication for chronic hepatitis C – building on the model of human immunodeficiency virus antiretroviral adherence research
Authors: WEISS J. J. , BRÄU N. , STIVALA A. , SWAN T. , FISHBEIN D. 
Published: March 2009

SummaryBackground Treatment of hepatitis C virus (HCV) infection with pegylated interferon/ribavirin achieves sustained virological response in up to 56% of HCV mono‐infected patients and 40% of HCV/human immunodeficiency virus (HIV)‐co‐infected patients. The relationship of patient adherence to outcome warrants study.Aim To review comprehensively research on patient‐missed doses to HCV treatment and discuss applicable research from adherence to HIV antiretroviral therapy.Methods Publications were identified by PubMed searches using the keywords: adherence, compliance, hepatitis C virus, interferon and ribavirin.Results The term ‘non‐adherence’ differs in how it is used in the HCV from the HIV literature. In HCV, ‘non‐adherence’ refers primarily to dose reductions by the clinician and early treatment discontinuation. In contrast, in HIV, ‘non‐adherence’ refers primarily to patient‐missed doses. Few data have been published on the rates of missed dose adherence to pegylated interferon/ribavirin and its relationship to virological response.Conclusions As HCV treatment becomes more complex with new classes of agents, adherence will be increasingly important to treatment success as resistance mutations may develop with suboptimal dosing of HCV enzyme inhibitors. HIV adherence research can be applied to that on HCV to establish accurate methods to assess adherence, investigate determinants of non‐adherence and develop strategies to optimize adherence.
Influence of the mechanical behaviour of brittle–ductile fold–thrust belts on the development of foreland basins
Authors: Simpson Guy D. H. 
Published: March 2009

ABSTRACTA two‐dimensional mathematical model considering coupling between a deforming elasto‐visco‐plastic fold–thrust belt, flexural subsidence and diffusional surface processes is solved using the Finite Element Method to investigate how the mechanical behaviour of brittle–ductile wedges influences the development of foreland basins. Results show that, depending mainly on the strength of the basal décollement, two end‐member types of foreland basin are possible. When the basal detachment is relatively strong, the foreland basin system is characterised by: (1) Highly asymmetrical orogen formed by thrusts concentrated in the incoming pro‐wedge. (2) Sedimentation on retro‐side takes place in one major foredeep basin which grows throughout orogen evolution. (3) Deposition on the pro‐side occurs initially in the foredeep, and continues in the wedge‐top before isolated basins are advected towards the orogen core where they become uplifted and exhumed. (4) Most pro‐wedge basins show an upward progression from low altitude, foredeep deposits at the base to high altitude, wedge‐top deposits near the surface. In contrast, when the basal detachment behaves weakly due to the presence of low viscosity material such as salt, the foreland basin system is characterised by (1) Broad, low relief orogen showing little preferential vergence and predominance of folding relative to faulting. (2) Deposition mainly in wedge‐top basins showing growth strata. (3) Many basins are initiated contemporaneously but form discontinuously due to the locus of active deformation jumping back and forth between different structures. Model results successfully reproduce first order observations of deforming brittle–ductile wedges and foreland basins. Moreover, the results support and provide a framework for understanding the existence of two main end‐member foreland basin types, simple and complex, associated with fold–thrust belts whose detachments are relatively strong and weak, respectively.
Replicative potential of human natural killer cells
Authors: Fujisaki Hiroyuki , Kakuda Harumi , Imai Chihaya , Mullighan Charles G. , Campana Dario 
Published: March 2009

SummaryThe replicative potential of human CD56+ CD3− natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4‐1BB ligand and interleukin 15 (K562‐mb15‐41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1·6 × 105 to 1·2 × 1011% (median, 5·9 × 106%; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase gene (TERT). TERT‐overexpressing NK cells continued to proliferate in response to K562‐mb15‐41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long‐lived NK cells had high cytotoxicity against myeloid and T‐lineage leukaemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B‐lineage leukaemic cells after expression of anti‐CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity. We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell‐based therapies.
Ex vivo expanded telomerase-specific T cells are effective in an orthotopic mouse model for pancreatic adenocarcinoma
Authors: Hassanin H , Serba S , Schmidt J , Märten A 
Published: March 2009

Summary
Telomerase activity is over-expressed in nearly all pancreatic carcinomas, but not in chronic pancreatitis. Here, we investigated various protocols for expansion of telomerase-specific T cells for adoptive cell transfer and their use in a syngeneic pancreatic carcinoma mouse model. Telomerase-specific T cells were generated by stimulation of splenocytes from peptide-immunized donor mice with either interleukin (IL)-2, IL-15, artificial antigen-presenting cells, anti-signalling lymphocyte activation molecule (SLAM) microbeads or allogeneic dendritic cells in combination with a limited dilution assay. T cells were tested for antigen specificity in vitro and for anti-tumour activity in syngeneic mice with orthotopically implanted tumours pretreated with cyclophosphamide. The immune cells from recipients were immunophenotyped. During a period of 2 weeks, the expansion approach using IL-2 was very successful in generating a high number of telomerase-specific CD8+ T cells without losing their function after adoptive cell transfer. Significantly slower tumour growth rate and less metastasis were observed after adoptively transferring telomerase specific CD8+ T cells, expanded using IL-2. Further investigations showed that anti-tumour efficacy was associated with a significant shift from naive CD8+ T cells to CD8+ central memory T cells, as well as recruitment of a high number of dendritic cells. Remarkable amounts of telomerase-specific T cells were detectable in the tumour. Generation of telomerase-specific T cells is feasible, whereat IL-2-based protocols seemed to be most effective and efficient. Antigen-specific T cells showed significant cytotoxic activity in a syngeneic, orthotopic mouse model, whereas central memory T cells but not effector memory T cells appear to be of high importance.
Changes in topsoil carbon stock in the Tibetan grasslands between the 1980s and 2004
Authors: YANG YUANHE , FANG JINGYUN , SMITH PETE , TANG YANHONG , CHEN ANPING , JI CHENGJUN , HU HUIFENG , RAO SHENG , TAN KUN , HE JIN‐SHENG 
Published: March 2009

AbstractClimate warming is likely inducing carbon loss from soils of northern ecosystems, but little evidence comes from large‐scale observations. Here we used data from a repeated soil survey and remote sensing vegetation index to explore changes in soil organic carbon (SOC) stock on the Tibetan Plateau during the past two decades. Our results showed that SOC stock in the top 30 cm depth in alpine grasslands on the plateau amounted to 4.4 Pg C (1 Pg=1015 g), with an overall average of 3.9 kg C m−2. SOC changes during 1980s–2004 were estimated at −0.6 g C m−2 yr−1, ranging from −36.5 to 35.8 g C m−2 yr−1 at 95% confidence, indicating that SOC stock in the Tibetan alpine grasslands remained relatively stable over the sampling periods. Our findings are nonconsistent with previous reports of loss of soil C in grassland ecosystems due to the accelerated decomposition with warming. In the case of the alpine grasslands on the Tibetan Plateau studied here, we speculate that increased rates of decomposition as soils warmed during the last two decades may have been compensated by increased soil C inputs due to increased grass productivity. These results suggest that soil C stock in terrestrial ecosystems may respond differently to climate change depending on ecosystem type, regional climate pattern, and intensity of human disturbance.
Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis
Authors: Li Ming , O’Sullivan Kim M. , Jones Lynelle K. , Lo Cecilia , Semple Timothy , Kumanogoh Atsushi , Kikutani Hitoshi , Holdsworth Stephen R. , Kitching Richard 
Published: March 2009

SummaryCD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100‐deficient (CD100−/−) mice. Fewer CD100−/− glomeruli exhibited crescent formation or severe histological changes. Antigen‐specific immune responses were reduced in CD100−/− mice. There was less interferon (IFN)‐γ and interleukin (IL)‐4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100−/− mice. Serum antigen‐specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4+ cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin‐B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal‐CD100 protein was predominantly in tubules, while plexin‐B1 was present in both glomeruli and tubules. To determine whether glomerular plexin‐B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100−/− mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100–glomerular plexin‐B1 interactions enhance macrophage recruitment to glomeruli.
Correlation between recombinase activating gene 1 ubiquitin ligase activity and V(D)J recombination
Authors: Simkus Carrie , Bhattacharyya Anamika , Zhou Ming , Veenstra Timothy D. , Jones Jessica M. 
Published: March 2009

SummaryThe really interesting new gene (RING) finger ubiquitin ligase domain of the recombinase activating gene 1 (RAG1) V(D)J recombinase protein adopts a standard cross‐brace architecture but co‐ordinates three zinc ions as opposed to the canonical two. We demonstrated previously that disruption of the conserved zinc co‐ordination sites resulted in loss of structural integrity and ubiquitin ligase (E3) activity and interfered with the ability of full‐length RAG1 to support recombination. Here we present evidence that amino acids surrounding the third, non‐canonical site also contribute to functional interaction with the ubiquitin conjugating (E2) enzyme CDC34, while certain residues on the RING domain’s surface important for interaction between other E2–E3 pairs are less critical to the functional RAG1–CDC34 interaction in this assay. Partial reduction of ubiquitin ligase activity was significantly correlated with reduction in the ability of RAG1 to support recombination of extra‐chromosomal substrates (r = 0·805, P = 0·009). While poly‐ubiquitin chains could be generated, RAG1 did not promote rapid chain extension following mono‐ubiquitylation of substrate, regardless of the E2 enzyme used. No single ubiquitin lysine mutant disrupted the ability of CDC34 to form ubiquitin chains on RAG1, and mass spectrometric analysis of the poly‐ubiquitylated products indicated ubiquitin chain linkages through lysines 48 and 11. These data suggest that RAG1 promotes a mono‐ubiquitylation reaction that is required for optimal levels of V(D)J recombination.
Ganglioside GT1b protects human spermatozoa from hydrogen peroxide‐induced DNA and membrane damage
Authors: Gavella Mirjana , Garaj‐Vrhovac Verica , Lipovac Vaskresenija , Antica Mariastefania , Gajski Goran , Car Nikica 
Published: March 2009

SummaryWe have reported previously that various gangliosides, the sialic acid containing glycosphingolipids, provide protection against sperm injury caused by reactive oxygen species (ROS). In this study, we investigated the effect of treatment of human spermatozoa with ganglioside GT1b on hydrogen peroxide (H2O2)‐induced DNA fragmentation and plasma membrane damage. Single‐cell gel electrophoresis (Comet assay) used in the assessment of sperm DNA integrity showed thatin vitrosupplemented GT1b (100 μm) significantly reduced DNA damage induced by H2O2(200 μm) (p < 0.05). Measurements of Annexin V binding in combination with the propidium iodide vital dye labelling demonstrated that the spermatozoa pre‐treated with GT1b exhibited a significant increase (p < 0.05) in the percentage of live cells with intact membrane and decreased phosphatidylserine translocation after exposure to H2O2. Flow cytometry using the intracellular ROS‐sensitive fluorescence dichlorodihydrofluorescein diacetate dye employed to investigate the transport of the extracellularly supplied H2O2into the cell interior revealed that ganglioside GT1b completely inhibited the passage of H2O2through the sperm membrane. These results suggest that ganglioside GT1b may protect human spermatozoa from H2O2‐induced damage by rendering sperm membrane more hydrophobic, thus inhibiting the diffusion of H2O2across the membrane.
Positive effects of soil nitrogen pulses on individuals can have negative consequences for population growth during drought in a herbaceous desert perennial
Authors: Peek Michael S. , Forseth Irwin N. 
Published: March 2009

Summary

Resource pulses generally result in a burst of biological activity at multiple scales. For plants, the increased activity is generally considered positive due to an overall up‐regulation of physiological activity during the pulse. Longer‐term effects remain an understudied aspect of resource pulses.
We monitored the short‐ and long‐term effects of nitrogen (N) pulse to the long‐lived desert perennial, Cryptantha flava. One group of plants were treated with a one‐time application of N in the spring of 1999, a second group received two N pulses (one in the spring of 1999 and one in the spring of 2000), and a third group received ambient N (controls).
In the short‐term, N‐pulse treated plants rapidly increased leaf N concentrations, which in turn increased physiological activity and growth. But these responses were mediated by the availability of precipitation.
In a year with above‐average precipitation, all plants increased in size, but N‐treated plants grew more and had higher reproductive outputs than control plants. However, when the N pulse was followed by below‐average precipitation in the next year, plants with the highest growth rates due to N pulses experienced greater reduction in size and reproduction coupled with increased mortality rates relative to controls.
At the population level a matrix model showed higher population growth rates in wetter years for N‐treated plants compared to controls, but in drier years, N‐treated plants showed lower growth rates. Size hierarchies were restructured as a result of the combination of variability in precipitation and N pulses creating more even size distributions.
Synthesis. The high degree of spatial heterogeneity of N pulses offers opportunities for enhanced growth and reproduction to individuals of C. flava within the larger population. Small plants with access to high soil N were able to maintain high survival, growth rates and reproduction as long as precipitation was adequate. However, increased N inputs probably resulted in a trade‐off between reproduction and survival in small plants when precipitation was limiting. The high degree of unpredictability of resources in time and space ultimately contributes to the size hierarchies in this population and the variability in population growth rates.
Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program
Authors: Janszky I. , Mukamal K. J. , Ljung R. , Ahnve S. , Ahlbom A. , Hallqvist J. 
Published: March 2009

Abstract.Objectives.  To assess the long‐term effects of chocolate consumption amongst patients with established coronary heart disease.Design.  In a population‐based inception cohort study, we followed 1169 non‐diabetic patients hospitalized with a confirmed first acute myocardial infarction (AMI) between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants self‐reported usual chocolate consumption over the preceding 12 months with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registries for 8 years.Results.  Chocolate consumption had a strong inverse association with cardiac mortality. When compared with those never eating chocolate, the multivariable‐adjusted hazard ratios were 0.73 (95% confidence interval, 0.41–1.31), 0.56 (0.32–0.99) and 0.34 (0.17–0.70) for those consuming chocolate less than once per month, up to once per week and twice or more per week respectively. Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes. In contrast, intake of other sweets was not associated with cardiac or total mortality.Conclusions.  Chocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI. Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds, confirmation of this strong inverse relationship from other observational studies or large‐scale, long‐term, controlled randomized trials is needed.
Major cysteine peptidases of Entamoeba histolytica are required for aggregation and digestion of erythrocytes but are dispensable for phagocytosis and cytopathogenicity
Authors: Irmer Henriette , Tillack Manuela , Biller Laura , Handal Ghassan , Leippe Matthias , Roeder Thomas , Tannich Egbert , Bruchhaus Iris 
Published: March 2009

SummaryCysteine peptidases of Entamoeba histolytica (EhCPs) are considered to be important pathogenicity factors. It has been described that under standard axenic culture conditions, only three (ehcp‐a1, ehcp‐a2 and ehcp‐a5) out of approximately 50 cysteine peptidase genes present in the E. histolytica genome are substantially expressed, thus representing the set of major EhCPs. In this study, transcriptional silencing of the major peptidase genes was used to characterize their physiological role in more detail. Analysing the transfectants a fourth major cysteine peptidase activity belonging to EhCP‐A7 could be characterized. Neither cytopathic activity nor phagocytosis of erythrocytes was altered in CP‐inactivated amoebae. However, a significant difference in haemolytic activity was observed. EhCP‐A1 and EhCP‐A7 apparently had no influence on haemolytic activity, whereas transfectants silenced for ehcp‐a5 as well as those silenced for all major peptidases showed a significant reduction in their haemolytic activity. Furthermore, cells silenced for ehcp‐a1 and ehcp‐a7 and more effectively cells silenced in all major ehcps were impaired in digesting of phagocytosed erythrocytes. Moreover, amoebae silenced for all major peptidase genes lost the ability to form aggregates of erythrocytes prior to phagocytosis.
Expression of immune modulator cytokines in human fulminant amoebic colitis
Authors: SIERRA‐PUENTE R. E. , CAMPOS‐RODRÍGUEZ R. , JARILLO‐LUNA R. A. , MUÑOZ‐FERNÁNDEZ L. , RODRÍGUEZ M. G. , MUÑOZ‐ORTEGA M. H. , VENTURA‐JUÁREZ J. 
Published: March 2009

SummaryHuman fulminant amoebic colitis (FAC) is characterized by ulceration and inflammation of the colon. The specific mixture of pro‐inflammatory and anti‐inflammatory cytokines may participate in either the host defense or in the pathogenesis of amoebic colitis. Therefore, we studied the expression of IL‐8, IL‐10, IL‐4, TGF‐β and IFN‐γ in human FAC patients and controls through immunohistochemistry analysis. The number of cells expressing IL‐8, IL‐4 and IL‐10 was significantly enhanced in all FAC samples compared to the control samples. However, the expression of TGF‐ β in patients was low in the colonic mucosa and high in the lamina propria compared with the control. No expression of IFN‐γ was found in the controls or FAC samples. The production of IL‐8 by intestinal epithelial cells may play a role in the pathogenesis of amoebic infection, because this cytokine attracts neutrophils, which lead to an inflammatory reaction that results in tissue damage. The predominant expression of the macrophage down‐regulating cytokines, IL‐4, IL‐10 and TGF‐β, or the Th2‐type immune response could inhibit a cell‐mediated immune response, which in turn would facilitate parasite invasion in these tissues.