bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in impact of HLA class I allele expression on HIV‐1 plasma virus loads at a population level over time
Authors: Koga Michiko , Kawana‐Tachikawa Ai , Heckerman David , Odawara Takashi , Nakamura Hitomi , Koibuchi Tomohiko , Fujii Takeshi , Miura Toshiyuki , Iwamoto Aikichi 
Published: January 2010

ABSTRACTHLA class I allele types have differential impacts on the level of the pVL and outcome of HIV‐1 infection. While accumulations of CTL escape mutations at population levels have been reported, their actual impact on the level of the pVL remains unknown. In this study HLA class I types from 141 untreated, chronically HIV‐1 infected Japanese patients diagnosed from 1995–2007 were determined, and the associations between expression of individual HLA alleles and level of pVL analyzed. It was found that the Japanese population has an extremely narrow HLA distribution compared to other ethnic groups, which may facilitate accumulation of CTL escape mutations at the population level. Moreover while they uniquely lack the most protective HLA‐B27/B57, they commonly express the alleles that are protective in Caucasians (A11:10.4%, A26:11.55%, B51:8.6% and Cw14:12.7%). Cross‐sectional analyses revealed no significant associations between expression of individual alleles and the level of the pVL. The patients were then stratified by the date of HIV diagnosis and the analyses repeated. It was found that, before 2001, B51+ individuals displayed significantly lower pVL than the other patients (median: 5150 vs. 18 000 RNA copies/ml, P= 0.048); however thereafter this protective effect waned and disappeared, whereas no changes were observed for any other alleles over time. These results indicate that, at a population level, some HLA alleles have been losing their beneficial effects against HIV disease progression over time, thereby possibly posing a significant challenge for HIV vaccine development. However such detrimental effects may be limited to particular HLA class I alleles.
Glutathione S‐transferase A4 is a positive marker for rat hepatic foci induced by clofibrate and genotoxic carcinogens
Authors: Shimizu Takeshi , Fan Yang , Yamana Daisuke , Miura Takuya , Nanashima Naoki , Yamada Toshiyuki , Tsuchida Shigeki 
Published: January 2010

Peroxisome proliferators (PP), including clofibrate (CF), are non‐genotoxic rodent carcinogens, and oxidative DNA damages are suggested as a causative event for carcinogenesis. Gene expression profiles differ between hepatic lesions induced by PP and genotoxic carcinogens. Our previous study revealed that expression of L‐bifunctional enzyme (enoyl‐CoA hydratase/3‐hydroxyacyl‐CoA dehydrogenase, BE) was repressed in preneoplastic lesions induced by PP, whereas it was enhanced in the surrounding tissues. In the present study, we immunohistochemically examined expression of the specific glutathione S‐transferase (GST) form, GST‐A4, which detoxifies 4‐hydroxy‐alkenal, the end‐product of lipid peroxides, and nuclear factor‐erythroid 2‐related factor 2 (Nrf2), a transcription factor for many genes encoding drug‐metabolizing enzymes and defending enzymes against oxidative stress, during rat hepatocarcinogenesis induced by CF and genotoxic carcinogens. GST‐A4 and Nrf2 were not expressed in BE‐negative foci at 8 weeks of CF administration, but were expressed in the foci at 60 weeks. GST‐A4‐positive foci appeared at later stages than BE‐negative foci, but its localization was coincidental with that of the latter foci. The areas of GST‐A4‐positive foci were larger than those of BE‐negative foci without GST‐A4 expression. Most GST‐A4‐positive foci were also positive for Nrf2. In rat livers induced by genotoxic carcinogens, GST‐P‐negative foci as well as GST‐P‐positive foci were demonstrated. GST‐A4 and Nrf2 were expressed in GST‐P‐negative foci, whereas they were not expressed in most GST‐P‐positive foci. Thus, GST‐A4‐positive foci developed in rat livers by CF and genotoxic carcinogen administration, indicating that the enzyme is a positive marker for hepatic foci induced by these different carcinogens.(Cancer Sci 2010; 101: 1093–1098)
The influence of environmental risk factors in hospitalization for gastro‐oesophageal reflux disease‐related diagnoses in the United States
Authors: THUKKANI N. , SONNENBERG A. 
Published: January 2010

Aliment Pharmacol Ther 31, 852–861SummaryBackground  The impact of gastro‐oesophageal reflux disease on hospitalization is unknown.Aim  To describe the characteristics of patients hospitalized for diagnoses related to gastro‐oesophageal reflux disease (GERD) and find potential environmental influences that affect their hospitalization.Methods  Data from the Healthcare Cost and Utilization Project were used to study the demographic characteristics of hospitalizations associated with GERD during 2003–2006. Data from the Centers for Disease Control were used for information about the US prevalence of obesity.Results  During 2003–2006, 0.5 million patients with a primary and 14.5 million patients with a secondary GERD‐related diagnosis became hospitalized in the US. Oesophageal reflux and hiatal hernia were more common in female than in male inpatients, whereas Barrett’s oesophagus and oesophageal adenocarcinoma were more common in male than in female inpatients. All GERD‐related diagnoses were more common in white people than non‐white people. Hospitalizations associated with oesophageal reflux, reflux oesophagitis and Barrett’s oesophagus showed resembling geographical distributions among different US states. The prevalence of obesity and the hospitalization for hiatal hernia or reflux oesophagitis were also characterized by similar geographical distributions.Conclusion  The large numbers of inpatients with a discharge diagnosis of GERD‐related conditions attest to the frequent occurrence and relevance of GERD in contributing to hospitalization in the US.
Meta‐analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel
Authors: KWOK C. S. , LOKE Y. K. 
Published: January 2010

SummaryBackground Recent studies have suggested an adverse interaction between proton pump inhibitors (PPI) and clopidogrel.Aim To perform a meta‐analysis of cardiovascular outcomes and mortality in patients taking clopidogrel, with and without concomitant PPI.Methods We searched MEDLINE, EMBASE, Cochrane Controlled Trials Register in October 2009, and checked conference abstracts for randomized and nonrandomized studies that reported the risk of cardiovascular events and mortality with PPI exposure in patients taking clopidogrel. We performed random effects meta‐analysis, stratified by study design and assessed heterogeneity using theI2statistic.Results Our review included 23 studies covering 93 278 patients. There was substantial heterogeneity in the meta‐analyses of major cardiovascular events (19 studies,I2 = 79%) or myocardial infarction (12 studies,I2 = 77%). Analysis of propensity‐matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association. Meta‐analysis of 13 studies showed no significant association between PPI use and overall mortality (RR 1.09, 95% CI: 0.94–1.26,P = 0.23,I2 = 60%).Conclusion As there are conflicting and inconsistent data regarding the adverse clopidogrel–PPI interaction, clinicians should focus on potential harm from ulcers/haemorrhage before deciding to omit PPIs in patients taking clopidogrel.
Angiosarcoma in FNA smears: diagnostic accuracy, morphology, immunocytochemistry and differential diagnoses
Authors: Pohar‐Marinšek Ž. , Lamovec J. 
Published: January 2010

Ž. Pohar‐Marinšek and J. Lamovec Angiosarcoma in FNA smears: diagnostic accuracy, morphology, immunocytochemistry and differential diagnoses Objective:  The aim of our study was to analyse the diagnostic accuracy in recognizing angiosarcoma from fine needle aspiration (FNA) samples and to determine morphological features of angiosarcoma in cytology.Methods:  FNA samples from 18 histologically confirmed angiosarcomas obtained between 1985 and 2009 were included in the study. Original cytological diagnoses were retrieved, smears reviewed and morphological features analysed: cellularity, smear pattern, cell morphology, contents of background. Outcome of immunocytochemistry was noted and additional reactions performed if material was available.Results:  There were 13 primary angiosarcomas and five recurrent tumours; nine tumours were epithelioid. Twelve tumours were cytologically diagnosed as malignant, three as suspicious and three were judged unsatisfactory. Only two primary tumours were diagnosed as vascular. According to morphology, tumours were divided into those with predominantly epithelioid cells and those with predominantly spindle cells. Within these two groups were variations due to grade of tumour. Cytomorphology did not correlate well with histology in mixed and spindle cell types of angiosarcomas. Immunocytochemistry was applied in seven cases, specific vascular marker CD31 only twice at the time of diagnosis and three times retrospectively.Conclusions:  Angiosarcomas are difficult to recognize on FNA smears when they lack the typical dual, spindle and epithelioid cell population and when they occur in internal organs where carcinomas are more common. Very few reliable data are available concerning specificity of CD31 on cytological material.
Can cytological features differentiate reactive renal tubular cells from low‐grade urothelial carcinoma cells?
Authors: Ohsaki H. , Hirakawa E. , Kushida Y. , Yokoshita S. , Nakamura M. , Kiyomoto H. , Haba R. 
Published: January 2010

H. Ohsaki, E. Hirakawa, Y. Kushida, S. Yokoshita, M. Nakamura, H. Kiyomoto and R. Haba Can cytological features differentiate reactive renal tubular cells from low‐grade urothelial carcinoma cells? Objective:  To compare the cytomorphological and immunocytochemical features of reactive renal tubular cells and low‐grade urothelial carcinoma cells (LG‐UCs).Methods:  We examined 15 cytological parameters in 38 cases with reactive renal tubular cells in renal disease and 20 cases of LG‐UCs from bladder cancer that had been diagnosed by histological examination. Voided urine cytological parameters evaluated were as follows: (i) maximum cell numbers of clusters, (ii) cannibalism, (iii) rosette‐like arrangement, (iv) hobnail‐shaped cells, (v) vacuolated cytoplasm, (vi) intracytoplasmic haemosiderin, (vii) irregular nuclear contours, (viii) chromatin pattern, (ix) prominent nucleoli, (x) cast encasement, (xi) casts, (xii) dysmorphic erythrocytes, (xiii) isomorphic erythrocytes, (xiv) necrosis, and (xv) vimentin reactivity. The above parameters were determined using Mann–Whitney U‐test and chi‐square test, with differences considered significant at P < 0.05.Results:  In reactive renal tubular cells, low to moderate cell numbers of clusters (fewer than 50 cells), rosette‐like arrangement, hobnail‐shaped cells, vacuolated cytoplasm, intracytoplasmic haemosiderin, euchromatin pattern, prominent nucleoli, dysmorphic erythrocytes and vimentin reactivity were present in significantly higher proportions compared with those in LG‐UCs. In LG‐UCs, high cell numbers of clusters (50 cells or more), cannibalism, heterochromatin pattern, isomorphic erythrocytes and necrosis were seen in significantly higher proportions. No significant differences were observed in irregular nuclear contours, cast encasement or casts.Conclusions:  Based on results of the present study, maximum cell numbers of clusters, cannibalism, rosette‐like arrangement, hobnail‐shaped cells, vacuolated cytoplasm, intracytoplasmic haemosiderin, chromatin pattern, prominent nucleoli, dysmorphic erythrocytes, isomorphic erythrocytes, necrosis, and vimentin reactivity were capable of distinguishing reactive renal tubular cells from LG‐UCs.
Value of computer‐assisted quantitative nuclear morphometry for differentiation of reactive renal tubular cells from low‐grade urothelial carcinoma
Authors: Ohsaki H. , Hirakawa E. , Kagawa K. , Nakamura M. , Kiyomoto H. , Haba R. 
Published: January 2010

H. Ohsaki, E. Hirakawa, K. Kagawa, M. Nakamura, H. Kiyomoto and R. Haba Value of computer‐assisted quantitative nuclear morphometry for differentiation of reactive renal tubular cells from low‐grade urothelial carcinoma Objective:  To assess whether computer‐assisted quantitative morphological parameters can be an effective tool for objectively distinguishing reactive renal tubular cells from low‐grade urothelial carcinoma cells (LG‐UCs) in voided urine.Methods:  Nuclear morphometry was performed by a computer‐assisted image analyser system on Papanicolaou‐stained cytological specimens. The circumference of reactive renal tubular cells (n = 40) or LG‐UC (n = 20) nuclei were manually traced, and the following nuclear morphometric parameters were analysed: (i) area, (ii) perimeter, (iii) roundness factor, (iv) maximum length, and (v) linear factor. For each nuclear measurement, we calculated the maximum, minimum, mean and standard deviation.Results:  The mean nuclear area and nuclear perimeter were higher in reactive renal tubular cells compared to the LG‐UCs. The mean of roundness and linear factors (reflecting a tendency for the nuclear outline to be regular and oval, respectively) were higher in LG‐UCs compared with reactive renal tubular cells. Among nuclear areas, the nuclear perimeter, roundness factors and maximum length did not show any significant differences between reactive renal tubular cells and LG‐UCs. On the other hand, the linear factor showed a mean higher value among LG‐UCs than reactive renal tubular cells (P = 0.023).Conclusions:  Of five quantitative nuclear morphological parameters, only linear factor was statistically significant in differentiating reactive renal tubular cells in renal disease from LG‐UCs.
Effect of sex hormone treatment on circulating adiponectin and subforms in Turner and Klinefelter syndrome
Authors: Høst C. , Bojesen A. , Frystyk J. , Flyvbjerg A. , Christiansen J. S. , Gravholt C. H. 
Published: January 2010

Eur J Clin Invest 2010; 40 (3): 211–219AbstractBackground  Sex hormones have been shown to influence levels of adiponectin. Furthermore, testosterone has been shown to alter the subform distribution of adiponectin, whereas the effects of oestradiol are equivocal. We investigated the impact of sex hormone replacement therapy (HRT) on circulating adiponectin and its subforms, fasting lipids and measures of insulin sensitivity in Turner syndrome (TS) and Klinefelter syndrome (KS) respectively.Materials and methods  We compared eight young TS patients on and off 2 months of HRT vs. eight age‐ and body mass index (BMI) matched healthy females as well as 19 untreated KS patients vs. 20 testosterone treated KS patients vs. 20 age and BMI matched healthy males. Total adiponectin and adiponectin subforms separated by fast protein liquid chromatography were measured using an in‐house assay. In addition, fasting levels of insulin, glucose and homeostasis model assessment estimates were determined.Results  In TS, total adiponectin levels were 10·5 ± 3·1 (mean ± SD) vs. 12·8 ± 3·5 mg L−1 (P = 0·02) and high molecular weight (HMW) adiponectin 5·8 ± 2·7 and 6·8 ± 1·9 mg L−1 (P = 0·02) on and off HRT respectively. Irrespective of HRT, total adiponectin and HMW adiponectin were similar to control values. In KS, total adiponectin levels were 6·5 (3·0–24·2) (median and range) and 9·3 (4·3–14·3) mg L−1 (P = NS) and HMW adiponectin was 2·5 (0·5–16·0) and 4·6 (1·3–8·6) mg L−1 (P = NS) with and without testosterone treatment respectively, and similar to controls.Conclusion  Short time HRT suppressed HMW and total adiponectin levels in TS patients. Testosterone treatment in KS patients had no effect on these parameters. In both groups of patients either adiponectin or the HMW subform seems to play no greater role in reflecting or mediating insulin sensitivity. Our data indicates that in patients with TS and KS, sex hormones have different effects on circulating adiponectin and its HMW subform than previously reported in other sex hormone deficient patients and healthy subjects.
Long‐term outcome after thrombectomy in acute myocardial infarction
Authors: Adlbrecht C. , Distelmaier K. , Bonderman D. , Beran G. , Redwan B. , Strunk G. , Binder T. , Jakowitsch J. , Probst P. , Heinze G. , Maurer G. , Lang I. M. 
Published: January 2010

Eur J Clin Invest 2010; 40 (3): 233–241AbstractBackground Current data appear in favour of thrombectomy for ST‐elevation myocardial infarction (STEMI). However, information on long‐term outcome after thrombectomy is limited. We performed a retrospective long‐term study to assess the risk of cardiac re‐hospitalizations and survival after discharge from the index hospitalization for STEMI.Methods Patients originally randomized to percutaneous coronary intervention (PCI) with thrombectomy vs. standard PCI were included in a retrospective long‐term observational study. The primary study endpoint was the combined risk for all‐cause death or cardiac re‐hospitalization after index discharge under optimal medical therapy. The cumulative number of cardiac hospitalization days and ventricular remodelling assessed by echocardiography and plasma biomarkers were secondary endpoints.Results Of 94 STEMI patients who had been randomized between 11/2000 and 03/2003, 89 patients consented to long‐term follow‐up. A total of 43 patients had been allocated to thrombectomy and 46 to standard primary PCI. The minimum follow‐up time was 1115 days. There was a significantly lower risk for death or cardiac re‐hospitalization for patients of the thrombectomy group (hazard ratio = 0·69, 95% CI: 0·49–0·98,P = 0·036). The incidence of recurrent myocardial infarction was not different (P = 0·343). No differences in cardiac remodelling were detected by echocardiography, with the exception that heart‐type fatty acid binding protein at 53·2 ± 17 months was lower in the thrombectomy group (P = 0·045).Conclusion Thrombectomy in STEMI may decrease the long‐term risk for death or cardiac re‐hospitalization.
Evaluation of localized and systemic immune responses in cutaneous leishmaniasis caused by Leishmania tropica: interleukin‐8, monocyte chemotactic protein‐1 and nitric oxide are major regulatory factors
Authors: Kumar Rajesh , Bumb Ram A. , Salotra Poonam 
Published: January 2010

SummaryWe have established Leishmania tropica as the causative agent of cutaneous leishmaniasis (CL) in the region of India where the disease is endemic. The association between localized and circulating levels of immune‐determinants in CL patients was evaluated. Reverse transcription–polymerase chain reaction analysis revealed up‐regulation of interferon‐γ (IFN‐γ), interleukin (IL)‐1β, IL‐8, tumour necrosis factor‐α (TNF‐α), IL‐10 and IL‐4 in dermal lesions at the pretreatment stage (n = 31) compared with healthy controls (P < 0·001) and a significant down‐regulation after treatment (n = 14, P < 0·05). The results indicated that an unfavourable clinical outcome in CL was not related to an inadequate T helper 1 (Th1) cell response, but rather to impairment in multiple immune functions. Comparative assessment of treatment regimes with rifampicin (RFM) or sodium antimony gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0·005), while no significant decrease was evident in the levels of IFN‐γ, TNF‐α and IL‐10 (P > 0·05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein‐1 (MCP‐1) (P < 0·001) and inducible nitric oxide synthase (iNOS) (P < 0·05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL‐8, and moderate expression of iNOS in dermal lesions. The expression levels of IL‐8, MCP‐1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme‐linked immunosorbent assay (ELISA). At the post‐treatment stage, the serum IL‐8 levels had decreased; however, the levels of MCP‐1 and NO remained high. These data suggest that IL‐8 is an effector immune‐determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP‐1‐mediated stimulation.
The Mongolian gerbil as a model for inflammatory bowel disease
Authors: Bleich Eva‐Maria , Martin Myriam , Bleich André , Klos Andreas 
Published: January 2010

SummaryMongolian gerbils are used as biomedical research models for a variety of diseases and are in some cases suited better than other rodents for basic research and therapeutic studies. The aim of this study was to establish and characterize a dextran sulphate sodium (DSS)‐induced model in gerbils for the human inflammatory bowel disease (IBD) and to utilize them for a therapeutic study in vivo. Four concentrations (0.5%, 1%, 2% and 4%) of DSS were administered via drinking water for 7 days; based on these results, a concentration of 3% DSS was given for 9 days in a second approach. Fluid uptake and general clinical condition were assessed daily using a clinical score. Caecum and colon were scored histologically. Fluid uptake was affected by addition of DSS to the drinking water. First clinical symptoms were observed at day 4 of DSS treatment with a considerable increase in clinical score parameters only in gerbils receiving 2% or 4% DSS. Histologically, ulceration and inflammation were observed predominantly in the caecum of gerbils treated with at least 1% DSS; reproducible inflammation in the colon required at least 2% DSS. Using 3% DSS for 9 days, considerably more inflammation was induced in the colon, comparable with lesions usually observed in the mouse model. Using an optimized protocol, DSS treatment induces reproducibly typhlocolitis in Mongolian gerbils, rendering them as a useful model for IBD.