bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of mouse brain microvascular endothelium using immuno‐laser capture microdissection coupled to a hybrid linear ion trap with Fourier transform‐mass spectrometry proteomics platform
Authors: Lu Qiaozhen , Murugesan Nivetha , Macdonald Jennifer A. , Wu Shiaw‐Lin , Pachter Joel S. , Hancock William S. 
Published: May 2008

AbstractThe purpose of this study was to identify the protein profile of the mouse brain microvascular endothelium in situ. This involved coupling of a double‐label, immuno‐laser capture microdissection (LCM) process with LTQ‐FT mass spectrometry to perform the in situ proteomic analysis. LCM was utilized to isolate cells from frozen mouse brain tissue sections. Following cell capture, samples were solubilized and proteins separated by gel electrophoresis in preparation for enzymatic digestion and LC‐MS analysis. Processed samples were subsequently analyzed using a linear IT coupled with a Fourier transform mass spectrometer (LTQ‐FT MS). Overall, in this study, 881 proteins were identified from a specific cell category using immuno‐guided LCM to probe these cell types along the entirety of the cerebral microvascular tree. The identification of sufficient numbers of proteins with high biological interest should allow us to study protein expression by specific cell types – as defined by certain cell markers – in complex tissues.
Screening for copy‐number alterations and loss of heterozygosity in chronic lymphocytic leukemia—A comparative study of four differently designed, high resolution microarray platforms
Authors: Gunnarsson Rebeqa , Staaf Johan , Jansson Mattias , Ottesen Anne Marie , Göransson Hanna , Liljedahl Ulrika , Ralfkiær Ulrik , Mansouri Mahmoud , Buhl Anne Mette , Smedby Karin Ekström , Hjalgrim Henrik , Syvänen Ann‐Christine , Borg Åke , Isaksson Anders , Jurlander Jesper , Juliusson Gunnar , Rosenquist Richard 
Published: May 2008

AbstractScreening for gene copy‐number alterations (CNAs) has improved by applying genome‐wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high‐resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross‐platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2–3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy‐number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy‐number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform‐specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large‐scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested. © 2008 Wiley‐Liss, Inc.
Equality of what in health? Distinguishing between outcome egalitarianism and gain egalitarianism
Authors: Tsuchiya Aki , Dolan Paul 
Published: May 2008

AbstractWhen deciding how to weigh benefits to different groups, standard economic models assume that people focus on the final distribution of utility, health or whatever. Thus, an egalitarian is assumed to be an egalitarian in the outcome space. But what about egalitarianism in the gains space, such that people focus instead on how equally benefits are distributed? This paper reports on a study in which members of the public were asked to rank a number of health programmes that differed in the distribution of benefits and final outcomes in ways that enabled us to distinguish between different types of egalitarianism. The results suggest that outcome egalitarianism dominates, particularly for differences in health by social class, but a sizeable minority of respondents appear to be gain egalitarians, especially when the health differences are by sex. These results have important implications for how we think about outcome‐based social welfare functions in economics. Copyright © 2008 John Wiley & Sons, Ltd.
Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen–positive chronic hepatitis B
Authors: Marcellin Patrick , Chang Ting-Tsung , Lim Seng G. Lee , Sievert William , Tong Myron , Arterburn Sarah , Borroto-Esoda Katyna , Frederick David , Rousseau Franck 
Published: May 2008

Abstract

Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and −50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV.

Conclusion:

Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (Hepatology 2008;48:750–758.)
Hyponatremia in cirrhosis: Pathogenesis, clinical significance, and management
Authors: Ginès Pere , Guevara Mónica 
Published: May 2008

Abstract

Hyponatremia is a frequent complication of advanced cirrhosis related to an impairment in the renal capacity to eliminate solute-free water that causes a retention of water that is disproportionate to the retention of sodium, thus causing a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of arginine vasopressin (or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction. Hyponatremia in cirrhosis is associated with increased morbidity and mortality. There is evidence suggesting that hyponatremia may affect brain function and predispose to hepatic encephalopathy. Hyponatremia also represents a risk factor for liver transplantation as it is associated with increased frequency of complications and impaired short-term survival after transplantation. The current standard of care based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by antagonizing specifically the effects of arginine vasopressin on the V2 receptors located in the kidney tubules, is being evaluated for their role in the management of hyponatremia. The short-term treatment with vaptans is associated with a marked increase in renal solute–free water excretion and improvement of hyponatremia. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. Treatment with vaptans represents a novel approach to improving serum sodium concentration in cirrhosis. (Hepatology 2008.)
Programmed death 1 expression during antiviral treatment of chronic hepatitis B: Impact of hepatitis B e-antigen seroconversion
Authors: Evans Alexander , Riva Antonio , Cooksley Helen , Phillips Sandra , Puranik Smrithi , Nathwani Amit , Brett Sara , Chokshi Shilpa , Naoumov Nikolai V. 
Published: May 2008

Abstract

Hyperexpression of the programmed death 1 (PD-1) molecule is a hallmark of exhausted T-cells, having a negative impact on T-cell activation and function. We studied longitudinally 18 hepatitis B e antigen (HBeAg)–positive patients undergoing treatment with direct antivirals (telbivudine or lamivudine) to determine the relationship between treatment-induced viremia reduction and HBeAg seroconversion with respect to PD-1 levels and T-cell reactivity. PD-1 expression was assessed by (1) flow cytometry and (2) quantitative real-time polymerase chain reaction; hepatitis B virus (HBV)–specific CD8+ T-cells were quantitated by pentamer staining; T-cell reactivity to HBV antigens was determined by interferon gamma (IFNγ) and interleukin 10 (IL-10) enzyme-linked immunosorbent spot (ELISPOT) assays; and central/effector memory phenotypes were defined by phenotypic markers. PD-1 expression correlated closely with viremia levels. On therapy, PD-1 decreased significantly on total CD8+ T-cells, HBV-specific CD8+ T-cells, and CD3+/CD8− T-cells both as the percentage of positive cells (

P

< 0.01) and as the mean fluorescent intensity (

P

< 0.05), and this was paralleled by a marked reduction of PD-1 messenger RNA levels (

P

= 0.001). HBeAg serocoversion (in 6/18 patients) resulted in a further PD-1 decrease with a 50% reduction in the frequency of PD-1+/CD8+ T-cells, which was not observed in patients remaining HBeAg-positive. The decrease in PD-1 expression was associated with increased frequencies of IFNγ-producing T-cells and decreased frequencies of IL-10 producing T-cells. At baseline, PD-1 expression correlated directly with the frequency of hepatitis B core antigen (HBcAg) central and effector memory phenotypes, whereas an inverse correlation was observed between PD-1 expression and HBcAg-specific effector phenotypes.

Conclusion:

These results demonstrate that in chronic HBV infection, both viremia levels and HBeAg drive PD-1 expression and resulting T-cell impairment. Treatment-induced suppression of HBV replication reduces PD-1 expression; however, additional immunotherapeutic interventions are needed for restoration of T-cell functions. (Hepatology 2008.)
Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks
Authors: Darbre Philippa D. , Harvey Philip W. 
Published: May 2008

AbstractThis toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters ofp‐hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not onlyin vitrobut alsoin vivousing healthy human subjects. Using a wide variety of assay systemsin vitroandin vivo, the oestrogen agonist properties of parabens together with their common metabolite (p‐hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co‐formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation. Copyright © 2008 John Wiley & Sons, Ltd.
CH/π hydrogen bonds determine the selectivity of the Src homology 2 domain to tyrosine phosphotyrosyl peptides: An ab initio fragment molecular orbital study
Authors: Ozawa Tomonaga , Okazaki Kosuke 
Published: May 2008

AbstractThe CH/π hydrogen bond is a weak molecular force occurring between CH groups (soft acids) and π‐systems (soft bases), and has been recognized to be important in the interaction of proteins with their specific ligands. For instance, it is well known that Src homology‐2 protein (SH2) recognizes its specific pTyr peptide in two key regions, pTyr‐binding region and specificity‐determining region, by the use of attractive molecular forces, including the CH/π hydrogen bond. We hypothesized that the CH/π hydrogen bond plays a key role in determining the selectivity of SH2 proteins, and studied this issue by the ab initio fragment molecular orbital (FMO) method. The FMO calculations were carried out, at the HF/6‐31G* and MP2/6‐31G* level, for SH2 domains of Src, Grb2, P85α(N), Syk, and SAP, in complex with corresponding pTyr peptides. CH/π hydrogen bonds have in fact been found to be important in stabilizing the structure of the complexes. We conclude that the CH/π hydrogen bond plays an indispensable role in the recognition of SH2 domains with their specific pTyr peptides, thus playing a vital role in the signal transduction system. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Polarizable continuum model with the fragment molecular orbital‐based time‐dependent density functional theory
Authors: Chiba Mahito , Fedorov Dmitri G. , Kitaura Kazuo 
Published: May 2008

AbstractThe polarizable continuum model (PCM) for describing the solvent effect was combined with the fragment molecular orbital‐based time‐dependent density functional theory (TDDFT). Several levels of the many‐body expansion were implemented, and the importance of the many‐body contributions to the singlet‐excited states was discussed. To calibrate the accuracy, we performed a number of the model calculations using our method and the regular TDDFT in solution, applying them to phenol and polypeptides at the long‐range corrected BLYP/6‐31G* level. It was found that for systems up to 192 atoms the largest error in the excitation energy was 0.006 eV (vs. the regular TDDFT/PCM of the full system). The solvent shifts and the conformer effects were discussed, and the scaling was found to be nearly linear. Finally, we applied our method to the lowest singlet excitation of the photoactive yellow protein (PYP) in aqueous solution and determined the excitation energy to be in reasonable agreement with experiment. The excitation energy analysis provided the contributions of individual residues, and the main factors as well as their solvent shifts were determined. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Effects of cryopreservation on CD4+ CD25+ T cells of HIV‐1 infected individuals
Authors: Seale Anna C. , de Jong Bouke C. , Zaidi Irfan , Duvall Melody , Whittle Hilton , Rowland‐Jones Sarah , Jaye Assan 
Published: May 2008

AbstractThe role of T regulatory cells (Tregs) in human immunodeficiency virus (HIV)‐1 infection, although not entirely clear, has recently been highlighted. Despite their lack of specificity, fluorochrome‐labeled CD4 and CD25 antibodies are common flow cytometric reagents used to identify these cells with immunosuppressive potential. Cryopreservation has previously been shown to alter the proportions of lymphocytes with certain phenotypes expressed in peripheral blood mononuclear cells (PBMCs). The aim of this study was to assess the effect of cryopreservation on CD4+ CD25+ T cells in PBMCs from HIV‐1+ individuals to guide the design of future studies on Tregs. We recruited 30 HIV‐1+ individuals and nine healthy controls. CD25 expression in CD4+ T cells was compared between fresh and frozen/thawed PBMC samples from the same time point. In this study, cryopreservation significantly decreased the proportion of CD4+ CD25+ T cells in PBMC samples from HIV‐1 infected subjects. This finding suggests that studies of CD4+ CD25+ T cells should be carried out on fresh samples to avoid bias introduced by cryopreservation. J. Clin. Lab. Anal. 22:153–158, 2008. © 2008 Wiley‐Liss, Inc.
Elevated serum level and gene polymorphisms of TGF‐β1 in gastric cancer
Authors: Li Xue , Yue Zhi‐Chao , Zhang Yun‐Yan , Bai Jing , Meng Xiang‐ning , Geng Jing‐Shu , Fu Song‐Bin 
Published: May 2008

AbstractTransforming growth factor (TGF)‐β1, as a candidate tumor marker, is currently of interest. In this study, serum TGF‐β1 levels in gastric cancer (GC) patients and healthy volunteers were measured using enzyme‐linked immunosorbent assay (ELISA). In addition, single nucleotide polymorphisms (SNPs) of the TGF‐β1 gene at codon 10 and codon 25 were identified by means of amplification refractory mutation system–polymerase chain reaction (ARMS‐PCR) and sequence analysis. Our results indicated that serum concentrations of TGF‐β1 in GC patients were significantly higher than those in the control, and positively correlated with tumor mass, invasion, metastasis, and clinical stage. The serum TGF‐β1 levels of patients recovering from radical resection were markedly lower than those before surgery. Meanwhile, no deoxyribonucleic acid (DNA) sequence variation at codon 25 of the TGF‐β1 gene was found and a TGF‐β1 gene polymorphism at codon 10 did not show obvious correlations with either TGF‐β1 expression or clinicopathological parameters of GC. Our evidence suggested that serum concentration of TGF‐β1 might be a novel tumor marker for GC and the polymorphisms of TGF‐β1 gene did not play a role as a determinant of serum TGF‐β1 concentration or as a genetic risk factor in the gastric carcinogenesis and progression. J. Clin. Lab. Anal. 22:164–171, 2008. © 2008 Wiley‐Liss, Inc.
Performance characteristics of a new rapid immunochromatographic test for the detection of antibodies to human immunodeficiency virus (HIV) types 1 and 2
Authors: Syed Iqbal H. , Balakrishnan P. , Murugavel K.G. , Suniti Solomon 
Published: May 2008

AbstractDiagnostic kits for the detection of human immunodeficiency virus (HIV) antibodies have reached an unprecedented number. But choice of an ideal, cost‐effective, and rapid test for HIV infection is of immense value for use in developing countries like India, where resources are limited. In this study we have evaluated the performance characteristics of the rapid immunochromatographic HIV test kit First Response HIV 1‐2.O. First, the laboratory archived 450 characterized plasma/serum specimens, which were tested on First Response HIV 1‐2.O. Second, a total of 134 consecutive voluntary counseling and testing (VCT) specimens were also tested and positive specimens were further confirmed with HIV TRI‐DOT. All these VCT specimens were cross‐checked with HIV double‐enzyme‐linked immunosorbent assay (ELISA) (Murex and Vironostika), and the results were matched. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and efficiency of First Response HIV 1‐2.O with the 450 characterized specimens was 100% for HIV‐1 with reference assay. The results in the VCT algorithm were correlating with double‐ELISA. In the HIV‐2 analysis, five HIV‐2‐positive specimens in First Response HIV 1‐2.O were found to be HIV‐2‐indeterminate on Western blot. HIV TRI‐DOT was unable to pick up two HIV‐2 Western blot–positive specimens. First Response HIV 1‐2.O has several advantages: low‐cost (U.S. $0.70); only 10 µL of specimen; involves only two steps; room temperature storage; ability to differentiate HIV‐1 and 2; and use of whole blood specimen. Hence this test kit could be suitable for initial screening in the HIV testing algorithm in resource‐limited settings. J. Clin. Lab. Anal. 22:178–185, 2008. © 2008 Wiley‐Liss, Inc.
Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with liver cancer
Authors: Jelski Wojciech , Zalewski Bogdan , Szmitkowski Maciej 
Published: May 2008

AbstractThe principal enzymes catalyzing the conversion of ethanol to acetate are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The activities of these enzymes are elevated in the serum during the course of alcoholism or cirrhosis. In previous investigations we have found elevated levels of ADH, ALDH, and class I ADH activity in liver cancer cells. It can suggest that these changes may be reflected by enzyme activity in the serum. In this work, the activity of ADH isoenzymes, and ALDH in the sera of patients with liver cancer was measured. Serum samples were taken from 64 patients (28 drinkers, 36 nondrinkers), with liver cancer. 25 patients had primary and 39 metastatic liver tumors. Total ADH activity was measured by photometric method with p‐nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorimetric method with 6‐methoxy‐2‐naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed the fluorimetric methods, with class‐specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with formaldehyde and class IV with m‐nitrobenzaldehyde as a substrate. A statistically significant increase of class I ADH isoenzymes was found in the sera of cancer patients. The median activity of this class isoenzyme in the total cancer group increased about 51% (2.94 mU/L) in the comparison to the control level (1.43 mU/L). The activity of the class I ADH isoenzyme was significantly higher in the sera of patients with metastatic tumors than with primary cancers. The activity of this class in the sera of drinkers and group of moderate drinkers was significantly higher in comparison to the control group and higher in the sera of heavy drinkers when compared with moderate drinking patients. The total ADH activity was significantly higher (44%) among patients with cancer than healthy ones. The activity of class I ADH isoenzymes was elevated only in the serum of patients with metastatic liver cancer. This increase of activity seems to be caused by the enzyme released from liver cancer cells and primary tumors originating in other organs. J. Clin. Lab. Anal. 22:204–209, 2008. © 2008 Wiley‐Liss, Inc.