bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)
Authors: Duchmann R , Kaiser I , Hermann E , Mayet W , Ewe K , BÜSchenfelde K-H MEYER ZUM 
Published: July 2010

SUMMARYHyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA), Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen, LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate, PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-γ), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.
Functional activity of the membrane-asssociated complement inhibitor CD59 in a pig-to-humanin vitromodel for hyperacute xenograft rejection
Authors: Heckl-ÖStreicher B , Binder R , Kirschfink M 
Published: July 2010

SUMMARYHyperacute rejection triggered by activation of the recipient's complement system represents the major barrier to successful xenotransplantation. Transfer of human membrane-associated complement regulators to donor organs has been suggested as one strategy to interfere with complement-mediated hyperacute xenograft rejection. Pigs are discussed as potential organ donors. We therefore investigated a putative protective function of the membrane-bound complement inhibitor CD59 in a pig-to-human in vitro model of hyperacute xenograft rejection. Aortic porcine endothelial cells were transfected with human CD59 cDNA. Expression of human CD59 was demonstrated by cytofluorimetric and RNA analysis. Removal of CD59 from the cell surface by phosphatidylinositol-specific phospholipase C (PI-PLC) demonstrated its production as a glycosyl phosphatidylinositol (GPI)-anchored protein. Functional activity of the transfected CD59 was tested by a lactate dehydrogenase (LDH) release assay for complement-mediated lysis. Porcine endothelial ceils expressing human CD59 were significantly protected from lysis by human serum complement compared with CD59- cells. The protective effect was abolished by preincubating the cells with anti-CD59 antibodies or PI-PLC. We calculated by Scatchard analysis that the established CD59+ cell line expressed a CD59 level comparable to that of human endothelial cells. Our results recommend the production of pigs transgenic for CD59.
Non-lymphoid and lymphoid cells in acute, chronic and relapsing experimental colitis
Authors: Palmen M J H J , Dieleman L A , Van Der Ende M B , Uyterlinde A , PeÑA A S , Meuwissen S G M , Van Rees E P 
Published: July 2010

SUMMARYIn rodents, intracolonic administration of ethanol 30% induces an acute colitis, while administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS) in ethanol induces a longer lasting colitis. In the acute and chronic stages of experimental colitis, lymphoid and non-lymphoid cells were studied in the colon by immunohistochemistry. During the acute inflammation a high damage score of the colon was observed, which was related to an increase in the number of macrophages and granulocytes. Also a change in distributional patterns of macrophage subpopulations was found. The chronic stage of TNBS–ethanol-induced colitis was characterized by an increase in the number of lymphocytes, especially T cells. These data suggest that macrophages and granulocytes are important in the acute phase of experimental colitis, while lymphocytes play a pivotal role in the chronic stage. As most inflammatory bowel disease (IBD) patients have relapses during the chronic disease, we attempted to induce a relapse during experimental colitis by giving a second i.p. or s.c. dose of TNBS. This resulted in increased damage scores of the colon, new areas of ulceration and a further increase in macrophage numbers. No effect on the number of granulocytes was seen. These results indicate that it is possible to mimic relapses in experimental colitis by a second administration of TNBS, and suggest that the rats had been sensitized by the first dose of TNBS, given into the colon.
Autoimmunity in ulcerative colitis: tropomyosin is not the major antigenic determinant of the Das monoclonal antibody, 7E12H12
Authors: Hamilton M I , Bradley N J , Srai S K S , Thrasivoulou C , Pounder R E , Wakefield A J 
Published: July 2010

SUMMARYUlcerative colitis (UC) has a proposed autoimmune pathogenesis. A 40-kD antigen (P40) has been isolated from UC colon, bound to immunoglobulin. Tropomyosin has been reported as the target antigen of a MoAb (7E12H12) raised against P40. We set out to investigate whether tropomyosin is the major antigenic determinant for 7E12H12. Formalin-fixed, paraffin-processed and cryostat sections of fresh frozen colon from patients with UC, Crohn's disease and normals, were immunostained with 7E12H12 and commercial anti-tropomyosin antibodies. In addition, the immunoreactivity of 7E12H12 with cytoskeletal components was examined on human endothelial cells (HUVEC) using anti-tropomyosin as a positive control. Con-focal microscopy was used to determine the subcellular localization of signal. An extract of total colonic protein from UC colon was prepared. Using a combination of Western and immunoblotting (dot-blots), the immunoreactivities of both tropomyosin (porcine and chicken) and colon protein extract with either 7E12H12 or commercial anti-tropomyosin were examined. Immunocytochemically, 7E12H12 localized to the apical and basolateral regions of plasma membrane, and to the supranuclear cytoplasm in colonic epithelium. Using anti-tropomyosin antibody it was not possible to identify the cytoskeleton in colonic epithelium. Cytoskeletal components were identifiable in HUVEC cultures with anti-tropomyosin antibody but not with 7EI2H12. P40 antigen was identified in the colon protein extract by immunoblotting with 7E12H12. There was clear immunoreactivity between anti-tropomyosin antibody and both chicken and porcine tropomyosin, and the colon protein extract. 7E12H12 did not bind to either chicken or porcine tropomyosin in appropriately controlled systems. We conclude that the pattern of immunostaining with 7E12H12 is not cytoskeletal, and there is no reactivity in immunoblots, between tropomyosin and 7E12H12. Tropomyosin is not the major target antigen of this antibody in ulcerative colitis.
Chloroquine inhibits T cell proliferation by interfering with IL-2 production and responsiveness
Authors: Landewe R B M , Miltenburg A M M , Verdonk M J A , Verweij C L , Breedveld F C , Daha M R , Dijkmans B A C 
Published: July 2010

SUMMARYChloroquine (Chi) is an anti-rheumatic drug that is widely used in the treatment of rheumatoid arthritis (RA). It seems that T ceils are important in the pathogenesis of RA, but it is not known whether Chl acts via inhibition of T cell function. We here present evidence that Chl, just like cyclosporine A (CsA), inhibits Tcell proliferation as induced with immobilized αCD3 MoAb in a concentration-dependent manner, at least partly through interfering with the production of IL-2 protein and the induction of IL-2 inRNA. Furthermore, Chi impedes the responsiveness of T cell clones to IL-2 since (1) the inhibition of αCD3 MoAb-induced proliferation by Chi could not be reversed by rlL-2 and (2) Chi directly blocks IL-2-driven proliferation of cloned T cells. Chi appeared to interfere with the internalization (50% inhibition) and degradation (total blockade) of rIL-2. Finally, the combination of Chi and CsA synergistically inhibited T ceil proliferation. We conclude that Chi may inhibit functional properties of human T cells. although the drug is 100-to 1000-folds less potent than CsA in inhibiting T cell proliferation and IL-2 production, respectively. It is speculated that the in vitro. effects of Chl might be relevant in explaining the anti-rheumatic effect of this drug in patients with RA.
Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy
Authors: Anselmi A , Vendrame D , Rampon O , Giaquinto C , Zanchetta M , De Rossi A 
Published: July 2010

Summary
Immune repopulation, despite virological failure, often occurs in children under highly active anti-retroviral therapy (HAART). The aim of this study was to analyse the characteristics of immune repopulation and activation in children with and without virological response to HAART. Fourteen human immunodeficiency virus type 1 (HIV-1)-infected children with suppression of HIV-1 plasma viraemia (virological responders, VR) and 16 virological non-responders (VNR) to therapy were studied at baseline and after approximately 2 years of HAART. During therapy, CD4+ T cells increased in both groups, but were higher in the VR than in the VNR group. All CD4+ T cell subsets (naive, central memory, effector/memory and CD38+) increased significantly in VR children, while there was a significant increase only in naive cells in VNR children. Naive CD8+ T cells and T cell receptor rearrangement excision circles (TREC), an indicator of thymic output, increased in both VR and VNR children. Activated CD8+CD38+ T cells decreased in VR but remained high in VNR children. Levels of circulating lipopolysaccharide (LPS), an indicator of microbial translocation, further increased in VNR children. In conclusion, HAART induced an increase in naive cells in all children, regardless of their virological response. However, the persistence of viraemia resulted in an impaired expansion of memory CD4+ T cells susceptible to HIV-1 infection, and together with the microbial translocation sustained the persistence of a high level of immune activation.
Programmed death-1 ligands-transfected dendritic cells loaded with glutamic acid decarboxylase 65 (GAD65) inhibit both the alloresponse and the GAD65-reactive lymphocyte response
Authors: He F-R , Zhu H-F , Huang H , Dai Y D , Shen X , Wang M , Li L , Xing W , Shen G-X 
Published: July 2010

SummaryType 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, such as glutamic acid decarboxylase 65 (GAD65), for which islet transplantation is a promising therapy. Therefore, the generation of tolerance aiming at both alloantigen and GAD65 will help therapeutic intervention greatly in T1D. In this study, we tested the effect of programmed death-1 ligands (PD-L1)-transfected dendritic cells (DC) loaded with GAD65 on the alloresponse and GAD65-reactive lymphocyte response. The DC2·4 cell line was transfected with PD-L1 and co-cultured with GAD65. BALB-c mice were primed, respectively, by intraperitoneal injection with GAD65, PD-L1-transfected- or non-transfected DC (PD-L1/DC or DC), and PD-L1-transfected- or non-transfected DC loaded with GAD65 (PD-L1/DC/GAD65 or DC/GAD65). Splenocytes of treated mice were isolated and restimulated in vitro with GAD65 or the various DC populations above being used as stimulators, respectively. In the mixed lymphocyte reaction, DC/GAD65 were able to stimulate both allogeneic and GAD65-reactive lymphocytes. However, PD-L1/DC/GAD65 were poorer than DC/GAD65 at activating the GAD65-reactive lymphocyte response. Further, although PD-L1/DC could inhibit the alloresponse, PD-L1/DC/GAD65 were more effective at down-regulating the GAD65-reactive lymphocyte response. More importantly, PD-L1/DC/GAD65-primed lymphocytes exhibited the weakest proliferation when again restimulated in vitro by PD-L1/DC/GAD65. Additionally, PD-L1/DC/GAD65 down-regulated interferon-γ and up-regulated interleukin-10 production by activated lymphocytes. Therefore, combined stimulation in vivo and in vitro by PD-L1/DC/GAD65 could inhibit both the alloresponse and the GAD65-reactive lymphocyte response, which may contribute to controlling diabetes and islet transplant rejection.
The use of reflective and reasoned portfolios by doctors
Authors: Saltman Deborah C. , Tavabie Abdollah , Kidd Michael R. 
Published: July 2010

AbstractRationale Reflective portfolios have been widely trailed in vocational programmes for health sciences education. While not raised explicitly yet, there is recognition that an essential part of a portfolio may still be missing – that is the experience of theoretical and analytic questioning that should occur after reflection.Aims and objectives In this paper, we argue that portfolios require both reflective and reasoned components to provide a more complete range of educational experiences for postgraduate doctors in the pursuit of higher qualifications.Methods We describe the differentiating features between the two components and conclude with some suggestions on how both reflective and reasoned components of portfolios may work synergistically through a series of case studies.Results The reflective style of portfolio, which is in current use, has been widely accepted as a major advance in postgraduate medical education at all levels. It provides an effective vehicle for encouraging self‐consideration and generalizability. It is an important adjunct where it functions as a personal development tool as well as a sophisticated log book. A reasoned or pedagogic element encourages more analytic activities: adding an additional component that can ground the portfolio in theory or research. The portfolio is then able to function in a range of academic spheres and provide a theoretical platform for the wide range of non‐clinical empirical work undertaken in clinical settings. The addition of a reasoned component also increases the emphasis on the introduction of new concepts outside the sphere of the learner's experience.Conclusions A portfolio containing both reflective and reasoned components is then able to function in a range of academic spheres and provide a theoretical platform for the wide range of non‐clinical empirical work undertaken in clinical settings. In an iterative mode, such a portfolio element can support a forum for questioning established concepts within a pedagogical environment – the essence of evidence‐based practice.
Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation: preliminary results
Authors: Hirsch D. , Odorico J. , Radke N. , Hanson M. , Danobeitia J. S. , Hullett D. , Alejandro R. , Ricordi C. , Fernandez L. A. 
Published: July 2010

Aims: Pancreatic islet transplantation (PIT) represents a potential curative treatment for patients with type 1 diabetes, but only 10–15% of patients remain insulin independent 5 years post‐transplant. It is not known whether intrinsic insulin resistance exacerbated by immunosuppression plays a pivotal role in low graft survival. The study objective was to understand the changes in insulin resistance, glucose effectiveness (Sg) and free fatty acid dynamics (FFAd) before and after PIT. Methods: Insulin sensitivity index (Si), Sg and FFAd were measured before and after PIT in 10 lean patients, 8 of whom reached insulin independence. Modified Bergman minimal model of frequently sampled intravenous glucose tolerance tests were performed pretransplant and at 12 months post‐transplant. Nine non‐diabetic control (NDC) subjects matched by age, gender and BMI were used. Results: Pretransplant Si and Sg were 3.5 ± 0.8 × 10−5/min/(pmol/l) and 0.74 ± 0.24 × 10−2/min, respectively. Si was significantly lower than matched NDCs [10.8 ± 0.6 × 10−5/min/(pmol/l), p < 0.004]; Sg did not reach statistical significance (1.27 ± 0.22 × 10−2/min, p = 0.25). Compared to pretransplant values, mean post‐transplant Si and Sg were 9.6 ± 1.3 × 10−5/min/(pmol/l)and 1.28 ± 0.22 ×10−2/min, respectively, indicating significant improvement for Si but not Sg (p = 0.008and p = 0.06). Twelve‐month post‐PIT compared to NDC values were not significantly different (p = 0.58 and 0.97, respectively). In addition, fractional disposal rate for FFA which directly depends on the endogenous insulin release (10–20 min) nearly normalized after PIT (p = 0.06). Conclusion: These preliminary findings demonstrate that PIT can restore glucose disposal and insulin sensitivity and partially correct glucose effectiveness and FFAd.
The Licensing of Barbers in the USA
Authors: Timmons Edward J. , Thornton Robert J. 
Published: July 2010

AbstractBarbering is one of the earliest professions to be licensed in the USA. This article discusses the origins of barber licensing, as well as its current status and scope, and then estimates the effects that such licensing has had on barbers' earnings. To estimate these effects we use micro‐level data from the 2000 US Census along with several measures of the strictness of state licensing of barbers. Our results suggest that certain licensing provisions may have increased barber earnings by between 11 and 22 per cent. The magnitude of our estimates is somewhat higher than those found in studies examining the effects of licensing in similar professions.
NORWEGIAN WAGE CURVES
Authors: Johansen Kåre 
Published: July 2010

ABSTRACTThe paper presents empirical evidence on wage formation in Norway using annual time series data for manufacturing industry. First, we show that long‐run effects on consumer prices and taxes depend strongly on the exact definition of the empirical variables. Using the implicit factor income deflator, the wedge between consumer's and producer's real wages is insignificant. Second, our results indicate that there is a long‐run tradeoff between the wage level and the unemployment ratio and the Phillips curve specification is firmly rejected. Third, the paper presents empirical evidence in favour of a strongly non‐linear wage curve. Fourth, our results support the long‐term unemployment hypothesis, as increased proportion of long‐term unemployment shifts the wage curve outwards and to the right.
PRACTITIONERS CORNER A POSITIVE SEMI‐DEFINITE COVARIANCE MATRIX FOR HAUSMAN SPECIFICATION TESTS OF CONDITIONAL AND MARGINAL DENSITIES
Authors: Ai Chunrong 
Published: July 2010

ABSTRACTWhen the joint density of data can be factorized into a conditional and marginal densities, Hausman test can be used for diagnosing misspecifications of these densities. However, since common covariance estimates of the difference of the two estimators used in Hausman test need not be positive semi‐definite in finite samples, the test statistic may be negative. This paper presents a simple and consistent covariance matrix which is positive semi‐definite in any finite sample.
SPECIFICATION TESTS FOR THE COMPETING RISKS DURATION MODEL: AN APPLICATION TO UNEMPLOYMENT DURATION AND SECTORAL MOVEMENT
Authors: Pudney Stephen , Thomas Jonathan 
Published: July 2010

ABSTRACTSThis study develops three specification tests for the competing risks duration model. They include a general test for misspecification and specific tests for heterogeneity and defective risk distributions. The last two tests involves null hypotheses located on the boundary of the parameter space, and we consider alternative formulations of the score test to take account of this. The tests are applied to models of unemployment duration in which displaced job seekers may become re‐employed in the pre‐unemployment industry or switch industries.
Nevirapine‐associated hepatotoxicity was not predicted by CD4 count ≥250 cells/μL among women in Zambia, Thailand and Kenya
Authors: Peters PJ , Stringer J , McConnell MS , Kiarie J , Ratanasuwan W , Intalapaporn P , Potter D , Mutsotso W , Zulu I , Borkowf CB , Bolu O , Brooks JT , Weidle PJ 
Published: July 2010

Objective
The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash‐associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) among women initiating nevirapine‐based antiretroviral therapy (ART).Methods
The Non‐Nucleoside Reverse Transcriptase Inhibitor Response Study was a prospective cohort study carried out in Zambia, Thailand and Kenya. Between May 2005 and January 2007, we enrolled antiretroviral‐naïve HIV‐infected women initiating nevirapine‐based ART. At enrolment and at weeks 2, 4, 8, 16 and 24, participants had serum alanine transferase (ALT) and aspartate transaminase (AST) measured and were evaluated clinically for hepatitis and rash.Results
Nevirapine‐based ART was initiated in 820 women and baseline ALT or AST results were abnormal (≥grade 1) in 113 (14%) women. After initiating nevirapine‐based ART, severe hepatotoxicity occurred in 41 (5%) women and rash‐associated hepatotoxicity occurred in 27 (3%) women. In a multivariate logistic regression model, severe hepatotoxicity and rash‐associated hepatotoxicity were both associated with baseline abnormal (≥grade 1) ALT or AST results, but not with a baseline CD4 cell count ≥250 cells/μL. Three participants (0.4%) died with symptoms suggestive of fatal hepatotoxicity; all three women had baseline CD4 count <100 cells/μL and were receiving anti‐tuberculosis therapy.Conclusion
Among women taking nevirapine‐based ART, severe hepatotoxicity and rash‐associated hepatotoxicity were predicted by abnormal baseline ALT or AST results, but not by a CD4 count ≥250 cells/μL. In resource‐limited settings where transaminase testing is available, testing should focus on early time‐points and on women with abnormal baseline ALT or AST results.
Successful control of methicillin‐resistantStaphylococcus aureusoutbreak at a university department of dermatology
Authors: Gilomen S , Ruef C , Held L , Cathomas A , French LE , Hafner J 
Published: July 2010

AbstractBackground Methicillin‐resistantStaphylococcus aureus(MRSA) is one of the leading strains among multiresistant hospital microflora. In 2003, we noted an increase in the number of MRSA strain 35 among patients at the University of Zurich, Department of Dermatology. At the end of 2003, we implemented additional policies in hospital hygiene, which significantly decreased the number of MRSA infections.Methods This is a retrospective study on 65 consecutive patients at the Department of Dermatology, University Hospital of Zurich, in whom MRSA contamination was newly diagnosed during the period of 2003–2008. All isolated strains were genotyped. We implemented additional policies as strict hand hygiene and avoidance of sharing the same ointment pots or tubes amongst patients. As soon as the skin disease was healed, decolonization of MRSA was undertaken by a 5‐day topical treatment.Results Of the 65 MRSA patients, 19 (29%) patients carried a genotypical strain (MRSA 35) that was identified to be specific for the Department of Dermatology. Three health care workers (HCWs) were tested positive. The outlined measures reduced the incidence of new transmissions of this specific strain MRSA 35 significantly (P = 0.001) with a complete disappearance of new transmissions of MRSA 35 in the year 2008. Of the 65 patients, 15 (23%) patients became long‐term carriers, among all (15/15; 100%) had persisting active skin lesions.Conclusions Strict hand hygiene and avoidance of sharing ointments among patients were highly effective measures in controlling an outbreak of MRSA. Complete of near‐to‐complete remission of the underlying dermatoses, skin lesions or chronic wounds, is a prerequisite for complete decolonization of MRSA carriers.