bluuebunny/crossref_metadata_2025_split huggingface dataset:
A close relationship of triplet repeat polymorphism in MHC class I chain‐related gene A (MICA) to the disease susceptibility and behavior in ulcerative colitis
Authors: Sugimura K. , Ota M. , Matsuzawa J. , Katsuyama Y. , Ishizuka K. , Mochizuki T. , Mizuki N. , Seki S.S. , Honma T. , Inoko H. , Asakura H. 
Published: March 2003

Abstract:Major histocompatibility complex (MHC) class I chain‐related gene A (MICA) has been found near the HLA‐B gene. The MICA molecule is exclusively expressed on gastrointestinal epithelium and recognized by intestinal epithelial γδ T cells, where it exhibits a triplet repeat polymorphism in the transmembrane region. We investigated the possible correlation between MICA genetic polymorphism and ulcerative colitis (UC). Eighty‐three patients with UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region of the MICA was determined by direct sequencing procedures after amplification by a polymerase chain reaction. A significantly higher allele and phenotype frequencies of MICA A6 allele were observed in patients with UC than controls (allele frequency: Pc=0.000011, phenotype frequency: Pc=0.0049 odds ratio=2.62). A6 homozygous patients with UC showed significantly earlier onset of UC than patients without the A6 allele (Pc=0.0042). Phenotypes of MICA A6 allele in Japanese are closely related to the disease susceptibility and behavior in UC. Examinations of MICA polymorphism in other ethnic groups may provide important information about the locus of primary responsible gene for UC.
ANGIOTENSINOGEN AND PLASMINOGEN ACTIVATOR INHIBITOR‐1 GENE POLYMORPHISM IN RELATION TO CHRONIC ALLOGRAFT DYSFUNCTION
Authors: Reis K , Arinsoy T , Derici U , Gonen S , Bicik Z , Soylemezoglu O , Yasavul U , Hasanoglu E , Sindel S 
Published: March 2003

Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long‐term, and current immunologic strategies have little effect on this condition. The renin‐angiotensin system (RAS) plays important roles in hypertension and progression of chronic renal disease. It is thought that plasminogen activator inhibitor‐1 (PAI‐1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI‐1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients (47 males and 35 females; mean age 34.87±11.22 years). One hundred healthy subjects (54 males and 46 females; mean age 35.54±10.26 years) were also investigated for AGT polymorphism, and 80 healthy subjects (45 males and 35 females; mean age 36.54±12.41) for PAI‐1 polymorphism. Genotypes were determined using polymerase chain reaction sequence‐specific primers, and polymerase chain reaction followed by restriction fragment length polymorphism analysis.Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than those without CAD. (P<0.05 and P<0.001, respectively) Presence of the MT genotype was significantly associated with CAD, and this genotype introduced a 3.5‐fold risk of CAD compared with the MM genotype (P<0.05; 95% confidence interval: 1.21–10.20). The transplant recipients with CAD also had significantly lower frequencies of the 5G/5G genotype and the 5G allele than those without CAD (P<0.001 and P<0.05, respectively). Presence of the 4G allele introduced a 1.94‐fold risk of CAD compared with the 5G allele (95% confidence interval: 1.05–3.66). Determination of AGT M235T and PAI‐1 genotypes before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction.
EFFECT OF BASILIXIMAB ON ACUTE REJECTION IN PEDIATRIC RENAL TRANSPLANTATION: RESULTS FROM TWO CENTERS
Authors: Duzova A , Bakkaloglu M , Dalgic A , Buyan N , Soylemezoglu O , Bakkaloglu A 
Published: March 2003

Acute rejection is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab (Simulect®), a 156‐kDa chimeric monoclonal antibody (human and murine) directed against the alpha chain of the interleukin (IL)‐2 receptor of human lymphocytes, on acute rejection in pediatric renal transplantation. Data were collected from two pediatric renal transplantation centers. Forty transplantations (22 males and 18 females; mean age 14.8±3.6 years) were performed between 1996 and 2001. Twelve of the grafts came from cadaveric donors and 28 from living‐related donors. Twenty‐four of the patients were on hemodialysis, 15 were on peritoneal dialysis, and one case was a pre‐emptive transplantation. All patients were placed on triple‐drug immunosuppression [prednisolone + (azathioprine or mycophenolate mofetil) +(cyclosporine or tacrolimus)]. Basiliximab was also administered in 17 cases. The respective rates of biopsy‐proven acute rejection in the basiliximab group and the standard‐regimen group were 0% vs. 17.4% (P>0.05) at 1 month post‐transplantation; 0% vs. 26.1% (P<0.05) at 3 months; and 0% vs. 26.1% (P<0.05) at 6 months. Thirty and 16 patients had completed 1‐ and 3‐year follow ups, respectively, at the time of writing; the 1‐ and 3‐year graft survival rates were 96% (29/30) and 81% (13/16), respectively.Basiliximab significantly reduced the rates of acute rejection at 3‐ and 6 months post‐pediatric renal transplantation. It was well tolerated by all patients, and caused no significant adverse effects. The effect of basiliximab on long‐term graft survival and chronic allograft dysfunction deserves further investigation.
Migration and atopic disorder in Swedish conscripts
Authors: Hjern Anders , Rasmussen Finn , Johansson Malin , Åberg Nils 
Published: March 2003

Hjern A, Rasmussen F, Johansson M, Åberg N. Migration and atopic disorder in Swedish conscripts. Pediatr Allergy Immunol 1999: 10: 209–215. © Munksgaard, 1999 We have studied asthma and allergic rhinitis prevalence in Swedish conscripts born 1973–1977 according to the military service conscription register in relation to the socio‐economic status and country of birth of the conscripts and their parents, and age when granted residency in Sweden. There was an increase in prevalence of asthma and allergic rhinitis over time in all groups irrespective of country of birth or ethnic origin. Conscripts who themselves were born in Africa, Asia, Latin America and the Mediterranean had a significantly lower risk for asthma and allergic rhinitis than Swedish‐born conscripts. The risk of atopic disorder among the foreign‐born conscripts increased with time of residency in Sweden. Conscripts with mothers from Latin America, Asia and Africa were identified as having the highest risk for atopic disorder among Swedish‐born conscripts with high socio‐economic status; the adjusted risk ratio (RR) for asthma was 2.6 (95% CI 1.7–4.0) and that for allergic rhinitis was 2.0 (1.5–2.6). The conscripts with mothers from the Mediterranean had the lowest risk for atopic disorders of the Swedish‐born conscripts with low socio‐economic status; the RR for asthma was 0.43 (0.34–0.56) and that for allergic rhinitis was 0.84 (0.76–0.93). This study demonstrates that factors related to migration and ethnicity are important determinants of atopic disorder among Swedish conscripts.
Substrates regulate the phosphorylation status of nitrate reductase
Authors: Rouby Marina B. , González Claudio A. , Kenis Juana D. 
Published: March 2003

The effect of substrates on the phosphorylation status of nitrate reductase (NR; EC 1.6.6.1) was studied. The enzyme was obtained from the first leaf of 7‐day‐old oat (Avena sativa L. cv. Suregrain) plants, grown in the light. When desalted crude extracts were incubated with ATP, NR was strongly phosphorylated, as evidenced by the inhibition of the enzyme's activity in the presence of Mg2+. NR sensitivity to Mg2+ remained unchanged when 10 mM nitrate was added to crude extracts after ATP. Addition of nitrate before or simultaneously with ATP slightly decreased Mg2+ inhibition of NR, which was strongly diminished in the presence of 10 mM NO3−+ 100 µM NADH. Incubation with NADH alone did not affect the enzyme's susceptibility to Mg2+ inhibition. When ammonium sulfate was added to crude extracts, NR was recovered in a 0‐40% saturation fraction (F1).After incubation of F1 with ATP, the sensitivity of the enzyme to Mg2+ inhibition remained low, but it strongly increased after mixing F1 with a 45‐60% saturation fraction (F2) suggesting that also in oats an additional factor (inactivating protein, IP), which probably binds to phospho‐NR, would be required to keep the phosphorylated enzyme inactive in a +Mg2+ medium. Addition of 10 mM NO3−+ 100 µM NADH together with desalted F2 did not prevent Mg2+ inhibition suggesting that NO3− did not interfere with IP binding to phospho‐NR. Again, incubation of F1 with both substrates during in vitro phosphorylation kept the enzyme active after adding F2, even in the presence of Mg2+, After in vitro phosphorylation, NR in crude extract was hardly reactivated when incubated alone or in the presence of 10 mM NO3− at 30°C. On the other hand, a strong and very rapid reactivation was found when the extract was incubated with both nitrate and NADH. Microcystine, an inhibitor of types 1 and 2A phosphoprotein phosphatases, inhibited the reactivation of phospho‐NR induced by the substrates.The results presented here show that the substrates could prevent NR phosphorylation and induce the enzyme's dephosphorylation, but they were effective only after their binding to the NR protein. Thereby, they seemed to affect the NR protein itself and not the phosphatase‐ or the kinase‐proteins. It has been reported that nitrate binding to the enzyme's active site induces conformational changes in the NR protein. We propose that this conformational change would prevent NR phosphorylation, by converting the enzyme into a form in which the site recognized by the protein kinase is no longer accessible, and, simultaneously, stimulate NR dephophorylation by allowing the specific phosphatases to recognize NR.
High‐dose acyclovir prophylaxis reduces cytomegalovirus disease in liver transplant patients
Authors: Barkholt L. , Lewensohn‐Fuchs I. , Ericzon B.‐G. , Tydén G. , Andersson J. 
Published: March 2003

Cytomegalovirus (CMV) is still a major pathogen in liver transplantation (LTX). The clinical efficacy of prophylactic high‐dose acyclovir therapy (800 mg qid) was assessed for the prevention of CMV infection and disease in liver recipients. Fifty‐five patients were enrolled in a prospective, randomised, double‐blind and placebo‐controlled trial; 28 on acyclovir vs. 27 on placebo. The therapy was given for 12 weeks. The patients were followed for 24 weeks.CMV infection was diagnosed in 60% (16 on acyclovir, 17 on placebo) and CMV disease developed in 38% (7 on acyclovir, 14 on placebo) of the patients. The total mortality was 27% (6 on acyclovir, 10 on placebo). Acyclovir delayed 32% of the CMV infections and prevented 59% of the CMV disease cases which occurred in the placebo cohort. The time to CMV disease was significantly prolonged in patients on acyclovir as compared to patients on placebo (P=0.013).Adverse events included neurotoxicity which occurred in 5 cases in the acyclovir, but none in the placebo arm, and nephrotoxicity which was detected in 6 patients in the acyclovir and 5 in the placebo arm, respectively.We conclude that acyclovir prophylaxis significantly reduced the incidence of CMV disease, and delayed the onset of CMV infection in liver transplant patients.
Characterization of a monoclonal anti‐porcine CD3 antibody
Authors: Huang Christene A. , Lorf Thomas , Arn J. Scott , Koo Gloria C. , Blake Tom , Sachs David H. 
Published: March 2003

Huang CA, Lorf T, Arn JS, Koo GC, Blake T, Sachs DH. Characterization of a monoclonal anti‐porcine CD3 antibody. Xenotransplantation 1999; 6: 201‐212. © Munksgaard, CopenhagenAbstract: Partially inbred miniature swine have been developed in this laboratory as a large animal model for studies related to transplantation tolerance and as a source of hematopoietic cells and organs for xenotransplantation. The identification of swine CD3 specific mAbs capable of activating or depleting T cells in vitro and inducing an immunosuppressive state in vivo greatly facilitates studies of the swine immune system, transplantation tolerance and xenotransplantation research. Flow cytometry was used to determine the phenotypic profile of the swine specific mAb 898H2‐6‐15 (2‐6‐15). The specificity of 2‐6‐15 was further defined biochemically by surface labeling and immunoprecipitation. The ability of this mAb to activate pig T cells in vitro was examined by several criteria including proliferation assays, calcium flux analysis and detection of surface CD25 upregulation by fluorescence activated cell sorter (FACS) analysis. Monoclonal antibody 898H2‐6‐15 is specific for swine CD3 and is capable of inducing proliferation and CD25 upregulation in cultured swine peripheral blood lymphocytes. In addition, it induces calcium flux in purified pig T cells. Surprisingly, in contrast to described antibodies to CD3 in swine and other species, the binding of this antibody to porcine CD3 is dependent on the presence of extracellular calcium. Thus calcium was required in order to immunoprecipitate labeled surface molecules for biochemical analysis and to stain cell surfaces for FACS analysis of swine lymphocytes. In this paper, we describe a new swine CD3 specific mAb, 898H2‐6‐15 (2‐6‐15) the characteristics of which make it an extremely useful tool for in vitro and in vivo studies of the swine immune system and xenotransplantation. The availability of swine T cell specific reagents should facilitate the monitoring of swine T cell engraftment and/or release amongst xenogeneic mixed chimeras and thymic transplant recipients as well as provide a means to treat potential GvHD across xenogeneic barriers. We are currently evaluating the in vivo effects of 2‐6‐15 in the pig.
Human serum induces apoptosis of xenogeneic cardiomyocytes in vivo and in vitro
Authors: Lucien Jamie , Shimada Munehiko , Watzka Stefan , Ogiwara Masanori , Brockhausen Inka , Sandhu Jasbir , Coles John G. 
Published: March 2003

Abstract: Discordant xenotransplantation is complicated by delayed xenograft rejection (DXR). Previous studies have demonstrated that anti‐apoptotic genes are protective against DXR. This study examines the hypothesis that apoptosis plays a role in human anti‐xenograft responses. C57BL/6 mice and NOD SCID mice were given a single intravenous injection of either a lethal dose (LD, survival < 30 min) or a sublethal dose (SLD) of human serum, and isolated pig and mouse rod‐shaped cardiomyocytes were exposed to human serum in vitro. In situ detection of apoptotic cells in mouse hearts was assessed using a terminal deoxynucleotidyl transferase‐mediated dUTP nicked‐end labeling assay. Mice transfused with human serum had approximately a 10‐fold increased percentage of apoptotic cells after SLD 18 h post‐injection compared with animals given saline, and a fourfold increase over LD. Administration of cobra venom factor (CVF) decomplemented SLD 18 h did not significantly (P > 0.05) alter the percentage apoptosis. The addition of 20 mM Gal‐α‐1,3‐Gal to SLD 18 h significantly (P < 0.05) reduced percentage apoptosis to levels comparable to saline treated control animals. In vitro using mouse and pig cardiomyocytes demonstrated parallel results as in vivo experiments.Human serum induces apoptosis of cardiomyocytes in immunocompetent and immunoincompetent mice in vivo, as well as mouse and pig cardiomyocytes in vitro. Further, this apoptotic response can be inhibited by the addition of Gal‐α‐1,3‐Gal without affecting the capacity of the serum to cause HAR. These results demonstrate that a putative human serum factor induces a delayed apoptotic injury of xenograft tissues, and supports the hypothesis that apoptosis may be an important mediator of DXR.
Isolation of mouse‐to‐rat cardiac xenograft‐infiltrating cells by ex vivo propagation
Authors: Lorant Tomas , Engstrand Mats , Tufveson Gunnar , Johnsson Cecilia 
Published: March 2003

Ex vivo propagation of graft infiltrating lymphocytes has become a useful method for the examination of the cellular response after allogeneic transplantation. The aim of the present study was to investigate if this method can be used also for isolation of xenograft infiltrating cells, and, if so, to further characterize these cells.The concordant mouse‐to‐rat heart transplantation model was used for the experiments. Recipient rats were treated either with 15‐deoxyspergualin (DSG) or with a combination of DSG and cyclosporine A (CyA) or left untreated. Transplants were removed beating on day 2 (untreated) or day 8 (DSG and CyA + DSG) and biopsies were incubated in culture medium for 48 h, resulting in propagation of cells from the biopsies into culture medium. The propagated cells were counted and phenotyped using flow cytometry. In parallel, the transplants were examined morphologically and immunohistochemically.Infiltrating cells could be isolated from all grafts in all groups. The number of propagated T lymphocytes during cellular rejection (DSG‐treatment) was about 3.5 times higher than during `non‐rejection' (CyA + DSG) and six times higher than during acute vascular rejection (untreated). These findings were supported both by the morphological and the immunohistochemical findings.In conclusion, we have shown that graft infiltrating lymphocytes can be isolated from xenogeneic heart transplants by incubation of biopsies for 48 h, resulting in spontaneous propagation of immune cells into culture medium. Propagated cells could be further characterized by flow cytometry. Thus, the technique presented here can be used as a tool for studies of xenogeneic cellular rejection.
Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience
Authors: Pascher Andreas , Sauer Igor M. , Hammer Claus , Gerlach Joerg C. , Neuhaus Peter 
Published: March 2003

Background: There are almost no prospective, controlled and randomized clinical trials comparing different approaches towards hepatic assist. In order to create a basis for comparing the value of the existing different hepatic assist methods this article offers a systematic review of the world experience with allogeneic or xenogeneic extracorporeal liver perfusion (ECLP). Methods: An Internet‐assisted search was conducted in the international literature published from 1964 to 2000. Only articles with a clear description of methodology and outcome of patients were included. For multivariate analysis of variance the general linear method (GLM) procedure was used. Differences within the groups were analyzed by chi‐square test. Data of 198 patients were included into the statistical analysis for systematic review. Results: The long‐term survival rate (SVR) of these patients was 26%, thus not exceeding published data concerning SVR under standard intensive care. Age below 40 years (P<0.029), coma stage lower than III–IV (P<0.003), total perfusion time over 10 hours (P<0.024), hepatitis B as cause for acute liver failure (ALF) (P<0.05) as well as use of baboon and human livers (P<0.02) were identified as independent positive prognostic markers for improved survival. ECLP as bridging therapy to liver transplantation was successful in 12 of 14 patients. Conclusion: ECLP using pig livers did not surpass the success of conventional intensive care treatment. An additional effect of transgenic expression of human regulators of complement regulation in porcine livers has not yet been proven. ECLP with human livers not suitable for liver transplantation might prove effective and practicable for temporary hepatic support. Bridging to liver transplantation by long‐term ECLP using porcine and human livers appears to have comparable efficacy as bioartificial support methods.
Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47
Authors: Crew Mark D. , Phanavanh Bounleut 
Published: March 2003

Crew MD, Phanavanh B. Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47. Xenotransplantation 2003; 10: 50–59. © Blackwell Munksgaard, 2003Direct recognition of porcine major histocompatibility complex (MHC) proteins by human T cells is well documented. Eliminating donor (porcine) MHC proteins may therefore be beneficial in pig‐to‐human xenotransplants. To this end, we have attempted to exploit viral stealth mechanisms to eliminate pig MHC class I cell‐surface expression. PK(15) (pig kidney) cells stably transfected with the herpes simplex virus (HSV) ICP47 gene [PK(15)‐ICP47 cells] exhibited a dramatic reduction of MHC class I cell‐surface expression when compared with untransfected PK(15) cells. To test the effect of down‐regulation of porcine MHC class I on human cellular immune responses, a human CD8+ enriched T cell line (anti‐PK15 T cells) with reactivity towards PK(15) cells was derived by repeated stimulation of human T cells with PK(15) cells stably transfected with the costimulatory molecule B7.1 [PK(15)‐B7.1 cells]. Anti‐PK15 T cells efficiently lyzed PK(15) cells but not PK(15)‐ICP47 (class I negative) cells. Consistent with effector function, anti‐PK15 T cells showed a robust proliferative response to PK(15)‐B7.1 cells but did not proliferate at all to PK(15)‐B7.1 cells which also expressed HSV ICP47. These results suggest that virus stealth technology can be exploited for xenotransplantation.
Orthodontic appliances made of organic polymer used in the metal allergic patient can withstand orthognathic surgery
Authors: Sakata M , Sa'do B , Nakata S , Morishita T , Nakasima A 
Published: March 2003

AbstractWe developed an orthodontic appliance completely made of organic polymer. The appliance was used for many years and proved very effective. It was used for the treatment of patients with metal allergy, and as a result, it is believed to be the best choice for treating metal allergics. In this report, we are presenting a surgical case with Class III malocclusion for a patient with metal allergy, and the concept of the appliance is briefly discussed.