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Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system. 下载免费PDF全文
R Eren I Lubin D Terkieltaub O Ben-Moshe A Zauberman R Uhlmann T Tzahor S Moss E Ilan D Shouval E Galun N Daudi H Marcus Y Reisner S Dagan 《Immunology》1998,93(2):154-161
An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested. 相似文献
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Mika Shapira Rootman Yael Goldberg Rony Cohen Nesia Kropach Inbal Keidar Rivka Friedland Gad Dotan Osnat Konen Helen Toledano 《Clinical genetics》2020,97(2):296-304
Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash-leaf like” hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance. 相似文献
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Spinal mobilisations are a common form of treatment intervention applied by physiotherapists in clinical practice to manage musculoskeletal pain and/or dysfunction. Previous research has demonstrated that mobilisations cause a hypoalgesic effect. However, there is very little research investigating the optimal treatment dose inducing this effect.AimTo investigate the effect of the number of sets (up to 5) and different durations (30 vs. 60 s) on pressure pain thresholds (PPTs) at different sites.MethodsThis single-blinded, randomised, same subject repeated measures crossover design included 19 asymptomatic healthy volunteers. The participants received 5 sets of either 30 or 60 s of postero-anterior mobilisations to L4 on different days. PPTs were measured immediately before, between and after the intervention at 4 different standardised sites.ResultsA 4-way ANOVA analysis revealed that there was no statistically significant difference between 30 versus 60 s of mobilisations. However, there was a tendency for PPT values to be higher for the 60 s intervention. All PPT measurements after the interventions were significantly higher than the baseline. Only the measurement after the 4th set of mobilisations was significantly higher than the measurement after the 1st set (p = 0.035).ConclusionsThe results suggest that in order to induce the greatest local hypoalgesia, at least 4 sets of mobilisations are required. The different durations of 30 versus 60 s of mobilisation may not change the extent of the hypoalgesic effect. 相似文献
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The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy. 总被引:1,自引:0,他引:1
Mali Ketzinel-Gilad Arie Zauberman Ofer Nussbaum Yariv Shoshany Ofer Ben-Moshe Orit Pappo Yaakov Felig Ehud Ilan Hanna Wald Shlomo Dagan Eithan Galun 《Hepatology research》2006,34(4):228-237
A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents. 相似文献
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Shemesh AA Rasooly I Horowitz P Lemberger J Ben-Moshe Y Kachal J Danziger J Clarfield AM Rosenberg E 《Archives of gerontology and geriatrics》2008,47(1):63-77
To assess factors that affect the adoption of healthy lifestyles among a variety of active Israeli seniors, a survey was conducted in 2002 at the Peiluyada, a physical activity-oriented health fair for seniors held annually in Israel from 1995 to 2002. A multi-language, self-administered questionnaire, assessing predisposing factors, barriers and health-protective behaviors, was fielded to potential participants. Response rate at the event was 51%. Hebrew and Arabic speakers generally characterized their health as good to very good, while Russian speakers' health was rated only poor to fair. Over 80% engaged in regular physical activity, were satisfied with their diet, and conformed to international nutritional recommendations. Vaccination coverage against influenza (81%) and pneumocccocus (58%) was highest among Arabic speakers, and lowest among Russian speakers (33.5% and 12%, respectively). Higher age (> or =75 years) was significantly associated with receiving a vaccination against influenza. Major barriers to exercise included low motivation and poor physical health or disability. Health-related dietary restrictions were the leading nutritional barrier. Prominent barriers to vaccination included concerns about vaccine effectiveness (39%) and side effects (29%). Leading cues to action were a recommendation from one's doctor (67%) and from a healthcare worker (51%). 相似文献
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Inbal A Lubetsky A Shimoni A Dardik R Sela BA Eskaraev R Levi I Tov NS Nagler A 《Bone marrow transplantation》2004,34(5):459-463
Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell transplantation (allo-SCT) conditioning regimens to prevent graft rejection and graft-versus-host disease. However, ATG was also found to be associated with increased incidence of thrombosis during organ transplantation. In the present study, we tested the coagulation status of 21 patients with hematologic malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG-based (10) conditioning treatment. We assessed several thrombophilia markers as well as circulating total and endothelial microparticles (TMP/EMP) and soluble CD40 ligand (CD40L). No significant difference in the mean values of prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic thrombophilia markers and levels of EMP, TMP or CD40L was observed between the ATG-treated and ATG-untreated patients, as well as before and after conditioning in each group separately. Platelet counts decreased significantly in ATG-treated patients; however, this decrease was not associated with clinical or laboratory evidence of disseminated intravascular coagulation. No patient developed thromboembolic event or veno-occlusive liver disease. Our results suggest that allo-SCT is not associated with increased hypercoagulability and addition of ATG to conditioning regimen has no significant procoagulant effect. 相似文献
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Possti Daniel Fahoum Firas Sosnik Ronen Giladi Nir Hausdorff Jeffrey M. Mirelman Anat Maidan Inbal 《Journal of neurology》2021,268(1):161-168
Journal of Neurology - The ability to maintain adequate motor-cognitive performance under increasing task demands depends on the regulation and coordination of neural resources. Studies have shown... 相似文献