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51.
52.
Johannes Reim Kevin McIntosh Stephen Martin Drachman Daniel B. 《Journal of neuroimmunology》1992,41(1):61-70
The pathogenesis of myasthenia gravis (MG) involves a T cell-dependent antibody-mediated autoimmune response directed against acetylcholine receptors (AChR). Inactivation of AChR-specific T cells should interrupt the immune response, resulting in therapeutic benefit. Since each individual's repertoire of T cells responds to a heterogeneous and unique spectrum of AChR epitopes presented in association with self-major histocompatibility complex (MHC) class II, an individualized approach is required to target all relevant AChR-specific T cells. The individual's own antigen-presenting cells (APC) can be used for this purpose, since they process and present the antigen appropriately, and express the correct MHC class II. A novel method of binding AChR to surface immunoglobulin with a heterobifunctional antibody conjugate allows us to use all B cells as APC. Conjugate-plus-AChR-treated B cells (AChR-APC) effectively targeted AChR-specific T cells, stimulating vigorous proliferative responses in a rat cell culture system. If APCs are 'fixed' with cross-linking reagents, they induce long-lasting or permanent 'anergy' of the specific T cells. We prepared AChR-APC, allowed them to process AChR in vitro, and fixed them with paraformaldehyde. Pre-culture of these fixed AChR-APC with AChR-specific T cells induced anergy: when restimulated with fresh AChR-APC, the T cells exhibited markedly reduced proliferative responses and IL-2 production, compared with responses of T cells pre-cultured with control fixed B cells. Implications for the design of antigen-specific therapeutic strategies for MG and other immune disorders will be discussed. 相似文献
53.
Arend Bökenkamp Bettina Bohnhorst Christian Beier Norbert Albers Gisela Offner Johannes Brodehl 《Pediatric nephrology (Berlin, Germany)》1994,8(2):181-185
Gingival hyperplasia is a common side-effect of immunosuppression with cyclosporine A. Nifedipine is often used to control hypertension in kidney graft recipients. Analysis of gingival status in 106 children transplanted at our centre, and treated either with azathioprine, cyclosporine A or both, revealed significantly higher degrees of gingival overgrowth in those children receiving a combination of cyclosporine A and nifedipine compared with those children treated with cyclosporine A or nifedipine alone. Seven children undergoing gingivectomy at our centre over the past few years had received this combination. After a change in the antihypertensive regimen, avoiding long-term nifedipine medication, and improved dental care with chlorhexidine gel, we noted a reduction in the degree of gingival hyperplasia. In the majority of patients, nifedipine could be replaced by a single drug, usually hydralazine. We therefore recommend avoiding calcium channel blockers in the long-term management of hypertension in patients receiving cyclosporine. 相似文献
54.
Johannes M. A. Van Gerven Johan P. Boot Herman H. P. J. Lemkes Jaap A. Van Best PhD 《Documenta ophthalmologica. Advances in ophthalmology》1992,80(2):183-188
The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (PBRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lenstransmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the PBRB by multiple regression analysis. The Pbrb was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p > 0.3]. The PBRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (Sirma) and (2) new vessels (Sneo): pbrb = A – B.SIRMA – C.Sneo with PBRB in nm/sec, A = 1.5 ± 0.5, B = 0.9 ± 0.2 and C = 1.7 ± 0.4, R2 = 0.65, p < 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities. 相似文献
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Marika A. Artz Johannes M. M. Boots Gerry Ligtenberg Joke I. Roodnat Maarten H. L. Christiaans Pieter F. Vos Philip Moons George Borm Luuk B. Hilbrands 《American journal of transplantation》2004,4(6):937-945
Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated. 相似文献
58.
Michael Weller Helmut Wilhelm Norbert Sommer Johannes Dichgans Horst Wiethölter 《Journal of neurology》1992,239(4):231-234
Summary Two patients are described with the triad of tonic pupil, hyporeflexia and segmental anhidrosis (Ross syndrome). Only 18 cases of this syndrome have been reported in the literature so far. While tonic pupil and reduced sweating can be attributed to the affection of postganglionic cholinergic parasympathetic and sympathetic fibres projecting to the iris and sweat glands, respectively, the pathogenesis of diminished or lost tendon jerks remains obscure. To identify the characteristic clinical features, the previous cases of Ross syndrome are reviewed. Recent evidence of subclinical disturbances of sweating in most patients with Adie's syndrome, i.e. tonic pupil and areflexia, casts doubt on the nosological concept of Ross syndrome as a distinct clinical entity. 相似文献
59.
Rainer Pankau Carl-Joachim Partsch Johannes Funda Wolfgang Günther Sippell 《American journal of medical genetics. Part A》1992,43(3):513-516
We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17α-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5α-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. © 1992 Wiley-Liss, Inc. 相似文献
60.
Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies. 相似文献