Influence of donor/recipient HLA-DR antigen disparities on cadaver kidney graft survival: an alternative for recipient selection.
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Biomedical subjects
Publications and source records attributed to E Dupont.
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In order to detect possible influences of donor (D)/recipient (R) HLA-DR antigen disparities on graft survival, 310 renal cadaver transplantations performed from January 1980 to July 1988 were analyzed. For each DR1 to DR7 specificity, 4 combinations were considered according to the presence (pos) or the absence (neg) of the antigen in the D and in the R. Logistic regression was used to study graft survival during two postoperative periods: A (month 1 to 3) and B (month 4 to 24). The following combinations exerted a beneficial effect on survival: DR5 and DR7 Dpos/Rneg for period A, DR4 Dpos/Rneg and DR5 Dneg/Rpos for period B, whereas DRw6 and DR7 Dneg/Rpos for period A, DR1 and DR2 Dpos/Rneg, DR2 and DRw6 Dneg/Rpos for period B exerted a detrimental effect. Graft survival at two years was similar (83%) in HLA-DR identical pairs and in recipients with beneficial and no detrimental HLA-DR disparities, contrasting with poorer outcome in patients with either mixed beneficial and detrimental HLA-DR disparities (67%: p less than 0.05) or detrimental (and no beneficial) HLA-DR disparities (55%: p less than 0.001). The use of relevant D/R HLA-DR disparities for predicting graft outcome could lead to results similar to those currently reported with the best HLA-matched kidneys, from a much smaller pool of recipients.
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Immune-mediated mechanisms and genetic factors are believed to be involved in the pathogenesis of Crohn's disease. We studied T- and B-cell subpopulation proportions and various functional assays, including proliferative responses to PHA and Con A, Con A-induced suppressive activity, and natural killer cell assay toward the K562 cell line, in the peripheral blood of 22 patients with inactive familial Crohn's disease and their 35 healthy relatives including nine families. HLA-A, -B, and -DR antigens were determined in all the subjects. With the exception of minor abnormalities of suppressor cell activity present in some relatives of two families, neither significant impairments of immunological parameters in patients or their relatives nor concordant segregation of HLA haplotypes and disease were observed. These data indicate that peripheral immune abnormalities previously described in patients with Crohn's disease do not constitute primary factors involved in the disease itself and that familial incidence in Crohn's disease cannot be linked to immunological markers presently studied.
Antibodies to the following synthetic peptide, SALGKLLDKVQAY, were purified by affinity chromatography and characterized by ELISA and immunoblotting. These antibodies, shown to be specific to the major protein constituent of isolated rat heart junctions: connexin 43, cross-reacted with a homologous protein in immunoreplicas of whole heart fractions of trout, frog, chicken, guinea pig, mouse and rat, suggesting a phylogenic conservation of connexin 43 in vertebrates. By immunoblotting of whole organ fractions it was also demonstrated that these antibodies cross-reacted with major proteins of Mr 32 and 22 kD in rat and mouse liver, of Mr 41 kD in rat cerebellum, of Mr 43 kD in uterus, stomach and kidney of rat, of Mr 46 and 70 kD in rat lens, suggesting that these proteins share common or related epitopes with the synthetic peptide and connexin 43.
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Flucuations in motor performance is a major problem in long-term levodopa treatment of Parkinsonian patients. A slow release preparation of levodopa with benserazide, Madopar HBS, has been developed in an attempt to decrease this problem. Eleven of 22 Parkinsonian patients with advanced disease and marked fluctuations experienced long-lasting benefit with reduction of their fluctuations in motor performance on treatment with Madopar HBS; 11 dropped out within the first 5 months of the trial. This was probably due to lack of experience with the effect of this new slow-release formulation. Nine patients (82%) required an additional dose of standard Madopar, especially in the morning. Significant improvements were found for akinetic phenomenon and dystonic cramps, and with the global evaluation of motor fluctuations. The occurrence of peak dose dyskinesia remained unchanged. No abnormalities in laboratory values were found.
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Peripheral blood mononuclear cells from 15 patients with alcoholic cirrhosis (AC) and 15 matched healthy controls were tested for their proliferative response to mitogens such as PHA and con A, tumour promoter PMA and OKT3 monoclonal antibody, for their capacity to produce IL-2 and to respond to recombinant IL-2 (rIL-2). The expression of IL-2 receptor (Tac) together with two other activation markers, the receptor for transferrin (T9) and Ia antigen have also been assessed. A profound decrease of proliferative response was observed after stimulation by lectins and PMA. IL-2 production was significantly decreased (0.39 +/- 0.07 versus 0.82 +/- 0.009 units; P less than 0.001) in alcoholic cirrhosis. Resting PBMC of these patients disclosed spontaneous responsiveness to rIL-2 without requiring prestimulation with PHA as observed in healthy subjects. This abnormal response was associated with significantly increased percentages of Tac (19.4 +/- 3.1 versus 5.1 +/- 1.1%; P less than 0.001), T9 (13.6 +/- 3.3 versus 6.6 +/- 1.1%; P = 0.04) and Ia positive cells (21.4 +/- 5.4 versus 11.5 +/- 1.4; P less than 0.05) in alcoholic cirrhosis. Defective proliferative activity and impaired IL-2 production, combined with an increase of lymphocytes bearing T cell activation markers and of rIL-2 responsiveness could represent in vitro correlates for mechanisms leading to immunoregulatory disturbances in cirrhotic patients.
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In this open study patients with advanced Parkinson's disease, who experienced pronounced fluctuations in symptoms while on standard L-dopa, were switched from Madopar/Sinemet to Madopar HBS. The dosage was adjusted until optimal response was obtained. The effect was unsatisfactory in 4 cases and side effects intervened in another 2. The remaining 16 patients exhibited substantial and frequently significant improvements with regard to both akinetic and dyskinetic phenomena. L-Dopa dosage was increased in all cases, and addition of standard L-dopa was required in one third of the cases. These benefits continued in the majority of patients.
Autonomic functions were studied after withdrawal of all medication in parkinsonian out-patients with short and long duration of disease and in age-matched healthy control subjects. Vagal heart control and noradrenergic response to standing were impaired and related to duration of symptoms of idiopathic parkinsonism. Cholinergic function of pupil motility was unchanged. The cholinergic dysfunction of heart rate variation, therefore, could be due to a specific loss of dopaminergic neurons in the vagal motor nucleus.
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