Chronic Antibody Mediated Rejection of Renal Allografts: Pathological, Serological and Immunologic Features in Nonhuman Primates

The pathogenesis of late renal allograft loss is heterogeneous and difficult to diagnose. We have analyzed renal allografts in nonhuman primates to determine the relationship between alloantibodies and the graft pathology of late graft loss. Seventeen Cynomolgus monkeys were chosen from among those on several protocols for renal allotransplantation with mixed chimerism induction so that animals with and without alloantibodies were included. All animals received transient CD154 blockade and short-term cyclosporine treatment until day 28. Serial blood samples were tested for alloantibodies. Protocol biopsies and autopsy kidneys were scored for pathology and C4d deposition. Group 1, defined by complete lack of C4d deposition (24 tissue samples; 8 recipients), had no detectable alloantibodies (33 serum samples; 1-7 samples per recipient) and no evidence of chronic rejection. Three survived greater than 2 years with normal function and histology. Group 2, defined as having C4d deposition in peritubular capillaries, all made alloantibodies (100%), and most grafts later showed chronic allograft glomerulopathy (89%), and/or arteriopathy (89%). All grafts in Group 2 failed (3-27 months). Pathologic lesions of typical of chronic rejection in humans develop in monkeys, correlate with antecedent alloantibodies/C4d deposition and predict chronic rejection rather than durable accommodation.     

Cutaneous, pulmonary and hepatic sarcoidosis associated with autoimmune complications during interferon-alpha treatment for hepatitis C virus infection

A patient with hepatitis C virus (HCV) infection was diagnosed with cutaneous, pulmonary and hepatic sarcoidosis following interferon alpha therapy. There are only a few cases of sarcoidosis associated with this treatment. This is the first case who not only developed sarcoidosis, but also autoimmune hypothyroidism and thrombocytopenia during interferon alpha therapy due to the immunomodulatory effects of the drug.     

血液透析对慢性肾功能衰竭患者血浆心钠素水平的影响

本文观察了15例慢性肾功能衰竭病人透析前后的血浆心钠素浓度改变.患者透析前血浆心钠素浓度较正常人明显增高(P相似文献   

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

氟中毒和氟砷中毒对胃粘膜的影响

作者通过内窥镜对新疆奎屯地区氟中毒患者３５名，氟砷中毒患者３２名，对照组２５名的胃粘膜进行观察，旨在了解氟元素和砷元素对胃粘膜的影响，在３个组中慢性胃炎的炎症程度与炎症活动性有显著性差异。２个中毒组间无显著性差异。结果表明在高氟区和高氟砷区患者的胃粘膜层病理改变主要是任性氟中毒引起，单纯性砷中毒并无协同作用。     

Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques

Abstract In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryp-tase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N=4), psoriasis (N=13), atopic eczema (N=7), lichen planus (N=6), interferon α2a injection sites (N=l) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase-and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages, (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages, (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.     

Experimental chronic dermatophytosis in human skin grafted to nude mouse: inoculation of Trichophytons and histopathological evaluation

Two strains of T. rubrum and one strain of T. mentagrophytes were inoculated into human skin grafted onto BALB/c nude mice by the needle puncture method. Infection was established in 1 of the 10 animals inoculated with fluffy colony type T. rubrum, 2 of the 10 animals inoculated with powdery colony type T. rubrum, and 7 of the 10 animals inoculated with granular colony type T. mentagrophytes, suggesting that the skin grafts are infectible by anthropophilic and zoophilic strains of dermatophytes. T. rubrum infection continued for a maximum of 9 weeks and T. mentagrophytes infection for more than 11 weeks. In the animals inoculated with T. mentagrophytes, fungal elements were localized in the stratum corneum of the human skin grafts. In the acute stage, microabscesses consisting of neutrophils were observed under the stratum corneum in contact with fungal elements; in the chronic stage, epidermal thickening and infiltration, mainly consisting of histiocytes and a smaller number of lymphocytes, was noted in the upper and middle dermis. Ultrastructural findings from the parasites were similar to those of dermatophytosis in man. This experimental system should be useful as a model of chronic dermatophyte infection in the human skin.     

前列腺素E1治疗慢性乙型肝炎黄疸的观察

目的观察前列腺素E1治疗慢性乙型肝炎重度黄疸的疗效。方法在综合治疗基础上，分别使用前列腺素E1（治疗组）和门冬氨酸钾镁（对照组）治疗慢性乙型肝炎重度黄疸患者各35例，并观察其症状、体征及肝、肾功能等，疗程4周。结果治疗组的症状、体征及肝功能指标及总有效率，均显著优于对照组，两组比较差异有显著意义（P〈0．05）。结论前列腺素E1治疗慢性乙型肝炎重度黄疸能显著地促进黄疸消退和改善肝功能。