Pathology and immunopathology research最新文献

ASLC is clinically and endoscopically similar to active idiopathic IBD, especially ulcerative colitis. While several histopathologic criteria have been described which are useful in distinguishing these conditions, the diagnosis can still be difficult. In this study, we review the use of immunofluorescence on formalin-fixed paraffin-embedded biopsies from patients with ASLC. While tissues from active IBD have a striking increase in the number of IgG- and a lesser increase in the IgA- and IgM-containing plasma cells in the lamina propria, tissues from ASLC have normal numbers of IgG-containing cells with only a slight increase in IgA- and IgM-containing cells. The use of immunofluorescence on these tissues can provide quantifiable information which may be a helpful diagnostic adjunct in distinguishing these alternatives if histopathologic evaluation is equivocal.

The use of immunoelectron microscopy in the evaluation of renal diseases represents a valuable addition to existing techniques. The ability to immunolabel immune-complex deposits for light- and heavy-chain determinants, and complement fractions virtually eliminates the need for traditional immunofluorescence. One of the main advantages of performing immunoelectron microscopy relates to the fact that immunologic events can be adequately correlated morphologically with the degree and type of tissue reactions in the various renal compartments. Immunopathogenetic mechanisms can be clearly evaluated with this technique. The need to submit specimens in different fixatives is eliminated and all diagnostic modalities can be performed on a single fragment of tissue. The examination of the thick sections prepared from plastic-embedded tissue for survey provides excellent material for interpretation of findings at the light-microscopic level. These sections can be stained with hematoxylin/eosin, trichrome, silver methenamine and PAS stains with excellent results. The time and resources needed for processing renal biopsies can be significantly reduced by utilizing the proposed methodology. Likewise, interpretation of results may benefit from utilization of the same fragment for all diagnostic modalities.

Polyinosinic-polycytidylic acid [poly(I,C)] is a double-stranded RNA that is a potent interferon (IFN) inducer in rodents and, when suitably complexed with poly-L-lysine and carboxymethylcellulose [poly(I,C)-LC], also in primates and humans. In addition, poly(I,C)-LC has shown significant therapeutic activity in a number of preclinical tumor models and significant toxicity in both the preclinical and clinical settings. To better understand the toxicity of this agent, particularly in light of the previously reported bell-shaped dose response curve for immunomodulation and therapeutic activity, we undertook a pharmacological/toxicological study of poly(I,C)-LC. These experiments revealed that the injection of toxic doses of poly(I,C)-LC significantly reduced the body weight of animals and induced serological and histological abnormalities. We found that poly(I,C) is the toxic moiety of poly(I,C)-LC and that both agents induced pulmonary thrombosis as well as hepatic necrosis. The hepatic necrosis was reflected in serum enzyme levels, with significant increases in ornithine carbonyl transferase, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase levels. In addition, reduced platelet counts indicated a significant increase in platelet consumption in agreement with the thrombosis. There were, however, only minor changes in prothrombin and activated prothrombin times. It was of interest that coincubating poly(I,C)-LC and peritoneal macrophages in vitro resulted in the production of tumor necrosis factor, which has a similar pattern of toxicity; this finding suggests that poly(I,C)-LC's pattern of toxicity may be associated with the induction of TNF and/or IFN.

In conclusion, IL-1 has multiple biologic activities relevant to rheumatic diseases. It mediates the acute-phase response, and exerts control over many metabolic functions of connective tissue, including muscle, bone, cartilage, synovium, and endothelium. IL-1 also has a profound effect on leukocyte function. Although few clinical studies have been reported, there is suggestive evidence that IL-1 plays a role in the pathogenesis of arthritis, scleroderma, SLE and vasculitis. That drugs useful in the therapeutic management of these conditions influence IL-1 activity provides indirect support for the involvement of IL-1 in pathogenesis. Clearly, further studies are needed in this area. With the recent development of recombinant preparations of IL-1, further investigation of IL-1 in connective tissue metabolism and clinical rheumatic disease can be carried out. Finally, the future development of pharmacologic agents specifically designed to alter IL-1 responses may allow specifically targeted therapy for rheumatic diseases.