Treatment of autoimmune diseases with antibodies to class II major histocompatibility complex antigens

The family of Fc receptors (FcR) for IgG play pivotal roles in affector, effector, and regulatory functions of cells of the immune system. Thus, changes in expression and activation of FcRs may contribute to a variety of disease manifestations that are the consequence of abnormalities in immune system function. Patients with diabetes mellitus are often plagued with recurrent bacterial and mycotic infections, as well as large and small vessel injury which may in part be immune mediated and which lead to organ dysfunction. Hormone-mediated changes in immune system function have been postulated to contribute to a variety of the complications experienced by patients with diabetes mellitus. It is the purpose of this review to summarize current knowledge regarding abnormalities in immune system function in diabetes mellitus with special emphasis on classical hormonal modulation of Fc receptor-mediated phagocytosis.     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。     

Circulating immune complexes and kidney lesions following 131I administration in mice with thyroglobulin antibodies

Immune complexes containing thyroglobulin have been described in kidneys of some patients with thyroid disease. We investigated the circulating immune complexes (with the Raji cell radioassay) and the kidney histopathology (by immunofluorescence and electron microscopy) in mice that received radioiodine to release thyroglobulin in the circulation, 2 or 4 weeks after immunization with mouse thyroglobulin in Freund's complete adjuvant. Circulating immune complexes and thyroglobulin, antibodies were found in all mice. Granular deposition of IgG, IgM, C3, and thyroglobulin, mainly in the mesangium but also in the capillary walls of the glomeruli, were observed in most of the mice. These experiments suggest that circulating immune complexes composed of thyroglobulin are responsible for the glomerular lesions. Hyperthyroid patients should be tested for thyroglobulin antibodies before treatment with radioiodine to avoid formation of thyroglobulin-containing circulating immune complexes.     

Thyroid function in mice with experimental autoimmune thyroiditis.

Mice of strains high and low responders to thyroglobulin were immunized with mouse thyroglobulin emulsified in Freund's complete adjuvant. Groups of mice were killed at weekly intervals and the serum thyroxine concentration was measured with a solid-phase RIA while the titre of thyroglobulin antibodies was determined by passive haemagglutination and the magnitude of thyroid infiltration with mononuclear cells was scored. In other groups of mice, similarly immunized, radioactive iodine uptake was measured at various times after immunization. In almost all mice the lowest level of thyroxine and the lowest radioiodine uptake were observed 2 weeks after immunization. There was no clear relationship between the thyroid function and the titre of thyroglobulin antibodies or the extent of the cellular infiltrates in the thyroid.     

CD8 expression on B cells in chronic lymphocytic leukemia: a case report and review of the literature

The expression of CD8, a restricted T-cell antigen, on B cells in B chronic lymphocytic leukemia is rare, and its significance, if any, remains unknown. We report herein a patient with B chronic lymphocytic leukemia in whom CD8 was strongly expressed on all B cells, both in the bone marrow and peripheral blood. The patient required no therapy for 6 years after being diagnosed as having B chronic lymphocytic leukemia. Then, when the disease progressed, he was treated with conventional doses of fludarabine phosphate (25 mg/m(2) daily for 5 days), but unlike other patients with B chronic lymphocytic leukemia he tolerated this therapy poorly. He received a total of only 4 series of fludarabine therapy, and following each course of treatment, he developed considerable myelosuppression. After the fourth course of therapy, his bone marrow failed to show any evidence of regeneration, and he died as a result of intercurrent respiratory tract infection 1 month after his last dose of fludarabine was given.     

Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects

Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm³, while that for males was 16.3 cm³ and that for females was 18.0 cm³. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.

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Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains

Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm³, mais il est chez les sujets masculins de 16,3 cm³ et chez les sujets de sexe féminin de 18 cm³. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.

     

Relationship of the quality and quantity of circulating anti-BSA antibodies to the severity of glomerulonephritis in rats with chronic serum sickness.

Chronic serum sickness glomerulonephritis, induced in hyperimmunized rats by daily intravenous administration of bovine serum albumin, occurs in three stages, mild, moderate and severe, with abrupt onsets and distinctive features of kidney pathophysiology and immunopathology. We have studied the relationship between circulating anti-BSA antibodies and the severity of glomerulonephritis at each stage. The total amount of antibodies declined gradually during the course of disease, to low concentrations in the most severe stage of kidney inflammation. High levels of immune complexes were present in the circulation while precipitating antibodies were maintained, and rats remained in the mill stage of disease, exhibiting no abnormalities of kidney function and only mesangial immunopathology. The start of the moderate stage of chronic serum sickness, identified by proteinuria and the accumulation of immune deposits along the glomerular basement membrane, was associated with the disappearance of precipitating antibodies from circulation. With the onset of the severe stage of disease, marked by depressed glomerular filtration and sodium excretion, circulating antibodies of high affinity were no longer detected and circulating immune complex levels were only marginally elevated above normal. The experiments reported here demonstrate that, in chronic serum sickness glomerulonephritis of rats, transitions from one stage of kidney disease to another can be inferred from changes in the population of circulating antibodies. Kidney histopathology, therefore, can be predicted reliably from serological data alone.