Pathology and immunopathology research最新文献

Enumeration of circulating T lymphocytes is crucial in the investigation of AIDS and related conditions. The single best measure of disease progression and prognosis is the absolute number of helper/inducer T lymphocytes in the peripheral blood. Although the phenotypic identification of a particular subset reflects no direct information on the function of the population, the information provided by the analysis furnishes new insight regarding racial differences in the immune deficiency associated with AIDS. The severity of the HIV illness in the African American population, as reflected by a decrease in the absolute number of circulating CD4+ lymphocytes, was marked compared to the Caucasian population with AIDS. Consequently, the CD4/CD8 ratio was lower in the African American HIV+ population. A higher level of activated mononuclear lymphocytes and NK cells in this population may indicate active disease. The incidence of life-threatening opportunistic infections such as PCP was greater in the adult/adolescent African Americans compared to Caucasians. In contrast, PGL was found more frequently in the Caucasian participants. Although the rate of HIV infection in the adult/adolescent African American population was not different from population estimates for the area under study, the incidence in the pediatric African American population was twice the population estimates for the race. This increased rate occurred in the parent-at-risk as well as in the hemophiliac group.

CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

We employed a purified mammalian (fetal calf) acetylcholine receptor (AChR) preparation to compare proliferation of peripheral blood mononuclear cells (PBMC) of patients with myasthenia gravis (MG) (n = 8) and normal controls (n = 6). PBMC of patients with MG demonstrated an enhanced proliferative response to AChR when compared to controls (mean stimulation index (SI) of 4.2 +/- 1.5 (SD) vs. 1.1 +/- 0.6; p less than 0.01) but no difference in the response to tetanus toxoid (7.1 +/- 3.9 vs. 11.1 +/- 10.8). These results suggest that MG patients exhibit a presumptive T-cell response to purified mammalian AChR that is not found in normal subjects. The nature of the proliferating cell and the interaction with B cells producing anti-AChR antibodies remain to be determined.

It is widely accepted that transfusions are beneficial to the outcome of renal allotransplantation. Whereas some investigators suggested that transfusions may induce both specific and nonspecific suppression of the cell-mediated immune response, others disagree. To lend clarity to this discrepancy, we collected 40 serum samples before and after blood transfusion therapy of first-time cadaveric renal allograft recipients and evaluated each for T cell and B cell cytotoxic antibodies using an Amos modified complement-dependent microlymphocytotoxicity assay. When greater than 10% of the panel cells reacted with a grade 4 or better, the panel was considered significant, and when a lymphocyte specificity was lysed by antibody-rich serum greater than 50% of the time, the antibody was considered specific. Control T and B cell PRA assays employed sera from 27 normal nontransfused volunteers of similar age and sex. Survival distributions of differences in the PRA before and after blood transfusions and posttransfusion PRA levels were compared using the Gehan generalized Wilcoxon test. Other factors which influence allograft survival such as HLA-A, -B and -DR matches, number of blood transfusions, immunosuppressive therapy, age, sex, parity, previous positive crossmatch, circulating cytotoxic antibodies matching the graft, prior dialysis, length of time on the waiting list, lapse of time between transfusion and transplantation and the underlying primary diagnosis were also considered using the Gehan generalized Wilcoxon test or the chi 2 approximation. Transfusion-related B cell cytotoxic antibodies, HLA-DR monospecific or multispecific antibodies and HLA-A, -B matching extended graft survival in a significant manner. Sex influenced the production of B and T cell transfusion-related cytotoxic antibodies with females producing greater quantities of antibodies than males. Parity and the production of monospecific or multispecific antibody were associated with an increase in transfusion-related B cell cytotoxic antibody. A difference in sex was not linked to the production of monospecific or multispecific HLA-DR antibodies. The majority of males failed to respond to multiple blood transfusions with the production of B cell cytotoxic antibodies although more than half were successfully grafted. All females and males who responded with the production of B cell cytotoxic antibodies monospecific or multispecific, with the exception of 1 female, demonstrated an allograft survival of greater than 1 year. In conclusion, differences between pre- and post-transfusion B cell PRAs and monospecific or multispecific HLA-DR antibodies identified in patient sera following transfusions were good predictors of renal allograft survival in both males and females.(ABSTRACT TRUNCATED AT 400 WORDS)