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Biomedical subjects

M J Parmely

Publications and source records attributed to M J Parmely.

7 recordsLinked to original sources

Immunosuppressive activity of isolated rat and human fetoproteins.

Alpha-fetoprotein (AFP) was purified from rat hepatoma sera and pooled human cord sera. Both AFP-rich fractions prepared by consecutive ion exchange and gel filtration chromatography and pure rat AFP prepared by liquid phase immunoabsorption lacked in vitro suppressive activity. Human AFP purified by affinity chromatography was suppressive, but so was similarly purified human cord albumin. Alteration of ionic conditions was shown to affect the activity of both human AFP and cord albumin. The primary mixed lymphocyte response, the generation of the secondary response, and the memory cell, per se, were all found to be sensitive to active human AFP under the appropriate culture conditions.

Animals

Colostral cell-mediated immunity and the concept of a common secretory immune system.

Historically colostrum and milk have been thought to confer immunity on the neonate only by virtue of their immunoglobulin content. Recently we have observed that colostrum also contains viable T lymphocytes capable of expressing cell-mediated immunity in vitro and have employed techniques of lymphocyte culture to elucidate the local nature of mammary tissue immunity at the T-cell level. The results indicate that the activity of colostral lymphocytes appears not to represent the total immunological experience of the mother but that they may contain reactive clones beneficial for the suckling. Colostral immunity appears to depend upon sensitizing events within the intestine and respiratory tract, followed by the migration of lymphoid precursors to the breast, suggesting a relationship between the expression of immunity at various secretory surfaces.

Animals

In vitro studies on the T-lymphocyte population of human milk.

Human milk lymphocytes (ML) can be partially purified and propagated in vitro as a means of assessing their immunological function. When exposed to a variety of stimuli known to activate T lymphocytes, ML respond in a unique manner that indicates a selected population of immunocompetent cells. ML are hyporesponsive to to nonspecific mitogens and respond in a reduced manner to histocompatibility antigens on allogeneic cells. In most cases, they are completely unresponsive to C. albicans although blood lymphocytes from the same patients respond to the antigen. The Kl capsular antigen of E. coli induces significant proliferation in lymphocytes obtained from milk, but fails to stimulate blood lymphocytes. This dichotomy of reactivity does not appear to result from suppressive factors or cells in milk or insufficient adherent cell function. Rather it appears to reflect the accumulation of particular lymphocyte clones in the breast and the local nature of mammary tissue immunity at the T-lymphocyte level.

Antigens, Bacterial

Antileukocyte antibody in postpartum and renal transplant subjects. A comparison of capillary agglutination and lymphocytotoxicity reactions.

Sera were obtained from 48 gravida II prenatal and 211 multiparous nonpregnant females and examined for leukocyte antibodies comparing a standard lymphocytotoxicity (CY) test with capillary agglutination (CA). Antibody was detected in 41% of the samples in both groups but only CA tests were positive with approximately one-half of the prenatal and three-fourths of the multiparous specimens. Although, CA reactions, when accompanied by positive CY responses, usually correlated with HLA, no correlation with HLA, 5b, or the neutrophil antigens was determined for 35 of the 48 sera reacting only by CA. As a model to test the specificity of CA positive-CY negative antisera, four extensively studied sera were further analyzed in 16 families. Independent segregation from the HLA complex and ABO and Rh antigens was confirmed and two of the sera appeared to detect separate clusters of reactions in conjunction with some of the other reagents. Pre- and postgraft samples obtained from 23 living related and 75 cadaveric renal transplanted patients were investigated and compared for graft function and prospective tissue typing. Although direct crossmatches were negative prior to surgery, 17.9% of the pretransplant samples from living related and 28.0% from cadaveric recipients contained detectable antibody when tested against a cell panel. Similar to the prenatal and multiparous groups, the majority of these responses were detected by CA. Following engraftment, antibody first became evident in 11 of 19 (58%) living related and in 23 of 53 (48.2%) cadaveric hosts. There was a striking association between the development of CA and CY antibody and failure, as contrasted to 100% 9-month or greater survival in 10 of 10 living related and 15 of 15 cadaveric transplants in whom only CA antibodies arose postoperatively. In total, these studies indicate that CA reacts with HLA antigens in common with CY tests. In addition, CA may detect HLA when CY is negative but many other reactions appear to be directed at non-HLA specificities. The relevance of CA-only responses to clinical transplantation remains uncertain, but we may speculate that they have an enhancing effect on the course of renal transplantation and are associated with important histocompatibility determinants.

Agglutination Tests

Effect of alpha-fetoprotein and other serum factors derived from hepatoma-bearing rats on the mixed lymphocyte response.

Serum alpha-globulin fractions isolated by physiocochemical techniques from normal adult Buffalo rats suppressed lymphocyte proliferation in vitro. The factors responsible for mixed lymphocyte culture suppression appeared to be strain specific since they were not demonstrable in the same fractions from normal LBN rat serum. Similar fractionation of the serum from Buffalo rats bearing the Morris Hepatoma 7777 obtained from two different sources also yielded suppressive protein fractions that differed both chemically and functionally. Both variants of this hepatoma produced high serum concentrations of alpha-fetoprotein (AFP), providing an opportunity to study the possible immunoregulatory role of their fetal-associated globulins. Fractions rich in AFP that lacked other serum alpha-globulins were obtained by gel filtration chromatography and were devoid of any in vitro immunosuppressive activity. When AFP that was further purified by immunoabsorption was added to mixed lymphocyte cultures, no effect was observed at doses below 400 mug/ml. The MLC response was augmented with higher doses, similar to albumin purified by the same methods.

Animals