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Biomedical subjects

M A Baird

Publications and source records attributed to M A Baird.

At least 19 recordsLinked to original sources
PubMed1992

Evidence that changes in expression of major histocompatibility complex antigens may underlie the immunosuppressive effect of heat-treated cells in vivo and in vitro.

The prior transfusion of heat-treated (60 degrees C for 1 hr) allogeneic spleen cells is known to bring about specific prolongation of the survival of subsequent donor strain heart allografts. In this communication we show that some polymorphic and monomorphic class 1 determinants on spleen cells are heat denatured so that they no longer provoke antibody formation in naive allogeneic hosts. By contrast, the heated cells remain able to provoke the formation of anti-class 2 antibodies. When measured in a binding assay, the levels of anti-class 2 antibodies are similar irrespective of whether the immunizing inoculum consists of normal or heated cells. In a cytotoxic assay, the antibodies produced following exposure to normal cells are cytotoxic; this activity is substantially reduced when the cellular immunizing inoculum is heated. Cells heated to 60 degrees C for 1 hr are unable to stimulate in a mixed lymphocyte reaction, but reactivity can be partially restored by the addition of exogenous IL-2 to the culture. From previous evidence it seems unlikely that suppressor cells play a major role in the immunosuppression effected by cells heated to 60 degrees C. The results presented in this communication suggest a possible role for anticlass 2 antibodies and also imply the defective production of a costimulatory signal that normally follows the presentation of allogeneic MHC antigens.

Animals↗
PubMed1989

A proposed growth regulatory function for the serologically detectable sex-specific antigen H-Ys.

It is widely believed that the serologically detectable sex-specific antigen H-Ys plays a major role in the primary determination of sex. The cellular distribution of the antigen, however, seems to be at odds with its postulated function. Consideration of this apparent paradox has prompted the suggestion that the H-Ys antigen functions as a growth regulator, and that its role in the primary determination of sex can be accounted for on this basis. Circumstantial evidence is adduced that H-Ys is a growth regulator in the embryo, and this is supported by evidence from several sources not immediately related to embryonic growth or development. Genes coding for growth regulators can function as oncogenes in situations involving disordered regulation, and it is suggested that this accounts for the high incidence of ovarian neoplasms in H-Ys positive, but not in H-Ys negative, female patients with 46,XY gonadal dysgenesis (Swyer's syndrome). A postulated growth regulatory function of H-Ys lends weight to the contention of others, not only that the direction of differentiation of the indifferent gonad in the embryo is determined by its growth rate, but also that a common mechanism underlies genotypic sex determination and environmental sex determination.

Animals↗
PubMed1989

A scheme for determining the prevalence of alcoholism in hospitalized patients.

As a part of an on-going effort to assess the prevalence of alcoholism among hospitalized patients, a structured technique was devised to document the prevalence of alcoholism in a large teaching hospital. A system of inpatient chart audit classification was developed to assess direct evidence of patient alcoholism. In addition, the reported prevalence of alcoholism as a discharge diagnosis was determined. An assessment of the degree of alcoholism was used to classify patients into severity levels. A determination was made of the relationship of hospital chart data classification level to other medical problems or treatments directly addressed by the physician(s) that would indicate that the alcohol abuse, if present, was considered. A retrospective chart audit was conducted for 809 consecutive adult admissions to a 350-bed urban university teaching hospital using a specific classification scheme for determining evidence of alcoholism. This technique revealed a reported prevalence of alcoholism in 4.3% of all nonobstetric admissions to this university hospital. However, a chart review technique using specific criteria for the diagnosis of probable alcoholism raised the estimated prevalence to 15.9%. When the chart contained a primary diagnosis of alcoholism, physicians' responses reflected treatment plans that addressed acute management of alcohol related medical complications but often did not document efforts to assist the patient with the underlying alcoholism/substance abuse.

Adult↗
PubMed1988

Immunosuppressive activity of class I antigens in the absence of antigen-presenting cells that are MHC-compatible with the host.

Pretransplant transfusions of heat-treated spleen and lymph node cells were shown to prolong the survival of DA strain heart grafts in 3 allogeneic host strains: BS, HS, and AS2. To examine whether MHC incompatibility was necessary for immunosuppression mediated by heat-treated cells, AS strain skin-graft recipients were pretreated with fresh or heated inocula from either MHC compatible or incompatible congenic donor strains, AS2.1L(AS) and AS.1F(AS2) prior to transplanting donor strain skin. Prolonged survival was observed only in the MHC-incompatible strain combination, and in this MHC-incompatible strain combination, and in this instance heated cells were conspicuously more immunosuppressive than fresh cells. To determine the effect of intra-MHC differences between donor and host on graft survival, cells from a recombinant donor strain (r22), which shared class II antigens with the graft donor strain and class I antigens with the host, were transfused prior to heart transplantation. Neither fresh nor heated r22 cells prolonged graft survival. Our data accord with the suggestion that in the absence of MHC-compatible antigen-presenting cells, foreign class I antigen is immunosuppressive.

Animals↗
PubMed1987

An immunochemical procedure for the purification of rat class I antigens (RT1.A/RT1.E) from detergent-solubilized erythrocytes.

An immunochemical procedure using two immunoaffinity columns for the isolation of rat Class I antigens from detergent-solubilized DA erythrocytes is described. The protocol yields a pure Class I preparation as assessed by silver staining of sodium dodecyl sulfate-polyacrylamide gels and comparison of the amino acid composition with that previously determined for H-2K/D. The antigen preparation is capable of specifically blocking the hemagglutination of DA erythrocytes by Class I-specific alloantiserum.

Amino Acids↗
PubMed1987

The H-Y antigen.

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Animals↗
PubMed1986

Prolonged survival of cardiac allografts in rats following the administration of heat-treated donor lymphocytes. A possible immunosuppressive role for class I major histocompatibility complex antigens.

Pretransplant transfusions of spleen and lymph node cells heated to 45 degrees C or 50 degrees C for 1 hr prolong the survival of subsequent donor-specific heart grafts in the fully allogeneic donor-host combination DA (RT1a)----AS (RT1l). The results are comparable to survival times recorded following pretransplant transfusions of purified donor specific red blood cells (RBC) in the same strain combination. Both class I and class II major histocompatibility complex (MHC) antigens are serologically detectable on heat-treated cells; by contrast only class I antigens are expressed on red blood cells. Although heat-treated cells stimulate alloantibody formation, they fail to provoke a proliferative response in an in vivo host-versus-graft assay. Both red blood cells and heat-treated inocula persist in the host for long periods, possibly an important consideration in relation to their capacity to prolong the survival of subsequent donor strain allografts. The experimental data support the contention that class I MHC antigens can be immunosuppressive in the context of allografting. The present results recall the experiments carried out early in the century, which used heat-treated tumor cells to prolong the survival of subsequent viable tumor allografts, and which are sometimes cited as the first example of active enhancement.

Animals↗
PubMed1986

Further observations on transfusion collapse curves in inbred rats.

Transfused allogeneic red blood cells (RBC) are very rapidly cleared from the host circulation in some strain combinations among inbred rats. The phenomenon, termed collapse curve clearance, an analogy with its human counterpart, is spleen-dependent. Allogeneic 51Cr-labeled red cells taken up by the spleen are retained for at least 6 weeks, and appear to represent a pool of intact cells that are destroyed no more quickly than syngeneic red cells. Sequential transfusions delivered at weekly intervals gradually abrogate rapid clearance, but a longer interval between injections allows the collapse curve pattern to persist. Increasing the dosage of donor red cells above the standard dose used in these experiments decreases the clearance rate, while reducing the dosage further accelerates clearance. Several attempts to implicate anti-RBC antibody, and to correlate the presence of such antibody with accelerated clearance, have failed. The grafting of an additional syngeneic spleen neither increases the proportion of allogeneic RBC removed from the circulation, nor reverses a temporary paralysis of the phenomenon induced by red cell overloading. These experiments imply that rapid clearance of allogeneic red cells is not mediated by a purely cellular mechanism, but that it requires a humoral substance that is readily exhausted, but fairly quickly replenished. The possibility that the rat equivalent of the H-2.7 mouse antigen might be responsible was considered, but appropriate experiments on mice have failed to support this idea. The findings in these experiments strengthen the analogy to the clinical event.

Animals↗
PubMed1986

H-Y antigen is not expressed on purified rat erythrocytes.

The presence of H-Y antigen on male rat erythrocytes was investigated using a high-titre H-Y antiserum in both ELISA, cellular absorption and syngeneic male to female erythrocyte transfusion studies. No evidence was found to suggest that H-Y antigen is expressed on rat erythrocytes. These data are in accord with recent findings of other investigators studying mouse H-Y serology.

Animals↗