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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 415 records · Page 23Linked to original sources

Sperm-related antigens, antibodies, and circulating immune complexes in sera of recently vasectomized men.

Sera from 35 men were collected before and at timed intervals subsequent to vasectomy and examined for the presence of (a) antibody reactive with human spermatozoa, (b) sperm-related antigen, and (c) circulating immune complexes (CIC). Fewer than 10% of the men examined were ever positive for antisperm antibodies. However, sperm-related antigens were elevated in the sera of 18, 18, and 26% of the mean at 2 wk, 2 mo, and 4 mo postvasectomy, respectively. CIC were detected in the sera of some vasectomized men by three different assays. The CIC in patients' sera were precipitated with polyethylene glycol, dissociated, and the individual CIC components identified by an enzyme-linked immunosorbent assay. Most, but not all, of the CIC contained antigen reactive with antisperm immunoglobulin (Ig)G and some also contained complement components C3 and/or Clq. IgA was identified in some of the CIC positive for IgG and sperm antigen and two men had IgM-containing CIC. Analysis of the CIC by sucrose gradient centrifugation revealed them to be heterogeneous in size.

Analysis of Variance↗

Studies on the exocytosis of cultured mast cells derived from mouse bone marrow.

Mast cells were obtained from mouse bone marrow cells cultured for 14 days in medium derived from Concanavalin A (Con A) stimulated mouse spleen cells. Upon passive sensitization of the cultured cells with immunoglobulin E (IgE), histamine release from mast cells was approximately 200% above control within 1 min of incubation with anti-IgE. The calcium inonophore A 23187 also evoked a concentration-dependent (10(-8) M to 6 x 10(-7) M) histamine release following a 6 min incubation. Transmission electron microscopy (TEM) demonstrated that the secretory granules of the cultured cells have a peripheral crystalline pattern, like that previously demonstrated for mast cells. Scanning electron microscopy (SEM) illustrated spherical cells with surfaces traversed by many ridge-like folds. Intragranular fusion, following exposure of the IgE-bearing cells to anti-IgE, led to accumulation of the granules into channels which, on study with both transmission and scanning electron microscopy, appeared to be associated with the cell surface.

Animals↗

T-cell subpopulations following thermal injury.

In this report, we have enumerated T-cell subsets as defined by receptors for immunoglobulin isotypes at 24 to 48 hours postburn. T cells possessing surface receptors for the Fc fragment of IgM represent a population of cells with helper activity, T mu cells, and T cells possessing surface receptors for the Fc fragment of IgG represent a population of cells with suppressor-cytotoxic function, T gamma cells. Significant alterations in the number and proportion of regulatory T cells was observed early in the course of severe burn trauma. A decrease in total T cells was accompanied by a drop in IgM-Fc binding lymphocytes, helper cells, in all burns greater than 20 per cent total body surface area. An increase in IgG-Fc binding lymphocytes was observed only in those patients who had sustained the most severe injuries, greater than 60 per cent total body surface area burn or greater than 25 per cent third-degree burn. These changes correlated linearly with the amount of full thickness injury, and the ratio of T mu:T gamma cells was significant at 24 to 48 hours postburn in predicting the risk of septic death.

Adolescent↗

Enrichment for CFU-C from murine and human bone marrow using soybean agglutinin.

Mouse bone marrow and spleen cells agglutinated by soybean agglutinin (SBA) or peanut agglutinin (PNA) were previously shown to be enriched for spleen colony-forming cells (CFU-S) and sufficiently depleted of graft-versus-host reaction producing cells to allow hematologic reconstitution of lethally irradiated allogeneic recipient mice. A similar enrichment for cells capable of forming colonies in soft agar culture (CFU-C) has now been found in the SBA-agglutinated fraction of mouse bone marrow cells, in contrast to the finding that in human bone marrow the majority of the CFU-C are in the fraction not agglutinated by SBA. Cytofluorometric studies with fluorescein-labeled SBA (FITC-SBA) revealed that the majority of both mouse and human bone marrow cells bind the lectin. Experiments mixing the human marrow fractions separated by SBA reveal that true enrichment for CFU-C is achieved in the unagglutinated fraction, as opposed to a possible depletion of a suppressor cell population. Granulocytic, monocytic, and mixed cell colonies were all enriched in the SBA-unagglutinated cell fraction from human bone marrow.

Animals↗

Helper cell factors restore antibody responses of allogeneic bone marrow chimeras: evidence for ineffective cellular interactions.

We investigated the nature of deficient antibody responses to SRBC in stable, fully allogeneic bone marrow chimeras. No evidence for a suppressor cell-mediated mechanism was found. Chimera spleens possessed adequate numbers of antigen-reactive B cells to produce a normal antibody response. Using separated chimera cell populations and soluble helper factors, we assessed the functional capabilities of chimera B cells, T cells, and macrophages. Our data suggest that the failure of allogeneic chimeras to produce antibody is not the result of impaired B cell, T cell, or macrophage function, but rather that it is due in ineffective cellular interactions that normally result in the generation of helper factors. In vitro stimulation of chimera macrophages with LPS, and of chimera spleen cells with Con A, resulted in the release of soluble helper factors that were capable of fully restoring chimera B cell responses.

Animals↗

Low serum thymic hormone levels in patients with chronic graft-versus-host disease.

We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p less than 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.

Adolescent↗

Generation of a monoclonal antibody against facteur thymique serique (FTS).

A monoclonal antibody against one of the thymic hormones, facteur thymique serique (FTS), was generated by hybridization between mouse NS-1 myeloma cells and BALB/c splenocytes, the latter obtained from BALB/c mice immunized with synthetic FTS coupled to mouse IgG. Enzyme-linked immunosorbent assay (ELISA) was developed and employed to detect the hybridoma secreting specific antibody. The monoclonal antibody (MA-FTS) was highly specific for FTS and did not cross-react with other thymic hormones or other unrelated peptides. MA-FTS could recognize FTS (or FTS-like molecule) in human serum and could absorb completely the FTS-like activity from human serum.

Animals↗

Distinguishing features of the immunology of Hodgkin's disease in children.

Laboratory tests of immunologic function were done in 96 children with Hodgkin's disease, at diagnosis and during and after treatment. Over the same period of time, 29 aged-matched control children were tested. The results presented in this report indicate that the immunology of childhood Hodgkin's disease has some features that distinguish it from the immunologic features of the disease in adults: (a) no progressive lymphopenia was found with advanced clinical stages; (b) peripheral blood T-lymphocyte counts were normal or high, and slight B lymphocytopenias were observed in children at all stages of the disease; (c) in spite of normal T-lymphocyte counts, a defective response to phytohemagglutinin stimulation was seen at diagnosis; and (d) recovery of the phytohemagglutinin response occurred with treatment and was related to modality of therapy and prognosis.

Adolescent↗

Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

The effect of dietary restriction on the expression of retroviral envelope glycoprotein, gp70, and the formation of gp70-anti gp70 immune complexes was investigated in lupus-prone NZB x NZW F1 hybrid mice. Restricting total calorie intake from the usual 20 to only 10 calories per day after weaning markedly reduced serum levels of both free and antibody-complexed gp70, prevented renal disease, and increased the life spans of these mice. The reduction in serum gp70 was evident after only 2 wk of feeding these animals the low-calorie diet, and the concentration remained virtually unchanged throughout the course of 10 mon experimentation. However, serum concentrations of the major structural protein, p30, of endogenous retroviruses were not altered by restricting calories. Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not. These results suggest that the expression of gp70 in serum is controlled independently of the production of complete viral particles, and regulated by a mechanism similar to that for other serum glycoproteins, such as haptoglobin.

Animals↗

Multivariate analysis of T-cell functional defects and circulating serum factors in Hodgkin's disease.

A comprehensive immunologic and serologic analysis was performed on 31 untreated patients with Hodgkin's disease. Immune evaluations stressed T-cell functional activity and included traditional parameters (PHA responsiveness and delayed hypersensitivity skin reactivity), as well as newer functional assays (T-cell colony formation, chemotaxis, spontaneous and antibody-dependent cytotoxicity, and concanavalin A-induced suppressor cell activity (CISA). Serum factors included ferritin, prostaglandins, zinc, copper, immune complexes, and thymic hormone activity. Every patient exhibited at least one T-cell or serum abnormality. The greatest percentage of patients exhibited T-cell defects in chemotaxis (85%), colony formation (81%). and PHA reactivity (64%). Immune defects were more common with advanced disease but were not related to absolute T-cell or monocyte count, skin test anergy, or abnormalities of T mu/T gamma cell proportions. Linear relationships were identified among abnormalities in the three assays employing mononuclear cells (PHA, colony formation, CISA) which may have reflected the inhibitory influence of monocytes present in the mononuclear cell preparations. Low serum zinc correlated with marked impairment of T-cell chemotaxis. Elevated prostaglandins were associated with high PHA reactivity and with depressed colony formation. Our results indicate that many complex factors, including intrinsic T-cell defects, contribute to the impaired immunity associated with Hodgkin's disease.

Adolescent↗

Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells.

A new procedure for enrichment of marrow precursors and removal of T lymphocytes from large volumes of human bone marrow, involving initial differential agglutination of T lymphocytes and mature marrow elements with soybean agglutinin, followed by rosetting with sheep red blood cells, was used to fractionate marrow cells from an HLA-A, B, DR non-identical, MLC non-reactive, paternal donor for transplantation into an infant with acute leukaemia. This transplant became completely engrafted and resulted in full recovery of normal, donor-derived haematopoietic function without graft-versus-host disease, sustained for 11 weeks after transplantation, at which time the patient's leukaemia recurred. Subsequently, the patient received chemotherapy and achieved a remission with regeneration of normal marrow cells of donor origin. The patient's course demonstrated the potential of lectin-separated marrow grafts to restore durable haematopoiesis, without graft versus host disease, in a lethally irradiated allogeneic host.

Agglutinins↗