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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 505 records · Page 28Linked to original sources
PubMed1980

A human soluble suppressor factor affecting lymphocyte responses in vitro.

A soluble suppressor factor (SSF) has been demonstrated in the supernatant of normal human peripheral blood lymphocyte cultures that exhibits suppressive activity toward the proliferative response of normal lymphocytes to concanavalin A or alloantigens in mixed lymphocyte culture (MLC) or toward pokeweed mitogen-stimulated immunoglobulin synthesis and secretion in vitro. Suppression of the proliferative response in MLC reached maximal levels when added SSF-containing supernatant approximated 20% by volume of the culture medium. Suppression in the MLC was found to act at the proliferative stage. SSF acts independently of cytotoxicity and is stable at 56 degrees C for 30 min but is inactivated at higher temperatures. Addition of SSF to the MLC as late as day 4 after initiation of the culture results in suppression of transformation. This factor(s) may regulate the magnitude of several immune responses in humans.

Antibody Formation↗
PubMed1980

Separation of antibody helper and antibody suppressor human T cells by using soybean agglutinin.

Soybean agglutinin (SBA) binds specifically to mouse B cells and has been used in the past to separate mouse B and T spleen cells by differential agglutination of the B cells. In the present study it was found that a major T-cell subpopulation of human peripheral blood mononuclear cells is agglutinated by SBA along with the B cells and monocytes. Tests of such cell surface markers as Fc receptors for IgG and IgM, as well as functional assays of antibody production by B cells, revealed that the SBA-agglutinated cell fraction contains the antibody helper T cells whereas the unagglutinated fraction is enriched with antibody suppressor T cells. Similar observations were made in tests of the proliferative response to mumps antigen. A recently prepared monoclonal antibody, anti-Leu 2a, which recognized the same thymus-dependent antigen previously defined by a heterologous anti-human T cell serum (alpha TH2), was found to define by indirect immunofluorescence a subpopulation of SBA- cells of intermediate staining intensity which was not detectable in the SBA+ population.

Antibody Formation↗
PubMed1980

Allogeneic hemopoietic stem cell transplantation using mouse spleen cells fractionated by lectins: in vitro study of cell fractions.

Mouse spleen cells sequentially agglutinated by soybean agglutinin (SBA) and peanut agglutinin (PNA) previously had been shown to be sufficiently depleted of graft-versus-host activity to allow reconstitution of lethally irradiated allogeneic recipient mice. We have now tested the extent of T-cell depletion in this cell fraction by various in vitro assays, including cytotoxicity testing with anti-Thy-1 antiserum, mitogenic response to the T-cell mitogens concanavalin A and phytohemagglutinin and allogeneic responsiveness in the mixed lymphocytes culture assay. By these criteria the SBA+, PNA+ spleen fraction, used previously in the in vivo experiments, was found to possess about 1% T-cell contamination. The slight contamination with T cells previously found in the singly agglutinated SBA fraction can be removed by a second fractionation with SBA, thus eliminating the possibility that a minor T-cell subpopulation bears receptors for SBA. Finally, we demonstrated that the twice-agglutinated fraction, by SBA and PNA or by SBA alone, contains a significant number of prothymocytes, thereby indicating that mouse prothymocytes bear receptors for both SBA and PNA. The implication of these findings to bone marrow transplantation in humans is discussed.

Animals↗
PubMed1980

Isolation and partial chemical characterization of the IgG Fc receptor of human T lymphocytes and production of an antiserum.

We report here the isolation of an IgG Fc receptor from normal human T lymphocytes. The purified receptor has a nonreduced and a reduced component of molecular weights 120,000 and 60,000, respectively, and it was functionally active in the in vitro blocking of rosette formation between T lymphocytes and IgG-coated ox erythrocytes. An antiserum raised to the Fc receptor and an isolated F(ab')2 fragment of this antiserum, also blocked rosette formation between T cells and IgG-coated ox erythrocytes. In contrast, rosette formation between T lymphocytes and IgM-coated ox or sheep erythrocytes was not blocked by the F(ab')2 fragment, demonstrating the marked specificity of this antiserum for the IgG Fc receptor. In addition, this antiserum did not block the Fc receptors of non-T cells, indicating that the T-cell IgG Fc receptor has unique antigenic determinants not shared with B cells.

Electrophoresis, Polyacrylamide Gel↗
PubMed1980

Animal model for immune dysfunction associated with adenosine deaminase deficiency.

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.

Adenosine↗
PubMed1980

Lymphoproliferative disorders of the T-cell series. A review.

Malignant diseases of the hematopoietic and lymphoid systems have been the subject of vigorous study in recent years. New methodologies, along with conventional techniques for identifying cell markers, now enable us to identify malignant cells with much greater specificity than in the past. Cell marker analysis has begun not only to extend our understanding of normal cell differentiation in the lymphoid and hematopoietic systems, but also to furnish more practical guidelines for approaching malignant disease, including more objective and reproducible classification, more accurate diagnosis and prognosis, more appropriate and more effective choice of treatment. Neoplasms of the T-cell series, which are the subject of this presentation, have in the past received less attention than the B-cell malignancies. More recent literature, however, shows increasing use of modern techniques in the analysis of T-cell malignancies, along with a corresponding increase in clinical resourcefulness. Different phenotypes of malignant cells have been correlated with the heterogeneous clinical and pathological features of T-cell neoplasms, suggesting a basis for their inconsistent responsiveness to treatment. As we develop a uniform system of classification and a generally accepted terminology for these heterogeneous and frequently puzzling disorders, we hope to gain further insight into pathogenetic mechanisms of the T-cell neoplasms, and to refine therapeutic measures for diseases which have defeated conventional therapy in the past.

Adolescent↗
PubMed1980

Platelet transfusion therapy and circulating immune complexes.

30 platelet transfusions were administered to 9 thrombocytopenic patients with acute leukemias. Using the Raji cell radioimmunoassay, the serum concentration for circulating immune complexes (CIC) were determined immediately before and 10--12 h after each transfusion therapy. Elevated serum concentrations for CIC were present in 14 of the pretransfusion samples. After platelet transfusion therapy, a significant (p < 0.02) decrease in the values of CIC occurred. In these 14 transfusion studies the mean percent platelet increment was considerably lower (0.10 > p > 0.05) than the mean for the 16 transfusion studies in which the pretransfusion values for CIC were normal. These results show that CIC probably play an important role in removing transfused platelets from the circulation. Conversely, platelets are able to remove CIC from the circulation.

Acute Disease↗
PubMed1980

Selective IgA deficiency and neoplasia.

From the Immunodeficiency Cancer Registry, it has appeared that there is an increasing frequency of neoplasia in individuals who have a selective absence of serum IgA. Approaching this question from another point of view, we have found that of 4,120 sera drawn in this cancer-oriented hospital, 12 sera had a total absence of IgA and 3 additional sera had less than 10 mg/dl. The incidence of IgA deficiency in a cancer hospital is thus 1 : 342 or 1 : 273, which is statistically similar to that previously found for other patient groups studied in the USA (average of two studies, 1 : 418), but it is substatistically increased over the incidence of IgA deficiency found in normal blood donors (average of five studies 1 : 1,677). Analysis of these sera by diagnostic categories showed that of 1,517 sera of patients with lymphoproliferative disorders, 6 were IgA deficient (frequency 1 : 253), and of 249 sera of patients with gastrointestinal neoplasm, 2 were IgA deficient (frequency 1 : 125). We conclude that, in the absence of IgA, certain organ systems, the gastrointestinal and lymphoid tissue may be at increased risk for malignant change and that the protective, anti-neoplastic role of IgA requires investigation.

Adult↗
PubMed1980

Plasma levels of beta-thromboglobulin and platelet factor 4 in relation to the venous platelet concentration.

The plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were determined in patients with various hematologic malignancies, and the results were related to simultaneously determined venous platelet counts. All studied patients were in a steady state. The plasma beta-TG concentrations were determined on 69 occasions and the values ranged from 0 to 82 ng/ml. In 33 instances, the venous platelet count was <25 x 10 (9/1) and in two thirds of these samples beta-TG was undedectable. The highest values for plasma beta-TG were found in patients with the highest venous platelet counts. A highly significant correlation (r=0.77, p <0.001) between the values for plasma beta-TG and venous platelet count was present. The plasma concentrations for PF-4 ranged from 0 to 50 ng/ml. Similarly, there was a highly significant relationship (r=0.78, p<0.001) between the values for PF-4 and venous platelet concentration. We conclude, if the plasma levels of beta-TG and PF-4 are used as markers of platelet activation in vivo, it is necessary to simultaneously consider the platelet concentration in the collected blood.

Adolescent↗
PubMed1980

Heterogeneity of b lymphocyte differentiation in severe combined immunodeficiency disease.

Pokeweed mitogen-induced B lymphocyte differentiation in vitro into antibody secreting plaque-forming cells (PFC) was investigated in nine patients with severe combined immunodeficiency having variable proportions of circulating B lymphocytes. When cultured by themselves, the peripheral blood mononuclear cells did not respond to stimulation with pokeweed mitogen in any patient. In the presence of irradiated allogeneic T cells as helpers, however, PFC responses were elicited in lymphocyte cultures from peripheral blood and/or bone marrow in some patients. In one of these patients, results of allogeneic co-culture experiments were suggestive of genetically restricted suppressor cells. In a single patient with deficiency of the enzyme adenosine deaminase, PFC were generated in bone marrow lymphocyte cultures only when they were supplemented with exogenous adenosine deaminase and allogeneic helper cells. A parallel study of T lymphocyte differentiation in vitro performed in fractionated bone marrow cells was suggestive of arrested differentiation at different steps along the differentiation pathway. In two patients with evidence of functional B cell precursors, deficiencies of helper T cell function could be attributed to differentiation defects at the level of the stem cells in one and the thymus in the other. The findings reported here further substantiate the heterogeneity of the severe combined immunodeficiency disease syndromes.

Adenosine Deaminase↗
PubMed1980

Human T lymphocytes and myeloid colony forming cells share common antigen.

Human peripheral blood T lymphocyte antigen has been detected by goat antisera raised to thymocytes of Rhesus monkey. An absorbed antiserum reacted in complement-mediated cytotoxicity reactions and absorption experiments with isolated human peripheral blood T lymphocytes, thymocytes, cells of T lymphocyte line, but not with B lymphocytes or cells of B lymphocyte line. Anti-T lymphocyte antibodies blocked the T lymphocyte rosette formation with sheep erythrocytes. By cytotoxicity test an average of 85% cells of unfractionated lymphocyte preparations and 98% cells of isolated T lymphocyte preparations were positive for the antigen. Peripheral blood granulocytes and monocytes were shown to lack the antigen by cytotoxicity and absorption tests. Lysis of bone marrow cells by the antiserum abolished granulocyte-macrophage colony formation in vitro. Absorption studies showed that myeloid colony forming cells express antigen common to T lymphocytes. The common antigen may be the membrane structure located close to the lymphocyte receptors for spontaneous binding of sheep erythrocytes. This common antigen probably represents an antigen characteristic of the T lymphocyte line which is shared with and thus may be inherited from the pluripotent stem cells.

Antilymphocyte Serum↗
PubMed1980

Receptors for immunoglobulin isotype on T and B lymphocytes from untreated patients with chronic lymphocytic leukaemia.

Peripheral blood lymphocytes from eighteen untreated patients with chronic lymphocytic leukaemia (CLL) were analysed for the proportions of T and B lymphocytes with receptors for IgM, IgG or IgA. T lymphocytes with Fc receptors for IgM (T mu cells) or IgA (T alpha) cells were found in proportions comparable to those found in the controls. However, the proportion of T lymphocytes with receptors for IgG (T gamma cells) was significantly increased (P < 0.001) resulting in an abnormally low ratio of T mu/T gamma (P < 0.001), when compared with normal controls. The proportion of B cells bearing Fc receptors for IgM, IgG or IgA was determined simultaneously. No significant differences were found between the normal controls and the patients with CLL. In vitro treatment of the purified T and B lymphocyte preparations with human leucocyte interferon, did not alter the proportions of the lymphocytes expressing Fc receptors for various immunoglobulin isotypes. The significance of these findings is discussed.

B-Lymphocytes↗
PubMed1980

Demonstration of IgG Fc receptors on spermatozoa and their utilization for the detection of circulating immune complexes in human serum.

The presence of Fc receptors, but not C3 receptors, on human and bovine spermatozoa was shown by sperm-induced rosette formation of antibody-treated ox erythrocytes and by immunofluorescence of aggregated human gammaglobulin (AHG) treated spermatozoa. Human and bovine spermatozoa bound AHG as well as circulating immune complexes (CIC) from human sera; monomeric IgG bound to these cells to a much lesser extent. Binding of AHG to the sperm surface also occurred when the AHG was suspended in either buffer or in serum that had been heated at 56 degrees C for 30 min. A bovine spermatozoa radioimmunoassay for the detection of immune complexes in human sera was developed and was shown to be comparable to the Raji cell radioimmunoassay (r = 0 . 81, P < 0 . 01) in the quantitation of soluble immune complexes from a variety of human sera. An enzyme-linked immunoassay was then developed, using bovine spermatozoa fixed to wells of microtitre plates, to simplify the immune complex detection assay. The technique provides an analysis that is rapid, does not require radioactive chemicals, expensive equipment, or cultured cells and yields values for immune complex determination both comparable and complementary to the Raji cell radioimmunoassay (r = 0 . 70, P < 0 . 01). The sperm assays detected soluble immune complexes in sera of vasectomized males, cancer patients and patients with autoimmune or dermatological diseases.

Animals↗
PubMed1980

Heterogeneity of cell lineages in L3 leukemias.

Five cases of adult leukemia with L3 morphology in bone marrow were studied for the presence of immunologic, metabolic, and enzymatic markers. Among the five patients, there were four males and female. Median age was 66 with a range of 16-80 yr. Median survival was only 5 mo. Serum lactate dehydrogenase (LDH) levels, 3H-thymidine labeling indices, and DNA/RNA content of the L3 lymphoblasts were markedly elevated. B-cell markers were found in three cases, two exhibiting surface membrane IgM-lambda, and one IgG-K. Terminal deoxynucleotidyl transferase (TdT) enzymatic activity was consistently low in this group. In one case, the L3 lymphoblasts displayed only surface Fc receptors demonstrated by the binding of aggregated IgG. TdT activity was found to be significantly increased. In another instance, the lymphoblasts formed spontaneous rosettes with sheep erythrocytes and exhibited paranuclear staining with acid phosphatase. TdT activity was found to be low. Although most of the L3 leukemias are neoplasias of B lymphocytes, other lineages may also express this morphology.

Adult↗