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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 307 records · Page 17Linked to original sources

AIDS and related conditions. One year's experience in St. Vincent's Hospital, Sydney.

Fifty-six patients were referred in 1983 for assessment in connection with AIDS and related disorders. Clinical and immunological classification of patients was carried out according to the NHMRC criteria. The presence of antibodies to an AIDS-associated retrovirus (ARV) was determined in some patients. Of the 32 patients who could be categorized, three patients had AIDS, and all three had serum antibodies to ARV. Fifteen patients had lymphadenopathy syndrome with impaired T-cell immunity. Ten of 12 patients tested had antibodies to ARV. Symptomatic illnesses resembling lymphadenopathy syndrome, but without immune defects, occurred in nine patients. By contrast, five patients who had no symptoms had impaired immunity, and in seven patients no clinical and immunological abnormalities were found. The classification proposed by the NHMRC was found to be useful in delineating several major clinical and immunological patterns of response to infection with the AIDS-associated retrovirus.

Acquired Immunodeficiency Syndrome↗

Contact tracing in the acquired immune deficiency syndrome (AIDS). Evidence for transmission of virus and disease by an asymptomatic carrier.

The sexual contacts of a patient with acquired immune deficiency syndrome were traced, and clinical, immunological, and serological evidence was obtained and evaluated. It was determined that the patient acquired the disease from a homosexual man who had no symptoms, but in whom laboratory evidence of immunodeficiency and serological evidence of exposure to the AIDS-associated retrovirus was found.

Acquired Immunodeficiency Syndrome↗

Immunoregulation in juvenile chronic arthritis.

The presence of hyperimmunoglobulinaemia and antinuclear antibodies in patients with juvenile chronic arthritis (JCA) suggests a possible role for immunoregulatory abnormalities in the pathogenesis of the disease. This is further supported by the demonstration in the sera of such patients of an autoantibody active against a suppressor inducer T cell subset. To identify immunoregulatory defects in JCA, a method of measuring concanavalin A (Con A)-inducible lymphocyte suppression of IgG production in vitro has been established. Peripheral blood mononuclear cells were cultured in the presence of either medium alone, pokeweed mitogen (PWM), Con A, or PWM together with Con A. IgG present in culture supernates at 8 days was measured by a double-antibody radioimmunoassay. Spontaneous IgG synthesis by lymphocytes by both patients and child controls was found to be more than double that of lymphocytes from adult control subjects. However, lymphocytes of children (patients or controls) did not show stimulation of IgG production in the presence of PWM. Con A-induced suppression of spontaneous IgG synthesis was reduced compared to adult controls in both patients (p less than 0.02) and child controls (p less than 0.05). Con A-induced suppression of IgG synthesis in the presence of PWM was also reduced compared to adult controls in both patients (p less than 0.01) and child controls (p less than 0.01) but was also reduced in the patient group compared to the child controls (p less than 0.01). Thus, spontaneous IgG synthesis in children is increased compared to adults, and IgG-producing cells appear less subject to regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cryptosporidiosis in the acquired immune deficiency syndrome.

Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

Acquired Immunodeficiency Syndrome↗

The effect of purified alpha 1 antitrypsin on PWM driven IgG synthesis.

As part of a study investigating the mechanisms for the association of alpha 1 antitrypsin (alpha 1 AT) deficiency with immune disorders, the effect of purified alpha 1 AT on PWM driven IgG synthesis of peripheral blood lymphocytes was investigated. This demonstrated that alpha 1 AT in physiological doses enhanced IgG synthesis in stimulated but not resting cells. This effect is probably due to the known inhibition by alpha 1 AT of macrophage function. Increasing number of macrophages are known to inhibit IgG synthesis in the PWM system suggesting that this apparently paradoxical enhancement by alpha 1 AT is probably due to inhibition of these cells.

Animals↗

Identification of the receptor for antigen and major histocompatibility complex on human inducer T lymphocytes.

Human T cell clones and monoclonal antibodies directed at their surface structures were used to define the receptor for the antigen and major histocompatibility complex on inducer T lymphocytes. The results indicated that the receptor is a single complex consisting of the monomorphic T3 molecule with a molecular weight of 20,000 to 25,000 and a clonotypic disulfide linked heterodimer Ti with a molecular weight of 90,000. Sepharose-bound monoclonal antibodies (anti-Ti4 or anti-T3) to the receptor could activate clonal proliferation and inducer function for B cell immunoglobulin secretion and thus substitute for the appropriate combination of major histocompatibility complex gene product and specific antigen.

Antibodies, Monoclonal↗

Human cytotoxic T cell clones directed at autologous virus-transformed targets: further evidence for linkage of genetic restriction to T4 and T8 surface glycoproteins.

Human cytotoxic T cell clones were generated against autologous EBV-transformed B lymphocytes. Whereas the majority of the clones expressed the T8 surface glycoproteins and showed a specificity for class I MHC gene products on the target cell, a minority expressed the T4 surface glycoprotein and demonstrated a class II specificity. Monoclonal antibodies to T4 and T8 inhibited cytotoxic effector function of reactive clones in a fashion analogous to their effect on alloreactive CTL clones. Each autoreactive T cell clone was cytotoxic for EBV-transformed B lymphocytes but not pokeweed mitogen-activated or resting autologous lymphocytes, suggesting a dual specificity for an MHC gene product as well as an antigen induced and/or encoded by virus. Taken together, the present findings provide further support for the notion that T4 and T8 serve as associative recognition elements on T lymphocytes for MHC gene products.

Antigens, Differentiation, T-Lymphocyte↗

Immunoregulatory human T lymphocytes triggered as a consequence of viral infection: clonal analysis of helper, suppressor inducer and suppressor effector cell populations.

The regulatory functions of a series of human T cell clones specific for an autologous Epstein-Barr virus transformed B lymphoblastoid cell line were examined. Two T4+ T cell clones, termed AT4II and AT4IV, and one T8+ clone, AT8III, were maintained in culture for greater than or equal to 9 months and were characterized in detail. Both T4+ clones provided helper function for autologous B cell immunoglobulin production when added to unstimulated peripheral blood mononuclear cells. In addition, these same clones produced soluble inducer factors after specific antigenic stimulation. However, when AT4II, AT4IV and their subclones were tested on pokeweed mitogen stimulated peripheral blood mononuclear cells, it was found that AT4IV provided help for immunoglobulin production whereas AT4II cells were strongly suppressive. This suppression by AT4II was indirect and required the presence of fresh, autologous, unirradiated T8+ cells. In contrast, the T8+ AT8III clone markedly inhibited Ig production by autologous B cells in the absence of any additional T8+ cells from peripheral blood and produced a soluble suppressor factor upon specific antigenic triggering. Thus, after stimulation with autologous Epstein-Barr virus transformed cells, at least three discrete regulatory human T cell populations can be defined at the clonal level: helper, inducer of suppression and suppressor effector clones.

Antibody-Producing Cells↗

Biosynthesis of immunoglobulin in human immunoproliferative diseases. II. Comparison of tumour cell mass in multiple myeloma measured by synthetic rate studies with that calculated from clinical staging systems.

Tumour cell mass (TCM) in patients with multiple myeloma has been measured by synthetic rate studies of bone-marrow tumor cells in culture. From the measurements of Salmon and co-workers, a simple clinical staging system in which TCM is calculated by a programmable pocket calculator has been developed. We have compared the measurement and calculation of TCM in patients with IgG and IgA multiple myeloma by these methods in our own laboratory. There was correlation between synthetic rate and serum IgG paraprotein concentration but not the serum IgA paraprotein concentration. In patients with IgG myeloma there was correlation between measured and calculated TCM as well as measured TCM and serum IgG paraprotein concentration, urine Bence-Jones protein excretion, and serum albumin concentration. Measured TCM also inversely correlated with haemoglobin concentration. In patients with IgA myeloma, however, there was no correlation between measured TCM and calculated TCM or any other individual clinical laboratory parameter. A number of problems have contributed to the overall failure of this method to measure and calculate TCM including methodological differences, definition of myeloma cells, proteolysis of newly synthesized paraprotein in culture, changes in synthetic rates with time and assessment of the degree of bone lesions by skeletal roentgenograms. We cannot recommend these methods as they stand to measure and calculate TCM in patients with multiple myeloma.

Adult↗

Glucocorticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes.

We studied the role of the T lymphocyte in GCS enhancement of PWM-stimulated IgG synthesis by human peripheral blood mononuclear cells. Purified T or B lymphocyte subpopulations were pretreated with 10(-6) M prednisolone or recombined at various T:B ratios and 10(-6) M prednisolone was added. PWM-stimulated IgG synthesis was measured in the culture supernatants at 8 days by radioimmunoassay. Addition of prednisolone to cultures of autologous and allogeneic reconstituted mixtures of T and B lymphocytes resulted in enhancement of PWM-stimulated IgG synthesis. This effect was observed with constant and increasing numbers of lymphocytes in culture, independent of T:B ratio and occurred with purified B lymphocytes containing monocytes. Pretreatment of purified B lymphocytes containing monocytes but not purified T lymphocytes with prednisolone enhanced PWM-stimulated IgG synthesis in reconstituted mixtures of T and B lymphocytes. We propose that GCS enhancement of PWM-stimulated IgG synthesis by human mononuclear cells is independent of T lymphocyte regulation.

B-Lymphocytes↗

Glucocorticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes. III. Common variable immunodeficiency.

We studied the effect of glucocorticosteroids (GCS) on IgG synthesis by peripheral blood mononuclear cells from 19 patients with common variable immunodeficiency (CVID). Purified T and B lymphocyte subpopulations from patients and normal subjects were recombined at various T : B ratios and cultured for 8 days unstimulated, stimulated with pokeweed mitogen (PWM) and in the presence of prednisolone. IgG synthesis was measured in the culture supernatants by radioimmunoassay. Enhancement of PWM-stimulated IgG synthesis by prednisolone at high T : B ratios was found in nine patients, four of whom produced negligible amounts of IgG with PWM alone. In four patients, enhancement by prednisolone of IgG synthesis by purified B lymphocytes was noted. In three out of eight patients whose IgG synthesis was increased by normal allogeneic T lymphocytes with PWM and prednisolone, negligible amounts of IgG were produced by similarly treated autologous combinations. T lymphocytes from CVID patients provided less help compared with normal T lymphocytes for IgG synthesis by normal B lymphocytes at high T : B ratios even in the presence of prednisolone. GCS in vitro enhance IgG synthesis by lymphocytes from some but not all patients with CVID by a mechanism which appears independent of GCS action on regulatory T lymphocytes.

Adolescent↗

In-vitro synthesis of an anti-BI cold agglutinin complicating a case of lymphoma.

A woman of 47 with lymphocytic lymphoma was found to have a high-titer cold autoagglutinin of anit-BI specificity. Her group B erythrocytes autoagglutinated of anti-BI specificity. Her group B erythrocytes autoagglutinated in vitro and the direct antiglobulin reaction was positive, but she had no symptom of cold intolerance, no evidence of hemolysis, and she could receive transfusions of compatible group O erythrocytes. In addition, evidence for synthesis of the autoantibody by the lymphoma cells was obtained by short-term bone-marrow culture.

ABO Blood-Group System↗

Corticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes.

The effects of the addition in vitro of corticosteroid on pokeweed mitogen (PWM) induced Ig synthesis by human peripheral blood lymphocytes were studied. IgG in supernatants produced under standardized culture conditions was measured by double antibody radioimmunoassay. The addition of 10(-6)M prednisolone caused a remarkable enhancement of PWM-stimulated IgG synthesis beginning at day 4 of culture and increasing at a faster rate than that in cultures with PWM alone. 10(-6)M prednisolone resulted in a geometric mean enhancement of 5.6-fold of PWM-stimulated IgG synthesis in all twenty-five normal controls studied. This enhancement occurred up to 3 days after the addition of PWM. 10(-6)M and 10(-5)M prednisolone resulted in significantly greater enhancement of PWM-stimulated IgG synthesis than 10(-7)M prednisolone. Hydrocortisone, prednisolone, methylprednisolone, betamethasone and dexamethasone at 10(-6)M were all equally effective in the enhancement of PWM-induced IgG synthesis.

Adrenal Cortex Hormones↗