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Biomedical subjects

J M Dwyer

Publications and source records attributed to J M Dwyer.

18 recordsLinked to original sources
PubMed1979

Evidence for defective immunoregulation in the syndrome of familial candidiasis endocrinopathy.

We studied three children with candidiasis endocrinopathy syndrome, together with their parents and five siblings, to explore the possibility that defective immunoregulation allows autoimmune phenomena to be involved in the pathogenesis of this syndrome. Inheritance of the syndrome appeared to be autosomal recessive. Immunologic abnormalities in this family included hypergammaglobulinemia, selective IgA deficiency, anergy, autoimmune endocrinopathies and active chronic hepatitis. Defective suppressor T-cell function was noted in the two surviving children with clinically apparent disease and in a clinically normal sibling. Analysis of the immunologic abnormalities in the family suggests that defective immunoregulation rather than disordered effector mechanisms may explain the large number of immunologic defects noted. These defects, in turn, may result in the clinical manifestation of the syndrome.

Adolescent↗
PubMed1979

Behaviour of human immunoregulatory cells in culture. I. Variables requiring consideration for clinical studies.

The suppressor function of lymphocytes stimulated with concanavalin A (Con A) provides a potential method for examining disorders of immunoregulation. Clinical application, however, requires definition of the culture conditions that influence the expression of normal suppressor cell activity. In the present studies culture conditions were modified until a sensitive assay for non-specific suppressor cell function was reproducible utilizing the response to varying doses of phytohaemagglutinin (PHA) as an indicator system. Practical conclusions included (1) that sensitivity was not lost if the suppressor cells and responder cells were allogenic; (2) that fresh responder cells were as sensitive as precultured responder cells; (3) that a wide range of Con A concentrations could induce suppressor activity; and (4) that the sensitivity of the assay was much enhanced by using suboptimal mitogen doses of PHA. Twelve percent of normal subjects gave false negative results but these could be avoided by studying cells at more than one time point after stimulation with Con A. Cells resting in culture for 7 days could be induced to suppress after stimulation with Con A and these suppressor cells were very sensitive to pharmacological doses of dexamethasone. Studies utilizing different times of cell pre-incubation before Con A stimulation and different periods of exposure to Con A revealed fluctuation in the induction of suppression that may represent alternating periods of suppression and amplifying activity among stimulated cells in vitro. Such variations will need to be taken into account in the application of this type of assay to clinical studies seeking disordered immunoregulation.

Cell Survival↗
PubMed1978

Effect of radiation on cell-mediated cytotoxicity and lymphocyte subpopulations in patients with ovarian carcinoma.

Lymphocyte subpopulations and cell-mediated cytotoxicity (CMI) were studied during radiation therapy in 16 patients with ovarian carcinoma. The total lymphocyte count became depressed in all patients. The depression was more marked among T cells, while the proportion of B cells remained unaffected. In patients with Stage I and II ovarian cancer, CMI was depressed significantly by radiotherapy after 7 days of treatment, remained low at 14 days but recovered despite continuation of radiation. This depression of CMI occurred at a delivered dose of 1,000 rads with subsequent recovery. Patients with Stage III ovarian cancer given pelvic and abdominal radiation were found to have no consistent depression of CMI, a finding similar to that in Stage III ovarian carcinoma patients given chemotherapy.

Adult↗
PubMed1978

Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis.

Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 agematched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P less than 0.001), mumps (P less than 0.001), trichophyton (P less than 0.025), and Candida albicans (P less than 0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD and Candida albicans were significant (P less than 0.02 and P less than 0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.

Antigens↗
PubMed1978

Terminal deoxyribonucleotidyl transferase activity in B-cell acute lymphocytic leukemia.

Moderately high levels of activity of the enzyme terminal deoxyribonucleotidyl transferase (TdT) were found in the leukemic cells of a patient with acute lymphyocytic leukemia. The proliferating cells were B lymphocytes bearing IgG antibody, and the disease was associated with an IgG monoclonal spike and a mediastinal mass. The observations in this case suggest that TdT is related more to the immaturity and proliferation of certain lymphoid stem cells than to their progress toward B- or T-cell differentiation.

Adolescent↗
PubMed1978

Hepatitis B in hemodialysis patients: significance of HBeAg.

Twenty-four HBsAg-positive (HBsAg+) hemodialysis patients were prospectively studied to assess (1) the prognostic value of HBeAg and its HBe1Ag and HBe2Ag components and (2) whether a difference in cellular immune status between HBeAg+ and HBeAg-negative (HBeAg-) patients could be defined. Sixteen patients were HBeAg+ and 8 were HBeAg- initially. After a mean follow-up period of 23.7 months, it was concluded that the initial presence of HBeAg correlated with the persistence of HBsAg because 15 of the 16 HBeAg+ patients were still HBsAg+ at death or last follow-up, whereas 7 of the 8 HBeAg- patients had become HBsAg- at a mean period of 3.8 months. HBe1Ag was consistently present in 15 of the 16 patients when HBeAg was detectable, whereas HBe2Ag fluctuated widely in individual patients over time. No difference in cellular immune status between HBeAg+ and HBeAg- patients could be defined; although both HBeAg+ and HBeAg- patients had a similar decrease in peripheral blood T cells and poor responsiveness to purified HBsAg, both groups of patients had stimulation indices to nonspecific mitogens within the normal range.

Adult↗
PubMed1977

The role of IgE in the immune response to neoplasia: a review.

The role of IgE in the immune response to neoplasia has received little attention despite suggestive evidence for an IgE response to tumor specific antigens. A complex interrelationship is known to exist between basophils, eosinophils, histamine, complement, and T cells. The latter cells are known to play a central role in the immune response to neoplasia and, in addition, are now considered important in the production and regulation of IgE, the molecule that may supply an important link between pharmacological and cellular dynamics of a successful anti-tumor response. The evidence for an IgE role in the immune response to tumors, the relationship between atopy and cancer, and the possible mechanisms whereby IgE could enhance tumor rejection are discussed in this review.

Animals↗
PubMed1977

Studies on the role of the thymus and T cells in the in vivo suppression of delayed hypersensitivity (desensitization): radiosensitivity of the mechanism inducing nonspecific anergy.

Guinea pigs immunized with two or more antigens can have their ability to manifest delayed hypersensitivity (DH) reactions to all these antigens temporarily blocked by the administration of large (mg) amounts of one or more of these antigens 9 days after immunization. This nonspecific anergy is called desensitization. This study presents evidence for the induction of the desensitized state by an active, radiosensitive, immunoregulatory mechanism involving the peripheralization of thymocytes. Desensitization was associated with 1) a marked reduction in thymic weight; 2) an increase in mature T cells in the peripheral blood; 3) decreased responsiveness of the lymphocytes in the spleen to concanavalin-A; and 4) markedly reduced numbers of mono-nuclear cells, basophils, and polymorphs at the skin sites of specific and nonspecific desensitization. Small doses of whole-body irradiation which left DH capacity intact prevented nonspecific desensitization, but did not prevent specific desensitization, suggesting that a radiosensitive cell was involved in the production of anergy.

Animals↗
PubMed1977

Identification of lymphocytes in percutaneous liver biopsy cores. Different T:B cell ratio in HB sAg-positive and -negative hepatitis.

The lymphocytes infiltrating the liver were isolated and characterized as T or B cells in three groups of patients: 20 patients with hepatitis B surface antigen (HB sAg)-positive acute and chronic hepatitis, 8 patients with HBsAg-negative chronic hepatitis with prior evidence for hepatitis B virus (HBV) infection, and 5 patients with HBsAg-negative chronic hepatitis without prior evidence for HBV infection. The predominant cell infiltrating the liver was shown to be a T cell in all categories; however, the ratio of T:B cells was significantly lower (1.96) in the patients without evidence for HBV infection than in the patients who were HBsAg-positive at (7.86), or before (8.85) the time of study. The significantly (P less than 0.001) higher number of B cells in the patients with chronic hepatitis of unknown etiology suggests that a different immunopathogenetic mechanism is operative in this group. A peripheral T lymphocytopenia was observed in patients with both antecedent and existent HBs-antigenemia, but not in the patients without evidence for HBV infection.

Acute Disease↗
PubMed1976

K cells at issue.

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Antibody-Dependent Cell Cytotoxicity↗
PubMed1976

Sarcoid.

Patients with sarcoidosis were separated into those treated or not treated with prednisone. Skin test reactivity of both groups was clearly diminished but a significant decrease in T-cells was seen only in the steroid-treated group and this was not sufficient to explain the profound energy. Lymphocyte stimulation studies generally revealed elevated baseline incorporation of [3H]thymidine and reduced stimulation. Factors were present in the plasmsa of 1/4 to 1/3 of the patients which suppressed normal lymphocyte stimulation. When cells from 3 sarcoid patients were precultured in vitro, recovery towards normal occurred with a drop of the elevated baseline and rise in peak response.

Adult↗