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Biomedical subjects

J Rygaard

Publications and source records attributed to J Rygaard.

At least 91 records · Page 5Linked to original sources

Suppressor cell activity and beta-cell function in insulin-dependent diabetics.

Immunological mechanisms may play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), and suppressor cell activity (SCA) has been found depressed at diagnosis. The aim of the present study was to elucidate whether patients with preserved beta-cell function display a different SCA than other patients. Sixteen patients without and 12 patients with beta-cell function after averagely 9 years' duration of IDDM were examined. The suppressive effect of lymphocytes was investigated after incubation with concanavalin A followed by inactivation. Suppression was measured as the ability of the lymphocytes to inhibit 3H-thymidine incorporation in concanavalin A stimulated normal donor lymphocytes. The main findings were: (1) No significant differences in SCA between patients with and without beta-cell function, and one of these patient groups had SCA significantly different from normal controls. (2) A correlation between SCA and administered dose of insulin among patients without beta-cell function. It is concluded that the actual SCA several years after diagnosis is not connected with the beta-cell function in patients with IDDM.

Adult↗

Suppressor cell activity in patients with newly diagnosed insulin-dependent diabetes mellitus: a prospective study.

Suppressor cell activity (SCA) was investigated longitudinally, at the time of diagnosis and during the remission period, in 17 patients with insulin-dependent diabetes mellitus (IDDM). The suppressive effect of lymphocytes from patients was investigated after incubation with concanavalin A followed by inactivation. Suppression was measured as the ability of the lymphocytes to inhibit 3H-thymidine incorporation in concanavalin A stimulated normal donor lymphocytes. The main findings were: I. SCA was reduced, on the average, at diagnosis but normal during the remission period. II. Patients with the lowest SCA at diagnosis showed significantly lower C-peptide values during the remission period than other patients. III. No relationship was found between on the one side various tissue types and on the other SCA, C-peptide values, insulin dose, and degree of glucaemic control, neither at diagnosis nor during remission. Previous studies have pointed to the significance of immune reactions in diabetogenesis. The findings in the present study may associate SCA with the development of IDDM.

Adult↗

Immunological reconstitution of tumour-transplanted and thymus-grafted nude mice.

Two different malignant tumours were transplanted prior to or after thymus grafts in nude mice, and the degree of immunological reconstitution was studied. All mice which rejected either of the tumour types had reconstitution as expressed by an excess of splenic plaque-forming cells. The level of response was dependent upon the age of the thymus graft and whether a tumour was transplanted or not. In contrast, the result of the phytohaemagglutinin stimulation assays of spleen cells were always subnormal in thymus-grafted as well as in thymus- plus tumour-transplanted mice.

Animals↗

Studies on lymphoid cells of adenoid tissue in relation to clinical findings.

Adenoid tissue was obtained at operation in 27 children admitted for adenoidectomy and in 6 controls. The occurrence of cells with cytoplasmic immunoglobulin was studied by immunofluorescence of tissue sections, and localization, number of cells and class of immunoglobulin were determined. No differences were found between patients and controls. Mononuclear leucocytes isolated from adenoid tissue and from blood were compared. In the patients, the proportions of B lymphocytes were higher in the tissue than in the blood, in particular IgG-, IgM- and IgD-carrying cells. Stimulation in vitro with polyclonal activators induced less thymidine incorporation in adenoid cells than in blood cells. Stimulation with heat-killed Haemophilus influenzae induced a high response inadenoid cells from 7/20 patients with negative nasopharyngeal culture for H. influenzae, whereas all 7 patients who harboured H. influenzae in the nasopharynx were low responders.

Adenoidectomy↗

Depressed suppressor cell activity in patients with newly diagnosed insulin-dependent diabetes mellitus.

Suppressor cell activity (SCA) was studied in twenty-eight patients with insulin-dependent diabetes mellitus (IDDM), both newly diagnosed and of longer standing. Suppressive effect of peripheral blood lymphocytes from the patients was tested after 48 hr of incubation with concanavalin A followed by inactivation. Suppression was measured as the ability of the lymphocytes to inhibit 3H-thymidine incorporation in concanavalin A-stimulated normal donor lymphocytes. SCA was expressed in relation to the activity of peripheral blood lymphocytes from simultaneously investigated healthy control individuals. The main findings were: (1) SCA was significantly depressed in newly diagnosed diabetics and (2) newly diagnosed patients displayed significantly lower SCA than did patients with duration of disease between 2 and 8 months and between 5 and 8 years, who had suppressor cell activities not significantly different from healthy individuals. Earlier studies have pointed to the significance of immune reactions in diabetogenesis. On this basis, and on the strength of our present findings, it is suggested that an impaired SCA, causing a decreased inhibition of aggressive lymphocytes, may be implicated in the pathogenesis of insulin-dependent diabetes mellitus.

Adult↗

Effects of thymus grafts in nude mice transplated with human malignant tumors.

The effect of neonatal thymus grafts implanted in nude mice previously transplanted with three different human malignant tumors - an adenocarcinoma of the colon, a malignant melanoma and a Burkitt's lymphoma - were studied. In all immunologically reconstituted animals tumord were rejected. Tumor rejection stated 2-3 weeks after thymus implantation, and was completed after 30-6 weeks. Histological examination of lymphoid tissues showed a correlation between immunological reconstitution and tumor rejection. The rejection process showed a characteristic histologic picture with 3 phases - an early, an intermediate and a late phase - these were similar in the three tumor types examined. The possible mechanisms of reconstitution and tumor rejection are discussed.

Adenocarcinoma↗

Lymphocytes of adenoid tissue.

Adenoid tissue was obtained at operation from 27 children admitted for adenoidectomy and from 6 controls. The occurrence of cells with cytoplasmic immunoglobulin was studied semiquantitatively by immunofluorescence microscopy of tissue sections, by which localization, number of cells and class of immunoglobulin were determined. No differences were found between patients and controls. Cells isolated from adenoid tissue were compared with mononuclear leukocytes obtained from the blood. More B lymphocytes were found in the tissue, in particular IgM-carrying cells. This was more pronounced in the patient group. Cells were stimulated in culture with polyclonal activators and microbial antigens. The response of adenoid lymphocytes to Haemophilus influenzae (HI) was high in 7/27 patients; all patients in whom throat culture was positive for HI were low responders.

Adenoidectomy↗

Passive transfer of diabetes mellitus from man to mouse.

Lymphocytes extracted from peripheral-blood samples from each of six patients with newly diagnosed insulin-dependent diabetes mellitus were transplanted into arthymic nude mice. At one or more sampling times (in the thirty-day study) blood sugar was higher in mice which had received lymphocytes from diabetic patients than in the control mice which had received lymphocytes from non-diabetic donors. Blood-sugar concentrations reached 260 mg/dl in some mice in the experimental group. This study demonstrates that lymphocytes may have an aggressive role in diabetogenesis. With this mouse experimental model mechanisms involved in diabetogenesis, and probably also in other disease in which lymphocytes are suspected of being involved in pathogenesis, could be investigated.

Adolescent↗

Is the diabetogenic effect of streptozotocin in part thymus-dependent?

Following a single injection of 200 mg streptozotocin/kg BW, 25 out of 25 normal mice became diabetic, whereas 12 ( = 20%) out of 50 athymic nude mice did not develop diabetes. In a multiple dosage experiment, where the same total dose was given over a 5 days period, 14 normal and 15 athymic nude mice all became diabetic, but nude mice had significantly lower blood glucose values. These results support our previous suggestion that a thymus dependent immune reaction is, in part, responsible for the diabetogenic effect of streptozotocin.

Animals↗

T-lymphocytes transfer streptozotocin induced diabetes mellitus in mice.

Diabetes mellitus induced by low dose treatment with streptozotocin in BALB/c mice was passively transferred to syngeneic recipients with a predominantly T-lymphocyte fraction of spleen cells. This fraction was prepared by density centrifugation and passage through an antimouse immunoglobulin coated column. Variation in numbers of injected cells in the range of 10(3) to 10(7) showed that the smaller cell numbers gave the highest blood sugar values. Athymic nude recipients of BALB/c background also developed diabetes following similar transplants. A preliminary result was that the highest blood sugars were seen after transplantation of T-lymphocytes treated by low dose irradiation (200 R). This may reflect a specific effect on T-suppressor lymphocytes.

Animals↗

Passive transfer of streptozotocin induced diabetes mellitus with spleen cells. Studies of synogeneic and allogeneic transfer to normal and athymic nude mice.

This study shows passive transfer of streptozotocin induced diabetes mellitus in mice. Transplants of spleen cells from BALB/c mice, streptozotocin treated for 5 days, induced diabetes in normal BALB/c recipients. Treatment of transplants with anti-theta and complement resulted in a significant decrease in the degree of diabetes. Athymic nude mouse recipients of BALB/c background also developed diabetes after transpant of spleen cells from both syngenic and allogenic (C-7/Bl/6) donors. It is concluded that passive transfer of chemically induced diabetes in mice is practicable, in both syngeneic and allogeneic combinations, and that thymus derived lymphocytes are significant in this process.

Animals↗