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Biomedical subjects

K Buschard

Publications and source records attributed to K Buschard.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effect of encephalomyocarditis (EMC) virus on murine foetal and placental growth monitored by quantification of maternal plasma levels of pregnancy-associated murine protein-2 and alpha-fetoprotein.

The present study demonstrates that pregnant mice seem to be more sensitive to encephalomyocarditis (EMC) infection than non-pregnant mice, and the infection results in significantly increased maternal plasma levels of insulin and pregnancy-associated murine protein-2 (PAMP-2), of placental origin, and alpha-fetoprotein (AFP), of foetal origin. Maternal plasma levels of PAMP-2 and AFP are correlated with placental and foetal growth respectively. This indicates that the EMC infection and the increased peripheral insulin levels lead to increased growth of the foetoplacental unit.

Animals↗
PubMed1986

Changes in T-lymphocyte subsets after elective surgery.

In seven patients undergoing elective cholecystectomy or vagotomy, helper and suppressor/cytotoxic T-cells were quantified by use of monoclonal antibodies (OKT) preoperatively and on postoperative days 2 and 7. The total number and percentage distribution of T-cells (OKT 3) did not change significantly in the study period and the total number of helper T-cells (OKT 4) was similar in the three tests, but the number of suppressor/cytotoxic T-cells (OKT 8) on postoperative days 2 and 7 showed significant rise from the preoperative value. Consequently, significant decrease in OKT 4/8 ratio was found 2 days (1.47 +/- 0.23) and 7 days (1.80 +/- 0.28) postoperatively, as compared with the preoperative ratio (2.85 +/- 0.44). Since reduced ratio of OKT 4/8 has been shown in disorders associated with diminished immunocompetence, our findings may be related to the increased susceptibility to bacterial infections seen in post-surgery patients.

Aged↗
PubMed1985

Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals.

A group of 36 diabetes-prone BB Wistar rats were given prophylactic insulin treatment with heat-treated bovine ultralente insulin (15 IU X kg-1 X day-1) from 50 to 142 days of age. The incidence of Type 1 (insulin-dependent) diabetes at the end of the treatment period was compared to that of 36 control animals given insulin only from the first day of glycosuria. At withdrawal of the prophylactic insulin treatment, 6 of 36 treated animals were insulin-dependent, while 15 of 36 control animals had developed diabetes (p less than 0.02). One control animal (day 153) and 2 insulin-treated animals (day 172 and 186) subsequently developed diabetes, yielding an overall diabetes incidence of 16 of 36 controls against 8 of 36 insulin treated (p less than 0.05). The finding that prophylactic insulin treatment of diabetes-prone BB Wistar rats reduced the incidence of diabetes suggests a relationship of the immune destruction of B cells to the endogenous insulin production/secretion rate.

Animals↗
PubMed1985

Pattern of distribution of T lymphocytes, Langerhans cells and HLA-DR bearing cells in normal human oral mucosa.

The tissue distribution of helper/inducer and suppressor/cytotoxic T cells, Langerhans cells (LC) and HLA-DR bearing cells was determined in normal oral mucosa by use of monoclonal antibodies OKT4, OKT8, OKT6 and OKIa1, respectively. OKT4+ and OKT8+ cells were invariably present in normal oral epithelium and in the lamina propria. OKT8+ cells were consistently seen inside the basal cell layer of the epithelium. The distribution of LC in oral epithelium showed regional variation. In palatal epithelium LC were evenly distributed in the basal half of the epithelium, whereas in buccal mucosa the highest concentration of LC was seen in the epithelium overlying the tips of connective tissue papillae. OKIa1 stained dendritic cells in the epithelium and plump cells with small dendritic processes in the connective tissue. Some of the latter were located close to the basal cells of the epithelium. The consistent relationship between immunocompetent cells and the epithelium of the oral mucosa suggests the presence of a local immunologic defence barrier in the oral mucosa.

Adolescent↗
PubMed1985

The thymus-dependent immune system in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. Animal model and human studies.

The aim of the present study was to investigate the possible role of the thymus-dependent immune system in the disease mechanisms underlying type 1 (insulin-dependent) diabetes mellitus. Both animal experiments and human studies were carried out. Firstly, a brief historical review is given of the scientific progress within the aetiology and pathogenesis of diabetes mellitus during the last few decades. Mention is made summarily of some elements of the thymus-dependent immune system, and the athymic nude mouse is presented. Three diabetic animal models are reported, viz. two exogenously provoked diabetes models in mice, virus-induced diabetes and diabetes induced by streptozotocin, besides the spontaneously diabetic BB rat. Insofar as the mouse models are concerned, experiments were carried out on both nude mice and normal thymus-intact mice. Encephalomyocarditis virus was used in the virus model and could after inoculation be isolated in large quantities from nude mice as well as normal thymus-intact mice. Only the latter developed diabetes; the C57 mice in the form of glucose intolerance and the BALB/c/BOM mice in the form of elevation of the mean blood glucose values to about threefold normal level. The nude mice exhibited only a very short-lasting virus antibody formation, while in the thymus-intact mice it was possible, as might be expected, to demonstrate high titres of neutralizing virus antibodies for months after the virus inoculation. In the streptozotocin model, where the streptozotocin was administered by repeated small injections, the nude mice developed considerably milder diabetes than the thymus-intact mice. This survey includes other experiments using various forms of immunosuppression (thymectomy, irradiation, treatment with antilymphocyte serum), which together supply evidence that the thymus-dependent immune system is involved in the pathogenesis of diabetes in the two mouse models mentioned as well as in the spontaneously diabetic BB rat, regardless of the different aetiologies in the models. On this background, clinical immunological studies in patients with type 1 diabetes were carried out. Firstly, studies are reported of subpopulations of the peripheral lymphocytes which, after labelling with monoclonal antibodies, were investigated by means of flow-cytometry. The number of cytotoxic/suppressor T-lymphocytes was found to be reduced at the time of diagnosis of type 1 diabetes, but increasing towards normal levels five months later. The helper T-cells were found to be slightly increased at diagnosis as compared with the values in controls, whereas there were no differences in the total T-lymphocyte counts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Pattern of distribution of blood group antigens on human epidermal cells during maturation.

The distribution in human epidermis of A, B, and H blood group antigens and of a precursor carbohydrate chain, N-acetyl-lactosamine, was examined using immunofluorescence staining techniques. The material included tissue from 10 blood group A, 4 blood group B, and 9 blood group O persons. Murine monoclonal antibodies were used to identify H antigen (type 2 chain) and N-acetyl-lactosamine. Human antisera were used to identify A and B antigens. In all groups N-acetyl-lactosamine and H antigen were found on the cell membranes of the spinous cell layer. N-acetyl-lactosamine was present mainly on the lower spinous cells whereas H antigen was seen predominantly on upper spinous cells or on the granular cells. Epithelia from blood group A or B persons demonstrated A or B antigens, respectively, but only if the tissue sections were trypsinized before staining. In such cases A or B antigens were found on the cell membranes in the granular cell layer.

ABO Blood-Group System↗
PubMed1984

A longitudinal study of virus antibodies in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus.

Seventeen newly diagnosed type 1 diabetics were studied longitudinally--at diagnosis, after 5 months and after 2 years, for antibodies against the following viruses: Coxsackie B3, B4 and B5, Echo 11, and Adeno 7a. The latter two were chosen because they had been isolated frequently in the area during the year the patients were diagnosed, whereas the Coxsackie viruses previously have been associated with the aetiology of type 1 diabetes. Coxsackie B4 antibody titres fell from the diagnosis and the 5 month study to the 2 year study (p less than 0.02), and, at this time, the average titre was also lower than in 37 healthy control individuals (p less than 0.05). Over the same period Coxsackie B3 antibody titres increased (p less than 0.05). Echo 11 antibody titres were higher in the patients at diagnosis (p less than 0.05), but, otherwise, no significant titre differences, compared with controls or titre changes, were found at any of the study times. Patients with lower suppressor cell activity at diagnosis displayed higher mean antibody titres regarding the five viruses together, than did patients with higher suppressor cell activity (p less than 0.05). No significant correlations were found between, on the one hand, the antibody titres and, on the other hand, C-peptide values, insulin dosage, degree of glycaemic control, or specific tissue type, HLA-B8 or HLA-DR3 and/or 4.

Adenoviruses, Human↗
PubMed1983

Virus-induced diabetes mellitus in mice and the thymus-dependent immune system.

The present study concerns the effect of the experimental diabetogenic encephalomyocarditis (EMC) virus on normal and athymic nude mice of BALB/c origin. The effect of simultaneous immunosuppressive pharmacological treatment with a derivative of cyclophosphamide in a relatively low dose (3 mg/mouse) was also studied. After inoculation with EMC virus, 36% of the normal mice, but none of the nude mice, developed diabetes mellitus and 93% of the normal mice, but none of the nude mice, developed paresis of one or more leg(s). When lower doses of EMC virus were given, few or none of the normal mice developed diabetes or paresis. After treatment with a cyclophosphamide-derivative, the number of paralysed mice increased. EMC virus in abundant amounts could be isolated from the pancreas and heart of all virus-inoculated mice, including the non-diabetic nude mice. Antibodies against EMC virus were found in all groups of virus-inoculated mice, although only in small amounts in nude and immunosuppressed normal mice. Histological examination revealed no significant differences between the islets of Langerhans of the experimental mice, diabetic as well as non-diabetic, and the control mice with respect to lymphocytic infiltration. It is concluded that the thymus-dependent immune system seems to be of decisive importance for the development of diabetes in this virus model.

Animals↗
PubMed1983

T lymphocyte subsets in patients with newly diagnosed type 1 (insulin-dependent) diabetes: a prospective study.

T lymphocyte subsets in peripheral blood from 11 newly diagnosed Type 1 (insulin-dependent) diabetic patients were studied prospectively at three time intervals: as soon as possible after diagnosis, 3 weeks and 5 months later. Lymphocytes were marked with monoclonal OKT antibodies and examined in a fluorescence-activated cell sorter. The percentage of T lymphocytes (OKT3) did not change significantly at the three study times. The percentage of helper/inducer T cells (OKT4) was high the first week after diagnosis, but decreased at the 5-month examination (p less than 0.05). The percentage of suppressor/cytotoxic T cells (OKT8) was low at diagnosis but increased at 3 weeks (p less than 0.02) and 5 months (p less than 0.01). The ratio OKT4/OKT8 lymphocytes was 2.28 at diagnosis, decreasing to 1.77 at 3 weeks and 1.87 at 5 months, compared with 1.46 for 16 age-matched control subjects. There was no significant change in the absolute number of lymphocytes. It is concluded that the distribution of T cell subsets was abnormal at the time of diagnosis, but changed towards normal within a few weeks, after which there was no significant change at 5 months. It is as yet unknown whether the high proportion of helper/inducer T cells and/or the low percentage of suppressor/cytotoxic T cells at diagnosis favour immune reactions involved in the pathogenesis of Type 1 diabetes.

Adolescent↗
PubMed1983

Alterations of peripheral T-lymphocyte subpopulations in patients with insulin-dependent (type 1) diabetes mellitus.

Subpopulations of peripheral T-lymphocytes were studied in two groups of patients with insulin-dependent diabetes mellitus (IDDM): eleven newly diagnosed diabetics and twenty-one patients having diabetes of long duration (13 +/- 1 yr). Monoclonal antibodies to the surface antigens of helper (OKT 4) and suppressor (OKT 8) T-cell subsets and to a common T-cell antigen (OKT 3) were used. The percentage of suppressor T-lymphocytes were found reduced in both the newly diagnosed patients (p less than 0.001) and the patients with long-term IDDM (p less than 0.05) in comparison with 16 age-matched healthy control persons. Furthermore, the newly diagnosed diabetics showed a lower percentage of suppressor T-cells (p less than 0.05) and a higher amount of helper T-cells (p less than 0.01) than the patients with long-term diabetes. Concerning the percentage of the total number of T-cells and the absolute number of lymphocytes, there were no significant differences between the patient groups and the controls. As earlier studies have pointed to the significance of immune reactions in diabetogenesis, a pathogenetic importance of the observed imbalance of subpopulations of T-lymphocytes in IDDM should be considered.

Adult↗
PubMed1983

Plasma from insulin-dependent diabetics inhibits theophylline sensitive T-lymphocytes demonstrated in E-rosette assay.

This study concerns the effect of plasma from patients with insulin-dependent (type 1) diabetes mellitus (IDDM) on the capacity of normal donor lymphocytes to form rosettes with sheep erythrocytes. Parallel incubations were made of normal allogeneic peripheral lymphocytes with plasma from patients with IDDM and from normal donors. Lymphocytes incubated with plasma from 16 patients with newly diagnosed IDDM displayed a mean rosette formation percentage of 48 +/- 2, but 54 +/- 1 when incubated with control plasma (p less than 0.01). Repeated study in the same patients in the remission period gave similar findings; 46 +/- 2 and 53 +/- 2 (p less than 0.01) respectively. After fractionation of the donor lymphocytes, the reduced rosette formation percentage, after incubation with plasma from the diabetics, was found to be within the theophylline sensitive fraction of the lymphocytes, while the rosette formation percentage in the theophylline resistant fraction was normal. The reduction in rosette formation capacity at the time of diagnosis seemed to be independent of the tissue type of the patient. No relationships were apparent between rosette formation percentages and C-peptide, blood glucose values or glucosuria, neither at time of diagnosis nor in the remission period. The glycaemic control was found to be of no significance in rosette formation percentages in a triple study of 7 patients; first badly controlled, then very well controlled, and, finally again poorly controlled, though without severe ketoacidosis. The theophylline sensitive fraction of T-lymphocytes has been assumed to include suppressor T-cells. It is not known at present whether the described inhibition of these lymphocytes is of any pathogenetic significance.

Adult↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1981

A model for the study of autoimmune diseases applied to pemphigus: transplants of human oral mucosa to athymic nude mice binds pemphigus antibodies in vivo.

The present paper describes a new in vivo method to study the action of pemphigus antibodies against human tissue. Oral mucosal biopsies from healthy donors were transplanted to athymic nude mice, which, a week later, were injected with serum from pemphigus patients. From 1 to 5 days after the injection the epithelial transplants were removed and preparations were studied by immunofluorescence microscopy. Pemphigus antibodies were demonstrated in preparations from each of 23 mice which had received pemphigus serum, but in none of 6 which had received control serum. Transplants from about 2/3 of the experimental mice showed intercellular edema of the basal layers of the epithelium and in transplants from 3 mice supra-basilar splitting of the epithelium was found. None of these changes was seen in the control mice. Passive transfer of human serum or lymphocytes to nude mice transplanted with human tissue may be use in future studies of autoimmune diseases, including pemphigus.

Adult↗
PubMed1980

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↗
PubMed1978

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↗