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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BB rat diabetic syndrome has been prevented by various immunosuppressive and reconstitution measures. We observed an effect of multiple blood samplings on diabetes incidence and examined its immunological correlates. Individual litters were divided into two groups; one was sampled and the other was sham sampled as the control group. Sixty-four diabetes-prone and 59 non-diabetes-prone rats were studied. The sampled rats had blood removed at 15 (28% of total blood volume), 30 (30%), 50 (21%), 75 (16%), and 120 days of age. The sham-sampled control rats had blood removed only at 120 days of age. The incidence of diabetes in the sampled group was markedly lower than that of their sham-sampled littermates (22 vs. 78%). This result was associated with a correction of their OX19+ (pan-T-lymphocytes) and W3/25+ (helper/inducer) T-lymphocyte-number defects. An increase in lymphocyte subsets was also seen in the non-diabetes-prone BB rats, significant for all but the OX19+ cells. Islet pathology and pancreatic insulin content were consistent with metabolic outcomes. The effect of blood withdrawal thus has implications for understanding the pathogenesis of both the diabetes syndrome and the lymphopenia of the BB rat. Furthermore, it suggests that a stimulation of lymphopoiesis by blood withdrawal (analogous to that of erythropoiesis) may be a hitherto unrecognized physiological response in normal animals.
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PMID:Diabetes prevention in BB rats by frequent blood withdrawal started at a young age. 296 14

We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.
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PMID:Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. 304 45

Laboratory studies occasionally are necessary for patients who have undergone hypotonic gastrointestinal examinations. To ascertain the effects of glucagon on these patients, we determined the biochemical and hematologic responses to doses of 0.25-2 mg of glucagon in a double-blind crossover study. When glucagon was given intravenously or intramuscularly in increasing doses, serum values for glucose and insulin increased linearly up to 1 mg with a slight decrease at 2 mg. After intravenous and intramuscular administration of glucagon, the white blood cell count and the percentage of neutrophiles and bands increased, and the percentage of lymphocytes decreased. Reports of side effects included one each of nausea and mouth dryness after intravenous glucagon and four reports of nausea and one of mouth dryness after intramuscular glucagon. No changes in the pulse and blood pressure could be attributed to glucagon administration.
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PMID:The laboratory response to glucagon dosages used in gastrointestinal examinations. 306 74

The effects of cyclosporin A (Cs-A) and insulin on peripheral lymphocytes in BB/W rats were studied. The cumulative incidence of overt diabetes in untreated BB/W rats was 72% up to 120 days of observation, whereas the incidence was 13% in Cs-A-treated rats. Lymphocytopenia, consisting of decreased OX19+ (pan T), W3/25+ (helper/inducer T) and OX8+ (cytotoxic/suppressor T) cells, was present in BB/W rats. Cs-A significantly decreased both the percentage and the absolute number of OX8+, OX6+ (Ia-positive) and OX12+ (B) cells, and augmented the ratio of W3/25+ to OX8+ cells in BB/W rats. On the other hand, insulin injection significantly decreased the percentage of OX6+ cells and the ratio of W3/25+ to OX8+ cells in BB/W rats. Thus, rearrangement of the ratio of helper/inducer T to cytotoxic/suppressor T cells and reduction in the number of Ia antigen-bearing cells could be important for the inhibitory effects of diabetes in BB/W rats upon treatment with Cs-A or insulin.
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PMID:Effects of cyclosporin A and insulin on peripheral lymphocytes in BB/W rats. 306 53

Diabetes-prone Bio-breeding/Worcester (DP) rats exhibit a severe T cell lymphopenia and autoimmune pancreatic insulitis. The present results indicate that the T cell lymphopenia is due in large part, if not entirely, to the absence of the RT-6+ peripheral T cell subset, which includes members of both the helper/inducer (W3/25) and suppressor/cytotoxic (OX 8) antigenic phenotypes. Delineation of the causal mechanism(s) for the selective absence of RT-6+ T cells in DP rats may provide important insights into the cellular basis of the insulin-dependent diabetes mellitus syndrome in these animals.
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PMID:Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. 307 5

Spontaneous diabetes was fully prevented in 65 BB/hooded (BB/h) highly diabetes-prone hybrid rats that were given five intraperitoneal injections (25 to 30 x 10(6) cells/injection) of fresh splenocytes or concanavalin A (ConA)-activated cultured splenocytes (blasts) from the diabetes-free Wistar-Furth or Long-Evans strains during the first 2 postnatal wk. Rats remained under observation for up to the age of 180-200 days. Of 70 littermate controls that received no cell injections, 63 developed overt diabetes before the age of 180 days. One intraperitoneal injection (25 x 10(6) cells) of splenocytes or blasts given during the first 36 h after birth was not as effective as multiple injections in preventing overt diabetes. Mild insulitis was present in 4 of 59 "protected" rats; small, discrete mononuclear infiltrates in periductular connective tissue and/or between pancreatic acini were observed in 27. Nondiabetic BB/h rats that were protected with splenocytes or blasts from diabetes-free strains had the same degree of lymphopenia in peripheral blood and spleen as age-matched, insulin-treated diabetic BB/h rats, but the level of islet cell surface antibodies in their serum was significantly lower. The same neonatal injections that protected rats from the development of spontaneous diabetes were completely ineffective in preventing the adoptive transfer of diabetes later in life by the injection of blasts from acutely diabetic BB/h rats.
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PMID:Prevention of spontaneous but not of adoptively transferred diabetes by injection of neonatal BB/hooded hybrid rats with splenocytes or concanavalin A blasts from diabetes-free strains. 339 42

We have studied the occurrence of two phenotypic components (pancreatic lymphocytic infiltration [PLI] of the pancreas and T lymphocytopenia) of the spontaneous insulin-dependent diabetic syndrome (IDDM) in the progeny of hybrids obtained by crossing BB diabetic rats with rats of inbred strains differing from the BB rat at the major histocompatibility complex, RT1. Both PLI and T lymphopenia were seen in animals with all three possible genotypes in both (BUF x BB) and (LEW x BB) lines. PLI was seen in all IDDM animals. T lymphopenia was strongly associated with overt IDDM in both lines (chi 2 = 22.28, p = 0.00002 and chi 2 = 19.28, p less than 0.00001). In addition, T lymphopenia was associated with PLI with and without IDDM in both lines (chi 2 = 8.32, p = 0.0039 an chi 2 = 3.95, p = 0.0467). Not all animals exhibiting PLI without overt IDDM had depressed T cells. Not all animals with T lymphopenia had PLI with or without IDDM. In both lines, the overt IDDM occurred only in animals with at least one RT1 u haplotype derived from the BB rat, confirming our previously reported association of IDDM and RT1. We interpret this evidence to suggest that the overt IDDM syndrome requires one MHC-linked gene and at least two non-MHC-linked genes, which determine susceptibility to PLI and to circulating T lymphocyte depression.
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PMID:Spontaneous diabetes mellitus syndrome in the rat. II. T lymphopenia and its association with clinical disease and pancreatic lymphocytic infiltration. 633 14

The BB rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) or an insulin-dependent diabetic (IDDM) syndrome. Passive transfer of insulitis from newly detected diabetic BB rats to nude mice has been achieved by intraperitoneal or intravenous injection(s) of blood and spleen lymphocytes. After a single injection of cells, 37% of the mice (n = 72) showed insulitis with a mean intensity of 1.9 +/- 0.3 (on a scale of 0 to 3). After three successive injections, 58% of the recipient mice (n = 12) showed insulitis with a mean intensity of 2.5 +/- 0.3. Only one of the control mice (n = 45) demonstrated mild insulitis. The small number of affected islets (13% after a single injection, 17% after three injections) probably explains the absence of random or post IP glucose hyperglycemia in the recipient mice. During this study the yield of lymphocytes in diabetic BB rats was found to be consistently lower than in control normal Wistar rats. This lymphopenia was found not only in the blood and the spleen but also in the thymus and the lymph nodes. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis alone or with IGT or IDDM were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed a marked decrease in the proportions of T+ lymphocytes in all tissues whereas the proportion of B(Ia+) lymphocytes was normal in blood, spleen, and thymus but increased in lymph nodes. However, in absolute terms both T+ and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues, except in the thymus was the one that includes helper T lymphocytes. This lymphopenia could be related to the presence of circulating antilymphocyte antibodies. These results strongly support a role for altered immunity in the etiology of the syndrome. If the observed anomalies of lymphocyte numbers and subsets are responsible, then a novel mechanism different from most other "autoimmune" disorders must be implicated.
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PMID:Passive transfer of insulitis and lymphopenia in the BB rat. 634 96

Insulin role in regulating the immunocompetent tissue structure was studied on experimental rats with alloxan diabetes. Tendency to a decrease in the mesenteric lymph node cortical area, accompanied by a fall in the small lymphocyte number, was observed. The lymphatic follicle area markedly diminished. The small lymphocyte and reticular cell content among cellular elements of the clear centers significantly augmented, whereas mitosis number and the percentage of mean and large lymphocytes decreased. Billroth's strand area diminished by one-third comparatively to that of the control. Simultaneously their number of plasma cells and small lymphocytes lowered. Therefore, alloxan diabetes is accompanied by a fall in the parameters of the thymus-dependent structural components of the mesenterial lymph nodes. Insulin deficit induces a decrease in the number of lymphocytes, capable of proliferation and diminishes their mitotic activity.
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PMID:[Reactivity of the lymph nodes of the root of the mesentery in the small intestine of rats with alloxan diabetes]. 634 19

Anti-islet immune reactions were studied in vitro in genetically diabetic homozygote C57BL/KsJ db/db mice, using murine islet cells as a target. Spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T-cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Anti-islet complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were also found in the sera of these mice. This anti-islet immunity was detectable as early as the tenth day of life and lasted throughout the entire life span of the animals. A significant lymphopenia was detected in thymus and spleen cell populations. None of these anomalies was found in control heterozygote mice. Thymic function was explored in the same mice by evaluating their serum thymic factor (FTS) levels using a rosette assay. The age-dependent decline of FTS levels was significantly accelerated in diabetic mice as compared with heterozygous littermates. Furthermore, FTS inhibitory immunoglobulins were detected in db/db mouse sera, which inactivated in vitro the biologic potency of synthetic FTS. Histologically, the thymus displayed an accelerated involution. It was shown by indirect immunofluorescence using anti-FTS monoclonal antibodies that the number of FTS+ cells was reduced in db/db mouse thymuses. Histologic study of the islets of Langerhans showed early signs of beta-cell hyperactivity and hypertrophy, followed by beta-cell rarefaction and profound dislocation of islet architecture. Insulitis was not detected.
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PMID:Anti-islet immunity and thymic dysfunction in the mutant diabetic C57BL/KsJ db/db mouse. 635 3


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