In 29 out of 30 type I diabetic patients the peripheral blood lymphocytes induced an insulin release from isolated rat islets which was regarded as a cytotoxic effect, i.e. a model of beta cell destruction in diabetes mellitus. In 11 out of 12 cases, this effect was inhibited by the in-vitro addition of lymphocytes from healthy probands. Thus the activation of cytotoxic T-cells demonstrated by this observation might be the consequence of a defect in suppressor cell function. Consequently, the transfusion in vivo of lymphocytes from healthy probands strongly reduced the cytotoxic reaction of the lymphocytes from newly diagnosed diabetic recipients in vitro.

Adolescent↗

PubMed1987

A follow-up study of cell-mediated cytotoxicity and beta cell function in type I diabetes.

In 20 patients with a newly diagnosed type I diabetes mellitus a cytotoxic effect of blood lymphocytes against beta cells of the pancreas of neonatal rats could be demonstrated. This effect remained nearly unchanged during the first 12 months of control. During the course up to 18 months, the cytotoxicity decreased significantly. After stimulation with glucose and glucagon, a C-peptide secretion was demonstrated in all patients during the first 12 months but it decreased thereafter. The follow-up study showed cell-mediated immune reactions against beta cells in type I diabetics as long as the existence of beta cells can be assumed on the basis of functional tests. Thus the immune process seems to depend on the presence of the specific antigen.

Adolescent↗

PubMed1987

Electron microscopical investigations on lymphocyte cytotoxicity against beta-cells in recent onset IDDM.

The effect of lymphocytes from patients with newly diagnosed insulin dependent diabetes on isolated rat or human islets during a 20 h in vitro incubation was investigated by morphological and biochemical methods. All stages of target cell reaction of lymphocytes against beta-cells were observed. Cytoplasmic projections towards and contacts with beta-cells, circumscribed lysis of the outer cell membrane at the contact side and complete lysis of beta-cells were seen. Such findings could not be registered with alpha- or other non beta-cells and in control experiments using lymphocytes from healthy persons. In some cases the lymphocytes were phenotyped using monoclonal antibodies by the indirect immuno-gold technique. It could be demonstrated that lymphocytes in contact with necrotic beta-cells were of the CD8+ve subset. In addition the morphological investigations were supplemented by quantitative biochemical studies measuring the non-secretory insulin release ("cytotoxic" release) from islets into the culture medium and their ability to respond to a consecutive stimulation by arginin with insulin and glucagon secretion. The mean cytotoxic insulin release was 11.3 +/- 1.5 ng/islet/20 h (n = 25) in the diabetic group versus 0.56 +/- 0.15 ng/islet/20 h (n = 15) in the control subjects (alpha less than 0.001). Functional testing of the islets following incubation with lymphocytes from diabetic patients showed diminished insulin (58.6 +/- 5.1%, n = 18, alpha less than 0.001) and unchanged glucagon response (103.0 +/- 3.4%, n = 10, n.s.) when compared with untreated islets (= 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique.

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases. We would conclude that it is not possible to recognize different lymphocyte subsets based only on their ultrastructure.

Antibodies, Monoclonal↗

PubMed1986

Cell-mediated immune reactions against B cells and defect of suppressor cell activity in type 1 (insulin-dependent) diabetes mellitus.

A cytotoxic effect of peripheral blood mononuclear cells from 22 out of 23 newly diagnosed Type 1 (insulin-dependent) diabetic patients against B cells of isolated rat islets was demonstrated. The addition of peripheral blood mononuclear cells from healthy subjects reduced the cytotoxic effect in 9 out of 10 patients. The addition of peripheral blood mononuclear cells from other diabetic patients was without significant effect in 14 out of 16 cases. The results indicate functional abnormalities of peripheral blood mononuclear cells in newly diagnosed Type 1 diabetes. Beside cytotoxic effects against B cells, a defect in the suppressor function seems to exist. The activation of T-lymphocytes might be a consequence of such a defect.

Adolescent↗

PubMed1986

Specific immunotherapy in insulin-dependent diabetes mellitus (preliminary report).

In 7 patients with newly diagnosed insulin-dependent diabetes mellitus a cytotoxic effect of blood lymphocytes against B-cells could be demonstrated by incubation of isolated rat islets with the lymphocytes. The addition of lymphocytes from healthy persons significantly reduced this effect in vitro. The transfusion of 1.9 X 10(9) - 1.5 X 10(10) lymphocytes from the parents to the patients produced a significant decrease of the cytotoxic effect of the lymphocytes from the patients. This effect could be demonstrated during the preliminary control period up to 12 weeks.

Adolescent↗

PubMed1984

[The effect of cisplatin on the healing of intestinal anastomosis in the rat. Microangiography and light microscopy studies].

The influence of a single dose cisplatin on wound healing of enterostomies in rats was investigated by measurement of the wound-breaking strength, microangiographically and histologically. Cisplatin (5 mg/kg body weight) was given on day-1 or day-5 preoperatively. Cisplatin led to a significant reduction of the wound-breaking strength, mostly marked on day +14 after operation. The reasons are: a reduced induction of connective tissue proliferation; an inhibition of proliferation of fibroblasts and endothelial cells, and a retardation of vessel proliferation.

Animals↗

PubMed1982

Portal hypertension: American Academy of Pediatrics Surgical Section survey--1981.

Hepatic (cirrhosis) accounts for a higher percentage of portal hypertension than extrahepatic portal vein obstruction. Some patients with extrahepatic portal hypertension (portal vein obstruction) have a more favorable clinical status. Nonoperative management (balloon tamponade, vasopressin) will usually succeed in controlling bleeding (both groups). Most patients can be stabilized before surgical procedure. Results of devascularization procedures are encouraging. Central splenorenal shunt was most commonly employed (both groups). The Warren shunt is gaining popularity. There are no clear advantages of any particular method of portosystemic shunting in either group. The results of shunt therapy in cirrhotic patients are comparable to those observed in patients with extrahepatic portal hypertension.

Arteriovenous Shunt, Surgical↗

PubMed1975

[Effect of reserpine on the potency of alpha receptor blockers].

The influence of rather low doses of reserpine (0.125--2.0 mg/kg) on the pressor effect of noradrenaline (NA) was studied in pithed rats. In addition it was investigated whether the blocking activity of alpha-sympathicolytic agents is influenced by pretreatment with reserpine. 24 h after injection of these doses of reserpine this drug only increased the pressor effect of lower doses of NA without shifting the dose-response curve to the left. As a rule in rats pretreated with reserpine the affinity of alpha-blocking agents (derivatives of phenylethylamine and phenoxyethylamine) to alpha-adrenoceptors is not considerably altered. Only two phenylethylamine derivates substituted with a p-hydroxy group possessed considerably higher blocking activity in reserpine pretreated animals than in rats not pretreated. The increase in sensitivity of blood vessels against low doses of NA (250 pg and 1 ng) observed in rats pretreated with reserpine is abolished even by alpha-blocking substances with low affinity to alpha-adrenoceptors.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Effect of Tenidap, a novel anti-inflammatory compound on islet lymphocytic infiltration and diabetes incidence in the non obese diabetic (NOD) mouse.

Tenidap, a novel compound inhibiting cyclooxygenase and lipoxygenase, also possessing an inhibitory effect on interleukin-1 secretion by in vitro activated macrophages, has been administered to the non obese diabetic (NOD) mouse to evaluate its action on the induction and progression of insulitis and the diabetes incidence. Animals were allocated to three groups (group A: control group; group B: 12 mg/kg/day Tenidap; group C: 36 mg/kg/day Tenidap); female animals only were followed up to investigate the effect on diabetes incidence. The administration of Tenidap influenced the natural course of insulitis in male NOD mice; thus, at 60 and 100 days of age the mean percentage of infiltrated islets was significantly reduced compared to control animals (p less than 0.02). Moreover the severity of lymphocytic infiltration at 60 days of age was reduced in male mice of group B and C compared to control mice (p less than 0.004 and p less than 0.0001, respectively) whereas at 100 days of age this difference was not significant. However the progression towards severe insulitis in male animals receiving Tenidap was halted compared to control animals. Tenidap had also a significant dose dependent effect at 60 days on the severity of lymphocytic infiltration (group B vs. group C, p less than 0.01). By contrast, this agent had no effect on the degree of insulitis and diabetes incidence in female NOD mice. In both sexes at the end of follow-up a significant reduction in body weight was observed in animals of Group C compared to control animals (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗