Skeletal muscle lipoprotein-lipase activity in insulin-dependent diabetic patients with and without albuminuria.

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria.

Estimation of pulmonary diffusion resistance and shunt in an oxygen status model.

A compartment model of the transport of oxygen from the alveoli to the tissues is described. In patients with both pulmonary shunt and alveolar resistance to diffusion of oxygen, the model is used to simulate their response to variations in the inspired oxygen fraction. These simulation results are compared to the responses from a patient with respiratory malfunction, indicating that the method can identify patients where not only a pulmonary shunt but also a high alveolar resistance to diffusion of oxygen is clinically significant.

Nicotinamide prevents interleukin-1 effects on accumulated insulin release and nitric oxide production in rat islets of Langerhans.

Nicotinamide (NA) prevents macrophage- and interleukin-1 (IL-1)-mediated beta-cell damage in vitro as well as diabetes development in animal models of insulin-dependent diabetes mellitus (IDDM). IL-1 beta-mediated inhibition of insulin release and damage to beta-cells are associated with intracellular production of nitric oxide (NO) radicals. Therefore, we studied whether NA prevented IL-1 beta-induced islet NO production, measured as nitrite release from isolated rat islets, and, if so, whether this action was associated with prevention of IL-1 beta-mediated inhibition of insulin release.

Repetitive exposure of pancreatic islets to interleukin-1 beta. An in vitro model of pre-diabetes?

The slowly progressing loss of glucose tolerance over years before clinical onset of Type 1 (insulin-dependent) diabetes mellitus may be due to repetitive immunological attacks on the pancreatic beta-cell mass. Accordingly, we studied the effects of repetitive exposure of isolated rat pancreatic islets to the beta-cytotoxic immune-mediator interleukin-1 beta. Islets were exposed thrice to 60 U/ml of recombinant interleukin-1 beta for 24 hr.

The whole-mount method as a technique for measuring experimental changes in airway goblet cell number.

The whole-mount staining method for mucous membranes was introduced as an experimental technique for measuring goblet cell density and for estimating the degree of goblet cell hyperplasia in the trachea of experimental animals. By this technique it was demonstrated that a single intratracheal instillation of lysed extract from human neutrophilic granulocytes in rats after 3 weeks caused a three-fold increase in the density of tracheal goblet cells as compared to control animals receiving saline. The increase is of 3-6 times greater magnitude than previously reported in similar experiments where the number of goblet cells was calculated from cross sections in a traditional manner.

Neutral red changes arginine-induced glucagon and insulin response in the rat.

Rats were treated with neutral red (amino-dimethyl-amino-toluaminozine hydrochloride, NR) twice weekly, 5 ml/kg b.wt.-1 of a 2% solution, for five weeks in order to investigate damage to pancreatic A-cells.

Genetically determined differences in newborn rat islet sensitivity to interleukin-1 in vitro: no association with the diabetes prone phenotype in the BB-rat.

This study was designed to investigate whether the genetic predisposition to insulin-dependent diabetes mellitus (IDDM) might be caused by an inherited increased sensitivity of the pancreatic B-cells to immune effector molecules e.g. the monokine interleukin 1 (IL-1), which is selectively cytotoxic to B-cells in vitro.

Mechanisms of pancreatic beta-cell destruction in type I diabetes.

The pathogenetic mechanisms leading to beta-cell destruction and insulin-dependent diabetes mellitus (IDDM) are major histocompatibility complex (MHC) nonrestricted and are MHC associated and beta-cell specific. The macrophage peptide hormone interleukin 1 (IL-1) may be the primary MHC-nonrestricted beta-cell-destructive molecule. Beta-Cell death most likely results from free radical induction by IL-1.

Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant.

Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.

Ultrastructural studies of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity.

Previous electron-microscopic studies of isolated islets of Langerhans exposed to the monokine interleukin-1 for 7 days have indicated that interleukin-1 is cytotoxic to all islet cells. To study the time-course and possible cellular specificity of interleukin-1 cytotoxicity to islets exposed to interleukin-1 for short time periods, isolated rat or human islets were incubated with or without 25 U/ml highly purified human interleukin-1 for 24 h. Samples of rat islets were taken after 5 min, 30 min, 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24 h and samples of human islets after 5 min, 30 min and 24 h of incubation and examined by electron microscopy in a blinded fashion.

Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans.

Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet contents of insulin and glucagon in a dose-dependent manner. A maximal effect on islet function was obtained with supernatant concentrations down to 5%. Supernatants of mononuclear cells stimulated with tuberculin were more potent than supernatants produced by lectin stimulation.

Irradiation protects against pancreatic islet degeneration and hyperglycaemia following streptozotocin treatment of mice.

Five daily injections of streptozotocin (40 mg/kg) produce islet inflammation, necrosis of pancreatic B cells and hyperglycaemia in the mouse. Anti-pancreatic autoimmunity has been suggested as part of the cause of these events. We have studied the possible effect of total-body irradiation in long-term studies (246 days) and report here that insulitis, islet necrosis and insulin depletion are reduced after irradiation.

Absence of H-2 genetic influence on streptozotocin-induced diabetes in mice.

Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male x C3H/Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of pancreatic B cells. Insulitis was found from days 9-25 after the first injection of streptozotocin.

Direct streptozotocin toxicity on dispersed mouse islet cells determined by [51]Cr-release.

Dispersed islet cells were prepared from collagenase-isolated lean mouse pancreatic islets by Dispase-II and subsequent mechanical treatment in calcium depleted media. An average yield of 600 cells per islet was obtained, 84% of the cells being beta-cells. Cells were incubated with radioactive chromium as a marker of cell viability.

Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy.

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more.

The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice.

Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced.

Unique eosinophil granules in a case of T-cell lymphoma.

A 41-year-old man developed intense itching without visible cutaneous changes, epigastric pressure pain, and a slight intolerance to alcohol. He was found to have persistent blood eosinophilia. The eosinophil granulocytes were of abnormal appearance in the light microscope: larger than normal, the nuclei were multilobulated (4-6 lobes), the cytoplasm contained atypical, large granules, ample glycogen, and up to 12 vacuoles.

A case of T-cell lymphoma with Sézary cells in the blood and bone marrow accompanied by peripheral T and B lymphocytosis.

A case of T-cell lymphoma occurred in a man, aged 66, whose symptoms started as itching and the appearance of 1-2 cm indurated plaques with central pustules on the skin of the trunk and face. A few months later generalized lymphomas and splenomegaly were present. Investigations of the lymphocytic subpopulations in situ in fresh frozen sections of lymphomas and skin showed only T cells.

Morphology of experimental, organ-specific insulitis of the mouse pancreas.

The morphologic and metabolic effect of a single intracutaneous injection of homologous endocrine pancreas in Freund's complete adjuvant (CFA) was studied in 100 mice and compared with control groups which had been (1) immunized with murine insulin in CFA, (2) injected with CFA alone, or had (3) received no treatment. There were no differences between the control groups as regards the morphology of the pancreatic islets, and the glucose tolerance was normal. Mice immunized with islet homogenate exhibited morphological changes in the form of degranulation and cytoplasmic disintegration.

Ca-activated ATPase activity in subcellular fractions of mouse pancreatic islets.

Ca-stimulated ATPase activity has been demonstrated in homogenates of mouse pancreatic islets. On subcellular fractionation Ca-ATPase activity was found in secretory granules, mitochondria, and microsomes, but not in the postmicrosomal fractions. Highest specific activity was found in the granules.

Autoimmune insulitis. Pathological findings in experimental animal models and juvenile diabetes mellitus.

Organ-specific, species non-specific anti-pancreatic cellular immunity has been reported as a feature associated with juvenile diabetes of short duration. In order to further elucidate a possible causal relation between autoimmunity and juvenile diabetes morphological studies were made on an autopsy material from 12 juvenile onset diabetics, dying within 1 year after the onset of the disease. Each patient was compared with 2 age and sex matched controls.