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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 325 records · Page 18Linked to original sources
PubMed1984

Absence of cytotoxicity of islet cell surface antibodies in vivo despite complement-mediated cytotoxic effects to islet cells in vitro.

Islet cell surface antibodies (ICSA) have been generated to investigate relations between recognition of specific antigens and cytotoxic reactions on pancreatic islet cells. Sera from rabbits which had been directly immunized with islet cells or intact rat islets exhibited positive immunofluorescence with both rat and rabbit pancreatic islet cells. Analysis by SDS polyacrylamide gel electrophoresis and autoradiography of islet cells proteins prelabeled with [35S]methionine revealed that these sera precipitated a specific protein of Mr 40000. Serum from immunized rabbits stimulated 51Cr-release in suspensions of dispersed islet cells prepared from neonatal rats. Absorption to lymphocytes and liver powder removed antibodies that were cytotoxic to lymphocytes but complement-mediated cytotoxicity against islet cells persisted. Circulating ICSA neither in rabbits nor in rats caused changes in blood glucose. Moreover, no major alterations of islet cells in the immunized rabbits were observed upon electron microscopic examination. It is concluded that ICSA are capable of recognizing specific islet cell antigens and thus mediate complement-dependent cytotoxic reactions in vitro, but the mere presence of ICSA is obviously not sufficient to induce diabetes in vivo under the conditions used.

Animals↗
PubMed1984

Autoimmune response directed to pancreatic beta cells in rats induced by combined treatment with low doses of streptozotocin and complete Freund's adjuvant.

Despite the existence of circumstantial evidence, a direct proof of an autoimmune basis for beta cell destruction in human type I diabetes has not yet been obtained. The present study was designed to test on Wistar rats whether a low-dose streptozotocin (SZ) treatment in combination with complete Freund's adjuvant (CFA) could be a useful approach to induce an autoimmune response to beta cells. Rats were weekly injected i.p. either with CFA or with SZ alone or with both CFA and SZ. Only the SZ-CFA-treated rats developed severe hyperglycemia. In these animals the pancreatic insulin content was nearly completely depleted. Only in SZ-CFA-treated rats cytotoxic autoantibodies to islet cells were found. The results show that in this new model of type I diabetes autoimmune reactions are involved in the destruction of beta cells.

Animals↗
PubMed1984

Metabolic and hormonal responses during a glucose controlled insulin infusion (Biostator) in subjects with impaired glucose tolerance.

The short-term effect of the glucose-controlled insulin infusion system (GCIIS) Biostator on metabolic and hormonal responses was studied in 10 non-obese subjects with glucose intolerance and insulin low response to glucose. Glucose tolerance characterized by means of a 2 h glucose infusion test (12 mg/kg/min) primed by i.v. injection of 0.33 g glucose/kg body weight was completely normalized by GCIIS. Results provide further support that normalization of glucose tolerance by means of GCIIS is accompanied by peripheral hyperinsulinaemia if compared with 33 non-obese healthy controls. Glucose-induced endogenous insulin secretion (C-peptide) was significantly reduced during the GCIIS study possibly due to inhibition of insulin secretion by exogenous insulin and/or by lower blood glucose concentration after normalization of glucose tolerance. Acute normalization of glucose tolerance in these patients failed to alter pancreatic glucagon, NEFA and glycerol responses but normalized paradoxical growth hormone response to glucose.

Adult↗
PubMed1984

Islet cell cytoplasmic and surface antibodies' prevalence and beta cell specificity of islet cell surface antibodies in some subjects with putative islet cell autoimmunity.

In human sera two methods of islet cell cytoplasmic antibody (ICA) detection (on Bouin-fixed or cryostate sections of human pancreas) and the islet cell surface antibody (ICSA) method on isolated rat islet cells were compared. The ICA detection on Bouin-fixed sections was more sensitive than that on cryostate sections. In two groups of subjects with putative islet cell autoimmunity ICA prevalence was higher than ICSA prevalence. However, a weak correlation between both types of antibodies was established. In one group of healthy subjects with cytotoxic serum against rat beta cells a high prevalence of ICSA was found, whereas none of them had ICA. Defined on the basis of a positive immunofluorescence on rat islet cells, ICSA positive sera of newly diagnosed IDDM patients reacted to a significantly higher percentage with beta cells than did normal controls. In conclusion, of all methods compared ICA detection on Bouin-fixed pancreas sections seems to be the most suitable method for the detection of an islet cell autoimmunity.

Acetates↗
PubMed1984

Glucagon antibodies alter Langerhans' islets.

The passive transfer of rabbit anti-glucagon antibodies into mice induces periinsular and intrainsular inflammation and hyperplasia of alpha cells. Active immunization of rabbits with heterologous glucagon induces alpha cell hyperplasia.

Animals↗
PubMed1984

Monoclonal antibodies to human insulin and their antigen binding behaviour.

Mouse monoclonal antibodies were raised against human insulin by somatic cell hybridization using the mouse myeloma line P3-X63-Ag8. Five cell lines were grown as ascites producing tumors. Insulin binding data were determined from six monoclonal antibodies by Scatchard analysis. Each anti-insulin hybridoma antibody gave a straight-line Scatchard plot confirming the homogeneity of their binding sites and their monoclonality. The equilibrium dissociation constants ranged from 2.20 X 10(-8) to 4.48 X 10(-10) mol/l. We could demonstrate positive as well as negative cooperativity of monoclonal insulin antibodies by performing insulin binding studies with defined mixtures of two different anti-insulin hybridoma antibodies.

Animals↗
PubMed1984

[Immunoreactive insulin in the CNS of human fetuses and newborn infants of metabolically healthy and diabetic mothers--an immunohistochemical study].

The cellular localization and regional distribution of "insulin-like immunoreactivity" and "C-peptide immunoreactivity" were studied in brains of fetuses and newborns from normoglycaemic and diabetic mothers using immunohistochemical techniques. It is shown that "insulin-like material" and "C-peptide-like material" occur in the same nerve cells. No differences in regard to the localization of both polypeptides exist between abort material from normoglycaemic and diabetic mothers.

Brain Chemistry↗
PubMed1984

[Acute hypotensive effect of a central dopaminergic agonist, piribedil, administered intravenously in the normotensive human].

Ten normotensive patients including 5 parkinsonian and 5 dystonic patients received 3 mg piribedil intravenously over a 15 min period. This dopamine receptor agonist rapidly induced a fall in blood pressure together with a simultaneous reduction in heart rate and temperature. No change was observed when patients (four) were pretreated with a dopamine receptor blocking agent, haloperidol. It is concluded that acute dopamine receptor stimulation leads to a decrease in blood pressure. The hypotension could be centrally-mediated since the hypothermia, considered to be central in origin, parallels the blood pressure and heart rate changes.

Antihypertensive Agents↗
PubMed1984

A cholinomimetic model of motion sickness and space adaptation syndrome.

The space adaptation syndrome is one of the more vexing problems confronted by our nation's astronauts during their journeys. This syndrome may be a variant of motion sickness, although this possibility has been questioned. Physostigmine, a centrally active cholinesterase inhibitor which increases brain acetylcholine, was found to cause a motion sickness-like syndrome--in psychiatric patients and normals--including nausea, emesis, malaise, dysphoria, increases in serum ACTH, beta-endorphin, cortisol, and prolactin, Neostigmine, a non-centrally acting cholinesterase inhibitor, and saline placebo caused no such effects. The above effects closely parallel those of motion sickness. Thus, the effects of physostigmine may be a convenient model for screening for treatments for motion sickness or space adaptation syndrome, or for predicting who will develop these syndromes.

Adaptation, Physiological↗
PubMed1984

[Surgical therapy of urogenital tuberculosis].

The surgical therapy of genitourinary tuberculosis is important as adjuvant treatment besides an appropriate anti-tuberculous drug therapy. During the years 1966-1983 surgical treatment was necessary in 46.1% (330 cases) of 715 patients. Cases, not treated properly for a long time, still have a high incidence of nephrectomy. Since 1976 more reconstructive operations and partial kidney resections have been carried out, resulting in a 5,6% rate of secondary nephrectomy. In up to 92.3% of the patients with these operations, renal function was not reduced or had improved. In cases with progressive tuberculosis of the upper urinary tract reconstructive surgical treatment is also recommended with good late results.

Adult↗
PubMed1983

Insulin- and glucagonlike peptides in the brain.

The cellular localization and regional distribution of insulin- and glucagonlike substance, C-peptide-like immunoreactivity, thiol:protein disulphide oxidoreductase, TPO (E.C.1.8.4.2.), and insulin/glucagon-specific proteinase, ISP (E.C.3.4.22.-), are studied in the CNS of man, adult and juvenile rats, mice, tortoises, and frogs by use of immunohistochemistry. Furthermore, the content of immunoreactive insulin, glucagon, and C-peptide was estimated in human cadaver brains by radioimmunoassay. It could be shown that insulinlike immunoreactive material is widely distributed in the human brain and the CNS of juvenile rats as well as in mice, whereas in the CNS of adult rats and nonmammalian animals (frogs, tortoises) the polypeptide is restricted to a few nerve cell populations. C-peptide immunoreactivity was demonstrated in human CNS in the same nerve cells as insulin. By use of two different glucagon-antisera it was revealed that gut-type glucagon occurs in many nerve cells of human and mouse brains, as well as in the CNS of juvenile rats. On the other hand, pancreas-type glucagon was less widely distributed in the human brain and nearly not detectable in the CNS of mice and rats. With the exception of neurosecretory nerve cells, there was a high degree of coincidence between the localization of insulin and TPO. The immunoreaction against the ISP antiserum was weak, but correlated well with the distribution of insulin-immunoreactivity. The occurrence of TPO and ISP in the brain demonstrates the ability of nervous tissue to degrade insulin and glucagon. By radioimmunoassay it was established that human brain contains insulin, glucagon and C-peptide at concentrations that exceed blood levels. We conclude from our data that, at least in part, cerebral insulin and glucagon are products of the brain itself.

Animals↗