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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 307 records · Page 17Linked to original sources
PubMed1985

Inhibition of glucagon release of isolated islets of Langerhans by monoclonal antibodies.

The presence of islet cell cytoplasmic antibodies (ICA) and islet cell surface antibodies (ICSA) at the time of diagnosis of type 1 (insulin-dependent) diabetes mellitus has been taken as evidence that autoimmune mechanisms are involved in the pathogenesis of the disease. The demonstration that ICSA in the presence of complement are preferentially lytic for beta-cells may be important in defining the role of these autoantibodies in the pathogenesis of type 1 diabetes. Because of the polyclonality of the immune response, the ICA and ICSA molecules of diabetic patient vary enormously in their binding parameters. For this reason we have generated monoclonal antibodies (MC-Ab) to islet cell antigens. In this study we investigate the effect of the two MC-Ab K28 A1 and K28 D6 resulted from the same fusion of the P3-X63-Ag8 murine myeloma cell line with the spleen cells of a Balb/c mouse immunized with rat islet cells on the hormone release of isolated rat islet in co-culture with the antibody-secreting hybridomas. The MC-Ab K28 D6 binds to both islet cell cytoplasmic and surface antigens, the K28 A1 is only reactive with cytoplasmic antigens. Surprisingly, in contrast to the monoclonal antibody K28 A1, K28 D6 enhanced the glucagon content and diminished the insulin secretion of the islets. Either the K28 D6 is directed to an epitope occurring on the beta- as well as alpha-cells or the antibody-mediated inhibition of the glucagon release results in a significantly reduced insulin secretion.

Animals↗
PubMed1985

Insulin recovery in pancreas and host organs of islet grafts.

The method of insulin determination is a useful tool for detecting surviving beta cells in the pancreas of diabetic animals and in organs used as sites of islet graft. Therefore, we have studied the insulin recovery in tissue homogenates. The data show that a high recovery rate of insulin (more than 95%) was reached, when the phosphoric acid-alcoholic tissue extract was stored at -20 degrees C and diluted with RIA buffer immediately before radioimmunoassay. When acid-ethanol supernatants were neutralized the recovery rate was diminished to 73.4 +/- 4.0% in pancreas and to 61.0 +/- 6.2% in liver homogenates, respectively. Glucagon was degraded when diluted extracts were stored at -20 degrees C for different periods of time. The diabetogenic action of streptozotocin (STZ) could be demonstrated for doses ranging between 30 and 55 mg/kg body weight. STZ caused a dose-dependent decrease of pancreatic insulin whereas the glucagon content was significantly enhanced in diabetic animals. The glucagon content was not normalized when normoglycemia was achieved by syngeneic islet transplantation. Insulin extracted from spleen used as a site for transplantation of 900 neonatal rat islets showed a high biological variation ranging from 0.7 to 6.4 nmol insulin per spleen, 10-100% of the content of the equivalent number of freshly isolated islets these animals received.

Animals↗
PubMed1985

Differences in molecular heterogeneity of glucagon-like immunoreactivity in plasma and liver metastases of a patient with alpha-cell tumor.

In the present study we characterized and compared the different molecular forms of glucagon-like immunoreactivity in extracts of peripheral plasma and hepatic metastases of a patient with pancreatic alpha-cell tumor. Plasma and tissue extracts were chromatographed on Sephadex G-50 columns. Immunoreactivity in the eluting fractions was assayed with an anti-glucagon antiserum that specifically recognizes the C-terminal region of the pancreas glucagon molecule. Total plasma glucagon-like immunoreactivity prior to surgery was 26.64 nmol/l and consisted of four peaks of immunoreactivity of apparent 9,000 mol wt, 5,800-5,400 mol wt, and 4,000 mol wt. Total glucagon-like immunoreactivity extracted from the hepatic metastasis was 47.41 nmol/g wet weight and eluted as two major peaks of immunoreactivity as follows: peak I, mol wt 3,800, corresponding to "true" 3,500 mol wt glucagon; peak II, mol wt 1,400, probably consisted of glucagon degradation products. The results clearly demonstrated that both plasma and glucagon-like immunoreactivity extracted from hepatic metastases were heterogeneous and comprised species corresponding not only to "true" glucagon but also to higher mol wt forms. The lack of higher mol wt forms of immunoreactivity in the hepatic metastases of the alpha-cell tumor suggests that this metastatic tumor tissue may contain an enzyme capable of converting the higher mol wt forms to smaller glucagon-like components whereas this degradative system seems to be defective in the primary tumor.

Adenoma, Islet Cell↗
PubMed1985

Measurement of plasma canine C-peptide by radioimmunoassay.

A sensitive radioimmunoassay (RIA) for canine C-peptide (CCP) was established using synthetic CCP, a specific antiserum, and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine-T method. Tracer preparations were used for long as 6 weeks after iodination. The standard curve ranges from 0.028 to 3.0 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.3 and 0.8 nmol/l. The average recovery of CCP added to plasma samples was 100.6% (n = 9). Canine insulin, porcine proinsulin, bovine proinsulin, and human C-peptide exhibited no cross-reactivity. The mean fasting plasma CCP concentration was 0.089 +/- 0.021 nmol/l in normal dogs and -0.005 +/- 0.007 nmol/l (mean +/- SEM) in diabetic dogs, respectively.

Animals↗
PubMed1985

Effects of physostigmine on pulse, blood pressure, and serum epinephrine levels.

In this study, the infusion of physostigmine in 14 patients with affective disorder who were pretreated with methscopolamine caused significant and often profound increases in the patients' epinephrine levels, pulse rates, and blood pressure. Since physostigmine is being used experimentally in the treatment of elderly subjects who have Alzheimer's disease, these cardiovascular effects may have clinical importance.

Adult↗
PubMed1985

[Current status and conservative and operative therapy of urogenital tuberculosis].

In each case the primary treatment of tuberculosis is a medicamentous therapy. Using the modern basis medication of isoniazid, rifampicin, ethambutol and streptomycin at present for the normal case the short-term therapy of maximally 12 months made its way. The operative treatment of the urogenital tuberculosis is only a part of the total therapy plan. Among 715 patients nearly half of them had to undergo at least one surgical intervention from 1966 to 1983. The nephrectomy rate of 22.3% is to be classified as high and is conditioned by progressing and extended changes of the kidneys, which are in most cases recognized too late. In 69 patients partial resections of the kidney were performed. Since 1976 the indication for this intervention was in 13 cases made only intraoperatively and at the same this the planned nephropyeloplasty was performed on account of disturbance of the urine flow. Good postoperative results encourage to perform plastic reconstructive measures also in changes of the kidneys of stage III.

Aged↗
PubMed1985

Complement-dependent cytotoxicity of monoclonal antibodies against islet cells.

Mouse monoclonal antibodies producing cell lines were generated against rat and human islet cells by somatic cell hybridization using the mouse myeloma cell line P3-X63-Ag8. Four hybrid cell lines are growing as ascites bearing tumors. All four monoclonal antibodies reacted with cytoplasmic islet cell antigens as detected by the indirect immunofluorescence technique on Bouin-fixed pancreatic sections of Wistar rats. Besides their binding to cytoplasmic antigens three of them also recognized antigens expressed at the islet cell surface. Moreover, two of these three monoclonal antibodies were capable of mediating complement dependent cytotoxicity against rat islet cells as revealed in a 51Cr-release assay.

Animals↗
PubMed1985

[Unilateral atrophic kidney and hypertension--the value of plasma renin determination for assessing the indications for nephrectomy].

In unilateral atrophic kidney and hypertension the nephrectomy is the therapy of choice. The nephrectomy is, however, indicated only then, when a causal pathogenetic connection of atrophic kidney and hypertension is proved. As criterion of the proof of such a connection according to our experiences the side-separated determination of the plasma renin activity in the venous blood of the kidneys stood the test. A renal vein renin quotient greater than 1.5, moreover, permits a rather reliable prognostic evidence concerning the behaviour of the postoperative blood pressure. In 26 out of 31 hypertensive patients with significant renal vein renin quotient who were nephrectomized for a unilateral atrophic kidney could be achieved a normalization of the blood pressure, in the other 5 patients an improvement of the blood pressure.

Adolescent↗
PubMed1985

[Micturition disorder as a sequela of sacral autonomic diabetic neuropathy].

Diabetic neuropathy may manifest itself also in the autonomous nervous system and thus lead to a functional disorder of the urinary bladder. Urodynamic studies carried out in 11 diabetic patients with unclear bladder dysfunction allowed 2 forms of bladder anomalies to be identified: 1. detrusor hyperreflexia, 2. hyporeflexia and areflexia of the detrusor. Whereas hyperreflexia is clinically characterised by signs of motor urgency, hyporeflexia is mainly identifiable by residual urine formation and recurrent infections of the urinary tract. Therapy depends on the type of dysfunction and consists of physiotherapeutic measures, drug therapy and occasionally surgery.

Aged↗
PubMed1985

[Urethral injuries--a retrospective analysis of therapeutic possibilities and late morbidity].

Injuries of the urethra confront traumatologists and urologists with common diagnostic and therapeutic problems. By an early interdisciplinary cooperation life-threatening early complications such as urosepsis, and late complications which are difficult to be corrected such as strictures of the urethra may be prevented and reduced, respectively. The accidental mechanisms and the diagnostic possibilities in injuries of the urethra are explained in detail. In 24 patients with anterior ruptures of the urethra and in 66 patients with posterior injuries of the urethra with the exception of 12 immediate operative reconstructions primarily a suprapubic and transurethral micturition was chosen. The posttraumatic results concerning the rate of stricture, the kind of removal of the stricture, the frequency of incontinence of urine and erectile impotence are analysed.

Humans↗
PubMed1984

Severe hyperglycaemia caused by autoimmunization to beta cells in rats.

The non-specific activation of the immune system by administration of complete Freund's adjuvant was examined in Wistar rats as a possible means of amplification of the specific immune response directed to pancreatic B cells caused by low dose non-diabetogenic multiple injections of streptozotocin. Rats were given intraperitoneally 0.5 ml of complete Freund's adjuvant to induce polyclonal lymphocyte activation and, 1 day later, the animals were given an intraperitoneal injection of 15 mg streptozotocin/kg body weight (group 1). This combined treatment was given twice at weekly intervals. In two further groups, rats were treated with complete Freund's adjuvant alone (group 2) or streptozotocin alone (group 3) with the same doses and at the same times. Only the rats in group 1 developed delayed but severe and persistent hyperglycaemia. In addition, significant complement-dependent cytotoxicity was detected in nine out of 15 rats (60%) in group 1 in islet cells, but not in spleen lymphocytes. The pancreatic insulin content of the rats in group 1 was depleted by up to 3.1 +/- 0.5%. With these experiments, a new animal model for insulin-dependent diabetes is described; complete Freund's adjuvant/streptozotocin diabetes. In many aspects, this model of diabetes parallels the development of insulin-dependent diabetes in man, including the humoral autoimmunity to islet cell antigens.

Animals↗
PubMed1984

Cerebral insulin-like immunoreactivity in rats and mice. Drastic decline during postnatal ontogenesis.

We studied the behavior of the insulin-like immunoreactivity in brains of rats and mice during the first 20 d post natum by immunohistochemistry and radioimmunoassay. It was found that a dramatic decline in the concentration of the peptide, accompanied by a strong reduction of immunoreactive cells, takes place during this period. A possible role of cerebral insulin as a promoter of nerve cell growth and development is briefly discussed.

Aging↗
PubMed1984

Insulin biosynthesis and secretion of isolated pancreatic islets of mice after the administration of anti-insulin serum of guinea pigs.

Comparative studies on the effect of intraperitoneal administration of 0.5 ml anti-insulin serum (AIS) of guinea pig or glucose (2 g/kg body wt) on biosynthesis and secretion of insulin were carried out in C 57 Bl/6 j mice. The islets of Langerhans isolated 1 hr after administration of AIS exhibited significantly increased biosynthesis and secretion of insulin during an incubation in presence of 5 mmol/l glucose. The result suggest that AIS may be a more potential stimulator of beta-cell function than glucose created by the decreased level of free insulin in early period of time following AIS administration.

Animals↗
PubMed1984

[Microsurgery in urology].

The use of microsurgical techniques offers operative perspectives also in urology. Microsurgery is indicated for reconstructive vascular surgery in the kidneys, in cases of erectile impotence, and in high maldescended testicles, for recanalisation of the vas deferens and in early childhood for plasty surgery of malformations of the upper urinary tract and such of the male genitals. Certain indications are presented under reference to own clinical experiences.

Adult↗
PubMed1984

Action of botulinum A toxin and tetanus toxin on synaptic transmission.

Intracellular recordings of the spontaneous activity from mammalian spinal cord neurons in culture demonstrated different sensitivities of excitatory and inhibitory synaptic transmission for the action of tetanus toxin (Tetx) and botulinum toxin type A (Botx). The effects of Tetx and Botx on spontaneous and nerve-evoked transmitter release were compared under identical experimental conditions in experiments on in vitro poisoned mouse diaphragms. At 37 degrees C completely paralyzed endplates are characterized by a very low frequency of spontaneous miniature endplate potentials (m.e.p.p.s) and by a 100% failure to evoke endplate potentials (e.p.p.s) in response to single nerve stimuli. Striking differences in the action of both toxins have been observed when the very low transmitter release probabilities of paralyzed nerve-muscle preparations were increased by tetanic nerve stimulation and/or application of potent K+-channel blockers and/or by reduction of temperature to 25 degrees C. While Botx did not change the short latency between nerve impulse and postsynaptic response, Tetx produced a temporal dispersion of the quantal release suggesting that the toxins act at different sites in the chain of events that result in transmitter release. To find further evidence to support the different actions of the toxins the spontaneous transmitter release was studied in more detail. Tetx blocked preferentially the release of so-called large mode m.e.p.p.s without affecting the frequency of the small mode ones. In contrast, Botx strongly inhibited both the small and large mode m.e.p.p.s.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗