Search PubMed⌕ Search

Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 271 records · Page 15Linked to original sources
PubMed1988

[Production and use of monoclonal glucagon and insulin antibodies--reduction of pancreatic insulin in rats by treatment with complete Freund's adjuvant].

Murine monoclonal antibodies against glucagon and insulin were generated by somatic cell hybridization and partially characterized. The monoclonal glucagon antibody K79bB10 exhibited no cross-reaction with gut glucagon. This antibody and the insulin antibody K36aC10 were found of very high concentration in ascites. An ascites dilution of 1:5,000 was used for immunohistochemical staining of insulin and glucagon on Bouin-fixed pancreatic tissue sections. By indirect immunofluorescence technique we could demonstrate a reduction of pancreatic insulin in Lewis rats after treatment with complete Freund's adjuvant. The glucagon staining was not altered. The results were confirmed by radioimmunoassay analysis of pancreatic insulin and glucagon content.

Animals↗
PubMed1988

[Extracorporeal shockwave lithotripsy in the treatment of urolithiasis--experiences from a center with the Piezolith 2200 and HM3 lithotriptors].

The Piezolith 2200 allows not only a qualitatively identical treatment of urolithiasis like the HM-Dornier systems or the Siemens Lithostar, but the application of lithotriptable urinary calculi could be extended to cardiac risk patients, to patients with skeletal deformities and to those with unusual body height and weight. As the piezolithotripsy does not cause pain, treatment is possible without anaesthesia or analgesia. Combined with internal ureteral stenting by self-retaining double-J-ureteral catheter also calculi with larger stone masses can be treated advantageously by exclusive piezolithotripsy as monotherapy. Multiple treatments by the piezolithotriptor are possible because of good focussing of the shock waves and the smaller parenchymal alteration. Lithotripsy of ureteral calculi is performed in the upper and lower part of the ureter. In small calculi the retrograde introduction of an ureteral catheter armed with an "ultrasound mirror" is necessary.

Combined Modality Therapy↗
PubMed1987

Treatment of children with neurogenic sarcoma. Experience at the Children's Hospital of Philadelphia, 1958-1984.

Twenty-four children aged 3 months to 18 years (median, 12 years) were treated for neurogenic sarcoma at the Children's Hospital of Philadelphia Cancer Research Center from 1958 through 1984. Sixteen patients had neurofibromatosis (NF). The tumors arose in an extremity or in the trunk (15 patients), the retroperitoneum-pelvis (6), or other sites (3). Twelve children underwent grossly complete excision of localized sarcoma; of them, five had no known residual tumor and seven had proven microscopic residual disease. Ten of the remaining 12 patients had grossly visible, residual localized disease, and two had lung metastases. After operation, nine were treated on a protocol with local radiation therapy (4000-6000 rad) plus vincristine, actinomycin D, and cyclophosphamide with or without Adriamycin (doxorubicin). The other 15 were treated variably. At 3 years, the proportion of tumor-free survivors was 9 of 24 (37.5%). The significant favorable factors were the initial surgical removal of all gross tumor (9 of 12 with tumor excision were tumor-free survivors at 3 years compared to none of 12 with gross residual sarcoma; P less than 0.01), and a tumor mitotic rate under one per high-power field. No significant correlation was found between tumor-free survival expectancy and age, race, sex, the presence of NF, the site and size of the primary tumor, or use of the chemoradiotherapy regimen. More effective treatment programs are needed for children with neurogenic sarcoma, especially for those with unresectable tumors.

Adolescent↗
PubMed1987

Biochemical, immunohistochemical and ultrastructural studies of the alteration of pancreatic beta cells resulting from the combined effects of complete Freund's adjuvant and non-diabetogenic doses of streptozotocin.

Injection of complete Freund's adjuvant (CFA) 24 h prior to treatment of rats with non-diabetogenic doses of streptozotocin (STZ) produced a reduction in pancreatic insulin content associated with ultrastructural changes and a decrease of the volume density of insulin-immunoreactive cells without affecting other islet cells. After one injection of CFA and STZ, pancreatic insulin content was decreased by 69% (p less than 0.01) within 48-96 h, while plasma glucose concentrations were not changed. The volume density of beta cells in pancreata of these rats was reduced by 40% (p less than 0.01) compared with citrate-saline treated control rats. No significant lymphocytic infiltration was detectable in islets, but the exocrine pancreas exhibited inflammatory lesions. Degranulation and vacuolation was evident by ultrastructural analysis. Following administration of CFA or STZ alone, pancreatic insulin content was insignificantly reduced, and major histopathological changes in pancreatic islets were apparently absent. These results support the hypothesis that activation of the immune system by CFA allows an anti-beta cell reaction to develop following exposure to the beta cell toxic agent STZ.

Animals↗
PubMed1987

Genetic control of diabetes induction by complete Freund's adjuvant combined with subdiabetogenic doses of streptozotocin in Lewis rats--evidence for transient cytotoxicity against beta cells.

The non-specific activation of the immune system by administration of complete Freund's adjuvant (CFA) was examined in two congenic Lewis rat strains LEW. 1A (RT1a) and LEW. 1W (RT1u) as a possible mean of amplification of the specific immune response, directed to pancreatic beta cells induced by multiple non-diabetogenic injections of streptozotocin (STZ). Rats were given intraperitoneally 0.5 ml CFA and 1 day later 25 mg/kg body weight STZ. This combined treatment was repeated twice at weekly intervals. Control groups received vehicle, STZ or CFA only with the same doses and at the same times. Only CFA/STZ-treated rats developed a persisting hyperglycaemia (greater than 15 mmol/l glucose) namely 3/18 (17%) LEW. 1W and 47/76 (62%) LEW. 1A rats. The pancreatic insulin content in these hyperglycaemic rats was reduced by 96.6% in LEW. 1A rats and by 93% in LEW. 1W rats measured 8 weeks after the last CFA/STZ treatment. The response to CFA indicated by an increase of number of peripheral leucocytes and relative spleen weight gain at 7 days after CFA administration, was higher in LEW. 1A rats compared with those of LEW. 1W rats. Spleen cells harvested 72 h/48 h after the first and second CFA/STZ administration showed a cytotoxic reaction to isolated syngeneic islets as measured by 51Cr-release in vitro. Control rats receiving vehicle, STZ or CFA only showed no cellular anti-islet cytotoxicity. The anti-islet cytotoxicity of spleen cells was only transient and disappeared after the third CFA/STZ administration. Anti-islet cytotoxic antibodies were not detectable in this short-term study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Generation and partial characterization of monoclonal antibodies reactive with islet cell antigens.

Islet cell antibodies have been detected in more than 60% of newly diagnosed type I diabetics. Their pathogenetic role is still unclear. We have generated monoclonal antibodies (mc-ab) reactive with islet cell antigens by fusing mouse myeloma cells with spleen cells from Balb/c mice immunized with pancreatic islet cells. Hybridomas producing islet cell surface antibodies (ICSA) were detected by indirect immunofluorescence on viable cells from rat islets or rat insulinoma. Cytoplasmic islet cell antibodies (ICA) were detected by indirect immunofluorescence on Bouin-fixed sections of mouse pancreas. The ICSA- and/or ICA-producing hybridomas were cloned twice by limiting dilution. This paper describes six different mc-ab. All hybrid cell lines obtained produced IgM antibodies. Four of them mediate complement-dependent cytotoxicity to viable rat islet cells. In the present study the heterogeneity of circulating ICSA is demonstrated. Also, a monoclonal beta cell surface autoantibody K56aF3 was produced by fusion of spleen cells from a mouse treated with sub-diabetogenic doses of streptozotocin in combination with complete Freund's adjuvant. It was cytotoxic against islet cells up to a dilution of 1:1,000 and it could inhibit the insulin secretion from neonatal rat islets cultured in RPMI 1640 as stimulated by glucose or by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine common with glucose. The latter effect was reversible as indicated by the recovery of insulin secretion in a subsequent culture period without mc-ab. These results suggest that circulating ICSA in type I diabetics may alter beta cell function and thereby contribute to the pathogenesis of type I diabetes.

Animals↗
PubMed1987

Measurement of insulin in human sera using a new RIA kit. 1. Insulin determination in the absence of insulin antibodies--conventional assay and micro modification.

A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 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 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 +/- 2.0% (n = 38) and 100.1 +/- 1.9% (n = 42), respectively. In addition to human insulin, porcine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40% on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated.

Humans↗
PubMed1987

Measurement of insulin in human sera using a new RIA kit. 2. Determination of free and total insulin--correlations to insulin antibody levels.

Using the micro-scale modification of a newly developed RIA kit for insulin, we established methods for the determination of free and total insulin in serum of insulin-treated diabetics. Precipitation with polyethylene glycol 6000 or acid alcohol extraction of sera was carried out to remove or to dissociate antibody-bound insulin. Both assays permit precise and accurate measurement of either serum insulin fraction. In 50 diabetic sera with tracer insulin binding of 0-97%, free (after equilibration of the sera at 37 degrees C) and total insulin levels as well as insulin antibody binding parameters were determined. There was a good correlation of free to total insulin levels with maximally 10-fold higher values of total insulin. Both free and total insulin were found to be correlated with the ability of the serum to bind insulin. In detail, binding affinities (i.e. the reciprocal of equilibrium dissociation constants) and binding site concentrations were evaluated which were shown to be positively correlated with free and total insulin levels as well. From these data we conclude that insulin antibodies in the serum may accumulate therapeutic insulin and function as a depot for delivering insulin in insulinopenic episodes (Keilacker et al., 1982 and 1986).

Diabetes Mellitus, Type 1↗
PubMed1987

Therapeutic response to progabide in neuroleptic- and L-dopa-induced dyskinesias.

The results of two trials conducted in human dyskinesia with progabide, a specific gamma-aminobutyric acid (GABA) receptor agonist, are reviewed. In one trial, 13 parkinsonian patients with L-DOPA-induced dyskinesia (LDD) and "on-off" fluctuations were included in a double-blind controlled trial progabide versus placebo. No change was observed during this trial in the severity of dyskinesia on progabide treatment but the drug significantly extended the "on" period as compared with placebo. In the second trial, 20 patients with neuroleptic-induced dyskinesia (TD) entered an open dose ranging trial with progabide. Fourteen of the 16 patients who completed the trial had a good-to-excellent therapeutic response. According to these results, progabide does not seem to have the same therapeutic benefit in LDD as TD. These data suggest that the hypothesis of a dopaminergic supersensitivity as a similar pathogenic substrate for both clinical conditions should be reconsidered. If this hypothesis remains the most consistent to explain the occurrence of LDD, the therapeutic effect of progabide in TD is an argument for an implication of the GABAergic system in the appearance of TD.

Adult↗
PubMed1987

Clinical trial of Madopar HBS in parkinsonian patients with fluctuating drug response after long-term levodopa therapy.

23 parkinsonian patients, 11 men and 12 women with an average age of 62 +/- 10 years, were recruited for an open substitution study of standard Madopar by Madopar HBS (hydrodynamically balanced system). All patients were presenting fluctuations in efficacy associated or not with abnormal involuntary movements. The patients in this study had been suffering from Parkinson's disease for 16 +/- 6 years and were severely disabled (Hoehn and Yahr grade III-V). The substitution was carried out dose for dose from one day to another. During the first month the dosage titration was aimed at finding the optimal therapeutic effect. After 120 days 13 patients were continuing the treatment while 10 had stopped it because of lack of therapeutic advantage. After 120 days, as compared to the initial state, end-of-dose fluctuations improved by 47%, the parkinsonian symptomatology by 54% and the abnormal involuntary movements improved by 33%. The daily dose of Levodopa had to be increased from 580 +/- 230 to 710 +/- 240 mg. The results obtained were excellent in 5 cases, good in 6 and moderate in 2 cases.

Aged↗
PubMed1987

Destruction of pancreatic beta cells in rats by complete Freund's adjuvant combined with non-diabetogenic doses of streptozotocin.

Non-specific activation of the immune system by complete Freund's adjuvant (CFA) in combination with non-diabetogenic doses of streptozotocin (STZ) was used to study autoimmune reactions against pancreatic islets. Male Lewis RT1a rats received either CFA (0.5 ml/kg) 24 hr prior to the injection of STZ (25 mg/kg), or CFA or STZ alone. The injections of CFA followed by STZ, but not CFA or STZ alone, produced a 69% (p less than 0.01) reduction in pancreatic insulin content associated with necrosis and a decrease of the relative volume density of insulin-immunoreactive cells without affecting other islet cells. Two injections of CFA and STZ induced hyperglycemia. This was associated with a depletion of pancreatic insulin and a significant reduction in the relative volume density of insulin-immunoreactive cells (p less than 0.01) and in the mean islet area (p less than 0.01). On day 20, after treatment with 3 injections of CFA and STZ, the animals developed persistent hyperglycemia. The pancreata in these rats contained less than 12% B-cells, and the insulin content was reduced by 96% (p less than 0.01). The main components of the remaining atrophic islets were glucagon- and somatostatin-immunoreactive cells. No significant lymphocytic infiltration into the islets was detectable, but the exocrine parenchyma exhibited severe inflammatory lesions. Degranulation and vacuolation of B-cells was evident by ultra-structural analysis. The volume densities of insulin containing cells and islet area were not changed after 3 injections of either CFA or STZ alone, although the pancreatic insulin content decreased by 61% (p less than 0.01) and 39% (p less than 0.05), respectively. These treatments did not produce an increase in plasma glucose. The present results demonstrate that CFA in combination with non-diabetogenic doses of the beta cytotoxic agent STZ induces B-cell destruction without significant insulitis. Our observations support the hypothesis that activation of the immune system by CFA allows an anti-B-cell immune reaction to develop following exposure to STZ.

Animals↗
PubMed1987

[Optimal production of murine monoclonal antibodies in ascites of syngeneic mice by a single whole body irradiation].

Hybridoma cells injected intraperitoneally into mice induce formation of ascites tumors producing ascites fluid with high levels of monoclonal antibodies. Several parameters affect the growth of the immunoglobulin-producing tumors in vivo. In the present study the average ascites tumor formation rate of 10 different hybridomas could be increased from 32% (n = 338 mice) to 77% (n = 112 mice) by only one whole body irradiation of paraffin-pretreated-Balb/c mice. Production of monoclonal antibodies was better in males because significantly (p less than 0.01) increased volume of ascites fluid. From the increased tumor formation rate in irradiated mice it is suggested that in non-irradiated recipients the tumor growth rate was lowered by immunological reactions against hybridoma cells provoked by cell surface neoantigens revealed by cell fusion and/or tumor-associated antigens of the myeloma parent cells as well as by altered antigen pattern caused by possible mutations in the myeloma cell line and/or Balb/c/K strain.

Animals↗
PubMed1987

[Nuclear medicine assessment of renal function in beagles before and after extracorporeal percutaneous lithotripsy with a piezoelectric instrument system].

High energy sound pulses which are generated piezoelectrically can be used for extracorporal lithotripsy as an alternative to shock-waves. Since several years a lithotripter for renal concrements based on piezoelectrical oscillators has been developed at the Department for Urology in Homburg/Saar; W.Germany. The present paper describes animal experiments which have been carried out with Beagle-dogs in order to prove that the sound pulses used for lithotripsy do not affect renal function. This function is measured by methods of nuclear medicine (131J-Hippuran Clearance with a modified evaluation). In addition it is evaluated by 111In labelled leucocytes if inflammatory processes in the kidney are suspected. It could be demonstrated that no detremental effects on the kidneys can be detected even with the most sensitive methods of nuclear medicine.

Animals↗
PubMed1987

[Controlled release levodopa-benserazide and changes in efficacy during treatment of Parkinson's disease].

Twenty-five patients, 12 men and 13 women, 42 to 79 years (mean 62) were studied to determine possible interest of a controlled release preparation of L. dopa combined with benserazide. All patients were experiencing fluctuations in efficacy over the last 8 +/- 4 years. Their Parkinson disease was of long duration, (16 +/- 5 years), severe (Hoehn and Yahr's stages III to V) and treated with L. dopa for 12 +/- 4 years. Results were evaluated in the short, medium and long term. During the initial period the new treatment was substituted for previous therapy on a dose for dose basis. Long term (300 days) results showed that "end of dose" fluctuations had been improved in 40 p. 100 of cases without concomitant reduction in therapeutic effects, duration of "ON" periods progressing by 60%. The frequency of drug intake was unaltered but daily dosage could be increased by 30% without increasing severity of abnormal movements to a similar degree. The administration of this new presentation can be recommended, especially when frequent fluctuations compromise long term therapeutic effects.

Adult↗
PubMed1987

Cytotoxic activity of sera from diabetic BB rats against BB rat islet--a functional study.

[3H] leucine incorporation into islet proteins, insulin secretion, hormone content (insulin, glucagon) and DNA synthesis were measured in cultured BB rat islets in a study to compare the effect of freshly prepared BB rat serum obtained from non-diabetic and newly diagnosed diabetic BB rats on islet functions. After exposure of isolated BB rat islet to a mixture of tissue culture medium and BB rat serum (1:1) for 24 hr, islet lysis was induced by 40% of the diabetic BB rat sera whereas the remaining 60% of diabetic BB rat sera tested did not influence islet functions as evidenced by insulin net production, glucose-induced insulin release and DNA synthesis measured in a subsequent culture period in TCM 199, 10 mmol/l glucose supplemented with 10% neonatal calf serum or short-term incubations. After exposure of islets to sera with anti-islet cytotoxicity the majority of islet cells were destroyed as indicated by a drastically reduced [3H] leucine incorporation into islet proteins and by a diminution of hormone and DNA content of islets. This toxicity against islets was overcome by heat treatment (58 degrees C, 30 min) of sera. The results indicate that heat-labile components in certain diabetic sera of BB rats can lyse the majority of islet cells in BB rat islets within 24 hr. Our assay may help to dissociate humoral and cellular components which cause the injury of beta cells and the onset of diabetes in BB rats.

Animals↗