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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 199 records · Page 11Linked to original sources
PubMed1990

The catabolism of endogenous adenine nucleotides in rat liver mitochondria.

The degradation of intramitochondrial adenine nucleotides to nucleosides and bases was investigated by incubating isolated rat liver mitochondria at 37 degrees C under non-phosphorylating conditions in the presence of oligomycin and carboxyatractyloside. Within 30 min the adenine nucleotides were degraded by about 25 per cent. The main products formed were adenosine and inosine the contents of which increased five- to sevenfold. Compartmentation studies revealed that about 50 to 60 per cent of the adenosine formed remained inside the organelles whereas inosine was almost completely released into the surrounding medium. Outside the mitochondria only very small amounts of adenine nucleotides were detected. Similar incubations in the presence of [14C]-adenosine yielded no [14C]-inosine ruling out extramitochondrial adenosine deamination. It is concluded that endogenous adenine nucleotides can be degraded in mitochondria via AMP dephosphorylation and subsequent adenosine deamination. A purine nucleoside transport system mediating at least the efflux of inosine from the mitochondria is suggested.

Adenine Nucleotides↗
PubMed1990

Effects of prostaglandin synthetase inhibitors on the upper urinary tract. Experimental studies on isolated preparations and urodynamic measurements in men.

Prostaglandin inhibitors such as indomethacin have been used for the treatment of renal colic. While opioids have a central analgesic effect, the effects of indomethacin are mainly peripheral, acting directly on the kidney. Pharmacourodynamic investigations of the upper urinary tract in men have demonstrated that intravenous indomethacin reduces renal pelvic pressure. These effects are more intense with indomethacin than with metamizol and are not found with hyoscine butylbromide. We have determined that indomethacin reduces the smooth muscle activity of human renal pelvis preparations in a tissue bath. These findings may represent a further possible direct effect of indomethacin on the upper urinary tract during the treatment of renal colic.

Adult↗
PubMed1990

Development of cytotoxic islet cell antibodies in rats following damage of the pancreas by complete Freund's adjuvant combined with a nondiabetogenic dose of streptozotocin.

The possible relationship between destruction of pancreatic beta cells and islet cell surface antibodies (ICSA) was examined in a rat model using complete Freund's adjuvant (CFA), a lymphocyte activator, in combination with the beta cell toxin, streptozotocin (STZ). In addition to this treatment, the rat insulinoma cell line, RIN5AH, as a readily accessible source of insulin-producing cells, was utilized to potentiate the production of ICSA. Intraperitoneal injections of CFA to male Lewis rats, followed 24 h later by a single nondiabetogenic dose of STZ, produced a 47% (p less than 0.01) reduction in pancreatic insulin content associated with degranulation and necrosis of insulin-immunoreactive cells. Eight weeks after treatment, ICSA were detectable that mediated the complement-dependent lysis of neonatal rat islet cells. Injections of RIN5AH cells, following treatment with CFA/STZ, did neither increase the severity of histopathological changes in the exocrine pancreas nor the extent of beta cell necrosis, but gave rise to higher levels of cytotoxic ICSA. Immunization with RIN cells alone, although increasing ICSA levels above those of the other experimental groups, produced no major histopathological changes. These results indicate that ICSA are the consequence of beta cell damage, and they are not capable of promoting or initiating beta cell necrosis in this model.

Animals↗
PubMed1990

The influence of protein malnutrition on T cell, natural killer cell, and lymphokine-activated killer cell function, and on biological responsiveness to high-dose interleukin-2.

Protein malnutrition is prevalent in cancer patients, however the influence of protein-calorie malnutrition on anti-tumor immune effector mechanisms is unclear. In addition, the effect of malnutrition on host immunological and biological responsiveness to recombinant interleukin-2 (rIL-2) is unknown. In Swiss mice (n = 100), we observed that T cell activation, T cell response to rIL-2, T suppressor cell generation, cytotoxic T lymphocyte development, and the cytolytic activity of LAK cells were not significantly impaired by two or three weeks of feeding with a 2.5% protein diet compared with mice fed an isocaloric diet in which protein calories constituted 24% of the total. In CBA/J mice (n = 100), we observed a significant (P less than 0.05) impairment of poly(I:C)-inducible natural killer cell function in mice ingesting the 2.5% diet. In both A/J (n = 40) and Swiss mice (n = 40), cytotoxic responses after 3 days treatment with rIL-2 (5 X 10(6) U/kg body wt. three times daily) were comparable in both dietary groups. These studies demonstrate that protein depletion is associated with impaired poly (I:C)-induced natural killer cell function in CBA/J mice. However, T cell function and biological responsiveness to high-dose rIL-2 were not significantly impaired.

Animals↗
PubMed1990

Hormonal responses to exhausting physical exercise: the role of predictability and controllability of the situation.

Psychological conditions which produce sustained activation have been clearly identified. Among these are the predictability and the controllability of the situation. We studied the impact of these psychological variables on hormone secretion (cortisol, ACTH, vasopressin, prolactin, and hGH plasma levels) under a standardized physical load. Sixteen subjects participated in four sessions each, one week apart, with the task of riding a bicycle until exhaustion. During three sessions, all experimental conditions were held identical to ensure the situation was a predictable as possible. During the fourth session, instructions induced a certain level of uncontrollability. Whereas physiological and performance measures did not vary with experience in the task, cortisol, ACTH, and vasopressin responses declined with increasing experience. This emphasizes the importance of the psychological definition of the situation for endocrine stress responses.

Adrenocorticotropic Hormone↗
PubMed1990

Decreased adrenergic sensitivity in patients with hypothyroidism.

Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

Adrenergic beta-Agonists↗
PubMed1990

Argyrophil and beta-endorphin immunoreactive cells in focal islet-cell adenomatosis and insulin-producing islet-cell adenomata.

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.

Adenoma↗
PubMed1990

Survival of islet isografts despite cytotoxicity against pancreatic islets measured in vitro.

In this study the in vivo relevance of spleen cell anti-islet cytotoxicity measured in vitro was examined by transplantation of 1,200 syngeneic islets into the spleen of rats receiving 0.5 ml complete Freund's adjuvant (CFA) 24 h before 25 mg/kg body weight streptozotocin (STZ) was given. Control rats receiving CFA or STZ alone remained normoglycaemic whereas 12 out of 21 CFA/STZ-treated rats developed a severe hyperglycaemia after three combined treatments. After the first and second combined treatment splenocytes showed a significant cytotoxicity (p less than 0.01) against syngeneic islets measured by 51Cr-release. This cytotoxicity was not detectable after the third combined treatment. The CFA/STZ-induced diabetes with a residual pancreatic insulin content of only 5% was permanently reversed by intrasplenic islet isografts, but, surprisingly, syngeneic islets survived too, if transplanted at the time when an anti-islet cytotoxicity was measured in vitro. From our results we conclude that the polyclonal activation by complete Freund's adjuvant potentiates the beta cell-toxic effect of a low dose of streptozotocin and induced a transient splenocyte-mediated anti-islet cytotoxicity not recurrent after islet transplantation. Furthermore, our findings reveal a discrepancy between organ-specific immune reactions measured in vitro and those affecting the beta cells in vivo.

Animals↗
PubMed1990

Radioiodination of peptide hormones and immunoglobulin preparations: comparison of the chloramine T and iodogen method.

Following optimization of the reaction conditions, e.g. concentration of oxidizing agents, reaction time, volume of reaction mixture, and pH, chloramine T and the new iodination reagent, Iodogen, were compared for their effectiveness in radioiodination of insulin, glucagon, human growth hormone (hGH), and rabbit anti-mouse IgG. The radioactive peptide hormones prepared were analyzed for the presence of aggregate and breakdown products by polyacrylamide gel electrophoresis (PAGE) at pH 8.9, the rabbit anti-mouse IgG was tested for the presence of low molecular weight damage products by gel filtration on Sephadex G-50. The results demonstrate that with respect to iodine incorporation, specific activity, and immunological reactivity either method can be used to prepare under carefully controlled conditions a wide range of tracers with high specific activity at minimal oxidation damage. These tracers are shown to be highly suitable in radioimmunoassays after previous purification by PAGE and gel filtration, respectively.

Chloramines↗
PubMed1990

Histopathological lesions in the pancreas of a rat model of diabetes induced with complete Freund's adjuvant and low-dose streptozotocin.

Neither injection of complete Freund's adjuvant (CFA) alone nor the administration of low doses of streptozotocin (STZ) to rats produced remarkable histopathological changes in the endocrine pancreas, but treatment with the combination of both resulted in necrosis of beta cells. When the combination of CFA/STZ was given two times, necrosis progressed, and the beta cell reserve was depleted to such an extend that persistent hyperglycemia ensued. These changes were associated with a significant reduction in the apparent islet size. A single injection of CFA induced pancreatitis and inflammatory lesions in the exocrine parenchyma with no insular involvement. Three injections caused extensive destruction of pancreatic acinar tissue but only moderate beta cell injury in the minority of islets. Apart from mild degranulation of beta cells, treatment with STZ did not produce histopathological changes in the pancreas. These results suggest that the acute inflammatory process induced by CFA may initially damage the beta cells, increasing thereby their susceptibility to the action of STZ.

Animals↗
PubMed1990

The possibility that pancreatic beta cell destruction leading to type 1 diabetes is initiated by the release of cytokines by polyclonal activation of the immune system.

The cause of the destruction of the insulin-producing beta cells leading to type 1 diabetes is still unknown. Over the last few years it has become clear that autoimmune abnormalities, such as insulitis, autoantibodies against islet cell antigens and cellular cytotoxicity to beta cells are associated with the onset of type 1 diabetes. Nevertheless, it is still uncertain whether immune phenomena observed in human beings correspond to primary or secondary events in the development of type 1 diabetes. We do not know why the process of becoming diabetic is so lengthy in a risk proband with a genetic and immunological predisposition. Whatever the explanation of genetic association to the pathogenesis of type 1 diabetes may be, it seems sure that environmental factors may decisively influence the outcomes. In this article we summarize evidence implying that cytokines released during polyclonal activation of the immune system may initiate the beta cell destruction leading via autoimmune mechanisms of beta cell killing to insulin-dependent diabetes mellitus.

Animals↗
PubMed1990

Influence of polyethylene glycol (PEG) extraction on the C-peptide determination in sera from insulin-dependent diabetic patients with circulating insulin antibodies.

To investigate whether the unexpectedly high C-peptide levels in some insulin-dependent diabetic (IDDM) patients are due to co-determination of proinsulin bound to circulating insulin antibodies, 36 randomly selected sera from IDDM patients were assayed for C-peptide immunoreactivity (CPR) after polyethylene glycol (PEG) extraction, preceding incubation with proinsulin binding antibodies (LAB + PEG) or without pretreatment of the sera. Recovery of proinsulin was checked by addition of 1 nmol/l proinsulin to all sera. Recovery was found to be 101.5 +/- 4.0%. The mean values of concentrations were significantly lower (p less than 0.001) after treatment with PEG and IAB + PEG compared to the untreated sera. There was also a significant difference (p less than 0.05) between sera extracted with PEG alone or after IAB + PEG-treatment. However, no correlation (p greater than 0.1) was found to bound insulin (total minus free insulin) or to insulin binding capacity (IBC) of the sera. If an antiserum is not available with very low cross-reactivity with proinsulin to determine human C-peptide then sera should not be extracted with PEG alone but after additional incubation with a proinsulin binding antiserum. In spite of the extraction in some cases unexplicably high C-peptide levels may still be expected.

C-Peptide↗
PubMed1990

Autoantibodies against insulin (IAA), C-peptide (CAA), and glucagon (GAA) in new-onset type 1 diabetic patients.

Autoantibodies against insulin, C-peptide, and glucagon were determined by radio-binding assay in 63 new-onset Type 1 (insulin-dependent) diabetic patients as well as in 70 controls. Plasma peptide binding was determined by means of 125I-labeled peptides and charcoal-dextran separation technique. Binding values exceeding the mean plus three standard deviations of the controls were considered as antibody-positive. Sixteen patients (25%) were positive for IAA, as 6 (10%) were positive for CAA and 2 (3%) for GAA. Of all control subjects, none were positive for either IAA or CAA, whereas 2 (2%) had GAA. The mean 125I-glucagon binding in the patients' group was, however, slightly enhanced and could be suppressed to normal values by excess unlabeled glucagon. The presence of IAA and/or CAA was significantly associated with more severe symptoms at diabetes manifestation. These results indicate that in new-onset Type 1 diabetics autoimmunity arises against all the insular peptides tested but is predominantly directed against those antigens secreted from the beta cells. Nevertheless, extremely low-binding GAA seem to be common in these patients. The determination of IAA/CAA might be useful in detecting a possible heterogeneity of Type 1 diabetes with regard to its clinical mode of manifestation.

Age Factors↗
PubMed1990

Prediction of salt sensitivity.

The overall prevalence of salt sensitivity was studied in 75 men stratified by diagnosis (hypertensive v normotensive) and race (black v white). All were studied in a crossover design employing a 200 mEq and 10 mEq Na/day. High salt led to a decrease in diastolic pressure for all groups (P less than .002). For systolic pressure, there was no salt effect on blood pressure across the whole group; however amongst the hypertensives, particularly the black hypertensives, high salt led to increases in systolic pressure (P less than .022). Obese patients were more likely to increase their systolic pressure in response to salt loading (P less than .05). The patients whose pressure increased on high salt were those who manifested less of a decrease in plasma levels of norepinephrine and renin in response to salt loading (both P less than .05). Systolic salt sensitivity was predicted with high statistical power (R = 0.689, P less than .00001) by a multiple regression equation employing: race; diagnosis; the change in renin and norepinephrine levels with diet; and the change in BP sensitivity to infused norepinephrine across the two diets. In view of the findings of increased norepinephrine, renin and diastolic pressure on low salt and in view of the particular physiological and epidemiological setting associated with systolic salt sensitivity, one wonders about the advisability of across-the-board recommendations of low salt diets for all hypertensive patients.

Adult↗
PubMed1990

Out-patient sclerotherapy of idiopathic left-sided varicocele in children and adults.

Between 1983 and 1989, 334 patients with idiopathic left-sided varicocele were referred for transfemoral sclerotherapy; 323 were adults and 11 were children. The standard site of injection of the sclerosing solution (Varicocid-Natriummorrhuat 55 mg, Benzylalkohol 20 mg) was the mid-portion of the spermatic vein. The upper third was injected only in cases where the catheter could not be negotiated further (e.g. abnormalities in the course of the spermatic vein or its drainage into the intrarenal veins). The amount of sclerosing material was predetermined fluoroscopically using contrast material. Occasionally, in cases of high catheter positioning, the Varicocid was injected fractionally. The amount injected was always between 1 and 3 ml. Of 80 patients studied 1 year later, varicoceles were still present in 3 (4%). The best results were achieved in patients with small varicoceles (Grade I), normal testicular volume and normal FSH levels; 29% showed an improvement in sperm count and 27% an increase in sperm motility, while sperm morphology improved in only 7%. The conception rate was 11%.

Adolescent↗
PubMed1990

Renin-producing renal cell carcinoma.

The pathogenetic relationship between tumor and hypertension was investigated in 40 patients with renal cell carcinoma. 15 of 40 patients were hypertensive. Four of these 15 patients with renal tumors and hypertension (26.7%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumor kidney to contralateral kidney ratio of between 6 and 7. In the same 4 cases the renin content in the renal tumor tissue was significantly higher than that in tissue from the adjacent tumor-free renal cortex of the ipsilateral kidney. Immunocytochemical demonstration of renin in the tumor was only possible in these 4 cases. In 3 of these patients blood pressure returned to normal following nephrectomy; in the 4th case there was a drop in blood pressure after nephrectomy. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumor.

Carcinoma, Renal Cell↗
PubMed1990

Nephrogenic adenoma of the bladder in a child--immunohistochemical and lectinhistochemical investigations.

A morphological study of a 6-year-old girl with a nephrogenic adenoma of the bladder is presented. The tumor developed 4 years after multiple reconstructive operations of the urinary tract. Immuno- and lectinhistochemically, the tubular structure of the lesion resembled that of a collecting tubule. A conservative approach was the treatment of choice in the absence of microscopically malignant changes.

Adenoma↗