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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 253 records · Page 14Linked to original sources

Purine compounds in mitochondria: a quantitative evaluation.

Applying a recently developed reverse-phase ion-pair HPLC technique we determined purine compounds in acid extracts of mitochondria isolated from rat and mouse liver, rat renal cortex, and hepatoma. Intramitochondrial purine nucleosides and bases were evaluated quantitatively for the first time. All mitochondria examined contain significant amounts of adenosine, guanosine, inosine, guanine, and hypoxanthine. Moreover, IMP was identified in all extracts. Adenine was detected in traces only. These results are in accordance with the concept of mitochondrial metabolism of purine compounds.

Animals↗

Optimization of the ion-pair high-performance liquid chromatographic separation of purine derivatives in erythrocytes, thymocytes and liver mitochondria.

Various methods are described for the analysis of purine derivatives in biological samples by ion-pair high-performance liquid chromatography (HPLC) with both gradient and isocratic systems. A new approach is proposed that is suitable for the separation of nuclei acid constituents in different cells with a specific enzymatic activity pattern. The ion-pair HPLC methods were developed for the analysis of erythrocytes, lymphocytes and mitochondria acid-soluble fractions in clinical and experimental studies of normal and altered nucleotide metabolism. The results of studies of purine metabolite redistribution in mouse liver mitochondria during a 30-min incubation at 37 degrees C and data on purine metabolic alterations in mouse thymocytes during hepatoma growth are discussed.

Animals↗

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 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin.

Animals↗

Aromatase-inhibitors of the androstenedione-type activate the 17 beta-hydroxysteroid-dehydrogenase in the rat testis tissue suspension model.

In an in vitro rat testis cell suspension model, the metabolism of tritiated testosterone, dihydrotestosterone and androstenedione was investigated. In the presence of aromatase inhibitors like 1-methyl-androsta-1,4-dien-3,17-dione (SH 489) and 4-hydroxy-androstenedione, the metabolism was shifted towards 17-keto forms. The same effect was observed in the presence of androstenedione, the parent compound of the two aromatase inhibitors. The consequent consideration of the whole labelled steroidal spectrum in each experiment leads to the conclusion that androstenedione and the derived aromatase inhibitors activate the 17 beta-hydroxysteroid-dehydrogenase in a product activating manner. Our results imply that aromatase inhibitors may regulate the intratissular levels not only of estrogens but also of other hormonally active steroids like dihydrotestosterone and 5-androstenedione.

17-Hydroxysteroid Dehydrogenases↗

Treatment of prevesical ureteral calculi by extracorporeal shock wave lithotripsy.

Since August 1985 extracorporeal shock wave lithotripsy has been performed in 39 patients with prevesical ureteral stones, including 3 with steinstrasse after extracorporeal shock wave lithotripsy of kidney stones. Female patients less than 40 years old were excluded because of the theoretical possibility of harm to the ovary by shock waves. Via a modified technique with the patient in a flat position, x-rays and shock waves enter through the foramen obturatum. High total power (high number of shocks and high kilovoltage) led to complete stone disintegration and a success rate of 95 per cent was achieved. While ureterorenoscopy should be more restricted, extracorporeal shock wave lithotripsy is the method of choice for the treatment of distal ureteral stones.

Female↗

Identification of monoclonal antibodies to pancreatic islet cells by immunoperoxidase staining.

Immunoperoxidase staining and enzyme-linked immunosorbent assay (ELISA) were used to identify monoclonal antibodies that reacted with pancreatic islet cells. All monoclonal antibodies produced against isolated human or rat pancreatic islets including one mouse autoantibody reacted with pancreatic islets in formalin-fixed pancreas sections, but not with rat kidney or thyroid. Reactivity was also found with suspensions of normal rat islet cells and rat insulinoma cells using a 3-stage immunoperoxidase procedure and an ELISA technique. Differences were observed in staining intensity between the various antigenic substrates tested suggesting variable cross-reactivity and/or number of epitopes. The sensitivity of the immunoperoxidase technique proved to be favourable for identification of monoclonal antibodies that recognize cellular constituents such as islet cell antigens present in low concentrations.

Animals↗

Differences in the behavioral profile of circling under amphetamine and apomorphine in rats with unilateral lesions of the substantia nigra.

In rats with severe depletion of striatal dopamine, produced by a unilateral injection of 6-hydroxydopamine into the substantia nigra, amphetamine (2 mg/kg) induces circling towards the side of the lesion and apomorphine (0.25 mg/kg) induces circling in the opposite direction. In Experiment 1 we showed that under apomorphine, circling may be related to an asymmetry in stepping, but under amphetamine it is not. Specifically, under apomorphine, rats rotate almost exclusively by stepping (backwards) with the contralateral hindlimb while pivoting on the ipsilateral hindlimb. In contrast, under amphetamine, they rotate using a variety of stepping patterns, and there is no consistent asymmetry in using one hindleg for stepping and the other one for bearing weight. Considering the stepping patterns, it is suggested that rotations induced by apomorphine and amphetamine involve at least one and two variables, respectively (turning and turning plus forward progression). Furthermore, the results of Experiment 2 revealed that under apomorphine the direction of circling in a pool of water is reversed by edges, but under amphetamine it is not. In particular, under apomorphine, rats swim in the contraversive direction when in the middle of the pool but in the ipsiversive direction when swimming along the edge of the pool. In contrast, under amphetamine, they show little attraction for the edge and continue swimming in the ipsiversive direction, regardless of their position in the pool. It seems, therefore, that different behavioral mechanisms may underlie the rotations induced by apomorphine and amphetamine.

Amphetamines↗

Screening monoclonal islet cell surface antibodies (ICSA) by radioimmunoassay--detection of crossreactivity with ICSA from insulin-dependent (type 1) diabetic patients.

A radioimmunoassay for the detection of monoclonal islet cell antibodies was developed using rat insulinoma cells as antigen carriers and 125I-labeled affinity-chromatographically purified anti-mouse Ig antibodies for detecting cell-bound mouse Ig. Prior to the assay cells had been attached to glass tubes by poly-dimethyl-diallyl ammonium chloride thus allowing to perform the assay as easy as a solid-phase immunoassay. Incubation protocol and cell number were chosen to ensure a high sensitivity of the assay. Results compared well with immunofluorescence findings. Of seven monoclonal islet cell antibodies tested for crossreactivity only one was displaceable by islet cell surface antibodies from diabetic sera. This antibody was induced by immunization with human islets whereas all others were from mice which had been autoimmunized with streptozotocin and complete Freund's adjuvant.

Animals↗

[Computed tomography of acute bacterial nephritis].

Five case reports are used to illustrate that it is possible by computed tomography to differentiate between acute diffuse, acute focal and abscess-forming types of renal infection. In acute diffuse renal inflammatory disease, intravenously injected contrast medium remains in various parts of the renal tissue after an interval of two to six hours following injection. Acute focal inflammatory disease and abscesses produce localised hypodense or isodense lesions. Sequential increase in density following a contrast bolus injection permits the distinction of focal nephritis from an abscess. These findings provides information concerning the type and duration of treatment.

Acute Disease↗

[Computed tomographic studies of the scrotal contents, particularly the testis].

CT examination of the testes was carried out in 49 patients for the investigation of testicular tumours. Hypodensity and inhomogeneity were typical of teratomas and hyperdensity and relative homogeneity of seminomas. Granulomatous orchitis and lymphomas showed the same characteristics as seminomas. Three testes in the abdomen could be localised and classified. One non-palpable primary tumour was found as well as an old partially calcified tumour, three old torsions and one lipo-sarcoma. In about 10% it was not possible to distinguish between tumour and inflammatory lesions. Compared with sonography, CT has advantages, particularly in the diagnosis of old torsion.

Abdominal Neoplasms↗

The effect of hypertension, sodium, and race on isoproterenol sensitivity.

The heart rate response to isoproterenol is felt to be an index of beta receptor sensitivity. We studied this response in 55 normotensive and mildly hypertensive men on two dietary salt intakes (10 meq sodium per day, and 200 meq sodium per day). There was no relationship between receptor functioning and diagnosis of hypertension. Similarly, age, relative body weight, and resting plasma catecholamines were unrelated to the heart rate response to isoproterenol. There was however, a significant three-way interaction between race, diagnosis, and dietary salt. Black hypertensives fail to down regulate their beta receptors' response to isoproterenol in the face of a high salt challenge (p less than .006).

Adult↗

Major blunt abdominal trauma due to child abuse.

We reviewed 15 years' experience with childhood trauma at two hospitals in different cities, one a city hospital, the other a children's hospital, to learn the extent, circumstances, presentations, and consequences of major blunt abdominal trauma due to child abuse. Some 10,000 children admitted to these hospitals for treatment of injuries from 1972 through 1986 provided the basis for the study; the incidence and severity of pediatric trauma at the two hospitals was similar, in that 13% of the visits to both hospitals' emergency rooms were for trauma, of which 5% resulted in admission. Major blunt abdominal trauma due to child abuse accounted for 22 of these cases, six at the former, 16 at the latter, and represented less than 0.50% of all abused children seen at both institutions. The average age was 24 mo; 14 were boys and eight were girls. In only two instances was the family unit intact; in both, the child was abused by the babysitter. Otherwise, the father, or the mother's "boyfriend," was responsible. Overall mortality was 45%, and was related both to type of injury and presenting signs. Of one who presented with an epigastric mass due to a pancreatic hematoma, none died; the pseudocyst which subsequently developed resolved on bowel rest and TPN. Of three who presented with bilious vomiting due to duodenal hematoma, none died; one required operative evacuation. Of five who presented with peritonitis due to duodenojejunal rupture, one died; this child presented greater than 24 hr following injury in profound septic shock. Of three who presented with hypovolemia due to moderate hemorrhage, none died; the former two were managed conservatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

Results in the use of extracorporeal piezoelectric lithotripsy (EPL) for treatment of urinary calculi.

The Piezolith 2200 as an extracorporeal shock wave lithotripter uses piezoelectrically generated, high-energy sonic impulses for treatment of urinary calculi; the shock wave generator is self-focussing. Localization of concrements is performed by means of ultrasound imaging. Treatment with the Piezolith 2200 is painless for the patient and thus possible without anesthesia and analgesia. We report on 806 cases of treatment involving a total of 572 kidneys in 567 patients (561 adults, 6 children) suffering from calculi of various sizes in the renal pelvis (n = 126), calculi in the calyces (n = 384), partial (n = 24) or full (n = 19) staghorn calculi, as well as calculi in the upper part of the ureter (n = 19). In 88% of these cases the concrements could be removed completely. Since cardiac activity is not influenced by piezoelectrically generated high-energy impulses, this procedure is particularly suited to the treatment of patients with heart problems.

Adult↗

Production of pro-insulin, C-peptide, and insulin in nesidioblastosis, focal islet-cell adenomatosis, and genuine insulomas. A correlated radioimmunochemical, immunohistochemical, and ultrastructural investigation with particular regard to the occurrence of argyrophil and pro-insulin immunoreactive cells.

Subtotal pancreatectomy specimens from one case of nesidioblastosis, one case of focal adenomatosis, and two cases of insulin-producing islet-cell tumours were studied with special reference to their production of pro-insulin, C-peptide and insulin, and their contents of argyrophil parenchymal cells. Specific immunostaining revealed the presence of abundant cells reacting with pro-insulin, C-peptide, and insulin antiserum; at least the great majority of them were obviously non-argyrophil cells. The content of extractable immunoreactive insulin (IRI) was higher in the cases of nesidioblastosis and focal adenomatosis than in the two insulomas. Molar ratios of IRI to C-peptide immunoreactivity (CPR) varied between 7 and 100. Gel filtration analysis of the extracts revealed two peaks of CPR, corresponding to 3,000 and 10,000 daltons, respectively. Ultrastructurally, the insulin cells in cases of nesidioblastosis and focal adenomatosis contained numerous typical beta granules. In the islet-cell neoplasms some "polycrine" islet cells were also found, containing typical as well as atypical granules with electron dense or pale cores. Some cells even showed a mixture of apparent beta and alpha granules. Despite structural differences and variable contents of IRI and CPR, the predominance of cells reactive with antibodies to pro-insulin, C-peptide, and insulin, and the absence of argyrophil pro-insulin cells in adenomatosis and insulomas indicates that the hormonal products of these parenchymal cells are not any chemically modified insulin or any other member of the insulin family.

Adenoma↗

Genetic control of susceptibility to severe hyperglycaemia evoked by CFA/SZ-induced immune response against beta cells in various rat strains.

A novel approach has previously been reported to induce an insulin-dependent (type 1) diabetes mellitus in Wistar and Lewis rats by subdiabetogenic dose of the beta cell toxic agent streptozotocin injected i.p. 24 h after a polyclonal activator of lymphocytes, the complete Freund's adjuvant, was administered. The results from a comparative study in Wistar rats and congenic Lewis rats of the haplotype RT1a and RT1u demonstrate that both the genetic background and genes linked to the major histocompatibility complex are probably involved in the genetic control of susceptibility to the induction of hyperglycaemia in this experimental diabetes model. The susceptibility to hyperglycaemia was strongly associated to the non-specific activation of the immune system by administration of complete Freund's adjuvant only. From these data it is suggested that the genetic control of diabetes induction in this animal model is caused by genetic control of the immune/autoimmune reactivity involved in the mechanisms of beta cell destruction.

Animals↗