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Biomedical subjects

F Ziegler

Publications and source records attributed to F Ziegler.

At least 19 recordsLinked to original sources

Analysis of the tissue distribution and inheritance of heteroplasmic mitochondrial DNA point mutation by denaturing gradient gel electrophoresis in MERRF syndrome.

MERRF (Myoclonic Epilepsy and Ragged-Red Fibres) syndrome is one of the maternally inherited diseases for which a mitochondrial DNA (mtDNA) point mutation has recently been identified. The mutation is always heteroplasmic, that is normal and mutant mtDNA coexist within the same individual. We studied mtDNA heteroplasmy in two families with MERRF syndrome, using a denaturing gradient gel electrophoresis technique that avoids the errors in the evaluation of wild/mutant mtDNA ratios caused by restriction enzyme cutting in the situation of amplification of a heteroplasmic DNA. In two patients, the proportion of muscle mutant mtDNA was in agreement with the severity of muscle mitochondrial proliferation, energy defect and fibre type I predominance. In nine patients from three generations of one family, mutant mtDNA proportion in leukocytes was in relative agreement with the clinical severity of the disease. Transmission of mutant mtDNA through these three generations did not show any tendency toward homoplasmy. Homogeneity of the mutant mtDNA proportion among different tissues from one patient was demonstrated in brain, liver, muscle and heart but a possibility of divergence of the mutant mtDNA proportion during mitosis was documented in cultured skin fibroblasts.

Adolescent

Genetic biochemical and pathophysiological characterization of a familial mitochondrial encephalomyopathy (MERRF).

Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a neuromuscular disorder characterized by mitochondrial myopathy and progressive myoclonus epilepsy. A heteroplasmic A to G transition mutation in the mitochondrial encoded tRNA(Lys) gene at nucleotide pair 8344 has been suggested to be linked to the MERRF-syndrome. We have investigated biochemically and histochemically muscle biopsies and studied the mitochondrial genomes of hair, blood and muscle tissue of a family including three cases of MERRF-syndrome as well as unaffected relatives within the maternal lineage. Sequence analysis of the mtDNAs, performed after amplification by the polymerase chain reaction (PCR), confirmed the A to G transition mutation in the tRNA(Lys) gene at position 8344. The additional point mutation at nucleotide pair 750 in the 12 S rRNA gene, which was also found by Shoffner et al. (1990), however, was absent in all investigated tissues. Quantitative analysis of the percentage of mutated mtDNA by mispairing PCR (Seibel et al., 1990) revealed variable contents in different tissues and individuals, including unaffected family members. Mitochondrial protein synthesis in cultured fibroblasts from MERRF patients revealed diminished incorporation of 35S-methionine into lysine-containing peptides.

Adolescent

Efficiency of enteral nitrogen support in surgical patients: small peptides v non-degraded proteins.

In a prospective study, 12 intensive care patients, after abdominal surgery, received three alternate six-day courses of two enteral diets with identical nitrogen (0.3 g N/kg per day) and energy (60 kcal/kg per day) supply. The protein hydrolysate (PH) diet contained enzyme-hydrolysed casein and lactoserum (60% small peptides), while the non-degraded protein (NDP) diet contained a nitrogen source of similar amino acid composition, but in the form of non-degraded proteins. The patients were randomised to receive either PH-NDP-PH or NDP-PH-NDP. Parameters reflecting protein metabolism were assessed in the plasma, urine, and stomal effluent on days 1, 6, 12, and 18, three hours after stopping the nutrition (t0), and one hour after restarting it (t1). Comparisons of t1 and t0 values showed that 13 amino acids (including the eight essential amino acids) increased significantly with the protein hydrolysate diet, but only two increased with the non-degraded protein diet. Similarly, with protein hydrolysate, insulin-aemia at t1 was significantly higher than at t0 and correlated with plasma leucine, phenylalanine, alanine, and lysine concentrations. In addition, significant improvements in plasma albumin, transferrin, and retinol binding protein concentrations were seen with protein hydrolysate, together with a significant decrease in the plasma phenylalanine/tyrosine ratio and urinary 3-methylhistidine excretion. We conclude that in patients in intensive care after abdominal surgery enteral support containing small peptides is more effective than an equivalent diet containing whole proteins in restoring plasma amino acid and protein levels.

Adult

Food intake, body and heart composition, and heart rate in T3 plus atenolol-treated rats.

Thyroid hormones and beta-blockers both affect energy balance and the heart. The interaction of 3,5,3'-triiodothyronine (T3) and the beta-blocker atenolol on some cardiac and energy balance parameters was therefore investigated. Stock-fed male Wistar rats (approximately 400 g) received 5 micrograms (expt 1) or 1.5 micrograms (expt 2) T3.100 g body wt-1.day-1 for 3 wk, with or without atenolol. In expt 3, rats were overfed with a "cafeteria" diet before and during the experiment and otherwise treated as in experiment 2. Compared with stock-fed (expt 1 and 2) or overfed (expt 3) controls, T3 caused an increase in food intake in experiments 1 and 2 but not in experiment 3. There was a large loss of body fat in all experiments, disproportionately greater than the body weight loss. Protein loss was significant only in experiment 1 and negligible in cafeteria rats. Heart rate and weight were increased, although heart composition remained unchanged. Atenolol, in a dose that abolished T3-induced tachycardia, did not modify any of the other T3 effects investigated, including the hypertrophy of the heart. These results indicate that T3-induced tachycardia can be abolished by concomitant treatment with a beta-blocker without altering parameters connected with energy balance, whereas protein loss caused by T3 can be attenuated by lowering the dose of T3 used and can be further blunted by dietary manipulation (cafeteria overfeeding).

Animals

[Representation of tumor and organ contours by projection radiography--an important supplement to radiotherapeutic treatment planning].

A special program developed in collaboration with the manufacturer ot the computer tomograph Somatom DR3 allows to transfer organ or tumor shapes from the transverse computed tomography scan to the localization radiograph (projection radiography). Some typical examples are presented in order to describe the possibilities offered for radiotherapy planning by this method. The procedure may be applied in all cases where neoplasms have to be irradiated or to spared and where this is of a decisive importance for simulator planning.

Female

[Reabsorption of the irrigation solute during percutaneous nephrolithotomy].

The publication of several accidents, possibly due to the reabsorption of irrigation solutions in the course of percutaneous nephrolithotomy, prompted the authors to quantify the amounts of glycine (1.50 per cent glycocol) reabsorbed in these operations, and to determine the metabolic consequences. In a prospective study of twelve patients subjected to fourteen percutaneous nephrolithotomies, the hemodilution parameters (natremia, protidemia, hematocrit and osmolality) and the amino acid content of the plasma were measured preoperatively, at operation, and immediately postoperatively. The study indicates that there is a hemodilution and reabsorption of irrigation solute comparable to that observed in transurethral resections of the prostate. The resultant hyperglycinemia probably explains the significant increase in ammonemia noted in all the patients. One theory is that hepatocellular insufficiency may increase this ammonemia. This might suggest the advisability of using saline solution, at least in these patients (that is, of course, in the absence of electrical lithotrity).

Adult

[Primary duodenal carcinoma. Clinico-radiologic study].

Primary carcinoma of the duodenum represents about 0.35% of all gastrointestinal carcinomas and is thus a rare disease. The radiological diagnosis of a duodenal origin is made more difficult by the close proximity of the pancreas, biliary system, right kidney and transverse colon. Histologically, duodenal malignant tumours are usually adenocarcinomas. Between 1973 and 1983, eight patients with primary duodenal carcinomas were diagnosed at the University of Tübingen. Average age of the patients was 67 years. There was no sex difference. Average survival was 3.3 years.

Adenocarcinoma

[Adverse effects of curative radiotherapy of prostate cancer].

The side effects of primary percutaneous radiotherapy in 100 patients with prostatic cancer were evaluated and classified into different degrees of gravity. It was shown that especially chronic side effects are benign in most of all cases. Severe - but not vitally dangerous - complications in bladder and intestine are rare (3%); their percentage corresponds roughly to the average mortality rate of surgical intervention (radical prostatectomy). Contrary to operation, troubles of the sexual function appear only in one third of the patients. Taking into consideration the similar therapeutic results of surgical intervention and radiotherapy, radiotherapy is more favorable with respect to side effects. This essential aspect should be considered when making a decision whether to apply a surgical or a radiotherapeutic treatment treatment.

Female

[Different stages of hyperostosis of the heads of the ribs in spondylosis hyperostotica].

Hyperostosis of the heads of the ribs represents a rare pattern and localization of spondylosis hyperostotica. The latter is combined with asymmetric extensions of the costovertebral surfaces, which are different from arthrotic alterations. A distinct preference is given to the upper glenoid surfaces. The scleroses of the heads of the ribs are also more pronounced in their cranial parts. Because of the pattern and different extent of the reported alterations a classification in five degrees of development and severity was possible.

Aged

Characterization of murine hepatoma BW7756. I. Selected biochemical properties of liver and hepatoma.

Selected biochemical properties, based on hepatocellular function, were assessed in the mouse hepatoma BW7756 and host and/or normal mouse liver. These biochemical properties included (a) alpha-fetoprotein (AFP) production, (b) lipid composition, (c) isozyme patterns and enzyme activities, and (d) cyclic AMP levels. The tumor evidenced an exponential growth phase and vigorous production of AFP in the first 3 weeks following transplant. The concentration of AFP in the sera of tumor-bearing mice increases roughly with the growth of the hepatoma. The percentage of total lipid in the hepatoma was greater than in either normal or host liver; however, the liver displayed more phospholipid than the tumor, while more triglyceride was demonstrable in the hepatoma. Of the 17 isozyme patterns analyzed, seven--acid phosphatase, malate dehydrogenase, aspartate amino-transferase, glucose-6-phosphate dehydrogenase, esterase, lactate dehydrogenase, and xanthine dehydrogenase--were different in the liver and the tumor. The cyclic AMP levels decreased in the tumor and the host spleen from day 10 to day 21; however, slight increases were noted in the tumor and host spleen and liver at day 28. These studies suggested 2--3 weeks posttransplantation as the optimal time for investigational use of this hepatoma.

Animals