Journal interview 14. Conversation with Wolf Schmidt.
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Biomedical subjects
Publications and source records attributed to W Schmidt.
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The regional distribution and cellular localization of aspartate aminotransferase (AspAT) as a glutamate and aspartate metabolizing enzyme was studied in the hippocampal formation, in dorsal root ganglia, and in superior cervical ganglia during the postnatal development of the rat. At birth, in all neuronal tissues studied the enzyme activity was rather low. Whereas in the dendritic layers of the hippocampal formation enzyme levels rose strikingly during the first weeks of postnatal life, those of peripheral ganglia remained remarkably stable. The high affinity uptake of [3H]labelled L-glutamate and D-aspartate were studied in surface autoradiograms of incubated slices of hippocampal formation during postnatal development of the rat. Our data indicate that the postnatal development of high affinity uptake capacity is parallel to the increase of histochemically demonstrable AspAT activity in the hippocampal formation suggesting that the enzyme may be involved in glutamate/aspartate neurotransmitter metabolism.
Three-dimensional interactive display of CT data from 23 cases of craniofacial and spinal pathology using a solids processing computer system was compared with conventional two-dimensional CT display. Three-dimensional display gave a more complete perspective of complex displacement patterns of facial and spinal fractures, and more clearly defined surface anatomy of osseous tumors and malformations. In 7 cases however, processing algorithms for three-dimensional display caused subtle anatomic features and non-displaced fractures to be obscured. These false negatives were clinically significant in cases of petrous bone pathology and in non-displaced spinal fractures that affected stability.
The haptoglobin phenotype has been estimated in patients suffering from chronic liver disease (n = 222) and acute hepatitis (n = 59) in comparison with the haptoglobin pattern of a normal population (n = 1726). The frequency of Hp 1-1 was significantly increased in non-alcoholic chronic liver disease (p = 5%; chi 2-test) in contrast to alcoholic disease. The highest incidence of Hp 1-1 occurred in cryptogenic cases (p = 1%). The follow-up of patients suffering from acute hepatitis failed to indicate any relationship between the haptoglobin phenotype and the course of hepatitis. The results suggest that Hp 1-1 is a genetic marker of special kinds of chronic liver diseases.
The hyperfractioned total body irradiation has advantages in tumor control rate, patient tolerance and survival. The technical application is simple and easy to integrate in the daily routine of a radiotherapy department. The reduced time in the life island and the low incidence of acute reactions increases the patients quality of life. It turned out, that single dose TBI is not very suitable. This was already stated by Lester Peters in 1980.
The content of collagen in the amniotic and chorionic connective tissue was determined with the quantitative investigation method of hydroxyprolin. Significant differences do not exist between the amount of collagen in the amniotic and chorionic connective tissue. The difference in the tension stability must be based on the variegating pattern of the collagen fibrils.
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Pathology and experimental bacteriology have, in scientific medicine, created fundamental methodical presuppositions for the description and recognition of etiologic entities. With the tumour-tetanus phenomen, two pathogenic principles--cancer growth and tetanus infection--coincide in a so far unknown manner. Analytical experiments have led to the novel idea of the mitosis-stimulated anaerobic tetanus infection. This specific pathomechanism and its mathematical model formed the basis for the development of the serological Clostridium-tumour test with nontoxic, apathogenic Butyricus Clostridia as test microbes. As viable diagnostic agents the test spores are subject to the 12th Regulation of the Drug Act of the GDR. Only the histopathological judgement allows for the detection of micro-tissue alterations following i.v. overdoses of spores. The test spores were confirmed as safe and effective, and the microbiological cancer test approved to be appropriate for a clinical trial.
The RF IV form of M13 DNA was synthesized enzymatically in vitro, using the viral (+)strand as template, to contain phosphorothioate-modified internucleotidic linkages of the Rp configuration on the 5' side of every base of a particular type in the newly-synthesized (-)strand. Twenty nine restriction enzymes were then tested for their reactions with the appropriate modified DNA types having a phosphorothioate linkage placed exactly at the cleavage site(s) of these enzymes in the (-)strand. Eleven of the seventeen restriction enzymes tested that had recognition sequences of five bases or more could be used to convert the phosphorothioate DNA entirely into the nicked form, either by simply allowing the reaction to go to completion with excess enzyme (Ava I, Ava II, Ban II, Hind II, Nci I, Pst I or Pvu I) or by stopping the reaction at the appropriate time before the nicked DNA is linearized (Bam HI, Bgl I, Eco RI or Hind III). Only modification of the exact cleavage site in the (-)strand could block linearization by the first class of enzymes. The results presented imply that the restriction enzyme-directed nicking of phosphorothioate M13 DNA occurs exclusively in the (+)strand.
High aminotransferase activities catalyzing the reactions between L-glutamate and L-glutamine and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, and 2-ketoisovalerate were observed in pancreatic B-cell mitochondria. While maximal rates of transamination with L-glutamate were observed in the presence of micromolar concentrations of keto acid, maximal rates of transamination with L-glutamine were recorded only in the presence of millimolar concentrations of keto acid. The insulin secretagogue 2-ketoisocaproate was the most effective transamination partner for L-glutamate, while the insulin secretagogue 2-ketocaproate was the most effective transamination partner for L-glutamine. Since B-cell mitochondria are well supplied with L-glutamate and L-glutamine, 2-ketoglutarate generation in the presence of these two neutral 2-keto acids may be an important prerequisite for their insulin secretory potency. High rates of transamination of 2-ketoglutarate were observed in the pancreatic B-cell mitochondria with the branched-chain amino acids L-leucine and L-valine, but not with L-norleucine. In connection with the ability of L-leucine to activate glutamate dehydrogenase, this high activity of the branched-chain amino acid aminotransferase in pancreatic B-cell mitochondria may provide an explanation for the insulin secretory potency of this amino acid.
Between March 1980 and July 1984, coronary angiography was performed on 461 consecutive patients (no age limit) with acute myocardial infarction, and the partially or completely obstructing thrombus lysed by selective intracoronary infusion of streptokinase. At the time of first coronary angiography 96 patients (21%) had a high degree of stenosis but no total occlusion of the infarct vessel (group A). In 365 patients (79%) there was complete occlusion which in 315 patients (86%) was removed successfully after an occlusion period of 213 +/- 87 minutes (group B). In 50 patients (14%) (group C) attempts at reperfusion failed. In 129 of 163 patients (79.1%) with one-vessel disease, PTCA (percutaneous transluminal coronary angioplasty) was successful. Patients with multiple-vessel disease and an occlusion time of less than four hours, on the other hand, were treated surgically within the first ten days (78 patients). In the remaining 254 patients conservative treatment was practised. Within the first 30 days there were seven deaths (14%) in group C, while among group A and B patients, under conservative treatment, 16 died (7.8%). After successful PTCA four patients (3.1%) died. The lowest mortality was among patients with a short occlusion time and early bypass operation (2.6%). The most frequent cause of death was cardiogenic shock (20 of 29 patients), more rarely ventricular fibrillation (3) or other causes (4). Ventricular rupture occurred in three patients, one of whom was saved by pericardial tap. One year later the mortality among the conservative group was 21.2%, after successful PTCA or bypass operation 9.3% and 6.4%, respectively.
We have examined the subcellular distribution of histone mRNA-containing polysomes in HeLa S3 cells to assess the possible relationship between localization of histone mRNAs and the regulation of cellular histone mRNA levels. The distribution of histone mRNAs on free and membrane bound polysomes was examined as well as the association of histone mRNA-containing polysomes with the cytoskeleton. The subcellular localization of histone mRNAs was compared with that of HLA-B7 mRNAs which encode a cell surface antigen. Histone mRNAs were localized predominantly on the free polysomes, whereas the HLA-B7 mRNA was found almost exclusively on membrane bound polysomes. However, both species of mRNA were found associated with the cytoskeleton. Interruption of DNA synthesis by hydroxyurea treatment resulted in a rapid and selective destabilization of histone mRNAs in each subcellular fraction; in contrast, the stability of HLA-B7 mRNA appeared unaffected. The results presented confirm that histone mRNAs are predominantly located on non-membrane bound polysomes and suggest that these polysomes are associated with the cytoskeletal framework.
Ten patients suffering from advanced myotonic dystrophy with severe myotonic symptoms were treated with 800-1200 mg/day of the anti-arrhythmic drug tocainide (Xylotocan). All patients reported a marked subjective improvement of myotonia, which was confirmed by objective tests. Except for a slight QT-prolongation in one patient, the ECG was not significantly altered by the treatment. Twenty-four-hour ECG after treatment disclosed that pre-existing ventricular arrhythmia disappeared in three cases. The occurrence of complex ventricular arrhythmia in two patients under treatment was not necessarily due to specific effects of the drug but might be explained by the high spontaneous variability of rhythm disorders. In these patients suffering from myotonic dystrophy with typical cardiomyopathy no deleterious effects of the drug were observed, especially no cardiac arrhythmias which would have necessitated interruption of treatment. Therefore, the authors recommend symptomatic therapy with tocainide for myotonia and paramyotonia congenita, as well as in myotonic dystrophy patients suffering from marked myotonic stiffness. ECG and 24-h ECG should be carefully recorded as necessary in any treatment with anti-arrhythmic drugs.
In a series of newly isolated AKR leukemias, some tumors expressed large amounts of both H-2K and H-2D molecules, while others had reduced levels of both antigens. The number of H-2 antigens expressed in steady state showed a consistent correlation with the rate of synthesis of the H-2 class I heavy chain and the beta-2 microglobulin (beta 2m) light chain, and with the amount of H-2- and beta 2m-specific mRNA present in the tumors. Stimulation of leukemic cells with interferon induced an increased transcription of both H-2 and beta 2m mRNA. These results suggest that there is a mechanism that regulates, at the transcriptional level, the coordinate expression of H-2K and H-2D heavy chains, and the beta 2m light chains encoded by genes on chromosomes 17 and 2, respectively.
DNA analysis was performed by flow cytometry (FCM) in 59 cases of different types of pituitary adenomas who underwent microsurgery and were actively followed over a period of 3-6 years. Aneuploid DNA patterns were detected in 12 (20%) cases. Frequency of aneuploidy was highest in prolactin-secreting (36%) as compared to 17% in GH- and 7% in non-secreting adenomas. Some adenoma parameters valid for tumour growth, such as rate of recurrences and mitotic index, were correlated with aneuploidy of the tumour. FCM studies are, therefore, recommended to gain further parameters for the estimation of proliferative activity of pituitary adenomas.