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Biomedical subjects

R Schnabel

Publications and source records attributed to R Schnabel.

At least 109 records · Page 6Linked to original sources
PubMed1990

Postmortem serum protein binding and brain concentrations of antiepileptic drugs in autoptic specimens from 45 epileptic patients.

The free fraction of antiepileptic drugs can, in certain diseases, be greatly increased in the serum. In order to study the significance of this increase for the concentration in the brain, the postmortem concentrations of phenytoin (PT), phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) in the serum (total and free), as well as in specimens of the frontal cortex of 45 epileptic patients who died from various causes, were determined. The postmortem free fractions were higher than reported in the literature and varied considerably from subject to subject. For PT the free fraction was 21.7% (median), for PB 68.0%, for CBZ 33.4%, and for its metabolite CE 53.6%. The values for a control group of 236 otherwise healthy epileptic patients were in agreement with those given in the literature, namely 10.4% for PT, 55.6% for PB, 20.9% for CBZ, and 42.5% for CE. Using a nonparametric correlation coefficient (Kendall T), the concentrations in the frontal cortex of the autopsied patients correlated with the postmortem free serum concentrations, especially for the substances with high protein binding (PT and CBZ), better (PT r = 0.88, PB r = 0.86, CBZ r = 0.87, CE r = 0.79) than with the total concentrations (PT r = 0.69, PB r = 0.80, CBZ r = 0.77, CE r = 0.77). The study indicates that in critically ill patients the determination of the free concentration in serum is indispensable. If treatment is orientated solely on the total concentration, unexpectedly high concentrations in the brain and hence possible intoxication of the patient in the critical or final state can result.

Anticonvulsants↗
PubMed1990

Early determination in the C. elegans embryo: a gene, cib-1, required to specify a set of stem-cell-like blastomeres.

The early somatic blastomeres founding the tissues in the C. elegans embryo are derived in a stem-cell-like lineage from the P cells. We have isolated maternal effect lethal mutations defining the gene cib-1 in which the P cells, P1-P3, skip a cell cycle and acquire the fates of only their somatic daughters. Therefore, the cib-1 gene is required for the specification of the stem-cell-like fate of these cells. The analysis of the development of these mutants suggests that the clock controlling the cell cycles in the early embryo is directly coupled to the fate of a cell and that there must be another developmental clock that activates the determinative inventory for the early decision-making.

Alleles↗
PubMed1990

Killer-cell activity in alcohol-originated diseases of the liver, and the effect of alcohol on the K-cell functions under in vitro conditions.

Non-specific cell immunity and, within it, the change in K-cell activity, can be relevant in alcohol-induced diseases of the liver. It was examined for this reason how alcohol in its different concentrations influences the activity of K-cells under in vitro conditions. Furthermore, the cytotoxic capacity of K-cells was defined in 22 chronic alcoholics and 112 patients with alcohol induced hepatopathies. The latter were divided into subgroups. Cytotoxic capacity of lymphocytes in the peripheral blood was determined in a test against human red blood cells. 123 healthy volunteers made up the control group. A high concentration of alcohol was needed to impede K-cell capacity under in vitro conditions. It is supposed that the gradual growth in K-cell activity registered in cases of alcohol-induced hepatopathy may point--though only indirectly--to the development of an antibody-dependent cellular cytotoxic reaction.

Alcoholism↗
PubMed1987

The glp-1 locus and cellular interactions in early C. elegans embryos.

Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans.

Alleles↗
PubMed1987

Adrenoleukodystrophy in an adult female. A clinical, morphological, and neurochemical study.

A 43-year-old female with adrenoleukodystrophy (ALD) is described, who developed spastic tetraparesis, suffered grand mal seizures, and became stuporous and demented during the last 5 years of her life. Computed tomography revealed symmetrical hypodense lesions in the peritrigonal regions. Adrenal insufficiency was not evident except for skin pigmentation. The ultrastructure of a rectal biopsy specimen showed inclusions with lamellae and interspersed clefts in macrophages of the submucosal layer. At autopsy, the adrenals were found to contain large foam cells filled with similar inclusions. The brain cortex and the spinal cord were histologically normal. However, cerebral white matter exhibited widespread demyelination which spared only the arcuate fibres. In regions of less severe demyelination scattered inflammatory cells were seen. On electron microscopy, aggregates of typical paired leaflets with distinct intermediate lines were demonstrated in perivascular macrophages. Histochemical study showed these cells to contain free as well as esterified cholesterol. Gas chromatographic analysis of very long chain fatty acids (VLFA) from the demyelinated cerebral white matter showed a marked increase of C26:0 fatty acid in cholesterol esters and above-normal values for C24:0 and C24:1 in gangliosides. It is suggested that the condition was a heterozygote form of X-linked ALD. Patients with neurodegenerative symptoms with or without adrenal insufficiency can easily be screened for X-linked ALD by VLFA analysis in blood or cultured fibroblasts.

Adrenal Glands↗
PubMed1987

Intracerebral granular cell tumor.

A case of a primary intracerebral granular cell tumor (GCT) in a 71-year-old woman is reported. The computed tomographic scan showed a contrast-enhancing, noncalcified mass in the left parieto-occipital region. The tumor was operated upon and the histological findings showed a granular cell tumor with mitotic activity. After radiation therapy the patient recovered well. The origin of intracerebrally growing GCT's remains unclear. Involvement of astrocytes is discussed. Primary GCT's of the cerebrum are potentially more malignant than those of the pituitary region.

Aged↗
PubMed1985

Morphology and pathogenesis of pneumoconiosis in dental technicians.

The morphology of pneumoconiosis occurring in dental technicians could be studied by systematic light and electron microscopical investigation of 30 lung preparations from such cases. Diffuse streaky fibrosis and, in some cases, nodular fibrosis was observed together with occasional formation of silicotic nodules that may lead to extensive transformation of the alveolar structure. The etiological relationship between occupational dust exposure and pulmonary changes could be documented by element analysis of dust deposits on histologic sections, and of dusts from grinding and polishing instruments collected in the laboratory. The energy-dispersive X-ray microanalysis used in this study helps to differentiate and delimit this form of pneumoconiosis. The pathogenesis is discussed on the basis of light and electron microscopic results and physicochemical analyses.

Adult↗
PubMed1985

Acute valproate intoxication with fatal outcome in an infant.

A healthy twenty-month-old boy ingested a maximal dose of valproate from which about 750 mg/kg were absorbed. Cerebral coma, which lasted for twenty hrs, was followed by an undisturbed period of approximately sixteen hrs. Death from cardiorespiratory failure due to severe bronchopneumonia occurred 46.5 hrs after the ingestion of the drug. The serum valproic acid concentration reached a peak of 1061 micrograms/ml within three hours, and fifteen minutes before death it had fallen to 187 micrograms/ml. The half-life of 16.6 hrs was within the range usually found. Metabolic acidosis, hypernatraemia and hyperosmolarity could be corrected, unlike the hypocalcaemia, which developed later. Bilirubin, GOT, GPT, gamma-GT, alkaline phosphatase, blood glucose, diastase, urea, creatinine, haemoglobin as well as PT and PTT and the platelet count were all normal. Leucopenia with 1,600 per microliter developed only during the bronchopneumonial stage. The histo-pathological findings were acute hypoxic damage of the myocardium, kidneys and certain neurones of vulnerable areas of the brain (neuronal microvesiculation and tigrolysis) in addition to a severe cerebral oedema in the final stage. A morphological substrate of an acute valproate encephalopathy was not demonstrable. The liver showed no necrosis or cholostasis. The vertebral marrow was inconspicuous. All the results indicate that liver function was not impaired in spite of the initial maximal concentration of valproic acid. In all probability the patient might have survived the acute valproate intoxication had it not been for the bronchopneumonia.

Brain↗
PubMed1984

Genome organization and transcription in archaebacteria.

The genome organization of the archaebacteria is investigated in three model systems: a) rRNA genes of various archaebacteria, b) a plasmid of 15.6 kb from Sulfolobus acidocaldarius which exists in free or integrated form, c) the 59 kb genome of phage phi H of Halobacterium halobium as a model for the unusual structural variability of DNA in this organism. Several variants of this phage have been isolated, their genomes differ by several insertions, a deletion, and an inversion. The frequent inversion and circularization of a 12 kb segment of DNA appears to be linked to the presence of two copies of an IS element at its flanks. DNA-dependent RNA polymerases have been isolated from a large number of archaebacteria including representatives of 4 families of the novel order Thermoproteales . As shown by immunological methods, they are closely related to those of eukaryotes. Two different types of RNA polymerase exist in the two main branches of the archaebacteria. The role of one component of the enzyme of Thermoplasma acidophilum was elucidated using an in vitro transcription system.

Archaea↗
PubMed1983

Structural homology between different archaebacterial DNA-dependent RNA polymerases analyzed by immunological comparison of their components.

The archaebacterial DNA-dependent RNA polymerases have a complex structure containing eight or more components. Immunochemical analysis shows an extensive homology between the components of the enzymes of nine different species. Two enzyme subtypes can be distinguished: that of the thermoacidophilic and/or sulfur-metabolizing archaebacteria with the composition BACDEFGHIJ and that of the methanogenic plus halophilic archaebacteria with the composition ABB'C(D).... Components B and B' of the latter subtype probably evolved by the division of the large component B of the BACD... type enzyme. The existence of the two subtypes corroborates the division of the archaebacteria into two phylogenetic main branches.

Journal Article↗