Search PubMed⌕ Search

Biomedical subjects

R Schnabel

Publications and source records attributed to R Schnabel.

At least 91 records · Page 5Linked to original sources
PubMed1994

glp-1 and inductions establishing embryonic axes in C. elegans.

Two successive inductions specify blastomere identities, that is complex cell lineages and not specific tissues, in a major part of the early C. elegans embryo. The first induction acts along the anterior-posterior axis of the embryo and the second along the left-right axis. During the first induction a specific lineage program is induced in the posterior of the two AB blastomeres present in the four cell embryo. During the second induction, almost all of the left-right differences of the embryo are specified by interactions between a single signalling blastomere, MS, and the AB blastomeres that surround it. In both cases the inductions break the equivalence of pairs of blastomeres. The inductions correlate with the cell-cell contacts to the inducing blastomeres. The stereotype cleavage patterns of the early embryo results in invariant cell-cell contacts that guarantee the specificity of the inductions. Both inductions are affected in embryos mutant for glp-1 suggesting that in both cases glp-1 is involved in the reception of the signal.

Animals↗
PubMed1994

Gastric antral vascular ectasia: a case report of a 10 year follow-up with special consideration of histopathological aspects.

The diagnosis of gastric antral vascular ectasia (GAVE) was made in a 67 year old patient with a ten year course of the disease, which was characterized by non-ulcerous dyspeptic symptoms in its early phase. The patient was treated successfully by antrectomy. The morphologic findings in the biopsy material ten to eight years before the operation corresponded with those of gastritis type C. The highly characteristic morphologic findings of sinusoidal capillary ectasia and multiple vascular thromboses appeared only in later biopsies taken during the work-up for iron deficiency anemia. The cause of the mucosal alterations was an acquired submucosal vascular anomaly (malformation).

Aged↗
PubMed1993

Antibody-dependent cell-mediated cytotoxicity (ADCC) in Parkinson's disease.

The possible role of a non-specific cell-mediated immune reaction in the pathogenesis of Parkinson's disease (PD) is discussed. It was found that the killer cell activity of PD patients below 60 years of age was significantly lower than in the older age groups or in the age-matched control group. On the other hand, it was also found that the killer cell activity of PD patients with severe symptoms (Hoehn-Yahr's IV, V stage) was significantly higher than that of the milder cases. These results support the hypothesis that an ADCC reaction--mediated by the killer cells--may play a role in the pathogenesis of PD.

Aged↗
PubMed1993

[Solitary intracranial late metastasis of a granulosa cell tumor of the ovary. Case report and review of the literature].

A 75-year old patient was admitted to hospital in June 1989. She was suffering from headache since three months. In the neurological examination a mild hemiparesis on the left side, personal changes and apractic disturbances could be found. 10 years before a granulosa-cell tumour of the left ovary was extirpated, postoperatively the patient received radiation and polychemotherapy. CT-scan and MRI of the head showed a tumour parieto-occipital on the right hemisphere with multiple cystic and solid areas. The tumour was extirpated in toto. The postoperative course was uneventful. Primary tumour of the left ovary and intracranial metastasis showed the same histological findings.

Aged↗
PubMed1993

Postmortem concentrations of phenobarbital, carbamazepine, and its metabolite carbamazepine-10,11-epoxide in different regions of the brain and in the serum: analysis of autoptic specimens from 51 epileptic patients.

Postmortem concentrations of phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex, and white matter, as well as cerebellum) of 51 deceased epileptic patients. The concentrations of PB and CBZ in the frontal cortex were approximately 1.4 times higher, and of CE were 1.1 times higher than the total concentrations in the serum. Furthermore, the concentrations of PB in the frontal cortex were approximately 2.1 times, of CBZ were 4.5 times, and of CE were 2.1 times higher than the free concentrations in the serum. The distribution of the three substances in the brain is rather homogeneous and seems to follow basic physicochemical principles. This means that the concentrations of the substances in the white matter are, depending on their lipophilicity, modestly but significantly higher than in the cortex. Small and in part statistically significant concentration differences between different regions of the cortex and also of the white matter may be explained by differences in the lipid content of the respective regions and by the lipophilicity of the respective substance. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical to those in the frontal cortex. Remarkably increased or decreased concentrations were not observed in any region of the brain.

Adolescent↗
PubMed1992

Cloning of human tumor cell lines in porous glass capillary tubes: a further development of the human tumor stem cell assay.

The conventional human tumor stem cell assay for cloning tumor cells for drug sensitivity testing is limited by its inability to test drug combinations. In an attempt to overcome this limitation, we cloned tumor cell lines within porous glass capillary tubes. In contrast to plastic porous tubes, the porous glass membranes were transparent, and colony formation could be judged on an inverted microscope. Human as well as animal cell lines showed sufficient colony growth. Colonies formed within these porous tubes were homogeneously distributed, and their morphology was similar to those formed in the common stem cell assay. Cloning efficiency and colony size depended on the mean pore diameter of the glass membrane, with best colony growth within tubes with a pore diameter ranging from 8.5 nm to 14 nm. A linear relationship between number of cells seeded and number of grown colonies could be demonstrated for the cell lines MDA-231 and Colo 201. Colony growth achieved within porous glass capillary tubes is comparable to that achieved in Petri dishes and in nonporous tubes. We conclude that the porous capillary cloning system meets the basic suppositions for a quantitative cloning assay. Moreover, the porosity of the glass membrane offers the possibility of variable perfusion of medium and drugs. Further investigations will focus on various perfusion modalities and chemosensitivity testing.

Animals↗
PubMed1992

Nuclear and mitochondrial changes of muscle fibers in AIDS after treatment with high doses of zidovudine.

Zidovudine (formerly azidothymidine) is a potent inhibitor of the human immunodeficiency virus (HIV) reverse transcriptase and represents the first approved drug showing clinical efficacy in HIV-associated diseases. However, considerable toxicity causing macrocytic anemia, neutropenia, and myopathy has been reported, with severe mitochondrial alterations as a special feature of this myopathy. The mitochondrial changes are consistent with the fact that zidovudine acts as an inhibitor of the mitochondrial gamma-polymerase. Electron microscopically, we could confirm the presence of severely altered mitochondria in a 32-year-old male, who developed a necrotizing myopathy after daily administration of 1,000 mg zidovudine over a period of 15 months. In addition, there were even more severe nuclear changes that, for the most part, have not been documented electron microscopically in HIV-related myopathy either with or without zidovudine treatment, especially in non-necrotic and non-regenerating fibers. Since various in vitro studies have shown interference of zidovudine with nuclear DNA metabolism even in human cell lines, we assume that the nuclear changes that we observed are at least in part related to zidovudine treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Aminopeptidases in the circumventricular organs of the mouse brain: a histochemical study.

The localization of four membrane-bound aminopeptidases--aminopeptidase A, aminopeptidase M, dipeptidylpeptidase IV, and gamma-glutamyl transpeptidase--known as characteristic enzymes of the blood-brain barrier was studied in the microvasculature of some circumventricular organs of the mouse brain (subfornical organ, area postrema, choroid plexus, and neurohypophysis). Enzyme activities were demonstrated histochemically in chloroform-acetone-pretreated cryostat sections applying an azo-coupling method. Reactions were evaluated using light microscopy and end-point microdensitometry. The results revealed differences in microvascular enzyme pattern between circumventricular organs and regions having a blood-brain barrier. Moreover, the cytochemical picture of the circumventricular organs themselves was not uniform. Dipeptidylpeptidase IV reaction showed a strongly reduced activity in the microvessels of all studied circumventricular organs. On the other hand, aminopeptidase M seemed to be present in both the leaky and the tight capillaries. Only a low activity of aminopeptidase A was found in parts of the choroid endothelium and the subfornical organ microvasculature. gamma-Glutamyl transpeptidase could neither be detected in the capillary part of the choroid plexus nor in the neurohypophysis. We are led to conclude that at least dipeptidylpeptidase IV might be involved in special mechanisms of the blood-brain barrier.

Aminopeptidases↗
PubMed1992

Postmortem concentrations of phenytoin in different regions of the brain and in the serum: analysis of autoptic specimens from 24 epileptic patients.

Postmortem concentrations of phenytoin (PHT) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex and white matter, as well as cerebellum) of 18 epileptic patients who died following chronic diseases (group A) and of six otherwise healthy epileptic patients who died suddenly and unexpectedly (group B). The free concentrations in the serum correlated considerably better (r = 0.987) than the total concentrations in the serum (r = 0.871) with the concentrations in the frontal cortex. The concentrations in the frontal cortex were about nine times that of the free serum concentrations. The data show that the PHT concentrations in the frontal, temporal and occipital cortex largely agree. The concentrations in the white matter were significantly higher (frontal region 54%, temporal region 30%, occipital region 36%) than in the cortex. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical with those in the frontal cortex. Regression analysis showed that on comparable total serum concentration the patients of group A had significantly higher free serum concentrations and significantly higher concentrations in the frontal cortex than the patients of group B. In respect of the concentration ratios cortex to serum free and in regard of the local distribution of PHT in the brain no difference, however, was found between those patients who died from chronic diseases and those who died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Relationship between the immune system and the diseases of the central nervous system.

Considering the eventual role of non-specific cell-mediated immune reactions in the pathogenesis of Parkinson's syndrome based on the destruction of dopaminergic cells of the substantia nigra the killer cell activity of patients suffering from this disease has been examined. According to the results the killer cell activity of Parkinson patients is significantly lower in the age group below 60 years as compared to the higher age groups. When comparing the age groups below 60 years, significantly lower activity was measured in the patients than in the controls. Killer cell activity is significantly higher in patients suffering from more severe conditions (Hoehn-Yahr's stage IV-V) when compared to the milder cases. These results suggest the possibility that killer cell-mediated ADCC reaction may play a role in the pathogenesis of the disease. The results of these examinations open new therapeutic perspectives. It may be hoped that, as a result of our increasing knowledge and technical progress in immunology, the damaged immune system could be selectively influenced and target specific immune therapy could be used in the near future by means of for instance inactivations of cytotoxic cells, elimination of antibodies or other immunological methods.

Age Factors↗
PubMed1991

[Serum aminoterminal type III procollagen peptide level and killer cell activity in patients with alcoholic liver diseases].

The authors examined the aminoterminal type III procollagen peptide level of serums and killer-cell activity peripheric blood lymphocytes with 75 patients suffering from ethanol originated liver diseases as well as control samples from 40 healthy volunteers. Determination of type III procollagen peptide (Fab) took place by the RIA method. The cytotoxic activity of killer-cells was tested against human red blood cells. Both in fatty liver and chronic alcoholic hepatitis the level of type III procollagen peptide increased, while in liver cirrhosis the same level reached a value three times of the normal. At the same time in cirrhosis hepatitis an increased killer-cell activity could be observed. Type III procollagen peptide values were also analysed in view of the cytotoxic capacity of killer-cells. At first ill, then healthy control individuals were divided into three groups according killer-cell activity values. Results have shown that in the group with a high level killer-cell activity average type III procollagen peptide values were significantly greater as compared to those of the medium or low level activity groups. These results might indicate a relation between a conditional antibody-dependent cellular cytotoxicity reaction and increasing collagen synthesis.

Female↗
PubMed1991

Cellular interactions involved in the determination of the early C. elegans embryo.

Classical work implied that early nematode embryogenesis is completely mosaic. This view was lately challenged by the demonstration that in C. elegans an early interaction has to occur to induce the production of muscle from a blastomere. Here, early embryonic blastomeres were inactivated by laser microsurgery. The cell lineages of irradiated embryos were compared to those of intact embryos. It is shown that one blastomere, MS, is required for the specification of mesodermal pharyngeal fates and another blastomere, P2, for the specification of hypodermal fates from the descendants of the AB blastomere, whereas the proper specification of the nervous system requires the presence of both. The irradiation of a third blastomere shows that interactions also occur within the ectoderm. I propose that the body plan of the C. elegans embryo may be established by two primary signals followed by secondary interactions. The suggested mechanisms are reminiscent of those involved in amphibian development.

Animals↗
PubMed1991

Early determinative events in Caenorhabditis elegans.

Classical developmental biology has distinguished two major modes of embryogenesis, determinate and indeterminate. Nematodes have been considered the chief paradigm for determinate and cell-autonomous development, but recent experiments on the early development of Caenorhabditis elegans suggest that most blastomeres of this nematode are, in fact, determined by interactions.

Animals↗
PubMed1991

Suppressors of the organ-specific differentiation gene pha-1 of Caenorhabditis elegans.

The embryonic lethal gene pha-1 of the nematode Caenorhabditis elegans is required for late differentiation and morphogenesis of the pharynx in the developing embryo. Revertants of two temperature-sensitive alleles of pha-1 were isolated with the aim of obtaining mutations in genes that interact with pha-1. By various methods of mutagenesis, chemical, X-ray, transposon, or by spontaneous reversion, 220 recessive revertants were obtained, defining three complementation groups. The largest, sup-35 on linkage group (LG) III, maps close to but is separable from pha-1. This suppressor can exert its effect either maternally or zygotically to allow survival of pha-1(ts) embryos. The other two, sup-36 and sup-37, are required zygotically and map on LGIV and LGV, respectively. We have not noted a phenotype distinguishing any of the suppressors from wild type except for suppression of pha-1. That suppression is the null phenotype of at least sup-35 is indicated by the high frequency of mutation and by the fact that heterozygotes carrying sup-35 and a deficiency spanning the locus are also able to suppress. Five spontaneous mutations in sup-35 were found to be associated with recombination.

Animals↗
PubMed1991

Familial Alzheimer disease: a large, multigeneration German kindred.

A German family with 21 members affected by Alzheimer disease (AD) was studied clinically and genetically. The diagnosis was histologically verified in three affected family members. Ancestors were traced through seven generations to a couple residing in East-Westfalia during the middle of the 19th century. Dementia was often accompanied by extrapyramidal features and myoclonus. No cases of Down syndrome or hematologic malignancy occurred in this family. Clinical manifestations, temporal progression, neurological testing, and neuropathological features do not differ from the more common sporadic form of AD. The inheritance pattern is most consistent with autosomal-dominant transmission.

Aged↗
PubMed1991

Autoantibody against liver cell membrane and killer cell activity in chronic liver diseases.

The aim of our present study was to examine the ADCC reaction against liver cell in various chronic liver diseases on the basis of indirect evidence. Forty-nine liver patients and one hundred and twenty-three healthy controls were examined. Anti-LSP autoantibody was determined on rat liver membrane by using the indirect immunofluorescent method. On the other hand, Killer-cell activity against human erythrocyte target cells was established in the lymphocytes of peripheral blood. Anti-LSP autoantibodies were demonstrated in seven patients and were associated with the high Killer-cell activity in six cases. Specific ADCC reaction to liver cell membrane can be assumed if anti-LSP autoantibody presence is topped with increased Killer-cell activity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1991

[Therapy-induced cerebro-renal oxalosis?].

Report on three cases of a cerebro-renal oxalosis. The clinical picture was characterized by subacutely appearing coma and cerebral paroxysms. Death occurred due to break-down of cerebral regulation. In all three cases the post-mortem examination showed massive subendothelial depositions of double refractive crystals in the cerebral vessels, in particular in the stem ganglia regions and in the renal tubuli. The crystals showed several features typical for calcium oxalate. The clinical picture appears as an infrequent complication within intensive medicine, in connection with parenteral administration of xylit. Differential diagnosis, pathogenesis and possible cofactors are discussed.

Aged↗