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R Gebhardt

Publications and source records attributed to R Gebhardt.

At least 127 records · Page 7Linked to original sources
PubMed1986

Specific chromosomal abnormalities characterize four established cell lines derived from malignant human gliomas.

The four permanent human glioma-derived cell lines reported here are the first such lines for which the karyotypes have been followed from the original biopsies through the establishment of the lines in culture. Although ploidy changes were seen, each line retained either distinctive marker chromosomes or the overall original chromosomal distribution allowing the origin of each line to be established with certainty. D-263 MG expresses glial fibrillary acidic protein, all lines except D-245 MG are tumorigenic in athymic mice, and each line displays a unique pattern with respect to in vitro growth parameters and expression of biochemically defined markers, oncofetal antigens and lymphoid-associated markers. D-245 MG and D-259 MG are able to grow in the absence of supplemental glutamine; glutamine synthetase was detected in these cell lines both by immunocytochemistry and by direct assay. Thus, the four permanent human glioma-derived cell lines described here are representative of glioma lines in their general characteristics. D-259 MG retains numerous double minute chromosomes (DMs), D-263 MG contains two marker chromosomes with breaks in 9p, and D-247 MG and D-245 MG with stemlines containing 96 and 89 chromosomes contain eight and six normal copies (respectively) of chromosome No. 7. The retention in these four cell lines of the most common chromosomal abnormalities seen in biopsies of malignant human gliomas provides the opportunity to investigate the meaning of these specific chromosomal changes.

Animals↗
PubMed1986

Differential effect of growth factors on growth stimulation and phenotypic stability of glutamine-synthetase-positive and -negative hepatocytes in primary culture.

In rat liver parenchyma, two subpopulations of hepatocytes can be distinguished by the absence or presence of the marker enzyme, glutamine synthetase (GS). Hepatocytes in the perivenous zone immediately adjacent to the hepatic venules in the liver acinus are positive for GS. Using autoradiography in combination with immunocytochemistry, the response of these two hepatocyte populations (GS positive and GS negative) to a variety of growth factors (defined compounds or complex stimuli) was investigated in vitro. Irrespective of the individual growth-promoting activity (which varied considerably), all stimuli led to much higher labeling indices in GS-negative cells as compared to GS-positive cells. In GS-negative cells, the strongest effect was exerted by serum obtained from partially hepatectomized rats (labeling index, 67%) and the conditioned media of JM1 and JM2 hepatoma cells (63%-82%), followed by a combination of insulin and either norepinephrine (46%) or epidermal growth factor (EGF; 42%). In contrast, serum had the weakest influence on GS-positive cells (0.3%), while the other potent stimuli enhanced the labeling index of these cells by between 6% and 15% within 48 h. The percentage of labeled nuclei was higher in mononucleated than in binucleated GS-positive hepatocytes. The time course of thymidine incorporation was also different for the two subpopulations. Under all growth-promoting conditions, the stimulation of GS-negative cells peaked between 72 and 96 h, while it increased continuously in GS-positive cells for at least 120 h, particularly in the case of serum. In proliferating cultures, both the absolute and the relative number of GS-positive hepatocytes decreased, while no such effect was found in various nonproliferating control cultures maintained at low and high cell density. Similar results were found for GS activity. In contrast, the hormonal induction of tyrosine aminotransferase (TAT) was not affected. It is suggested that these differences in the growth response of GS-positive and -negative cells contribute to the acinar gradient in hepatocyte proliferation that occurs during liver regeneration. Furthermore, the striking phenotypic instability of GS-positive cells that have undergone DNA synthesis and mitosis supports the hypothesis that cellular reprogramming depends on passage through the cell cycle.

Animals↗
PubMed1986

[Effect of aging on the sex distribution of depressive disorders].

The effects of age on sex differences in depression were studied in an inpatient-sample of the Department of Psychiatry, Free University Berlin. The dependent variable depression was defined by nosological classification (ICD) and by the severity of the Depressive Syndrome of the AMP-Rating Scale on admission. With the exception of the 40-49 years olds women were more often diagnosed as depression compared to men, the preponderance of women was significant till the age of 40. With regard to the Depressive Syndrome women manifested a more pronounced symptomatology up to the age of 70. The difference diminished for male and female patients 50-69 years old and changed to a higher score for men older than 70. The results were discussed in comparison to other findings published in the last years.

Adolescent↗
PubMed1985

Dexamethasone restores hormonal inducibility of ornithine decarboxylase in primary cultures of rat hepatocytes.

Induction of ornithine decarboxylase by various hormones was studied in quiescent primary cultures of adult rat hepatocytes maintained in a chemically defined medium. The following results were obtained: Enzyme activity rose transiently during the first day of cultivation in hormone-untreated cells. During this phase, insulin increased ornithine decarboxylase activity. Inducibility by insulin was maintained for more than 40 h only after pretreatment with 0.1 microM dexamethasone. Enzyme activity could be induced by 1 nM insulin and peaked after 7 h. Inducibility by glucagon and growth hormone required pretreatment with the glucocorticoid hormone. Ornithine decarboxylase activity was maximal 5 h after glucagon addition. Concentrations down to 0.1 nM were effective. Pretreatment with dexamethasone was most effective, when the hormone was present during the first 20 h of cultivation. The effect of the glucocorticoid during the pretreatment phase was diminished by colchicine and to a lesser extent by cytochalasine B. We suggest that part of the permissive effect of dexamethasone could be mediated by changes in the cytoskeleton and the function of hormone receptors. The fact that induction of ornithine decarboxylase was exerted by several hormones despite the absence of cell proliferation and DNA synthesis may indicate that polyamine biosynthesis has an important role in the quiescent hepatocyte.

Animals↗
PubMed1985

Sex differences in the psychopathology of inpatients.

In a sample of more than 2000 patients from the Department of Psychiatry of the Free University of Berlin (58.8% men, and 41.2% women), the sex differences in the diagnostic distribution and in the severity of the depressive symptomatology were investigated on the basis of data documented by the AMP system. Due to patient selection by the hospital, men with depressive neuroses were found to be over-represented contrary to expectation; depressive psychoses, however, were prevalent in women as expected. In the total group of patients, depressive symptomatology at the symptom and syndrome levels prevailed in women. Within homogeneous diagnostic groups, depressiveness in minor depressive disorders like depressive neuroses was more severe in women, but in psychotic depression men were more seriously depressed than women. Attempts are made to interpret these findings on the basis of constitution-biological and role-theoretical concepts, but especially on the basis of sex-specific help-seeking behaviour.

Depressive Disorder↗
PubMed1985

Primary culture of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. V. Disturbance of the cellular membrane and bile canalicular ultrastructure induced by chlorpromazine.

In the present paper rat hepatocytes in primary monolayer culture were used to investigate the adverse effects of chlorpromazine (CPZ) at the cellular level. As revealed by thin sectioning many of the ultrastructural alterations were comparable to those described for the isolated perfused rat liver under the influence of CPZ. Alterations comprised short-term effects, such as dilation of the rough endoplasmic reticulum and the nuclear envelope, and long-term effects including huge accumulations of myeloid bodies within the cytoplasm as well as dilation and diverticulation of bile canaliculi. Freeze-fracturing revealed the dislocation of intramembrane particles in the sinusoidal plasma membrane which could be detected as early as 30 min after exposure to CPZ. As judged from filipin cytochemistry, alterations in the cholesterol content seems to play a minor role in the process of membrane damage except at the sinusoidal surface where a reduction of cholesterol content may contribute to the impairment of membrane functions. It is concluded that CPZ exerts its cholestatic effect primarily by a rapid disturbance of the membrane architecture of the sinusoidal surface and secondarily by other interactions with the bile secretory apparatus.

Animals↗
PubMed1983

Glutamate uptake by cultured rat hepatocytes is mediated by hormonally inducible, sodium-dependent transport systems.

Glutamate uptake by rat hepatocytes in primary monolayer culture was found to be mediated by a Na+-independent and by two Na+-dependent transport systems of high and low affinity. Inhibition studies with cysteate and other model amino acids rules out the participation of the neutral amino acid transport systems A, ASC, and N and revealed that the Na+-dependent agencies represent unequivocally anionic transport systems. Na+-dependent uptake of glutamate in isolated hepatocytes was slow compared to the Na+-independent portion, but increased spontaneously during cultivation. In the presence of dexamethasone it was stimulated about 10-fold at the second day of cultivation.

Animals↗
PubMed1983

Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture.

The distribution of glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.1)] among rat liver parenchymal cells in situ and in primary culture was investigated by indirect immunofluorescence using a specific antiserum. In intact liver, the enzyme was found to be localized exclusively within a very small population of the parenchymal cells surrounding the terminal hepatic venules. Other parts of the parenchyma including non-parenchymal cell types did not stain for this enzyme. Heterogeneity was preserved during isolation of liver parenchymal cells and persisted in cultured cells for at least 3 days. Despite alterations in enzyme activity due to the adaptation of the cells to the culture conditions or due to the hormonal stimulation of the enzyme activity, no change in the relative number of cells expressing this enzyme could be detected. This rather peculiar localization of glutamine synthetase demonstrates an interesting aspect of liver zonation and might have important implications for liver glutamine and, more generally, nitrogen metabolism. Furthermore, it raises the question of whether there might be a phenotypic difference among liver parenchymal cells.

Ammonia↗
PubMed1983

[Validity of the syndrome scales in the AMDP-system].

To examine the validity of the syndrome scales of the AMDP system, various diagnostic groups as defined by the ICD were described by these scales and distinguished from each other by discriminant analyses. As a comparison the same diagnostic groups were distinguished using the syndrome scales of the AMP system. The analyses using the AMDP system were performed in a sample of 659 patients of the Psychiatric Clinic of the Free University of Berlin during 1979-1980, the analyses with the AMP system in a sample of 2269 patients of the same clinic during the period 1971-1976. It could be shown that different endogenous and organic psychoses as well as neuroses can be described in their psychopathology and discriminated from each other by means of the syndrome scales of the AMDP system. The validity of the syndrome scales in relation to this criterion could be proved. Moreover, we found a high similarity between the results with the AMDP system and the results with the AMP system, which demonstrates that the two systems compare well.

Adult↗
PubMed1983

[Scale formation in the AMDP (Society for Methodology and Documentation in Psychiatry) system].

The psychopathological and somatic symptoms documented by the AMDP-system on the admission of 1654 patients to the Psychiatric Clinics of the Universities in München und 659 patients in Berlin were factor analyzed. Eight factors could be extracted which describe the psychopathology on eight syndrome-scales. These factors could be cross-validated by factor analyses on random samples. In correspondence with the factors of the AMP-system the following syndromes were found: paranoid-hallucinatory, depressive, psycho-organic, manic, hostility, autonomic, apathy, obsessive-compulsive. For each of the 70 items which were associated with a factor we computed the percentage occurrence and item-scale-intercorrelations, for each of the eight syndrome-scales reliability-coefficients, intercorrelations and T-transformations. For further data-reduction second-order-factors were also computed.

Adult↗
PubMed1983

Disappearance of visible bile canaliculi caused by vinblastine in primary cultures of rat hepatocytes.

Treatment of cultured hepatocytes with vinblastine resulted in the inhibition of the reformation of biliary spaces (at times earlier than 16 h) or in the disappearance of preformed bile canaliculi (at times later than 24 h) detectable on both the light and electron microscopical level. Concomitantly the preferential localization of leucine aminopeptidase around the lucid biliary spaces was lost without any change in the specific activity of this enzyme. Despite these alterations the performance of the cultured cells (e.g., urea synthesis) was not impaired by the exposure to the drug. The effect of vinblastine was mimicked by colchicine, but not by lumicolchicine, indicating that microtubules might play a role in the structural organization of the biliary pole.

Alkaline Phosphatase↗
PubMed1983

Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. III. Properties of the biliary transport of immunoglobulin A revealed by immunofluorescence.

The present study was designed to investigate whether or not the vesicle-mediated, biliary transport of polymeric immunoglobulin A operates in primary cultures of rat hepatocytes. Using immunofluorescence techniques, immunoglobulin A of human or rat origin added to a time-dependent process around and within presumptive bile canaliculi. As a transitory event preceding this accumulation, an intensive particulate fluorescence was detected within the cytoplasm of the hepatocytes. Secretory component could be localized by a faint fluorescence in the cytoplasm and at the margin of bile canaliculi, where the fluorescence was accentuated concomitantly to the accumulation of immunoglobulin A. Translocation of immunoglobulin A could be blocked by an antiserum against secretory component, whereas colostral immunoglobulin A already containing secretory component was not transported. These findings suggest that the pathway for the biliary secretion of immunoglobulin A is active in cultured hepatocytes and provide evidence for the reconstruction of a functionally intact biliary polarity by these cells.

Animals↗
PubMed1983

Depressive syndromes and scales in the AMDP-system.

The Association for Methodology and Documentation in Psychiatry was founded in 1965 by a group of psychiatrists from Germany, Switzerland and Austria. It developed a uniform and comprehensive system for the documentation of psychopathological, somatic, and anamnestic findings, the AMP-System. In 1979 a revised system was introduced, the AMDP-System. In the AMP-System there are 5 suggestions as to syndrome scale construction based on analyses of data of psychiatric clinics in Munich (2 samples), in Zurich (1 sample), and in Berlin (2 samples). The corresponding syndromes of the different solutions are highly intercorrelated. In the AMDP-System final syndrome scales were constructed on the basis of combined samples of the psychiatric clinics of the universities in Munich and in Berlin. The AMDP syndrome scales show a high similarity with the AMP syndrome scales, whereby a good comparability is ensured between older studies using the AMP- and present studies using the AMDP-System. All syndrome scale solutions include, besides 6 or 7 other syndromes, like a paranoid-hallucinatory and a manic syndrome, two syndromes especially pertinent to the assessment of depressive states: the depressive and the apathy syndromes. The syndromes are described and it is shown how they and other syndromes discriminate different depressive diseases (defined by ICD-diagnoses). There is a considerable overlap in psychology between the diagnostic groups - in spite of a remarkable good discrimination of these groups by psychopathological syndromes - therefore the patients were classified de novo by cluster analysis in more homogenous groups regarding psychopathology. The results are illustrated by some "depressive" clusters in comparison to depressive diagnostic groups.

Depression↗
PubMed1983

Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. IV. Disintegration of bile canaliculi and disturbance of tight junction formation caused by vinblastine.

Treatment of cultured hepatocytes with vinblastine or colchicine caused striking perturbations of the structural organization of the biliary pole and of the junctional complexes. During the early hours of cultivation the reassociation of the bile canaliculi was impaired by the drug, whereas at later times in culture preformed canaliculi were disintegrated to small vesicular remnants lacking microvilli. Vinblastine did not impair tight junction formation per se. However, under the influence of the drug, tight junctional strands associated in an atypic manner perpendicular to the upper surface of the hepatocytes, whereas those strands lining the canaliculi were decomposed to smaller entities and dislocated within the lateral membrane. Concomitantly to the structural disintegration of the biliary pole an accumulation of vesicles in the pericanalicular cytoplasm was noted. As indicated by numerous filipin-induced lesions, they were characterized by a high content of membrane cholesterol. The apical pole and the contiguous membrane on the other hand contained only very few filipin-cholesterol lesions. These findings suggest that antimicrotubular drugs impair the fusion of pericanalicular vesicles with the luminal membranes of the canaliculi, thus interrupting the delivery of membraneous material to the apical pole. In addition, microtubules seem to play an important role in the coordinated development and the structural fixation of the biliary pole of cultured hepatocytes.

Animals↗
PubMed1982

[A statistical comparison of the different factor analyses of the AMP-system (author's transl)].

The intercorrelations of five different factor-analytically derived syndrome solutions of the AMP-system were computed. The syndromes were based on the psychopathological symptoms of 2,269 patients on admission to the psychiatric clinic of the Free University of Berlin. The syndromes which were similar in content in the solutions of different clinics could be shown to intercorrelate quite highly. Only the different syndromes of stupor and obsession-compulsion did not show the same high degree of similarity. Between the syndromes of the solution of one clinic as well as between the solutions of different clinics high intercorrelations were computed comparing non-corresponding syndromes; this could be demonstrated for the syndromes of mania with hostility and of apathy with stupor and depression. For building syndromes in the AMDP-system in the near future the aim for independence of the syndromatic scales seems to be important.

Factor Analysis, Statistical↗