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R Gebhardt

Publications and source records attributed to R Gebhardt.

At least 145 records · Page 8Linked to original sources
PubMed1982

Biliary secretion of sodium fluorescein in primary monolayer cultures of adult rat hepatocytes and its stimulation by nicotinamide.

Addition of sodium fluorescein to primary cultures of rat hepatocytes resulted in a rapid uptake of the dye by the hepatocytes and a subsequent accumulation in bile canaliculi-like structures. A similar distribution was obtained with fluorescein diacetate. Concentrations of Na-fluorescein accumulating within canaliculi varied over a wide range, often far exceeding that used in the medium. Ouabain strongly blocked cellular uptake, thus also impairing secretion of Na-fluorescein, whereas colchicine affected neither process. Taurolithocholate had virtually no influence on uptake, but markedly reduced the number of fluorescent canaliculi. Furthermore, fluorescent canaliculi could be discharged by addition of I M-sucrose in Hank's buffer, without affecting viability of the cultured cells. The percentage of canicular structures accumulating high amounts of Na-fluorescein markedly increased during cultivation for 7 days, concomitant with the progressive development of originally small and sporadic canaliculi into an anastomosing network of slender channels. This canalicular proliferation was strikingly reinforced by 20 mM-nicotinamide, resulting in an impressive network of canaliculi within 2-3 days. Nicotinamide also supported the secretion of Na-fluorescein, which could be stimulated further by addition of dehydrocholate. These results suggest that cultured hepatocytes are able to re-create a functional biliary polarity at least with respect to the biliary secretion of Na-fluorescein.

Animals↗
PubMed1982

Alterations in activity and ultrastructural localization of several phosphatases on the surface of adult rat hepatocytes in primary monolayer culture.

Several enzymes associated with the hepatocyte cell surface, alkaline phosphatase (AP), 5'-nucleotidase (5'N), Mg++- and total Na+K+Mg++-ATpase, were assayed and localized cytochemically in order to gain insight into alterations of the plasma membrane components during reassociation of hepatocytes in primary monolayer culture. During a period of 4 days the activities of 5'nucleotidase and alkaline phosphatase increased spontaneously up to three- and four-fold, respectively. Dexamethasone reinforce the rise of alkaline phosphatase activity but retarded the increase of that of 5'nucleotidase. However, after the third day the level of 5'nucleotidase activity converged with the untreated controls. The activities of Mg++- and Na+K+Mg++-ATPase, which closely paralleled each other, remained essentially unchanged throughout cultivation and were not affected by dexamethasone. Cytochemical demonstration of alkaline phosphatase, 5'nucleotidase and Mg++-ATPase, using the lead salt method, revealed the potential presence of reaction product on the whole cell surface. However, the cells did not react uniformly, particularly on bile canalicular membranes. This heterogeneity seems to be due to different stages of canalicular development and to different functional states of the cultured hepatocytes.

5'-Nucleotidase↗
PubMed1982

Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. I. Distribution of filipin-cholesterol complexes during de novo formation of bile canaliculi.

Hepatocytes in primary monolayer culture reconstitute structural intact bile canaliculi sealed by tight junctions. Using filipin as a cytochemical marker for cholesterol-like membrane components in conjunction with the techniques of freeze fracture and thin sectioning, we have studied the distribution of cholesterol during the development of the biliary pole of cultured hepatocytes. It was found that the development of bile canaliculi is characterized in its very early stage by huge accumulations of filipin-cholesterol complexes located at distinct domains of the contiguous membrane. They were surrounded by junction formation zones almost devoid of these complexes, in which the alignment of intramembranous particles takes place. Maturation of the bile canaliculi was accompanied by dispersion of cholesterol within the canalicular membrane and its removal by segregation of cholesterol-rich membrane whorls and vesicles into the lumen. Finally, the luminal membranes, and particularly the areas studied with microvilli, contained only very few filipin-cholesterol complexes. In some cases, these seemed to be still arranged in small clusters. These alterations suggest a crucial role of cholesterol-rich membrane domains during initiation of a biliary polarity. On the other hand, cholesterol-poor (thus probably more fluid) areas might be required for the assembly of tight junctions, and appear to constitute the secretory active apical membrane present in the mature bile canaliculus.

Animals↗
PubMed1982

Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. II. Taurolithocholate-induced alterations of canalicular morphology and of the distribution of filipin-cholesterol complexes.

Hepatocytes in primary monolayer culture treated with taurolithocholate showed distinct ultrastructural changes localized primarily to the bile canalicular membrane. These alterations comprised disturbance and proliferation of tight junctions, dilatation of the canaliculi, loss of microvilli, thickening of the pericanalicular ectoplasm, and bizarre lamellar transformations of canaliculi. In freeze-fracture replicas the lamellae projecting into the canalicular lumen were found to be devoid of intramembranous particles. Localization by the use of filipin of cholesterol in plasma membranes of taurolithocholate affected hepatocytes revealed an extensive accumulation of cholesterol in membranes of dilated canaliculi, and also in outpouchings of the contiguous membrane in the ultimate vicinity. Furthermore, a pronounced segregation of cholesterol-rich membrane material into the lumen of dilated canaliculi and into enlargements of the intercellular space could be observed in thin sections. In contrast, a total absence of cholesterol was noted in the lamellar projections of the bizarre transformed canaliculi. The reliability of these findings and their consequences for the mechanism of taurolithocholate-induced cholestasis are discussed and it is suggested that the incorporation of cholesterol into the canalicular membrane reflects only one aspect of the cholestatic effect of taurolithocholate. An additional aspect seems to comprise the dislocation of membrane bound proteins and perhaps other membrane components. This is probably caused by independent mechanisms.

Animals↗
PubMed1981

[Building syndromes in the AMP-system (author's transl)].

The symptoms of 2269 psychiatric patients on admission, documented by the AMP (PAS) system, were factor-analysed to build syndromes of psychopathology. The nine syndromes could be cross-validated. We believe a useful description of the findings on admission can be made by the following syndromes: paranoid-hallucinatory, manic, psycho-organic, depressive, apathetic, hostile, stuporous, somatic, compulsive. The correlation with other syndromes based on AMP by other scientists is substantial. For each item we computed the percentage of occurrence and the item-scale correlation, and for the syndrome-scales reliability, intercorrelations and T-transformations. We calculated the mean profiles for some diagnostic groups to test some aspects of the validity of the syndromes. It was demonstrated that a differentiation is possible.

Adult↗
PubMed1981

[The potential of psychopathological symptoms to differentiate diagnostic groups (author's transl)].

We investigated the extent psychiatric illnesses can be differentiated by means of psychopathological symptoms. The present condition of 2269 patients was analyzed; they had been admitted to the psychiatric clinic of the Free University of Berlin during 1971-1976, as documented by the AMP (PAS) documentation system. The most frequent diagnosis in the sample was schizophrenia (32%), followed by neurosis (22%), affective psychosis (14%), addiction (6.7%), and organic psychosis (6.2%). We could demonstrate that even such diagnostic groups are usually discernible by symptoms, where the differential diagnosis is often difficult. Organic psychosis vs paranoid schizophrenia and depressive neurosis vs depressive psychosis can be determined, but manic syndromes in schizoaffective psychosis vs manic syndromes in affective psychosis are hardly discernible. The potential to differentiate, however, only pertains to diagnostic groups, since many individual patients cannot accurately be classified into diagnostic groups by psychopathological symptoms alone. Only a few symptoms are pathognomonic, and if there are pathogomonic symptoms characterizing a diagnostic group, only a few patients in this group show these symptoms. These results indicate, at least for the high number of patients without severe and typical symptomatology, that we must: 1. Achieve better differentiation on the diagnostic axis "psychopathology" by means of empirically derived syndromes instead of isolated symptoms. 2. Use other diagnostic axes (like etiology and course) for differential diagnostic purposes.

Adult↗
PubMed1981

[The problem of insuring the diagnosis of psycho-organic syndrome. A comparison between medical judgments and psychometric test results (author's transl)].

A comparison was made between diagnostic decisions made by psychiatrists about memory and affective disturbances which are assumed to be typical of Psycho-Organic Syndrome and the results of psychometric evaluations of mental functioning. Some correlations could be demonstrated, especially for memory. However, the classification of individual patients showed a high percentage of different assignments between inferences of psychiatrists and test results; very often the patient was categorized as disturbed by the psychiatrist but not by tests. The claim to replicate the medical diagnosis by means of special testing of mental disorders has been critically discussed and rejected. The main goal of psychometric testing in this field seems to be a differential analysis of the performance of patients which is the basis for goal-oriented training programs.

Adolescent↗
PubMed1979

Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes.

Parenchymal cells from adult rat liver, cultured in perifused monolayers, increased the levels of urea-cycle enzymes between 15% and 60% in response to glucagon within 24 h. This stimulation was drastically enhanced by the simultaneous presence of dexamethasone, especially in the case of argininosuccinate synthetase and argininosuccinate lyase, which increased nearly threefold. Dexamethasone itself produced only negligible stimulation, but exerted a similar effect on the stimulatory action of glucagon, if it was exclusively present during 6 h prior to the glucagon treatment, suggesting a permissive action of this hormone. The effect of glucagon, particularly in the presence of dexamethasone, was mimicked by dibutyryl adenosine 3':5'-monophosphate, whereas epinephrine was ineffective. All stimulations induced by hormones or dibutyryl adenosine 3':5'-monophosphate were abolished by cycloheximide, suggesting the involvement of protein synthesis in the induction process. Using the usual culture technique with a discontinuous supply of medium no significant effect of glucagon and dexamethasone could be measured. This striking difference between both culture systems indicates that perifusion is the more adequate in vitro system for studies of the regulation of enzyme levels. Possible reasons for the failure of hormonal stimulation of urea-cycle enzymes in normal monolayer culture are discussed.

Animals↗
PubMed1978

[Comparison of k therapies after determination of success and failure].

To compare k therapeutic methods, N patients are suggested to be assigned to k therapies at random. The effect of each therapy is rated to be present or absent. The resulting k x 2 contingency table is evaluated according to one of the following questions: 1) Do the k therapies differ in their effects? 2) Is a given therapy more effective than the k-1 remaining therapies? 3) Is a given therapy more effective than a competitive therapy? The methods are exemplified by a numerical example from treatments of schizophrenics.

Adolescent↗
PubMed1977

AMP (PAS) and BPRS: a comparison of two assessment methods.

The aim of this investigation was to contribute to the validation of the AMP(PAS) system. As a criterion we used the BPRS because it has been accepted as one of the most widely used scales in the English-speaking countries. Our study includes the following steps: a) comparison of AMP syndromes and BPRS dimensions by computation of a factor analysis of both scales; b) comparison of each homogeneous group found by cluster analysis techniques of the AMP with its values on the BPRS: c) comparison of discriminative power of both scales concerning different groups (nosological or found by cluster analysis) by discriminant analysis. In a sample of 70 female patients with acute psychiatric symptoms we found that both scales describe psychopathological phenomena and classify patients in a very similar way. However, we were able to classify patients into homogenous groups by cluster-analysis techniques in a more consistent manner with AMP than with BPRS. Both scales gave better results in description and classification of psychoses than of neuroses, although the AMP system separates psychotic patients from neurotic patients more accurately than the BPRS. Our results suggest that the AMP system permits a more differentiated psychopathological description and a more accurate and consistent classification of psychiatric patients than the BPRS, at least in the special patient sample used for this investigation.

Adjustment Disorders↗