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Biomedical subjects

K Hübner

Publications and source records attributed to K Hübner.

At least 91 records · Page 5Linked to original sources

Neuroblastoma X glioma hybrid cells synthesize enkephalin-like opioid peptides.

Partially purified extracts from neuroblastoma X glioma hybrid cells 108CC15 inhibit, like opioids, the prostaglandin E1-evoked formation of cyclic AMP in a dose-dependent manner in the same hybrid cells. The inhibition is prevented by the opioid antagonist naloxone. In addition, the same extract competes with [3H]naloxone and [3H]Leu-enkephalin for binding to opioid receptors of hybrid cell membranes and to a specific antiserum, respectively. The opioid activity in the extracts is destroyed by carboxypeptidase A and leucine aminopeptidase, but not by trypsin. Further purification of the extracts by HPLC, TLC, or high-voltage paper electrophoresis reveals in each case two active fractions which behave like Met- and Leu-enkephalin. The Met-enkephalin-like, but not the Leu-enkephalin-like, fraction is inactivated by treatment with BrCN. Dimethylaminonaphtylsulfonyl (dansyl) derivatives of Met- and Leu-enkephalin correspond to [3H]dansyl derivatives of Met-like substances from hybrid cells. Three to four times as much Met-enkephalin-like as Leu-enkephalin-like material is present in the extract. The overall concentration of opioid peptides in the hybrid cells varies between 0.03 and 1.0 pmol Leu-enkephalin equivalents per mg protein. The amount of opioids in the hybrid cells is strongly dependent on the cell density. The findings suggest that neuroblastoma X glioma hybrid cells contain opioid peptides that are very similar, if not identical, to Met- and Leu-enkephalin. Opioid activity can also be detected in other neuronal cell lines and even in glioma cells.

Alprostadil↗

[Sequential chemotherapy of malignant non-Hodgkin's lymphoma of high degree of malignancy in stages III and IV].

A sequential combination chemotherapy was used in the treatment of advanced high-grade malignant non-Hodgkins' lymphomas (NHL) from July 1978 to August 1980. The lymphomas were classified according to the Kiel-classification. Cyclophosphamide, vincristine, bleomycin, prednisone (phase A) were followed by a combination of adriamycin, cytosine arabinoside, 6-thioguanine and prednisone (phase B). Patients received four cycles of both combinations. No maintenance therapy was given. 20 patients with centroblastic, lymphoblastic or immunoblastic NHL were included in the study. The overall remission rate was 95% (19 out of 20 patients). 15 (75%) patients entered complete remission. The median duration of complete remission was 28.7 months. The probable survival rate of the patients entering complete remission is 64.5% at two years. Clinical prognostic factors, bone marrow infiltration, extralymphatic organ involvement other than skin and a tumor mass greater than 10 cm in diameter in a single location significantly affected remission induction and survival. All patients with favourable prognosis are still alive in unmaintained complete remission 14 to 38 months after start of treatment. Patients with unfavourable prognosis had a complete response rate of 64% and a median survival of 14.8 months.

Adult↗

Production and regulation of enkephalin-like peptides in neuroblastoma x glioma cells.

Partially purified extracts from neuroblastoma x glioma hybrid cells inhibit via opioid receptors the PGE1-elicited formation of cyclic AMP in the same hybrid cell system. The purification of extracts reveals two active fractions very similar to Met- and Leu-enkephalin by several criteria including treatment with cyanogen bromide. On an average, the intracellular concentration of opioids in hybrid cells is 0.1 pmol per mg protein. The concentration is strongly dependent on the cell density. Furthermore, the content in the hybrids of enkephalin-like peptides is specifically elevated by glucocorticoids.

Cells, Cultured↗

Beneficial effect of somatostatin in phalloidin-intoxicated rats. Influence on survival rate, biochemical and morphological data, and 3H-demethylphalloin absorption rate by the liver.

The effect of somatostatin in phalloidin-intoxicated rats was studied. Animals were given phalloidin i.p. 1.2 mg/kg (LD 90-100). Somatostatin, 250 microgram/animal, was administered i.p. in saline 5 min prior and s.c. in protamine-sulphate/ZnCl2 suspension 30 min prior and 30 min after intoxication, unless stated otherwise. In vivo and in vitro uptake studies of the toxin were performed. Liver enzymes (GPT, GLDH) and kallikrein-like activities were determined in blood obtained by orbital venipuncture. Light and electron microscopy was carried out. Somatostatin treatment led to an increase in survival rate. Of the 20 treated rats six died whereas of the 20 untreated animals 18 died. A dose dependency was proven effective when half of the initial dose of somatostatin was given. In vivo and in vitro uptake studies of the toxin demonstrate that somatostatin does not alter uptake rate by rat livers. Liver enzymes remained elevated in treated and control rats. Kallikrein-like activities showed a 61% decline in treated animals whereas they rose up to 120% in controls as compared to pretreatment conditions. Light and electron microscopy reveals less severe lesions in somatostatin-treated animals. A possible interaction of somatostatin in shock development is discussed, phalloidin seems to be a suitable tool for further investigations concerning cell protection by somatostatin.

Alanine Transaminase↗

Dermorphins, opioid peptides from amphibian skin, act on opioid receptors of mouse neuroblastoma x rat glioma hybrid cells.

Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybrid cells. In the presence of 7 nM-[3H]Leu-enkephalin, the concentrations at which they caused 50% inhibition of [3H]enkephalin binding (IC50 values) are 0.1 micro M and 0.3 micro M, respectively. In contrast, the synthetic L-Ala2-dermorphin shows very low affinity for the opioid receptors. In addition, like other opioid peptides, dermorphin and hyp6-dermorphin inhibit the elevation by prostaglandin E1 (PGE1) of the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (IC50 values 0.2 micro M and 0.4 micro M, respectively). The inhibition is prevented by the opiate antagonist naloxone, L-Ala2-dermorphin is at least three orders of magnitude less potent in inhibiting the PGE1-evoked increase in the level of cyclic AMP. The results show that peptides with an amino acid sequence quite different from that of the enkephalins can bind to opioid receptors of the hybrid cells.

Amphibians↗

[Peritoneoscopy and liver biopsy in the diagnosis of liver disease (author's transl)].

In two prospective studies including 962 patients and one retrospective study including 165 patients the problem was investigated, to what extend ultrasonography might change the diagnostic value of clinical examination, peritoneoscopy, guided liver biopsy and blind liver biopsy. It turned out, that liver biopsy is the method of choice in diffuse-parenchymatous disease (e.g. chronic active hepatitis, chronic persistent hepatitis, fatty liver), whereas laparoscopy is to be preferred if focal lesions (e.g. liver carcinoma) are present. Diffuse liver disease was present in 80% of the cases investigated; in this group of patients the diagnostic value of blind biopsy is equivalent to the diagnostic value of guided biopsy. Thus, blind biopsy does yield satisfactory results in most patients if it is possible to differentiate between diffuse and focal disease by ultrasonography. Such differentiation could be achieved in 77-98% of our cases, thus ultrasonography could intake a decrease in numbers of peritoneoscopies and an increase of blind liver biopsy.

Biopsy, Needle↗

Alpha-1-antitrypsin deficiency: fulminant course in early infancy.

A severe course of alpha-1-antitrypsin deficiency in two children with Pi ZZ genotype is demonstrated. Clinically both infants presented with signs indistinguishable from biliary atresia with acholic stools and a low I131-rose bengal excretion over 72 h. Rapid development of liver fibrosis documented by serial liver biopsies, indicated a bad prognosis. The infants died at the age of 6 and 15 months. The extent of fibrosis is estimated to be the most useful prognostic sign in prediction of the probable outcome in alpha-1-antitrypsin deficiency.

Bile Ducts↗

Identity of malonyl and palmitoyl transferase of fatty acid synthetase from yeast. Functional interrelationships between the acyl transferases.

Functional interrelationships between the acyl transferases of yeast fatty acid synthetase were investigated. In binding assays with synthetase modified by 5,5'-dithiobis(2-nitrobenzoic acid), 4--5 malonyl transferase entities per multienzyme complex molecule could be titrated. In the presence of palmitoyl-CoA these malonyl transferases were found inaccessible to malonyl-CoA, whereas the acetyl transferases were reactive towards acetyl-CoA. Between four and five palmitoyl transferase entities per synthetase equivalent were found reactive towards palmitoyl-CoA, the palmitoyl binding being inhibited by malonyl-CoA. Following palmitoyl binding the acetyl transferases were found towards acetyl-CoA. Substrate model assays were consistent with these data. It is concluded that malonyl and palmitoyl transferases are closely coupled enzyme components of the multienzyme complex which are fairly independent of the acetyl transferase entities. The molecular basis for the observed coupling will be given in the following paper.

Acyltransferases↗

Identity of malonyl and palmitoyl transferase of fatty acid synthetase from yeast. 2. A comparison of active-site peptides.

Active-site peptides of malonyl and palmitoyl transferase from yeast fatty acid synthetase were isolated and sequenced to try to prove the hypothesis [J. Ayling, R. Pirson & F. Lynen (1979) Biochemistry 11, 526--533] that both enzymes are identical. For this purpose synthetase modified with 5,5'-dithiobis(2-nitrobenzoic acid) was labelled with either [14C]malonyl or [14C]palmitoyl residues followed by proteolytic digestion of the labelled protein. [14C]Malonyl-peptides were isolated by conventional purification procedures; their structures were determined by a combination of methods. [14C]Palmitoyl-peptide material was purified by high-performance liquid chromatography and the structure determined by solid-phase Edman degradation and other analytical methods. Serine was identified as the acyl acceptor group in both transferases. Comparison of the sequence data available shows that the sequence around the acyl acceptor group in both cases is identical. This proves the identity of malonyl and palmitoyl transferase.

Acyltransferases↗

[The pseudo-Ainhum syndrome].

A 39 year old woman is reported who has congenital constrictions on several fingers and toes as well as on both lower legs. Ainhum and Ainhum-like syndromes are briefly discussed.

Adult↗