Search PubMed⌕ Search

Biomedical subjects

K Fink

Publications and source records attributed to K Fink.

At least 91 records · Page 5Linked to original sources
PubMed1987

Facilitation of serotonin (5-HT) release in the rat brain cortex by cAMP and probable inhibition of adenylate cyclase in 5-HT nerve terminals by presynaptic alpha 2-adrenoceptors.

Stimulation-evoked tritium overflow was examined in superfused rat brain cortex slices (stimulus: electrical impulses; 3 Hz) and synaptosomes (stimulus: potassium 12 mmol/l) preincubated with 3H-5-HT. 1. In slices and synaptosomes, the evoked 3H overflow was facilitated by forskolin and 8-Br-cAMP, but was not affected by AH 21-132 (an inhibitor of cAMP phosphodiesterase; cis-6-(p-acetamidophenyl)-1,2,3,4,4a,10b-hexahydro-8,9-dimethoxy-2-methylbenzo [c] [1,6]-naphthyridine). In the presence of AH 21-132, the facilitatory effect of forskolin on evoked overflow was increased. 2. In slices, AH 21-132 or combined administration of forskolin plus AH 21-132 did not change the percentage of basal or evoked 3H overflow represented by unmetabolized 3H-serotonin (about 30% and 60%, respectively). 3. In slices, cocaine or 6-nitroquipazine, an inhibitor of serotonin uptake, did not influence the increase in evoked overflow produced by forskolin plus AH-21-132. Forskolin plus AH 21-132 did not alter the inhibitory effect of serotonin (examined in the presence of 6-nitroquipazine) and the facilitatory effect of metitepin (a serotonin receptor antagonist) on evoked 3H overflow, but considerably decreased the inhibitory effect of clonidine or B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[5,4-d]-azepine). The present results suggest that the serotoninergic nerve terminals in the rat brain cortex are endowed with an adenylate cyclase, which is negatively coupled to the presynaptic alpha 2-adrenoceptors, but is not linked to the presynaptic autoreceptors.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Effects of RU 24969 on serotonin release in rat brain cortex: further support for the identity of serotonin autoreceptors with 5-HT1B sites.

Rat brain cortex slices and synaptosomes preincubated with [3H] serotonin were used to study the effects of the 5-HT1 receptor agonist RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole) on the electrically (3 Hz) evoked 3H overflow from superfused slices and the potassium (12 mmol/l)-evoked 3H overflow from superfused synaptosomes. In slices superfused in the presence of 6-nitroquipazine (an inhibitor of serotonin uptake), the electrically evoked overflow was inhibited by RU 24969 and the reference compound serotonin (maximum inhibition obtainable: by about 50 and 60%, respectively; IC25 and IC30: 33 and 150 nmol/l, respectively). The inhibitory effect of RU 24969 on the evoked overflow was attenuated by cyanopindolol (a beta-adrenoceptor blocker with antagonistic properties at 5-HT1 receptors). In the absence of 6-nitroquipazine, RU 24969 did not increase the basal efflux and tended to be more potent in inhibiting the evoked overflow than in the presence of 6-nitroquipazine. The correlation of the release-inhibiting potencies of serotonin receptor agonists with their affinities for 5-HT1B binding sites (Engel et al., 1986) was slightly improved by inclusion of RU 24969, whereas that with the affinities for 5-HT1A binding sites (which was worse than the former correlation) was not changed. In synaptosomes superfused in the presence of 6-nitroquipazine, RU 24969 inhibited the potassium-evoked overflow. The inhibitory effect of RU 24969 was antagonized by cyanopindolol, which by itself did not affect the evoked overflow. It is concluded that RU 24969 acts as a highly potent agonist (with an intrinsic activity of about 0.8) at the presynaptic serotonin autoreceptor in the rat brain cortex. Furthermore, the present results support the assumption that these receptors belong to the 5-HT1B subtype.

Animals↗
PubMed1986

[Pathogenesis and therapy of rheumatoid inflammation].

By initial 3H-thymidine labelling an enhanced monocyte proliferation in the bone marrow of patients with rheumatoid arthritis is demonstrated. The significant monocyte proliferation correlates positively with the erythrocyte sedimentation rate but shows a negative correlation with age. The high significance of the mononuclear phagocyte (MNP) system in the pathogenesis of rheumatoid arthritis is seriously underlined by the experimental findings in our allergic arthritis model. Benoxaprofen as an inhibitor of the lipoxygenase pathway and of the inflammatory monocyte influx significantly suppresses the experimental allergic synovitis. These findings stress upon the important role of the MNP-system in the pathogenesis of rheumatoid arthritis and demonstrate the significance of the monocytes/macrophages as an important target-cell system for antirheumatic drugs.

Adolescent↗
PubMed1984

Vindesine in advanced breast cancer, lymphoma and melanoma. A Colorado Clinical Oncology Group study.

Fifty-six patients with advanced metastatic carcinoma of the breast, melanoma and lymphoma were treated with the new vinca alkaloid vindesine in a prospective Phase II study. The dose was 3 mg/M2 by I.V. bolus once a week for a minimum of two doses. Patients who failed to respond to four I.V. doses were treated with 48-h intravenous infusions at a dose of 1.5 mg/M2 per 24 h. Of the 26 evaluable patients with breast cancer, there were only two incomplete responses and four patients who experienced stabilization of disease. Of the 12 evaluable patients with melanoma, no responses were seen with four patients experiencing stabilization of disease. Of the 11 patients with non-Hodgkin's lymphomas, there was one complete remission which persisted for 26 months and two partial remissions. No additional responses were seen when the mode of administration was changed to 48-h infusion in three patients with breast cancer, five patients with melanoma and one patient with lymphoma. Significant toxicities included neutropenia in 24 patients and nausea and vomiting in two patients. There were no drug related deaths. Previously reported experience with vindesine in these tumors is reviewed as well.

Adolescent↗
PubMed1984

Combination chemotherapy with BCNU, vincristine, mitomycin-C and prednisone in refractory breast carcinoma. A pilot study.

21 patients with metastatic breast cancer, refractory to conventional agents, were treated with a combination of BCNU, vincristine, mitomycin-C and prednisone given every 4 weeks. Only three of the nineteen (15.8%) evaluable patients were observed to have a partial remission, whereas four experienced stabilization of tumor. The sites which responded included skin lesions in two patients and a pleural effusion in 1 patient. This combination resulted in moderate to severe thrombocytopenia in five patients, but was otherwise well tolerated. This pilot study therefore suggests that these four agents in the schedule and doses given do not appear to be superior to any of these agents used singly for advanced, refractory breast cancer.

Adenocarcinoma↗
PubMed1983

[Immunomodulation with symptomatically effective antirheumatic agents].

As antigen-presenting and/or monokine-secreting cells, macrophages play a major role in immunoregulation. Proteases of macrophage origin (cathepsin G, elestase , thrypsin and pronase) act on cell surfaces of different cell lines, inducing cell activation, e.g. of B-lymphocytes. T-lymphocytes might be stimulated by the activating factor LAF. Other macrophage products (CSF, FIM ) control monocyte production in bone marrow. While lymphocytes are the target cell lines for classical immunosuppressive agents, mononuclear phagocytes are kept for the major cell population affected by antiinflammatory drugs. The presented study outlines the significance of the mononuclear-phagocyte-system in antiinflammatory drug research. The inhibiting potency of antiinflammatory drugs on the monocyte-macrophage cell line as an additional immunoregulatory principle should be discussed.

Animals↗
PubMed1983

[Immunomodulation by symptomaticly active antirheumatic agents].

As antigen-presenting and/or monokine-secreting cells, macrophages play a major role in immunoregulation. Proteases of macrophage origin (cathepsin G, elestase, thrypsin and pronase) act on cell surfaces of different cell lines, inducing cell activation, e.g. of B-lymphocytes. T-lymphocytes might be stimulated by the activating factor LAF. Other macrophage products (CSF, FIM) control monocyte production in bone marrow. While lymphocytes are the target cell lines for classical immunosuppressive agents, mononuclear phagocytes are kept for the major cell population affected by antiinflammatory drugs. The presented study outlines the significance of the mononuclear-phagocytesystem in antiinflammatory drug research. The inhibiting potency of antiinflammatory drugs on the monocyte-macrophage cell line as an additional immunoregulatory principle should be discussed.

Animals↗
PubMed1983

[Pharmacology of potential antidepressants of the N-L-phenylalanyl-beta-phenylalkylamine class].

The spectrum of the pharmacological activities of N-L-phenylalanyl L-2-amino-1-phenylpropane (13), the most active representative of the investigated L-N-phenylalanyl-beta-phenylalkylamines 11-20, comprises adrenergic (noradrenaline potentiation on the vas deferens of the rat, tetrabenazine antagonism in the mouse), as well as cholinergic blocking (acetylcholine antagonism on the jejunum of the rat, oxotremorine antagonism in the mouse, anti-aggressive activity in isolated mice) and localanesthetic properties (inhibition of conduction in the ventricular strip of the frog heart) as described for antidepressants. In its pharmacological behavior 13 meets rather an antidepressant than a psychotonic drug. The conception of a partial metabolic liberation of the latent amphetamine component in 13 and a certain contribution of amphetamine to the effect of 13 is supported by the fact that at higher dosages a shortening of the hexobarbital narcosis and an increase of the spontaneous activity in mice is seen.

Animals↗
PubMed1980

Additional data from two kindreds with genetically induced deficiencies of erythrocyte pyrimidine nucleotidase.

Two subjects, not previously reported in detail, had severe inherited deficiencies of erythrocyte pyrimidine nucleotidase. This was manifested hematologically by moderate hemolytic anemia with splenomegaly, morphologically by punctate basophilic stippling of Wright's stained erythrocytes, and biochemically by intraerythrocytic accumulation of pyrimidine nucleotides, elevated concentrations of reduced glutathione, and partial deficiencies of ribosephosphate pyrophosphokinase. All 5 of their children were asymptomatic and phenotypically normal except for intermediate reductions in activities of pyrimidine nucleotidase consistent with heterozygosity for an autosomal recessive defect.

5'-Nucleotidase↗
PubMed1979

Purine metabolism in microplasmodia of Physarum polycephalum.

The uptake and utilization of purine nucleosides and purines in microplasmodia of Physarum polycephalum were investigated. The results revealed a unique pattern, namely that exogenous purine nucleosides are readily taken up and metabolised, while free purine bases are hardly taken up. The pathways of incorporation have been elucidated in studies with whole cells and with cell-free extracts. The ribonucleosides (adenosine, inosine and guanosine) can be converted into ribonucleotides in two ways; either directly catalysed by a kinase or by a phosphorolytic cleavage to the free base (adenine, hypoxanthine and guanine respectively) which can then be activated by a purine phosphoribosyltransferase. Apparently the purine phosphoribosyltransferases do not react with exogenous purine bases. The deoxyribonucleosides (deoxyadenosine, deoxyinosine and deoxyguanosine) are also phosphorolysed by purine nucleoside phosphorylase to adenine, hypoxanthine and guanine respectively. A portion of deoxyadenosine is directly phosphorylated to dAMP. It appears that only a minor part of the soluble nucleotide pool can be synthesised from exogenous supplied nucleosides and that none of the deoxyribonucleosides specifically label DNA. There is no catabolism of the purine moiety. In agreement with the above findings, we have found that analoguees of purine nucleosides are more toxic than their corresponding purine base analogues.

Adenosine↗
PubMed1979

Cell-mediated cytotoxic responses of spleen cells from mice bearing primary, chemically induced tumors.

Sarcomas were induced in C57BL/6 mice by using 3-methylcholanthrene. Spleen cells taken from these mice bearing primary, chemically induced tumors and from matched control mice were assessed for the capacity to generate cell-mediated cytotoxic cell activity after in vitro sensitization. Spleen cells from tumor-bearing mice generated strong cell-mediated cytotoxic responses against alloantigens and antigens on syngeneic cells.

Animals↗
PubMed1978

Pyrimidine metabolism in microplasmodia of Physarum polycephalum.

If microplasmodia of Physarum polycephalum are exposed to 14C-labelled pyrimidine nucleosides or bases, an unusual pattern of metabolism is found. Only the nucleosides are taken up. Analysis of the distribution of the radioactivity in the cells revealed that ribonucleosides and deoxyribonucleosides are incorporated into nucleotides; however, a substantial catabolism takes place. Thus incubation with [2-14C]pyrimidine nucleosides readily gives rise to [14C]O2, particularly in the case of [2-14C]thymidine. Due to this a significant part of the trichloroacetic-acid-insoluble radioactivity from exogenously supplied [2-14C]thymidine is not associated with DNA. The pattern of labelling of nucleoside triphosphates from exogenously supplied nucleosides indicated that the de novo synthesis of nucleotides was only partly repressed. An unusual conversion of deoxycytidine into cytidine was noted. Enzyme analysis on cell-free extracts revealed that pyrimidine nucleosides can be salvaged by kinases and that their initial catabolism is initiated by hydrolases. Incubation of microplasmodia with pyrimidine analogues showed that only nucleoside analogues are toxic. The experimental results have led us to propose a scheme for the metabolism of pyrimidine nucleosides and bases in Physarum polycephalum.

Biological Transport↗
PubMed1977

Synthesis of transfer RNA during the synchronous nuclear division cycle in Physarum polycephalum.

1. The synthesis of tRNA during the synchronous nuclear division cycle in plasmodia of Physarum polycephalum has been investigated using an isotope dilution procedure and compared to the pattern of synthesis of rRNA. 2. The synthesis of both tRNA stops during mitosis. As the genes for the two types of RNA are not linked, this finding suggests that cessation of synthesis during nuclear division is a common characteristic of all types of transcription, supporting earlier work using pulse labelling and autoradiography to investigate the same problem.

Cell Division↗
PubMed1977

Lead poisoning. Further observations on erythrocyte pyrimidine-nucleotidase deficiency and intracellular accumulation of pyrimidine nucleotides.

Pyrimidine nucleotides, detectable in normal erythrocytes only in trace quantities if at all, were found to comprise 7-80% of the intracellular nucleotide pools in nine subjects with severe lead over-burden. Blood lead concentrations ranged from approximately equal to 200- to 400-microgram/dl packed cells, and the greatest accumulations of pyrimidine-containing nucleotides occurred in the two subjects with the highest blood lead levels. Most of the patients had mild or moderate anemia and moderate basophilic stippling evident in Wright's-stained peripheral smears. Pyrimidine nucleotidase activities were inhibited to 13-28% of the mean activity in normal control erythrocytes and even more so (5-15%) when compared to specimens with increased reticulocytes and young cells. Reticulocytosis was absent in two subjects and modest to moderate in the remainder, but erythrocyte assays revealed the substantial elevations in populations of young mean cell age. Inappropriately low reticulocyttial elevations in glucose-6-phosphate dehydrogenase expected in populations of young mean cell age. Inappropriately low reticulocyte responses may reflect hematopoietic suppressive effects of lead at a variety of metabolic loci.

Cell Count↗