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Biomedical subjects

M Kafka

Publications and source records attributed to M Kafka.

18 recordsLinked to original sources
PubMed1998

The effect of EDTA as an anticoagulant on the osmotic fragility of erythrocytes.

The osmotic fragility test is used to determine the extent of red blood cell haemolysis produced by osmotic stress. Since the quality of this test may easily be influenced by environmental and technical factors we have determined osmotic fragility reference values in our own conditions. The results show significantly increased osmotic resistance of erythrocytes in our conditions vs the published values for blood samples anticoagulated with heparin. Furthermore, the use of EDTA as an anticoagulant increased the osmotic fragility of red blood cells as compared with heparin. We conclude that EDTA can be used as an anticoagulant for the osmotic fragility test in order to simplify routine procedures. However, every laboratory should determine its own reference values which would reflect the local environmental and technical factors.

Adolescent↗
PubMed1997

Distamycin-A derivatives potentiate tumor-necrosis-factor activity via the modulation of tyrosine phosphorylation.

The cytotoxic activities of 2 novel distamycin-A derivatives, FCE 24517 and FCE 25450A, alone and in combination with tumor-necrosis factor-alpha (TNF), were studied. Both drugs, especially FCE 25450A, analyzed extensively here, inhibited the growth of HL60 promyelocytic cells, and human SV80 and murine L929 transformed fibroblasts in a dose-dependent manner. The growth-inhibitory potential of sequential exposure to the distamycin-A analogs and TNF was determined. A 4-hr treatment of L929 fibroblasts with 100-1,000 ng/ml FCE 25450A, followed by 2 ng/ml TNF, resulted in a synergistic anti-proliferative effect. The synergism of FCE 24517 with TNF was less profound. Experiments to elucidate the mechanism underlying the cooperation revealed that FCE 25450A pre-treatment almost completely abolished the elevated tyrosine phosphorylation of a 137-kDa and other membranal proteins and prevented the de-phosphorylation of another protein band observed in L929 cells in the presence of TNF. FCE 25450A alone induced no changes in the phosphotyrosine profile of the cells. The effect of FCE 25450A was counteracted by the tyrosine-phosphatase inhibitor orthovanadate. In parallel, the inhibitor also diminished the antiproliferative action of the FCE 25450A/TNF combination. These findings suggest that, beyond their cytotoxic effects as single agents, the distamycin derivatives increase the sensitivity of cells to TNF. This effect is governed via the inhibition of TNF-induced tyrosine phosphorylation of specific proteins which are probably involved in the development of TNF resistance. Thus, protein de-phosphorylation might provide an additional mechanism of action of these novel distamycin-A-derived drugs.

Animals↗
PubMed1996

The roles of protein phosphorylation/dephosphorylation in tumor necrosis factor antitumor effects.

The roles of protein phosphorylation and dephosphorylation in the tumor necrosis factor (TNF) cytotoxic and antiproliferative effects on L-929-transformed fibroblasts were explored. Genistein and erbstatin, specific inhibitors of tyrosine kinase, had antiproliferative but not cytotoxic effects on the cells by themselves and synergistically enhanced the cytotoxic and antiproliferative effects of TNF-alpha. Immunoblot analysis with a monoclonal antiphosphotyrosine antibody revealed that TNF, administered for 5-180 min, induced tyrosine dephosphorylation of two pairs of membranal proteins, 34-36 kDa and 50-52 kDa, and potentiated tyrosine phosphorylation of a 115-kDa protein in both the cytosolic and membranal fractions of the cells. A very brief exposure (30 sec) to TNF induced rapid phosphorylation of several proteins, whereas genistein, but not inhibitors of other protein kinases, enhanced this effect of TNF. The results suggest that TNF activity could be potentiated by the inhibition of tyrosine phosphorylation and point to specific proteins that are dephosphorylated on tyrosine in response to TNF.

Animals↗
PubMed1994

Rapid interferon-gamma-stimulated tyrosine phosphorylation of cytosolic and membranal proteins in HL-60 promyelocytic cells.

The involvement of tyrosine phosphorylation in the early stages of interferon-gamma (IFN gamma)-induced monocytic differentiation of HL-60 cells was studied. Immunoblotting analysis demonstrated that IFN gamma induced rapid changes in the tyrosine phosphorylation of several endogenous cytosolic and membranal proteins. The most prominent of these polypeptides was a 84 kDa protein. In membranes, the IFN gamma-induced phosphorylation of this protein was detectable in 5 min, remained elevated for 3 h and declined thereafter, while a gradual decrease in the phosphotyrosine content was observed in cytosols. In parallel, a 40% increase in the phosphotyrosine phosphatase activity was detected in the later stages of IFN gamma treatment. Rapid changes in tyrosine phosphorylation were detected also in a 64 kDa protein. In contrast, 2-day exposure to IFN gamma was needed to potentiate significantly the tyrosine phosphorylation of a 36 kDa membranal polypeptide. These data support the involvement of tyrosine phosphorylation in the early stages of IFN gamma-induced monocytic differentiation of HL-60 cells.

Cell Differentiation↗
PubMed1994

[The birthing stool--an obstetrical risk?].

During 1992, 140 women out of a total of 1122 used the delivery chair at the department for obstetrics and gynaecology at the LKH Mödling. We compared them to a control group in the supine position. In order to evaluate the safety of deliveries on the delivery chair, we studied the duration of the stages of labour, rate and degree of soft tissue injuries, maternal blood loss, fetal outcome and complications in the puerperium. The use of the delivery chair showed no increased risk to either the mother or the fetus and therefore represents an appropriate alternative to the traditional supine position for delivery.

Adolescent↗
PubMed1990

Mechanism of interaction between interferon-gamma and antineoplastic agent on the differentiation of HL-60 promyelocytic cells.

Exposure of HL-60 promyelocytic leukemia cells to a combination of interferon-gamma (IFN gamma) and 5-fluorouracil (5-FU), at concentrations ineffective by themselves, induced a significant differentiation into monocyte-like cells. This phenomenon was accompanied by a synergistic antiproliferative effect. Further characterization of these two activities of the IFN gamma/5-FU combination on HL-60 cells was carried out. Whereas a brief pretreatment of the cells with IFN gamma followed by 5-FU was sufficient to exert the synergistic antiproliferative action, the effect on differentiation was dependent on a prolonged concomitant exposure to both drugs. In an attempt to gain more insight into the biochemical mechanisms of these phenomena, we have examined the effects of RNA and protein synthesis inhibitors and of cytoskeleton disrupting agents on the actions of IFN gamma. Inhibition of RNA or protein synthesis by actinomycin D or cycloheximide did not prevent the antiproliferative action of IFN gamma nor the induction of monocytic differentiation, yet these two compounds blocked the priming effect of IFN gamma on the potentiation of 5-FU action. Actinomycin D synergistically potentiated the antiproliferative action of IFN gamma. Colchicine, vinblastine, and cytochalasin B, disrupting the microtubular and microfilament structure, did not interfere with the actions of IFN gamma; higher concentrations of the drugs even improved the priming effect. Exogenous thymidine, known to counteract the antiproliferative effect of 5-FU, also blocked the antigrowth action but not the differentiation induced by the IFN gamma/5-FU combination. The results suggest the existence of two different mechanisms of the IFN gamma/5-FU synergism: one governing the antiproliferative action via an effect on thymidine synthetase, inducible by a short-term IFN gamma pretreatment and dependent on de novo RNA and protein synthesis; and the other mediating the induction of differentiation requiring a long-term exposure of the cells to both drugs. From a clinical point of view, drug combinations such as IFN gamma and 5-FU, inducing differentiation as well as inhibiting proliferation, may suggest a new approach to the treatment of leukemia.

Cell Differentiation↗
PubMed1987

[Neuroendocrine changes in the climacteric].

In order to investigate the relationship between hot flushes and LH-peaks, we applied GnRH-Analogon for pharmacological hypophysectomy. Although the gonadotropin serum levels could be normalized, none of the women showed a cessation of the flushes. Therefore it can be assumed that not gonadotropins, but neurotransmitters are involved in the development of flushes. The determination of the serum-level of vasointestinal peptide in the course of a TRH-test showed high VIP levels only in two climacteric women. To verify the suspected relation of VIP to the climacterium, a larger collective of women has to be checked.

Climacteric↗
PubMed1985

Partial deletion of distal 17q.

A newborn female was found to have a deletion of the terminal portion of 17q. Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity. The unbalanced translocation was inherited from the mother, who had a reciprocal translocation involving the terminal portions of 2p and 17q. To the best of our knowledge, this is the first report of a liveborn infant with deletion of the distal portion of 17q with the exception of reports of patients with ring chromosome 17.

Abnormalities, Multiple↗
PubMed1985

Biological alterations in the primary affective disorders and other tricyclic-responsive disorders.

Noradrenergic function was studied in patients with primary affective disorder and other tricyclic-responsive disorders including obsessive-compulsive disorder, anorexia nervosa and panic attack/agoraphobia in medication-free states. Pre-synaptic noradrenergic activity was assessed by assaying plasma concentrations of norepinephrine (NE) and its metabolite 3-methoxy,4-hydroxyphenylglycol (MHPG). Noradrenergic receptor responsiveness was evaluated by measuring plasma growth hormone (GH), MHPG, and NE responses to clonidine. Binding of tritiated dihydroergocriptine (3H-DHE) and biochemical responsiveness of alpha 2-adrenergic receptors were measured in platelet preparations. These studies suggest that noradrenergic activity may be altered in several tricyclic-responsive disorders and are consistent with the possibility that tricyclic antidepressants may serve to stabilize a dysregulated noradrenergic system in patients from several diagnostic categories.

Adult↗
PubMed1983

Testicular steroidogenesis in the camel (Camelus dromedarius) during the mating and the nonmating seasons.

Enzyme reactions in the camel testis involved in androgen synthesis were studied to determine the factors which account for the low testosterone production during the non-mating season (NMS). Testes excised during the NMS were found to have a relatively high activity of the 3 beta-hydroxysteroid dehydrogenase systems of pregnenolone, 17 alpha-hydroxypregnenolone, and dehydroepiandrosterone, but the 4-ene-17 alpha-hydroxylase and 4-ene-17,20-lyase systems were apparently less active than the 5-ene-17 alpha-hydroxylase and 5-ene-17,20-lyase. On the other hand, testes excised during the mating season (MS) were found to have a relatively high activity of 4-ene-17 alpha-hydroxylase, 4-ene-lyase, and 17 beta-hydroxysteroid oxidoreductase. The 19-hydroxylation and aromatizing activities for testosterone and androstenedione were not detected in testes excised in either season. It is proposed that during the NMS the predominant route of testosterone biosynthesis is pregnenolone leads to 17 alpha-hydroxypregnenolone leads to dehydroepiandrosterone leads to androst-5-en-3 beta, 17 beta-diol leads to testosterone.

17-alpha-Hydroxypregnenolone↗
PubMedDate not supplied

New combination of 5-fluorouracil and interferon-gamma effective against human myeloid leukemia in vitro.

The therapeutic potential of recombinant interferon gamma (IFN gamma) alone or in combination with two cytotoxic drugs - 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C) - was studied in vitro on two myeloid leukemia systems: HL60 promyelocytic cell line and chronic granulocytic leukemia (CGL) progenitor cells. When applied individually, IFN gamma and the drugs inhibited in a dose-dependent manner HL60 cell colony formation in semisolid culture. Moreover, IFN gamma or the cytotoxic drugs dose-dependently reduced the colony formation of CGL progenitor cell in agar. When added in combination, IFN gamma potentiated synergistically the inhibitory action of 5-FU in both systems. The most pronounced potentiation was detected at concentrations of 0.5 microgram/ml 5-FU and 50 U/ml IFN gamma. On the contrary, the antiproliferative effect of Ara-C was enhanced only subadditively when combined with IFN gamma. In view of the present findings, which are supported by new evidence from the literature, the use of 5-FU in leukemia should be reconsidered. The results further imply the potential value of combined treatment of 5-FU and IFN gamma in leukemia.

Cell Line↗