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Biomedical subjects

A Szepesi

Publications and source records attributed to A Szepesi.

32 records · Page 2Linked to original sources
PubMed1993

Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes.

A serum-free cell culture system for human T lymphocytes was used to investigate the synthesis and metabolism of several important cell cycle-regulated proteins (p62c-fos, p110Rb, and p34cdc2 and its homologs) and the possible roles of iron and essential free fatty acids in regulating cell cycle progression. Following stimulation with phorbol dibutyrate (PDB) and ionomycin under serum-free conditions, resting T cells entered the cell cycle, as evidenced by a burst of synthesis of p62c-fos and an increase in the amount of the p33 homolog of the cdc2 kinase. However, in the absence of other additions, cells were arrested in the G1 phase of the cell cycle. Supplementation of the medium with two components, iron and linoleic acid (LA), permitted activated cells to progress through the G1 phase of the cycle and initiate DNA synthesis. Under these conditions p110Rb became phosphorylated and p34cdc2 was synthesized similar to T cells proliferating in normal serum-containing medium. The addition of iron, without LA, had little effect on activated cells; however, the addition of LA, in the absence of added iron, had profound effects. RNA accumulated to levels characteristic of cells at the G1/S interface, phosphorylation of p110Rb was almost complete, and p34cdc2 was synthesized, although at lower levels than in proliferating cells. However, no DNA synthesis was detected; under these conditions the cells appeared to be blocked at or near the G1/S border. Since there was a possibility that some component of the cell culture system could provide "trace" amounts of iron, and also to further delineate the role of iron in this system, cells were activated in medium containing LA and deferoxamine (10 microM), a chelator of iron. The accumulation of p34cdc2 was now reduced to nearly undetectable levels although phosphorylation of p110Rb was not substantially affected. It therefore appears that synthesis of p34cdc2 requires a low amount of iron, a finding which may define a possible regulatory point in the cell cycle for iron before its well-recognized role in regulating S phase entry by acting as a cofactor for the enzyme ribonucleotide reductase.

CDC2 Protein Kinase↗
PubMed1992

Rapamycin inhibits the phosphorylation of p70 S6 kinase in IL-2 and mitogen-activated human T cells.

Phosphorylation of 40S ribosomal protein S6 is regulated in part by the mitogen-activated p70 S6 kinase (p70s6k). Following the addition of IL-2 to the IL-2 dependent human cell line Kit225, or mitogenic activation of resting human T cells, a rapid phosphorylation of p70s6k was observed by immunoblotting. Rapamycin (RAP), a potent suppressor of T-cell proliferative responses, markedly inhibited the phosphorylation of p70s6k induced by IL-2 in Kit225 cells or by the mitogens added to resting T cells. Other immunosuppressants such as cyclosporin A or an FK506 analogue were without effect. Moreover, the effect of RAP was restricted to p70s6k; it did not inhibit the phosphorylation of p90rsk, another kinase which utilizes the S6 protein as a substrate. These data indicate for the first time that RAP may target the pathway leading to p70s6k phosphorylation during human T-cell proliferation.

Amino Acid Sequence↗
PubMed1992

Regulation of synthesis of p34cdc2 and its homologues and their relationship to p110Rb phosphorylation during cell cycle progression of normal human T cells.

In yeast, the protein kinase p34cdc2 plays a role in regulating both the G2 to M and G1 to S phase transitions. The discovery of multiple homologues of the protein in cells of higher eukaryotic organisms suggests that different cell cycle regulatory events may be performed by different kinases in such cells. Here, the synthesis and metabolism of the human forms of these proteins are described in a normal human cell type, peripheral blood T lymphocytes that have been stimulated to enter the cell cycle in vitro. Using a carboxyl-terminus antiserum specific for true p34cdc2, the protein could first be found in T cells at about 24 to 30 h after stimulation, just before the initiation of DNA synthesis. Three forms of the enzyme could be resolved by denaturing gel electrophoresis: an unphosphorylated form with an apparent molecular mass of 34,500 daltons and two phosphorylated derivatives. In cells synchronized at G2/M phase with nocodazole, p34 was almost entirely in the unphosphorylated form whereas the phosphorylated derivatives were more predominant in cultures arrested at the G1/S border with aphidicolin. The relationship of p34 synthesis to the phosphorylation of p110Rb, an event known to be associated with passage through late G1 and/or the G1/S phase transition, was also investigated. It was noted that p110Rb phosphorylation began before p34 synthesis first became detectable. Furthermore, it appeared that the two events could be largely uncoupled by treating cells with deferoxamine (10 microM), an iron chelating agent that arrests T cells at a point in late G1 phase but substantially before the G1 to S phase transition. Under these conditions, p110Rb phosphorylation was almost completely accomplished in the absence of significant p34 synthesis, a finding that suggests that most or all of p110 phosphorylation is performed by kinases other than p34. Because of this observation, extracts were next examined for p34-like molecules using an antibody against the so-called PSTAIRE domain found in all cdc2 homologues identified to date. A species of protein with a mobility slightly less than true p34 was found, even in resting T cells. Upon stimulation, this protein increased slightly in amount, and a second protein with a mobility greater than p34, a putative p33cdk2, was seen. Not only was the appearance of these proteins not inhibited by deferoxamine but they accumulated in cultures treated with the drug, suggesting that p33, and not p34, may be the G1 phase kinase for p110Rb.(ABSTRACT TRUNCATED AT 400 WORDS)

CDC2 Protein Kinase↗
PubMed1992

[Experience with ciprofloxacin therapy of salmonellosis gastroenteritica].

Five days' ciprofloxacin treatment resulted quick clinical improvement in all of the 45 patients with salmonella gastroenteritis and stool cultures of 35 patients became negative. The advantages of ciprofloxacin treatment are analysed in comparison with previous antibiotics. Indications for new quinolones in the treatment of salmonella gastroenteritis are summarized. It is emphasized that antibiotic therapy is unnecessary in mild cases of salmonella gastroenteritis. This is demonstrated on the basis of case reports of 12 patients with symptomatic treatment too.

Adolescent↗
PubMed1992

[Bicycle accidents].

Authors analyse the 1684 bicycle accidents, observed in the county Vas in one year, compared with the international data. It is underlined that no sufficient attention is given to the bicycle accidents, reaching 6 per cents of all traumas, and the increase of which can be still expected, and to the prophylaxis of these accidents. Especially endangered were found the little children transported on bicycles, those aged 11-14 years and the drunken drivers. Prophylactic measures are suggested.

Accidents, Traffic↗
PubMed1991

[Incidence of fractures of the proximal femur and the distal end of the forearm (results of a Vas County survey compared to international data)].

Authors analysing the one year material of injured in one county, state the age and sex specific incidence in the two types of fractures. Compared with other European data they found difference in male/female distribution: the values concerning women are substantially lower in the county Vas, those of men are on the other side equal. To clear the difference and the tendency further examinations are thought to be necessary, especially regarding the increasing importance of femoral fractures of the hip region in public health and national economy.

Europe↗
PubMed1990

[Bilateral fractures of the proximal end of the radius].

Authors describe in connection with two cases of their own the vulnerability of the elbow joint originating from the physiological valgus position of this joint, i.e. the effect of the so-called "valgus stress". In the available literature no description of bilateral synchronous fracture of the radial head was found. They think, because of the bilateral injury, the correct operative therapy with the aim of reaching whole function, the stable osteosynthesis promising good result even in the fracture of the radial neck with major dislocation allowing also an early functional treatment, important.

Adult↗
PubMed1978

[The importance of primary operation from the point of view of mortality in patients with femoral neck fractures. I. Comparative study of mortality after primary and delayed operations. The part played by the patients age (author's transl)].

Authors with regard to primary or delayed surgical treatment analyse the mortality of 2,612 patients with proximal femur fractures treated in the National Institute of Traumatology during the years 1971--75. Within this material 2,055 case history of surgically treated femoral neck and pertrochanteric fractures are evaluated. An important difference in favour of primary intervention was found between the mortality of primary and delayed operations both in femoral neck and pertrochanteric fractures. In pertrochanteric fractures the mortality increased gradually starting from the day of injury. Regarding age related mortality, there was a significant difference in each age group in favour of primary operations. Thus the increased mortality encountered after delayed operations can't be explained by a selection with regard to age.

Age Factors↗