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Biomedical subjects

Z Csapó

Publications and source records attributed to Z Csapó.

At least 19 recordsLinked to original sources
PubMed2006

Effects of intracellular calcium chelation and pifithrin-alpha on deoxynucleotide metabolism in human lymphocytes.

Previously, we have found that activation of deoxycytidine kinase elicited by various DNA-damaging chemical agents could be prevented by BAPTA-AM, a cell-permeable calcium chelator or by pifithrin-alpha, a pharmacological inhibitor of p53. Here, we show that stimulation of deoxycytidine kinase by UV-light also is calcium-dependent and pifithrin-alpha-sensitive in tonsillar lymphocytes, while thymidine kinase 1 activity is stabilised in the presence of BAPTA-AM. Importantly, both UV-irradiation and calcium chelation decreased the incorporation of labelled deoxycytidine and thymidine into DNA. Pifithrin-alpha dramatically reduced the labelling of both the nucleotide and DNA fractions, possibly due to inhibition of transmembrane nucleoside transport.

Benzothiazoles↗
PubMed2003

Adjuvant chemotherapy following surgery in the management of uterine sarcomas.

OBJECTIVE: The aim of this study was to investigate the use of imaging tools in the diagnosis of uterine sarcomas, and to evaluate the effect of the adjuvant chemotherapy for uterine sarcomas. PATIENTS AND METHODS: The data of 29 patients with uterine sarcomas who received cytostatic polychemotherapy between 1990 and 2000 at the Oncological Division of the Ist Department of Obstetrics and Gynecology, Semmelweis University were evaluated by the authors. Symptoms leading to diagnosis and methods of diagnosis were examined. Vascular changes shown by two-dimensional, color and pulsed Doppler ultrasonography were observed. For staging the currently accepted FIGO method was adopted. Most of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). In each case we administered adjuvant combination chemotherapy according to the CYVADIC-protocol. The effect of adjuvant chemotherapy was evaluated. RESULTS: Six patients had Stage I, ten had Stage II, 11 had Stage III, and two had Stage IV disease. The mean age of the patients was 53.6 years with a range of 22 to 77 years. Histopathologic distribution included nine leiomyosarcomas (LMS), 13 mixed mesodermal sarcomas (MMS), and seven endometrial stromal sarcomas (ESS). Although most patients experienced neutropenia following cytotoxic chemotherapy, other non-hematologic adverse effects were easy to control. The average progression-free interval was 22.14 months, in which no significant difference was found between the histologic types. Different stages showed highly varied responses: surprisingly, patients in Stage IV with lung metastases were documented to have the longest progression-free survival. The three-year survival rate for all stages was demonstrated in 34.4% of cases. Patients with progressive disease had an average survival period of 4.4 months. CONCLUSIONS: These findings suggest that adjuvant cytostatic therapy for patients with distant metastasis confined to a single organ may produce better results than expected.

Adult↗
PubMed2002

Color Doppler ultrasonography in the differentiation of uterine sarcomas from uterine leiomyomas.

OBJECTIVE: The aim of this study was to investigate uterine vascularity in cases of uterine leiomyomas and uterine sarcomas, as well as to determine the efficiency of uterine blood flow analysis in differentiating between them. MATERIALS AND METHODS: Transvaginal color and pulsed Doppler findings obtained from 117 patients with histologically proven uterine leiomyoma and 12 with uterine sarcoma were retrospectively assessed. RESULTS: The mean intratumoral resistance index (RI) and pulsatility index (PI) were significantly lower and the intratumoral peak systolic velocity (PSV) was significantly higher in patients with sarcomas than in patients with uterine leiomyomas. Marked reduction of RI and PI and increased PSV could be found in 14 of the leiomyoma cases which showed large size and/or necrotic, degenerative and inflammatory changes. When a cut-off value of 0.5 for the RI was considered, the detection rate for uterine sarcoma was 67% and the false-positive rate was 11.8%. CONCLUSION: These results suggest that the intratumoral RI detected by color and pulsed Doppler ultrasonography in themselves could be poor for the preoperative differential diagnosis of uterine sarcoma.

Adult↗
PubMed2002

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism.

A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms. The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.

Alopecia↗
PubMed2001

[Lymphoepithelial cyst of the pancreas].

Authors present a case of a retroperitoneal lymphoepithelial cyst, which occurs rarely in this localisation. The histological picture is reminiscent of a branchiogen cyst. Usually it is recognised accidentally, with US or CT examinations performed for other reasons. In case the general condition of the patient is satisfactory, the surgical removal of such a tumour is recommended, since it is almost impossible to differentiate from more harmful lesions by CT or US examination, and if there are no tumour cells on the smears obtained by fine needle aspiration, there is always the doubt of sampling error.

Aged↗
PubMed2001

Activation of deoxycytidine kinase by inhibition of DNA synthesis in human lymphocytes.

Deoxycytidine kinase (dCK, EC.2.7.1.74) is a key enzyme in the intracellular metabolism of 2-chlorodeoxyadenosine, 1-beta-D-arabinofuranosylcytosine, difluorodeoxycytidine, and other drugs used in chemotherapy of different leukaemias and solid tumours. Recently, stimulation of dCK activity was shown by these analogues and by other genotoxic agents such as etoposide and NaF, all of which cause severe inhibition of DNA synthesis in cell cultures. Here we describe that direct inhibition of DNA polymerases by aphidicolin stimulated dCK activity in normal lymphocytes and acute myeloid leukaemic cells, as well as in HL 60 promyelocytic cell cultures. Increased dCK activity was not due to new protein synthesis under our conditions, as measured by immunoblotting. Partial purification by diethylaminoethyl-Sephadex chromatography revealed that the activated form of dCK survived purification procedure. Moreover, it was possible to inactivate purified dCK preparations by recombinant protein phosphatase with Ser/Thr/Tyr dephosphorylating activity. These data suggest that the activation of dCK may be due to phosphorylation, and that deoxynucleoside salvage is promoted during inhibition of DNA synthesis in human lymphocytes.

Aphidicolin↗
PubMed2001

Modulation of human deoxycytidine kinase activity as a response to cellular stress induced by NaF.

Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside salvage supplying resting lymphocytes with DNA precursors for synthesis and repair. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results showed that Cladribine treatment of human lymphocytes increased several fold the activity of dCK without increasing the amount of dCK protein itself (Sasvári-Székely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible post-translational modification was suggested. This theory was further investigated using NaF as an inhibitor of protein phosphatases. It was shown that NaF treatment of cells elevated dCK activity while inhibiting DNA synthesis. The possible mechanism of dCK activation/inactivation induced by exposure of cell cultures to different agents is discussed.

Cells, Cultured↗
PubMed2000

Rapid analysis of covalently and non-covalently fluorophore-labeled proteins using ultra-thin-layer sodium dodecylsulfate gel electrophoresis.

Gel electrophoresis is one of the most frequently used tools for the separation of complex biopolymer mixtures. In recent years, there has been considerable activity in the separation and characterization of protein molecules by sodium dodecylsulfate (SDS) gel electrophoresis with particular interest in using this technique to separate on the basis of size and to estimate molecular mass and protein purity. Although the method is informative, it is cumbersome, time consuming and lacks automation. In this paper we report an automated, high-performance SDS gel electrophoresis system that is based on electric-field-mediated separation of SDS-protein complexes using an ultra-thin-layer platform. The integrated fiber optic bundle-based scanning laser-induced fluorescence detection technology readily provided high sensitivity, real-time detection of the migrating solute molecules. Rapid separations of covalently and non-covalently labeled proteins were demonstrated in the molecular mass range 14,000 to 205,000 in less than 9 and 16 min, respectively. Excellent quantitation and lane-to-lane migration time reproducibility were found for all the solute components using the multilane separation platform. The limit of detection was found to be 1.5-3 ng/band for both labeling methods, with excellent linearity over a six times serial double-dilution range. Molecular mass calibration plots were compared for both covalently and non-covalently labeled proteins. A linear relationship was found between the molecular mass and electrophoretic mobility in the case of covalently labeled samples, while a non-linear relationship was revealed for the non-covalently labeled samples.

Calibration↗
PubMed1999

[Practice of fetal pathological examination].

Authors report on the practice and most important genetic questions of fetopathological examinations. A so called genetic-morphologic approach is suggested. The observer needs special knowledge to recognize major and minor signs of defects in fetuses in the second, or sometimes even in the first trimester. Spontaneous abortions in the first trimester are caused mainly by chromosome aberrations. In the second trimester the main causes of spontaneous abortions are maternal in origin or secondary to intrauterine infection. Medical legal aspects are also reviewed. For proper documentation a photo or X-ray must be taken. Cytogenetic and molecular genetic methods are also very important tools, therefore examination must be performed before fixation. For the first time in Hungary fetal biometric data are presented with correlation between gestational age and different organ weights. Our aim is to promote better understand of fetal malformations and disorders.

Abortion, Induced↗
PubMed1999

Trisomy 12 in juvenile granulosa cell tumor of the ovary during pregnancy. A report of two cases.

BACKGROUND: Granulosa cell tumors constitute only 5% of ovarian neoplasms, and their coexistence with pregnancy is extremely rare. Juvenile granulosa cell tumor has a good prognosis if it is confined to the ovary, but this type behaves more aggressively than the adult type at advanced stages. CASES: We report on successful completion of two singleton pregnancies and deliveries of normal infants in two young women with juvenile granulosa cell tumor diagnosed and treated during pregnancy. This tumor has rarely been described in association with pregnancy. The presence of trisomy 12 as a single chromosomal abnormality was detected in these two tumors. Both tumors were localized strictly to the ovary, so conservative surgery was applied and proved sufficient to remove all tumor tissue. Follow-up showed no signs of recurrence 18 and 53 months after the interventions. CONCLUSION: These cases support the contention that trisomy 12 is a nonrandom chromosome abnormality in juvenile granulosa cell tumors and that pregnancy may affect nuclear stability in this tumor.

Abdominal Pain↗
PubMed1999

Hyperreactio luteinalis in a normal singleton pregnancy. A case report.

BACKGROUND: Hyperreactio luteinalis rarely occurs in normal singleton pregnancy. About 50 such cases have been published. This case is noteworthy because it resulted in extremely enlarged ovaries and was accompanied by a hyperandrogenic state and high level of human chorionic gonadotropin. CASE: A gravida was referred to our department because of large, bilateral, cystic ovaries diagnosed by ultrasonography in the 28th week of gestation. Markedly elevated levels of androgens and human chorionic gonadotropin were noted. During the following six weeks the ovarian masses enlarged, and the hyperandrogenic state worsened. Cesarean section and, because of a bleeding right adnexectomy, left ovarian resection were performed. Histology confirmed the presumed diagnosis of hyperreactio luteinalis. The placenta was unremarkable. Seventeen weeks after surgery the hormone levels were normal. CONCLUSION: Our case suggests the possibility that in certain cases of hyperreactio luteinalis, an idiopathic elevation of human chorionic gonadotropin, can occur even in normal singleton pregnancies. Furthermore, it calls attention to the necessity of ultrasonographic demonstration of ovaries even during late pregnancy.

Adult↗
PubMed1998

[Comparative study of meropenem and amikacin/metronidazole combination in the treatment of severe abdominal surgical infections].

The authors compared in a prospective, randomized study the efficacy of amikacin/metronidazole combination and meropenem monotherapy in serious, intra-abdominal infections needing surgical treatment. There were 31 evaluable patients. Fifteen patients were involved to the meropenem and 16 to the combination group. The average age were 46 years in the meropenem group and 50 in the other one, the APACHE II score was similar (12.9 and 12.5). Among the examined parameters, only the white blood cell number decrease showed significant difference between the study groups. In the meropenem group 5.05 x 10(9), while in the comparator group 3.57 x 10(9) (p < 0.01). At the end of the study period, the infection was cured in the case of 11 patients in the meropenem and 9 patients in the control-group. At the end of the treatment the average APACHE II score decreased to 7.6 and to 9.6 points respectively. Clinically both therapies proved to be effective and well tolerated but the microbiological assessment revealed that meropenem tended to cover all pathogens of the mostly polymicrobial infections (12 cases, 43%) more frequently, than amikacin/metronidazole combination (9 cases, 33%). The Gram negative bacteria showed sensitivity to both meropenem and amikacin, but their majority were inhibited by meropenem at a concentration 1 or 2 orders of magnitude lower, than by amikacin. The therapeutic dose of meropenem is not toxic; therefore, it can be safely administered in poor general condition, frequently with renal impairment. We did not observed serious adverse event during the study period.

Abdomen↗
PubMed1998

Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine (Cladribine) in human lymphocytes.

Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis.

Antineoplastic Agents↗
PubMed1998

Activation of deoxycytidine kinase during inhibition of DNA synthesis in human lymphocytes.

Deoxycytidine kinase was shown to be activated during 2-chlorodeoxyadenosine (CdA) treatment of human lymphocytes, under the conditions when the DNA synthesis is inhibited. As the increase of dCK activity was shown in crude protein extracts, without an increase in the amount of dCK protein, shown by immunostaining after SDS-PAGE, a secondary modification of the protein structure was considered. NaF treatment of cells in the concentration range of 5-20 mM gave a similar activation of dCK, suggesting a possible role of phosphatases and/or a possibility of a G-protein related phenomenon. Using the same conditions, no effect of CdA or NaF was found on the thymidine kinase activity of cell extracts. Alternatively, activation of catabolic pathways could be considered, however, the increase in dCK activity was not influenced either by the removal of 5'-nucleotidases, or by the inhibition of deaminases.

Cladribine↗
PubMed1998

Similar changes were induced by Cladribine and by gemcitabine, in the deoxypyrimidine salvage, during short-term treatments.

Short term treatments (1-2 hrs) of human tonsillar lymphocytes by Cladribine (2-Chloro-deoxyadenosine, CdA) have suggested a new target for CdA, the inhibition of dCMP deaminase (Sasvári et al. 1994; BBRC 203, 1378). Further investigations have shown, that the dCMP-deaminase activity could be inhibited by 2-Cl-dAMP in cell free extracts of lymphocytes. The pool size of dUMP (measured by an antibody against dUMP) was also decreased in WiDr colon cancer cells by CdA. The new antimetabolite against solid tumours, Gemcitabine (2',2'-difluoro-deoxycytidine, dFdC), had similar effects on the salvage of thymidine (dThd) and deoxycytidine (dCyd) as CdA. The Ki values for 3H-dThd and 3H-dCyd incorporation into DNA were 0.16 uM and 1.0 uM dFdC, respectively. The labeling of the TTP pool increased 6-7 times, while of dCTP pool only 1.5-1.7 times, suggesting a decrease of the size of corresponding pools. Similarly to CdA, the labeling as well as the concentration of dUMP was also decreased by dFdC. Both analogues are able to increase the deoxycytidine kinase activity, necessary for their phosphorylation and therapeutic action in cells. The target(s) for the two different drugs seems to be common.

Antimetabolites, Antineoplastic↗
PubMed1998

Deoxycytidine kinase can be also potentiated by the G-protein activator NaF in cells.

Recently, it has been shown, that 2-Chloro-deoxyadenosine (1), a series of analogues, and other DNA synthesis inhibitors, increased the deoxycytidine kinase (dCK) enzyme activity in different cells, without influencing thymidine kinase isoenzymes (TK1, TK2), dCMP-deaminase and thymidylate synthase (TS) activities (2,3). The dCK activity was 2-4 times higher in analogue treated cells, than in controls, which can not be explained by metabolic pool imbalance induced by the drugs. New mRNA and protein synthesis of dCK could not be detected, thus post-translational modification has been suggested for potentiation the activity of the dCK (1). Because secondary modifications of enzymes usually involve the signalling processes in cells, the universal G-protein activator fluorine ions were tested. dCK activity of human lymph node lymphocytes were increased 2-times, if cells were incubated in the presence of NaF for 1-2 hrs in cultures, while TK activity was not changed. The formation of dUTP from dCyd, was also enhanced by NaF, in parallel of dCK potentiation.

Cells, Cultured↗
PubMed1998

Serological responses of patients with ectopic pregnancy to epitopes of the Chlamydia trachomatis 60 kDa heat shock protein.

Clinical and histopathological correlations of immunoreactivity to Chlamydia trachomatis and to epitopes of the C. trachomatis 60 kDa heat shock protein (hsp60) among women with ectopic pregnancy were evaluated in a case-control study. Serological responses to 13 synthetic peptides corresponding to major epitopes of the chlamydial hsp60 were determined in 67 women treated for ectopic pregnancy and 45 women with uncomplicated pregnancy in utero. Plasma cell salpingitis was detected in 29 (43.3%) of the ectopic patients. Its presence correlated with antibodies to two hsp60 epitopes, encompassing amino acids 260-271 and 411-422 (P = 0.02). Antibodies to these two epitopes, along with five other epitopes, also correlated with peritubal adhesion formation in ectopic pregnant patients (P < 0.01). Antibodies to epitopes 260-271 and 188-199 also correlated with a history of pelvic inflammatory disease (PID; P = 0.05). Patients with ectopic pregnancy were also more likely than their intrauterine pregnant controls to have present anti-chlamydial immunoglobulin G (P < 0.005). Women positive for both C. trachomatis and hsp60 epitope antibodies had an increased prevalence over controls of salpingitis, pelvic adhesions or history of PID (P < 0.05). In contrast, patients who were positive for only C. trachomatis antibodies or only hsp60 epitope antibodies did not differ from antibody-negative patients in each of these categories.

Adult↗