Biomedical subjects

Katalin Nagy

Publications and source records attributed to Katalin Nagy.

7 recordsLinked to original sources

PubMed2003

Interferon-gamma-induced sensitization of colon carcinomas to ZD9331 targets caspases, downstream of Fas, independent of mitochondrial signaling and the inhibitor of apoptosis survivin.

We have demonstrated previously a Fas-dependent component in thymineless death of human colon carcinoma cells. Importantly, the cytotoxic effects of thymidine deprivation induced by 5-fluorouracil (FUra) combined with leucovorin (LV) was enhanced by IFN-gamma, and the synergism was shown to be dependent on Fas, FUra-induced DNA damage, and independent of p53. Subsequently we examined the potential for synergistic interactions between IFN-gamma and the specific thymidylate synthase inhibitor, ZD9331. IFN-gamma sensitized colon carcinomas to ZD9331-induced apoptosis and loss in clonogenic survival, also dependent on ZD9331-induced DNA damage, independent of p53. Synergism occurred in HCT116, demonstrating previously RNA-mediated FUra/LV cytotoxicity that could not be potentiated by IFN-gamma. Manipulation of the Fas death receptor pathway from the level of the receptor (Nok1/Nok2, Fas overexpression, and DN-FADD) to the mitochondria (Bcl-xL and Bcl-2) did not modulate ZD9331 +/- IFN-gamma-induced cytotoxicity in HT29, with the exception that Nok1/Nok2-blocking antibodies partially protected HT29 from the cytotoxic activity of ZD9331 alone. However, IFN-gamma alone (but not ZD9331) up-regulated the expression of caspases -3, -4, -7, and -8, and in combination with ZD9331 demonstrated enhanced caspase activation and cleavage of poly(ADP-ribose) polymerase that was not prevented by overexpression of Bcl-2. Additionally, IFN-gamma increased the activity of the proteasome in HT29, leading to selective down-regulation of the antiapoptotic protein survivin, whereas simultaneously increasing Fas expression. However, reduction in the survivin:Fas ratio by transfection of survivin small interfering RNA and/or overexpression of Fas did not affect sensitivity of HT29 to ZD9331 +/- IFN-gamma. Data demonstrate that IFN-gamma combined with ZD9331 is synergistic in additional cell lines that demonstrate RNA-mediated FUra/LV cytotoxicity, and that a major target of interaction is at the level of caspases, downstream of Fas, and independent of involvement of either the mitochondria or survivin.

Antineoplastic Agents↗

PubMed2003

[Cross-sectional survey on the nutritional and life-style habits of secondary school students in Hungary].

INTRODUCTION: The national representative survey of secondary school students (age: 15-18 years) was undertaken between 1997 and 2000. The authors presented the data related to the nutritional and life-style habits. METHODS: The data for 6,347 students (48.4% boys and 51.6% girls) were evaluated. The anonymous questionnaire contained inquiries on nutritional rhythm, food frequency, use of vitamin and mineral supplements, smoking, alcohol and drug consumption habits, regular physical activity and family background (qualification, smoking, alcohol consumption). Within the frame of personal interviews the authors collected data on students' history with regard to occurrence of diabetes mellitus, other chronic diseases and in girls the time of the first menstruation. Concerning parents' history the authors collected information on the incidence of hypertension, myocardial infarction, diabetes mellitus, and stroke. STATISTICAL EVALUATION: Data were recorded in Data-Ease database system, in forms of individual records. The individual records were converted to be suitable for the statistical evaluation by SPSS for windows 9 statistical program pack. Data are presented as means and percent distribution. RESULTS: The nutritional rhythm of students was irregular. The daily consumption of milk, dairy products, fruits, fresh vegetables and vegetable dishes was insufficient. Eighty percent of students added extra salt to foods. More than 49% of students regularly consumed some forms of vitamin and/or mineral supplements. Thirty five percent of boys and 30% of girls smoked daily, 14.6% of boys and 5.9% of girls consumed alcohol at least once a week. Fifteen percent of boys and 11% of girls already tried taking drugs at least once. Only 50% of boys and 31% of girls were involved in a regular physical activity. Twenty two percent of fathers and 25% of mothers had university qualifications, whereas intermediate qualifications were recorded in 63 and 59%, lower qualifications occurred in 8 and 13% of parents, respectively. The incidence of smoking was 42% for fathers and 36% for mothers. Weekly alcohol consumption was recorded in 11%, daily consumption in 7% among fathers, the same figures for mothers were 4-4%, respectively. The incidence of hypertension, myocardial infarction, diabetes mellitus, and stroke was 26; 3.4; 5.4 and 1.5% in fathers and 32.9; 4.2; 6.6 and 1.5% in mothers. CONCLUSIONS: The data collected in the complex nutritional hygienic survey revealed serious deficiencies in the nutritional and life style habits of secondary school students. These factors considerably contribute to the unfavorable statistics of nutrition related non-infectious diseases in adulthood.

Adolescent↗

PubMed2003

[Cut-off values for the diagnosis of obesity and hypertension based on epidemiologic measurements in Hungarian youth].

INTRODUCTION: A representative nutritional hygienic survey was performed in a population of secondary school students (ageing from 15 to 18 years) between the years of 1997 and 2000. Herewith, the authors give an account on the anthropometric and blood pressure studies. METHODS SAMPLING: the representative sampling sites were selected randomly. In the capital three-stage, in the counties four-stage stratified groups were assigned for the studies. The data for 3071 girls and 3274 boys were evaluated. Anthropometric parameters determined were as follows, body mass, body height, waist and hip circumference. The body mass index (BMI) and the waist/hip ratio was calculated. Blood pressure values were recorded using OMRON M4 automatic device. Repeated blood pressure measurements were performed twice at least > or = two weeks apart if the systolic blood pressure was 135 and/or the diastolic pressure was > or = 85 mmHg. Statistical analysis was performed using SPSS for Windows 9.0. RESULTS: Out of the anthropometric parameters the gender and age-specific percentile distribution is given in regard to body mass, body height, body mass index (BMI), waist circumference, and waist/hip ratio. There was a strong relationship between the waist circumference and BMI. Elevated blood pressure values were found at the first recording in 14.1% of boys and in 2.5% of girls. In students who presented three times, the incidence of high blood pressure was 7.5% in boys and 1.1% in girls. Only 1% of students was aware of his or her hypertension. CONCLUSIONS: The representative survey provides reference values concerning body mass, body height, BMI, waist circumference, waist/hip ratio and blood pressure values in the age group of 15 to 18 years. It also provides data for the prevalence of hypertension and gives cut off values for the diagnosis of leanness, overweight and obesity.

Adolescent↗

PubMed2003

Development of radioimmunoassay for the measurement of human leptin in serum.

BACKGROUND: Leptin is a 16 kDa polypeptide hormone encoded by the obese gene (ob) and secreted by adipose tissue. This hormone plays a major role in energy homeostasis and regulation of food intake and body weight. It also affects the metabolic, neuroendocrine and reproductive systems. MATERIAL AND METHODS: Labelling of recombinant human leptin with (125)I was best performed by the Chloramine-T method. New Zealand white rabbits were immunised with recombinant human leptin, cross-reaction of obtained antisera was analyzed with 10 different antigens. The separation of bound and free fractions was performed using the second antibody - PEG method. RESULTS: The obtained tracer had specific activities of 2.8-3.3 kBq/ microg and had a stability of 5 weeks. A highly specific polyclonal antibody was obtained without measurable cross-reaction against the analysed antigens. Concentrations of human leptin were measured by a single overnight incubation assay with a sensitivity of 0.5 ng/ml and a measuring range of 0.5-100 ng/ml. The intra-assay and inter-assay coefficient of variation was under 6% and 8%, respectively. Recovery ranged from 88% to 106%. CONCLUSIONS: Serum human leptin concentrations can be accurately and precisely measured by this new radioimmunoassay. Preliminary results obtained from the measurement of serum leptin in lean, overweight and obese patients are presented. Serum leptin concentrations correlated with body mass index and were significantly higher in women than in men, except for obese patients.

Animals↗

PubMed2002

[Postoperative vomiting].

INTRODUCTION: Nausea and vomiting following general anaesthesia are among the most frequent adverse reactions causing complications, the relief of which is an absolute demand. 5-HT3 receptor antagonists, such as ondansetron, belonging to the latest class of antiemetics were launched more than a decade ago. PATIENTS/METHODS: Efficacy and tolerability of ondansetron injection in prevention of postoperative nausea and vomiting were investigated in a prospective, randomised, double-blind, placebo controlled, three-armed clinical study in 148 patients undergoing laparoscopic cholecystectomy. Moreover the authors also investigated the effect of timing of dosing, i.e. whether the administration of antiemetic drug before starting anaesthesia has any advantage comparing its use at the end of operation. RESULTS: While using a standard surgical and anaesthesia method vomiting after laparoscopic cholecystectomy occurred in a frequency of 44.7% of the patients in the placebo group, whereas the figures decreased significantly after administration of 4 mg ondansetron at the end (28.9%) or before (25.5%) anaesthesia. Inclusively the frequency of severe cases decreased from 19.2% of control group up to 8.9% and 4.3% in the active groups, respectively. CONCLUSIONS: Intravenous administration of 4 mg ondansetron effectively reduces vomiting occurring in more than 40% of patients after laparoscopic cholecystectomy, especially the frequency of severe cases, and mainly if administered before operation. The preparation is safe; no clinical or laboratory adverse reactions, complications have been observed in the studied patients.

Adult↗

PubMed2002

Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis.

Formation of lymphatic metastasis is the initial step of generalized spreading of tumor cells and predicts poor clinical prognosis. Lymphatic vessels generally arise within the peritumoral stroma, although the lymphangiopoietic vascular endothelial growth factors (VEGF)-C and -D are produced by tumor cells. In a carefully selected collection of human cervical cancers (stage pT1b1) we demonstrate by quantitative immunohistochemistry and in situ hybridization that density of lymphatic microvessels is significantly increased in peritumoral stroma, and that a subset of stromal cells express large amounts of VEGF-C and VEGF-D. The density of cells producing these vascular growth factors correlates with peritumoral inflammatory stroma reaction, lymphatic microvessel density, and indirectly with peritumoral carcinomatous lymphangiosis and frequency of lymph node metastasis. The VEGF-C- and VEGF-D-producing stroma cells were identified in situ as a subset of activated tumor-associated macrophages (TAMs) by expression of a panel of macrophage-specific markers, including CD68, CD23, and CD14. These TAMs also expressed the VEGF-C- and VEGF-D-specific tyrosine kinase receptor VEGFR-3. As TAMs are derived from monocytes in the circulation, a search in peripheral blood for candidate precursors of VEGFR-3-expressing TAMs revealed a subfraction of CD14-positive, VEGFR-3-expressing monocytes, that, however, failed to express VEGF-C and VEGF-D. Only after in vitro incubation with tumor necrosis factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to synthesize VEGF-C de novo. In conclusion VEGF-C-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer.

Antigens, CD↗

PubMedDate not supplied

TGF beta 1 kills lymphoma cells using mitochondrial apoptotic pathway with the help of caspase-8.

It is a known paradox that many TGF beta 1-producing tumor cells are resistant to this, otherwise, inhibitory cytokine. In a lymphoma of B-cell origin exogenous TGF beta 1 was able to induce apoptosis, suggesting that the apoptosis program can be switched on. The apoptosis induction was independent of the death receptors but dependent on mitochondrial pathway and caspase-3. Probably due to the weak starting signal, caspase-3 further activated caspase-8 which, through the Bid cleavage and Bax translocation into the mitochondria, provided an autocatalytic support for the apoptotic program. There is a time-gat between the early activation of Smad-dependent TIEG and the accumulation of ROS, therefore other participants that start the increase in mitochondrial membrane permeability should be identified.

Apoptosis↗