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Biomedical subjects

B Nagy

Publications and source records attributed to B Nagy.

At least 19 recordsLinked to original sources

Replicon typing of F18 fimbriae encoding plasmids of enterotoxigenic and verotoxigenic Escherichia coli strains from porcine postweaning diarrhoea and oedema disease.

The presence of fimbrial adhesin F18 is frequently found in enterotoxigenic Escherichia coli (ETEC) and verotoxigenic E. coli (VTEC) strains responsible for diarrhoea and oedema disease of weaned pigs. The F18 adhesin occurs in two antigenic variants: F18ab is characteristic of VTEC while F18ac is more typical for ETEC. F18 encoding plasmids of 17 phenotypically characterized porcine E. coli isolates (10 ETEC, 6 VTEC and 1 ETEC/VTEC) were tested with a DNA probe for F18 fimbrial adhesin and with replicon probes for the RepFIa, RepFIb and for the RepFIc family of basic replicons. In all the cases, the F18 probe hybridized to only one plasmid band of size higher than 42MDa. All F18 plasmids were determined to be unireplicon plasmids belonging to the RepFIc replicon family of the F incompatibility complex. There was no difference between F18ac plasmids of ETEC and F18ab plasmids of VTEC strains in terms of replicon type or subtype. However, the size of F18ab plasmids of the VTEC strains varied between 42 and 98MDa, in contrast to F18ac plasmids of ETEC strains (constantly approximately 98MDa).

Adhesins, Escherichia coli↗

Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia - a cDNA array study.

Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.

Acute Disease↗

Torovirus detection in faecal specimens of calves and pigs in Hungary: short communication.

Bovine torovirus is an established aetiological agent of disease in cattle, while porcine torovirus has only been isolated from healthy animals. Evidence for the presence of torovirus has been described in several European countries and also in the United States. A survey was performed to detect toroviruses in Hungary by means of sampling ten swine and nine bovine herds. Rectal swabs and faecal specimens were collected from diarrhoeic calves and from weaned piglets. The samples were tested by the reverse transcription-polymerase chain reaction (RT-PCR) using torovirus-specific primers and the positive samples were further examined by electron microscopy (EM). Torovirus was detected in 4 diarrhoeic calves (out of 111) and in 10 healthy weaned pigs (out of 200 tested), representing two of the 9 calf herds and two of the 10 pig herds tested. This is the first report of exact diagnosis of torovirus in Hungary.

Animals↗

[First attempts in preimplantation genetic diagnosis: genetic analysis].

Preimplantation genetic diagnosis is a new approach for the prevention of genetic disorders, which provides a healthy pregnancy avoiding the need for its possible termination. The combination of in vitro fertilization techniques and single cell molecular genetic diagnosis allows only unaffected embryos to be selected for transfer to the uterus. It is an acceptable alternative of prenatal diagnosis for certain couples. Here we report our first attempts in the application of fluorescent PCR for sex determination and the detection of the delta-F508 mutation in human blastomeres. We modelled clinical PGD situations as we performed sex determination on 23 preembryos. Sex determination was successful is 20 preembryos (83%). We performed the detection of the delta-F508 mutation on 23 preembryos, which was successful in 20 preembryos (87%). Our experience suggests, that the established fluorescent PCR analysis is a reliable method for PGD, which enables us to apply it for clinical preimplantation genetic diagnosis.

Blastomeres↗

The association of serum lipoprotein(a) levels, apolipoprotein(a) size and (TTTTA)(n) polymorphism with coronary heart disease.

BACKGROUND: The association between lipoprotein(a) levels, apolipoprotein(a) size and the (TTTTA)(n) polymorphism which is located in the 5' non-coding region of the apo(a) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects. METHODS: Lp(a) levels were measured by ELISA, apo(a) isoform size was determined by SDS-agarose gel electrophoresis, and analysis of the (TTTTA)(n) was carried out by PCR. For statistical calculation, both groups were divided into low (at least one apo(a) isoform with < or = 22 Kringle IV) and high (both isoforms with >22 KIV) apo(a) isoform sizes, and into low number (<10 in both alleles) and high number of (> or =10 at least one allele) TTTTA repeats. RESULTS: Lp(a) levels were higher (P=0.007), apo(a) isoforms size < or =22 KIV and TTTTA repeats > or = 10 were more frequent (P=0.007 and 0.01) in cases than in controls. Lp(a) levels were found to be increased with low apo(a) weight in both groups (both P<0.0001). In multivariate logistic regression analysis, only the Lp(a) levels (P=0.005) and (TTTTA)(n) polymorphism (P=0.002) were found to be significantly associated with CHD. CONCLUSION: Nevertheless, these results indicate that in CHD patients the (TTTTA)(n) polymorphism has an effect on Lp(a) levels which is independent of the apo(a) size.

Adult↗

FADD null mouse embryonic fibroblasts undergo apoptosis after photosensitization with the silicon phthalocyanine Pc 4.

Oxidative stress, such as photodynamic therapy with the silicon phthalocyanine Pc 4 (Pc 4-PDT), can induce apoptosis and tumor necrosis factor alpha (TNF) production. TNF receptors, as well as other death receptors, have been implicated in stress-induced apoptosis. To assess directly the role of FADD, a death receptor-associated protein, in induction of apoptosis post-Pc 4-PDT, embryonic fibroblasts from FADD knock out (k/o) and wild-type (wt) mice were used. Pc 4-PDT induced casp-3 activation and apoptosis in both cell types. In the presence of zVAD, a pancaspase inhibitor, Pc 4-PDT-induced apoptosis was abrogated in both cell lines. Fumonisin B1 (FB), an inhibitor of ceramide synthase, had no effect on apoptosis after Pc 4-PDT in either cell line. Similar to Pc 4-PDT, exogenous C6-ceramide bypassed FADD deficiency and induced zVAD-sensitive apoptosis. In contrast to Pc 4 photosensitization, TNF did not induce either apoptosis or ceramide accumulation in FADD k/o cells. In the absence of FADD deficiency, TNF-induced apoptosis was zVAD-sensitive and FB-insensitive. Induced ceramide levels remained elevated after cotreatment with TNF and zVAD in FADD wt cells. Taken together, these data provide genetic evidence for a lack of FADD requirement in Pc 4-PDT- or C6-ceramide-induced apoptosis. FB-sensitive ceramide production accompanies, but does not suffice, for apoptosis after Pc 4 photosensitization or TNF.

Adaptor Proteins, Signal Transducing↗

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients.

The central role of chemokines in the pathogenesis of atherosclerosis has been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly higher among CAD patients than among controls (P<0.005; OR=2.2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5Delta32 mutations are at reduced risk for severe CAD.

Adult↗

Distinct gene expression profiling in chronic lymphocytic leukemia with 11q23 deletion.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with regard to its clinical course. The limitations of the methods currently available for prognostic assessment in CLL do not allow accurate prediction of the risk of disease progression in individual patients. The recently developed cDNA array technique provides a unique opportunity to study gene expression in various malignancies. To identify new molecular markers for prognostication of CLL patients, we analyzed cDNA arrays by using hierarchical clustering and standard statistic t-test on 34 CLL patients. We found significant expression differences in 78 genes compared to the reference tonsillar B lymphocytes. A cluster of genes, LCP1, PARP, BLR1, DEK, NPM, MCL1, SLP76, STAM, HIVEP1, EVI2B, CD25, HTLF, HIVEP2, BCL2, MNDA, PBX3, EB12, TCF1, CGRP, CD14, ILB, GZMK, GPR17 and CD79B, was associated (P < 0.05) with the unfavorable 11q deletion and also with the unfavorable Binet stages B and C. We present here gene expression profiling that is associated with CLL patients with the 11q23 deletion. Many of the genes in the cluster have not previously been shown to be related to the initiation or progression of CLL. These novel findings provide fundamental information for further attempts to understand the interaction of the clustered genes in the leukomogenesis of CLL in order to better design treatments aimed at specific molecular target(s).

Aged↗

[Mutation analysis of the beta-catenin gene in epithelial carcinomas of the ovaries].

beta-catenin is a continuously expressed cytoplasmic protein that has an important role is both E-cadherin-mediated cell-cell adhesion and in activation of Wnt/Wingless transcriptional pathway. The accumulation of stabilized beta-catenin caused by the mutation of the exon 3 of beta-catenin gene can stimulate the T-cell factor/Lymphoid enhancing factor-mediated transcriptional activation. The activation of transcriptional pathway may through oncogenes is an important step of the oncogenesis in solid tumors. In this study we analyzed mutations in exon 3 of the beta-catenin gene in 18 sporadic epithelial ovarian tumors. Three mutations were found from these 18 ovarian tumor samples which contained 8 serous, 3 mucinous, 5 endometrioid, one malignant Brenner-type tumor and one transitional cell carcinoma. Two mutations occurred in endometrioid-type (in 47 and 55 codons) and one in serous-type (in 47 codon) ovarian carcinomas, and both mutations were missense and somatic. The patients with mutated beta-catenin gene appeared from the younger patients under the age of 50. Our results suggest that the stabilization of beta-catenin protein by the mutation of CTNNB1 gene can contribute to the multistep process of the oncogenesis of epithelial ovarian tumors. Furthermore these mutations mostly occurs in the endometrioid-type of EOT, but can appear in other types such as serous-type ovarian tumor.

Adult↗

[Pre- and perinatal aspects of hemophilia A and B].

Authors investigate in a retrospective study obstetrical and genetical data in 20 years period of 149 pregnancies of patients turning to genetical counselling because of haemophilia A and B. In case of heterozygote mother there have been fetal determination of sex, and in case of male fetus, there have been DNA examination in 23 of the 35 cases. In case of sick male fetus the couple made a decision on keeping the pregnancy or not, knowing well the genetical risk. Haemophilia A occurred in case of 135 pregnancies (98 pregnancies of 55 heterozygote mothers, and 37 pregnancies from 20 sick fathers). Haemophilia B occurred in case of 14 pregnancies (9 pregnancies of 3 heterozygote mothers, and 5 pregnancies from 4 sick fathers). In case of haemophilia A heterozygote pregnant women there were 32 proven male fetuses, and in 22 cases there have been DNA examinations. In 16 cases there have been artificial abortions (in 10 cases proven disease by DNA examination), and 4 sick male newborns were born from the 16 deliveries (the disease was proven during pregnancy by DNA examination). One male newborn (healthy) was born from the 3 proven male fetuses of haemophilia B heterozygote pregnant women, in 2 cases there have been artificial abortions (in one case on the basis of DNA diagnostics). In cases of heterozygote mothers (haemophilia A and B altogether) the ration of the spontaneous abortions was 13.1%. The rations of the premature deliveries (8.2%) and the Caesarean sections (8.2%) were not higher than the national average. The ration of the bleeding complications during pregnancy was 18.7%, in 2.7% of the cases transfusion was necessary. In case of sickness of the father (in heterozygote female fetuses the haemostasis may change from the fetal side) the ration of the bleeding complications during pregnancy was 18.2%. In connection with delivery, obstetrical bleeding complications occurred in 12.2%, atonia in 2%, abrasion after delivery in 4.1, transfusion in 10.2% in cases both of haemophilia A and B heterozygote mothers. From the neonatological complications in one case there was cerebral haemorrhage, and in one case bleeding from the umbilical stump. (Both newborns were male with haemophilia.) In connection with delivery there was no haematoma developing on the skull of the newborns, there was no need of giving transfusion. In case of sickness of the fathers the ration of the instrumental uterine examination was 6.7%, there were no neonatological and other obstetrical complications.

Abortion, Induced↗

Fumonisin B1 does not prevent apoptosis in A431 human epidermoid carcinoma cells after photosensitization with a silicon phthalocyanine.

Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), an apoptosis inducer, is associated with accumulation of ceramide in various cell lines. The role of ceramide in Pc 4-PDT-induced apoptosis was investigated in A431 cells. Caspase-3 (casp-3) was activated and TUNEL positive cells began to appear 30 and 60 min post-Pc 4-PDT, respectively. A rapid increase (10 min) in cellular ceramide levels was observed after Pc 4-PDT. Induced ceramide accumulation was maintained over 60 min, Acid sphingomyelinase, a ceramide-generating enzyme, was inhibited after photosensitization with Pc 4, suggesting that the enzyme was not required for stimulated ceramide accumulation. Co-treatment of A431 cells with fumonisin B1, a ceramide synthase inhibitor, and Pc 4-PDT led to a decrease in ceramide levels without any effect on induced casp-3 activity or apoptosis. In the presence of zVAD, a pan-caspase inhibitor, apoptosis was abolished, while ceramide levels remained elevated after Pc 4-PDT. Exposure of A431 cells to exogenous C6-ceramide for 22 h, led to induction of apoptosis, and the process was abrogated by zVAD. In conclusion, C6-ceramide-, like Pc 4-PDT-induced apoptosis, is zVAD-sensitive. Furthermore, Pc 4 photosensitization can lead to apoptosis without FB-sensitive elevation in ceramide levels upstream of caspases.

Acyltransferases↗

Characterization of intestinal cnf1+ Escherichia coli from weaned pigs.

Escherichia coli isolated from 204 cases of porcine postweaning diarrhoea were tested by PCR for the genes of cytotoxic necrotic factors (CNF) and of cytolethal dystending toxin (CDT). Selected strains were also examined by PCR for the presence of papC-, sfa-, f17-, f18-, and afa-specific sequences encoding P, S, F17, F18 fimbriae and afimbrial adhesins. A 5.9% (12/204) of the strains had cnf1 gene, and two of them had cdt gene as well. Further six cdt+ strains were detected which were cnf-negative. Most of the cnf1+ strains belonged to serogroups O2, O6, O8, O54 characteristic of necrotoxic E. coli (NTEC) of humans. All the cnf1+ strains possessed the genes for P or S fimbriae or both, but were negative for F4, F17, or F18 or afimbrial adhesins. Results suggest that these enteric isolates may have entero- and/or uropathogenic significance in weaned pigs, and may have zoonotic potential for humans.

Animals↗

Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase.

OBJECTIVE: To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women. STUDY DESIGN: One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates. RESULTS: Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90-20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24-6. 48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia. CONCLUSION: Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

Adult↗

Apolipoprotein E allele distribution in trisomy 13, 18, and 21 conceptuses in a Hungarian population.

Reports documented a higher frequency of apolipoprotein E (apoE) allele epsilon 4 among mothers of children diagnosed with Down syndrome. We studied the prevalence of apoE alleles among 56 conceptuses with trisomy 13, trisomy 18, or trisomy 21. The presence of the 3 most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism, and trisomy status was detected by fluorescent polymerase chain reaction followed by DNA fragment analysis and by conventional cytologic methods. We found no significant difference in the distribution of apoE alleles in the group of trisomy 21 fetuses compared with samples from healthy blood donors. The odds of having trisomy 18 for the apoE epsilon 4 group was 3-fold as high as for apoE epsilon 3 allele compared with the healthy control group. Furthermore, a statistically significant association was found for those with trisomy 18 and apoE epsilon 4, while for those with trisomy 13 and apoE epsilon 4, the test showed no significant association. The observed apoE allele epsilon 3 frequencies among patients with Down syndrome and healthy control subjects may help explain and support previous work that did not find high rates of atherosclerosis among these persons. The role of apoE alleles in the development of trisomies needs further study.

Adult↗

Epidemiology and characterization of animal Salmonella enterica subspecies Enterica serotype typhimurium DT104 in Hungary.

Reports on the internationally emerging significance of multiresistant zoonotic Salmonella in animals and man prompted studies to estimate the significance of multiresistant Salmonella enterica subspecies enterica serotype Typhimurium (S. Typhimurium) phage type DT104 of animal origin in Hungary. A collection of 231 strains (primarily of goose, turkey, poultry and porcine origin from the years 1997-1998) was tested for resistance against 7 selected antibiotics (ampicillin, chloramphenicol, enrofloxacin, nalidixic acid, streptomycin, tetracycline and sulphamethoxazole). Strains with resistance against 3 or more were defined as multiresistant. All strains were phage typed using Felix-Callow's S. Typhimurium phage typing system, and 91 of them (suspect DT104) were also typed according to Anderson's definitive typing (DT) system. In this study, 14% of animal strains from 1997-1998 was classified as DT104, for which turkey, pig and duck seemed to be the main carriers, and the multiresistant non-DT104 strains represented a further 6% of this collection. The prevalence of DT104 was highest among strains of turkey origin (50%), followed by strains of pig (29%), chicken (25%), duck (19%), and goose (3%) origin. The other DT104 related phage types (DT12 and U302) were only detected in the case of 4 strains (2 of porcine, and one each of turkey and of goose origin). The DT104 corresponded to the Felix-Callow types 2/3 or 2c/3 in each case, except in the case of 3 turkey strains where they corresponded to type 35/3. Nalidixic acid resistance was detected in all multiresistant turkey strains and in some of other animal origin but none of these strains were resistant to enrofloxacin. A retrospective analysis (based on the above relationship) indicated that S. Typhimurium strains corresponding to DT104 could be present and increase in the Hungarian farm animal population from about 2% to 20% between 1985 and 1990, in a manner similar to the emergence of human DT104, as reported elsewhere (Pászti et al., 2000). The 91 suspect DT104 strains were also tested for plasmid profile and for spvC gene indicating the presence of the large serotype specific plasmid (Ssp). No characteristic plasmid profile could be attributed to S. Typhimurium DT104. The serovar-specific large plasmid was detected by PCR for spvC in 100% of DT104 strains and in 77% of the non-DT104 strains. The virulence of two DT104 strains was tested in orally infected day-old chicks and compared with virulence of 4 non-DT104 strains. Higher colonizing virulence of DT104 strains could be established as compared to the other strains.

Animals↗

[Benign tumor of the small intestine causing recurrent hemorrhage].

The authors reported a 56-year-old man, who suffered from repeated massive gastrointestinal bleeding. The source of the bleeding was leiomyoma of the ileum. Abdominal computertomography and selective enterography confirmed the tumour's localisation. After partial resection of the ileum the patient had no more complaints.

Gastrointestinal Hemorrhage↗