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Tivadar Tulassay

Publications and source records attributed to Tivadar Tulassay.

32 records · Page 2Linked to original sources
PubMed2003

Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-low-birth-weight infants with necrotizing enterocolitis.

BACKGROUND/PURPOSE: Altered production of immunoregulatory cytokines is associated with the development of necrotizing enterocolitis (NEC) in preterm very low-birth-weight (VLBW) infants. According to data obtained in adults, functional genetic polymorphisms influence cytokine production capacity. The aim of this study was to evaluate whether functional polymorphisms of interleukin (IL)-1beta, IL-4 receptor alpha-chain (IL-4ra), IL-6, and IL-10 genes might be associated with the risk of NEC in VLBW infants. METHODS: Dried blood spot samples of 46 VLBW infants with NEC were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Samples from 90 VLBW infants without NEC were used as controls. RESULTS: Infants with NEC carried the mutant variant of IL-4ra less frequently than controls (0.125 v 0.224; P <.05) even after adjustment for risk factors of NEC. No significant differences were found in the allelic frequencies of IL-1beta, IL-6, and IL-10 genes between NEC and control infants. CONCLUSIONS: Carrier state of IL-4ra mutant allele might be associated with lower risk of NEC in VLBW infants. This genetic variant is associated with enhanced IL-4 effect. IL-4 is a major regulator of Th1-Th2 shift. The authors hypothesize that infants carrying the IL-4ra mutant allele might have Th2 skewness that might defend against the development of NEC.

Alleles↗
PubMed2003

Genetic variants of TNF-[FC12]a, IL-1beta, IL-4 receptor [FC12]a-chain, IL-6 and IL-10 genes are not risk factors for sepsis in low-birth-weight infants.

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-4 receptor alpha-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1 beta and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.

Alleles↗
PubMed2003

The effect of physiologic hyperinsulinemia during an oral glucose tolerance test on the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in healthy young adults born with low and with normal birth weight.

Several data support that adrenal hyperandrogenism affects women with low birth weight (LBW). We also found an association between serum dehydroepiandrosterone (DHEA) and fasting insulin levels. The aim of our study was to detect the acute effects of reactive hyperinsulinemia during oral glucose tolerance test (OGTT) on DHEA(S) levels in LBW men and women. Fifty three men and 47 women (of those, 37 men and 33 women were LBW) were enrolled. DHEA, DHEAS, and insulin levels were measured before and during OGTT. Cortisol was also measured. DHEA/cortisol ratio during OGTT was calculated to analyze the acute effect of hyperinsulinemia on DHEA levels. During OGTT, DHEA and cortisol levels decreased in each individual, independently of gender and birth weight. Serum DHEAS decreased to a minor (but significant) extent only in LBW women (p<0.05). The rate of DHEA/cortisol increased in both gender, independently of birth weight. The increase of the rate of DHEA/cortisol during OGTT was associated with maximal insulin response (r = 0.45, p<0.05) and with the insulin(AUC) (r = 0.48, p<0.05) in women. Our results suggest that reactive hyperinsulinemia during OGTT might activate the androgen pathway of adrenal cortex including DHEA production. Therefore acute hyperinsulinemia might counterbalance to some extent the diurnal decrease of DHEA during OGTT.

Adult↗
PubMed2002

[Correlations of low birth weight and diseases in adulthood. The hypothesis, the facts and the doubts].

During the past 15 years more than hundred studies confirmed the association between low birth weight and the cardiovascular morbidity and mortality. The association is explained, at least partly, by the fact, that low birth weight is inversely related to type 2 diabetes, hypertension and dyslipidemia in adulthood. Several pathophysiological mechanism are implicated in the higher susceptibility of individuals born with low birth weight. Data suggest that in addition to the intrauterine retardation the sudden break of fetal development and the accelerated pace of early postnatal growth might also play a role in the pathogenesis of these chronic diseases. The authors summarize their conclusions based on the available results of epidemiological and experimental studies. They also introduce the data suggesting an association between altered bone metabolism and low birth weight. Finally, the authors present those data, that cast doubts on the reliability of associations between low birth weight and adulthood chronic diseases.

Adult↗
PubMed2002

Interleukin genetic variants and the risk of renal failure in infants with infection.

Systemic infection is a major risk factor for the development of neonatal acute renal failure (ARF). We investigated whether genetic polymorphisms of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 genes leading to a more intense inflammatory response might predispose very low birth weight (VLBW) infants to the development of ARF in severe infection. The medical records of 92 VLBW newborns (birth weight under 1,500 g) with systemic infection were analyzed. ARF developed in 38 infants during the 1st postnatal week, while 54 neonates exhibited normal renal function. The variants of TNF-alpha, IL-1beta, IL-6, and IL-10 genes were determined from dried blood samples with polymerase chain reaction and restriction fragment length polymorphism methods. The allele frequencies did not differ in ARF and in non-ARF babies, while the (TNF-alpha /IL-6) AG/GC or AG/CC haplotypes were more often present in ARF (26% vs. 6%, P<0.01). The single presence of TNF-alpha, IL-1beta, IL-6, and IL-10 variants does not influence the development of ARF, but the constellation of TNF-alpha and IL-6 genetic variants is associated with ARF. We hypothesize that the simultaneous presence of these polymorphisms might lead to an enhanced inflammatory response in the kidneys in babies with infection.

Acute Kidney Injury↗
PubMed2002

Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease.

BACKGROUND AND AIMS: We investigated the coexistence of dehydroepiandrosterone sulfate (DHEAS) and testosterone deficiency in men with inflammatory bowel disease (IBD) and their relationship with bone homeostasis. PATIENT AND METHODS: In 45 men with IBD (25 with ulcerative colitis, 20 with Crohn's disease) the testosterone and DHEAS levels were examined in relationship to bone mineral density, osteocalcin levels, and urinary deoxypyridinoline excretions. RESULTS: We detected osteoporosis in 10 and osteopenia in 22 patients at the lumbar spine and/or femoral neck. Lower testosterone levels were measured in 20. Lower DHEAS levels were present in 23 patients; these had higher deoxypyridinoline excretion and lower lumbar spine and femoral neck BMD T scores than patients with normal DHEAS. DHEAS and BMD were correlated at the lumbar spine and the femoral neck. Associations remained significant after adjustment for age, weight, steroid use, and inflammatory activity. No independent effect of testosterone deficiency was detected on bone parameters. CONCLUSION: DHEAS deficiency may contribute to the bone loss of men with IBD. This putative action of DHEAS on bone turnover is contrary to the common effect of testosterone deficiency and steroid therapy.

Adult↗
PubMed2002

Birth weight and renal function.

Low birth weight due to premature birth or to intrauterine growth retardation adversely affects normal renal development. In the period immediately after birth, the short-term renal-related consequences of low birth weight are an increased risk of acute renal failure as well as transient imbalance of fluid and electrolyte homeostasis. Epidemiological studies show that low birth weight adults are at risk of developing chronic renal disease. There are thought to be several causes for this phenomenon. Adult low birth weight subjects have an increased incidence of hypertension and type 2 diabetes, both of which are well-established risk factors for chronic renal injury. Moreover, interference with normal kidney development, as seen in low birth weight babies, results in a lower than normal number of nephrons, which might also play a role in the renal disturbances.

Acute Kidney Injury↗
PubMed2002

Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin.

BACKGROUND: Postischemic organ dysfunction is influenced by gender and sexual steroids. METHODS: To compare the susceptibility of the kidney to postischemic failure between sexes, the left vascular pedicle was clamped for 50 minutes in anesthetized male and female Wistar rats. Survival rate, renal and systemic hemodynamics and renal prepro-endothelin (pp-ET) mRNA expression were measured. RESULTS: Eight percent of males as compared to 75% of females survived for more than 7 days. Previous orchidectomy of mature rats or sexual immaturity improved the rate of 7 day survival to 67% and 58%, respectively, as compared to intact males (P < 0.05). Estradiol treatment of mature male animals also resulted in a significantly better survival. Ovariectomy, sexual immaturity or testosterone treatment had no impact on the course of renal failure in females. The early postischemic recovery of renal blood flow was delayed due to a dramatic increase in renal vascular resistance in male versus female rats. The expression of pp-ET gene in the kidneys was increased at 5 minutes following reperfusion and was significantly higher 2 hours after ischemia in males, but not in females. Pretreatment with the endothelin A receptor antagonist LU 135252 provided indistinguishable survival rates in intact male and female rats after warm renal ischemia. CONCLUSION: Female rats enjoy relative protection against postischemic renal failure. Furthermore, in intact males the effects of androgens upon ischemic kidney damage seem to be mediated by endothelin-induced vascular changes.

Animals↗
PubMed2002

Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus.

OBJECTIVE: Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. DESIGN AND METHODS: One hundred and seven children with T1DM (T1DM for 5 Years; age, 1-14 Years; boys/girls, 57/50; body mass index, 17.0+/-2.3 kg/m(2); haemoglobin A(Ic) (HbA(Ic)), 7.87+/-1.05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ("a", "b", "f", "t" and "u" alleles respectively) were investigated. RESULTS: The "t" and "T" alleles miss the Hardy-Weinberg equilibrium (P<0.01) in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the "b", "a" and "u" alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ("b"+"a"+"u" present/absent: healthy, 0/53; diabetic, 13/37; P<0.005). In boys the prevalence of "b"+"a"+"u" genotype was similar in T1DM and controls. CONCLUSIONS: The impact of the "t" allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the "b", "a" and "u" alleles greatly increases the probability of T1DM in girls.

Adolescent↗
PubMedDate not supplied

Genetic polymorphisms of vascular endothelial growth factor and angiopoietin 2 in retinopathy of prematurity.

Angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) contribute to development of retinopathy of prematurity (ROP). We aimed to test whether polymorphisms of these factors are associated with ROP. VEGF(-2578) and Ang2(-35) polymorphisms were analyzed with PCR-RFLP method in 200 preterm infants without ROP or with ROP stages 1-5. Our results suggest that there is no association between carrier state of VEGF(-2578) and Ang2(-35) and risk of ROP in preterm infants. The prevalence of VEGF(-2578) "A" allele was lower in preterm boys with severe ROP (stages 4-5) than in those without or with mild ROP (stages 1-3).

Alleles↗
PubMedDate not supplied

Comparative promoter analysis of doxorubicin resistance-associated genes suggests E47 as a key regulatory element.

Working under the assumption that up- or downregulation of genes implicated in chemoresistance may be the result of altered function of regulatory transcription factors (TF), over-represented TF-binding sites of gene lists previously associated with doxorubicin resistance were the target of our search. First, a data warehouse was set up containing 52 genes which were present in at least two gene lists; of those, proximal promoter sequences (1 kb upstream and 0.05 kb downstream of the transcriptional start sites) could be retrieved from genomic databases for 45 genes using the EZ-Retrieve. The TOUCAN tool MotifScanner, which searches the TRANSFAC database, was used to detect TF-binding sites (TFBSs) in our set of sequences. The statistics tool of the Java program TOUCAN was applied to the data with the appropriate expected frequencies file to compare the measured prevalence to a background model. The most significantly over-represented TFBS was that of E47 (p=0.00024, prevalence: 0.2 vs. background: 8.19E-6). In summary, based on the results of our analysis it is hypothesized that the E47 transcription factor may contribute to doxorubicin resistance.

Antibiotics, Antineoplastic↗