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Biomedical subjects

L Nagy

Publications and source records attributed to L Nagy.

At least 55 records · Page 3Linked to original sources
PubMed1999

Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods.

We previously reported that mice lacking the RARgamma gene and one or both alleles of the RARbeta gene (i.e., RARbeta+/-/RARgamma-/- and RARbeta-/-/RARgamma-/- mutants) display a severe and fully penetrant interdigital webbing (soft tissue syndactyly), caused by the persistence of the fetal interdigital mesenchyme (Ghyselinck et al., 1997, Int. J. Dev. Biol. 41, 425-447). In the present study, these compound mutants were used to investigate the cellular and molecular mechanisms involved in retinoic acid (RA)-dependent formation of the interdigital necrotic zones (INZs). The mutant INZs show a marked decrease in the number of apoptotic cells accompanied by an increase of cell proliferation. This marked decrease was not paralleled by a reduction of the number of macrophages, indicating that the chemotactic cues which normally attract these cells into the INZs were not affected. The expression of a number of genes known to be involved in the establishment of the INZs, the patterning of the autopod, and/or the initiation of apoptosis was also unaffected. These genes included BMP-2, BMP-4, Msx-1, Msx-2, 5' members of Hox complexes, Bcl2, Bax, and p53. In contrast, the mutant INZs displayed a specific, graded, down-regulation of tissue transglutaminase (tTG) promoter activity and of stromelysin-3 expression upon the removal of one or both alleles of the RARbeta gene from the RARgamma null genetic background. As retinoic acid response elements are present in the promoter regions of both tTG and stromelysin-3 genes, we propose that RA might increase the amount of cell death in the INZs through a direct modulation of tTG expression and that it also contributes to the process of tissue remodeling, which accompanies cell death, through an up-regulation of stromelysin-3 expression in the INZs. Approximately 10% of the RARbeta-/- /RARgamma-/- mutants displayed a supernumerary preaxial digit on hindfeet, which is also a feature of the BMP-7 null phenotype (Dudley et al., 1995, Genes Dev. 9, 2795-2807; Luo et al., 1995, Genes Dev. 9, 2808-2820). BMP-7 was globally down-regulated at an early stage in the autopods of these RAR double null mutants, prior to the appearance of the digital rays. Therefore, RA may exert some of its effects on anteroposterior autopod patterning through controlling BMP-7 expression.

Animals↗
PubMed1999

No association between D2 dopamine receptor (DRD2) "A" system alleles, or DRD2 haplotypes, and posttraumatic stress disorder.

BACKGROUND: Association studies between marker alleles at the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders, including posttraumatic stress disorder (PTSD). METHODS: We studied allele frequency of the DRD2 TaqI "A," "B," and "D" system markers in 52 European-American subjects with diagnoses of PTSD (based on structured interviews). RESULTS: Frequency of the A1 allele in this sample was .15, not significantly different from the .19 allele frequency seen in 87 control subjects. We were thus unable to replicate the previous reports of allelic association between the DRD2 TaqI "A1" allele and PTSD. There were also no significant differences in allele frequency for the "B" or "D" systems. We then computed three marker (TaqI "A," "B," and "D" system) haplotypes for the sample; DRD2 haplotype frequencies also did not differ between control subjects and subjects with PTSD. CONCLUSIONS: We conclude that DRD2 alleles are not associated with PTSD in this sample, and that genetic variation at the DRD2 locus is not likely to be an important contributor to risk for this disorder.

Adult↗
PubMed1999

Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus, secondary antiphospholipid syndrome and IgM monoclonal paraproteinaemia.

In this case report, a woman is described who developed systemic lupus erythematosus at the age of 36 years affecting the central nervous system and kidneys, showing the serological evidence of an acquired C1 inhibitor deficiency, but also developing an antiphospholipid syndrome and IgM lambda type paraproteinemia. During the 25 years follow-up she did not show any signs of angioedema. Although the immunological abnormalities are still constantly present, the disease has been quiescent since the past three years. The possible pathophysiology of clinical and laboratory features are discussed.

Antibodies, Anticardiolipin↗
PubMed1999

Regulation of macrophage gene expression by peroxisome-proliferator-activated receptor gamma: implications for cardiovascular disease.

The peroxisome-proliferator-activated receptor gamma is a member of the nuclear receptor superfamily that functions as a key transcriptional regulator of cell differentiation and lipid metabolism. In addition, peroxisome-proliferator-activated receptor gamma is now recognized to be the biological receptor for the thiazolidinedione class of antidiabetic drugs, which includes troglitazone and rosiglitazone. Recent evidence indicates that peroxisome-proliferator-activated receptor gamma is expressed at high levels in macrophages, including the foam cells of atherosclerotic lesions. Oxidized low-density lipoprotein, which plays a central role in lesion development, can activate peroxisome-proliferator-activated receptor gamma by providing the cell with oxidized fatty acid ligands of the receptor. The elucidation of a peroxisome-proliferator-activated receptor gamma signalling pathway in macrophages provides a mechanism by which oxidized lipids may directly regulate gene expression in the context of the atherosclerotic lesions. A number of potential target genes for peroxisome-proliferator-activated receptor gamma in these cells have been identified. Some, such as the type B scavenger receptor CD36 are induced by peroxisome-proliferator-activated receptor gamma ligands, whereas others, such as scavenger receptor type A, inducible nitric oxide synthetase and certain cytokines, are repressed. Given the widespread clinical use of thiazolidinediones, it is important to consider the influence of these drugs on the risk of atherosclerosis. The net effect of peroxisome-proliferator-activated receptor gamma ligands on the atherogenic process is likely to reflect a balance between local effects in the artery wall and systemic effects on lipid metabolism.

Animals↗
PubMed1999

Risk factors for psychological stress among international business travellers.

OBJECTIVES: This study investigated sources of self reported psychological stress among international business travellers at the World Bank, following up on a previous study showing that travellers submitted more insurance claims for psychological disorders. Hypotheses were that work, personal, family, and health concerns, as well as time zone travel, contribute to travel stress. METHODS: A travel survey was developed from focus groups and consisted of questions about these potential sources of travel stress. Surveys were sent to a random sample of staff, stratified by number of travel missions, age range, and sex. Canonical correlation analyses estimated the association between key survey items on sources of stress and two measures of travel stress. RESULTS: 498 staff completed the survey. More than a third reported high to very high travel stress. Correlations between predictors and travel stress showed that social and emotional concerns (such as impact of travel on family and sense of isolation) contributed the most to such stress, followed by health concerns, and workload upon return from travel. Surprisingly, time zone travel did not contribute to the self reported stress of these travellers. There were few modifiers of stress, although respondents suggested that a day of rest after travel and reduced workloads would help. CONCLUSIONS: The current study confirms clinical impressions about several correlates of travel stress. Similar research with travellers in other organisations could help to determine whether the findings from this study are valid and what measures can be taken to reduce the psychological health risks to travellers.

Adaptation, Psychological↗
PubMed1999

Effect of transfusion on the endothelium dependent dilatation of brachial artery in patients with chronic anemia.

The effect of changes in the main determinants of whole blood viscosity after red blood cell transfusion on endothelium dependent dilatation of brachial artery was studied in patients treated with symptoms of chronic anemia. 10 patients were involved in the study, 8 males, 2 females, mean age 52.7+/-18.7 years. Following blood tests performed at hospital admission: hemoglobin (Hgb), red blood cell count (RBC), hematocrit (Hct), white blood cell count, platelet count, plasma total protein, fibrinogen, plasma viscosity, BUN, creatinine, cholesterol, triglycerides. Flow mediated dilatation of brachial artery (FMD) was determined by Doppler method. Blood tests and FMD study were repeated after transfusion. The main determinants of whole blood viscosity increased after transfusion. The increases of Hgb, RBC, Htc were highly significant. The central flow velocity in brachial artery decreased at rest and during hyperemia as well. FMD of brachial artery was not changed significantly after transfusion. The change in factors determining whole blood viscosity did not cause a significant change in FMD. The probable explanation for this is that the increase of whole blood viscosity is associated with a decrease of central flow velocity. These two counteracting changes can equal each other.

Adult↗
PubMed1999

[Unusual coordination behavior of D-fructose towards dimethyltin(IV)2+: metal-promoted deprotonation of alcoholic hydroxyl groups in aqueous solutions at low pH].

To study the effect of the conformation of sugar hydroxy groups on metal complexation processes, complex formation of eight saccharides (D-fructose, L-sorbose, L-arabinose, D-arabinose, D-glucose, D-sorbitol, 2-deoxy-D-glucose and D-saccharose) with dimethyltin(IV)2+ cations was investigated in aqueous solution by potentiometric equilibrium measurements, 13C NMR, polarimetric and Mössbauer spectroscopic methods. The experimental results proved that deprotonation of D-fructose and L-sorbose is caused by the coordination of dimethyltin(IV)2+ in the unusual low pH interval 4-6 in contrast to the other saccharides deprotonated in analogous way at pH > 8. Increasing the pH of the solution resulted in the formation of further complexes. Stability and composition of the species was determined by potentiometric studies. 13C NMR measurements led to the assignment of the sugar OH groups participating in the processes. Mössbauer investigations in the quick-frozen solutions permitted the determination of the stereochemistry of tin(IV) in the complexes.

Alcohols↗
PubMed1999

[Comparative pharmacokinetics of 800 mg of acyclovir-containing Telviran and Zovirax tablets in healthy volunteers].

The authors performed a detailed comparative clinical and pharmacokinetic study with two 800 mg acyclovir containing tablets, namely the Telviran (EGIS Pharmaceuticals Ltd.) and the Zovirax (Wellcome Foundation Ltd.). The determination of the detailed pharmacokinetic parameters and the relative bioavailability was carried out on 24 healthy male volunteers in a two way, open, randomised, cross-over design study after single dose administration. The plasma concentration of acyclovir was determined by a newly developed and validated highly sensitive (LLOQ = 10 ng/ml) HPLC-UV bioanalytical method after sample preparation with RP-18 solid phase extraction method (SPE). The individual pharmacokinetic parameters calculated from the time-plasma concentration curve (tmax, Cmax, AUC0-infinity, AUC0-16, AUC0-t, AUC0-z, AUCRest, t beta 1/2, MRT, Cmax/AUC0-infinity) were compared with statistical methods (ANOVA, ANOVAlog, Confidence interval, Schuirmann, Wilcoxon tests). On the basis of the results of the statistical evaluation and the clinical study, there was no significant difference found between the two acyclovir containing preparations. The comparative pharmacokinetic study demonstrated, that the relative bioavailability of the 800 mg Telviran and Zovirax tablets are equivalent and the two products are bioequivalent.

Acyclovir↗
PubMed1999

In vitro and in vivo effects of formamidines in locust (Locusta migratoria migratorioides).

In vivo and in vitro experiments were used to study the effects of formamidines in the locust, Locusta migratoria migratorioides. In vivo the lethal and the antifeeding effects, in vitro the inhibition of the binding of a selective 3H-ligand to the receptors of octopamine, tyramine, dopamine, serotonin and gamma-amino butiric acid were studied. We have demonstrated that demethylchlordimeform is specific agonist to octopamine receptor, having high affinity to octopamine receptor, a moderate affinitiy to tyramine receptor and a low affinity to dopamine, serotonin and to gamma-amino butiric acid receptors. The demethylated chlordimeform analogoues, demethylchlordimeform and didemethylchlordimeform have higher affinity to the octopamine receptor than the parent compound. The formamidines had a toxic and an antifeeding effects when injected into the locust. The half lethal doses (LD50) and the feeding inhibition were correlated with the affinity of the compounds (Ki). The ring substitutions of the mulecule have alterated the both affinity and in vivo effect of the compounds. The most effective ring substitution pattern is 2,4-disubstitution with a combination of methyl groups or halogens. Our results suggest that the lethal effect of formamidines is mediated through the octopamine receptor.

Amidines↗
PubMed1998

[Effect of chronic anemia on the endothelium-dependent dilatation of the brachial artery].

UNLABELLED: The effect of changes in main determinants of whole blood viscosity after red blood cell transfusion on endethel dependent dilatation of brachial artery was studied in patients treated with transfusion because of symptoms of chronic anaemia. PATIENTS AND METHODS: 10 patients were involved, 8 females 2 males, mean age 50.9 +/- 16.6 years. Following blood tests were performed at hospital admission: hemoglobin, red blood cell count, heamatocrit, white blood cell count, platelet count, plasma total protein, fibrinogen, plasma viscosity, blood urea nitrogen, creatinine, cholesterol, triglicerides. Flow mediated dilatation of brachial artery was determined, too. Blood tests and flow mediated dilatation study were repeated after transfusion. RESULTS: The main determinants of whole blood viscosity increased after transfusion. The increase of hemoglobin, red blood cell count, hematocrit were highly significant. The central flow velocity in brachial artery decreased at rest and during hyperemia as well. The flow mediated dilatation of brachial artery wasn't significantly changed by transfusion. CONCLUSIONS: Change of determinants of whole blood viscosity caused by transfusion didn't change the flow mediated dilatation of brachial artery. The probable reason for this that the increase of whole blood viscosity in associated with the decrease of central flow velocity. These two counteracting changes probably equal each other.

Aged↗
PubMed1998

Retention behaviours and separation of carboxylic acids by ion-exchange chromatography.

The use of high-performance suppressed ion chromatography for the separation of aliphatic carboxylic acids has become an attractive and viable method during the past years. This paper summarises and critically concludes that some new results have been achieved in separation and detection of low-molecular-mass organic anions. Theoretical and practical considerations of ion-exchange selectivity to control retention behaviour are presented. The major factors that determine the separation ability of ion-exchange chromatography (pKa values, the aliphatic nature and valency of solutes, eluent pH and the chemical composition of stationary phases) are discussed. The question of isocratic vs. gradient elution and different separation modes are examined briefly. The potentials and limitations of the developed methods and their specific application areas are outlined.

Carboxylic Acids↗
PubMed1998

[Clinicopathology of aortic dissection].

A population based study was carried out over a 25-year period (1972-1997) to disclose the clinical and pathological features of aortic dissection based on the analysis of 79 (71 acute and 8 chronic) consecutive cases of disease observed in an defined population of 106,000 inhabitants. Of the 79 patients 65 (82.3%) were admitted to hospital and 14 (17.7%) died out of hospital. Their ages ranged from 36 to 97 years (mean, 65.4 yrs), 49 (62.0%) were men and 30 (38.0%) were women with means 61.2 and 69.1 years, respectively. The male/female ration was 1.6:1. All but two operated patients died. The pain was the leading symptom. Every patients had some kind of cardiovascular and respiratory signs. Neurologic symptoms occurred in 27/65 (41.5%) patients. In five patients the clinical picture of abdominal catastrophe and in two patients renal failure occurred. The major vessels were affected in 32/75 (42.7%) autopsies. Aortic rupture were seen in 64/79 (81.0%) cases. Five spontaneous healings were observed. The hypertension, the advantaged age and the arteriosclerosis are regarded as the mean predisposing factors.

Acute Disease↗
PubMed1998

Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma.

Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARgamma-dependent transcription through a novel signaling pathway involving scavenger receptor-mediated particle uptake. Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARgamma. Our data suggest that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that PPARgamma may be a key regulator of foam cell gene expression.

Animals↗
PubMed1998

PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL.

The formation of foam cells from macrophages in the arterial wall is characterized by dramatic changes in lipid metabolism, including increased expression of scavenger receptors and the uptake of oxidized low-density lipoprotein (oxLDL). We demonstrate here that the nuclear receptor PPARgamma is induced in human monocytes following exposure to oxLDL and is expressed at high levels in the foam cells of atherosclerotic lesions. Ligand activation of the PPARgamma:RXRalpha heterodimer in myelomonocytic cell lines induces changes characteristic of monocytic differentiation and promotes uptake of oxLDL through transcriptional induction of the scavenger receptor CD36. These results reveal a novel signaling pathway controlling differentiation and lipid metabolism in monocytic cells, and suggest that endogenous PPARgamma ligands may be important regulators of gene expression during atherogenesis.

Alitretinoin↗
PubMed1998

Role of the histone deacetylase complex in acute promyelocytic leukaemia.

Non-liganded retinoic acid receptors (RARs) repress transcription of target genes by recruiting the histone deacetylase complex through a class of silencing mediators termed SMRT or N-CoR. Mutant forms of RARalpha, created by chromosomal translocations with either the PML (for promyelocytic leukaemia) or the PLZF (for promyelocytic leukaemia zinc finger) locus, are oncogenic and result in human acute promyelocytic leukaemia (APL). PML-RARalpha APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF-RARalpha patients respond very poorly, if at all. Here we report that the association of these two chimaeric receptors with the histone deacetylase (HDAC) complex helps to determine both the development of APL and the ability of patients to respond to retinoids. Consistent with these observations, inhibitors of histone deacetylase dramatically potentiate retinoid-induced differentiation of RA-sensitive, and restore retinoid responses of RA-resistant, APL cell lines. Our findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease.

Antineoplastic Agents↗
PubMed1998

A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effects of proband comorbidity.

BACKGROUND: We used contemporary family-epidemiological methods to examine patterns of comorbidity and familial aggregation of psychiatric disorders for anorexia and bulimia nervosa. METHODS: Direct interviews and blind best-estimate diagnostic procedures were used with diagnostically "pure" groups of probands with eating disorders and a matched control group. Lifetime prevalence rates of eating disorders, mood disorders, substance use disorders, anxiety disorders, and selected personality disorders were determined in female probands with restricting anorexia nervosa (n=26) or bulimia nervosa (n=47), control women (n=44), and first-degree biological relatives (n=460). RESULTS: Relatives of anorexic and bulimic probands had increased risk of clinically subthreshold forms of an eating disorder, major depressive disorder, and obsessive-compulsive disorder. Familial aggregation of major depressive disorder and obsessive-compulsive disorder was independent of that of anorexia nervosa and bulimia nervosa. These relatives also had increased risk of other anxiety disorders, but the mode of familial transmission was not clear-cut. The risk of substance dependence was elevated among relatives of bulimic probands compared with relatives of anorexic probands, and familial aggregation was independent of that of bulimia nervosa. The risk of obsessive-compulsive personality disorder was elevated only among relatives of anorexic probands, and there was evidence that these 2 disorders may have shared familial risk factors. CONCLUSIONS: There may be a common familial vulnerability for anorexia nervosa and bulimia nervosa. Major depressive disorder, obsessive-compulsive disorder, and substance dependence are not likely to share a common cause with eating disorders. However, obsessional personality traits may be a specific familial risk factor for anorexia nervosa.

Adolescent↗
PubMed1998

Chronic post-traumatic radial instability of the metacarpophalangeal joint of the finger. Long-term results of ligament reconstruction.

Chronic painful post-traumatic instability of the radial collateral ligament complex of the metacarpophalangeal joint of a finger was treated by tendon graft reconstruction in 24 patients. Seventeen patients (20 joints) were available for a retrospective study at a mean follow-up time of 105 months. Eighty percent of the joints showed excellent or good results, with relief of pain, return of adequate stability, a near normal range of motion and absence of degenerative changes.

Chronic Disease↗