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J Sólyom

Publications and source records attributed to J Sólyom.

At least 19 recordsLinked to original sources
PubMed2006

Two-site entropy and quantum phase transitions in low-dimensional models.

We propose a new approach to study quantum phase transitions in low-dimensional lattice models. It is based on studying the von Neumann entropy of two neighboring central sites in a long chain. It is demonstrated that the procedure works equally well for fermionic and spin models, and the two-site entropy is a better indicator of quantum phase transition than calculating gaps, order parameters, or the single-site entropy. The method is especially convenient when the density-matrix renormalization-group algorithm is used.

Journal Article↗
PubMed2006

Potential advantage of N363S glucocorticoid receptor polymorphism in 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients. DESIGN: CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively. METHODS: The CYP21 gene of 200 CAH patients was analyzed by allele-specific PCR. The GR gene was tested for N363S by PCR followed by restriction fragment length polymorphism. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, dehydroepiandrosterone (DHEA), aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed. RESULTS: The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference between the carriers and non-carriers in either the substitution doses, the hormonal, or the auxiological parameters. CONCLUSIONS: The association of sensitizing the GR variant with impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimes.

Adrenal Hyperplasia, Congenital↗
PubMed2005

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Limited value of serum steroid measurements in identification of mild form of 21-hydroxylase deficiency.

BACKGROUND: ACTH stimulation test is widely used as a basic diagnostic method for non-classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). However, the interpretation of this test has not been definitely established. To determine the cut-off values of basal and post-ACTH serum 17-OHP concentrations, data of patients with suspected 21-OHD has been analysed. PATIENTS AND METHODS: Two hundred and eighty-seven patients with postnatal/peripubertal virilization were investigated. Serum steroid concentrations were measured by RIA, urinary steroid profile was determined by capillary gas chromatography and mutation analysis of CYP21 gene was performed by allele specific PCR. 21-OHD was diagnosed by elevated serum 17-OHP concentrations, high level of the urinary 17-OHP metabolites and/or homozygosity for CYP21 mutations. RESULTS: Twenty-one patients of the total of 287 subjects (7.3 %) were identified as having 21-OHD. The numbers of 21-OHD patients compared to total numbers of patients with different ranges of serum 17-OHP were as follows: basal values below 3.5 ng/ml (mean + 1 SD) 0/225; between 3.5 - 6.6 ng/ml 3/41; above 6.6 ng/ml (mean + 2 SD) 18/21. Post-ACTH values below 6.4 ng/ml (mean + 1 SD) 0/226, between 6.4 - 10.3 ng/ml 0/35, above 10.3 ng/ml (mean + 2 SD) 21/26. CONCLUSION: There are patients with inappropriate peripubertal virilization who have slightly elevated 17-OHP concentrations. In this subgroup of patients more sensitive and specific methods are needed to establish the diagnosis of 21-OHD. Therefore we suggest performing an ACTH stimulation test in patients with a morning 17-OHP level above 3.5 ng/ml. Furthermore, urinary steroid profile and/or CYP21 gene analysis are needed in patients with a stimulated 17-OHP value between 10 and 30 ng/ml. These tests will distinguish between patients with non-classical 21-OHD and patients with other disorders.

Adolescent↗
PubMed2001

[Androgen insensitivity syndrome. Clinical features and molecular genetics].

Androgen insensitivity syndrome (AIS) is an X-linked hereditary disorder caused by the mutation of the androgen receptor gene leading to variable phenotypes according to the depth of the hormonal resistance. There is a lack of knowledge regarding the criteria used to decide the management of infants with partial AIS, particularly with respect to sex of rearing. Therefore a national survey of patients with AIS in Hungary has been decided to compose a database for analyzing current practice. Preliminary results of the analysis for the mutations in the androgen receptor gene of Hungarian patients with AIS has been presented. The authors suggest that guidelines for clinicians on appropriate diagnostic and management strategies for AIS patients, particularly in the case of suspected partial AIS, would be helpful.

Androgen-Insensitivity Syndrome↗
PubMed2001

Growth patterns and final height in congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency. Results of a multicenter study.

BACKGROUND: Longitudinal growth and bone age (BA) development are the most important clinical parameters for monitoring adequate glucocorticoid replacement in children with congenital adrenal hyperplasia (CAH). AIM OF THE STUDY: To analyze the growth pattern of patients treated for CAH of the salt wasting (SW) and simple virilizing (SV) clinical forms; to evaluate final height as compared to reference data and individual target height; to evaluate the course of BA development. PATIENTS AND METHODS: A large database of 598 patients with CAH was created in 5 Central European countries and growth data of 341 treated patients with 21-hydroxylase deficiency were analyzed retrospectively. The patients were of Caucasian origin. Centiles were constructed in a cross-sectional manner and an additional longitudinal analysis was performed in order to evaluate the pubertal growth spurt by applying particular statistical methods (Preece-Baines model). RESULTS: The growth of SW CAH patients was impaired in infancy and early childhood (0-3 years of age), but followed normal patterns in childhood until puberty. In contrast, children with SV CAH had normal patterns of growth in infancy and early childhood and were considerably taller than healthy references during childhood. In the longitudinal study, peak height velocity in both boys and girls was normal, but it occurred at an earlier age than in the standard population. The final height of patients with CAH was reduced in comparison to both the reference and the individual target height. No correlations were found between final height and age at the start of the therapy in SV patients or between final height and year of birth. BA was advanced in both types of CAH, but more accelerated in SV patients. CONCLUSION: Characteristic growth patterns for treated SV and SW CAH children were identified, with a normal pubertal growth spurt and reduced final height being observed.

Adolescent↗
PubMed2001

Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries.

Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Correlation of blood-spot 17-hydroxyprogesterone daily profiles and urinary steroid profiles in congenital adrenal hyperplasia.

OBJECTIVE: To compare the value of blood-spot 17-hydroxyprogesterone (17-OHP) daily profiles and urinary steroid excretion in untreated and treated patients with congenital adrenal hyperplasia (CAH). PATIENTS: Ten patients with CAH were investigated during steroid replacement therapy (Group 1), and 11 patients were investigated without treatment (Group 2). METHODS: Capillary blood samples were collected for measurement of blood-spot 17-OHP values by non-chromatographic radioimmunoassay. Steroid profiles of 24-h urine samples were analyzed by gas chromatography. RESULTS: There was a close correlation between the individual daily means of blood-spot 17-OHP measurements and the pregnanetriol/ tetrahydrocortisone ratio in both groups of patients (Group 2: r=0.839, p<0.001; Group 1: r=0.686, p<0.001). Almost the same correlation was found between the blood-spot 17-OHP value and the sum of three 17-hydroxyprogesterone metabolites/the sum of three cortisol/cortisone metabolites ratio (Group 2: r=0.918, p<0.001; Group 1: r=0.741, p<0.001). CONCLUSIONS: Blood-spot 17-OHP measurements and 24-h urinary steroid profile have the same impact in identification and monitoring therapy of children with CAH.

17-alpha-Hydroxyprogesterone↗
PubMed1999

[Presence of antibodies to human herpesvirus type 6 and 7 in Hungarian children].

Prevalence of antibodies to variants HHV-6A and B as well as HHV-7, the time of primary infections are not know in Hungarian children. Therefore, antibodies to these viruses were studied in 21 healthy children aged between 6 and 18 months. Lymphoid cultures were infected with standard virus strains for indirect immunofluorescence. IgM, IgG and high avidity IgG after 8M urea treatment were quantified in serial dilutions of sera. It was established that, three of 13 boys had low level (1:20) IgG or IgM antibodies to HHV-6A, but all girls were negative. With exception of one girl and one boy, all had antibodies to HHV-6B in different titres (1:20 to 1:640 by immunofluorescence), in 9 cases only IgM, in further 4 cases only low avidity IgG were detected. Children studied gradually acquired symptom-free HHV-6B infection between age of 8 and 18 months. Antibodies to HHV-7 were found in 3 boys and one girl before their age of 12 months, but the majority were infected after that age. Approximately three quarters of children acquired either HHV-6B or HHV-7 before age of 18 months. More than half of the children were infected with HHV-6B prior to HHV-7. Antibody level to HHV-6B was slightly higher in boys, while that to HHV-7 was higher in girls. In Hungary, childhood infection with HHV-6A seems to be a very rare event. Epidemiology of HHV-6B primary infection is similar to that of industrial countries, while that of HHV-7 resembles data of developing world: onset of antibodies occurs 1 or 2 years earlier than in the industrial nations.

Antibodies, Viral↗
PubMed1999

Serum osteocalcin and insulin-like growth factor I levels in children with congenital adrenal hyperplasia.

Patients with the virilizing forms of congenital adrenal hyperplasia (CAH) need a life-long glucocorticoid replacement therapy and also an additional mineralocorticoid replacement in cases with the salt-wasting form of the disease. Glucocorticoids are reported to decrease the serum osteocalcin levels and to inhibit the effects of insulin-like growth factor I (IGF-I). To collect data on the age related patterns of osteocalcin and IGF-I production in patients with CAH, measurements of these compounds have been carried out in a considerably large sample of treated CAH patients and control subjects in childhood and adolescence. Data of 62 patients between 0. 3-19 years of age were compared to the data of 188 control children. Osteocalcin and IGF-I were determined by radioimmunoassay. A lower than normal level of serum osteocalcin was found in both male and female patients at chronological ages above 11.6 and 9.6 years, respectively. Furthermore, no pubertal osteocalcin peak could be seen when data were evaluated according to the bone age. Serum IGF-I levels were higher in male CAH patients at the chronological age of 0.3-15.5 years and in female patients at the chronological age of 4. 6-9.5 years. In pubertal years serum IGF-I concentrations were lower in CAH patients when data were evaluated according to the bone age. We conclude that serum osteocalcin is decreased during and after puberty in CAH patients on replacement doses of glucocorticoids. Normal to elevated serum levels of IGF-I in treated CAH cases suggest that the shorter final height of these patients may not be due to the decreased activity in the growth hormoneIGF-I axis, but rather to the advanced bone maturation and the premature epiphyseal fusion.

Adolescent↗
PubMed1999

Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders, causing impaired secretion of cortisol and aldosterone from the adrenal cortex, with subsequent overproduction of adrenal androgens. The most common enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To determine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatrics, Budapest, Hungary, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 167 patients (representing 306 unrelated chromosomes and 56.2% of the total group of patients). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mutations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes. 1999)

Adrenal Hyperplasia, Congenital↗
PubMed1998

Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II.

UNLABELLED: Two boys presenting with infection-triggered, life-threatening salt-loss and hyperkalaemia were published in 1991 in the European Journal of Pediatrics. In both boys, the diagnosis of corticosterone methyl oxidase (CMO) deficiency type II has been established on the basis of determinations of plasma and urinary steroids. We had the opportunity to perform a molecular genetic study in one of the two boys. This boy had an elevated plasma 18-hydroxycorticosterone/aldosterone ratio which is pathognomonic for CMO deficiency type II. Sequence analysis of the CYP11B2 gene revealed a homozygous single base exchange in codon 185 of CYP11B2 causing an amino acid substitution Thr185Ile. CONCLUSION: A Thr185Ile mutation in the CYP11B2 gene was found in a patient with CMO deficiency type II. This mutation may change the secondary structure of the enzyme leading to its decreased activity.

Amino Acid Substitution↗
PubMed1997

[Androgen-producing adrenocortical adenoma in childhood. Pitfalls of differential diagnosis].

A two-year-old girl presented with clitoromegaly and an abdominal mass. Diagnostic procedures including sonography, computerized tomography, scintigraphy and measurement of catecholamines in urine excluded neuroblastoma, but suspected Wilms-tumor. Before completing the steroid measurements therapy was initiated according to Wilms-tumor (preoperative cytostatic therapy followed by surgical removal of the tumor). Morphology of the tumor, the serum and urinary steroid profile proved a benign adrenocortical adenoma producing mainly delta 5-steroids including the weak androgen, dehydroepiandrosterone.

Adenoma↗
PubMed1997

[Adrenoleukodystrophy].

7-year-old boy with adrenoleukodystrophy is presented with the typical clinical picture, biochemical findings and review of the literature. The obligate carrier status of the mother and the asymptomatic adrenoleukodystrophy of the 5-year-old brother are biochemically proved. Therapeutic regime of Lorenzo's oil has been introduced to the young brother, and the question of bone marrow transplantation is discussed.

Adrenoleukodystrophy↗
PubMed1997

Hypertelorism and hypospadias associated with a de novo apparently balanced translocation between 8q22.3-23 and 20p13.

A de novo apparently balanced translocation involving chromosomes 8 and 20 was found in a 14-year-old boy with minor anomalies, mild skeletal abnormalities and ambiguous external genitalia including perineoscrotal hypospadias, rudimentary fused labioscrotal folds, bilateral cryptorchidism, and small penis. The karyotype was 46,XY, t(8;20)(q22.3-23;p13). No signs of other conditions known to be associated with structural anomalies of either chromosome 8 or 20 were present and incomplete masculinisation of the external genitalia appears to be the main component of the phenotype. Clinical and biological studies showed apparently normal testicular function in utero and after birth. Examinations excluded 5 alpha-reductase deficiency or a block in any enzymatic steps of testosterone, glucocorticoid and mineralocorticoid biosynthesis. Coding sequences of the sex-determining gene (SRY) and androgen receptor gene (AR) were found to be identical to those of a normal male excluding their role in the cause of the present condition. Since several other reports describe the association of hypospadias and hypertelorism with deletions or translocations involving 8q, we suggest that a locus necessary for male sex differentiation is located at distal 8q.

Abnormalities, Multiple↗
PubMed1996

[17 beta-hydroxysteroid dehydrogenase defect: female phenotype with 46,XY karyotype].

Deficiency of the 17 beta-hydroxysteroid dehydrogenase (17b-HSD-d) causes female external genital phenotype in spite of 46,XY karyotype and presence of testes due to disorder in biosynthesis of testosterone. However, marked somatic and genital virilization occurs during puberty. Clinical and laboratory investigation of three cases are presented with typical elevation of the precursor steroid androstenedione, and decrease of product steroid testosterone. All the three patients were reared as girls. During puberty orchidectomy was performed in two cases and vaginoplasty in one case. Estrogen replacement therapy contributed to development of female secondary sex characteristics.

17-Hydroxysteroid Dehydrogenases↗
PubMed1995

Testicular development in an SRY-negative 46,XX individual harboring a distal Xp deletion.

A case of a true hermaphrodite presenting with a karyotype of 46,X,del(X)(p21.1-->pter) is described. The testis-determining gene, SRY, was not detected in DNA prepared from either peripheral blood lymphocytes or from a gonad biopsy. The patient also presented with a series of discrete somatic abnormalities, including abnormal skin and retinal pigmentation, and mental retardation. The extent of the Xp deletion was mapped by Southern blotting. X chromosome replication studies of lymphoblast cells prepared from the patient indicated that the deleted X chromosome was inactivated in all cells examined. It is suggested that the phenotype of the patient is caused by the unmasking of a recessive allele(s) on the grossly intact X chromosome. The relationship between the Xp deletion, the intersex phenotype, and the possible role of an Xp locus involved in human sex determination is discussed.

Child↗