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Biomedical subjects

J Zeman

Publications and source records attributed to J Zeman.

At least 19 recordsLinked to original sources
PubMed2001

[Analysis of the most frequent mutations in girls with Rett syndrome].

BACKGROUND: Rett syndrome is an X-linked dominant neurodevelopmental disorder affecting 1 from 10,000 to 15,000 females worldwide. The responsible gene, encoding methyl-CpG binding protein 2 was recently identified. Methyl-CpG binding protein 2 is thought to act as a global transcriptional repressor. In the methyl-CpG binding protein 2 gene are known 5 prevalent mutations that cause Rett syndrome. Four of them are detectable by restriction analysis. In this study we present the results of the molecular study of four prevalent mutations in the gene for methyl-CpG binding protein 2 in Czech and Slovak patients with Rett syndrome. METHODS AND RESULTS: 22 females with Rett syndrome were investigated by methods of molecular biology. Restriction analysis and direct sequencing of PCR products revealed in methyl-CpG binding protein 2 gene 3 different mutations (T158M, R168X, R270X) in six unrelated patients with Rett syndrome. Mutation R306C, frequent in Great Britain and Sweden, was not detected in our group of patients with Rett syndrome. CONCLUSIONS: The diagnosis of Rett syndrome and genetic counselling in affected families should go out from the close cooperation of the pediatric, neurologic, and genetic departments with the specialized laboratories dealing with the molecular biological diagnosis.

Adolescent↗
PubMed2001

[Congenital aplastic anemia caused by parvovirus B19 infection].

Human parvovirus B19 causes the fifth disease (erythema infectiosum) in childhood. Intrauterine infection by parvovirus in immunocompromised fetus can lead to the severe congenital aplastic anemia. Here we report the case of 2.5-year-old girl with congenital infection with parvovirus B19. The girl was born as a pre-term baby with hydrops, congenital aplastic anemia, and low level of immunoglobulins IgG and IgM. She depended on the repeated blood transfusions and she did not respond to erythropoietin therapy. The parvovirus B19 infection in bone marrow was detected by polymerase chain reaction and its therapy started with intravenous administration of immunoglobulins. Hemoglobin reached normal level one year later, but low levels of parvovirus B19 were detectable for another 6 months. Immunoglobulin treatment was finished when the virus could not be detected in the circulation. However, one-month later parvovirus B19 DNA was detected again. The two months course of immunoglobulin treatment was repeated, and the DNA analysis of blood cells for parvovirus B19 has been negative since then. Five months after the final withdrawal of the immunoglobulin therapy the girl is in a good shape and all lab tests, except for the decreased levels of IgM, are within the normal range. The PCR monitoring of the presence of parvovirus B19 DNA in blood and bone marrow cells during and after the treatment of congenital aplastic anemia caused by parvovirus B19 chronic infection becomes the necessity for the rational therapy.

DNA, Viral↗
PubMed2001

Magneto infrared absorption in high electron density GaAs quantum wells.

Magneto infrared absorption measurements have been performed in a highly doped GaAs quantum well which has been lifted off and bonded to a silicon substrate, in order to study the resonant polaron interaction. It is found that the pinning of the cyclotron energy occurs at an energy close to that of the transverse optical phonon of GaAs. This unexpected result is explained by a model taking into account the full dielectric constant of the quantum well.

Journal Article↗
PubMed2001

Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange.

X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta-oxidation. We examined the ABCD1 gene in probands from 11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/T in the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively.

5' Untranslated Regions↗
PubMed2001

A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome c oxidase-deficient leigh syndrome and hypertrichosis.

Leigh syndrome is a rare pediatric neurodegenerative disorder attributed to impaired mitochondrial energy metabolism. Mutations in SURF1 have been described in several patients with Leigh syndrome associated with cytochrome c oxidase deficiency. We report a new 18-bp deletion (821del18), spanning the splice donor junction of exon 8 of SURF1, in an infant presenting with cytochrome c oxidase-deficient Leigh syndrome and hypertrichosis. cDNA sequencing demonstrated that this deletion results in a messenger lacking exon 8. RT-PCR experiments suggested a rapid degradation of the aberrant mRNA species from the 5'-end.

Alternative Splicing↗
PubMed2001

Pulmonary storage with emphysema as a sign of Niemann-Pick type C2 disease (second complementation group). Report of a case.

A case is described of Niemann-Pick type C2 disease presenting an infantile pneumopathic phenotype known to occur in this recently established, second, minor complementation group of Niemann-Pick type C (NPC) disease. However, the pulmonary involvement was unique, being dominated, in addition to the usual storage macrophage infiltration of the alveolar and septal compartments, by irregular emphysema attributed to storage cell migration into the bronchiolar lumen. The latter modified considerably the X-ray findings and hindered the initial clinical diagnosis. Otherwise, the storage phenotype, including the range of stored lipids, storage distribution, and cell and organ pathology, was found to be identical to that in the whole Niemann-Pick type C disease group dominated by NPC1. The biochemical findings (cholesterol esterification level) corresponded to the classical biochemical phenotype. Emphysema should thus be considered as a variant of the pulmonary NPC2 storage process, governed most probably by an epigenetic mechanism responsible for storage macrophage migration into the bronchiolar compartment.

Emphysema↗
PubMed2001

Socialization of children's emotion regulation in mother-child dyads: a developmental psychopathology perspective.

This study investigated the socialization of children's emotion regulation in 25 physically maltreating and 25 nonmaltreating mother-child dyads. Maltreating mothers and their 6- to 12-year-old children were recruited from two parenting programs affiliated with Children's Protective Services with a control group matched on race, SES, child gender, and child age. Children and their mothers were interviewed individually about their (a) management of emotional expression. (b) strategies for coping with emotional arousal, and (c) anticipated consequences following emotional displays. Compared to controls, maltreated children expected less maternal support in response to their emotional displays, reported being less likely to display emotions to their mothers, and generated fewer effective coping strategies for anger. Maltreating mothers indicated less understanding of children's emotional displays and fewer effective strategies for helping children to cope with emotionally arousing situations than nonmaltreating mothers. Further, findings indicated that maternal socialization practices (e.g., providing support in response to children's emotional display, generating effective coping strategies for their child) mediate the relation between child maltreatment and children's regulation of emotional expression and emotional arousal. These findings suggest that children's emotion regulation strategies are influenced by their relationship with their social environment (e.g.. physically maltreating, nonmaltreating) and that the experience of a physically maltreating relationship may interfere with children's emotional development.

Affect↗
PubMed2000

[Clinical picture of homocystinuria with cystathionine beta-synthase deficiency in 19 Czech and Slovak patients].

BACKGROUND: Homocystinuria due to cystathionine beta-synthase deficiency is an autosomal recessive disorder of methionine metabolism. It manifests with vascular, central nervous system and connective tissue disturbances, and phenotypically resembles Marfan's syndrome. We analysed the clinical course of homocystinuria in Czech and Slovak patients. METHODS AND RESULTS: The group of homocystinuric patients consisted of 19 individuals (12 males and 7 females) aged 5-32 years (average age 18 years), who were diagnosed between 1980 and 1999. The overall incidence of homocystinuria in the Czech and Slovak Republics was 1:287,000. The proportion of pyridoxine-responsive patients was 47%. The average follow-up period was 10 years (range 1 month to 19 years). The prevalence of the individual signs in the group was as follows: lens dislocation--95% of patients, progressive myopia--79%, marfanoid habitus--74%, kyfoscoliosis--68%, osteoporosis--63%, psychomotor retardation--58%, other neurologic symptomatology--58% and tromboembolism--21%. The average delay between the first sign of the disease and the time when the diagnosis was made was 4 years (range 1 to 14 years). At the time of diagnosis the average levels of metabolites in plasma were as follows: total homocysteine 348 mumol/l (range 211-536), free homocystine 70 mumol/l (range 0-203) and methionine 359 mumol/l (range 75-937). CONCLUSIONS: Both the clinical course of homocystinuria due to the cystathionine beta-synthase deficiency and its incidence in the Czech and Slovak Republics are similar to those in other populations. Since homocystinuria is a treatable disease, it should be included in the differential diagnosis of Marfan's syndrome, tromboembolism and severe psychomotor retardation.

Adolescent↗
PubMed2000

Emotion management skills in sexually maltreated and nonmaltreated girls: a developmental psychopathology perspective.

Research has demonstrated that children who experience familial sexual maltreatment are at risk for developing psychological difficulties characterized by emotional and behavioral dysregulation. Surprisingly, however, little attention has been directed toward identifying processes in emotional development that differ in maltreated and nonmaltreated children. From a developmental psychopathology perspective, the present study examined emotion management skills (i.e., emotional understanding, emotion regulation) in 21 sexually maltreated girls and their nonmaltreated peers to determine how the experience of sexual maltreatment may interfere with normative emotional development. Findings indicated that sexually maltreated girls, in comparison to their nonmaltreated peers, demonstrate lower emotional understanding and decreased ability to regulate their emotions in accordance with cultural expectations. Further, maltreated girls expected less emotional support and more relational conflict from parents in response to sadness displays and from parents and peers in response to anger displays. These findings will be discussed from the functionalist approach to emotional development, emphasizing the importance of social context (e.g., maltreating, nonmaltreating) in the development of children's emotion management skills.

Adaptation, Psychological↗
PubMed2000

New insights in cardiac structural changes in patients with Fabry's disease.

BACKGROUND: Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase leading to the pathologic intracellular deposition of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventricular (LV) changes and the severity of valvular involvement. METHODS: Clinical evaluation (disease severity scaling, laboratory tests, and echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). RESULTS: LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P <.001). The degree of LVH was independently associated with age and the logarithm of alpha-galactosidase activity (r(2) = 0.70, P <.001). The predominant LV geometric patterns were concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardiomyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor structural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The presence of LVH or valvular changes was associated with increased disease severity. CONCLUSIONS: Echocardiographically detectable cardiac involvement is frequent with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently observed but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the major manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitation. Valvular and especially LV structural changes may serve as a useful marker of disease severity.

Adolescent↗
PubMed2000

[Prenatal diagnosis in families with cytochrome C oxidase disorder].

OBJECTIVE: Cytochrome c oxidase (COX) deficiency presents with severe impairment of brain, muscle or heart. Prenatal diagnosis in affected families is difficult because the disease may be caused by mutations in nuclear or mtDNA. This study shows the results of prenatal diagnosis in two families where the first child died because of a generalised COX defect. In both cases the low activity of COX was accompanied by a low content of the enzyme. SUBJECTS: In the first family the amniocentesis was performed during the second pregnancy and cultured amniocytes showed a marked decrease of COX activity and ATP production. Based on decision of the parents the pregnancy was terminated. Analysis of the foetal tissues confirmed a generalised COX defect. In the second family the nuclear origin of the COX defect was found using transmitochondrial cybrids derived from COX-deficient fibroblasts of the affected child. In the successive pregnancy with dizygotic twins a combined amniocentesis and chorionic villi biopsy has been performed. Prenatal diagnosis was based in both foetuses on three independent approaches. COX activity, the ATP production and protein content of COX complex was measured in cultivated foetal cells. The results of all investigations excluded a putative COX defect and both children are healthy at the age of 2 and half years. CONCLUSION: Prenatal diagnosis of COX disorders is available in families with the generalised form of the disease based on a nuclear origin of COX deficiency. Three independent approaches to characterise COX at a functional, enzymatic and protein level may be used.

Cytochrome-c Oxidase Deficiency↗
PubMed1999

[Lysosomal acid lipase deficiency. Overview of Czech patients].

Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage of triacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediated LDL endocytosis are affected (liver, kidneys). There are two basic phenotypes. The fatal infantile phenotype (Wolman's disease) with generalized storage of both types of apolar lipids. This form was diagnosed in this country only once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterized by the storage of CE (which gave this entity the name of cholesteryl storage disease--CESD). Its main sign is affection of the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotic transformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increased VLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipids is a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases of CESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy with hepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patients with permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quite incidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis was established in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) and molecular genetic level (mutation in enzyme locus). In all instances mutation of G934A was found leading to reduction and loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations were heterozygous. In one instance for technical reasons only one allele was analyzed. In three instances a point "missense" mutation was found: T323A (Trp74Arg), T4(75)A (Asp124Glu), A210T (Asp36Gl), in one instance a "nonsense" mutation: C233T (Arg44-stop) and twice a deletion mutation delta C673-5 and delta G1068-8 leading to impairment of the reading frame and to premature stop of the codon.

Adult↗
PubMed1999

[Postmortem diagnosis of Fabry disease in a female heterozygote leading to the detection of undiagnosed manifest disease in the family].

The authors detected on necropsy in a 63-year-old woman with the clinical diagnosis of hypertension, atherosclerosis of the coronary and peripheral arteries, thromboembolism into the cerebral circulation and impaired cardiac conductivity lysosomal storage identified by histochemical and electronoptic analyses along with lipid chromatography as Fabry's disease. The stored lipids were neutral glycosphingolipids of the globo series globotriaosylceramide) and of the gala- series (galabiosylceramide) which accumulated as a result of deficient activity of the degrading enzyme alpha galactosidase A. Marked accumulation of these specific lipids was found in cardiomyocytes, in smooth muscles (of the media in arteries of the heart, kidneys, liver, spleen, lungs) in podocytes and mesangial cells of renal glomeruli, in epithelia of Henle's loop and in the distal tubules. In the vascular endothelium the storage was at the borderline of detectability. Accumulation did not lead to detectable organ disorders with the exception of the heart where it participated, no doubt, significantly in the cardiocyte hypertrophy. Examination of relatives revealed in the proband's son (age 41 years) a combination of renal, cardiac and skin changes typical for Fabry's disease which, however was not clinically diagnosed. The diagnosis was confirmed by proving of alpha-galactosidase A deficiency in the peripheral leucocytes and point mutation L293X in the VIth exon of the appropriate gene. In a granddaughter (age 15 years) biochemical and molecular genetic methods revealed the heterozygous state of Fabry's disease in preclinical stage.

Adolescent↗
PubMed1999

[Leber's hereditary optic neuropathy].

BACKGROUND: Leber's hereditary neuropathy of the optic nerve (LHON) is manifested by bilateral affection of the eyes with acute or subacute loss of vision. The disease is caused by point mutations in the mitochondrial DNA (mtDNA) and is one of the most frequent mitochondrial diseases in the population. In patients with LHON 18 different point mutations in the mtDNA were described which correlate partly with the rate of progression of the disease and the severity and prognosis of the final affection of vision. METHODS AND RESULTS: The submitted paper deals with the results of molecular genetic examinations in three families with clinical manifestations of LHON. In three patients in the first family a homoplasmic mutation of mtDNA G3460A was found. In the second family in a young man with severely impaired vision a heteroplasmic mutation G3460A was found associated with a higher ratio of mutated mtDNA molecules than in his mother who is clinically healthy. In the third family the presence of homoplasmic mutation of mtDNA in position G11778A was detected. CONCLUSIONS: The diagnosis of LHON and genetic counselling in affected families should be based on close collaboration of ophthalmological and genetic departments with specialized laboratories engaged in molecular biological diagnosis of mitochondrial diseases.

DNA, Mitochondrial↗
PubMed1999

Defective kinetics of cytochrome c oxidase and alteration of mitochondrial membrane potential in fibroblasts and cytoplasmic hybrid cells with the mutation for myoclonus epilepsy with ragged-red fibres ('MERRF') at position 8344 nt.

We have investigated pathogenic effects of the tRNA(Lys) A8344G mutation associated with the syndrome myoclonus epilepsy with ragged-red fibres (MERRF) by using fibroblasts and fibroblast-derived cytoplasmic hybrid cells harbouring different percentages of mutated mitochondrial DNA (mtDNA). The activity of cytochrome c oxidase (COX) in patient fibroblasts with 89% mutated mtDNA was decreased to 20% of the control levels. COX exhibited altered kinetics, with a decreased V(max) for both the low-affinity and high-affinity phases; however, the K(m) values were not significantly changed. The substrate-dependent synthesis of ATP was decreased to 50% of the control. Analysis of the mitochondrial membrane potential, DeltaPsi, in digitonin-treated cells with tetramethylrhodamine methyl ester (TMRM) with the use of flow cytometry showed a 80% decrease in DeltaPsi at state 4 and an increased sensitivity of DeltaPsi to an uncoupler in fibroblasts from the patient. The investigation of transmitochondrial cytoplasmic hybrid clones derived from the patient's fibroblasts enabled us to characterize the relationship between heteroplasmy of the MERRF mutation, COX activity and DeltaPsi. Within the range of 87-73% mutated mtDNA, COX activity was decreased to 5-35% and DeltaPsi was decreased to 6-78%. These results demonstrate that the MERRF mutation affects COX activity and DeltaPsi in different proportions with regard to mutation heteroplasmy and indicate that the biochemical manifestation of the MERRF mutation exerts a very steep threshold of DeltaPsi inhibition.

Adenosine Triphosphate↗
PubMed1999

[Various manifestations of the A8344G mtDNA heteroplasmic mutation in 4 families with the MERRF syndrome].

BACKGROUND: The most frequent manifestation of mitochondrial DNA (mtDNA) mutation 8344 A-->G is MERRF syndrome (Myoclonic Epilepsy and Myopathy with Ragged Red Fibres). Less frequent symptoms include ataxia, perceptive type of deafness, cardiomyopathy or external ophthalmoplegia and mental and motor retardation in children. We describe heterogeneity of clinical symptoms and results of biochemical and molecular investigations in four families with the heteroplasmic mutation 8344 A-->G in mtDNA. METHODS AND RESULTS: In co-operation with paediatric, neurological and genetic specialists from the Czech and Slovak Republic we found in 1993-1998 at the enzymatic or molecular level more than 90 children and adults with impaired mitochondrial energy metabolism. Heteroplasmic mutation 8344 A-->G in mtDNA was found in four families. Ataxia and progressive muscle weakness appeared in the first proband with 50% of mutated copies of mtDNA in muscle at the age of 30 years. The second proband with 95% of mutated mtDNA had his first clinical symptoms--muscle hypotonia, cardiomyopathy and mental and motor retardation--in infancy while his four relatives with 25-50% mutated mtDNA lack so far clinical symptoms. In a female from the third family with 50% mutated mtDNA in muscle the disease manifested at the age of 42 years with progressive external ophthalmoplegia (PEO) and muscle weakness. In the fourth proband with 50% of mutated mtDNA in blood the disease started in infancy with spastic quadruparesis and arrested mental and motor development. Enzymatic and histochemical investigation in muscle biopsy in two probands revealed lower cytochrom c oxidase activity. Ragged-red fibres were found only in one adult patient. CONCLUSIONS: MtDNA mutation 8344 A-->G can manifest by heterogeneous symptoms. A higher percentage of mutated mtDNA is usually associated with more serious forms of the disease, but there is not always a correlation between the degree of heteroplasmy and severity of the disease or the age of the first clinical symptoms.

Adult↗
PubMed1999

Complex approach to prenatal diagnosis of cytochrome c oxidase deficiencies.

Different severe disorders of cytochrome c oxidase (COX) have been described in children, but only the defects with autosomal inheritance are suitable for prenatal diagnosis. To perform prenatal diagnosis of fatal infantile COX deficiency a complex approach has been used which combined determination of the genetic origin of the defect, and detailed analysis of the function, content and subunit composition of the enzyme in cultured fetal cells. The tissues and cultured fibroblasts of the patient with Leigh's syndrome showed a COX deficiency of systemic character. The decrease of COX activity to 5-11 per cent was accompanied by proportionally decreased content of the assembled COX enzyme. With the help of transmitochondrial cybrids derived from patient fibroblasts it was proven that the COX defect was of nuclear origin. In a successive pregnancy, the function of oxidative phosphorylation (OXPHOS) was analysed in cultured amniocytes by substrate-stimulated ATP production and COX activity was compared with the activity of citrate synthase. The amount and composition of OXPHOS complexes was estimated by two-dimensional (Blue Native/SDS) polyacrylamide gel electrophoresis and was verified immunochemically with specific antibodies. Three independent lines of evidence provided us with reliable data on the function of COX and OXPHOS in fetal cells which were sufficient to rule out the expected enzymatic defect within three weeks after amniocentesis.

Adenosine Triphosphate↗