Biomedical subjects

L Dvoráková

Publications and source records attributed to L Dvoráková.

At least 19 recordsLinked to original sources

PubMed2006

An unusual cause of renal amyloidosis secondary to gout: the first description of familial occurrence.

BACKGROUND: AA amyloidosis caused by the chronic inflammation accompanying gouty arthritis is extremely rare and familial occurrence has not been described so far. CASE REPORT: We present the case of two brothers (47 and 44 years old) with 7- and 10-year history of hyperuricaemia and chronic tophaceous gout with polyarticular involvement. The enzymatic assay performed in their erythrocytes proved the partial hypoxanthine-guanine phosphoribosyl transferase deficiency (Kelley-Seegmiller syndrome), the genetic defect of purine metabolism. Later on they developed proteinuria and chronic renal insufficiency /CRI/. Renal biopsy disclosed the combination of AA amyloidosis and gouty nephropathy in both the cases. Despite the standard treatment the older brother progressed to chronic renal failure. On the contrary, the younger one being longterm treated with oral colchicin have stabilized CRI. CONCLUSIONS: Only several cases of AA renal amyloidosis until recently, secondary to gout have been reported. Our case represents the first report of familial occurrence of this extremely rare disease.

Adult↗

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↗

PubMed1998

Intracerebroventricular administration of quinolinic acid induces a selective decrease of inositol(1,4,5)-trisphosphate receptor in rat brain.

[3H]inositol(1,4,5)-trisphosphate (IP3) binding studies have shown decreased [3H]IP3 binding to brain tissue in several neurodegenerative diseases, including Alzheimer's and Huntington's diseases. In addition, previous results obtained from brains of Alzheimer patients indicated a reduction of IP3-receptor protein correlated to neuronal loss. The neurotoxic effect of the glutamate receptor agonist quinolinic acid (QUIN) was therefore examined with respect to the level of IP3-receptor immunoreactivity in rat brain. Neuronal lesions were estimated with antibodies to marker proteins for striatal medium-sized spiny neurons (dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000; DARPP-32), synaptic vesicles (synaptophysin), mitochondria (phosphate-activated glutaminase; PAG) and glial cells (glial fibrillary acidic protein; GFAP). Injection of QUIN into rat neostriatum induced a massive loss of striatal medium-sized spiny neurons, and led to a comparable loss of IP3-receptor and PAG immunoreactivity, suggesting a neuronal localisation of both these proteins. In an effort to induce less pronounced excitotoxic damage, intracerebroventricular infusion of QUIN was performed. Following this lesion, the neostriatum showed a negligible loss of DARPP-32 immunoreactivity (-11+/-5%), but contained only 43+/-3% of IP3-receptor immunoreactivity levels compared to controls. In the hippocampus, cerebellum and entorhinal cortex, the IP3-receptor loss was less pronounced. The decrease in the level of IP3-receptor immunoreactivity appears to be selective with respect to the other proteins studied, and the IP3-receptor thus shows extreme sensitivity to QUIN neurotoxicity in the neostriatum.

Animals↗

PubMed1996

Relationship between kinetic properties of gamma-glutamyl transpeptidase and the structure of its saccharide moiety.

Gamma-glutamyl transpeptidase (EC 2.3.2.2; GGT) is a plasma-membrane bound glycoenzyme, the saccharide moiety of which is rather heterogeneous and organ specific. It has been stated that GGT catalyses three types of reactions, i.e., hydrolysis, transpeptidation and autotranspeptidation. The initial velocity equation, involving all these reactions, is shown in the present report. Mathematical analysis of the equation resulting in a definition of the constant of half saturation (Khs). The value of Khs was used for characterization of kinetics of GGT from rat organs differing in the structure of GGT oligosaccharide chains. No significant organ differences were found, when the Khs values of GGT from the brain, kidney and pancreas equalled 0.61 mM, 0.68 mM and 0.68, respectively. On the contrary, when two different glycoforms of GGT from the pancreas were compared, distinct values of Khs were obtained (1.43 mM and 0.67 mM, respectively). It is therefore being suggested that the saccharide chains of GGT are involved in its kinetic properties. However, this effect is masked when the enzyme, non-fractionated into glycoforms, is analysed, even though the saccharide moiety is specific for the organ studied.

Animals↗

PubMed1996

Long-term prognosis of infants of diabetic mothers. Relationship between metabolic disorders in newborns and adult offspring.

The aim of our study was to find out whether the metabolic disorders in the newborns of insulin-dependent diabetic mothers (NDM) in the neonatal adaptation period could be associated with their condition in adulthood. We examined 148 children of diabetic mothers (CDM) aged 20.75 +/- 0.31 years (mean +/- SE); 11 were diabetic patients, while in the remaining 137 CDM, the oral glucose tolerance test (OGTT) was performed. CDM were compared with 31 matched control offspring of healthy mothers. Of the characteristic abnormalities occurring in NDM, the following were present in our study: macrosomia, hypoglycaemia, hyperlactacidaemia, hyperbilirubinaemia. In adulthood, the sum of the blood glucose and plasma insulin values during OGTT, body mass index (BMI) and blood pressure were determined. The observed abnormalities and the degree of their relevance in the neonatal period were not related to the sum of blood glucose and plasma insulin levels, BMI and blood pressure in adulthood, but the values of all these parameters in adulthood were significantly higher in CDM than in controls (P < 0.05-0.001).

Adult↗

PubMed1996

[Dermatoglyphics--an attempt to predict diabetes].

Dermatoglyphs do not change throughout life. The authors sought their "predictive type" for diabetes with regard to the possibility of early prediction and thus prevention of the development of diabetes, in particular type 2. They used a point score of the abnormality in three qualitative and two quantitative signs and found, as compared with the normal population, in groups of subjects with impaired glucose tolerance, DM II and DM I deviations with an increasing significance. The frequency of thus assessed abnormalities in each subject on both hands (0-10) was compared in relations to the diagnosis and family-history of diabetes and the authors evaluated the incidence of different abnormalities in the whole group of 300 subjects and in sub-groups. After statistical evaluation the authors conclude that the abnormality of the qualitative sign of the C line (lacking or reduced) could be considered as another early predictive factor: in the offsprings of diabetics for both types of diabetes, in the remainder for DM type 1.

Dermatoglyphics↗

PubMed1996

Analysis of kinetic properties of gamma-glutamyl transpeptidase from rat kidney.

The initial rate kinetics of rat kidney gamma-glutamyl transpeptidase were measured using L-gamma-glutamyl-p-nitroanilide and glycyl-glycine as the donor and the acceptor substrate, respectively. Experimental data were fitted with the initial rate equation, and the obtained results indicated that: (1) Michaelis constants for transpeptidation (Kb), autotranspeptidation (Ka), and hydrolysis (Kh) are 8.56 mmol/l, 2.02 mmol/l and 0.005 mmol/l, respectively. (2) The maximum rate of transpeptidation (Vb) exceeds that of hydrolysis (Vh) and autotranspeptidation (Va) 160 times and 5 times, respectively. (3) A comparison of the ratios of maximal rate: Michaelis constant of individual reactions shows that hydrolysis is approximately 10 times more efficient than the remaining two reactions. (4) Under routine conditions used for gamma-glutamyl transpeptidase estimation, transpeptidation is the prevalent reaction.

Animals↗

PubMed1995

[Risk of diabetes mellitus, variations in glucose tolerance, insulin secretion and lipid parameters in offspring of diabetic mothers].

BACKGROUND: Children of diabetic mothers are a relatively new population group which started its existence due to revolutionary changes in the treatment of insulin-dependent diabetes during pregnancy. In the Institute for the Care of Mother and Child since the fifties comprehensive care of diabetic mothers was concentrated and thus it became possible to follow-up a relatively large group of their children to adult age. METHODS AND RESULTS: The authors investigated 176 children of diabetic mothers (CDM) aged 20.75 +/- 0.31 years. All mothers suffered from insulin-dependent diabetes mellitus (IDDM). In 7.95% CDM diabetes developed at the age of 11-23 years (IDDM in 4.54% and NIDDM in 3.41% of CDM). An impaired glucose tolerance was revealed in 6.25%. The mean blood sugar level during the oral glucose tolerance test was significantly higher than in a control group of 31 subjects of the same average age without a family-history of diabetes (p < 0.01). The ratio of insulinaemia to the blood sugar level was markedly higher not only when the glucose tolerance was impaired (p < 0.005) but also in CDM with a normal glucose tolerance (p < 0.025). The total cholesterol and triacylglycerol levels did not differ from the control group. In the group of DDM with an impaired glucose tolerance the non-esterified fatty acid levels were higher, as compared with controls (p < 0.05). CONCLUSIONS: The results of the described group of CDM which is one of the groups followed-up for the longest period reported in the literature indicate the risk of children of diabetic mothers and the necessity to follow-up and screen subclinical signs of the disease.

Adolescent↗

PubMed1994

Altered glutamate binding following quinolinate lesions in developing rat brain.

To define the ontogeny of "excitotoxic" neurodegeneration further, bilateral intracerebroventricular injection of N-methyl-D-aspartate agonist, quinolinate (QUIN), was administered to rats at Postnatal Days 12, 30, and 50. Excitotoxic injury was quantified by means of changes in [3H]glutamate binding to membranes isolated from the entorhinal cortex, hippocampal formation, cerebellum, and medulla oblongata 4 days after the injection of QUIN. Binding was significantly decreased only in the hippocampal formation of 30- and 50-day-old rats (by 25 and 32%, respectively). In contrast, binding to cortical membranes was elevated by 29 and 56% at Postnatal Days 30 and 50, respectively. Observed changes in the binding of glutamate were due to modifications in the equilibrium binding constants rather than in the density of the receptors. In the cerebellum, which exhibited the highest developmental increase, the statistically significant decrease of the binding (by 36%) following QUIN lesion was only observable on Day 30. The effects of QUIN lesions were not statistically significant in the medulla oblongata. The results suggest that in 30- and 50-day-old rats QUIN can be implicated in neurodegeneration of the entorhinohippocampal complex.

Animals↗

PubMed1994

Relationship between gamma-glutamyl transpeptidase activity and sialic acid content in some organs and brain regions of the developing rat.

The activity of gamma-glutamyl transpeptidase (GGT) and the sialic acid (SA) content were found to be specific in five brain regions of 7- and 50-day-old rats. While a low GGT activity was accompanied by high sialylation in the whole brain a high GGT activity and low sialylation were observed in kidney and pancreas. Similar findings were obtained for some brain regions investigated. However, the developmental differences were not characterized by such relationship. Concanavalin A affinity chromatography of GGT from brain of 7- and 50-day-old rats revealed no remarkable changes in GGT sialylation although the enzyme activity is almost 3 times higher in brain membranes of the older group. It can be concluded that in spite of an apparent relationship between GGT activity and membrane sialylation, the amount of SA linked to the GGT molecule is not related to differences in enzyme activity.

Aging↗

PubMed1994

[Complications in insulin-dependent diabetic mothers during pregnancy and the long-term prognosis for their children].

The authors investigated whether vascular complications of insulin-dependent diabetic pregnant women can influence on a long-term basis their children in adult life. In a group of 169 children of diabetic mothers (CDM) 12 developed diabetes during childhood and adolescence; in the remaining 157, age 20.75 +/- 0.31 (SE) the following tests were made: oral glucose tolerance test (OGTT), insulin level, parameters of the lipid metabolism, and blood pressure was assessed. CDM were divided into three groups: 1. CDM whose mothers had diabetic complications; according to White's classification of diabetes during pregnancy they belonged into class D and F (n = 10). 2. CDM whose mothers were classified with regard to diabetes during pregnancy as class B and C with subsequent toxaemia of pregnancy (n = 27), 3. CDM of mothers class B and C without toxaemia of pregnancy (n = 117). All investigated groups of CDM had significantly higher sums of blood sugar and insulin levels during the OGTT (P < 0.01), as compared with the control group (n = 31). In the first group of CDM the values were significantly higher than in the third group of CDM. As to cholesterol and triacylglycerol levels, the differences were not significant, the non-esterified fatty acid levels were higher in the second group than in controls (P < 0.05). In the first two groups also a higher systolic pressure was recorded than in controls (P < 0.01). Two children of the first group, two children of the second group and eight children of the third group of CDM developed diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

[The importance of doppler echocardiography in type I diabetics].

Impaired flow through the mitral orifice in diastole is frequently encountered in patients with IHD, hypertension, cardiomyopathies and type II diabetes. The authors examined 40 type I diabetics, age 26 +/- 5.5 years, with a duration of diabetes of 15.8 +/- 7.5 years. The control group was formed by 40 non-diabetic patients comparable as to age and sex. 7.5 years. The control group was formed by 40 non-diabetic patients comparable as to age and sex. During Doppler echocardiography the ratio of early and late peak flow velocity through the mitral orifice (A/E) was evaluated and the time of isovolumic relaxation of the left ventricle (IVRT). The investigated values of A/E and IVRT were higher in diabetics than in controls (p < 0.001). Diabetics with positive microalbuminuria had higher A/E and IVRT values than diabetic with normal microalbuminuria. No relationship was found with the duration of diabetes but there is a relationship of the investigated values and compensation of diabetes (p < 0.05). At a check-up examination after six months no change of the investigated parameters was observed. The authors assume that Doppler echocardiography could become in future a non-invasive method for assessment of late complications of diabetes.

Adult↗

PubMed1992

Evidence that deprotonation of serine-55 is responsible for the pH-dependence of the parvalbumin Eu3+ 7F0-->5D0 spectrum.

The Eu(III)7F0-->5D0 excitation spectra of the parvalbumins are highly pH-dependent. Below pH 6.0, they exhibit a sharp, partially resolved doublet centered near 5,795 A. However, as the pH is raised, the spectrum becomes increasingly dominated by a much broader signal near 5,784 A. This behavior has been traced to the Eu(III) ion bound at the CD site, but the identity of the moiety undergoing deprotonation remains uncertain. Site-specific mutagenesis studies on the parvalbumin-like protein known as oncomodulin now suggest that the species in question is a liganding serine hydroxyl group. Specifically, replacement of serine-55 by aspartate (the residue present at the corresponding position in the EF site) affords a protein that retains two functional lanthanide binding sites, but fails to undergo the pH-dependent spectral alteration. By contrast, replacement of aspartate-59 by glycine (the corresponding EF site residue) fails to abolish the pH-dependent behavior.

Animals↗

PubMed1992

Developmental changes in the activity of membrane-bound gamma-glutamyl transpeptidase and in the sialylation of synaptosomal membranes from the chick embryonic brain.

gamma-Glutamyl transpeptidase (GGT) is a membrane-bound sialoglycoprotein. The developmental changes in GGT activity and in sialic acid content were determined in a crude synaptosomal membrane fraction from the cerebral hemispheres of the chick embryo between days 11 and 19 of incubation. The GGT activity increased almost eightfold during the examined developmental period, while sialic acid content rose significantly only between days 11 and 15. Cortical administered on day 13 significantly increased GGT activity. On the other hand, the content of membrane bound sialic acid was not substantially affected. The value of the GGT apparent Michaelis constant (Kmapp) for gamma-glutamyl-p-nitroanilide in the presence of 20 mmol.l-1 glycylglycine was 1.5 mmol.l-1 and cortisol did not influence it. However, Vmax was increased by this hormone. The affinity of GGT to concanavalin A (ConA) did not change during development. Neither the administration of cortisol nor neuroaminidase treatment had any effect on the interaction of GGT with ConA. Desialylation of crude synaptosomal fraction did not change GGT activity. The results presented here suggest no developmental nor functional relationship between the activity of GGT and the level of sialylation in synaptosomal membranes from the cerebral hemispheres of the chick embryo.

Animals↗

PubMed1992

Fractionation of gamma-glutamyl transpeptidase from the rat brain, kidney and pancreas by concanavalin A affinity chromatography.

gamma-Glutamyl transpeptidase (GGT) in tissue extracts from five brain regions, the kidney and pancreas of 50-day-old rats was examined for its specific activity and affinity to immobilized concanavalin A (Con A). According to their descending GGT activity, the tissue extracts were classified in the following order: kidney >> pancreas >> olfactory bulbs > medulla oblongata > hippocampus > cerebellum > frontal cortex. Using different concentrations of methyl-alpha-D-mannopyranoside for the elution of GGT from Con A-Sepharose column, the enzyme from brain regions could be separated into five fractions, two of which contained about 75% of the total GGT activity without regional differences in elution profiles. Almost complete GGT activity in kidney tissue extracts was eluted in a single peak whereas the enzyme from pancreas exhibited two peaks.

Animals↗

PubMed1992

[Hypertrophy of neonates in diabetic mothers and their long-term prognosis].

Hundred and seventy five infants of diabetic mother born and followed up carefully in the Institute for the Care of Mother and Child were examined at a mean age of 20.75 +/- 4.08 years. The purpose of the investigation was to assess the relationship of hypertrophy of neonates of diabetic mothers to other deviations in neonates and their long-term prognosis. In neonates with a marked degree of hypertrophy the authors recorded significantly more frequently hypoglycaemia, early asphyctic syndrome, impaired respiration and neurological symptoms. Children born as hypertrophic developed equally frequently diabetes (8.7%) as children of diabetic mothers who did not develop hypertrophy (8.0%). Abnormal glucose tolerance was recorded in those with hypertrophy in 6.6%, in the group without hypertrophy in 5.0%. As compared with the offspring of healthy mothers, they suffered significantly more frequently from higher blood sugar levels and higher insulinaemia (sigma C ad sigma I) during the oGTT. The body weight expressed as BMI and systolic blood pressure were also higher than in the control group. None of the investigated indicators in adult age was associated with body weight and the degree of hypertrophy. The development of diabetes is determined more by genetic factors.

Adult↗

PubMed1991

Early stages of diabetes mellitus in first-degree relatives of insulin-dependent and non-insulin-dependent diabetics.

This work deals with preclinical stages of diabetes mellitus in 494 first-degree relatives of insulin-dependent and non-insulin-dependent diabetics: 182 parents and 66 siblings of diabetic children, 176 offspring of diabetic mothers and in 70 offspring of both non-insulin-dependent diabetic parents. In these persons the family history, oral glucose tolerance test and insulin secretion were studied, blood levels of lipids and fibrinogen were investigated, neurological examination was performed, the neurocirculatory deviations and changes on the fundus were observed and HLA antigens were typed in comparison with the control groups. Long-term follow-up proved, that offspring of both non-insulin-dependent diabetic parents are the most homogenous group. Fluctuating development of abnormalities of glucose tolerance during a long period from a relative early age of 30-40 years with primary insulin resistance, compensatory hyperinsulinism and its delayed secretion and later with relative insulin deficiency are characteristic. Such development is associated with an increase body weight and of blood pressure and often with elevated lipid and fibrinogen levels.

Diabetes Mellitus↗

PubMed1990

[Is the measurement of the pulse wave rate useful in the diagnosis of the early stages of arterial atherosclerosis of the lower extremities in type I diabetics?].

The authors examined the rate of the pulse wave (RPW) on the arteries of the lower extremities in a group of 60 type I diabetics and in a control group of 60 subjects without diabetes. The aim of the examination was to find out whether in diabetes threatened by early development of atherosclerosis preclinical signs of stiffening of the arteries with a fast spread of the pulse wave are present. The authors found in diabetics significantly higher values of RPW, as compared with non-diabetics, starting from the fourth decade. In subjects under 30 years the RPW in the two groups did not differ. In diabetics significant linear correlations were revealed between RPW values and age and RPW values and the duration of diabetes--i.e. with advancing age and longer duration of diabetes RPW rises. In diabetics with peripheral neuropathy significantly higher RPW values were recorded, as compared with diabetics without this complication. Assessment of the RPW by ultrasound is a non-invasive useful examination which makes it possible to detect among type I diabetics subjects with preclinical signs of stiffening of the arteries of the lower extremities which is considered an initial stage of atherosclerosis.

Adult↗