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J Socha

Publications and source records attributed to J Socha.

At least 37 records · Page 2Linked to original sources
PubMed1998

Clustering of private mutations in the congenital chloride diarrhea/down-regulated in adenoma gene.

An inherited defect in intestinal anion exchange, congenital chloride diarrhea (CLD), was recently shown to be caused by mutations in the down-regulated in adenoma (DRA) gene. A three base pair deletion resulting in the loss of an amino acid valine (V317del) in the predicted CLD/DRA protein was shown to be responsible for all CLD cases in a Finnish founder population. Two additional mutations, H124L and 344delT, were found in Polish CLD patients. Here, we screened for additional mutations in a set of 14 CLD families of Polish, Swedish, North American, and Finnish origin using primers that allowed mutation searches directly from genomic DNA samples. We found eight novel mutations in the CLD/DRA gene. The mutations included two transversions, one transition, one insertion, and four small deletions. Of 11 sequence alterations detected so far, nine lie clustered in three short segments that are 49 bp, 39 bp, and 65 bp in size, respectively. These short segments span only 6.7% of the total cDNA length, suggesting functional importance or mutation-prone DNA regions of the corresponding CLD/DRA protein domains.

Amino Acid Sequence↗
PubMed1998

Essential fatty acid metabolism in infants with cholestasis.

Long-chain polyunsaturated fatty acids are important for the growth and early development of the central nervous system. Cholestatic infants suffer from fat malabsorption and disturbed lipid metabolism and therefore may be at risk of developing polyunsaturated fatty acid depletion. The aims of this study were to determine essential fatty acid status in cholestatic infants and to study the relationship to disease severity, degree of undernutrition, antioxidant status and mode of feeding. Twenty-four-hour dietary records were obtained in 34 cholestatic infants, and measurements were taken of skin fold thicknesses, bilirubin levels, activities of serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, prothrombin time, serum concentrations of albumin, bile acids, total lipids, phospholipids, cholesterol, vitamins A and E, the fatty acid composition of plasma phospholipids and plasma lipid peroxides expressed as thiobarbiturate reactive substance (TBARS). Plasma phospholipid fatty acids and TBARS were also determined in 12 age-matched healthy control infants. The cholestatic patients had very low percentage values of phospholipid essential fatty acids, particularly linoleic acid ( 18:2omega-6, median 14.74% vs 20.76% in controls, p < 0.001) and its major metabolite arachidonic acid (20:4omega-6, 6.80 vs 7.87%, p=0.04). The patients' essential fatty acid depletion was reflected by increased levels of the non-essential fatty acids, Mead acid (20:3omega-9, 0.74 vs 0.21%, p < 0.001) and palmitoleic acid (16:1omega-7, 2.20 vs 0.43%, p < 0.001). Polyunsaturated fatty acid profiles did not differ between infants with biliary atresia (n=13) and those with intrahepatic cholestasis (n=21), or between 17 infants with severe malnutrition (all skin folds < 10th percentile) and mild malnutrition (at least two skin folds > 10th percentile). TBARS were significantly higher in cholestatic patients than in controls (2.74 vs 0.85 nmol ml(-1), p < 0.001) and correlated with direct (r=0.41, p=0.02) and total bilirubin. The daily dietary intake of linoleic acid (per 100 kcal) correlated with plasma phospholipid linoleic acid (r=0.38,p=0.037) and total omega-6 fatty acids (r=0.38,p=0.036). Breastfed cholestatic infants (n=6) had higher values of the omega-3 long-chain polyunsaturated fatty acids docosapentanoic acid (22:5omega-3, 0.47 vs 0.28%, p=0.0006) and docosahexanoic acid (22:6omega-3, 2.39 vs 1.73%, p=0.01) than formula-fed infants, while disease severity was similar in the two groups. In conclusion, cholestatic infants are at high risk of essential fatty acid depletion, which appears to be related to fat malabsorption, hepatic essential fatty metabolism, enhanced lipid peroxidation and dietary intake.

Body Height↗
PubMed1998

Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait.

Congenital chloride diarrhea (CLD) is an inherited intestinal disorder caused by mutations in the down-regulated in adenoma gene. In Finland, the disease is prevalent because of a founder effect, and all but one of the CLD-associated chromosomes carry the same mutation, V317del. In Poland, another area with a high incidence of CLD, as many as seven different mutations have been detected so far. A third known cluster of CLD, around the Persian Gulf, has not been genetically studied. We studied the allelic diversity of CLD in Poland, in Saudi Arabia and Kuwait, and in three isolated families from North America and Hong Kong. Altogether, eight novel mutations were identified, making a total of 19 known CLD gene mutations. The Polish major mutation I675-676ins was found in 47% of the Polish CLD-associated chromosomes. Haplotype analysis and clustering of the I675-676ins mutation supported a founder effect and common ancestral origin. As in Finland, a major founder effect was observed in Arab patients: 94% of the CLD-associated chromosomes carried a nonsense mutation, G187X, which occurred in either a conserved ancestral haplotype or its derivative. Our data confirm that the same locus is mutated in all cases of CLD studied so far. In Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone. This suggests that mutations in the CLD locus are not rare events. Although the disease is thought to be rare, undiagnosed patients may not be uncommon.

Chlorides↗
PubMed1997

Essential fatty acid status in children with cholestasis, in relation to serum bilirubin concentration.

The liver plays a central role in the metabolism of polyunsaturated fatty acids. We studied the relationship between essential fatty acid (EFA) status and indicators of liver function in 15 children with chronic cholestasis aged 9 months to 3.4 years (median, 1.3 years). Compared with 13 control children, the patients studied had low percentage values of phospholipid EFAs, particularly of the omega-6 fatty acids linoleic acid (18:2omega-6) and arachidonic acid (20:4omega-6). Fatty acid values exhibited an inverse relationship to serum bile acids, as well as to serum bilirubin. Bilirubin values were unrelated to the EFA precursors linoleic acid and alpha-linolenic acid but correlated inversely with the long-chain metabolites arachidonic acid (r = -0.75; p = 0.001), docosapentaenoic acid (22:5omega-3; r = -0.63; p = 0.01), and docosahexaenoic acid (22:6omega-3; r = 0.72; p = 0.002). We conclude that children with chronic cholestasis are at a high risk for EFA deficiency, which increases with progressive elevation of serum bilirubin. Hepatic conversion of essential precursor fatty acids into their long-chain metabolites may be increasingly impaired with advancing severity of liver disease.

Arachidonic Acid↗
PubMed1997

Treatment of cholestatic children with water-soluble vitamin E (alpha-tocopheryl polyethylene glycol succinate): effects on serum vitamin E, lipid peroxides, and polyunsaturated fatty acids.

BACKGROUND: Treatment of vitamin E-deficient cholestatic children with water-soluble alpha-tocopherol polyethylene glycol succinate (TPGS) was previously shown to normalize vitamin E status and to improve neurological outcome. METHODS: Because vitamin E plays an important role as a free-radical scavenger, we studied the effects of long-term TPGS supplementation on lipid peroxidation and polyunsaturated fatty acid status in 15 children ages 9 months-3.4 years (median, 1.3 years) with chronic cholestasis with low serum vitamin E concentrations [1.95 (0.8-3.7) mg/L; median (1st-3rd quartile)]. The previous supplementation of alpha-tocopherol was replaced by a 20% solution of TPGS in one daily dose of 20 IU/kg. Serum alpha-tocopherol, plasma lipid peroxides expressed as thiobarbiturate reactive substance concentration (TBARS) and plasma phospholipid fatty acid profile were estimated at baseline and again after 1 month in all 15 patients, and after 1 year of TPGS therapy in 11 patients. RESULTS: alpha-Tocopherol was significantly increased after 1 month [6.9 (4.4-8.4) mg/L; p = 0.008] and rose further after 1 year [9.7 (7.2-14.9) mg/L]; similar results were obtained for the ratio vitamin E/total lipids. TBARS concentrations were significantly higher in cholestatic children at baseline [2.9 (1.5-3.32) nmol/ml] than in a control group [1.2 (1.1-1.3) nmol/ml; p = 0.0006], but were not changed significantly during TPGS therapy [after 1 year 2.34 (1.9-3.0) nmol/ml]. Compared with controls, the contributions of polyunsaturated fatty acids to total phospholipid fatty acids were markedly decreased in cholestatic patients at baseline [27.7 (22.4-31.5)% versus 36.9 (34.5-39.0)%; p = 0.001] and did not show major changes after 1 year of TPGS supplementation. CONCLUSIONS: We conclude that oral TPGS supplementation of cholestatic children can quickly normalize serum vitamin E levels but does not improve the increased lipid peroxidation and poor polyunsaturated fatty acid status.

Child, Preschool↗
PubMed1996

Is growth hormone a feasible adjuvant in the treatment of children after small bowel resection?

The aim of our study was to assess the metabolic consequences of short-term administration of growth hormone in children after gut resection and influence on polyamine production in red blood cells (RBC). Twelve children aged 4-60 months were studied. All children remained on parenteral nutrition and 11 also received oral feeding. Total non-protein energy intake was 429 +/- 86 kJ/kg body weight (BW)/day. Recombinant growth hormone (GH) was administered subcutaneously at a dose of 0.3 IU/kg BW/day for 10 days. Resting energy expenditure (REE; kJ/kg BW/day) was: 316.07 +/- 54.08 before and 346.04 +/- 54.40 during GH administration (P < 0.02), but daily weight gain before GH administration was significantly lower than during treatment. A significant increase of polyamine concentrations was observed in the RBC (spermidine: 30.1 +/- 15.1 and 43.8 +/- 24.9 nmol/ml packed RBC, P < 0.003; spermine: 15.6 +/- 5.1 and 19.6 +/- 10.6 nmol/ml packed RBC, P < 0.02) and in jejunal mucosa (spermidine: 172.10 +/- 142.35 nmol/g tissue and 193.92 +/- 108.15 nmol/g tissue). The authors concluded that increased polyamine concentrations in the RBC and jejunal mucosa reflect a cellular response to GH administration. The anabolic effect of GH results in higher weight gain, although increased REE may indicate increased energy requirements during GH treatment.

Journal Article↗
PubMed1996

Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea.

A major transport function of the human intestine involves the absorption of chloride in exchange for bicarbonate. We have studied a recessively inherited defect of this exchange, congenital chloride diarrhoea (CLD; MIM 214700). The clinical presentation of CLD is a lifetime, potentially fatal diarrhoea with a high chloride content. The CLD locus was previously mapped to 7q3 adjacent to the cystic fibrosis gene (CFTR). By refined genetic and physical mapping, a cloned gene having anion transport function, Down-regulated in adenoma (DRA), was implicated as a positional and functional candidate for CLD. In this study, we report segregation of two missense mutations, delta V317 and H124L, and one frameshift mutation, 344delT, of DRA in 32 Finnish and four Polish CLD patients. The disease-causing nature of delta V317 is supported by genetic data in relation to the population history of Finland. By mRNA in situ hybridization, we demonstrate that the expression of DRA occurs preferentially in highly differentiated colonic epithelial cells, is unchanged in Finnish CLD patients with delta V317, and is low in undifferentiated (including neoplastic) cells. We conclude that DRA is an intestinal anion transport molecule that causes chloride diarrhoea when mutated.

Adenoma↗
PubMed1996

Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease.

Serum and salivary IgA and IgG antigliadin antibodies were determined by an enzyme-linked immunosorbent assay in 18 children with villous atrophy and 30 children on a gluten-free diet for coeliac disease in whom normal intestinal mucosa was found. Serum IgA anti-endomysium antibodies were also determined by an immunofluorescence method in these children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the highest sensitivity (100 and 94.4%, respectively), followed by serum IgA antibodies to gliadin (72.2%), salivary IgA antigliadin (61.2%) and IgG antigliadin (50%) antibodies. The highest specificity was found for serum IgA anti-endomysium (100%) and IgA antigliadin (96.6%) antibodies and salivary IgA and IgG antigliadin antibodies (93.3%), while serum IgG antigliadin antibodies were found to be least specific (63.3%).

Adolescent↗
PubMed1996

Disorders of magnesium homeostasis in the course of liver disease in children.

Magnesium deficiency can develop in patients with acute or chronic liver disease as a result of low dietary magnesium intake, low intestinal absorption or renal magnesium loss caused by natriuretic drugs. The aim of this study was to evaluate magnesium homeostasis in 39 children: 10 with acute liver failure due to Amanita phalloides poisoning. 14 with chronic liver diseases without cholestasis, and 15 with chronic liver diseases with cholestasis. Serum magnesium and fractional and 24 h urinary magnesium excretion were measured in all the children. Magnesium retention after intravenous infusion was also evaluated. Tissue magnesium deficit was found in 30 per cent of children with acute or chronic liver disease.

Adolescent↗
PubMed1996

[Autoimmune enteropathy--difficulties in diagnosis and treatment].

We describe a 42-month-old child with protracted diarrhoea that began at 6 months of age. Severe secretory diarrhoea persisted despite therapy with exclusion diets, total parenteral nutrition, chemotherapeutics, antisecretory drugs. The diagnosis of autoimmune enteropathy with total villous atrophy and anti-enterocyte antibodies was established at 16 months of age. Prednisone therapy induced a clinical remission. After dose reduction, clinical relapse occurred, complicated with HCV infection with elevated serum alanine aminotransferase activity. Increasing the prednisone dose did not result in clinical improvement. Treatment with cyclosporine induced clinical remission. After 10 months cyclosporine therapy is still continued and the boy is doing well.

Autoimmune Diseases↗
PubMed1995

[Intestinal microflora and antibiotic therapy].

Antibiotic therapy is one of the major factors leading to disturbances in the intestinal flora. This can lead to chronic diarrhea and life threatening pseudomembranous colitis. Much attention had recently been focused on so-called translocation of endotoxins and bacteria through the intestinal wall which lead to systemic infection, shock and multiorgan failure. Prevention is based on the proper choice of antibiotic and administration of lactic-acid bacteria.

Anti-Bacterial Agents↗
PubMed1995

[Changes in the gastrointestinal system of children with inflammatory systemic connective tissue diseases].

Functional and morphological changes of the gastrointestinal system were assessed in patients suffering from juvenile chronic arthritis, juvenile systemic erythematosus and juvenile systemic scleroderma. The results of endoscopic investigation of the gastrointestinal tract showed inflammatory changes and cardiac and pylorus atony. Ultrasonography results suggested hepatic and pancreatic inflammatory changes, steatosis and/or amyloidosis. The above-mentioned changes were confirmed by morphological investigation (biopsy and/or autopsy). The results of the capacity tests performed in JCA (systemic form) patients revealed an impairment of liver detoxication function, and pancreas and bowel functional capacity as well. Additionally, intolerance against lactose, casein and alpha- and beta-lactoglobulin was found in most of the patients. Some symptoms of malnutrition were observed in all of them. Such factors as underlying disease severity, adverse drug effects, environmental factors (infections, nutrition) were taken into consideration as probable causes of the gastrointestinal system damage.

Adolescent↗
PubMed1995

[Wilson disease with HCV infections].

In this paper we describe liver-related Wilson's disease in two sisters. The elder died of liver failure. Our patient, a 13-year old girl has hepatitis C coinfection. Gradual improvement was observed after Cuprenil, Zincteral and interferon (Intron A).

Adjuvants, Immunologic↗
PubMed1995

[Giant-cell hepatitis in a 10-year-old boy].

In this paper we present a 10-year-boy with viral giant-cell hepatitis with a immune component. We observed clinical, biochemical and histological improvement after treatment.

Bilirubin↗