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.

[Alpha 1-antitrypsin as an endogenous marker of protein-losing enteropathies]. / Alpha 1-antytrypsyna endogennym markerem jelitowej ucieczki bialka.

A novelty of the present studies is the use of alpha 1-antitrypsin (A-1--AT) as an endogenous marker of enteric protein loss. Enteric clearance of alpha 1-antitrypsin was determined in 10 patients with the symptoms of PLE, and in 6 healthy individuals. Alpha 1-Antitrypsin concentration has been assayed in single, random samples of feces collected from 42 patients and 12 healthy individuals (normal values: 1.31 +/- 0.72 mg/g of feces). Markedly increased enteric clearance and A-1-AT concentrations in single, random samples of feces have been found in patients with enteric lymphangiectasis, Crohn's disease, ulcerative colitis, and constrictive pericarditis, slightly lower in coeliac, chronic diarrhoea, nonspecific hemorrhagic colitis, esophagitis, lambliasis, hypogammaglobulinemia, Wiskott-Aldrich syndrome, Rendu-Osler-Weber syndrome, hepatitis in newborn, and Gilbert's disease. Statistically significant positive clearance has been noted (r = 0.997; p less than .001). A single assay of A-1-AT in feces is simple, repeatable, and sensitive technique in the diagnosis and evaluation of these diseases in which the symptoms of enteric protein loss are seen.

Fructosamine in human and bovine semen.

We detected the presence of fructosamine in human and bovine semen. In seminal plasma of healthy normozoospermic men (N = 17) fructosamine was found in 53% of the cases (fru+). In fru+ semen samples the concentration of fructosamine was (mean +/- S.E.M., N = 9) 0.45 +/- 0.09 mmol/L and varied from 0.15 to 0.75 mmol/L. It was 3-12 times lower than in blood serum of healthy men. In semen of infertile men (N = 57) fructosamine was present only in 21% of the cases and its concentration was lower than in fertile men i.e. (mean +/- S.E.M., N = 12) 0.27 +/- 0.007 mmol/L. In bulls (N = 98) fructosamine was found in semen of 82% of animals. In fru+ semen samples the concentration of fructosamine was (mean +/- S.E.M., N = 80) 0.77 +/- 0.12 mmol/L and varied from 0.30 to 1.15 mmol/L. We did not find any correlation between the concentration of fructosamine on one hand, and that of fructose and glucose on the other hand, in either human or bull semen. The difference in the frequency of fructosamine appearance in semen of fertile and infertile men suggests that fructosamine may be in some way involved in the process of fertilisation.

[Indicators of the identity of aspirates from the oral cavity of newborn infants and the amniotic fluid: pH, protein levels and the activity of trypsin inhibitor]. / Wskazniki identycznosci aspiratu z jamy ustnej noworodka z wodami plodowymi: pH, stezenie bialka, aktywnosc inhibitora trypsyny.

The aim of the study was to establish the biochemical identity as regards pH, protein content and trypsin inhibitor activity between the aspirate from the various sites of the newborn oral cavity and the amniotic fluid. It has been found that only correctly collected aspirate from the oral cavity without any admixture of the subepiglottic or gastric content is identical with amniotic fluid. Measurement of trypsin inhibitor activity in the improperly collected aspirate with pH below 5 must not be performed. The examination of the correctly sampled aspirates from the newborn oral cavity could be a source of the new early information regarding survival and the clinical condition of the newborn.

[Activity and molecular form of intestinal gamma-glutamyltransferase (GGT) EC 2.3.2.2. in celiac disease]. / Aktywnosc i postac molekularna jelitowej gammaglutamylotransferazy (GGT) EC 2.3.2.2. w celiakii.

It has been shown that GGT activity in the duodenal biopsy homogenates of the children with coeliac disease (n-10) in remission (1 to 3 years of gluten-free diet) is lower than in those with other gastrointestinal tract diseases (n-6). In children with coeliac disease after gluten challenge (1 g of gluten) kg BW for 3 to 6 months) the GGT activity decreased fourfold (n-10). After a few months of gluten challenge there was in coeliac children (n-5) a marked predominance of GGT without sialic acid (the asialic GGT). Similarly there was a prevalence of this form (n-5) in the gut tissue of 3 month old human fetus. In the homogenates of the duodenal bioptates of the children with other gastrointestinal tract diseases (n-6) there was a predominance of the sialic form of the GGT. In the gut tissue of children older than 3 years (n-6) and adults who died of reasons other than gastrointestinal a marked predominance of the sialic form of GGT was found. It has been suggested that presence of asialic form of GGT in coeliac disease is connected with the lectin-like activity of gluten. The process of sialization or desialization takes place within or outside enterocytes. It changes the gut permeability and causes a secondary reaction to the penetrating allergens.

[Multi-indicator biochemical and clinical evaluation of occupational exposure of workers in the petrochemical industry. II. Results of the search for early clinico-biochemical signs of exposure to toxic substances present in the petrochemical industry. Analysis of the results of 5-year epidemiological studies]. / Wielowskaznikowa ocena biochemiczno-kliniczna narazenia pracownikówprzemyslu petrochemiczego. Cz. II. Wyniki poszukiwan wczesnych objawów kliniczno-biochemicznych narazenia na toksyczny wplyw substancji wystepujacych w przemysle petrochemicznym. Analiza wyników 5-letnich badan epidemiologicznych.

The activities of GGT (EC 2.3.2.1.) and glycine transaminidase (EC 2.6.2.1.) increased in all studied groups after at minimum four years of exposure to: acetobenzene, furfurol, ethylene--derivatives, polypropylene and butadiene. Besides these universal indicators the specific ones were found for a particular group of exposure: for acetobenzene--sialic acid, haptoglobine and IgA, for furfurol--sialic acid and haptoglobine, for ethylene--derivatives--haptoglobine, ceruloplasmine and the activity of arginase of the red blood cells, for polypropylene--IgA, for butadiene--proteolytic activity. These changes are treated as a manifestation of adaptive processes--the answer of the body to the environmental stimuli but not as the signs of early damage. The need of verification of the results by prospective studies is stressed.

[Multi-indicators in the biochemical and clinical evaluation of exposure of workers in the petrochemical industry. I. Preliminary epidemiologic screening studies]. / Wielowskaznikowa ocena biochemiczno-kliniczna narazenia pracowników przemyslu petrochemicznego. CZ. I. Wstepne badania epidemiologiczno-skriningowe.

Eleven non-routine biochemical and clinical indicators (selected of 26 preliminarily estimated) in Petrochemical Plant workers and in controls, localized in an increasing distance from the Plant (3-18-40 km), have been measured. Even in the 3 km distance, no effects of the Petrochemical Plant have been found. All the exposed groups exhibited changes in enzymes GGT and TA. We estimate these indicators as universal. The concentration of haptoglobin (Hp) changed in 3 groups, whereas sialic acid and arginase--in 2 exposed groups.

[Intestinal arginase in the phylogenetic development of animals]. / Arginaza jelitowa w rozwoju filogenetycznym zwierzat.

The activity of intestinal arginase was studied in 31 species belonging to the types Annelides, Arthropoda and Chordata. Large variations of the enzyme activity were tested. The differences were of 2 orders of magnitude--100 times. Four groups were selected: animals with very low arginase activity up to 0.20 microM of ornithine/mg of protein/15 min; this group comprises both phylogenetically lower and higher animals (cockroach, locust, frog, duck, domestic hen, broiler chicken, horse, hyppopotamus, ox, sheep, antelope); animals with rather low activity up to 0.22 to 0.60 microM of ornithine/mg of protein/15 min (crayfish, herring, salmon, bream, cod, pike-perch, mink, fox, dog. man); animals with moderate activity up to 0.63 to 1.15 microM of ornithine/mg of protein/15 min (pigeon, coypu, guinea-pig, hog); animals with high activity up 1.15 to 9.26 microM of ornithine/mg of protein/15 min (rabbit, rat, hamster, mouse). According to the profile the activity of the enzyme along the long axis of the intestine two groups of animals could be separated: one in which arginase activity is the same over the whole length of the intestine, in animals with very low and rather low arginase activity, and the second in which there is a distinct topographical differentiation of activity (the highest in the jejunum decreasing gradually with differing gradients) in animals with moderate and high arginase activity. Intestinal arginase activity in quails in ontogenic development from the birth up to 233 days, show 2 peaks--one at 9 and the second at 23 days.

Studies on L-arginase in developing rat small intestine, brain, and kidney. I. Ontogenic evolution of arginase isoenzymes.

The adult patterns of arginase isoenzymes in rat intestine, kidney, and brain are nearly identical and consist of two forms, cationic A1 and anionic A4. In this paper, the organ-specific maturation of the enzyme equipment in these tissues is reported. The activity of arginase in all tissues studied could be detected on the 13th to 16th days of gestation. In fetal intestine and kidney the arginase activity is low, and persists up to the weaning time when the rapid, 10-fold rise of the enzyme activity occurs. However, the adult pattern of arginase isoenzymes in these tissues is accomplished in different ways. In the intestine, arginase A1 appears in fetal life and is the only form of the enzyme till the 19th to 21st days of postnatal life when the second form of arginase, A4, appears and rapidly accumulates, being exclusively responsible for the rise of the total enzyme activity at the time of weaning. In kidney, arginase A1 alone is present in the early fetal period. Arginase A4 appears 3-4 days before birth and its activity persists unchanged within the first 2 weeks of postnatal life. The intensive rise in total specific activity of kidney arginase at weaning is due to the accumulation of preexisting arginase A4. In brain, the adult pattern of arginase isoenzymes is achieved earlier than in other tissues. Both forms, A1 and A4, occur on Days 13-14 of gestation.

Studies on L-arginase in developing rat small intestine, brain, and kidney. II. Effect of hydrocortisone and thyroxine.

The influences of hydrocortisone and thyroxine on the developmental changes of arginase activity in intestine, kidney, and brain of suckling rats were studied. A single injection of hydrocortisone (50 mg/kg) into rats aged 9 days evoked premature increase of jejunal arginase activity due to precocious formation of arginase A4. Arginase A4 can be detected about 48 hr after hydrocortisone injection, whereas in intact rats the enzyme appears in the intestinal mucosa on the 19th-21st days of postnatal life. After hydrocortisone administration to rats aged 6 days, a similar pattern of arginase activity in jejunum was observed. Under the same conditions, the influence of hydrocortisone on kidney arginase was weaker. The hormone did not have any influence on the activity of brain arginase. Daily injection of thyroxine (2 mg/kg) to 6-day-old rats (for 6 consecutive days) caused a precocious increase of the arginase activity in intestine. Under the same conditions, only a slight increase of the arginase activity was observed in kidney, whereas in brain the activity was unaffected.