Biomedical subjects
K Pittschieler
Publications and source records attributed to K Pittschieler.
Expression of the VLA family of integrins in coeliac intestinal mucosa.
The integrins, a family of cell surface proteins, mediate cell adhesion and may influence within the intestinal mucosa processes such as migration and/or proliferation and differentiation of enterocytes and lymphocytes. The aim of this study was to examine the distribution pattern of integrin subunits (VLA alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, beta1 chains) in normal intestinal mucosa and in that of patients with active coeliac disease (CD) and CD in remission. Immunohistochemical techniques and double immunostainings with monoclonal antibodies were used for investigation of the VLA alpha family of integrins and beta1 chain distribution. While the majority of the findings are consistent with the few data previously reported in the literature, surprising is the finding of a lack of expression of VLAalpha1 on the intraepithelial lymphocytes in the coeliac mucosa. The deficient VLA alpha1 expression on IEL in coeliac but not in normal mucosa may imply a genetic variation or a specific deficiency of gene expression during T cell differentiation and activation.
Endoscopic diagnosis of duodenal stenosis.
Explore the source record for details and available documents.
Coeliac disease: screened by a new strategy.
The incidence of coeliac disease is different throughout Europe. The aim of our study was to investigate its true prevalence using antigliadin and endomysial antibodies in 4615 healthy adults within two different population groups in Northern Italy: 140 were positive for antigliadin antibodies (AGA), 111 only for AGA IgG, 17 for AGA IgA and 12 for IgG and IgA. Of those positive for AGA, nine had an abnormal small-intestine mucosa and were positive for endomysium antibodies (EmA) using the umbilical cord test, a novel methodology. The prevalence, 163/100,000 in the Italian group and 216/100,000 in the German group, is much higher than what was assumed. The positive predictive value of the EmA, confirmed by biopsy, is 100%, that of AGA IgG 2%, of AGA IgA 12% and of the combined AGA IgA and IgG 33%. AGA positive but EmA negative patients displayed normal histological features and distributions of alpha/beta and gamma/delta T-cell receptors on intraepithelial lymphocytes. We can therefore conclude that antigliadin antibodies are not an ideal tool for screening purposes; the umbilical cord EmA test is superior owing to its optimal sensitivity, specificity, high positive predictive value and low cost.
Neutropenia, granulocytic hypersegmentation and coeliac disease.
A 7-year-old girl was admitted to hospital with a 2-month history of profound weakness. Anaemia, marked neutropenia and hypersegmentation of the granulocytes were the major laboratory findings. These abnormal haematological data were due to significant folate deficiency caused by active coeliac disease diagnosed by both the presence of antigliadin and endomysium antibodies and typical histological features of the small intestine. The haematological abnormalities resolved within 3 weeks following a gluten-free diet and iv supplementation of folic acid.
Heterozygotes and liver involvement.
Explore the source record for details and available documents.
Endomysium antibodies in coeliac disease: an improved method.
The ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.
Reactivity of gliadin and lectins with celiac intestinal mucosa.
The binding patterns of gliadin and selected lectins to jejunal biopsy specimens obtained from children with total villous atrophy during active celiac disease (CD; 19 patients) and in remission (16 patients) were examined by light microscopy. Three categories of carbohydrate-specific lectins were chosen for the study: those recognizing mannose/glucose residues, those recognizing N-acetyl-glucosamine/glucose (glcNAc/glc) residues, and those recognizing N-acetylgalactosamine/galactose (galNAc/gal) residues. The galNAc/gal lectins, with the exception of phaseolus vulgaris agglutinin variants, presented a typical staining of the luminal surface of the jejunal mucosa obtained from CD patients. However, these lectins displayed no reactivity to jejunal sections of CD patients in remission or control biopsies that included healthy children (25 children) and patients suffering from cow milk protein allergy (10 children). The glcNAc/glc lectin showed a strong preferential recognition of CD jejunal tissue but also bound with less intensity to specimens from patients with cow milk allergies and healthy children. Unlike other galNAc/gal lectins, phaseolus vulgaris agglutinin variants were indistinguishable in their binding patterns to the mucosa of control groups and CD patients in remission and failed to react to CD biopsies. The mannose/glc lectins were not distinctive in their binding patterns. In all cases, lectin binding was specifically inhibited by the lectins' competitive saccharides. Atypical of lectin binding patterns, gliadin reactivity was restricted to intracellular areas of enterocytes and was unique to active CD mucosa. The distinctive binding patterns of lectins and gliadin provide a diagnostic tool to distinguish patients with active CD from those in remission or patients with other intestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
Vitamin E and liver damage in MZ heterozygous infants with alpha 1-antitrypsin deficiency.
Low levels of alpha 1-antitrypsin can predispose affected infants to develop a wide spectrum of liver diseases. Heterozygous PiMZ carriers can be affected by a subclinical liver involvement in the first six months of life. The liver damage appears to be mediated by the activity of toxic oxygen waste products originating from partially unchecked proteases which can cause enough damage to impair hepatic function significantly. In the present study it was found that the antioxidant properties of vitamin E were able to reduce the frequency of liver dysfunction in PiMZ carriers at two but not at five months of age. Liver damage is highly related to low levels of alpha-tocopherol in the plasma. These findings show that oxidative free radicals can promote liver damage in inadequately protected young infants, such as those affected by alpha 1-antitrypsin deficiency. The protective role of vitamin E in relation to the developmental expression of other antioxidant scavengers is discussed.
Williams syndrome and coeliac disease.
Explore the source record for details and available documents.
Liver involvement in infants with PiSZ phenotype of alpha 1-antitrypsin deficiency.
Between July 1985 and June 1989, 19,432 newborns were screened during the first days of life to determine their Pi (protease inhibitor) phenotype. Fourteen infants were identified to be carriers of the PiSZ phenotype. Their clinical and biochemical follow-up data were recorded at 2, 5, and 12 months of age; only one case underwent a liver biopsy due to repeated abnormal liver enzymes. Three of 14 PiSZ infants showed some hepatic dysfunction at 2 and 5 months of age, but at 12 months all patients had normal liver function tests. None of them had clinical, biochemical, or morphological signs of neonatal cholestasis. The clinical and biochemical data related to the liver involvement are similar to those of the PiMZ phenotype, though the serum levels of alpha 1-antitrypsin in PiSZ carriers match those of the PiZZ group.
Adipsic hypernatremia in two sisters.
We describe two sisters with chronic hypernatremia, lack of thirst, and inappropriate osmoregulated vasopressin secretion. Only one sister, who presented with microcephaly and developmental delay, showed signs of dysplasia of the midline structures (ie, septum pellucidum and corpus callosum) and a large intracranial cyst. Neither sister showed any signs of thirst, even when osmolality exceeded 337 mmol/kg. In both patients, the vasopressin secretion did not respond to either osmotic or nonosmotic stimuli or was suppressed by a water load. Plasma osmolality values returned to normal after treatment with forced hydration and a vasopressin analogue, desamino-D-arginine vasopressin. These findings indicate a severe defect in the hypothalamic osmoreceptors that control thirst and vasopressin secretion. To our knowledge, this is the first report of such a disorder in two sisters.
Dumping syndrome after combined pyloroplasty and fundoplication.
Dumping syndrome in infancy is a rare complication following gastric surgery. We describe an 11-month-old infant affected by recurrent peptic oesophagitis who underwent a combined Nissen fundoplication and pyloroplasty. Early dumping symptoms such as irritability, pallor, sweating, abdominal distension and watery diarrhoea were observed postoperatively after bolus feeding. Gastric emptying, measured after the administration of 150 ml of regular cow milk mixed with 200 microCi (8 MBq) of technetium-99m sulfur colloid (99mTc-SC), demonstrated an early rapid and massive emptying of the isotopes into the small intestine, followed by duodenogastric reflux and a second wave of emptying and reflux at 9 min. The initial pattern of gastric emptying and duodenogastric reflux was followed by a slow emptying phase with half-emptying time of 81 min. Isotope studies should be used to investigate motility disorders caused by this type of anti-reflux operation.
Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development.
Superoxide dismutase is the main scavenger of superoxide radicals in the mammalian body. The liver has high levels of two types of superoxide dismutase enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present study was to investigate the content of two distinct superoxide dismutases in liver during the perinatal transition from a hypoxic to a hyperoxic environment. Both isozymes were purified to homogeneity and used as immunogens in rabbits. Antisera raised were found to recognize only polypeptides of molecular weight 16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases, respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic activity and protein as assessed by immunoquantitation increased 10-fold during the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount of Mn superoxide dismutase content increased only twofold to adult levels during the first week of life. Neither of the superoxide dismutases showed an alteration in specific activity or apparent molecular weight in rat livers during ontogeny. These results show that the levels of two intracellular superoxide dismutases are differentially elevated during the perinatal period. It is suggested that each dismutase plays a different physiological role for superoxide scavenging in liver as a function of the hypoxic/hyperoxic environment at birth.
Liver disease and heterozygous alpha-1-antitrypsin deficiency.
From 1985 to 1988 14,938 newborns were screened during the first days of life to determine their protease inhibitor phenotype (Pi) and 467 PiMZ and 456 PiMS were identified. Of these 101 PiMZ and 135 PiMS were followed-up and their clinical, biochemical and, in selected cases, histological data were recorded at two, five and twelve months of age. Nineteen out of 101 PiMZ infants showed hepatic dysfunction at two months, eight at five, and one at twelve months of age, respectively. In 20 of 135 PiMS infants, liver function tests were abnormal at two months, in ten at five and in none at twelve months. It appears that PiMZ and PiMS phenotypes can be associated with hepatic dysfunction during the first six months of life. The marked variability of serum levels of alpha-1-antitrypsin in heterozygotes, make Pi-typing in all cases of neonatal hepatitis advisable. This should also be done for screening purpose.
Oxidative radicals and liver involvement of infants with alpha-1-antitrypsin deficiency.
Low levels of alpha-1-antitrypsin can predispose deficient infants to the development of hepatitis and cirrhosis. Heterozygous PiMZ carriers can be affected by a subclinical liver involvement during their first half year of life. One pathogenic hypothesis of liver damage is that the process seems to be mediated by the activity of toxic oxygen waste products. In the present investigation it was found that the antioxidant vitamin E was able to significantly reduce the frequency of liver involvement in PiMZ carriers at two months of age but not at five months. These findings indicate that oxidative free radicals can promote liver damage in inadequately protected young infants, such as in alpha-1-antitrypsin deficiency. The protective role of vitamin E in relation to the developmental expression of other anti-oxidant scavengers is discussed.
Cow's milk protein-induced colitis in the breast-fed infant.
A 3-month-old boy is described who developed an inflammatory proctocolitis during exclusive breast feeding. The major symptom was bloody diarrhea. No growth failure or constitutional symptoms were present. Bacterial, viral, and parasitic infection was excluded. The colonoscopic findings of focal ulceration, edema, and increased friability and the histologic picture with a marked eosinophilic infiltration were indicative of an allergic intestinal reaction. The infant responded favorably to the withdrawal of the mother's milk and the initiation of hydrolyzed casein formula. The challenge with cow's milk led to a clinical relapse resembling the initial manifestation.
Alpha 1-antitrypsin typing test evaluated.
Explore the source record for details and available documents.