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S Auricchio

Publications and source records attributed to S Auricchio.

At least 55 records · Page 3Linked to original sources

In vitro activities of A-gliadin-related synthetic peptides: damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa.

BACKGROUND: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH(2)-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated. METHODS: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought. RESULTS: Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25 positive cells. CONCLUSIONS: Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.

Amino Acid Sequence↗

Diagnostic value of various serum antibodies detected by diverse methods in childhood celiac disease.

The diagnostic performances of antiendomysium IgA detected on monkey esophagus and human umbilical cord smooth muscle, of antireticulin IgA, and of antigliadin IgA and IgG were calculated in 74 children with celiac disease (CD) or other gastrointestinal disorders. We also compared four methods for gliadin antibody detection. With a diagnostic specificity of 100%, diagnostic sensitivity was 94% for antireticulin IgA, 93% for antiendomysium IgA when detected on human umbilical cord smooth muscle, and 97% when detected on monkey esophagus. The diagnostic sensitivity for gliadin antibody was highest with an ELISA procedure, followed by fluorogenic detection (94% for IgG, 91% for IgA, 97% with IgA and IgG combined). Because of its high diagnostic sensitivity and ease and speed of use, the combined antigliadin IgG and IgA antibody assay is suitable for screening large groups of patients. In IgG- or IgA-positive cases, the more demanding and more specific antiendomysium IgA evaluation is required to confirm suspected CD.

Animals↗

The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.

Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.

Adult↗

Upper gastrointestinal motor abnormalities in children with active celiac disease.

Although from the clinical point of view a GI motor disorder can be suspected in celiac disease, objective evidence for this is still lacking. We therefore conducted a study on children with active celiac disease to detect possible GI motor abnormalities in this disease. Fourteen children (age range, 1-13 years) were studied; they underwent fasting and fed manometric recordings in the gastroduodenojejunal area. Four patients were restudied after a 6-month gluten-free diet. Data were compared with those obtained in eight control children. As compared with controls, celiac disease patients showed a shorter duration of activity fronts (p < 0.01) and a significant (p < 0.01) reduction of the postprandial antral motility index; furthermore, > 90% of the patients displayed marked fasting and/or fed motor abnormalities, suggesting a neuropathic disorder. Interestingly, gut dysmotilities disappeared in the four subjects reassessed after the gluten-free diet. It is concluded that celiac disease frequently affects the motor behavior of the gut and that its effects may be reversed by appropriate diet.

Adolescent↗

Differentiation of cows' milk intolerance and gastro-oesophageal reflux.

The aim of this study was to compare a non-invasive test of small bowel permeability with a more invasive approach involving endoscopy, mucosal biopsy, and oesophageal pH monitoring for rapidly differentiating gastro-oesophageal reflux (GOR) and cows' milk intolerance in 25 infants with persistent vomiting. Each subject underwent a cellobiose/mannitol permeability study, upper gastrointestinal endoscopy with oesophageal and small bowel biopsies, and a 24 hour pH study. Reflux disease and/or cows' milk intolerance was responsible for vomiting in 24 (96%) of the subjects. Sixteen (64%) of the infants had GOR alone, four (16%) had GOR and cows' milk intolerance, and four (16%) had cows' milk intolerance alone. Morphometric analysis of small bowel biopsies was abnormal in 19% of the patients with GOR alone and in 67% with cows' milk intolerance with or without GOR. The permeability test was abnormal in only 6% of the patients with GOR but in 100% with GOR and cows' milk intolerance and in 100% with cows' milk intolerance alone. The non-invasive permeability study aimed at rapid determination of cows' milk intolerance should pre-empt a more invasive approach in the evaluation of infants with persistent vomiting.

Cellobiose↗

Long-term follow-up of children with chronic idiopathic constipation.

To determine the outcome of chronic idiopathic constipation, we followed 62 children with chronic idiopathic constipation (mean age: 5.2 +/- 2.8 years) for a period of five years. Each child received the same initial treatment over a 12-week period and was then followed every three months. After five years from diagnosis, chronic idiopathic constipation persisted in 52% of the children; 47% who remained symptomatic were > 10 years old at the time of the five-year evaluation. Of the 27 who were constipated in the first year of life, 63% remained constipated after five years. Children who recovered within the five-year interval were significantly different from those that remained symptomatic in age of onset of constipation (P < 0.05) and family history of constipation (P < 0.05). After five years, both severity of abdominal pain and degree of soiling significantly decreased in both the recovered and unrecovered groups (P < 0.05). This study suggests that chronic idiopathic constipation persists for > or = 5 years in at least half of children. Early age of onset and family history of constipation are predictive of persistence. Abdominal pain and soiling improve in long-term follow-up irrespective of constipation outcome.

Child↗

Mosaic regulation of lactase in human adult-type hypolactasia.

BACKGROUND/AIMS: We have previously shown that in the proximal-jejunum of hypolactasic humans, just a few villus enterocytes express lactase protein and activity. In the present study, we compared the distribution of lactase messenger RNA (mRNA), protein, and activity in villus enterocytes in tissues obtained from subjects with persistent high lactase activity and those with hypolactasia. METHODS: Immunohistochemical and enzymohistochemical staining was performed on closely adjacent sections of human proximal jejunum from 5 individuals with persistent high lactase activity and 32 with hypolactasia. In all the persistent and in 9 hypolactasic samples, in situ hybridization was also performed using a digoxygenin-labeled RNA probe. RESULTS: In persistent tissues, lactase mRNA, protein, and activity were present in all villus enterocytes. In hypolactasic tissues, lactase mRNA was detected only in some villus enterocytes; some of them also expressed protein and activity, whereas others did not. In 8 of these hypolactasic samples, a variable number of villus enterocytes with lactase mRNA and protein did not express lactase activity. CONCLUSIONS: Various types of enterocytes are present even on a single villus from individuals with adult-type hypolactasia. These results show that different mechanisms control lactase expression in enterocytes on the same villus.

Adult↗

Antroduodenojejunal manometry in the diagnosis of chronic idiopathic intestinal pseudoobstruction in children.

We analyzed the antroduodenojejunal (ADJ) manometric patterns in a group of 19 consecutive children (mean age, 53 months; range, 5 months to 14 years) referred for suspected chronic idiopathic intestinal pseudoobstruction. Diagnosis was based on typical symptoms, absence of extraintestinal diseases, and structural lesions of the gut at endoscopy and radiology. Surgical full-thickness intestinal biopsies were evaluated in nine patients. Manometry of the stomach and small bowel was performed in the fasting and fed state with a multilumen perfused probe. All patients showed severe abnormalities of ADJ motor activity that were not seen in the eight controls (mean age, 38.2 months; range, 1-9 years). In 12 patients, manometric patterns suggesting neuropathic disease were detected with fasting and/or fed sustained and incoordinated duodenojejunal phasic waves, aberrant propagation and/or configuration of phase III of the inter-digestive motility complex, inability of a meal to convert a fasting into a fed pattern, and prolonged groups of fasting and fed nonpropagated phasic waves. In seven of these patients, histology revealed marked changes of the intrinsic neurons. In four cases, manometry disclosed features suggestive of a myogenic disease, including severe fasting and fed infrequent low-amplitude contractions, sometimes with some degree of propagation; in two of these cases, histology showed morphological abnormalities of smooth muscle cells of the gut wall. In three patients, manometry revealed signs suggestive of mechanical obstruction of the gut, such as repetitive post-feeding clusters and simultaneous repeated broad-based waves; in these patients, more detailed x-ray studies showed organic obstructive causes (ileal lymphoma, Hirschsprung's disease, and intestinal malrotation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cellular basis of adult-type hypolactasia.

In the proximal jejunum and distal ileum of adult rabbits and rats, the lactase protein and lactase activity are present only in patches of enterocytes, located principally on the lower part of the villi, whereas in the mid-small intestine, lactase is present in all the villus enterocytes. In the proximal jejunum of adult rabbits, only a few vertical continuous sheets of lactase-positive enterocytes arise from the base of the villus, suggesting that the patchy expression of lactase may have a clonal origin. In the proximal jejunum of adult humans with persistent high lactase activity, all the villus enterocytes express lactase; on the contrary, a patchy expression of lactase protein and lactase activity is present in hypolactasic tissues. The patches of lactase-positive enterocytes are scattered randomly on the surface of the villus, suggesting that in hypolactasic humans the enterocyte heterogeneity occurs as a consequence of mechanisms that do not have a clonal origin.

Adult↗

Effects of gluten enriched diet on the small intestinal mucosa of normal mice and mice with graft versus host reaction.

This study looked at the effect of extra dietary gluten on the intestinal architecture of both normal mice and those with an ongoing mucosal delayed hypersensitivity reaction. BDF1 normal mice and mice in which a graft v host reaction (GvHR) had been induced, both weaned on gluten free diet, were allocated for three weeks to three different dietary regimens: gluten free, 'normal' (3.6% gluten), and gluten enriched (15.8% gluten). In normal mice receiving the gluten containing diet, shorter villi, deeper crypts, and higher crypt cell production rate were noted when compared with those receiving gluten free diet: these changes were more pronounced in those receiving the gluten enriched diet. GvHR mice showed shorter villi and an increase in both crypt length and crypt cell production rate when compared with normal mice, but the presence of gluten in their diet did not produce additional damage. Both in normal and in GvHR mice receiving gluten containing diet there were no signs of systemic (cell mediated or humoral) or mucosal immune reactions (raised intraepithelial lymphocyte counts or enhanced epithelial Ia expression) to gliadin. In conclusion, increasing the dietary gluten content produces significant changes in the mucosal architecture of normal mice; mice with GvHR enteropathy do not show additional damage resulting from dietary gluten.

Animals↗

Morphological method for the diagnosis of human adult type hypolactasia.

The primary adult type hypolactasia is the most common form of genetically determined disaccharidase deficiency. This study examined a large and homogeneous population of the south of Italy: surgical biopsy specimens of proximal jejunum from 178 adult subjects have been assayed for disaccharidase activities; the expression of lactase protein and lactase activity has also been investigated on tissue sections by immunomorphological and enzymohistochemical techniques. Histograms of lactase to sucrase ratio were found to provide a useful distribution of the lactase activity; a lactase to sucrase ratio of 0.17 was found to show discrimination between tissues with persistence of high lactase activity and tissues with adult type hypolactasia. In all 28 subjects with persistent high lactase activity, a uniform distribution of lactase protein and lactase activity in all villus enterocytes was detected, whereas in all 150 subjects with adult type hypolactasia a variable number of villus enterocytes failed to express the lactase. Moreover in hypolactasic samples the lactase activity on tissue sections was constantly detected later than in samples with persistent high lactase activity. The absolute correlation between the immunohistochemical and enzymohistochemical features and the assessment of lactase activity in intestinal homogenates suggests that the morphological criteria are an alternative method for the diagnosis of adult type hypolactasia in human biopsy specimens from proximal small jejunum.

Adult↗

Analysis of lactase processing in rabbit.

The proteolytic processing of rabbit intestinal lactase-phlorizin-hydrolase (LPH) was studied by pulse-chase and continuous labeling experiments in organ culture from 15-day-old rabbits in the presence of glycosylation and processing inhibitors. Monensin and brefeldin A inhibited the two proteolytic cleavages of the precursor indicating that they are post-Golgi events as previously reported for the unique cleavage of LPH in man. The inhibition was not related to a concomitant alteration glycosylation; in fact, if trimming was blocked by MDNM the abnormal glycosylated precursor was proteolytically processed normally. Finally the use of the anti-microtubular drug colchicine strongly inhibited both cleavages and caused accumulation of the complex-glycosylated precursor form the brush border fraction indicating that proteolytic events depend on intact microtubule (transport).

Animals↗

In vitro biosynthesis of lactase in suckling and adult rabbits. Regulatory mechanisms involved in the decline of the lactase activity.

Steady state forms, levels and the in vitro biosynthesis of lactase-phlorizin hydrolase (LPH) proteins have been studied in proximal and middle intestine of suckling and adult rabbits. In most adult tissues the lactase activity and the LPH protein content were low and the synthesis rate of the 200 kDa lactase precursor was reduced in comparison to suckling tissues. In a few tissues with low enzymatic activity the LPH protein content was relatively high, and high lactase synthesis occurred. In addition, the ratio (labeled lactase)/(lactase protein) was lower in the middle jejunum of the adult rabbit than in the proximal region. Both decreased synthesis of LPH precursor and increased turnover or inactivation of the enzyme may cause the decline of the lactase activity.

Animals↗

Fasting and postprandial mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease.

In order to define the mechanisms of gastroesophageal reflux (GER) in children, we performed simultaneous intraluminal esophageal motility and pH studies in 24 children with symptomatic reflux and abnormal prolonged pH probe study, ten (group A) without endoscopic and histologic esophagitis, 14 (group B) with endoscopic and histologic esophagitis. Median (ranges) age (years) was 5.0 (6 months-10 years) and 3.0 (6 months-12 years), respectively. Recordings were done for 1 hr before and 1 hr after feeding apple juice (15 ml/kg; pH 4.0). All episodes of GER in group A patients and 77.1% in group B patients were accounted for by abrupt transient lower esophageal sphincter (LES) relaxation (TLESR); 22.9% of reflux events in group B patients occurred during gradual drifts of LES pressure (LESP) to undetectable levels. Esophageal refluxate exposure (mean percentage time with esophageal pH < 4.0), the rate of TLESR (number of episodes/hr), and the percentage of TLESRs associated with reflux significantly increased in the fed period both in group A (18.5 +/- 5.4%, 6.2 +/- 2.65, 87.1%) and in group B (29.7 +/- 6.5, 7.8 +/- 3.05, 84.9%) as compared to the fasting state (group A: 10.8 +/- 3.9, 3.9 +/- 3.17, 46.1%; group B: 16.1 +/- 2.6, 4.14 +/- 3.06, 55.17%) (p < 0.01). The rate of LESP drifts (number of episodes/hr) was also significantly higher postprandially (4.85 +/- 1.24 vs 1.8 +/- 0.9, p < 0.01); furthermore there was a postfeeding increase of the LESP drift percentage associated with reflux (79.41% vs 46.15%, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Mosaic differentiation of human villus enterocytes: patchy expression of blood group A antigen in A nonsecretors.

BACKGROUND: The authors have shown that a mosaicism of brush border antigens may occur spontaneously on enterocytes of small intestine in human adult-type hypolactasia. The present paper gives another example of spontaneously occurring mosaicism as indicated by the patchy expression of blood group antigens on villus enterocytes. METHODS: Thirty-five individuals were examined by immunomorphological techniques with antibodies against blood group antigens. RESULTS: In 4 of 16 A blood group individuals, the blood group antigens were expressed only in some villus enterocytes. The individuals with this mosaic pattern were all shown to be nonsecretors. The A antigen in the positive enterocytes of these individuals was only present as the ALe(b) structure, whereas ALe(y) and ALe(d) were also present in the secretors. The patches of positive enterocytes were randomly distributed along the villus wall. CONCLUSIONS: A nonsecretor individuals express the blood group antigens only in some villus enterocytes; this mosaicism does not arise from a heterogeneous population of stem cells within the crypts but rather reflects subtle differences in the pattern of differentiation between monoclonally derived epithelial cells on the villus.

ABO Blood-Group System↗

Surface staining on the villus of lactase protein and lactase activity in adult-type hypolactasia.

BACKGROUND: We have shown in previous studies the presence of a patchy pattern of lactase protein expression in the proximal jejunum of hypolactasic humans, adult rabbits, and rats. The present study investigated the mechanisms underlying the heterogeneous expression of lactase on the villus. METHODS: Proximal jejunal tissue from 18 adult humans and 12 adult rabbits was examined using enzymocytochemical and surface-staining techniques for lactase protein and activity. RESULTS: In the proximal jejunum of hypolactasic humans and adult rabbits, lactase activity is patchily distributed on the villus enterocytes. In humans, the patches of lactase-positive enterocytes are randomly distributed on the villus, whereas in rabbits, vertical, continuous sheets of positive enterocytes arise from the base of the villus. CONCLUSIONS: The presence of enterocytes without lactase activity is one of the mechanisms causing adult-type hypolactasia in the proximal jejunum of humans and mammals. The patchy pattern of lactase in rabbits suggests a clonal origin with heterogeneity of the cells arising from the crypts. In hypolactasic humans, the enterocyte heterogeneity occurs as a consequence of mechanisms that do not have a clonal origin.

Age Factors↗