PubMed Health⌕ Search

Biomedical subjects

S Auricchio

Publications and source records attributed to S Auricchio.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1992

In vitro biosynthesis of lactase in preweaning and adult rabbit.

Lactase is synthesized as a high-mannose large precursor (200 kDa) which is subsequently complex-glycosylated (215 kDa) and split into the 150 kDa mature form. The regulatory mechanisms responsible for the decline of activity at weaning are not yet known. We have set up in vitro cultures of intestinal mucosa from suckling and adult rabbit and found that suckling and adult animals synthesize the same four forms of lactase-phlorizin hydrolase (LPH) but with a different distribution. In the proximal adult small intestine there is very little 180 kDa form, which is most probably a product of the 215 kDa complex-glycosylated precursor. The 180 kDa form comprises a greater percentage of total LPH in the middle of the small intestine in adult and particularly in suckling rabbits. In the latter tissue this form is apparently more stable than in the adult tissue. Posttranscriptional control of lactase synthesis is therefore different in the various parts of the adult small intestine, and it is different in the suckling as compared to adult tissue.

Age Factors↗
PubMed1992

Reversal of gastric electrical dysrhythmias by cisapride in children with functional dyspepsia. Report of three cases.

Three children (ages 5, 7.6, and 8 years), with recurrent unexplained upper abdominal symptoms such as vomiting, epigastric pain, anorexia, early satiety and without structural or mucosal abnormalities of gastrointestinal tract, underwent electrogastrography (EGG)--recording of gastric electrical activity using cutaneous electrodes positioned on the epigastric region and connected to a recording polygraph. Frequency of EGG signals was analyzed by fast Fourier transform. Significant changes of fasting and fed gastric myoelectrical activity (tachygastria, bradygastria, flatline pattern) were recorded in the three patients; furthermore, gastric emptying (GE) of a solid-liquid mixed meal, measured by ultrasonography, was significantly prolonged in them. A follow-up study was carried out after an eight-week course with oral cisapride: in all patients symptoms improved, GE time normalized, and EGG analysis showed normal electrical rhythm. It is suggested that gastric dysrhythmias can play a pathogenetic role in patients with functional gastrointestinal symptoms and that symptomatic improvement is accompanied by normalization of gastric electrical rhythm.

Child↗
PubMed1992

Patchy expression of lactase protein in adult rabbit and rat intestine.

Enzymatic and immunohistological analyses of lactase were performed at different stages of development and within different regions of the small intestine of the rabbit and rat. As previously reported, there seems to be a sharp decline of lactase activity on weaning but variable and higher levels of activity are seen in adult animals. Two monoclonal antibodies to rat lactase were available to study the protein in rats. Four monoclonal antibodies to human lactase were shown to cross-react with rabbit lactase and used for the rabbit studies. Immunohistological analysis of small intestine of adult rabbits and rats showed residual lactase protein within the enterocytes throughout the small intestine. In the middle of the small intestine (lower jejunum, upper ileum), uniform staining of the brush border was observed. In the proximal and distal regions, a patchy pattern of staining was observed. This pattern, which resembles that observed in adult hypolactasic humans, indicates an underlying heterogeneity of enterocyte differentiation.

Age Factors↗
PubMed1992

Electrogastrography in non-ulcer dyspepsia.

Fasting and fed gastric electrical activity was recorded by cutaneous electrodes (electrogastrography) in 14 children with unexplained recurrent symptoms of upper intestinal dysfunction, and in 10 controls. The unexplained symptoms included vomiting, epigastric pain, fullness, and early satiety. Mean (SD) age was 7.0 (3) and 7.5 (2) years, respectively. Gastric emptying time of a solid-liquid meal was also measured by real time ultrasonography in all subjects (patients and controls). In all patients radiography and endoscopy excluded structural and focal abnormalities of the gastrointestinal tract. Gastric emptying time was significantly more prolonged in patients than in controls. It was also found that there were appreciable irregularities of gastric electrical rhythm (tachygastria, bradygastria, flat line pattern, and mixed arrhythmia) in 12 fasting and 10 fed patients, whereas controls showed short and rare episodes of arrhythmia during both fasting and fed recording periods. The percentage distribution of the total electrogastrographic energy power across three frequency bands of electrical activity (low, normal, and high) showed that patients were different from controls both for reduced activity of normal frequency and for increased incidence of high and low abnormal frequencies. It is concluded that gastric electrical abnormalities are found in a high proportion of children with recurrent unexplained upper gastrointestinal symptoms. Electrogastrography can be a valuable tool in the assessment of these patients.

Child↗
PubMed1992

Gliadin induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with coeliac disease mucosa.

Jejunal biopsies from 16 treated coeliac disease patients and from nine controls were cultured with and without a peptic-tryptic digest of gliadin. Cultures with a peptic-tryptic digest of maize prolamins were also undertaken. Frozen sections of baseline and cultured mucosa were stained by immunofluorescence with an anti-HLA-DR monoclonal antibody. Before culture the villous epithelium from both controls and treated coeliac disease expressed DR molecules while the crypt epithelium did not. When biopsies from treated coeliac disease were cultured with gliadin the expression of DR was enhanced in the crypt epithelium in eight of 14 cultures and in 11 of 14 was reduced or absent on the villous epithelium. No change was observed in control cultures. We conclude that gliadin is capable of inducing HLA-DR on the crypt epithelium of in vitro cultured coeliac disease mucosa, providing indirect evidence that gliadin may activate cell mediated immune mechanisms within the small bowel mucosa. This model could prove useful in identifying the immunogenic sequence(s) of gliadins and related prolamins.

Celiac Disease↗
PubMed1991

Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease.

In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was significantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying.

Bile Acids and Salts↗
PubMed1991

Compliance of adolescents with coeliac disease with a gluten free diet.

A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population.

Adolescent↗
PubMed1990

Amines protect in vitro the celiac small intestine from the damaging activity of gliadin peptides.

Proteins and peptides responsible for the celiac small intestinal lesion inhibit both the enterocyte recovery of in vitro cultured flat celiac mucosa and the in vitro development of fetal rat intestine. They also agglutinate K 562 (S) cells. Using these three in vitro systems (cultured human celiac and rat fetal intestine and cell agglutination), it is shown that several small-molecular-weight amines, mostly the polyamines spermidine and spermine, prevent and reverse K 562 (S) cell agglutination induced by gliadin peptides, whereas they do not prevent cell agglutination induced by concanavalin A and wheat germ agglutinin. Some of these amines also protected in vitro developing fetal rat intestine and flat celiac mucosa from the damaging effect of gliadin peptides. This protective effect may be related to the trophic activity exerted by amines on the intestine and/or the effect of amines on the functions of intestinal brush border or intracellular membranes involved in the intestinal handling of gliadins.

Abdomen↗
PubMed1990

Mannan and oligomers of N-acetylglucosamine protect intestinal mucosa of celiac patients with active disease from in vitro toxicity of gliadin peptides.

Wheat flour and other cereals toxic for celiac patients contain an alcohol-soluble protein fraction that, under experimental conditions simulating in vivo protein digestion, yields peptides that agglutinate undifferentiated K 562(S) cells. In contrast, cereals well tolerated in celiac disease (i.e., rice and maize) do not. Furthermore, purified A-gliadin peptides that damage in vitro-cultured flat celiac mucosa are powerful agglutinins for K 562(S) cells, whereas A-gliadin peptides that do not show any adverse in vitro effect on celiac intestine lack agglutinating activity. Mannan, acetylglucosamine, and its oligomers (N,N'-diacetylchitobiose and N,N',N"-triacetylchitotriose) were able to prevent and reverse cell agglutination induced by peptides from all the toxic cereals. Moreover, mannan and N,N',N"-triacetylchitotriose exhibited a protective effect on intestinal mucosa specimens of patients with active celiac disease cultured with wheat protein-derived peptides. These data are consistent with the hypothesis that the agglutinating and toxic peptides are bound by carbohydrates.

Acetylglucosamine↗
PubMed1989

A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease.

Coeliac disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities. Here we use a new DNA-based method of HLA-DP typing to analyse the distribution of DP beta alleles in a group of coeliac disease patients and healthy controls. Two specific DP beta alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DP beta sequences suggests that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DP beta alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQ alpha and beta alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DP beta allele are at increased risk for coeliac disease.

Alleles↗
PubMed1989

Unchanging clinical picture of coeliac disease presentation in Campania, Italy.

Four hundred and sixty-three new diagnoses of coeliac disease in children were made during 1973 to 1986 in our department. The distribution of new diagnoses per year did not show any decreasing trend in the period 1973 to 1986. No changing trend in breast feeding attitudes was found in the region during the same period. Analysis of the clinical pattern showed a constant distribution of age at diagnosis, onset of first symptoms and nature of symptoms throughout the period studied. These data suggest that coeliac disease is predominantly genetically determined and its expression is modulated by individual and environmental factors. The stability of the observed prevalence of the disease is parallel to the unchanging pattern of breast feeding attitudes in the region.

Adolescent↗
PubMed1989

Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats.

Lactase is an enterocyte brush-border membrane beta-glycosidase that splits lactose, the sugar of milk. In mammals, including many human populations, intestinal lactase activity is very high in the suckling and declines to low levels after weaning. There are two human adult lactase phenotypes, one in which high lactase activity persists and another in which it declines. Two alleles have been postulated to explain these different phenotypes. In the present study lactase mRNA levels have been investigated in the small intestine (a) of rabbits and rats, at different ages, considered as models for mammals, and (b) of human adults with the two lactase phenotypes. In rabbits and rats, high levels of lactase mRNA are present up to the weaning period, a time at which a consistent decrease of this mRNA is found, a decrease that parallels that of lactase activity. It is surprising that after this period adult animals of both species express again high levels of lactase mRNA, whereas lactase activity remains at very low levels. Our results suggest that in the adult rabbits and rats the main control of lactase gene expression is likely to be at a posttranscriptional level. Similarly, in man no clear difference was found at the RNA level between adults with hypolactasia and adults with persistent high lactase activity, a result that also indicates a posttranscriptional control of lactase expression.

Adult↗
PubMed1988

In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease.

Specific peptides of known amino acid sequence were prepared from alpha-gliadin (A-gliadin) by cleavage of the protein with cyanogen bromide and chymotrypsin and purification of the resulting peptides. The three peptides derived from the cyanogen bromide cleavage spanned the complete sequence of A-gliadin (266 residues). Four peptides derived from chymotryptic digestion covered the N-terminal sequence through residue 68. These peptides were tested for toxicity in celiac disease by organ culture of biopsied small intestinal tissues taken from patients with active celiac disease. Enterocyte height was used as a measure of peptide effect on cultured tissues. Five of seven peptides tested significantly inhibited increase of enterocyte height in the cultures and were considered toxic on this basis. The largest common sequences among the toxic peptides were -pro-ser-gln-gln- and -gln-gln-gln-pro-; these sequences were absent from the nontoxic peptides. The relationship of these sequences to the damaging effect of gliadins on the small intestinal mucosa in celiac disease remains to be investigated.

Biopsy↗
PubMed1988

Gluten-sensitive enteropathy in childhood.

Genetic and environmental factors (breast feeding, probably viral infections) play a role in the expression of the disease. Prevalence of GSE in childhood did not substantially decrease in the last 15 years in all European countries, where GSE is still more common in infantile age and presents frequently gastrointestinal symptoms. A decrease has been reported in childhood in several United Kingdom areas and in Finland, where the clinical presentation is changing, shifting upward with age and coming closer to the adult type of the disease. The following clinical problems have been reported in the recent literature: enamel hypoplasia; monosymptomatic short stature; arthritis and other immunologic diseases; association with diabetes, atopy, Iga deficiency, and probably Down's syndrome. Delay in puberty and other peculiar problems of the disease have been described in adolescents. Tests assessing the permeability of the small intestine and the blood levels of antigliadin antibodies have recently gained success as noninvasive tools for the diagnosis of the GSE. The gluten should be withdrawn from the diet and the challenge with gluten should be performed not before 12 months of gluten-free diet with an accurate timing of the biopsy on the basis of the antigliadin and antireticulin antibodies, to avoid clinical and growth damage. Celiac children do require a permanent gluten-free (and not poor) diet. In reality, too many celiac adolescents are off-diet.

Adolescent↗
PubMed1987

The biosynthesis of intestinal sucrase-isomaltase in human embryo is most likely controlled at the level of transcription.

Although sucrase-isomaltase appears in the small intestine at quite different stages of development in man as compared with most mammals, we find that in human embryo also the appearance of sucrase-isomaltase mRNA closely parallels that of sucrase and isomaltase activities, as we have previously found to be the case in baby rabbits. Also, in the proximal-distal gradient of human embryonic intestine (proximal small intestine greater than distal small intestine greater than colon) the levels of these enzyme activities and those of the corresponding mRNA correlate closely. Finally, glucocorticosteroid treatment of a human colon carcinoma cell line (Caco-2) in vitro or of baby rabbits in vivo leads to a parallel increase of both sucrase and isomaltase activities and of sucrase-isomaltase mRNA. We conclude that in man also, in spite of the different timing in development, the biosynthesis of sucrase-isomaltase is most likely to be controlled at the level of transcription or perhaps of the mRNA stability.

Animals↗
PubMed1987

Modulated expression of human homeobox genes in differentiating intestinal cells.

Homeobox genes (Hox genes) control segmentation and segment specificity in Drosophila. Hox genes have been detected in several species from insects to vertebrates. Differential and stage-related expression has been observed in human embryonic tissues as well. We have investigated whether the cell line Caco-2 and human adult intestine express Hox genes. Caco-2 is a cell line derived from a human colon carcinoma and exhibits a spontaneous enterocytic differentiation after cellular confluency in vitro. At 7, 14 and 21 days after seeding we have found that Hox-2.3 and one Hox-3 gene hybridize to poly(A)+RNA in a stage-related fashion. Moreover, the 21 days pattern of hybridization resembles that one observed in adult small intestine. The Caco-2 cell line provides a model system that allows a detailed analysis of cellular factors controlling transcription and stability of Hox gene products.

Adult↗