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Biomedical subjects

S Auricchio

Publications and source records attributed to S Auricchio.

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

Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non-persistence polymorphism.

A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.

Alleles↗
PubMed1998

Early childhood feeding practices in southern Italy: is the Mediterranean diet becoming obsolete? Study of 450 children aged 6-32 months in Campania, Italy. Cultural Paediatric Association.

With increasing affluence, the traditional food choices of Mediterranean populations are changing. The changes appear to begin in early infancy, with increased consumption of processed foods. To determine current consumption patterns of the diets of 450 toddlers, 6-32 months old, enrolled from 17 paediatric practices in the Campania region of Italy, quantitative data were collected for 7 d, using calibrated feeding bottles, cups and dishes. Automated food analysis was employed and quality control was performed on a sub-sample. The average daily intake was 373 kJ/kg. Forty-three percent of energy was provided by carbohydrates, while fats supplied 39%, 45% of fats were saturated and 46.7% were monosaturated (primarily olive oil). Proteins provided 18% of daily energy; most (81.4%) were of animal origin. Fibre was virtually absent from the study children's diet. Total daily cholesterol reached an average value of 191 mg/d, corresponding to 201 mg/4.2 mJ. The intake per kg of cholesterol increased with age in the first year, while proteins and fats decreased. Dairy products were the main source of energy, fats and cholesterol. Vegetables and legumes were a minor source of energy at all ages: the consumption of fruit decreased with age. Although the overall pattern of feeding of this cohort remains favourable compared with other children groups in developed countries, consumption of whole milk and full fat dairy products may be reduced to equilibrate the diet.

Age Factors↗
PubMed1998

Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings.

BACKGROUND: CD3 and gamma delta cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings. Aim- To establish an in vitro system for assessing immunological changes induced by gluten in the rectum. PATIENTS AND METHODS: Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated. RESULTS: In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group. CONCLUSIONS: Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.

Adolescent↗
PubMed1997

DNA fragmentation is a feature of cystic fibrosis epithelial cells: a disease with inappropriate apoptosis?

Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR gene, which result in disrupted chloride secretions with inspissated mucous secretions by exocrine glands. Nick-end labelling was used to assess DNA fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two control lung tissues. In CF small intestine median 46% (range: 30-82) villus enterocytes show DNA fragmentation (vs. 3% (range: 1-7) in controls P < 0.001) and median 37.5% (range: 23-79) crypt enterocytes show Ki67 antigen (P < 0.001). In CF airways 57% (range: 54-70) of epithelial cells show DNA fragmentation. Inappropriate high DNA fragmentation is a feature of various CF epithelia. This could have great impact in understanding the mechanisms leading to disease.

Adolescent↗
PubMed1997

Lactase persistence versus decline in human adults: multifactorial events are involved in down-regulation after weaning.

BACKGROUND & AIMS: In nonhuman mammals, lactase activity declines during or after weaning. In contrast, about one half of the human species maintains high lactase activity even in adulthood. To clarify this difference, this study examined some parameters for which contrasting observations have been reported in connection with lactase decline. METHODS: Lactase activity, lactase messenger RNA (mRNA) levels, and in vitro lactase biosynthesis were determined in normal jejunal samples from a large group of white adults, all born in or near Naples. RESULTS: Of 44 individuals, 10 were lactase persistent and 34 were hypolactasic. Biosynthesis of prolactase correlated well with lactase mRNA levels, indicating transcriptional control; it did less so with steady-state lactase activity. Examination of lactase mRNA levels and lactase activity/lactase mRNA ratios revealed a heterogeneous pattern of lactase mRNA level, lactase synthesis, and activity in both lactase persistent and hypolactasic subjects. CONCLUSIONS: Both transcriptional and posttranscriptional factors cause the decline of intestinal lactase. This probably explains the multifarious observations that most studies on adult-type hypolactasia have reported. The single overriding factor distinguishing lactase-persistent subjects from hypolactasic subjects is the high rate of lactase biosynthesis.

Adult↗
PubMed1997

Identical T-cell receptor beta chain rearrangements are present in T cells infiltrating the jejunal mucosa of untreated celiac patients.

The intestinal mucosal lesion in celiac disease is characterized by a predominant T-cell infiltration of both epithelium and lamina propria. However, a restricted use of T-cell receptors (TCR) in T lymphocytes infiltrating the jejunal mucosa of celiac patients has not been reported. Based on an immunohistochemical survey of jejunal biopsies from a cohort of untreated celiac patients, we demonstrated a small but significant increase of V beta 8.1/2+ T cells in the lamina propria, but not in the epithelium nor in the peripheral blood. Sequence analysis indicated the existence of a variable degree of clonality of V beta 8+ T cells in the celiac mucosa. More importantly, the recurrence of identical CDR3 regions in some patients was also observed. The altered distribution of V beta 8+ T cells and the presence of identical CDR3 regions in celiac patients, but not in controls was independently confirmed by CDR3 size analysis in a further cohort of patients. These findings suggest that disease-specific variations of the TCRBV8 repertoire are present in the small intestinal mucosa of untreated celiac patients.

Amino Acid Sequence↗
PubMed1997

Compliance to a gluten-free diet in adolescents, or "what do 300 coeliac adolescents eat every day?".

BACKGROUND/AIMS: Compliance to a gluten-free diet is currently an important issue in the care of both adolescent and adult coeliac patients. The aim of this study was evaluate the compliance to a gluten-free diet and the dietary habits in general of coeliac teenagers and young adults. PATIENTS AND METHODS: A total of 306 adolescents and young adults were followed in a coeliac clinic. They were grouped on the basis of: strict compliance to a gluten-free dietary regimen (n = 223, 73%); dietary transgressions 2-3 times/month (n = 46, 15%); and frequent transgressions or a full gluten-containing diet (n = 37, 12%). RESULTS: The physical growth status was optimal in the male patients, and less so in the females, but was not related to compliance. Symptoms were very rare in all groups. Compliance to the diet was related to sex (females better than males), age (younger better than older), good school grades, and good self-esteem. CONCLUSIONS: The teen-agers studied consumed an average of about 11.32 kg/month of gluten-free products provided by the Italian Health System. Gluten-free pasta and bread were the daily choices. The mean cost for each patient was estimated to be Italian Lire 242,640 (ECU 124) per month or ECU 1,490/year.

Adolescent↗
PubMed1996

Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease.

BACKGROUND: Diagnosis of many immune-mediated diseases is helped by detection of antibodies directed against the pathogenetic (self or foreign) antigen. In coeliac disease (CD), we have a situation in which antiendomysial antibodies (EMA), which are not specific for the pathogenetic antigen, reach a specificity and sensitivity of detection of CD approaching 100%, whereas detection of antibodies against gliadin (AGA), the pathogenetic antigen, is far less specific and sensitive in diagnosis. No direct evidence of a relation between gluten/gliadin challenge and EMA production exists. We tried to establish whether the small intestine of CD patients is the site of EMA production and whether gliadin challenge could induce their release. METHODS: Small intestine biopsy samples from treated (23) and untreated (16) CD patients and controls (18) were cultured in vitro for 24-48 h in the presence of gliadin, another alimentary antigen, or medium. EMA and AGA were detected in the supernatants of these organ culture biopsy samples by ELISA and immunofluorescence technique, respectively. FINDINGS: No EMA were found in the culture supernatants of biopsy samples of 18 controls, whereas they were detected in the culture supernatants of all 16 untreated CD patients irrespective of gliadin challenge. Conversely, EMA were not detected in supernatants of biopsy samples cultured in medium only from 23 treated CD patients, but were detected in 17 of the 23 biopsy samples challenged with gliadin. INTERPRETATION: Our results suggest that a more complex pathogenetic mechanism than normally accepted is involved in CD. Furthermore, our findings raise the possibility that EMA, or the antigen recognised by them, are involved directly in the pathogenesis of CD.

Antibody Formation↗
PubMed1996

Gluten-sensitive enteropathy.

Gluten-sensitive enteropathy is induced by dietary wheat gliadin and related proteins in genetically susceptible individuals. Most evidence suggests that the mucosal lesion represents an immunologically mediated injury triggered by gluten in the context of a particular assortment of major histocompatibility complex genes. The amino acid residues of gliadin and related proteins responsible for toxicity have not been identified; in vitro systems are available, but definitive conclusions must rely on in vivo jejunal challenges. At a conservative estimate, symptomatic gluten-sensitive enteropathy affects approximately 1 in 1000 individuals in Europe; however, it is now becoming clear that a greater proportion of individuals has clinically silent disease, and probably many others have a minor form of the the enteropathy. In most countries, the clinical presentation has changed over the past few years coming closer to the adult type of the disease, and the age of onset of symptoms is shifting upward. Liver, joint, hematologic, dental, and neurologic symptoms are increasingly being recognized. Several diseases are associated the gluten-sensitive enteropathy, such as IgA deficiency, insulin-dependent diabetes mellitus, and a range of other autoimmune diseases. Tests based on the measurement of antigliadin and antiendomysium antibodies have gained success as noninvasive screening tests; however, the ultimate diagnosis still is based on the finding of a severe histologic lesion of the jejunum while the patient is on a gluten-containing diet and on its disappearance once the gluten is excluded from the diet. A lifelong, strict GFD is mandatory for celiac children. Among other long-term problems, an increased risk of intestinal lymphoma has been reported in patients on a normal gluten-containing diet.

Adult↗
PubMed1996

Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients.

BACKGROUND & AIMS: Mucosal cell-mediated immune response is considered the central event in the pathogenesis of celiac disease. In cultured intestinal explants from celiacs in remission, we have characterized the early stages of gliadin-induced immune activation. METHODS: Intestinal biopsy specimens (15 treated celiacs and 13 controls) were cultured with gliadin or maize prolamine digests for 24 hours as well as for 1, 2, 4, 6, 8, and 12 hours in some subjects. The expression of immunologic markers was detected by immunocytochemistry. RESULTS: Gliadin challenge may initiate two parallel pathways, one of which leads to T-cell activation and another that precedes it. Epithelial cells overexpress DR molecules after 1 hour, and in a second stage T lymphocytes become fully activated. Moreover, T lymphocytes migrate in the upper mucosal layers. T lymphocytes that migrate in the higher lamina propria compartments are mainly CD4+ and show markers of activation; migrating intraepithelial lymphocytes are CD8+ and do not express these markers. CONCLUSIONS: In vitro gliadin challenge is a suitable model to reproduce various immunologic features of celiac lesions; these may be caused by different pathways. The comprehension of these phenomena is essential to clarify the distinctive pathogenic mechanisms leading to disease and may help in defining novel therapeutic approaches.

CD3 Complex↗
PubMed1996

In siblings of celiac children, rectal gluten challenge reveals gluten sensitization not restricted to celiac HLA.

BACKGROUND & AIMS: Inflammatory changes in the rectum of patients with celiac disease after local instillation of gluten have been reported. The aim of this study was to examine rectal mucosa after local gluten challenge in children with celiac disease and their siblings. METHODS: Rectal biopsy specimens were obtained before and 6 hours after rectal challenge with a peptictryptic digest of gliadin in 33 children with treated celiac disease, 12 controls, and 19 siblings of children with celiac disease. Epithelium and lamina propria volumes were determined, and CD3+ and gamma delta + lymphocytes were counted. RESULTS: After local instillation of gliadin, a significant increment in the absolute number of intraepithelial lymphocytes was noted in patients with celiac disease but not in controls. Immunohistochemical analysis showed a significant increase in CD3+ and gamma delta + cells, with the gamma delta/CD3 ratio remaining unchanged after challenge. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis was used to classify 6 of 13 siblings as having celiac disease. The positivity was not associated with the presence of the heterodimer encoded by the DQA*0501 DQB1*0201 alleles in any of the siblings. CONCLUSIONS: All patients with celiac disease were identified by rectal gluten challenge. Approximately half of the siblings reacted to rectal instillation of gluten. The genetic background of such sensitization to gluten remains to be elucidated.

Adolescent↗
PubMed1996

Gluten-sensitive disease with mild enteropathy.

BACKGROUND & AIMS: Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens and possibly showing milder changes of mucosal architecture. Ten patients with symptoms suggesting celiac disease and serum antiendomysium antibodies with normal mucosal architecture were studied. METHODS: Immunohistochemical detection of mucosal immune activation and HLA typings were performed. RESULTS: Mucosal immune activation, with normal mucosal architecture and normal gamma/delta+ intraepithelial lymphocytes counts, was found on a gluten-containing diet. In 3 of 6 patients, multiple biopsy specimens showed one sample with severe villous atrophy. Clinical and immunomorphologic features were strictly gluten dependent. The mucosal immune activation was elicited in vitro by gliadin. Only 4 patients had the typical HLA typing of celiac disease. CONCLUSIONS: Gluten-sensitive celiac-like symptoms may occur in patients with serum antiendomysium antibodies, apparently normal intestinal mucosa, and HLA typing not commonly associated with celiac disease. These patients should undergo multiple biopsies, and signs of immunologic activation should be sought accurately; in the presence of mucosal immune activation, a trial with a gluten-free diet should be encouraged to detect gluten dependency. In vitro immunologic response of small intestinal mucosa to gliadin may support the diagnosis of gluten-sensitive enteropathy.

Adult↗
PubMed1996

Latent and potential coeliac disease.

Under the umbrella of coeliac disease (CD), or gluten-sensitive enteropathy, the concepts of silent, latent and potential CD have recently been introduced. While silent CD is marked by severe damage to the jejunal mucosa in the absence of clinical symptoms, both latent and potential CD are characterized by jejunal mucosa that would be reported as normal by most clinical pathologists in an individual on a gluten-containing diet. As opposed to potential coeliac patients, latent subjects sometimes in their life have had a flat jejunal biopsy which recovered on a gluten-free diet. Latent coeliac patients are often symptomatic; neither high titres of gliadin antibodies nor mucosal changes (including raised intraepithelial lymphocyte counts) are obligate features of latent CD, although the presence of elevated endomysial antibodies is probably the best predictor of progression towards villous atrophy. The term potential CD has been proposed for those subjects who do not have, and have never had, a jejunal biopsy consistent with overt CD, and yet have immunological abnormalities similar to those found in coeliac patients. Good markers of potential CD include the presence of serum endomysial antibodies, a high count of intraepithelial lymphocytes and subtle pathological alteration such as increased density of intraepithelial lymphocytes expressing gamma delta T cell receptor, signs of activated mucosal cell-mediated immunity, coeliac-like intestinal antibody pattern, and positive rectal gluten challenge.

Antibodies↗
PubMed1996

Defective 'gut processing' of gliadin in mice with graft-versus-host enteropathy.

The gut mucosa plays an important role in the induction of oral tolerance. Extending previous observations, we have here shown that serum containing gut-absorbed gliadin induces suppression of the specific systemic immune response in recipient mice parenterally immunized with gliadin. Graft-versus-host reaction (GvHR) has profound effects on the gut mucosa, representing a model of immune-mediated enteropathy. The aim of our work was to investigate the gut handling and processing of gliadin in mice with GvHR. Binding to enterocytes, passage through the epithelium, and ability of the epithelium to convert this antigen into a tolerogenic form were assessed in BDF1 mice weaned on gluten-free diet, 2 weeks after the induction of a semiallogeneic GvHR. Binding of gliadin peptide B3144 to enterocytes was similar in controls and GvHR mice. After feed, serum levels of gliadin were comparable in the two groups of mice, but when serum collected from GvHR mice and containing gut-absorbed gliadin was transferred intraperitoneally into naive recipient mice, this did not induce suppression of the specific immune response. These experiments indicate that during GvHR enteropathy the ability of the intestine to convert gliadin into a tolerogenic form is lost. Defective antigen gut processing may contribute to the observed failure in oral tolerance induction.

Animals↗