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Biomedical subjects

Ron Shaoul

Publications and source records attributed to Ron Shaoul.

At least 19 recordsLinked to original sources
PubMed2006

Elevated expression of FGF7 protein is common in human gastric diseases.

Growth alterations within the gastric mucosa during chronic gastric inflammation are key steps in gastric cancer development. FGF7, a specific mitogen for epithelial cells, is implicated in epithelial tissue repair and cancer. We investigated FGF7 expression in normal human stomach, and in 35 cases from various gastric pathologies including 23 gastritis and 8 adenocarcinoma cases. Modest FGF7 protein levels were detected in the normal mucosal gland epithelium and in stromal fibroblasts. FGF7 protein levels, however, were markedly increased in the mucosal epithelium of all gastric inflammation cases. A similar elevated expression was also observed in gastric adenocarcinoma. Upregulation of FGF7 protein was associated with a modest increase in FGF7 mRNA expression. Interestingly, high levels of FGF7 anti-sense (AS) RNA were observed in the gastric pathologies, at the same sites where FGF7 protein was upregulated. Altogether, these findings suggest a role for FGF7 in maintaining gastric mucosa integrity, and that FGF7 protein levels are regulated mainly by posttranscriptional mechanisms. The elevated FGF7 protein levels in gastric inflammation and gastric cancer, together with the known oncogenic potential of FGF7, implicate excessive FGF7 signaling in gastric tumorigenesis, and point to FGF7 as an attractive target for gastric cancer prevention and treatment.

Adenocarcinoma↗
PubMed2006

Polymorphisms in the TNF-alpha promoter and variability in the granulomatous response in patients with Crohn's disease.

Granulomas may be found in 30-70% of patients with Crohn's disease (CD). The etiology of granuloma formation in CD is presently unknown. Elevated levels of TNF-alpha are found within granuloma tissue, and are required to maintain granuloma formation in animal models. TNF-alpha production has been shown to influenced by TNF-alpha promoter polymorphisms. We hypothesized that heterogeneity for granulomas in CD might be influenced by the TNF-alpha promoter genotype. Patients with confirmed CD that had undergone full colonoscopy with multiple biopsies and/or surgical resection, served as the study group. One hundred healthy individuals served as a control population for genotyping. Patients and controls underwent genotyping for four TNF-alpha polymorphisms: 238G/A, 308 G/A,857 C/T, and 863 C/A. Inclusion and exclusion criteria were met in 155 patients (1-68 y). Polymorphisms in the TNF promoter were found in 16.6% (238G/A), 14.5% (308 G/A), 36.6% (857 C/T) and 30.7% (863G/A). No significant association was found for any of the individual polymorphisms with presence or absence of granulomas. In conclusion, we did not find an association between individual polymorphisms in the TNF-alpha promoter and presence of granulomas in CD. The reason for heterogeneity in granuloma formation in patients with CD remains elusive.

Adult↗
PubMed2006

Ileal lymphonodular hyperplasia is not associated with NOD2/CARD15 mutations.

INTRODUCTION: Lymphonodular hyperplasia (LNH) is a mass of lymphoid tissue that has been described in the terminal ileum, colon and duodenum mainly in children. Controversy exists regarding the benign nature of LNH. The combination of chronic abdominal pain and hematochezia leads many of these patients to undergo investigations for inflammatory bowel diseases. NOD2/CARD15 on chromosome 16 has been identified as a susceptibility gene for Crohn disease (CD). No study has yet examined the possible association of NOD2/CARD15 mutations with patients with LNH. The purpose of this study was to investigate the presence of NOD2/CARD15 mutations in patients with clinically proven LNH. METHODS: Children and young adults with gastrointestinal symptoms diagnosed as having terminal ileum LNH were eligible for the study. RESULTS: The study group consisted of 32 patients (15 males and 17 females), age range 3-23 years, mean 13.1 +/- 5 years. Twenty-seven (84%) had abdominal pain, 3 (9%) had rectal bleeding. The duration of symptoms ranged from 1-60 months (17.9 +/- 14.5). Only 2 patients (6.2%) were found to be heterozygote for the NOD2/CARD15 mutation (1007 fs), whereas all of the others did not carry any of the 3 common mutant alleles. This number is significantly lower (P < 0.001) than the mutation prevalence demonstrated in both pediatric and adult Israeli CD patients. CONCLUSIONS: NOD2/CARD15 mutations are not associated with LNH. This may strengthen the lack of association between CD and LNH that has been previously reported. We suggest that genotyping NOD2/CARD15 may help to distinguish LNH from inflammatory bowel diseases in selected patients.

Adolescent↗
PubMed2006

The safety of mineral oil in the treatment of constipation--a lesson from prolonged overdose.

There have been concerns regarding the interference in the absorption of fat-soluble vitamins in long-term treatment with mineral oil; however, there is no clear evidence in the literature to support this claim. We present a case report illustrating the effect of prolonged (5 months) large doses of mineral oil on the fat-soluble vitamin absorption in a 17-year-old girl.

Adolescent↗
PubMed2006

Persistent cough and failure to thrive: a presentation of foreign body aspiration in a child with asthma.

Severe failure to thrive (FTT) in a child with asthma and a persistent cough should not be explained solely by asthma and warrants a thorough and prompt evaluation. The finding of a foreign body in our case was surprising, because it does not usually present as or lead to FTT. Good clinical judgment and habits could prevent the course of events that we described in this case. Following are the key lessons to be learned from this presentation: (1) maintain a high index of suspicion for foreign body aspiration, even in toddlers with asthma, (2) pay special attention to a child with FTT, (3) be aware of localizing findings on physical examination and chest radiographs, and (4) perform a chest radiograph no later than after 1 month of chronic cough.

Asthma↗
PubMed2005

Crohn's disease and recurrent appendicitis: a case report.

The clinical diagnosis of classic Crohn's disease (CD) of the small bowel is based on a typical history, tender right lower quadrant fullness or mass, and characteristic radiographic findings of the terminal ileum. Appendicitis may as well present with chronic or recurrent symptoms and this presentation may be confused with CD. We herein describe the case of a young teenage girl with a presumptive diagnosis of CD, who was ultimately diagnosed as having chronic nongranulomatous appendicitis. The literature on the subject is reviewed.

Adolescent↗
PubMed2005

The surgical manifestations of the intestinal tract in Kawasaki disease.

Kawasaki disease (KD) is an inflammatory condition of unknown etiology. It involves mainly the skin, mucous membranes, lymph nodes, and myocardium. It may involve the gastrointestinal tract; however, it rarely presents as a surgical abdomen. We present a case of a young child with suspected small bowel obstruction who was subsequently diagnosed with KD. We review the surgical presentations of the intestinal tract in KD.

Female↗
PubMed2005

Neurological manifestations of an acute abdomen in children.

The acute abdomen in the pediatric age group is not infrequently fraught with diagnostic pitfalls. The younger the patient, the more problematic the presentation can be. Among the more unusual manifestations of an acute abdomen is an apparent encephalopathic picture. We present 2 cases which serve to illustrate the diagnostic difficulties encountered.

Abdomen, Acute↗
PubMed2005

A polymorphism in the TNF-alpha promoter gene is associated with pediatric onset and colonic location of Crohn's disease.

OBJECTIVES: Studies suggest that pediatric onset of Crohn's disease (CD) may demonstrate more frequent upper intestinal and colonic location and in male gender, in comparison to adults. Variability in age of onset (AOO) and location of disease have not been adequately explained to date. NOD2/CARD15 is highly expressed in the ileum, while TNF-alpha expression is distributed throughout the gastrointestinal tract. We hypothesized that polymorphisms that affect TNF-alpha function may influence variability of disease location and AOO of CD. METHODS: We evaluated two CD cohorts based on AOO (pediatric and adult onset) and 100 ethnically matched healthy controls. Patients were evaluated for AOO, disease location, and genotyped for the presence of polymorphisms in NOD2/CARD15 and in the TNF-alpha promoter region. RESULTS: Early AOO was associated with male gender, upper intestinal involvement, and a polymorphism in the binding site for NF-kappaB (TNF-863A polymorphism). NOD2 mutations and TNF-863A polymorphism had equivalent but opposite effects on disease location, with a strong combined effect (p= 0.004 corrected for multiple testing). NOD2/CARD15 was associated with ileal involvement, while presence of TNF-863A was inversely associated with ileal disease (OR = 0.42, p= 0.008) and positively associated with isolated colitis (OR = 2.16, p= 0.008, OR = 2.12, p= 0.03 corrected) and familial disease (p= 0.004). CONCLUSIONS: Pediatric onset of CD in our population was associated with a frequent polymorphism in the binding site for NF-kappaB in TNF-alpha promoter but not to defined NOD2/CARD15 disease-associated mutations. This polymorphism is associated with colitis and familial disease. NOD2/CARD15 mutations and the TNF-863C/A polymorphism have equivalent but opposite effects on disease location. These findings may help explain differences in CD phenotype.

Adult↗
PubMed2005

Lineage development in a patient without goblet, paneth, and enteroendocrine cells: a clue for intestinal epithelial differentiation.

We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. By using antibodies to protein markers of each cell line, including some that are expressed early in the differentiation process, we aimed to study lineage development in this patient. From our data, we surmise that there may be a two-step process in lineage commitment. The stem cell may commit to an absorptive cell or a granule-containing cell. The daughter cell that is committed to the granule lineage then further commits to a goblet, enteroendocrine, or Paneth cell lineage.

Adolescent↗
PubMed2005

[Mary Mallon, Mr. N and Mr. Koch as well].

Societal attitudes towards disease carriers is not ideal and is often associated with prejudice. This phenomenon was well documented in the era of Robert Koch who was one of the leading scientists claiming that disease carriers might cause epidemics. The authors recount the tale of two salmonella typhi carriers, Mr. N and Mary Mallon, who were responsible for transmitting typhoid. These cases highlight the problematic nature of the subject and the need for an enhanced medical and legal-social treatment model aimed at improving the status of disease carriers and limiting their impact on society.

Carrier State↗
PubMed2005

[The importance of nutrition in inflammatory bowel disease in children].

Many children with inflammatory bowel disease, mainly Crohn's disease, suffer from malnutrition and growth retardation. Maintenance of adequate nutrition is extremely important in the management of pediatric patients with Crohn's disease. This can usually be achieved by exclusive elemental formulae and polymeric formulae and rarely necessitates the use of parenteral nutrition. This review presents an update on the nutritional aspects of inflammatory bowel disease in children.

Child↗
PubMed2004

Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children.

BACKGROUND: The quantity and quality of mucins are affected in inflammatory bowel disease (IBD) both because of a reduction in the number of goblet cells and a decrease in the number of sugar residues per oligosaccharide side chain. Alteration in the types of mucins and aberrant location may contribute to the underlying pathology by affecting the mucus barrier function or may instead be a response to inflammation. The authors used the periodic acid-Schiff/Alcian blue stain to distinguish neutral and acidic mucins, and used specific antibodies to the mature goblet cell mucin MUC2, MUC2 core antigen, foveolar cell mucin MUC5AC, and gastric trefoil factor (TFF1), to characterize their presence and distribution in colonic tissue sections from patients with IBD. RESULTS: Both core and mature MUC2 were expressed in all colonic goblet cells from patients with ulcerative colitis (UC) and Crohn disease and from healthy controls. MUC5AC and TFF1, which are not normally expressed by colonic tissue, also were expressed in scattered goblet cells, coexpressing with MUC2. In areas of goblet cell depletion, MUC2 was present in cytoplasmic granules of flattened, cuboidal, nongoblet-cell-like surface cells. The staining was more intense and homogenous with the MUC2 core antibody, suggesting expression of relatively immature mucin. Some of these cells also coexpressed MUC5AC but to a lesser extent. These findings are not unique to IBD but were also found in other types of intestinal inflammation. CONCLUSION: The study confirms earlier observations that MUC2 is the major colonic mucin in IBD. It appears in two forms: mature MUC2 in goblet cells and immature MUC2 especially in secretory granules of cells that are not phenotypically goblet cells. MUC5AC and TFF1 expression in goblet cells is common in IBD and other inflammatory conditions of the colon. These changes may represent a nonspecific repair function of the colon cells to compensate for damage to barrier function.

Adolescent↗