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Biomedical subjects

S Rolland

Publications and source records attributed to S Rolland.

10 recordsLinked to original sources
PubMed2004

Eosinophilic esophagitis in children: symptoms, histology and pH probe results.

AIM: To review the authors' experience with eosinophilic esophagitis. METHODS: Between 1993 and 2001, the authors identified 12 patients with eosinophilic esophagitis defined on histologic criteria (> or = 20 eosinophils per high-power field in the distal esophageal epithelium). The authors reviewed medical records for details of clinical presentation; laboratory data; radiologic, endoscopic, and histologic findings; and the results of continuous esophageal pH probe monitoring. RESULTS: Seventy-five percent of the patients were male. The median age at presentation was 10.8 years (range, 1-17 years). Commonly reported symptoms were dysphagia with solid food (66%), epigastric pain (42%), food impaction (50%), and vomiting (8%). Food allergy was reported in 50% and asthma in 33%. Peripheral eosinophilia (> 700/mm3) was found in 42%. Upper gastrointestinal series performed in eight patients, showed esophageal luminal narrowing in three. Computed tomography, performed in two patients, revealed thickening of the esophageal wall. Esophageal pH probe monitoring, performed in nine patients, revealed no abnormal acid reflux. All of the monitored patients had episodic alkalinization of the esophagus. Upper endoscopic analysis revealed white specks on the esophageal mucosa in 42%, esophageal narrowing in 33%, esophageal rings in 25%, and esophageal furrowing in 8%. The mean eosinophils per high-power field was 65 (range, 20-200). Histologic characteristics included juxtaluminar (33%) and peripapillary clusters of eosinophils (33%), increased papillary height (50%), and basal cell hyperplasia (34%). CONCLUSION: Solid food dysphagia was the most common feature of eosinophilic esophagitis in our patients. Alkalinization of the esophagus was found in all nine pH probe recordings of eosinophilic esophagitis patients and may represent a previously unreported characteristic of the condition.

Adolescent↗
PubMed2001

Extensive characterization of genetic alterations in a series of human colorectal cancer cell lines.

A number of genetic alterations have been described in colorectal cancers. They include allelic losses on specific chromosomal arms, mutations of oncogenes, tumor suppressor genes and mismatch repair genes, microsatellite instability in coding repeat sequences of target genes and methylation defects in gene promoters. Since these alterations have been reported by different groups on different tumors and cell lines, the complete repertoire of genetic alterations for any given tumor sample remains unknown. In the present study, we analysed a series of 22 colorectal cancer cell lines for 31 different genetic alterations. We found significant correlations between mutational profiles in these colorectal cell lines associated with differences in mismatch repair status. This panel of colon cancer cell lines is representative of the genetic heterogeneity occurring in sporadic colorectal carcinoma. Our results may prove to be very useful for understanding the different biological pathways involved in the development of colon cancer, and for groups studying cellular biology and pharmacology on the same cell lines.

Base Pair Mismatch↗
PubMed2001

Evolution of instability at coding and non-coding repeat sequences in human MSI-H colorectal cancers.

A number of human genes containing coding mononucleotide repeat sequences are particularly prone to mutations in tumors with defects in mismatch repair (MMR) genes (MSI-H cancers). In a large series of MSI-H colorectal tumors, we looked for mutations in 25 coding repeats contained in eight genes already known to be mutated in these cancers or in 17 other genes with an expected role in carcinogenesis. Mutations were found in 19 of the 25 candidate genes. Using a maximum likelihood statistical method, they were separated into two different groups that differed significantly in their mutation frequencies, and were likely to represent mutations that do or do not provide selective pressures during MSI-H tumoral progression, respectively. Three new target genes were found (GRB-14, RHAMM, RAD50). Our results provide evidence that MSI-H tumoral progression involves the cumulative mutations of a large number of genes. For each MSI-H tumor we calculated indexes representing the number of mutations found in genes of these groups. We also evaluated a shortening index at both the Bat-25 and Bat-26 non-coding mononucleotide tracts that are known to be almost always unstable in MSI-H cancers. A significant correlation was observed between instability at both coding and non-coding repeats, suggesting that Bat-25 and Bat-26 could be used as simple phenotypical markers of the tumoral evolution. A preferential order of mutations was deduced. During this process, hMSH3 alterations, a target gene encoding for a MMR protein, was found to play an important role by increasing the instability phenomenon characterizing these cancers.

Base Pair Mismatch↗
PubMed2000

The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.

The human T cell transcription factor-4 (hTCF-4) interacts functionally with beta-catenin in the Wnt signaling pathway, which regulates many developmental processes. Moreover, inappropriate reactivation of this pathway attributable to APC or beta-catenin mutations has been described in colorectal cancers. Because only the human TCF-4 cDNA sequence was known, we determined its genomic structure. A total of 17 exons, of which 5 were alternative, were identified. Moreover, four alternative splice sites were observed either experimentally or in silico by a BLAST approach in expressed sequence tag databases. The alternative use of three consecutive exons localized in the 3' part of the hTCF-4 gene changes the reading frames used in the last exon, leading to the synthesis of a number of hTCF-4 isoforms with short, medium, or long-size COOH-terminal ends. We next screened the entire hTCF-4 gene for mutations in a series of 24 colorectal cancer cell lines by denaturing gradient gel electrophoresis and/or direct sequencing. Besides an already described deletion of an A in an (A)9 coding repeat in four cases, we found DNA variants in eight cases for a total of 12 variants, of which 8 were coding. These include one frameshift mutation in the beta-catenin binding domain (exon 1), and one missense mutation in exon 4. In the remaining six cases, nonsense or frameshift mutations were localized in the 3' part of the gene. These latter alterations have as a common consequence to decrease the proportion of the long COOH-terminal hTCF-4 isoform, which contains two binding domains for c-terminal binding protein, a protein implicated in the repression of the TCF family transcriptional activity. Thus, loss of the TCF-4 capacity to interact with COOH-terminal binding protein could be an important event during colorectal carcinogenesis by modifying Wnt signaling.

Alternative Splicing↗
PubMed1998

Adjacent cooperation of proteins on DNA are not representative of long-distance interactions.

The cI repressor of bacteriophage lambda is better-fitted to the proximal interactions in which it naturally takes part than to the long-distance cooperative interactions on DNA for which it has become representative. The first observation in support of this statement is the ambiguity of an untypical DNAase I footprint which has become a diagnostic for DNA circularisation (and thus for the capacity of the protein to control expression at a distance). However, it was also observed without effective DNA looping when lac repressor binds to nearly contiguous sites. Additionally, the surface of interaction between the two dimers seems to be more important than the one commonly admitted (via some contacts between the flexible arms), the biological function of the repressor is lost when the sites are separated and loops have not been observed for large separation of the sites. In fact, naturally distant interactions can conform to shorter distances, as an intrinsic property of DNA looping. On the contrary, interactions which are naturally optimised for contiguity are generally constrained to proximity. Alternative protein-protein contacts are generally responsible for this situation (cf. CRP versus NRI in Escherichia coli).

Bacteriophage lambda↗
PubMed1998

Wernicke-Korsakoff syndrome in Sydney hospitals after 6 years of thiamin enrichment of bread.

OBJECTIVES: To estimate the incidence of Wernicke's encephalopathy (WE) and Korsakoff's psychosis (KP) before and after the introduction of thiamin enrichment of bread in Australia. DESIGN AND SUBJECTS: Inpatient records were examined in 17 major public general hospitals in greater Sydney for the 4 years 1993-96 (inclusive) with the International Classification of Diseases (ICD) 9 diagnoses 265.1 (WE), 291.1 and 294.0 (KP). Relevant clinical data were recorded on a specially designed form so that cases could be classified as confirmed or probable WE, confirmed or probable KP, confirmed or probable Wernicke-Korsakoff syndrome (WE + KP) or not WE or KP. The average number of cases of WE + KP was 38 acute (new) cases and 69 total (acute + chronic) cases per annum for all the hospitals combined. RESULTS: This study used the same methods as our earlier retrospective examination of Wernicke-Korsakoff cases in essentially the same hospitals for 1978-93. Records for 1993 were thus pulled twice and, while individual cases (using hospital index number) did not always coincide, the total numbers for 1993 were 69 and 70. For the 5 years after 1991 the number of acute cases of WE and KP in Sydney hospitals was 61% of the number for the 5 years before 1991 (P<0.01). There is, however, no continuing downward trend. CONCLUSIONS: These results are consistent with a 40% reduction of the incidence of acute WE and KP since bread has been enriched with thiamin. The disease complex has, however, not been eliminated. To achieve this, further public health action would be needed, such as addition of thiamin to beer.

Bread↗