p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.     

Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice

Deafness is the most common form of sensory impairment in humans. Mutations in unconventional myosins have been found to cause deafness in humans and mice. The mouse recessive deafness mutation, Snell's waltzer, contains an intragenic deletion in an unconventional myosin, myosin VI (locus designation, Myo6). The requirement for Myo6 for proper hearing in mice makes this gene an excellent candidate for a human deafness disorder. Here we report the cloning and characterization of the human unconventional myosin VI (locus designation, MYO6) cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human gene makes it now possible to determine if mutations in MYO6 contribute to the pathogenesis of deafness in the human population.     

Effect of mechanical treatment on healing after third molar extraction

The aim of this study was to determine the effect of subgingival scaling and root planing on healing of the distal surface of second molars following extraction of third molars. Twenty-eight patients with contralateral erupted third molars and pocket depths greater than or equal to 3 mm on the distal surface of the second molars participated in this study. Measurements of supragingival bacterial plaque, bleeding on probing, pocket depth, and relative attachment level were performed at baseline and 2 months after treatment. Extraction of contralateral third molars was carried out simultaneously. The experimental site received thorough scaling and root planing of the distal surface of the second molar, while the control site received extraction alone. Experimental sites showed significant improvement in all clinical parameters assessed compared to the control sites. In conclusion, periodontal lesions on the distal of second molars can be significantly improved following scaling and root planing after extraction of third molars.     

Study of sialated neoglycoconjugates by surface enhanced Raman scattering spectroscopy

Neoglycoconjugates based on polyacrylamide and sialic acid with N-acetylneuraminic acid or sialooligosaccharides as side chains were studied by surface-enhanced Raman scattering (SERS) spectroscopy. It had previously been found that these polymers can effectively inhibit influenza virus adhesion. This study revealed the possibility to evaluate, based on the intensity of SERS signals, the overall availability for interaction and the conformational freedom of sialic acid residues in glycoconjugates. The dependence of these two factors on the structure and density of sialylated side chains was studied. The uniformity of distribution of sialylated side chains in conjugates was shown. Comparison of the results of the SERS spectroscopic study of the conjugates and the data on their inhibitory effect on the adhesion of specific strains of influenza virus allowed the identification of the conjugates for which the availability and conformational freedom of sialic acid are the main factors determining their inhibitory properties. A conclusion was also reached about the predominance of one of the mechanisms (competitive inhibition or steric stabilization) in the inhibitory properties of the specific conjugates.     

The value of the Parenting Scale for measuring the discipline practices of parents of middle school children

The psychometric properties of the Parenting Scale (Arnold, O'Leary, Wolff, and Acker, 1993), a 30-item instrument originally developed to assess the discipline practices of parents of preschool children, were examined for parents of middle school students. Subjects were 298 parents of middle school student identified as at-risk for problem behavior. An exploratory factor analysis identified two factors labeled 'Overreactivity' and 'Laxness', closely resembling two of the factors found by Arnold et al., but each of these factors contained only six items. Confirmatory factor analyses, using data from the first two assessments, replicated this factor structure. The factors were significantly correlated with measures of parents' behavior, with scales from the child Behavior Checklist and Parent Daily Reports, and with the Beck Depression Inventory. The Laxness factor was less robust than the Overreactivity factor.     

An antagonist for the leukemia inhibitory factor receptor inhibits leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, and oncostatin M

The leukemia inhibitory factor receptor (LIF-R) is activated not only by LIF, but also by cardiotrophin-1, ciliary neurotrophic factor with its receptor, and oncostatin M (OSM). Each of these cytokines induces the hetero-oligomerization of LIF-R with gp130, a signal-transducing subunit shared with interleukin-6 and interleukin-11. The introduction of mutations into human LIF that reduced the affinity for gp130 while retaining affinity for LIF-R has generated antagonists for LIF. In the current study, a LIF antagonist that was free of detectable agonistic activity was tested for antagonism against the family of LIF-R ligands. On cells that express LIF-R and gp130, all LIF-R ligands were antagonized. On cells that also express OSM receptor, OSM was not antagonized, demonstrating that the antagonist is specific for LIF-R. Ligand-triggered tyrosine phosphorylation of both LIF-R and gp130 was blocked by the antagonist. The antagonist is therefore likely to work by preventing receptor oligomerization.