Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families

In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535.     

Antioxidants protect against increased risk of atherosclerosis induced by exposure to cigarette smoke: Histological and biochemical study

Background and objectivesThis study aimed to assess the dose-dependent effect of antioxidants in protection against cardiovascular changes induced by exposure to cigarette smoke.Design and settingThis was an experimental study, conducted at King Fahd Medical Research Center, King Abdulaziz University.Materials and methodsThis study was carried out on 57 male albino rats divided into nine groups. Rats of experimental groups were exposed to cigarette smoke from a total of 100 cigarettes per week for four weeks in a specially designed chamber. The antioxidants used (vitamin C, E, and B-carotene) were administrated at low (9, 7.2, and 0.27 mg/day) and high doses (18, 14.4, and 0.54 mg/day), respectively, through gastric feeding tubes. The lipid profile was estimated, and the carotids and heart were removed, weighed, and then processed, and the carotid intima-media thickness was measured. Statistical analysis was performed using the Statistical Package for Social Sciences.ResultsThe lipid profile was significantly improved in all groups treated with low or high doses of antioxidants after or during the exposure to cigarette smoke. Improvement was marked in the group treated with a high dose of antioxidants.The histological changes, as well as the intima-medial thickness of the carotid artery induced by exposure to cigarette smoke, have been improved by treatment with antioxidants (at either low or high doses), either after or during exposure to cigarette smoke. Improvement was marked in the group treated with a low dose of antioxidant. Treatment with antioxidants could not improve degenerated cardiac muscle fibers, while they could reduce the thickness of the branches of the coronary vessels.ConclusionThese results indicated that antioxidants ameliorated the cigarette smoke contribution to atherosclerosis, but they could not completely reverse the changes induced by cigarette smoke. Simultaneous intake of antioxidants could ameliorate the cigarette-smoke-induced changes apart from those of the heart.     

1D2DSimScore: A novel method for comparing contacts in biomacromolecules and their complexes

The biologically relevant structures of proteins and nucleic acids and their complexes are dynamic. They include a combination of regions ranging from rigid structural segments to structural switches to regions that are almost always disordered, which interact with each other in various ways. Comparing conformational changes and variation in contacts between different conformational states is essential to understand the biological functions of proteins, nucleic acids, and their complexes. Here, we describe a new computational tool, 1D2DSimScore, for comparing contacts and contact interfaces in all kinds of macromolecules and macromolecular complexes, including proteins, nucleic acids, and other molecules. 1D2DSimScore can be used to compare structural features of macromolecular models between alternative structures obtained in a particular experiment or to score various predictions against a defined “ideal” reference structure. Comparisons at the level of contacts are particularly useful for flexible molecules, for which comparisons in 3D that require rigid-body superpositions are difficult, and in biological systems where the formation of specific inter-residue contacts is more relevant for the biological function than the maintenance of a specific global 3D structure. Similarity/dissimilarity scores calculated by 1D2DSimScore can be used to complement scores describing 3D structural similarity measures calculated by the existing tools.     

Xenoantisera to human DR antigens: Serological and immunochemical characterization

Antibodies to DR antigens were detected using serological and immunochemical tests in sera from rabbits and goats immunized with cultured human B-lymphoid cells mixed with an anti-T-cell xenoantiserum or with partially purified DR antigens. After absorption with human red blood cells, cultured melanoma cells, and/or T-lymphoid cells, DR xenoantisera become specifically cytotoxic to B lymphocytes. Three out of nine sera tested with a panel of T-depleted peripheral lymphocytes and chronic lymphocytic leukemia cells showed correlation with DR alloantisera submitted to the Seventh International Histocompatibility Workshop. Although the correlation coefficients were lower than those obtained with DR alloantisera, the results obtained suggest that DR xenoantisera may recognize allotypic specificities.     

Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit the growth of medullary thyroid carcinoma (MTC) cells in vitro. However, the mechanism of inhibition of MTC cell growth by indomethacin and its potency have yet to be revealed. We examined the effect of indomethacin on three different MTC cell lines (TT cells, DRO 81-1 cells and HRO 85-1 cells) and two non-MTC cells. The mechanism of indomethacin action in MTC cells was investigated by analyzing intracellular prostaglandin level, apoptosis, and cell cycle in TT cells. Indomethacin inhibited cell growth of all three MTC cell lines but not normal thyroid cells or anaplastic thyroid carcinoma cells. Indomethacin at 10 microM or greater showed a dose response inhibition of cell growth. Indomethacin at 25 muM, a putative therapeutic serum indomethacin level, showed potency similar to 100 to 200 nM sunitinib, a receptor tyrosine kinase inhibitor. To examine whether prostaglandin depletion might determine the inhibition of MTC cell growth, we created different prostaglandin E2 (PGE2) levels in TT cells using three different NSAIDs. A profound PGE2 depletion by indomethacin-ester, a potent cyclooxygenase (COX) II inhibitor, showed the least inhibition of cell growth. Indomethacin did not increase apoptosis of TT cells. Indomethacin, but not naproxen or indomethacin-ester, reduced cell cycle progression into S phase; this was unrelated to the degree of PGE2 depletion. The expression of phosphorylated retinoblastoma (pRb) protein that shifts cells from G(1) to S phase was reduced after exposure to indomethacin. In conclusion, indomethacin has specific anti-tumor effect on MTC cells, probably by reducing cell cycle progression into S phase rather than by prostaglandin depletion. Since no drug therapy is currently available for MTC, indomethacin may be one of the therapeutic candidates.     

Expression of ERBB gene family in females with breast cancer and its correlation with clinicopathological characteristics of the disease

Molecular Biology Reports - Breast cancer (BC) is the most prevalent and fatal cancer in women. Given that there are very few studies investigating the overexpression of four members of ERBB genes,...