Cancer in Italian migrant populations. The United States of America.
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Biomedical subjects
Publications and source records attributed to P Reynolds.
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The three macrolide-resistance-encoding genes, tlrC from Streptomyces fradiae, srmB from Streptomyces ambofaciens, and carA from Streptomyces thermotolerans, encode proteins that possess significant sequence similarity to ATP-dependent transport proteins. The N-terminal and C-terminal halves of these proteins are very similar to each other and contain highly conserved regions that resemble ATP-binding domains typically present within the superfamily of ATP-dependent transport proteins. These observations suggest that the mechanism by which these genes confer resistance to macrolides is due to export of the antibiotics, a process that is driven by energy derived from ATP hydrolysis.
Developmental defects of enamel were assessed in 15-year-old children born and continuously resident in three communities in the north east of England. In naturally fluoridated Hartlepool (F = 1.0-1.3 ppm), artificially fluoridated Newcastle (F = 1.0 ppm) and non-fluoridated Middlesbrough (F < 0.2 ppm) 361, 356 and 376 children respectively were examined. Conventional clinical recording and a photographic technique where colour slides are assessed at random were used and compared. Scoring in both assessments was done by using a modified version of both the Murray and Shaw index and the developmental defects of enamel index. In the clinical assessment more white lines and diffuse opacities were found in the fluoridated areas than in the non-fluoridated area. More opacities were recorded using the photographic assessment than with the clinical assessment, but a similar trend of an increased prevalence of white lines and diffuse opacities was observed using the photographic method. Overall, there was only a small increase in the prevalence of milder forms of enamel defects in fluoridated compared with non-fluoridated areas.
The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme (E2) that is required for DNA repair, damage-induced mutagenesis, and sporulation. We have cloned the two human RAD6 homologs, designated HHR6A and HHR6B. The two 152-amino acid human proteins share 95% sequence identity with each other and approximately 70% and approximately 85% overall identity with the homologs from yeasts (S. cerevisiae and Schizosaccharomyces pombe) and Drosophila melanogaster, respectively. Neither of the human RAD6 homologs possess the acidic C-terminal sequence present in the S. cerevisiae RAD6 protein. Genetic complementation experiments reveal that HHR6A as well as HHR6B can carry out the DNA repair and mutagenesis functions of RAD6 in S. cerevisiae rad6 delta mutants.
The RAD6 gene of the yeast Saccharomyces cerevisiae is required for DNA repair, for DNA damage-induced mutagenesis, and for sporulation, and it encodes a ubiquitin-conjugating enzyme. We have cloned the RAD6 homolog from Drosophila melanogaster and find that its encoded protein displays a very high degree of identity in amino acid sequence with the homologous RAD6 proteins from the two divergent yeasts, S. cerevisiae and Schizosaccharomyces pombe, and from human. Genetic complementation studies indicate that the Drosophila RAD6 homolog can functionally substitute for the S. cerevisiae RAD6 gene in its DNA-repair and UV-mutagenesis functions but cannot substitute in sporulation. The high degree of structural and functional conservation of RAD6 in eukaryotic evolution suggests that the various protein components involved in RAD6-dependent DNA repair and mutagenesis functions have also been conserved.
The contribution of circulating anti-La(SS-B) antibody to the hypergammaglobulinaemia seen in primary Sjögren's syndrome is unknown. In this study levels of anti-La(SS-B) antibody directed against three immunodominant epitopes of the anti-La(SS-B) autoantigen were measured by ELISA in 84 anti-La(SS-B)+ sera using purified recombinant protein and antibody affinity-purified against the three anti-La(SS-B) fusion proteins. There was marked variation in the amounts of IgG anti-La(SS-B) antibody detected, with levels ranging from 0.02 mg/ml to 11 mg/ml. The anti-La(SS-B) levels were greater than 1 mg/ml in 61% of patients; in 18% of sera the anti-La(SS-B) level constituted 10% or more of the total serum IgG. However, other patients were seen with marked hypergammaglobulinaemia and low anti-La(SS-B) concentrations. These results support an antigen-driven mechanism for the anti-La(SS-B) response and suggest that anti-La(SS-B) antibody production is regulated independently of other immunoglobulins.
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The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin conjugating enzyme and is required for DNA repair, DNA-damage-induced mutagenesis and sporulation. Here, we show that RAD6 and the rhp6+ gene from the distantly related yeast Schizosaccharomyces pombe share a high degree of structural and functional homology. The predominantly acidic carboxyl-terminal 21 amino acids present in the RAD6 protein are absent in the rhp6(+)-encoded protein; otherwise, the two proteins are very similar, with 77% identical residues. Like rad6, null mutations of the rhp6+ gene confer a defect in DNA repair, UV mutagenesis and sporulation, and the RAD6 and rhp6+ genes can functionally substitute for one another. These observations suggest that functional interactions between RAD6 (rhp6+) protein and other components of the DNA repair complex have been conserved among eukaryotes.
Zezuru adults and children take into account concepts of evil in directing their lives, especially in managing incidents of trauma and sickness. Using the story The Turn of the Screw by Henry James to reflect on these notions, evil is traced in the expressions heard and treatment sessions witnessed during two years research with 60 traditional healers in Mashonaland, Zimbabwe. Evil, particularly as evidenced in witchcraft and possession by aggrieved spirits, is part of a discourse on human suffering--illness, misfortune, death--within a specific community. Healers' treatment of children and their conceptions of childhood form the base for a discussion of evil.
The association between social connections and cancer incidence, mortality, and prognosis during 17 years of follow-up was examined in a population-based sample of 6,848 adults who lived in Alameda County, California, in 1965. Estimates of relative hazards were derived from Cox regression modeling, adjusting for age, smoking, physical health at baseline, alcohol consumption, and adjusted household income. Women who were socially isolated were at significantly elevated risk of dying of cancer of all sites and of smoking-related cancers. Social connections were not prospectively associated with cancer incidence or mortality among men, but men with few social connections showed significantly poorer cancer survival rates. These patterns of risk are consistent with the biology of different cancer outcomes. They also suggest a different role for social isolation in cancer among men and women.
A preliminary comparison of the reported incidence of Kaposi's sarcoma among males under 60 years of age residing in San Francisco was conducted using merged San Francisco AIDS Registry and California Tumor Registry (CTR) data. For the years 1980-1986, the number of cases reported by both registries was similar. However, only 961 (72.3%) of the 1,330 cases appearing in either registry appeared in both. Of the 160 Kaposi's sarcoma cases in the AIDS registry only, 11 (6.9%) were included in the CTR with another cancer diagnosis. Of the 209 Kaposi's sarcoma cases occurring only in the CTR, 109 (52.2%) were included in the AIDS registry with another diagnosis. The number of cases included in either or both registries was about 20% more than in either alone. Data sharing between the staff of these registries is precluded by confidentiality constraints.
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Tear gas has gained widespread acceptance as a means of controlling civilian crowds and subduing barricaded criminals. The most widely used forms of tear gas have been o-chlorobenzylidenemalononitrile and omega-chloroacetophenone. Proponents of their use claim that, if used correctly, the noxious effects of exposure are transient and of no long-term consequences. The use of tear gas in recent situations of civil unrest, however, demonstrates that exposure to the weapon is difficult to control and indiscriminate, and the weapon is often not used correctly. Severe traumatic injury from exploding tear gas bombs as well as lethal toxic injury have been documented. Moreover, available toxicological data are deficient as to the potential of tear gas agents to cause long-term pulmonary, carcinogenic, and reproductive effects. Published and recent unpublished in vitro tests have shown o-chlorobenzylidenemalononitrile to be both clastogenic and mutagenic. Sadly, the nature of its use renders analytic epidemiologic investigation of exposed persons difficult. In 1969, eighty countries voted to include tear gas agents among chemical weapons banned under the Geneva Protocol. There is an ongoing need for investigation into the full toxicological potential of tear gas chemicals and renewed debate on whether their use can be condoned under any circumstances.
To assess left ventricular (LV) diastolic filling in children with pressure overload hypertrophy, 12 patients with LV outflow obstruction (7 with aortic valve stenosis and 5 with aortic coarctation) and 12 healthy, age-matched control subjects were examined. Each child underwent M-mode echocardiography and pulsed Doppler examination of the LV inflow. The patients with LV outflow obstruction had cardiac catheterization and balloon angioplasty. Their echo/Doppler examinations were performed in the catheterization laboratory before and immediately after balloon angioplasty. From the M-mode echocardiogram, the LV cavity dimensions and wall thicknesses, LV mass and shortening fraction were measured. The following measurements were made from the Doppler recording: peak velocities at rapid ventricular filling (peak E) and during atrial contraction (peak A), ratio of peak E to peak A velocities, total area under the Doppler curve, percent of the total Doppler area occurring in the first one-third of diastole (0.33 area fraction), percent of the total area occurring under the E wave (E area fraction), percent of the total area occurring under the A wave (A area fraction) and the ratio of E area to A area.(ABSTRACT TRUNCATED AT 250 WORDS)
We report that the genes for the homologous Saccharomyces cerevisiae RAD10 and human ERCC-1 DNA excision repair proteins harbor overlapping antisense transcription units in their 3' regions. Since naturally occurring antisense transcription is rare in S. cerevisiae and humans (this is the first example in human cells), our findings indicate that antisense transcription in the ERCC-1-RAD10 gene regions represents an evolutionarily conserved feature.
Procaryotic and eucaryotic cells possess mechanisms for arresting cell division in response to DNA damage. Eucaryotic cells arrest division in the G2 stage of the cell cycle, and various observations suggest that this arrest is necessary to ensure the completion of repair of damaged DNA before the entry of cells into mitosis. Here, we provide evidence that the Saccharomyces cerevisiae RAD9 gene, mutations of which confer sensitivity to DNA-damaging agents, is necessary for the cell cycle arrest phenomenon. Our studies with the rad9 delta mutation show that RAD9 plays a role in the cell cycle arrest of methyl methanesulfonate-treated cells and is absolutely required for the cell cycle arrest in the temperature-sensitive cdc9 mutant, which is defective in DNA ligase. At the restrictive temperature, cell cycle progression of cdc9 cells is blocked sometime after the DNA chain elongation step, whereas cdc9 rad9 delta cells do not arrest at this point and undergo one or two additional divisions. Upon transfer from the restrictive to the permissive temperature, a larger proportion of the cdc9 cells than of the cdc9 rad9 delta cells forms viable colonies, indicating that RAD9-mediated cell cycle arrest allows for proper ligation of DNA breaks before the entry of cells into mitosis. The rad9 delta mutation does not affect the frequency of spontaneous or UV-induced mutation and recombination, suggesting that RAD9 is not directly involved in mutagenic or recombinational repair processes. The RAD9 gene encodes a transcript of approximately 4.2 kilobases and a protein of 1,309 amino acids of Mr 148,412. We suggest that RAD9 may be involved in regulating the expression of genes required for the transition from G2 to mitosis.
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