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Biomedical subjects

B J Stone

Publications and source records attributed to B J Stone.

At least 19 recordsLinked to original sources
PubMed2004

CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women.

We examined CYP1A1 (I462V) and GSTM1 null polymorphisms in 200 female cases and 144 female controls selected from a population-based case-control study of lung cancer conducted in northeast China, where the rates of lung cancer among Chinese women are especially high. The CYP1A1 codon 462 point mutation in exon 7 (I462V) causes an Ile-Val substitution near the heme binding site. This mutation correlates with inducibility of aryl hydrocarbon hydrolase (AHH) activity, which activates polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke and in indoor air pollution from coal-burning stoves, a risk factor for lung cancer in this study population. We found that the CYP1A1 I462V genotype (combined ile/val and val/val) was significantly associated with lung cancer risk. The odds ratio (OR) was 2.5 (95% confidence interval [CI], 1.55-4.03) after adjustment for significant risk factors such as age, ever smoking status, family history of cancer, and eye irritation when cooking. The association was more pronounced among non-smokers (OR=3.67; 95% CI, 1.85-7.28) than among smokers (OR=1.74, 95% CI, 0.85-3.54). In contrast, we did not find a significant association with the GSTM1 null genotype. In summary, our case-control study of lung cancer among women in northeast China revealed an elevated risk associated with the CYP1A1 I462V genotype, but no interaction with smoking or indoor air pollution was found.

Air Pollution, Indoor↗
PubMed2000

Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-up.

Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m3-year was 0.21/(mg/m3-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure.

Adult↗
PubMed2000

Occupation and prostate cancer risk in Sweden.

To provide new leads regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit), general (2-digit), and specific (3-digit) industries and occupations, were calculated. Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations: farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess risk in these occupations and industries.

Agricultural Workers' Diseases↗
PubMed1999

The Legionella pneumophila prp locus; required during infection of macrophages and amoebae.

Transposon mutagenesis was performed using mTn 10phoA to identify Legionella pneumophila genes that are expressed under certain in vitro conditions, and are required for intracellular replication. Of the 1653 PhoA fusions examined, 19 PhoA(+)fusion mutants were isolated and screened for differential expression of fusion proteins after growth at 30 or 37 degrees C, in the presence of low iron, or increased magnesium concentrations. The mutants were examined for their cytopathogenicity and intracellular replication within U937 macrophage-like cells and the protozoan Hartmannella vermiformis. One of the mutants generated, BS10, was defective in its multiplication within U937 macrophage-like cells and H. vermiformis. The defect in BS10 was complemented with a cosmid clone containing the wild type locus. The open reading frame interrupted by the insertion was homologous to prpD of Salmonella typhimurium and mmgE of Bacillus subtilis.

Alkaline Phosphatase↗
PubMed1999

Natural competence for DNA transformation by Legionella pneumophila and its association with expression of type IV pili.

We have recently described the expression of two pili of different lengths on the surface of Legionella pneumophila (B. J. Stone and Y. Abu Kwaik, Infect. Immun. 66:1768-1775, 1998). Production of long pili requires a functional pilEL locus, encoding a type IV pilin protein. Since type IV pili in Neisseria gonorrhoeae are associated with competence for DNA transformation, we examined the competence of L. pneumophila for DNA transformation under conditions that allowed the expression of type IV pili. We show that L. pneumophila is naturally competent for DNA transformation by isogenic chromosomal DNA and by plasmid DNA containing L. pneumophila DNA. Many different L. pneumophila loci are able to transform L. pneumophila after addition of plasmid DNA, including gspA, ppa, asd, and pilEL. The transformation frequency is reduced when competing DNA containing either L. pneumophila DNA or vector sequences is added to the bacteria, suggesting that uptake-specific sequences may not be involved in DNA uptake. Competence for DNA transformation correlates with expression of the type IV pili, and a pilEL mutant defective in expression of type IV pili is not competent for DNA transformation. Complementation of the mutant for competence is restored by the reintroduction of a cosmid that restores production of type IV pili. Minimal competence is restored to the mutant by introduction of pilEL alone. We conclude that competence for DNA transformation in L. pneumophila is associated with expression of the type IV pilus and results in recombination of L. pneumophila DNA into the chromosome. Since expression of type IV pili also facilitates attachment of L. pneumophila to mammalian cells and protozoa, we designated the type IV pili CAP (for competence- and adherence-associated pili).

Bacterial Proteins↗
PubMed1998

Different fates of Legionella pneumophila pmi and mil mutants within macrophages and alveolar epithelial cells.

Alveolar epithelial cells, which constitute the majority of the alveolar surface, may represent a potential niche for intracellular replication of Legionella pneumophila that has been largely overlooked. We examined the phenotypes of a bank of 121 macrophage-defective mutants of L. pneumophila (designated as pmi and mil) for their cytopathogenicity to and intracellular survival and replication within human alveolar epithelial cells. Our data showed that 91 of 121 mutants that were defective (modest-severe) in macrophages exhibited wild type-like phenotypes in human type I alveolar epithelial cells. In contrast, the other 30 mutants were defective in both macrophages and alveolar epithelial cells. Transmission electron microscopy of the intracellular infection by three mutants showed that the defect in intracellular replication in macrophages and epithelial cells was associated with a defect in recruitment of the RER around the phagosome. Differences in attachment to macrophages and epithelial cells were also exhibited by some of the mutants. Pulmonary infection studies of A/J mice showed that a mutant defective in macrophages but not in alveolar epithelial cells replicated like the wild type strain in the lungs of A/J mice. In contrast, a mutant defective in both macrophages and alveolar epithelial cells failed to replicate and was killed. We conclude that certain distinct genetic loci of L. pneumophila are uniquely required for intracellular survival and replication within phagocytic but not epithelial cells, which may be important in vivo.

Animals↗
PubMed1998

The incidence of regurgitation during cardiopulmonary resuscitation: a comparison between the bag valve mask and laryngeal mask airway.

The risk of gastric regurgitation and subsequent pulmonary aspiration is a recognised complication of cardiac arrest--a risk which may be further increased by the resuscitative procedure itself. The purpose of this study was to compare the incidence of gastric regurgitation between the bag valve mask (BVM) and laryngeal mask airway (LMA). The resuscitation data collection forms of 996 patients who underwent in-hospital cardiopulmonary resuscitation over a 3.5 year period were reviewed. Of these, 199 patients were excluded from the study because there was no airway management involving a BVM or LMA. The incidence and timing of regurgitation was studied in the remaining 797 patients. Regurgitation was recorded to have occurred at some stage in 180 of these patients (22.6%). However, 84 regurgitated prior to CPR (46.7% of those patients who regurgitated). These patients were excluded from further analysis as regurgitation could not have been affected by any form of ventilation. Of the remaining 713 patients, BVM ventilation was used in 636 cases. In 170 of these the LMA was also used following the BVM. Where the patient was ventilated with the BVM alone or BVM followed by ETT the incidence of regurgitation during CPR was 12.4%. The LMA was used during resuscitation in 256 cases of which 170 had BVM ventilation prior to the LMA. Where the patient was ventilated with the LMA alone or LMA followed by ETT the incidence of regurgitation during CPR was 3.5%. The study confirms experience reported in earlier studies that when an LMA is used as a first line airway device, regurgitation is relatively uncommon.

Cardiopulmonary Resuscitation↗
PubMed1998

Expression of multiple pili by Legionella pneumophila: identification and characterization of a type IV pilin gene and its role in adherence to mammalian and protozoan cells.

Legionella pneumophila expresses pili of variable lengths, either long (0.8 to 1.5 microm) or short (0.1 to 0.6 microm), that can be observed by transmission electron microscopy. We have identified a gene in L. pneumophila with homology to the type IV pilin genes (pilEL). An insertion mutation was constructed in pilEL and introduced into the L. pneumophila wild-type strain by allelic exchange. The pilin mutant is defective for expression of long pili. Reintroduction of the pilin locus on a cosmid vector restores expression of the long pili. The L. pneumophila pilEL mutant exhibited approximately a 50% decrease in adherence to human epithelial cells (HeLa and WI-26 cells), macrophages (U937 cells), and Acanthamoeba polyphaga but had a wild-type phenotype for intracellular replication within these cells. Southern hybridization analysis showed that the pilEL locus is present in L. pneumophila serogroups 1 through 13 but is variable in 16 other Legionella species. The presence of a type IV pilin gene and its expression by L. pneumophila may provide an advantage for colonization of lung tissues during Legionnaires' disease and invasion of amoebas in the environment.

Amino Acid Sequence↗
PubMed1997

Transcriptional regulation of the macrophage-induced gene (gspA) of Legionella pneumophila and phenotypic characterization of a null mutant.

Expression of the global stress protein gene (gspA) is induced during the intracellular infection of macrophages and upon exposure of Legionella pneumophila to in vitro stress stimuli. Transcription of gspA is regulated by two promoters, one of which is regulated by the sigma 32 heat-shock transcription factor. We utilized a gspA promoter fusion to a promoter less lacZ to probe the phagososmal 'microenvironment' for the kinetics of exposure of intracellular L. pneumophila to stress stimuli. Expression through the gspA promoter was constitutively induced by approx. 16-fold throughout the intracellular infection, and occurred predominantly through the sigma 32-regulated promoter. Expression of the gspA promoter was induced approx. 4.5-fold, 5-, 11- and 9-fold upon exposure of L. pneumophila to heat shock, oxidative stress, acid shock, and osmotic shock, respectively. An isogenic insertion mutant of L. pneumophila in gspA (strain AA224) was constructed by allelic exchange in the wild-type strain AA200. Compared to in vitro-grown wild-type strain AA200, AA224 was more susceptible to all four in vitro stress stimuli. The wild-type phenotypes were restored to strain AA224 by complementation with a plasmid containing wild-type gspA. There was no difference between the wild-type strain and the gspA mutant in cytopathogenicity to U937 cells or in their kinetics of intracellular replication within macrophages and amoebae. However, compared to in vitro-grown bacteria, macrophage-grown and amoebae-grown AA200 and AA224 showed an equal and dramatic increase in resistance to in vitro stress stimuli. Our data showed that regardless of the capacity of L. pneumophila to subvert the microbicidal mechanisms of the macrophage, intracellular L. pneumophila is exposed to a high level of stress stimuli throughout the intracellular infection. Although the GspA protein is required for protection of the bacteria against in vitro stress stimuli, and is induced during intracellular multiplication, the loss of its function is probably compensated for by other macrophage-induced and stress-induced proteins within the intracellular environment.

Alleles↗
PubMed1996

Cancer risks among iron and steel workers in Anshan, China, Part I: Proportional mortality ratio analysis.

A standardized proportional mortality ratio (SPMR) study of 8,887 deaths during 1980-1989 among male workers in a large integrated iron-steel complex in Anshan, China, was conducted to provide clues to occupational risk factors. Accidents and cancer accounted for a higher proportion of deaths among the iron-steel workers than among the general male population (SPMR = 1.21; 95% CI = 1.12-1.31 and 1.14; 95% CI = 1.10-1.18, respectively). Among all workers, SPMRs were significantly elevated for stomach, lung, and colorectal cancers (SPMR = 1.37, 1.37, 1.38, respectively), but not other cancers. Risks of stomach cancer appeared to be highest among workers employed in jobs with exposure to iron and coal dust, whereas significant increases in colorectal cancer were seen for loading and other dusty jobs and for administrative and sedentary jobs without dust exposure. Risks of lung cancer appeared increased for a variety of jobs throughout the complex, especially those with probable high levels of exposure to polycyclic hydrocarbons and asbestos. Risk of esophageal cancer was significantly elevated for fire-resistant brick makers, and risk of nonmalignant respiratory disease was significantly elevated for those employed as furnace workers, foundry workers, and fire-resistant brick makers.

Accidents, Occupational↗
PubMed1996

Cancer risks among iron and steel workers in Anshan, China, Part II: Case-control studies of lung and stomach cancer.

Nested case-control interview studies of lung cancer (610 incident cases), stomach cancer (292 incident cases), and 959 controls were conducted to follow up leads from a proportional mortality analysis of deaths among male workers in a large integrated iron-steel complex in Anshan, China. For lung cancer, after adjusting for the significant non-occupational risk factors (smoking, other pulmonary disease, family history of lung cancer, and low consumption of fruit or tea), risks were significantly elevated for those employed for 15 or more years in smelting and rolling (OR = 1.5, CI = 1.1-2.2), in the fire-resistant brick factory (OR = 2.9, CI = 1.4-5.9), in general loading (OR = 2.5, CI = 1.0-6.1), and as coke oven workers (OR = 3.4; CI = 1.4-8.5). For stomach cancer, after adjusting for consumption of pickled vegetables, prior gastric diseases, family history of stomach cancer, low intake of fruits and vegetables, and education, risks were significantly elevated for those employed for 15 or more years in ore sintering and transportation (OR = 2.1, CI = 1.0-4.4), in the fire-resistant brick factory (OR = 2.5, CI = 1.1-5.8), in general loading (OR = 3.2, CI = 1.2-8.9), as boilerworkers and cooks (OR = 2.6, CI = 1.2-5.6), and as coke oven workers (OR = 5.4, CI = 1.8-16.0). For both lung and stomach cancers, significant dose-response gradients were observed for exposure to total dust and benzo(a)pyrene, but not for specific chemical components of dust. Overall, long-term steel workers with exposure to workplace pollutants had a 40% increased risk of both lung and stomach cancers. These case-control studies confirm many of the occupational findings reported in the proportionate mortality analysis, and suggest avenues for further work to evaluate the carcinogenicity of individual components of dust.

Adult↗
PubMed1996

Learning disabilities and learned helplessness: a heuristic approach.

This study investigated whether students with learning disabilities exhibited learned helpless behavior at a greater rate than their normal achieving peers when confronted with reading failure. Forty-five third grade students from a suburban elementary schools were participants in the study. Thirty of the subjects were classified as having a learning disability (LD) and the remaining 15 subjects were from regular education (RE) classrooms. Fifteen of the students with LD were placed in the treatment group and the remaining fifteen were placed in the control group. All the regular education students were placed in the treatment group. After randomly assigning the students with LD into either a treatment (stressed) group or a control (nonstressed) group, the stressed students were administered a reading instrument in order to measure how they dealt with failure. A one-way ANCOVA was conducted to determine whether significant differences existed between the groups based on their posttest scores. The results indicate that stressed students with LD have a significantly more difficult time recovering from stress than their regular education peers.

Child↗
PubMed1995

Recent cancer trends in the United States.

BACKGROUND: Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer. PURPOSE: We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns. METHODS: Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population. Similar rates were computed using national mortality data. Cancers were ranked according to the change in incidence rates over the two periods. RESULTS: Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due largely to rising rates for prostate cancer among men and for breast and lung cancers among women. National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining. Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non-Hodgkin's lymphoma, and melanoma among young and middle-aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons. CONCLUSIONS: Trends in cancer incidence and mortality differ. For most cancers, incidence rates are rising, while mortality rates are generally stable or declining. IMPLICATIONS: Much of the recent increase in cancer incidence can be explained by known factors. Improved detection appears to account for most of the increases in breast cancer among women and prostate cancer among men. On the other hand, cigarette smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non-Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified.

Age Distribution↗
PubMed1995

Esophageal cancer and occupation in a cohort of Swedish men.

Using the Cancer Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of esophageal cancer incidence by industry and occupation for men in Sweden. A general reduction in esophageal cancer incidence was found among agricultural and professional workers, whereas excess incidence was found among business, sales, and some craftsmen and production jobs. Elevated incidence was associated with several specific industries, including the food (SIR = 1.3, p < 0.05), beverage and tobacco (SIR = 1.8, p < 0.05) industries, vulcanizing shops within the rubber industry (SIR = 4.7, p < 0.01), and certain automotive building industries. Incidence also was increased among brewery workers (SIR = 4.2, p < 0.01) and butchers (SIR = 2.1, p < 0.01), and among individuals with certain service jobs, particularly waiters in the hotel and restaurant industry (SIR = 3.1, p < 0.01). Some of the occupational associations may be explained by lifestyle factors such as alcohol drinking and smoking, whereas others are specific and tend to support those of earlier investigations. This study adds to the evidence of a small but possibly important role of occupation in esophageal cancer etiology.

Adenocarcinoma↗
PubMed1995

Occupational risks for cutaneous melanoma among men in Sweden.

A population-based linked-registry was used to evaluate incidence of malignant melanoma of the skin among Swedish men by industry and occupation. There were 3850 cutaneous melanoma cases identified in the 19-year follow-up of men employed in 1960. New associations were observed for men employed in the breweries and malt-processing industry and in shoe fabrication from leather and skins. Several findings supported associations previously reported in other countries, including an excess risk among workers in basic chemical production and the printing industry and among professional, technical, and white-collar workers. Risk overall was not increased among farmers, despite a significant excess of melanoma of the face, neck, and scalp. Although this linked registry analysis lacked information about specific agents, duration of employment, and occupational and recreational sun exposures, it did provide leads for new associations and confirmed previous ones. Nevertheless, because of these limitations, etiologic clues must be interpreted cautiously.

Adolescent↗
PubMed1995

Salmonella enteritidis has a homologue of tolC that is required for virulence in BALB/c mice.

The ability of Salmonella to invade tissue culture cells is correlated with virulence. Therefore, the tissue culture invasion model has been used extensively to study this process and to identify the bacterial genes involved and their products. Described here is the further characterization of a Salmonella enteritidis mutant (SM6T) originally identified as a non-invasive for tissue culture cells. A chromosomal DNA fragment complementing this defect was cloned and sequenced. The derived protein sequence is 89% identical to TolC from Escherichia coli, an outer membrane protein required for the signal peptide-independent transport of alpha-haemolysin and colicin V. Therefore, sinA was renamed tolC and is referred to in this text as tolCs to distinguish it from tolC of E. coli. TolCs and TolC are functionally similar since tolC can complement the invasion-defective phenotype of a tolCs mutant, and tolCs is required for export of alpha-haemolysin by Salmonella. The tolCs mutant is avirulent for mice when administered by the oral route, suggesting that the gene is important for virulence. Further characterization of the tolCs mutant indicated that like tolC mutants it is more sensitive than the wild-type strain to various detergents, antibiotics and dyes. This mutant is more sensitive to Triton X-100 only when associated with the monolayer, and the invasion-defective phenotype appears to be artifact of this sensitivity. In addition, the tolCs mutant is more sensitive to the bactericidal activity of human serum. Therefore, the avirulent phenotype could be the result of an inability to secrete a necessary virulence factor, or an increased sensitivity to complement and detergents as a result of a subtle alteration in the lipopolysaccharide (LPS) associated with tolC mutations.

Amino Acid Sequence↗
PubMed1994

Occupation and stomach cancer in a cohort of Swedish men.

Using the Cancer-Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of stomach cancer incidence by industry and occupation for men in Sweden. Nearly 17,000 stomach cancer cases were diagnosed during the 19 years of follow-up. Stomach cancer incidence was elevated among miners and quarrymen, farmers and fishermen, and craftsmen and production workers. Men who held white collar jobs, including professional and technical, administrative and management, clerical, and sales jobs, had a reduction in stomach cancer incidence. Examination of specific jobs revealed generally elevated rates of stomach cancer among men who may be exposed to dusty work environments, such as quarry workers, stone cutters, circular and plane operators, construction workers, crane operators, heavy laborers, and shop and construction metal workers. These occupational associations mostly were observed for stomach cancers of noncardia origin, and no significant associations were found with cardia cancers. We had no information on dietary or other potential confounding factors and cannot make inferences about the role of occupation per se, but the current findings support those of earlier investigations and add to the evidence of a small but significant occupational role in stomach carcinogenesis.

Dust↗