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Biomedical subjects

Y Mao

Publications and source records attributed to Y Mao.

At least 253 records · Page 14Linked to original sources

Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides.

Animals↗

DNA binding to crystalline silica characterized by Fourier-transform infrared spectroscopy.

The interaction of DNA with crystalline silica in buffered aqueous solutions at physiologic pH has been investigated by Fourier-transform infrared spectroscopy (FT-IR). In aqueous buffer, significant changes occur in the spectra of DNA and silica upon coincubation, suggesting that a DNA-silica complex forms as silica interacts with DNA. As compared to the spectrum of silica alone, the changes in the FT-IR spectrum of silica in the DNA-silica complex are consistent with an Si-O bond perturbation on the surface of the silica crystal. DNA remains in a B-form conformation in the DNA-silica complex. The most prominent changes in the DNA spectrum occur in the 1225 to 1000 cm-1 region. Upon binding, the PO2- asymmetric stretch at 1225 cm-1 is increased in intensity and slightly shifted to lower frequencies; the PO2- symmetric stretch at 1086 cm-1 is markedly increased in intensity and the band at 1053 cm-1, representing either the phosphodiester or the C-O stretch of DNA backbone, is significantly reduced in intensity. In D2O buffer, the DNA spectrum reveals a marked increase in intensity of the peak at 1086 cm-1 and a progressive decrease in intensity of the peak at 1053 cm-1 when DNA is exposed to increasing concentrations of silica. The carbonyl band at 1688 cm-1 diminishes and shifts to slightly lower frequencies with increasing concentrations of silica. The present study demonstrates that crystalline silica binds to the phosphate-sugar backbone of DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Non-Hodgkin's lymphoma and agricultural practices in the prairie provinces of Canada.

OBJECTIVES: The aim of this study was to provide an update of a cohort study (1971-1985) that previously reported a significant trend in the risk of non-Hodgkin's lymphoma among male Saskatchewan farm operators according to fuel-oil expenditures and herbicide spraying for farms less than 1000 acres (2570 hectares) by including two additional Canadian prairie provinces, two additional years of follow-up, and data from the 1981 Census of Agriculture. METHODS: Information on farmers from 1971 records of the Census of Agriculture was linked to 1971 records of the Census of Population, to 1981 records of the Census of Agriculture, and to death records. Poisson regression was used to estimate risks according to herbicide spraying and fuel and oil expenditures. RESULTS: The addition of a further two years of follow-up resulted in lower risk estimates associated with herbicide spraying for Saskatchewan. No excess risk was observed between herbicide spraying and non-Hodgkin's lymphoma for Alberta or Manitoba in the 1971 data. However, a significantly increased risk of non-Hodgkin's lymphoma according to acres sprayed with herbicides was observed for the three provinces combined when the herbicide spraying data from the 1981 Census of Agriculture was used [> or = 380 acres (> or = 939 hectares) sprayed, rate ratio 2.11, 95% confidence interval 1.1-3.9]. CONCLUSIONS: Although the current results are not entirely consistent with the original Saskatchewan analysis, they support the overall finding of an association between herbicides and risk of fatal non-Hodgkins lymphoma. Prospective cohort studies are needed to overcome the limitations of existing epidemiologic studies.

Adult↗

[A genetic study of adult polycystic kidney disease].

The 3'HVR has been considered as the most useful probe in making the linkage analysis of adult polycystic kidney disease (APKD). We examined three APKD families using this probe. Their polymorphism information was then computed for linkage study using LINKAGE package and computer programme HOMOG for homogeneity test. One family was defined as non PKD 1, because the disease locus was failed to show linkage to the 3'HVR marker. Of the other two families, one can still not be identified as non PKD1, but had distinguishable meiotic recombinations, another was in favour of linkage to 3'HVR and therefore judged to be PKD1. The presence of genetic heterogeneity could significantly reduce the value of linked probe analysis as a tool for gene diagnosis of APKD.

Adolescent↗

Retinoic acid regulates ornithine decarboxylase gene expression at the transcriptional level.

Retinoic acid (RA) is important for normal mammalian development and growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the biosynthesis of the polyamines, and we have previously shown that ODC mRNA levels are suppressed by RA in human skin cells. Using HeLa cells, we now show that treatment with 0.5 microM RA for 24 h suppresses endogenous ODC mRNA levels and the expression of a transfected ODC/chloramphenicol acetyltransferase plasmid (Kpn-ODCCAT), containing sequences from -1450 to +810 of the human ODC gene. Co-transfection with either the alpha-RA receptor (alpha-RAR) or a chimeric alpha-RA/oestrogen receptor (alpha-RAER) followed by treatment with the cognate hormone suppresses expression of Kpn-ODCCAT and Not-ODCCAT, which contains sequences from -250 to +514. Liganded alpha-RAR suppresses the activity of Kpn-ODCCAT more markedly than does liganded alpha-RAER (98% and 80% suppression, respectively), whereas both receptors have very similar effects on Not-ODCCAT expression (73% and 67% suppression, respectively). The unliganded alpha-RAR suppresses Kpn-ODCCAT by 76%, whereas unliganded alpha-RAER has no significant effect. These data show that RA regulates ODC-gene expression at the transcriptional level, and that alpha-RAR, but not alpha-RAER, can confer full hormonal responsiveness. This suggests that the activating function present in the alpha-RAR ligand-binding domain is required for full transcriptional regulation.

Animals↗

Prostate cancer trends in Canada: rising incidence or increased detection?

OBJECTIVES: To analyse trends in the incidence and mortality rates of prostate cancer in Canada according to age distribution, temporal pattern and provincial variation; to determine any association with the rate of prostatectomy; and to determine whether any observed increase in the rate of prostate cancer was due to an increase in the detection rate. DESIGN: Descriptive epidemiologic study based on Canadian population data from 1959 to 1989 and chart review from one Canadian hospital. SETTING: The chart review was conducted at the Ottawa Civic Hospital. SUBJECTS: The data on prostate cancer trends were obtained from the Canadian population. Charts were reviewed for two groups of patients: (a) men discharged from inpatient care during 1976 and 1986-87 with prostate cancer first diagnosed in the same year and (b) men who underwent transurethral resection of the prostate (TURP) during 1976 and 1986. OUTCOME MEASURES: Incidence and mortality rates of prostate cancer, rates of prostatectomy and TURP, and correlations between them. From the hospital data, changes between 1976 and 1986-87 in distribution of cancer stages, distribution of cases detected incidentally after surgery for suspected benign prostatic hypertrophy and average number of slides analysed per gram of tissue obtained from prostatectomy. RESULTS: The epidemiologic data showed that the age-adjusted incidence rates increased by 72% overall, an increase seen in all age groups over 60 years. The mortality rates increased by 29% overall, primarily in men over 85 years old. The prostatectomy rate increased by 55%. There were significant linear correlations between the national and provincial incidence rates of prostate cancer and the TURP rates. The chart review revealed that during 1976, 53% of the cases of prostate cancer diagnosed were localized, as compared with 75% in 1986-87 (p < 0.01). The proportion of tumours diagnosed incidentally in men undergoing TURP increased by 11%, whereas the number of procedures did not increase. Significantly more slides per gram of tissue were analysed in 1986-87 than in 1976 (p < 0.01). CONCLUSIONS: The correlations between the incidence rates of prostate cancer and those of TURP suggest that increased treatment of benign prostatic disease has led to increased detection of prostate cancer. Extrapolation of the data obtained from the chart review indicates that the increase in observed incidence rates can be attributed to an increase in the rate of localized disease and thus primarily to early detection rather than to elevated risk. However, because the rate of death from prostate cancer was elevated in elderly men, increases in exposure to unestablished risk factors cannot be ruled out.

Age Factors↗

Farming and prostate cancer mortality.

Although farmers appear to be at an increased risk of prostate cancer, the specific exposures which produce the excess risk remain unexplained. This study was based on a retrospectively assembled cohort of male Manitoba, Saskatchewan, and Alberta, Canada, farmers age 45 years or older identified in the 1971 Canadian censuses of population and agriculture. The cohort was linked to the Canadian National Mortality Database using an iterative computer record linkage system for the period June 1971 to the end of 1987. A total of 1,148 prostate cancer deaths and 2,213,478 person-years were observed. Using Poisson regression, the study examined the relation between the risk of dying from prostate cancer and various farm practices as identified on the 1971 Census of Agriculture, including exposure to chickens, cattle, pesticides, and fuels. A weak, but statistically significant, association was found between number of acres sprayed with herbicides in 1970 and risk of prostate cancer mortality. When the analysis was restricted to farmers believed to be subject to the least amount of misclassification, the risk associated with acres sprayed with herbicides increased (rate ratio (RR) = 2.23 for 250 or more acres sprayed; 95% confidence interval (CI) 1.30-3.84; test for trend, p < 0.01). No other farm exposure examined was associated with any detectable pattern of increased or decreased risk. These findings encourage further research to examine the effects of herbicides on prostate cancer.

Aged↗

Trends in rates of admission to hospital and death from asthma among children and young adults in Canada during the 1980s.

OBJECTIVE: To update reports of increases in the rates of admission to hospital and death from asthma among children and young adults in Canada during the 1970s by examining data for the 1980s. DESIGN: Age-standardized rates were calculated from data for people less than 35 years of age at the time of death from asthma, bronchitis or other respiratory conditions (from 1980 through 1989) and at the time of admission to hospital for treatment of these diseases (from 1980 through 1988). Standardized mortality ratios were calculated with the death rate for Canada as the expected rate. SETTING: Data for all of Canada were examined by sex, age group and province. RESULTS: In contrast to sharp increases in the rate of death from asthma observed from 1970 through the early 1980s among Canadians less than 35 years of age, the rate showed no net change between 1980 and 1989; on average, there were 58 deaths in this age group annually. During the decade, the rates of death from asthma were three times higher in Saskatchewan and Alberta than in Newfoundland. The national rate of hospital admission/separation for asthma, however, increased greatly, though changes in the rate varied by province. Increases of over 90% were observed in Prince Edward Island and New Brunswick, whereas little overall change occurred in Newfoundland, Manitoba and Saskatchewan. The rate of hospital admission/separation for asthma was highest in Prince Edward Island and lowest in Manitoba and British Columbia. Although the rates of hospital admission/separation for asthma among boys aged less than 15 years of age were consistently 50% higher than those among girls of that age, the rate among people aged 15 through 34 years was twice as high among females as males. A slight decrease in the rates of death from respiratory conditions other than asthma was observed, together with a steady, fairly substantial decline in the rates of hospital admission/separation for these conditions. CONCLUSIONS: Whether there is any relation between increases in rates of admission to hospital for asthma and trends in the rates of death from asthma during the decade will require further study.

Adolescent↗

Binding of the cationic dye, Janus green B, as a measure of the specific surface area of crystalline silica in aqueous suspension.

Twelve preparations of crystalline silica, with a wide range of particle sizes, were assayed by a new method, which measures surface adsorption of the cationic dye Janus green B to crystalline silica samples in a buffered aqueous suspension. The same samples were also assayed for total surface area by the Brunauer-Emmett-Teller (BET) method of surface adsorption of nitrogen gas. A strong linear correlation was found between the two methods of measurement (r = 0.977). Reproducible specific surface area measurements by the Janus green B adsorption method were made on 2-mg samples using ordinary visible wave-length spectrophotometric equipment, whereas the BET method necessitated sample sizes in excess of 100 mg and more specialized instrumentation. Five size-fractionated preparations from the same Min-U-Sil alpha-quartz sample showed an increase in BET surface area and Janus green B binding per unit weight with decreasing particle size. Among four standard alpha-quartz samples tested, Min-U-Sil 5 and F600 had the lowest specific surface areas, whereas DQ-12 and Chinese standard alpha-quartz had much higher surface areas. The synthetic silica preparations cristobalite and tridymite had intermediate surface areas. Binding by the cationic dye Janus green B is consistent with a surface charge mechanism and provides a useful new technique for the assessment of surface characteristics of crystalline silica samples. Its linear relationship to surface area suggests that the ratio of aqueous surface charge to surface area is constant for different crystalline silica preparations. Comparison of surface areas for different preparations of crystalline silica is important in understanding the relative activities of these preparations in studies on mechanisms of silicosis and silica-induced lung cancer.

Azo Compounds↗

Oxidative DNA damage by crystalline silica.

Using a simple DNA strand breakage assay, we detected the production of oxidant species, probably hydroxyl free radicals, in buffered suspensions of crystalline silica at pH 7.4. DNA damage was affected by the presence of oxygen and was accelerated by superoxide dismutase and by hydrogen peroxide. Deferoxamine blocked damage by hydrogen peroxide and silica but accelerated DNA damage by silica alone and by superoxide dismutase and silica. DNA damage was blocked by catalase and by the scavenging agents dimethyl sulfoxide and sodium benzoate. Chemical etching of crystalline silica to remove impurities by treatment of the surface with hydrofluoric acid resulted in markedly diminished DNA damaging ability. Even preparations of crystalline silica previously characterized as highly pure contained trace iron impurities in amounts significant enough to produce oxygen free radicals in aqueous suspension. Both superoxide and Fenton reaction oxidants were produced. We conclude that silica is able to mediate DNA strand breakage in vitro and that this DNA damage may be an important factor in silica toxicity.

Catalase↗

Multiple myeloma mortality and agricultural practices in the Prairie provinces of Canada.

A cohort study of agricultural practices and the mortality experience (1971 to 1987) of male farmers in Manitoba, Saskatchewan, and Alberta has been conducted. The census records of 156, 242 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population were linked to mortality records through 1987. We observed associations between multiple myeloma mortality and fuel/oil expenditures (relative risk for top quartile of exposure = 1.69, 95% confidence interval = 1.08 to 2.65). No significant associations were found between multiple myeloma and herbicide use or with selected sociodemographic variables.

Adult↗

Elementary identification of a gnathosonic classification using an autoregressive model.

This was an investigation to determine the feasibility of an autoregressive (AR) model for establishing characteristic parameters from recorded occlusal sounds and develop their classification. Thirty four normal subjects with intact natural dentitions were selected for the study. The subjects' occlusal sounds from both sides of their faces respectively were sampled, and the gnathosonic classification (Class A, B and C) was established by observing the original recorded wave pattern and measuring the duration. Then, a 20 order AR model was calculated with the collected data, and the AR model coefficients were found to be similar to the indices of Bayes' discriminatory analysis. The total conformation rates of the modelled left and right occlusal sounds to the classification, estimated by Bayes' discriminant functions were 97.06% and 88.24% respectively. AR coefficients representing the characteristics of human occlusal sounds can be helpful in their classification and allow computer diagnosis of occlusal disorders.

Acoustics↗

Patterns of recurrence and survival in AMI patients in Canada.

OBJECTIVE: To describe the patterns of recurrence and survival of patients following their first acute myocardial infarction (AMI). DESIGN: A retrospective follow-up study based on the population of Nova Scotia and Saskatchewan from 1981-85. SUBJECTS: The analyses were performed on patients aged 25 to 75 years (n = 2083) who had been admitted to hospital with their first AMI during 1981 from the provinces of Nova Scotia and Saskatchewan. MAIN RESULTS: The rate of recurrence of AMI was 10% in men and 7% in women, regardless of age. Median time to recurrence was 13 to 15 months in men and seven months in women. After the first AMI, mortality rates were higher in women one week and one month after the initial infarction, reaching statistical significance (only in the 55- to 74-year-old age group)--P < 0.01 and P < 0.02, respectively. Five-year mortality rates were significantly higher in the older age groups (P < 0.01), but were similar in men and women. CONCLUSIONS: Reinfarction occurs more quickly in women, who also appear to be at a higher risk of death during the first month, and especially during the first week, postinfarction.

Adult↗

Herbicides and cancer.

Herbicides are a heterogeneous class of chemicals used in agriculture, forestry, and urban settings to kill weeds, shrubs, and broad-leaved trees. The role of herbicides in the etiology of cancer is controversial. Potential studies for review were identified through a MEDLINE search and from a check of references in related review articles. This review of the literature shows reasonable evidence suggesting that occupational exposure to phenoxy herbicides results in increased risk of developing non-Hodgkin's lymphoma. Several studies have noted large increases in risk of soft-tissue sarcomas with phenoxy herbicide exposure. In contrast, others have failed to observe increased risks, and evidence of an exposure-risk relationship is lacking. Although there have been too few appropriate studies for adequate assessment of risk of cancer at other sites, some findings have linked herbicide exposure with cancers of the colon, lung, nose, prostate, and ovary as well as to leukemia and multiple myeloma. Future studies must better identify and quantify the nature of herbicide exposures. In the interim, it seems only prudent to monitor and promote safety practices among persons occupationally exposed to phenoxy herbicides, particularly farmers and professional sprayers.

Animals↗

Increasing incidence of primary malignant brain tumors: influence of diagnostic methods.

BACKGROUND: The incidence of brain cancer has increased dramatically over the last decades in most developed countries. Whether these trends can be attributed to improved diagnosis is not clear. PURPOSE: To determine the effect of new imaging technology on increased rates of brain cancer, we assessed the level of detection for neurological disorders when computed tomography (CT) and magnetic resonance imaging (MRI) results were not available. METHODS: A neurologist performed a blind review of hospital charts from 356 randomly selected patients, hospitalized between 1985 and 1989 for neurological disorders, including brain cancer. All prediagnosis information except CT and MRI results was used as a basis for diagnostic re-evaluation. Also, a random sample of 151 brain cancer patients diagnosed between 1960 and 1965 was selected for a description of diagnostic methods used during that period. RESULTS: A comparison between the original diagnoses and the re-evaluations for patients in the 1985-1989 sample indicated that there was, among the diseases selected, a 24% misclassification when CT scans and MRI were not available. In particular, 20% of brain tumors were undetected (95% confidence interval = 15%-25%), and 10% of non-tumor disorders were inaccurately labeled as brain tumors in the absence of these tests. The repeatability of the re-evaluations was 86%. CONCLUSIONS: Among elderly North Americans, at least twofold increases in brain cancer incidence were observed over the last two decades. Since our findings show that CT scans and MRI are responsible for the detection of about 20% of brain tumors, we conclude that other factors also are responsible for the observed trends.

Adolescent↗

Risk assessment of physical activity and physical fitness in the Canada Health Survey mortality follow-up study.

The effect of physical fitness and physical activity on all-cause mortality and mortality due to cardiovascular disease (CVD), cancer and other causes was examined using a population-based representative sample of the Canadian population. A total of 691 deaths occurred among persons age 30-69 during the 7-year follow-up period. Of these, 37, 33 and 30% died of CVD, cancer and other causes, respectively. The effect of each risk factor on mortality was assessed using logistic regression analysis. Adjustment was made for age, sex, smoking and body mass index in the case of mortality due to CVD, all causes and causes other than CVD and cancer. Models for mortality due to cancer included adjustment for age, sex, smoking and alcohol consumption. For all cause mortality, those individuals who did not pass the physical fitness tests had significantly higher risks of death than those that passed. For CVD mortality, subjects whose physical activity was moderate were protected, and those who did not pass the physical fitness tests had substantially higher risks of death due to CVD. The risk of death due to cancer was not significantly related to physical activity or physical fitness. Persons who failed the physical fitness tests had significantly elevated risks of death due to causes other than CVD or cancer. Our findings support the conclusion that persons who are physically fit have an overall reduced risk of death independent of other major risk factors. Moderate levels of physical activity appear to be protective against cardiovascular disease.

Adult↗

Genetic dissection of autoimmune type I diabetes in the BB rat.

The BB rat is among the best models of insulin-dependent diabetes mellitus--with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T-cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, which is tightly linked to the neuropeptide Y (Npy) gene on chromosome 4, a gene linked to the major histocompatibility complex (MHC) on chromosome 20, and a third unmapped gene for which the Fischer rat strain carries an allele conferring resistance.

Animals↗