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Biomedical subjects

Y Mao

Publications and source records attributed to Y Mao.

At least 127 records · Page 7Linked to original sources

Passive and active smoking and breast cancer risk in Canada, 1994-97.

BACKGROUND: Studies comparing ever smokers with never smokers have found little increase in breast cancer risk. However, the five published studies examining passive smoking and breast cancer have all suggested associations with both passive and active smoking, particularly premenopausal risk. METHODS: We analyzed data collected through the Canadian National Enhanced Cancer Surveillance System, from 805 premenopausal and 1512 postmenopausal women with newly diagnosed (incident), histologically confirmed, primary breast cancer and 2438 population controls. The mailed questionnaire included questions on breast cancer risk factors and a lifetime residential and occupational history of exposure to passive smoking. RESULTS: Among premenopausal women who were never active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer odds ratio (OR) of 2.3 (95% confidence interval [CI] 1.2-4.6). Passive exposure showed a strong dose-response trend (test for trend p = 0.0007) with an OR of 2.9 (95% CI 1.3-6.6) for more than 35 years of passive residential and/or occupational exposure. When premenopausal women who had ever actively smoked were compared with women never regularly exposed to passive or active smoke, the adjusted OR for breast cancer was also 2.3 (95% CI 1.2-4.5). Among postmenopausal women who were never-active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer OR of 1.2 (95% CI 0.8-1.8) and an OR of 1.4 (95% CI 0.9-2.3) for the most highly exposed quartile of women. The adjusted OR for postmenopausal breast cancer risk for ever-active smokers compared with women never regularly exposed to passive or active smoke was 1.5 (95% CI 1.0-2.3). Statistically significant dose-response relationships were observed with increasing years of smoking, increasing pack-years and decreasing years since quitting. Women with 35 or more years of smoking had an adjusted OR of 1.7 (95% CI 1.1-2.7). CONCLUSIONS: Active and passive smoking may be associated with increased breast cancer risk, particularly premenopausal risk.

Adult↗

Study of the electrochemical behavior of mitoxantrone and its determination at a Co-C modified ultramicroelectrode.

In 0.005 mol dm-3 Tris-0.05 mol dm-3 NaCl buffer solution (pH 7.10), the electrochemical behavior of mitoxantrone was studied by linear-sweep voltammetry and cyclic voltammetry at a Co-carbon fiber ion implantation modified ultramicroelectrode. A sensitive reduction peak was obtained. The peak potential was -0.798 V (vs. SCE), the peak current was proportional to the concentration of mitoxantrone over the range of 2.0 x 10(-7)-6.0 x 10(6) mol dm-3 and the detection limit was 4.2 x 10(-8) mol dm-3. This method was applied to the direct determination of mitoxantrone in urine. Recoveries were in the range 95.4-105.8%. The reduction process was quasi-reversible with absorptive characteristics at a Co-C ultramicroelectrode. According to Laviron's theory, the electrode reaction rate constant ks and the electron transfer alpha of mitoxantrone were 4.4 s-1 and 0.48, respectively. The composition and depth distribution of elements on the surface of the Co-C ultramicroelectrode were determined by Auger electron spectroscopy. The experiments showed that Co was implanted into the surface of the carbon fiber, and the Co-C ultramicroelectrode had good stability and reproducibility.

Journal Article↗

Parental cigarette smoking, hard liquor consumption and the risk of childhood brain tumors--a case-control study in northeast China.

In this study we examine the effect of parents' lifestyles on the risk of childhood brain tumors. Parents of 82 children newly diagnosed with primary malignant brain tumors and 246 individually matched hospital controls were interviewed in the hospital wards between September 1991 and December 1996. Data were collected on socioeconomic status, parental lifestyle prior to and during the pregnancy, and family history. Odds ratios and 95% confidence intervals were derived through conditional logistic regression. The risk of childhood brain tumors was associated with paternal use of hard liquor prior to the pregnancy: the odds ratios were 3.72 (95% CI = 1.91-7.26) for < or = 15 years of hard liquor consumption and 4.06 (95% CI = 1.09-15.21) for > or = 16 years of hard liquor consumption compared with never consuming hard liquor (test for trend p = 0.0001); the odds ratios increased with increasing lifetime hard liquor consumption. There is little evidence to support an association between childhood brain tumors and parents' smoking prior to or during pregnancy.

Adolescent↗

Clues to the aetiological heterogeneity of testicular seminomas and non-seminomas: time trends and age-period-cohort effects.

BACKGROUND: Most previous epidemiological studies have treated testicular cancer as a single entity. However, some investigators suggest that testicular seminomas and non-seminomas may have different risk profiles. We examine the time trends in incidence of the two main histological types separately. METHODS: From 1970 through 1995, 7296 cases of testicular cancer were registered in the Canadian provinces of Ontario, Saskatchewan and British Columbia. In addition to analyses of the secular trends by age group and birth cohort, an age-period-cohort (APC) model with standard Poisson assumptions was fitted to the data to assess the time effects. RESULTS: The age-adjusted incidence rate for seminomas increased by 53%, from 1.5 per 100 000 males in 1970-1971 to 2.3 per 100 000 males in 1994-1995. Non-seminomas increased by 91%, from 1.1 to 2.1 per 100 000 males over the same period. Non-seminomas were more frequent at young ages whereas seminomas dominated in older ages. In contrast to seminomas, non-seminomas occurred predominantly among adolescent men (15-19 years), with a fourfold increase between 1970-1971 and 1994-1995. Age-period-cohort modelling showed that the increase in the risk of both seminomas and non-seminomas followed a birth cohort pattern, but with differences in birth cohorts in addition to significantly distinct age patterns. CONCLUSIONS: Our findings support the hypothesis postulating aetiological heterogeneity in the development of seminomas and non-seminomas. We suggest that epidemiological studies of testicular cancer treat seminomas and non-seminomas separately.

Adolescent↗

Alcohol, tobacco and coffee consumption and the risk of pancreatic cancer: results from the Canadian Enhanced Surveillance System case-control project. Canadian Cancer Registries Epidemiology Research Group.

The relationship between alcohol, tobacco and coffee consumption and pancreatic cancer was investigated using population-based case-control data obtained from eight Canadian provinces. Our findings are based on analyses performed on 583 histologically confirmed pancreatic cancer cases and 4813 controls. Questionnaire data were obtained directly from 76% of the cases. Male subjects with 35 or more cigarette pack-years had an increased risk of developing pancreatic cancer relative to never smokers (OR= 1.46, 95% CI 1.00-2.14). Similarly, women reporting at least 23 cigarette pack-years of smoking had an odds ratio of 1.84 (95% CI 1.25-2.69). For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer. Coffee drinking was not related to pancreatic cancer. More work is needed to clarify the role of these and other potentially modifiable risk factors as a means to reduce the incidence of this disease for which treatment results remain disappointing.

Adult↗

Is occupation a risk factor for thyroid cancer? Canadian Cancer Registries Epidemiology Research Group.

A Canadian case-control study explored the etiology of thyroid cancer, including occupational exposure. Analysis of job history from 1272 thyroid cancer patients and 2666 controls revealed statistically significant risks among the following occupations: Wood Processing, Pulp and Papermaking (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.11-5.83); Sales and Service (OR = 1.26, 95% CI = 1.05-1.52); and Clerical (OR = 0.81, 95% CI = 0.67-0.97). ORs were adjusted for age, sex, province, cigarette smoking, education, self-reported exposure to radiation at work, and duration of employment. Exposure to ionizing radiation or electromagnetic fields at work (inferred from job histories) did not affect risk, nor did socioeconomic status, measured by education, income, or occupational prestige. Possible explanations for the results and further investigations are discussed.

Adult↗

Mechanism of action of camptothecin.

Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I-mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potentials roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed.

Animals↗

dCtBP-dependent and -independent repression activities of the Drosophila Knirps protein.

Transcriptional repressor proteins play essential roles in controlling the correct temporal and spatial patterns of gene expression in Drosophila melanogaster embryogenesis. Repressors such as Knirps, Krüppel, and Snail mediate short-range repression and interact with the dCtBP corepressor. The mechanism by which short-range repressors block transcription is not well understood; therefore, we have undertaken a detailed structure-function analysis of the Knirps protein. To provide a physiological setting for measurement of repression, the activities of endogenous or chimeric Knirps repressor proteins were assayed on integrated reporter genes in transgenic embryos. Two distinct repression functions were identified in Knirps. One repression activity depends on dCtBP binding, and this function maps to a C-terminal region of Knirps that contains a dCtBP binding motif. In addition, an N-terminal region was identified that represses in a CtBP mutant background and does not bind to the dCtBP protein in vitro. Although the dCtBP protein is important for Knirps activity on some genes, one endogenous target of the Knirps protein, the even-skipped stripe 3 enhancer, is not derepressed in a CtBP mutant. These results indicate that Knirps can utilize two different pathways to mediate transcriptional repression and suggest that the phenomenon of short-range repression may be a combination of independent activities.

Alcohol Oxidoreductases↗

Development of a multifrequency conductance catheter-based system to determine LV function in mice.

Transgenic mice offer a valuable way to relate gene products to phenotype, but the ability to assess the cardiovascular phenotype with pressure-volume analysis has lagged. Conductance measurement offers a method to generate an instantaneous left ventricular (LV) volume signal in the mouse but has been limited by the volume signal being a combination of blood and LV muscle. We hypothesized that by developing a mouse conductance system that operates at several simultaneous frequencies, we could identify and correct for the myocardial contribution to the instantaneous volume signal. This hypothesis is based on the assumption that mouse myocardial conductivity will vary with frequency, whereas mouse blood conductivity will not. Consistent with this hypothesis, we demonstrated that at higher excitation frequency, greater end-diastolic and end-systolic conductance are detected, as well as a smaller difference between the two. We then empirically solved for LV blood volume using two frequencies. We combined measured resistivity of mouse myocardium with an analytic approach and extracted an estimate of LV blood volume from the raw conductance signal. Development of a multifrequency catheter-based system to determine LV function could be a tool to assess cardiovascular phenotype in transgenic mice.

Animals↗

Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals.

The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.

Animals↗

Non-Hodgkin's lymphoma and occupational exposure to chemicals in Canada. Canadian Cancer Registries Epidemiology Research Group.

BACKGROUND: The incidence of non-Hodgkin's lymphoma (NHL) has been increasing in Canada. This study assessed the effect of occupational exposure to specific chemicals on the risk of NHL. PATIENTS AND METHODS: Mailed questionnaires were used to obtain data on 1469 newly diagnosed, histologically confirmed NHL cases and 5073 population controls between 1994 and 1997 in eight Canadian provinces. Data was collected on socioeconomic status, life-style, diet, occupation, and years of exposure to any of 17 chemicals. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. RESULTS: The study found an increased risk of NHL among males exposed to benzidine, mineral, cutting, or lubricating oil, pesticides, and herbicides. Compared with non-exposure to each specific chemical, the adjusted ORs were 1.9 (95% CI: 1.1-3.4) for benzidine, 1.3 (95% CI: 1.0-1.5) for mineral, cutting, or lubricating oil, 1.3 (95% CI: 1.0-1.6) for herbicides, and 1.3 (95% CI: 1.0-1.6) for pesticides. Excess risk of NHL among females was associated with exposure to pesticides and wood dust. ORs increased with increasing exposure in years to benzidine and herbicides for males and with increasing exposure years to wood dust for females. These trends were statistically significant (P < 0.05). CONCLUSIONS: The findings in this study suggest that occupational exposure to specific chemicals plays an important role in the development of NHL in Canada.

Adult↗

Effects of lipid on low-density and high-density lipoprotein receptors in hepatic stellate cell from rat liver.

OBJECTIVE: To study the effects of lipid (triglyceride and very low-density lipoprotein) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptors in the hepatic stellate cell (HSC) from the rat liver. METHODS: HSC were isolated and cultured from the liver of Wistar rats by in situ perfusion with pronase and collagenase and density gradient centrifugation with Nycodenz. Radioligand conjugation assay with (125)I-LDL and (125)I-HDL(3) was detected for the effects of lipid on LDL and HDL receptor of HSC. RESULTS: LDL and HDL receptors were found on the membrane of the rat HSC. The lipid might increase the binding of LDL to LDL receptor, but decrease the binding of HDL(3) to HDL receptor. CONCLUSION: LDL and HDL receptors on the HSC membrane may have an important role in the metabolism of lipoprotein and the regulation of cholesterol. These results provided the basis of theory and experimentation for the genesis of fatty liver and liver fibrosis.

Animals↗

Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1.

Sulindac sulfone (Exisulind) induces apoptosis and exhibits cancer chemopreventive activity, but in contrast to sulindac, it does not inhibit cyclooxygenases 1 or 2. We found that sulindac sulfone and two potent derivatives, CP248 and CP461, inhibited the cyclic GMP (cGMP) phosphodiesterases (PDE) 2 and 5 in human colon cells, and these compounds caused rapid and sustained activation of the c-Jun NH2-terminal kinase 1 (JNK1). Rapid activation of stress-activated protein/ERK kinase 1 (SEK1) and mitogen-activated protein kinase kinase kinase (MEKK1), which are upstream of JNK1, was also observed. Other compounds that increase cellular levels of cGMP also activated JNK1, and an inhibitor of protein kinase G (PKG), Rp-8-pCPT-cGMPS, inhibited JNK1 activation by the sulindac sulfone derivatives. Expression of a dominant-negative JNK1 protein inhibited CP248-induced cleavage of poly(ADP-ribose) polymerase, a marker of apoptosis. Thus, it appears that sulindac sulfone and related compounds induce apoptosis, at least in part, through activation of PKG, which then activates the MEKK1-SEK1-JNK1 cascade. These studies also indicate a role for cGMP and PKG in the JNK pathway.

Apoptosis↗

Orius software: calculation of rates and epidemiologic indicators, and preparation of graphical output.

Orius software produces disease surveillance statistics, including output for the Health Canada Web site "Cancer Statistics Online" and on-demand statistics at the Web site for the North American Association of Central Cancer Registries. It allows flexibility in accessing data; storing, modifying and customizing requests; and producing statistical results and graphical output. Results include age-standardized or age-sex-standardized rates, standardized incidence/mortality ratios (observed-to-expected ratios) in which one area is optionally selected as the reference, potential years of life lost, average annual percent change, Mantel-Haenszel and maximum likelihood rate ratios, and the comparative incidence figure.

Epidemiologic Methods↗

Temporary and permanent focal cerebral ischemia in the mouse: assessment of cerebral blood flow, brain damage and blood-brain barrier permeability.

OBJECTIVE: To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model. METHODS: CD-1 mice (n = 126) had permanent middle cerebral artery occlusion for 24 h, or temporary occlusion for either one hour followed by 23 h of reperfusion or 2 h of occlusion with 22 h of reperfusion. The middle cerebral artery was occluded by insertion of a suture through the internal carotid artery. Reperfusion was established by suture withdrawal. The degree of occlusion and the extent of reperfusion were determined using laser Doppler. Infarct volume was measured with 2, 3, 5-triphenyl tetrazolium chloride staining, and the blood-brain barrier disruption was demonstrated using albumin immunohistochemistry. RESULTS: Blood flow decreased to 14%-19% of baseline in both the permanent and temporary occlusion groups and was restored to 51%-75% of baseline after reperfusion. The infarct volume was smaller in the 1 h/23 h temporary occlusion group (P < 0.05) than in either the 24 h permanent occlusion group or the 2 h/22 h temporary occlusion group. Blood-brain barrier disruption was also smaller in the 1 h/23 h temporary occlusion group than in either the 24 h permanent occlusion or the 2 h/22 h temporary occlusion group (P < 0.05). CONCLUSION: Permanent or temporary middle cerebral artery occlusion causes reproducible brain injury in the mouse. Blood-brain barrier disruption and infarct volume remain important markers of focal cerebral ischemia.

Animals↗

99mTc-MIBI and 99mTc-MDP scintimammography for detecting breast carcinoma.

OBJECTIVE: To assess the value of scintimammography with both 99mTc-MIBI and 99mTc-MDP in detecting breast cancer. METHODS: A total of 35 women with clinical findings of suspicious breast lesions were studied with both 99mTc-MIBI and 99mTc-MDP scintimammography. All patients underwent surgery within one week and the final diagnostic results (histopathological) were obtained. RESULTS: Eighteen of 35 abnormalities of breast were pathologically confirmed as breast cancer and 17 as benigN lesions. In this group of patients studied, the sensitivity, specificity and accuracy of 99mTc-MIBI scintimammography were 77.8%, 88.2% and 82.9%, respectively and those of 99mTc-MDP scintimammography were 72.2%, 88.2% and 80.0%, respectively. There was no significant difference between 99mTc-MIBI and 99mTc-MDP scintimammography. CONCLUSION: This study showed the high diagnostic accuracy of both 99mTc-MIBI and 99mTc-MDP scintimammography in detecting breast cancer. Both can be used as non-invasively assess breast cancer invasiveness before surgery.

Adult↗

[Attenuation of reperfusion injury in the mouse transfected interleukin-1 receptor antagonist].

OBJECTIVE: To investigate the therapeutic effects of overexpression of interleukin-1 receptor antagonist (IL-1ra), administered by gene transfer, on the transient cerebral ischemic injury in an experimental mice suture model. METHODS: Adenovirus vector encoding human IL-1ra gene (Ad.RSVIL-1ra) or LacZ gene (Ad.RSVLacZ) or normal saline was administered by injection into the right lateral ventricle in adult CD-1 mice. Five days after the virus injection, the mice received 1 h transient middle cerebral artery occlusion with 23 h reperfusion. Surface cerebral blood flow was measured using laser Doppler flowmetry. Brain infarct volume was evaluated on the sections with hematoxylin-eosin staining. Blood-brain barrier (BBB) permeability was determined using immunostaining of extravasated endogenous albumin. The number of intracellular adhesion molecular-1-positive vessels was determined by immunohistochemistry. RESULTS: The infarct volume in the Ad. RSVIL-1ra transfected mice was markedly reduced compared with the Ad. RSVLacZ transfected or saline mice (36.0 +/- 5.3 mm(3) vs 60.0 +/- 6.2 mm(3), 69.5 +/- 6.3 mm(3), P < 0.05). BBB disruption area was also smaller in the Ad. RSVIL-1ra transfected mice than in the Ad. RSVLacZ transfected and saline mice (P < 0.05). The expression of intracellular adhesion molecular-1 (ICAM-1) positive vessels in the ischemic cortex and basal ganglia was greatly attenuated in the Ad. RSVIL-1ra transfected mice (cortex: 135 +/- 23, vs 311 +/- 40 and 357 +/- 51 pound sterling basal ganglia: 90 +/- 21, vs 207 +/- 43 and 259 +/- 43, P < 0.05. CONCLUSION: IL-1ra has neuroprotective property during ischemia/reperfusion injury. Overexpression of IL-1ra via gene transfer can attenuate the expression of ICAM-1 in the ischemic area.

Adenoviridae↗