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Biomedical subjects

Y Mao

Publications and source records attributed to Y Mao.

At least 37 records · Page 2Linked to original sources

Population dynamics in the Penna model.

We build upon the recent steady-state Penna model solution [J. B. Coe, Y. Mao, and M. E. Cates, Phys. Rev. Lett. 89, 288103 (2002)] to study the population dynamics within the Penna model. We show that any perturbation to the population can be broken into a collection of modes each of which decay exponentially with its respective time constant. The long time behavior of population is therefore likely to be dominated by the modes with the largest time constants. We confirm our analytical approach with simulation data.

Adaptation, Physiological↗

Recursive approach to random sequential adsorption.

We present a generalization of Renyi's [A. Renyi, Trans. Math. Stat. Prob. 4, 205 (1963)] classical solution to the one-dimensional random sequential adsorption (RSA) problem, to the case where particle sizes are drawn from an arbitrary distribution, a process known as competitive RSA. We formulate the process using recursive relations, and without explicitly solving the equations, we extract limiting behavior which leads to exact analytic expressions for the final coverage. Our analysis is confirmed by computer simulations.

Journal Article↗

Survival of women with breast cancer in Ottawa, Canada: variation with age, stage, histology, grade and treatment.

This study examined the 5-year survival of 2192 breast cancer women diagnosed between 1994 and 1997 in Ottawa, Canada, by age, TNM stage, histology, grade and treatment, including assessment of the independent value of variables in defining prognosis. Our results showed that age, stage, treatment and grade significantly influenced outcome regardless of the confounding factors considered, with histology failing to achieve significant independent prognostic information. The survival rates were highest at ages 50-69 years for stage I and at ages 40-49 years for stages II-IV. The rates were lowest at ages or=70 years for stages III-IV. The differences in survival between grade 1 and grade 3 were 9% in stage I and 20% in stage II. The treatment leading to the best survival was surgery plus radiation for stages I-II and surgery combined with chemotherapy for stages III-IV. Lobular carcinoma had a better prognosis than ductal carcinoma; this can be explained by more grade 1 and less grade 3 cases in lobular carcinoma. The worse prognosis for young patients than other ages can be explained by their higher proportion of poorly differentiated cancers. Stage I patients aged 50-69 years having the best survival is likely due to the earlier diagnosis achieved through screening.

Adult↗

Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis.

BACKGROUND: Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracellular matrix (ECM) synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels is still unclear. OBJECTIVE: Using cDNA microarray technology, the alteration of gene expression profiles was determined for human dermal fibroblasts in vitro in the presence of asiaticoside (30 microg mL(-1)). Fifty-four genes, with known functions for cell proliferation, cell cycle progression and synthesis of ECM, were significantly upregulated in our 'genome-nest' expression profile at various time points. Furthermore, the mRNA levels and protein production of certain genes responsible for ECM synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. RESULTS: We found that there is a close correlation between the gene profile, mRNA and protein production in the response of the cells to asiaticoside stimulation. CONCLUSIONS: This information could be used for exploring the response of the target genes to asiaticoside in fibroblasts.

Blotting, Northern↗

Analytical solution of a generalized Penna model.

In 1995 Penna introduced a simple model of biological aging. A modified Penna model has been demonstrated to exhibit behavior of real-life systems including catastrophic senescence in salmon and a mortality plateau at advanced ages. We present a general steady-state, analytic solution to the Penna model which is able to deal with arbitrary birth and survivability functions. This solution is employed to solve standard variant Penna models studied by simulation. Different Verhulst factors regulating both the birth rate and external death rate are considered.

Aging↗

A human homolog of the yeast gene encoding tRNA 2'-phosphotransferase: cloning, characterization and complementation analysis.

The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2'-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiae

Amino Acid Sequence↗

Characterization of two novel KRAB-domain-containing zinc finger genes, ZNF460 and ZNF461, on human chromosome 19q13.1-->q13.4.

This study reports the cloning and characterization of two novel human zinc finger protein cDNAs (ZNF460 and ZNF461) from a fetal brain cDNA library. The ZNF460 cDNA is 3,135 bp in length encoding a 562-amino-acid polypeptide and the ZNF461 cDNA is 2,548 bp encoding a 563-amino-acid protein. Both of the proteins contain a KRAB A+B box and eleven C2H2 type zinc finger motifs. ZNF461 shows high similarity with the rat GIOT-1 gene (GIOT1). The ZNF460 gene mapped to 19q13.4 with 3 exons, and ZNF461 mapped to 19q13.1 with 6 exons. Both of the two genes are ubiquitously expressed in normal human tissues and the abundance of the ZNF460 mRNA is relatively low.

Amino Acid Sequence↗

Solvable senescence model showing a mortality plateau.

We present some analytic results for the steady states of the Penna model of senescence, generalized to allow genetically identical individuals to die at different ages via an arbitrary survival function. Modeling this with a Fermi function (of modest width) we obtain a clear mortality plateau late in life: something that has so far eluded explanation within such mutation accumulation models. This suggests that factors causing variable mortality within genetically identical subpopulations, which include environmental effects, may be essential to understanding the mortality plateau seen in many real species.

Journal Article↗

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Adult↗

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

Angiogenesis Inhibitors↗

Renal cell carcinoma and occupational exposure to chemicals in Canada.

This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

Adult↗

Active and passive smoking and the risk of stomach cancer, by subsite, in Canada.

This study assessed the influence of active and passive smoking on the risk of stomach cancer by subsite. Mailed questionnaires were used to obtain information on 1171 newly diagnosed histologically confirmed stomach cancer cases and 2207 population controls between 1994 and 1997 in eight Canadian provinces. Data were collected on socio-economic status, lifestyle and passive smoking status. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. Compared with those who had never smoked, there was strongly increased risk for ex- and current smokers among subjects with cardial stomach cancer. For men with cardial cancer, the adjusted ORs were 1.9 (95% CI 1.2-3.0) and 2.6 (95% CI 1.6-4.3) for ex-smokers and current smokers, respectively, with a similar pattern among women. Among men, the adjusted ORs were lower for subsites of stomach cancer other than cardia. These findings suggest that active and passive smoking may play an important role in the development of cardial stomach cancer.

Adult↗

Risk factors for male breast cancer in Canada, 1994-1998.

Relatively little attention has been paid to the aetiology of male breast cancer and the current understanding of female breast cancer, primarily related to reproductive events, cannot be readily transferred to understanding the cancer in males. However, since male breast cancer occurs in the absence of factors related to childbearing and menstruation, its aetiology may provide special insights into the causes of breast cancer in women. We examined lifestyle risk factors for male breast cancer as part of a Canadian, multi-site, population-based, case-control study. Eighty-one newly diagnosed, histologically confirmed cases and 1905 male controls aged 42-74 were analysed using unconditional logistic regression. Increased risks were found for men with a mother or sister with breast cancer (adjusted odds ratio (OR) 3.65, 95% confidence interval (95% CI) 1.62-8.19). Higher physical activity levels (moderate, and strenuous recreational plus occupational) were associated with a decreased risk of male breast cancer (highest quartile, adjusted OR 0.48, 95% CI 0.26-0.91). Similarly, higher risks were associated with higher weight 2 years before interview (2.19, 95% CI 1.08-4.43), maximum weight (OR 2.66) and higher body mass index (OR 1.60). Higher vegetable consumption and coffee consumption were associated with decreased risk, whereas higher beta-carotene, vitamin E and calcium supplementation were associated with statistically significant increased risk. The small number of cases and multiple comparisons preclude strong conclusions, but our study is consistent with studies suggesting obesity and family history increase risk, and physical activity decreases risk of breast cancer.

Adult↗

Isolation and characterization of a human novel RAB (RAB39B) gene.

Rab proteins are small-molecular-weight GTPases that control vesicular trafficking in eukaryotic cells. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone encoding a novel Rab protein, which showed 74.2% identity with previously isolated Rab39A at the amino acid level. RAB39B was expressed in a variety of human tissues and located in human chromosome Xq28. It consisted of two exons spanning 3764 bp of human genomic DNA.

Adult↗

Molecular cloning and characterization of a novel human gene (ANP32E alias LANPL) from human fetal brain.

Leucine-rich acidic nuclear protein (LANP) is a member of the leucine-rich repeats (LRRs) superfamily. Here we report on a human homologue of LANP, encoded by the gene ANP32E (alias LANPL). The gene was cloned and identified during large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 70% amino acid identity with rat LANP. According to bioinformatics analysis, ANP32E is located on chromosome 1q22. RT-PCR analysis indicates that ANP32E was expressed in human peripheral blood leukocytes, colon, small intestine, prostate, thymus, spleen, skeletal muscle, liver and kidney.

Amino Acid Sequence↗

Cloning, expression and characterization of a novel human REPS1 gene.

Ral is a member of the small GTPase-binding protein (G protein) family, and plays an important role in the Ras-RalGDS signal transduction pathway. A series of recent findings reveal several important downstream target proteins of Ral, such as RalBP1, Reps1, and others. Here we report another binding partner for RalBP1, which we have isolated from the human fetal brain library. The human REPS1 protein shares 83% amino acid identity with the mouse Reps1 protein. Northern blot analysis shows that the REPS1 is expressed in a variety of tissues, with the strongest expression in the heart and testis.

Adult↗

Increasing thyroid cancer incidence in Canada, 1970-1996: time trends and age-period-cohort effects.

We examined time trends in thyroid cancer incidence in Canada by age, time period and birth cohort between 1970 and 1996. Age-specific incidence rates by time period and birth cohort were calculated and age-period-cohort modelling used to estimate effects underlying the observed trends. Overall age-adjusted incidence rates of thyroid cancer doubled, from 3.3 and 1.1 per 100 000 in 1970-72 to 6.8 and 2.2 per 100 000 in 1994-96, among females and males respectively. Almost all the increase between 1970-72 and 1994-96 was due to papillary carcinoma of the thyroid. Age, birth cohort and period effects significantly improved the fit of the model for females, while age and birth cohort effects were significant determinants of the incidence among males. There were significant differences in the patterns/curvature for age, period and birth cohort effects between women and men. Our results suggest that the increases in thyroid cancer incidence in Canada may be associated with more intensive diagnostic activities and change in radiation exposure in childhood and adolescence. Temporal changes in reproductive factors among young women may explain some of the gender differences observed.

Adolescent↗