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T Zheng

Publications and source records attributed to T Zheng.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lactation and breast cancer risk: a case-control study in Connecticut.

In this report, we examined the relationship between lactation and breast cancer risk, in a case-control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30-80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR = 0.83, 95% CI, 0.63-1.09). An OR of 0.53 (95% CI, 0.27-1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23-0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.

Adult↗
PubMed2001

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.

Body Weight↗
PubMed2001

Use of the tetracycline-controlled transcriptional silencer (tTS) to eliminate transgene leak in inducible overexpression transgenic mice.

The doxycycline-inducible reverse tetracycline transactivator (rtTA) is frequently used to overexpress transgenes in a temporally regulated fashion in vivo. These systems are, however, often limited by the levels of transgene expression in the absence of dox administration. The tetracycline-controlled transcriptional silencer (tTS), a fusion protein containing the tet repressor and the KRAB-AB domain of the kid-1 transcriptional repressor, is inhibited by doxycycline. We hypothesized that tTS would tighten control of transgene expression in rtTA-based systems. To test this hypothesis we generated mice in which the CC10 promoter targeted tTS to the lung, bred these mice with CC10-rtTA-interleukin 13 (IL-13) mice in which IL-13 was overexpressed in an inducible lung-specific fashion, and compared the IL-13 production and phenotypes of parental mice and the triple transgenic CC10-rtTA/tTS-IL-13 progeny of these crosses. In the CC10-rtTA-IL-13 mice, IL-13, mucus metaplasia, inflammation, alveolar enlargement, and enhanced lung volumes were noted at base line and increased greatly after doxycycline administration. In the triple transgenic tTS animals, IL-13 and the IL-13-induced phenotype could not be appreciated without doxycycline. In contrast, tTS did not alter the induction of IL-13 or the generation of the IL-13 phenotype by doxycycline. Thus, tTS effectively eliminated the baseline leak without altering the inducibility of rtTA-regulated transgenes in vivo. Optimal "off/on" regulation of transgene expression can be accomplished with the combined use of tTS and rtTA.

Animals↗
PubMed2001

Antioxidants prevent ethanol-induced contractions of canine cerebral vascular smooth muscle: relation to alcohol-induced brain injury.

The present study was designed to test the hypothesis that alpha-tocopherol (Vit. E) and pyrrolidine dithiocarbamate (PDTC) might exert direct effects on alcohol-induced contractions of canine basilar cerebral arteries. After precontraction of arterial ring segments with ethanol, PDTC (10(-8)-10(-6) M) and Vit. E (10(-6)-10(-4) M) induced concentration-dependent relaxations of cerebral arteries, compared to untreated controls. The effective concentrations producing approximately 50% of the maximal relaxation responses (EC(50) values) were about 2.48+/-0.09 x 10(-7) M for PDTC, and 1.87+/-0.10 x 10(-5) mM for Vit. E, respectively. Preincubation of these arterial rings with EC(50)'s of PDTC or Vit. E for 40 min attenuate markedly the contractions produced by alcohol, at concentrations of 1-400 mM. However, both PDTC and Vit.E do not relax equi-potent precontractions induced by either KCl or prostaglandin F(2alpha) (PGF(2alpha)) or inhibit their contractions. These data suggest that alcohol-induced contractions of cerebral arteries are mediated via excitation-contraction coupling pathways different from those used by KCl or receptor-mediated agonists such as PGF(2alpha). The present results, when viewed in light of other recently published data, suggest that antioxidants may prove useful in the amelioration and treatment of alcohol-induced brain damage and strokes.

Animals↗
PubMed2001

Use of protein kinase C inhibitors results in rapid [Mg(2+)](i) mobilization in primary cultured rat aortic smooth muscle cells: are certain kinase C isoforms natural homeostatic regulators of cystolic free Mg(2+).

The effects of five different protein kinase C inhibitors--calphostin C, chelerythrine, bisindolylmaleimide I, staurosporine and Gö6979--on intracellular free magnesium ([Mg(2+)](i)) content and mobilization were investigated in primary, cultured rat aortic smooth muscle cells. All these protein kinase C inhibitors significantly and rapidly increased [Mg(2+)](i) both in normal media (1.2 mM Mg(2+)) and in Mg(2+) free media. These data suggest that the increments of [Mg(2+)](i), induced by the diverse protein kinase C inhibitors, are derived from the release of bound intracellular Mg(2+) and that activation of protein kinase C isozymes are normally responsible for helping to maintain basal levels of [Mg(2+)](i) in rat aortic smooth muscle cells.

Alkaloids↗
PubMed2001

Randomized trial of supplemental beta-carotene to prevent second head and neck cancer.

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

Adult↗
PubMed2001

Sex steroid hormones exert biphasic effects on cytosolic magnesium ions in cerebral vascular smooth muscle cells: possible relationships to migraine frequency in premenstrual syndromes and stroke incidence.

Clinically, it is known that: (1) magnesium (Mg) supplementation relieves premenstrual problems (e.g., migraine, bloating and edema) occurring in the late luteal phase of the menstrual cycle; and (2) migraine syndromes, particularly in women, are associated with deficits in brain and serum ionized Mg levels. We investigated whether concentrations of sex steroid hormones, found in the serum during the menstrual cycle of women, are associated with changes in the levels of cytosolic free magnesium ions ([Mg2+]i in single cultured canine cerebral vascular smooth muscle cells. The resting level of [Mg2+]i in these cells was 645 +/- 89 microM before exposure to sex steroid hormones. Exposure of these vascular cells to a low concentration of estrogen (10 pg/ml) failed to interfere with the levels of [Mg2+]i. However, exposure to estrogen, at concentrations ranging from 40 to 200 pg/ml, induced significant loss of [Mg2+]i in a concentration-dependent manner. At a concentration of 200 pg/ml estrogen, the level of [Mg2+]i decreased approximately 30% in comparison with controls. Progesterone produced biphasic effects on the levels of [Mg2+]i, depending on its concentration. Exposure of the cultured cells to a low concentration of progesterone (0.5 ng/ml) resulted in an increased level of [Mg2+]i (from 690 +/- 50 microM to 753 +/- 56 microM, p < 0.05). However, when these cells were exposed to higher concentrations of progesterone (i.e., from 5.0 to 20 ng/ml), the cellular levels of [Mg2+]i were decreased significantly. The higher the estrogen or progesterone concentration, the lower the levels of [Mg2+]i. In contrast, testosterone, a male hormone, didn't produce any significant alteration in [Mg2+]i levels in these cerebral vascular smooth muscle cells. These data indicate that low, physiological concentrations of female sex hormones, estrogen and progesterone, help cerebral vascular smooth cells sustain normal concentrations of [Mg2+]i, which are beneficial to vascular function, whereas high levels of estrogen and progesterone deplete, significantly, [Mg2+]i in cerebral vascular smooth muscle cells, possibly resulting in cerebrovasospasms and reduced cerebral blood flows related to premenstrual syndromes, migraine and stroke risk. Our findings could provide new insight into the mechanism whereby migraine occurs frequently in the late luteal phase in the premenstrual syndrome. In addition, our results demonstrate that female sex steroids but not testosterone (in physiologic concentrations) can exert direct effects on [Mg2+]i in cerebral vascular cells.

Animals↗
PubMed2001

Occupation and leukemia: a population-based case-control study in Iowa and Minnesota.

BACKGROUND: Studies have suggested that risk of leukemia may be associated with occupational or industrial exposures and risk may vary by the histological type of the disease. METHODS: A population-based case-control study was conducted in Iowa and Minnesota to evaluate the association between various occupations, industries, and occupational exposures and leukemia risk. A total of 513 cases and 1,087 controls was included in the study. A lifetime occupational history and other risk factor information were collected through in-person interviews, and a job-exposure matrix was used to assess possible risks associated with specific exposures. RESULTS: A significantly increased risk of leukemia was observed among agricultural service industries and among nursing and healthcare workers. Janitors, cleaners, and light truck drivers also experienced increased risk. Those employed in plumbing, heating and air conditioning industries, and sales of nondurable goods (such as paints and varnishes) had an increased risk. Printers, painters, and workers in the food and metal industries had a nonsignificantly increased risk of leukemia. Analyses by specific exposures and histology of leukemia showed that risk of leukemia associated with occupational or industrial exposures may vary by histological type of the disease. CONCLUSIONS: An increased risk of leukemia among workers employed in agricultural industries, nursing and healthcare workers, and in a few occupations with possible exposure to solvents is consistent with earlier studies. Associations of risk with occupations not observed previously deserve further assessment. Published 2001 Wiley-Liss, Inc.

Adult↗
PubMed2001

Importance of extracellular Ca2+ and intracellular Ca2+ release in ethanol-induced contraction of cerebral arterial smooth muscle.

The present study was designed to investigate the roles of extracellular Ca2+ ([Ca2+]0) influx and intracellular free Ca2+ ([Ca2+]i) release in ethanol-induced contractions of isolated canine cerebral arteries and primary cultured, cerebral vascular smooth muscle cells. Ethanol (20-200 mM) produced significant contractions in isolated canine basilar arterial rings in a concentration-dependent manner. Removal of [Ca2+]0 and pretreatment of canine basilar arterial rings with verapamil (an antagonist of voltage-gated Ca2+ channels), thapsigargin (a selective antagonist of the sarcoplasmic reticulum Ca2+ pump), caffeine plus ryanodine (a specific antagonist of ryanodine-sensitive Ca2+ release), or heparin (an inositol 1,4,5,-trisphosphate [InsP3]-mediated Ca2+ release antagonist) markedly attenuated (approximately 50%-80%) ethanol-induced contractions. The absence of [Ca2+]0 and preincubation of primary single smooth muscle cells obtained from canine basilar arteries with verapamil, thapsigargin, heparin, or caffeine plus ryanodine markedly attenuated (approximately 50%-80%) the transient and sustained elevations in [Ca2+]i induced by ethanol. Results of the present study suggest to us that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores (both InsP3 sensitive and ryanodine sensitive) are required for ethanol-induced contractions of isolated canine basilar arteries.

Animals↗
PubMed2001

IL-11: insights in asthma from overexpression transgenic modeling.

The evolution of our understanding of IL-11 mirrors, in many ways, the problems that are faced by investigators in the post-genome era and the types of techniques that might need to be used to deal with these issues. IL-11 was discovered as a soluble factor in fibroblast supernatants that stimulated the proliferation of "IL-6-dependent" plasmacytoma cells. It was subsequently demonstrated to be an important stimulator of platelet reconstitution and a pleiotropic regulator of nonrespiratory tissues. In the lung, IL-11 is produced by a variety of structural cells and eosinophils in response to a variety of stimuli, including TGF-beta, major basic proteins, and viruses. IL-11 is also detected in exaggerated quantities at sites of virus infection. Its potential effector functions at these sites were defined with constitutive and inducible overexpression transgenic modeling systems which demonstrated that IL-11 causes nodular mononuclear infiltrates, airway remodeling with subepithelial fibrosis, airways obstruction, and airways hyperresponsiveness and can block alveolar development when expressed during development. In accord with these murine findings, IL-11 is selectively expressed in eosinophils and epithelial cells in patients with moderate and severe asthma where expression correlates directly with disease severity and inversely with FEV(1). Studies using transgenic mice also demonstrated that IL-11 inhibits antigen-induced tissue inflammation. Thus IL-11 might be an important regulator of inflammatory and remodeling responses in the asthmatic airway.

Animals↗
PubMed2001

Occupational risk factors for brain cancer: a population-based case-control study in Iowa.

A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.

Adult↗
PubMed2001

Agricultural exposure to carbamate pesticides and risk of non-Hodgkin lymphoma.

Recent epidemiological studies have suggested an increased risk of non-Hodgkin lymphoma (NHL) from carbamate insecticide use among farmers. To further explore the possible relationships, we conducted a pooled analysis of three population-based case-control studies conducted in four midwestern states in the United States. A total of 985 white male subjects and 2895 control subjects were included in this analysis. Unconditional logistic regression was used to estimate the association and control for confounding. Compared with nonfarmers, farmers who had ever used carbamate pesticides had a 30% to 50% increased risk of NHL, whereas farmers without carbamate pesticide use showed no increased risk. Analyses for individual carbamate pesticides found a more consistent association with Sevin but not carbofuran, butylate, or S-ethyl dipropylthiocarbamate plus protectant. Among farmers using Sevin, the risk of NHL was limited to those who personally handled the product, those who first used the product for > or = 20 years before their disease diagnosis, and those who used the product for a longer period. These associations persisted after adjusting for other major classes of pesticides. These results suggest an increased risk of NHL associated with carbamate pesticide use, particularly Sevin. Further investigation of the association is warranted.

Adult↗
PubMed2001

Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle.

We investigated the relationships of two potential intracellular signaling pathways, protein kinase C (PKC) and phosphatidylinositol 3-kinases (PI3Ks), to ethanol-induced contractions in cerebral arteries. Ethanol (20-200 mM) induces concentration-dependent constriction in isolated canine basilar arteries that is inhibited in a concentration-dependent manner by pretreatment of these vessels with 10(-9)-10(-3) M Gö-6976 (an antagonist selective for PKC-alpha and PKC-betaI), 10(-10)-10(-4) M bisindolylmaleimide I (a specific antagonist of PKC), and 10(-10)-10(-4) M wortmannin or 10(-8)-10(-2) M LY-294002 (selective antagonists of PI3Ks). Ethanol-induced increases in intracellular Ca(2+) concentration (from approximately 100 to approximately 500 nM) in canine basilar smooth muscle cells are also suppressed markedly (approximately 20-70%) in the presence of a similar concentration range of Gö-6976, bisindolymaleimide I, wortmannin, or LY-294002. This study suggests that activation of PKC isoforms and PI3Ks appears to be an important signaling pathway in ethanol-induced vasoconstriction of cerebral blood vessels.

Androstadienes↗
PubMed2001

Ethanol-induced contractions in cerebral arteries: role of tyrosine and mitogen-activated protein kinases.

BACKGROUND AND PURPOSE: The relationship between alcohol consumption and stroke appears complex; moderate ingestion is associated with reduced stroke risk, while heavy intake is associated with increased stroke risk. Ethanol has been shown both experimentally and epidemiologically to induce hemorrhagic and ischemic strokes, which are associated with cerebral vasoconstriction. Ethanol is known to induce contraction in isolated cerebral arteries and intact microvessels from diverse mammalian animals. The relationships between ethanol-induced contractions in cerebral arteries, intracellular free Ca(2+) ([Ca(2+)](i)), tyrosine kinases (including the src family), and mitogen-activated protein kinases (MAPK) were investigated in the present study. METHODS: Cerebral arterial muscle tension and [Ca(2+)](i) were quantified by an isometric contraction technique and direct visualization of Ca(2+) in single cells. RESULTS: Ethanol induces concentration-dependent contractions in intact canine basilar arteries, which are attenuated significantly by pretreatment of the arteries with low concentrations of an antagonist of protein tyrosine kinases (genistein); an src homology 2 (SH2) domain inhibitor peptide; a highly specific antagonist of p38 MAPK (SB-203580); a potent, selective antagonist of MEK1/MEK2 (U0126); and a selective antagonist of mitogen-activated protein kinase kinase (MAPKK) (PD-98059). IC(50) levels obtained for these 5 antagonists are consistent with reported K:(i) values for these tyrosine kinase, MAPK, and MAPKK antagonists. Ethanol induces transient and sustained increases in [Ca(2+)](i) in primary single smooth muscle cells from canine basilar arteries, which are markedly attenuated in the presence of genistein, an SH2 domain inhibitor peptide, SB-203580, U0126, and PD-98059. Several specific antagonists of known endogenously formed vasoconstrictors do not inhibit or attenuate either the ethanol-induced contractions or the elevation of [Ca(2+)](i). CONCLUSIONS: The present study suggests that activation of protein tyrosine kinases (including the src family) and MAPK appear to play important roles in the ethanol-induced contractions and the elevation of [Ca(2+)](i) in smooth muscle cells from canine basilar arteries. The results could be used to suggest that selective antagonists of protein tyrosine kinases and MAPK may be useful both prophylactically and therapeutically in alcohol-induced strokes.

Animals↗
PubMed2001

[Effect of unprepared and prepared "he zi" on contraction of isolated trachea smooth muscle in rabbits].

Isolated trachea smooth muscle in rabbits induced by Ach or KCl was adopted to study the effect of unprepared and prepared "He Zi". The results showed that unprepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by Ach or KCl, and that prepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by KCl. The results also showed that prepared "He Zi" could significantly inhibit the contraction induced by Ach. The inhibition effect may not be associated with cGMP, adrenergic receptor, and release of NO and prostaglandin, and was epithelium independent. Maybe the different content of tannic acid contributed to the different effect between unprepared and prepared "He Zi".

Acetylcholine↗
PubMed2001

Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection. Here, we report the expression, regulation, and biological effect of interleukin (IL)-8 in KS. AIDS-KS cell lines expressed higher levels of IL-8 than either human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle (AoSM) cells or fibroblast cells (T1). The inflammatory cytokine IL-1beta up-regulated IL-8 expression in a time- and concentration-dependent manner in KS cell lines. IL-8 antisense oligonucleotides specifically reduced IL-8 mRNA and protein levels and inhibited KS cell growth in a dose-dependent manner. In addition, supernatant from a KS cell line induced the growth of HUVECs and angiogenesis in chicken chorioallantoic membrane assays, both of which were inhibited by IL-8 neutralizing antibody. Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease.

Animals↗