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Biomedical subjects

M Tseng

Publications and source records attributed to M Tseng.

At least 19 recordsLinked to original sources

RNA polymerase II transcription is required for human papillomavirus type 16 E7- and hydroxyurea-induced centriole overduplication.

Aberrant centrosome numbers are detected in virtually all human cancers where they can contribute to chromosomal instability by promoting mitotic spindle abnormalities. Despite their widespread occurrence, the molecular mechanisms that underlie centrosome amplification are only beginning to emerge. Here, we present evidence for a novel regulatory circuit involved in centrosome overduplication that centers on RNA polymerase II (pol II). We found that human papillomavirus type 16 E7 (HPV-16 E7)- and hydroxyurea (HU)-induced centriole overduplication are abrogated by alpha-amanitin, a potent and specific RNA pol II inhibitor. In contrast, normal centriole duplication proceeded undisturbed in alpha-amanitin-treated cells. Centriole overduplication was significantly reduced by siRNA-mediated knock down of CREB-binding protein (CBP), a transcriptional co-activator. We identified cyclin A2 as a key transcriptional target of RNA pol II during HU-induced centriole overduplication. Collectively, our results show that ongoing RNA pol II transcription is required for centriole overduplication whereas it may be dispensable for normal centriole duplication. Given that many chemotherapeutic agents function through inhibition of transcription, our results may help to develop strategies to target centrosome-mediated chromosomal instability for cancer therapy and prevention.

Amanitins↗

Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication.

Cyclin-dependent kinase 2 (CDK2) has been proposed to function as a master regulator of centrosome duplication. Using mouse embryonic fibroblasts (MEFs) in which Cdk2 has been genetically deleted, we show here that CDK2 is not required for normal centrosome duplication, maturation and bipolar mitotic spindle formation. In contrast, Cdk2 deficiency completely abrogates aberrant centrosome duplication induced by a viral oncogene. Mechanistically, centrosome overduplication in MEFs wild-type for Cdk2 involves the formation of supernumerary immature centrosomes. These results indicate that normal and abnormal centrosome duplication have significantly different requirements for CDK2 activity and point to a role of CDK2 in licensing centrosomes for aberrant duplication. Furthermore, our findings suggest that CDK2 may be a suitable therapeutic target to inhibit centrosome-mediated chromosomal instability in tumor cells.

Animals↗

Decompressive craniectomy with lattice duraplasty.

A method of opening dura for decompressive craniectomies is described. Numerous cuts intersecting in a lattice pattern allow the dura to expand in a gradual and controlled manner minimising the chances of cortical laceration or venous kinking on the craniectomy edge.

Adult↗

Area-level characteristics and smoking in women.

OBJECTIVES: This study examined whether area-level characteristics are associated with individual smoking behavior among women. METHODS: Analyses included 648 women enrolled as control patients in the Carolina Breast Cancer Study (1993-1996). Smoking and covariate information was obtained from interviews. Area-level characteristics included census block-group education level, poverty, unemployment, car-home ownership, crowding, and, for 431 women, city-level crime rates. RESULTS: In multivariate logistic regression models, no area characteristics were clearly associated with a history of smoking. Among those who had ever smoked, continued smoking was associated with living in low-education areas (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.0, 2.9), high-unemployment areas (OR = 1.7, 95% CI = 1.0, 2.8), and high-crime areas (OR = 1.6, 95% CI = 0.8, 3.2). CONCLUSIONS: The present findings are consistent with a growing literature suggesting that area-level social and economic disadvantage influences individual smoking behavior.

Adult↗

Radiologic placement of central venous catheters: rates of success and immediate complications in 3412 cases.

OBJECTIVE: To determine the success and immediate complication rates associated with 3412 central venous catheter placements performed in an interventional radiology suite. METHODS: Success and immediate complication rates were prospectively recorded for 3412 consecutive patients who had central venous catheters radiologically placed at a tertiary care centre between July 1993 and October 2000. The indication for placement and the insertion site were also recorded. RESULTS: The most common indication for both short- and long-term venous access was hemodialysis, and the right internal jugular vein was the most common site for catheter insertion. Placement was successful for 98.8% of tunnelled lines and 99.3% of temporary catheters. The rate for immediate complications (including pneumothorax, air emboli, bleeding and arterial puncture) for tunnelled catheter placements was 3.8% and for temporary catheter placements was 1.6%; no major complications were documented. CONCLUSION: Our results lend further evidence to the claim that the success and immediate complication rates of radiologically placed central venous catheters compare favourably with blind placement and surgical placement of central venous catheters.

Adolescent↗

Correlates of the "western" and "prudent" diet patterns in the us.

PURPOSE: Underlying the diversity and changeability of US eating habits are fundamental dietary patterns shaped by common sociohistorical experiences. Currently, little is known of what patterns exist or their associations with sociodemographic/lifestyle factors. We examined these issues in third National Health and Nutrition Examination Survey data.METHODS: Analyses were based on 5,794 US-born, white participants. Interviews included a 60-item food frequency questionnaire (FFQ) and questions on sociodemographics and health behaviors. Dietary patterns were identified by principal components analysis on FFQ responses. Component scores representing intake level of each pattern were dichotomized at the median. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: We identified two primary dietary patterns-a "western" pattern characterized by processed and red meats, eggs, potatoes, and refined grains, and a "prudent" pattern characterized by cruciferous vegetables, greens, carrots, salads, and fresh fruits. The two patterns occurred across geographic regions and in both women and men. After age- and sex-adjustment, the "western" diet was associated with rural residence (OR = 1.9, 95% CI 1.7-2.2), working class status (OR = 1.4, 95% CI 1.2-1.6), and lack of high school completion (OR = 1.6, 95% CI 1.4-1.8). The "prudent" diet was associated with high school completion (OR = 2.8, 95% CI 2.5-3.3) and behaviors reflecting greater health awareness, such as daily physical activity (OR = 2.0, 95% CI 1.8-2.2), non-smoking (OR = 2.1, 95% CI 1.8-2.4), and supplement use (OR = 1.8, 95% CI 1.6-2.0).CONCLUSIONS: The two dietary patterns resemble those found in previous US studies. Findings regarding correlates agree with social histories describing the emergence of those patterns. Principal components analysis is potentially useful for identifying fundamental dietary patterns for future investigations of diet-disease associations.

Journal Article↗

Food intake patterns and gallbladder disease in Mexican Americans.

OBJECTIVE: Results of previous studies on diet and gallbladder disease (GBD), defined as having gallstones or having had surgery for gallstones, have been inconsistent. This research examined patterns of food intake in Mexican Americans and their associations with GBD. DESIGN: Cross-sectional. SUBJECTS: The study population included 4641 Mexican Americans aged 20-74 years who participated in the 1988-94 third National Health and Nutrition Examination Survey (NHANES III). GBD was diagnosed by ultrasound. Food intake patterns were identified by principal components analysis based on food frequency questionnaire responses. Component scores representing the level of intake of each pattern were categorized into quartiles, and prevalence odds ratios (POR) were estimated relative to the lowest quartile along with 95% confidence intervals (CI). RESULTS: There were four distinct patterns in women (vegetable, high calorie, traditional, fruit) and three in men (vegetable, high calorie, traditional). After age adjustment, none were associated with GBD in women. However, men in the third (POR = 0.42, 95%CI 0.21-0.85) and fourth (POR = 0.53, 95%CI 0.28-1.01) quartiles of the traditional intake pattern were half as likely to have GBD as those in the lowest quartile. CONCLUSIONS: These findings add to a growing literature suggesting dietary intake patterns can provide potentially useful and relevant information on diet-disease associations. Nevertheless, methods to do so require further development and validation.

Adult↗

Eating frequency and risk of colorectal cancer.

Case-control studies have found elevated risk of colorectal cancer with higher eating frequency. The present analyses, the first to examine this association using prospectively collected information, utilized nationally representative data from the Epidemiologic Follow-Up Study of the First National Health and Nutrition Examination Survey (NHEFS). The study population included 9,978 subjects followed from 1982-84 to 1992. Colorectal cancer cases (n = 141) were identified by self-report, hospital records, and death certificates. Interviews conducted in 1982-84 provided information on meal and snack frequencies and covariates of interest. Relative risk (RR) of colorectal cancer and 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, gender, and race and energy, alcohol, total fat, and fiber intake. Compared with those eating < 3 times/day, those eating 3-4 times/day had an RR of 0.66 (95% CI = 0.42-1.03) and those eating > 4 times/day had an RR of 0.74 (95% CI = 0.41-1.32). The association was due to decreased risk with more meals rather than more snacks per day. Given limitations of previous studies as well as the possibility of a protective effect of higher eating frequency through improved glycemic control, the present findings suggest that the influence of eating frequency on colorectal cancer risk is more complex than has been previously supposed and merits additional study.

Adult↗

Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study.

Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson's disease, an autosomal recessive disorder that leads to abnormal copper accumulation. Given the potency and uniqueness of the anticopper action of TM and its lack of toxicity, we hypothesized that TM would be a suitable agent to achieve and maintain mild copper deficiency to impair neovascularization in metastatic solid tumors. Following preclinical work that showed efficacy for this anticopper approach in mouse tumor models, we carried out a Phase I clinical trial in 18 patients with metastatic cancer who were enrolled at three dose levels of oral TM (90, 105, and 120 mg/day) administered in six divided doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a surrogate marker for total body copper. Because anemia is the first clinical sign of copper deficiency, the goal of the study was to reduce Cp to 20% of baseline value without reducing hematocrit below 80% of baseline. Cp is a reliable and sensitive measure of copper status, and TM was nontoxic when Cp was reduced to 15-20% of baseline. The level III dose of TM (120 mg/ day) was effective in reaching the target Cp without added toxicity. TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.

Adult↗

Country of birth and prevalence of gallbladder disease in Mexican Americans.

OBJECTIVES: This research sought to describe the association between country of birth and gallbladder disease (GBD) in Mexican Americans, identify subgroups at especially high risk, and identify risk factors that may mediate a birthplace-GBD association. DESIGN: Cross-sectional. METHODS: Our study population included 4157 Mexican Americans aged 20-74 who participated in the 1988-94 third National Health and Nutrition Examination Survey. GBD was diagnosed by ultrasound. Information on country of birth, education, income, and selected GBD risk factors was obtained from interviews. Prevalence odds ratios (POR) for GBD in Mexico- vs. US-born Mexican Americans were estimated by unconditional logistic regression, along with 95% confidence intervals (CI). To evaluate the extent to which GBD risk factors mediated the birthplace-GBD association, PORs for country of birth were compared in models with and without additional covariates. RESULTS: Age-adjusted GBD prevalence was lower in Mexico- than in US-born Mexican-American women (POR = 0.70, 95% CI 0.50, 0.98) and men (POR = 0.63, 95% CI 0.40, 0.97). The difference was especially pronounced among subjects of lower socioeconomic status. Despite substantial differences in GBD risk factor distributions by birthplace, none could completely explain the prevalence difference. CONCLUSIONS: The observation that GBD prevalence is higher among US-born Mexican Americans is consistent with research showing poorer health in this group. Further research is needed to identify strategies for reducing morbidity from GBD in Mexican Americans.

Adult↗

Serum ferritin concentration and recurrence of colorectal adenoma.

Both body iron stores and dietary iron intake have been reported to increase risk of colorectal neoplasms. We assessed whether serum ferritin concentration was associated with recurrence of colorectal adenomas among 733 individuals with baseline determinations of ferritin as part of a multicenter clinical trial of antioxidant supplements for adenoma prevention. All study participants had at least one adenoma removed within 3 months before enrollment, and 269 of them developed one or more adenomas between follow-up colonoscopies conducted 1 and 4 years after enrollment. Baseline serum ferritin concentrations were analyzed both as a log-transformed continuous variable and as a categorical variable, defined as whether iron stores were nonreplete and low (ferritin < or =30 microg/liter), nonreplete and borderline (31-70 microg/liter), replete and adequate (71-160 microg/liter), or replete and high (>160 microg/liter). Analyses were based on multiple logistic regression models, including age, sex, study center, energy, alcohol, fiber, folate, and total fat intake, number of months between colonoscopic examinations, smoking status, and aspirin use. Overall, there was no statistically significant linear association between log ferritin concentration and adenoma recurrence (P = 0.33). Risk of adenoma recurrence was modestly increased among participants with ferritin concentrations >70 microg/liter relative to those with lower ferritin (odds ratio, 1.39; 95% confidence interval, 0.96-2.02). This result seemed more pronounced among women than men. Dietary intake of iron and red meat was inversely associated with adenoma recurrence among participants with replete iron stores but not consistently associated among those with nonreplete stores. Our findings suggest that any role of iron stores and dietary iron in influencing risk of colorectal adenoma recurrence is likely complex.

Adenoma↗

DNA binding and aggregation properties of the vaccinia virus I3L gene product.

The vaccinia virus I3L gene encodes a single-stranded DNA-binding protein which may play a role in viral replication and genetic recombination. We have purified native and recombinant forms of gpI3L and characterized both the DNA-binding reaction and the structural properties of DNA-protein complexes. The purified proteins displayed anomalous electrophoretic properties in the presence of sodium dodecyl sulfate, behaving as if they were 4-kDa larger than the true mass. Agarose gel shift analysis was used to monitor the formation of complexes composed of single-stranded DNA plus gpI3L protein. These experiments detected two different DNA binding modes whose formation was dependent upon the protein density. The transition between the two binding modes occurred at a nucleotide to protein ratio of about 31 nucleotides per gpI3L monomer. S1 nuclease protection assay revealed that at saturating protein densities, each gpI3L monomer occludes 9.5 +/- 2.5 nucleotides. In the presence of magnesium, gpI3L promoted the formation of large DNA aggregates from which double-stranded DNA was excluded. Electron microscopy showed that, in the absence of magnesium and at low protein densities, gpI3L forms beaded structures on DNA. At high protein density the complexes display a smoother and less compacted morphology. In the presence of magnesium the complexes contained long fibrous and tangled arrays. These results suggest that gpI3L can form octameric complexes on DNA much like those formed by Escherichia coli single-stranded DNA protein. Moreover, the capacity to aggregate DNA may provide an environment in which hybrid DNA formation could occur during DNA replication.

Cloning, Molecular↗

Enhancement of hypothermic heart preservation with fructose 1, 6-diphosphate.

BACKGROUND: We hypothesized that the addition of fructose 1, 6-diphosphate (FDP) to a hypothermic heart preservation solution could improve metabolic recovery because it has several beneficial effects. MATERIALS AND METHODS: Twenty adult Sprague-Dawley rats were used to study hypothermic heart preservation. The hearts were removed under general anesthesia and preserved at 4 degrees C in Euro-Collins solution (30 ml/kg) for 8 h. In the study group (N = 10), FDP (5 mM) was added to the Euro-Collins solution. In the control group (N = 10), no FDP was added. Heart function was studied after preservation using a working heart model. The ability of various concentrations of fructose 1,6-phosphate to passively diffuse through an egg phosphatidylcholine multilamellar vesicle (MLV) membrane bilayer was examined. RESULTS: Cardiac output ranged from 17.0 +/- 1.9 to 24.9 +/- 1.6 ml/min in the study group vs 2.0 +/- 1.0-12.3 +/- 1.7 ml/min for controls, average aortic flow was 10. 8 +/- 1.4 ml/min in the study group vs -1.3 +/- 1.6 ml/min for controls, and maximum LV generated power was 22.8 +/- 1.7 J/min vs 10.1 +/- 1.6 J/min for controls. Coronary flow, left ventricular stroke volume and stroke work, and myocardial oxygen consumption were much higher in the study group than in the control group. Coronary vascular resistance was lower in the study group than in the control group. Electron microscopic study indicated that many myocytes displayed patches of swollen mitochondria in the control group, but was rarely observed in the study group. The addition of 50 mM FDP caused substantial changes in MLV permeability. No dose of sucrose buffers outside the vesicles resulted in a significant changes of MLV permeability. CONCLUSIONS: Our results indicate that the addition of FDP to Euro-Collins solution significantly improves hypothermic rat heart preservation, and FDP appeared to cross the membrane bilayer.

Animals↗

Dietary intake and gallbladder disease: a review.

OBJECTIVE: Dietary intake has long been looked upon as a potentially modifiable risk factor for gallbladder disease (GBD), here defined as either having gallstones or having had surgery for gallstones. This paper reviews the epidemiological evidence for an association between dietary intake and GBD, focusing on six dietary factors that have received the most attention in studies in this area: energy intake, fatty acids, cholesterol, carbohydrates and fibre, calcium and alcohol. The objectives of this review are to evaluate the potential usefulness of altering the diet to prevent GBD and to consider future research in this area. DESIGN: We reviewed all English-language epidemiological studies on diet and cholelithiasis that were cross-sectional, cohort or case-control in design and that were indexed in the Medline database from 1966 to October 1997. RESULTS: A positive association was suggested with simple sugars and inverse associations with dietary fibre and alcohol. No convincing evidence was found for a role for energy intake or intake of fat or cholesterol. Variable means of ascertaining cases and inaccurate measurement of dietary intake may contribute to variation in results across studies. CONCLUSIONS: Some specific components of the diet that may affect GBD include simple sugars, fibre and alcohol, but whether risk for GBD can be reduced by altering intake of a specific dietary factor has not been established. Although no specific dietary recommendations can be made to reduce risk of GBD per se, a 'healthy' diet aimed at reducing risk of other diseases might be expected to reduce risk for GBD as well.

Alcoholic Beverages↗

Calculation of population attributable risk for alcohol and breast cancer (United States).

OBJECTIVES: Because of increasing evidence that alcohol may be causally associated with breast cancer, we reconsider the population attributable risk (PAR) for alcohol and breast cancer for the US adult female population using an effect estimate from a meta-analysis and incorporating a revised perspective on measurement error correction. METHODS: To estimate PAR, we employed a formula appropriate to use with an adjusted effect estimate. To estimate intermediate quantities needed to apply that formula, we used adjusted relative risk estimates from a previously published meta-analysis, as well as SEER cancer statistics and general population data from the third National Health and Nutrition Examination Survey. We used relative risk estimates uncorrected for measurement error. RESULTS: The estimated age-adjusted PAR for alcohol and breast cancer was 2.1%. CONCLUSIONS: Because of the modest association between alcohol and breast cancer and the generally moderate level of alcohol intake among US women, the proportion of breast cancer attributable to alcohol intake is small. Widespread efforts to reduce alcohol consumption would not have a substantial impact on breast cancer rates in this population. While selected subgroups of women might benefit from decreasing alcohol consumption, specific profiles for such women have yet to be defined and defended.

Adult↗

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD).

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg(-1) of BPD intravenously 5 min to 180 min before light treatment of 150 J cm(-2) 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction.

Animals↗