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T M Becker

Publications and source records attributed to T M Becker.

At least 19 recordsLinked to original sources
PubMed2005

Impaired inhibition of NF-kappaB activity by melanoma-associated p16INK4a mutations.

The cyclin-dependent kinase inhibitor p16INK4a has been identified as tumor suppressor and melanoma predisposition gene. While its cell cycle inhibitory ability is important in protecting cells from uncontrolled growth and possible tumor formation, other functions of p16INK4a are likely to contribute to its nature as a tumor suppressor. p16INK4a binding and inhibition of the transcription factor NF-kappaB has been shown and is consistent with the reports of abnormally increased NF-kappaB activity in various cancers including melanoma. Here, we present evidence that wild type p16INK4a binds to the NF-kappaB subunit RelA more efficiently than melanoma-associated p16INK4a mutations. Furthermore, whereas wild type p16INK4a strongly inhibits NF-kappaB transcriptional activity, a subset of melanoma-associated p16INK4a mutants show reduced NF-kappaB inhibitory function. p16INK4a does not affect NF-kappaB nuclear translocation or DNA binding, suggesting a mechanism that reduces NF-kappaB transactivation activity.

Active Transport, Cell Nucleus↗
PubMed2001

Functional impairment of melanoma-associated p16(INK4a) mutants in melanoma cells despite retention of cyclin-dependent kinase 4 binding.

PURPOSE: Melanoma-associated germ-line mutations affecting the tumor suppressor and cyclin-dependent kinase (CDK) inhibitor, CDKN2A/p16(INK4a) have been identified in >100 melanoma-prone families. To predict the melanoma risk for carriers of specific mutations, it is useful to test the function of the mutant proteins in biochemical assays; however, it is unclear how well these results correlate with their cellular effects. We examined the relationship between loss of CDK binding by mutant proteins and various measures of cellular growth in melanoma cells. EXPERIMENTAL DESIGN: The cellular activities of four melanoma-associated p16(INK4a) mutations (Arg24Pro, Ala36Pro, Met53Ile, and Val126Asp) were compared by use of inducible expression in stably transfected melanoma cells, deficient in expression of the endogenous protein, and compared with their ability to bind CDK4. RESULTS: The cell cycle-inhibitory activity of all of the mutants was profoundly reduced, and partially retained capacity for CDK4 binding in functional assays did not correlate with significant preservation of cell cycle-regulatory function. CONCLUSION: Testing of p16(INK4a) interactions with CDKs in protein-binding assays is an unreliable predictor of mutant p16(INK4a) function in cells. In addition to exhibiting reduced stability, these mutant proteins may also be defective in interaction with cellular targets other than CDKs.

Cell Division↗
PubMed2001

Serum carotenoids and risk of cervical intraepithelial neoplasia in Southwestern American Indian women.

The objective of this research was to evaluate the association between serum carotenoids and cervical intraepithelial neoplasia (CIN) among Southwestern American Indian women. Cases were American Indian women with biopsy-proven CIN II/III cervical lesions (n = 81) diagnosed between November 1994 and October 1997. Controls were American Indian women from the same clinics with normal cervical epithelium (n = 160). All of the subjects underwent interviews and laboratory evaluations. Interviews evaluated demographic information, sexual history, and cigarette smoking. Serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured by high performance liquid chromatography. Cervical human papillomavirus infection was detected using a PCR-based test. Increasing levels of alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were associated with decreasing risk of CIN II/III. In addition, the highest tertiles of beta-cryptoxanthin (odds ratio = 0.39, 95% confidence interval = 0.17-0.91) and lutein/zeaxanthin (odds ratio = 0.40, 95% confidence interval = 0.17-0.95) were associated with the lowest risk of CIN. In conclusion, specially targeted intervention efforts to increase consumption of fruits and vegetables may protect Southwestern American Indian women from developing CIN.

Adult↗
PubMed2000

Risk factors for cervical intraepithelial neoplasia in southwestern American Indian women.

The authors assessed risk factors for cervical intraepithelial neoplasia (CIN) among southwestern American Indian women using case-control methods. Cases were New Mexico American Indian women with biopsy-proven grade I (n = 190), grade II (n = 70), or grade III (n = 42) cervical lesions diagnosed between November 1994 and October 1997. Controls were American Indian women from the same Indian Health Service clinics with normal cervical epithelium (n = 326). All subjects underwent interviews and laboratory evaluations. Interviews focused on history of sexually transmitted diseases, sexual behavior, and cigarette smoking. Laboratory assays included polymerase chain reaction-based tests for cervical human papillomavirus infection, tests for gonorrhea and chlamydia, wet mounts, and serologic assays for antibodies to Treponema pallidum, herpes simplex virus, and hepatitis B and C viruses. In multiple logistic regression analysis, the strongest risk factors for CIN II/III among American Indian women were human papillomavirus type 16 infection (adjusted odds ratio (OR) = 7.6; 95% confidence interval (CI): 2.4, 23.2), any human papillomavirus infection (OR = 5.8; 95% CI: 3.3, 10.0), low income (OR = 3.3; 95% CI: 1.7, 6.2), and history of any sexually transmitted disease (OR = 2.0; 95% CI: 1.1, 3.5). Unlike previous research, this study found no strong associations between CIN and sexual activity or cigarette smoking.

Adolescent↗
PubMed2000

Data model for the elimination of matrix effects in enzyme-based flow-injection systems.

This contribution presents a new conceptional enzyme-based flow injection analysis (FIA) system for the process and quality control of food processing and biotechnological systems. It provides the determination of different analytes in distinct process media on the base of a common experimental set-up. In contrast to known comparable systems, analysis is performed without the commonly used sample preparation and dilution steps. Instead, the adaptation to the necessary measurement range is realized by optimization of intrinsic system parameters. The central principle of the work presented is the elimination of occurring interferences by the heterogeneous matrix of the process sample. Based on a particular injection mode, the application of dehydrogenases as indicator enzymes and a specially developed data model using cognitive methods, cross sensitivities of the detector as well as disturbed reaction rates of the enzymes could be almost completely compensated. Two applications are presented, the analysis of ethanol in non-alcoholic beer and the online determination of D-/L-lactate during a lactic acid fermentation, which reveal the advantage of the developed system.

Alanine Transaminase↗
PubMed2000

Contraceptive and reproductive risk factors for cervical intraepithelial neoplasia in American Indian women.

OBJECTIVES: To evaluate contraceptive and reproductive risk factors for cervical intraepithelial neoplasia (CIN) in southwestern American Indian women. METHODS: We conducted a clinic-based case-control study. Cases were American Indian women with biopsy-proven CIN I, CIN II or CIN III. Controls were from the same clinics and had normal cervical epithelium. All subjects underwent structured interviews focused on contraceptive and reproductive factors. Laboratory assays included polymerase chain reaction (PCR)-based tests for cervical human papillomavirus (HPV) infection. RESULTS: We enrolled 628 women in the study. The strongest risk factors for CIN II/III included HPV infection (adjusted odds ratio [OR] = 7.9, 95% CI : 4.7-13.2), and low income (OR = 3.1, 95% CI : 1.7-5.7). The use of an intrauterine device (IUD) ever (OR = 3.0, 95% CI : 1.4-6.1) and currently (OR = 4.1, 95% CI : 1.1-14.6), and > or = 3 vaginal deliveries (OR = 5.2, 95% CI : 2.4-11.1) were associated with CIN II/III. History of infertility was also associated with CIN II/III (OR = 2.1, 95% CI : 1.0-4.2). CONCLUSIONS: The data suggest that history of infertility, IUD use and vaginal deliveries were associated with CIN among American Indian women.

Adolescent↗
PubMed2000

Serum micronutrients and cervical dysplasia in Southwestern American Indian women.

We carried out a clinic-based case-control study to assess serum micronutrients as risk factors for cervical dysplasia among Southwestern American Indian women, a group with high rates of cervical preinvasive lesions. Cases were American Indian women with biopsy-proven cervical intraepithelial neoplasia (CIN I or CIN II/III). Controls were from the same Indian Health Service clinics with normal cervical epithelium. We interviewed women about histories of sexually transmitted diseases, sexual behavior, diet, hygienic practices, cigarette smoking, and reproductive factors. Laboratory assays included serum for retinol (vitamin A), ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), and red blood cell folate levels, DNA for human papillomavirus (HPV) typing, and tests for other sexually transmitted diseases. The strongest risks for cervical dysplasia were associated with cervical HPV infection [odds ratio (OR) = 3.2, 95% confidence interval (CI) = 2.2-4.6 and OR = 7.9, 95% CI = 4.8-13.1 for CIN I and CIN II/III, respectively]. With adjustments made for HPV infection and other relevant confounders, subjects in the lowest serum retinol quartile were at increased risk of CIN I compared with women in the highest quartile (OR = 2.3, 95% CI = 1.3-4.1). The data suggest that low serum alpha-tocopherol was associated with CIN I/III, although the adjusted OR was not statistically significant (OR = 2.0, 95% CI = 0.9-4.8). Low serum ascorbic acid and red blood cell folate were not associated with cervical dysplasia.

Adolescent↗
PubMed1999

Effect of cervical carcinoma in situ and its management on pregnancy outcome.

OBJECTIVE: To assess the effect of cervical carcinoma in situ (CIS) and its management on subsequent pregnancy outcome. METHODS: We used a population-based retrospective cohort design that included record linkage between cancer data and birth records. The Cancer Surveillance System records of women with CIS (n = 1851, 312 diagnosed during pregnancy) diagnosed between 1984 and 1992, were linked to birth certificates of their first subsequent deliveries after CIS diagnosis. The comparison group (n = 9201) was a random sample of women without CIS who gave birth during the same years. The outcome measures were preterm and low birth weight infants subsequent to CIS diagnosis and treatment. Treatments included no therapy, dilation and curettage or endocervical curettage, cryosurgery or laser vaporization, and conization. RESULTS: Women with CIS who were not treated with conization had a small increased risk of preterm delivery (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.0, 2.0) and no increased risk of low birth weight infant (OR 1.0, 95% CI 0.7, 1.6), compared with women without CIS, after adjusting for maternal smoking, race, parity, marital status, and history of induced pregnancy termination. Women with CIS who had conization were more likely to deliver premature infants (OR 1.6, 95% CI 1.2, 2.0) than women without CIS, after adjusting for the same confounding factors. The apparently increased risk of low birth weight (OR 1.8, 95% CI 1.4, 2.4) seemed to be a reflection of premature delivery. CONCLUSION: The risk of prematurity increased after conization for CIS and did not increase when women with CIS had other procedures.

Adult↗
PubMed1998

Increasing incidence of colon and rectal cancer among Hispanics and American Indians in New Mexico (United States), 1969-94.

OBJECTIVES: This study evaluates time trends in colon and rectal cancer incidence and mortality among the three major race/ethnic groups (Hispanics, American Indians, and non-Hispanic Whites) in New Mexico (United States). METHODS: We used data from the New Mexico Tumor Registry (NMTR) and computed average annual age-standardized incidence and mortality rates. Colon cancer incidence rates were further examined by anatomical subsite. Estimated annual percent change (EAPC) in incidence and mortality over time were computed using Poisson regression. RESULTS: Invasive colorectal cancer incidence rates increased from 1969-89 in all three race/ethnic groups, but decreased among non-Hispanic Whites in 1990-94, while rates continued to increase among minority populations, especially among minority men. Over the 26-year period, EAPC in colon cancer incidence among men was 3.6 percent for Hispanics, 4.7 percent for American Indians, and 0.7 percent for non-Hispanic Whites. Right-sided colon cancers were more common among American Indian women, and among all women aged 65 years and older. Mortality rates decreased steadily among non-Hispanic Whites over the study period, especially among women. CONCLUSIONS: Studies are needed to identify important modifiable risk factors and to develop strategies to increase the use of colorectal cancer screening-procedures among the minority populations.

Age Factors↗
PubMed1998

Colorectal cancer incidence and survival among Alaska Natives, 1969-1993.

BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined. METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington. RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend towards improvement over time. CONCLUSIONS: Alaska Natives had substantially higher colorectal cancer incidence rates compared to western Washington whites. Rates were particularly high for Aleut and Eskimo women. These data suggest a need for intensified secondary prevention strategies for this high-risk population, while further research is needed to identify modifiable risk factors.

Actuarial Analysis↗
PubMed1997

Differential expression of p16INK4a and p16beta transcripts in B-lymphoblastoid cells from members of hereditary melanoma families without CDKN2A exon mutations.

Mutations in the CDKN2A (p16INK4a) tumour suppressor gene on chromosome 9p21 are associated with inherited predisposition to melanoma, yet some 9p-linking hereditary melanoma families show no mutations in this gene. Splicing of CDKN2A exons 2 and 3 to an alternative first exon produces a transcript (p16beta) encoding a protein with cell cycle regulatory properties. We have analysed allele-specific expression levels of both the p16INK4a and p16beta transcripts in B-lymphoblastoid cells from 18 members of hereditary melanoma kindreds including four unrelated control individuals. In 15 of the 18 individuals examined, steady-state levels of each transcript either originated equally from each parental chromosome, or one parental chromosome was dominant for both transcripts. However, in three affected members of two 9p-linking hereditary melanoma kindreds, without exonic CDKN2A mutations, this pattern of coordinate expression was disrupted. In these individuals there was underexpression of the p16beta transcript, relative to the p16INK4a transcript, from the chromosome segregating with disease susceptibility. Loss of coordinate expression of the p16INK4a and p16beta transcripts may be an alternative genetic basis for melanoma susceptibility in certain 9p-linking kindreds.

Alternative Splicing↗
PubMed1997

Ethnic differences in uterine corpus cancer incidence and mortality in New Mexico's American Indians, hispanics and non-Hispanic whites.

BACKGROUND: Although ethnic and radical differences in uterine corpus cancer incidence and mortality have been reported worldwide, few published data have addressed the epidemiology of uterine cancer among US American Indians and Hispanics. METHODS: We reviewed uterine corpus cancer incidence and survival data from New Mexico's population-based cancer registry collected from 1969 to 1992, and examined State vital records data for uterine cancer deaths collected from 1958 to 1992, focusing on ethnic differences in occurrence and outcomes of uterine malignancies. RESULTS: Non-Hispanic white women had age-adjusted incidence rates that were substantially higher (20.8 per 100,000) than rates for Hispanics (10.3) and American Indians (6.0) over the 24-year period. Uterine cancer mortality rates were also higher for non-Hispanic whites and Hispanics than for American Indian women, although mortality rates were substantially lower than incidence rates. Five-year survival for uterine cancer was comparable among all groups for all stages combined (87.3% for non-Hispanic whites, 81.4% for Hispanics, and 84.6% for American Indians). CONCLUSIONS: Our population-based data show ethnic differences in uterine corpus cancer incidence rates for non-Hispanic white women that were double those for Hispanics, and triple those for American Indian women. Ethnic differences in survival were comparable. Aetiologic studies are warranted to investigate the dramatic ethnic differences in occurrence of uterine cancer.

Adenocarcinoma↗
PubMed1996

Decreasing rates of cervical cancer among American Indians and Hispanics in New Mexico (United States).

Minority women in New Mexico (United States)--including American Indian and Hispanic women--have shown disproportionately high incidence rates of invasive cervical cancer during the 1960s and 1970s. Several public health programs in New Mexico were directed toward early detection of cervical cellular abnormalities, particularly targeting the state's minority women. To evaluate the effectiveness of these programs, we examined the New Mexico Surveillance, Epidemiology, and End Results (SEER) data collected from 1969-92, and calculated average annual, age-specific, and age-adjusted incidence rates by ethnic group (American Indian, Hispanic, and non-Hispanic White) for five-year time intervals. We also calculated age-adjusted mortality rates for cervical cancer in the same ethnic groups using state vital records. Age-adjusted incidence rates for invasive cervical cancer show substantial temporal decreases, especially for minority women in the state. The age-adjusted incidence rate decreased by 66 percent, from 30.3 to 10.3 per 100,000 for American Indian women, and by 61 percent, from 26.1 to 10.2 per 100,000 for Hispanic women. A stage shift to earlier stages of cervical neoplasia occurred over the study period, with a substantially higher proportion of in situ compared with invasive cancers diagnosed in the most recent cf the most remote time period. The ratio of incidence rates of in situ to invasive cancers changed dramatically for both American Indian and Hispanic women. Cervical cancer mortality rates decreased steadily among Hispanic women from 1958 to 1992; the decrease among American Indian women was less stable and fluctuated due to small numbers. Ongoing targeted screening programs should help to reduce cervical cancer incidence and mortality further in New Mexico.

Adult↗
PubMed1996

Short-term fluctuations in the detection of cervical human papillomavirus DNA.

OBJECTIVE: To obtain point and cumulative prevalence estimates of cervical human papillomavirus (HPV) infection using two HPV DNA detection methods with different end point sensitivities; compare cervical swab and cervicovaginal lavage specimen collection methods for subsequent evaluation by polymerase chain reaction (PCR); and evaluate potential effects of the menstrual cycle on HPV DNA detection. METHODS: Seventy-two college women participated in a 10-week follow-up study. Cervical samples were obtained for HPV DNA detection and typing at each clinic visit, and information was collected concerning menstrual cycle and sexual and hygienic behaviors. Human papillomavirus DNA was detected by the ViraPap HPV DNA dot-blot assay and a broad-spectrum PCR HPV DNA amplification system. RESULTS: On a weekly basis, point prevalence for HPV infection by the ViraPap assay ranged from 4.2 to 9.7%, and the cumulative prevalence was 13.9%. Point prevalence by the broad-spectrum PCR assay ranged from 20.8 to 47.2%, and the cumulative HPV prevalence was 58.3%. Using cervicovaginal lavage specimens, we found lower cervical HPV prevalence estimates when compared with cervical swab specimens in the HPV PCR-based assay. No correlation between HPV DNA detection and phase of menstrual cycle was observed. CONCLUSION: Short-term HPV DNA detection is highly variable within individuals; therefore, single-point measurements of cervical HPV have limitations when assessing an individual's HPV status. The relationship between short-term and long-term HPV DNA persistence profiles may prove relevant to determining the risk of developing cervical intraepithelial neoplasia.

Adult↗
PubMed1996

Stroke risk factor knowledge in university students.

Cerebrovascular disease is the third leading cause of mortality in this country and is a leading cause of disability. To develop successful prevention programs to decrease the incidence of stroke, individuals should adopt cerebrovascular-healthy behaviors during youth, rather than in middle or old age, when risks for stroke are highest. The authors assessed the knowledge of stroke risk factors in university students presenting to a student health neurology clinic over a 14-month period. Half of the 98 students surveyed thought stress, a very weak risk factor, was a causative factor in the development of stroke. Only one third named hypertension or smoking as a risk factor. No significant gender, ethnic, or age differences were observed in student identification of stroke risk factors. These data indicate that university students have an incomplete understanding of the characteristics that are risk factors for stroke. This knowledge deficit is likely to have a negative influence on students' health behaviors.

Adolescent↗
PubMed1996

Tool-related injuries among amateur and professional woodworkers.

Although woodworking is a popular hobby and the woodworking industry employs thousands of workers nationwide, few studies have examined injuries associated with this activity, especially in relation to woodshop tool use. We conducted a survey of amateur and professional woodworkers (n = 283) in New Mexico to determine histories and rates of tool-specific injuries. Injuries associated with woodshop tool use were reported by 64% of all respondents. Hammers, chisels/gouges, and table saws were most frequently reported in association with injuries, although the highest tool-specific injury rates were associated with use of jointer-planers (4.9 injuries per 1000 person-hours of use), chisels/ gouges (3.3 injuries), and drill presses (3.1 injuries). One third reported tool use-associated injuries that were severe enough to require professional medical attention; 5% of all respondents suffered partial amputations. Courses in the safe use of shop tools may help to reduce rates of injuries among woodworkers.

Accidents, Occupational↗
PubMed1996

Ovarian cancer incidence and mortality in American Indian, Hispanic, and non-Hispanic white women in New Mexico.

Although ethnic and racial differences in ovarian cancer incidence and mortality have been reported worldwide, few published data have addressed the epidemiology of ovarian cancer among U.S. American Indians and Hispanics. We reviewed ovarian cancer incidence and survival data from New Mexico's population-based cancer registry collected from 1969 to 1992, and examined state vital records data for ovarian cancer deaths collected from 1958 to 1992, focusing on ethnic differences in occurrence and outcomes of ovarian malignancies. Non-Hispanic white women had age-adjusted incidence rates that were slightly higher (13.3/100,000) than rates for American Indians (11.4) and Hispanics (10.7) over the 24-year period. Ovarian cancer mortality rates were also higher for non-Hispanic whites than for minority women. Neither incidence rates nor mortality rates for ovarian cancer improved over the span of the study period. In addition, the stage at diagnosis did not shift substantially over time for any of the ethnic groups studied, nor did the distribution of various histopathological types shift proportionately. Only slight improvement was observed in 5-year survival over the time period of the study, with greater gains among younger (50 years old or less) versus older women. Ethnic differences in ovarian cancer incidence and mortality were apparent in our population-based data. However, our analysis indicated no reduction in ovarian cancer incidence or mortality in our state over the past quarter century and only slight improvement in 5-year survival.

Adenocarcinoma↗