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Biomedical subjects

L L Moore

Publications and source records attributed to L L Moore.

At least 19 recordsLinked to original sources

BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults.

BACKGROUND: It is unclear whether the increased risk of colon cancer associated with obesity differs for men and women, by distribution of body fat, or by location of the tumor. The primary goal of this study was to address these questions. METHODS: Eligible subjects from the Framingham Study cohort were classified according to body mass index (BMI) and waist size during two age periods: 30-54 y (n=3764) and 55-79 y (n=3802). All eligible men and women were cancer-free at baseline and had complete information on the following potential confounders: age, sex, education, height, activity, smoking, and alcohol. There were 157 incident lifetime cases of colon cancer among those followed beginning at 30-54 y of age and 149 lifetime cases among those whose follow up began at 55-79 y. Subjects were stratified further by gender, activity, and tumor location. The Cox Proportional Hazards Models were used to adjust for possible confounding by the above-described factors. RESULTS: A BMI >/=30 led to a 50% increased risk (95% CI: 0.92-2.5) of colon cancer among middle-aged (30-54 y) and a 2.4-fold increased risk (95% CI: 1.5-3.9) among older (55-79 y) adults. The BMI effect was stronger for men than for women and for cases occurring in the proximal colon. These adverse effects generally diminished when waist was added to the multivariable models. A larger waist size (>/=99.1 cm (39 in) and 101.6 cm (40 in) for women and men, respectively) was associated with a two-fold increased risk of colon cancer; this risk increased linearly with increasing waist size and was evident for both proximal and distal colon cancer. There was no attenuation of these effects when BMI was added to the multivariable models. A larger waist had a particularly adverse effect among sedentary subjects (relative risk (RR)=4.4 for middle-aged adults; RR=3.0 for older adults). CONCLUSION: These findings suggest that waist circumference is a stronger predictor of colon cancer risk than is BMI, and that central obesity is responsible for an increased risk of cancer of both the proximal and distal colon.

Adult↗

Television viewing and change in body fat from preschool to early adolescence: The Framingham Children's Study.

OBJECTIVE: To prospectively examine the relation between television watching and body fat change in children from preschool to early adolescence. METHODS: In a longitudinal study, 106 children were enrolled during preschool years (mean age 4.0 y) and followed into early adolescence (mean age 11.1 y). Parents completed an annual questionnaire on the child's television and video habits. Body mass index (BMI), triceps skinfolds, and sum of five skinfolds were recorded yearly at annual clinic visits. Longitudinal statistical analyses were carried out using mixed modeling procedures to control for potential confounding by a number of factors. RESULTS: Television watching was an independent predictor of the change in the child's BMI, triceps, and sum of five skinfolds throughout childhood. Its effect was only slightly attenuated by controlling for the baseline body fat, level of physical activity (as measured repeatedly by Caltrac accelerometer), percent of calories from fat, total calorie intake, or the parents' BMI or education. By age 11, children who watched 3.0 h or more of television per day had a mean sum of skinfolds of 106.2 mm, compared with a mean sum of skinfolds of 76.5 mm for those who watched less than 1.75 h per day (P=0.007). Furthermore, the adverse effect of television viewing was worse for those children who were also sedentary or had a higher-fat diet. CONCLUSIONS: Children who watched the most television during childhood had the greatest increase in body fat over time. Healthy lifestyle education designed to prevent obesity and its consequences should target television-watching habits of children.

Adolescent↗

HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres.

The centromere plays a critical role in the segregation of chromosomes during mitosis. In mammals, sister centromeres are resolved from one another in the G2 phase of the cell cycle. During prophase, chromosomes condense with sister centromeres oriented in a back to back configuration enabling only one chromatid to be captured by each half spindle. To study this process, we identified a centromere protein (CENP)-C-like protein, holocentric protein (HCP)-4, in Caenorhabditis elegans based on sequence identity, loss of function phenotype, and centromeric localization. HCP-4 is found in the cytoplasm during interphase, but is nuclear localized in mitosis, where it localizes specifically to the centromere. The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F-like protein, HCP-1, indicating an ordered assembly pathway. Loss of HCP-4 expression by RNA-mediated interference resulted in a failure to generate resolution of sister centromeres on chromosomes, suggesting that HCP-4 is required for sister centromere resolution. These chromosomes also failed to form a functional kinetochore. Thus, the CENP-C-like protein HCP-4 is essential for both resolution sister centromeres and attachment to the mitotic spindle.

Amino Acid Sequence↗

The feasibility of using rural health workers to determine cause of death in remote regions of Cameroon, West Africa.

The validity of the recent Global Burden of Disease Study (GBDS) was compromised by the lack of adult mortality data in developing countries, particularly in Sub-Saharan Africa. Verbal autopsies, in which health workers (HW), using questionnaires and algorithms, interview surviving family members to determine the cause of death, have proven useful in establishing priorities for the allocation of limited health care resources. Most reports, however, have come from large population centers. The feasibility of using health workers trained in verbal autopsy methodology to operate in remote rural areas of Africa has had limited testing. The records of 40 villagers who died in a Mission Hospital of the Northwest Province of Cameroon were reviewed, and the hospital discharge diagnosis, made by the attending physician, compared with that obtained by HW who administered a verbal autopsy to the family. In 70% of the cases the physician and HW were in exact agreement. Such a method, if confirmed in other studies among rural populations, may be an important approach to determining cause of death in many developing countries.

Cameroon↗

Parental eating attitudes and the development of obesity in children. The Framingham Children's Study.

OBJECTIVE: To investigate the extent to which parents' degree of dietary self-control, as measured by self-reported dietary restraint, disinhibition, and perceived hunger, affects the development of excess body fat in the child. DESIGN: Prospective observational study. SUBJECTS: Ninety-two 3-5y old children and their parents, enrolled in 1987 in the Framingham Children's Study. MEASUREMENTS: Self-reported levels of parental dietary restraint, disinhibition and perceived hunger were estimated using Stunkard and Messick's Three-Factor-Eating Questionnaire. Anthropometric measurements (height, weight and skinfold measurements at five sites) were obtained yearly for children and parents. The child's activity level was measured on multiple days each year using Caltrac accelerometers. Energy intake and percentage of calories from total fat were estimated from multiple sets of food diaries, collected each year. All analyses were adjusted for the following potential confounders: child's sex and baseline values for age, height, mean physical activity level, total calories and percentage of calories from fat as well as the educational levels of the parents at baseline. RESULTS: Over 6y, children's body fat increased linearly with increasing levels of self-reported parental disinhibition (eg 6y increase in the child's sum of five skinfolds was 34.4, 45.8 and 59.2 mm across increasing tertiles of parental disinhibition, P=0.012). Overall, children whose parents had higher dietary restraint scores had greater increases in body fatness than children whose parents had the lowest levels of restraint. When both parents had above average scores on dietary disinhibition or restraint, the children had greater increases in body fat (on all anthropometry measures) than when only one parent or when neither parent had high scores on those factors. Parental scores on the perceived hunger scale had no clear effect on body fat change of children. Since disinhibition and dietary restraint frequently co-exist, we then examined the joint effect of these two factors. The children with the greatest increases in body fat were those whose parents scored high on both factors. In the final analysis, we found that dietary restraint adversely affected the child's body fat only when associated with high parental disinhibition. CONCLUSION: This study suggests that parents who display high levels of disinhibited eating, especially when coupled with high dietary restraint, may foster the development of excess body fat in their children. This association may be mediated by direct parental role modeling of unhealthy eating behaviors, or through other indirect, and probably subconscious, behavioral consequences such as the suppression of the child's innate regulation of dietary intake.

Anthropometry↗

Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus?

Although rates of adult-onset diabetes mellitus increase with increasing obesity, there is little evidence that weight loss in overweight individuals can reduce their risk of developing diabetes. Using data from the Framingham Study, we examined the effects of sustained and nonsustained weight loss on risk of diabetes mellitus among 618 overweight (body mass index > or =27) subjects 30-50 years of age. To separate sustained from nonsustained weight loss, we examined weight change in two consecutive 8-year periods. Subjects who had stable weight (+/- 1 lb per year) during both periods served as the referent group for all analyses. Sustained weight loss led to a 37% lower risk of diabetes [relative risk (RR) = 0.63; 95% confidence interval = 0.34-1.2], and this effect was stronger for more obese (body mass index > or =29) subjects (RR = 0.38; 95% confidence interval = 0.18-0.81). Those who lost 8.1-15 lb had a 33% reduction in diabetes risk, whereas those losing more had a 51% reduction in risk. Regardless of the amount of weight lost, those who regained the lost weight had no reduction in diabetes risk (RR = 1.1 and 1.2 for those who lost 8.1-15 and >15 lb, respectively). We conclude that a modest amount of sustained weight loss can substantially reduce the risk of diabetes mellitus in overweight individuals.

Adult↗

A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus.

This study was designed to evaluate the effects of maternal obesity and diabetes mellitus on the risk of nonchromosomal congenital defects. We used data from 22,951 pregnant women enrolled in a prospective cohort study of early prenatal exposures and pregnancy outcome. The relative risks [prevalence ratios (PRs)] of major nonchromosomal congenital defects associated with obesity and diabetes, alone or in combination, were calculated using multiple logistic regression analysis. In this study, in the absence of diabetes, obese women (body mass index > or =28) had no higher risk, overall, of having an offspring with a major defect [PR = 0.95; 95% confidence interval (CI) = 0.62-1.5]. Their offspring, however, did have a higher prevalence of certain types of defects, including orofacial clefts; club foot; cardiac septal defects; and, to a lesser extent, hydrocephaly and abdominal wall defects. Women with pre-existing or gestational diabetes who were not obese also had no excess risk overall of having offspring affected by a major defect (PR = 0.98; 95% CI = 0.43-2.2), although they did have a higher prevalence of musculoskeletal defects. The pregnancies of women who were both obese and diabetic were 3.1 times as likely (95% CI = 1.2-7.6) to result in an offspring with a defect than were those of nonobese, nondiabetic women, which suggests that obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies. The defects were largely craniofacial or musculoskeletal.

Adult↗

HCP-1, a protein involved in chromosome segregation, is localized to the centromere of mitotic chromosomes in Caenorhabditis elegans.

To learn more about holocentric chromosome structure and function, we generated a monoclonal antibody (mAb), 6C4, that recognizes the poleward face of mitotic chromosomes in Caenorhabditis elegans. Early in mitosis, mAb 6C4 stains dots throughout the nucleoplasm. Later in prophase, mAb 6C4 stains structures on opposing faces of chromosomes which orient towards the centrosomes at metaphase. Colocalization with an antibody against a centromeric histone H3-like protein and the MPM-2 antibody, which identifies a kinetochore-associated phosphoepitope present in a variety of organisms, shows that the mAb 6C4 staining is present adjacent to the centromere. Expression screening using mAb 6C4 identified a protein in C. elegans that we named HCP-1 (for holocentric protein 1). We also identified a second protein from the C. elegans genome sequence database, HCP-2, that is 54% similar to HCP-1. When expression of HCP-1 is reduced by RNA interference (RNAi), staining with mAb 6C4 is eliminated, indicating that hcp-1 encodes the major mAb 6C4 antigen. RNAi with hcp-1 and hcp-2 together results in aberrant anaphases and embryonic arrest at approximately 100 cells with different amounts of DNA in individual nuclei. These results suggest that HCP-1 is a centromere-associated protein that is involved in the fidelity of chromosome segregation.

Amino Acid Sequence↗

A one year study of the macular pigment: the effect of 140 days of a lutein supplement.

A low density of macular pigment may represent a risk factor for age-related macular degeneration (AMD) by permitting greater blue light damage. This study was carried out to determine the effects on macular pigment optical density of dietary supplementation with lutein, one of the pigment constituents. Two subjects consumed lutein esters, equivalent to 30 mg of free lutein per day, for a period of 140 days. Macular pigment optical density was determined by heterochromatic flicker photometry before, during, and after the supplementation period. Serum lutein concentration was also obtained through the analysis of blood samples by high-performance liquid chromatography. Twenty to 40 days after the subjects commenced taking the lutein supplement, their macular pigment optical density began to increase uniformly at an average rate of 1.13+/-0.12 milliabsorbance units/day. During this same period, the serum concentration of lutein increased roughly tenfold, approaching a steady state plateau. The optical density curve eventually levelled off 40 to 50 days after the subjects discontinued the supplement. During the same 40 to 50 days, the serum concentration returned to baseline. Thereafter, little or no decrease in optical density was observed. The mean increases in the macular pigment optical density were 39% and 21% in the eyes of the two subjects respectively. In conclusion, the modest period of supplementation has been estimated to have produced in the subjects a 30 to 40% reduction in blue light reaching the photoreceptors, Bruch's membrane, and the retinal pigment epithelium, the vulnerable tissues affected by AMD.

Adult↗

Stage-specific expression of the Leishmania mexicana paraflagellar rod protein PFR-2.

A screen for Leishmania mexicana genes encoding promastigote-specific flagellar proteins resulted in isolation of genes encoding the major components of the paraflagellar rod. One of these, PFR-2, was characterized extensively. PFR-2 genes are present in the genome as a tandem array of three genes designated PFR-2A, PFR-2B, PFR-2C. PFR-2A and PFR-2B are encoded by a 3.1 transcript while PFR-2C is encoded by a 3.8-kb transcript that has a 3' UTR different from that of the 3.1-kb transcript. Both of these mRNAs were 15-fold more abundant in promastigotes than in amastigotes. Two transcripts immediately upstream of the locus were constitutively expressed while two downstream transcripts were fourfold more abundant in promastigotes than in amastigotes. The PFR genes will provide a good model system for analysis of stage-specific gene regulation in Leishmania as well as assist in the characterization of the function and organization of the paraflagellar rod.

Amino Acid Sequence↗

Community-acquired pneumonia in Oklahoma: characteristics and management of hospitalized Medicare beneficiaries.

The Oklahoma Foundation for Medical Quality initiated a cooperative project to evaluate the management of community-acquired pneumonia in Oklahoma Medicare beneficiaries. We reviewed the medical records of 767 patients discharged with a principal diagnosis of pneumonia during fiscal year 1993 from 20 hospitals. Of the 757 cases that met criteria for analysis, 92 (12%) died during hospitalization. There were significant differences between patients who survived and those who died with respect to patient age, admission source, and absence of indicators of severe pneumonia. Deviations from the American Thoracic Society guidelines for the treatment of community-acquired pneumonia were demonstrated with regards to the collection of routine sputum gram stains and cultures, blood cultures, and thoracentesis. We also demonstrated variations between hospitals in the timing of the first dose of antibiotic administered after admission of the patient. Based on this project, there appear to be opportunities for improvement in the care provided to patients admitted to the hospital with pneumonia.

Aged↗

Carotid endarterectomy in Oklahoma Medicare beneficiaries: patient characteristics and outcomes.

BACKGROUND AND OBJECTIVES: Ischemic stroke represents the third leading cause of death and the most common cause of permanent disability in the United States. Carotid endarterectomy has been widely utilized as a procedure to reduce the risk of stroke and represents the most commonly performed peripheral arterial surgery. This cooperative project was initiated to assess the appropriateness of carotid endarterectomies performed on Medicare beneficiaries and the postoperative outcomes (mortality and stroke) in these patients. METHODS: Retrospective review was performed on the inpatient medical records of 774 patients who underwent 813 carotid endarterectomy procedures in eight hospitals during calendar years 1993 and 1994. Medicare claims data were also analyzed for all carotid endarterectomies performed in Oklahoma during calendar years 1992 through 1995. RESULTS: A history of transient ischemic attack or stroke in the distribution of the operated carotid artery was documented in 57% of the cases. The majority of patients had preoperative ultrasound imaging of the carotid arteries and a preoperative angiogram was performed before 96% of the procedures. Accepted indications for the surgery were documented for 98% of the procedures. Stroke or death within 30 days of the date of the carotid endarterectomy occurred after 4.9% (0-8.8% by hospital) of the procedures. CONCLUSIONS: This project demonstrated considerable variation between hospitals in the outcomes of patients undergoing carotid endarterectomy and the potential for improved care of patients with regard to discharge planning, education, and use of anticoagulant or antiplatelet medications postoperatively.

Adult↗

Risk profiles for non-communicable diseases in rural and urban schoolchildren in the Republic of Cameroon.

OBJECTIVES: In developing countries, there is evidence that the median age of the population and the life expectancy at birth are increasing as a result of decreasing fertility rates and infant mortality. The result is an aging population more prone to non-communicable diseases such as diabetes, cancer, or heart disease later in life. In addition, changing lifestyle factors such as tobacco use, physical inactivity, and high fat diets, may accelerate the emergence of such chronic diseases as major causes of death and disability in these countries, particularly in urban areas. To test the premise that urban living predisposes residents to reduced activity levels, less healthy diets, cigarette smoking, elevated blood pressure, and increased body fat early in life, we studied rural/urban differences in these risk factors among schoolchildren in the Republic of Cameroon. METHODS: One hundred and nineteen Class 7 schoolchildren (50 urban and 69 rural) were interviewed concerning diet, physical activity, smoking, and alcohol use; blood pressure and anthropometric measurements were also taken. RESULTS: Physical activity among rural children was more than twice that of urban children, and most of the activity for rural children was work-related. Rural children consumed fewer foods containing fat and more fruits and vegetables. Adjusting for age, systolic and diastolic blood pressures of urban boys were higher than those of rural boys, and among urban children there was a trend toward a larger age-adjusted mean body mass index (BMI). There were no differences in alcohol or tobacco use between urban and rural children. CONCLUSIONS: In this study, urbanization was associated with a less active lifestyle and a dietary pattern that was higher in fat and lower in fruit and vegetable intake. Since risk factors for non-communicable diseases tend to appear early in life and track into adulthood, it is important to identify those children, or groups of children, with unfavorable risk profiles and to structure health education and promotion programs to modify these trends.

Adolescent↗

Teratogenicity of high vitamin A intake.

BACKGROUND: Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest. METHODS: Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. RESULTS: For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation. CONCLUSIONS: High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.

Abnormalities, Drug-Induced↗