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Biomedical subjects

R A Bell

Publications and source records attributed to R A Bell.

At least 19 recordsLinked to original sources

Influence of serum-free culture conditions on steroid 5alpha-reductase mRNA expression in rat C6 glioma cells.

Immunocytochemical studies previously showed that serum deprivation resulted in the appearance of steroid 5alpha-reductase (5alpha-R) in the cytoplasm of rat C6 glioma cells. To determine whether this increase in cytoplasmic 5alpha-R was due to changes in 5alpha-R gene expression, the effect of serum deprivation on 5alpha-R mRNA expression was examined. No significant change in the mRNA levels was observed in cells grown in serum-free culture medium. Therefore, the appearance of 5alpha-R immunoreactivity in the cell cytoplasm observed under serum-free conditions is probably not due to changes in 5alpha-R gene expression.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Phenylethanolamine N-methyltransferase gene expression. Sp1 and MAZ potential for tissue-specific expression.

Phenylethanolamine N-methyltransferase (PNMT) promoter-luciferase reporter gene constructs (pGL3RP863, pGL3RP444, and pGL3RP392) transfected into COS1, RS1, PC12, NIH/3T3, or Neuro2A cells showed the highest basal luciferase activity in the Neuro2A cells. DNase I footprinting with Neuro2A cell nuclear extract identified protected PNMT promoter regions spanning the -168/-165 and -48/-45 base pair Sp1/Egr-1 binding sites. Gel mobility shift assays and transient transfection assays using site-directed mutant PNMT promoter-luciferase reporter gene constructs indicated that the elevated basal luciferase activity in the Neuro2A cells was mediated by Sp-1. Furthermore, activation of the PNMT promoter by Sp1 depends on both its binding affinity for its cognate target sequences and its intracellular concentrations. When Sp1 levels were increased through an expression plasmid, luciferase reporter gene expression rose well beyond basal wild-type levels, even with either Sp1 binding element mutated. Finally, another transcription factor expressed in the Neuro2A cells competes with Sp1 by interacting with DNA sequences 3' to the -48 base pair Sp1 site to prevent Sp1 binding and induction of the PNMT promoter. The DNA consensus sequence, Southwestern analysis, and gel mobility shift assays with antibodies identify MAZ as the competitive factor. These findings suggest that Sp1 may potentially contribute to the tissue-specific expression of the PNMT gene, with the competition between Sp1 and MAZ conferring additional tissue-specific control.

Binding Sites

Direct-to-consumer prescription drug advertising and the public.

OBJECTIVE: Drug manufacturers are intensely promoting their products directly to consumers, but the impact has not been widely studied. Consumers' awareness and understanding of, attitudes toward, and susceptibility to direct-to-consumer (DTC) drug advertising were examined. DESIGN: Random-digit dialing telephone survey with a random household member selection procedure (completion and response rates, 58% and 69%, respectively). SETTING: Respondents were interviewed while they were at their residences. PARTICIPANTS: Complete data were obtained from 329 adults in Sacramento County, California. MEASUREMENTS AND MAIN RESULTS: Outcome measures included awareness of advertisements for 10 selected drugs, misconceptions about DTC advertising, attitudes toward DTC ads, and behavioral responses to such promotions. The influence of demographic characteristics, health status, attitudes, beliefs, and media exposure on awareness and behaviors was examined. On average, respondents were aware of advertisements for 3.7 of the 10 drugs; awareness varied from 8% for Buspar (buspirone) to 72% for Claritin (loratadine). Awareness was associated with prescription drug use, media exposure, positive attitudes toward DTC advertising, poorer health, and insurance status. Substantial misconceptions were revealed; e.g., 43% thought that only "completely safe" drugs could be advertised. Direct-to-consumer advertisements had led one third of respondents to ask their physicians for drug information and one fifth to request a prescription. CONCLUSIONS: Direct-to-consumer advertisements are reaching the public, but selectively so, and affecting their behaviors. Implications for public policy are examined.

Adult

Epidemiology of tobacco use among Lumbee Indians in North Carolina.

BACKGROUND: Little is known regarding tobacco use among the Lumbee Indians in southeastern North Carolina, despite high prevalence of use and ties to tobacco-related agriculture. This report describes current and early childhood tobacco use in this population. METHODS: A cross-sectional telephone survey of 400 adult Lumbee Indians was done in Pembroke, Robeson County, NC. Information was collected on demographics, tobacco use, knowledge and practices related to tobacco agriculture, and ceremonial tobacco use. RESULTS: 17.8% and 18.2% of the sample reported current and former smokeless tobacco (ST) use, and 26% and 19.5% reported current and former cigarette (CG) use, respectively. 17.3% reported ever use of both CG and ST. Current ST use was associated with older age, childhood involvement in tobacco-related agriculture, and less education. Current CG use was associated with younger age, male sex, less education, having never been married, infrequent church attendance, and fewer close friends or relatives. Early initiation of ST and CG use was more common among women, while early initiation of CG use was more common among persons who were younger and had lower levels of education. CONCLUSIONS: Current ST use is unusually common among Lumbee adults, while CG use reflects rates found in other populations. These data show different patterns of CG use and ST use, and suggest that strategies for tobacco use cessation must target each specific product.

Adolescent

The Abuela Project: safe cheese workshops to reduce the incidence of Salmonella typhimurium from consumption of raw-milk fresh cheese.

OBJECTIVES: A multiagency intervention was implemented in Yakima County, Wash, to reduce the incidence of Salmonella serotype Typhimurium infections resulting from eating queso fresco (fresh cheese) made from raw milk, a traditional food in the Hispanic diet. METHODS: A pasteurized-milk queso fresco recipe with taste and texture acceptable to the Hispanic community was developed. Trained Hispanic volunteers conducted safe cheese workshops, which were attended by more than 225 persons. RESULTS: Workshop participants' acceptance of the new recipe was excellent and positive behavior changes were maintained over 6 months. CONCLUSIONS: Educational interventions in Hispanic communities can reduce the incidence of Salmonella Typhimurium associated with eating queso fresco.

Adolescent

Predictors of failure to return for HIV test result and counseling by test site type.

The objective of this study was to determine the primary predictors of failure to return (FTR) for HIV test results and counseling by test site type from among those variables collected during the pretest, risk assessment session. The study sample consisted of 366,280 clients tested for HIV antibodies over an 18-month period at publicly funded testing sites throughout California. The FTR rate for the entire sample was 16.4%. The most significant predictor of FTR was the site type at which resting took place, with those testing at sexually transmitted disease clinics four times, and mobile testing clients over three times, more likely to fail to return than alternative test site clients. Independent predictors of FTR differed dramatically across the types of testing sites examined. Implications of these results for devising site-specific counseling strategies to reduce FTR are examined and possible effects on FTR of more rapid testing procedures and home testing are considered. Suggestions for future research are outlined.

AIDS Serodiagnosis

Abnormal urinary protein excretion in African Americans with type 2 diabetes mellitus.

The purpose of this investigation was to determine the prevalence and correlates of abnormal urinary albumin excretion and to examine the possible additive effects of cardiovascular risk factors on urinary albumin excretion in African Americans with type 2 diabetes mellitus. One hundred fifty-one African-American subjects who met WHO criteria for type 2 diabetes were included in this cross-sectional analysis. Subjects were identified through computerized medical records from a family medicine clinic and a community health center. Urinary albumin excretion ratios (UAER) were determined from overnight samples. The prevalence of abnormal urinary protein excretion was 51%. Of those with abnormal protein excretion, 36% had microalbuminuria and 15% had macroalbuminuria. Diabetes duration, waist to hip ratio, blood pressure, and total- and LDL cholesterol were significantly higher in subjects with macroalbuminuria. Regression analysis indicated that mean arterial blood pressure, diabetes duration and total cholesterol were independently associated with UAER. Mean UAER significantly increased with the addition of one or more syndrome X risk factors to pure diabetes. Our results indicate that African Americans with type 2 diabetes mellitus have a high prevalence of abnormal urinary protein excretion, which is associated with a clustering of additional cardiovascular risk factors. The fact that this increased risk was associated with hypertension indicates that screening for albuminuria in this population is essential and that a majority of African Americans with diabetes may be at risk for developing cardiovascular complications.

Albuminuria

Advertisement-induced prescription drug requests: patients' anticipated reactions to a physician who refuses.

BACKGROUND: Drug manufacturers increasingly encourage patient prescription drug demand through the use of direct-to-consumer (DTC) advertisements. We describe patients' forecasts of their reactions if their doctor were to deny an advertisement-motivated drug request and then identify significant predictors of these reactions. METHODS: We conducted a random phone survey of 329 Sacramento adults (response rate = 69%). Key outcomes were respondents' perceived likelihood of reacting to the nonfulfillment of a prescription request by becoming disappointed, trying to persuade the physician to reconsider, seeking a prescription from a different physician, and changing physicians. We also assessed associations between the likelihood of these reactions and respondents' evaluations of their physician's communication skills; attitudes toward, assumptions about the regulation of, and past responses to DTC advertising; health status; and demographic characteristics. RESULTS: Disappointment was the most likely reaction (46%). One fourth of the respondents anticipated resorting to persuasion and seeking the prescription elsewhere, while only 15% considered terminating their relationship with their physicians. Subjects who anticipated reacting in these 4 ways reported lower satisfaction with their physicians, evaluated DTC advertising more favorably, and possessed more confidence in the government's regulation of these advertisements. CONCLUSIONS: A sizable fraction of patients believed they would react negatively if their physician refused to provide a prescription for a drug advertised in the general media. Avenues for dealing effectively with patients' advertising-induced requests for prescription drugs are needed.

Adolescent

Probing the "active site" of diamine oxidase: structure-activity relations for histamine potentiation by O-alkylhydroxylamines on colonic epithelium.

The responses of the canine colonic epithelium to histamine are potentiated by O-alkylhydroxylamines. A study of a series of such compounds suggested that active compounds had the structure R-O-NH2, substitution of a nitrogen led to total loss of activity. The locus of the potentiation effect was traced to the inhibition of diamine oxidase. A new series of aliphatic and aromatic O-alkylhydroxylamines were synthesized to explore further the structure-activity relations of this effect. The potentiating effects of these compounds were determined by examining the changes in short circuit current (Isc) produced by histamine and from the activity of a soluble preparation of diamine oxidase. We found that 1) branched compounds are less active than their straight chain counterparts, 2) greater steric bulk of the aliphatic substituent decreased activity, 3) the presence of a double bond had no significant effect though a triple bond reduced activity, 4) longer straight chain compounds were less active than the shorter chain derivatives and 5) all benzylic compounds were less active than the straight chain aliphatics. O-1-benzyl was inactive however the meta or para oxygen substituted compounds as well as the O-(1-E-Cinnamyl) derivative were active. A current model for the action of diamine oxidase proposes a crucial role for a trihydroxyphenylalanine quinone cofactor as part of the active site together with a copper atom. Using molecular modeling based on our inhibition data we are able to define the region of space that is just beyond the reactive carbonyl of the trihydroxyphenylalanine residue at the active site of diamine oxidase. We suggest that a negatively charged species, such as an aspartate or a glutamate, resides in a trough about 7 to 8 A from the trihydroxyphenylalanine carbonyl carbon and this species aids in the strong selective binding of substrates such as putrescine and histamine.

Amine Oxidase (Copper-Containing)

Phenylethanolamine N-methyltransferase gene expression: synergistic activation by Egr-1, AP-2 and the glucocorticoid receptor.

The gene encoding the epinephrine synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), is transcriptionally activated by Egr-1, AP-2, and the glucocorticoid receptor (GR). Stimulation by AP-2 requires its synergistic interaction with an activated GR. The present studies show that the GR also cooperates with Egr-1 or the combination of Egr-1 and AP-2 to activate the PNMT promoter. Together Egr-1, AP-2, and the GR can induce PNMT promoter-mediated luciferase reporter gene expression beyond the sum of their independent contributions as well as synergistically activate the endogenous PNMT gene leading to marked increases in PNMT mRNA. Examination of the effects of mutation of the AP-2 or Egr-1 binding sites on PNMT promoter activation by DEX and the factor binding to the remaining intact site or by all three transcriptional activators showed changes in luciferase reporter gene expression which suggest that DNA structure may be altered thereby reducing or enhancing synergistic activation. It also appears that the -165 bp Egr-1 site may not be critical for the synergism observed between Egr-1, AP-2 and the GR. When the glucocorticoid response element (GRE) within the PNMT promoter was mutated, PNMT promoter activation by Egr-1 and DEX, AP-2 and DEX or all three showed both inhibition and enhancement, even when the GRE was completely eliminated. These observations indicate that induction of PNMT gene transcription may occur either through GR interaction with other transcriptional proteins after binding to its cognate GRE or through direct protein-protein interaction in the absence of GRE binding. While the mechanisms by which Egr-1 and the GR and Egr-1, AP-2 and the GR function cooperatively to stimulate PNMT promoter activity remain to be elucidated, this synergistic stimulation of the PNMT promoter by these factors may provide important in vivo and in vitro regulatory control of the PNMT gene.

Animals

Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study.

OBJECTIVE: Diabetic retinopathy (DR) is a major cause of visual impairment and blindness in adults. Antioxidant nutrients, such as vitamins C and E and beta-carotene, may be protective of some eye disorders, such as cataract and age-related macular degeneration, but a relationship between these nutrients and DR has yet to be defined. The purpose of this study was to examine the relation between dietary and supplement intakes of vitamins C, E, and beta-carotene and the risk of DR. DESIGN: Both cross-sectional and longitudinal data were collected from participants in the San Luis Valley Diabetes Study, including non-Hispanic white and Hispanic adults in southern Colorado. PARTICIPANTS: A total of 387 participants with type 2 diabetes completed at least 1 complete retinal examination and 24-hour dietary recall (including vitamin supplement use). MAIN OUTCOME MEASURES: Type 2 diabetes was defined according to World Health Organization criteria. DR was assessed by retinal photographs, using the Airlie House criteria to classify DR as none, background, preproliferative, or proliferative. Data for both eyes, from up to three clinic visits per participant, were used for analysis. Ordinal logistic regression analysis was used, taking advantage of multiple clinic visits by individual participants and observations from both eyes, to assess the risk for increased DR severity over time as a function of changes in intake of vitamin C, vitamin E, and beta-carotene. Six categories of intake for each nutrient (first to fourth quintiles and ninth and tenth deciles) were considered to ascertain any potential threshold effect. Analyses accounted for age, duration of diabetes, insulin use, ethnicity, glycated hemoglobin, hypertension, gender, and caloric intake. RESULTS: An increase over time in vitamin C intake from the first to ninth deciles was associated with a risk for increased severity of DR (odds ratio = 2.21, P = 0.01), although excess risk was not observed for the tenth decile or the second through fourth quintiles compared to the first quintile. Increased intake of vitamin E was associated with increased severity of DR among those not taking insulin (odds ratios = 2.69, 2.59, 3.33, 5.65, 3.79; P < 0.02, for an increase over time from the first to the second through fourth quintiles and ninth and tenth deciles, respectively). Among those taking insulin, increased intake of beta-carotene was associated with a risk for severity of DR (odds ratio = 3.31, P = 0.003, and 2.99, P = 0.002, respectively, for the ninth and tenth deciles compared to the first quintile). CONCLUSIONS: No protective effect was observed between antioxidant nutrients and DR. Depending on insulin use, there appeared to be a potential for deleterious effects of nutrient antioxidants. Further research is needed to confirm associations of nutrient antioxidant intake and DR.

Adult

Glucocorticoid-dependent action of neural crest factor AP-2: stimulation of phenylethanolamine N-methyltransferase gene expression.

AP-2 is a vertebrate transcription factor expressed in neural crest cells and their derivative tissues, including the adrenal medulla, where epinephrine is produced. AP-2 is shown to stimulate expression of the gene encoding the epinephrine biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT). However, stimulation of the PNMT gene by AP-2 requires glucocorticoids and appears to be mediated through the interaction of AP-2 with activated type II glucocorticoid receptors. Mutation of AP-2 and/or glucocorticoid receptor binding elements within the PNMT promoter disrupts the ability of AP-2 and glucocorticoids to induce PNMT promoter activity. These findings suggest, in the case of PNMT, that AP-2 stimulates gene expression through a novel glucocorticoid-dependent mechanism.

Adrenal Medulla

Body fat, fat distribution, and psychosocial factors among patients with Type 2 diabetes mellitus.

Diabetes, a risk factor for cardiovascular disease, requires lifestyle modifications (diet, exercise, weight loss). The relations between body mass index, waist-hip ratio (WHR), and psychosocial indicators, such as affect and stress, among 302 diabetic patients from a clinic and a neighborhood health center were analyzed. Data included stress and mood scale responses, body size (height, weight, and WHR) and potential confounders (physical activity, energy intake, and diabetes duration). In univariate analyses, body mass index was positively associated with stress and inversely associated with positive affect only in women. Multiple regression analyses indicated that stress was associated with body mass index and negative mood was associated with the WHR. The findings suggested that stress and affect may be important correlates of body fat among women with Type 2 diabetes, leading to more complications. Healthcare providers can help women with Type 2 diabetes lose weight and lower the risk of cardiovascular disease by recognizing and helping them deal with these psychosocial issues.

Adult

Barriers to nutritional well-being for rural elders: community experts' perceptions.

Older adults use public and private services, as well as personal resources, to meet nutritional needs. In-depth interviews conducted with 73 service providers and community experts in two rural North Carolina counties were analyzed for these experts' perceptions of barriers to adequate nutrition for older adults. Perceived barriers included characteristics of the county and programs, transportation, and kin, as well as older adult medical and economic conditions, food habits, knowledge, and attitudes. The importance given each of these domains varied by respondents' area of expertise. Community experts and providers may not see the connection between their services and nutritional well-being of older adults.

Aged

The effects of a managed care educational program on faculty and trainee knowledge, attitudes, and behavioral intentions.

PURPOSE: To assess the state of managed care knowledge and attitudes and to evaluate the effects of a two-day course on participants' knowledge, attitudes, and behavioral intentions. METHOD: In 1996, the University of California, Davis, Medical School invited all medical students, residents, faculty, and administrators to participate in one of two sessions of a two-day course on managed care. Participants in the first session were given both pre- and post-course questionnaires. Participants in the second session were given only post-course questionnaires. The questionnaires measured objective knowledge, attitudes, and behavioral intentions. Participants (other than administrators) who completed the questionnaires also received a follow-up questionnaire six months after the seminar. RESULTS: The two sessions were attended by 818 UC Davis medical students, residents, faculty, and administrators: after excluding 33 non-physician administrators, 428 completed survey packets (55%) were available for full analysis. Before the course, participants in the first session correctly answered on average only 46% of 32 questions about managed care knowledge. Course attendance was associated with significant gains in knowledge (to 67% correct, p < .001) and a marked increase in appreciation for the cost-control effectiveness of managed care (from 3.35 to 3.98 on a five-point scale, p < .001). Knowledge gains were greatest among medical students; changes in attitudes and behavioral intentions were least among residents. Among respondents to a follow-up survey, the changes were partially sustained six months later. CONCLUSION: Within this academic medical center, baseline levels of managed care knowledge were low among faculty as well as among trainees, and attitudes reflected a blend of negativism and wishful thinking. An intensive two-day educational program effectively increased knowledge and changed selected attitudes among critical academic constituencies. Other academic medical centers may wish to consider presenting similar programs in order to orient their faculties and trainees to the economic realities of the foreseeable future.

Academic Medical Centers

Medical examiner cases associated with previously undiagnosed diabetes mellitus, North Carolina, 1994.

BACKGROUND: Approximately half of the 16 million Americans with diabetes mellitus (DM) are unaware they have the disease; the epidemiology of death from previously undiagnosed DM is unclear. We report medical examiner (ME) cases of death from DM in North Carolina in 1994 to determine the number and characteristics of these cases. METHODS: Deaths from DM ICD-9 were identified and reviewed. RESULTS: Of the 42 cases ascertained from ME records, 6 had previously undiagnosed DM, 5 had diabetes ketoacidosis, and 1 had nonketotic hyperosmolar hyperglycemia. Mean patient age at death for all cases was 42 years (range, 35 years to 57 years). Four patients felt bad at least 24 hours before death, indicating that they are not technically "sudden deaths." CONCLUSIONS: We provide a limited epidemiologic perspective of the phenomenon of death from undiagnosed DM. We suggest further investigation of mortality from previously undiagnosed diabetes.

Adolescent