The internet and the globalisation of medical education.
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Clinical Competence↗
Biomedical subjects
R B Harris
Publications and source records attributed to R B Harris.
Joint effects of citrus peel use and black tea intake on the risk of squamous cell carcinoma of the skin.
BACKGROUND: Differences in tea drinking habits and/or citrus peel use are likely to vary by populations and could contribute to the inconsistencies found between studies comparing their consumption and cancer risk. METHODS: A population-based case-control study was used to evaluate the relationships between citrus peel use and black tea intake and squamous cell carcinoma (SCC) of the skin. Moreover, we assessed the independent and interactive effects of citrus peel and black tea in the development of SCC. RESULTS: Hot and iced teas were consumed by 30.7% and 51.8% of the subjects, respectively. Peel consumption was reported by 34.5% of subjects. Controls were more likely than were cases to report citrus peel use (odds ratio (OR) = 0.67) and hot tea intake (OR = 0.79). After adjustment for hot and iced tea intake, the ORs associated with citrus peel use were 0.55 and 0.69, respectively, whereas the corresponding adjusted ORs for hot and iced tea intake after adjustment for citrus peel use were 0.87 and 1.22 respectively. Compared with those who did not consume hot black tea or citrus peel, the adjusted ORs associated with sole consumption of hot black tea or citrus peel were 0.60 and 0.30, respectively. Subjects who reported consumption of both hot black tea and citrus peel had a significant marked decrease (OR= 0.22; 95% CI = 0.10 - 0.51) risk of skin SCC. CONCLUSION: These results indicate that both citrus peel use and strong (hot) black tea have independent potential protective effects in relation to skin SCC.
Age Distribution↗
Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults.
Risk factors for non-melanoma skin cancer among populations with evidence of precursor damage are not well described. We examined and compared risk factors associated with the development of cutaneous basal-cell (BCC) or squamous-cell (SCC) carcinoma among a group of 918 adults with significant sun damage (> or = 10 clinically assessable actinic keratoses) but no prior history of skin cancer. These adults were participants in a 5-year skin chemoprevention trial between 1985 and 1992, who had been randomized to the placebo group and followed for occurrence of skin cancer. During the study, a total of 129 first SCC and 164 first BCC lesions were diagnosed. The overall BCC and SCC incidence rates for this group of men and women, mean age 61 years, were 4,106 and 3,198 per 100,000 person-years, respectively. Different constitutional and exposure factors were independently associated with BCC compared to SCC. Only increased age independently predicted BCC occurrence among this population. In contrast, older age along with male gender, natural red hair color and adult residence in Arizona for 10 or more years independently predicted SCC occurrence. The substantial incidence of skin cancer found among this population confirms the need for active dermatological monitoring among individuals with multiple visible actinic lesions.
Adult↗
Overexpression of agouti protein and stress responsiveness in mice.
Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the beta-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.
Adrenocorticotropic Hormone↗
The regulation of total body fat: lessons learned from lipectomy studies.
Surgical removal of body fat (partial lipectomy) is a means of directly reducing fat such that metabolic and behavioral responses can be readily attributed to the lipid deficit. If total body fat is regulated, then lipectomy should trigger compensatory increases in nonexcised white adipose tissue (WAT) mass and/or regrowth at excision sites. Many species, including laboratory rats and mice, show lipectomy-induced compensatory recovery of body fat. Those animals exhibiting naturally occurring annual adiposity cycles, such as ground squirrels and hamsters, do so most impressively reaching seasonally appropriate body fat levels indistinguishable from controls. Reparation of the lipid deficit occurs without an increase in food intake, and generally through enlargement of non-excised WAT mass, rather than regrowth of excised WAT. A body fat regulatory system involving humoral and sensory neural inputs to the brain as well as sympathetic neural outputs from brain to adipose tissue is presented. Collectively, the lipectomy model appears useful for testing mechanisms controlling adiposity, or individual depot growth, and offers insight into how lipid stores fluctuate naturally.
Adipose Tissue↗
Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985-1996.
This report describes trends in the incidence of various nonmelanoma skin cancers in a region of high ultraviolet exposure. The Southeastern Arizona Skin Cancer Registry routinely identified cases of skin cancer between 1985 and 1996 through pathology logs and reports from dermatology offices and laboratories in 3 Arizona counties. The incidence rates for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) for non-Hispanic whites were 3 to 6 times higher than the incidence rates from more northern regions. The rates for non-Hispanic whites were approximately 11 times greater than rates for Hispanics. Furthermore, there was no constant increase in the incidence of nonmelanoma skin cancers. The incidence of SCC, in particular, demonstrated a plateau or even a modest decline between 1985 and 1996. Thus the incidence rates of both SCC and BCC in Arizona, although among the highest in the world, do not appear to be increasing as rapidly as predicted elsewhere.
Adolescent↗
Metabolic responses to leptin in obese db/db mice are strain dependent.
Obese, diabetic C57BL/Ks db/db mice that lack the long-form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin. Here we compared responses to leptin in two strains of db/db mice: C57BL/6J mice that are hyperglycemic and hyperinsulinemic and C57BL/Ks that are hyperglycemic and normo- or hypoinsulinemic. Chronic intraperitoneal infusion of 10 microgram leptin/day partially reversed hyperglycemia in C57BL/6J male mice but exaggerated the diabetic state of female mice. Bolus intraperitoneal injections of 40 microgram leptin/day did not effect glucose in either strain of male db/db mice, whereas chronic intraperitoneal infusion of 20 microgram leptin/day significantly reduced fasting blood glucose in male mice from both strains, especially C57BL/6J mice. Food intake, body weight, rectal temperature, and body fat did not change. Chronic intraperitoneal infusion of 10 microgram leptin/day significantly reduced body fat in lean db/+ C57BL/6J but not in C57BL/Ks mice. Thus peripherally administered leptin is active in mice that have only short-form leptin receptors, and the response is dependent on the method of leptin administration and the background strain.
Adipose Tissue↗
Changes in rat adipocyte and liver glucose metabolism following repeated restraint stress.
Rats exposed to repeated restraint weigh less than controls even 8 weeks after stress. Stress-induced weight loss is lean tissue, but the post-stress difference in weight between control and restrained rats is lean and fat mass. Whole-body glucose clearance is enhanced 1 day after stress, but adipocyte glucose utilization is inhibited and muscle glucose transport is unchanged. The studies described here demonstrated that glucose transport was increased in both restrained and pair-fed rats, but that glycogen synthesis was increased only in restrained rats, which may account for the improved whole-body glucose clearance. Adipocyte glucose transport was inhibited and adipose plasma membrane beta-adrenergic receptor number was increased 1 day post-stress in restrained rats when weight loss was lean tissue, but were not different from control rats 5 days post-stress, when both fat and lean tissue were reduced. Thus, repeated restraint induces reversible changes in adipocyte metabolism that may represent a transition from the catabolic state of stress to a new energetic equilibrium in rats that maintain a reduced body weight for an extended period of time.
Adipocytes↗
Can Internet-based continuing medical education improve physicians' skin cancer knowledge and skills?
We sought to determine whether an Internet-based continuing medical education (CME) program could improve physician confidence, knowledge, and clinical skills in managing pigmented skin lesions. The CME program provided an interactive, customized learning experience and incorporated well-established guidelines for recognizing malignant melanoma. During a 6-week evaluation period, 354 physicians completed the on-line program as well as a pretest and an identical posttest. Use of the CME program was associated with significant improvements in physician confidence, correct answers to a 10-question knowledge test (52% vs 85% correct), and correct answers to a 15-question clinical skills test (81% vs 90% correct). We found that the overall improvement in clinical skills was due to a marked increase in specificity and a small decrease in sensitivity for evaluating pigmented lesions. User satisfaction was extremely high. This popular and easily distributed online CME program increased physicians' confidence and knowledge of skin cancer. Remaining challenges include improving the program to increase physician sensitivity for evaluating pigmented lesions while preserving the enhanced specificity.
Computer-Assisted Instruction↗
Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies.
Epidemiological studies suggest that tea drinking may reduce the risk of cardiovascular diseases and cancers. Although tea is an important source of antioxidant phytochemicals, variation in preparation techniques may translate to variation in antioxidant capacity. However, most large-scale epidemiological studies use regular food frequency questionnaires to estimate tea intake, and nationally available nutrient analysis databases do not include levels of black tea polyphenols. The Arizona Tea Questionnaire (ATQ) was designed as a tool for collecting more complete dietary tea consumption information, and a database was developed after analyzing 40 black tea samples (brewed, instant, and sun tea) for polyphenols. This study assesses the reliability and relative validity of the ATQ and polyphenol database. Relative validity of estimates of black tea consumption was tested by comparing the ATQ with the traditional Arizona Food Frequency Questionnaire and four days of food records. The ATQ was tested for reproducibility of estimates of black (hot and iced) tea consumption and levels of black tea polyphenol intake. Correlations between two measures of intake taken 2 months apart ranged from 0.72 for black hot tea to 0.86 for black sun tea. Mean intakes (range) of total flavonoids for black tea consumers were 80.8 (3.0-588.0) mg/day at the first ATQ and 102.4 (4.5-802.3) mg/day at the second ATQ (r = 0.83, P < 0.001). The ATQ provided highly reproducible estimates of both total tea consumption and individual tea polyphenol intake. This instrument may be a useful tool in studies of the associations between tea consumption, tea polyphenols intake, and risk for chronic disease.
Adult↗
Functional analysis of human ornithine decarboxylase alleles.
It has been known for > 10 years that there are two alleles of the human ornithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intron 1. We have sequenced a large portion of each of the two alleles, including some of the 5' promoter region, exon 1, intron 1, and exon 2, and determined that a single nucleotide polymorphism at base +317 (relative to transcription start site) is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in >900 North American DNA samples. On the basis of its location between two closely spaced Myc/Max binding sites (E-boxes), we speculated that the single nucleotide polymorphism at base +317 could have functional significance. Results of transfection assays with allele-specific reporter constructs support this hypothesis. The promoter/regulatory region derived from the minor ODC allele (A allele) was more effective in driving luciferase expression in these assays than the identical region from the major allele (G allele). Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposures, especially those that up-regulate c-MYC expression.
3T3 Cells↗
Identification of urocortin mRNA antisense transcripts in rat tissue.
Urocortin (UCN) has 45% sequence homology with corticotropin releasing factor (CRF) and binds to CRF receptors. We used reverse-transcriptase-polymerase chain reaction to demonstrate the presence of UCN RNA in various brain regions and in peripheral tissues. Ribonuclease protection assay (RPA) using sense and antisense riboprobes demonstrated the presence of a naturally occurring antisense UCN RNA transcript in a number of tissues. Northern blot indicated that the antisense transcript was the same size as sense UCN. RPA, using probes that covered bases 1 to 560 of 579 bp sequence of rat UCN, indicated that the antisense sequence was complementary to sense UCN but did not contain an open reading frame. Sense and antisense UCN RNA were co-expressed in all tissues that contained levels of either transcript detectable by RPA. Sense RNA expression was greater than antisense in the midbrain, the two transcripts were expressed equally in the hypothalamus and antisense was expressed at higher levels than sense in the liver, heart, and skeletal muscle. Antisense RNA expression was stress responsive, suggesting that it may play a role in regulating transcription or translation of UCN mRNA.
Animals↗
Residues F16-G33 and A784-N823 within platelet thrombospondin-1 play a major role in binding human neutrophils: evaluation by two novel binding assays.
The thrombospondin-1 (TSP1) structural requirements within its heparin-binding domain (HBD)(30 kd) or within the other domains of the molecule (450 kd) that interact with neutrophils (PMNs) have not been delineated. Synthetic peptides based on the HBD, a TSP1 proteolytic fragment lacking the HBD, a large C-terminal domain of TSP1 (210 kd), a TSP1 recombinant fragment (rTSP1(784-932)), and a monoclonal antibody directed against the TSP1 type 3 repeats (mAb D4.6) were utilized to map such structural requirements on TSP1. Synthetic peptides containing a heparin-binding motif and encompassing residues F16-G33 or A74-S95 of TSP1 competed quantitatively with iodine 125-labeled TSP1 for binding to heparinagarose beads. However, only F16-G33 was a competitor of TSP1 binding to PMNs, suggesting that the sequence F16-G33 within the HBD plays a role in PMN binding. The interaction site within the 450-kd fragment was further narrowed. A TSP1 -derived proteolytic fragment (210 kd), a recombinant TSP1 fragment (rTSP1(784-932)), and a type 3 repeat anti-TSP1 monoclonal antibody (mAb D4.6) competed for the binding of 125I-labeled TSP1 to PMNs. The N-terminal of rTSP1(784-932) and C-terminal sequence analysis of TSP1-210 kd delineated the structural requirements for the second binding region for PMNs-namely, residues A784-N823.
Amino Acid Sequence↗
Older adults need guidance to meet nutritional recommendations.
OBJECTIVE: The purpose of this study was to compare the diet of healthy, free-living senior volunteers to the dietary reference intakes (DRIs) and Food Guide Pyramid recommendations. METHODS: This study was a cross-sectional assessment of dietary habits, as measured using a standardized food frequency questionnaire, among 1,740 healthy Southwestern U.S. adults, aged 51 to 85 years. Assessment of independently-living volunteers to chemoprevention trials provides an efficient mechanism to profile typical dietary habits among the older adult population. RESULTS: Daily estimated macronutrient intakes exceeded recommended proportions of protein and fat. In contrast, more than 60% of this senior population reported dietary vitamin D, vitamin E, folate and calcium intakes below estimated average requirements (EAR). Based on the Food Guide Pyramid recommendations, fewer than 10% of the older adults consumed the recommended daily dairy and grain servings. More females than males consumed recommended vegetable (49% versus 40%) and fruit (53% versus 48%) servings (p < 0.05). More males consumed recommended grain (11% versus 7%) and protein (78% versus 73%) servings (p < 0.05) than females. CONCLUSIONS: Mean micronutrient intakes compared well with DRIs, although fewer than one-half of these older adults consumed recommended levels for vitamin D, vitamin E, folate, and calcium or daily food servings of dairy, grains, vegetables or fruits. Since the beneficial aspects of foods are not limited to essential nutrients, nutrition recommendations to older adults may be improved by emphasizing daily servings of nutrient-dense choices within the Food Pyramid.
Aged↗
Leptin--much more than a satiety signal.
Much attention has focused on the effects of leptin as a central satiety agent. There is now a significant amount of evidence that leptin is active in the periphery. This review focuses on the ability of leptin to modify insulin sensitivity, tissue metabolism, stress responses, and reproductive function. Leptin's effect on several of these systems is mediated via the hypothalamic-pituitary axis. Therefore, although in vitro studies provide evidence for direct effects on specific tissues and metabolic pathways, it is essential to consider the interactions between leptin and other regulatory factors in vivo. Little is known about the regulation of peripheral receptor expression or the production of binding proteins. Both of these factors determine the bioactivity of circulating leptin and have the potential to induce a peripheral resistance to leptin, similar to the central "leptin resistance" observed in obese subjects. Future research will clarify which of the endocrine and metabolic actions of peripheral leptin are of physiological relevance and which should be considered a pharmacological manipulation.
Adipose Tissue↗
A developmental switch affecting growth of fatty rats.
Fatty (fa/fa) rats accumulate more adipose mass than their littermates soon after birth, but they first appear obese during the fourth week of life. We analyzed the effects of fa genotype on growth of pups housed with their dams through 4 wk of age. The fa genotype effects on daily gain were undetectable from 7 to 22 days of age but became highly significant (P = 10(-18)) at 23 days of age. When litters were reduced to 4 pups, fa genotype effects on daily gain also became detectable at 23 days of age. The fa genotype effects on daily gain, stomach contents weight, liver weight, and plasma insulin of rats killed from 20 to 24 days of age displayed a marked genotype by age interaction, becoming highly significant at 23 days of age. These changes occur without the environmental changes induced by separating pups from their dams. These observations suggest that a developmental switch triggers hyperphagia and rapidly increases growth rate of fatty rats after 22 days of age.
Aging↗
Fat intake and risk of squamous cell carcinoma of the skin.
The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin.
Adult↗