Measurement of changes in soft tissue mass and fat mass with weight change: pencil- versus fan-beam dual-energy X-ray absorptiometry. Health ABC Study.
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Biomedical subjects
Publications and source records attributed to T Harris.
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BACKGROUND: TSEN (MNS33) is a low-incidence antigen in the MNS blood group system encoded by hybrid glycophorin genes. TSEN is expressed by a unique amino acid sequence that results from the junction of GPA(58) to GPB(27), if the GPB carries S antigen. Until this study, only one example of anti-TSEN had been found. Antibody screening red blood cells (RBCs) positive for both S and s (ref. No. C873) reacted with four patient sera. Initially, the RBCs had been typed as S+s+, but later were typed as S-s+ in another laboratory. Two other RBC samples, one from a volunteer blood donor (D.L.), the other from a patient whose serum contained anti-En(a)FR (J.S.), also gave anomalous results when tested with anti-S. We suspected the presence of TSEN-positive hybrids on all three RBC samples. MATERIALS AND METHODS: Reactive sera (O.B., E.C., S.K., R.F.) were tested against RBCs with normal MNS phenotypes and with TSEN-positive RBCs. The RBCs of D.L., J.S. and C873 were tested with anti-S whose reactivity with S+s+ TSEN+ RBCs had been established previously, and with the original example of anti-TSEN. Immunoblotting was performed on the C873, D.L. and J.S. RBC membranes using a monoclonal antibody to an epitope common to both glycophorin A and glycophorin B. RESULTS: The sera from O.B., E.C., S.K. and R.F. were strongly reactive on the indirect antiglobulin test with TSEN+ RBCs. The RBCs of C873, D.L. and J.S. were typed as TSEN+. Immunoblotting pattern of D.L. and C873 were consistent with TSEN heterozygotes, while that of J.S. was consistent with a TSEN homozygote. CONCLUSIONS: Based on the estimated number of screening events with C873 RBCs, the incidence of anti-TSEN is approximately 1 in 20,000 sera. The antibody is found in patients with and without documented exposure to allogeneic RBCs. All known examples of anti-TSEN are IgG, but their clinical significance is not known.
BACKGROUND: An excess of both depression and undesirable life events in first-degree relatives of probands with depression as compared with controls has been reported. This association may have reflected a familial factor in common. AIMS: To examine the familiality of life events and depression and whether there may be a common familial factor influencing vulnerability to depression and the experiencing of life events. METHOD: In a sib-pair design, 108 probands with depression and their siblings were compared with 105 healthy controls and their siblings for psychopathology and life events. RESULTS: The lifetime relative risk of depressive disorder in the siblings of depressed subjects as compared with siblings of controls was 9.74, although these groups did not differ in the life events measures. Several categories of events showed significant sibling correlations, but this was due to the same event affecting both members of the pair. CONCLUSIONS: Although depressive disorder was strongly familial, the familial effects on life events were largely explained by shared experiences. There was no evidence for a common factor influencing both depression and life events.
OBJECTIVE: To assess the relationship between impaired glucose tolerance and both vascular dementia and AD. BACKGROUND: Diabetes and abnormalities of glucose metabolism have been associated with stroke and poor cognitive function. In addition, glycoproteins and glycosylation have been postulated to be associated with the development of neuritic plaques characteristic of AD. METHODS: A historical prospective cohort study of Japanese-American men (n = 3,774), who were examined at ages 45 to 68 (1965 through 1968) and again at ages 71 to 93 (1991 through 1993). Measurements were obtained by clinical and home examinations: assessment of glucose intolerance (nonfasting 1 hour after glucose load) from 1965 through 1968 and history of diabetes diagnosed by a physician at examinations given from 1965 through 1968 and from 1976 through 1978. At the 1991 through 1993 examinations, the Cognitive Assessment Screening Instrument (CASI)-an instrument designed for use in cross-cultural settings combining features of the Folstein Mini-Mental State Examination, the Modified Mini-Mental State Examination, and the Hasegawa Dementia Screening Scale-was used. Diagnosis and classification of AD and vascular dementia were made by a consensus panel using neuropsychologic assessment data, a neurologist's evaluation, and information from a family informant. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria were used to establish dementia, and subclassification by cause was based on other published criteria. RESULTS: No association between AD and diabetes, present either 25 or 15 years previously, was found after adjustment for age and education in a multiple regression model. A significant association was found between impaired glucose tolerance at baseline and vascular dementia (p < 0.01). CONCLUSIONS: These findings confirm expected relationships between impaired glucose tolerance and stroke-related dementia but do not support an association of disordered glucose metabolism with AD.
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OBJECTIVE: To assess the efficacy and safety of an external urethral barrier for the management of mild to moderate stress urinary incontinence in adult women. METHODS: Four hundred eleven women with the symptom of stress urinary incontinence in 12 United States centers participated. Additional inclusion and exclusion criteria were applied before protocol device use, and ultimately 390 subjects began device use. Outcome measures for efficacy and safety were assessed. Efficacy was evaluated by the number of leakage episodes using a voiding diary, subjective urinary leakage severity, incontinence impact scores, and pad testing. Safety was evaluated by symptom assessment, urinalysis, urine culture, measurement of postvoid residual urine volume, vulvar cytology, vaginal culture, and (n = 81) cystometric testing. RESULTS: Efficacy was indicated by statistically significant reductions in the number of leakage episodes, subjective leakage severity scores, incontinence impact scores, and pad-test loss during device use. The data also indicated that the device was safe, as evidenced by the lack of statistically significant changes in the percentage of subjects with urinary tract infections during device use or in postvoid residual urine volume and cystometric indices. Symptoms of vulvar irritation or lower urinary tract discomfort occurred in a small percentage of subjects but were generally transient, and only three women discontinued using the device. CONCLUSION: The external urethral barrier appears to be a safe nonsurgical alternative to absorbent products for the management of mild to moderate stress urinary incontinence in adult women.
OBJECTIVES: To evaluate the validity, reliability and feasibility of the TOSCE, a new means of formative assessment for medical students, from the perspectives of examiners, simulated patients and students. DESIGN: Teams of five students rotate through five clinical stations, performing one of four tasks in turn, whilst the fifth member of the team 'rests'. SETTING: St George's Hospital Medical School, London. SUBJECTS: Third-year medical students, their examiners and simulated patients. RESULTS: All participants felt the TOSCE session had high validity although some students were unfamiliar with some subjects. Stations were double-marked and agreement rates and Cohen's Kappa ranged from 67 to 94% and 0.04-0.88, respectively. Analysis of the causes of disagreement led to improved marking schedules and enhanced reliability. CONCLUSIONS: The feasibility of the exercise as a formative assessment was demonstrated by the confidence of the staff participating both as examiners and simulated patients and from the majority of students who welcomed the learning experience.
OBJECTIVES: The prevalence of depression increases with age, as does the prevalence of higher levels of the cytokine interleukin-6 (IL-6). This analysis was performed to determine the association between increased levels of this cytokine and depression in a population-based sample. DESIGN: Cross-sectional cohort study. SETTING: Rural and urban counties in North Carolina. PARTICIPANTS: Community-dwelling older people. MEASUREMENTS: The association between IL-6 and other biologic variables with self-report depression was examined in 1686 persons aged 70 years and older in the third in-person survey wave (1991) of the Duke Established Population for Epidemiologic Studies of the Elderly (EPESE). Bivariate associations were established by the Spearman correlation, adjusted for age. A stepwise linear logistic regression model was used to derive a final model to assess multivariable effects on CES-D scores. RESULTS: Depression was correlated with IL-6 (P = .011), D-Dimer (P = .017), alpha-1-globulin (P = .023), alpha-2-globulin (P = .002), and beta globulin (P = .012). After controlling for age, race, and gender, IL-6 levels remained the only biologic variable significantly associated with depression (P = .035). CONCLUSION: These data suggest that the inflammatory marker, IL-6, is associated with depression in older people in this cross-sectional study. These results are compatible with the hypothesis of cytokine (IL-6) stimulation in geriatric depression as part of an overall immunoendocrine dysregulation.
OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a marker of cumulative estrogen exposure, is associated with cognitive function in nondemented older women. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland, Minneapolis, Minnesota, the Monongahela Valley near Pittsburgh, Pennsylvania, and Portland, Oregon. PARTICIPANTS: We evaluated 8333 older community-dwelling women enrolled in the Study of Osteoporotic Fractures who were not taking estrogen replacement. MEASUREMENTS: Calcaneal and hip BMD were measured at baseline and at follow-up (4-6 years later); vertebral fractures were ascertained radiologically at year 6. Women were administered a modified Mini-Mental State Exam, Trails B, and Digit Symbol at baseline and at follow-up. RESULTS: Compared with women with higher bone mineral density, women with low baseline BMD had up to 8% worse baseline cognitive scores (P = .001) and up to 6% worse repeat cognitive scores (P = .001), even after multivariate adjustments. For 1 SD decrease in baseline hip BMD or calcaneal BMD, women had a 32% (95% CI, 19-47%) or a 33% (95% CI, 20-48%) greater odds of cognitive deterioration (worst 10th percentile of change). Women with vertebral fractures had lower cognitive test scores and a greater odds of cognitive deterioration than those without fractures (OR = 1.29; 95% CI, 1.03-1.60). CONCLUSIONS: Women with osteoporosis, whether measured by baseline BMD, reductions in BMD, or vertebral fractures, have poorer cognitive function and greater risk of cognitive deterioration. Our findings suggest a link between two of the most common conditions affecting older women. Further understanding of this association may be important for new treatment and prevention directions.
OBJECTIVE: Infection with the hepatitis C virus (HCV) becomes chronic in 85% of the infected individuals. We studied risk factors that may predict clearance of HCV. METHODS: A case-control study compared the association between risk factors and viral clearance. Viral clearance was defined as presence of a positive HCV antibody test plus negative HCV test by polymerase chain reaction (PCR). Forty-four cases and 214 controls with persistent viremia were identified in a database of patients evaluated at the Gastroenterology Clinic of the University of New Mexico. RESULTS: Of all 258 HCV-antibody-positive patients, 17% had a negative test by PCR. The multivariate logistic regression revealed that a history of parenteral exposure and a long time interval since the most recent exposure were both associated with an increased likelihood of persistent viremia, whereas subjects who had been monogamous for longer time periods were more likely to have cleared HCV from their serum. A low serum level of ferritin also conferred protection against persistent viremia. Case and control subjects did not differ with respect to their demographic characteristics, occurrence of comorbid disease, previous medical history, occurrence of sexually transmitted diseases, blood group, and risky health or sexual practices. CONCLUSIONS: These data suggest that route of exposure and time when exposure occurred are important in the development of persistent HCV infection.
Hyperplasia of airway smooth muscle (ASM) contributes to the airway hyperresponsiveness that characterizes asthma. We have investigated the relationship between cAMP-induced growth arrest of ASM cells and thrombin-stimulated, extracellular-regulated protein kinase (ERK) activity, cyclin D1, and the restriction protein retinoblastoma. The beta(2)-adrenergic receptor agonist albuterol (100 nM) inhibited DNA synthesis after incubation with ASM for periods as brief as 1 h when these coincided with the timing of the restriction point. Inhibition of thrombin-stimulated DNA synthesis by albuterol (1-100 nM), 8-bromo-cAMP (300 microM), or prostaglandin E(2) (1 microM) was accompanied by a reduction in cyclin D1 protein levels. The ERK kinase inhibitor PD98059 (3-30 microM) attenuated thrombin-stimulated ERK phosphorylation and activity and the increase in cyclin D1 protein levels, as did albuterol (1-100 nM) or 8-bromo-cAMP (300 microM). In contrast, neither albuterol (100 nM) nor PD98059 (30 microM) reduced cyclin D1 mRNA levels between 4 and 20 h after thrombin addition, which suggests that elevation of cAMP regulates cyclin D1 by a post transcriptional mechanism. The proteasome inhibitor MG132 (30 and 100 nM) and the calpain I inhibitor N-acetyl-Leu-Leu-leucinal (10 microM) attenuated the reduction in thrombin-stimulated cyclin D1 levels in ASM exposed to albuterol (100 nM), 8-bromo-cAMP (300 microM), or the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM). Thus, the cAMP-induced arrest of ASM in the G(1) phase of the cell cycle is associated with a proteasomal degradation of cyclin D1 protein and a reduced protein retinoblastoma phosphorylation that prevents passage through the restriction point.
We have previously shown that glucocorticoids inhibit mitogen-stimulated proliferation of human cultured airway smooth muscle (ASM) cells. The present study analyzed the effect of glucocorticoids on key regulatory pathways leading to passage of cells through the restriction point of the cell cycle, including those mediated by extracellular-regulated kinases (ERK) 1 and 2; the ERK upstream regulator MAPK kinase (MEK1); cyclin D1 levels; and levels and phosphorylation of retinoblastoma protein (pRb). Fluticasone propionate, a new inhaled glucocorticoid, was at least 10-fold more potent than dexamethasone in inhibiting thrombin-stimulated DNA synthesis and increases in cell number. Thrombin-stimulated increases in the levels and hyperphosphorylation of pRb were inhibited by glucocorticoids, which also reduced thrombin-stimulated cyclin D1 protein and messenger RNA (mRNA) levels. PD98059 (10 microM), an inhibitor of MEK1 activation, markedly attenuated thrombin stimulation of ERK activity and phosphorylation, DNA synthesis, and cyclin D1 levels. However, glucocorticoids had no effect on ERK activity or phosphorylation at 5 min, 2 h, or 12 h after addition of thrombin. In conclusion, glucocorticoid-induced reduction of cyclin D1 mRNA and protein levels, and of pRb phosphorylation, is sufficient to account for inhibition of ASM proliferation. Furthermore, these inhibitory effects of glucocorticoids on cyclin D1 and pRb occur on a component of the mitogen signaling cascade that is either downstream of or parallel to the ERK pathway.
BACKGROUND: Earlier work on the protective role of social support in onset and course of depressive disorder suggested that its provision might be relevant for outcome. AIMS: To evaluate volunteer befriending as an intervention among women with chronic depression in inner London. METHOD: A randomised controlled trial, with a waiting list control design, with outcome measured as Present State Examination (PSE)-based full or partial remission after one year. RESULTS: A statistically significant effect upon remission was found for befriending. Other treatments monitored naturalistically did not relate to remission, nor did initial duration of chronic episode or comorbidity, but there was an association with initial PSE score. The findings are discussed in relation to standard drug-trial results and to another befriending intervention with the elderly. CONCLUSIONS: The results are not unpromising. Additional trials with less restricted intake conditions, and in more naturalistic general practice settings, might confirm volunteer befriending as a useful adjunct to current treatments.
BACKGROUND: Volunteer befriending promoted remission of chronic depression when clinical and other treatment variables were controlled. AIMS: To examine the role of other psychosocial factors relevant for outcome. METHOD: Factors measured at baseline interview were examined in multivariate analyses along with psychosocial factors occurring during follow-up, such as 'fresh-start' experiences and new severe events and difficulties. RESULTS: Fresh-start experiences and a standard attachment style were found to enhance chances of remission, with new severe stressors and markedly poor coping strategies liable to prevent it, with volunteer befriending continuing to play a role. CONCLUSIONS: The positive result reported in the preceding paper is unlikely to be an artefact. However, fresh-start experiences, absence of new severe stressors and standard attachment style were more important predictors of remission. This knowledge might profitably be incorporated into the evaluation of existing treatments.
OBJECTIVES: This study examined the relationship between body mass index (BMI), weight change, and arthritis in women. METHODS: Data were taken from the 1982-1984 National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study of 3617 women, aged 25 to 74 years. RESULTS: Women with a BMI greater than 32 at initial interview were at significantly higher risk of developing arthritis than women with a BMI of 19 to 21.9. Compared with stable-weight women with a BMI of less than 25, women who were obese at initial interview (BMI > 29) and who subsequently maintained their weight or gained more than 10% of their body weight were at significantly higher risk of developing arthritis. CONCLUSIONS: Attaining and maintaining a healthy weight may reduce the risk of developing arthritis.
OBJECTIVE: To examine the relationship between stressful life events and alterations in glycemic control in adults with diabetes. RESEARCH DESIGN AND METHODS: The occurrence of stressful experiences was recorded using the life Events and Difficulties Schedule of Brown and Harris in 55 adults with type 1 diabetes. The two most recent measures of glycemic control (HbA1c) were obtained from medical records, with poor glycemic control defined by the sample median (> or =7.7%). RESULTS: Subjects whose control deteriorated over time or who remained in poor glycemic control were significantly more likely to report severe personal stressors (SPS) in the month before HbA1c measurement, compared with subjects whose control remained fair or whose control improved (43 and 25% vs. 7 and 0%; P = 0.000). Subjects whose control remained fair or whose control improved were significantly more likely to report only positive life events during the same time period (80 and 11% vs. 0 and 0%, respectively; P = 0.000). Multiple regression analysis demonstrated that SPS, sex, and lack of further education were all significantly associated with either remaining in poor control or deterioration of control. CONCLUSIONS: The study has shown that recent severe stressors are associated with poorer glycemic control. Positive life events were associated with fair or improved glycemic control. This study has its limitations, and future studies should be prospective in design. While it is not always possible to avoid stress, learning to recognize and cope with stressors may help individuals with diabetes maintain good glycemic control and improve overall quality of life.
Facial images can be enhanced by application of an algorithm--the caricature algorithm--that systematically manipulates their distinctiveness (Benson & Perrett, 1991c; Brennan, 1985). In this study, we first produced a composite facial image from natural images of the six facial expressions of fear, sadness, surprise, happiness, disgust, and anger shown on a number of different individual faces (Ekman & Friesen, 1975). We then caricatured the composite images with respect to a neutral (resting) expression. Experiment 1 showed that rated strength of the target expression was directly related to the degree of enhancement for all the expressions. Experiment 2, which used a free rating procedure, found that, although caricature enhanced the strength of the target expression (more extreme ratings), it did not necessarily enhance its purity, inasmuch as the attributes of nontarget expressions were also enhanced. Naming of prototypes, of original exemplar images, and of caricatures was explored in Experiment 3 and followed the pattern suggested by the free rating conditions of Experiment 2, with no overall naming advantage to caricatures under these conditions. Overall, the experiments suggested that computational methods of compositing and caricature can be usefully applied to facial images of expression. Their utility in enhancing the distinctiveness of the expression depends on the purity of expression in the source image.
The glycosyltransferase termed GlcNAc-TIII is dedicated to the transfer of a single N-acetylglucosamine (GlcNAc) residue (the bisecting GlcNAc), to a subset of N-glycans in glycoproteins. The addition of this GlcNAc is differentially regulated during development and is induced in certain cancers, particularly in hepatic tumorigenesis. To investigate a functional role for the bisecting GlcNAc in the development of liver cancer, the Mgat3 gene that codes for GlcNAc-TIII, was inactivated by targeted gene disruption, and the susceptibility of Mgat3-/- mice to tumor induction was tested. After a single injection with diethylnitrosamine and subsequent treatment with phenobarbitol for 6 months, Mgat3+/+ and Mgat3+/- mice had grossly enlarged livers that contained numerous tumors. By stark contrast, Mgat3-/- mice had livers of normal size, and only 50% of mice had one to four small tumors. However, histological examination showed that Mgat3-/- livers had significant numbers of basophilic foci, and by 10-12 months after diethylnitrosamine injection, tumors had developed in Mgat3-/- mice. Therefore, initiation occurred in Mgat3-/- mice but progression was severely retarded. Assays for Mgat3 gene expression in tumor tissue gave an unexpected result. In contrast to the situation in the rat, hepatic tumor formation in the mouse was not accompanied by a dramatic increase of GlcNAc-TIII activity nor of glycoproteins with a bisecting GlcNAc, nor of Mgat3 gene expression in tumor tissue from wild-type mice. The data suggest that a glycoprotein factor with the bisecting GlcNAc facilitates tumor progression in liver. In the absence of the bisecting GlcNAc in Mgat3-/- mice, the factor is reduced in activity, and tumor progression is severely retarded.