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Biomedical subjects

G Nelson

Publications and source records attributed to G Nelson.

At least 19 recordsLinked to original sources

Effect of dietary conjugated linoleic acid (CLA) on metabolism of isotope-labeled oleic, linoleic, and CLA isomers in women.

The purpose of this study was to investigate the effect of dietary CLA on accretion of 9c-18:1, 9c,12c-18:2, 10t,12c-18:2, and 9c,11t-18:2 and conversion of these FA to their desaturated, elongated, and chain-shortened metabolites. The subjects were six healthy adult women who had consumed normal diets supplemented with 6 g/d of sunflower oil or 3.9 g/d of CLA for 63 d. A mixture of 10t,2c-18:2-d4, 9c,11t-18:2-d6, 9c-18:1-d8, and 9c,12c-18:2-d2, as their ethyl esters, was fed to each subject, and nine blood samples were drawn over a 48-h period. The results show that dietary CLA supplementation had no effect on the metabolism of the deuterium-labeled FA. These metabolic results were consistent with the general lack of a CLA diet effect on a variety of physiological responses previously reported for these women. The 2H-CLA isomers were metabolically different. The relative percent differences between the accumulation of 9c,11t-18:2-d6 and 10t,12c-18:2-d4 in plasma lipid classes ranged from 9 to 73%. The largest differences were a fourfold higher incorporation of 10t,12c-18:2-d4 than 9c,11t-18:2-d6 in 1-acyl PC and a two- to threefold higher incorporation of 9c,11t-18:2-d6 than 10t,12c-18:2-d4 in cholesterol esters. Compared to 9c-18:1-d8 and 9c,12c-18:2-d2, the 10t,12c-18:2-d4 and 9c,11t-18:2-d6 isomers were 20-25% less well absorbed. Relative to 9c-18:1, incorporation of the CLA isomers into 2-acyl PC and cholesterol ester was 39-84% lower and incorporation of 10t,12c-18:2 was 50% higher in 1-acyl PC. This pattern of selective incorporation and discrimination is similar to the pattern generally observed for trans and cis 18:1 positional isomers. Elongated and desaturated CLA metabolites were detected. The concentration of 6c,10t,12c-18:3-d4 in plasma TG was equal to 6.8% of the 10t,12c-18:2-d4 present, and TG was the only lipid fraction that contained a CLA metabolite present at concentrations sufficient for reliable quantification. In conclusion, no effect of dietary CLA was observed, absorption of CLA was less than that of 9c-18:1, CLA positional isomers were metabolically different, and conversion of CLA isomers to desaturated and elongated metabolites was low.

Adsorption↗

Considering genetic profiles in functional studies of immune responsiveness to HIV-1.

Over the last two decades HIV-1 has spread worldwide and has now surpassed malaria as the leading cause of infectious disease mortality in adults (http://www.who.int/infectious-disease-report/pages/ch1text.html). The clinical course and outcome of HIV-1 infection are highly variable among individuals. Most individuals infected with HIV develop AIDS within 10 years. However about 1-5% remain relatively healthy for 15 years or more (long-term nonprogressors), while others progress to AIDS within the first 2-3 years after infection (rapid progressors). A small number of individuals are resistant to infection, while some individuals appear to eliminate the virus. Factors that influence susceptibility to infection and rate of disease progression are a combination of viral, host, and environmental determinants. With few exceptions, genetic resistance to infectious diseases is likely to involve a complex array of host genetic effects involving variants that have very subtle, but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic effects on HIV-1 disease, yet we likely have uncovered only a fraction of the total picture. The greater our knowledge of various effects on HIV disease, the more likely we will be able to predict disease outcome on an individual-by-individual basis. While this may seem obvious, there is no standard practice of taking into account the genetic profile (i.e. genotypes at loci known to associate with rate of AIDS progression) of subjects used in functional studies of immune responsiveness to HIV-1. Here, we propose an approach for assessing overall genetic risk on an individual basis, and suggest that this information be considered when selecting comparison groups in studies of immune responses to HIV and/or in the interpretation of data derived from such studies.

Acquired Immunodeficiency Syndrome↗

Mammalian sweet taste receptors.

The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery.

Animals↗

Validation of genetic case-control studies in AIDS and application to the CX3CR1 polymorphism.

New polymorphisms have been recently identified in CX3CR1, a coreceptor for some HIV-1 strains, one of which was associated with a strong acceleration of HIV disease progression. This effect was observed both by a case-control study involving 63 nonprogressors (NP) from the asymptomatic long-term (ALT) cohort and Kaplan-Meier analysis of 426 French seroconverters (SEROCO cohort). These results prompted us to analyze these polymorphisms in 244 nonprogressors (NPs) and 80 rapid progressors (RPs) from the largest case-control cohort known to date, the GRIV cohort. Surprisingly, the genetic frequencies found were identical for both groups under all genetic models (p >.8). The discrepancy with the previous work stemmed only from the difference between GRIV NPs versus ALT NPs. We hypothesized this might be due to the limited number of NPs in ALT (n = 63) and in this line we reanalyzed the data previously collected on GRIV for over 100 different genetic polymorphisms: we effectively observed that the genetic frequencies of some polymorphisms could vary by as much as 10% (absolute percentage) when computing them on the first 50 NP subjects enrolled, on the first 100, or on all the NPs tested (240 study subjects). This observation emphasizes the need for caution in case-control studies involving small numbers of subjects: p values should be low or other control groups should be used.However, the association of the CX3CR1 polymorphism with progression seems quite significant in the Kaplan-Meier analysis of the SEROCO cohort (426 individuals), and the difference observed with GRIV might be explained by a delayed effect of the polymorphism on disease. Further studies on other seroconverter cohorts are needed to confirm the reported association with disease progression.

CX3C Chemokine Receptor 1↗

Building value-based partnerships: toward solidarity with oppressed groups.

We propose a value-based conceptualization of partnership, defining partnership as relationships between community psychologists, oppressed groups, and other stakeholders, which strive to achieve key community psychology values (caring, compassion, community, health, self-determination, participation, power-sharing, human diversity, and social justice). These values guide partnership work related to the development of services or supports, coalitions and social action, and community research and program evaluation. We prescribe guidelines for building such partnerships and conclude by considering some of the challenges in implementing value-based partnerships.

Community Health Planning↗

Unexpected surface chemistry in capillaries for electrophoresis.

Good and reproducible capillary quality is needed to develop robust methods and to facilitate method transfer in CE. Physical surface defects no longer play a major role in variability of fused-silica capillaries. Nevertheless, problems are frequently being reported when buffers in the pH range between 4 and 7 are used. Thus the surface chemistry has been studied by X-ray photoelectron spectroscopy. Silicon-carbon bindings have been found on inner capillary surfaces for electrophoresis. This binding type is not completely removed by pre-conditioning with 1 M NaOH for 30 min. This corresponds to the result, that capillaries provide more stable migration times, especially in the pH range 4-7, when they are pre-conditioned for longer than 1 h. The origin of this Si-C bond is still not quite clear. They could be caused by graphite which is used during the fabrication of the raw cylinders prior to capillary drawing. Further investigations are intended in order to understand if there are any differences in surface carbon content from batch to batch and if this can influence experimental results in CE. A better understanding of the surface chemistry should not only improve robustness in CE, but also help to facilitate and accelerate capillary pre-conditioning and rinsing procedures to remove strongly adsorbed analytes or matrices.

Electrophoresis, Capillary↗

Programs for the promotion of family wellness and the prevention of child maltreatment: a meta-analytic review.

OBJECTIVE: The objectives were to determine the effectiveness of programs in promoting family wellness and preventing child maltreatment and to identify factors that moderate program success. METHOD: Meta-analysis, employing a 3-step model testing procedure, was used to review 56 programs designed to promote family wellness and prevent child maltreatment. RESULTS: The effect sizes for proactive interventions were larger at follow-up than at post-assessment, while the effect sizes for reactive interventions were higher at post-assessment than follow-up. The lowest effect sizes for home visitation programs on child maltreatment were for programs with 12 or fewer visits and less than a 6-month duration. Intensive family preservation programs with high levels of participant involvement, an empowerment/strengths-based approach, and a component of social support had higher effect sizes than programs without those elements. Also, both home visitation and intensive family preservation interventions achieved higher effect sizes with participants of mixed socioeconomic status (SES) than participants with low SES. CONCLUSIONS: The total mean weighted effect size was .41, indicating that outcomes for the intervention group exceed 66% of those in control/comparison groups. The findings from this review demonstrated that child maltreatment can be prevented and that family wellness can be promoted.

Adult↗

Risk of mesothelioma from exposure to crocidolite asbestos: a 1995 update of a South African mortality study.

OBJECTIVE: To find the risk of developing mesothelioma in a cohort born in 1916-36 in Prieska, Northern Cape Province, South Africa. METHODS: A birth cohort mortality study was carried out in a small town in the Northern Cape Province, South Africa, with a history of crocidolite asbestos mining and milling. The cohort comprised all white births registered in the magisterial district of Prieska from 1916 to 1936, inclusive (2390). Causes of death due to mesothelioma and other cancers as recorded on medical certificates of cause of death were investigated. Person-years analysis was used to calculate mortalities due to mesothelioma, other respiratory cancers, and other non-respiratory cancers. Proportional cancer mortalities were also calculated for mesothelioma and other specific neoplasms. RESULTS: The follow up rate for the cohort was 74.3% in 1995, and 683 traced members (38.6%) had died. Cause of death was unknown for 6.4% of deaths. There were 118 cases of cancer, 28 of them from mesothelioma, giving a cause specific mortality for mesothelioma of 277 (170-384) per 10(6) person-years. The rates for men and women were 366 and 172 per 10(6) person-years, respectively. The mortality for lung cancer (29 deaths) was 287 (135-436) per 10(6) person-years, and that for other non-respiratory cancers (60 deaths) was 593 (442-745). Two cases of laryngeal and four of colon cancer were observed. All cancer mortality, mesothelioma, and lung cancer proportional cancer mortality ratios were increased. CONCLUSION: The mortality for mesothelioma in men was twice that in women, probably because men were more likely to have had both occupational and environmental exposure to asbestos. Nevertheless, the mortality in women was still high and is probably indicative of the environmental exposure as white women were rarely employed in the asbestos industry in the Prieska area. Due to the long latency from first exposure to diagnosis of the neoplasm, the cause specific mortality in this cohort could be expected to increase rapidly over the next 10 years.

Adolescent↗

FIGO stage IIIC endometrial carcinoma with metastases confined to pelvic lymph nodes: analysis of treatment outcomes, prognostic variables, and failure patterns following adjuvant radiation therapy.

OBJECTIVES: This study was undertaken to evaluate the prognostic significance of isolated positive pelvic lymph nodes on survival and to analyze other prognostic variables, overall survival, and failure patterns in surgically staged endometrial carcinoma patients with positive pelvic lymph nodes and negative para-aortic lymph nodes following radiation therapy (RT). METHODS: Between January 1, 1987, and December 31, 1997, 782 women underwent primary treatment for uterine cancer at Indiana University Medical Center. Through a review of the medical records, we identified 58 patients with pathologic stage IIIA, 27 patients with pathologic stage IIIB, and 77 patients with pathologic stage IIIC endometrial carcinoma. Patients with pathologically positive or unsampled para-aortic lymph nodes and patients who received preoperative radiation therapy were excluded, leaving a study group of 17 patients with nodal metastases confined to pelvic lymph nodes. Thirteen patients received adjuvant pelvic RT using AP-PA or four-field technique. A median dose of 5040 cGy was delivered. Four patients received whole abdominal irradiation (WAI) delivering a median dose of 3000 cGy. Two patients received vaginal cuff boosts of 1000 and 3560 cGy to 0.5 cm from the vaginal surface mucosa via Cs-137 brachytherapy. Two patients also received adjuvant chemotherapy (cis-platinum and doxorubicin) and/or hormonal therapy (megestrol acetate). Disease-free and overall survivals were estimated using the Kaplan-Meier method of statistical analysis and prognostic variables were analyzed using the log-rank test. RESULTS: With a median follow-up of 51 months the actuarial 5-year disease-free survival was 81% and the actuarial 2-year and 5-year overall survival rates were 81 and 72%, respectively. Univariate analysis revealed that positive peritoneal cytology in conjunction with positive pelvic lymph nodes imparts a greater risk of recurrence and decreased overall survival. There were no pelvic and/or upper abdominal failures, but there were recurrences in the para-aortic lymph nodes (two patients) and distantly (two patients). CONCLUSION: Surgery followed by postoperative pelvic RT is a viable treatment option for pathologically staged stage IIIC endometrial carcinoma with disease confined to the pelvic lymph nodes. Failures in the para-aortic region suggest a possible role for extended-field RT. Patients with positive peritoneal cytology in conjunction with nodal metastasis fared poorly with pelvic RT. Studies evaluating the efficacy of WAI are ongoing. Finally, substages within FIGO stage IIIC are recommended in an effort to better understand and define treatment strategies which might be appropriate for these patients.

Actuarial Analysis↗

Radiation safety system of the B-Factory at the Stanford Linear Accelerator Center.

The radiation safety system of the B-Factory accelerator facility at the Stanford Linear Accelerator Center is described. The radiation safety system, which is designed to protect people from prompt radiation exposure due to beam operation, consists of the access control system and the radiation containment system. The access control system prevents people from being exposed to the very high radiation levels inside a beamline shielding enclosure. The access control system consists of barriers, a standard entry module at every entrance, and beam stoppers. The radiation containment system prevents people from being exposed to the radiation outside a shielding enclosure due to either normal or abnormal operation. The radiation containment system consists of power limiting devices, shielding, dump and collimator, and an active radiation monitoring system. The inter-related elements for the access control system and radiation containment system, as well as the associated interlock network, are described. The policies and practices used in establishing the radiation safety system are also compared with the regulatory requirements.

California↗

Intra-arterial Cereport (RMP-7) and carboplatin: a dose escalation study for recurrent malignant gliomas.

OBJECTIVE: Animal and human studies have shown increased delivery of radiolabeled compounds across the blood-brain-tumor barrier using intra-arterial (IA) Cereport (RMP-7; Alkermes Inc., Cambridge, MA) with a radiolabeled tracer. This present study assesses the safety, tolerance, and preliminary efficacy of the IA administration of carboplatin with Cereport. METHODS: An open-label dose escalation study of IA Cereport (10-300 ng/kg) with 100 mg of IA carboplatin was conducted in 11 patients with recurrent malignant gliomas and 1 patient treated adjuvantly after radiation therapy. Tumor size and laboratory and clinical statuses were assessed. RESULTS: Adverse events were mainly neurological in nature and corresponded to the anatomic location of the tumor. Karnofsky performance scale scores did not decline, overall, for those patients who had tumor response. Tumor shrinkage was observed in three of six evaluable patients who received a dose of 300 ng/kg with durable responses of 60, 64, and 106+ weeks. CONCLUSION: Previous studies have demonstrated increased permeability in human gliomas using IA Cereport. This study demonstrates durable imaging responses using 100 mg of IA carboplatin in combination with Cereport. The drug combination in this patient population seems to be safe and acceptable, providing a novel means of antitumor dose intensification.

Adult↗

From housing to homes: a review of the literature on housing approaches for psychiatric consumer/survivors.

In this paper, we review the literature on housing for psychiatric consumer/survivors since the publication of the Nelson and Smith Fowler (1987) review more than a decade ago. First, we review research and propose a definition to contrast key features of three approaches to housing: (a) custodial, (b) supportive, and (c) supported. Second, we examine studies of the relationships between the characteristics of housing and adaptational outcomes for residents (e.g., personal empowerment). Third, we review studies which have examined out-comes for residents for these three different housing approaches. We conclude by critically reflecting on the values and research of the different approaches to housing, to make recommendations for future policy and planning, practice, and research.

Custodial Care↗

Organizational change towards the empowerment-community integration paradigm in community mental health.

As a part of a larger study of change towards the values of an empowerment-community integration paradigm in community mental health, we examined changes in 3 mental health organizations in 1 community. Using qualitative methods, we focused on: (a) change pathways, (b) organizational change outcomes, and (c) the factors which helped and hindered change outcomes. We found evidence of a paradigm shift in the values and related practices within the organizations. Our results and themes are discussed and aimed at understanding and integrating knowledge about organizational change and the empowerment-community integration paradigm in community mental health.

Community Mental Health Services↗

A quantitative comparison of dibenzo[a,l]pyrene-DNA adduct formation by recombinant human cytochrome P450 microsomes.

Dibenzo[a,l]pyrene (DB[a,l]P), an extremely potent environmental carcinogen, is metabolically activated in mammalian cells and microsomes through the fjord-region dihydrodiol, trans-DB[a,l]P-11, 12-diol, to syn- and anti-DB[a,l]P-11,12-diol-13,14-epoxides (syn- and anti-DB[a,l]PDEs). The role of seven individual recombinant human cytochrome P450s (1A1, 1A2, 1B1, 2B6, 2C9, 2E1, and 3A4) in the metabolic activation of DB[a,l]P and formation of DNA adducts was examined by using (32)P postlabeling, thin-layer chromatography, and high-pressure liquid chromatography. We found that, in the presence of epoxide hydrolase, only P450 1A1 and P450 1B1 catalyzed the formation of DB[a,l]PDE-DNA adducts and several unidentified polar adducts. Human P450 1A1 catalyzed the formation of DB[a, l]PDE-DNA adducts and unidentified polar adducts at rates threefold and 17-fold greater than did human P450 1B1 (256 fmol/h/nmol P450 versus 90 fmol/h/nmol P450 and 132 fmol/h/nmol P450 versus 8 fmol/h/nmol P450, respectively). P450 1A1 DNA adducts were derived from both anti- and syn-DB[a,l]PDE at rates of 73 fmol/h/nmol P450 and 51 fmol/h/nmol P450, respectively. P450 1B1 produced adducts derived from anti-DB[a,l]PDE at a rate of 82 fmol/h/nmol, whereas only a small number of adducts were derived from syn-DB[a,l]PDE (0.4 fmol/h/nmol). These results demonstrated the potential of human P450 1A1 and P450 1B1 to contribute to the metabolic activation and carcinogenicity of DB[a,l]P and provided additional evidence that human P450 1A1 and 1B1 differ in their stereospecific activation of DB[a,l]P. Mol. Carcinog. 26:74-82, 1999. Published 1999 Wiley-Liss, Inc.

Animals↗

The relationship between housing characteristics, emotional well-being and the personal empowerment of psychiatric consumer/survivors.

In this research, we examine the relationships between the housing characteristics and dimensions of community adaptation for 107 psychiatric consumer/survivors. Hypotheses about which housing characteristics best predict which dimensions of adaptation were made based on previous research and theory. Using a longitudinal research design, we found, after controlling for demographic variables and prior adaptation, that the number of living companions, housing concerns, and having a private room all significantly predicted different dimensions of community adaptation. The findings partially support our theoretical expectations and illuminate the relationship between physical, social and organizational aspects of community-based housing and the adaptation of psychiatric consumer/survivors. We discuss the implications of the results for policy and practice in providing housing for this population.

Activities of Daily Living↗