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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 253 records · Page 14Linked to original sources

Human immunodeficiency virus infection in rural areas and small cities of the southeast: contributions of migration and behavior.

The design of education and prevention strategies to stem the spread of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in rural areas depends on having accurate patterns of risk behavior and transmission in local areas. Interviews were conducted with people in rural areas and small cities in Delaware, Florida, Georgia and South Carolina who were at least 18 years old and infected with HIV in order to describe demographic characteristics, migration patterns and risk behaviors. Interviews were conducted with 608 people. Most respondents were male (66 percent), black (63 percent of men, 85 percent of women) and had been infected through sexual contact (67 percent of men, 66 percent of women). Most (65 percent) had lived away from a rural area or small city for at least one month; of those, 71 percent had moved from an urban area. Twenty-seven percent of respondents indicated they had been infected locally. People with a history of injection drug use were less likely to have been infected locally than those who had no history of injection drug use (6 percent vs. 26 percent among men, 3 percent vs. 40 percent among women, P < 0.001). Further understanding of the role of socioeconomic factors in HIV transmission in rural areas and small cities is needed. Programs designed to prevent HIV acquisition among people living in rural areas and small cities in the Southeast should focus on sexual behavior.

Adolescent↗

EDG receptors as a therapeutic target in the nervous system.

EDG receptors are a family of closely related G-protein-coupled receptors, so-called since the first family member to be cloned is encoded by an endothelial differentiation gene. Of the six family members identified, five use lysophospholipids as their endogenous ligands. The sixth receptor, EDG-6, remains an orphan. These receptors activate multiple secondary-messenger pathways involving coupling to Gi, Gq/11, and G12/13 trimeric guanine nucleotide-binding proteins and are thought to play an important role in cell growth, development and maintenance, and cytoskeletal-dependent changes. EDG receptors are expressed in most mammalian cells and tissues, each subtype having a distinct distribution pattern, raising the possibility of tissue-specific biological roles that could be explored in drug-discovery programs. In this study the distribution of EDG-receptor mRNA within the nervous system has been investigated. As seen in peripheral tissues, these receptors appear to be discretely localized within specific brain regions and cell types. For example, EDG-1, -3, -4 receptors are confined to neuronal cells, EDG-2 receptors to white matter tracts, while EDG-5 receptors appear to be expressed in various cell types, including neuronal cells, white matter tracts, and ependymal cells. EDG-6-receptor mRNA was not detected in the nervous system. Speculation as to the role of these receptors in physiological/pathophysiological processes, particularly those involving cell development, proliferation, maintenance, migration, differentiation, plasticity, and apoptosis can be made from such distribution studies. EDG receptors located in brain neuronal cells might, for example, influence apoptosis and be involved in cell rescue following ischemic damage or during the early stages of progressive neurodegenerative diseases. Those restricted to oligodendrocytes might play a crucial role in myelination and offer a potential target in the treatment of demyelinating diseases, such as multiple sclerosis. In order to explore the role of these receptors, it is necessary to identify selective compounds. To this end we have developed an agonist-induced [35S]GTP gamma S binding assay using an HEK cell line expressing a pertussis-toxin-insensitive human-EDG-2-receptor-rat-Gi alpha 1-fusion protein. Such as assay system overcomes the problems associated with the almost ubiquitous responsiveness of mammalian cells to lysophospholipid. This assay lends itself to high throughput application, opening up the possibility of identifying compounds to further probe the therapeutic potential of EDG receptor manipulation.

Animals↗

A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1.

Although combination antiretroviral therapy has resulted in a considerable improvement in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, the emergence of resistant virus is a significant obstacle to the effective management of HIV infection and AIDS. We have developed a novel phenotypic drug susceptibility assay that may be useful in guiding therapy and improving long-term suppression of HIV replication. Susceptibility to protease (PR) and reverse transcriptase (RT) inhibitors is measured by using resistance test vectors (RTVs) that contain a luciferase indicator gene and PR and RT sequences derived from HIV-1 in patient plasma. Cells are transfected with RTV DNA, resulting in the production of virus particles that are used to infect target cells. Since RTVs are replication defective, luciferase activity is measured following a single round of replication. The assay has been automated to increase throughput and is completed in 8 to 10 days. Test results may be useful in facilitating the selection of optimal treatment regimens for patients who have failed prior therapy or drug-naive patients infected with drug-resistant virus. In addition, the assay can be used to evaluate candidate drugs and assist in the development of new drugs that are active against resistant strains of HIV-1.

Antiviral Agents↗

Genotyping of verocytotoxin-producing Escherichia coli O157: comparison of isolates of a prevalent phage type by fluorescent amplified-fragment length polymorphism and pulsed-field gel electrophoresis analyses.

We applied the high-resolution genotyping technique fluorescent amplified-fragment length polymorphism (FAFLP) analysis to 71 isolates of a single phage type (PT8) of pulsed-field gel electrophoresis (PFGE)-characterized verocytotoxin-producing Escherichia coli O157. Twenty-seven similar, but not identical, groupings were defined by both FAFLP analysis and the PFGE profiles. Given the FAFLP analysis conditions described here, these two methods exhibited equivalent discriminatory powers.

Bacteriophage Typing↗

Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice.

Galpha15 activates phospholipase Cbeta in response to the greatest variety of agonist-stimulated heptahelical receptors among the four Gq class G-protein alpha subunits expressed in mammals. Galpha15 is primarily expressed in hematopoietic cells in fetal and adult mice. We disrupted the Galpha15 gene by homologous recombination in embryonic stem cells to identify its biological functions. Surprisingly, hematopoiesis was normal in Galpha15(-/-) mice, Galpha15(-/-) Galphaq(-/-) double-knockout mice (which express only Galpha11 in most hematopoietic cells), and Galpha11(-/-) mice, suggesting functional redundancy in Gq class signaling. Inflammatory challenges, including thioglycolate-induced peritonitis and infection with Trichinella spiralis, stimulated similar responses in Galpha15(-/-) adults and wild-type siblings. Agonist-stimulated Ca(2+) release from intracellular stores was assayed to identify signaling defects in primary cultures of thioglycolate-elicited macrophages isolated from Galpha15(-/-) mice. C5a-stimulated phosphoinositide accumulation and Ca(2+) release was significantly reduced in Galpha15(-/-) macrophages. Ca(2+) signaling was abolished only in mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor couples to both Galpha15 and Galphai in vivo. Signaling evoked by other receptors coupled by Gq class alpha subunits appeared normal in Galpha15(-/-) macrophages. Despite discrete signaling defects, compensation by coexpressed Gq and/or Gi class alpha subunits may suppress abnormalities in Galpha15-deficient mice.

Animals↗

Exercise dependence, social physique anxiety, and social support in experienced and inexperienced bodybuilders and weightlifters.

OBJECTIVES: To investigate psychological correlates of exercise dependence in experienced and inexperienced bodybuilders and weightlifters. Secondary objectives included measuring social physique anxiety, bodybuilding identity, and social support among bodybuilders and weightlifters. METHODS: Thirty five experienced bodybuilders, 31 inexperienced bodybuilders, and 23 weightlifters completed the bodybuilding dependence scale, a bodybuilding version of the athletic identity measurement scale, the social physique anxiety scale, and an adapted version of the social support survey-clinical form. RESULTS: A between subjects multivariate analysis of variance was calculated on the scores of the three groups of lifters for the four questionnaires. Univariate F tests and follow up tests indicated that experienced bodybuilders scored significantly higher than inexperienced bodybuilders and weightlifters on bodybuilding dependence (p<0.001), social identity and exclusivity subscales of bodybuilding identity (p<0.001), and social support scales (p<.001), and significantly lower on social physique anxiety (p<0.001). CONCLUSION: Experienced bodybuilders exhibit more exercise dependence, show greater social support behaviour, and experience less social physique anxiety than inexperienced bodybuilders and weightlifters.

Adult↗

An epidemiological study of the relative importance of damp housing in relation to adult health.

STUDY OBJECTIVE: To examine the association between damp housing and adult health, taking into account a wide range of other factors that may influence health and could confound this relation. PARTICIPANTS AND SETTING: A general population sample of adults, aged 18-64, from Oxfordshire, Buckinghamshire, Berkshire and Northamptonshire. DESIGN: Secondary analysis of responses to a postal questionnaire survey carried out in 1997 with a 64% response rate (8889 of 13 800). Housing dampness was assessed by self report. Health was measured by responses to a series of questions including presence of asthma and longstanding illness generally, use of health services and perceived health status (the SF-36). The effect of damp was examined using the chi(2) test and one way analysis of variance. Significant associations with the various health outcomes were further explored taking into account 35 other housing, demographic, psychosocial and lifestyle variables using stepwise logistic and linear regression. MAIN RESULTS: Bivariate analyses indicated that damp was associated with the majority of health outcomes. Regression modelling however, found that being unable to keep the home warm enough in winter was a more important explanatory variable. Worry about pressure at work and to a lesser extent about money, showed an independent association with perceived health status equal to or greater than that of the housing environment, including cold housing, and that of health related lifestyles. CONCLUSIONS: This study shows that being unable to keep the home warm enough in winter is more strongly associated with health outcomes than is damp housing. However, as cold and damp housing are closely related, it is likely that their combined effects are shown in these results. The importance of worry as an independent predictor of health status needs testing in other studies. Its prevalence and relative importance suggest that it may be a significant determinant of public health.

Adolescent↗

Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals.

A workshop was held to critically discuss the need for a nonrodent species and the role of the dog in regulatory toxicity testing of pharmaceuticals; to discuss opportunities to reduce and refine the use of dogs in preclinical toxicology; and to identify a number of specific recommendations which could be feasibly achieved to move the process forward. To facilitate a preliminary evaluation of the contribution of dog studies to the risk assessment process, anonymised, unpublished data were provided from fully evaluated, repeat-dose toxicity studies in the rat and dog. Results of the International Life Sciences Institute (ILSI) Human Toxicity Project were also presented and discussed. Analysis of the data demonstrated that the dog can provide additional toxicity information, which, in some cases, was shown to be predictive for humans. Discussions indicated that there is potential for achieving a reduction in dog use and several possible approaches were identified. To further the progress of this initiative, there is a need to collate the results of pharmacology, toxicology, and clinical studies to address some of the proposed approaches. One of the outcomes of the workshop will be the establishment of a steering group to co-ordinate data collation for further analysis.

Animal Testing Alternatives↗

Changes in calcium kinetics in adolescent girls induced by high calcium intake.

To identify the mechanism/s whereby calcium retention is increased by calcium intake in adolescent girls, kinetic studies were performed using stable calcium isotope tracers. Girls (n = 10; 12 +/- 1 yr old, mean +/- SD) were studied while on a controlled diet containing a low (21.2 mmol/day) and a high (47.4 mmol/day) calcium intake, in randomized order, using a cross-over design. Studies were separated by 1 month. Calcium tracers were administered after 1 week on the study diet, orally and iv; and serum, urine, and feces were collected for the following 14 days. Tracers were measured using fast atom bombardment mass spectrometry, and kinetic data were analyzed by compartmental modeling. Biochemical markers of bone turnover were measured in serum and urine samples. On high (compared with low) calcium intake, fractional absorption did not differ, absorbed calcium increased (19.6 +/- 7.5 vs. 8.0 +/- 2.5 mmol/day, mean +/- SD, P: < 0.001), calcium excreted in urine increased (2.8 +/- 1.7 vs. 2.1 +/- 1.1 mmol/day, P: < 0.01), calcium retained in bone increased (14.5 +/- 8.9 vs. 3.2 +/- 3.6 mmol/day, P: < 0.001), bone formation did not change, and bone resorption decreased by 32%. These changes, measured by kinetics, were corroborated by changes in markers of bone turnover. We conclude that increased bone retention of calcium, with high calcium intake in adolescent girls, is attributable to an increase in absorption and a decrease in bone resorption.

Adolescent↗

Segmental cervical spine motion during orotracheal intubation of the intact and injured spine with and without external stabilization.

OBJECT: The purpose of this study was to establish a cadaveric model for evaluating cervical spine motion in both the intact and injured states and to examine the efficacy of commonly used stabilization techniques in limiting that motion. METHODS: Intubation was performed in fresh human cadavers with intact cervical spines, following the creation of a C4-5 posterior ligamentous injury. Movement of the cervical spine during direct laryngoscopy and intubation was recorded using video fluoroscopy and examined under the following conditions: 1) without external stabilization; 2) with manual in-line cervical immobilization; and 3) with Gardner-Wells traction. Subsequently, segmental motion of the occiput through C-5 (Oc-C5) was measured from digitized frames of the recorded video fluoroscopy. The predominant motion, at all levels measured in the intact spine, was extension. The greatest degree of motion occurred at the atlantooccipital (Oc-C1) junction, followed by the C1-2 junction, with progressively less motion at each more caudal level. After posterior destabilization was induced, the predominant direction of motion at C4-5 changed from extension to flexion, but the degree of motion remained among the least of all levels measured. Traction limited but did not prevent motion at the Oc-C1 junction, but neither traction nor immobilization limited motion at the destabilized C4-5 level. CONCLUSIONS: Cadaveric cervical spine motion accurately reflected previously reported motion in living, anesthetized patients. Traction was the most effective method of reducing motion at the occipitocervical junction, but none of the interventions significantly reduced movement at the subaxial site of injury. These findings should be considered when treating injured patients requiring orotracheal intubation.

Aged↗

HIV/AIDS consultations.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

A prospective study of positive tuberculin reactions in women with or at risk for HIV-1 infection. HER Study Group. HIV Epidemiology Research.

We prospectively studied 1310 women with or at risk for HIV-1 infection to assess subsequent tuberculin reactions in those with > or = 10 mm induration. Forty-seven HIV-positive and 57 negative women had tuberculin reactions > or = 10 mm induration; reversions to reactions < 10 mm occurred in 44% and 46% of those retested, respectively (P = NS). Among seropositives, reversions were associated with lower CD4+ lymphocyte count (P = 0.02). Of a total of 45 subsequent tuberculin tests in seropositive women, only two (4%) resulted in 5-9 mm induration, both at CD4+ counts < 500/mm3. Three (30%) of an additional 10 seropositive women with maximal reactions of 5-9 mm induration reported prior tuberculosis exposure, a significantly lower proportion than the 36/47 (77%) with reactions > or = 10 mm induration (P < 0.01), but not different than women with maximal reaction sizes < 5 mm (219/814, 27%). This study suggests that reversions of > or = 10 mm tuberculin reactions to 5-9 mm are rare. In HIV-positive persons, especially those with CD4+ lymphocyte counts > or = 500/mm3, reaction sizes of 5-9 mm often may not indicate Mycobacterium tuberculosis infection.

AIDS-Related Opportunistic Infections↗

Adolescent infectious disease challenges.

The 20th century brought incredible changes throughout the world and one of the most far-reaching results has been in the arena of public health, which, according to the CDC, means that people now live an average of 30 years longer. Despite these achievements, there are other diseases and health problems to handle. The expansion of world travel has led to increased chances for acquiring rare or exotic diseases. The shrinking world also means that people from other countries arriving in the U.S. bring the risk of new and re-emerging strains of old pathogens and other health problems. The ease of accessibility of antibacterial products means that their overuse and misuse continues to add to the ever-growing problem of drug-resistant bacteria. Gaps in adolescent immunization schedules and adolescent risk-taking behaviors are still at alarming levels. Large percentages of adolescents are either underinsured or uninsured, leading to delays in receiving effective and complete health care. Physicians have the chance to influence adolescent behaviors, and play and important role in helping to reduce these risks through informed decision making for these adolescents.

Adolescent↗