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Biomedical subjects

N Smith

Publications and source records attributed to N Smith.

At least 73 records · Page 4Linked to original sources
PubMed2000

Expression of penile neuronal nitric oxide synthase variants in the rat and mouse penile nerves.

Penile erection is mediated by nitric oxide (NO) synthesized by the neuronal nitric oxide synthase (nNOS). In the rat penis, the main nNOS mRNA variant, PnNOS, differs from cerebellar nNOS (CnNOS) by a 102 base pair insert encoding a 34-amino acid sequence. In the mouse, two nNOS mRNAs have been identified: nNOSalpha, encoding a 155-kDa protein, and an exon 2-deletion variant, nNOSbeta, encoding a 135-kDa protein that lacks a domain where a protein inhibitor of nNOS (PIN) binds. We wished to determine whether PnNOSalpha and beta are expressed in the rat penis and are located in the nerves and whether the beta form persists in the potent nNOS knock-out mouse (nNOS( big up tri, open big up tri, open)). A PnNOS antibody against the insert common to both PnNOSalpha and beta detected the expected 155-kDa protein in PnNOSalpha-transfected cells. This antibody, and the one common to PnNOS/CnNOS, showed (on Western blots) the 155- and 135-kDa nNOS variants in rat penile tissue during development and aging. PnNOSalpha mRNA and its subvariants were found as the main nNOS in the penile corpora, the cavernosal nerve, and the pelvic ganglia, with lower levels of PnNOSbeta mRNA. In tissue sections, PnNOS protein was immunodetected in the penile nerve endings in the rat and in the nNOS wild-type and nNOS( big up tri, open big up tri, open) mice. An antibody against the sequence encoded by exon 2 did not react (on Western blots) with the 135-kDa band, which confirms that this protein is the beta form. In conclusion, both PnNOSalpha and beta are expressed in the rat penis at all ages and are located in the nerves. The beta form may allow nitric oxide synthesis during erection to be partially insensitive to PIN. The residual expression of PnNOS, and possibly CnNOS, in the penis of the nNOS( big up tri, open big up tri, open) mouse occurs through transcription of the beta mRNA, and this may explain the retention of erectile function when the expression of nNOSalpha is disrupted.

Amino Acid Sequence↗
PubMed2000

The implementation and evaluation of a healthy communities process in central Alberta: some implications for public health practice.

This article describes the implementation and evaluation of a Healthy Communities Initiative (HCI) by the David Thompson Health Region in central Alberta, Canada. The HCI model provided for a facilitated, community-based, strategic planning process. Its key steps include development of a shared vision of health, assessment of needs and strengths, selection of key priority areas for action, and implementation of strategies to achieve change. A three-level evaluation model was developed, which incorporates project-level evaluation, cluster-level evaluation, and critical reflection on the David Thompson Health Region's own capacity to engage in community development work.

Alberta↗
PubMed2000

Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors.

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8(+) T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8(+) T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in "fresh" killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.

CD8-Positive T-Lymphocytes↗
PubMed2000

Cycling safety: injury prevention in Oxford cyclists.

OBJECTIVE: To assess injury prevention measures used by cyclists in Oxford and to detect any differences between wearers and non-wearers of cycling helmets. METHOD: A prospective observational survey of a series of cyclists passing a single point on a busy city road in reduced lighting. Two observers jointly recorded four measures of injury prevention: use of front or rear light, high visibility (reflective or fluorescent) clothing, and cycling helmet. The use of the first three interventions was analysed in relation to helmet use/non-use. RESULTS: A total of 392 cyclists were observed over one hour. Fourteen (3.6%) were observed to use all four studied measures, while 137 (34.9%) used none of them. The frequency of measures observed was: lit front light 190 (48.5%), lit rear light 197 (50.2%), both lights on 163 (41.6%), helmet on 104 (26.5%), and high visibility clothing 39 (9.9%). Despite the helmet using group's smaller size, it contained a significantly higher proportion of cyclists with lit front light (60.6% v 44.1%), lit rear light (61.5% v 46.2%), and high visibility clothing (27.9% v 3.5%), than the non-helmet group (p < or = 0.01). Whereas only 22% of the helmet users had no other observed measures, 47.2% of non-users did so. CONCLUSION: Cycling helmet users were significantly more likely to use collision prevention measures in conditions of reduced visibility. Explanations may include higher levels of risk awareness and greater knowledge of safe cycling practices in the smaller, helmet using group. However, current measures by cyclists in a major cycling centre may be insufficient to prevent collisions and consequent serious injury or death.

Bicycling↗
PubMed2000

Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1 or TSC2 genes, coding hamartin and tuberin, respectively. Immunofluorescence analysis of tuberin and hamartin performed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segment, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it colocalizes with renin. In positive epithelial cells, tuberin localizes to the cytoplasm as well as the apical membrane. Hamartin, however, preferentially localizes to the apical membrane. The two proteins colocalize at the apical membrane of type A intercalated cells and connecting tubule cells, whereas in type B intercalated cells they reveal a variable pattern of expression. The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC.

3T3 Cells↗
PubMed2000

The occupation of gardening in life-threatening illness: a qualitative pilot project.

This qualitative pilot study was completed as an exploratory study of the meaning of gardening using attention restoration theory. Three women with breast cancer who garden for leisure were recruited from a cancer support group. Each participant was interviewed at her home on two occasions. To complement the qualitative data, participants also completed the Perceived Restorativeness Scale (PRS) (Hartig, Korpela, Evans, & Garling, 1996). The interviews revealed six major themes some of which were concerned with the interactions between the gardener and the garden, and others which focused on gardening within the context of having cancer. The qualitative and quantitative outcomes supported the perspective of attention restoration theory. Spirituality was interwoven throughout the comments of two participants but was less important for one participant. The implications of this study for practice and future research are discussed.

Adult↗
PubMed1999

Accommodated xenografts survive in the presence of anti-donor antibodies and complement that precipitate rejection of naive xenografts.

Hamster hearts transplanted into transiently complement-depleted and continuously cyclosporin A (CyA)-immunosuppressed rats survive long-term despite deposition of anti-donor IgM Abs and complement on the graft vascular endothelium. This phenomenon is referred to as "accommodation." The hypothesis tested here is that accommodated xenografts are resistant to IgM Abs and complement that could result in rejection of naive xenografts. After first hamster hearts had been surviving in cobra venom factor (CVF) + CyA-treated rats for 10 days, a time when the anti-donor IgM Ab level was maximal and complement activity had returned to approximately 50% of pretreatment levels, naive hamster hearts or hamster hearts that had been accommodating in another rat for 14 days were transplanted into those rats carrying the surviving first graft. The naive hearts were all hyperacutely rejected. In contrast, a majority of regrafted accommodating hearts survived long-term. There was widespread Ab and activated complement deposition on the vascular endothelium of accommodating first hearts, second accommodating hearts, and rejected second naive hearts. However, only the rejected naive hearts showed extensive endothelial cell damage, myocardial necrosis, fibrin deposition, and other signs of inflammation. Accommodating first and second hearts but not rejected second naive hearts expressed high levels of the protective genes A20, heme oxygenase-1 (HO-1), bcl-2, and bcl-xL. These data demonstrate that accommodated xenografts become resistant to effects of anti-donor IgM Abs and complement that normally mediate rejection of xenografts. We hypothesize that this resistance involves expression by accommodated xenografts of protective genes.

Adoptive Transfer↗
PubMed1999

Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity.

Aniline Compounds↗
PubMed1999

Ventricular filling patterns of the right and left ventricles in normally grown fetuses: a longitudinal follow-up study from early intrauterine life to age 1 year.

OBJECTIVE: Our goal was to determine the effects of advancing age on the Doppler diastolic filling indexes from early gestation to 1 year of life. STUDY DESIGN: Seventy-nine fetuses were studied. Initial Doppler studies were started at about the 16th week of gestation and repeated every 4-6 weeks until term, on postnatal day 1 and 2, and at ages 6 weeks, 6 months, and 12 months. A minimum of 5 returning Doppler waveforms were traced and analyzed for (1) peak early flow velocity, (2) late peak atrial flow velocity, (3) total area area under the curve, and (4) the acceleration and deceleration phases. The stiffness of the ventricles was estimated. Slopes of the curves for each of the parameters were analyzed for differences across time periods and between right and left ventricles. RESULTS: (1) Heart rate significantly decreased with advancing age. (2) Left ventricular and right ventricular peak early flow velocity and late peak atrial flow velocity significantly increased during fetal life but not during the 1st year. (3) Atrial predominance was found during fetal life but not during the first year. (4) The deceleration phase of filling significantly increased during the fetal period. (5) Ventricular stiffness progressively decreased during the fetal period. (6) Increased ventricular filling shifted from a right-sided dominance in utero to a left-sided dominance after birth. CONCLUSIONS: (1) Fetuses have stiffer fetal ventricles than neonates. (2) The diastolic filling patterns in normally grown fetuses mimic those of the diseased adult heart. We speculate that this maturation process may be affected in fetuses born prematurely or small for gestational age.

Echocardiography, Doppler↗
PubMed1999

New insights into Titan's organic chemistry in the gas and aerosol phases.

Titan, the largest satellite of Saturn, with a dense atmosphere very rich in organics, and many couplings in the various parts of its "geofluid", is a reference for studying prebiotic chemistry on a planetary scale. New data have been obtained from experiments simulating this organic chemistry (gas and aerosol phases), within the right ranges of temperature and a careful avoiding of any chemical contamination. They show a very good agreement with the observational data, demonstrating for the first time the formation of all the organic species already detected in Titan atmosphere including, at last, C4N2, together with many other species not yet detected in Titan. This strongly suggests the presence of more complex organics in Titan's atmosphere and surface, including high molecular weight polyynes and cyanopolyynes. The NASA-ESA Cassini-Huygens mission has been successfully launched in October 1997. The Cassini spacecraft will reach the Saturn system in 2004 and become an orbiter around Saturn, while the Huygens probe will penetrate into Titan's atmosphere. In situ measurements, in particular from Huygens GC-MS and ACP instruments, will provide a detailed analysis of the organics present in the air, aerosols, and surface. This very ambitious mission should yield much information of crucial importance for our knowledge of the complexity of Titan's chemistry, and, more generally for the field of exobiology.

Aerosols↗
PubMed1999

The place of general practitioners in the management of out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: The involvement of general practitioners in community based resuscitation of out-of-hospital cardiac arrest has been found to be effective in improving survival rates. The aim of the study was to assess the potential for including general practitioners in Nottinghamshire in the resuscitation of out-of-hospital cardiac arrest victims by first determining whether they had the skill, experience and equipment to provide cardio-pulmonary resuscitation in the community; and second to ascertain what proportion of them would be prepared to establish a 'rapid response' scheme for patients requiring resuscitation. METHODS: A postal questionnaire survey, between March and April 1997, of all 738 general practitioners in Nottinghamshire who serve, in total, a population of 1 million. RESULTS: A total of 592 general practitioners (80%) responded to our survey. The majority worked in a predominantly urban environment and carried out their own out-of-hours on-call duties. Of them 93% had previous experience in cardiopulmonary resuscitation (median of 3 years), while 72.1% had experience of advanced life support, including use of a defibrillator but not recently (median of 8 years). General practitioners in rural practices were more likely to be trained in advanced life support (ALS), had more recent experience in cardiopulmonary resuscitation (including defibrillation) and were more willing to be involved in any proposed local resuscitation scheme. Only 9% of general practitioners carried a defibrillator when on-call and only 13% had access to a defibrillator within their practice premises. Of the general practitioners surveyed 349 (59%) reported a willingness to participate in a 'rapid response cardiac arrest' scheme and general practitioners who had no formal advanced life support training were as willing to become involved in such a scheme as those who were trained in ALS. CONCLUSIONS: General practitioners may have an important role to play in improving the survival outcome of out-of-hospital cardiac arrest as many are ALS trained and have recent experience in resuscitation. However, few have access to a defibrillator and many do not have recent experience of defibrillation. Any proposed local resuscitation scheme would be particularly applicable to rural general practitioners as many have recent training in ALS, recent experience in advanced life support and most of all, are more willing to participate in such a scheme.

Attitude of Health Personnel↗
PubMed1999

Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen.

In tissues, collagen forms the scaffold for cell attachment and migration, and it modulates cell differentiation and morphogenesis by mediating the flux of chemical and mechanical stimuli. We are constructing biomimetic environments by immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three-dimensional (3-D) templates. The cell-binding peptide can be expected to transduce mechanical forces. In their physiological environment, periodontal ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have examined the behavior of human PDLF in culture on particulate bovine anorganic bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of radiolabeled precursors in DNA and protein were consistent with the presence of larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron microscopic examination showed that cultures on ABM-P-15 generated highly oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red stained the matrix of particle associated cells and inter-particle cellular bridges in P-15-associated cultures, indicating mineralization. 3-D colony formation and ordering of cells along with increased mineralization suggests that the coupling of cells to the ABM matrix through P-15 may provide a biomimetic environment permissive for cell differentiation and morphogenesis. Our studies suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when seeded with PDLF, these matrices may serve as tissue engineered substitutes for autologous bone grafts.

Animals↗
PubMed1999

No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer.

Endogenous hormone exposure is known to alter breast cancer susceptibility and genes responsive to such hormones are plausible candidates for predisposition genes. We have examined polymorphisms in genes for two members of the nuclear receptor superfamily which are expressed in breast tissue and known to moderate rates of cell proliferation in a case-control association study: the androgen receptor (AR) and the vitamin D receptor (VDR). We have used two series of Caucasian female breast cancer cases, one incident and one prevalent, and compared both with two sets of matched controls from the East Anglian region of Britain. Since the results are similar in the two series we have combined them. The AR poly[Gly](n) and poly[Gln](n) tracts were genotyped in a total of 508 female breast cancer cases and 426 controls. The VDR TaqI polymorphism was analysed in 951 cases and 627 controls drawn from the same population series. There were no significant differences between cases and controls for either the AR or VDR polymorphisms. Compared with individuals with two short alleles (<22 repeats) of the AR poly[Gln](n) tract, the odds ratios and 95% confidence intervals (95% CI) for individuals with one or two long alleles were 0.82 (95% CI 0.62-1.09) and 1.31 (95% CI 0.87-1.97), respectively. Heterozygotes and homozygotes for the VDR TaqI cutting site had odds ratios of 1.01 (95% CI 0.81-1.27) and 0.97 (95% CI 0.71-1.32), respectively. None of the AR or VDR polymorphisms investigated has a major effect on risk of breast cancer in the British population.

Adult↗