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E Wood

Publications and source records attributed to E Wood.

At least 37 records · Page 2Linked to original sources
PubMed2001

Promoter characteristics of two cyp19 genes differentially expressed in the brain and ovary of teleost fish.

Teleost fish are characterized by exceptionally high levels of neural estrogen biosynthesis when compared with the brains of other vertebrates or to the ovaries of the same fish. Two P450arom mRNAs which derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (b>>a) and ovary (a>>b) and have a different developmental program (b>>a) and estrogen upregulation (b only). A polymerase chain reaction (PCR)-based genomic walking strategy was used to isolate the 5'-flanking regions of the goldfish (Carassius auratus) cyp19 genes. Sequence analysis of the cyp19b gene approximately 1.8 kb upstream of the transcription start site revealed a TATA box at nucleotide (nt) -30, two estrogen responsive elements (EREs; nt -351 and -211) and a consensus binding site (NBRE) for nerve growth factor inducible-B protein (NGFI-B/Nur77) at -286, which includes another ERE half-site. Also present were a sequence at nt -399 (CCCTCCT) required for neural specificity of the zebrafish GATA-2 gene, and 16 copies of an SRY/SOX binding motif. The 5'-flanking region ( approximately 1.0 kb) of the cyp19a gene had TATA (nt -48) and CAAT (nt -71) boxes, a steroidogenic factor-1 (SF-1) binding site (nt -265), eight copies of the SRY/SOX motif, and two copies of a recognition site for binding the arylhydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) heterodimer. Both genes had elements previously identified in the brain specific exon I promoter of the mouse aromatase gene. Cyp19a- and -b/luciferase constructs showed basal promoter activity in aromatase-expressing rodent pituitary (GH3) cells, but differences (a>>b) did not reflect expression in fish pituitary in vivo (b>>a), implying a lack of appropriate cell factors. Consistent with the onset of cyp19b expression in zebrafish embryos, microinjection of a green fluorescent protein (GFP) reporter plasmid into fertilized eggs revealed labeling in neural tissues at 30-48 h post-fertilization (hpf), most prominently in retinal ganglion cells (RGC) and axon-like projections to the optic tectum. Expression of a cyp19a/GFP reporter was not detectable up to 72 hpf. Tandem analysis of cyp19a and cyp19b promoters in living zebrafish embryos can be a useful approach for identifying cis-elements and cellular factors involved in the correct tissue-specific, spatial, temporal and estrogen regulated expression of aromatase genes during CNS and gonadal development.

Animals↗
PubMed2001

Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish.

Teleost fish are characterized by exceptionally high levels of brain estrogen biosynthesis when compared to the brains of other vertebrates or to the ovaries of the same fish. Goldfish (Carassius auratus) and zebrafish (Danio rerio) have utility as complementary models for understanding the molecular basis and functional significance of exaggerated neural estrogen biosynthesis. Multiple cytochrome P450 aromatase (P450arom) cDNAs that derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (P450aromB>>A) and ovary (P450aromA>>B) and have a different developmental program (B>>A) and response to estrogen upregulation (B only). As measured by increased P450aromB mRNA, a functional estrogen response system is first detected 24-48 h post-fertilization (hpf), consistent with the onset of estrogen receptor (ER) expression (alpha, beta, and gamma). The 5'-flanking region of the cyp19b gene has a TATA box, two estrogen response elements (EREs), an ERE half-site (ERE1/2), a nerve growth factor inducible-B protein (NGFI-B)/Nur77 responsive element (NBRE) binding site, and a sequence identical to the zebrafish GATA-2 gene neural specific enhancer. The cyp19a promoter region has TATA and CAAT boxes, a steroidogenic factor-1 (SF-1) binding site, and two aryl hydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) binding motifs. Both genes have multiple potential SRY/SOX binding sites (16 and 8 in cyp19b and cyp19a, respectively). Luciferase reporters have basal promoter activity in GH3 cells, but differences (a>>b) are opposite to fish pituitary (b>>a). When microinjected into fertilized zebrafish eggs, a cyp19b promoter-driven green fluorescent protein (GFP) reporter (but not cyp19a) is expressed in neurons of 30-48 hpf embryos, most prominently in retinal ganglion cells (RGCs) and their projections to optic tectum. Further studies are required to identify functionally relevant cis-elements and cellular factors, and to determine the regulatory role of estrogen in neurodevelopment.

Animals↗
PubMed2001

A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity.

Earlier we reported potent cRaf1 kinase inhibitors with a key acidic phenol pharmacophore that had, at best, adequate cellular efficacy. To improve the cellular potency, phenol isosteres and prodrugs were investigated. Many phenol isosteres were synthesized and tested, but failed to provide adequate enzyme potency. A prodrug approach resulted in a 2- to 17-fold improvement over the parent compound in cell-based efficacy.

Antineoplastic Agents↗
PubMed2000

Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy.

OBJECTIVE: To characterize the relationship between plasma viral load (pVL) suppression and triple drug antiretroviral therapy, and the accompanying changes in CD4 cell counts. METHOD: Retrospective study of 465 participants in a HIV/AIDS Treatment Program who initiated triple drug therapy between August 1996 and May 1998. Participants were divided into three groups according to their pVL response: (i) non-responders (NR; n = 112) exhibited pVL persistently > 500 copies/ml over the study period; (ii) partial responders (PR; n = 100) achieved a pVL < 100 copies/ml at least once and subsequently rebounded to > 500 copies/ml; and (iii) full responders (FR; n = 253) achieved a pVL < 500 copies/ml and sustained this level for the remainder of the study period. For each group, the accompanying changes in absolute and fractional CD4 cell counts were evaluated. RESULTS: The median net change in pVL per person from baseline to the end of the observation period was -0.37, -2.27, and -2.56 log10 copies/ml for NR, PR and FR, respectively. During weeks 68-83, the median CD4 cell count (x 10(6) cells/l) was 150 [interquartile range (IQR) 90-370], 380 (IQR 300-480) and 525 (IQR 305-705) for NR, PR and FR, respectively. Median changes in CD4 cells (x 10(6) cells/l) were -20 (IQR -90 to 40), 150 (IQR 30-250) and 240 (IQR 110-365) for NR, PR, and FR, respectively. The net percentage change in CD4 cells per person was 0% (IQR -34-31), 54% (IQR 6-160), and 83% (IQR 39-173) for NR, PR, and FR, respectively. By weeks 68-83, the median fractional CD4 cells was 0.16 (IQR 0.07-0.22), 0.22 (IQR 0.15-0.28), and 0.26 (IQR 0.17-0.34) for NR, PR and FR respectively. CONCLUSIONS: An optimal CD4 cell count response appears to be coupled with continued pVL suppression. Our data indicate that maximal suppression of viral replication should remain the primary goal of therapy.

Adult↗
PubMed2000

Extent to which low-level use of antiretroviral treatment could curb the AIDS epidemic in sub-Saharan Africa.

BACKGROUND: Despite growing international pressure to provide HIV-1 treatment to less-developed countries, potential demographic and epidemiological impacts have yet to be characterised. We modelled the future impact of antiretroviral use in South Africa from 2000 to 2005. METHODS: We produced a population projection model that assumed zero antiretroviral use to estimate the future demographic impacts of the HIV-1 epidemic. We also constructed four antiretroviral-adjusted scenarios to estimate the potential effect of antiretroviral use. We modelled total drug cost, cost per life-year gained, and the proportion of per-person health-care expenditure required to finance antiretroviral treatment in each scenario. FINDINGS: With no antiretroviral use between 2000 and 2005, there will be about 276,000 cumulative HIV-1-positive births, 2,302,000 cumulative new AIDS cases, and the life expectancy at birth will be 46.6 years by 2005. By contrast, 110,000 HIV-1-positive births could be prevented by short-course antiretroviral prophylaxis, as well as a decline of up to 1 year of life expectancy. The direct drug costs of universal coverage for this intervention would be US$54 million--less than 0.001% of the per-person health-care expenditure. In comparison, triple-combination treatment for 25% of the HIV-1-positive population could prevent a 3.1-year decline in life expectancy and more than 430,000 incident AIDS cases. The drug costs of this intervention would, however, be more than $19 billion at present prices, and would require 12.5% of the country's per-person health-care expenditure. INTERPRETATION: Although there are barriers to widespread HIV-1 treatment, limited use of antiretrovirals could have an immediate and substantial impact on South Africa's AIDS epidemic.

Africa South of the Sahara↗
PubMed2000

Antiretroviral medication use among injection drug users: two potential futures.

OBJECTIVE: To model the potential impact of HIV infection rates and the use of antiretroviral medication on life expectancy and mortality in the Downtown Eastside of Vancouver, British Columbia, Canada, from 1999 to 2006. DESIGN: Population projections were made to estimate the population of the Downtown Eastside in the year 2006. METHODS: Two scenarios were modelled to predict the impact of HIV infection and antiretroviral use on mortality and life expectancy. The use of antiretroviral therapy was estimated to be 80% in the first scenario and 20% in the second. The prevalence of HIV by age and sex, and by year infected was estimated using data from the Vancouver Injection Drug User Study. RESULTS: If the level of antiretroviral therapy use among HIV-positive individuals was 80% at baseline, then we estimate that the life expectancy at birth in the year 2006 will be 60.8 years for men and 72.8 years for women, and 172 AIDS deaths will occur between 1999 and 2006. In contrast, if the present level of antiretroviral medication use persists, the life expectancy at birth in the year 2006 will be 56.9 years for men and 68.6 years for women, and 503 AIDS deaths will occur between 1999 and 2006. CONCLUSION: Our analysis suggests that if the low levels of antiretroviral therapy use persist, life expectancy in Vancouver's Downtown Eastside will soon be on a par with many of the world's least developed countries. Our findings highlight the large health status decline that can be expected in many inner city neighbourhoods if low levels of antiretroviral use persist. Although reasonable coverage targets for injection drug users (IDU) have not been established, the expanded use of antiretroviral medication is urgently needed to avert a drastic decline in health status.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Depressive symptoms decline among persons on HIV protease inhibitors.

OBJECTIVE: To ascertain whether initiation of protease inhibitors was associated with a change in depressive symptoms among persons infected with HIV. METHODS: Study subjects included men and women who were enrolled in the HIV/AIDS Drug Treatment Program and who had completed an annual participant survey before and after initiating triple combination therapy with a protease inhibitor. Depressive symptoms were assessed using the Centre for Epidemiologic Studies-Depression scale (CES-D). Statistical analyses to determine the change in CES-D total and subscale scores before and after protease inhibitor use were conducted using parametric and multivariate methods. RESULTS: Our analysis was restricted to 453 participants. Of these 234 (52%) were depressed at baseline (CES-D score > or = 16). Compared with nondepressed participants, depressed participants were slightly younger (p = .048), less likely to be employed (p < .001) and more likely to have an annual income less than $10,000 per annum (p < .001). After adjusting for CD4 count, employment status, income, age, and CES-D total or subscale score at baseline, we found a significant improvement in total scale score (p = .001) and depressive mood (p = .002), positive affects (p = .005), and somatic symptoms (p = .011) subscale scores at follow-up. There was no significant change in the interpersonal relations score over the study period. CONCLUSION: Our findings indicate that in addition to conferring impressive clinical benefits, protease inhibitor use is associated with a significant improvement in HIV-positive individuals' mental health.

Adult↗
PubMed2000

The end of the line: has rapid transit contributed to the spatial diffusion of HIV in one of Canada's largest metropolitan areas?

The objective of this study is to describe the relationship between socio-demographic characteristics and the geographic distribution of persons with HIV in the metropolitan area surrounding Vancouver, British Columbia. Specifically, we sought to determine the location of persons with HIV and the population based characteristics related to the rate of anti-HIV medication use. In addition, we investigated the relationship between the distribution of persons on anti-HIV medications and the city's monorail "SkyTrain" route. The residences of persons on anti-HIV therapy were linked to Census Tracts. Data from the most recent census were used to create a socio-demographic profile of each geographic area. The spatial relationship between the distribution of persons on anti-HIV therapy and the path of the monorail was assessed by digitizing the SkyTrain route over a digital Census Tract map. Statistical analyses were used to determine the characteristics of Census Tracts associated with the rate of anti-HIV medication use. The overall rate of anti-HIV medication use in the Census Tracts that are within 1 km of SkyTrain was 66 per 100,000 population, whereas the rate was only 22 in the non-proximal Census Tracts. Multivariate analyses indicated that persons on anti-HIV therapy were significantly less likely to reside where there is a higher proportion of the population female, and were more likely to reside in areas with a higher proportion of the population of First Nations or Aboriginal descent, a higher population density, and in areas within 1 km of the SkyTrain route. Our analyses suggest that neither migration, nor a heightened access to therapy explain these findings. The environment surrounding the SkyTrain may have been conducive to the spatial diffusion of HIV, and could be the focus of targeted public health interventions. The mechanisms responsible for the clustering of persons on anti-HIV medications around the SkyTrain require further investigation.

Adult↗
PubMed2000

Determinants of geographic mobility among participants in a population-based HIV/AIDS drug treatment program.

This study was undertaken to determine the geographic distribution and patterns of migration of persons with HIV in British Columbia. Our analysis was restricted to all HIV-positive men and women aged 18 years and over who had completed a participant survey and were enrolled in the HIV/AIDS Drug Treatment Program between September 1992 and September 1997. Patterns of migration were determined by examining participants whose postal code changed between July 1995 and September 1997. Statistical analysis were carried out using both parametric and non-parametric methodologies. Stepwise logistic regression was used to determine baseline predictors of migration. The final multivariate model revealed that residing in a census subdivision with a population less than 100,000, being heterosexual, acquiring HIV through intravenous drug use, and the absence of AIDS at baseline were all independently associated with moving census subdivisions during the period of observation. In summary, our analyses demonstrate the need for the continued study of the evolving geography and migration patterns of persons with HIV.

Adult↗
PubMed2000

The gross motor function classification system for cerebral palsy: a study of reliability and stability over time.

Children with cerebral palsy (CP) experience a change in motor function with age and development. It is important to consider this expected change in offering a prognosis, or in assessing differences in motor function after an intervention. The Gross Motor Function Classification System for CP (GMFCS) has been developed for these purposes. This study was based on a retrospective chart review of 85 children with CP followed from < or =2 to > or =12 years of age. The GMFCS was applied to clinical notes by two blinded raters four times throughout the study. Interrater reliability was high (G=0.93). Test-retest reliability was high (G=0.79). The positive predictive value of the GMFCS at 1 to 2 years of age to predict walking by age 12 years was 0.74. The negative predictive value was 0.90. The GMFCS can validly predict motor function for children with CP. The results are discussed in terms of their implications for clinical practice and future research.

Cerebral Palsy↗
PubMed2000

Health related quality of life among persons with HIV after the use of protease inhibitors.

OBJECTIVE: This study was conducted to determine the effect of the use of HIV protease inhibitors on the quality of life among persons infected with HIV. METHODS: Subjects were participants in the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program who had completed two annual participant surveys, one prior to initiating therapy with a protease inhibitor and one after. Quality of life was measured using the Medical Outcomes Study Short Form Health Survey (MOS-SF). Statistical analyses were conducted using parametric and multivariate methods. RESULTS: Our analysis was based on 179 HIV-positive individuals. Compared to quality of life at baseline, we found no statistically significant changes in the health perception, pain, physical, role and social functioning MOS-SF subscale scores at follow-up. The measure of mental health was the only component to decline significantly over time. Subanalyses found significant increases in the measures of health perception (p = 0.004), physical (p = 0.037), role (p < 0.001) and social functioning (p = 0.053) for individuals with a low baseline quality of life. For those with a higher quality of life before starting a protease inhibitor containing regimen we observed a significant decline in the subscales of mental health (p = 0.001), physical (p = 0.007), role (p = 0.021) and social functioning (p = 0.003) over the study period. CONCLUSIONS: Our findings indicate that despite strict dosage requirements and adverse side effects associated with protease inhibitor use patients are on the whole maintaining their quality of life after starting on a protease inhibitor containing regimen. Continued follow-up of this cohort will be required to determine the long term implications of these observations.

Adult↗
PubMed1999

A telomerase component is defective in the human disease dyskeratosis congenita.

The X-linked form of the human disease dyskeratosis congenita (DKC) is caused by mutations in the gene encoding dyskerin. Sufferers have defects in highly regenerative tissues such as skin and bone marrow, chromosome instability and a predisposition to develop certain types of malignancy. Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing. Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif. Telomerase adds simple sequence repeats to chromosome ends using an internal region of its RNA as a template, and is required for the indefinite proliferation of primary human cells. We find that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomerase activity and have shorter telomeres than matched normal cells. The pathology of DKC is consistent with compromised telomerase function leading to a defect in telomere maintenance, which may limit the proliferative capacity of human somatic cells in epithelia and blood.

Adult↗
PubMed1999

Social inequalities in male mortality amenable to medical intervention in British Columbia.

The objective of this study is to examine the rates of mortality among different social classes and socioeconomic groups of British Columbian males from causes of death amenable to medical intervention. We examined the rates of avoidable mortality from the causes of death published by Charlton, excluding causes of death restricted to women as well as perinatal deaths. For the purposes of our study, we determined a population at risk using 20% samples of occupational data for men from the 1981, 1986 and 1991 censuses conducted by Statistics Canada. For the analysis of mortality by social class, individuals were divided into five social class levels based on occupation using an adaptation of the UK Registrar General's Social Class Scale. In addition, three levels of socioeconomic analysis were performed using the Blishen Index classification system. Once individuals were assigned to a social class in each classification system, the death rates from each amenable cause was calculated and standardized to the total population. For almost every cause of death examined, the rate of mortality was higher in individuals of lower social and socioeconomic classes than in individuals of the upper social and socioeconomic classes. These results were consistent regardless of the social class component, education, occupation, or income was being measured. The mortality gradient was most notable in deaths due to hypertensive heart disease, tuberculosis, asthma and pneumonia and bronchitis. Due to the fact that these causes of death were observed to be consistently higher in the lower social classes, we feel that specific measures aimed at improving survival from these conditions in lower social classes could help to amend the social class disparity.

Adolescent↗
PubMed1999

Experience in treating persons with HIV/AIDS and the legalization of assisted suicide: the views of Canadian physicians.

The objective of this study is to determine the opinions of a random sample of Canadian family physicians and a population of non-specialist physicians known to provide care to persons with HIV/AIDS about the legalization of physician assisted suicide for persons with HIV disease. In addition, we have attempted to ascertain the physician characteristics that may be associated with a favourable or negative opinion. Self-administered, anonymous questionnaires were mailed to 2,890 family physicians across Canada. Logistic regression analysis was used to determine whether physician characteristics were predictive of agreement with the legalization of physician assisted suicide. Of the respondents who had an opinion, 60% agreed with the legalization of physician assisted suicide. Multivariate analyses indicated that physicians who were living in the provinces of British Columbia (BC), Ontario, or Québec (OR = 1.63, 95% CI: 1.10, 2.43) and who provided routine follow-up care (OR = 1.85, 95% CI: 1.30, 2.63) or palliative care (OR 1.66, 95% CI: 1.13, 2.44) to those with HIV disease were more likely to agree with legalization of physician assisted suicide. This analysis demonstrates a strong support for the legalization of physician assisted suicide for persons with HIV disease among physicians experienced in providing care to those affected.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Roots as a site of hydrogen sulfide uptake in the hydrocarbon seep vestimentiferan Lamellibrachia sp.

Vestimentiferan tubeworms have no mouth or gut, and the majority of their nutritional requirements are provided by endosymbiotic bacteria that utilize hydrogen sulfide oxidation to fix CO(2) into organic molecules. It has been assumed that all vestimentiferans obtain the sulfide, O(2) and CO(2) needed by the bacteria across the plume (gill) surface, but some live in locations where very little sulfide is available in the sea water surrounding the plume. We propose that at least some of these vestimentiferans can grow a posterior extension of their body and tube down into the sea-floor sediment, and that they can use this extension, which we call the 'root', to take up sulfide directly from the interstitial water. In this study of the vestimentiferan Lamellibrachia sp., found at hydrocarbon seeps in the Gulf of Mexico at depths of approximately 700 m, we measured seawater and interstitial sulfide concentrations in the hydrocarbon seep habitat, determined the structural characteristics of the root tube using transmission electron microscopy, characterized the biochemical composition of the tube wall, and measured the sulfide permeability of the root tube. We found that, while the sulfide concentration is less than 1 (micro)mol l(-)(1) in the sea water surrounding the gills, it can be over 1.5 mmol l(-)(1) at a depth of 10-25 cm in sediment beneath tubeworm bushes. The root tube is composed primarily of giant (&bgr;)-chitin crystallites (12-30 % of total mass) embedded in a protein matrix (50 % of total mass). Root tubes have a mean diameter of 1.4 mm, a mean wall thickness of 70 (micro)m and can be over 20 cm long. The tubeworm itself typically extends its body to the distal tip of the root tube. The root tube wall was quite permeable to sulfide, having a permeability coefficient at 20 degrees C of 0. 41x10(-)(3 )cm s(-)(1), with root tube being 2.5 times more permeable to sulfide than trunk tube of the same diameter. The characteristics of the root suggest that it reaches down to the higher sulfide levels present in the deeper sediment and that it functions to increase the surface area available for sulfide uptake in a manner analogous to a respiratory organ.

Animals↗
PubMed1999

A new tactic for Triatoma infestans control: fabrics impregnated with beta-cypermethrin.

Triatoma infestans is the most important vector of Chagas' disease in Argentina. Experiences from Argentine national campaigns have shown indoor spraying to control triatomine bugs is both expensive and difficult. An alternative control method may be the use of pyrethroid-impregnated fabrics (PIFs), which could be both a practical and cheap complement to conventional control measures. In this study, a formulation of emulsifiable concentrate of beta-cypermethrin [alpha-cyano-3-phenoxybenzyl-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxilate] pyrethroid was used to impregnate different fabrics. The fabrics were then tested for their efficacy and persistence in killing Triatoma infestans. Insects attempting to penetrate or grasp the fabric in search of blood meals were poisoned by the exposure to the absorbed pyrethroid. Laboratory bioassays showed that the insecticidal effect of the PIFs with a dosage of 0.2 g/m2 lasted longer on wool than on cotton or rayon. Eight months after impregnation, a residual efficacy of 100% was found for wool, 80% for rayon-cotton fabrics, and 50% for rayon-polyester fabrics. In addition, beta-cypermethrin-impregnated fabrics showed a better repellency effect than did fabrics impregnated with either deltamethrin or cypermethrin. For field trials, fabrics were impregnated either in the laboratory or "in situ" at a dosage of 1 g beta-cypermethrin/m2 and then dried. The PIFs were placed inside homes, either under the roof or under the bed mattress. The field trials showed the PIF approach to be very effective in keeping dwellings free of triatomine bugs for at least one year and found a high degree of acceptability among the houses' residents.

Animals↗