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S Lewis

Publications and source records attributed to S Lewis.

At least 73 records · Page 4Linked to original sources
PubMed2001

A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding.

OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

Adolescent↗
PubMed2001

Synthesis and evaluation of novel aldose reductase inhibitors: Effects on lens protein kinase Cgamma.

PURPOSE: To synthesize novel aldose reductase inhibitors (ARI) that will normalize losses in protein kinase Cgamma (PKCgamma) observed during diabetes and galactosemia. METHODS: ARI were synthesized as tricyclic pyrones 1-6 (HAR-1 through HAR-6) from 3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and (5aS,7S)-7-isopropenyl-3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and were tested by inhibition of aldose reductase enzyme activity in vitro and by inhibition of polyol formation in lens epithelial cells in culture. Identified compounds were further tested in galactosemic rat lens in vivo for (a) normalized PKCgamma levels by Western blot, (b) reduction of phosphorylation of the gap junction protein Cx46 by analyses of co-immunoprecipitated proteins, and (c) by normalization of gap junction activity as measured by dye transfer. RESULTS: HAR-1 (1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran-3-acetic acid) was identified as an ARI with IC50 for aldose reductase inhibition at 2 nM. Polyol accumulation in lens epithelial cells was reduced by 80% at 10 microM. Rats fed 40% galactose for 9 days had an 80% reduction in PKCgamma levels which were normalized by HAR-1 at 100 mg/kg/day, fed orally. Phosphorylation of Cx46 was increased by 50% and this was normalized in HAR-1 treated rats (6 day treatment). Gap junction activity of galactosemic rats was reduced by 55% and this was normalized by HAR-1 in six day-treated rats. CONCLUSIONS: HAR-1 is a novel ARI which normalized losses of PKCgamma, changes in Cx46 phosphorylation, and gap junction activity.

Acetates↗
PubMed2001

Testing for colon neoplasia susceptibility variants at the human COX2 locus.

BACKGROUND: Siblings and other first-degree relatives of patients with "sporadic" (i.e., apparently nonfamilial) colorectal cancer or precursor adenomatous colon polyps have an increased risk of developing colon neoplasia. This observation suggests the presence of inherited genetic determinants for sporadic colon neoplasia. Mice homozygous for a null cyclooxygenase 2 (COX2) (also called PTGS2) allele have a dramatically reduced susceptibility to the development of intestinal adenomas. In humans, use of pharmacologic inhibitors of COX2 enzyme activity are associated with reduced risk of colon neoplasia. This study examined whether the human COX2 locus may be linked to colon neoplasia in humans. METHODS: We used the affected sibling-pair method to test for linkage of the human COX2 locus to colon neoplasia. RESULTS: We examined 74 concordantly affected sibling pairs from 46 sibships with colon neoplasia. One hundred five siblings from these sibships were diagnosed with either colorectal cancer or colon adenomatous polyps before age 65 years. No linkage between COX2 and colon neoplasia was found by use of a multipoint model-free linkage analysis (estimate of allele sharing was 0.44; standard error = +/-0.04; 95% confidence interval = 0.36 to 0.52). Moreover, even allowing for heterogeneity, the potential that a COX2 colon neoplasia susceptibility variant was present within a substantial subset of these sibships was strongly excluded under either a recessive or a dominant inheritance model (95% confidence to exclude a model in which 2.7% or more of the sibling pairs harbor a dominant susceptibility allele). CONCLUSIONS: This study of concordantly affected sibling pairs thus demonstrates that variations in the COX2 gene are unlikely to be a source of individual susceptibility to colon neoplasia in humans.

Adenomatous Polyposis Coli↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

Understanding the mechanism of ice binding by type III antifreeze proteins.

Type III antifreeze proteins (AFPs) are present in the body fluids of some polar fishes where they inhibit ice growth at subzero temperatures. Previous studies of the structure of type III AFP by NMR and X-ray identified a remarkably flat surface on the protein containing amino acids that were demonstrated to be important for interaction with ice by mutational studies. It was proposed that this protein surface binds onto the (1 0 [\bar 1] 0) plane of ice with the key amino acids interacting directly with the water molecules in the ice crystal. Here, we show that the mechanism of type III AFP interaction with ice crystals is more complex than that proposed previously. We report a high-resolution X-ray structure of type III AFP refined at 1.15 A resolution with individual anisotropic temperature factors. We report the results of ice-etching experiments that show a broad surface coverage, suggesting that type III AFP binds to a set of planes that are parallel with or inclined at a small angle to the crystallographic c-axis of the ice crystal. Our modelling studies, performed with the refined structure, confirm that type III AFP can make energetically favourable interactions with several ice surfaces.

Amino Acid Sequence↗
PubMed2001

Trends in passive smoking in cystic fibrosis, 1993-1998.

We set out to study trends in exposure to passive smoking in children with cystic fibrosis over a 5-year period. We also evaluated the effects of this exposure on lung function. Cross-sectional data were collected on 52 children in 1998 and compared with similar data collected on 56 children in 1993. Within these two groups, there were 34 children who were studied on both occasions. Data collected included: questionnaire information about family smoking habits; forced expiratory volume in 1 sec (FEV1); forced vital capacity (FVC); and measurements of urinary and salivary cotinine levels. Salivary cotinine was more closely related to family smoking behavior than urinary cotinine concentrations (r for salivary cotinine = 0.54, P < 0.001; r for urinary cotinine = 0.37, P = 0.008). In 1993, 26/56 (46%) households contained at least one smoker (smoking households) compared with 23/52 (44%) in 1998. In 1993, a median of 15 cigarettes was smoked/day in smoking households compared to 20 cigarettes/day in 1998. In the longitudinal group, there was a small, nonsignificant reduction in mean urinary cotinine levels (geometric mean, 1993 = 5.03 ng/mL; 1998 = 4.76 ng/mL; P = 0.4). There was no significant difference between the smoking and nonsmoking households in change in lung function over 5 years (fall in FEV1 in smoking households, 10.3% vs. 11.2% in nonsmoking households; P = 0.87). We conclude that in a group of children with cystic fibrosis followed over 5 years, there was little reduction in passive smoking exposure. We did not show a relationship between such exposure and decline in lung function. A larger study will be necessary to determine whether such an effect is present. .

Adolescent↗
PubMed2001

Endoplasmic oleoyl-PC desaturase references the second double bond.

The regiospecificity for the gene product of fad2,(1) the microsomal oleoyl-PC desaturase from higher plants, differs from some previous suggestions. Rather than only referencing the carboxyl group (a Delta(12) desaturase) or the methyl terminus (an omega-6 desaturase), this desaturase locates the second double bond in its substrates by first referencing the existing double bond. This specificity was demonstrated for the oleoyl-PC desaturase cDNA from the developing seeds of peanut (Arachis hypogaea L) expressed in yeast (Saccharomyces cerevisae). The expressed enzyme was capable of desaturating monounsaturated fatty acyl groups in membrane lipids. Endogenous palmitoleate was desaturated to cis, cis 9,12 hexadecadienoate (9(Z)12(Z)C16:2), endogenous oleate to linoleate (9(Z)12(Z) octadecadienoate), and cis 10-nonadecenoate (provided as a supplement in the growth medium) to 10(Z)13(Z)C19:2. The rule, Delta(x+3) where x=9 is the double bond location in the substrate, best describes the consistent placement of the second double bond in the above monounsaturated substrates for the oleoyl-PC desaturase of higher plants.

Cytoplasm↗
PubMed2001

Editorial.

Explore the source record for details and available documents.

Forecasting↗
PubMed2001

Hsp70 expression in Enteromorpha intestinalis (Chlorophyta) exposed to environmental stressors.

Numerous studies have indicated that stress proteins have potential as biomarkers of exposure to environmental contaminants. Analysis of stress proteins in animals, especially Hsp70, has dominated this research area despite increasing interest in the use of plants as pollution monitors. In the present study Hsp70 expression in Enteromorpha intestinalis has been investigated under exposure to a variety of stressors, to evaluate the potential use of Hsp70 as a biomarker of contaminant exposure in this seaweed. E. intestinalis was exposed to thermal stress, copper under differing conditions of nutrient availability and the triazine herbicide Irgarol 1051. Measurements were also taken to compare Hsp70 with conventional sublethal endpoints of toxicity such as growth and fluorescence induction parameters such as Fv/Fm. E. intestinalis exhibited a typical heat shock response. Hsp70 expression was increased with copper exposure, but proved to be a relatively insensitive biomarker of copper exposure compared to growth measurements. Nutrient limitation enhanced copper toxicity and significantly impaired growth, Fv/Fm and Hsp70 production. Fv/Fm and growth were strongly affected by Irgarol 1051 exposure, but Hsp70 levels were unaltered following exposure to the herbicide. The implications of using Hsp70 expression in E. intestinalis as a biomarker are discussed.

Chlorophyta↗
PubMed2001

Impact of rural hospital closures in Saskatchewan, Canada.

Canada's health care system has undergone major changes since 1990. In Saskatchewan, 52 small rural hospitals funded for less than eight beds stopped receiving funding for acute care services in 1993. Most were subsequently converted to primary health care centers. Since then, concerns have been raised about the impact of the changes on rural residents' access to care, their health status, and the viability of rural communities. To assess the impact of hospital closures on the affected communities, we conducted a multi-faceted, province-wide study. We looked at hospital use patterns, health status, rural residents' perceptions of the impact of these hospital closures, and how communities responded to the changes. We found the hospital closures did not adversely affect rural residents' health status or their access to inpatient hospital services. Despite widespread fears that health status would decline, residents in these communities reported that hospital closures did not adversely affect their own health. Although some communities continue to struggle with changes to health care delivery, others appear to have adapted as a result of strong community leadership, the development of widely accepted alternative services, and local support for creating innovative solutions. Good rural health care does not depend on the presence of a very small hospital that cannot, in today's environment, provide genuinely acute care. It requires creative approaches to the provision of primary care, good emergency services, and good communication with the public on the intent and outcomes of change.

Attitude to Health↗
PubMed2001

Zanthoxylum piperitum, an Asian spice, inhibits food intake in rats.

UNLABELLED: We investigated the effects of a total extract from Zanthoxylum piperitum fruit, of the volatile components of extract, and of a non-volatile fraction containing the major alkylamides of Zanthoxylum (NVA) on food intake in rats. In Experiment 1, three groups (A, B, C) of mildly food deprived rats were given one hour long feeding trials during which they were offered choices between an oat-bran wafer paired with vegetable oil and a wafer paired with a Zanthoxylum preparation in vegetable oil. Trials were divided into three blocks of two tests each. During Blocks 1 and 3, two wafers coated with vegetable oil were offered to establish baseline consumption. During Block 2, Group A was given choices between wafers coated with oil and wafers coated with total extract. Group B was offered oil coated wafers and wafers coated with the NVA fraction. Group C received two oil coated wafers. One was served on top of a screened dish containing a sample of total extract. In this manner, the rats were exposed to volatile compounds emanating from the extract but could not contact the extract. The second wafer was served on top of a screened sample of oil. RESULTS: In Blocks 1 and 3 trials, the rats fed indiscriminately from both wafers. During Block 2, total extract, the NVA fraction and the volatile compounds from extract all significantly reduced food consumption. In Experiment 2, habituation to the NVA fraction and to the volatile constituents of extract was examined in two additional groups (D, E), using the methods described above. Baseline consumption was tested in Blocks 1 and 3 by offering two oil coated wafers. During Block 2, group D was given 10 trials with oil coated and NVA-fraction coated wafers. Group E was given 10 trials with oil coated wafers paired with the volatile constituents of total extract and with those of oil. RESULTS: Both groups failed to habituate to the Zanthoxylum stimuli. Wafers treated with the NVA fraction and wafers paired with the volatile constituents of extract were avoided throughout the 10 test days.

Animals↗
PubMed2001

Needs-based cognitive-behavioural family intervention for carers of patients suffering from schizophrenia: 12-month follow-up.

OBJECTIVE: To examine longer-term effectiveness of a needs-based family intervention for carers and out-patients suffering from schizophrenia. METHOD: Seventy-nine unselected patient-carer pairs were recruited from a geographical area and allocated randomly to one of two conditions. One group received needs-based cognitive-behavioural family intervention in combination with general family support plus the standard care. The control group received the general family support and standard care only. RESULTS: Analysis was carried out on an intention-to-treat basis. There was a significant advantage for family intervention, in terms of relapse (37% relapsed compared to 72%, NNT=3) and on other clinical measures. Treatment group and medication compliance were significant and independent predictors of relapse. There was a significant reduction in carer needs in the intervention group. CONCLUSION: Family intervention directed at carers' needs within a standard mental health service can produce benefits for patients beyond the term of intervention.

Adult↗
PubMed2001

Role of IgE in primary murine Schistosomiasis mansoni.

Schistosoma mansoni infection proceeds in normal mice in the absence of detectable levels of polyclonal or specific immunoglobulin (Ig)E until worms mature and deposit eggs. Hence, the course of a primary S. mansoni infection is not expected to vary appreciably in mice with defects in the IgE production. Experimental increase of IgE production early after infection may, however, influence worm development. In the first approach towards this goal, BALB/c mice were injected with interleukin(IL)4 to raise the level of endogenously synthesized IgE. A significant increase in serum polyclonal IgE and antischistosome IgG1 during the prepatent period was not associated with significant changes in worm and egg burden or liver pathology. During the second approach, mice were injected with IgE which was affinity purified from serum of BALB/c mice infected for 16 weeks with S. mansoni. The purified IgE bound to carbohydrate-independent epitopes of soluble antigens from 3 h larvae, adult worms and eggs and recognized the schistosomular surface membrane. No differences in worm and egg load or granuloma number and size were noted between untreated and exogenous IgE-injected mice. Together, the data demonstrate that by itself IgE does not influence the outcome of infection in primary murine S. mansoni.

Animals↗