Forest plots: trying to see the wood and the trees.
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Adrenergic beta-Antagonists↗
Biomedical subjects
S Lewis
Publications and source records attributed to S Lewis.
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↗
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↗
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↗
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↗
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↗
Gaucher's disease. Nose bleeds and bruising.
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Adult↗
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↗
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↗
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↗
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↗
Unrecognised anaphylaxis to propofol or fentanyl.
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Anaphylaxis↗
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↗
Immune response to blood transfusion in very-low-birthweight infants.
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Antibody Formation↗
A case-control study of risk factors for asthma in New Zealand children.
OBJECTIVE: As in other English-speaking countries, asthma is a major and increasing health problem in New Zealand. This study examined the risk factors for asthma in children aged 7-9. METHODS: Cases and controls were randomly selected from participants in the Wellington arm of the International Study of Asthma and Allergies in Childhood (ISAAC). Cases were children with a previous diagnosis of asthma and current medication use (n=233), and controls were children with no history of wheezing and no diagnosis of asthma (n=241). RESULTS: After controlling for confounders, factors significantly associated with asthma were maternal (OR=3.36, 95% CI 1.88-5.99) and paternal asthma (OR-2.67, 95% CI 1.42-5.02), and male sex (OR=1.81, 95% CI 1.17-2.81). Children from social classes 5 and 6 or with unemployed parents (OR=2.32, 95% CI 1.22-4.44) were significantly more likely to have asthma than children in social classes 1 and 2. There was no significant association between having polio vaccination (OR=2.48, 95% CI 0.83-7.41), hepatitis B vaccination (OR=0.66, 95% CI 0.42-1.04) or measles/mumps/rubella vaccination (OR=1.43, 95% CI 0.85-2.41) and asthma. CONCLUSIONS: This study has confirmed the associations of family history and lower socio-economic status with current asthma in 7-9 year old children. The role of vaccinations requires further research.
Asthma↗
Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial.
BACKGROUND AND PURPOSE: We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation (AF), identify the main factors associated with early death, and assess the effect of treatment with different doses of subcutaneous unfractionated heparin (UFH) given within 48 hours. METHODS: We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial, first for all treatment groups combined. Then, among patients with AF, we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset. RESULTS: A total of 3169 patients (17%) had AF. Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID, 773 to UFH 5000 IU SC BID, and 1612 to no heparin. Within each of these groups, half of the patients were randomly assigned to aspirin 300 mg once daily. Compared with patients without AF, patients with AF were more likely to be female (56% versus 45%), to be old (mean age, 78 versus 71 years), to have an infarct on prerandomization CT (57% versus 47%), and to have impaired consciousness (37% versus 20%). The initial ischemic stroke type was more often a large-artery infarct (36% versus 21%). A lacunar stroke syndrome was less common (13% versus 26%). Death within 14 days was more common in patients with AF (17% versus 8%) and more often attributed to neurological damage from the initial stroke (10% versus 4%). The frequency of recurrent ischemic or undefined stroke was not significantly different (3.9% versus 3.3%). The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU (n=784), UFH 5000 IU (n=773), and to no-heparin (n=1612) groups were as follows: ischemic stroke, 2.3%, 3.4%, 4.9% (P=0.001); hemorrhagic stroke, 2.8%, 1.3%, 0.4% (P<0.0001); and any stroke or death, 18.8%, 19.4% and 20.7% (P=0.3), respectively. No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent. CONCLUSIONS: Acute ischemic stroke patients with AF have a higher risk of early death, which can be explained by older age and larger infarcts but not by a higher risk of early recurrent ischemic stroke, although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type (1.3% versus 0.9%). In patients with AF the absolute risk of early recurrent stroke is low, and there is no net advantage to treatment with heparin. These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF.
Acute Disease↗