Biomedical subjects
M Lewis
Publications and source records attributed to M Lewis.
Characterization of an atrazine-degrading Pseudaminobacter sp. isolated from Canadian and French agricultural soils.
Atrazine, a herbicide widely used in corn production, is a frequently detected groundwater contaminant. Fourteen bacterial strains able to use this herbicide as a sole source of nitrogen were isolated from soils obtained from two farms in Canada and two farms in France. These strains were indistinguishable from each other based on repetitive extragenic palindromic PCR genomic fingerprinting performed with primers ERIC1R, ERIC2, and BOXA1R. Based on 16S rRNA sequence analysis of one representative isolate, strain C147, the isolates belong to the genus Pseudaminobacter in the family Rhizobiaceae. Strain C147 did not form nodules on the legumes alfalfa (Medicago sativa L.), birdsfoot trefoil (Lotus corniculatus L.), red clover (Trifolium pratense L.), chickpea (Cicer arietinum L.), and soybean (Glycine max L.). A number of chloro-substituted s-triazine herbicides were degraded, but methylthio-substituted s-triazine herbicides were not degraded. Based on metabolite identification data, the fact that oxygen was not required, and hybridization of genomic DNA to the atzABC genes, atrazine degradation occurred via a series of hydrolytic reactions initiated by dechlorination and followed by dealkylation. Most strains could mineralize [ring-U-(14)C]atrazine, and those that could not mineralize atrazine lacked atzB or atzBC. The atzABC genes, which were plasmid borne in every atrazine-degrading isolate examined, were unstable and were not always clustered together on the same plasmid. Loss of atzB was accompanied by loss of a copy of IS1071. Our results indicate that an atrazine-degrading Pseudaminobacter sp. with remarkably little diversity is widely distributed in agricultural soils and that genes of the atrazine degradation pathway carried by independent isolates of this organism are not clustered, can be independently lost, and may be associated with a catabolic transposon. We propose that the widespread distribution of the atrazine-degrading Pseudaminobacter sp. in agricultural soils exposed to atrazine is due to the characteristic ability of this organism to utilize alkylamines, and therefore atrazine, as sole sources of carbon when the atzABC genes are acquired.
Social class, smoking and the severity of respiratory symptoms in the general population.
STUDY OBJECTIVE: The prevalence of respiratory symptoms has been found in some studies to vary with social class. One explanation of this link may be the effect of exposure to cigarette smoke. To investigate this, the relation between social class, smoking and respiratory symptoms was explored in a population based survey. DESIGN: A cross sectional survey using a validated questionnaire. SETTING: Two general practices in Staffordshire, United Kingdom. PATIENTS: A random sample of 4237 patients aged 16 and over from two general practices in Staffordshire were mailed a questionnaire enquiring about respiratory symptoms and their severity. MAIN RESULTS: The severity of respiratory symptoms increased with increasing exposure to cigarette smoke and was greater among manual social classes. Current smokers (odds ratio (OR) = 2.9, 95% confidence limits (CI) 2.3, 3.6), past smokers (OR = 1.5, 95% CI 1.2, 1.8) and passive smokers (OR = 1.4, 95% CI 1.0, 1.8) were more likely to report the more severe respiratory symptoms compared with non-smokers. Responders from social class V (OR = 2.4, 95% CI 1.3, 4. 4) were more likely to report the more severe respiratory symptoms compared with social class I, as were responders from social classes IIIM (OR = 1.3, 95% CI 0.9, 1.9) and IV (OR = 1.4, 95% CI 0.9, 2.1). These effects were independent of each other. CONCLUSIONS: This study has shown that social class is linked to the severity of respiratory symptoms, independently of smoking. Although the need to reduce and quit smoking in manual class households remains a crucial preventive issue, other mechanisms by which social class differences may influence symptom occurrence and severity need to be explored.
Intravenous immunoglobulin causing reversible posterior leukoencephalopathy syndrome?
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Congenital internal carotid artery aneurysm with absence of the petrous portion of the contralateral internal carotid artery.
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Library requirements and problem-based learning: The Medical Sciences Library, The University of the West Indies.
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Does psychological status predict the presentation in primary care of women with a menstrual disturbance?
Thirty per cent of women aged 35 years and over suffer from heavy menstruation, but only 7% have consulted a doctor in the previous six months, suggesting that a significant number of these women do not consult a general practitioner. There is evidence that women who report heavy menstruation are more likely to have symptoms of psychological disturbance. This study sets out to determine whether the presence of symptoms of anxiety and depression might be linked to subsequent consultation for increased vaginal bleeding in primary care.
Atrial fibrillation: a comparison of methods to identify cases in general practice.
The importance of atrial fibrillation as a treatable risk factor for stroke is well established. Less is known about how to find previously unidentified cases within the community so that antithrombotic treatment can be offered to a wider group of at-risk patients. The aim of our study was to examine ways to improve the efficiency of practice-based screening for atrial fibrillation, including issues of time and financial cost. We used different combinations of pulse palpation and interpretation of 12-lead and bipolar electrocardiographs as carried out by practice nurses. The best strategy for the detection of atrial fibrillation in a practice population would appear to be to screen all eligible subjects by nurse pulse palpation, followed by 12-lead electrocardiograph readings in those who have a pulse suggestive of atrial fibrillation. The electrocardiograph interpretation can be undertaken effectively by a trained nurse.
Community care management. Advanced practice nurses as care managers.
A group of advanced practice nurses partnered with a major insurer in the design and implementation of a care coordination model for high-risk older adults. This article will discuss the process of such an undertaking, highlighting the successes and barriers encountered. The key elements of this program included early identification and regular reassessment of each member's acuity level; fostering close partnerships between individual or teams of APRNs and groups of physicians; and uninterrupted clinical management of high-risk members across the health care continuum. This model was designed to achieve the following outcomes: to support the physician management of high-risk, chronic individuals; to increase or maintain the health of members; and to reduce health care costs. Outcome studies have demonstrated a substantial net savings by decreasing acute care admissions by 54%, reducing hospital days by 42%, and trimming primary care physicians' and specialists' visit costs by 37%. There was a 33% reduction in the overall costs of health care for members enrolled in this program. Physicians and members both rated their satisfaction with the APRN-based model of care as very high.
Anemia management: recognizing opportunities and improving outcomes through nursing interventions.
In the symposium "Anemia Management: Recognizing Opportunities and Improving Outcomes Through Nursing Interventions," Gail Wick discussed the nephrology nurse as a clinical change agent in the management of anemia of chronic renal failure. Matthew Lewis discussed the profile of sodium ferric gluconate complex, a new parenteral iron product, and Jamie Foret described his clinic's experience and research with this product. These discussions highlight how nurses, using effective and safe tools such as sodium ferric gluconate complex, can improve outcomes for hemodialysis patients.
Different population dynamics of human T cell lymphotropic virus type II in intravenous drug users compared with endemically infected tribes.
The phylogeny of human T cell lymphotropic virus type II (HTLV-II) was investigated by using strains isolated from Amerindian and Pygmy tribes, in which the virus is maintained primarily through mother-to-child transmission via breast-feeding, and strains from intravenous drug users (IDUs), in which spread is mainly blood-borne via needle sharing. Molecular clock analysis showed that HTLV-II has two different evolutionary rates with the molecular clock for the virus in IDUs ticking 150-350 times faster than the one in endemically infected tribes: 2.7 x 10(-4) compared with 1.71/7.31 x 10(-7) nucleotide substitutions per site per year in the long terminal repeat region. This dramatic acceleration of the evolutionary rate seems to be related with the mode of transmission. Mathematical models showed the correlation of these two molecular clocks with an endemic spread of HTLV-II in infected tribes compared with the epidemic spread in IDUs. We also noted a sharp increase in the population size of the virus among IDUs during the last decades probably caused by the worldwide increase in intravenous drug use.
Quinone reductase inhibitors block SAPK/JNK and NFkappaB pathways and potentiate apoptosis.
A variety of environmental stresses stimulate the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEKK) > stress-activated protein kinase (SAPK)-ERK kinase (SEK) > SAPK/c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase cascade and coordinately activate the transcription factor NFkappaB. Mechanisms of stress activation upstream of MEKK1 have not been precisely determined. Redox mechanisms involving sulfhydryls are likely because N-acetyl-cysteine at millimolar concentrations blocks stress signals. Because intracellular sulfhydryl concentrations can be regulated through redox cycling involving reactive quinones (1), we tested the ability of quinone reductase inhibitors to alter stress signaling. Several quinone reductases are inhibited by dicoumarol, a coumarin derivative. Dicoumarol prevented SAPK activation in vivo by chemical cell stressors and also prevented SAPK activation induced by expression of the tumor necrosis factor alpha (TNFalpha) receptor-associated protein TRAF2 but not by expression of truncated active MEKK1. Other coumarin derivatives failed to block SAPK activation, but other inhibitors of quinone reductases, particularly menadione, similarly blocked SAPK activation. Cells deficient in a major quinone reductase, NQO1, displayed hypersensitivity to dicoumarol stress inhibition, whereas SAPK in cells reconstituted with the NQO1 gene displayed relative dicoumarol resistance. Consistent with the proposed role of overlapping upstream signaling cascades in activation of NFkappaB, dicoumarol also blocked NFkappaB activation in primary macrophages stimulated with either lipopolysaccharide or TNFalpha. In addition, dicoumarol strongly potentiated TNFalpha-induced apoptosis in HeLa cells, probably by blocking the anti-apoptotic effect of NFkappaB. The ability of dicoumarol to simultaneously inhibit SAPK and NFkappaB activation and to potentiate apoptotic cell death suggests that SAPK is not an obligate participant in apoptosis. Dicoumarol, currently in clinical use as an oral anticoagulant, represents a potential therapeutic inhibitor of the SAPK and NFkappaB response.
Pragmatic randomised controlled trial of local corticosteroid injection and naproxen for treatment of lateral epicondylitis of elbow in primary care.
OBJECTIVE: To compare the clinical effectiveness of local corticosteroid injection, standard non-steroidal anti-inflammatory drugs, and simple analgesics for the early treatment of lateral epicondylitis in primary care. DESIGN: Multicentre pragmatic randomised controlled trial. SETTING: 23 general practices in North Staffordshire and South Cheshire. PARTICIPANTS: 164 patients aged 18-70 years presenting with a new episode of lateral epicondylitis. INTERVENTIONS: Local injection of 20 mg methylprednisolone plus lignocaine, naproxen 500 mg twice daily for two weeks, or placebo tablets. All participants received a standard advice sheet and co-codamol as required. MAIN OUTCOME MEASURES: Participants' global assessment of improvement (five point scale) at four weeks. Pain, function, and "main complaint" measured on 10 point Likert scales at 4 weeks, 6 months, and 12 months. RESULTS: Over 2 years, 53 subjects were randomised to injection, 53 to naproxen, and 58 to placebo. Prognostic variables were similar between groups at baseline. At 4 weeks, 48 patients (92%) in the injection group were completely better or improved compared with 30 (57%) in the naproxen group (P<0.001) and 28 (50%) in the placebo group (P<0.001). At 12 months, 43 patients (84%) in the injection group had pain scores </=3 compared with 45 (85%) in the naproxen group and 44 (82%) in the placebo group (P>0.05). CONCLUSIONS: Early local corticosteroid injection is effective for lateral epicondylitis. Outcome at one year was good in all groups, and effective early treatment does not seem to influence this.
Single- and double-proton-transfer in the aggregate between cytosine and guaninediazonium ion.
[formula: see text] The structure of "guaninediazonium ion" in its aggregate with cytosine has been explored with ab initio and density functional methods. The hydrogen-bonded aggregate between cytosine and guaninediazonium ion, 1, is a stable minimum, 3. While the isolated enol tautomer of guaninediazonium ion, 2, is significantly more stable than 1, the tautomeric aggregate 4 that results from double-proton-transfer in 3 is almost isoenergetic with 3. Most interesting and entirely unexpected is the finding that neither 3 nor 4 is predicted to be the thermodynamically predominant structure. Instead, single-proton-transfer to cytosine results in the most stable cytosinium-guaninediazo complex, 5.
Transcriptional inhibition of stromelysin by interferon-gamma in normal human fibroblasts is mediated by the AP-1 domain.
The expression of the major matrix-degrading metalloproteinase, stromelysin (SL), is modulated by a variety of cytokines and growth factors. Interferon-gamma (IFN-gamma) is a potent modulator of SL expression, either inhibiting or activating expression in a cell-specific manner. We have investigated the mechanisms involved in the regulation of SL gene expression in cultured human fibroblasts by IFN-gamma. Reverse transcription-polymerase chain reaction (RT-PCR) assays confirmed the previously reported profound inhibitory response of SL mRNA expression to IFN-gamma [Amaldi et al., 1989]. For evaluation in transient gene expression assays, 1.2-kilobase (kb) pairs (-1214 to +14 relative to the transcription start site), and shorter, deletion mutant fragments of the SL promoter were cloned into appropriate chloramphenicol acetyltransferase transferase (CAT) expression vectors. The SL promoter along this region contains an active polyomavirus enhancer A-binding protein-3 (PEA-3) site at -216 and an activator protein-1 (AP-1) site at -70. Treatment of transfected neonatal foreskin fibroblasts with 300-500 U/ml IFN-gamma resulted in down-regulation of both basal and IL-1beta-induced CAT gene expression. IFN-gamma also decreased CAT expression when placed under the control of a synthetic multimeric AP-1 site construct. Gel-shift assay data indicate a decrease in specific binding to AP-1 oligonucleotide of nuclear extract from IFN-gamma and PMA/IFN-gamma-treated cells. The suppression of SL expression by IFN-gamma, in human fibroblasts therefore is mediated through the AP-1 element.
Should we accept all comers?
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Morphological and taxonomic affinities of the Olduvai ulna (OH 36).
The OH 36 ulna derives from Upper Bed II in the Olduvai Gorge, and is dated to circa 1.1-1.2 Myr. Multivariate analyses incorporating data from samples of modern humans, common and pygmy chimpanzees, gorillas, orangutans, and two other early hominin ulnae, Omo L40-19 and KNM-BK 66, suggest that OH 36 belonged to an individual with powerful forearms consistent with a locomotor repertoire that included arboreal locomotion. However, there is no compelling evidence that it made regular use of its forelimbs as supports when travelling on the ground. When compared with levels of intra- and intertaxon size and shape variation in the comparative sample (humans, chimpanzees, gorillas), the differences between OH 36, KNM-BK 66, and Omo L40-19 are compatible with OH 36 differing from the other two fossil hominin ulnae to the extent that modern humans differ from modern great apes. KNM-BK 66 and Omo L40-19 differ from each other in overall size and shape only to the degree that would be expected within any of the individual modern comparative samples. Based on these analyses, there is no evidence to support the hypothesis that OH 36 and Omo L40-19 belong to the same species of fossil hominin, or to two species that shared a similar forelimb locomotor repertoire. We suggest that OH 36 has the greater claim to be assigned to Paranthropus boisei, and we recommend that for the time being the latter be referred to the tribe Hominini gen. et sp. indet. The surprising result of these analyses is the overall size and shape similarity between Omo L40-19 and KNM-BK 66, two fossils that are separated in time by more than 1.5 million years, and which have traditionally been assumed to represent hominin species with quite different locomotor patterns.
Age and gender differences in children's and adolescents' adaptation to sexual abuse.
OBJECTIVE: How children manifest psychological distress following the discovery of sexual abuse requires a better understanding of individual differences in developmental capacities and vulnerabilities. This study examined how age at the time of the abuse discovery and gender of victim are related to psychological distress. METHOD: One hundred and sixty-nine participants (96 children, 73 adolescents) were interviewed within 8 weeks of discovery of the abuse. Multivariate analyses were used to examine how age at discovery, and gender, with abuse characteristics as covariates, were related to shame, attribution style, depression, self-esteem, and traumatic events sequelae. RESULTS: Adolescents compared to children report a higher level of depressive symptoms, negative reactions by others, and lower levels of self-esteem, social support, and sexual anxiety. Girls compared to boys report higher levels of intrusive thoughts, hyperarousal, sexual anxiety, personal vulnerability, and perceiving the world as a dangerous place and lower levels of eroticism. CONCLUSIONS: These findings suggest the importance of considering individual differences in age and gender for understanding patterns of symptom expression. Treatment strategies need to reflect these individual differences in adjustment, such as targeting issues of sexual anxiety for girls and self-esteem for adolescents.