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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 19 recordsLinked to original sources
PubMed2006

Quantifying the magnetic advantage in magnetotaxis.

Magnetotactic bacteria are characterized by the production of magnetosomes, nanoscale particles of lipid bilayer encapsulated magnetite, that act to orient the bacteria in magnetic fields. These magnetosomes allow magneto-aerotaxis, which is the motion of the bacteria along a magnetic field and toward preferred concentrations of oxygen. Magneto-aerotaxis has been shown to direct the motion of these bacteria downward toward sediments and microaerobic environments favorable for growth. Herein, we compare the magneto-aerotaxis of wild-type, magnetic Magnetospirillum magneticum AMB-1 with a nonmagnetic mutant we have engineered. Using an applied magnetic field and an advancing oxygen gradient, we have quantified the magnetic advantage in magneto-aerotaxis as a more rapid migration to preferred oxygen levels. Magnetic, wild-type cells swimming in an applied magnetic field more quickly migrate away from the advancing oxygen than either wild-type cells in a zero field or the nonmagnetic cells in any field. We find that the responses of the magnetic and mutant strains are well described by a relatively simple analytical model, an analysis of which indicates that the key benefit of magnetotaxis is an enhancement of a bacterium's ability to detect oxygen, not an increase in its average speed moving away from high oxygen concentrations.

Biophysics↗
PubMed2006

Surgical delay in the management of dog bite injuries in children, does it increase the risk of infection?

Dog bites are contaminated wounds and convention dictates that any surgical treatment should be performed at the earliest opportunity. This practice, however, may be in direct conflict with NCEPOD guidelines to reduce night time operating. We audited our treatment of dog bite injuries in children over a 5-year period (1998-2002) to determine whether delaying surgery to conform to operating guidelines increased the incidence of infection. A retrospective case note study identified 118 patients admitted to Sheffield Children's Hospital with dog bite injuries. Details of their injury, treatment and outcome were recorded. There were 70 males and 48 females and an average age of 6.6 years (range 1-15 years). The most common type of injury was a single laceration (32%) and the most frequent site of injury was the face (59%). The majority of wounds (68%) were cleaned and dressed before theatre and 89% were closed directly after minimal debridement. All patients received prophylactic antibiotics. Of the 114 patients that required surgery, 57 (50%) were operated on within 12 h of their injury and 57 (50%) after 12 h. There were three cases of infection in the early group (<12 h) and none in the delayed group (>12 h). We suggest that delaying the surgical treatment of dog bites in children to avoid operating at night does not increase the infection rate.

Animals↗
PubMed2005

Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors.

A novel pyridothiophene inhibitor of PTP1B was discovered by rational screening of phosphotyrosine mimics at high micromolar concentrations. The potency of this lead compound has been improved significantly by medicinal chemistry guided by X-ray crystallography and molecular modeling. Excellent consistency has been observed between structure-activity relationships and structural information from PTP1B-inhibitor complexes.

Crystallography, X-Ray↗
PubMed2005

Effects of polycyclic aromatic hydrocarbons on germination and subsequent growth of grasses and legumes in freshly contaminated soil and soil with aged PAHs residues.

The relevance of germination trials for screening plants that may have potential for use in the phytoremediation of PAH contaminated land was evaluated. The germination and subsequent growth of 7 grass and legume species were evaluated in soil spiked with a pure PAH mixture or coal tar and soil from a former coking plant heavily contaminated with aged PAHs. None of these treatments adversely affected germination of the plants. However, apart from Lolium perenne all species exhibited reduced growth in the coking plant soil after 12 weeks growth when compared to the untreated soil. In the coal tar spiked soil 4 out of the 7 species showed reduced growth, as did 3 out of the 7 in the soil spiked with a mixture of 7 PAHs. Therefore, germination studies alone would not predict the success of subsequent growth of the species tested in the ranges of soil PAH levels studied.

Biodegradation, Environmental↗
PubMed2005

A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation.

In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek: mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause - among other relevant side-effects - an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary- adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident.

Amino Acids↗
PubMed2005

DNA methylation in lysogens of pathogenic Burkholderia spp. requires prophage induction and is restricted to excised phage DNA.

Burkholderia mallei-specific phage PhiE125 encodes DNA methyltransferases in both the lysogenic and replication modules within its genome. Characterization of DNA methylation in recombinant systems, specifically in PhiE125 lysogenic strains of B. mallei and Burkholderia thailandensis, revealed that, upon induction, cytosine methylation was targeted specifically to the phage episome but not the phage provirus or the host chromosome.

Bacteriophages↗
PubMed2004

The SIS extracellular matrix scaffold-preliminary results of use in congenital diaphragmatic hernia (CDH) repair.

There is no ideal bio-tensile material for tissue replacement in paediatric surgical conditions. A variety of materials have been described to replace or reinforce tissue deficits in congenital diaphragmatic hernia (CDH). The problems with these materials range from extensive surgery to body wall deformity and hernia recurrence. The ideal graft would be safe, strong, have the potential to grow and not require replacement, not affect chest wall development or produce deformity, and have minimal risk of recurrence. Surgisis is a biomaterial composed of porcine intestinal submucosa that provides inherent tensile strength as a collagen lattice and is ultimately replaced by native collagen tissue. Our objective was to prospectively assess the utility of Surgisis as a replacement graft in a cohort of 10 children undergoing primary or recurrent CDH repair. The graft was well tolerated, and there was no recurrence of herniation. We conclude that Surgisis collagen mesh may be a useful alternative for tissue replacement or reinforcement in difficult cases of CDH and diaphragmatic agenesis. The biological framework of Surgisis may also prove useful in other situations of complex tissue loss in children.

Extracellular Matrix↗
PubMed2004

Physicochemical evolution and molecular adaptation of the cetacean and artiodactyl cytochrome b proteins.

Cetaceans have most likely experienced metabolic shifts since evolutionarily diverging from their terrestrial ancestors, shifts that may be reflected in the proteins such as cytochrome b that are responsible for metabolic efficiency. However, accepted statistical methods for detecting molecular adaptation are largely biased against even moderately conservative proteins because the primary criterion involves a comparison of nonsynonymous and synonymous substitution rates (dN/dS); they do not allow for the possibility that adaptation may come in the form of very few amino acid changes. We apply the MM01 model to the possible molecular adaptation of cytochrome b among cetaceans because it does not rely on a dN/dS ratio, instead evaluating positive selection in terms of the amino acid properties that comprise protein phenotypes that selection at the molecular level may act upon. We also apply the codon-degeneracy model (CDM), which focuses on evaluating overall patterns of nucleotide substitution in terms of base exchange, codon position, and synonymy to estimate the overall effect of selection. Using these relatively new models, we characterize the molecular adaptation that has occurred in the cetacean cytochrome b protein by comparing revealed amino acid replacement patterns to those found among artiodactyls, the modern terrestrial mammals found to be most closely related to cetaceans. Our findings suggest that several regions of the cetacean cytochrome b protein have experienced molecular adaptation. Also, these adaptations are spatially associated with domain structure, protein function, and the structure and function of the cytochrome bc(1) complex and its constituents. We also have found a general correlation between the results of the analytical software programs TreeSAAP (which implements the MM01 model) and CDM (which implements the codon-degeneracy model).

Adaptation, Physiological↗
PubMed2004

Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria.

Despite consistent evidence that premenstrual dysphoria (PMD) is not characterized by abnormalities in basal ovarian hormone secretion, the possibility remains that PMD is associated with an abnormality in the regulation of the hypothalamic-pituitary-ovarian (HPO) axis. We studied HPO axis regulation in 11 women with prospectively confirmed PMD and 20 asymptomatic controls, during both the follicular and luteal phases of the menstrual cycle. Plasma levels of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), were obtained before and after stimulation with gonadotropin-releasing hormone (GnRH) (100 microg intravenously). Potential diagnostic- and menstrual cycle phase-related diferences in basal and plasma hormone levels were analyzed by repeated-measures analysis of variance. No significant differences were observed between women with PMD and controls in either basal or stimulated levels of FSH and LH. Stimulated FSH was significantly increased and stimulated LH was significantly decreased during the follicular compared with the luteal phase in both women with PMD and controls. These data are consistent with prior findings of normal basal reproductive hormone levels in women with PMD. Our data suggest the absence in women with PMD of an abnormality of dynamic ovarian function as measured by GnRH stimulation.

Adult↗
PubMed2004

Glutamic acid decarboxylase 67 (GAD67) gene expression in discrete regions of the rostral preoptic area change during the oestrous cycle and with age.

Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, is important to the timing and amplitude of the gonadotrophin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge on pro-oestrus. Data suggest that GABA input in the preoptic area must decrease for a normal LH surge to occur in young rats. We have previously found that ageing alters the timing and amplitude of the LH surge. Therefore, this study focused on changes in GAD(67) gene expression, a reflection of GABA synthesis, in two regions of the rostral preoptic area, the organum vasculosum of the lamina terminalis (OVLT) and the anteroventral periventricular nucleus (AVPV) during the oestrous cycle and with age. We assessed the possibility that the expression of GAD(67) mRNA in these regions displays time-related and age-dependent changes on pro-oestrus. Our results demonstrate that, with age, overall expression of GAD(67) mRNA decreases in the area surrounding the OVLT and in the AVPV. Young rats display a diurnal rhythm in GAD(67) mRNA in both regions. GAD(67) mRNA expression is high during the early morning hours of pro-oestrus and then declines around the time of the GnRH-induced LH surge. In addition, the diurnal rhythm disappears in the AVPV and is attenuated in the area surrounding the OVLT of middle-aged proestrous rats. These findings suggest that a loss of rhythmicity in GAD(67) gene expression and maintenance of inhibitory tone on proestrous afternoon may alter the timing and amplitude of the LH surge, as previously observed in middle-aged rats.

Aging↗
PubMed2004

Evolution of duplicated growth hormone genes in autotetraploid salmonid fishes.

A defining character of the piscine family Salmonidae is autotetraploidy resulting from a genome-doubling event some 25-100 million years ago. Initially, duplicated genes may have undergone concerted evolution and tetrasomic inheritance. Homeologous chromosomes eventually diverged and the resulting reduction in recombination and gene conversion between paralogous genes allowed the re-establishment of disomic inheritance. Among extant salmonine fishes (e.g. salmon, trout, char) the growth hormone (GH) gene is generally represented by two functional paralogs, GH1 and GH2. Sequence analyses of salmonid GH genes from species of subfamilies Coregoninae (whitefish, ciscos) and Salmoninae were used to examine the evolutionary history of the duplicated GH genes. Two divergent GH gene paralogs were also identified in Coregoninae, but they were not assignable to the GH1 and GH2 categories. The average sequence divergence between the coregonine GH genes was more than twofold lower than the corresponding divergence between the salmonine GH1 and GH2. Phylogenetic analysis of the coregonine GH paralogs did not resolve their relationship to the salmonine paralogs. These findings suggest that disomic inheritance of two GH genes was established by different mechanisms in these two subfamilies.

Animals↗
PubMed2004

Access to health care in South Africa--the influence of race and class.

OBJECTIVES: The first democratic government elected in South Africa in 1994 inherited huge inequities in health status and health provision across all sections of the population. This study set out to assess the impact of the new government's commitment to address these inequities and implement policies to improve population health in general and address inequalities in health care in particular. DESIGN: A 1998 household survey assessed many aspects of health delivery, including their own perceived and actual access to health care among different segments of South African society. RESULTS: Race was the main predictor of perceived changes in access to health care, with black, coloured-and Indian respondents significantly more likely to feel that access had improved since 1994, compared with white respondents. Socio-economic status (SES) was the main predictor of actual access to health care, with low and middle SES classes significantly less likely to access care when ill. CONCLUSIONS: One-third of respondents perceived health care access to have improved between 1994 and 1998, and this response was partially determined along racial lines. About one-quarter reported an inability to access health care when they required it, and this response was partially determined along socio-economic lines. This set of contrasting responses suggests that at a political level perceptions are largely influenced by race, but at the operational level actual access is influenced by SES.

Adult↗
PubMed2003

Release studies of benzalkonium chloride from hydrogel in a freshwater environment.

The use of underwater optical sensors to monitor pollution and climate change processes has led to the development of robust instruments able to be deployed in lakes and seas for months at a time. However, despite this improvement in their durability they are subject to biofouling on their optical ports resulting in erroneous readings. The use of hydrogel coatings containing the cationic surfactant benzalkonium chloride (BAC) has been shown to prevent the development of biofouling for up to 12 weeks in the marine environment. In this study the use of hydrogel coatings in the freshwater environment was less successful with fouling visible at 2 weeks. In both field and laboratory studies a rapid initial loss of BAC from the hydrogel film was observed. The loss is a combination of diffusive and mass flow but the period from 12 to 50 h appeared to fit to diffusion kinetics and a diffusion coefficient of 7.3 x 10(-8) cm2 s(-1) (13 degrees C) was calculated, an order of 10 times greater than that found in seawater. Subsequently the rate of loss of the residual BAC, for which a diffusion coefficient of 5.7 x 10(-10) cm2 s(-1) (15 degrees C) was measured, was too low to prevent the early stages of biofouling.

Benzalkonium Compounds↗
PubMed2002

Creutzfeldt-Jakob disease in Australia 1970-1999.

OBJECTIVE: To ascertain all persons who developed a transmissible spongiform encephalopathy (TSE) within Australia during the 30-year period 1970 to 1999 through a comprehensive national surveillance program and subject the group to detailed epidemiologic analysis. METHODS: Cases were ascertained through reviews of morbidity separation coding data from all university-affiliated tertiary referral hospitals, as well as the centralized data bases of state and territory health departments, regular national death certificate searches, and semiannual mailout questionnaires to all neurologists and pathologists throughout Australia. Prospective monitoring commenced in September 1993. RESULTS: A total of 387 patients were confirmed as having TSE during this epoch. The majority of cases were sporadic Creutzfeldt-Jakob disease (CJD) (90.7%), with 7.2% heredofamilial and 2.1% iatrogenic. Over this 30-year period, the national average annual sporadic CJD incidence rate per million progressively increased from 0.31 for the decade 1970 through 1979 to 0.77 for 1980 through 1989, reaching 1.03 for 1990 through 1999. Death certificates were found to have a false-positive rate of 11.5% and sensitivity of 83.0% for sporadic CJD. CONCLUSIONS: Within Australia, there has been a gradual increase in the incidence of transmissible spongiform encephalopathy over the three-decade period 1970 through 1999, peaking in 1999 at 1.4/million/year for sporadic Creutzfeldt-Jakob disease. This increase is believed secondary to improved case ascertainment. Variant Creutzfeldt-Jakob disease was not identified during this period. Age- and sex-adjusted comparisons showed a decline in incidence rates in the elderly in both sexes, usually from age 74 years. Death certificates were a useful but imperfect method of case detection.

Adult↗
PubMed2002

Hepatic xenobiotic metabolism of cylindrospermopsin in vivo in the mouse.

Cylindrospermopsin (CYN) is a hepatotoxin isolated from the blue-green alga Cylindrospermopsis raciborskii. The role of both glutathione (GSH) and the cytochrome P450 enzyme system (P450) in the mechanism of toxicity of CYN has been previously investigated in in vitro systems. We have investigated the role of GSH and P450 in vivo in mice. Mice pre-treated with buthionine sulphoximine and diethyl maleate to deplete hepatic GSH prior to dosing with 0.2mg/kg CYN showed a seven-day survival rate of 5/13 while the control group rate was 9/14. Dosing mice with 0.2mg/kg CYN produced a small decrease in hepatic GSH with a characteristic rebound effect at 24h. The magnitude of this effect is however small and combined with the non-significant difference in survival rates after GSH depletion suggest depletion of GSH by CYN could not be a primary mechanism for CYN toxicity. Conversely, pre-treatment with piperonyl butoxide, a P450 inhibitor, protected mice against CYN toxicity giving a survival rate of 10/10 compared with 4/10 in the control group (p < 0.05 Chi squared) and was protective at doses up to 0.8 mg/kg, suggesting activation of CYN by P450 is of primary importance in the mechanism of action.

Alkaloids↗