Biomedical subjects

Andrew Myers

Publications and source records attributed to Andrew Myers.

5 recordsLinked to original sources

PubMed2006

Analysis of proline reduction in the nosocomial pathogen Clostridium difficile.

Clostridium difficile, a proteolytic strict anaerobe, has emerged as a clinically significant nosocomial pathogen in recent years. Pathogenesis is due to the production of lethal toxins, A and B, members of the large clostridial cytotoxin family. Although it has been established that alterations in the amino acid content of the growth medium affect toxin production, the molecular mechanism for this observed effect is not yet known. Since there is a paucity of information on the amino acid fermentation pathways used by this pathogen, we investigated whether Stickland reactions might be at the heart of its bioenergetic pathways. Growth of C. difficile on Stickland pairs yielded large increases in cell density in a limiting basal medium, demonstrating that these reactions are tied to ATP production. Selenium supplementation was required for this increase in cell yield. Analysis of genome sequence data reveals genes encoding the protein components of two key selenoenzyme reductases, glycine reductase and d-proline reductase (PR). These selenoenzymes were expressed upon the addition of the corresponding Stickland acceptor (glycine, proline, or hydroxyproline). Purification of the selenoenzyme d-proline reductase revealed a mixed complex of PrdA and PrdB (SeCys-containing) proteins. PR utilized only d-proline but not l-hydroxyproline, even in the presence of an expressed and purified proline racemase. PR was found to be independent of divalent cations, and zinc was a potent inhibitor of PR. These results show that Stickland reactions are key to the growth of C. difficile and that the mechanism of PR may differ significantly from that of previously studied PR from nonpathogenic species.

Amino Acid Isomerases↗

PubMed2005

Restless legs syndrome prevalence and impact: REST general population study.

BACKGROUND: Restless legs syndrome (RLS), a common sensorimotor disorder, has a wide range of severity from merely annoying to affecting sleep and quality of life severely enough to warrant medical treatment. Previous epidemiological studies, however, have failed to determine the prevalence of those with clinically significant RLS symptoms and to examine the life effects and medical experiences of this group. METHODS: A total of 16 202 adults (aged >/=18 years) were interviewed using validated diagnostic questions to determine the presence, frequency, and severity of RLS symptoms; respondents reporting RLS symptoms were asked about medical diagnoses and the impact of the disorder and completed the Short Form-36 Health Survey (SF-36). Criteria determined by RLS experts for medically significant RLS (frequency at least twice a week, distress at least moderate) defined "RLS sufferers" as a group most likely to warrant medical treatment. RESULTS: In all, 15 391 fully completed questionnaires were obtained; in the past year, RLS symptoms of any frequency were reported by 1114 (7.2%). Symptoms occurred at least weekly for 773 respondents (5.0%); they occurred at least 2 times per week and were reported as moderately or severely distressing by 416 (2.7%). Of those 416 (termed RLS sufferers), 337 (81.0%) reported discussing their symptoms with a primary care physician, and only 21 (6.2%) were given a diagnosis of RLS. The SF-36 scores for RLS sufferers were significantly below population norms, matching those of patients with other chronic medical conditions. CONCLUSION: Clinically significant RLS is common (prevalence, 2.7%), is underdiagnosed, and significantly affects sleep and quality of life.

Adolescent↗

PubMed2005

Increasing reading speed by using colours: issues concerning reliability and specificity, and their theoretical and practical implications.

By using techniques for precision ophthalmic tinting, individuals who report perceptual distortion of text can often find a colour of illumination that eliminates the distortions and increases reading speed. Most individuals choose green or blue hues, but there is considerable variability. We investigated how specific the colour has to be to obtain optimal reading speed. Individuals who habitually wear coloured filters for reading were asked to read text illuminated by coloured light (without using their filters). Reading speed was measured repeatedly with light of different colours. The colour (chromaticity) at which reading was fastest was consistent from one test session to the next. It was different from one individual to another, but highly specific for each individual: departures of colour from optimum by about 6 JNDs eliminated most of the speed advantage conferred by the optimal colour. It was difficult to attribute the consistency and specificity simply to familiarity with the tint or immediate memory for the colour of illumination. A consecutive sample of 1000 tint prescriptions was analysed numerically. For most prescriptions the variation in chromaticity with different types of lighting was not such as to remove all the potential benefit of the tint, as judged from a model of the effect of chromaticity on reading speed. The exceptions were the few tints that were weakly saturated or purple in colour. Across participants, reading speed was not consistently related to the scotopic energy, to the energy captured by any cone class, or to opponent colour processes. The reading was generally slowest with white light, and not with the colour complementary to the optimum. Explanations in terms of magnocellular deficits and cortical hyperexcitability are briefly discussed.

Adolescent↗

PubMed2004

Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study.

OBJECTIVES: To assess the frequency, impact, and medical response to the restless legs syndrome (RLS) in a large multi-national primary care population. METHOD: Questionnaire surveys of matched patients and primary care physicians (PCPs) in five modern industrialized western countries. RESULTS: An RLS screening questionnaire was completed by 23,052 patients: 2223 (9.6%) reported weekly RLS symptoms; 1557 of these patients had medical follow-up questionnaires completed both by themselves and by their physician. An RLS sufferer subgroup (n=551) likely warranting treatment was defined as reporting at least twice weekly symptoms with appreciable negative impact on quality of life. A total of 88.4% of RLS sufferers reported at least one sleep-related symptom. Most reported impaired sleep consistent with a diagnosis of insomnia. Out of 551 sufferers, 357 (64.8%) reported consulting a physician about their RLS symptoms, but only 46 of these 357 (12.9%) reported having been given a diagnosis. PCPs reported that 209 (37.9%) RLS sufferers consulted them about RLS symptoms, but only 52 (24.9%) were given an RLS diagnosis. In most countries, sufferers, regardless of diagnosis, were prescribed therapies not known to be effective in RLS. CONCLUSIONS: RLS significantly impairs patients' lives, often by severely disrupting sleep. The marked under-diagnosis and inappropriate treatment of RLS indicates that PCPs need better education about this condition. Recognizing how often disrupted sleep results from RLS should improve diagnosis.

Drug Therapy↗

PubMed2003

A spatio-temporal dipole simulation of gastrointestinal magnetic fields.

We have developed a simulation of magnetic fields from gastrointestinal (GI) smooth muscle. Current sources are modeled as depolarization dipoles at the leading edge of the isopotential ring of electrical control activity (ECA) that is driven by coupled cells in the GI musculature. The dipole moment resulting from the known transmembrane potential distribution varies in frequency and phase depending on location in the GI tract. Magnetic fields in a homogeneous volume conductor are computed using the law of Biot-Savart and characterized by their spatial and temporal variation. The model predicts that the natural ECA frequency gradient may be detected by magnetic field detectors outside the abdomen. It also shows that propagation of the ECA in the gastric musculature results in propagating magnetic field patterns. Uncoupling of gastric smooth muscle cells disrupts the normal magnetic field propagation pattern. Intestinal ischemia, which has been experimentally characterized by lower-than-normal ECA frequencies, also produces external magnetic fields with lower ECA frequencies.

Action Potentials↗