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Biomedical subjects

G Payne

Publications and source records attributed to G Payne.

At least 19 recordsLinked to original sources

Concurrent comparison of three water contact measurement tools in four endemic villages of the Philippines. The schistosomiasis transmission ecology in the Philippines project (STEP).

BACKGROUND: Schistosomiasis japonica is a chronic helminthic infection contracted through contact with water infested with Schistosoma japonicum. The infection is associated with severe disease and is an important public health concern in Philippines. OBJECT: To estimate the agreement in the frequency of water contact between bimonthly interviews, self-administered diaries and observations. METHODS: A total of 286 individuals were followed over either a 4 or a 6 months period. Agreement between direct observation and both the bimonthly and diary methods were estimated. RESULTS: The agreement between the observation and the bimonthly interview was 71.8% when days without any water contacts were considered, but decreased to 23.3% when only days with at least some water contact were considered. The agreement between the observation and the diary was 78.7% when days without any water contacts were considered and 40.8% when only days with some water contacts were considered. CONCLUSIONS: Agreement about the degree of water contact is poor between the different measurement tools. This has important implications for future research, since a high degree of measurement error can severely bias any results from studies involving water contact.

Adult↗

Management and outcomes of acute coronary syndrome with minimal myocardial necrosis: analysis of a large prospective registry from a non-interventional centre.

The aim of this study was to assess the clinical risk of minimal myonecrosis below the cut-off for acute myocardial infarction (MI) in comparison with other grades of acute coronary syndrome (ACS). One-thousand four hundred and sixty seven consecutive patients with ACS admitted between May 2001 and April 2002 were studied in a non-interventional centre. Patients were divided into unstable angina (UA) (cTnT < 0.01 microg/l), non-ST elevation ACS with minimal myonecrosis (0.01 or= 0.1 microg/L) and ST elevation myocardial infarction (STEMI). UA (n = 638) was associated with the fewest events at 6 months (2% cardiac death or MI). Patients with any myonecrosis (n = 829) had worse outcomes (6-month cardiac death or MI 18.3-23.3%). Compared with ACS patients with minimal myonecrosis, UA patients were at significantly lower risk (OR 0.21, 95% CI 0.12-0.45, p < 0.001), NSTEMI patients were at similar risk (OR 1.45, 95% CI 0.89-2.35, p = 0.13), and STEMI patients were at higher risk (OR 2.12 95% CI 1.26-3.85, p = 0.008) in adjusted analyses. Nearly 85% of cardiac deaths occurred within 6 months. The risk of adverse events was higher among patients managed by non-cardiologists (OR 1.66, 95% CI 1-2.75, p = 0.049). Patients with non-ST elevation ACS and minimal myonecrosis are a high-risk group more comparable with NSTEMI and clearly distinguishable from patients with UA.

Aged↗

Participant recruitment in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a practice-based, randomized, multicenter clinical trial in 42,419 high-risk hypertensive patients aged 55 years and older; 10,356 of these patients are also in a lipid-lowering trial component. The purpose of the antihypertensive component is to determine whether the occurrence of fatal coronary heart disease and/or nonfatal myocardial infarction differs between patients randomized to diuretic (chlorthalidone) and those randomized to either calcium antagonist (amlodipine), angiotensin-converting enzyme inhibitor (lisinopril), or alpha-adrenergic blocker (doxazosin) therapy. (The doxazosin arm has been discontinued.) The purpose of the lipid-lowering component is to determine whether lowering low-density lipoprotein cholesterol with a 3-hydroxymethyl-glutaryl coenzyme A reductase inhibitor (pravastatin) in moderately hypercholesterolemic patients will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT recruited patients from a variety of practice settings from February 1994 through January 1998. Sites were paid for randomizations and are paid for completed follow-up visits and documented study events. Communication and monitoring were facilitated by nine regional coordinator teams. It was recognized from the outset that patient recruitment would be a very large task because of the number of participants (> 40,000) needed, the ambitious nature of the goal for recruitment of African-Americans (> 55%), and the knowledge that many investigators had limited experience recruiting participants for clinical trials. Multiple adjustments in the initial ALLHAT overall recruitment plan facilitated achievement of sample size goals for both components of the trial. The experience obtained from this large trial should be valuable for the planning and implementation of successful recruitment in future trials.

Aged↗

Growth factors inactivate the cell death promoter BAD by phosphorylation of its BH3 domain on Ser155.

The Bcl-2 family protein BAD promotes apoptosis by binding through its BH3 domain to Bcl-x(L) and related cell death suppressors. When BAD is phosphorylated on either Ser(112) or Ser(136), it forms a complex with 14-3-3 in the cytosol and no longer interacts with Bcl-x(L) at the mitochondria. Here we show that phosphorylation of a distinct site Ser(155), which is at the center of the BAD BH3 domain, directly suppressed the pro-apoptotic function of BAD by eliminating its affinity for Bcl-x(L). Protein kinase A functioned as a BAD Ser(155) kinase both in vitro and in cells. BAD Ser(155) was found to be a major site of phosphorylation induced following stimulation by growth factors and prevented by protein kinase A inhibitors but not by inhibitors of the phosphatidylinositol 3-kinase/Akt pathway. Growth factors inhibited BAD-induced apoptosis in both a Ser(112)/Ser(136)- and a Ser(155)-dependent fashion. Thus, growth factors engage an anti-apoptotic signaling pathway that inactivates BAD by direct modification of its BH3 cell death effector domain.

Amino Acid Sequence↗

Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer.

BACKGROUND: To avoid the late sequelae associated with cranial radiation therapy in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has found increasing application as a means of preventing the development of overt central nervous system disease in childhood acute leukaemia. However, acute and chronic neurotoxicity has been described following HDMTX therapy, and the long-term intellectual outcome in children treated in this way is inadequately documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a noninvasive, quantitative way of assessing aspects of cerebral metabolism, which has not previously been applied to the study of children undergoing central nervous system directed therapy. PROCEDURE: To evaluate the potential role of (1)H-MRS in the investigation of related neurotoxicity, 11 children who had received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS, magnetic resonance imaging. Neuropsychological assessments were performed on the children who had more than 1 year of follow-up time since last methotrexate treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were undertaken. Eight patients had spectra of adequate quality. Comparisons between (1)H-MRS metabolite ratios and normal controls were made. RESULTS: Patients had a low choline/water ratio compared to controls (P < 0.01). No differences between patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen. Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the patients (104.1) was in the normal range. CONCLUSIONS: It is postulated that choline depletion in the brains of these patients may reflect subclinical disturbances of myelin metabolism as a result of methotrexate therapy and may represent a possible avenue of treatment in patients with clinical chronic methotrexate-related neurotoxicity.

Adolescent↗

Re-engineering the soft machine: the impact of developing technology and changing practice on diagnostic radiographer skill requirements.

This paper describes research to investigate the extent to which new technology and changing work practices in diagnostic imaging have changed the skill requirements of working radiographers. Interviews were conducted with radiography managers, radiologists and industry representatives. While changes in technology were viewed as having a significant impact on skill requirements, levels of resourcing and both national and local policy were seen as key factors driving changes in work practice. Respondents believed that significant changes would be required to pre- and post-registration training requirements for radiographers in the light of changing practice.

Clinical Competence↗

Socio-economic re-structuring and employment: the case of minority ethnic groups.

The consequences of major changes in employment, due to the decline of manufacturing and the growth of the service sector, have not been well-documented, nor theorized, in the sociology of ethnic relations, even in recent studies. For example, Blumer's classic argument that economic development adapts to 'race relations', rather than the reverse as predicted by the modernization school, has not been either empirically resolved or conceptually applied to the UK. By adapting data from the Labour Force Survey and the Census, the paper begins to fill this gap with a detailed account of three main minority ethnic groups, and a separate analysis of male and female employment. It is demonstrated that, contrary to assumptions that members of the minority ethnic groups suffered most from de-industrialization, they actually did rather well, and in some cases did better than the majority population. These findings are re-conceptualized as collective social mobility, as part of a review of a number of conceptual frameworks in the light of the data.

Employment↗

Expression of the insulin-like growth factor I receptor C terminus as a myristylated protein leads to induction of apoptosis in tumor cells.

The insulin-like growth factor I receptor (IGF-IR) has been shown to mediate mitogenesis and suppression of apoptosis. Certain mutations in the COOH terminus of the receptor abrogate the antiapoptotic activity but not the mitogenic activity. However, truncation of the receptor by deletion of the COOH-terminal 108 amino acids enhances suppression of apoptosis by the IGF-IR, which suggests that the COOH terminus has a negative regulatory role. To investigate this further, a series of mammalian expression vectors were generated that encoded either the COOH terminus of the receptor or the COOH terminus plus the kinase domain. In some cases, the first 16 amino acids of SRC were included at the NH2 terminus to provide a site for myristylation. In transient transfection assays, the membrane-targeted COOH-terminal construct, MyCF, was found to induce apoptosis in MCF-7 breast carcinoma cells and C6 glioblastoma cells, whereas the COOH-terminal construct without the myristylation signal, CF, was poorly cytotoxic. MyKCF, which encodes the kinase domain as well as the COOH terminus, had intermediate cytotoxicity. The cytotoxicity of MyCF was diminished by point mutations that were previously shown to abrogate suppression of apoptosis in the context of the full-length receptor. MCF-7 cells stably expressing the CF or the MyCF proteins exhibited decreased clonogenicity in soft agar and increased sensitivity to UV irradiation. These results indicate that expression of the IGF-IR COOH terminus promotes apoptosis of tumor cells, possibly by interfering with signals necessary for cell survival.

Acylation↗

The optimal pacing rate: an unpredictable parameter.

A three phase relation has been demonstrated between increasing heart rate and cardiac output at rest. Phase I with cardiac output increasing with increasing heart rate, phase II a plateau, and phase III decreasing cardiac output with any further increase in heart rate. The "optimal rate" can be defined as the heart rate at the onset of phase II. Twenty patients were studied, 13 male, mean age 60 years (range 31-71 years). All had chronic complete heart block and established DDD pacing. A maximal exercise test was performed to determine peak sinus rate. Exercise hemodynamics were measured using an ambulatory monitor (Capintec Vest), which permits measurement of relative cardiac output and relative ejection fraction. The patients were programmed to VVI pacing at a rate of 60 beats/min and performed three exercise tests at different workloads. The order of workloads was randomized and selected from a range (0, 25, 50, or 75 W) depending on fitness. After 3-minute stabilization, the VVI pacing rate was increased at 1-minute intervals until higher than peak sinus rate giving a total exercise time of 12 minutes. The "optimal rate band" was determined at each workload. The mean of this "optimal rate band" for each workload varied in a nonlinear manner. There was no correlation between "mean optimal rate" and age or the peak rate predicted by the Astrand formula. Current definitions of chronotropic incompetence are inaccurate. Are some of these people at their "optimal rate" already? The arbitrary selection of rate response curves on age related criteria may lead to an impaired hemodynamic response.

Adult↗

Posttranslational modifications of meningococcal pili. Identification of a common trisaccharide substitution on variant pilins of strain C311.

Neisseria meningitidis pili are filamentous protein structures that are essential adhesins in capsulate bacteria. Pili of adhesion variants of meningococcal strain C311 contain glycosyl residues on pilin (PilE), their major structural subunit. Recent studies have shown that a novel O-linked trisaccharide substituent, not previously found as a constituent of glycoproteins, is present within a peptide spanning amino acid residues 50 to 73 of the PilE molecule. The structure was shown to be Gal beta 1-4 Gal alpha 1-3 diacetamidotrideoxyhexose which is directly attached to pilin. Pilins derived from galactose epimerase (galE) mutants lack the digalactosyl moiety, but retain the diacetamidotrideoxyhexose substitution. These studies confirm our previous observations that meningococcal pili are glycosylated and provide the first structural evidence for the presence of covalently linked carbohydrate on pili. We have identified a completely novel protein/carbohydrate linkage on a multimeric protein that is an essential virulence determinant in N. meningitidis.

Amino Acid Sequence↗

Discovery of a novel protein modification: alpha-glycerophosphate is a substituent of meningococcal pilin.

Pili, which are filamentous protein structures on the surface of the meningitis-causing organism Neisseria meningitidis, are known to be post-translationally modified with substituents that affect their mobility in SDS/PAGE and which might play a crucial role in adherence and bloodstream invasion. Tryptic digests of pili were analysed by fast atom bombardment and electrospray MS to identify putative modifications. Serine-93 was found to carry a novel modification of alpha-glycerophosphate. This is the first time that alpha-glycerophosphate has been observed as a substituent of a prokaryotic or eukaryotic protein.

Amino Acid Sequence↗

Outcome-based practice: disclosure rates of child sexual abuse comparing allegation blind and allegation informed structured interviews.

The way in which children are interviewed can make the difference between prosecution, or continued abuse. There is a clear need for the development of an interview style that is acceptable in the legal system without compromising disclosure rate. This study was conducted to compare the disclosure rate of alleged child sexual abuse victims interviewed in a formal forensic setting with a structured "allegation informed" technique versus a structured "allegation blind" technique. The only difference between techniques was that the interviewer did not know the allegation for condition "allegation blind." Of the 1,535 interviews, 1,330 or 86.64% were conducted "allegation blind," 196 or 12.76% were conducted "allegation informed" and for 9 or .6% the interview type was unknown. The "allegation blind" interview technique yielded a statistically higher disclosure rate (chi 2 p = 0.378). Further research is warranted.

Adolescent↗

Erythropoietin treatment of erythropoietin-deficient anemia without renal disease during pregnancy.

BACKGROUND: The use of recombinant human erythropoietin in pregnancy has been described in patients with renal impairment. We present a patient with a hypoproliferative anemia with low serum erythropoietin levels and no renal disease or other known cause for this type of anemia, who was treated with recombinant human erythropoietin. CASE: A 29-year-old white woman who became pregnant after leuprolide acetate and menopausal gonadotropin therapy developed a moderate anemia (hemoglobin 8.5 g/dL) in early pregnancy. The only important laboratory findings were a hypoproliferative marrow and a low serum erythropoietin level. She was treated successfully with injections of recombinant human erythropoietin. Her pregnancy was otherwise uncomplicated and her pre-delivery hemoglobin level was 12 g/dL. CONCLUSION: Hypoproliferative anemia in pregnancy with low erythropoietin levels and no renal disease can be treated successfully with recombinant human erythropoietin.

Adult↗

Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain.

During T-cell activation, Ser59 in the unique N-terminal region of p56lck is phosphorylated. Mutation of Ser59 to Glu59 mimics Ser59 phosphorylation, and upon CD4 crosslinking, this mutant p56lck induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56lck. Mutant and wild-type p56lck have similar affinities for CD4 and similar kinase activities. In glutathione S-transferase fusion proteins, the p56lck Src homology 2 (SH2) domain with the SH3 domain and the unique N-terminal region (including Ser59) has a different binding specificity for phosphotyrosyl proteins than the SH2 domain alone. Either deletion of the unique N-terminal region or mutation of Ser59 to Glu59 in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser59 regulates the function of p56lck by controlling binding specificity of its SH2 domain.

Amino Acid Sequence↗

Usefulness of culture in the diagnosis of Clostridium difficile infection.

Between January and April 1993, culture for Clostridium difficile and a faecal cytotoxin assay were performed on 500 selected specimens. Isolates from culture-positive patients from whom faecal samples were cytotoxin negative were also examined in vitro for cytotoxin production. The significance of a positive culture result in the absence of faecal cytotoxin was assessed. Forty-one of the 500 specimens were toxin positive. In only 25 of these was Clostridium difficile examination specifically requested. Six of nine culture-positive cytotoxin-negative patients (11 specimens) had recently received antibiotics. In four of these, Clostridium difficile was considered to be of possible clinical significance. Culture and in vitro determination of toxin production of isolates may aid in the diagnosis of some additional cases, but cytotoxin detection remains the single optimal routine laboratory method for diagnosis.

Adult↗

Meningococcal pilin: a glycoprotein substituted with digalactosyl 2,4-diacetamido-2,4,6-trideoxyhexose.

Neisseria meningitidis pili are filamentous protein structures that are essential adhesins in capsulate bacteria. Pili of adhesion variants of meningococcal strain C311 contain glycosyl residues on pilin (PilE), their major structural subunit. Despite the presence of three potential N-linked glycosylation sites, none appears to be occupied in these pilins. Instead, a novel O-linked trisaccharide substituent, not previously found as a constituent of glycoproteins, is present within a peptide spanning amino acid residues 45 to 73 of the PilE molecule. This structure contains a terminal 1-4-linked digalactose moiety covalently linked to a 2,4-diacetamido-2,4,6-trideoxyhexose sugar which is directly attached to pilin. Pilins derived from galactose epimerase (galE) mutants lack the digalactosyl moiety, but retain the diacetamidotrideoxyhexose substitution. Both parental (#3) pilins and those derived from a hyper-adherent variant (#16) contained identical sugar substitutions in this region of pilin, and galE mutants of #3 were similar to the parental phenotype in their adherence to host cells. These studies have confirmed our previous observations that meningococcal pili are glycosylated and provided the first structural evidence for the presence of covalently linked carbohydrate on pili. In addition, they have revealed a completely novel protein/saccharide linkage.

Amino Acid Sequence↗