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Biomedical subjects

G Miles

Publications and source records attributed to G Miles.

18 recordsLinked to original sources

Differential expression of group I metabotropic glutamate receptors in human motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis.

Glutamate excitotoxicity has been suggested to play a role in amyotrophic lateral sclerosis, since overstimulation of post-synaptic glutamate receptors by accumulated extracellular glutamate leads to motoneuron cell death. It is however unclear as to why some groups of motoneurons degenerate in this disease while other groups remain relatively intact even during terminal stages of the disease. Our previous studies in the rat showed differential expression of group I metabotropic glutamate receptors in motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis. Here we have extended this study to normal human brains. In situ hybridization showed that transcripts of both metabotropic glutamate receptor (mGluR) 1 and mGluR5 were expressed in motoneurons in both the resistant motor nucleus III and the vulnerable motor nucleus XII. Immunolabeling of mGluR1alpha and mGluR5 was found in both motoneurons and glia-like cells in all the motor nuclei and the ventral horn of the cervical spinal cord studied. Quantitative analysis of optical density measurements showed higher levels of mGluR1alpha protein expression but lower levels of mGluR5 protein expression in the vulnerable motoneuron pool (VII, XII and spinal cord) than in the resistant motoneuron pool (III, IV and VI). This differential expression of group I metabotropic glutamate receptor proteins within vulnerable motoneuron pools may predispose these neurons to degeneration as seen in amyotrophic lateral sclerosis.

Central Nervous System↗

The staphylococcal leukocidin bicomponent toxin forms large ionic channels.

The genes encoding the F and S components of a leukocidin, LukF (HlgB) and LukS (HlgC), a pore-forming binary toxin, were amplified from the Smith 5R strain of Staphylococcus aureus both with and without sequences encoding 3'-hexahistidine tags. The His-tagged components were expressed in Escherichia coli and purified under nondenaturing conditions. In addition, the two unmodified proteins and the His-tagged versions were produced in an E. coli cell-free in vitro transcription and translation system. An SDS-stable oligomer of approximately 200 kDa appeared when both components were cotranslated in the presence of rabbit erythrocyte membranes. Hemolytic activity of the combined components against rabbit erythrocytes was measured for both in vitro- and in vivo-produced polypeptides, yielding similar HC(50) values of approximately 0.14 microg/mL. The pore-forming properties of the recombinant leukocidin were also investigated with planar lipid bilayers of diphytanoylphosphatidylcholine. Although leukocidins and staphylococcal alpha-hemolysin share partial sequence identity and related folds, LukF and LukS produce a pore with a unitary conductance of 2.5 nS [1 M KCl and 5 mM HEPES (pH 7.4)], which is more than 3 times greater than that of alpha-hemolysin measured under the same conditions. Therefore, if the leukocidin pore were a cylinder, its diameter would be almost twice that of alpha-hemolysin. In addition, the leukocidin pore is weakly cation selective and exhibits gating at low positive potentials, while alpha-hemolysin is weakly anion selective and gates only at high potentials. Taken together, these data suggest that the structure of the oligomeric pore formed by the leukocidin examined here has diverged significantly from that of alpha-hemolysin.

Animals↗

Level of functioning, severity of illness, and smoking status among chronic psychiatric patients.

It was hypothesized that chronic psychiatric patients who had quit smoking would be more functional and have lower Brief Psychiatric Rating Scale (BPRS) scores than those who continued to smoke. We interviewed 300 chronic psychiatric patients followed in the community. Fourteen percent were former smokers and nearly 11% had never smoked. Fifty-six percent of the sample were current smokers who had no intention of quitting, 13% were considering quitting, and 6% were seriously preparing to quit or had actually quit for a short period. When compared with current smokers, former smokers were more likely to live independently (p < .026) and less likely to have a drug or alcohol problem (p < .013). A random sample of current smokers were compared with former smokers on the BPRS. Former smokers had lower total BPRS scores (p < .03), and lower withdrawal/retardation subscale scores (p < .0058) than current smokers. We concluded that better functioning patients who smoked would be more likely to quit.

Adult↗

Home dialysis: its costs and problems.

A short description is given of the starting and the running of a home dialysis unit for chronic renal failure. The cost of training and treating 22 home dialysis patients, over an 18-month period is recorded. The annual maintenance costs of patients on home hemodialysis are found to be no more, and often less, than those of the institutional care of any other chronic malady. Furthermore, the prospects for full rehabilitation are good. This being so, home dialysis cannot be regarded as a costly luxury but a treatment which every suitable candidate may reasonably expect.

Adult↗

Spreading the word.

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Asia↗

Community spirit.

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Cambodia↗

The dietary habits of young people.

Adolescence is a time when patterns of behaviour can be set for life. This research project sought to listen to young people and understand the things that influence their acceptance of and accessibility to a healthy diet.

Adolescent↗