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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 19 recordsLinked to original sources

Targeting deletion (homoeologous chromosome pairing locus) or addition line single copy sequences from cereal genomes.

We describe here a protocol for obtaining clones containing sequences present in low copy-number from genomic DNA where moderately and highly repeated sequences predominate. Specific chromosomal regions can be targeted by using deletion or addition line material. We have used this protocol to identify a sequence which has been deleted in both the tetraploid and hexaploid wheat mutants for the homoeologous chromosome pairing locus.

Chromosome Deletion

Stimulation of specific immune responses to simian immunodeficiency virus using chimeric hepatitis B core antigen particles.

Subunit approaches to vaccines against viral diseases have resulted in the development of a number of methods for presentation of defined epitopes to the immune system. We have exploited a highly immunogenic presentation system based on hepatitis B core antigen (HBcAg) particles to produce a number of candidate vaccines against simian immunodeficiency virus (SIV). Recombinant particles have been produced in bacteria which carry multiple copies of defined or predicted neutralizing epitopes of SIV at a number of different sites within the particle. In parallel, a number of synthetic peptide-based SIV vaccines have been produced based on homology to reported neutralizing epitopes in human immunodeficiency virus. Although potent immune responses were elicited against both particulate and peptide forms of the antigen, neutralizing antibodies were not induced as judged by available assays.

Acquired Immunodeficiency Syndrome

Urethral instability.

Urethral instability is still evolving as a clinical entity. Using pressure variation of 15 cm water or more at the point of maximum urethral pressure (MUP), urethral pressure profilometry on patients referred for urodynamic assessment for lower urinary tract symptoms revealed urethral instability in 6.4% of 608 patients. The close association between urethral and detrusor instability was noted. Urethral instability appears to be a cause of frequency and urgency of micturition, and its presence increase the risk of urinary incontinence.

Adult

Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat.

This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.

Albuminuria

Facilitating peer group teaching within nurse education.

Nurse teachers have an obligation to explore every teaching and learning method in order to prepare students to be able practitioners. In the wider educational field peer tutoring has been used to foster a deeper understanding of a subject area. Experiments using this method have been carried out extensively in America and are becoming more widespread in this country; however very little material is available on the use of this method in nurse education. The following article explains the use of peer tutoring as a method for developing teaching skills amongst student nurses. Two groups of learners were used in this exercise, the senior learners acting as peer tutors. Evaluation by nurse teachers and both groups of learners was favourable and the peer tutors were able to identify the benefits they received from the exercise.

Education, Nursing

RS 30026: a potent and effective calcium channel agonist.

1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked. 5. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 nm Bay K 8644, with a much smaller shift in the presence of 500nm Bay K 8644. RS 30026 (100 and 500nM) caused concentration-dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. 6. RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Reversal of hepatic encephalopathy and alteration in amino acid profiles after blocking a surgical splenorenal shunt by interventional radiological techniques.

Portal-systemic shunts are effective in preventing haemorrhage from varices in portal hypertension, but at the price of hepatic encephalopathy. We describe the blockage of a splenorenal shunt using interventional radiology, in a patient with incapacitating chronic encephalopathy. The procedure successfully reversed encephalopathy, without haemodynamic disturbances or haemorrhage from recurrent varices and was associated with a return of the plasma amino acid profile towards normal, with a reduction in aromatic amino acids and an increase in branch chain amino acids. This observation supports the hypothesis that changes in plasma amino acid profiles in patients with portal-systemic shunting are due to the diversion of portal blood rather than the underlying chronic liver disease.

Amino Acids

The influence of diving variables on perceptual and cognitive functions in professional shallow-water (abalone) divers.

Shallow-water diving is regarded as a hazardous occupation due to such dangers as decompression sickness and carbon monoxide poisoning. Recent studies have demonstrated impairments in the neurological and neurobehavioral functioning of professional shallow-water divers, yet the reasons for these deficits are not clear. In this study 80 professional abalone divers were studied using a range of neurobehavioral tests and questioned closely on their diving experience. Multiple linear regression analysis was then performed to determine the extent to which characteristics of the diver's occupation influenced neurobehavioral impairment. The results demonstrated that divers who were at greatest risk of decompression sickness due to their diving technique showed the clearest functional impairments. In particular problems of visual function, psychomotor abilities, and short-term memory were most evident. It appears that professional shallow-water diving is not necessarily a hazardous occupation provided that safe diving practices are observed. However, divers who fail to observe these practices and put themselves at risk of decompression sickness are likely to have impairments in neurobehavioral function which affect their everyday life, and more importantly their responses in emergency situations.

Adult

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg-1 min-1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non-invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg-1 min-1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/- 0.08 l min-1 m-2 (mean +/- s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/- 44 dyn s cm-5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg-1 min-1 should be evaluated as a selective pulmonary vasodilator.

Adenosine

In vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis.

Vancomycin resistance exhibited by Enterococcus faecalis isolates V583, V586, and V587 is described. The vancomycin MICs ranged from 32 to 64 micrograms/ml. Although resistant to vancomycin, the isolates were susceptible to teicoplanin (MIC, less than or equal to 0.5 micrograms/ml). Such a glycopeptide susceptibility profile has not been previously described for E. faecalis. Time kill studies showed that vancomycin resistance adversely affected the synergistic activity that vancomycin and aminoglycoside combinations usually demonstrate against enterococci. However, the ability to detect vancomycin resistance varied with the susceptibility testing method used. Whereas broth microdilution, broth macrodilution, and agar dilution methods detected resistance, disk-agar diffusion and the AutoMicrobic system Gram-Positive GPS-A susceptibility card (Vitek Systems Inc., Hazelwood, Mo.) did not. To detect vancomycin resistance reliably and establish the incidence of such E. faecalis isolates, adjustments in some susceptibility testing methods may be necessary.

Anti-Bacterial Agents