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Biomedical subjects

P Poole

Publications and source records attributed to P Poole.

8 recordsLinked to original sources

Rhizobium leguminosarum nodulation gene (nod) expression is lowered by an allele-specific mutation in the dicarboxylate transport gene dctB.

To identify host genes that might influence nod (nodulation) gene expression in Rhizobium leguminosarum, a nodC-phoA reporter plasmid (carrying nodD) was introduced into a chemically mutagenized population of a R. leguminosarum strain lacking a symbiotic plasmid. The transconjugants were screened for expression of alkaline phosphatase (PhoA) on plates containing hesperetin, an inducer of nod genes, and a mutant with reduced expression was identified. When the nodC-phoA plasmid was cured from the mutant and the symbiotic plasmid pRL1Jl introduced, the mutant formed nodules, but symbiotic nitrogen fixation was less than 20% of normal. When the nodC-phoA allele was introduced on pRL1Jl a low level of nod gene induction was found. The reduced nodC expression appeared to be caused by a decrease in expression of the regulatory gene nodD, since expression of a nodD-lacZ fusion was also lower in the mutant than in the control. These mutant phenotypes and the low nitrogen fixation were complemented with a plasmid (plJ1848) from a R. leguminosarum cosmid library. DNA hybridization confirmed that plJ1848 was not from the symbiotic plasmid and showed that a DNA insertion was present in the mutant. The complementing region of plJ1848 was defined by transposon mutagenesis; DNA sequencing revealed that it carried the dicarboxylic acid transport (dct) genes. However, the mutant grew well with succinate as sole C-source. Genetic analysis revealed that the mutant appeared to contain IS50 in the regulatory gene dctB and that this mutation caused the reduction in nod gene expression. The effect was allele-specific since other mutations in dctB did not influence nod gene expression. Surprisingly, the mutant had a constitutive high level of succinate transport, indicating that the mutation caused unregulated expression of dctA the structural gene for dicarboxylic acid transport. This in some way appears to have lowered the expression of nodD, indicating that the nodD promoter may be influenced by the metabolic status of the cells or by expression of dctD in the absence of dctB.

Alkaline Phosphatase

Direct measurement of hydration-related dynamic changes in lysozyme using inelastic neutron scattering spectroscopy.

Inelastic neutron scattering spectroscopy is used to investigate dynamic changes in lysozyme powder at two different low D2O hydrations (0.07g D2O/g protein and 0.20 g D2O/g protein). In the higher hydration sample, the inelastic scattering between 0.8 and 4.0 cm-1 energy transfer is increased and the elastic scattering is decreased. The decreased elastic scattering suggests increased atomic amplitudes of motion and the increased 0.8 to 4.0 cm-1 scattering suggests increased motions in this frequency range. Comparison with normal mode models of lysozyme dynamics shows that the inelastic difference occurs in the frequency region predicted for the lowest frequency, largest amplitude, global modes of the molecular [M. Levitt, C. Sander and P.S. Stern, J. Mol. Biol. 181, 423 (1985). B. Brooks and M. Karplus, Proc. Natl. Acad. Sci (U.S.A) 82, 4995 (1985), R.E. Bruccoleri, M. Karplus and J.A. McCammon, Biopolymers 25 1767 (1986)]. Our results are consistent with a model in which an increased number of low frequency global modes are present in the higher hydrated sample.

Energy Transfer

Long-term study of management of rheumatoid arthritis.

A 10-year study of the management of rheumatoid arthritis was conducted to compare a programme consisting of rest and anti-inflammatory and antirheumatic drugs with one consisting of maintenance of activity, anti-inflammatory and antirheumatic drugs, and systemic steroids where necessary. During this period subjects who did not respond to the treatment allocated went on to a combined treatment programme of rest, anti-inflammatory and antirheumatic drugs, and steroids. Among those who remained in the trial for the 10 years, there was little difference between the two groups in morning stiffness, number of inflamed joints, functional capacity, grip strength, number of American Rheumatism Association criteria present, and whether they remained on their original treatment programme or switched to the combined programme. However, in those who started in the steroid group, the condition of several joints tended to be better clinically and radiologically than in those of the other group during and at the end of 10 years of the original treatment programme, at time of transfer to the combined programme, and at the completion of the combined programme. Both groups had as many complications of disease and treatment, and adverse effects attributable to steroids seemed to be restricted to those with severe disease who had not responded to their original programme. A policy of maintaining physical activity plus the judicious use of steroids where required produces, in the long term, results as good as or probably better than a regimen of bed rest and no steroids.

Acute Disease

Clomipramine and age: an interaction study.

The metabolism of an appreciable number of drugs has been shown to be influenced by age. In a study designed to assess plasma levels of clomipramine in twenty-eight patients aged between 65 and 75 years and fourteen patients over 75 years of age and compare them with the levels achieved by a control group of patients aged between 18 and 40 years, the severity of depression was assessed initially and after 7, 14, 21 and 28 days using the General Practitioner Clinical Research Group Scale. Clomipramine was administered in a single dose of 25 mg either in the morning or in the evening. In general there were similar improvements in total score and in individual items on the rating scale in all three groups of patients. More drug related drop-outs occurred in the group of elderly subjects and in extreme age the response to treatment was slower although the end result of treatment was the same as that seen in younger subjects. Some side-effects such as constipation, tremor, ataxia and vertigo were commoner in older subjects.

Adolescent

Operation Wild Dog.

'Operation Wild Dog' was the title given to an incredible escapade by two Army Dental Corps soldiers who decided to mount their own two-man raid on occupied France in 1942. In an attempt to forestall claims of desertion, they involved Prime Minister Winston Churchill and, when they ultimately faced a court martial, were lauded in the press for their daredevil exploits. Inspired by raids carried out by Special Services units on Norway, Italy and France, Sergeant Peter King, a regular soldier and dental clerk orderly, and Private Thomas Leslie Cuthbertson, a trainee dental mechanic, set about their unofficial raid, outlined below.

England