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J M Matthews

Publications and source records attributed to J M Matthews.

At least 37 records · Page 2Linked to original sources
PubMed1994

Single versus parallel pathways of protein folding and fractional formation of structure in the transition state.

Protein engineering and kinetic experiments indicate that some regions of proteins have partially formed structure in the transition state for protein folding. A crucial question is whether there is a genuine single transition state that has interactions that are weakened in those regions or there are parallel pathways involving many transition states, some with the interactions fully formed and others with the structural elements fully unfolded. We describe a kinetic test to distinguish between these possibilities. The kinetics rule out those mechanisms that involve a mixture of fully formed or fully unfolded structures for regions of the barley chymotrypsin inhibitor 2 and barnase, and so those regions are genuinely only partially folded in the transition state. The implications for modeling of protein folding pathways are discussed.

Amino Acid Sequence↗
PubMed1994

Extrapolation to water of kinetic and equilibrium data for the unfolding of barnase in urea solutions.

Assumptions about the dependence of protein unfolding on the concentration of urea have been examined by an extensive survey of the equilibrium unfolding of barnase and many of its mutants measured by urea denaturation and differential scanning calorimetry. The free energy of equilibrium unfolding and the activation energy for the kinetics of unfolding of proteins are generally assumed to change linearly with [urea]. A slight downward curvature is detected, however, in plots of highly precise measurements of logku versus [urea] (where ku is the observed rate constant for the unfolding of barnase). The data fit the equation logku = logkuH2O* + mku*.[urea] - 0.014[urea]2, where mku* is a variable which depends on the mutation. The constant 0.014 was measured directly on four destabilized mutants and wild-type, and was also determined from a global analysis of data from > 60 mutants of barnase. Any equivalent deviations from linearity in the equilibrium unfolding are small and in the same region, as determined from measurements on 166 mutants. The free energy of unfolding of barnase, delta GU-F, appears significantly larger by 1.6 kcal mol-1 when measured by calorimetry than when determined by urea denaturation. However, the changes in delta GU-F on mutation, delta delta GU-F, determined by calorimetry and by urea denaturation are identical. We show analytically how, in general, the curvature in plots of activation or equilibrium energies against [denaturant] should not affect the changes of these values on mutation provided measurements are made over the same concentration ranges of denaturant and the curvature is independent of mutation.

Bacillus↗
PubMed1994

Beta-adrenoceptor subtypes in the atrioventricular conducting system and myocardium of spontaneously hypertensive rats: effects of angiotensin-converting enzyme inhibition by perindopril.

Quantitative autoradiography was used to determine the density and distribution of beta 1- and beta 2-adrenoceptors in the atrioventricular (AV) conducting system and surrounding myocardium of spontaneously hypertensive rats (SHR) after chronic infusion of perindopril (1 mg/kg/day) for 14 days by osmotic mini-pumps. Systolic blood pressure (SBP) was measured for a period of 4 weeks (2 weeks before and 2 weeks during perindopril infusion) in control and treated animals. Animals infused with vehicle (water) had a mean SBP of 248 mm Hg (measured on day 29); animals treated with perindopril had lower SBP (121 mm Hg, day 29). Perindopril treatment also prevented development of cardiac hypertrophy in SHR. beta-Adrenoceptor densities were measured in the AV node, His bundle, left and right bundle branches (LB, BB), interventricular and interatrial septa (IVS, IAS), mitral valve (MV), right papillary muscle, left and right ventricles (LV, RV), left and right atria (LA, RA), and apex. Perindopril produced no significant change in beta-adrenoceptors in any cardiac region examined. The results suggest that under experimental conditions in which perindopril treatment prevented cardiac hypertrophy and decreased SBP, there was no significant interaction between the renin-angiotensin system (RAS) and beta-adrenoceptor system in rat heart.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Alpha-helix stability in proteins. II. Factors that influence stability at an internal position.

The solvent-exposed residue Ala32 in the second alpha-helix of barnase was replaced by all other naturally occurring amino acids and the concomitant effects on the protein stability were determined. The results are assumed to reflect both the distinct conformational preferences of the different amino acids and also possible intrahelical interactions. The conformational preferences may be fully rationalized by invoking only a few physical principles. The results agree well with recently experimentally determined rank-order of helix-forming tendencies determined on a model peptide. There is very weak correlation between the results and the experimental host-guest values. There is a weak correlation between our results and the statistical helix propensities and a slightly better correlation with the positional-dependent statistical parameters of J. S. Richardson, and D. C. Richardson.

Amino Acid Sequence↗
PubMed1991

Cross-Resistance to Herbicides in Annual Ryegrass (Lolium rigidum) : III. On the Mechanism of Resistance to Diclofop-Methyl.

Annual ryegrass (Lolium rigidum) biotype SLR 31 is resistant to the postemergent graminicide methyl-2-[4-(2,4-dichlorophenoxy)phenoxy]-propanoate (diclofop-methyl). Uptake of [(14)C](U-phenyl)diclofop-methyl and root/shoot distribution of radioactivity in susceptible and resistant plants were similar. In both biotypes, diclofop-methyl was rapidly demethylated to the biocidal metabolite diclofop acid which, in turn, was metabolized to ester and aryl-O-sugar conjugates. Susceptible plants accumulated 5 to 15% more radioactivity in dicloflop acid than did resistant plants. Resistant plants had a slightly greater capacity to form nonbiocidal sugar conjugates. Despite these differences, resistant plants retained 20% of (14)C in the biocidal metabolite diclofop acid 192 hours after treatment, whereas susceptible plants, which were close to death, retained 30% in diclofop acid. The small differences in the pool sizes of the active and inactive metabolites are by themselves unlikely to account for a 30-fold difference in sensitivity to the herbicide at the whole plant level. Similar high-pressure liquid chromatography elution patterns of conjugates from both susceptible and resistant biotypes indicated that the mechanisms and the products of catabolism in the biotypes are similar. It is suggested that metabolism of diclofop-methyl by the resistant biotype does not alone explain resistance observed at the whole-plant level. Diclofop acid reduced the electrochemical potential of membranes in etiolated coleoptiles of both biotypes; 50% depolarization required 1 to 4 mum diclofop acid. After removal of diclofop acid, membranes from the resistant biotype recovered polarity, whereas membranes from the susceptible biotype did not. Internal concentrations of diclofop acid 4 h after exposing plants to herbicide were estimated to be 36 to 39 micromolar in a membrane fraction and 16 to 17 micromolar in a soluble fraction. Such concentrations should be sufficient to fully depolarize membranes. It is postulated that differences in the ability of membranes to recover from depolarization are correlated with the resistance response of biotype SLR 31.

Journal Article↗
PubMed1990

Cross-Resistance to Herbicides in Annual Ryegrass (Lolium rigidum): I. Properties of the Herbicide Target Enzymes Acetyl-Coenzyme A Carboxylase and Acetolactate Synthase.

Lolium rigidum biotype SR4/84 is resistant to the herbicides diclofop-methyl and chlorsulfuron when grown in the field, in pots, and in hydroponics. Similar extractable activities and affinities for acetyl-coenzyme A of carboxylase (ACCase), an enzyme inhibited by diclofop-methyl, were found for susceptible and resistant L. rigidum. ACCase activity from both biotypes was inhibited by diclofop-methyl, diclofop acid, haloxyfop acid, fluazifop acid, sethoxydim, and tralkoxydim but not by chlorsulfuron or trifluralin. Exposure of plants to diclofop-methyl did not induce any changes in either the extractable activities or the herbicide inhibition kinetics of ACCase. It is concluded that, in contrast to diclofop resistance in L. multiflorum and diclofop tolerance in many dicots, the basis of resistance to diclofop-methyl and to other aryloxyphenoxypropionate and cyclohexanedione herbicides in L. rigidum is not due to the altered inhibition characteristics or expression of the enzyme ACCase. The extractable activities and substrate affinity of acetolactate synthase (ALS), an enzyme inhibited by chlorsulfuron, from susceptible and resistant biotypes of L. rigidum were similar. ALS from susceptible and resistant plants was equally inhibited by chlorsulfuron. Prior exposure of plants to 100 millimolar chlorsulfuron did not affect the inhibition kinetics. It is concluded that resistance to chlorsulfuron is not caused by alterations in either the expression or inhibition characteristics of ALS.

Journal Article↗
PubMed1990

Prognostic value of cytophotometric analysis of DNA in lymph node aspirates from patients with non-Hodgkin's lymphoma.

To classify cases of non-Hodgkin's lymphoma in terms of expected clinical behaviour and survival, kinetic parameters measured by cytophotometry were assessed in 62 patients between 1978 and 1987. The influence of the number of cells with increased DNA content (more than 2N) on survival was evaluated. Analyses were carried out on the small samples obtained by needle aspiration biopsy of lymph nodes before treatment, using microdensitometry and Feulgen staining. Patients whose lymphomas contained less than 6% of cells with increased DNA content had a mean survival of 81.3 months and those whose lymphomas contained 6% or more of such cells had a mean survival of 18.5 months. A significant difference in survival using the same criteria was also noticed for patients with both low grade lymphomas and those with intermediate and high grade lymphomas. It is concluded that cytophotometric analysis of lymph node aspirates is of prognostic value in the initial assessment of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1989

Skin disease in haemophiliacs with and without antibodies to the human immunodeficiency virus (HIV): further evidence of altered disease behaviour in different risk groups?

Forty-one patients routinely attending the Oxford Haemophilia Centre entered a controlled, blind investigation in order to determine whether HIV antibody status was related to the presence of skin disease. Twenty-four of the 41 patients (58.5%) were HIV antibody positive and none had any general symptoms. Comparison of the HIV antibody positive group with the HIV antibody negative group and with non-haemophiliac controls showed an increased prevalence of four HIV-associated dermatoses: 11 patients had seborrhoeic dermatitis (10 HIV antibody positive and one HIV antibody negative (P less than 0.05 chi 2 test], eight patients had folliculitis (six HIV antibody positive), four patients had mucocutaneous candidiasis, all were HIV antibody positive, and three patients had onychomycosis, all were HIV antibody positive. None of these conditions was seen in a group of 16 non-haemophiliac controls. These findings are different from those reported from a similar study of comparable groups of homosexual men and these results may be further evidence to support the belief that the behaviour of HIV infection differs between haemophiliacs and other risk groups.

Adolescent↗
PubMed1987

Acquired haemophilia and rheumatoid arthritis.

Four patients with classical rheumatoid arthritis who developed acquired haemophilia are described. They developed a spontaneous bleeding diathesis and diagnosis was based on low or absent Factor VIII levels and the presence of a circulating anticoagulant directed against Factor VIII. The course is variable and cyclophosphamide together with control of the underlying rheumatoid arthritis are recommended as treatment.

Aged↗
PubMed1986

Entrapped ovary syndrome.

Formulation of pelvic cysts afer proctectomy is an entity which is described in this paper with the cause supposed to be due to descent of the ovary from an intraperitoneal to an extraperitoneal position at the time of proctectomy. A simple surgical technique for fixing the ovary out of the pelvis to prevent this complication is described.

Adult↗
PubMed1984

Use of a purified outer membrane protein F (porin) preparation of Pseudomonas aeruginosa as a protective vaccine in mice.

The outer membrane protein F (porin) from the PAO1 strain of Pseudomonas aeruginosa was purified by two different methods. One procedure involved separation by column chromatography of proteins extracted from isolated outer membranes, whereas the other involved extraction from gels after slab polyacrylamide gel electrophoresis of proteins extracted from cell envelopes. Both procedures yielded protein F preparations which successfully immunized mice from subsequent challenge with the PAO1 strain. The protein F preparations contained small quantities of lipopolysaccharide (LPS). This level of LPS contamination protected immunized mice from challenge with the homologous LPS serotype strain. However, immunization of mice with protein F preparations from the PAO1 strain also afforded protection against challenge with two different LPS serotype strains. This protective ability was lost when the protein F preparation was treated with papain before use as a vaccine. These observations support the conclusion that protein F has protective ability, which is not due to LPS contamination, when given as a vaccine. After immunization with the protein F preparation, mice showed an increase in antibody titer to the purified protein F preparation by enzyme-linked immunosorbent assay. Mice were protected passively by administration of rabbit antisera raised to the protein F preparation. These results indicate that the protein F preparation elicits a specific humoral antibody response in immunized animals. Our results suggest that purified protein F has potential as an effective vaccine for P. aeruginosa.

Animals↗
PubMed1977

A comparison of coagulation factor replacement with and without prednisolone in the treatment of haematuria in haemophilia and Christmas disease.

A double-blind controlled study was carried out to investigate the effectiveness of treatment with factor VIII or factor IX concentrate and a reducing dose of prednisolone in contolling haematuria in patients with haemophilia and Christmas disease. 41 episodes of haematuria were studied in 30 different patients. No appreciable benefit was observed in the treated, as compared with the control group and this is at variance with the results of the few studies reported elsewhere.

Clinical Trials as Topic↗