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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 469 records · Page 26Linked to original sources
PubMed1987

The establishment of a mood disorders unit.

The establishment within a general hospital psychiatry ward of a mood disorders unit (MDU), a specialised facility for the assessment and treatment of patients with affective disorders, is described. The aims include provision of a clinical service, a teaching resource for affective disorders and the development of a research centre. Details are provided of the organisation of the MDU, the development of programs for management of patients and the difficulties encountered. In the first year, 164 patients were assessed, of whom 36 were judged not to have a primary mood disorder. For the remainder, the most common DSM-III diagnosis was major depressive episode (n = 68), with about half having the melancholic sub-type. It is argued that a specialised diagnosis-related facility is feasible within a general hospital psychiatry service with area health commitments.

Affective Disorders, Psychotic↗
PubMed1987

Effect of meal size and composition on the bioavailability of ketoprofen (Oruvail).

Seven young male volunteers received a single oral dose of Oruvail (ketoprofen 200 mg capsule) on two occasions, immediately after either a light/lean or a heavy/fatty meal at breakfast time. Administration of ketoprofen immediately following the heavy meal slightly, but significantly, delayed the absorption of the drug, as evidenced by mean (+/- S.D.)Tmax values of 6.7 (+/- 1.0) and 9.0 (+/- 1.4) hours respectively. Changing the type of meal had no statistically significant effect on the maximum plasma level, apparent plasma elimination half-life (t 1/2 h), area under the plasma level versus time curve, total plasma clearance, and urinary recovery of total ketoprofen, indicating that the bioavailability (and the systemic level) of ketoprofen was not affected by meal composition.

Administration, Oral↗
PubMed1986

Is there Ca2+(Sr2+)-3-hydroxybutyrate symport in rat-liver mitochondria? A reappraisal.

The observation in this laboratory that respiration and Sr2+ import were stimulated by the addition of 3-hydroxybutyrate to suspensions of N-ethylmaleimide-treated mitochondria respiring in state 6, after the addition of Sr2+, in a sucrose medium containing choline as substrate, led to the proposal by Moyle and Mitchell [(1977) FEBS Lett. 84, 135-140] that there is a Ca2+(Sr2+)-3-hydroxybutyrate symporter in rat liver mitochondria. However, experiments described in the present paper support a different interpretation. Under the conditions of the experiments by Moyle and Mitchell, the rate of respiration and the poise of Sr2+ accumulation are mainly limited, not by delta mu H+, but by lack of respiratory substrate. Even though N-ethylmaleimide is a potent inhibitor of 3-hydroxybutyrate dehydrogenase, we have found that, somewhat surprisingly, under the special conditions of these experiments, sufficient 3-hydroxybutyrate dehydrogenase activity remains available to account for the 3-hydroxybutyrate-dependent respiratory stimulation and Sr2+ import.

3-Hydroxybutyric Acid↗
PubMed1986

Proton translocation by cytochrome oxidase in (antimycin + myxothiazol)-treated rat liver mitochondria using ferrocyanide or hexammineruthenium as electron donor.

When O2 was injected into an anaerobic suspension of valinomycin-treated rat liver mitochondria inhibited with rotenone, antimycin, and myxothiazol, a small amount of O2 (0.23-0.33 ng-atom of O/mg of protein) was reduced extremely rapidly (within the 2 s time-resolution of the oxygen electrode). The subsequent steady-state rate of flow of electrons to oxygen was very low [less than 3 nequiv. X s-1 X (g of mitochondrial protein)-1]. In the presence of valinomycin there was a rapid ejection of protons synchronous with the rapid phase of O2 consumption corresponding to 0.38-0.61 nequiv. of H+ X (mg of mitochondrial protein)-1. When valinomycin was replaced by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) there was a rapid alkalification of the medium corresponding to 0.20-0.42 nequiv. of H+ X (mg of mitochondrial protein)-1. When 2 mM-Fe(CN)6(4-) was present to re-reduce endogenous cytochrome c, O2 consumption was still biphasic but the second phase of O2 consumption was very much more rapid [600 nequiv. X s-1 X (g of protein)-1], and resulted in the virtually complete consumption of the O2 in the pulse within 4 s. With 60 microM-Ru(NH3)6(2+) as reductant, O2 consumption was even faster [1200 nequiv. X s-1 X (g of protein)-1]. In a medium containing 150 mM-choline chloride with Ru(NH3)6(2+) as reductant, the proton per reducing equivalent stoichiometry (delta H+O/e-) was +0.95 in the presence of valinomycin and -0.94 in the presence of FCCP. In choline chloride medium containing Ru(NH3)6(2+) and valinomycin, there was an uptake of K+ ions corresponding to 1.86 K+/e-. It is concluded that nearly 1 proton is translocated outwards through cytochrome oxidase per oxidizing equivalent injected in this medium. In low ionic strength sucrose-based medium, with Ru(NH3)6(2+) as reductant, delta H+O/e- was 1.05 in the presence of valinomycin, and -0.71 in the presence of FCCP. It is concluded that the translocation of protons is accompanied by net acid production in this medium.

Animals↗
PubMed1986

Measurement of the proton-motive stoichiometry of the respiratory chain of rat liver mitochondria: the effect of N-ethylmaleimide.

The apparent proton-motive stoichiometry as measured by the oxygen-pulse technique in KCl medium is depressed by the rapid uptake of inorganic phosphate, unless endogenous phosphate is depleted or uptake is inhibited. In sucrose or choline chloride media, where the internal pH is more acid than in KCl media, uptake may be greatly diminished. In the absence of significant phosphate uptake, the observed stoichiometry of around 8, obtained with no added substrate or respiratory inhibitors, appears to be characteristic of NADH oxidation without significant participation of the proton-translocating NAD(P) transhydrogenase. A mechanistic stoichiometry of at least 8 is indicated.

Animals↗
PubMed1986

The development of performance and cost indicators for preschool immunisation.

The organisation, premises, and staffing of three child health clinics of different types in an inner city area have been studied and related to information on immunisation derived from their computerised child register and other returns, together with some simple estimates of cost. Differences were found between overall uptake of different antigens, consent rate, compliance after consent had been given, and the median age at immunisation for children allocated to each clinic. Thus consent to pertussis immunisation varied from 90% in one clinic to 69% in the other two. In the clinic with the high consent rate, however, only 66% of those whose parents had consented actually received all three doses compared with 82% and 85% in the other clinics. The median age of immunisation also showed pronounced differences between the clinics--314, 351, and 375 days, respectively, for the third dose of the triple course. There were differences in characteristics of the clientele served by each clinic and in staffing and facilities, which led to differences in costs, as well as contributing towards the variable patterns of uptake. We suggest that indicators such as these, largely available from the child health computer system, are used systematically to identify ways of improving uptake and increasing cost effectiveness.

Ambulatory Care Facilities↗
PubMed1986

Malignant conversion and metastasis of mouse skin tumors: a comparison of SENCAR and CD-1 mice.

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of SENCAR and Charles River CD-1 mice, using a three-stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (DMBA) (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) (stage II), papilloma-bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-n-oxide (R-NQO), the promoter TPA, or solvent (acetone). Similar final carcinoma yields were found in the mice treated in stage III with TPA or acetone, although carcinomas developed earlier in the TPA-treated mice. In contrast, treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both SENCAR and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of TPA treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The heterogeneity of papillomas with regard to progression to carcinomas is demonstrated by the low rate of conversion of TPA-dependent papillomas and the high rate of conversion of persistent papillomas in CD-1 mice. The carcinomas that develop using the three-stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with MNNG, urethane, 4-NQO, TPA, or acetone, but treatment with urethane substantially increased metastases to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Chemiosmotic coupling in cytochrome oxidase. Possible protonmotive O loop and O cycle mechanisms.

Using the principle of specific vectorial ligand conduction, we outline directly coupled protonmotive O loop and O cycle mechanisms of cytochrome oxidase action that are analogous to protonmotive Q loop and Q cycle mechanisms of QH2 dehydrogenase action. We discuss these directly coupled mechanisms in the light of available experimental knowledge, and suggest that they may stimulate useful new research initiatives designed to elucidate the osmochemistry of protonmotive oxygen reduction in cytochrome oxidase.

Biological Transport↗
PubMed1985

Molecular mechanics of protonmotive F0F1 ATPases. Rolling well and turnstile hypothesis.

The reversible protonmotive F0F1 ATPases perform the uniquely important function of balancing the forces, and interconverting the potential energies, of phosphoryl transfer and proton translocation. The molecular mechanics of the processes of ligand conduction catalysed by the F0F1 ATPases is therefore especially interesting. This paper summarises the main structural and functional knowledge of the F0F1 ATPases in the light of current mechanistic hypotheses, and suggests a new type of rotating subunit hypothesis, which is related to that recently developed for bacterial flagellar motors.

Adenosine Diphosphate↗
PubMed1985

Induction of papillomas with a high probability of conversion to malignancy.

Papillomas induced by standard initiation-promotion protocols progress to carcinomas at a low frequency. Experimental protocols were developed to elicit papillomas with a higher probability of malignant conversion. SENCAR mice initiated by 7,12-dimethylbenz[a]anthracene were promoted by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 5, 10, 20 or 40 weeks. With promotion for 10 weeks or more, a peak of papilloma incidence at 16-20 weeks was followed by a 35-40% decrease within 3 months. A much lower papilloma response was seen in mice promoted for 5 weeks, but these papillomas persisted. The yield of malignant tumors was similar in all four groups, with 20-25 carcinomas per group of 30 mice. Thus, the papillomas induced by the first few TPA treatments are much more likely to progress to carcinomas than those which appear later. In a separate study, initiated Charles River CD-1 mice were promoted with TPA for either 12 or 52 weeks. Acetone solvent treatment was begun at Week 13 in the group treated 12 weeks with TPA. At Week 16, the papilloma incidence was identical in the two groups of mice. However, by Week 28, the papilloma yield in the continuous TPA group had increased and was twice that of the acetone group, in which papillomas had regressed. The first carcinoma arose 14 weeks earlier with continuous TPA, but the final number of carcinomas per group of 40 mice was 17 with TPA and 20 with acetone. Neither the increase in papillomas in TPA-treated mice nor the regression of papillomas after cessation of promotion with TPA affected the final carcinoma yield. This result suggests that TPA-dependent papillomas are very unlikely to progress to carcinomas. In a third experiment, promotion of initiated SENCAR mice with mezerein resulted in a small number of papillomas which had a much higher probability of progression to carcinomas than the large number of papillomas promoted by TPA. The ability to induce papillomas promoted by TPA. The ability to induce papillomas with a known probability of conversion to carcinomas will facilitate the identification of markers associated with malignant progression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Development and progression of diabetic eye disease in Newcastle (1977-1984): rates and risk factors.

A prevalence study of diabetic eye disease was conducted in Newcastle during 1977-1978. Ophthalmoscopic retinopathy was found in 49% of 1210 clinic diabetics, while vision-threatening retinopathy (VTR) (proliferative signs of maculopathy) occurred in 13%. Maculopathy was the commonest cause of visual loss, occurring frequently in subjects with non-insulin-dependent diabetes. This group has now been followed for up to seven years (including 70% at four years); incidence rates for the development of retinopathy and for progression to a vision-threatening stage can now be estimated. The study found that diabetics with no retinopathy developed this at a rate of 8% per year, while only 0.4% per year progressed to VTR. However, once any retinopathy was present, progression to VTR occurred in 6% per year (2% proliferative and 4% maculopathy); and if any retinal signs indicating the presence of capillary closure were noted the rate was 13% per year. These rates are for the group overall: however, certain parameters were found to influence the progression in individual patients. Included were the age at onset and the duration of diabetes, the presence of poor control (particularly in older diabetics on oral agents) or associated nephropathy. An analysis of these data and their implications for routine eye screening of diabetics is presented.

Australia↗
PubMed1985

Properties of lactate dehydrogenase in a psychrophilic marine bacterium.

Lactate dehydrogenase (EC 1.1.1.27) from Vibrio marinus MP-1 was purified 15-fold and ammonium activated. The optimum pH for pyruvate reduction was 7.4. Maximum lactate dehydrogenase activity occurred at 10 to 15 degrees C, and none occurred at 40 degrees C. The crude-extract enzyme was stable between 15 and 20 degrees C and lost 50% of its activity after 60 min at 45 degrees C. The partially purified enzyme was stable between 8 and 15 degrees C and lost 50% of its activity after 60 min at 30 degrees C. The thermal stability of lactate dehydrogenase was increased by mercaptoethanol, with 50% remaining activity at 42 degrees C.

Hydrogen-Ion Concentration↗