Search PubMed⌕ Search

Biomedical subjects

P Rogers

Publications and source records attributed to P Rogers.

At least 145 records · Page 8Linked to original sources

Plasma catecholamines following exercise in hypertensives treated with pindolol: comparison with placebo and metoprolol.

This study re-examines the proposal that beta-adrenoceptor blockers with intrinsic sympathomimetic activity decrease plasma noradrenaline levels. Thirteen patients (aged 29-65 years) with uncomplicated essential hypertension were randomly allocated to a three period, double-blind cross-over trial. The treatment periods, each of 3 weeks duration, were composed of placebo, pindolol (5 mg twice daily) and metoprolol (100 mg twice daily), dispensed in identical capsules. At the end of each treatment period, patients were exercised on a bicycle ergometer to a predetermined workload. Blood pressure and heart rate were measured before, immediately on completion of exercise and after 10 min post-exercise rest. Blood samples for plasma noradrenaline and adrenaline determination were also collected at these times. Blood pressures were similar during treatment with pindolol and metoprolol. As expected, heart rate was consistently lower during metoprolol treatment. Basal, pre-exercise plasma noradrenaline and adrenaline were similar at the end of each treatment period. However, the increase following exercise was significantly greater during metoprolol treatment. The post-exercise increase during pindolol treatment was indistinguishable from that in the placebo period. These findings, in a randomised placebo-controlled study, therefore demonstrate that pindolol does not influence basal or exercise-stimulated plasma noradrenaline and adrenaline concentrations. This is best explained by a lack of effect of pindolol on the plasma clearance of catecholamines, which is impaired by beta-adrenoceptor blockers devoid of intrinsic sympathomimetic activity.

Adult↗

Some studies on the metabolism of labelled molybdenum compounds in cattle.

An initial experiment showed that [99Mo]di- and trithiomolybdates could be detected in bovine plasma after the introduction of [99Mo]molybdate into the rumen. It was felt that this justified the use of [99Mo]trithiomolybdate for the subsequent studies made of plasma thiomolybdate metabolism in vivo in cattle. Rapid intravenous injection of [99Mo]trithiomolybdate into cattle showed that doses of 50 mg Mo were subject to extensive hydrolysis over the first few minutes postinjection, but at lower dose rates this was reduced so that tracer doses (less than 1.5 mg Mo) were relatively stable. The plasma metabolism was unaffected by copper status within the limits of the experiments (that is, liver copper levels down to 9 mg/kg d.m.) The disappearance of [99Mo] and [35S]trithiomolybdate (1 mg Mo) from plasma was delayed for up to 10 hr by the immediate preinjection of copper, although no chemical modification of the thiomolybdate appeared to occur.

Animals↗

Sulphate conjugation limits fluctuations in free catecholamines in phaeochromocytoma.

More than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA) circulate in blood as sulphates, and it has been proposed that sulphate conjugation contributes to the inactivation of catecholamines (CA). Sulphate conjugation rapidly responds to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma-free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free + sulphates) NA were markedly elevated before compared with 1-4 months after surgery. Similar elevations were seen in free and total A and free DA. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (17 +/- 4.1 and 13.7 +/- 4.4 ng/ml, respectively), whereas only small differences in free NA levels were present (4.1 +/- 1.5 and 4.3 +/- 1.8 ng/ml). These differences between total and free levels were also apparent for A and DA, but to a lesser degree. In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in free levels for the other two patients, respectively. Mean blood pressure (BP) varied less than 8 mmHg in these patients. These findings suggest that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.

Adrenal Gland Neoplasms↗

Clinical implications of developments in in vitro fertilisation.

During February 1979 to December 1983, 831 infertile couples were treated by in vitro fertilisation and embryo transfer. The problems they faced included deciding on the number of oocytes to be collected at laparoscopy, the numbers to be donated or fertilised, the numbers of embryos to be transferred and frozen, and whether abnormal embryos should be used for research or discarded. The 831 patients received a total of 1530 treatment cycles. Of the 763 patients for whom complete data were available, 136 (17.8%) became pregnant. The rate of pregnancy, however, increased dramatically from 7.4% when only one embryo was transferred to 21.1% and 28.1% when two and three embryos were transferred, respectively. The chance of multiple pregnancy also increased with the number of embryos transferred, but the risk (2% for twins) was far outweighed by the relatively poor result after transferring a single embryo. Out of 40 embryos freeze-thawed, 23 survived thawing and were transferred; of these, 4 (17%) resulted in pregnancy. Thirty four transfers of donor oocyte embryos also resulted in four pregnancies (12%), but two of these ended in abortion. Neither microscopy nor any other available test can determine the potential of an oocyte to result in pregnancy, so that discarding oocytes that may look abnormal simply reduces the chances of conception--both for the patient and for any prospective recipient of donor oocyte embryos. In any case, abnormal embryos tend to die when growth is allowed to continue in vitro. Probably all oocytes harvested from a patient should be inseminated and the utilisation of the embryos decided once the number developed is known.

Embryo Transfer↗

Regulation and coupling of argECBH mRNA and enzyme synthesis in cell extracts of Escherichia coli.

Cell extracts from Escherichia coli were used to study both transcription and coupled translation of the argECBH gene cluster. Argininosuccinase (the argH enzyme) and N-acetylornithinase (the argE enzyme) were synthesized for 90 to 120 min, and hybridizable argECBH mRNA was synthesized for 60 min after the addition of a lambda or phi 80 dargECBH DNA template. L-Arginine (2.5 mM) repressed synthesis by argR+ extracts of argECBH mRNA 2-, to 3-fold, argE enzyme 5- to 8-fold, and argH enzyme 20- to 60-fold. Repression was specific for L-arginine, and argR extracts were insensitive to added L-arginine. The argECBH mRNA made under conditions of restricted protein synthesis had reduced ability to function in the formation of the argE and argH enzymes and was found to be predominantly 6 to 8S in sucrose density gradients. When protein synthesis was allowed, the mRNA formed was functional, and large amounts of 14 to 23S argECBH mRNA appeared on sucrose gradients. An S-100 supernatant freed of ribosomes was capable of producing hybridizable arg mRNA, but significant functional message was only produced when ribosomes were present. When purified RNA polymerase was used, the formation of short 6 to 8S argECBH mRNA was dependent upon added rho protein. The data suggest that rho-dependent sites in the argECBH operon allow early termination of mRNA synthesis when transcription is not coupled to active enzyme synthesis.

Amidohydrolases↗

Positive control of expression of the argECBH gene cluster in vitro by guanosine 5'-diphosphate 3'-diphosphate.

By using a cell-free system derived from Escherichia coli, it was found that guanosine 5'-diphosphate 3'-diphosphate (ppGpp) was a positive effector for expression of both wings of bidirectionally transcribed argECBH gene cluster. A 7- to 20-fold increase in the synthesis of both argininosuccinase (the argH enzyme) and N-acetylornithinase (the argE enzyme) resulted with added ppGpp (0.2 mM optimum). Synthesis of hybridizable argECBH mRNA was enhanced only 30 to 100% by added ppGpp. Of the various guanosine nucleotides tested, only pppGpp mimicked ppGpp. Added ppGpp had no important effect upon (i) measurable argE or argH enzyme activity, (ii) total protein synthesis in the cell-free system, or (iii) the rate of decay of hybridizable argECBH mRNA. With extracts of an argR+ strain, added ppGpp had no effect on the repression of enzyme or mRNA synthesis by L-arginine. By using a two-stage system in which the bulk of argECBH mRNA was synthesized while protein synthesis was delayed, we showed that ppGpp acted at some point during transcription.

Escherichia coli↗

Mucosal microvascular architecture of the fundus and body of human stomach.

Vascular casts of human oxyntic mucosa, examined by scanning electron microscopy, revealed that (a) arterial breakup occurs only at the submucosal aspect of the mucosa, there being no arterial vessels further into the mucosa and (b) mucosal capillaries drain into the infrequent mucosal venules only in the most luminal region of the lamina propria immediately underlying the surface mucus cells; the mucosal venules do not receive capillary tributaries deeper within the mucosa. Thus, blood flow in the mucosal exchange vessels can only occur in a unidirectional fashion, from the serosal to the luminal aspect. Using transmission electron microscopy, an often intimate association was seen between the fenestrated mucosal capillaries and parietal cells. These findings are together incorporated into a hypothesis that proposes vascular transport of HCO3-, released interstitially by secreting parietal cells, from deep within the mucosa toward the surface epithelium, thereby assisting gastric mucosal defense against luminal acid.

Arterioles↗

The effect of ascorbic acid on plasma sulfate conjugated catecholamines after eating bananas.

The effects of eating bananas, a rich source of biogenic amines, on the plasma concentration of free and sulfate conjugated norepinephrine (NE) and dopamine (DA), and free epinephrine (E), were examined in normal male subjects before and after treatment with ascorbic acid, 2 g daily for 7 days. There were no significant changes in the levels of free NE or E in any subjects after eating a banana, either before or after ascorbic acid. Plasma free DA became detectable in some subjects, but the overall changes were not significant. Sulfate conjugated DA and NE increased markedly after banana ingestion, as previously demonstrated in our laboratory. After ascorbic acid treatment the rise in sulfate conjugated NE was attenuated, presumably because ascorbic acid acts as a competitive inhibitor of sulfate conjugation. In contrast, the rise in conjugated DA was potentiated after ascorbic acid treatment. This may be indicative of the higher affinity of DA for phenolsulfotransferase, an inhibitory effect of ascorbic acid on dopamine-receptor coupling or of ascorbic acid protecting DA from oxidation in the gut.

Adult↗

The determination by radiochemical assay of argininosuccinase produced in an Escherichia coli system in vitro.

A highly sensitive radiochemical assay used to measure the synthesis and regulation of the product of the argH gene, argininosuccinase, in an Escherichia coli system in vitro is described. With L-[guanidino-14C]argininosuccinic acid as a substrate, and in the presence of excess arginase and urease, 14CO2 is collected in a simply designed micro-vessel. With this method less than 1 nmol of product can be measured in the presence of various concentrations of L-arginine.

Argininosuccinate Lyase↗

Molecular weight determination of two genetically linked cell surface murine antigens: ThB and Ly-6.

Various murine tumor lines were screened by FACS analysis for the surface antigens ThB and Ly-6.2. Positive cell lines were used for immunoprecipitation studies. A monoclonal ThB-specific antibody immunoprecipitated a unique acidic protein of approximately 16 000 daltons from several positive tumors and from concanavalin A (Con-A) and LPS activated splenic lymphocytes. Monoclonal Ly-6.2-specific antibody was used to immunoprecipitate a 33 500 dalton protein that was shown to exist in four similarly sized forms with different basic charges. In the course of these studies, the apparent molecular weight of the surface antigen T 30, immunoprecipitated with a monoclonal T 30-specific antibody from the cell line EL4, was found to be approximately 25 000 daltons.

Animals↗

Differential sensitivity of lymphocyte subsets to corticosteroid treatment.

Corticosteroid treatment of SJL mice produced a marked decrease in the number of viable lymphocytes obtained 48 hr later from the thymus, spleen and lymph node but no change in peripheral blood. Within the residual lymphocyte population there was a fall in the relative number of splenic B cells with increasing dose; in contrast the proportion of B cells increased in the lymph nodes. The most marked change however was a dose-related increase inthe Lyt-2+ population in all of the lymphoid organs examined including the thymus though, in this organ alone, the lowest dose caused a pronounced reduction in the Lyt-2+ population, since most immature thymocytes are Lyt-2+. These findings support the concept that mature thymocytes have phenotypic identity with peripheral T cells and provide a basis for the immunosuppressive action of corticosteroids.

Animals↗

Estimation of body fat in normal and obese mice.

1. Lee Index (weight (g0.33) divided by nasoanal length (mm)), density, body water and proportional weight of the gonadal fat pad were tested as estimates of body fat in a normal population of mice and a population which included obese mice. 2. In a normal population only body water and fat-pad weight correlated significantly with body fat. 3. In a population of normal and obese mice all four indices correlated significantly with body fat. 4. Lee Index had little advantage over weight:length as an estimate of body fat, and density did not correlate well enough to be used as a method of estimation. 5. Proportional weight of the gonadal fat pad is recommended as a simple reliable estimate of body fat in normal or obese mice.

Adipose Tissue↗