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Biomedical subjects

A Bishop

Publications and source records attributed to A Bishop.

At least 55 records · Page 3Linked to original sources

Methoxatin (PQQ) in guinea-pig neutrophils.

PQQ, also called methoxatin, has been isolated from guinea-pig neutrophils. The organic cations diphenyleneiodonium (DPI) and diphenyliodonium (BPI) and the aromatic o-diamine 4,5-dimethylphenylenediamine (DIMPDA) sequester synthetic PQQ and inhibit its redox-cycling activity in a model system. Standards were made of adducts of tritiated PQQ with unlabeled DIMPDA and of unlabeled PQQ with tritiated DPI or DIMPDA. PQQ adducts were isolated from guinea-pig neutrophils with each of the tritiated inhibitors. They were separated and defined by high-performance liquid chromatography (HPLC). Tiron, a disodium benzene disulphonic acid, broke the DPI-PQQ adduct isolated from neutrophils and released free PQQ. Both DPI and DIMPDA, as well as BPI, blocked O2.- release by stimulated neutrophils. The blockade exerted by these inhibitors was released by the addition of PQQ to the cell suspensions. The data demonstrate the presence of PQQ in guinea-pig neutrophils and suggest that it has a possible role, direct or indirect, in the O2.(-)-producing respiratory burst.

Animals↗

Aspects of the release of superoxide by leukocytes, and a means by which this is switched off.

Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (O2-), it is possible that a component or components, might have been overlooked. Furthermore, O2- production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off O2- production by stimulated leukocytes. This article offers evidence that methoxatin (PQQ), a redox-cycling orthoquinone, might be involved in O2- production by leukocytes. This is based on the fact that inhibitors of O2- production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored O2- release. With respect to turning off cellular O2- release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked O2- release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.

Chromatography, High Pressure Liquid↗

Characterization of the glycine-dependent redox-cycling activity in animal fluids and tissues using specific inhibitors and activators: evidence for presence of PQQ.

Pyrroloquinoline quinone, a redox cofactor first isolated from bacteria, efficiently catalyzes the nonenzymatic oxidation of glycine in the presence of nitroblue tetrazolium. We report that certain metallic cations and heterocyclic aromatic cations, like the N-methyl phenazonium cation and aryl-iodonium compounds, strongly and specifically inhibit this redoxcycling activity. The inhibition by metal cations is reversed by Tiron and that of the aromatic cations by Tiron and thyroxine. These inhibitors and activators affect authentic PQQ and the redox-activity of putative PQQ isolated from biological sources in a similar manner. This indicates that pyrroloquinoline quinone occurs naturally in animal tissues and fluids.

Animals↗

Effect of streptozotocin-diabetes on the level of VIP mRNA in myenteric neurones.

The effect of streptozotocin-induced diabetes on the production of vasoactive intestinal polypeptide messenger RNA in the myenteric neurones of 8 weeks diabetic rat intestine was examined using in situ hybridization. Total ganglion cell number per length (mm) of tissue section was measured using NADH diaphorase histochemistry. Although ganglion cells were more numerous in the control preparations compared with diabetic samples, a significantly greater number of vasoactive intestinal polypeptide messenger RNA-containing cells was detected in the diabetic tissues. These observations suggest that there is either a decrease in the breakdown of vasoactive intestinal polypeptide messenger RNA or an increase in its synthesis in myenteric neurones of diabetic rat intestine.

Animals↗

Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease.

OBJECTIVE: To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN: 40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING: Tertiary referral centre. SUBJECTS: Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES: Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS: Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS: The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral vascular surgery.

Aged↗

Detection and quantitation of 17F formation during the cyclotron production of 13N.

The positron emitter 17F has been identified for the first time as a radioactive contaminant formed during 13N production. It was determined that 17F made up 18% of the short-lived radioactivity previously thought to be exclusively 15O. Mathematical deconvolution of decay curve data was employed as a complement to radioanalytical techniques. The nuclidic composition of the effluents from the proton bombardment of (a) water, (b) dilute ethanol and (c) 13C powder/water slurry was determined and compared with previous literature values.

Fluorine Radioisotopes↗

Regioselective radiofluorodestannylation with [18F]F2 and [18F]CH3COOF: a high yield synthesis of 6-[18F]Fluoro-L-dopa.

A protected 6-trimethylstannyl dopa derivative 6 has been synthesized for the first time as a precursor for the preparation of 6-[18F]fluoro-L-dopa. The tin derivative 6 readily reacted with electrophilic radiofluorinating agents such as [18F]F2 and [18F]AcOF. The [18F]fluoro intermediate 7 was easily hydrolyzed with HBr and the product 6-[18F]fluoro-L-dopa was isolated after HPLC purification in a maximum radiochemical yield of 25%, ready for human use. The various intermediates, the stannyl precursor 6 and the final product (after 18F decay) were all fully characterized by 1H, 13C, 19F and 119Sn NMR as well as high resolution mass spectroscopy.

Dihydroxyphenylalanine↗

A community health program for the elderly.

The few existing health education programs for the elderly of a southeastern Pennsylvania community focused on illness rather than prevention. After several nurses conducted a survey of healthy seniors, they developed a stress-reduction program--a first step toward assisting the elderly to maintain health and independence.

Aged↗

The growth of liver cells in the pancreas after intra-splenic implantation: the effects of portal perfusion.

A newly developed rat model of portal diversion, in which the pancreas gland is perfused by splanchnic effluent, has been used to monitor the effects of such portal perfusion on the development of isolated hepatocytes within the pancreatic parenchyma. Two groups of animals (control and portally-perfused) received intra-splenic hepatocyte implants (2 x 10(6) cells). The development of liver cells in the pancreas was then assessed histologically 10 days-9 months later. Portal diversion did not alter the incidence of hepatocytes within the pancreas as a whole (70% of all animals). However hepatocyte-islet rosettes (the intimate association between liver cells and endocrine tissue) were found in a significantly higher percentage of portally-perfused pancreases (92%) in comparison to controls (43%) 6 and 9 months after implantation. It appears that liver cell translocation from the spleen to the pancreas is dependent largely on factors associated with the implantation procedure itself. The growth of liver cells specifically around the islets of Langerhans, however, seems to be positively influenced by portal factors. These studies provide further evidence for the theory that extrahepatic liver cells are susceptible to local and systemic growth factors in a similar way to homotopic hepatocytes in the intact liver.

Animals↗

The Apo(a) gene: structure/function relationships and the possible link with thrombotic atheromatous disease.

The last 25 years have witnessed an exponential increase of interest in the lipoprotein Lp(a). The structure of the gene encoding for its unique apo protein, Apo(a) has been determined resulting in possible structure/function relationships which may explain the close association between elevated levels of Lp(a) and atheromatous vascular disease. These findings may have profound therapeutic implications for the future treatment of the hyperlipidaemias and hypercholesterolaemia in particular.

Apolipoproteins A↗

Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population.

A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.

Adult↗

The use of epidural analgesia in postoperative vascular surgical patients.

Patients undergoing vascular surgical procedures can be higher risk patients. The goal is to provide the best pain management modality with the fewest significant side effects. Nurses can make a critical difference in the successful use of epidural analgesia by understanding how it works, monitoring for and treating side effects and complications that may occur, providing patient education, monitoring pain control and assuring patient safety. Overall, epidural analgesia does provide excellent analgesia and has many benefits for the vascular surgical patient.

Analgesia, Epidural↗

Segmental intestinal absorption of ranitidine: investigative and therapeutic implications.

The absorption of ranitidine from different segments of the intestinal tract was studied in a subject who had an anatomically divided small intestine. The results indicate that the drug is maximally absorbed from the small bowel rather than the stomach. Subsequent animal studies have shown that absorption of ranitidine in dogs is primarily duodenal followed by jejunal and ileal. The lack of gastric absorption, with predominantly small bowel absorption, may have investigational and therapeutic implications in a variety of gastrointestinal diseases.

Animals↗