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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 343 records · Page 19Linked to original sources
PubMed1980

Zinc transport in normal human leucocytes: dependence upon media composition.

1. The transport of zinc has been studied in normal human leucocytes incubated in both a tissue culture medium and Krebs buffer. 2. 65Zn influx is characterized by an initial rapid phase followed by a slower influx. 65Zn influx is directly dependent upon the extracellular zinc concentration. 3. Net zinc influx could only be demonstrated in Krebs buffer at zinc concentrations in excess of 4.3 mumol/l and in tissue culture fluid at zinc concentrations in excess of 43.1 mumol/l. 4. A 65Zn efflux rate constant of approximately 1.0 per h was observed in both 4.3 and 15.4 mumol of zinc/l of Krebs buffer or tissue culture fluid. 5. In a zero external zinc Krebs buffer the 65Zn efflux rate constant fell to 0.57 per h and was accompanied by a small net zinc efflux.

Biological Transport↗
PubMed1980

Growth and the plasma concentrations of growth hormone and prolactin in chicks: effects of "environmental enrichment", sex and strain.

1. The effects of including novel objects in the environment ("environmental enrichment") on body-weight gain, relative body-weight gain, gain: food ratio, plasma growth hormone (GH) and prolactin concentrations in male and female broiler and layer chicks was investigated. 2. Environmental enrichment improved body-weight gain, relative body-weight gain and gain : food ratio but had no effect on circulating GH or prolactin concentrations. 3. Weight gain and gain : food ratio were greater in the broilers than in the layer chicks, while plasma GH and prolactin (females only) concentrations were less. 4. There were no sex differences in weight gain and relative weight gain but gain : food ratio was significantly greater in females than in males. In both strains plasma GH concentrations were higher in male than in female broilers.

Animals↗
PubMed1980

Immune-enhanced phagocytosis of Neisseria gonorrhoeae by macrophages: characterization of the major antigens to which opsonins are directed.

antisera were prepared in rabbits against whole organisms of colony type 1 Neisseria gonorrhoeae strains F62 and B (fron gonococcal urethritis) and 7122 (a strain typical of those associated with disseminated gonococcal infection), and against purified outer membrane components from the same strains including pili and principal outer membrane protein. Antibody levels to pili, principal outer membrane protein and lipopolysaccharide were determined using a quantitative enzyme-linked immunosorbent assay. Each antiserum was heat-inactivated and tested for opsonic for its homologous strain, and this immune-enhanced phagocytosis was decreased by adsorption with homologous purified outer membrane components: pili greater than lipopolysaccharide greater than principal outer membrane protein. Opsonic activity was approximately equal for antiserum to purified pili and antiserum to the whole organisms for each of the three strains, and purified antibody to pili was highly opsonic. The F(ab')2 fragments of antibody to pili were not opsonic, indicating a role for the Fc receptor on the phagocyte membrane in immune-enhanced phagocytosis of gonococci.

Antigen-Antibody Reactions↗
PubMed1980

Resolution of basic gonococcal outer membrane proteins by nonequilibrium pH gradient electrophoresis.

Outer membrane proteins from opaque and transparent colonial variants of strain F62 of Neisseria gonorrhoeae were analyzed by two-dimensional electrophoresis with isoelectric focusing in the first dimension and sodium dodecyl sulphate-polyacrylamide gel electrophoresis in the second. Most of the higher-molecular-weight proteins focused sharply in the acidic region of the gel. In contrast, the principal outer membrane protein, a 31,000-molecular-weight protein, and the opacity-associated proteins remained near the origin (at the basic end of the gel) without focusing. However, when the samples were loaded on the acidic end of an isoelectric focusing gel and subjected to nonequilibrium pH gradient electrophoresis, these proteins behaved as basic proteins. In addition, three distinct opacity-associated heat-modifiable proteins could be identified. No other differences in the protein composition of outer membranes from opaque and transparent variants were apparent. Amino acid analysis of the principal outer membrane protein indicated that its net positive charge may result from partial amidation of its acidic residues. The unexpected observation that the major surface proteins of the gonococcus are basic may have implications for intragonococcal adhesion and for gonococcal interactions with mammalian cells.

Amino Acids↗
PubMed1980

Reduced leucocyte zinc in liver disease.

The zinc content of peripheral blood leucocytes has been measured in normal controls and in three groups of patients with liver disease. A significant reduction in leucocyte zinc, but not erythrocyte zinc, was observed in patients with primary biliary cirrhosis, alcoholic cirrhosis, and active chronic hepatitis. It is suggested that the nucleated tissues of some patients with liver disease are therefore zinc deficient, and that leucocyte zinc may prove of value in the assessment of the zinc status of such patients.

Chronic Disease↗
PubMed1980

A sensitive and specific assay for pentamethylmelamine in plasma: applicability to clinical studies.

A sensitive and specific procedure for measuring plasma levels of pentamethylmelamine (PMM), a chemotherapeutic agent currently undergoing phase I trials, has been developed. PMM was isolated (recovery greater than 95%) from 3-ml plasma samples by cation exchange chromatography followed by solvent extraction, and was quantitated by selected ion monitoring with a gas chromatograph/mass spectrometer. Deuterium-labeled PMM was synthesized and used as an internal standard; standard curves were prepared by plotting m/e 196/199 ratios versus concentrations, and were linear in the range of 0.05-50.0 microM. The coefficient of variation for repeated measurements was less than 1% at all concentrations studied. To test the applicability of this method to clinical studies, plasma clearances of PMM were measured in two studies in each of three cancer patients receiving 80-mg/m2 doses of PMM as 1-hour iv infusions. Peak plasma concentrations, observed immediately after the end of the infusions, averaged 4.1 microM (SE = 0.6 microM). Plasma elimination was found to be biphasic; a short initial half-life (approximately 27 minutes) was followed by a longer elimination half-life of 133 minutes (SE = 35 minutes). Measurements in two patients indicated that less than 0.1% of the administered PMM was excreted unchanged in the urine in 24 hours, suggesting that hepatic metabolism of PMM may be a major contributor to plasma clearance of the drug in man.

Aged↗
PubMed1979

Enzyme-substrate and enzyme-inhibitor complexes of triose phosphate isomerase studied by 31P nuclear magnetic resonance.

The complex formed between the enzyme triose phosphate isomerase (EC 5.3.1.1.), from rabbit and chicken muscle, and its substrate dihydroxyacetone phosphate was studied by 31P n.m.r. Two other enzyme-ligant complexes examined were those formed by glycerol 3-phosphate (a substrate analogue) and by 2-phosphoglycollate (potential transition-state analogue). Separate resonances were observed in the 31P n.m.r. spectrum for free and bound 2-phosphoglycollate, and this sets an upper limit to the rate constant for dissociation of the enzyme-inhibitor complex; the linewidth of the resonance assigned to the bound inhibitor provided further kinetic information. The position of this resonance did not vary with pH but remained close to that of the fully ionized form of the free 2-phosphoglycollate. It is the fully ionized form of this ligand that binds to the enzyme. The proton uptake that accompanies binding shows protonation of a group on the enzyme. On the basis of chemical and crystallographic information [Hartman (1971) Biochemistry 10, 146--154; Miller & Waley (1971) Biochem. J. 123, 163--170; De la Mare, Coulson, Knowles, Priddle & Offord )1972) Biochem. J. 129, 321--331; Phillips, Rivers, Sternberg, Thornton & Wilson (1977) Biochem. Soc. Trans. 5, 642--647] this group is believed to be glutamate-165. On the other hand, the position of the resonance of D-glycerol 3 phosphate (sn-glycerol 1-phosphate) in the enzyme-ligand complex changes with pH, and both monoanion and dianon of the ligand bind, although dianion binds better. The substrate, dihydroxyacetone phosphate, behaves essentially like glycerol 3-phosphate. The experiments with dihydroxy-acetone phosphate and triose phosphate isomerase have to be carried out at 1 degree C because at 37 degrees C there is conversion into methyl glyoxal and orthophosphate. The mechanismof the enzymic reaction and the reasons for rate-enhancement are considered, and aspects of the pH-dependence are discussed in an Appendix.

Animals↗
PubMed1979

Spectrophotometric studies on the interaction between triose phosphate isomerase and inhibitors.

The binding of ligands to chicken muscle triose phosphate isomerase was studied. Changes in u.v. absorbance of the enzyme were used to measure binding, and the dissociation constant was determined over a range of pH values. The ligands were 2-phosphoglycollate and rac-glycerol 3-phosphate (only the D-isomer, sn-glycerol 1-phosphate, binds appreciably). Non-linear regression was used to fit calculated curves to the experimental points and hence to compare different models. Both active sites in the dimeric enzyme probably bound 2-phosphoglycollate, without any interaction between the sites. The results of crystallographic analysis [phillips, Rivers, Sternberg, Thornton & Wilson (1977) Biochem. Soc Trans. 5, 642--647], and experiments on the 1H, 13C and 31P n.m.r. of enzyme or 2-phosphoglycollate were combined with the present results to provide the basis for a model in which binding depends on glutamic acid-165 being protonated and on the ligant being fully ionized; additionally, binding affects the ionization of one histidine residue (probably histidine-100). The binding of the glycerol 3-phosphate, on the other hand, was independent of pH over the range pH 6.5--8.5 but decreased at lower pH values. This is explained on a model in which the binding of the monoanion of the ligand is markedly affected by the protonation of a residue in the enzyme, but the binding of the dianion is only slightly affected by this ionization.

Animals↗
PubMed1979

Intraperitoneal contrast infusion for assessment of intraperitoneal fluid dynamics.

For patients undergoing intraperitoneal ("belly bath") chemotherapy, it is useful to verify the distribution of infusion fluid. For this reason, 10 patients were examined by computed tomography (CT) after intraperitoneal instillation of dialysate mixed with water soluble contrast material. The extent of intraperitoneal distribution was assessed, and in two patients filling defects, presumably representing tumor, were identified.

Adult↗
PubMed1978

High volume intraperitoneal chemotherapy ("belly bath") for ovarian cancer. Pharmacologic basis and early results.

The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease. Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology, pharmacokinetics, and the therapeutic effectiveness of this treatment modality. This technique has been virtually ignored until recently, because little success has been achieved with it except in one study (Rutledge, 1966), in which large intraperitoneal fluid volumes were used. The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity. Biomedical engineers, pharmacologists, and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer. Following mathematical pharmacokinetic modeling and toxicologic studies in rat, a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated. Results in three patients confirm the practicality of this approach, and further investigation is warranted.

Animals↗
PubMed1978

Quantitative measurement of phagocytosis of Neisseria gonorrhoeae by mouse peritoneal macrophages.

The simultaneous labeling of gonococci with [6-3H]uracil and of mouse peritoneal macrophages with L-[U-14C]leucine permits a quantitative assessment of the association of gonococci with macrophages under various experimental conditions. Colony-type T1 (piliated) gonococci associated more than T4 (nonpiliated) organisms at 4 degrees C, but at 37 degrees C the association of T4 gonococci with macrophages exceeded that for the T1 organisms. The association of T1 gonococci with macrophages could be enhanced as much as 70-fold by homologous rabbit antisera prepared against whole, formaldehyde-treated organisms. This immune enhancement represented primarily increased phagocytosis rather than surface attachment, as shown by its inhibition at 4 degrees C or with 2-deoxyglucose. The data further suggested that this enhanced phagocytosis was mediated via the Fc receptor for immunoglobulin G.

Animals↗