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Biomedical subjects

D H Jones

Publications and source records attributed to D H Jones.

At least 163 records · Page 9Linked to original sources
PubMed1985

Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: tumoricidal effects and distribution studies.

Monoclonal antibody UJ13A radiolabelled with isotopes of iodine has been shown to selectively localize to human neuroblastoma xenografts. When 131I-UJ13A conjugates were given to nude mice at high doses (100-150 microCi), tumours temporarily disappeared, only to regrow. No selection for neuroblastoma cells that were UJ13A - negative was observed. Distribution studies on mice receiving radiolabelled UJ13A demonstrated the antibody is rapidly lost from the blood of animals. This cannot be accounted for by selective uptake into xenografts or any other mouse organ examined. We concluded there is a rapid equilibration of isotope between intra- and extravascular spaces in the animal. The rapid, biphasic loss of UJ13A from the blood of mice may explain why so little injected antibody can target to the human tumour xenografts.

Animals↗
PubMed1985

Fc receptor-mediated binding and endocytosis by human mononuclear phagocytes: monomeric IgG is not endocytosed by U937 cells and monocytes.

Fc receptor-mediated endocytosis of monomeric IgG1 by human mononuclear phagocytes was evaluated under conditions where aggregated IgG and insulin readily undergo receptor-mediated internalization. U937 cells or normal human peripheral blood monocytes were incubated at 37 degrees C in the absence of free radioligand after having first bound 125I-IgG1 at 0 degrees C. To determine the amount of cell-associated IgG1 internalized after varying periods of 37 degrees C incubation, surface-bound IgG1 was removed by sequential exposure of cells at 0 degrees C to a nonspecific proteinase for 1 h and to acetic acid at pH 3.2 for 3 min. The failure to develop a proteinase- and acid-resistant fraction, similar to that seen over time at 37 degrees C in parallel experiments with 125I-insulin and 125I-aggregated IgG, and the lack of degradation of the IgG1 released into the medium from the same cells over time show that these cells do not endocytose and degrade monomeric IgG by an Fc receptor-specific mechanism and suggest that constitutive recycling without degradation is unlikely to be occurring. These data fulfill one prediction of the hypothesis that receptor-receptor interaction triggers Fc receptor-mediated endocytosis.

Cells, Cultured↗
PubMed1985

Two distinct classes of IgG Fc receptors on a human monocyte line (U937) defined by differences in binding of murine IgG subclasses at low ionic strength.

We have defined two distinct classes of IgG Fc receptors (FcR) on cells of a human monocytic line (U937) by analyzing the direct binding of murine IgG subclasses in medium of low ionic strength. Four lines of evidence support this contention. The binding of aggregated murine IgG2b (AggmIgG2b) to U937 and Daudi cells was enhanced at low ionic strength, whereas monomeric murine IgG2a (mIgG2a) did not bind to Daudi cells and its high affinity binding to U937 cells was unaffected by changes in ionic strength. Double reciprocal inhibition experiments with U937 cells indicated that the binding of both ligands was inhibited 30 to 135 times more efficiently by the homologous ligand than by the heterologous one. That is, the binding of 125I-AggmIgG2b was inhibited 50% by 3.5 micrograms/ml of AggmIgG2b and 100 micrograms/ml of mIgG2a. Similarly, the binding of 125I-mIgG2a was inhibited 50% by 2.5 micrograms/ml of mIgG2a and only 44% by 243 micrograms/ml of AggmIgG2b. A monoclonal antibody of the IgG2b subclass raised against an IgG FcR on K562 cells inhibited binding to U937 cells of AggmIgG2b but not of mIgG2a. Trypsinization of U937 cells abrogated by 32% the binding of mIgG2a but did not affect the binding of AggmIgG2b. Human IgG inhibited binding of both AggmIgG2b and mIgG2a to U937 cells. We propose that the newly recognized FcR that binds AggmIgG2b is the human homologue of the murine macrophage IgG2b/1 FcR (FcRII), and that the previously described 72,000 dalton high-affinity FcR on U937 cells that binds mIgG2a is the human equivalent of the murine macrophage IgG2a FcR (FcRI).

Animals↗
PubMed1985

The jugular vein as an interposition graft in the distal splenorenal shunt.

The selective distal splenorenal shunt is the preferred portal decompression procedure for patients with refractory bleeding esophageal varices. An autogenous jugular vein interposition graft in the distal splenorenal position obviates the tedious struggle associated with mobilizing the splenic vein from the pancreatic substance, thereby lessening blood loss, avoiding postoperative pancreatitis and shortening operative time. An autogenous jugular vein interposition distal splenorenal shunt can, therefore, be performed with less morbidity while affording the same physiologic benefits as the standard distal splenorenal shunt.

Adult↗
PubMed1984

Stability of the complex formed between French bean (Phaseolus vulgaris) phenylalanine ammonia-lyase and its transition-state analog.

Phenylalanine ammonia-lyase forms trans-cinnamate from L-phenylalanine, and thus stands at a gateway to secondary metabolism in higher plants. L-alpha-Amino-oxy-beta-phenylpropanoic acid (L-AOPP), a very effective competitive inhibitor of this enzyme, is most probably a transition-state analog for the elimination reaction. A preparation of phenylalanine ammonia-lyase (PAL), obtained from diluted suspension cultures of French bean cells, was used to investigate the binding of this compound in vitro. After extensive dialysis, the inhibitor remained tightly bound to the enzyme unless both an increased temperature and L-phenylalanine were provided, when the spectrophotometer trace of enzyme activity gradually approached linearity. Under such optimal catalytic conditions (37 degrees C; 25 mM L-phenylalanine; pH 8.8), dissociation of the enzyme-ligand complex took place with a half-time of approx 10 min. (This is much longer than reported for the enzyme from maize.) The consequences of these findings are discussed for investigations where L-AOPP is applied in vivo. These experiments have shown that the irreversible binding of the transition-state analog under appropriate conditions (0-4 degrees C, no L-phenylalanine) gave continued protection against attack on the enzyme by an excess of borohydride. By titrating the enzyme with increasing concentrations of analog and measuring the degree of protection afforded, the active-site concentration has been estimated. The turnover number (kcat = 0.8 s-1) given by this novel approach is of the same order of magnitude as previously reported from extensive purification of enzyme from other species.

Ammonia-Lyases↗
PubMed1984

A comparison of avian and rodent S-9 liver homogenates in the Ames test.

Avian S-9 liver homogenates were obtained from phenobarbital, 3-methylcholanthrene (3-MC), polychlorinated biphenyl (Aroclor 1254) induced and control chickens. These homogenates were tested for their capacity to metabolically activate benzo[a]pyrene (B[a]P) and cyclo-phosphamide in the Salmonella typhimurium assay. Liver homogenates from 3-MC, Aroclor 1254 and phenobarbital induced chickens were more active in converting B[a]P to its ultimate mutagenic form than was S-9 obtained from Aroclor 1254 induced rats. However, Aroclor 1254 induced rat S-9 was superior to Aroclor 1254 induced avian S-9 in metabolically activating cyclophosphamide.

Animals↗
PubMed1984

HLA DR typing of aspirin sensitive asthmatics.

Previous studies have suggested associations of HLA, A, B and C loci antigens with specific subgroups of asthma. We applied DR antigen typing to the aspirin sensitive subgroup to look for similar correlations. Our results show no statistically significant increase in any known DR antigen nor any correlation with A or B locus typing. We did find a non-statistically significant increase in the number of subjects with blank typing at the DR locus, (i.e., a presently unidentified antigen), raising the question of whether a correlation may exist with an as yet undefined antigen.

Aspirin↗