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Biomedical subjects

J R Harrison

Publications and source records attributed to J R Harrison.

49 records · Page 3Linked to original sources
PubMed1986

Inhibition of phorbol ester stimulated interleukin 2 production by copper(II) complexes.

Superoxide dismutase mimetic copper(II) complexes, such as copper(II)(3,5-diisopropylsalicylate)2 (CuDIPS), inhibit phorbol ester stimulated tumor promotion in mouse skin. Therefore, CuDIPS was tested as a potential inhibitor of another effect of phorbol esters, induction of interleukin 2 (IL2) synthesis, in the mouse thymoma cell line EL4. CuDIPS inhibited phorbol ester induced IL2 production in a concentration dependent manner with a 50% inhibitory concentration of about 10 microM. However, the ligand 3,5-diisopropylsalicylic acid also inhibited the induction of IL2 by phorbol esters (50% inhibitory concentration, 15 microM). Since the superoxide dismutase mimetic activity of CuDIPS is not stable in the presence of ethylenediaminetetraacetic acid, the effects of CuDIPS could be due to the free ligand and not to the intact metallocomplex. Consequently, a series of extremely stable copper(II) macrocyclic compounds was synthesized, and the reduction potential, superoxide dismutase mimetic activity, and ability to inhibit phorbol ester induced IL2 production were determined for each. Of the copper(II) macrocyclic complexes studied, only the most potent superoxide dismutase mimetic compound was found to inhibit phorbol ester induced IL2 production. Copper(II) complexes had to be added no later than 4 following phorbol ester administration to be effective inhibitors of the IL response, suggesting that these compounds act subsequent to the binding of phorbol esters but prior to the transcription of IL2 messenger RNA. Adherence of EL4 cells to substrate in response to phorbol esters was unaffected by copper(II) compounds. In summary, copper(II) compounds with appropriate reduction potentials can act within a defined time period to inhibit some, but not all, of the effects of phorbol esters on EL4 cells.

Animals↗
PubMed1986

An effect of CO2 on the maximum safe direct decompression to 1 bar from oxygen-nitrogen saturation.

An investigation into the maximum safe decompression step from oxygen nitrogen saturation to 1 bar was carried out with and without the presence of 0.02 bar carbon dioxide. The series, Islander 1, involved 13 teams of 5, fully informed, male volunteers carrying out simulated dives. One group of 6 teams carried out dives in an atmosphere of 0.4 bar oxygen, balance nitrogen (O2-N2); another group of 7 teams used an atmosphere of 0.38 bar oxygen, 0.02 bar carbon dioxide, balance nitrogen (O2-N2-CO2). The dives consisted of a 48-h stay at 1.7 or 1.8 bar to saturate the tissues, followed by decompression to 1 bar air at 0.5 bar/min. Two decompression parameters were studied; the incidence of decompression sickness (DCS) in the 24 h postdecompression, and the incidence and grade of venous gas emboli (VGE) in the first 6 h postdecompression. The grade of VGE was assessed using the Kisman-Masurel scoring system which produces a bubble grade with the subject at rest and after movement. No significant difference was found in the incidence of DCS between the two groups. Twenty subjects were decompressed from 1.7 bar using each mixture, without signs or symptoms of DCS. However, after decompression from 1.8 bar there were 2 cases of DCS in 10 subjects in the O2-N2 group and 2 cases in 15 subjects in the O2-N2-CO2 group. The incidence of detectable VGE was always lower in the O2-N2-CO2 group at both saturation pressures; at 1.7 bar the VGE incidence was lower by 40% (P less than 0.05) at rest and by 55% (P less than 0.001) after movement. At 1.8 bar the reduction was 3% (NS) at rest and 30% (NS) after movement. The results indicate that decompression from 1.8 bar to 1 bar, with or without the presence of 0.02 bar carbon dioxide, is likely to produce more than 5% DCS.

Adult↗
PubMed1982

Enzymatic diagnosis of the mucopolysaccharidoses: experience of 96 cases diagnosed in a five-year period.

We assessed lysosomal exohydrolase activities in homogenates of cultured skin fibroblasts and peripheral blood leucocytes of approximately 550 patients referred from throughout Australasia and suspected of having a mucopolysaccharidosis. Of these, 96 patients from 80 families were diagnosed as being homozygous deficient for a particular lysosomal enzyme activity. Clinical phenotype varied considerably within each of the enzyme-deficient states. This did not correlate with the level of "residual" enzyme activity in leucocyte or fibroblast homogenates. It was not always possible to discriminate heterozygotes from normal controls by enzyme assay of leucocyte or fibroblast homogenates in this study of a large number of mucopolysaccharidoses Type II by means of a single hair root assay system.

Clinical Enzyme Tests↗
PubMedDate not supplied

Effects of ionizing radiation on fixed-ratio escape performance in rats.

Adult male rats pressed a lever to terminate scrambled footshock according to a fixed-ratio 20 schedule (FR escape). Separate groups of rats received a single whole-body exposure to 4.5 or 7.5 Gray (Gy) of gamma photon radiation or were sham irradiated. The first postirradiation test session began 5 min after the end of the irradiation. The 4.5 Gy dose failed to produce any significant changes in performance over six weeks of testing after exposure. In contrast, response rates after irradiation with 7.5 Gy were decreased over the first four weeks postexposure. Reductions in response rate were due to both an increase in the latency to the first response of a ratio and to a reduction in running response rate. Performance recovered to preirradiation control levels during weeks 5-6 after exposure to 7.5 Gy. Body weights were decreased dose-dependently to a minimum of 91% of preirradiation control values during the third week after exposure to 7.5 Gy. A significant positive correlation existed for changes in the weekly average response rates and body weights at this dose. When a total dose of 7.5 Gy was delivered as 1.5 Gy per day for five consecutive days (dose fractionation), there were no significant changes in performance over eight weeks of testing although reversible decreases in response rates occurred in three of six rats. By comparison with previous studies these results demonstrate that FR escape performance may provide a more sensitive index of radiation-induced behavioral disruption than performance maintained by several other schedules of negative reinforcement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Clathrin light chains and secretory vesicle binding proteins are distinct.

Recently, several groups have initiated studies on cytosolic proteins that bind to isolated secretory vesicle membranes in the presence of Ca2+ in order to identify proteins that may regulate exocytosis. Two major chromaffin granule binding proteins, of molecular weights 32,000 (32K) and 34,000 (34K), were reported to have the same mobility on one-dimensional SDS gels as clathrin-associated light chains from the adrenal medulla, and the 34K granule binding protein the same one-dimensional peptide map as the 34K clathrin light chain. These observations support the hypothesis that Ca2+-dependent recruitment of soluble light chains to the vesicle membrane may nucleate the assembly of a clathrin coat and initiate endocytosis. Here we report that two-dimensional peptide maps of the clathrin light chains and of all chromaffin granule membrane binding proteins in the 30K range are distinct, and therefore fail to support this hypothesis. It has also been suggested that some or all of the vesicle binding proteins require calmodulin for their interaction with the membrane. However, we find that antagonism of calmodulin by trifluoperazine does not prevent the association of the other cytosolic proteins with the chromaffin granule membrane.

Adrenal Medulla↗