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Biomedical subjects

M F Robinson

Publications and source records attributed to M F Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effects of supplementation with high-selenium wheat bread on selenium, glutathione peroxidase and related enzymes in blood components of New Zealand residents.

The effects of supplementation with high-Se wheat bread on selenium (Se) concentrations, glutathione peroxidase (EC 1.11.1.9, GSHPx) activities and related enzymes in the prevention of lipid peroxidation were studied. Four New Zealand women were supplemented with 200 micrograms Se daily for 8-13 weeks followed by a post-dosing period of 9-12 weeks. GSHPx activities increased in whole blood, erythrocytes, plasma and platelets of all subjects but increases were considerably less than those of Se concentrations in whole blood, plasma and erythrocytes. During the post-dosing period Se concentrations and GSHPx activities fell to levels which were in most cases somewhat higher than baseline values. Glutathione-S-transferase activities in erythrocytes, plasma and platelets did not change during the study, nor did superoxide dismutase in erythrocytes and platelets, erythrocyte catalase or plasma alpha-tocopherol. Thus Se supplementation of healthy New Zealand subjects increased GSHPx activities but did not produce any adaptive changes in other components of the lipid peroxidation defense mechanisms.

Adult↗
PubMed1985

Urinary excretion of selenium by New Zealand and North American human subjects on differing intakes.

Lower renal plasma clearances of selenium (CSe 0.1-0.2 ml min-1), indicating excretion of a smaller proportion of Se presented to the kidneys, were found in New Zealand (NZ) residents with low plasma Se ((Se)p 50-70 ng ml-1) on customary intakes below 30 micrograms d-1 Se. North American subjects consuming 80 micrograms d-1 with (Se)p 120-140 ng ml-1 had CSe between 0.2 and 0.3 ml min-1. Several weeks' supplementation with high-Se bread increased NZ subjects' (Se)p to 120-175 ng ml-1 and CSe to 0.4-0.7 ml min-1. (Se)p remained elevated when supplementation ceased, but CSe returned to the basal range within a few days. Americans' clearances showed no such abrupt decrease when their dietary intake was similarly reduced. The NZ residents thus appeared to excrete selenium more sparingly than others. Rapid alterations in clearance after supplements and single doses were probably due to changes in the proportions of different forms of selenium in the plasma.

Adaptation, Physiological↗
PubMed1984

Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes.

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).

Antigen-Antibody Complex↗
PubMed1983

Selenium and risk factors for cardiovascular disease in New Zealand.

Blood selenium (Se) concentrations and glutathione peroxidase (GSHPX) activities were measured in 118 men (39 +/- SD 15 yr) and 112 women (42 +/- 16 yr) randomly selected from the total respondents (1192) to health survey in Milton, a low soil-selenium area in Otago. GSHPx activities were marginally lower for men (11.9 +/- 3.2 units/g Hb) than for women (12.9 +/- 3.8 units/g Hb). Blood, erythrocyte and plasma selenium concentrations were about the same for both sexes and means for all subjects (61 +/- 15; 73 +/- 19; 49 +/- 12 ng Se/ml) were almost identical with a control group of Otago blood donors. No differences in blood levels could be associated with smoking, use of oral contraceptives, arthritis and/or rheumatism, or anti-hypertensive drugs. No relationship was found for the men or women between any of the parameters of selenium status and any of the parameters of risk factors for cardiovascular disease measured in the health survey: age, Quetelet's index, total skinfolds, systolic and diastolic pressure, pulse rate, plasma lipids and lipoprotein lipid concentrations. Moreover no relationship was found for the subgroups (36% group) of men and of women with plasma selenium below 45 ng Se/ml. This study indicates that if selenium is important it does not operate through the risk factors of cardiovascular disease as presently understood.

Adolescent↗
PubMed1983

The interaction of lymphocyte surface-bound immune complexes and neutrophils.

Neutrophils can be stimulated directly by a variety of stimulants resulting in the production of highly reactive oxygen derivatives. Included in these stimulants are peripheral blood lymphocytes with bovine serum albumin-anti-bovine serum albumin immune complexes (BSA-IC) or aggregated gamma-globulin (AHG) bound to their surface receptors. Through the use of chemiluminescence (CL) studies, we found that B lymphocytes preincubated with AHG stimulated neutrophils to a much greater extent than similarly preincubated T lymphocytes. Preincubated Raji cells (a B lymphoblastoid cell line) were also capable of stimulating neutrophils. We further demonstrated that after periods of mixed incubation with neutrophils, lymphocytes with surface-bound AHG did show an abnormal proliferative response to pokeweed mitogen (PWM), but not to phytohemagglutinin (PHA). This was not due to loss of cell viability, as judged by chromium release cytotoxicity assays and trypan blue exclusion, or to neutrophil enzyme release. The data suggest that neutrophils, stimulated with lymphocyte surface-bound immune complexes, are capable of producing an environment of in vitro oxidant stress. This stress, although not great enough to cause a significant decrease in lymphocyte viability, can cause impaired lymphocyte function. Physiologically, this may relate in the long term to immunologic malfunction observed in patients with high levels of circulating immune complexes.

Antibodies, Anti-Idiotypic↗
PubMed1983

The origin of chemiluminescence produced by neutrophils stimulated by opsonized zymosan.

The luminol-dependent chemiluminescence (CL) of neutrophils phagocytosing zymosan is inhibited by superoxide dismutase (SOD), catalase, sodium benzoate, and 2,5-dimethyl furan. In the present report it is shown that inhibition by SOD and 2,5-dimethyl furan is diminished and removed, respectively, by the omission of glucose from the incubation medium. Zymosan-induced CL is also inhibited by inhibitors of arachidonic acid (AA) metabolism, including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin, and aspirin, by prostaglandins E1 and E2, theophylline, and dibutyryl cyclic AMP (cAMP), and by the addition of AA, sodium fluoride, and xanthine oxidase plus xanthine to the cell suspension. These findings lead us to postulate that the metabolism of AA via the lipoxygenase (and cyclooxygenase) pathway(s) is the source of CL observed in neutrophils after phagocytosis. Reactive oxygen species produced as a result of activation of NAD(P)H oxidase provide oxidizing agents for the oxidation of AA along these pathways. It is also suggested that elevated levels of cAMP induced by prostaglandins synthesized via the cyclooxygenase pathway may play a role in the regulation of the zymosan-induced CL response.

Arachidonic Acids↗
PubMed1982

Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.

A six year old female presented with a recent history of pyoderma gangrenosum involving her legs and arms associated with an episode of Mycoplasma-like pneumonia. This was followed by Aspergillus osteomyelitis involving her left ulna and right femur. Both the skin lesions and the osteomyelitis responded to prolonged treatment with antifungal and antibiotic agents. Investigation of this patient revealed (1) an elevated serum IgE (4,800 units/ml), (2) defect in neutrophil chemotaxis that appeared to be due to immune complexes, (3) an abnormal nitroblue tetrazolium (NBT) result (0 percent stimulated and unstimulated), and (4) depressed mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen, negative results of intradermal skin tests, and negative dinitrochlorobenzene (DNCB) sensitization. The patient's clinically unaffected sibling had similar findings except for a positive DNCB response. In both children, intracellular bacterial killing of catalase-positive and negative organisms was normal. Kindred studies revealed widespread T-cell abnormalities consistent with autosomal dominant inheritance. Tissue typing studies showed that affected siblings shared the A1, B8, DR3 haplotype. This kindred is unique in that both the proband and the sibling have abnormalities of both the hyper-IgE syndrome and chronic granulomatous disease.

Child↗
PubMed1982

Measurement of circulating immune complexes in human sera by enzyme immunoassay.

Two methods, based on enzyme immunoassay, are described for the detection and quantitation of circulating immune complexes (CIC) in human sera. Aggregated human gamma globulin (AHG) or immune complexes in human sera are bound to complement receptors on Raji cells or to Clq adsorbed on to the plastic surface of microtitre plates. The bound complexes are subsequently detected using peroxidase-conjugated anti-human immunoglobulin antisera. The assays offer a benefit over previously described assays in that they use cheap, commercially available antisera and enable the detection of immune complexes composed of varying immunoglobulin classes.

Animals↗
PubMed1982

Effect of prolonged supplementation with daily supplements of selenomethionine and sodium selenite on glutathione peroxidase activity in blood of New Zealand residents.

Glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities and selenium (Se) concentrations in blood of 12 New Zealand residents were followed during prolonged supplementation with physiological doses (100 microgram Se) of sodium selenite (selenite-Se) or selenomethionine (Semet-Se). GSH-Px activities increased in all subjects but at 17 wk the mean increase was not significantly greater for Semet-Se (6.2 +/- SD 3.2 units/g Hb) than for selenite-Se (3.7 +/- 1.8 units/g Hb). After dosing ceased, GSH-Px activities for most subjects returned to predosing values in 17 to 40 wk, but in some subjects activities remained high. Increases in Se concentrations in whole blood, erythrocytes, and plasma were greater after Semet-Se than after selenite-se. Se concentrations tended to plateau after selenite-Se while after Semet-Se they continued to rise as long as dosing continued. Enzyme activity of one of four subjects supplemented daily with 500 microgram selenite-Se was unchanged, despite a great increase in plasma Se. Blood Se and GSH-Px of 23 New Zealand residents who ingest regular large doses (0.5 to 3 mg Se) mainly of selenite-Se showed that those who dosed weekly had greater values than the less frequent dosers. Three subjects showed extremely high values. It is suggested that each individual might have an optimal level of GSH-Px activity, so that the level reached is a balance between Se intake and other factors, including possible stressor effect of selenite.

Adult↗
PubMed1982

Cimetidine treatment of azotemic secondary hyperparathyroidism.

Cimetidine, an antagonist to histamine H2-receptors, reportedly lowers serum calcium and/or serum immunoreactive parathyroid hormone (iPTH) concentrations in some patients with primary and secondary (azotemic) hyperparathyroidism. We administered the drug orally (300 mg every 6 h) to five normal volunteers and four azotemic patients with secondary hyperparathyroidism who were not undergoing chronic hemodialysis. The normal persons and one azotemic patient took the drug for 5 weeks, and the remaining azotemic patients took it for 1 week. Before treatment, all patients had elevated levels of serum iPTH (two different assay systems), with or without elevated serum calcium concentrations, and increased urinary excretion of cAMP (per 100 ml glomerular filtrate). Cimetidine treatment caused no changes in serum calcium, phosphorus, or iPTH or in urinary cAMP (expressed as nanomoles per g creatinine). Serum creatinine, however, increased significantly in patients (P less than 0.02) and control subjects (P less than 0.025), which yielded statistically significant but spurious increases of urinary cAMP when expressed per 100 ml glomerular filtrate. We conclude that short term cimetidine administration has no effect on parathyroid function in normal persons or those with azotemic hyperparathyroidism. Because of its confusing effect on serum creatinine and a possible (albeit rare) adverse effect on renal function, the drug should be used with caution in azotemic patients not yet requiring chronic dialysis.

Adult↗
PubMed1981

Effect of daily supplements of selenium on patients with muscular complaints in Otago and Canterbury.

The alleged beneficial effect of selenium (Se) on fibromuscular rheumatism in residents of low soil-Se areas of New Zealand has been explored. Three dosing trials, two of them double blind trials, using physiological daily supplements (100 micrograms Se) of sodium selenite or selenomethionine and a placebo have been carried out. Blood Se and glutathione peroxidase (EC 1.11.1.9; GSHPX) activities were monitored and clinical assessment of the efficacy of the treatment was made during the trials. Blood Se and GSHPX activities rose in all patients who received Se whereas those in control groups remained more or less constant throughout the study. Clinical assessment of muscular symptoms showed that approximately half of the patients in both trial groups and placebo groups responded to treatment. Thus we have been unable to give conclusive evidence of a response to Se supplementation for relief of muscular complaints.

Adolescent↗
PubMed1981

Therapeutic plasmapheresis in systemic lupus erythematosus. Effect on immune complexes and antibodies to DNA.

The effect of plasmapheresis in 8 patients with systemic lupus erythematosus (SLE) was investigated. Drug treatment was maintained at a constant level for at least 4 weeks before plasmapheresis. Levels of immune complexes were measured by a Raji cell radioimmunoassay, and by a solid-phase C1q-binding assay. Antibodies to ds-DNA and ss-DNA were measured by the Farr assay. In all cases, immune complexes and antibodies were lowered by plasmapheresis. In 5 patients, plasmapheresis was followed by a rapid rebound of complexes and antibody to pretreatment levels. In 3 in whom plasmapheresis was followed by treatment with cyclophosphamide for 1 month, a sustained immunochemical and clinical improvement followed, lasting in 2 cases for up to 3 years.

Adolescent↗
PubMed1980

Selenium in human health and disease with emphasis on those aspects peculiar to New Zealand.

Evidence is accumulating to suggest that selenium (Se) is an essential trace element for man and is reviewed with emphasis on those aspects peculiar to New Zealand. The extremely low Se levels in New Zealand soils results in a low Se content of foods, low dietary intakes, low urinary excretions, and low blood Se concentrations and glutathione peroxidase activities. Of these, plasma Se gives a short-term index of nutritional status while erythrocyte Se and glutathione peroxidase activities give a long-term index. The consequences of the low Se status of New Zealanders are not immediately apparent as a deficiency disease has not been detected in residents consuming a normal diet. However a Se-responsive muscular syndrome has been described in a surgical patient on total parenteral nutrition. Similar groups that might be vulnerable to a Se deficiency are children with metabolic disorders consuming synthetic protein diets, premature babies and infants during the first few months of life, and patients with cancer whose lowered dietary intake is coupled with the traumatic nature of their disease. Other groups that have been studied in relation to a possible role for Se in specific illnesses are patients with cardiovascular disease and hypertension, rheumatoid arthritis and other muscular syndromes and surgical patients with or without cancer. It is not yet possible to predict a minimum Se requirement for health but it appears that the intake of New Zealanders might be on the borderline. At present supplementation by the general population is not justified, but may be necessary for certain vulnerable groups such as patients on restricted diets. The most effective means of supplementation for increasing the Se status of New Zealanders is under study.

Adolescent↗