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Biomedical subjects

M F Robinson

Publications and source records attributed to M F Robinson.

At least 37 records · Page 2Linked to original sources

Chemiluminescence of peripheral polymorphonuclear leukocytes from adult periodontitis patients.

Polymorphonuclear leukocytes (PMN's) constitute a primary host resistance factor against infection. This study investigated the chemiluminescent (CL) response of peripheral blood PMN's isolated from human subjects with adult periodontitis. 32 subjects were categorized on the basis of age and periodontal disease status into 4 equal groups--young healthy, young diseased, old healthy and old diseased. PMN CL was stimulated using heat-killed, serum-opsonized Fusobacterium nucleatum--a specific periodontopathic gram-negative anaerobe, and Escherichia coli as a gram-negative control organism. The results showed a statistically significant enhancement (p less than 0.05) in the CL response, which was cell associated, in the young diseased subjects. This was not seen in the old subjects (p greater than 0.05), suggesting that in periodontal disease in young subjects the peripheral blood PMNs may be in a metabolically activated state. There was nevertheless a degree of variability between individual subjects within each of the 4 clinical groups.

Adult↗

Selenium in human nutrition in New Zealand.

New Zealand's soil has a low concentration of selenium (Se), and its residents have a lower Se status than do most other peoples. However, New Zealanders do not suffer from the Se-responsive ills that afflict their farm animals and some people in China. New Zealanders, particularly those in the South Island, may have adapted to their low Se environment by thriftiness in urinary excretion of Se. Low glutathione peroxidase activities in their tissues have not resulted in noticeable damage or changes. The enzyme activity can be raised to a plateau by Se supplements, but there is no evidence that supplementation leads to better health. Since patterns of coronary heart disease, hypertension, and cancer in New Zealand resemble those in other Western countries, no direct link between these diseases and Se level is likely.

Humans↗

Inhibitory effect of [Tyr34]bPTH-(7-34)-amide on bPTH-(1-34) ability to reduce uterine contraction.

Synthetic bovine parathyroid hormone containing the 1-34 NH2-terminal amino acids [bPTH-(1-34)] inhibits uterine contraction stimulated by a variety of agonists. Previously, we reported that the parathyroid hormone analogue [Nle8, Nle18, Tyr34]bPTH-(3-34)amide [NTA-(3-34)] antagonized this effect of bPTH-(1-34) while the analogue [Tyr34]bPTH-(7-34)amide [bPTH-(7-34)] used in this study stimulated uterine contraction. However, contrary to this previous report, bPTH-(7-34) in the present study failed to initiate a contractile response and instead resulted in an inhibitory response to the bPTH-(1-34) effect on uterine contraction in a dose-related manner. The inhibitory response of bPTH-(7-34) was further confirmed by demonstrating that this preparation of bPTH-(7-34) was capable of blocking bPTH-(1-34)-stimulated adenylate cyclase activity on particulate fractions of osteoblast-like cells from neonatal mouse calvarial. These results are consistent with those in the literature for the antagonistic effect of the 7-34 PTH fragment.

Acetylcholine↗

Unusually high intake and fecal output of cadmium, and fecal output of other trace elements in New Zealand adults consuming dredge oysters.

The concentration of cadmium in the New Zealand dredge oyster Tiostrea lutaria (commonly known as a Bluff oyster) is sufficiently high so that the ingestion of just one oyster can more than double a normal daily dietary intake of cadmium for a New Zealand adult. A survey of 75 adults (18-76 years old) associated with the oyster fishing industry in Bluff, Southland, New Zealand, was carried out before and at the end of the oyster season. Preseason intakes (from dietary history questionnaires and from 3-day fecal collections) of cadmium, selenium, zinc, copper, and manganese were normal for a New Zealand adult not consuming Bluff oysters. The subjects were classified according to their reported average oyster consumption during the 6 months of the oyster fishing season; the subjects who consumed more oysters were more likely to smoke cigarettes. The end-season fecal output of cadmium confirmed the reported average oyster intakes: Category I (0-5 oysters/week): 15 +/- 8 (mean +/- SD) micrograms Cd/day; Category II (6-23 oysters/week): 84 +/- 134 micrograms Cd/day; Category III (24-71 oysters/week): 129 +/- 144 micrograms Cd/day; Category IV (72+ oysters/week): 233 +/- 185 micrograms Cd/day. The fecal output of selenium as well was increased by the consumption of many oysters but the fecal outputs of zinc, copper, and manganese were not. Using fecal cadmium excretion to predict dietary cadmium intake, 8-15% of the subjects in this study were identified as having an intake of cadmium which has been associated with an increased prevalence of tubular proteinuria. The highest individual daily fecal excretion of cadmium at the end of the season was 580 micrograms Cd/day, i.e., a daily excretion equivalent to more than 10 times above the weekly intake provisionally considered tolerable (400-500 micrograms Cd/week; WHO, 1972). Continued investigations on this population group will determine whether there are any health consequences of these extremely high cadmium intakes.

Adult↗

Selenium and vitamin E supplementation: activities of glutathione peroxidase in human tissues.

Twenty-seven New Zealand women received daily for 4 wk, 200 micrograms selenium as sodium selenite, 170 mg alpha-tocopherol acetate, or a placebo. Se supplementation raised platelet selenoglutathione peroxidase (Se-GSHPx, p less than 0.001) and also Se and Se-GSHPx in whole blood and plasma. Se concentrations and Se-GSHPx activities in liver biopsies taken after supplementation were greater (p less than 0.05) for the Se group and a good correlation was found between Se and Se-GSHPx in liver and muscle for all subjects. Platelet Se-GSHPx correlated well with Se and Se-GSHPx in liver, indicating its suitability for assessing Se bioavailability. This is the first reported study of relationships between Se and Se-GSHPx in human liver and muscle tissue and platelet Se-GSHPx after Se supplementation. These observations verify in man relationships observe in animal studies, giving support to assumptions made in methods for assessing Se status and bioavailability in man, in particular the use of platelet GSHPx.

Adaptation, Physiological↗

Blood selenium and glutathione peroxidase activity of populations in New Zealand, Oregon, and South Dakota.

The relationship of whole blood selenium (Se) to glutathione peroxidase (GPX) activity was examined for individuals in New Zealand, Oregon, and South Dakota who represented, respectively, populations with exposure to low, medium, and high amounts of Se. The mean (respective) blood Se levels were 60, 200, and 400 ng/ml. Intergroup differences in blood Se levels were highly significant (P less than 0.001). GPX assays were performed using two variations of an enzyme-coupled procedure to assess the equivalence of the two methods. Despite a fourfold difference in absolute activities measured by these methods, the GPX activities were highly correlated (r = .86) between procedures. Average blood GPX activity was significantly lower (P less than 0.001) for the New Zealand group compared with the other two groups, but there was no difference in GPX activities between the Oregon and South Dakota groups. Linear regression of GPX vs. Se values within each group indicated a significant correlation of these parameters only in the New Zealand group (r = .46, P less than 0.01). Comparison of these parameters for combined data from all three groups also showed a significant positive correlation (r = .60, P less than 0.001). A saturation model (In GPX = k1 + k2 (Se)-1)) fits the combined data better (r = .80, P less than 0.01) than does direct comparison of the two parameters. These results suggest that GPX activity is an appropriate indicator of human Se status only in populations with below normal exposure to Se, as activity of this enzyme is saturated at relatively low levels.

Glutathione Peroxidase↗

The absence of adaptive changes in tissue activities of glutathione-S-transferase, superoxide dismutase and catalase following selenium and vitamin E supplementation in subjects with low selenium status.

Three groups of New Zealand women were given daily in a double blind randomised study, 200 micrograms Se as sodium selenite, 170 mg alpha-tocopherol or a placebo for 4 wk. Activities of glutathione-S-transferase, superoxide dismutase and catalase were assayed in erythrocytes, plasma and platelets and in liver and muscle biopsy tissues. No changes in activities of any of these tissue enzymes were observed in any of the three groups. There were also no changes in non-selenium dependent glutathione peroxidase activities in liver or plasma. The lack of changes in any of these enzymes following selenium supplementation suggests that adaptive changes to the low selenium status of these subjects had not occurred through these lipid peroxidation defense mechanisms.

Adult↗

Prevention of gastric mucosal lesions following aortic cross-clamping.

Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).

Allopurinol↗

Altered platelet lipoxygenase activity in patients with low selenium.

1. Arachidonic acid metabolism through the lipoxygenase pathway in platelets was investigated in 11 patients with low selenium (Se) nutritional status and compared with 14 patients with a normal Se status. 2. Plasma and whole blood Se levels, as well as plasma, whole blood and platelet glutathione peroxidase (GSHPx) activity, were measured in both groups and found to be significantly lower in the group with low Se status. 3. Studies on [14C]arachidonic acid stimulated platelets demonstrated that reduced conversion of the active metabolite 12-hydroperoxyeicosatetraenoic acid to 12-hydroxyeicosatetraenoic acid occurred in patients with low Se nutrition. 4. Changes in [14C]arachidonic acid metabolism are attributed to reduced activity of the seleno-enzyme GSHPx. The effects of other factors cannot be entirely excluded.

Arachidonic Acid↗

Cyclosporin-A-induced gingival enlargement. A case report.

Cyclosporin-A (CsA)-induced gingival enlargement has been reported in a small number of cases but may involve up to one third of all patients taking CsA. The present study reports a case of CsA-induced gingival enlargement during suppressive therapy for myasthenia gravis. Gingival tissues were examined histologically, histochemically, and immunohistologically. The basic tissue response seemed to be a dental plaque- and trauma-induced fibroblastic response characterized by large aggregations of plasma cells, macrophages and helper T lymphocytes. The reactive areas rapidly matured into noninflamed fibrocytic tissue. The suppressive effect of CsA appears responsible for removal of sectors of the normal immune response and, in combination with an elevated number of macrophages, may be instrumental in initiating a fibrous hyperplastic response.

Adult↗

Characterization of soluble cyclic AMP phosphodiesterases and partial purification of a major form in human leiomyoma of the uterus.

Human leiomyoma of the uterus contained seven forms of cyclic AMP phosphodiesterase in the crude cytosol as revealed by a specific activity stain on non-denaturing polyacrylamide gel electrophoresis. The enzymes from human myometrium and normal uterus showed an identical activity pattern. Ferguson plot analysis showed four different molecular weight species of Mr 229,000 +/- 4,000, 186,000 +/- 4,000, 174,000 +/- 4,000 and 162,000 +/- 4,000. The Mr 174,000 species comprised four differently charged forms. Sucrose density gradient centrifugation of the crude cytosol revealed the presence of three molecular weight species sedimenting at 11.8S, 8.1S and 3.6S. The Michaelis constant (Km) for the band 1 form which displayed linear kinetics was 5 microM and the band 2 form which produced non-linear kinetics had Km values of 5.8 and 37 microM.

3',5'-Cyclic-AMP Phosphodiesterases↗

The production of hydroxyl radical by human neutrophils stimulated by arachidonic acid--measurements by ESR spectroscopy.

Human neutrophils incubated with sodium arachidonate generated hydroxyl radicals. The radical formed an adduct with the spin trap 5', 5-dimethyl-l-pyrroline-N-oxide (DMPO) and was subsequently detected by electron spin resonance (ESR) spectroscopy. The ESR signal was inhibited by mannitol and superoxide dismutase but not by catalase. Removal of glucose from the reaction mixture or the presence of glucose metabolic inhibitors including 2-deoxy-D-glucose and 3-O-methyl-D-glucose did not affect the production of hydroxyl radical by the neutrophils. The ESR signal was, however, inhibited by the lipoxygenase inhibitors nordihydroguaiaretic acid and N-ethylmaleimide. The involvement of lipoxygenase in the production of hydroxyl radical was demonstrated by the trapping of the radical with DMPO in a reaction mixture of soybean lipoxygenase and arachidonic acid (AA). These findings support our previous postulation that the metabolism of AA via the lipoxygenase pathway is a source of hydroxyl radical in stimulated neutrophils.

3-O-Methylglucose↗

Urinary and fecal excretions and absorption of a large supplement of selenium: superiority of selenate over selenite.

A correction needs to be made to the form of selenium used in earlier studies; what was believed to be selenite-Se in solution is now known to have been selenate-Se. In the present study, excretion of Se was followed in 13 women after ingestion of 1 mg Se as selenite or selenate in solution. Fecal excretion of selenate-Se was less than for selenite-Se reflecting a higher apparent absorption [94 +/- 4% (SD), 62 +/- 14%, respectively]. Peak excretion of Se occurred 3 h earlier for selenate-Se than for selenite-Se and was 6 times higher. Total urinary excretion of selenate-Se was 3 times that of selenite-Se and still 2 times as high when expressed as % absorbed dose. Total recovery of Se in urine and feces was similar for both forms. There was remarkable agreement between these results and those reported earlier for selenate-Se (Selovet-1) and selenite-Se.

Adult↗

Cross-clamping of the thoracic aorta. Influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol, and superoxide dismutase on spinal cord blood flow and paraplegia in baboons.

There is a high incidence of paraplegia associated with thoracic aortic cross-clamping, even when cardiopulmonary bypass or shunts are used. In 56 adult baboons, spinal cord blood flow (SCBF), vascular anatomy, and paraplegia rates were evaluated. Tissue blood flow was measured by radioactive microspheres. Various procedures were used to increase SCBF and to prevent ischemia-reperfusion injury. It was found that the rate of paraplegia was inversely correlated with neural tissue ischemia (SCBF) and directly correlated with reperfusion hyperemia. Two methods completely prevented paraplegia. These two methods were a thoracic shunt with occlusion of the infrarenal aorta or cerebrospinal fluid drainage plus intrathecal papaverine injection, both of which were associated with an increased SCBF. Furthermore, papaverine dilated the anterior spinal artery (ASA) (p = 0.007) and increased the blood flow through the lower ASA. Whereas procedures utilizing a calcium channel blocker (flunarizine), allopurinol, superoxide dismutase (SOD), laminectomy alone, and a thoracoabdominal shunt not perfusing the arteria radicularis magna (ARM) all failed to prevent paraplegia, allopurinol (p = 0.026) and SOD (p = 0.004) did prevent gastric stress lesions, indicating that their failure to prevent paraplegia was not due to a lack of activity. Of great clinical interest is that, if a shunt is used and the ARM is perfused, infrarenal aortic cross-clamping increases SCBF, thus preventing paraplegia. Intrathecal application of papaverine proved to be even more effective in increasing SCBF and also completely prevented paraplegia. As this is a safer procedure than the insertion of shunts, this is the method of choice for the prevention of paraplegia associated with thoracic aortic cross-clamping. The preliminary trial using intrathecal papaverine in human beings has thus far shown no adverse side effects from the drug, and no paraplegia has occurred.

Allopurinol↗

Effect of a megadose of ascorbic acid, a meal and orange juice on the absorption of selenium as sodium selenite.

Urinary and faecal excretions of selenium were measured for five days following a dose of 1 mg Se as sodium selenite in ten young women after an overnight fast. The selenite was taken two hours before a meal or mixed with 1 g ascorbic acid; or with a continental type breakfast providing 4.5-5.6 micrograms Se and 0.6-0.8 mg Cu, with or without 200 ml orange juice (60 mg ascorbic acid). The light meal appeared to have little effect on selenite-Se absorption, and orange juice appeared even to assist it. But the availability of Se was reduced almost to zero when selenite and 1 g ascorbic acid were taken together well before the meal.

Adult↗

Selenium absorption by canine jejunum.

Deficiency of the trace element selenium causes disease in domestic animals and may also be implicated in the pathogenesis of some human illness. In this study, the triple-lumen perfusion method was used to measure the rate of absorption of trace quantities of selenium (50 micrograms/liter in a physiological electrolyte solution) from the jejunum when given as D,L-selenomethione, D,L-selenocystine, or sodium selenite to healthy dogs in vivo. Selenium absorption from the test segment (expressed as percent administered dose per centimeter +/- SEM) was 1.97 +/- 0.04 from D,L-selenomethionine, 1.15 +/- 0.06 from D,L-selenocystine, and 0.51 +/- 0.07 from sodium selenite (P less than 0.01, N = 5). In separate studies in four anesthetized dogs, the jejunum was perfused with L-[75Se] selenomethionine while concentrations of 75Se were measured in the portal venous blood; these studies established that [75Se]selenomethionine disappearing from the gut lumen corresponded quantitatively to 75Se appearing in the portal venous effluent (74 +/- 6%) and incorporated into intestinal tissue (24 +/- 5%). These results are consistent with the hypothesis that the absorption of amino acid-bound selenium is accelerated by the specific amino acid active transport mechanisms in the gut mucosa. Sodium selenite is absorbed more slowly, possibly by simple diffusion through the intestinal mucosa, than the amino acid-bound selenium compounds.

Animals↗