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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 613 records · Page 34Linked to original sources

Effects of ascorbate on normal and abnormal leucocyte functions.

The stimulatory effects of ascorbate on neutrophil motility in vitro and in vivo and lymphocyte transformation to mitogens following ingestion or intravenous injection of ascorbate have been found to be related entirely to inhibition of the autooxidative effect of the myeloperoxidase/hydrogen peroxide/halide system (MPO/H2O2/halide system). Stimulation of neutrophil migration and lymphocyte transformation following a single intravenous injection of 1 g of ascorbate was associated with inhibition of the MPO/H2O2/halide system. The immunostimulatory activity and peroxidase inhibitory activity was related entirely to the serum ascorbate level. The relationship between inhibition of the peroxidase/h2O2/halide system and stimulation of neutrophil motility and lymphocyte mitogen-induced transformation was further established by using the horseradish peroxidase (HRP)/H2O2/halide system in vitro. Neutrophils and lymphocytes, exposed to this system, manifested markedly impaired chemotactic responsiveness and mitogen-induced transformation, respectively. However inclusion of ascorbate with the peroxidative system protected the neutrophils and lymphocytes from these inhibitory effects. Further studies in 3 patients with chronic granulomatous disease (CGD) and 10 patients with bronchial asthma suggested that ascorbate may be of value to improve the primary immunological abnormalities (neutrophil motility and antimicrobial activity) in CGD and the secondary abnormalities (neutrophil motility and lymphocyte transformation) found in some individuals with bronchial asthma.

Antibody Formation↗

Increased leucoattractant binding and reversible inhibition of neutrophil motility mediated by the peroxidase/H2O2/halide system: effects of ascorbate, cysteine, dithiothreitol, levamisole and thiamine.

Human blood neutrophils manifested markedly decreased motility following exposure to the horseradish peroxidase (HRP)/H2O2/halide system in vitro. These cells were protected from this inhibitory effect (of the HRP/H2O2/halide system) by inclusion of concentrations in the reaction system of ascorbate, cysteinee, levamisole and thiamine which stimulate neutrophil migration and inhibit activity of the HRP/H2O2/halide system. The reversible nature of the oxidative inhibition of migration was demonstrated by exposing neutrophils to the HRP/H2O2/halide system for 15 min followed by washing to remove the components of the peroxidative system, and subsequent addition of ascorbate, cystein, levamisole, thiamine and the reducing agent, dithiothreitol. Neutrophils so treated completely recovered normal or increased motility induced by the leucoattractants endotoxin-activated serum or synthetic chemotactic tripeptide f-met-leu-phe. This reversible loss of migratory responsiveness following exposure of neutrophils to the HRP/H2O2/halide system was not associated with decreased cell viability or adherence. However, membrane oxidation was accompanied by increased uptake of radiolabelled f-met-leu-phe and degranulation. The increased leucoattractant uptake was decreased by ascorbate, levamisole and thiamine. These agents also prevented oxidation of the neutrophil membrane by the HRP/H2O2/halide system as measured indirectly by inhibition of iodination.

Adult↗

Airline pilot disability: economic impact of an airline preventive medicine program.

The current economic crisis facing most major United States airlines has forced a close examination of airline-sponsored activities. The effectiveness of one airline's pilot preventive medicine program was estimated by comparing disability experience of its pilots against the experience of a larger population of airline pilots. The preventive medicine program at the studied airline was shown to reduce disability experience by one-third, while saving the airline better than $6 million annually. This program yielded the airline better than a 6-1 return on investment during the years studied.

Accidents, Aviation↗

Venous thrombo-embolism and raised alpha-1-antitrypsin levels. A possible causal relationship between excessive neutral protease inhibition and defective granulocyte-induced fibrinolysis.

The finding of 4 cases of venous thrombosis in patients with raised serum alpha 1-antitrypsin (AAT) levels has focused attention on the role of the inhibitors of leucocyte protease or granulocyte-induced fibrinolysis. A composite fibrin plate assay was devised to determine the fibrinolytic and fibrinolytic-inhibitor potential of viable circulating granulocytes, mononuclear cells and platelet-free plasma. A plasmin-dependent and a plasmin-independent pathway were identified in circulating granulocytes, a biological function which appeared to be completely absent from the mononuclear fraction. In order to explore the effect of AAT on the cellular fibrinolytic pathway, viable granulocyte and plasma fractions were exposed to the inhibitor in a purified system as well as to several aliquots of plasma containing an excess of AAT obtained from a patient with venous thrombo-embolic disease. The unequivocal inhibition of granulocyte fibrinolytic activity by pure AAT solutions as well as by plasma with a raised AAT level would seem to provide further evidence that by counteracting protease liberated by cellular elements, notably the granulocyte, the patient is deprived of a vital component of the fibrinolytic defence mechanism.

Adult↗

Immunological assessment of patients with rheumatoid arthritis--evaluation of the effects of propranolol.

Some humoral and cellular immune functions were evaluated in a group of 10 patients with rheumatoid arthritis before and after 3 months of treatment with the beta-blocking agent propranolol. Humoral parameters measured were serum immunoglobulins including IgE, auto-antibodies, C-reactive protein, total haemolytic complement activity and the complement components C3 and C4. Cellular functions assessed were polymorphonuclear leucocyte chemotaxis, phagocytosis and postphagocytic nitroblue tetrazolium reduction, hexose monophosphate shunt activity and myeloperoxidase-mediated iodination of ingested protein; lymphocyte transformation to the mitogens phytohaemagglutinin and concanavalin A was also investigated. No alteration of humoral factors and neutrophil functions was observed following propranolol administration (40 mg 3 times a day), but lymphocyte transformation was significantly increased. Improved lymphocyte function did not correlate with clinical improvement.

Adult↗

Familial chronic mucocutaneous candidiasis successfully treated with oral ketoconazole.

A father and son, both suffering from chronic mucocutaneous candidiasis, were successfully treated with oral ketoconazole, a water-soluble imidazole compound. No toxic side-effects occurred during treatment. Treatment was given for about 8 months with diminishing does of ketoconazole. The disease cleared completely about half-way through the course of treatment and did not relapse within 1 month of discontinuing the drug. The only immunological abnormality was a depression in vitro of neutrophil chemotaxis. This became normal during therapy and was regarded as being a result of the disease and not as its cause.

Administration, Oral↗

Evaluation of neutrophil and lymphocyte function in subjects with iron deficiency.

Neutrophil function was studied in a group of 15 children, 7 with iron deficiency (4 with iron deficiency anaemia) and 8 age-matched controls; by clinical and laboratory criteria, all were uninfected. In a second group of 28 children, 14 iron-deficient (6 with iron deficiency anaemia) and 14 controls, numbers of circulating T and B lymphocytes and responsiveness to the mitogens phytohaemagglutinin and concanavalin A were assessed. Levels of salivary IgA were estimated in every patient. Neutrophil chemotaxis to autologous endotoxin-activated serum and control serum, phagocytosis of Candida albicans and post-phagocytic nitro-blue tetrazolium reduction were similar in both the iron-deficient and control groups. Likewise, levels of secretory IgA, serum immunoglobulins, total haemolytic complement and complement components, and numbers of T and B lymphocytes were comparable in both iron-deficient groups and the control group. However, transformation to both mitogens was reduced in the group with iron deficiency anaemia.

Anemia, Hypochromic↗

Replacement of mouse LM fibroblast choline by a sulfonium analog. Effects on membrane properties as determined by virus probes.

A sulfonium analog of choline ('sulfocholine', a natural phospholipid constituent of diatoms) was metabolically incorporated into mouse LM fibroblasts cultured in serum-free medium. Subconfluent cultures of LM cells were able to utilize sulfocholine as sole choline source and to increase in cell number for 3 days of incubation; thereafter a decrease in cell number was observed. In contrast, cultures of LM cells seeded to confluency showed no decrease in cell number up to at least 10 days when maintained, with daily medium changes, in medium containing either choline or the sulfonium analog. Such confluent cultures, maintained for 7 days in sulfocholine-containing medium, showed virtually complete replacement of cellular phosphatidylcholine and greater than 50% replacement of cellular sphingomyelin by their respective sulfonium analogs. The functional exchangeability of natural phosphatidylcholine and sphingomyelin with their sulfonium analogs to participate in normal cell membrane-mediated activities was demonstrated by comparatively assaying the abilities of sulfocholine- and choline-maintained cells to incorporate and replicate certain animal viruses known to possess membrane-dependent steps in various phases of their replication cycles. No difference was detected between the abilities of sulfocholine- and choline-maintained cells to take up vesicular stomatitis virus or mengo virus, or to replicate vesicular stomatitis virus, mengo virus or mouse hepatitis virus.

Animals↗