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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 433 records · Page 24Linked to original sources
PubMed1977

Functional studies on human peritoneal eosinophils.

A number of functional studies were performed on essentially pure eosinophil preparations obtained from the ascitic fluid of a patient with eosinophilic gastroenteritis. These cells responded to chemotactic factors including a bacterial factor, partially purified C5a, and factors generated from serum or ascitic fluid. The chemotactic activity generated in the patient's ascitic fluid was capable of attracting both neutrophils and eosinophils, was dependent on the presence of complement components, and was identified as C5a. Metabolic studies demonstrated that particle ingestion by eosinophils was associated with a marked increase in hexose monophosphate shunt activity ([1-14C]glucose oxidation), H2O2 formation ([14C]formate oxidation), superoxide anion generation, chemiluminescence, thyroid hormone degradation, iodination, and estrogen binding. This postphagocytic metabolic burst by eosinophils was qualitatively similar to that observed in neutrophils, but for several parameters the eosinophil response was greater than the neutrophil response.

Chemotaxis↗
PubMed1977

Defective neutrophil chemotaxis in juvenile periodontitis.

Neutrophil chemotaxis was evaluated in nine patients with juvenile periodontitis, with normal subjects and patients with the adult form of periodontitis as controls. Defective chemotactic responses were observed in neutrophils from seven of nine juvenile patients, and a reduced level of complement-derived chemotactic activity was demonstrated in serum from four patients. These determinations were normal in all the patients with adult periodontitis. Serum from five of the juvenile patients contained a heat-stable, non-dialyzable factor that markedly inhibited the chemotaxis of normal neutrophils. Thus the characteristic tissue destruction seen in juvenile periodontitis may be, at least in part, a consequence of a failure of host defense mechanisms.

Adolescent↗
PubMed1977

Transbronchial lung biopsy: A review of 85 cases.

Transbronchial lung biopsy using the fibreoptic bronchoscope was carried out in 85 patients. There were no serious complications; two patients had a 10% pneumothorax and 17 had slight haemoptysis lasting less than 24 hours. The problems of interpreting small biopsy specimens are considered. Satisfactory specimens were obtained without fluoroscopic guidance, particularly in diffuse and lobar lesions. A histological diagnosis was made in 62% of diffuse lesions and compatible histology was found in a further 22%. In a further case Pneumocytis carinii infection was diagnosed. Blind biopsy of discrete periheral lesions was less successful with only one positive diagnosis in 12 patients.

Adult↗
PubMed1977

Histamine modulation of eosinophil migration.

Preincubation of eosinophils with 10(-5) M or higher concentrations of histamine inhibited the eosinophil chemotactic response to endotoxin-activated serum whether by using the nucleopore filter assay and counting the cells migrating through the filter, or by using the Zigmond-Hirsch assay and counting the cells at each 10-mum interval. When the H2-receptor sites on the eosinophils were blocked by metiamide, the inhibitory capacity of histamine was prevented. Preincubation of eosinophils with 10(-6) M histamine increased the number of responding eosinophils to endotoxin-activated serum and this enhancement was blocked by an H1-receptor antagonist. Isoproteronol and aminophylline inhibited eosinophil movement and increasing concentrations of dibutryl cyclic AMP inhibited eosinophil migration. Concentrations of histamine that consistently resulted in inhibition of eosinophil movement stimulated an increase in cyclic AMP that was prevented by blocking the H2-receptor but not the H1-receptor. Thus, histamine-dependent inhibition of the eosinophil chemotactic response to other agents is mediated through the H2-receptor and is associated with an increase in the intracellular level of cyclic AMP whereas histamine dependent enhancement of eosinophil migration to other agents appears to be mediated through the H1-receptor. Eosinophils behave as a heterogeneous population as assessed by the ability of histamine to augment or inhibit cell migration. This may reflect differences in H1 to H2 receptor density or cell responsiveness to receptor stimulation. The chemoattractant activity of histamine itself is not influenced by H1 or H2 receptor antagonists, thus it is possible that an eosinophil has a third type of histamine receptor.

Bucladesine↗
PubMed1977

Myeloperoxidase--H2O2--halide system: cytotoxic effect on human blood leukocytes.

Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human blood leukocytes is demonstrated, employing 51Cr release and dye exclusion assays. Cytotoxicity is dependent on enzymatically active myeloperoxidase, H2O2, or a peroxide-generating enzyme system and either chloride or iodide. Cell damage is rapid, with maximal levels of 51Cr release occurring within 30--60 min. Approximately equal sensitivity to the peroxidase system is observed for polymorphonuclear leukocytes and mononuclear leukocytes. Since myeloperoxidase and H2O2 are released from polymorphonuclear leukocytes under certain conditions, such as during particle ingestion, it is suggested that peroxidase-mediated leukocyte injury may be an important feature of the inflammatory response.

Chlorides↗
PubMed1977

Iodination by human polymorphonuclear leukocytes: a re-evaluation.

The conversion of iodide to a trichloroacetic acid-precipitable form (iodination) by polymorphonuclear leukocytes (PMN's) has been re-evaluated as a measure of neutrophil function. Optimum conditions are described which result in an iodination value for normal cells during the phagocytosis of zymosan of 64.1 +/- 13.2 (S.D.) nmol. per 10(7) PMN's per hour. Iodination is inhibited by agents which decrease phagocytosis, inhibit myeloperoxidase-catalyzed reactions, or degrade H2O2 and is stimulated by superoxide dismutase, an enzyme which catalyzes the conversion of the superoxide anion to oxygen and H2O2. When patients' cells and normal serum are employed, the iodinating capacity of the patients' cells is evaluated. It is low in patients with myeloperoxidase deficiency and chronic granulomatous disease, and an intermediate value was observed in a carrier of chronic granulomatous disease. When normal cells and patients' serum are employed, the iodination reaction is an indirect measure of the opsonic activity of the patients' serum. The decreased opsonic activity for zymosan of human sera deficient in the fourth or third component of complement was demonstrated in this way. Thus measurement of iodination is a convenient and sensitive screening test for cellular or humoral abnormalities of the phagocytic process.

Humans↗
PubMed1976

Mediator release from basophil granulocytes in chronic myelogenous leukemia.

Mediator release from the leukocytes of two patients with chronic myelogenous leukemia and basophilia was studied using rabbit antihuman IgE antibody. The release of histamine, slow reacting substance of anaphylaxis (SRS-A), platelet activating factor (PAF), chemotactic activity for neutrophils and eosinophils, and an inhibitor of eosinophil migration was observed. However, the release of SRS-A from the basophils of one patient and the release of chemotactic activity from both patients displayed unusual properties. During acceleration of the disease process, the basophils of one patient released maximal SRS-A activity at progressively lower concentrations of anti-IgE. Both patients released a high molecular weight factor (M.W. greater than 20,000) which enhanced the migration of neutrophils and eosinophils and a low molecular weight chemotactic factor (M.W. less than 500) which selectively attracted eosinophils. A double peak of eosinophil chemotactic activity was routinely observed for the low molecular weight factor; this was shown to represent the eosinophil chemotactic activity of histamine with relative inhibition of migration at the histamine peak. There was little release of the tetrapeptides, ECF-A, in these patients which facilitated demonstration of this eosinophilotactic activity of histamine. These results suggest that the eosinophil chemotactic activity observed in acute allergic reactions is the net effect of the release of multiple chemotactic factors.

Antibodies↗
PubMed1976

Cytotoxicity for tumor cells of cationic proteins from human neutrophil granules.

Cationic proteins purified from human polymorphonuclear leukocyte granules exert a cytotoxic effect on mammalian tumor cells. This effect is time and concentration dependent, is inhibited by the anionic agent heparin, and is enhanced by preheating the cationic proteins. Other strongly basic proteins (histone, protamine) also exhibited cytotoxic activity. Myeloperoxidase isolated from human leukocytes is cytotoxic when combined with H2O2 and chloride. Under these conditions, the potency of the myeloperoxidase-mediated system is greater than that of the cationic proteins.

Animals↗
PubMed1976

Interactive effects of salinity and phosphorus nutrition of the concentrations of phosphate and phosphate esters in mature photosynthesizing corn leaves.

The effects of salinity on corn plants (Zea mays L.) are influenced by the concentration of nutrient orthophosphate. Salinity (-2 bars each of NaCl and CaCl(2)) was more injurious in combination with a high concentration of orthophosphate (2 mm) (that gave optimum yields in the absence of salinity) than it was with a lower concentration (0.1 mm). With 2 mm orthophosphate, salinity seemed to damage the plant mechanisms that normally regulate the internal concentration of orthophosphate resulting in excessive accumulation and P toxicity. On the other hand, with 0.1 mm orthophosphate, salinity decreased orthophosphate concentration in mature leaves. This effect was paralleled by decreases in the concentration of adenosine 5'-triphosphate and in the energy charge of the adenylate system, indicating an orthophosphate deficit. Even so, plants survived salinity better under these conditions than in the presence of 2 mm orthophosphate. The data indicated that salinity affected the phosphorylated state of the adenine nucleotides only indirectly through its effect on the concentration of orthophosphate in the cells.Salinity, especially in the presence of 2 mm orthophosphate, resulted in an increase in the concentrations of sugar phosphates in mature photosynthesizing leaves, suggesting that translocation rather than photosynthesis was a limiting process. Decreased translocation could be a secondary effect of decreased growth. However, a decreased translocation rate could cause decreased growth by limiting the supply of essential metabolites reaching growing tissues.

Journal Article↗
PubMed1976

Infective endocarditis: a survey of cases in the South-East region of Scotland, 1969-72.

The incidence and characteristics of infective endocarditis were studied in a defined community over a four-year period. Seventy-eight cases were found, giving an incidence of 16 cases permillion per year. The commonest presenting features were those of infection; 53% had cardiac failure and 37% evidence of emboli when first seen. Twenty-three cases occurred on rheumatic heart valves, 13 on valvular prostheses, and 19 in previously normal hearts. Streptococcus viridans was the commonest organism, but there was a relatively high incidence of staphylococcal infection. Only four cases were preceded by dental manipulation, and no source for the infection was found in 46 patients. The mortality rate was 46%, cardiac failure and embolic phenomena accounting for 65% of deaths. It is unlikely that earlier diagnosis or cardiac surgery would have reduced the mortality appreciably.

Adolescent↗
PubMed1976

Defective neutrophil chemotaxis in bone marrow transplant patients.

Infection is a frequent cause of death in patients receiving bone marrow transplants. Although lymphocyte dysfunction has been observed in a few such patients, no systematic study of neutrophil function has yet been reported. Neutrophil chemotaxis was evaluated by a 51Cr-radioassay after bone marrow transplantation in 34 patients with acute leukemia or aplastic anemia. The response to a chemotactic stimulus (C5a) was severely depressed (less than 35% of normal) in 18 patients, moderately depressed (35-65% of normal) in an additional 6, and normal in 10 subjects. The mean response in the absence of graft vs. host disease and antithymocyte globulin administration was 73.3+/-9.2% (SE) in contrast to 29.7+/-9.6% (P is less than 0.01) in patients with graft vs. host disease treated with antithymocyte golbulin. Both graft vs. host disease and antithymocyte globulin were implicated since the presence of either factor alone was associated with depressed chemotaxis (31.1+/-4.9% for graft vs. host disease, P is less than 0.01; 17.0+/-7.8% for antithymocyte globulin, P is less than 0.02). When normal neutrophils were incubated with antithymocyte globulin in vitro, their chemotactic response was markedly suppressed in the absence of a cytotoxic effect. Transplant patients with defective chemotaxis experienced significantly more infections than those with normal chemotaxis, and analysis of specific etiologic agents showed that this was predominantly related to bacterial pathogens. Chemotactic inhibitors were detected in the sera of seven patients and elevated IgE levels were found in nine subjects, eight of whom had graft vs. host disease. Generation of chemotactic activity by endotoxin activation of serum was reduced in five patients. The results demonstrate a severe defect in neutrophil chemotaxis in some bone marrow transplant patients and suggest that neutrophil dysfunction may predispose to infection in such patients.

Acute Disease↗
PubMed1976

Generation of a neutrophil chemotactic agent by spermatozoa: role of complement and regulation by seminal plasma factors.

The interactions of polymorphonuclear leukocytes, spermatozoa, seminal plasma, and serum have been examined in an in vitro leukocyte chemotaxis system. Bovine or human spermatozoa have no neutrophil chemotactic activity alone, but generate potent activity when incubated with serum. Generation of this activity requires magnesium, but not calcium ions and is blocked by pre-heating the serum. Chemotactic activity is generated normally in serum deficient in immunoglobulins or C4, but is not produced in serum deficient in C3. Thus, spermatozoa activate complement via the alternative pathway. The chemotactically active agent has been identified as the low m.w. C5 cleavage product (C5a) on the basis of heat stability, gel filtration characteristics, and specific inhibition by anti-serum to C5. The spermatozoal constituents responsible for complement activation are largely heat stable, resistant to diisopropyfluorophosphate and on gel filtration compise a heterogeneous group of large m.w. materials. Bovine seminal plasma has no neutrophil chemotactic activity alone; considerable activity, however, is generated by incubating low, but not high concentrations of seminal plasma with serum. The chemotactic agent produced in serum is C5a. Bovine seminal plasma also contains potent heat labile inhibitors of chemotaxis. Two distinct inhibitors differing in m.w. (50 to 100,000 and 15,000) and heat stability have been isolated. The inhibitors appear to act directly on the neutrophil rather than on the chemotactic factor. Human seminal plasma exhibits slight chemotactic activity alone but does not generate significant additional activity on incubation with serum. In contrast to the inhibitory activity of bovine seminal plasma, the human material contains heat-stable, nondialyzable factors which enhance the neutrophil chemotactic response. These studies document a specific mechanism for the directed migration of polymorphonuclear leukocytes toward spermatozoa. The findings may provide an explanation for the observed in vivo leukocyte accumulation in the female genital tract in association with spermatozoa and seminal plasma. The biologic significance of this phenomenon relates to potential leukocyte-spermatozoa interaction which may influence the likelihood of fertilization.

Animals↗
PubMed1975

The selective eosinophil chemotactic activity of histamine.

Histamine diphosphate was shown to selectively attract human eosinophils from mixed granulocyte populations when over 20% eosinophils were used in a modified Boyden chamber chemotactic assay system. This effect of histamine is abolished by incubation with diamine oxidase (histaminase) and was generated by decarboxylation of L-histidine. A linear dose dependent increase in eosinophil migration was observed between 3 X 10(-7) M and 1.25 X 10(-6) M, while higher concentrations of histamine inhibited the migration of eosinophils. The attractant activity of histamine was not inhibited by H-1 or H-2 receptor antagonists, however, the inhibition of migration observed at higher histamine concentrations was reversed by metiamine, an H-2 receptor antagonist. The effects of histamine upon eosinophil migration were demonstrable using three different assays: (a) counting cells that had traversed 5-mum pore, 12-mum thick polycarbonate filters, (b) counting cells that had migrated various distances into a 3-mum pore, 145-mum cellulose nitrate filters, or (c) measuring the number of cells that had traversed an upper polycarbonate filter and migrated into a lower cellulose nitrate filter using 15Cr-labeled cells. The ability of histamine to enhance eosinophil migration was shown to be dependent upon the presence of a concentration gradient; histamine did not cause a dose-dependent increase in random motility. Furthermore, preincubation of the eosinophils with histamine deactivate the cells to further stimulation by histamine or by C5a. It is concluded that in low doses histamine is a chemoattractant for human eosinophils, while in higher doses histamine inhibits eosinophil migration. These observations may relate to the influx and localization of eosinophils in immediate hypersensitivity reactions.

Amine Oxidase (Copper-Containing)↗