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Biomedical subjects

R M Cook

Publications and source records attributed to R M Cook.

At least 37 records · Page 2Linked to original sources

Effects of dexamethasone in a model of lung hyperresponsiveness in the rat.

In rats, Sephadex treatment on days 0, 2 and either 4 or 5 resulted in a blood and lung eosinophilia, an increase in lung cell fragility, an increase in the functional activity of peritoneal eosinophils in vitro and a sustained increased responsiveness of lung parenchymal strips to KCl, 5-hydroxytryptamine (5-HT) and carbachol that was not associated with oedema or gross fibrosis. The corticosteroid dexamethasone, when given before each injection of Sephadex, reduced all these effects of Sephadex. When given 30 min after the last injection of Sephadex, dexamethasone had no effect on the number of blood and lung eosinophils but it did reduce the functional activity of peritoneal eosinophils, the increased lung cell fragility and the hyperresponsiveness to 5-HT. Repeated administration of dexamethasone to rats with an established hyperresponsiveness that was no longer associated with cellular inflammation had minimal effects on this hyperresponsiveness.

Animals↗

The effects of dietary protein on age and weight at the onset of puberty in Brown Swiss and Zebu heifers in the tropics.

The effects of dietary protein level on age and weight at onset of puberty were studied in the Mexican tropics using 12 Brown Swiss and 12 Zebu heifer calves in a completely randomized block design. The calves were weaned at 3 mo of age. They were confined in individual pens and fed either an adequate protein (12.8%) or a high protein (16.4%) diet ad libitum through the onset of puberty, which was defined as the first ovulation. To detect the first ovulation, heifers were palpated at 8 mo of age and then every 2 wk. At the detection of a developing follicle or any behavioral sign of estrus, they were palpated daily. Ovulation was confirmed by palpation of a corpus luteum. A blood sample for the determination of plasma progesterone concentration was taken with each palpation. There was a significant effect of breed on age at the onset of puberty, which was 9.4 and 12.3 mo for the Brown Swiss and Zebu heifers, respectively. Weight at puberty was 233 kg, independent of breed. Dietary protein had no effect on the onset of puberty. Brown Swiss heifers reach puberty earlier than Zebu heifers. Heifers in the tropics fed according to NRC recommendations reach puberty at ages comparable to those in temperate climate. This suggests that, if managed properly, calving age for Brown Swiss and Zebu heifers can be 24 and 27 mo, respectively. This is a considerable improvement from 36 to 48 mo of age now common in the area of study.

Journal Article↗

Primary angiosarcoma of the oral cavity.

Primary malignant vascular tumours of the oropharynx are rare. This report is of a 69-year-old Vietnamese female with a malignant vascular lesion involving the floor of the mouth and the pharynx.

Aged↗

Effects of isoacids, urea, and sulfur on ruminal fermentation in sheep fed high fiber diets.

The effects of isoacids, urea N, and S on ruminal fermentation of sugarcane bagasse- or corn stover-based diets were studied in sheep. Acetate production was taken as a measure of the fermentation rate. For the sugarcane bagasse diet, neither urea nor S supplementation changed ruminal acetate production. When N and S were combined, acetate production was 44% higher (3.16 vs. 2.18 mol/d). Similar effects were noted for the corn stover diet. Increasing the level of isoacids from .1 to .2 g/kg BW per d in the diet did not change acetate production for either diet. However, N supplementation of the sugarcane bagasse diet containing the low level of isoacids resulted in a 49% greater acetate production (2.86 vs. 1.91 mol/d). Acetate production was 90% higher (3.74 vs. 1.97 mol/d) when the diet containing the high level of isoacids was supplemented with N. The corresponding increases for corn stover were 12% (2.64 to 2.95 mol/d) and 35% (2.88 to 3.87 mol/d). The results suggest that NH3 N provided by the basal diet was more limiting than isoacids. Once the N deficiency was corrected, isoacids became limiting. Ruminal digestion of high fiber diets low in N was improved by supplementation with urea, isoacids, and S.

Acetates↗

Eosinophil accumulation in rats injected with Sephadex particles.

Intravenous injection of Sephadex G200 particles into rats on days 0, 2 and 5 caused an increase in eosinophil numbers in blood and lung tissues. Peak numbers were obtained on days 3-12 and thereafter declined to approach control values by day 21. The rise in eosinophil numbers was paralleled by an increase in lung cell fragility as measured by a transient reduction in the number of viable cells isolated from parenchymatous tissue following the digestion of lung fragments in vitro. This decrease in lung cell viability was not seen in rats given a single injection of Sephadex. Dexamethasone, dapsone and isoprenaline given before each injection of Sephadex reduced lung and blood eosinophil numbers and prevented lung cell death. Aspirin and indomethacin were without effect. Incubation of normal lung tissues with disrupted peritoneal eosinophils reduced the numbers of viable cells recovered. No such effects were seen using intact eosinophils and disrupted or intact neutrophils and mononuclear cells. This system provides a model of lung cell damage associated with eosinophil infiltration in vivo.

Animals↗

Factor XI deficiency disclosed following haemorrhage related to a dental extraction. Brief review and case report.

Factor XI deficiency is a relatively common hereditary coagulation disorder manifested generally as diffuse oozing from a surgical site. Dentists may be the first to discover this deficiency and other coagulopathies after simple tooth extraction. A case is reported which illustrates a typical presentation of this disorder. The need for haematological examination and special dental care is discussed.

Factor XI Deficiency↗

Dose response of dairy cows to ammonium salts of volatile fatty acids.

In previous studies ammonium salts of a mixture of isobutyrate, 2-methylbutyrate, isovalerate, and valerate were fed in a corn silage, corn, corn gluten meal, and urea diet to Holstein cows throughout lactation to define the optimum level of ammonium salts of milk production. The objective of this work was to conduct another dose response study using other forage and protein sources and to determine the effects of decreasing VFA intakes as lactation advanced. The concentrate portion of the diet contained 0, .4, .8, 1.2, or 1.6% ammonium salts of VFA. The forage to concentrate ratio was 50:50, 60:40, and 70:30 for the first, middle, and last third of lactation, respectively. The study was conducted at four university locations using 191 Holstein cows. Feeds used included corn silage, alfalfa silage or hay, corn, soybean meal, minerals, and vitamins. Treatment x location interactions were significant for milk yield during early lactation. During mid- and late lactation, supplemental VFA (.8%) improved milk and protein yield. Milk composition was not greatly affected by feeding VFA. In mid-lactation, cows fed .8% ammonium salts of VFA ate more feed than did controls. Feed efficiencies were similar among groups throughout the experiment. Cows fed VFA tended to gain less BW during lactation than did controls. Health and reproduction were not different among groups.

Animal Feed↗

Eosinophils and the granulomatous reaction in rats injected with Sephadex particles.

Treatment of rats with a single intravenous injection of 0.5 mg Sephadex G200 caused a blood and lung eosinophilia first detected on day 2, peaking on day 7 and declining to control levels by days 28 and 84 respectively. The increase in eosinophil numbers was accompanied by the development of pulmonary granulomas reaching their maximum size 2-7 days after Sephadex treatment and persisting for 84 days. This reaction was characterised by an early infiltration with polymorphonuclear leucocytes followed by increased numbers of mononuclear cells. Few eosinophils were associated with the Sephadex particles but large numbers were found in the adventitial layers of the lung. There was an increase in the size of the granulomas in rats given Sephadex on days 0, 2 and 5 compared with the response in rats given a single injection of Sephadex. The inflammation was more intense and more eosinophils were detected in the blood, alveolar tissues and adventitia. The effects of drugs given before each injection of Sephadex were evaluated. Dexamethasone, dapsone and isoprenaline reduced the blood and tissue eosinophilia but had no effect on the number of granulomas. Dexamethasone and dapsone, but not isoprenaline caused a slight reduction in the size of the inflammatory reaction around the Sephadex particles. Indomethacin had no effect on the granuloma formation, nor did it reduce the eosinophilia. Isoprenaline and indomethacin increased the proportion of eosinophils associated with the granuloma, although in neither instance did this reach significance.

Animals↗

Effect of the combination of monensin and isoacids on rumen fermentation in vitro.

Effects of isoacids, monensin, or a combination of them on fermentation by mixed rumen bacteria were investigated using a continuous culture technique. The culture was allowed to stabilize for 4 d before treatments were imposed. Comparisons between treatments were made on d 11 and 12 of the culture. Isoacids (equal proportions of isobutyric, 2-M-butyric, isovaleric, and valeric acids) at 15 mg/dl of culture media increased acetate (6.17 vs. 5.48 meq/dl) and total VFA production (8.93 vs. 7.87 meq/dl) compared with that of controls. Monensin at 150 micrograms/dl reduced acetate (3.74 vs. 6.02 meq/dl) and VFA (6.84 vs. 8.54 meq/dl) but increased propionate (2.28 vs. 1.74 meq/dl) relative to control. The combination of isoacids and monensin increased acetate relative to monensin alone (5.24 vs. 3.74 meq/dl) but did not alter the effect of monensin on propionate concentration (2.32 vs. 2.28 meq/dl). It is concluded that monensin decreases acetate production by 35% and when isoacids are added to the cultures containing monensin, acetate production is restored.

Animals↗

The preparation and application of functionalised synthetic oligonucleotides: III. Use of H-phosphonate derivatives of protected amino-hexanol and mercapto-propanol or -hexanol.

Syntheses of H-phosphonate salts (4a-e) of N/S-protected alcohols such as 6-aminohexan-1-ol, 3-mercaptopropan-1-ol and 6-mercaptohexan-1-ol are described using 2-chloro-5,6-benzo-1,3,2-phosphorin-4-one (2) as the phosphonylating agent. The H-phosphonate salts (4a-e), in the presence of pivaloyl chloride or adamantoyl chloride as an activator, were coupled to the 5'-end of synthetic oligonucleotides on solid supports to produce amino or thio-linked oligonucleotides. Following deprotection and purification, fluorescent dyes, biotin derivatives and poly-L-lysine-maleimide were separately attached to the functionalised oligonucleotides. Identical derivatized oligomers were obtained with cyanoethyl-N,N-diisopropylamidite chemistry and amidites (5a-e) of the respective alcohols.

1-Propanol↗

Immunological properties of chemically produced fragments of rye grass pollen extract.

Two fragment pools, one of MW greater than 10,000 and the other of MW between 1,000 and 10,000, were prepared by the sequential treatment of rye grass pollen extract with cyanogen bromide (cleavage at Met-X) and 2-nitro-5-thiocyanobenzoic acid (cleavage at X-Cys). Electrophoretic analysis of the two pools showed that none of the major components of the whole extract remained intact. Characterisation of the two fragment pools by radioimmunoassay showed that whilst they both lost the ability to bind to human anti-rye IgE antibodies, they largely retained their reactivity towards both human and mouse anti-rye IgG antibodies. In addition, the higher molecular weight pool retained its ability to stimulate extract-specific T cells, after accessory cell processing. This separation of the immunological properties of rye grass pollen extract by chemical cleavage is seen as a basis for the development of novel immunotherapy agents.

Animals↗

Cytotoxic activity of rat granulocytes against Mesocestoides corti.

Rat eosinophils or neutrophils were purified from peritoneal washings which had been enriched either for eosinophils by infection with the parasite Mesocestoides corti or by intravenous injection with Sephadex G200 particles, or for neutrophils by the intraperitoneal injection of glycogen. Neither eosinophils nor neutrophils attached to or damaged live M. corti parasites in vitro although they did lyse chick erythrocytes in the presence of rat anti-chick red blood cell antibody, with the neutrophils showing the highest level of cytotoxicity and the eosinophils from the infected rats the lowest. Neutrophils gave a specific antibody-dependent cytotoxic response to chick erythrocytes coated with solubilized M. corti extract, a response not seen with eosinophils. The cytotoxicity shown by neutrophils could not be blocked by adding eosinophils or sera obtained from chronically infected rats although it was reduced by incubating the neutrophils with cell-free supernatants obtained from the spleen cells of infected rats following stimulation with solubilized parasite extract in vitro. Eosinophils from infected rats expressed fewer membrane Fc receptors for antibody than did neutrophils or eosinophils from uninfected animals. Incubation of neutrophils and eosinophils from uninfected rats with the immune spleen cell supernatants reduced Fc receptor expression to levels similar to those seen with eosinophils from infected animals. These same supernatants had no effect on the expression of granulocyte complement receptors. It is suggested that infection of rats with M. corti can lead to the production of an antigen-specific suppression capable of impairing the antibody-dependent activity of granulocytes in vitro.

Animals↗

Induction of allergen-specific T cells by conjugates of N-formyl-methionyl-leucyl-phenylalanine and rye grass pollen extract.

A conjugate of the biologically active peptide N-formyl-methionyl-leucyl-phenylalanine and rye grass pollen extract (F-MLP/rye), previously shown to react with rye grass pollen extract-specific T cells, induced the formation of allergen-specific T cells in mice. Lymph node cells prepared from mice immunized with either native extract or F-MLP/rye gave an enhanced response to unmodified rye grass pollen allergens in vitro. Syngeneic spleen macrophages were able to present the unmodified allergens to T cells obtained from both groups of mice causing their proliferation in vitro. Conjugation of the peptide into the extract brought about an extensive reduction in its reactivity with grass pollen-specific human IgE, and a loss of its ability to induce specific IgG antibody in guinea-pigs. A state of delayed hypersensitivity specific for rye grass pollen extract was produced in guinea-pigs by immunization with either the F-MLP/rye or unmodified extract. It is concluded that conjugates such as F-MLP/rye or other T' allergoids could be used as probes to investigate whether changes in T cell activity are important in immunotherapy.

Allergens↗

Effect of chemotactic agents on rat and guinea pig eosinophil cytotoxicity in vitro.

Purified guinea pig and rat peritoneal eosinophils were examined for their ability to mediate an antibody-dependent cell cytotoxic reaction against 51Cr-labelled chick red blood cells in the presence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), leukotriene B4, eosinophil chemotactic factor of anaphylaxis, or histamine. Guinea pig eosinophils were induced either by repeated intraperitoneal injections of polymyxin B sulphate or by a single intraperitoneal injection of saline. Using subagglutinating concentrations of antibody, the antibody-dependent cell cytotoxic response was significantly enhanced with FMLP, leukotriene B4, and eosinophil chemotactic factor of anaphylaxis. Histamine was without effect. Rat eosinophils were induced either by three intravenous injections of Sephadex G-200 followed by saline intraperitoneally, by a single intraperitoneal injection of saline, or by infection with the parasite Mesocestoides corti. None of the materials examined was able to enhance the cytotoxic activity of the rat eosinophil preparations over the range tested, in the presence of subagglutinating concentrations of antibody. The antibody-dependent cell cytotoxic response of eosinophils from infected animals was significantly reduced compared with those from Sephadex/saline-treated rats. Incubation of eosinophils obtained from infected animals with FMLP in the presence of agglutinating concentrations of antibody restored eosinophil cytotoxicity. None of the other materials was active. It is concluded that the ability of rat and guinea pig eosinophils to be activated in vitro is partly species related and partly due to the method of cell induction. Differences between the two species may be important when establishing animal models of eosinophil function.

Animals↗

Relationship between neutrophil infiltration and tissue eosinophilia in the rat.

Infection of rats with the parasite Mesocestoides corti increased the numbers of neutrophils, eosinophils and mononuclear cells in the blood. These peaked 11 days after infection and had declined to control levels by day 24. Increased number of eosinophils and mononuclear cells were also present in the peritoneal cavities of rats 24 days after infection. These gradually declined to reach control values by day 81. Intraperitoneal administration of glycogen to uninfected rats and to rats that had been infected for 24 and 81 days caused a transient increase in blood neutrophil numbers, maximal at 4 h. Although glycogen increased the numbers of neutrophils in the peritoneal cavities of uninfected animals and animals infected for 81 days, it did not increase the number of peritoneal neutrophils in rats that had been infected 24 days earlier. These results suggest that neutrophil infiltration can be impaired in animals undergoing an inflammatory response characterized by increased numbers of eosinophils.

Animals↗