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Biomedical subjects

J H Harrison

Publications and source records attributed to J H Harrison.

At least 19 recordsLinked to original sources
PubMed1991

Effect of somidobove sustained release administration on the lactation performance of dairy cows.

Lactation performance was determined on 190 multiparous Holsteins from five herds supplemented with 0, 320, 640, or 960 mg of somidobove every 28 d. The experiment consisted of 21 d of pretreatment and treatment periods of various lengths, depending upon stage of lactation of animals at first administration. Somidobove beginning in early (28 to 45 d in milk), mid (111 to 166 d in milk), or late (166 to 334 d in milk) stages of lactation consisted of 9, 6, or 3 administrations. Milk and 3.5% FCM yields were increased by each dose of somidobove in all stages. Milk composition and dry matter and energy intakes were similar among treatments within stage. Milk to DMI ratio and milk energy to net energy intake ratio were improved by somidobove. Gain was positive for all treatments, but less in somidobove-supplemented cows. Lower body weight and condition score at the completion of somidobove treatment resulted. For early cows, days to first estrus and days to first breeding were similar; however, total number of inseminations for cows receiving somidobove was twofold greater than control, resulting in a longer calving interval. Results demonstrated efficacy of somidobove administered every 28 d to lactating dairy cattle for increased milk yield.

Animals↗
PubMed1990

The use of rapeseed screenings in diets for lactating cows and subsequent effects on milk yield and composition.

This trial was to determine the effect of dietary rapeseed screenings on milk production, milk composition, and feed intake of lactating dairy cows. Pelleted rapeseed screenings were fed at 0, 7, and 14% of diet DM. Assignment of 36 multiparous Holstein cows was based upon parity and previous lactation performance. The experimental period was from parturition through wk 16 of lactation. The control ration had 3.1% ether extract, whereas the ration with 14% rapeseed screenings had 5.4% ether extract. The rapeseed screenings contained 52.2% of C18:1 and 24.2% of C18:2 as percentage of total fatty acids. There were no significant effects of dietary treatment on milk yield or feed intake. There were significant increases in milk fatty acids C18:1 and C18:2 for cows consuming the diets with rapeseed screenings. Treatment did not significantly affect milk protein percentage as measured by Kjeldahl N or by the infrared method. Increased unsaturated fatty acids in the milk of cows fed rapeseed screenings had no apparent effect on infrared fat analysis. There was no interaction of treatment and milk fat analysis method (infrared versus Babcock). Dietary treatment did not affect blood serum nonesterified fatty acid concentrations over the 16-wk period. In conclusion, rapeseed screenings, fed at levels up to 14% of the diet, did not affect milk yield, milk protein, or milk fat percentage but did change milk fatty acid composition.

Amino Acids↗
PubMed1989

Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone.

Dapsone, a sulfone compound used in the treatment of leprosy and, more recently, Pneumocystis carinii pneumonia, produces as a major side effect a hemolytic anemia. This anemia is characterized by oxidation of hemoglobin to methemoglobin and increased splenic uptake of red blood cells. Using a rat model, Grossman and Jollow (J. Pharmacol. Exp. Ther. 244: 118-125, 1988) found that dapsone hydroxylamine (DDS-NOH), a dapsone metabolite, is responsible for its hemolytic effect in vivo. DDS-NOH also promotes hemoglobin binding to SH groups on rat red cell membrane proteins (Budinsky et al., FASEB J. 2: A801, 1988). Since the binding of hemoglobin and other reagents (e.g., N-ethylmaleimide) to membrane SH groups has been associated with increased K transport in red blood cells, we examined the effect of DDS-NOH on K efflux from rat red blood cells in vitro. Cells shrink when exposed to DDS-NOH (100 microM) in media with plasma-like ionic composition. This shrinkage is prevented if extracellular K is raised to 110 mM or if intra- and extracellular Cl are replaced by methylsulfate (MeSO4), suggesting involvement of a K-Cl cotransport pathway. Indeed, 100 microM DDS-NOH produces a 4- to 5-fold increase in K efflux in cells containing Cl but less than a 2-fold increase in cells containing MeSO4. This stimulatory effect is specific for K; Na efflux is slightly inhibited by 100 microM DDS-NOH. The concentrations of DDS-NOH required for half-maximal stimulation of Cl-dependent K efflux (53 microM) is similar to its half-maximal hemolytic concentration in rats (approximately 100 microM). Furthermore, the stimulation of Cl-dependent K efflux by DDS-NOH is greater than 80% reversed by subsequent treatment of the cells with dithiothreitol, suggesting involvement of SH groups. Our results indicate that DDS-NOH exposure stimulates an apparent K-Cl cotransport in rat red blood cells, resulting in cell shrinkage under physiological ionic conditions. Since shrinkage of red blood cells renders them less deformable (Mohandas et al., J. Clin. Invest. 66: 563-573, 1980), this suggests a pathophysiological mechanism whereby DDS-NOH exposure in vivo could promote increased splenic uptake of red blood cells and hemolytic anemia.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

Effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility of grass-legume forage.

Grass-legume forage was used to evaluate the effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility during 57 d of ensiling. Chopped forage (DM = 28%) was ensiled in 4 to 6-kg quantities and treated as: 1) control, 10(3) epiphytic lactic acid bacteria; 2) 10(5) added lactic acid bacteria; and 3) 10(6) added lactic bacteria/g of wet forage. Samples were obtained for analyses on d 0, 1, 2, 3, 6, 10, 14, 29, and 57 of fermentation. Treated silages were observed to have: 1) greater quantities of lactic acid bacteria, 2) a greater proportion of homofermentative lactic acid bacteria, and 3) lactic acid bacteria with greater biological activity. Addition of each amount of lactic acid bacteria: 1) increased the rate of utilization of water-soluble carbohydrate and decline in pH, 2) limited the formation of NH3 N, and 3) increased the in vitro digestibility of DM and ADF. No differences were observed in the lactic acid content of the silages after 57 d of fermentation.

Ammonia↗
PubMed1989

Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice.

The severity of bleomycin (BLM)-induced pulmonary fibrosis in mice varies markedly among several different murine strains. We have examined the DNA from lungs of sensitive (i.e., C57BL/6N) and resistant (i.e., BALB/c) strains of mice using a nucleoid sedimentation technique to detect early in vivo changes in the integrity of DNA after intravenous BLM. Mice received intravenous injections of BLM (80 mg/kg) or vehicle; lung nucleoids were prepared 15 min to 6 hr later. BLM produced striking decreases in nucleoid sedimentation distance versus paired controls in both strains within 15 min after injection, indicating extensive DNA scission. Repair of DNA strand breaks was complete in the resistant (BALB/c) mice by 5 hr; in contrast, only partial repair occurred in the sensitive (C57BL/6N) strain during that time. We then examined lungs for subsequent changes in steady state poly-(A)+ RNA levels and mRNA levels for lung matrix proteins (type I procollagen, type III procollagen, and fibronectin). Steady state levels of poly-(A)+ RNA were depressed to 50% of control 1 through 6 days after BLM injection in the lungs of sensitive mice. Resistant mice had pulmonary poly-(A)+ RNA levels similar to those of C57BL/6N mice, except for a 2-fold elevation 1 day after BLM injection. BLM injection affected the steady state levels of mRNA encoding lung matrix proteins differently than total poly-(A)+ RNA. Fibronectin mRNA/poly(A)+ RNA was elevated 2-fold 1 day after BLM treatment only in the sensitive strain and remained elevated at 3 and 6 days. In contrast, alpha 2I procollagen mRNA increased in both murine strains and alpha 1III procollagen mRNA decreased in both strains. Thus, a 7-fold or greater increase in the type I: type III procollagen mRNA ratio was seen in both strains 3 to 6 days after BLM injection. These data demonstrate that BLM treatment rapidly produces extensive pulmonary DNA damage in vivo, that persistence of DNA damage rather than the initial level of strand scission is associated with sensitivity to BLM lung disease in these mice, and that changes in the levels of mRNA encoding pulmonary matrix proteins occur in vivo within 1 to 3 days after intravenous BLM treatment.

Animals↗
PubMed1988

The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein.

Previous studies from several laboratories have shown that thrombin is inactivated by tetranitromethane with the formation of nitrotyrosine. The inactivation is characterized by an apparently greater loss of fibrinogen-clotting activity than activity toward synthetic ester substrates, suggesting that the residues modified by tetranitromethane are involved in the interaction of thrombin with fibrinogen. This study was designed 1) to determine the effect of solvent conditions on the rate of modification and the stoichiometry of the reaction of tetranitromethane with bovine alpha-thrombin; 2) to identify the residue(s) modified; and 3) to characterize the modified enzyme with respect to its interaction with peptide nitroanilide substrates and fibrinogen. The inactivation of thrombin by tetranitromethane proceeded more rapidly in 50 mM Tris, pH 8.0, than in 50 mM sodium phosphate, 100 mM NaCl, pH 8.0. Approximately 10% fibrinogen-clotting activity remained at maximal inactivation. A study of the effect of tetranitromethane concentration on the rate of inactivation suggested that the loss of activity was the result of the modification of 1 mol of tyrosine/mol of thrombin. A similar result was obtained from the analysis of the extent of inactivation as a function of the extent of protein modification. Structural analysis of the modified protein showed substantial modification at both Tyr71 and Tyr85. Enzyme kinetic studies were performed with the modified protein and a control thrombin with N2-tosylglycylprolylarginine p-nitroanilide. H-D-phenylalanylpipecolylarginine p-nitronailide, and purified bovine fibrinogen. With all three substrates, a substantial decrease in kcat was observed, whereas there was essentially no change in Km. These results suggest that, contrary to previous suggestions, the modification of Tyr71 and Tyr85 in thrombin does not influence the binding of substrates, but rather influences active site reactivity.

Animals↗
PubMed1988

In vivo digestibility of corn and sunflower intercropped as a silage crop.

Six nonlactating Holstein cows in a 3 x 3 Latin square total collection digestion trial were used to evaluate three low DM (less than 26%) silage types: 1) corn; 2) corn and sunflower intercropped and 3) sunflower. Feeding periods consisted of a 7-d adjustment followed by a 5-d collection period. Dry matter intake was similar for the three treatments; 12.5, 12.1, and 12.0 kg, respectively. Percent apparent digestibilities for DM, NDF, and N for corn and corn-sunflower were similar and greater than for sunflower: DM (69.6, 68.2, 57.4); NDF (68.1, 61.5, 51.6); and N (66.3, 66.5, 63.6). No differences were observed for digestibilities of ADF, hemicellulose, starch, or for N retention. Percent ether extract digestibility was greatest for corn-sunflower and sunflower silage when compared with digestibility of corn silage (82.5, 77.9, vs. 66.3). Major changes in rumen fermentation patterns were not observed as evidenced by rumen molar proportions of propionate, isobutyrate, isovalerate, valerate, or acetate to propionate ratios. No difference was observed for rumen NH3 N (2.7, 3.2, 4.1 mg/dl, respectively). Corn and sunflower intercropped silage had intermediate concentrations of fat, fiber, and protein when compared with those of corn or sunflower silages.

Animal Feed↗
PubMed1988

Plasma and pulmonary pharmacokinetics of bleomycin in murine strains that are sensitive and resistant to bleomycin-induced pulmonary fibrosis.

Previous studies have shown that C57Bl/6N mice are sensitive and BALB/c mice are resistant to the pulmonary fibrotic effects of bleomycin (BLM). We assessed the plasma elimination and pulmonary content of BLM in C57Bl/6N and BALB/c mice treated with a single dose of [3H]BLM (80 mg/kg i.v.) to determine whether these murine strains show corresponding differences in BLM pharmacokinetics and pulmonary disposition after systemic administration of the drug. Serial blood samples were obtained from each animal and lungs were collected after pulmonary lavage or vascular perfusion with saline. Administration of BLM (80 mg/kg i.v.) produced significant elevations in lung hydroxyproline (35%) in C57Bl/6N but not in BALB/c mice. In contrast, BALB/c mice were more sensitive to pulmonary fibrosis induced with cyclophosphamide (200 mg/kg i.p.) compared to C57Bl/6N mice, indicating that strain sensitivity to pulmonary fibrosis is drug specific in these mice. BLM showed first order plasma elimination kinetics over 30 min in both strains with a shorter half-life in the sensitive strain (9.6 +/- 0.3 min in C57Bl/6N vs. 12.7 +/- 1.9 min in BALB/c). Plasma elimination deviated from first order kinetics after 30 min in both strains and plasma levels of BLM were up to 2-fold higher in the resistant strain over a 3-hr time course. Radioactivity in saline-perfused lungs was also significantly higher (1.5-2-fold) in BALB/c mice for least 1 hr after BLM injection. A similar fraction of the total lung radioactivity (approximately 80%) was recovered from both strains by pulmonary lavage, suggesting that BLM enters the alveolar spaces relatively freely in each strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Dietary fiber and early weaning on growth and rumen development of calves.

Holstein calves were assigned to treatments of 1) pelleted prestarter (22% protein and 12% fat) and starter containing 10% alfalfa; 2) prestarter and starter containing 20% alfalfa; 3) no prestarter and starter containing 10% alfalfa; and 4) no prestarter and starter containing 20% alfalfa. Calves assigned to treatments 1 and 2 were fed 3.64 kg milk/d for 2 wk and calves assigned to treatments 3 and 4 were fed 3.64 kg milk/d for 3 wk and 1.82 kg milk/d for wk 4. Calves on treatments 2 and 3 were heavier at 10 wk but body weights and heights were similar by 6 mo. Rumen fluid and plasma measures were similar among treatments. Bull calves were assigned to treatments 1 and 3 and necropsied at 3 or 6 wk. Dry feed intakes to 3 wk and volatile fatty acid concentrations were greater for calves on treatment 1 than those on treatment 3. Wet weights of the empty reticulorumens were greater for calves on treatment 1 than those on treatment 3. Papillary development was not affected by weaning system. Calves weaned at 17 d and fed a prestarter have earlier rumen development than calves fed no prestarter and weaned later.

Animals↗
PubMed1987

High dose continuous infusion of bleomycin in mice: a new model for drug-induced pulmonary fibrosis.

Bleomycin (BLM) produces pulmonary fibrosis in mice when given as a single intratracheal injection, a single i.v. injection or multiple s.c. injections. All of these models are associated with significant disadvantages including a variable distribution of lesions, high mortality or a requirement for multiple procedures. We have developed a convenient method of BLM treatment that avoids these difficulties and yields extensive, reproducible pulmonary fibrosis in mice. Osmotic minipumps containing BLM (100 mg/kg) were implanted s.c. in C57Bl/6 mice and the drug was delivered as a continuous s.c. infusion over 1 week. No mortality occurred over the first 5 weeks after pump placement whereas i.v. BLM (80 mg/kg) produced 50% mortality within 2 weeks. BLM given by pump infusion produced a greater increase (P less than .05) in lung hydroxyproline after 6 weeks (70%) than a similar total dose given as multiple s.c. injections (40%). Lungs from pump-treated mice showed confluent subpleural fibrosis involving almost 50% of the pleural surface and evidence of subpleural alveolar collapse. Mice receiving i.v. or s.c. injections showed involvement of only 10 to 15% of the pleural surface. BALB/c mice were resistant to pulmonary fibrosis after pump implantation, indicating a murine strain difference in pulmonary responsiveness to BLM administered by constant infusion. This superior model for drug-induced pulmonary fibrosis uses a single procedure and provides an extensive, reproducible lung lesion. Additionally, our studies suggest that dysfunction of the pulmonary epithelium may play an important role in progressive pulmonary disease after BLM treatment.

Animals↗
PubMed1987

Contribution of aniline metabolites to aniline-induced methemoglobinemia.

Methemoglobinemia after aniline and certain aniline derivatives is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compounds. However, three aniline metabolites--phenylhydroxylamine, 2-aminophenol, and 4-aminophenol--catalyze methemoglobin formation in erythrocyte suspensions and, hence, could contribute to methemoglobin formation in vivo after aniline. To determine the relative contributions of these aniline metabolites to aniline-induced methemoglobinemia in rats, we determined time courses of methemoglobinemia in rat erythrocyte suspensions and in rats after treatment with 2- and 4-aminophenol, phenylhydroxylamine, and aniline. The relative potencies for methemoglobin production in vitro after phenylhydroxylamine, 2-aminophenol, and 4-aminophenol were about 10:5:1, based on both peak and area of the methemoglobin versus time curve. Approximate minimum concentrations for observable methemoglobin formation in vitro from these compounds were 20, 50, and 200 microM, respectively. Compared with the in vitro data, the relative potencies of the aminophenols for methemoglobinemia in rats after intraperitoneal injections were reduced with respect to phenylhydroxylamine (to 100:4:1, respectively), apparently as a result of rapid in vivo clearance of the aminophenols. Subsequent experiments, in which the time courses of the aniline metabolites were determined in blood after toxic doses of aniline, demonstrated that only phenylhydroxylamine (measured as phenylhydroxylamine + nitrosobenzene) accumulated to blood levels exceeding the minimum concentration required for methemoglobin production in vitro. In addition, blood levels of phenylhydroxylamine remained in the toxic range throughout most of the methemoglobinemic response after aniline treatment. These data are consistent with phenylhydroxylamine being the sole mediator of aniline-induced methemoglobinemia in these rats.

Aminophenols↗
PubMed1986

Subunit equilibria of porcine heart citrate synthase. Effects of enzyme concentration, pH, and substrates.

Porcine heart citrate synthase, a dimeric protein of Mr = 100,000 composed of two identical subunits, is shown to undergo a monomer-dimer equilibrium. The extent of dimerization is found to be dependent on the concentration of citrate synthase, pH, ionic strength, and the specific buffer system employed. Oxaloacetate and citrate, substrates for the forward and reverse reaction catalyzed by citrate synthase, affect dimerization at concentrations of the protein which exists as monomer in their absence. The dissociation of citrate synthase dimers has been demonstrated utilizing the techniques of gel permeation chromatography, fluorescence polarization, fluorescence energy transfer, and heat denaturation. Earlier studies of citrate synthase quarternary structure found the protein to be nondissociable except under denaturing conditions or extensive modification; however, most former studies were performed at relatively high protein concentration, ionic strength, and pH, conditions which stabilize the dimer. In light of recent evidence derived from x-ray crystallographic studies showing amino acid residues from one subunit contributing to the citrate and CoA binding sites of the other, the dissociation into monomers would be expected to have profound effects on citrate synthase activity and regulation, as well as overall tricarboxylic acid cycle activity.

Animals↗
PubMed1986

Effect of prepartum selenium treatment on uterine involution in the dairy cow.

Selenium injections and oral vitamin E supplementation prepartum were related to: postpartum uterine involution (decrease in uterine size per unit time) and days to minimum uterine size in a 2 X 2 factorial design. Complete data were analyzed from 64 cows. Groups were selenium plus vitamin E, vitamin E, selenium, and control. Factors significantly affecting uterine size between 14 and 50 d postpartum were cow weight, days postpartum-linear, days postpartum-quadratic, day X metritis, and day X metritis X selenium treatment. Days to minimum uterine size were significantly less in cows with metritis and selenium treated when compared with cows with metritis and not selenium treated (32.9 vs. 35.8).

Animals↗
PubMed1986

Role of aniline metabolites in aniline-induced hemolytic anemia.

Hemolytic anemia after aniline and aniline-related drugs such as dapsone and primaquine is thought to be mediated by active/reactive metabolite(s) formed during the hepatic clearance of the parent compounds. To determine whether any of the known metabolites of aniline contribute to the hemolytic response seen in rats given aniline, rats were infused with isologous 51Cr-labeled erythrocytes 24 hr before administration of aniline or aniline metabolites. The time course of blood radioactivity was followed in individual rats by serial sampling from the orbital sinus and the time required for blood radioactivity to fall by 50% (T50Cr) was used as a measure of in vivo erythrocyte survival. Aniline HCl produced a dose-dependent reduction in the T50Cr. Acetanilide also reduced the T50Cr, but was less potent than aniline. Aminophenols (2-, 3- and 4-) in similar doses did not significantly alter the T50Cr. In contrast, phenylhydroxylamine produced a dose-dependent decrease in the T50Cr with approximately 10 times the potency of aniline. The T50Cr was also decreased in a concentration-dependent manner for labeled erythrocytes incubated in vitro with phenylhydroxylamine, then readministered to rats, indicating a direct toxic effect of phenylhydroxylamine on erythrocytes. In addition, the area under the blood time course curve for phenylhydroxylamine plus nitrosobenzene was equivalent in rats administered equitoxic doses of aniline or phenylhydroxylamine, indicating that sufficient phenylhydroxylamine is formed in vivo during aniline clearance to account for aniline's toxicity. These results suggest that phenylhydroxylamine is the active metabolite that mediates aniline-induced hemolytic anemia.

Anemia, Hemolytic↗
PubMed1985

Concomitant purification of three porcine heart mitochondrial enzymes: citrate synthase, aspartate aminotransferase, and malate dehydrogenase.

The mitochondrial enzymes citrate synthase, malate dehydrogenase, and aspartate aminotransferase were purified to homogeneity from porcine hearts by use of Bio-Rex 70, carboxymethylcellulose CM32, and Affi-Gel blue chromatography. This procedure provides relatively rapid, large-scale preparation of the three enzymes based on their differential binding to commercially available cation-exchange resins followed by a final affinity chromatography step.

Ammonium Sulfate↗
PubMed1985

Regulation of mitochondrial malate dehydrogenase: kinetic modulation independent of subunit interaction.

Porcine heart mitochondrial malate dehydrogenase (EC 1.1.1.37), a dimeric enzyme of Mr = 70,000, is both allosterically activated and inhibited by citrate. Using an affinity elution procedure based upon citrate binding to malate dehydrogenase, the isolation of pure heterodimer (a dimeric species with one active subunit and one iodoacetamide-inactivated subunit) has been achieved. Investigations utilizing this heterodimer in conjunction with resin-bound monomers of malate dehydrogenase have allowed the formulation of a definite conclusion concerning the role of subunit interactions in catalysis and regulation of this enzyme. The citrate kinetic effects, oxaloacetate inhibition, malate activation, and the effects of 2-thenoyl-trifluoroacetone (TTFA) are shown to be independent of interaction between catalytically active subunits. Previous kinetic data thought to support a reciprocating catalytic mechanism for this enzyme may be reinterpreted upon closer analysis in relation to an allosteric, conformationally specific binding model for malate dehydrogenase.

Allosteric Regulation↗
PubMed1985

Measurement of water kinetics with deuterium oxide in lactating dairy cows.

Following intravenous infusion with approximately 300 mg deuterium oxide per kg body weight, blood was drawn from lactating Holsteins (Trial 1, n = 4, and Trial 2, n = 5) at suitable intervals for up to 12 days while the cows were maintained on dietary regimens to which they were well adapted. Time results for deuterium oxide concentration in blood were described best by the three-compartment open model system, which showed that the central, shallow peripheral, and deep peripheral body water compartments contained 27.1, 25.0, and 23.2% body weight in trial 1 and 33.7, 27.1, and 19.9% body weight in trial 2. Total body water estimates averaged 75.3 and 80.7% body weight during trials 1 and 2. Estimates for biological half-life of water were 4.6 and 3.2 days and those for water turnover were 68.9 and 109.7 liters/day, respectively. The data fitted the two-compartment open model system when observations made prior to 25 min post-administration were excluded from the analyses, because the central and shallow peripheral compartments were apparently lumped into one. Blood sampling at 0.5, 1, and 1.5 days following infusion and thereafter at 1-day intervals was adequate for the estimates of the one compartment open model system. Estimates of total body water, water biological half-life, and water turnover were similar for the different models. It is concluded that the three-compartment open model provides greater detail and insight into the water dynamics of lactating dairy cows having regular access to food and water, whereas the two- and one-compartment open model systems provide good approximations only.

Animals↗