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Biomedical subjects

J H Harrison

Publications and source records attributed to J H Harrison.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Vitamin E and selenium for reproduction of the dairy cow.

Selenium injections and oral vitamin E supplementation prepartum were related to incidence of retained placenta, metritis, and cystic ovaries in a 2 X 2 factorial experiment. Groups were: 1) selenium and vitamin E, 2) vitamin E, 3) selenium, and 4) control. Incidence of retained placenta was 17.5% in cows of groups 2, 3, and 4, whereas it was reduced to 0% in cows receiving both selenium and vitamin E. Incidence of metritis was 60% for cows injected with selenium and 84% for those not receiving selenium. Cystic ovaries were diagnosed in 19% of cows injected with selenium, and incidence was 47% for cows not treated with selenium. Supplementation of vitamin E was required in addition to selenium for prevention of retained placenta of cows fed stored ensiled forage, and prepartum selenium injections were effective for reducing the incidence of metritis and cystic ovaries during the early postpartum period.

Animals↗

Effect of selenium intake on selenium utilization by the nonlactating dairy cow.

Total collection digestion trials were used to study selenium absorption and retention as related to selenium intake in nonlactating dairy cows. Relationship between selenium absorption and retention was linear over selenium intakes from 400 to 3100 micrograms/day. Regression analysis showed partial selenium absorption of 51% over total range of intake and 41% retention of dietary selenium intake. Also, negative selenium balances could occur when nonlactating cows are fed selenium-deficient diets without a supplemental source of selenium.

Animals↗

Effect of vitamin E and selenium supplementation on incidence of clinical mastitis and duration of clinical symptoms.

Incidence of clinical mastitis and duration of clinical symptoms for complete lactations were evaluated for 80 cows randomly assigned to one of four groups: vitamin E supplemented- and selenium injected, selenium injected, vitamin E supplemented, and controls. Vitamin E supplementation and selenium injection were during the dry period. Log-linear analysis of incidence data revealed a significant 37% reduction of clinical mastitis by vitamin E. Incidence was not affected by selenium alone, nor was there any evidence for interaction of vitamin E with selenium on incidence. However, duration of clinical symptoms (calendar months clinical/quarter lactating) was reduced by 46% for the selenium group, 44% for the vitamin E group, and 62% for the vitamin E-selenium group as compared to controls. We conclude that dairy cow diets deficient of vitamin E may elevate incidence of clinical mastitis. Selenium deficiency may result in greater duration of clinical symptoms, and selenium may interact with vitamin E. Coliform bacteria and species of streptococcus other than Streptococcus agalactiae were isolated from 70% of the clinical cases.

Animals↗

Effect of dietary calcium on selenium absorption by the nonlactating dairy cow.

Eleven nonlactating Holstein cows in late gestation were used to study the effect of dietary calcium concentration on apparent selenium absorption. Digestion trials with total collection helped to estimate apparent absorption of specific nutrients. Mean daily selenium intake ranged from 900 to 1700 micrograms per day. Regression analysis indicated apparent selenium absorption was maximum when dietary calcium was .8% of dry matter intake. Amounts of dietary calcium less or greater than .8% of dry matter intake reduced apparent selenium absorption. Dietary calcium quantitatively affected apparent selenium absorption in amounts of nutritional significance when selenium was provided from natural feedstuffs.

Animals↗