Search PubMed⌕ Search

Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 361 records · Page 20Linked to original sources
PubMed1986

Hepatic mitochondrial activity in two breeds of chicken.

Respiration rates and efficiencies of oxidative phosphorylation of hepatic mitochondria from mature Hubbard White Mountain Cross broiler and White Leghorn layer hens were compared. Broiler hen mitochondria consistently tended to exhibit higher succinate-supported State 3 respiration rate, respiratory control ratio, and ratio of adenosine diphosphate to oxygen, although breed differences were not statistically significant. Within-breed variation in mitochondrial activity was not associated with body weight or egg production. Hepatic tissue of broiler hens yielded significantly more protein in the mitochondrial fraction than tissue of layer hens. In vitro mitochondrial mixtures representing equal wet tissue weights from each breed showed mitochondrial activity intermediate between the two breeds.

Animals↗
PubMed1985

The pharmacological modification of secretory responses.

Electrolyte transport across the intestinal mucosa can be modulated by several neurotransmitters, hormones and drugs. Opiate agonists and endogenous opioid peptides inhibit electrolyte secretion both in vitro and in vivo. These drugs appear to act at several levels. Thus, opioid effects can be elicited at the local mucosal level. Secondly, antisecretory effects can be demonstrated when opioids are administered into the brain. These central effects appear to involve activation of the sympathetic innervation of the intestine. Thirdly, some antidiarrhoeal drugs such as loperamide may have ancillary non-opiate-like actions that contribute to their effectiveness. In cases of inflammatory bowel disease where local concentrations of inflammatory mediators such as kinins and eicosanoids may be high, non-steroidal anti-inflammatory drugs may be effective in treating diarrhoeal symptoms. The existence of many types of receptors on mucosal cells indicates that several pharmacological approaches exist for the potential modulation of electrolyte transport.

Animals↗
PubMed1985

The use of quaternary narcotic antagonists in opiate research.

Quaternary ammonium derivatives of narcotic antagonists are commonly used in determining sites of action of opiates in the central nervous system and the periphery because it is widely assumed that they do not readily cross the blood-brain barrier, in contrast to their relatively non-polar tertiary counterparts. However, these compounds possess several unique pharmacological properties which have not been taken into consideration in the design of numerous investigations. This article reviews the current state of knowledge concerning the pharmacology of the quaternary narcotic antagonists, examines their use in physiological and behavioral studies of action of opiates, and proposes guidelines for the design of experiments involving these compounds.

Animals↗
PubMed1985

Effect of Eimeria acervulina infection in chicks fed excess dietary cobalt and/or manganese.

Two trials were conducted with male Cobb chicks to investigate the interaction between experimental Eimeria acervulina infection and dietary excesses of Co and Mn. Eimeria acervulina infection depressed rate and efficiency of weight gain, increased bone mineral retention and exacerbated Co toxicity. A significant Co X Mn interaction was observed in growth rate and efficiency of gain and in Co and Mn concentration in some tissues as well. This interaction was present both in uninfected chicks and in coccidiosis-infected chicks. Excesses of dietary Co and Mn increased tissue Co and Mn concentrations, respectively. Excess Co also increased Mn accumulation in kidney, bile and the tibia.

Animal Feed↗
PubMed1985

Thallium induced changes in behavioral patterns: correlation with altered lipid peroxidation and lysosomal enzyme activity in brain regions of male rats.

The effects of exposures to low levels of heavy metals is a complex and serious problem. Thallium is a metal which produces behavioral sequelae in human poisoning and is potentially hazardous with low level exposures. A test battery is presented which utilizes biochemical and behavioral testing to assess the effects of low levels of thallium on central nervous system chemistry and function in rats. The doses of thallium used (4 and 8 mg/kg) produced no overt signs of behavioral toxicity but did produce dose-related increases in lipid peroxidation and activation of the lysosomal enzyme beta-galactosidase in selected brain regions. At these dose levels, thallium also selectively altered the patterns of behavior. The study suggests that the target regions of thallium in the brain include the cortex, the cerebellum and the brainstem. The dose-response relationships, found for certain pairs of behavioral acts, were correlated with biochemical changes in one or more brain regions.

Animals↗
PubMed1985

A comparison of methods for organ-weight data adjustment in chicks.

An experiment was conducted with 168 Arbor Acre X Peterson unsexed, crossbred broiler chicks to compare methods of expressing organ-weight data and to assess changes in organ weights and physiological parameters as body weight (97 to 791 g) and age (5 to 26 days) increased. Actual wet weight of liver, heart, intestine, spleen, and pancreas and percent bone ash increased (P less than .01) as age and body weight increased. Tibia length-to-width ratio decreased (P less than .01) as age and body weight increased. Blood hemoglobin, hematocrit, and plasma protein were not affected (P greater than .1) by age or by body weight. Liver, heart, and intestinal weight decreased (P less than .01) and spleen weight increased (P less than .01) as body weight and age increased when these tissue weights were expressed as percent of body weight. Liver weight adjusted for body weight by covariance analysis, however, remained constant; adjusted heart and intestinal weights decreased (P less than .01), and adjusted spleen weights increased (P less than .01) with increasing age and body weight. The covariate, body weight, was not significant (P greater than .1) for pancreas weight, tibia length-to-width ratio, and percent bone ash. Except for spleen, adjustment by covariance analysis more effectively reduced variation due to body weight than did expression as percent of body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Effect of citric and ascorbic acids on performance and intestinal pH of chicks.

An experiment was conducted to investigate the effect of one percent dietary citric and ascorbic acid additions on performance and intestinal pH of young chicks. The citric and ascorbic acid additions did not affect chick performance or pH of the duodenal lumen contents. Also, pH of the duodenal lumen contents was not affected by 1:2 to 1:8 dilutions with distilled water.

Animals↗
PubMed1985

Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa.

The antisecretory properties of opiates in the guinea-pig ileum have been shown previously to be mediated through interactions with delta-like opiate receptors present in the intestinal mucosa. The present investigation examined the development of tolerance to opioid-induced alterations in intestinal ion transport processes. Osmotic minipumps continuously delivering the prototypic delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) (5 micrograms/hr) or the potent mu-opiate agonist fentanyl (10 micrograms/hr) over a 5-day period were implanted s.c. into guinea pigs; control animals did not receive chronic drug infusions. DADLE, DADLE ethylamide and [D-Ala2,D-Met5]enkephalin dose-dependently decreased base-line transepithelial potential difference and short-circuit current in isolated segments of ileal mucosa from untreated control animals, with an order of potency of DADLE greater than [D-Ala2, D-Met5 enkephalin greater than DADLE ethylamide. In tissues from DADLE-infused animals, the antisecretory dose-effect curves of the three enkephalin analogs displayed downward shifts to the right compared to control conditions. In contrast, the potency of DADLE was significantly increased in tissues from animals chronically infused with and rendered physically dependent upon fentanyl. The administration of the opioid antagonists naloxone, diprenorphine or the selective delta-opioid antagonist M 154, 129 produced no significant changes in short-circuit current of mucosal segments from either DADLE- or fentanyl-infused animals. Chronic administration of either DADLE or fentanyl did not significantly alter the effects of nonopioids, bombesin, somatostatin or epinephrine, on ion transport; however, the efficacy but not the potency of neurotensin in increasing short-circuit current was attenuated after chronic DADLE infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Fibrinogen Irvine: a qualitatively abnormal fibrinogen associated with the predisposition to recurrent visceral and peripheral venous thrombosis.

A slow clotting dysfibrinogen with delayed anodal immunoelectrophoretic mobility and impaired fibrinopeptide A release has been identified in a patient with recurrent portal vein and deep venous thrombosis. Affected family members tested in the initial screening were asymptomatic. The proband's father died of pulmonary embolism at age 44 years and had mesenteric thrombosis at necropsy. The association of a plasma protein abnormality with visceral thrombosis is unusual and has never been observed previously with a dysfibrinogen. The qualitative abnormality is transmitted as an autosomal codominant and is tentatively designated, fibrinogen Irvine.

Adult↗
PubMed1984

Analysis of bacteriophage phi X174 gene A protein-mediated termination and reinitiation of phi X DNA synthesis. I. Characterization of the termination and reinitiation reactions.

The phi X174 (phi X) gene A protein-mediated termination and reinitiation of single-stranded circular (SS(c] phi X viral DNA synthesis in vitro were directly and independently analyzed. Following incubation together with purified DNA replication enzymes from Escherichia coli, ATP, [alpha-32P]dNTPs, and either the phi X A protein and phi X replicative form I (RF I) DNA, or the purified RF II X A complex, the phi X A protein was detected covalently linked to newly synthesized 32P-labeled DNA. Formation of the phi X A protein-[32P]DNA covalent complex required all the factors necessary for phi X (+) SS(c) DNA synthesis in vitro. Thus, it was a product of the reinitiation reaction and an intermediate of the replication cycle. Identification of this complex provided direct evidence that reinitiation of phi X (+) strand DNA synthesis involved regeneration of the RF II X A complex. Substitution of 2',3'-dideoxyguanosine triphosphate (ddGTP) for dGTP in reaction mixtures resulted in the formation of covalent phi X A protein 32P-oligonucleotide complexes; these complexes were trapped analogues of the regenerated RF II X A complex. They could not act catalytically due to the presence of ddGMP residues at the 3'-termini of the oligonucleotide moieties. Reaction mixtures containing ddGTP also yielded nonradioactive (+) SS(c) DNA products derived from circularization of the displaced (+) strand of the input parental template DNA. The formation of the phi X A protein-32P-oligonucleotide complexes and nonradioactive (+) SS(c) DNA were used to assay both reinitiation and termination reactions, respectively. Both reactions required DNA synthesis from the 3'-hydroxyl primer at nucleotide residue 4305 which was formed by cleavage of phi X RF I DNA by the phi X A protein. Elongation of this primer by 18, but not 11 nucleotides was sufficient to support each reaction. Reinitiation reactions proceeded rapidly and were essentially complete after 90 s. In contrast, when ddGTP was replaced with dGTP in reaction mixtures, DNA synthesis proceeded with linear kinetics for up to 10 min. These results suggested that in the presence of all four dNTPs, active templates supported more than 40 rounds of DNA synthesis.

Bacteriophage phi X 174↗
PubMed1984

Analysis of bacteriophage phi X174 gene A protein-mediated termination and reinitiation of phi X DNA synthesis. II. Structural characterization of the covalent phi X A protein-DNA complex.

In the preceeding paper (Brown, D. R., Roth, M. J., Reinberg, D., and Hurwitz, J. (1984) J. Biol. Chem. 259, 10545-10555), it was shown that following bacteriophage phi X174 (phi X) DNA synthesis in vitro using purified proteins, the phi X A protein could be detected covalently linked to nascent 32P-labeled DNA. This phi X A protein-[32P]DNA complex was the product of the reinitiation reaction. The phi X A protein-[32P]DNA complex could be trapped as a protein-32P-oligonucleotide complex by the inclusion of ddGTP in reaction mixtures. In this report, the structure of the phi X A protein-32P-oligonucleotide complex has been analyzed. The DNA sequence of the oligonucleotide bound to the phi X A protein has been determined and shown to be homologous to the phi X (+) strand sequence immediately adjacent (3') to the replication origin. The phi X A protein was directly linked to the 5' position of a dAMP residue of the oligonucleotide; this residue corresponded to position 4306 of the phi X DNA sequence. The phi X A protein-32P-oligonucleotide complex was exhaustively digested with either trypsin or proteinase K and the 32P-labeled proteolytic fragments were analyzed. Each protease yielded two different 32P-labeled peptides in approximately equimolar ratios. The two 32P-labeled peptides formed after digestion with trypsin (designated T1 and T2) and with proteinase K (designated PK1 and PK2) were isolated and characterized. Digestion of peptide T1 with proteinase K yielded a product which co-migrated with peptide PK2. In contrast, peptide T2 was unaffected by digestion with proteinase K. These results suggest that the phi X A protein contains two active sites that are each capable of binding covalently to DNA. The peptide-mononucleotide complexes T1-[32P]pdA and T2-[32P]pdA were isolated and subjected to acid hydrolysis in 6.0 N HCl. In each case, the major 32P-labeled products were identified as [32P] phosphotyrosine and [32P]Pi. This indicates that each active site of the phi X A protein participates in a phosphodiester linkage between a tyrosyl moiety of the protein and the 5' position of dAMP.

Bacteriophage phi X 174↗
PubMed1984

Risk factors associated with retrolental fibroplasia.

The eyes of infants who were premature or had exposure to increased ambient oxygen from 1979 to 1981 were examined. Of 1012 neonates, 19 were found to have acute retrolental fibroplasia (RLF) grade III or worse in at least one eye. Sixteen also had chronic lung disease (CLD), and when compared to 25 control patients who had CLD but not grade III or more RLF, they were found to consistently have lower blood CO2 tensions (PCO2), lower pH values, higher inspired oxygen concentrations (FIO2S) and a higher incidence of seizure disorders (100% vs. 48%). We could not show that an elevated PCO2 increased the risk for developing RLF. Infants with either chronic lung disease or chronic lung disease and seizures had a high risk for developing RLF grade III (39% and 57%, respectively).

Carbon Dioxide↗
PubMed1984

Adrenal mediation of ethanol's inhibition of benzo[a]pyrene metabolism.

Previous studies in rats have demonstrated that acute ethanol (1 h) at high doses inhibits xenobiotic metabolism and that the effect is modulated by the adrenals. In this paper, we report a similar phenomenon for benzo[a]pyrene (BaP) metabolism but the inhibitory effect is restricted to detoxication without effect on activation routes. Rats were administered ethanol (5 g/kg) orally and sacrificed 1 h later. Microsomes were isolated and assayed for capacity to metabolized BaP to activated and detoxified products. Ethanol treatment inhibited detoxication, as evidenced by approximately 50% decrease in 3-hydroxy-BaP formation. There was little effect on metabolic routes forming activated products, as indicated by no change in the rate of dihydrodiol formation. To determine the role of the adrenals in ethanol's inhibitory effect towards detoxication, a similar experiment was performed in adrenalectomized (ADX) rats. ADX alone slightly decreased 3-hydroxy-BaP formation, but treatment with ethanol resulted in no significant differences from ADX controls. Corticosterone administration to ADX rats resulted in an inhibition of the formation of all metabolites. The data suggest that acute ethanol inhibits the detoxication of BaP without effecting activation and that this effect is mediated by the adrenals. This would be expected to increase the proportion of carcinogenic metabolites.

Adrenal Glands↗
PubMed1984

Effect of rifampin and bacitracin on nasal carriers of Staphylococcus aureus.

Anterior nares cultures from 664 hospital personnel identified 165 (24.8%) as carriers of Staphylococcus aureus. Persistent carriers (17.8%) were identified and randomly assigned to one of four treatment groups: rifampin (600 mg once a day for 5 days), bacitracin ointment (topically applied three times a day for 10 days), combined rifampin and bacitracin, and control (no treatment). Bacitracin ointment was ineffective in eliminating S. aureus from the anterior nares and had a postreatment carrier rate equal to the control rate. Rifampin therapy caused a highly significant reduction (79%) in carriage; however, combined therapy was not as effective as treatment with rifampin alone. Of 132 strains of staphylococci isolated before and after treatment, all were susceptible to less than 0.016 micrograms of rifampin per ml. This study demonstrates that rifampin may be an effective antistaphylococcal antibiotic and could be used to control the carrier state in high-risk situations.

Adult↗
PubMed1984

Adrenergic mediation of the intestinal antisecretory action of opiates administered into the central nervous system.

The antisecretory effects of the stable enkephalin analogs, [D-Ala2-Met5] enkephalinamide (DAMA) and [D-Ala2-D-Leu5] enkephalin, and the opiate drug morphine were evaluated on fluid secretion induced by cholera toxin in isolated loops of the jejunum and proximal and distal ileum in anesthetized rats. Intracerebroventricular administration of DAMA (0.03-3 micrograms) or [D-Ala2-D-Leu5] enkephalin (1.0-10 micrograms) dose-dependently reduced secretion in the jejunum without affecting fluid movement in the other small intestinal segments. Morphine in doses up to 30 micrograms i.c.v. had no significant antisecretory effects. Intravenous administration of DAMA, at doses up to 3000 micrograms/kg, had little effect on intestinal fluid accumulation. The antisecretory action of DAMA (3 micrograms i.c.v.) was completely blocked by pretreatment with the alpha adrenergic antagonist phentolamine and after peripheral sympathectomy induced by guanethidine. In contrast, DAMA activity was preserved in adrenal demedullated rats. DAMA had no significant effects upon mean arterial blood pressure or on blood acid-base balance. These results suggest that the antisecretory effects of opiates are, at least partly, mediated at sites within the central nervous system. These actions are probably a consequence of increased activity in sympathetic nerve fibers innervating the upper small intestine.

Animals↗