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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 325 records · Page 18Linked to original sources
PubMed1989

Regulation of ion transport in porcine gallbladder: effects of VIP and norepinephrine.

The objective of this study was to investigate the effects of vasoactive intestinal peptide (VIP) and norepinephrine (NE) on Na and Cl transport across the isolated porcine gallbladder. Serosal addition of either VIP or secretin increased the short-circuit current (Isc). The half-maximal effect for VIP was 84.3 nM. The effect of VIP was mimicked by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). Replacement of Cl with gluconate nearly abolished the effect of 8-BrcAMP on Isc, whereas HCO3 replacement with N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid buffer had no effect. Transepithelial flux measurements indicated that 8-BrcAMP stimulates net Cl secretion and inhibits Na absorption. Norepinephrine inhibits VIP-stimulated changes in Isc as well as the basal Isc. NE does not, however, reverse the effects of 8-BrcAMP on Isc. The effects of NE are antagonized by yohimbine (alpha 2-adrenergic receptor antagonist) but not prazosin (an alpha 1-adrenergic receptor antagonist). VIP causes a 2.5-fold increase in cAMP content in the gallbladder epithelium. This increase is blocked by NE. Serosal tetrodotoxin did not inhibit the peptide effects, indicating that VIP receptors are localized on the epithelium. Depolarization of submucosal nerves with veratrine inhibited the basal Isc and was reversible with yohimbine. This result indicated that sympathetic nerve pathways regulate Na and Cl absorption in vitro.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Blood pressure responses to cyclic blood volume changes in awake and anesthetized dogs.

A dynamic analysis of blood pressure regulation was performed in conscious and anesthetized dogs. The mean arterial pressure (MAP) responses to 5 and 10% sinusoidal changes in total blood volume with cycle lengths of 1, 4, and 8 min were measured in anesthetized 1) control dogs, 2) carotid and vagal baroreflex (CVB)-denervated animals, and 3) spinal-ablated dogs; in addition, the MAP responses to 10% sinusoidal blood volume changes with cycle lengths ranging from 0.25 to 8 min were measured in conscious control and CVB-denervated dogs. The presence of the baroreflexes in both the conscious and anesthetized control dogs essentially eliminated MAP excursions during the cyclic volume changes. The MAP changes in both the conscious and anesthetized denervated dogs were large. However, the responses in the anesthetized denervated dogs were linear, stationary, and cycle-length insensitive with respect to the sinusoidal forcing function, whereas the responses in the conscious CVB-denervated dogs were nonlinear, nonstationary, and cycle-length dependent. These results indicate that the cardiovascular system in the anesthetized CVB-denervated and spinal-ablated dogs is passive or "hydraulic" in nature; conversely, factors other than the carotid and vagal baroreflexes appear to exist that alter the arterial pressure responses to cyclic blood volume perturbations in the conscious CVB-denervated dogs.

Anesthesia, General↗
PubMed1989

Microprocessor-based analysis of sympathetic nerve traffic.

Two systems based on microcomputers with analog-to-digital (A/D) converters were developed to measure sympathetic nerve activity. The first utilized a relatively inexpensive computer and A/D converter and an analog technique to count nerve traffic "spikes" above a reference voltage. The second system, which required a more expensive microcomputer and A/D converter, used digital methods exclusively to count spikes and integrate nerve activity. These systems produced accurate and reliable indexes of nerve traffic. The digital system could also be used to store the nerve signal to magnetic disk, thereby allowing the later use of more complex analytical procedures and the possibility of comparing the results of different analyses performed upon a single data set.

Animals↗
PubMed1989

24-hour blood pressure recordings in Dahl rats on high- and low-salt diets.

The goal of this study was to determine if the baroreflex abnormality previously shown in Dahl-sensitive (DS) rats would increase blood pressure and heart rate (HR) variability. Mean arterial pressure (MAP) and HR were sampled every 2 s for 24 h from Dahl-resistant (DR) and DS rats on low- and high-salt diets (n = 12-13 in each group). MAP +/- SD was significantly elevated in the DS rats on high-salt diets (DSH); the SD of MAP in the DSH rats was also significantly higher compared with similar measurements in rats on high-salt diets (DRH) and DS rats on low-salt diets (DSL) when SD was divided by MAP. MAP was higher at night than during the day in the DSH rats. In contrast, HR and HR variability were not significantly different between the groups. The baroreflex control of HR, determined by means of graded injections of phenylephrine, was least in the DSH rats and increased, respectively, with DSL rats, DRH rats, and DR rats on low-salt diets. There was no significant correlation between the baroreflex control of HR and MAP or the SD of MAP in the DSH rats, suggesting that there is not a simple relationship between baroreflex gain and the overall behavior of MAP in DSH rats.

Animals↗
PubMed1989

Cytoplasmic genetic effects and growth of hybrid mice.

Variation in cellular biochemical functions controlled by cytoplasmic genes was studied in relation to phenotypic differences between progeny of reciprocal hybrid female mice. Least squares procedures were used to test for differences in mitochondrial respiratory metabolism and in capacity for ATP synthesis, and differences in growth of progeny of hybrid dams. Under identical nuclear influences, mitochondria of A/J and C57BL/6J cytoplasms differed (P less than .10 to P less than .01) from those of BALB/cJ cytoplasm in energy conservation. No differences were detected in mitochondrial efficiency between BALB/cJ cytoplasm evaluated in different nuclear environments. Three-way cross progeny of C57BL/6J x BALB/cJ reciprocal hybrid females mated to DBA/2J males differed (P less than .05) in litter weight at weaning and 1 wk and 2 wk postweaning. The F2 progeny of reciprocal C57BL/6J x BALB/cJ dams and F2 and three-way cross progeny of reciprocal A/J x BALB/cJ dams did not differ in weight at any age measured. Across all genotypes of dam, rank correlations of mitochondrial traits with F2 litter weights were nonsignificant. Observed variation in mitochondrial functions partially controlled by cytoplasmic genes did not limit mouse growth under these experimental conditions.

Adenosine Triphosphate↗
PubMed1989

Molecular analysis of cytoplasmic genetic variation in Holstein cows.

Mitochondrial DNA from Holstein maternal lineages implicated to express cytoplasmic genetic effects on lactation traits was subcloned and screened for molecular polymorphisms. Sixteen of 35 lineages sampled differed from the most common mitochondrial DNA form by at least one restriction endonuclease cleavage site in the 4.3 kilobase segment examined. Variation existed in the region that regulates DNA replication and transcription as well as in transfer and ribosomal ribonucleic acid coding regions of the DNA. The index of nucleotide diversity calculated from polymorphism frequencies indicated that the minimum extent of variation between two random lineages was 1.16 x 10(-4) nucleotide differences per base pair in the segment examined. Presence of a HpaII marker near nucleotide 360 was associated with lower (P less than .001) milk fat percentages. Molecular markers indicated that pedigrees may not be sufficient to separate true cytoplasmic lineages for quantitative genetic analyses. These findings provide a molecular genetic basis for further study of cytoplasmic effects on phenotypic variation in Holstein cattle.

Animals↗
PubMed1989

Neurohormonal regulation of ion transport in the porcine distal jejunum. Actions of neurotensin and its natural homologs.

The tridecapeptide neurotensin (NT) is present at high concentrations within the mammalian gut, although its physiological function is undefined. In this study, the actions of NT and structurally related peptides neuromedin N (NM-N) and xenopsin were characterized on ion transport in the porcine distal jejunal mucosa in vitro. The serosal-side administration of these peptides elicited rapid changes in transmural potential difference and short-circuit current (Isc) which were greater in mesenteric than in antimesenteric segments. NT-induced elevations in Isc were dependent upon external permeant anions and were associated with net Cl transport in both segments. In mesenteric segments, NT and its homologs increased Isc with the order of potency: NT greater than NM-N greater than xenopsin. NT produced tachyphylaxis to its own actions and to those of NM-N; NM-N was ineffective in producing tachyphylaxis. Isc elevations produced by NT were inhibited by the neuronal conduction blocker tetrodotoxin (0.1 microM) or the Ca++-channel blocker dl-verapamil (100 microM) and reduced in Ca++-free media. Antagonists to the enteric transmitters acetylcholine, ATP, 5-hydroxytryptamine, substance P and histamine did not alter Isc responses of mesenteric segments to NT. Serosal administration of vasoactive intestinal peptide (10 nM) did not resemble the effects of NT. The magnitude of Isc responses to these agonists was smaller in antimesenteric segments. These results indicate that NT-related peptides present in mucosal endocrine cells or nerves of the porcine jejunum may modulate Cl transport through mechanisms that involve the Ca++-dependent release of unknown enteric neurotransmitters. Moreover, there appear to exist within the distal jejunum circumferential differences in mucosal responses to NT and other neurohumoral factors.

Animals↗
PubMed1988

Neuromedin U octapeptide alters ion transport in porcine jejunum.

The gut neuropeptide, neuromedin U octapeptide (NMU-8) produced transient elevations in short-circuit current (EC50 = 0.7 nmol/l) after its contraluminal administration to sheets of porcine distal jejunal mucosa in vitro. Mucosal responses to NMU-8 were unaffected by 1 mumol/l atropine or hexamethonium, but were abolished by tetrodotoxin (0.1 mumol/l), dependent upon extracellular Cl, and underwent tachyphylaxis upon repeated peptide application. NMU-8 did not affect contractility of isolated jejunal longitudinal muscle. Thus, NMU-8 appears to selectively modify intestinal ion transport through interactions with non-cholinergic enteric neurons.

Animals↗
PubMed1988

An analysis of the effects of galanin on gastric acid secretion and plasma levels of gastrin in the dog.

The effects of galanin on gastric acid secretion and plasma levels of gastrin were studied in conscious dogs chronically fitted with gastric fistulas. Continuous i.v. infusion of galanin (2 micrograms.kg-1.h-1) for 2 h did not affect unstimulated total acid output or plasma levels of gastrin. In contrast, simultaneous i.v. infusion of galanin (1-2 micrograms.kg-1.h-1) inhibited the bombesin-stimulated output of acid whereas the effects of bombesin on gastrin output were not significantly modified. Galanin (2-4 micrograms.kg-1 i.v.) also depressed the secretory response to 2-deoxy-D-glucose without significantly affecting plasma gastrin levels. Galanin (2-4 micrograms.kg-1 i.v.) did not depress bethanechol-stimulated gastric acid output or inhibit histamine-stimulated gastric acid secretion. These findings indicate that glanin inhibits the bombesin- and 2-deoxy-D-glucose-stimulated secretion of gastric acid in conscious dogs by an action which is probably exerted at the level of the cholinergic nerve terminals.

Animals↗
PubMed1988

Actions of centrally administered neuropeptides on rat intestinal transport: enhancement of ileal absorption by angiotensin II.

Recent evidence suggests that opioids and other peptides may act within the CNS to modulate intestinal fluid and ion transport. In this study, the brain peptides bombesin and angiotensin II were examined for their ability to alter water flux across the small intestine after their intracerebroventricular (i.c.v.) administration to rats. In addition, changes in mean arterial pressure and respiratory frequency were determined after peptide treatment to assess the physiological specificity of their CNS actions. Bombesin, administered by i.c.v. bolus injections (10-1000 ng/rat) or continuous infusion (100 ng/min), rapidly elevated blood pressure and respiration, but had no significant effect on water transport in proximal jejunum or distal ileum in situ (as measured by single-pass perfusion with [14C]polyethylene glycol as non-absorbed water marker). Angiotensin II rapidly increased blood pressure and enhanced ileal absorption 30 min after its i.c.v. bolus injection at 0.1-1 microgram, but had no effect on jejunal transport or respiration. These effects were inhibited in rats pretreated with either the angiotensin antagonist [Sar1, Val5, Ala8]angiotensin II (5 micrograms i.c.v.) or the alpha-adrenoceptor antagonist, phentolamine (1 mg/kg i.v.). In contrast, atropine methylnitrate (0.1 mg/kg i.v.) pretreatment inhibited the proabsorptive, but not the pressor effects of angiotensin. These results indicate for the first time that angiotensin II promotes fluid absorption in the rat intestine by an action within the CNS. The mechanisms underlying this novel action of angiotensin appear to differ from those responsible for its hypertensive action.

Angiotensin II↗
PubMed1988

An improved method of purification of transforming growth factor, type beta from platelets.

Platelets contain high concentrations of TGF-beta and for this reason have been the primary source of materials for its purification. The yield from acid-ethanol extracts of platelets has been reported to be 0.5 microgram/unit of platelets. We have developed a method which yields approximately 2 micrograms/unit of platelets from acid-ethanol extracts. The use of an ion-exchange column followed by RPLC results in a homogeneous product in less time and with fewer manipulations than the previously published methods. A tritiated thymidine incorporation assay using the CC164 cell line is described for the quantitation of TGF-beta.

Blood Platelets↗
PubMed1988

Receptor regulation of ion transport in the intestinal epithelium.

The active transport of ions by the intestinal epithelium is regulated by a number of enteric neurotransmitters, hormones and other substances. Our knowledge of the receptors mediating the actions of these substances is generally fragmentary. This review summarizes current knowledge on the location and functional characteristics of transmitter receptors regulating transport function in the small intestine, highlighting recent research on cholinergic and bradykinin receptors.

Animals↗
PubMed1988

Identification of human papillomavirus type 11 E4 gene products in human tissue implants from athymic mice.

A new method has recently been described for the growth of human papillomavirus type 11 (HPV11), an agent associated with genital warts, in human tissue xenografts implanted under the renal capsules of athymic nude mice (J. W. Kreider et al., 1986, J. Virol. 59, 369-376; 1987, J. Virol. 61, 590-593). With this model it is now possible to study productive HPV11 infection under controlled laboratory conditions. To identify proteins encoded by the HPV11 E4 open reading frame in infected implants, we have cloned an HPV11 E4 genomic DNA fragment representing all of the E4 region thought to be expressed in vivo, as evidenced by cDNA cloning and R loop mapping. The cloned HPV11 fragment was expressed in Escherichia coli as a cro-beta-galactosidase E4 fusion protein (Gal-E4 fusion). Rabbit antibodies raised against the Gal-E4 fusion protein were affinity purified using an HPV11 E1 E4 fusion protein. The E1--E4 protein was synthesized independently by expressing an HPV11 E1--E4 cDNA in E. coli using a second expression vector. Affinity-purified anti-E4 antibodies identified putative E4 proteins of 10 and 11 kDa in both the condylomatous cyst walls and in the desquamated cells in the cavities of HPV11-infected human skin implants from athymic mice. Similar proteins were not detected in uninfected controls. Implications for use of the athymic mouse system are discussed.

Animals↗
PubMed1988

Actions of gastrin-releasing peptide and related mammalian and amphibian peptides on ion transport in the porcine proximal jejunum.

The 27-amino acid peptide gastrin-releasing peptide (GRP) and the decapeptide neuromedin B (NMB) are structurally related to bombesin (BB) and exist within the mammalian small intestine. We examined the actions of porcine GRP and NMB on ion transport in the porcine proximal jejunum in vitro and compared their activities to those of their respective C-terminal amphibian homologs BB and ranatensin (RT). The 4 peptides transiently increased potential difference and short-circuit current (Isc) in jejunal mucosal sheets after their serosal administration in subnanomolar concentrations with an order of potency: GRP approximately RT greater than or equal to NMB greater than BB. BB and RT were more effective in elevating Isc than GRP and NMB; all peptides had variable effects on tissue conductance. Mucosal Isc responses to GRP (1 nM) were due in part to a stimulation of net Cl- secretion. GRP-induced Isc increases were halved by serosal furosemide (0.3 mM) and reduced by 65% and 90% in tissue bathing solutions lacking Cl- or Cl- and HCO3-, respectively. Tetrodotoxin reduced Isc responses to the peptide by 40%; GRP activity remained unaffected after blockade of gut muscarinic or nicotinic cholinergic receptors by atropine or hexamethonium, respectively. These results suggest that GRP and its natural homologs stimulate active electrogenic Cl- secretion in the porcine jejunum through interactions with GRP receptors located in the intestinal mucosa and submucosa.

Amphibians↗
PubMed1988

Changes in rat lung microsomal lipids after p-xylene: relationship to inhibition of benzo[a]pyrene metabolism.

The relationship between p-xylene's effects on microsomal membranes, cytochrome P-450, and benzo[a]pyrene (BaP) metabolism was studied. p-Xylene (1 g/kg, ip, 1 h) inhibited 3-hydroxy BaP (3-OH) formation and decreased arylhydrocarbon hydroxylase (AHH) activity approximately 40% in rat lung microsomes. BaP dihydrodiol and quinone formation were unchanged by p-xylene administration. Cytochrome P-450 was below the limit of detection in lung microsomes from p-xylene-treated rats. Total phospholipid (PL) and phosphatidylcholine (PC) in microsomal membranes were decreased 28% and 17%, respectively. Cholesterol (CL), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and sphingomyelin (SM) were unchanged. The net activity of enzymes involved in the synthesis of PC, phosphatidylethanolamine-N-methyltransferase I and II (PMT I and PMT II), was slightly elevated by p-xylene. PL/CL and PC/PE ratios, indicators of membrane fluidity, were decreased 34% and 13%, respectively, in microsomes from p-xylene-treated rats. Analysis of fluidity by fluorescence polarization showed that the actual fluidity of treated microsomes was slightly decreased (5%) as compared to controls. The decrease in P-450, PL, and PC is considered to contribute to the inhibition of BaP metabolism.

Animals↗
PubMed1988

Mitochondrial respiratory metabolism and performance of cattle.

Two groups of cows were sampled to study variation of mitochondrial metabolism. The first group included 10 lactating and five gestating Holstein cows, representing available phenotypic extremes for milk yield. The second group included 13 Angus, 13 Brangus and 13 Hereford cows, representing available extremes within breeds for growth breeding value ratios. Consistently poor mitochondrial samples were obtained from gestating cows; these were excluded from analyses. Linear correlations of Holstein mitochondrial respiratory activities with sire-predicted difference for milk and milk fat ranged from -.35 to .15. Correlations of dam and cow indices and cow yields for milk with acceptor-stimulated mitochondrial respiration, oxidative phosphorylation efficiency (adenosine diphosphate:oxygen ratio [ADP:O ratio]) and adenosine triphosphate (ATP) synthesis rate were .25 to .48, consistently higher than for milk fat, -.06 to .17. No differences among beef breeds in mitochondrial respiration rates, coupling of respiration to phosphorylation, ADP:O ratio or ATP synthesis rate were detected by repeated measures analyses of variance. No patterns were evident among correlations of the mitochondrial characteristics and growth and milk traits in beef cattle. These initial findings indicate that variability in the mitochondrial respiratory activities measured has less relation to weaning and yearling growth traits of beef cattle than to milk yield of Holstein cattle.

Animals↗