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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 271 records · Page 15Linked to original sources

Symptoms of depression among older African-Americans: an analysis of gender differences.

Using data from a community-based sample of African-Americans, this study investigated the association between gender and depressive symptoms among 148 African-Americans who are 65 years of age and older. Findings indicated no gender difference in overall level of depressive symptomatology. Further analyses suggest that the lack of a gender difference in depressive symptoms was attributable to similarities in risk factors related to stressful life events and the social roles associated with employment and childrearing.

Black or African American↗

Factors associated with detection of human papillomavirus E4 and L1 proteins in condylomata acuminata.

The E4 and L1 gene products of human papillomavirus (HPV) types 6 and 11 are detected in variable amounts in condylomata acuminata. To study factors associated with detection of these proteins, biopsy specimens containing HPV-6 or -11 were analyzed for E4 protein, L1 protein, and HPV copy number. Seventeen of 50 women biopsied were pregnant. Nine men were also biopsied. Both the E4 and L1 proteins were found more frequently in lesions from pregnant women than from nonpregnant women or men. Both proteins were more often detected in lesions from women than from men. E4 gene products were more often detected in lesions in which L1 protein was detected and a higher HPV copy number was present. Detection of E4 gene products correlates with the detection of L1 protein in condylomata acuminata caused by HPV-6 or -11.

Adult↗

External gamma-ray counting of selected tissues from a Thorotrast patient.

Results of gamma-ray measurements of selected tissues from a patient who was injected with Thorotrast almost 36 y ago are reported. The purposes of this study were: 1) to determine the relative tissue distribution and activities of specific radionuclides in the 232Th decay chain, specifically 228Ra (as measured by 228Ac), 212Pb, and 224Ra (measured directly and as measured by 212Pb), and 2) to evaluate the level of radioactive disequilibrium among the daughter products. The spleen and liver had the highest concentrations of radioactivity. Bone also appears to be a long-term sink for 232Th daughter products based on estimates from a small portion of one rib. Larynx and esophagus contained measurable activity, which may have been due to their proximity to the "Thorotrastoma." Radioactivity in the remaining measured tissues were low, as expected. Secular equilibrium could be demonstrated in bone, pancreas, larynx, esophagus, and breast. Significant disequilibrium was observed for spleen, liver, kidney, and red blood cells. Radioactivity measurements reported here will be useful in estimating radiation doses to selected tissues. Such dose estimates are valuable in refining current risk estimates (e.g., liver) and in identifying tissues at risk for further epidemiologic studies. These results, while consistent with other published studies, should be interpreted with caution since measurements were made on only one patient.

Aged↗

Heart rate control in awake dog after selective SA-nodal parasympathectomy.

Selective surgical sinoatrial (SA)-nodal parasympathectomy (PSX) was used to distinguish the role of the cardiac autonomic nerves in heart rate (HR) control in awake dogs (n = 8) during rest and behavioral arousal. Resting HR increased from 85 +/- 9 beats (mean +/- SE) before surgery to 114 +/- 6 beats after denervation (P less than 0.05). Atrioventricular (AV)-nodal block occurred during the first 1-3 wk post-PSX, but subsequently resolved. Dogs were behaviorally conditioned by following a 30-s tone (CS+) by a 0.5-s shock. Before denervation the CS+ evoked an initial, rapidly developing tachycardia (phase 1), which was followed by a more slowly developing, but larger, phase 2 tachycardia. The selective SA-nodal parasympathectomy essentially abolished the phase 1 conditional HR response (magnitude: 23 +/- 5 vs. 5 +/- 2 beats, pre- vs. postdenervation, respectively). The phase 2 HR increase was similar before and after the denervation (magnitude: 44 +/- 6 vs. 33 +/- 6 beats; rate of increase: 5 +/- 1 vs. 6 +/- 1 beats/s, pre- vs. post-PSX). Beta-Blockade (propranolol, 1 mg/kg) after PSX decreased phase 2 (magnitude: 7 +/- 3 beats; rate of increase: 1 +/- 0.3 beats/s). These data reveal a sterotypic pattern of change in cardiac autonomic nervous drive during a sudden arousal from rest. Phases 1 and 2 appear to be selective and specific indexes of changes in SA-nodal parasympathetic and sympathetic tone, respectively. The selective denervation unmasks during stress a component of HR control that occurs in the absence of adrenergic or cholinergic mechanisms. These data suggest that multiple interactions occur within the intrinsic ganglion plexuses of the heart with respect to HR control.

Animals↗

Effect of chronic hypoxia on breathing and EMGs of respiratory muscles in awake ponies.

Breathing, diaphragmatic and transversus abdominis electromyograms (EMGdi and EMGta, respectively), and arterial blood gases were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in intact (n = 11) and carotid body-denervated (CBD, n = 9) awake ponies. In intact ponies, arterial PCO2 was 7, 5, 9, and 11 Torr below control (P less than 0.01) at 1 and 10 min and 5 and 24-48 h of hypoxia, respectively. In CBD ponies, arterial PCO2 was 3-4 Torr below control (P less than 0.01) at 4, 5, 6, and 24 h of hypoxia. In intact ponies, pulmonary ventilation, mean inspiratory flow rate, and rate of rise of EMGdi and EMGta changed in a multi-phasic fashion during hypoxia; each reached a maximum during the 1st h (P less than 0.05), declined between 1 and 5 h (P less than 0.05), and increased between 5 and 24-48 h of hypoxia. As a result of the increased drive to the diaphragm, the mean EMGdi was above control throughout hypoxia (P less than 0.05). In contrast, as a result of a sustained reduction in duration of the EMGta, the mean EMGta was below control for most of the hypoxic period. In CBD ponies, pulmonary ventilation and mean inspiratory flow rate did not change during chronic hypoxia (P greater than 0.10). In these ponies, the rate of rise of the EMGdi was less than control (P less than 0.05) for most of the hypoxic period, which resulted in the mean EMGdi to also be less than control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Physical activity, ageing, and psychological well-being: an overview of the research.

Research has shown that physical activity leads to greater psychological well-being for many young and middle-aged individuals. This paper reviews studies to determine whether there is also evidence for an association between physical activity and psychological well-being across the life span, or in the elderly. Several methodological problems related to exercise, ageing, and psychological well-being are explored. Although an association between exercise and mental well-being in the elderly is noted, there is little experimental evidence to support a conclusion that physical activity is causally related to enhanced psychological well-being in the elderly. Methodological problems, a paucity of well-controlled studies, and equivocal findings regarding the topic make it premature to conclude that physical activity leads to enhanced mental health in elderly persons.

Affect↗

Norepinephrine and alpha-2 adrenoceptors modulate active ion transport in porcine small intestine.

The effects of norepinephrine (NE) were examined on active ion transport in the porcine distal jejunum under base-line conditions and after electrical transmural stimulation (ETS). Serosal administration of NE decreased basal short-circuit current across sheets of muscle-stripped jejunal submucosa-mucosa in vitro. These effects were absent in tissues pretreated with the neuronal conduction blocker, tetrodotoxin. NE stimulated net Na secretion in tissues which displayed basal net Na and Cl absorption and increased net Cl absorption in tissues which displayed net Na absorption and Cl secretion under base-line conditions. Moreover, NE inhibited short-circuit current elevations produced by ETS (300 pulses at 10 Hz, 0.5 msec pulse duration, 2.8 mA cm-2), the ganglionic stimulant dimethylphenyl-piperazinium or the gut peptide neurotensin. In contrast, NE did not alter mucosal responses to the directly acting secretagogues forskolin and carbachol. The inhibitory action of NE on mucosal responses evoked by ETS were selectively antagonized by the alpha adrenoceptor blockers phentolamine and yohimbine. Moreover, the selective alpha-2 adrenoceptor agonists p-aminoclonidine, UK-14,304 and oxymetazoline and the NE releasing agent tyramine mimicked the inhibitory effects of NE on ETS-evoked mucosal responses. Desipramine, a blocker of neuronal NE uptake, produced a 1000-fold increase in the potency of NE at concentrations less than 1 nM. These results suggest that NE modulates active ion transport by interacting with alpha-2 adrenoceptors located on submucosal neurons of the porcine small intestine.

Adrenergic alpha-Agonists↗

Substance P produces sodium and bicarbonate secretion in porcine jejunal mucosa through an action on enteric neurons.

The neuropeptide substance P (SP) produces transient elevations in short-circuit current (Isc), a measure of active ion transport, across sheets of small intestinal mucosae from several animal species, but the ionic basis of this action remains unknown. The aim of this study was to test the hypothesis that SP promotes electrogenic anion secretion in the porcine proximal jejunum, an intestinal segment analogous to the human upper small intestine. Sheets of jejunal mucosa with attached submucosa responded to serosal (S), but not luminal (L) addition of 0.1 microM SP with a transient increase in Isc that was reduced in tissues pretreated with the Na(+)-K(+)-Cl- cotransport inhibitor bumetanide (10 microM) or bathed in media lacking Cl- or HCO3- ions. SP produced biphasic effects on transepithelial Na+ and Cl- fluxes; it initially stimulated a L-directed Na+ secretory flux during a 5-min period in which peptide-induced Isc elevations were maximum. The return of the Isc to base-line levels was temporally associated with an increase in L-directed Cl- transport. Both effects of SP were absent in tissues either pretreated with the neuronal conduction blocker tetrodotoxin (0.1 microM) or bathed in HCO3(-)-deficient media. Bumetanide abolished the Na+ secretory actions of SP, but did not affect peptide-induced Cl- secretion. pH-Stat titration experiments revealed that mucosal sheets alkalinized the L bathing medium at a rate twice that of the S medium. SP simultaneously increased and suppressed L and S alkalinization, respectively; this effect presumably represents HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurokinin receptors and mucosal ion transport in porcine jejunum.

Neurokinin (NK) peptides such as substance P (SP) may modulate epithelial ion transport in the small intestine. The present study was undertaken to examine the pharmacological mechanisms by which SP and its endogenous homologs NKA and NKB affect active electrolyte transport in the mucosa of porcine jejunum. Neurokinins and NK agonist analogs increased short circuit current, a measure of active ion transport, across sheets of jejunal mucosa-submucosa with the order of potency: SP greater than [beta-Ala8]NKA4-10 greater than or equal to [Sar9,Met(O2)11]SP greater than NKA = Arg-NKB greater than NKB after their addition to the serosal aspect of tissues (SP EC50 = 11 nM). Epithelial responses to SP or NKA underwent rapid autotachyphylaxis and unidirectional cross-tachyphylaxis after repeated peptide administration. The neuronal conduction blocker tetrodotoxin significantly reduced NK efficacy. SP activity was significantly reduced in tissues pretreated with the muscarinic cholinoceptor blocker atropine or the eicosanoid synthesis inhibitor eicosa-5,8,11,14-tetraynoic acid. NK peptides increased contractility in longitudinally oriented strips of jejunal smooth muscle with an order of potency: [Sar9,Met(O2)11]SP greater than SP greater than Arg-NKB = [beta-Ala8]NKA4-10 greater than or equal to NKB = NKA (SP EC50 = 11 nM). SP-induced contractions were reduced by 70 to 80% in tissues pretreated with atropine or the neuronal Ca++ channel blocker, omega-conotoxin. [125I]Bolton-Hunter-substance P (BHSP) bound specifically to a single population of sites in slide-mounted sections of mucosa-submucosa and smooth muscle with Kd = 0.3 and 0.1 nM and Bmax = 18 and 31 fmol/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Patterns of social affiliation as predictors of depressive symptoms among urban blacks.

This paper focuses on patterns of social affiliation viewed historically as sociocultural adaptations to stresses associated with minority group status. Data are from a community-based sample of 927 Black adults residing in a large metropolitan area. Specifically, this analysis assesses the extent to which patterns of social affiliation such as close family ties, religious involvement, and participation in voluntary associations diminish the detrimental impact of chronic economic strain on the level of depressive symptoms. The findings provide no support for a sociocultural adaptation explanation. Moreover, the results show an unexpected relationship among religious involvement, chronic economic strain, and depressive symptoms. At the most intense levels of religious involvement, a significantly higher level of depressive symptomatology was evident among those experiencing chronic economic strain. In contrast, those with less religious involvement had fewer depressive symptoms when experiencing chronic economic strain. Implications of findings are discussed relative to social changes affecting patterns of affiliation and sociocultural adaptation in Black communities.

Adolescent↗

Position- and fibre type-dependent selectivity by regenerating motor axons in reformation of the topographical projection to the glutaeus muscle in the adult toad (Bufo marinus).

The toad glutaeus magnus muscle receives a topographical innervation dependent on the rostrocaudal origins of glutaeus motor axons on the spinal cord. The same projection is re-established in adult animals after cutting the glutaeus muscle nerve and allowing regenerating axons to reinnervate the muscle (Brown and Everett (1990) J. Comp. Neurol. 292:363-372). To determine whether the topographically selective reinnervation of the glutaeus muscle comes about because of genuine positional qualities associated with the pre- and post-synaptic tissues, we undertook two different experimental procedures: first, the nerve supply to the muscle was cut and redirected to ensure that regenerating axons entered the muscle via entirely novel pathways; and second, the triceps femoris nerve was cut so that the glutaeus muscle was reinnervated from a large pool of motor axons which were mostly foreign but segmentally appropriate. The motor projection to the muscle was determined by the glycogen depletion procedure; single glutaeus motor axons were repetitively stimulated in vitro to deplete muscle fibres of their stores of glycogen. The spatial location of fibres belonging to single motor units could then be determined by staining sections of the muscle histochemically for glycogen. A similar to normal projection was re-established after both experiments in that rostrally located motor axons innervated mostly the ventral portion of the muscle and caudal axons mostly the dorsal portion of the muscle. "Intermediate" axons synapsed predominantly with fibres in the middle of the muscle. Furthermore, the arrangement of fibre types in the muscle could not fully account for the reformation of the topographical projection by a type matching mechanism, although a secondary role for fibre types in the subsequent refinement of the projection was clearly suggested by our findings. Our results provide evidence for a distinction between at least two determinants that influence the reinnervation of muscle: positional cues and fibre types, with the former taking precedence over the latter.

Animals↗

Modulation of Na+, Cl- and HCO3- transport by carbachol in pig distal jejunum.

Acetylcholine and cholinomimetics such as carbachol are potent stimulants of epithelial Cl- secretion in the small and large intestines of several mammalian species. In this study, the effects of carbachol were characterized in vitro on active ion transport in sheets of submucosa-mucosa from the distal jejunum of swine. Carbachol (10 microM) produced an increase in serosa-positive short-circuit current (Isc) in this tissue after its serosal, but not luminal administration. The Na(+)-K(+)-Cl- transport blocker bumetanide (10 microM) produced a 50% decrease in the carbachol-induced Isc elevation after its serosal administration. Peak increases in Isc evoked by carbachol were significantly reduced by 60-85% in tissues bathed in media lacking Cl-, HCO3-, or both anions. The initial drug-induced increase in net charge transfer from serosa to lumen was dependent upon both HCO3- and Cl-, whereas sustained elevations in charge transfer were dependent upon extracellular Cl- only. Radiotracer flux analyses revealed that the drug decreased net Na+ absorption and increased Cl- secretion. In the absence of HCO3-, carbachol decreased Cl- absorption. The effects of carbachol on HCO3- transport were examined by pH-stat titration. The drug rapidly alkalinized the luminal medium immediately after its serosal administration. These results suggest that carbachol stimulates electrogenic anion secretion in the mucosa of the porcine distal jejunum. Furthermore, the ability of carbachol to inhibit spontaneous Na+ absorption is dependent upon extracellular HCO3-.

Animals↗

Cholinergic neurons and muscarinic receptors regulate anion secretion in pig distal jejunum.

The neurotransmitter acetylcholine is thought to modulate epithelial ion transport in the mammalian small intestine. In this study, the non-selective acetylcholine agonist, carbachol, produced rapid changes in short-circuit current (Isc), an electrical measure of active anion secretion, across isolated sheets of the distal jejunal mucosa-submucosa from swine. The potency of carbachol in elevating Isc was decreased 26-fold in the presence of 10 nM atropine, but remained unchanged by 1-100 microM hexamethonium or 0.1 microM tetrodotoxin. The acetylcholine antagonists produced little or no decrease in spontaneous Isc, whereas tetrodotoxin decreased Isc by 54 microA/cm2. [3H]Quinuclidinyl benzilate (QNB), a muscarinic acetylcholine receptor blocker, bound to a single species of sites within the mucosa-submucosa with a KD = 38 pM and Bmax = 94 fmol/mg protein. Selective muscarinic acetylcholine receptor blockers competed with [3H]QNB for this site with a rank order of affinity indicative of an interaction with a M3-muscarinic acetylcholine receptor. Specific [3H]QNB binding sites were autoradiographically localized in the jejunal wall to the epithelium, submucosa and muscularis propria. Transmural electrical stimulation (3-600 pulses/10 s, 0.5 ms, 60 V) of the mucosa-submucosa produced increases in Isc which were dependent upon the number of impulses delivered and did not undergo tachyphylaxis upon repeated stimulation. Responses to electrical transmural stimulation were inhibited by atropine and hexamethonium, as well as the respective neuronal Na+ and Ca2+ channel blockers tetrodotoxin and omega-conotoxin GVIA, suggesting that electrical transmural stimulation depolarizes submucosal cholinergic neurons which terminate on ion-transporting epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Detection of human papillomavirus types 6 and 11 E4 gene products in condylomata acuminatum.

Polyclonal antiserum to an Escherichia coli-produced beta-galactosidase/E4 fusion protein of human papillomavirus type 6b (antiserum 256), and affinity purified HPV 11 anti-E4 antibodies were tested for reactivity in Western blots with bacterially expressed trpE/E4 fusion proteins of HPV types 6b, 11, 16, and 18. To further characterize the affinity purified anti-E4 antibodies, a dot-immunobinding assay was performed using overlapping synthetic HPV 11 E1E4 peptides as antigens. Protein extracts of condylomata acuminatum from 18 patients containing HPV type 6 or 11 DNA sequences were tested in Western blots using antiserum 256 or affinity purified HPV 11 anti-E4 antibodies. In the Western blots of the trpE proteins, antiserum 256 identified the HPV types 6b and 11 fusion proteins; the affinity purified HPV 11 anti-E4 antibodies identified only the HPV 11 fusion protein. In the dot-immunobinding assay, three HPV 11 peptides were recognized, each containing a shared 8 amino acid sequence that differs significantly from the corresponding sequences of HPV types 6b, 16, or 18. In the Western blots of protein extracts from 18 condylomata acuminatum samples shown to contain HPV types 6 or 11 DNA, putative E4 gene products were identified in six samples by antiserum 256. The affinity purified HPV 11 anti-E4 antibodies identified putative E4 gene products in one of these same six lesions, which was shown to contain HPV 11 sequences by the Southern blot method. All six samples containing E4 gene products were from women. Three of these women were pregnant, one had serum antibodies to the human immunodeficiency virus, and one was a renal transplant recipient receiving glucocorticoids.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Regulation of ion transport in porcine distal colon: effects of putative neurotransmitters.

Porcine distal colon epithelium was mounted in Ussing chambers and bathed with porcine Ringer's solution. The effects of vasoactive intestinal polypeptide, norepinephrine, and carbamylcholine on Na and Cl fluxes and transepithelial electrical parameters were determined after their serosal administration. Vasoactive intestinal peptide increased the Cl-dependent component of the short-circuit current with a half-maximal effect at 115 nmol/L. Transepithelial Na and Cl flux studies demonstrated that the increase in current was caused by stimulation of Cl secretion. Norepinephrine also stimulated Cl secretion and increased the serosal-to-mucosal Na flux, producing a half-maximal effect at 1.6 mumol/L. Selective blockade of alpha 1 adrenoceptors by 0.5 mumol/L prazosin produced an eightfold decrease in norepinephrine potency. Carbamylcholine produced a significant increase in Cl secretion and decreased absorption of both Na and Cl with a concentration of 10 mumol/L producing a half-maximal effect. The muscarinic cholinoceptor blocker atropine (0.1 mumol/L) produced a 22-fold decrease in carbamylcholine potency. The effects of all three transmitter substances were unaffected after pretreatment of tissues with the neuronal conduction-blocker tetrodotoxin or an inhibitor of arachidonic acid metabolism. These results indicate that (a) vasoactive intestinal polypeptide stimulates Cl secretion without affecting Na absorption; (b) norepinephrine acting through alpha 1 adrenoceptors stimulates net Cl secretion and activates a serosal-to-mucosal Na transport mechanism; and (c) carbamylcholine acting through muscarinic receptors stimulates Cl secretion and inhibits Na and Cl absorption.

Animals↗