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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 307 records · Page 17Linked to original sources
PubMed1990

Neurotensin binding sites in porcine jejunum: biochemical characterization and intramural localization.

Neurotensin is present in high concentrations in the mammalian gut, especially in enteroendocrine cells of the mucosa. Exogenous neurotensin has been shown to alter ion transport by the mucosa and contractile activity of intestinal smooth muscle. The purpose of this study was to determine the distribution of neurotensin binding sites within the intestinal wall. Initially, biochemical characteristics of [125I]neurotensin binding sites were determined within two preparations of the distal porcine jejunum: (1) the mucosa and submucosa, and (2) the circular and longitudinal muscle with their intramural plexuses. Ligand binding data for the preparation including the mucosa and submucosa indicated that [125I]neurotensin bound specifically to two sites having apparent equilibrium dissociation constants of approximately 0.046 and 0.37 nM. A binding site with a dissociation constant of approximately 0.38 nM was confirmed for the preparation of muscle and associated intramural plexuses. Xenopsin and neurotensin were equipotent to neurotensin in competing for these binding sites; neuromedin N was approximately 40 times less potent in the preparation of mucosa and submucosa. Receptor autoradiography was used to determine the distribution of [125I]neurotensin binding sites within the wall of the jejunum. Autoradiograms of [125I]neurotensin bound to cross sections of the proximal and distal jejunum showed that the highest densities of silver grains were associated with the internal submucosal ganglia, external submucosal plexus and myenteric ganglia. A moderate density of silver grains was associated with the circular muscle. The localization of neurotensin binding sites to submucosal ganglia is consistent with observations that neurotensin effects on active anion secretion by the mucosa are blocked by tetrodotoxin. Immunohistochemical localization of neurotensin in the porcine jejunum demonstrated a limited population of neurotensin immunoreactive cells within the mucosal epithelium. It is possible that neurotensin released from these cells in the mucosa as well as neurotensin-related peptides released from enteric neurons may be the endogenous ligands for the binding sites visualized in this study.

Animals↗
PubMed1990

A temporally detailed reanalysis of the conditional heart rate response in dog.

We used rapid (500 Hz) digital sampling to derive a detailed analysis of the HR conditional response in dog (n = 11) to a 30-sec tone (CS+) followed by a 1/2-sec shock. We found an initial bradycardia at 1.5 +/- 1.0 sec in 6 of 11 dogs from a pre-CS+ control of 85 +/- 26 bpm (mean +/- SD) to 74 +/- 25 bpm (p less than 0.05). In 9 of the 11 dogs there was a subsequent rapid (19.9 +/- 6.7 bpm/sec) increase (+26 +/- 10 bpm) in HR lasting from 1.3 +/- 0.9 to 2.7 +/- 1.0 sec. This was followed by a second, larger (+41 +/- 16, p less than 0.05), but slower (4.0 +/- 2.4 bpm/sec, p less than 0.05) tachycardia which lasted from 4.9 +/- 1.0 to 13.5 +/- 2.6 sec. The peak HR (131 +/- 27 bpm) was attained at 15.0 +/- 3.8 sec, after which HR fell slowly (-2.4 +/- 1.4 bpm/sec) to an average of 92 +/- 29 bpm at 28.6 +/- 1.4 sec (i.e., approximately 1.4 sec prior to shock delivery). This analysis revealed trends in the conditional HR response which were not discernible in individual trials and were obscured in the more traditional analyses of the conditional HR response.

Animals↗
PubMed1990

Hemodynamic and arrhythmogenic effects of aversive stress during myocardial ischemia.

Pavlovian conditioning was accomplished in two groups of dogs by following a 30-s tone (the CS+) with a short (less than or equal to 1 s) electric shock). An inflatable occluder was implanted around the left circumflex coronary artery in all animals. The CS+ was presented to Group I dogs (n = 6) during control (i.e., no coronary occlusion) and at 30 s and 3 min after the onset of a 4-min left circumflex coronary occlusion. The CS+ evoked a robust increase in heart rate and blood pressure in the control state. A conditional cardiovascular response was still evoked during the acute coronary occlusion despite the evolving myocardial ischemia. No increase in ventricular ectopic beats occurred during the CS+. An anterior myocardial infarction (16.8 +/- 1.7% of left ventricular mass, mean +/- SEM) was created in Group II dogs (n = 8) at the time of surgery. A CS+ was presented, as above, both alone and 1 min after the beginning of a 2-min left circumflex coronary occlusion. There were significant differences in the conditional response in heart rate, left ventricular (systolic) pressure (LVP) and d(LVP)/dt for trials given during the coronary occlusion compared with no occlusion. These dogs were then classified as 'resistant' or 'susceptible' to ventricular arrhythmias approx. 4 weeks later using an exercise and coronary occlusion test. Three of five susceptible dogs, but none of three resistant dogs, evidenced increased severity of arrhythmias during the CS+. We conclude that the nature of the cardiovascular response to behavioral stress during myocardial ischemia depends in part upon the timing of the CS+, the presence or absence of a resident myocardial infarction and the status of the autonomic reflexes controlling the heart.

Animals↗
PubMed1990

Actions of neuropeptide Y on basal, cyclic AMP-induced and neurally evoked ion transport in porcine distal jejunum.

Neuropeptide Y (NPY) and its homolog, peptide YY, are present respectively in neurons and endocrine cells within the mammalian small intestine. In this study, we examined the actions of NPY on ion transport in the porcine distal jejunum mucosa-submucosa in vitro. Peptide YY and NPY were equieffective in producing rapid and sustained decreases in basal short-circuit current (Isc), a bioelectrical measure of active ion transport, eliciting half-maximal decreases at respective serosal concentrations of 0.8 and 30 nmol/l. NPY-induced changes in Isc were due to increased mucosa-to-serosa and net Cl fluxes and were not affected by the absence of extracellular HCO3 ions. NPY activity was correlated with the magnitude of the basal Isc and appeared to depend on the spontaneous production of eicosanoids. The peptide also decreased Isc stimulated by forskolin and 8-bromo-cyclic AMP, but the ionic bases for this effect were complex and differed from those determined under basal conditions. NPY attenuated increases in Isc produced by electrical stimulation of enteric neurons with an IC50 = 5 nmol/l. The actions of the peptide on basal and cyclic AMP-induced ion transport were abolished by the neuronal conduction blocker tetrodotoxin, but not by the opiate antagonist naloxone. The alpha-adrenoceptor blocker phentolamine diminished the effects of NPY on basal, but not cyclic AMP-induced Isc. These results indicate that NPY is capable of modulating NaCl transport in the porcine jejunal mucosa under several different conditions. Furthermore, the effects of the peptide are mediated in part through noradrenergic nerves as well as enteric neurons of unknown chemical identity.

Animals↗
PubMed1990

Human papillomavirus infections of the genital tract.

Infection of the genital tract by HPV is a sexually transmitted disease of increasing prevalence. The association of HPV infection with genital tract malignancies is of great concern, and further studies are needed to clarify this association. Few investigators believe at this time that proof of a direct causative role exists for HPV in these cancers, but indirect evidence of such a role is abundant. There are many clinical forms of HPV infection of the genital tract, and few clinicians can easily recognize them all. Treatment of condyloma acuminatum is difficult and frustrating. Cryotherapy with liquid nitrogen is the safest and most effective therapy for most forms of condyloma acuminatum. Recurrence of condyloma acuminatum is common with all presently used forms of therapy, probably owing to latent HPV infection in normal-appearing skin. No form of treatment is ideal for all forms of condyloma acuminatum, but without continued efforts to find better therapeutic modalities and preventative measures, the epidemic of genital HPV infection will continue unchecked.

Condylomata Acuminata↗
PubMed1990

Racial differences in prevalence of phobic disorders.

Few community-based field studies have examined racial differences in the prevalence of phobia disorders. Using data from two sites of a large epidemiologic survey, this study investigates risk factors associated with the one-month prevalence of phobia disorders from 2340 black and 3936 white respondents. Findings indicate that recent prevalence is higher for blacks than whites, with racial differences remaining even when demographic and socioeconomic factors are held constant. Additional significant risk factors for recent phobia pertained to site and being female, being young, and having low education attainment.

Adolescent↗
PubMed1990

Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise.

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.

Blood Pressure↗
PubMed1990

Intrinsic neuroregulation of ion transport in porcine distal jejunum.

The roles of spontaneous and electrically stimulated neural activity on mucosal ion transport were examined in the distal jejunum of the pig, an omnivorous species whose digestive function bears similarities to that of humans. Serosal administration of the neuronal conduction blocker tetrodotoxin (TTX; 0.1 mumol/l), the presynaptic Ca channel blocker omega-conotoxin GVIA (0.1 mumol/l) and the ganglionic-blocking agent hexamethonium (0.1 mmol/l) decreased basal short-circuit current (Isc) across sheets of jejunal mucosa-submusa in vitro. The TTX-induced change in Isc was attributable to an increase in net Cl absorption. Electrical transmural stimulation (ETS; 300 pulses at 0.5, 3 or 10 Hz, 0.5-msec pulse width, 2.8 mA cm-2) of the mucosa-submucosa produced a frequency-dependent increase in Isc and an increase in net anion secretion. TTX, conotoxin and hexamethonium produced concentration-dependent decreases of the ETS-evoked increase in Isc, indicating that ETS depolarizes enteric neurons and suggesting that cholinergic neurons synapsing with submucosal neurons play a significant role in mediating ETS-evoked ion transport. The ETS-induced Isc appears to be mediated by neurons containing acetylcholine but not substance P or vasoactive intestinal polypeptide. These results suggest that submucosal noncholinergic neurons tonically limit Cl but not Na absorption. Electrical depolarization of submucosal neurons evokes anion secretion which appears to be mediated by cholinergic neurons as well as neurons of unknown chemical identity.

Acetylcholine↗
PubMed1990

Neurohormonal regulation of ion transport in the porcine distal jejunum. Actions of somatostatin-14 and its natural and synthetic homologs.

The tetradecapeptide somatostatin-14 (SS-14) has been found to alter electrogenic ion transport in the rat, guinea pig and rabbit intestinal mucosa in vitro. In this study, the actions of SS-14 and related peptides on mucosal ion transport were investigated in the intestinal tract of the pig, a species whose digestive physiology is similar to man. The contraluminal- but not luminal-side administration of SS-14 (1-1000 nmol/l) to sheets of mucosa-submucosa obtained from different regions of the porcine small intestine and colon produced rapid, sustained decreases in short-circuit current (lsc), a measure of active ion transport, that were localized to segments of the distal jejunum. The magnitude of this peptide action was greater in tissues manifesting a serosapositive basal potential difference greater than 0 mV than in those displaying a spontaneous potential difference less than 0 mV. Under basal conditions, SS-14 produced a maximum decrease in distal jejunal lsc which was nearly twice that produced by its synthetic analog SMS 201,995 (octreotide); the two peptides inhibited lsc with similar potencies. SS-14 (10 nmol/l) increased the lumen-to-serosa transepithelial Cl flux and eliminated net residual flux. Mucosal lsc responses to SS-14 were absent in tissues bathed in HCO3-free media. Peptide actions were generally resistant to inhibitors of epithelial anion exchange, Na-proton exchange and NaCl cotransport. The adenylate cyclase activator forskolin (1 mumol/l) and the cyclic AMP analog 8-bromo-cyclic AMP (0.3 mmol/l) evoked net Cl secretion which was associated with rapid and sustained elevations in lsc.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Compartmental and topographical distributions of axons in nerves to the amphibian (Bufo marinus) glutaeus muscle.

The present work seeks to determine if axons to an amphibian muscle are segregated in nerve trunks between the spinal cord and muscle according to their primary nerve destination or their topographical projection in the muscle. The distribution of axons to different compartments and subcompartments of the amphibian (Bufo marinus) glutaeus muscle has been determined in transverse sections of spinal and limb nerves after retrogradely labelling the axons with horseradish peroxidase. Glutaeus axons were dispersed widely through spinal nerves 8 and 9 but loosely gathered together in one quadrant of the sciatic nerve after passing through the lumbar plexus. Glutaeus axons became tightly clustered to the exclusion of other axons along the length of the triceps femoris nerve after it divides from the sciatic nerve. Furthermore, axons destined for one of the two glutaeus primary nerve branches segregate from those of the other branch at the level of the triceps femoris nerve before the glutaeus nerve forms. On the other hand, motoneurones that subserve a primary branch are not segregated, but are found throughout the rostrocaudal extent of the glutaeus motoneurone pool. Injection of horseradish peroxidase under the epimysium of either the ventral or the dorsal surfaces of the glutaeus muscle labelled motoneurones preferentially in either the rostral or caudal part of the motoneurone pool, respectively. This confirms studies that have shown a topographical projection from the spinal motoneurone pool onto the glutaeus muscle. However, there was no segregation of dorsally projecting axons in the glutaeus and primary nerve branches. Thus, glutaeus axons segregate according to their muscle compartmental projections well before entering the muscle, but they show no organization in nerves with respect to their topographical projections within a compartment.

Animals↗
PubMed1989

Breath hydrogen excretion as a screening test for the early diagnosis of necrotizing enterocolitis.

We measured breath H2 excretion in 122 neonates from birth to 1 month of age. The patients weighed less than 2000 g at birth and thus were at risk for developing necrotizing enterocolitis (NEC). Hydrogen excretion was normalized for the quality of the expired air by dividing by the carbon dioxide pressure of the gas sample. The mean (+/- SD) peak H2/CO2 ratio was significantly different between the seven patients who subsequently developed NEC (9.4 +/- 2.7 ppm/mm Hg) and the 115 patients who did not (5.0 +/- 3.5 ppm/mm Hg). The prevalence of NEC was 5.7% in the present study. Defining a positive test as one with a ratio value of greater than or equal to 8.0 ppm/mm Hg, the resulting screening test had a sensitivity of 86% and a specificity of 90%. The screening test yielded a 33% predictive value of a positive test and a 99% predictive value of a negative test. High H2 excretion occurred eight to 28 hours before the earliest clinical signs of NEC. Breath H2 excretion is a simple noninvasive test that may be useful in the management of the premature neonate at risk for the development of NEC.

Breath Tests↗
PubMed1989

Studies on Tanapox virus.

Virus characterization studies were performed to meliorate the taxonomic status of three currently unclassified, serologically related viruses: Tanapox virus (causes vesicular skin lesions in humans), Yaba-like disease (YLD) virus (causes vesicular skin lesions in monkeys), and Yaba monkey tumor virus (YMTV, causes epidermal histiocytoma). These studies included (1) microscopic observations of Tanapox virus cytopathic effect and morphogenesis during its 6-day cytolytic-type growth at 35 degrees in CV-1 monkey kidney cells; (2) resolution of Tanapox virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of nonenveloped and double-enveloped virus particles purified by velocity sedimentation in sucrose and CsCl density gradients; and (3) restriction endonuclease DNA comparison of the three viruses. DNA analysis showed that six recent Tanapox virus isolates from patients in Zaire, Africa, were identical to Tanapox virus, Kenya strain, from 1957 from a patient in the Tana River Valley. In addition, BamHI, MluI, and PstI cleavage sites mapped on the DNA of Kenya Tanapox virus, and PstI sites mapped on DNA of YLD virus differentiated YLD and Tanapox viruses as separate strains. On the other hand, YMTV shared few restriction endonuclease sites with Tanapox and YLD viruses, although all three cross-hybridized extensively. These studies along with published viral characteristics, support the formation of a new poxvirus genus: the suggested name is Yatapoxvirus, and the genus currently comprises two species, Tanapox virus and YMTV.

Cells, Cultured↗
PubMed1989

Jejunal proabsorptive actions of selective opiate agonists administered via the cerebral ventricles.

Non-selective enkephalin analogs, such as [D-Ala2, Met5]enkephalinamide, have been found to increase jejunal absorption in the rat and dog after their intracerebroventricular administration. In the present investigation, experiments were designed to characterize the brain opiate receptor subtype mediating this action in the rat proximal jejunum in situ and to assess the involvement of extrinsic sympathetic nerves innervating this gut region in opioid-induced absorption. Changes in jejunal water transport were examined in rats pretreated with bolus i.c.v. doses (less than or equal to 1 microgram) of the respective mu-, delta-, or kappa-opiate agonists [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAGO), [D-Pen2, D-Pen5]enkephalin or U-50488 and infused intravenously with the secretagogue prostaglandin E1 (PGE1, 5 micrograms/kg-min). In saline-pretreated rats, PGE1 produced large, time-dependent decreases in jejunal fluid absorption. Of the opiate agonists examined, only DAGO in submicrogram doses significantly inhibited PGE1 actions 60 to 90 min after its administration. Extirpation of the celiac and superior mesenteric ganglia, major sources of sympathetic neurons innervating the upper gut, significantly attenuated both the antiabsorptive actions of PGE1 and the proabsorptive actions of DAGO (0.3 micrograms, i.cv.). These results suggest that CNS mu-opiate receptors modulate jejunal absorption in the rat, an action mediated through extrinsic sympathetic nerves innervating the upper small intestine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Stability of the heart rate power spectrum over time in the conscious dog.

The purpose of this experiment was to test the stability of the heart rate (HR) power spectrum over time in conscious dogs. HR was recorded for 1 h for each of six animals on 2 days. A Fast Fourier transform was used to derive the HR power spectrum for the 12 contiguous 5-min epochs comprising the 1-h recordings. Changes in frequency and amplitude of the various spectral peaks were quantitatively examined. We confirm the presence of two major concentrations of power centered around 0.02 (low frequency peak) and 0.32 Hz (high frequency peak). However, we observed variations in these spectral peaks, especially their amplitudes, both within each hour and from day 1 to day 2. The amplitudes of these two spectral peaks tended to vary reciprocally. HR power spectra based on 5 min of recorded data were also derived from an additional eight animals in both the lying and standing positions; the power spectra from these short recordings were sufficiently sensitive to detect redistributions in power due to changes in posture in all eight dogs. We conclude that: 1) data should be recorded for relatively long periods (e.g., 1 h) to characterize the HR power spectrum; 2) some variability in frequency and amplitude will persist across spectra even when based on longer data bases; 3) care should be taken to ensure that the subject's behavioral state is stable within the recording period; 4) shorter (e.g., 5 min) data bases are not suitable except for detecting relatively robust changes in the HR power spectrum.

Animals↗