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Biomedical subjects

J L Conklin

Publications and source records attributed to J L Conklin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Nitric oxide modulates a calcium-activated potassium current in muscle cells from opossum esophagus.

Nitric oxide mediates nerve-induced hyperpolarization of circular smooth muscle of the esophagus. Two mechanisms are proposed to explain this hyperpolarization: an increase in K+ current or a decrease in Cl- current. These studies test the hypothesis that nitric oxide increases a K+ current in esophageal smooth muscle. Three outward K+ currents are present in circular smooth muscle cells from the opossum esophagus. One current is a Ca(2+)-activated K+ current (IKCa2+). This current is inhibited by charybdotoxin. Whole cell currents were recorded from isolated opossum esophageal smooth muscle cells using the whole cell patch-clamp technique. These studies showed that IKCa2+ is activated at potentials more positive than -30 mV. Bath application of S-nitroso-L-cysteine increased IKCa2+ by 50% above control levels throughout the entire activation range of potentials. The enhanced current was reversible on washout. Either charybdotoxin, an inhibitor of IKCa2+, or (R)-p-8-(4-chloropenylthio)-guanosine 3',5'-cyclic monophosphorothioate, an inhibitor of protein kinase G, antagonized the increase in outward current induced by S-nitroso-L-cysteine. These data suggest that nitric oxide activates IKCa2+ via the guanosine 3',5'-cyclic monophosphate-protein kinase G signal transduction pathway.

Animals↗
PubMed1995

Co-localization of manganese superoxide dismutase and NADH diaphorase.

Manganese superoxide dismutase (Mn SOD), mitochondrial enzyme, defends against the toxic effects of superoxide radical (O2.-) in pathological processes by catalyzing the conversion of O2.- to hydrogen peroxide (H2O2). The activity of another enzyme, NADH diaphorase, forms the basis for a histochemical method used commonly to demonstrate nerve cell bodies in the enteric plexuses. We found identical patterns of localization of Mn SOD immunoreactivity and NADH diaphorase activity in brain, esophagus, stomach, colon, liver, and kidney. NADH diaphorase enzymatic activity co-migrated with complexes of Mn SOD on a non-denaturing gel. This suggests that the NADH diaphorase may in some way be related to Mn SOD.

Animals↗
PubMed1995

Effects of recombinant human hemoglobin on motor functions of the opossum esophagus.

Chemically altered hemoglobins are being investigated as blood substitutes. They may affect numerous biological processes since free hemoglobin binds nitric oxide (NO). Nitric oxide is a neural mediator of relaxation of the lower esophageal sphincter (LES) and esophageal peristalsis. We hypothesize that recombinant human hemoglobin (rHb1.1) alters esophageal motor function by scavenging NO. Contraction of transverse muscle strips from the opossum esophagus and LES was monitored. Transmembrane potential differences of circular smooth muscle from the esophagus were recorded using glass microelectrodes. Intrinsic esophageal nerves were stimulated electrically. Esophageal manometries were performed with a low-compliance perfused-catheter system. The activity of the enzyme NO synthase was determined with the citrulline assay. Recombinant hemoglobin diminished nerve-induced relaxation of LES muscle but did not alter LES tone. Circular esophageal muscle responded to nerve stimulation with an inhibitory junction potential and a mechanical off response. Recombinant hemoglobin diminished the inhibitory junction potential and shortened the latency of the off response. It increased the velocity of esophageal peristalsis, decreased the amplitudes of these contractions and diminished LES relaxation. Cyanomethemoglobin had little effect on nerve- or swallow-induced responses. Hemoglobin did not inhibit the activity of NO synthase. Recombinant human hemoglobin appears to alter esophageal motor function by scavenging NO.

Amino Acid Oxidoreductases↗
PubMed1994

Acute gastritis associated with spiral organisms from cats.

Numerous studies implicated Helicobacter pylori as one causative agent producing gastritis and dyspepsia. Recent reports focus on another bacterium, Gastrospirillum hominis, as a possible pathogen producing gastritis. We report a 30-year-old researcher who became acutely ill with epigastric pain indicative of esophagitis or peptic ulcer disease. Gastritis and a gastric ulcer were observed endoscopically. Histological examination of the gastric mucosa revealed an acute gastritis and large spiral-shaped organisms. The spiral forms were present in large quantities in the gastric mucosa of experimental animals (cats) handled by the patient in his research. Electron microscopy confirmed that the organisms from the cat and patient were morphologically identical. The patient was successfully treated with bismuth subsalicylate. His symptoms resolved and the organisms were cleared from his stomach. This study provides evidence that another bacterium, a Gastrospirillum, may cause gastritis in man and may be transmitted from animal to man.

Adult↗
PubMed1994

Nerve-mediated nitric oxide production by opossum lower esophageal sphincter.

Antagonists of nitric oxide synthesis inhibit nerve-induced hyperpolarization and relaxation of muscle from the opossum lower esophageal sphincter. These studies test the hypothesis that nitric oxide is released during stimulation of intrinsic esophageal nerves. The intrinsic nerves were stimulated with an electrical field (10-sec trains of 1-msec, 30-V pulses delivered at 10 Hz). Nitric oxide production was measured with a DASIBI model 2108 Chemiluminescence NO Analyzer. NG-Nitro-L-arginine, an inhibitor of NO synthase, antagonized nerve-induced relaxation the lower esophageal sphincter. Nerve stimulation increased NO production from 0.50 +/- 0.04 nmol/min/100 mg tissue to 0.87 +/- 0.07 nmol/min/100 mg tissue (P < 0.01). NG-nitro-L-arginine inhibited both basal (0.030 +/- 0.09 nmol/min/100 mg tissue, P < 0.05 vs baseline) and stimulated (0.38 +/- 0.10 nmol/min/100 mg tissue, P < 0.01 vs stimulated). These studies support the hypothesis that nerve stimulation releases nitric oxide from the lower esophageal sphincter.

Amino Acid Oxidoreductases↗
PubMed1994

Eosinophilic cholecystitis, appendiceal inflammation, pericarditis, and cephalosporin-associated eosinophilia.

A patient with eosinophilic cholecystitis and accompanying eosinophilic appendiceal inflammation, eosinophilic pericarditis, and peripheral eosinophilia is described. Review of the nine previously reported cases of eosinophilic cholecystitis suggests that this is the first case with closely associated eosinophilic appendiceal inflammation and pericarditis as manifestations of a systemic hypereosinophilic syndrome. The possible etiologic role of cephalosporin hypersensitivity is discussed.

Adult↗
PubMed1994

Vasoactive intestinal contractor: localization in the opossum esophagus and effects on motor functions.

BACKGROUND/AIMS: Vasoactive intestinal contractor (VIC), an endothelinlike peptide and a putative gastrointestinal hormone, contracts gastrointestinal smooth muscle. The aim was to study VIC in relation to esophageal function. METHODS: Intramural nerves in opossum esophageal smooth muscle strips were stimulated in the presence of various concentrations of VIC and were stained for VIC immunoreactivity. RESULTS: VIC caused an atropine-resistant increase in the amplitude of nerve-induced contractions of the circular muscle. VIC alone contracted longitudinal muscle, and this effect was nearly eliminated by 1 mmol/L atropine. VIC caused an atropine-resistant increase in the resting tone of the lower esophageal sphincter muscle, but it did not affect nerve-induced relaxation of that muscle. VIC-immunoreactive nerve fibers occurred in the longitudinal muscle layer, in the muscularis mucosae, and around the ducts of esophageal glands. A few such fibers were found in the circular muscle layer. Nerve fibers and cell bodies of the myenteric plexus showed VIC immunoreactivity. In the stomach, immunoreactive nerve fibers occurred in muscularis mucosae and circular muscle but not in longitudinal muscle. CONCLUSIONS: VIC is localized in neuronal elements of the opossum esophagus and excites contractions in esophageal smooth muscle.

Animals↗
PubMed1994

Neuromuscular control of the oropharynx and esophagus in health and disease.

The oropharynx and esophagus convey swallowed materials from the mouth to the stomach and protect the airways from aspiration. These functions are subserved by complex neuromuscular interactions that coordinate the timing of the peristaltic contractions of the swallowing organs. The oropharynx and upper esophagus are composed of striated muscle, whereas the distal esophagus is composed of smooth muscle. The central nervous system completely controls peristalsis in the striated muscle organs. In the distal esophagus, neuromuscular mechanisms intrinsic to the esophagus control peristalsis. Diseases of the striated muscle, of the smooth muscle, or of the nervous system can lead to a derangement of peristalsis and disrupt the propulsion of swallowed materials to the stomach.

Deglutition↗
PubMed1994

Roles of Triton X-100 in NADPH-diaphorase histochemistry.

Triton X-100 is widely but not universally used in NADPH-diaphorase histochemical staining. We investigated its effect on the staining and examined nitroblue diformazan (NBF) production under the influence of Triton X-100. Exposure of opossum esophagus, intestine, and colon tissues to Triton X-100 before staining enhanced staining of nerve cells and fibers and suppressed staining of non-neural structures. Long exposures and high concentrations nearly abolished the staining of non-neural structures and decreased the staining of nerves. The use of an incubation medium containing Triton X-100 achieved the best staining of nerve cells and fibers. Addition of Triton X-100 to the incubation medium changed its color from yellow to purple; in the presence of tissues, this color change occurred much more quickly. Spectral analysis showed that Triton X-100 increases the rate of NBF formation in the presence of tissue supernatant. Triton X-100 increases it less in the absence of tissue supernatant. Therefore, Triton X-100 improves the histochemical staining, probably by catalyzing the activity of NADPH-diaphorase, by keeping the extracellular NBF in solution and thus suppressing the staining of non-neural structures, and by increasing the permeability of cell membranes.

Animals↗
PubMed1993

Characterization and mediation of inhibitory junction potentials from opossum lower esophageal sphincter.

BACKGROUND: Activating nonadrenergic, noncholinergic (NANC) nerves of the lower esophageal sphincter (LES) hyperpolarizes and relaxes its circular smooth muscle. This relaxation is mediated by nitric oxide (NO) or an NO-containing compound. These studies were undertaken to compare the electrophysiological responses of circular smooth muscle from the LES and esophagus in response to NANC nerve stimulation and to test the hypothesis that NO mediates LES hyperpolarization. METHODS: The transmembrane potential difference was recorded with glass microelectrodes. Nerve-mediated membrane responses were evoked by electrical pulses of 0.5 msec duration and 50 V amplitude. RESULTS: Responses of LES muscle differed from those of the esophageal muscle. The duration of hyperpolarization was much longer in sphincteric muscle. The depolarization that followed hyperpolarization of esophageal muscle was not observed in sphincteric muscle. NG-nitro-L-arginine, an inhibitor of NO synthase, attenuated the nerve-induced hyperpolarization. L-arginine, the substrate for NO synthase, antagonized the effect of NG-nitro-L-arginine. Exogenous NO hyperpolarized of the smooth muscle membrane. CONCLUSIONS: These data support the hypothesis that NO or an NO-like compound may mediate nerve-induced hyperpolarization of the opossum LES.

Animals↗
PubMed1992

Guanylate cyclase inhibitors: effect on inhibitory junction potentials in esophageal smooth muscle.

Electrical field stimulation (EFS) of nerves intrinsic to the opossum lower esophageal sphincter (LES) produces LES relaxation, an increase in its guanosine 3',5'-cyclic monophosphate (cGMP) content, and hyperpolarization of its circular muscle membrane potential difference. Activation of esophageal nerves produces an analogous hyperpolarization of the circular esophageal smooth muscle. These studies test the hypothesis that cGMP is an intracellular mediator of this hyperpolarization. The transmembrane potential difference of circular smooth muscle cells was recorded with glass microelectrodes. Nerve-mediated smooth muscle hyperpolarization was evoked by EFS (1 ms, 50 V pulses). Forskolin, an activator of adenylate cyclase, and sodium nitroprusside, an activator of guanylate cyclase, produced hyperpolarization. Cystamine and methylene blue, inhibitors of guanylate cyclase, blocked the hyperpolarization elicited by sodium nitroprusside, but not that by forskolin. Both also reversibly abolished the hyperpolarization evoked by EFS. Membrane-permeable derivatives of cGMP produced a concentration-dependent hyperpolarization. These data support the hypothesis that cGMP is an intracellular mediator of nerve-induced esophageal smooth muscle hyperpolarization.

Animals↗
PubMed1992

Guanylate cyclase inhibitors: effect on tone, relaxation, and cGMP content of lower esophageal sphincter.

Relaxation of the lower esophageal sphincter (LES) results from activation of its intrinsic innervation. This relaxation is associated temporally with an increase in the guanosine 3',5'-cyclic monophosphate (cGMP) content of the muscle. This study tests the hypothesis that variations in the production of cGMP mediate resting LES tone and nerve-induced relaxation. We examined the effects of guanylate cyclase inhibitors, such as cystamine and methylene blue (MB), on the resting tone, resting membrane potential, electrical field stimulation (EFS)-induced relaxation, and cGMP content of circular smooth muscle from the LES of the opossum. Strips of sphincter muscle were placed in a tissue bath and stretched to 125% resting length. Both cystamine and MB increased the resting tone of LES muscle in a concentration-dependent manner (EC50 = 1.1 +/- 0.2, n = 12, and 1.6 +/- 0.4 mM, n = 10, respectively). The increase in tone by cystamine was not blocked by tetrodotoxin, atropine, or propranolol. Cystamine (1 mM) did not alter the resting membrane potential of circular muscle cells of the LES. The removal of extracellular Ca2+ by the addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 4 mM) and nifedipine (1 microM) shortened the duration but not the amplitude of the response to cystamine. Pretreatment with caffeine (5 mM) in the presence of EGTA and nifedipine to deplete intracellular Ca2+ stores blocked the increase in tone by cystamine. Cystamine (1 mM) failed to inhibit LES relaxation induced by EFS. Carbachol, at a concentration that induced a similar increase in base-line tone, attenuated the nerve-mediated relaxation. Cystamine did not alter basal cGMP levels, but inhibited the rise in cGMP induced by EFS. The data indicate that cystamine increases LES tone but does not inhibit EFS-induced relaxation, even though it inhibits EFS-induced increases in cGMP content. The increase in tone is dependent on the presence of intracellular Ca2+ stores.

Animals↗
PubMed1991

Enteric neural modulation of slow-wave activity in cat colon.

These studies test the hypothesis that the generation of colonic slow waves can be modulated by stimulation of intrinsic enteric nerves and attempt to identify a neurotransmitter that may be responsible for this change in slow-wave activity. Isolated segments from the mid-colon of the cat generated regular, continuous slow waves at 6.5 +/- 1.1 cpm. Activation of the intrinsic nerves by electrical field stimulation transiently reduced the rate of slow-wave generation to 4.7 +/- 0.7 cpm (P less than 0.001). The response to electrical stimulation was blocked by tetrodotoxin and alpha-chymotrypsin. The following antagonists were not effective in blocking the response: atropine, hexamethonium, phenoxybenzamine, propranolol, methysergide, naloxone, or imidazole. Vasoactive intestinal polypeptide (5 x 10(-7) M) decreased slow wave frequency to 4.5 +/- 0.4 cpm. Vasoactive intestinal polypeptide (VIP) fragment 10-28 inhibited the effect of electrical field stimulation but also decreased the slow-wave frequency. VIP-immunoreactive nerves were much more abundant in the plexus submucosus extremus than in the circular muscle of the muscularis externa. Thus, pacemakers for colonic slow waves may be modulated by intrinsic colonic nerves, and vasoactive intestinal polypeptide may be the neurotransmitter responsible for this modulation.

Animals↗
PubMed1991

Multifocal colitis associated with an epidemic of chronic diarrhea.

An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea.

Adolescent↗
PubMed1991

Hypertrophic smooth muscle in the partially obstructed opossum esophagus. Excitability and electrophysiological properties.

Partial obstruction of the opossum esophagus leads to thickening of the circular muscle, hypertrophy of smooth muscle cells, and diminution of the extracellular space. The pharmacological and electrophysiological properties of this hypertrophied muscle were studied. Carbachol produced phasic and tonic contractions of the circular muscle. The EC50 for tonic contractions was greater for hypertrophied than for normal muscle (21.1 +/- 3.9 mumol/L vs. 4.8 +/- 2.2 mumol/L; P less than 0.05). The resting membrane potential difference of hypertrophied muscle (-50.8 +/- 0.2 mV) was similar to that of normal muscle (-50.0 +/- 0.2 mV). Electrical stimulation of intrinsic nerves in the normal muscle produced a hyperpolarization followed by a depolarization of smooth muscle membrane potential. Hypertrophied muscle responded either with an attenuated hyperpolarization or no hyperpolarization, both of which were followed by a depolarization. The space constant in the long axes of the hypertrophied circular muscle cells was greater than normal (4.4 +/- 0.2 mm vs. 3.4 +/- 0.1 mm; P less than 0.001). The threshold potential for initiation of action potentials was more negative for hypertrophied (-43.2 +/- 0.4 mV) than for normal circular muscle (-41.6 +/- 0.2 mV; P less than 0.005). These data indicate that alterations in neuromuscular function accompany the hypertrophy of esophageal smooth muscle.

Animals↗
PubMed1991

Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle.

Nonadrenergic noncholinergic (NANC) nerves of the opossum esophagus mediate relaxation of circular muscle from the lower esophageal sphincter (LES) and the off contraction of circular esophageal muscle. The latencies between the end of the stimulus and the off contraction describe a gradient so that the latency is longest in muscle from the caudad esophagus. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase, and NO were used to test the hypothesis whether NO is a mediator of these nerve-induced responses. Both electrical field stimulation (EFS) of intrinsic esophageal nerves and exogenous NO relaxed LES muscle. Only EFS-induced relaxation was inhibited by L-NNA [half-maximal response (EC50) = 60.0 +/- 20.0 microM]. L-Arginine, the substrate for NO synthase, reversed the inhibitory effect of L-NNA. Exogenous NO did not contact circular esophageal muscle. Both the amplitude (EC50 = 14.7 +/- 4.0 microM) and the latency of the off contraction (EC50 = 41.1 +/- 5.6 microM) were diminished by L-NNA. L-Arginine prevented the action of L-NNA. NG-nitro-L-arginine also attenuated the gradient in the latency of the off response by shortening latencies in muscle from the caudad esophagus. It had no effect on cholinergic nerve-induced contraction of longitudinal esophageal muscle. These data support the hypothesis that NO or an NO-containing compound may be a mediator of NANC nerve-induced responses of the esophagus and LES.

Animals↗