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Biomedical subjects

J Ren

Publications and source records attributed to J Ren.

At least 289 records · Page 16Linked to original sources

Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans.

BACKGROUND/AIMS: Normal inhibition of lower esophageal sphincter (LES) tone occurs during swallowing and belching. However, it is known that it may occur independently of these functions. The aim of this study was to characterize the effect of pharyngeal water stimulation on resting LES pressure. METHODS: The effect of rapid-pulse and slow continuous intrapharyngeal injection of minute increments of water on the resting tone of the upper and LES of 14 healthy young volunteers was evaluated by concurrent manometry, submental electromyography, and respirography. RESULTS: At a threshold volume, pharyngeal water injection induced an isolated LES relaxation in all volunteers. The threshold volume inducing LES relaxation by rapid-pulse injection, 0.16 +/- 0.01 mL, was significantly lower than that with slow continuous injection (0.5 +/- 0.05 mL) (P < 0.05). The duration and magnitude of LES relaxation were not volume dependent. The duration of LES relaxation induced by rapid-pulse injection was significantly longer than that of swallows. CONCLUSIONS: Minute amounts of liquid injected into the pharynx induce LES relaxation different from that of the normal swallow. Neither the duration nor the magnitude of this relaxation is volume dependent. Whereas the contribution of this finding to the mechanism of transient LES relaxation remains to be ascertained, it may partially explain the variability of the basal LES pressure.

Adult↗

Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum.

BACKGROUND & AIMS: Acid has been shown to stimulate calcitonin gene-related peptide (CGRP) release from peripheral sensory afferent nerve endings in the stomach. The aim of this study was to determine whether endogenous CGRP was involved, by a neurocrine mechanism, in acid-mediated stimulation of somatostatin and inhibition of gastrin release. METHODS: A two-compartment sleeve of antral mucosal/submucosal tissue was perfused to determine sensory nerve and endocrine cell responses to luminal acid. CGRP receptor antagonist, CGRP8-37, was used to inhibit the actions of endogenously released CGRP. RESULTS: Perfusion of the antral sleeve lumen with media of increasing hydrogen ion concentration caused pH-dependent increases in CGRP and somatostatin release and decrease in gastrin release. CGRP8-37 inhibited significantly basal somatostatin (-36%) and stimulated basal gastrin (+65%) release (P < 0.02). Furthermore, CGRP8-37 administration prevented luminal acid-mediated inhibition of gastrin release and stimulation of somatostatin release. These results indicate that CGRP8-37 prevented acid-mediated feedback inhibition of gastrin release and acid-induced feedforward somatostatin release. CONCLUSION: These results suggest that CGRP plays an important role in the response of antral D and G cells to luminal acid and that local effector action of endogenous CGRP participates in regulation of antral regulatory peptide secretion.

Analysis of Variance↗

Esophagopharyngeal distribution of refluxed gastric acid in patients with reflux laryngitis.

BACKGROUND & AIMS: A variety of otolaryngological abnormalities have been attributed to the contact of gastroesophageal refluxate with respective structures of the aerodigestive tract. The aim of this study was to determine and compare the pharyngoesophageal distribution of gastric acid refluxate between patients with proven laryngitis attributed clinically to gastroesophageal reflux and three control groups. METHODS: An ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring technique was used to measure reflux parameters in the pharynx, proximal esophagus, and distal esophagus. RESULTS: Between-group comparison showed no significant difference in the reflux parameters in the distal esophagus between the studied groups. A significantly higher percentage of distal reflux episodes reached the proximal esophagus in the laryngitis group than in the control groups (P < 0.01), and the number of pharyngeal reflux episodes and time of acid exposure were significantly higher in the laryngitis group than in the control groups (P < 0.001). CONCLUSIONS: Compared with normal controls and patients with gastroesophageal reflux disease, pharyngeal reflux of gastric acid is significantly more prevalent and the ratio of proximal to distal esophageal acid reflux episodes is significantly increased in patients with posterior laryngitis. Simultaneous three-site ambulatory pharyngoesophageal pH monitoring may provide supporting evidence when the diagnosis of reflux-induced aerodigestive tract lesions is considered.

Adult↗

Deglutitive aspiration in patients with tracheostomy: effect of tracheostomy on the duration of vocal cord closure.

BACKGROUND/AIMS: Deglutitive aspiration in patients with tracheostomy has been attributed to impaired laryngeal movement, loss of protective laryngeal reflexes, and uncoordinated laryngeal closure. The aim of this study was to determine the effect of tracheostomy on the duration of deglutitive vocal cord closure. METHODS: Using concurrent videoendoscopy, respirography, and submental electromyography, deglutitive vocal cord closure and its temporal relationship with deglutitive apnea was compared between patients with tracheostomy and normal volunteers. RESULTS: Between-group comparison showed that the duration of vocal cord adduction/abduction in patients with tracheostomy was significantly shorter than that of normal volunteers (P < 0.05). Contrary to normal volunteers, in patients with tracheostomy, 5-mL water swallows significantly increased the duration of vocal cord adduction/abduction compared with that of dry swallows (P < 0.05). In addition, in patients with tracheostomy, deglutitive apnea and submental electromyography were not coordinated with vocal cord kinetics. CONCLUSIONS: Although the vocal cords close completely during swallowing in patients with tracheostomy, their duration of closure is significantly shorter compared with normal volunteers. Coordination of deglutitive vocal cord kinetics, apnea, and submental electromyography is altered in patients with tracheostomy. Contrary to normal controls, duration of deglutitive vocal cord closure in patients with tracheostomy is modified by the presence of liquid bolus.

Adult↗

High resolution structures of HIV-1 RT from four RT-inhibitor complexes.

We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.015 A for all data to 2.2 A. The structures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic interactions and arise from induced shape complementarity achieved by conformational rearrangement of the enzyme and conformational/configurational rearrangement of the compounds.

Amino Acid Sequence↗

Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors.

The structure of unliganded HIV-1 reverse transcriptase has been determined at 2.35 A resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor, HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but there is a significant repositioning of a three-stranded beta-sheet in the p66 subunit (containing the catalytic aspartic acid residues 110, 185 and 186) with respect to the rest of the polymerase site. This suggests that NNIs inhibit RT by locking the polymerase active site in an inactive conformation, reminiscent of the conformation observed in the inactive p51 subunit.

Antiviral Agents↗

Transparent gasbag tie-over for persistent pressure and inspection in free skin grafting.

A simple tie-over dressing using a transparent gasbag, which has been used successfully in skin grafting on rabbits and human beings, allows objective pressure survey and subjective direct inspection of the underlying grafted skin. Moreover, if hematoma or any other complication is recognized, the gasbag can be deflated and removed, being reapplied after the hematoma is expressed or the complication is treated.

Animals↗

The simulation of urban system dynamics in Atlantic Canada, 1951-1991.

"A dynamic urban model is used to study the post-war evolution of the Atlantic Canada urban system. The computer-based simulation model is calibrated for the period 1951-86 and then employed to predict the 1991 population of each CMA and CA within the system. The simulation results show that, to a large extent, the evolution of the system can be understood in terms of endogenous system dynamics rather than exogenous events. Specifically, competition among the cities of the region is a significant factor in the urban system evolution. The high degree of abstraction of the model means that data requirements for application are minimal, and the calibration procedure is relatively simple. The successful predictions show that the model can yield useful results in spite of its simplicity." (SUMMARY IN FRE)

Americas↗

Effect of aging on the secondary esophageal peristalsis: presbyesophagus revisited.

In this study we determined the effect of aging on the capability of the human esophagus to generate secondary peristalsis. We studied nine healthy young (35 +/- 2 yr, 25-45 yr) and nine healthy elderly (74 +/- 3 yr, 70-83 yr) volunteers. We stimulated secondary peristalsis by intraesophageal air injection and balloon distension. All young volunteers exhibited secondary esophageal peristalsis. In four elderly volunteers, secondary peristalsis could not be elicited with injection of any of the tested air volumes. Frequency of stimulation of secondary peristalsis and lower esophageal sphincter (LES) relaxation in response to intraesophageal air distension in the elderly was significantly lower than that in the young (P < 0.01). Stimulation of secondary peristalsis by balloon distension was less consistent compared with the air injection. In conclusion, 1) in the elderly, compared with the young, secondary esophageal peristalsis is either absent or is evoked less frequently after esophageal distension, and complete LES relaxation in response to esophageal air distension is less frequent, and 2) in both young and elderly, secondary esophageal peristalsis is induced more frequently after generalized esophageal distension by air than its segmental distension by a balloon.

Adult↗

Mechanism and timing of nasopharyngeal closure during swallowing and belching.

The mechanism(s) of nasopharyngeal closure (NPC) and its temporal relationship with other biomechanical events during swallowing and belching were studied in seven healthy volunteers, aged 26-39 yr, by concurrent videoendoscopic, videofluoroscopic, and manometric technique. Analysis of the videoendoscopic recordings showed that deglutitive NPC consisted of elevation of the soft palate and adduction of the superior pharyngeal constrictor muscle. Videofluoroscopy identified only the palatal elevation clearly. During belching, however, only palatal elevation occurred. Deglutitive NPC ranged between 0.73 and 0.94 s (0.8 +/- 0.04 SE), with a tendency to be longer with larger swallowed volumes. Onset of NPC was identified earlier endoscopically than as seen fluoroscopically. Complete NPC preceded the arrival of barium bolus into the pharynx, and this pattern was seen for all volumes tested. Manometric onset of upper esophageal sphincter (UES) relaxation was seen before the onset of NPC, but the physical opening of the UES as seen fluoroscopically occurred after complete closure of the nasopharynx. We conclude the following: 1) The mechanism of NPC during swallowing and belching is different. During swallowing, NPC has two tiers of closure, palatal elevation and superior pharyngeal muscle adduction; during belching only palatal elevation occurs. 2) NPC is tightly coordinated with other biomechanical events during swallowing and belching.

Adult↗

Prostaglandin E2 contracts vascular smooth muscle and inhibits potassium currents in vascular smooth muscle cells of rat tail artery.

There is evidence to suggest that PGE2 plays an important role in the regulation of vascular smooth muscle tone. To determine the cellular basis of this action, we studied the effect of PGE2 on force in helical muscle strips from rat tail artery. PGE2 evoked a sustained contractile response. The contractile response was concentration-dependent, with an EC50 value of 9.6 microM. Patch-clamp studies were conducted to investigate the effects of PGE2 on K channels in isolated vascular smooth muscle cells from rat tail artery. Current-clamp studies showed that PGE2 (1 microM) depolarized the membrane by 15.9 +/- 1.3 mV. Under voltage-clamp conditions, a voltage-dependent, delayed outward rectifier K current was generated by stepwise depolarization from a holding potential of -80 mV. The current, which was activated at -45 to -40 mV and showed almost no inactivation, was inhibited by 45% using 10 mM TEA. PGE2 inhibited the outward K current in a concentration-dependent manner, with EC50 values of 3.5 microM and 4.9 microM in primary and subcultured cells, respectively. The PGE2 receptor antagonist sodium meclofenamate abolished the PGE2-induced K current inhibition. Furthermore, the intracellular application of guanosine 5'-O(-)[2-thiodiphosphate] (GDP beta S), a G protein inhibitor, and pretreatment of the cells with cholera toxin prevented the PGE2-induced inhibition, whereas application of pertussis toxin did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Role of energy metabolism in nutrition management of critically ill patients].

Indirect calorimetric measurements were made with a MedGraphics Critical Care Monitor (CCM) desktop analysis system in the observation of critically ill and malnourished patient's energy expenditure. In 15 critically ill patients, predicted energy requirements based on 1.75 times BEE calculated by Harris-Benedict formula or corrected Harris-Benedict formula averaged 32.7% and 27.8% greater than metabolic expenditure measured by indirect calorimetry respectively. In the 20 unstressed malnourished patients, predicted energy requirements based on the Harris-Benedict (BEE) formula averaged 15% to 20% higher than metabolic expenditure measured by indirect calorimetry. When the critically ill patients' total energy intakes were 1.2 times resting energy expenditure, their nutritional state could be maintained in normal conditions. While the malnourished patients were provided with 1.5 x REE in energy intake, the malnourished state could be reversed. We believed that the critically ill and malnourished patients' energy expenditures are better measured than predicted and their nutritional regimens should be guided under the computerized indirect calorimetry.

Adult↗

[Effects of over feeding on the energy expenditure and substrates oxidative rate in surgical patients].

In this study, computerized indirect calorimetric measurements were made using a medical graphics critical care monitor (CCM) desktop analysis system in the observation of metabolic state of 20 patients complicated with external gastrointestinal fistula. While these malnourished patients were provided with 1.5 x REE in total energy intake, the malnutrition state could be reversed. But with 1.75 or 2.0 x REE or up total energy intake, the general nutritional state could not be improved faster, the O2 consumption and CO2 production and energy expenditure increased, while the net glucose oxidation increased and net lipid oxidation decreased or net lipogenesis occurred simultaneously. We believed that superfluous energy intake is harmful to critically ill patients and may lead to cell injury and dysfunction.

Adolescent↗

The N-glycosidase mechanism of ribosome-inactivating proteins implied by crystal structures of alpha-momorcharin.

BACKGROUND: alpha-Momorcharin (alpha MMC) is a type I ribosome-inactivating protein. It inhibits protein synthesis by hydrolytically removing a specific adenine residue from a highly conserved, single-stranded loop of rRNA. RESULTS: Here we describe the determination and refinement of the crystal structures of alpha MMC in the native state and in complexes with the product, adenine, and a substrate analogue, formycin 5'-monophosphate (FMP) at high resolution. Both adenine and the base of FMP are tightly bound; the ribose of bound FMP adopts a strained, high-energy conformation, which may mimic the structure of the transition state. CONCLUSIONS: These structures indicate that residues Tyr70, Glu160 and Arg163 of alpha MMC are the most critical for catalysis. We propose that the strained conformation of the ribose in the target adenosine weakens the glycoside bond. Partial protonation mediated by Arg163 then facilitates N-glycoside bond cleavage, leading to the formation of an oxycarbonium ion intermediate which is stabilized by the negatively-charged Glu160. Tyr70 adopts subtly different conformations in the three structures implying that it may be important in substrate recognition and perhaps catalysis.

Amino Acid Sequence↗

Developmental regulation of beta-galactoside alpha 2,6-sialyltransferase in small intestine epithelium.

A striking biochemical alteration to the epithelium of the small intestine upon weaning is the loss of microvillar sialic acids. Antibody and cDNA probes to the beta-galactoside alpha 2,6-sialyltransferase (SiaT-1, EC 2.4.99.1) were used to characterize the expression of this sialyltransferase in the small intestine of suckling rats. SiaT-1 mRNA and protein in the intestinal epithelium are rapidly lost upon weaning, in agreement with the loss of mucosal sialic acids and general sialyltransferase activity. Developmental repression of SiaT-1 is manifested in a proximal to distal gradient; SiaT-1 mRNA and protein are lost first from the duodenum and persist the longest in the ileum. We have previously documented that SiaT-1 gene expression can be transcriptionally initiated from a number of distinct tissue-specific promoter regions. Here, by criteria of mRNA mobility on agarose gels, primer extension analysis, and differential Northern hybridization, we show that the promoter previously considered to be liver-specific is operative in SiaT-1 expression in the small intestine of suckling animals. Comparison of this SiaT-1 promoter region with promoter regions of other genes exhibiting dual intestine-hepatic tissue specificity revealed a number of striking sequence similarities. Regulatory implications and consequences of small intestinal SiaT-1 expression in suckling but not in weaned animals are discussed.

Animals↗

Presynaptic muscarinic receptors modulate acetylcholine release from rat antral mucosal/submucosal nerves.

The purpose of the present studies was to determine whether autoinhibition of acetylcholine release could be demonstrated in vitro from mucosal/submucosal neurons in rat antrum. Rat antral mucosal/submucosal tissues preloaded with [3H]choline were perifused and [3H]acetylcholine release measured under basal and stimulated conditions. Carbachol inhibited both spontaneous and evoked (electrical field stimulation, KCl) acetylcholine release from rat antral tissues: 1 x 10(-5) M carbachol inhibited basal [3H]ACh release maximally to -38.2 +/- 3.1% (P < 0.001 vs control). The nonselective muscarinic antagonist atropine enhanced both basal and stimulated acetylcholine release and abolished carbachol-induced inhibition of acetylcholine release. Pirenzepine, a muscarinic M1 receptor antagonist, inhibited acetylcholine release and did not alter carbachol-induced inhibition of acetylcholine release. In conclusion, acetylcholine release from rat antral mucosal/submucosal neurons is regulated negatively by a presynaptic feedback mechanism involving M2 and/or M3 receptors, while presynaptic M1 receptors facilitate release of neurotransmitter.

Acetylcholine↗