Biomedical subjects

J Ren

Publications and source records attributed to J Ren.

At least 235 records · Page 13Linked to original sources

PubMed1998

[Effect of recombinant human growth hormone with total parenteral nutrition on albumin synthesis in patients with peritoneal sepsis].

OBJECTIVE: To investigate the effect of recombinant human growth hormone (rhGH) in combination with total parenteral nutrition (TPN) on albumin synthesis in patients with peritoneal sepsis. METHOD: 17 patients with peritoneal sepsis were divided randomly into two groups. The control group received TPN only for 7 days, and the GH group received both rhGH (12 U/d) and TPN for 7 days. The TPN scheme and other treatment were the same in the two groups. RESULT: Serum albumin, prealbumin, and transferrin concentration were increased in patients in the GH group (P < 0.01), but no apparent effect was observed in the control group (P > 0.05). CONCLUSION: In condition of serious peritoneal sepsis, TPN can not increase albumin, prealbumin, and transferrin synthesis alone, whereas rhGH in combination with TPN significantly increase the synthesis of visceral proteins.

Adolescent↗

PubMed1998

[Determination of total Ca in the lung tissue of rats by FAAS].

Determination of total Ca in the Lung Tissue of Rats by FAAS was described, with a mixed microemulsion consisting of sodium dodecyl sulfate, N-dodecyl, N-dimethyl benzol ammonium bromide and nonyl phenol polyethyeneoxy ether. Comparing the result of the microemulsion FAAS with that of solution FAAS showed that the former was better than the latter in sensitivity, precision, selectivity and linearity of the calibration curve, with a detection limit of 1.92 microg x cm(-3), relative standard deviation of 1.92% (n = 10) and linear regressive coefficient of 0.9998 of the calibration curve over 0-20 microg x cm(-3) calcium. The method was applied to determine calcium amount in the lung tissue of rats, and the results were in accordance with those odtained by the conventional solution FAAS, in which a sample was reduced to ashes at a high temperature.

Analytic Sample Preparation Methods↗

PubMed1998

Simultaneous determination of methylenetetrahydrofolate reductase C677T and factor V G1691A genotypes by mutagenically separated PCR and multiple-injection capillary electrophoresis.

The C677T mutation of the methylenetetrahydrofolate reductase gene and the G1691A (Leiden) mutation of the factor V gene are established risk factors for thromboembolic disease. We here present an assay for the simultaneous genotyping of these common genetic variants. The assay involves a strategy based on multiplex mutagenically separated PCR performed in a single tube containing six primers. Separation of the resulting four PCR products (197, 207, 233, and 246 bp) was performed by capillary electrophoresis coupled with laser-induced fluorescence detection. The time for the automated electrophoresis was reduced to 2.5 min per sample by performing the capillary electrophoresis analysis in a multiple-injection mode.

Automation↗

PubMed1998

Chemical mismatch cleavage combined with capillary electrophoresis: detection of mutations exon 8 of the cystathionine beta-synthase gene.

Mutation detection by chemical mismatch cleavage (CMC) is based on the chemical modification and cleavage at the site of mismatched C or T in heteroduplexes, using hydroxylamine or osmium tetroxide (OsO4) as chemical probes. In the present study, we evaluated CMC in combination with capillary electrophoresis (CE) by determining the common T833C and G919A mutations in exon 8 of the cystathionine beta-synthase gene in heterozygous and homozygous samples. A 186-bp fragment encompassing exon 8 was amplified by PCR with both primers labeled with 5'-fluorescein. Labeled single strands of 40 and 61 nucleotides (nt) were formed from the coding strand of the T833C sample and non-coding strand from the G919A sample, respectively. These single-stranded DNA (ssDNA) products were analyzed under denaturing conditions by CE with short-chain linear polyacrylamide as the sieving matrix and were detected by laser-induced fluorescence (LIF), using a sensitive, one-channel sheath-flow detector. The CE-LIF format afforded relatively high resolution of ssDNA (down to 1 nt), precise size assessment of CMC products, sensitive detection with small sample requirements, and fast analysis. Thus, CMC combined with CE-LIF is suitable for screening of known mutations, giving expected CMC products, but will also detect unknown mutations, the locations of which are indicated by the fragment sizes.

Cystathionine beta-Synthase↗

PubMed1998

Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.

Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.

Allosteric Site↗

PubMed1998

Dietary magnesium supplementation attenuates ethanol-induced myocardial dysfunction.

Hypomagnesemia is positively correlated with a number of cardiovascular abnormalities and recent evidence suggests that magnesium supplementation prevents ethanol-induced development of hypertension. The purpose of our study was to assess whether dietary magnesium supplementation effectively reverses or attenuates chronic ethanol-induced cardiac dysfunction, both at the tissue and the cellular level. Therefore, the influence of dietary magnesium supplementation during chronic ethanol ingestion on the mechanical properties of cardiac muscle was studied using isolated papillary muscles and ventricular myocytes from rat heart. In addition, the acute effects of ethanol on cardiac muscle from animals chronically exposed to ethanol in the absence and presence of dietary magnesium supplementation were also examined. Chronic ethanol exposure caused significant cardiac, hepatic, and renal enlargement, increased systolic blood pressure, and produced hypomagnesemia. After chronic ethanol exposure, the baseline force generating capacity of papillary muscles was markedly depressed and was associated with a significant slowing in the maximum velocities of contraction and relaxation. By contrast, in isolated myocytes, long-term ethanol exposure increased the extent of cell shortening associated with a significant reduction in the duration of relengthening and an increase in both the maximum velocities of shortening and relengthening. Dietary magnesium supplementation among animals chronically ingesting ethanol effectively normalized heart size, systolic blood pressure, and reduced plasma ethanol concentration. Magnesium supplementation also attenuated chronic ethanol-induced depression of contractile force and increased the extent of cell shortening. As expected, acute ethanol exposure caused a dose-dependent inhibition of both isometric force and isotonic shortening associated with a decrease in the intracellular calcium transient. However, the extent of the acute ethanol-induced reduction in isometric force and isotonic shortening was always slightly greater among preparations from animals chronically exposed to ethanol. Dietary magnesium supplementation normalized the acute inhibitory action of ethanol on isometric force, isotonic shortening, and the intracellular calcium transient. Our results suggest that dietary magnesium supplementation may attenuate chronic ethanol-induced alterations in baseline myocardial mechanical function and normalize the cardiac response to acute ethanol exposure.

Animals↗

PubMed1997

Transmembrane orientation of hydrophobic alpha-helices is regulated both by the relationship of helix length to bilayer thickness and by the cholesterol concentration.

A fluorescence-based approach to evaluate the regulation of transmembrane orientation of alpha-helices has been developed to examine the behavior of a membrane-inserted alpha-helical peptide with a 19 residue hydrophobic sequence. The emission lambdamax of a Trp residue in the helix was used to determine its location in the bilayer. To calibrate this method, Trp lambdamax and depth (determined by parallax analysis of fluorescence quenching) were measured for transmembrane peptides with Trp at different positions. Transmembrane orientation of the alpha-helix was found to be destabilized by differences between the width of the bilayer and the length of the hydrophobic sequence (i.e., hydrophobic mismatch). When bilayer width exceeded the length of the hydrophobic segment, mismatch induced formation of a nontransmembraneous orientation close to the polar/hydrocarbon interface. By manipulation of bilayer width in situ, it was found that the transmembrane and nontransmembrane orientations could interconvert. Cholesterol altered the transmembrane/nontransmembrane equilibrium to a degree consistent with its tendency to increase bilayer thickness. Evaluation of the energetics of transmembrane vs nontransmembrane insertion showed increased mismatch of a helix with bilayer width by the equivalent of just one hydrophobic residue can destabilize transmembrane orientation by roughly 0.5 kcal/mol. Inclusion of 30 mol % cholesterol in a bilayer can alter transmembrane insertion stability by 3-5 kcal/mol. Thus, physiologically relevant variations in both the hydrophobic helix length/membrane thickness ratio and the cholesterol levels influence transmembrane insertion significantly.

Amino Acid Sequence↗

PubMed1997

Activation of human somatostatin receptor type 2 causes inhibition of cell growth in transfected HEK293 but not in transfected CHO cells.

Somatostatin (SS) is known to have an antiproliferative effect on cell growth via somatostatin receptors (SSTR). The purpose of this study was to transfect cell lines with human SSTR2 and determine the subsequent effect on cell growth in response to SSTR agonist. Heterologous Chinese hamster ovary (CHO-K1) and human embryonic kidney 293 (HEK) cells were transfected with SSTR2 cDNA using lipofectin. Stable transformants were selected by G418 and confirmed by 125I-SS binding and RT-PCR. Binding studies were performed in the presence of 10(-6) to 10(-12) M SS-14, SS-28, SS analogue RC-160, SSTR2 agonist NC-9-74, and SSTR5 agonist DC-37-39. Cell growth was determined by counting cell numbers after 48 hr incubation in the presence of 10(-6) to 10(-12) M SSTR2 agonist NC-9-74. Binding of 125I-SS-14 to transfected CHO and transfected HEK293 cells showed that the cells had high affinity for SS-14, SS-28, NC-9-74, and RC-160 but low affinity for DC-37-39. Incubation with 10(-6) to 10(-12) M NC-9-74, showed that 1 nM to 1 microM NC-9-74 significantly inhibited transfected HEK293 cell growth but did not affect growth on transfected CHO cells (n = 4 for each dose, P < 0.01). The two cell lines transfected with the human SSTR2 showed similar high affinity for SS-14, SS-28, RC-160, and SSTR2 agonist but not SSTR5 agonist. The SSTR2 agonist NC-9-74 significantly inhibited transfected HEK293 cell growth but not CHO cells. These data suggest that activation of SSTR2 was more efficiently coupled to the signal transduction pathway of antiproliferation in the transfected HEK293 cells.

Animals↗

PubMed1997

Purification and properties of alpha-mannosidase II from Golgi-like membranes of baculovirus-infected Spodoptera frugiperda (IPLB-SF-21AE) cells.

An alpha-mannosidase II-like activity was identified in baculovirus-infected Spodoptera frugiperda (IPLB-SF21-AE) cells. The enzyme responsible was purified from Golgi-type membranes to apparent homogeneity by using a combination of steps including DEAE-cellulose, hydroxyapatite, concanavalin A-Sepharose and gel filtration chromatography. The molecular mass of this purified protein was approx. 120 kDa by SDS/PAGE under reducing conditions and approx. 240 kDa under non-reducing conditions, indicating that the enzyme is a disulphide-linked dimer. Substrates demonstrated to undergo hydrolysis with this enzyme were GlcNAc-Man5-GlcNAc-GlcNAc (non-reduced and reduced) and p-nitrophenyl alpha-d-mannopyranoside. The oligosaccharide substrate was converted into GlcNAc-Man3-GlcNAc-GlcNAc through an intermediate GlcNAc-Man4-GlcNAc-GlcNAc. Treatment of the isolated intermediate oligosaccharide with endoglycosidase H resulted in its conversion into GlcNAc-Man4-GlcNAc. This indicated that it contained the alpha-1,3-linked mannose residue on the alpha-1,6-linked mannose arm and showed that the alpha-1,6-linked mannose residue on the alpha-1,6-linked mannose arm had been preferentially hydrolysed by the mannosidase. The oligosaccharide lacking the beta-1,2-linked GlcNAc residue on the alpha-1,3-linked mannose arm (Man5-GlcNAc-GlcNAc) was not hydrolysed in the presence of the enzyme. Metal ions were not required for enzymic activity on any of the substrates, but Cu2+ was strongly inhibitory. The activity of the enzyme was inhibited at low concentrations of swainsonine, but much higher concentrations of 1-deoxymannojirimycin were required to achieve inhibition. All of these properties are characteristic of mannosidase II enzymes from other eukaryotic tissues. The presence of mannosidase II in lepidopteran insect cells would allow entry of N-linked glycoproteins into the complex processing reaction pathway or into the terminal Man3-GlcNAc-GlcNAc pathway.

Animals↗

PubMed1997

Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor.

The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. The nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting the polymerase active site upon binding in a nearby pocket. Despite being potent and of generally low toxicity, their clinical use has been limited by rapid selection for resistant viral populations. The 2.65-A resolution structure of the complex between HIV-1 RT and the bis(heteroaryl)piperazine (BHAP) NNI, 1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4- [3-(1-methyl-ethylamino) pyridinyl] piperazine (U-90152), reveals the inhibitor conformation and bound water molecules. The bulky U-90152 molecule occupies the same pocket as other NNIs, but the complex is stabilized quite differently, in particular by hydrogen bonding to the main chain of Lys-103 and extensive hydrophobic contacts with Pro-236. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. When bound, part of U-90152 protrudes into the solvent creating a channel between Pro-236 and the polypeptide segments 225-226 and 105-106, giving the first clear evidence of the entry mode for NNIs. The structure allows prediction of binding modes for related inhibitors [(altrylamino)piperidine-BHAPs] and suggests changes to U-90152, such as the addition of a 6 amino group to the pyridine ring, which may make binding more resilient to mutations in the RT. The observation of novel hydrogen bonding to the protein main chain may provide lessons for the improvement of quite different inhibitors.

Acquired Immunodeficiency Syndrome↗

PubMed1997

First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells.

Cholecystokinin (CCK)-A and CCK-B receptors are highly homologous members of the seven transmembrane domain G-protein-coupled receptor superfamily. Genes of both receptors contain five exons and share a similar exon-intron organization. To determine the structural basis of CCK-A receptor (CCK-AR) functionally coupled to Gs, a series of chimeric mutants were constructed by replacing exons of human CCK-B receptor (CCK-BR), from the second to the fifth (last) exon, with human CCK-AR counterparts. Binding and signal transduction properties of wild-type and chimeric receptors were examined in stably transfected HEK-293 cells. Chimeric receptors that maintained high affinity binding to CCK exhibited dose-dependent increases in intracellular calcium mobilization similar to both wild-type receptors. However, only the wild-type CCK-AR and chimeric mutants containing the second exon of CCK-AR were able to mediate significantly greater increases in intracellular cAMP content and adenylyl cyclase activity compared with wild-type CCK-BR. A CCK-BR mutant was further constructed by replacing five amino acids, Gly-Leu-Ser-Arg-(Arg)-Leu, in the first intracellular loop with the corresponding five CCK-AR specific amino acids, Ile-Arg-Asn-Lys-(Arg)-Met. The resultant receptor maintained high affinity binding to both CCK and gastrin and dose-dependent calcium responses similar to wild-type CCK-BR. However, this first intracellular loop mutant also gained positive cAMP responses to both sulfated CCK-8 and gastrin-17 with EC50 values of 8.5 +/- 1 nM and 23 +/- 7 nM, respectively. These data suggest that the first intracellular loop of CCK-AR is essential for coupling to Gs and activation of adenylyl cyclase signal transduction cascade.

Adenylyl Cyclases↗

PubMed1997

Analysis of single-strand conformation polymorphism by capillary electrophoresis with laser-induced fluorescence detection using short-chain polyacrylamide as sieving medium.

A rapid analysis of single-strand conformation polymorphism (SSCP) by capillary electrophoresis with laser-induced fluorescence (CE-LIF) detector was developed using a short-chain, linear polyacrylamide (PA) as sieving medium. Capillary filling of this low-viscosity medium and medium replacement were carried out by commercial capillary electrophoresis instruments. The approach was successfully applied to detect the C677T mutation of methylenetetrahydrofolate reductase gene. The influences of factors such as the concentration of polymers, voltage, temperature, and additives on the SSCP analysis were systematically investigated. Using 6% PA sieving medium and high electric field, four strands were resolved within 11 min in a DNA sample heterozygous for the C677T mutation, and a characteristic pattern was apparent for each of the three genotypes. When using multiple injection mode, the average analysis time per sample was reduced to about 4 min. In conclusion, our results indicate that CE-LIF may be an alternative to conventional SSCP analysis based on slab gel electrophoresis for the detection of genetic mutations. The technique is simple and rapid and is well suited to analysis of large numbers of clinical samples.

Acrylic Resins↗

PubMed1997

Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.

BACKGROUND: Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. METHODS AND RESULTS: In a canine model, we evaluated myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P < .001) and was associated with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15 +/- 2% to 30 +/- 3%, P < .02) and GLUT-1 (41 +/- 4% to 58 +/- 3%, P < .03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular in the nonischemic region. However, significant GLUT-4 surface labeling was found in the ischemic region. CONCLUSIONS: Translocation of the insulin-responsive GLUT-4 transporter from an intracellular storage pool to the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation to the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.

Animals↗

PubMed1997

Postischemic infusion of Cu/Zn superoxide dismutase or SOD:Tet451 reduces cerebral infarction following focal ischemia/reperfusion in rats.

Oxygen-free radicals play a major role in neuronal cell injury following cerebral ischemia/reperfusion. The free-radical scavenging enzyme, Cu/Zn superoxide dismutase (SOD-1), ameliorates various types of brain injury resulting from temporary CNS ischemia. We have compared the cerebroprotective properties of human SOD-1 (hSOD-1) with a novel recombinant SOD-1 hybrid protein, SOD:Tet451, composed of hSOD-1 linked to the neuronal binding fragment of tetanus toxin (TTxC). Following 2 h of temporary middle cerebral artery occlusion, rats infused with equivalent activities of either hSOD-1 or SOD:Tet451 for the initial 3 h of reperfusion showed reductions in cerebral infarct volume of 43 and 57%, respectively, compared to saline-treated controls (P < 0.01). Serum hSOD-1 concentrations in rats receiving SOD:Tet451 were seven-fold higher than those in rats receiving the native enzyme. Animals treated with SOD:Tet451 also demonstrated an extended persistence of hSOD-1 in the bloodstream during drug washout as compared to animals given free enzyme. Immunohistochemical examination of brain sections from an SOD:Tet451-treated ischemic rat showed positive immunoreactivity in the ipsilateral cerebral cortex using either anti-TTxC or anti-human SOD-1 antibodies. Our results document that both hSOD-1 and SOD:Tet451 significantly reduce brain infarct volume in a model of transient focal ischemia/reperfusion in rats. Additionally, our findings suggest that the cerebroprotective effects of SOD-1 may be enhanced by neuronal targeting as seen with the hybrid protein SOD:Tet451.

Animals↗

PubMed1997

Coordination of deglutitive glottal function and pharyngeal bolus transit during normal eating.

BACKGROUND & AIMS: Deglutitive glottal function during the preparatory phase of swallowing and its coordination with bolus transit during normal eating are important for airway protection. The aim of this study was to examine this coordination during consumption of a normal meal. METHODS: Fifteen healthy volunteers were studied using a videoendoscopic and videofluoroscopic technique. RESULTS: A total of 207 liquid and 470 solid bolus swallows were analyzed. In 60% of liquid and 76% of solid food swallows, the bolus was seen in the pharynx before a swallow was initiated. Entry of boluses into the pharynx was associated with brief partial adduction of the vocal cords. Solid food entered and traversed the pharynx at the midline, whereas liquid bolus was split around the larynx and rejoined in the hypopharynx. Swallowing was initiated significantly earlier when bolus made contact with the upper third of the epiglottis compared with vallecula or pyriform sinuses. CONCLUSIONS: In more than half of the instances, during normal eating, food enters the pharynx during the preparatory phase before a swallow is initiated, the path of pharyngeal transit of solid bolus is different from that of liquid bolus, and the epiglottal edge appears to be the most sensitive trigger zone for swallowing.

Adult↗

PubMed1997

Ondansetron exhibits the properties of a local anesthetic.

UNLABELLED: The purpose of this study was to determine whether ondansetron (OND) has local anesthetic effects. Using a patch-clamp technique, we showed that OND concentration dependently blocked Na channel currents in freshly isolated neurons of rat brains with a 50% inhibition concentration of 12 microM. The blockade started immediately when OND was applied to the cell body using a fast perfusion system, reached a plateau within 15 s, and recovered to the control level within 30 s after washout of the OND-containing solution. Because this is a known property of local anesthetics, we used the tail-flick technique to verify this effect in vivo in Sprague-Dawley rats (n = 46). OND was injected subcutaneously into the tail at the doses of 0.08, 0.16, and 0.2 mg. The tail-flick latency increased 2 min after OND injection, reaching the plateau within 5 min. This effect was dose-related, lasting from 10 to 25 min. These preliminary data indicate that OND, a selective 5-HT3 receptor antagonist, might serve as a prototype molecule for development of a novel series of local anesthetics. IMPLICATIONS: Ondansetron is a drug used to prevent vomiting, especially in cancer patients after chemotherapy. We found that it also causes numbness when injected under the skin. This new action may contribute to its role in "calming the stomach." We studied the effect of ondansetron on the isolated brain cells of live rats.

Anesthetics, Local↗

PubMed1997

Frequency of gastroesophageal reflux events induced by pharyngeal water stimulation in young and elderly subjects.

Earlier studies have shown that isolated complete lower esophageal sphincter (LES) relaxation occurs as a result of pharyngeal water stimulation. Association of these relaxations with gastroesophageal reflux has not been studied systematically. Our aim was to determine this association in young and elderly subjects during precibal and postprandial periods. We studied 8 young subjects and 10 elderly subjects for 1 h before and 2 h after a 1,000-cal meal. In both groups, during the precibal period, negligible LES relaxation induced by pharyngeal water stimulation resulted in gastroesophageal reflux. In the postprandial period, gastroesophageal reflux events occurred after 16% of pharyngeal water injections in young subjects and after 44% in elderly subjects (P < 0.05). Intraabdominal length of the LES in elderly subjects was significantly shorter compared with younger subjects (P < 0.05). We conclude that gastroesophageal reflux events induced by pharyngeal water stimulation in the postprandial period are significantly increased compared with those of the precibal period and are significantly more prevalent in the elderly compared with the young. These differences seem to be associated with a significantly shorter intra-abdominal segment of the LES in the elderly.

Adult↗

PubMed1997

Effect of pharyngeal water stimulation on esophageal peristalsis and bolus transport.

Sensory stimuli originating from the pharynx inhibit esophageal peristalsis induced by a dry swallow. Our aims were to determine the effect of these stimuli on esophageal bolus transport and esophageal peristalsis induced by swallowing different volumes of liquid and semisolid boluses. We studied nine healthy volunteers age 35 +/- 4 yr in the supine position by intraluminal esophageal manometry as well as concurrent videofluoroscopy and manometry. In all subjects progression of peristalsis induced by swallowing of different volumes of water and mashed potato boluses was inhibited at all sites by pharyngeal water injection. Threshold volume for inhibition of the peristalsis induced by swallows of 5 and 10 ml of water was similar but significantly higher compared with dry swallows (P < 0.05). Pharyngeal water injection invariably halted transit of the barium boluses through the esophagus. Sensory impulses originating from the pharynx 1) inhibit esophageal bolus transit and 2) are capable of overcoming the facilitating effect of a liquid bolus on the swallowing apparatus. This phenomenon may explain the mechanism of some of the failed esophageal peristalsis observed in clinical practice.

Adult↗