Biomedical subjects

W M Sun

Publications and source records attributed to W M Sun.

At least 73 records · Page 4Linked to original sources

PubMed2000

Search for CP violation in B+/- --> J/psiK+/- and B+/- --> psi(2S)K+/- decays.

We present a search for direct CP violation in B+/--->J/psiK+/- and B+/--->psi(2S)K+/- decays. In a sample of 9.7x10(6) B&Bmacr; meson pairs collected with the CLEO detector, we have fully reconstructed 534 B+/--->J/psiK+/- and 120 B+/--->psi(2S)K+/- decays with very low background. We have measured the CP-violating charge asymmetry to be [+1.8+/-4.3(stat)+/-0.4(syst)]% for B+/--->J/psiK+/- and [+2.0+/-9. 1(stat)+/-1.0(syst)]% for B+/--->psi(2S)K+/-.

Journal Article↗

PubMed2000

Long-term effects of pyloromyotomy on pyloric motility and gastric emptying in humans.

OBJECTIVE: The aim of this study was to determine the long term effects of pyloromyotomy for infantile hypertrophic pyloric stenosis (IHPS) on gastric emptying and pyloric motility. METHODS: Concurrent measurements of gastric emptying and antropyloroduodenal pressures were performed in six volunteers (aged 24-26 yr) who had had pyloromyotomy performed in infancy because of IHPS, and in six normal subjects. Subjects were studied on 2 days, once sitting and once in the left lateral position. Gastric emptying of 300 ml 25% dextrose labeled with 20 MBq 99mTc sulfur colloid was measured. Antropyloroduodenal motility was evaluated with a sleeve/multiple sidehole manometric assembly, which was also used to deliver an intraduodenal triglyceride infusion at 1.1 kcal/min for 60 min, starting 30 min after ingestion of the dextrose. RESULTS: In both body positions, gastric emptying and intragastric distribution of the drink did not differ between the two groups. In both groups and postures, the amount emptied was less during intraduodenal lipid infusion. The number (p<0.01) and amplitude (p<0.02) of isolated pyloric pressure waves (IPPWs) was greater in the control subjects, whereas basal pyloric pressure was greater in the pyloromyotomy subjects (p<0.02). In both groups, the rate of gastric emptying in the sitting position was related to the number of IPPWs (r> or =0.40, p<0.05), but not to basal pyloric pressure. CONCLUSIONS: These results indicate that, in adults who have had pyloromyotomy for IHPS in infancy, patterns of pyloric motility are abnormal; pyloric tone is higher, whereas the number and amplitude of phasic pyloric pressure waves are less. In contrast, the overall rate of gastric emptying of a nutrient liquid meal is normal. These observations are consistent with the concept that the stomach has the capacity to compensate for changes in pyloric motility to minimize effects on gastric emptying.

Adult↗

PubMed1999

Effects of hyperglycemia on cortical response to esophageal distension in normal subjects.

Acute changes in the blood glucose concentration affect the intensity of gastrointestinal sensations. The aim of this study was to examine the effects of hyperglycemia on cortical potentials evoked by esophageal distension. In 16 healthy volunteers, a balloon was positioned in the lower esophagus. A series of 50 distensions was performed at both a lower volume (producing definite sensation) and a higher volume (producing unpleasant sensation), at blood glucose concentrations of 5 and 13 mmol/liter. Triphasic cortical potentials were recorded from a midline scalp electrode (Cz). During euglycemia, interpeak amplitudes were greater at the higher than the lower balloon volume (P < 0.005). At the lower balloon volume, the interpeak amplitudes were greater during hyperglycemia than euglycemia (P < 0.05). There was no effect of the blood glucose concentration on amplitude at the higher balloon volume. We conclude that in healthy subjects, the amplitude of the cortical response to moderate, but not unpleasant, esophageal distension is greater during hyperglycemia when compared to euglycemia. These observations are consistent with the concept of increased intensity of gut sensation during hyperglycemia.

Adolescent↗

PubMed1999

The effect of hyperglycaemia on cerebral potentials evoked by rapid rectal distension in healthy humans.

BACKGROUND: Acute hyperglycaemia affects the perception of sensations arising from the gastrointestinal tract. The mechanisms responsible for this effect are unknown. Recordings of cerebral evoked potentials (EPs) can be used to assess the integrity of visceral afferent pathways. Our aim was to determine whether hyperglycaemia affects EPs elicited by rectal distension in healthy humans. MATERIALS AND METHODS: Twelve healthy men, aged 19-31 years, were studied. A manometric catheter, incorporating a rectal balloon, was positioned 7-10 cm from the anal verge. Balloon distensions at both 'low' ( approximately 20 mL) and 'high' ( approximately 28 mL) volumes were performed, in a single-blind, randomized order, during both euglycaemia (4 mmol L-1) and hyperglycaemia (12 mmol L-1). EPs were recorded from a midline scalp electrode (Cz, International 10-20 system) and averaged for each series of 50 distensions. EP latencies and interpeak amplitudes were calculated. RESULTS: Polyphasic EPs were recorded in all but one subject. Although the blood glucose concentration had no significant effect on the latencies of the EP peaks elicited by either 'low'- or 'high'-volume balloon distension, the interpeak amplitude (P1-N1) was greater during hyperglycaemia than during euglycaemia at the 'low' balloon volume (6.3 +/- 1.2 microV vs. 4.8 +/- 1.0 microV, P < 0.05). The blood glucose concentration had no significant effect on the perception of rectal balloon distension. CONCLUSIONS: We conclude that in normal subjects acute hyperglycaemia increases the amplitude of the cerebral EP elicited by rectal balloon distension at low balloon volumes, suggesting that the effects of hyperglycaemia on gastrointestinal sensation may be mediated by central mechanisms.

Adult↗

PubMed1998

Acute effects of therapeutic irradiation for prostatic carcinoma on anorectal function.

AIM: The incidence of anorectal symptoms after radiotherapy (RTH) for localised pelvic malignant disease is unclear. In addition, the effects of pelvic irradiation on both anorectal motility and sensory function are poorly defined. A prospective study was therefore performed on 35 patients (55-82 years of age) with localised prostatic carcinoma before and four to six weeks after RTH to assess its effects on anorectal function. METHODS: Anorectal symptoms were assessed by questionnaire. Anorectal pressures at rest and in response to voluntary squeeze, rectal distension, and increases in intra-abdominal pressure were evaluated with perfused sleeve side hole manometry. Rectal sensation was tested during graded balloon distension. Rectal compliance was calculated by the pressure-volume relation obtained during the testing of rectal sensation. Ultrasound was used to determine anal sphincter structure and integrity. RESULTS: RTH had no effect on anal sphincter morphology. The frequency of defecation increased after RTH (7 (3-21) v 10 (3-56) bowel actions a week; p < 0.01). After RTH, 16 patients had faecal urgency and eight faecal incontinence, compared with five and one respectively before RTH (p < 0.01 for each). Basal and squeeze sleeve recorded pressures were reduced after RTH (54 (3) v 49 (3) mm Hg (p < 0.05) and 111 (8) v 102 (8) mm Hg (p < 0.01), before and after RTH respectively; means (SEM)). Rectal compliance was reduced after RTH (1.2 v 1.4 mm Hg/ml, p < 0.05). After RTH, threshold volumes for perception of rectal distension were lower in the 16 patients who either experienced faecal urgency for the first time (13 patients) or reported worsening of this symptom (three patients) compared with the remaining patients (34 (4) v 48 (5) ml respectively, p < 0.05). CONCLUSION: Faecal incontinence (23%) is a common problem four to six weeks after RTH for prostatic carcinoma and is associated with minor reductions in anal sphincter pressures. The high prevalence of faecal urgency in patients after RTH may be related to alterations in rectal perception of stool.

Aged↗

PubMed1998

Effect of glucose supplementation on appetite and the pyloric motor response to intraduodenal glucose and lipid.

The effects of different macronutrients on appetite and pyloric motility and the impact of short-term dietary glucose supplementation on these responses were evaluated. Ten males (aged 19-38 yr) received isocaloric (2.9 kcal/min) intraduodenal infusions of glucose and lipid while antropyloroduodenal motility and appetite were assessed by manometry and visual analog scales, respectively. Effects of each intraduodenal nutrient on appetite and motility were evaluated before and after 7 days of dietary supplementation with glucose (400 g daily). Initially, both nutrients caused a similar rise in pyloric tone, but intraduodenal lipid was a more potent stimulus of phasic pyloric motility (P = 0.05) and suppressed appetite more (P = 0.013) than intraduodenal glucose. After dietary glucose supplementation, the increase in pyloric tone during intraduodenal glucose was attenuated. Although intraduodenal lipid remained a more potent stimulant of phasic pyloric motility (P = 0.016), it no longer decreased appetite. We conclude that in healthy young males 1) intraduodenal infusion of lipid is a more potent stimulus of phasic pyloric motility and suppresses appetite more than intraduodenal glucose and 2) dietary glucose supplementation alters both the appetite suppressant effect of intraduodenal lipid and the pyloric motor response to intraduodenal glucose infusion.

Adult↗

PubMed1998

Effects of nitroglycerin on liquid gastric emptying and antropyloroduodenal motility.

The effects of the nitric oxide donor nitroglycerin on gastric emptying and antropyloroduodenal motility were evaluated in nine healthy male subjects (ages 19-36 yr). Antropyloroduodenal pressures were recorded with a manometric assembly that had nine side holes spanning the antrum and proximal duodenum and a pyloric sleeve sensor; gastric emptying was quantified scintigraphically. In each subject, the emptying of 300 ml of 25% glucose labeled with 99mTc was assessed on two separate days during intravenous infusion of either nitroglycerin (5 micrograms/min in 5% dextrose) or 5% dextrose (control). Studies were performed with the subject in the supine position; blood pressure and heart rate were monitored. Nitroglycerin had no significant effect on blood pressure or heart rate. Nitroglycerin slowed gastric emptying (P < 0.02), and this was associated with greater retention of the drink in the proximal stomach (P < 0.05). In both nitroglycerin and control studies, ingestion of the drink was associated with an increase in the number of isolated pyloric pressure waves (P < 0.05) and antral pressure wave sequences (P < 0.05). Nitroglycerin reduced the number of isolated pyloric pressure waves (P < 0.05), basal pyloric pressure (P < 0.05), and the number of antral pressure wave sequences (P < 0. 05), but not the total number of antral pressure waves. The rate of gastric emptying and the number of isolated pyloric pressure waves were inversely related during control (P = 0.03) and nitroglycerin (P < 0.05) infusions. We conclude that in normal subjects, 1) gastric emptying of 300 ml of 25% glucose is inversely related to the frequency of phasic pyloric pressure waves, and 2) nitroglycerin in a dose of 5 micrograms/min inhibits pyloric motility, alters the organization but not the number of antral pressure waves, and slows gastric emptying and intragastric distribution of 25% glucose.

Adult↗

PubMed1997

Spatial patterns of fasting and fed antropyloric pressure waves in humans.

1. Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with individual gastric contractions. 2. In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum. 3. Pressure wave sequences that occurred during phase II fasting contractions (n = 221) and after food (n = 778) were evaluated. 4. The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade-29% after food and 42% during fasting (P < 0.05); purely synchronous-23% fed and 17% fasting; and purely retrograde-6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences 'skipped' individual recording points. 5. The spatial patterning of gastric pressure wave sequences is diverse, and may explain the differing mechanical outcomes among individual gastric contractions. 6. Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during individual gastric contraction sequences.

Adult↗

PubMed1997

Hyperglycemia affects gastric electrical rhythm and nausea during intraduodenal triglyceride infusion.

Hyperglycemia slows gastric emptying and increases the intensity of perception of gastric distension during fasting and small intestinal nutrient stimulation. In order to examine the possibility that abnormalities of gastric electrical rhythm may be associated with the effects of hyperglycemia, the gastric electrical rhythm (cutaneous electrogastrogram) and the perception rating scores for upper gastrointestinal sensations (visual analog scale) were examined. Studies were performed during intraduodenal triglyceride infusion in 10 healthy volunteers under euglycemic and hyperglycemic (approximately 15 mmol/liter) conditions. During fasting, hyperglycemia had no effect on either gastric electrical rhythm or sensation. Intraduodenal triglyceride infusion was associated with an increase in bradygastria (<2.4 cpm) during both euglycemia (33 +/- 9%) and hyperglycemia (36 +/- 10%, P < 0.05 vs baseline for each). During intraduodenal triglyceride infusion, tachygastria (>3.6 cpm) was more prevalent during hyperglycemia when compared to euglycemia (25 +/- 10% vs 1 +/- 1%, P < 0.05) and the perception rating scores for nausea and abdominal discomfort were greater during hyperglycemia (P < 0.05 for both). The intensity of nausea correlated with the proportion of time spent in tachygastria (r = 0.64, P < 0.01). These data are consistent with the concept that postprandial upper gastrointestinal symptoms in patients with diabetes mellitus may be modulated by the blood glucose concentration.

Adult↗

PubMed1997

Pyloric motor response to central and peripheral nitric oxide in the ferret.

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

Animals↗

PubMed1997

Relation between postprandial satiation and antral area in normal subjects.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P < 0.001) and hunger decreased (P < 0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r > 0.56, P < 0.05), the increase in antral area (r > 0.59, P < 0.05), and the scintigraphic content of the distal stomach (r > 0.57, P < 0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

Adult↗

PubMed1997

Acute hyperglycaemia affects anorectal motor and sensory function in normal subjects.

BACKGROUND: The pathogenesis of anorectal dysfunction, which occurs frequently in patients with diabetes mellitus, is poorly defined. Recent studies indicate that changes in the blood glucose concentration have a major reversible effect on gastrointestinal motor function. AIMS: To determine the effects of physiological changes in blood glucose and hyperglycaemia on anorectal motor and sensory function in normal subjects. SUBJECTS: In eight normal subjects measurements of anorectal motility and sensation were performed on separate days while blood glucose concentrations were stabilised at 4, 8, and 12 mmol/l. METHODS: Anorectal motor and sensory function was measured using a sleeve/sidehole catheter incorporating a balloon, and electromyography. RESULTS: The number of spontaneous anal relaxations was greater at 12 mmol/l than at 8 and 4 mmol/l glucose (p < 0.05 for both). Anal squeeze pressures were less at a blood glucose of 12 mmol/l when compared with 8 and 4 mmol/l (p < 0.05 for both). During rectal distension, residual anal pressures were not significantly different between the three blood glucose concentrations. Rectal compliance was greater (p < 0.05) at a blood glucose of 12 mmol/l when compared with 4 mmol/l. The threshold volume for initial perception of rectal distension was less at 12 mmol/l when compared with 4 mmol/l (40 (20-100) ml versus 10 (10-150) ml, p < 0.05). CONCLUSIONS: An acute elevation of blood glucose to 12 mmol/l inhibits internal and external anal sphincter function and increases rectal sensitivity in normal subjects. In contrast, physiological changes in blood glucose do not have a significant effect on anorectal motor and sensory function.

Acute Disease↗

PubMed1997

Progressive defect in biliary GSH secretion in streptozotocin-induced diabetic rats.

This study examined the effect of streptozotocin-induced diabetes on biliary reduced glutathione (GSH) efflux. Biliary GSH efflux was measured before and after acivicin, an irreversible inhibitor of gamma-glutamyl transpeptidase (GGT). One week after streptozotocin treatment, liver GGT activity doubled in diabetic rats but was inhibited by approximately 90% after acivicin to levels comparable to controls. Despite maximal GGT inhibition, biliary GSH efflux in untreated diabetic rats decreased progressively to approximately 10% of control levels by week 4 and was partially restored by insulin. The mechanism for the decrease in biliary GSH efflux was not increased paracellular permeability. GSH transport kinetics, ATP-stimulated taurocholate, and oxidized glutathione (GSSG) transport in canalicular liver plasma membrane prepared from diabetic and control rats were similar. Inhibition of protein kinase C (PKC) with high-dose H-7 increased biliary GSH efflux in diabetic animals to near control basal levels. In conclusion, streptozotocin-induced diabetic rats exhibit a progressive impairment in biliary GSH transport. One of the responsible mechanisms is heightened PKC tone in diabetic animals.

Animals↗

PubMed1997

Current techniques of assessing defecation dynamics.

The pathophysiology of defecation disorders is multifactorial. An ideal test should identify the underlying cause(s) and provide guidelines for treatment. Unfortunately, there is no such single test. But several techniques are available that could provide comprehensive information regarding the changes in defecation dynamics. Among these, anorectal manometry offers the most useful test for clinicians. Manometry may provide objective evidence for impaired rectal sensation, poor rectoanal coordination, weak anal sphincters or changes that support a diagnosis of obstructive defecation. Other tests such as the balloon expulsion test may serve as screening tools for patients with constipation. In a patient with fecal incontinence, anal endosonography may localize the sphincter defect and aid surgical reconstruction. The pudendal nerve latency test may provide a pathophysiological basis for a weak anal sphincter. Imaging techniques such as defecography may provide useful information regarding rectal prolapse or levator ani dysfunction. Ideally, the clinician should utilize these tests either to confirm a clinical suspicion or to provide new information that could aid management. This review provides an update regarding the various tests that are available for assessing defecation and provides some practical guidelines for performing manometry.

Anal Canal↗

PubMed1997

Effects of loperamide oxide on gastrointestinal transit time and anorectal function in patients with chronic diarrhoea and faecal incontinence.

BACKGROUND: Loperamide improves anorectal function in patients with chronic diarrhoea. We wished to investigate whether the prodrug loperamide oxide has similar effects. METHODS: Eleven patients with chronic diarrhoea and faecal incontinence participated in a randomized, placebo-controlled, double-blind, crossover study of the effects of loperamide oxide (4 mg twice daily for 1 week). RESULTS: Loperamide oxide reduced wet stool weight and improved the patients' ratings of symptoms. Mouth-to-caecum transit time was not altered, but whole-gut transit time was prolonged. There were limited effects on anorectal function, but the mean minimum basal pressure mainly contributed by the internal anal sphincter (IAS) was increased, as was the mean volume infused before leakage occurred in the saline continence test. CONCLUSION: Loperamide oxide is effective in the treatment of diarrhoea with faecal incontinence; normalization of colon transit time and an increase in the tone of the IAS seem to be the main determinants of efficacy.

Adult↗

PubMed1996

Regulation of gamma-glutamylcysteine synthetase by protein phosphorylation.

We previously reported that the activity of gamma-glutamylcysteine synthetase (GCS; EC 6.3.2.2), the rate-limiting enzyme in GSH synthesis, can be acutely inhibited approximately 20-40% by agonists of various signal transduction pathways in rat hepatocytes [Lu, Kuhlenkamp, Garcia-Ruiz and Kaplowitz (1991) J. Clin. Invest. 88, 260-269]. We have now examined the possibility that GCS is phosphorylated directly by activation of protein kinase A (PKA), protein kinase C (PKC) and Ca2+/calmodulin-dependent kinase II (CMK). Phosphorylation of GCS was studied using both purified rat kidney GCS and cultured rat hepatocytes by immunoprecipitating the reaction product with specific rabbit anti-(rat GCS heavy subunit) (anti-GCS-HS) antibodies. All three kinases, PKA, PKC and CMK, phosphorylated rat kidney GCS-HS in a Mg(2+)-concentration-dependent manner, with the highest degree of phosphorylation occurring at 20 mM Mg2+. The maximum incorporation of phosphate in mol/mol of GCS was 1.17 for PKA, 0.70 for PKC and 0.62 for CMK. The degree of phosphorylation was correlated with the degree of loss of GCS activity, and no additional inhibition occurred when GCS was phosphorylated by all three kinases, suggesting that the kinases phosphorylated the same site(s). Phosphoamino analysis showed that all three kinases phosphorylated serine and threonine residues. Two-dimensional phosphopeptide mapping demonstrated that all three kinases phosphorylated the same five peptides, both PKA and PKC phosphorylated two other peptides, and only PKA phosphorylated one additional peptide. Phosphorylation of GCS decreased its Vmax for cysteine and glutamate without changing its K(m). Finally, treatment of cultured rat hepatocytes with dibutyryl cAMP and phenylephrine significantly increased the phosphorylation of GCS, suggesting a potentially important physiological role. In summary, we have demonstrated that GCS is phosphorylated and suggest that phosphorylation/dephosphorylation may regulate GCS activity.

Animals↗

PubMed1996

A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function.

PURPOSE: To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS: Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity.

Adult↗

PubMed1996

Role of two recently cloned rat liver GSH transporters in the ubiquitous transport of GSH in mammalian cells.

Recently our laboratory has cloned both the rat canalicular and sinusoidal GSH transporters (RcGshT and RsGshT, respectively; Yi, J., S. Lu, J. Fernandez-Checa, and N. Kaplowitz. 1994. J. Clin. Invest. 93:1841-1845; and 1995. Proc. Natl. Acad. Sci. USA. 92:1495-1499). The current work characterized GSH transport and the expression of these two GSH transporters in various mammalian cell lines. The average cell GSH levels (nmol/10(6) cells) were 25, 22, 32, 13, and 13 in HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. GSH efflux was temperature dependent and averaged 0.018, 0.018, 0.012, 0.007, and 0.019 nmol/10(6) cells/min from HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. Dithiothreitol (DTT), which stimulates rat sinusoidal GSH efflux, stimulated GSH efflux only in HepG2 and HeLa cells which was partially reversed by subsequent cystine treatment. GSH uptake (1 mM plus 35S-GSH) was temperature dependent, linear up to 45 min, and Na+-independent with average rates of 1.12, 0.91, 0.45, and 0.45 nmol/10(6) cells/30 min for HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. BSP-GSH (2mM), which cis-inhibits sinusoidal GSH uptake in rat liver and HepG2 cells, inhibited GSH uptake only in HeLa cells. mRNA and polypeptide of RcGshT are expressed in all cells whereas those of RsGshT are expressed only in HepG2 and HeLa cells. In conclusion, bidirectional GSH transport, mediated by the "canalicular" GSH transporter, is ubiquitous in mammalian cells. Sinusoidal GSH transporter expression is more restricted, being present in HepG2 and HeLa cells. DTT and BSP-GSH affect GSH transport only in cells expressing the sinusoidal transporter confirming their selective action on this transporter.

Animals↗