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Biomedical subjects

L Y Cheung

Publications and source records attributed to L Y Cheung.

At least 37 records · Page 2Linked to original sources
PubMed1992

Basolateral K+ conductances in surface epithelium of Necturus antrum: effects of Ca2+ and divalent cations.

Intracellular microelectrode techniques were used to characterize basolateral membrane K+ conductances in isolated Necturus antral mucosa. Exposure of tissues to progressively higher levels of serosal K+ (4, 20, 40, or 60 mM) resulted in progressively greater depolarizations of basolateral membrane potentials and decreases in membrane resistance, consistent with the presence of a significant K+ conductance. Ba2+ (2 mM) partially blocks these conductances. Exposure of tissues to increased levels of serosal Ca2+ (from 1.8 to 6.8 mM) elicited significant hyperpolarization of basolateral potentials and decreases in basolateral resistance. These effects are also elicited by Sr2+ (5 mM), but not by Mg2+ (5 mM). Ba2+ (5 mM) elicits complex and time-dependent effects, but transiently elicits an effect similar to high Ca2+. Ion substitutions in the serosal perfusate suggest that the Ca(2+)-induced effects are due to enhancement of basolateral K+ conductances. Further work is necessary to identify the processes that mediate this increase in basolateral K+ conductance and to evaluate the physiological significance of this change in membrane permeability to K+.

Animals↗
PubMed1992

Relative potency of endothelin analogues on changes in gastric vascular resistance.

The purpose of this study was to examine the effects of several endothelin analogues on the gastric microcirculation. We measured changes in vascular resistance of an ex vivo gastric segment of chloralose-anesthetized dogs. Changes in luminal pressure were used to quantitate contractile force. Graded doses of endothelin-2 (ET-2), endothelin-3 (ET-3), [Ala3,11]endothelin (Ala-ET), and the COOH-terminal hexapeptide (ET-C) were infused intra-arterially to the stomach. ET-2 and Ala-ET produced dose-related sustained increases in vascular resistance (10(-10) to 10(-8) M), with Ala-ET less potent than ET-2. In contrast, ET-3 was a weak vasoconstrictor while ET-C had no significant effects. There were no detectable changes in filtration with any of these analogues. However, the force of gastric contractions was significantly attenuated by both ET-2 and Ala-ET in a dose-dependent manner. We found that endothelin analogues produced sustained vasoconstriction of the gastric segment with a potency order of ET-2 greater than Ala-ET-3 much greater than ET-C. Our results suggest that endothelin analogues are potent vasoconstrictors but have little effect on filtration across the gastric vasculature.

Animals↗
PubMed1991

Surgical options in postgastrectomy syndromes.

The various operations performed for the treatment of peptic ulcer disease can lead to a variety of iatrogenic disorders collectively referred to as the "postgastrectomy syndromes." Although the etiology of most of these disorders remains unclear, loss of vagal innervation and bypass, ablation, or destruction of the pylorus clearly are involved in the pathogenesis of most, if not all, of these disorders. Unfortunately, there often is also a poorly understood psychological element involved in the pathogenesis. Of all ulcer operations, proximal gastric vagotomy results in the fewest physiologic abnormalities and the mildest postoperative symptoms. The continued popularity of this operation should effect a marked reduction in the incidence of disabling postgastrectomy syndromes. Fortunately, symptoms severe enough to necessitate remedial operation are uncommon, and conservative medical management is always indicated and usually suffices. When disabling symptoms are refractory, a thorough evaluation of the patient and an accurate classification of the syndrome are essential to guarantee a satisfactory result from surgical intervention. Although numerous surgical procedures have been developed to deal with the different syndromes, with varied results, the Roux-en-Y procedure has emerged as the operation of choice for most, if not all, postgastrectomy syndromes. However, the Roux-en-Y procedure has not been universally successful, and this operation can itself lead to the recently recognized postgastrectomy state of Roux-en-Y stasis syndrome. Prevention therefore remains the best form of therapy, and remedial operation should not be undertaken until adequate time has elapsed since the original operation and all forms of conservative treatment have failed.

Diarrhea↗
PubMed1991

Gastric contractions produce phasic changes in perfusion pressure.

This study examined the relationship between motility and perfusion pressure of an ex vivo segment of the canine stomach perfused at constant flow. Changes in luminal pressure were used to quantitate contractile force. Under control conditions, spontaneous contractions increased luminal pressure by 18.8 +/- 1.1 mmHg and gastric perfusion pressure by 14.2 +/- 0.8 mmHg. Changes in luminal and perfusion pressures during contractions were highly correlated (r2 = 0.963, P less than 0.0001, 109 observations in 5 dogs). In separate studies, we assessed the effects of atropine, neostigmine (an acetylcholinesterase inhibitor), and bethanechol (a muscarinic cholinergic agonist). Atropine attenuated the peristaltic-induced changes in perfusion pressure in a concentration-dependent manner (10(-9) to 10(-6)M) with nearly total inhibition at the highest dose. Neostigmine (10(-9) to 10(-6) M) and bethanechol (10(-8) to 10(-5) M) stimulated contractions, resulting in dose-related increases in luminal and perfusion pressures. Our results demonstrate that cholinergic-dependent contractions produce marked, phasic changes in gastric perfusion pressure.

Animals↗
PubMed1990

Characteristics of duodenal wall gastrinomas.

Fifteen patients with duodenal wall gastrinomas (DWGs) and the Zollinger-Ellison syndrome have been treated since 1960. In 6 of 11 patients, DWGs were recognized at operation and totally excised. In four patients, the tumor was subsequently found in the proximal duodenum of the surgical specimens. In 12 patients, DWGs were single and lymph node metastases were present in 8. In three patients, DWGs were multiple and lymph node metastases were present in two. All DWGs were submucosal and all were located in the first or second portions of the duodenum except one found in the fourth portion. Tumor size ranged from 1 to 15 mm, and nine were less than 5 mm. Of 12 patients with single DWGs, 9 have remained eugastrinemic after resection (mean follow-up: 5.5 years). None of the patients with multiple DWGs became eugastrinemic after surgery. DWGs are characteristically single, small or microscopic, submucosal, located in the proximal duodenum, rarely metastasize to the liver, and are usually curable by surgical resection.

Duodenal Neoplasms↗
PubMed1990

Effect of histamine and 1,4-methylhistamine on gastric vascular resistance in dogs.

The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine-induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation.

Animals↗
PubMed1990

Feeding induces lipid accumulation and increased Na+ transport in in vitro Necturus antrum.

We investigated the effects of feeding on lipid accumulation and transepithelial transport using in vitro Necturus gastric antral mucosae. Antra from fed Necturi were examined for lipid accumulation using light, fluorescence, histochemical, and electron microscopy. Ussing chambers were used for measurement of potential difference (PD), transepithelial resistance (Rt), short-circuit current (Isc), and unidirectional fluxes of 22Na+ and [3H]mannitol. Light microscopy of antra from 2-day postfed animals showed many intracellular lipid granules in surface mucous epithelial cells. These granules could be distinguished from other intracellular organelles by their high affinity for osmium and the lipid fluorescent probe Nile red. Glycoprotein cytochemical staining showed these granules to be distinct from the epithelial cell mucous granules. Electron microscopy showed the lipid granules to be part of a membranous reticular network. Two-day postfed animals also had a approximately 3.5-fold increase in amiloride-sensitive Isc and PD, a decrease in Rt, and an increased luminal-to-serosal Na+ fluxes. Transepithelial [3H]mannitol fluxes were low and remained unchanged in both fasted and 2-day postfed animals. After 2 days of feeding, the PD and Isc began to decrease followed by a secondary increase in Rt. Feeding Necturi a corn oil diet did not induce the appearance of either cellular lipid or alterations in Isc but produced a transient increase in Rt. Our data show that feeding (goldfish) to Necturi causes an increase in both lipid accumulation and amiloride-sensitive Na+ transport in gastric antral cells.

Amiloride↗
PubMed1989

Electron-cytochemical localization of alkaline phosphatase to G cells of Necturus maculosus antrum.

Electron-cytochemical localization of alkaline phosphatase activity was performed on G cells of Necturus maculosus antral mucosa. Alkaline phosphatase activity was localized to the nuclear membrane, the Golgi/endoplasmic reticulum, and the limiting membranes of G cell peptide-secretion vesicles. There was no specific localization of alkaline phosphatase activity to the plasma membrane. Treatment of the tissues with levamisole (an alkaline phosphatase inhibitor) did not markedly reduce the specific alkaline phosphatase activity. Specific lead deposition was reduced by removal of the substrate from the reaction mixture. The results from this study on N. maculosus G cells demonstrate that alkaline phosphatase activity can be found in a non-mammalian gastric endocrine cell and that specific activity was localized primarily to those intracellular structures involved with protein biosynthesis.

Alkaline Phosphatase↗
PubMed1989

Effects of aspirin and acetic acid on intracellular pH in necturus gastric mucosa.

Intracellular microelectrode techniques were employed to examine the effects of luminal aspirin and acetic acid on intracellular pH and cell membrane potential in the surface epithelial cells of Necturus antrum. Antral mucosa was mounted in a modified Ussing chamber, and intracellular pH was determined from the difference between the potentials recorded by intracellular conventional and pH-sensitive microelectrodes. Under neutral conditions (pH7), aspirin (5 mM) hyperpolarized (-7.5 +/- 1 mV, p less than 0.0001) and acetic acid (5 mM) depolarized (+4 +/- 0.08 mV, p less than 0.001) cell membrane potential. Neither agent had any significant effect on intracellular pH. Under acidic conditions (pH 4.5), aspirin (5 mM) reduced the intracellular pH from 6.99 +/- 0.03 to 6.87 +/- 0.04 (p less than 0.001) and depolarized cell membrane potential from -36.7 +/- 1.5 to -30.3 +/- 1.6 mV, p less than 0.001). Similarly, acetic acid (5 mM) acidified the cells (-0.20 +/- 0.02, p less than 0.001) and depolarized cell membrane potential (+9.6 +/- 1.9 mV, p less than 0.01). These changes suggest that, in the absence of luminal acid, small organic acids, such as aspirin and acetic acid, may have complex effects on the ionic conductances of the surface cell membranes without altering intracellular pH. In contrast, under acidic conditions, these agents increase the permeability of the apical cell membrane-to-acid back-diffusion from the gastric lumen.

Acetates↗
PubMed1989

Effects of parathyroid hormone on cyclic-AMP concentrations of in vitro Necturus maculosus gastric antrum.

The effects of bovine parathyroid hormone (bPTH1-84) on the stimulation of intracellular cyclic-AMP [cAMP] were investigated in an in vitro preparation of Necturus maculosus antral mucosa. When the antrum was exposed to 1, 5, 10, or 100 nM bPTH1-84, there was an approximately 2-fold nonlinear increase in tissue [cAMP] over basal values. The pretreatment of the antral mucosa with 1 mM isobutylmethylxanthine (IBMX, a phosphodiesterase inhibitor) increased with detectability of mucosal [cAMP]. The addition of 1, 5, 10, or 100 nM bPTH1-84 to tissues pretreated with IBMX resulted in an approximately 3.5-fold linear increase in mucosal [cAMP] over basal values. The time course of the generation of mucosal cAMP to 10 nM bPTH1-84 resulted in a small but significant transient increase at 2.5 min after the addition of bPTH1-84 but no change in the medium [cAMP]. In tissues pretreated with 1 mM IBMX the response to 10 nM bPTH1-84 was a large biphasic increase of [cAMP] at 2.5 min that progressively declined to near basal values by 15 min. There was also a significant sustained increase in the [cAMP] in the bathing medium at 2.5 min of tissues pretreated with IBMX followed by 10 nM bPTH1-84. These results suggest the presence of an adenylate cyclase that can be activated by a mammalian bPTH1-84 in elevating intracellular cAMP levels in the N. maculosus antral mucosa.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Effects of cations and pH on apical membrane potential of in vitro Necturus antrum.

The surface epithelial cells of the gastric mucosa transport Na+ from lumen to serosa. The first step in this process is the entry of Na+ through an amiloride-sensitive Na+ channel at the apical membrane. The exact function(s) of this Na+ transport are unknown, but it has been suggested that it might help the stomach to withstand an acid load. The present study was undertaken to examine the effects of low luminal pH and the alkali cations Li+, K+, Rb+, and Cs+ on the amiloride-sensitive Na+ permeability of the apical membrane of Necturus antral cells by measuring the changes in apical membrane voltage (Vmc) using conventional microelectrode techniques. Isosmolar replacement of luminal NaCl (pH 7.25) with LiCl caused a depolarization of the Vmc, a decrease in transepithelial resistance (Rt), and an increase in the transepithelial potential (Vmc), whereas replacement with KCl, RbCl, or CsCl caused a hyperpolarization of the Vmc, an increase in Rt, and a decrease in the Vmc. Luminal acidification from pH 7.25 to pH 3.00 caused very similar changes with all the cation solutions tested, hyperpolarizing the Vmc, increasing Rt, and reducing the Vmc to near 0 mV. Acidification of the luminal NaCl solution from pH 7.25 to pH 2.00 caused a progressive hyperpolarization of the Vmc similar to the effects seen with luminal amiloride (10(-4) M) in pH 7.25 NaCl solutions or luminal Na+-free (N-methyl-D-glucamine) Ringer at pH 7.25. These results demonstrate that 1) of the cations tested only Li+ can substitute for Na+ in maintaining the Vmc, and 2) external H ions (low luminal pH) block cation permeability of the apical membrane.

Amiloride↗
PubMed1988

Effects of platelet-activating factor on canine gastric mucosal blood flow and permeability to luminal acid.

Recent studies suggest that platelet-activating factor, a newly described phospholipid released during acute inflammation, may predispose the gastric mucosa to acute ulceration. This study was performed to evaluate whether this substance might contribute to acute injury through its effects on mucosal microcirculation or by increasing permeability of the gastric mucosa to luminal acid. Platelet-activating factor was infused at a rate of 1 microgram/min directly into the artery supplying a chambered segment of canine gastric corpus and both significantly decreased venous outflow and mucosal blood flow and enhanced the efflux of volume, sodium ions, and potassium ions into the lumen. Thus, as in other capillary beds, platelet-activating factor appeared to induce stasis of flow and local accumulation of interstitial fluids which then leaked into the lumen. Platelet-activating factor did not significantly alter the back-diffusion of hydrogen ions into the mucosa. Thus, platelet-activating factor may not directly influence mucosal permeability to luminal acid, and it may predispose the gastric mucosa to acute injury through its effects on the microvasculature and other aspects of the inflammatory process.

Animals↗
PubMed1988

Thomas G Orr Memorial Lecture. Pathogenesis, prophylaxis, and treatment of stress gastritis.

In the last decade, significant progress has been made in understanding the basic mechanisms involved in the development of acute stress gastritis. Many of the experimental observations have been applied in our clinical approaches to patients at high risk. A strong impression exists among investigators that efforts to improve ventilatory support, correct abnormalities in cardiac output and intravascular volume, and maintain adequate nutrition in critically ill patients may have contributed to the decreased incidence and prevalence of stress gastritis over the past decade. In addition, reduction of intragastric acidity, either by titration with antacids or administration of H2 antagonists, further prevented stress gastritis in these patients. We have every reason to believe that progress will continue at the same rate in the decades before us in this area of investigation.

Gastritis↗
PubMed1988

Outcome of lymph node involvement in patients with the Zollinger-Ellison syndrome.

Prognosis of gastrinoma patients with metastases to lymph nodes only is uncertain, and the true nature of isolated nodal gastrinomas remains controversial. The purpose of this study was to determine the outcome of such patients and whether nodal gastrinomas may occur as primary lesions. Eleven patients with nodal involvement but without hepatic metastases are reported (mean follow-up of 129 months). Primary gastrinomas were located in the duodenum in seven (Group 1) and not identified in four (Group 2). In Group 1, five patients remained eugastrinemic after excision of all gross tumors and gastrectomy (n = 4) or pancreaticoduodenectomy (n = 1), one patient had residual disease and died of other causes (survival of 88 months), and one patient had MEA-I syndrome with multiple gastrinomas (follow-up of 126 months). In Group 2, three patients became eugastrinemic after nodal excision and total gastrectomy (mean follow-up of 212 months) and may represent primary nodal gastrinomas, and in one patient, liver metastases developed and the patient died. Four deaths occurred in a 27-year period, but only one was tumor-related. There was no significant difference in 20-year survival rates between the two groups (85% vs. 75%). It is concluded that 1) lymph node gastrinomas are usually metastatic from primary duodenal lesions, 2) although rare, nodal gastrinomas may occur as primary lesions, and 3) in the absence of hepatic metastases, lymph node gastrinomas, whether primary or metastatic, have a good prognosis and should not deter aggressive surgical treatment.

Adolescent↗
PubMed1987

Protective effect of exogenous phospholipid on aspirin-induced gastric mucosal injury.

The protective effects of exogenous phospholipid on aspirin-induced gastric mucosal injury were examined in a canine chamber model which provided two separate segments of mucosa supplied by a single vascular pedicle. In each dog, one segment was treated with a suspension of surface-active phospholipid, similar in composition to that normally present in the gastric mucosa, whereas the other segment served as the control. Pretreatment of the test segments significantly prevented aspirin-induced disruption of the mucosal barrier as evidenced by an increase in potential difference and a decrease in acid back-diffusion and sodium ion and potassium ion flux. These findings were associated with a marked reduction in the degree of mucosal injury. Our results support the recent hypothesis that surface-active phospholipid plays an important role in gastric mucosal defense against the damaging effects to luminal acid.

Animals↗
PubMed1987

Effects of luminal hyperosmolality on cellular and paracellular ion transport pathways in necturus antrum.

Using microelectrode techniques, the electrical properties of the cell membranes and paracellular pathway of the surface epithelium in Necturus antrum were studied under control conditions and during exposure to mucosal solutions made hyperosmotic by addition of sucrose or urea. Sucrose (500 mmol/kg) significantly decreased apical membrane resistances (Ra, from 5501 +/- 841 to 3789 +/- 597 omega X cm2, p less than 0.01), and basolateral membrane resistances (Rb, from 3805 +/- 646 to 2594 +/- 429 omega X cm2, p less than 0.05). The paracellular pathway resistance (Rs) increased significantly from 720 +/- 57 to 822 +/- 71 omega X cm2 (p less than 0.001). Urea (500 mmol/kg) more markedly diminished the apical and basolateral resistances (Ra, from 4303 +/- 663 to 1914 +/- 286 omega X cm2, p less than 0.001; and Rb, from 2600 +/- 474 to 1034 +/- 213, p less than 0.001). In contrast to sucrose, urea-containing solutions significantly decreased Rs (from 682 +/- 78 to 398 +/- 57 omega X cm2, p less than 0.001). Electron micrographs revealed dilatation of lateral intercellular spaces and disruption of desmosomes in tissues exposed to urea, but no visible alterations in tissues exposed to solutions containing sucrose. The resistance of the cellular pathway to ion permeation was thus diminished during exposure to both solutes. In contrast, changes in resistance of the paracellular pathway appeared to depend on the effects of each solute on dimensions and structures of the intercellular pathways.

Animals↗
PubMed1987

Endoscopic measurements of canine colonic mucosal blood flow using hydrogen gas clearance.

We have examined the feasibility of hydrogen (H2) clearance for endoscopic measurements of colonic mucosal blood flow in anesthetized dogs. In 6 animals, measurements of H2 clearance did not differ significantly in different regions of the sigmoid colon and they were highly reproducible (p less than 0.001) on different days. In a total of 12 dogs, measurements of H2 clearance correlated closely with those obtained using radioactive microspheres under resting conditions and, in 4 dogs, during infusion of vasopressin (slope = 0.94, p less than 0.001). In 8 dogs, ligation of the major arteries supplying the sigmoid colon resulted in an acute 60% decrease in sigmoid mucosal blood flow (p less than 0.001); however, in 5 animals that survived the procedure, mucosal blood flow returned nearly to control levels as early as 3 days after operation. Endoscopic H2 clearance thus appears to be feasible for measuring mucosal blood flow in the colon. Serial measurements of H2 clearance may prove useful in characterizing the role of mucosal blood flow in the pathogenesis of various forms of human colonic disease.

Animals↗