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J M Scheiman

Publications and source records attributed to J M Scheiman.

66 records · Page 4Linked to original sources
PubMed1992

Role of prostaglandin E2 in cholinergic-mediated glycoprotein synthesis in canine antrum.

We studied the mechanism of cholinergic stimulation of mucin synthesis in canine antral explants, including the role of PGE2 as an intermediate messenger. Isolated antral mucosa was incubated with 10(-5) M carbachol (Cb), 10(-5) M indomethacin (IND), 10(-5) M pirenzepine (PZ), 10(-5) M Cb + 10(-5) M PZ, 10(-5) M Cb + 10(-5) M IND, and 10(-5) M IND + PGE2 (10(-8), 10(-7) and 10(-6) M) in the presence or absence of [3H]glucosamine. After 24 hr, total glycoprotein synthesis was quantitated by Sepharose-4B chromatography and by 10% TCA/1% PTA precipitation with lipid extraction. PGE2 released into the media was measured by radioimmunoassay (RIA). Cb significantly increased total glycoprotein synthesis and produced a significant increase in PGE2 release. The increase in glycoprotein synthesis and the release of PGE2 was blocked by the addition of muscarinic antagonist PZ. The addition of IND significantly inhibited glycoprotein synthesis and almost entirely suppressed PGE2 secretion. IND also inhibited the effect of Cb on glycoprotein synthesis and PGE2 release. Moreover, PGE2 (10(-6) and 10(-7) M) significantly increased the glycoprotein synthesis in the canine stomach. This suggests the coordinate participation of PGE2-releasing cell population in modulation of glycoprotein synthesis in gastric mucosa.

Animals↗
PubMed1992

Effect of sucralfate on components of mucosal barrier produced by cultured canine epithelial cells in vitro.

The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repair, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro. Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively). Indomethacin pretreatment significantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucous barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was noted, although a significant increase in surface active phospholipid release was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract.

Cytochrome P450 enzymes are capable of converting procarcinogens into either active mutagens or inactive metabolites. Because the distribution of these enzymes may be important for tissue susceptibility to procarcinogens, the expression and induction of CYP1A genes in the human alimentary tract were investigated. Endoscopic biopsy specimens were obtained from buccal mucosa, esophagus, gastric body, antrum, duodenum, and colon of 6 healthy volunteers before and 1 week after taking 20 mg of omeprazole daily. Tissue specimens were analyzed for the presence of CYP1A1 and 1A2 transcripts using hybridization methods and the polymerase chain reaction. P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin. CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer. Omeprazole (20 mg/day for 1 week) induced CYP1A1 mRNA and enzymatic activity in 5 of 6 volunteers. The one individual who did not initially respond had a marked increase in both mRNA and enzymatic activity after receiving 60 mg of omeprazole daily for 1 week. After treatment with omeprazole, two individuals had low levels of CYP1A1 mRNA in several other alimentary tissues as well as low levels of CYP1A2 mRNA in the duodenum. The expression and induction by a pharmaceutical agent of CYP1A genes may have implications for intestinal metabolism of ingested xenobiotics including procarcinogens.

Adult↗
PubMed1992

Regulation of canine gastric mucin synthesis and phospholipid secretion by acid secretagogues.

Key components of the mucous gel include the glycoprotein mucin and surface-active phospholipids. In the present study, mucin production and release of the surface-active phospholipid phosphatidylcholine (PC) into the medium were measured with an isolated canine mucous cell culture system. Stimulation of glycoprotein synthesis in response to 10(-4) mol/L histamine (160% +/- 9% of control, P < 0.01), 10(-6) mol/L gastrin (129% +/- 7%, P < 0.01), and 10(-6) mol/L carbamylcholine (129% +/- 7%, P < 0.01) was observed by metabolic labeling, whereas prostaglandin E2 (PGE2) had no effect. The effect of histamine was blocked by the H2 receptor antagonist cimetidine but not the H1 receptor antagonist diphenhydramine (P < 0.01). Activators of adenylate cyclase and cyclic adenosine monophosphate analogs significantly stimulated mucin synthesis (P < 0.05). A 7.8% +/- 1.7% increase in mucin above basal levels after 24 hours was observed with a solid-phase immunoassay in control wells, whereas histamine, gastrin, and carbamylcholine increased total mucin by 14% +/- 0.7%, 17% +/- 4.3%, and 20.4% +/- 4%, respectively (all P < 0.01), and PGE2 had no significant effect. PC release was stimulated by the administration of histamine, carbamylcholine, gastrin (108%-110% of control, P < or = 0.05), and PGE2 (120% of control, P < 0.01). The acid secretagogues histamine, gastrin, and carbamylcholine stimulated mucin synthesis and PC release. PGE2 has no direct role in the synthesis of canine gastric mucin but stimulates release of surface-active phospholipids. The mechanisms responsible for acid secretion provide for the coordinated production of the primary layer of defense against the injurious effects of low pH.

Animals↗
PubMed1992

Pathogenesis of gastroduodenal injury due to nonsteroidal antiinflammatory drugs: implications for prevention and therapy.

Nonsteroidal antiinflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation by interfering with the ability of the proximal gastrointestinal tract to maintain its defensive capabilities. Mucosal defense is composed of three critical components: preepithelial, epithelial, and postepithelial. Preepithelial defense is composed of the mucous gel containing mucin, bicarbonate, and surface-active phospholipids. The epithelial component includes the surface cells, their apical tight junctions, and membrane transporters. Postepithelial defense is maintained by mucosal blood flow, which is essential for both defense and repair. NSAIDs interfere with each component of mucosal defense via direct toxic effects along with cyclooxygenase inhibition and depletion of endogenous prostaglandins. Although NSAID injury is dependent on luminal acid, attempts to prevent NSAID injury by acid suppression using H2-receptor antagonists in humans have had limited success, whereas complete inhibition of acid secretion with proton pump inhibition may have promise. Prostaglandins appear most effective for prevention of NSAID injury, sucralfate appears ineffective, and bismuth compounds have not been studied extensively. Recent evidence suggests that NSAID ulcers heal quickly with proton pump inhibitors compared with H2-receptor antagonists in patients who continue NSAID therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Synthesis and prostaglandin E2-induced secretion of surfactant phospholipid by isolated gastric mucous cells.

Lipids, particularly surface-active phospholipids, have been proposed to provide an important protective barrier in the gastric mucosa. The predominant surface-active phospholipid in the pulmonary surfactant complex is dipalmitoylphosphatidylcholine. To determine whether the gastric epithelium synthesizes and secretes this phospholipid, primary cultures of canine gastric mucous cells isolated by counterflow elutriation were studied. During the 24-hour period of culture, the gastric mucous cells incorporated 3H-choline into phosphatidylcholine, with dipalmitoylphosphatidylcholine representing 13.8% +/- 0.6% of the phosphatidylcholine synthesized. When mucous cell preparations with greater chief cell contamination were studied, they incorporated significantly less precursor into dipalmitoylphosphatidylcholine. Administration of prostaglandin E2, a cytoprotective agent, to the cultured mucous cells for 1 hour led to a significant increase in phosphatidylcholine release, reaching a maximum of 120.4% +/- 4.2% (P less than 0.001) at 10(-6) mol/L. No significant stimulation of phospholipid release by prostaglandin E2 was seen in the fractions containing a greater proportion of chief cells. To further establish the relationship between mucin and phospholipid secretion, two gastric cancer cell lines, Hs746T and KATO III, were studied. Using immunocytochemical and biochemical techniques, mucin synthesis and secretion were confirmed by these cell lines. The Hs746T cells were significantly more active in the secretion of both mucin and phospholipid than the KATO III cells. The Hs746T line secreted 5.7-fold more mucin and 7.3-fold more phospholipid than KATO III cells during a 24-hour period of culture. The association between mucin and phospholipids in an aqueous solution was also studied. Purified mucin in the concentration of 0.5-2 mg/mL of glycoprotein led to a significant dose-dependent increase in phospholipid solubility, suggesting the formation of a glycoprotein-phospholipid complex. The current studies indicate that the gastric mucous cell is the source of surfactant phospholipids as well as mucin. The synthesis and release of mucin and phospholipid are functions of the mucous cell that play a critical role in the primary defense of gastric epithelium.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.

Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

Animals↗
PubMed1990

Characterization of mucous cell synthetic functions in a new primary canine gastric mucous cell culture system.

Mucin is a critical component of the protective layer secreted by gastrointestinal mucous cells. A detailed understanding of the molecular processing of gastric mucin and the physiology of its secretion has been limited by the lack of an adequate model for their study. We have developed a primary culture system of canine gastric mucous cells that has permitted us to study their synthetic and secretory functions. It was found that [3H]glucosamine used for metabolic labeling studies was incorporated into both mucin and lipid components of gastric mucus. To measure mucin with this model, a new immunoassay was developed to quantitate canine gastric mucin. Mucin was purified from the canine stomach, a polyclonal antibody was generated, and an enzyme-linked immunosorbent assay for gastric mucin was established. Mast cells were frequent contaminants of the gastric mucous cell preparation, and two methods were developed to limit their contamination. A new culture system has been developed for the study of gastric mucous cells. These cells synthesize and secrete both mucin and phospholipids. This system will permit us to study the molecular processing of mucin and the physiology of its production and release.

Animals↗
PubMed1989

Salicylsalicylic acid causes less gastroduodenal mucosal damage than enteric-coated aspirin. An endoscopic comparison.

The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication-free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2-3) (P = 0.01). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin.

Adolescent↗
PubMedDate not supplied

Utility of a linear array ultrasound endoscope in the evaluation of suspected pancreatic disease.

Endoscopic ultrasonography (EUS) is currently being used to evaluate and stage pancreaticobiliary malignancies and neuroendocrine tumors, and to perform aspiration for cytologic diagnosis. There are currently two different commercially available EUS systems for clinical use. One system uses a mechanical radial sector scanner oriented in a plane perpendicular to the long axis of the endoscope, and the other uses an electronic convex scanner that is oriented in the long axis of the endoscope. The vast majority of the current literature reports experience using the radial scanning device in the evaluation of pancreaticobiliary abnormalities. We prospectively evaluated the linear probe as the sole instrument for EUS in 26 patients with suspected pancreatic disease. The results of the endoscopic ultrasound examination were compared with the results of surgery or long-term clinical follow-up. The sensitivity and specificity of linear array EUS for benign pancreatic disease were 93.8% and 88.2%, respectively. The sensitivity and specificity for malignant disease of the pancreas were 80.0% and 88.9%, respectively. The linear array echoendoscope, employed as the only instrument for evaluation of the pancreas, is accurate in the evaluation of pancreatic disease. The addition of EUS-guided pancreatic biopsy would be anticipated to improve the sensitivity of the linear array instrument for detecting malignancy.

Endoscopes↗
PubMedDate not supplied

NSAID-induced peptic ulcer disease: a critical review of pathogenesis and management.

Nonsteroidal anti-inflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation. Age greater than 60 years, a prior history of ulcer disease, and concomitant corticosteroid use are important risk factors for ulcer development. NSAIDs interfere with mucosal defense via direct toxic effects in addition to cyclooxygenase inhibition and subsequent depletion of endogenous prostaglandins. While all NSAIDs are ulcerogenic, drugs which avoid topical injury and do not inhibit mucosal prostaglandins appear to have lesser risk of toxicity. Although NSAID injury requires luminal acid, prophylactic use of H2 receptor antagonists has been disappointing, preventing duodenal injury only. Greater acid suppression with proton pump inhibition appears promising. Prostaglandins are effective for prevention of NSAID-induced gastroduodenal injury, but are not well tolerated. Recent evidence suggests NSAID ulcers heal rapidly with proton pump inhibitors compared to H2 receptor antagonists in those patients who require continued NSAID therapy.

Anti-Inflammatory Agents, Non-Steroidal↗