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Biomedical subjects

W Silen

Publications and source records attributed to W Silen.

At least 73 records · Page 4Linked to original sources
PubMed1987

Secretagogue-induced changes in intracellular pH and amylase release in mouse pancreatic acini.

The response of the intracellular pH (pHi) to stimulation of enzyme secretion in pancreatic acini was measured using the fluorescent dye 2'-7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Acini suspended in pH 7.40 buffer demonstrated cytoplasmic alkalinization of 0.17, 0.14, and 0.15 pH units 2 min after addition of the secretagogues carbachol (10(-5) M), caerulein (10(-10) M), and bromo-A23187 (10(-6) M). Corresponding net stimulated amylase secretion over 30 min was 9.2, 10.3, and 5.6% of total content, respectively. Pretreatment of acini with atropine blocked the pHi rise induced by carbachol; addition of atropine 2 min after the carbachol did not reverse the alkalinization. Acini suspended in Ca2+ free buffer containing 0.1 or 0.2 mM ethylene glycol tetraacetic acid showed 0.21 and 0.10 pH unit alkalinization in response to caerulein (10(-10) M) and carbachol (10(-5) M) but no change in pHi after addition of bromo-A23187. Amylase release in response to increasing concentrations of caerulein was maximal at 10(-10) M, with decreasing rates of amylase release at higher drug concentrations (10(-8), 10(-7) M). Alkalinization in response to stimulation of secretion was maximal at 10(-8) M caerulein (0.30 pH units at 2 min) but was of lesser magnitude at 10(-7) M. Pancreatic acini demonstrated autoregulation of pHi over a range of external pH from 7.4 to 7.1. Net amylase release over 30 min in response to 10(-5) M carbachol was sustained at normal levels in buffers of pH varying between 7.7 and 6.5. In contrast, cytoplasmic alkalinization in response to carbachol occurred only in buffers with pH values between 7.40 and 7.10. These results indicate that amylase release occurs over a wide range of pHi and is not invariably associated with secretagogue-induced alkalinization.

Amiloride↗
PubMed1987

The clinical problem of stress ulcers.

True stress ulcers are primarily superficial gastric fundic lesions that occur in the clinical setting of severe shock, trauma, burns, and sepsis, especially peritonitis. They are to be clearly differentiated from Cushing's ulcers, exacerbation of pre-existent chronic ulcers, and drug-induced gastritis, all of which have completely different pathogenetic mechanisms. The etiology of true stress ulcers is most importantly related to ischemia and tissue acidosis, although luminal acid and pepsin are requisite for ulceration to occur. The sole clinical manifestation of stress ulcers is hemorrhage. Prophylaxis with antacids alone, or with a combination of antacids and H2 receptor antagonists is highly efficacious if luminal pH is carefully monitored. The treatment of exsanguinating hemorrhage, once established, carries with it an extremely high morbidity and mortality.

Antacids↗
PubMed1986

Effect of simulated systemic administration of aspirin, salicylate, and indomethacin on amphibian gastric mucosa.

The effects of 20 mM aspirin (ASA), 20 mM sodium salicylate (SA), or 10(-4) M indomethacin placed in the nutrient solution (N) to stimulate systemic administration were investigated at pHN 7.3 in Ussing-chambered amphibian gastric mucosae. In histamine-stimulated tissues, the initial rise and subsequent rapid fall in potential difference, rise in resistance, and inhibition of hydrogen ion (H+) secretion induced by SAN did not occur with ASAN unless hydrolysis of ASAN produced a SAN of greater than 3 mM. In metiamide-treated tissues, 20 mM SAN caused an immediate fall in potential difference and an increase in resistance; 2 mM SAN and 20 mM ASA produced similar qualitative electrical changes, but only those induced by ASA were reversible. IndomethacinN caused no significant changes in potential difference, resistance, or H+ secretion in histamine- or metiamide-treated tissues. Despite producing highly significant reductions in generation of prostaglandin E2, and prostaglanndin F2 alpha and 6-keto prostaglandin F1 alpha, ASAN and indomethacin caused no surface ulceration. Sodium salicylate placed in the nutrient solution caused only a small reduction in prostaglandin F2 alpha, without change in the other prostaglandins, and produced extensive edema in the lamina propria, histologically. We conclude the following: (a) The inhibition of H+ secretion and electrical changes caused by SAN in histamine-treated gastric fundus are not observed with ASAN unless there is hydrolysis to [SAN] greater than 3 mM. (b) Our data strongly implicate the SAN in ASAN-containing solutions as being responsible for the electrical effects and inhibition of H+ secretion. (c) There is no correlation in vitro between inhibition of prostaglandin synthesis and the electrical or morphologic changes produced by nutrient exposure to ASA, SA, or indomethacin.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy.

Edema of the arm can be a significant complication following treatment of breast cancer. To determine the risk of arm edema and factors associated with this risk in patients treated with primary radiotherapy, we reviewed the records of 475 women with early breast cancer treated between 1968 and 1980. During this period, the use of axillary surgery prior to radiation gradually increased, and all patients received full axillary irradiation until late in the series. Based on the surgeon's report, the extent of axillary surgery was classified as either a sampling, a lower dissection, or a full dissection. Edema of the arm was scored on clinical grounds and ranged from mild hand swelling to an increased arm circumference of 8 cm. At 6 years, the actuarial risk of developing arm edema was 8% for the entire study population. This risk was 13% for 240 patients who had axillary surgery and 4% for 235 patients not undergoing axillary surgery (p = 0.006). For patients undergoing axillary surgery, the risk of arm edema was 37% with full dissection compared to 5% with sampling (p = 0.0003), and 8% with lower dissection (p = 0.03). The risk of arm edema at 6 years was 28% if more than ten nodes were removed, and 9% if one to ten nodes were removed (p = 0.03). However, the extent of axillary dissection was stronger predictor of subsequent edema than was the number of nodes obtained. The role of axillary irradiation could not be evaluated since 91% of patients received axillary irradiation. The use of chemotherapy, the site or size of the primary tumor, clinical nodal status, patient age and weight, type of suture, the use of a drain, and subsequent local or distant failure did not appear to be significant risk factors. We conclude that the combination of full dissection and full axillary irradiation results in an unacceptably high risk of arm edema.

Arm↗
PubMed1986

Transforming growth factor alpha inhibits secretion of gastric acid.

Transforming growth factor alpha (TGF-alpha), a protein secreted by transformed cells and related to epidermal growth factor (EGF), was tested for its effects on gastric acid secretion. Guinea pig gastric mucosae were mounted in Ussing chambers and the rate of acid release was monitored by the pH-stat method. When administered prior to the secretagogue, TGF-alpha prevented the histamine-induced increase in the rate of acid secretion. Similarly, TGF-alpha caused a decrease in the rate of acid release in tissues that had already been stimulated with histamine. These data show that TGF-alpha inhibits gastric acid secretion in a manner similar to EGF and that the two growth factors share at least one physiological action unrelated to their mitogenic properties.

Animals↗
PubMed1986

Chloride transport of frog gastric fundus: effects of omeprazole.

Omeprazole (10(-4) M) inhibited H+ secretion and increased potential difference (PD), resistance, and short-circuit current (Isc) in chambered bullfrog gastric mucosa, but the electrical changes developed only in tissues previously exposed to histamine. Net chloride transport (JnetCl) did not change after omeprazole under short-circuited conditions, and Isc increased to become equal to JnetCl. Under open-circuit conditions, JnetCl was reduced by 38%, the decrement attributable to the concomitant increase in PD, as evidenced by a linear relationship between JnetCl and PD in omeprazole-treated mucosae clamped to different PD (0-45 mV). The effect of omeprazole on PD and Isc could be blocked by metiamide and was absent in spontaneously resting tissues. HEPES nutrient solutions did not alter the electrical response or Cl- transport after omeprazole. In Na+-free solutions, omeprazole induced only a transient rise in PD and Isc. We conclude that omeprazole uncouples H+ and Cl- secretion. This Cl- secretion is electrogenic and dependent upon stimulation by histamine. Both Na+ and HCO3- seem to be involved in movement of Cl- across the basolateral membrane.

Animals↗
PubMed1985

Pathogenetic factors in erosive gastritis.

Under physiologic conditions, luminal acid and pepsin are absolute requirements in the development of erosive gastritis and ulceration. Even the injurious effects of most drugs are potentiated by acid and pepsin. Although the importance of luminal acid has long been recognized, only in the last 10 years has evidence accrued showing the detrimental effects of tissue acidosis in producing injury to the gastric mucosa. It now seems clear that by whatever means it is produced, e.g., through reduced mucosal blood flow, metabolic or respiratory acidosis, or inhibition of acid secretion with subsequent decreased "alkaline tide," tissue acidosis plays a profound role in the pathogenesis of erosive gastritis and ulceration. The gastric mucosal barrier is now recognized as the anatomic integrity of the surface epithelium, rather than as an ethereal physiologic barrier. This barrier is maintained as an intact layer under physiologic conditions by a newly described rapid repair process called restitution.

Acid-Base Imbalance↗
PubMed1985

A rapid method for culturing guinea pig gastric mucous cell monolayers.

A method has been developed for growing confluent primary cultured monolayers of guinea pig gastric mucous cells suitable for in vitro electrophysiological, transport, and pharmacological studies. Isolated mucous cells were enriched on a one-step Percoll density gradient and plated on fibronectin-coated plastic dishes or in small cups with holes containing glutaraldehyde-fixed Vitrogen gels. These cups were designed to fit in Ussing chambers. Mucous cells attached, proliferated, and formed confluent monolayers in 3 d. The low cuboidal cells contained periodic acid Schiff-positive mucous granules that were negative by Bowie and indirect immunofluorescent staining for pepsinogen. Electron microscopy revealed polarized mucous cells with microvilli, mucous granules, microfilaments, small mitochondria, some vacuoles, and junctional complexes that excluded wheat germ agglutinin-peroxidase. No basal lamina was present. Monolayers could be maintained for over 2 wk but subcultures were not made. The cultures were virtually free of fibroblasts. Epithelial sheets produced by this simple and rapid method can be used for electrophysiological, ion transport, and pharmacological studies.

Animals↗
PubMed1985

In vitro protection of amphibian gastric mucosa by nutrient HCO3- against aspirin injury.

The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues. The severe surface cell and oxyntic gland injury seen in histamine-stimulated tissues after a 3-h exposure to 20 mM ASA at luminal pH 4.5 in HCO3- -free nutrient solution (HEPES) was prevented by including 18 mM or 48 mM HCO3- in the nutrient solution. At luminal pH 3.0, 48 mM HCO3- in the nutrient solution delayed the histologic damage to the surface epithelium and oxyntic glands caused by a 30-min exposure to 20 mM luminal ASA, but it afforded no protection to a 60-min exposure. This protection of the gastric epithelium by a high nutrient [HCO3-] did not occur in metiamide-treated tissues at luminal pH 3.0. Although the injury to antral epithelial cells exposed to 20 mM luminal ASA at luminal pH 3.0 or 4.5 was less severe than that in fundic mucosae, 48 mM HCO3- in the nutrient solution also afforded clear protection in this tissue. A high nutrient [HCO3-] prevented the sharp fall in the potential difference observed in fundus exposed to ASA at luminal pH 4.5 and delayed the fall in potential difference observed in fundic and antral mucosae exposed to ASA at luminal pH 3.0. The high nutrient [HCO3-] did not prevent the increase in resistance observed in tissues during ASA exposure at luminal pH 4.5 and 3.0. The electrical data reflect not only the damaged surface and oxyntic cells caused by ASA, but also the complex effects of ASA on active and passive ion transport. We conclude the following: (a) The mucosal injury to the fundus and antrum caused by luminal ASA is prevented by 48 mM HCO3- in the nutrient solution when luminal pH is 3.0 and by 18 mM HCO3- when luminal pH is 4.5. Absence of nutrient HCO3- accentuates the injury caused by luminal ASA. (b) The luminal pH, concentration, and time of exposure influence the depth and severity of ASA injury to the fundic and antral mucosa. (c) The electrophysiologic and morphologic changes after ASA exposure are not interrelated, due to the complex effects of ASA on the ion transport and morphology of the gastric epithelium.

Animals↗
PubMed1985

Perineal hernias after proctectomy. A new approach to repair.

Perineal herniation of pelvic organs rarely occurs after abdominoperineal resection of the rectum, but it does present a difficult surgical dilemma. The case of a patient with perineal herniation of the small bowel and urinary bladder into a proctectomy wound has been described. This was repaired using a transabdominal pelvic sling with Marlex followed by gracilis muscle transplantation. Review of the literature yielded 18 previous case reports of perineal hernia after proctectomy, and the results of various surgical approaches have been detailed and discussed. The technique of gracilis muscle transplantation offers a definite advantage when the hernia occurs in a contaminated perineal wound.

Crohn Disease↗
PubMed1985

Recurrent hyperparathyroidism due to implantation of parathyroid tissue.

Recurrence of hyperparathyroidism after initially successful primary operation is usually caused by inadequate resection of diseased tissue or recurrent carcinoma. Since it is known that normal parathyroid tissue may be autotransplanted into a muscle bed, it is plausible that inadvertent implantation of parathyroid tissue spilled at operation may occur. In four of 23 reoperations for hyperparathyroidism in an 11 year period, we found evidence that iatrogenic parathyroid implantation had occurred. Two of the four patients had multiple parathyroid implants in the previous operative field, and one of these patients had documented spillage of a cystic adenoma during the original operation. Another two of the four patients were found to have recurrent adenomas containing suture material at sites of previous excision of the adenomas. No patient had gross or histologic evidence of parathyroid carcinoma. We conclude that inadvertently spilled parathyroid tissue may implant in the neck or mediastinum and cause persistent or recurrent hypercalcemia. Therefore, all efforts should be made to handle the parathyroid glands only by their pedicles and not to crush, suture, or violate the capsule. Needle aspiration of parathyroid cysts could lead to implantation along the needle tract.

Adenoma↗
PubMed1985

Effects of epidermal growth factor on acid secretion from guinea pig gastric mucosa: in vitro analysis.

Epidermal growth factor (EGF) has been tested on guinea pig gastric mucosa mounted in Ussing chambers to investigate the suitability of using in vitro methods for examining EGF's effects on acid secretion. Epidermal growth factor reduced the rate of histamine-induced acid secretion to near basal levels when applied to the serosal gastric surface at nanomolar concentrations. Inhibitory effects were evident 10-15 min after EGF treatment and were maximal by 40 min. Cyclic adenosine monophosphate-induced secretion was also reduced by EGF, although the effect occurred more slowly than in histamine-treated tissues. Epidermal growth factor increased transmucosal resistance in histamine-treated, but not cyclic adenosine monophosphate-treated mucosa; potential difference was unaffected. Nerve growth factor had no effect when tested in the in vitro system. The EGF binding protein was found to enhance slightly the inhibitory activity of EGF on acid secretion. When applied to the luminal (mucosal) gastric surface, EGF inhibited secretion marginally but only at micromolar concentrations. These results indicate that EGF acts directly upon cells within the gastric mucosa, and is most effective when applied to the serosal gastric surface. They further suggest that in vitro preparations of intact gastric mucosa can be used for analyzing the inhibitory effects of EGF on gastric acid secretion.

Animals↗
PubMed1985

Requirements for restitution of the surface epithelium of frog stomach after mucosal injury.

In frog fundic mucosae mounted in Ussing chambers, exposure to luminal 1 M NaCl for 10 min caused a sharp immediate decrease in potential difference, resistance, short circuit current, and acid secretion, but within 4-6 h these readings had returned toward control values. After initial severe destruction of surface epithelial cells, gradual morphologic restitution occurred within 4-6 h. A Ca2+-free nutrient solution and 4 mM ethylenediaminetetraacetic acid administered after injury prevented both physiologic and morphologic restitution. A Ca2+-free nutrient solution administered alone after injury prevented physiologic recovery, but although narrow gaps and lack of tight junctions were found between some cells, there was near-complete epithelial cell coverage. The addition of 2 mM Ca2+ to these tissues 3 h after injury effected rapid recovery of electrophysiologic parameters and a complete closure of the intercellular spaces. Cytochalasin B (3 X 10(-3) M nutrient) prevented physiologic recovery and mucosal restitution. Neither cycloheximide nor colchicine had any effect on the normal process of restitution. Autoradiography of [3H]thymidine incorporation showed no increase in labeling within 4 h of hyperosmolar injury. We conclude that adequate Ca2+ is required for complete restitution of gastric mucosa after hyperosmolar injury, and that restitution occurs by migration of persisting viable gastric pit cells.

Animals↗
PubMed1985

Duodenojejunostomy for the pancreaticobiliary complications of duodenal diverticulum.

A Roux-en-Y duodenojejunostomy has been used as treatment of pancreaticobiliary disease associated with duodenal diverticula in three patients with good results. This approach removes the diverticulum from the food stream, thereby solving the problems of recurrent cholangitis and pancreatitis caused by food stasis in the diverticulum, without having to excise the diverticulum or perform a gastrectomy and vagotomy.

Aged↗
PubMed1985

Transepithelial transport of guinea pig gastric mucous cell monolayers.

Guinea pig gastric mucous epithelial cells were isolated, enriched, cultured in collagen cups, and put into Ussing chambers for electrophysiological studies. The cultured mucous cell monolayers, which retain the morphology of surface cells found in the intact tissue, had a maximal resistance (R) of 272 +/- 12 omega X cm2 and a potential difference (PD) of -3.8 +/- 0.4 mV (apical negative) between 4 and 10 days later (n = 33). The current-voltage and conductance-concentration relationships of the cultures were both nonlinear (n = 12). In addition, NaCl concentration gradients across the monolayer also gave asymmetrical and nonlinear dilution potentials, with the side of lower chemical potential always becoming electrically negative (n = 10). Calculation of the average Cl(-)-to-Na+ permeability ratio at pH 7.4 was 1.35, indicating a slightly greater conductance of anions over cations. Amiloride (0.1-1.0 microM) had no effect on PD or R when given from the apical or basal side (n = 18), but at higher concentrations (0.1-1.0 mM) there was a decrease in the PD. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid at 10(-4) M increased R from the apical side only (n = 14), and acetazolamide at 5 X 10(-4) M reduced the PD to -0.5 mV (n = 8). Only ouabain at 10(-4) M from the serosal side was effective in reducing the monolayer PD to zero. This culture preparation will prove useful for future studies in determining specific functions for this gastric cell type and how those functions relate to barrier function in the stomach.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗