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Biomedical subjects

W Silen

Publications and source records attributed to W Silen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Influence of Cl- on pH(i) in oxynticopeptic cells of in vitro frog gastric mucosa.

The effect of Cl- on intracellular pH (pH(i)) was studied using sheets of frog (Rana catesbeiana) fundic mucosa in which oxynticopeptic cells were selectively loaded with the acetomethoxy ester form of the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF/AM). Before the measurement of pH(i), tissues were exposed to either 10(-5) M forskolin in the serosal solution (stimulated tissues) or 3 x 10(-4) omeprazole in the serosal solution (inhibited tissues). In HCO3- and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffers, pH(i) increased significantly after removal of Cl- from serosal and luminal solution, both in stimulated and inhibited tissues. The presence of Cl- in the luminal solution prevented this rise in pHi, an effect abolished by serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 3 x 10(-4) M) but not by serosal amiloride (10(-3)M). In the presence of serosal Cl-, pH(i) increased after exposure to serosal DIDS, more prominently in the stimulated than in the inhibited tissues. These results confirm the presence of a Cl(-)-HCO3-exchanger in the basolateral membrane of oxynticopeptic cells in intact sheets of mucosa and suggest that luminal Cl- contributes to the regulation of pH(i) in oxynticopeptic cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Effect of basolateral acidification on the frog oxynticopeptic cell.

The effects of intracellular acidosis induced by acidification of the basolateral (nutrient) perfusate on the structure and function of the oxynticopeptic cell were studied in in vitro frog gastric mucosa. Changing the pH of the unbuffered nutrient perfusate (UNB) from 7.2 to 3.5 acidified the oxynticopeptic cell with no change in potential difference (PD) or resistance (R). Intracellular pH (pHi), PD, and R were 7.05 +/- 0.01, 16 +/- 1 mV, 165 +/- 7 omega.cm2 before and 6.44 +/- 0.01, 16 +/- 2 mV, 170 +/- 9 omega.cm2 after nutrient acidification. Acid secretion (H+) increased from 0.86 +/- 0.07 to 1.88 +/- 0.18 mu eq.cm-2.h-1. Addition of forskolin to tissues perfused with nutrient pH (pHn) 3.5 decreased PD to 2 +/- 2 mV and further increased H+ to 3.07 +/- 0.19 mu eq.cm-2.h-1. By light and electron microscopy oxynticopeptic cells perfused with UNB, pHn 3.5, appeared normal. Oxynticopeptic cells in tissues pretreated with omeprazole and then exposed to UNB, pHn 3.5, had extensive morphological damage. On increasing the pH of the nutrient perfusate from 3.5 to 7.2 there was prompt recovery of pHi in untreated and forskolin-stimulated mucosae (pHi 6.87 +/- 0.06 and 6.85 +/- 0.04) but no recovery of pHi in tissues pretreated with omeprazole or cimetidine (pHi 6.26 +/- 0.04 and 6.44 +/- 0.06, n = 6, 30 min after reexposure to UNB, pHn 7.2). We conclude that in a secreting mucosa intracellular acidification of the oxynticopeptic cell to pHi 6.4 is associated with normal morphology, PD, R, and increased H+, and that intracellular acidosis is not de facto deleterious.

Animals↗
PubMed1990

Leakage of HCO3- and mucosal restitution.

When the integrity of the gastric mucosa is destroyed, there is a large passive diffusion of interstitial HCO3- from the nutrient side to the luminal side of the tissue. In the absence of nutrient HCO3-, rapid repair of superficial mucosal injuries is slowed markedly down or does not take place at all. The effects of a high degree of luminal acidification, which prevents rapid repair, can be counteracted by high concentrations of nutrient HCO3-. The importance of nutrient HCO3- is emphasized by the finding that luminal acid may destroy both the fibrin network beneath which restitution occurs and the basal lamina along which viable cells must migrate to re-establish epithelial continuity. At the present time, it is not known whether the preventive effects of HCO3- against ulceration in a variety of systems are dependent upon leakage of HCO3- toward the surface, or whether nutrient HCO3- actually enters cells in order to regulate intracellular pH.

Acid-Base Imbalance↗
PubMed1989

In situ carcinoma of the breast.

In situ carcinoma of the breast is a proliferation of potentially malignant cells within the lumen of the ductal-lobular system and is classified as ductal or lobular in type. It has become an increasingly frequent clinical management problem, primarily because of its enhanced detection by screening mammography. In this paper, we discuss the problems in histologic diagnosis, the natural history, presentation, and options for management of these two forms of in situ carcinoma.

Breast Neoplasms↗
PubMed1989

Effect of PCO2 on intracellular pH in in vitro frog gastric mucosa.

Steady-state intracellular pH (pHi) in 0, 5, and 10% CO2-buffered Ringer solution in sheets of in vitro frog gastric antral or fundic mucosa has been measured using the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In tissues perfused with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-100% O2 buffer [extracellular pH (pHo) = 7.14], steady-state pHi in antral surface cells was 7.08 +/- 0.06 (n = 8), in fundic oxynticopeptic cells 6.91 +/- 0.03 (n = 13), in the muscularis mucosa 7.58 +/- 0.06 (n = 4). In mucosae perfused with 17.8 mM HCO3- -95% O2-5% CO2 buffer (pHo = 7.14), steady-state pHi in antral surface cells was 6.97 +/- 0.02 (n = 22), in fundic oxynticopeptic cells 7.00 +/- 0.04 (n = 18), and in fundic muscularis mucosa 7.39 +/- 0.05 (n = 8). In fundic oxynticopeptic cells perfused with 35.6 mM HCO3- -90% O2-10% CO2 (pHo = 7.14) steady-state pHi was 6.77 +/- 0.07 (n = 4). In tissues equilibrated initially with 100% O2 and changed to 5% CO2, antral surface cells acidified by 0.21 pH units and fundic oxynticopeptic cells by 0.10 pH units, with restoration of pHi to resting levels within 30 and 10 min, respectively. Exposure of tissues initially equilibrated with 5% CO2 to 100% O2 alkalinized antral surface cells by 0.22 pH units and fundic oxynticopeptic cells by 0.23 pH units, with only partial recovery of pHi by 30 min. These data suggest that steady-state pHi is equivalent in surface and oxynticopeptic cells and is lower than in the muscularis mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of CO2 on pHi in rabbit parietal, chief, and surface cells.

We investigated the pH recovery mechanisms in rabbit parietal, chief, and surface cells during pH shifts induced by introduction or removal of exogenous CO2-HCO3-. Intracellular pH (pHi) was measured using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescin (BCECF). Gastric cells were highly purified by density gradient centrifugation and elutriation. When cells suspended in N-2-hydroxyethylpiperazene-N'-2-ethanesulfonic acid (HEPES)-100% O2, extracellular pH (pHo) 7.4, were exposed to 24 mM HCO3- -5% CO2, pHo 7.4, all cells quickly acidified by 0.3-0.4 pH units. Almost complete pH-recovery occurred within 15 min. In parietal cells, 70% of this recovery was dependent on the presence of extracellular Na+ (Nao+) and was blocked by 1 mM amiloride. The Na+-independent recovery was blocked by intracellular Cl- depletion or by 0.4 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In chief cells and surface cells no recovery occurred in the absence of NaO+, and 1 mM amiloride blocked pH recovery in Na+-containing buffer. On removal of HCO3- -CO2, the cells alkalinized, and subsequent pH recovery was fast, substantially extracellular Cl- (ClO-) and DIDS inhibitable in parietal cells but slow and ClO- -independent in chief and surface cells. These results suggest that during intracellular acidification the Na+-H+ exchanger is the major pH regulator in these three gastric cell types even in the presence of HCO3-. During alkalinization the Cl- -HCO3-(OH-) exchanger is the predominant pH recovery mechanism in parietal, but not in chief and surface cells. In parietal cells, this exchanger is also involved in recovery from acidification.

Amiloride↗
PubMed1988

Effect of ethanol on frog gastric mucosa. Electrophysiologic and morphologic correlations.

The effects of and recovery from luminal ethanol (0%-100%) were assessed in the in vitro chambered frog gastric mucosa. At concentrations of 5%-10%, the potential difference decreased during exposure, but recovered after washout. No gross or light microscopic changes were observed. During exposure to 20%-40% ethanol, potential difference and short circuit current decreased and resistance increased, with only partial recovery after removal of the alcohol. Acid secretion ceased at 20% ethanol and alkalinization of the luminal solution was observed at greater than or equal to 30% ethanol. Microscopy of this group showed discharge of mucus, separation of oxynticopeptic cells from the basal lamina, and slough of surface epithelium. At 60%-100% ethanol, potential difference and short circuit current decreased and resistance increased markedly but there was no recovery. Microscopy showed changes similar to those of the intermediate group (20%-40%), except that surface epithelial cells were fixed to the basal lamina rather than sloughing. The morphologic effects of 100% ethanol in vivo were similar to those in vitro. Pretreatment with 10(-5) M 16,16-dimethyl prostaglandin E2 did not prevent either the electrophysiologic or the histologic changes caused by 20% and 30% ethanol. We conclude that there is a gross discrepancy between the functional and morphologic findings after high concentrations of luminal ethanol.

Animals↗
PubMed1988

Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer.

The time-course of local failure following conservative surgery and radiotherapy (S+RT) for early breast cancer is not well established. We therefore examined the time-course and patterns of breast recurrence as a first site of treatment failure in a group of 607 AJCC clinical Stage I or II invasive breast carcinomas treated from 1968-81. Sixty-seven patients had a breast failure (11%), corresponding to 5- and 10-year actuarial rates of 10% and 16%. The hazard rate (i.e., the risk per unit time of a failure) for any breast failure increased over the first 2 years, was fairly constant at about 2.5%/year over the period from 2 to 6 years after treatment, and then decreased to about 1%/year at 8 years. The majority of failures were at or near the primary tumor site (33 true recurrences (TR) and 15 marginal misses (MM). In addition there were 12 failures at sites at least several cm from the boosted volume (E), 6 recurrences in the skin without a parenchymal mass (S), and 1 patient with an unclassifiable failure. Recurrences at or near the primary site (TR/MM) occurred earlier (median 38.5 mo, range 12-87 mo) than recurrences at distant sites in the breast (E) (median 64.5 mo, range 26-90). The hazard rate for TR/MM increased over the first 2-1/2 years to reach approximately 2%/year, remained at that level till about 5 years after treatment, and then decreased to about 0.5%/year at 8 years following RT. By contrast, the hazard rate for E increased slowly with time to approximately 1%/year at 5 years, with little change in the rate after that time. We conclude that the time-course of the development of local recurrence after S+RT is protracted. The majority of failures appear at or near the primary tumor site; these are seen mainly in the first 7 years following RT. Recurrences at distant sites in the breast have an even more protracted time-course. Such recurrences are rare in the first 4 years following RT. Our results emphasize the need to obtain long follow-up in these patients, both to detect these recurrences promptly and to properly evaluate the results of S+RT.

Adult↗
PubMed1988

Experimental models of gastric ulceration and injury.

There are inumerable experimental models of gastric mucosal epithelial injury. Many of these currently in wide use can be regarded as unphysiological and severe, rarely encountered in humans. An analysis of more physiological and simple models indicates that little is known of the events that ultimately cause cellular death, even in simple and easily controllable systems. A review of acceptable measures of gastric mucosal injury is presented. It is suggested that studies of subtle physiological injuries at the cellular level are more likely to yield meaningful insights into the causation of gastric mucosal ulceration.

Animals↗
PubMed1988

Gastroduodenal hemorrhage and perforation in the postoperative period.

The distinction between stress ulceration and acute exacerbations of chronic peptic ulcer disease is rarely made in the context of postoperative hemorrhage or perforation of the upper part of the gastrointestinal tract. We reviewed our recent experience during a three and one-half year period with 31 emergency operations performed for gastroduodenal hemorrhage or perforation. Seven patients were convalescing from extensive surgical procedures unrelated to gastroduodenal ulcer disease at the time of hemorrhage or perforation. These complications tended to occur about one week after the initial operation. Six of these seven patients had duodenal ulcer disease; prior ulcer disease or current use of ulcerogenic drugs could be documented in all six. Only one of these seven patients had true stress ulceration. There were 143 patients with active peptic ulcer who underwent an extensive surgical procedure unrelated to ulcer disease. Three of these 143 patients required surgical intervention for complications of ulcer disease during the convalescent period. Our experience suggests that a common setting for emergency operations for peptic ulcer hemorrhage or perforation is during convalescence from an unrelated surgical procedure. A history of peptic ulcer disease or use of ulcerogenic agents should alert the surgeon to the possibility of postoperative hemorrhage or perforation. These complications most commonly reflect chronic duodenal ulcer disease or diathesis and not true stress ulceration.

Acute Disease↗
PubMed1987

Parenteral aspirin and sodium salicylate are equally injurious to the rat gastric mucosa.

The effects of parenteral aspirin (ASA) or sodium salicylate (SA) on the gastric mucosa were investigated in anesthetized pylorus-ligated rats 3 h after a bolus intravenous injection of ASA or SA, 150 mg/kg, or NaCl (control). Aspirin or SA produced similar extensive gross mucosal hemorrhagic lesions and similar microscopic damage in the presence of luminal acid (luminal pH 1.3 +/- 0.05). Neither ASA nor SA produced gastric mucosal injury with intragastric instillation of saline (luminal pH 3.7 +/- 0.5). Pretreatment for 1 h with luminal or subcutaneous 16,16-dimethyl prostaglandin E2 completely prevented the formation of red streaks in ASA-treated rats but not in SA-treated rats, although prostaglandin E2 pretreatment significantly reduced the gross lesion area in SA-treated rats (p less than 0.05). We conclude the following: (a) Intravenous SA is as damaging as intravenous ASA as long as luminal acid is present. (b) 16,16-Dimethyl prostaglandin E2 completely protected the gastric mucosa from injury by intravenous ASA, and to a lesser extent by intravenous SA. (c) In view of the damaging effects of SA on the gastric mucosa and the rapid conversion of ASA to SA, the mechanism of the gastric mucosal injury by intravenous ASA is much more complex than simple inhibition of endogenous prostaglandin synthesis.

Animals↗
PubMed1987

Gastric autonomic nerve (GAN) tumor and extra-adrenal paraganglioma in Carney's triad. A common origin.

Carney's Triad comprises a triad of neoplasms: gastric stromal tumor, extra-adrenal paraganglioma (usually functional), and pulmonary chondroma. At least two of these are needed for the presumptive diagnosis of the Triad. This report presents a patient who had resected a gastric tumor and nonfunctional extra-adrenal paraganglioma. The gastric tumor resembled a gastric leiomyosarcoma by light microscopy, but electron microscopy revealed it to be a gastric autonomic nerve (GAN) tumor. Based on this evidence it appears that both the gastric lesions and the paragangliomata of Carney's Triad are tumors of the autonomic nervous system. Thus, the Triad may be a disorder of the autonomic nervous system rather than a multiple endocrine neoplasia syndrome or multiple hamartoma syndrome.

Adolescent↗