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W Silen

Publications and source records attributed to W Silen.

At least 19 recordsLinked to original sources
PubMed1992

Microbiologic assessment of tissue biopsy samples from ileal pouch patients.

Tissue biopsy samples from patients with and without ileal pouches were examined by electron microscopic and microbiologic culture techniques to determine the numbers and types of microorganisms closely associated with or within the tissue biopsy samples. The disease status of each patient was determined by endoscopic and histopathologic methods. Of the 78 biopsy samples included in this study, 64 (82%) yielded obligately anaerobic and/or facultative bacteria when they were cultured. Fourteen of the 78 samples (17.9%) were negative by culture. Of the positive samples, 54 contained facultatively anaerobic bacterial species and 50 yielded obligately anaerobic species. The total counts for facultatively anaerobic bacteria for samples from patients with pouchitis were significantly greater than for samples from patients in control groups. In addition, the number of samples from patients with normal pouches that did not contain obligate anaerobes was significantly less than that from patients with pouchitis; 4 of 23 and 6 of 12 samples, respectively (P less than 0.043). For samples in which organisms were detected, there was agreement with electron microscopic detection of bacteria in 23 of 27 samples, for an overall sensitivity of electron microscopy compared with that of culture of 85%. The qualitative studies resulted in the characterization of 273 isolates comprising 77 different phenotypes. The specificity of these findings in patients with ileal pouchitis is discussed.

Bacteria, Anaerobic↗
PubMed1992

Prostaglandin stimulates Cl(-)-HCO3- exchange in amphibian oxynticopeptic cells.

Prostaglandins, shown to stimulate Cl- transport in epithelial cells of several different tissues, protect gastric mucosa against physiological injury induced by luminal acid. To clarify the relationship between the stimulation of Cl(-)-transport and the protection of gastric mucosa, the effect of prostaglandin on Cl(-)-HCO3- exchange in oxynticopeptic cells (OPC) was examined in intact sheets of in vitro frog gastric mucosa, in which OPC were selectively loaded with the pH-sensitive fluorescent dye 2',7'-bis(carboxyethyl)-5(6')-carboxyfluorescein (BCECF). In omeprazole (0.3 mM)-pretreated frog fundic mucosae, in which H+ secretion was totally inhibited, 16,16-dimethyl prostaglandin E2 (dmPGE2) induced a significant decrease in intracellular pH (pHi) in OPC simultaneously with a significant increase in pHi in adjacent muscularis mucosae, an effect abolished by removal of ambient Cl- or addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (0.5 mM). dmPGE2 accentuated the rates of alkalinization of OPC after either removal of ambient Cl- or addition of serosal H2DIDS. During exposure to luminal or serosal acid, dmPGE2 significantly attenuated acidification of OPC induced by the exogenous H+, effects abolished either by removal of ambient Cl- or by addition of H2DIDS (0.5 mM). These results suggest that 1) dmPGE2 stimulates extrusion of HCO3- through the basolateral Cl(-)-HCO3- exchanger in resting OPC (H+ secretion inhibited) and that 2) relatively high extracellular [HCO3-] on the basolateral surface afforded by dmPGE2 protects OPC from acidification during exposure to luminal or serosal acid.

Animals↗
PubMed1992

Influence of acid secretory state on Cl(-)-base and Na(+)-H+ exchange and pHi in isolated rabbit parietal cells.

Parietal cell apical proton secretion is accompanied by apical Cl- secretion, K+ cycling, and the generation of intracellular base. We examined the ability of the parietal cell to maintain intracellular pH (pHi) during its transformation from the resting to the stimulated state and evaluated the ion transport mechanisms involved in the maintenance of ionic equilibrium. Isolated rabbit parietal cells were loaded with the pH-sensitive fluorescent dye BCECF, and pHi was monitored in maximally stimulated, resting (absence of a secretagogue), and omeprazole-inhibited cells. Although [14C]aminopyrine (AP) accumulation increased up to 30-fold above basal during stimulation, the mean pHi of maximally stimulated cells was not different from that of inhibited cells both immediately and late after stimulation in an extracellular pH range from 6.2 to 7.8 in either HEPES or CO2/HCO3- buffer. When the stilbene DIDS was added 2 min after stimulation of acid formation, pHi rapidly increased (0.09 +/- 0.02 vs. 0.04 +/- 0.02 pH units in unstimulated cells in 6 min), indicating an increased base efflux through a DIDS-sensitive transporter (most likely the Cl(-)-base exchanger). Stimulation of acid secretion did not change the transport capacity, apparent affinity for extracellular Cl-, or dependency of the anion flux rate on pHi of the DIDS-sensitive base exporter. For a given pHi, amiloride-inhibitable proton efflux rates during pHi recovery from an acid load were identical in resting and stimulated cells, suggesting that neither the transport capacity not the pHi set point of the parietal cell Na(+)-H+ exchanger is altered by cAMP-dependent stimulation of acid formation. We conclude that, during the cAMP-mediated stimulation of acid formation in isolated rabbit parietal cells, the pHi remains constant, but an increased base efflux occurs without a change in the transport capacity of the involved base extrusion mechanisms or an inhibition of the parietal cell base loading mechanisms. Whether changes in the intracellular Cl- concentration on stimulation of acid formation initiate the increased base efflux and whether additional ion transporters are involved in the maintenance of ion homeostasis during acid secretion remain to be determined.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Effects of hypoxia on function and morphology of in vitro frog gastric mucosa.

The effects of gaseous hypoxia and reoxygenation on oxynticopeptic (OPC) and surface mucous cells (SMC) were examined in in vitro bullfrog gastric fundic mucosae mounted in Ussing chambers. Forskolin-stimulated H+ secretion, transmucosal potential difference (PD), and electrical resistance (R) were monitored in tissues incubated in HCO3(-)-free or HCO3(-)-containing buffer. At serosal pH (pHs) 7.2, 1 h of hypoxia with 100% N2 resulted in a decrease in PD, increase in R, and complete inhibition of H+ secretion. After 30 min of hypoxia, the morphology of OPC changed from the secretory to the nonsecretory state without recognizable cytopathology. Destructive changes in OPC increased progressively at pHs 7.2 as the hypoxic period was prolonged from 4 to 24 h. After 4 h of reoxygenation following 12-24 h of hypoxia, OPC remained necrotic and H+ secretion showed no recovery, whereas in some areas where SMC were exfoliated adjacent SMC showed epithelial restitution. The recovery of H+ secretion and PD during 2 h of reoxygenation after 4 h of hypoxia at pHs 6.0 and 6.8 was less than that at 7.2 and 8.0 and was greater in the presence of serosal HCO3- than its absence at pHs 7.2. These results suggest that, in in vitro frog gastric mucosa, 1) OPC are more vulnerable to hypoxia than SMC, 2) basolateral acidosis exaggerates hypoxic injury of OPC, and 3) serosal HCO3- protects OPC from hypoxic injury.

Animals↗
PubMed1992

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1991

Effect of luminal acid on intracellular pH in oxynticopeptic cells in intact frog gastric mucosa.

The effect of changes in luminal [H+] on intracellular pH in oxynticopeptic cells was examined using intact sheets of frog (Rana catesbeiana) gastric mucosa in which oxynticopeptic cells were selectively loaded with the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The serosal solution was buffered with either HCO3- or N-2-hydroxymethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Luminal pH was decreased from 7.2 to 1.5 and changed back to 7.2. In stimulated (forskolin-treated) tissues, intracellular pH decreased at luminal pH 1.5 only in HEPES, with complete recovery at 7.2. In resting (omeprazole-treated) tissues, intracellular pH began to decrease at luminal pH 2.0 in HEPES and at 1.5 in HCO3-, with complete recovery at 7.2 in both. In resting tissues bathed in Cl(-)-free HEPES, the recovery of intracellular pH at luminal pH 7.2 was completely prevented by serosal amiloride (1 mmol/L) but was not affected by serosal 4,4'-diisothiocyanatodihydrostilbene-2-2'-disulfonic acid (H2-DIDS; 0.5 mmol/L). In resting tissues bathed in Cl(-)-free HCO3-, the recovery of intracellular pH at luminal pH 7.2 was not affected by amiloride but was prevented partially by H2-DIDS and completely by combination of H2-DIDS and amiloride or by removal of ambient Na+. These results suggest that during exposure to high luminal [H+]: (a) stimulated oxynticopeptic cells maintain a steady intracellular pH more readily than resting cells; (b) serosal HCO3- protects oxynticopeptic cells from intracellular acidosis; and (c) both Na+/H+ exchange and Na(+)-HCO3- cotransport are involved in the recovery from intracellular acidosis in resting oxynticopeptic cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.

Breast Neoplasms↗
PubMed1991

H(+)-K(+)-ATPase contributes to regulation of pHi in frog oxynticopeptic cells.

The effect of intracellular acidosis on luminal H+ secretion and the role of H(+)-K(+)-ATPase in regulation of intracellular pH (pHi) in oxynticopeptic cells (OPC) (measured with a pH-sensitive fluorescent dye) were examined in intact sheets of in vitro frog (Rana catesbeiana) gastric mucosa. Intracellular acidosis of OPC induced by decreasing pH in the serosal solution (pHs) from 7.2 to 6.0 reversibly increased forskolin-stimulated H+ secretion without increasing endogenous histamine release. The observed increase in H+ secretion was unaffected by either 1 mM cimetidine or 1 mM histamine, but was accentuated by 1 mM amiloride, an effect abolished by 0.3 mM omeprazole. Steady-state pHi values in stimulated or resting OPC at pHs 7.2 were not significantly different. However, pHi in OPC was significantly higher in stimulated than in resting tissues at pHs 6.9, a difference accentuated by decreasing pHs to 6.4 or by 1 mM amiloride. Amiloride completely prevented recovery from intracellular acidosis induced by pHs 6.4 or 6.9 in omeprazole-treated tissues, but only partially mitigated recovery in cimetidine- or forskolin-treated tissues. At pHs 6.4, high luminal [K+] (100 mM) increased H+ secretion and hastened recovery of pHi in cimetidine-treated tissues in the presence of amiloride. These results suggest that, in intact sheets of in vitro frog gastric mucosa, 1) intracellular acidosis stimulates luminal H+ secretion via histamine-independent mechanisms and 2) H(+)-K(+)-ATPase contributes to the recovery of OPC from intracellular acidosis.

Acidosis↗
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↗