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Biomedical subjects

S A Wank

Publications and source records attributed to S A Wank.

49 records · Page 3Linked to original sources
PubMed1988

Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: a prospective study.

We examined prospectively the criteria for medical management in 16 patients with Zollinger-Ellison syndrome who had had previous gastric surgery. Each patient received sufficient antisecretory medication to lower gastric acid output to less than 10 mEq/h during the last hour before the next dose of drug. The 7 patients with a vagotomy but no gastric resection were symptom-free and had no mucosal disease. Of 9 patients with a partial gastrectomy, 7 had mucosal disease, with or without symptoms, and 6 of the 7 patients had acid outputs of 5-10 mEq/h. In these patients, antisecretory medication was increased to reduce output to less than 5 mEq/h and symptoms and mucosal abnormalities resolved in each patient. Patients with Zollinger-Ellison syndrome and a vagotomy can be treated safely by reducing acid secretion to less than 10 mEq/h, but in patients with a partial gastrectomy, acid secretion must be reduced to less than 5 mEq/h, and adequacy of therapy must be checked further by endoscopy.

Adolescent↗
PubMed1988

Prospective study of chemotherapy in patients with metastatic gastrinoma.

Ten consecutive patients with metastatic gastrinoma that increased in size over time were studied prospectively during treatment with monthly cycles of streptozotocin (3 g/m2), 5-fluorouracil (1.2 g/m2), and adriamycin (40 mg/m2) to determine the response rate and time-courses of changes during chemotherapy and to assess various methods of evaluating the effect of chemotherapy. Forty percent of patients demonstrated an initial objective response (greater than or equal to 25% decrease in tumor size with no new lesions) and 60% failed chemotherapy (greater than or equal to 25% increase in tumor size or appearance of new lesions). The mean dose of streptozotocin was 27 g/m2 with objective responses occurring at 3.7 +/- 0.7 mo and failures at 4.5 +/- 0.7 mo. Responses lasted 9.7 +/- 2.8 cycles and no complete responses occurred. Survival was not significantly different in responders versus nonresponders (26 +/- 11 vs. 15 +/- 4.8 mo, p greater than 0.1). Changes in serum gastrin concentration, basal acid output, or sensitivity to a given dose of histamine H2-receptor antagonist did not reflect changes in tumor size. Computed tomography and angiography were the best methods to assess changes in tumor size during chemotherapy, whereas liver-spleen scan and ultrasound were relatively insensitive. All patients developed side effects with chemotherapy: 100% had vomiting, 80% alopecia, 40% transient proteinuria, and 20% leukopenia. The present results indicate that chemotherapy with streptozotocin, 5-fluorouracil, and adriamycin is much less effective in patients with extensive metastatic gastrinoma than previously reported. Computed tomography scanning is the method of choice to assess changes in tumor size. Changes in serum gastrin concentration, acid secretion, or tumor size assessed by liver-spleen scan or ultrasound are not sensitive indicators of the tumor response during chemotherapy.

Adult↗
PubMed1988

Kinetics of binding of cholecystokinin to pancreatic acini.

In the present study we examined the kinetics of binding of iodinated COOH-terminal octapeptide of cholecystokinin (125I-CCK-8) to its receptors on dispersed acini prepared from guinea pig pancreas. At 37 degrees C, binding of 125I-CCK-8 reached a steady state after 60 min of incubation. Dissociation of bound 125I-CCK-8 was biphasic, indicating that the labeled peptide binds in two distinct states: a rapidly dissociating state and a slowly dissociating state. Binding of 125I-CCK-8 in the rapidly dissociating state was maximal within 3 min of incubation, did not depend on incubation temperature or cellular energy metabolism, could be stripped by 0.5 M potassium thiocyanate, and showed accelerated dissociation with CCK-8 or dibutyrylguanosine 3',5'-cyclic monophosphate (Bt2cGMP). Binding of 125I-CCK-8 in the slowly dissociating state was maximal after 60 min of incubation, was decreased by reducing the incubation temperature or inhibiting cellular energy metabolism, was not stripped by 0.5 M potassium thiocyanate, and did not show accelerated dissociation with CCK-8 or Bt2cGMP. Increasing the concentration of 125I-CCK-8 increased the fraction of radioactivity bound in the rapidly dissociating state. When binding of 125I-CCK-8 reached a steady state, nearly all of the bound radioactivity was in the slowly dissociating state. Computer analysis of the inhibition of 125I-CCK-8 by CCK-8 under experimental conditions where the rapidly dissociating state predominates demonstrated a complete loss of high-affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Prospective study of the ability of computed axial tomography to localize gastrinomas in patients with Zollinger-Ellison syndrome.

The ability of routine computed tomography (CT) performed with oral and intravenous contrast to localize gastrinomas in 61 consecutive patients with Zollinger-Ellison syndrome was evaluated prospectively. The results of CT scanning were subsequently evaluated in all patients by either surgery, autopsy, or percutaneous biopsy. Thirteen of 14 patients with CT scans positive for hepatic metastases and 5 of 13 patients with CT scans negative for hepatic metastases were found to have gastrinoma in the liver. For gastrinoma metastatic to the liver, CT scanning had a specificity of 98%, a sensitivity of 72%, a positive predictive value of 93%, and a negative predictive value of 90%. Twenty-two of 23 patients with positive extrahepatic CT scans and 15 of 33 patients with negative extrahepatic CT scans were found to have extrahepatic gastrinomas. For extrahepatic gastrinoma, CT scanning had a specificity of 95%, a sensitivity of 59%, a positive predictive value of 96%, and a negative predictive value of 54%. The ability of CT scan to detect gastrinomas both in the liver and extrahepatically was directly related to tumor size, detecting 0% of tumors less than 1 cm and 83%-95% of tumors greater than 3 cm. The location of the extrahepatic gastrinoma was also an important determinant in that approximately 80% of pancreatic gastrinomas but only 35% of extrapancreatic gastrinomas were detected. The present results indicate that because of its convenience and accuracy, CT scanning with oral and intravenous contrast material should be the initial procedure to evaluate the extent of gastrinoma. A positive CT scan is almost always correct; therefore, a CT scan detecting metastatic gastrinoma to the liver would avoid unnecessary surgery and, if positive for extrahepatic gastrinoma, would assist the surgeon in finding the gastrinoma. A negative CT is less reliable; therefore, patients should undergo other localizing studies before exploratory laparotomy.

Biopsy↗
PubMed1987

Role of selective angiography in the management of patients with Zollinger-Ellison syndrome.

To determine the ability of selective abdominal angiography to localize gastrinoma in patients with Zollinger-Ellison syndrome, selective angiography was performed in 70 consecutive patients and the results were assessed prospectively by either surgery, autopsy, or percutaneous biopsy. In addition, to define the role of angiography in the management of patients with gastrinoma, we compared the results of angiography with those of computed tomography (CT) scanning in 58 patients who underwent both tests. For gastrinoma in the liver, angiography had a specificity of 100% and a sensitivity of 86% with a positive predictive value of 100% and a negative predictive value of 94%. For extrahepatic gastrinoma, angiography had a specificity of 94% and a sensitivity of 68%, a positive predictive value of 97% and a negative predictive value of 53%. Comparison of CT scanning and angiography demonstrated that for hepatic tumor CT demonstrated 72% and angiography 89% of tumors, and the combination detected all tumors with no false-positive results. Outside the liver, CT scanning detected 57%, angiography 70%, and the combination 73% of tumors with a false-positive rate of 7%. These results indicate that if a CT scan is performed first, then the addition of selective angiography will detect a further 28% of hepatic tumors and a further 16% of extrahepatic tumors, but that 24% of extrahepatic tumors will still be missed. Angiography is a useful adjunct to CT particularly in patients in whom surgery is contemplated.

Abdomen↗
PubMed1987

Famotidine: effective treatment of Zollinger-Ellison syndrome.

The ability of famotidine to control gastric acid hypersecretion in 32 patients with Zollinger-Ellison syndrome was compared to that of cimetidine or ranitidine. Equipotent doses of each drug were determined in nine patients and famotidine was nine times more potent than ranitidine and 32 times as potent as cimetidine. Famotidine had a 30% longer duration of action than either ranitidine or cimetidine. The 32 patients were treated with famotidine for a mean follow-up of 10.5 months. No hematologic, biochemical, or clinical toxicity occurred. Famotidine appears to be the histamine H2-receptor antagonist of choice in the treatment of Zollinger-Ellison syndrome.

Adult↗
PubMed1986

Famotidine in the therapy of gastric hypersecretory states.

The histamine (H2)-receptor antagonist famotidine was compared with ranitidine and cimetidine in its ability to control gastric acid hypersecretion in 33 patients with gastric hypersecretory states (32 patients with Zollinger-Ellison syndrome and one patient with idiopathic hypersecretion). Equipotent doses of each drug were determined in nine patients and used to determine relative onset of action, duration of action, and potency. Each drug had a similar time course of onset with a maximal effect at three to four hours after oral ingestion. The duration of action of famotidine was 30 percent longer than that of either cimetidine or ranitidine. In terms of relative potency, famotidine was nine times more potent than ranitidine and 32 times more potent than cimetidine. Thirty-two patients underwent long-term famotidine treatment for up to 34 months (mean, 10 months) with a duration in 21 patients of at least six months, in nine patients of at least 12 months, and in six patients of at least 24 months. The mean daily maintenance dose with famotidine was 0.33 g per day (range, 0.05 to 0.8 g). Prior to famotidine therapy, 27 patients were taking ranitidine and the mean daily dose required was 2.3 g per day (range, 0.6 to 5.4 g), whereas six patients were taking cimetidine and the mean daily dose was 4.6 g per day (range, 1.2 to 9.0 g). Fourteen of the 32 patients required an anticholinergic agent in addition to ranitidine or cimetidine to maintain control, whereas only five patients required an anticholinergic agent with famotidine. Gastric acid hypersecretion was controlled in seven patients with less frequent dosing with famotidine than with cimetidine or ranitidine. Long-term treatment with famotidine was not associated with any hematologic or biochemical toxicity or clinical side effects. These results demonstrate that famotidine has a similar onset of action to other H2-receptor antagonists but has a 30 percent longer duration of action and is nine times more potent than ranitidine and 32 times more potent than cimetidine. Famotidine is safe and highly effective in the long-term treatment of gastric hypersecretory states.

Adult↗
PubMed1984

Phase separation of the receptor for immunoglobulin E and its subunits in Triton X-114.

Above its critical micelle concentration, Triton X-114 in solution forms two phases at room temperature: a lower phase containing supramicellar aggregates and an upper phase largely depleted of detergent. This property of the detergent is potentially useful for separating under mild conditions proteins that bind detergent from those that do not (Bordier, C. (1981) J. Biol. Chem. 256, 1604-1607). We studied the distribution of the receptor for immunoglobulin E (IgE) and its subunits in the two phases. IgE and IgE complexed either with intact receptors or with the alpha chains of the receptor alone are principally partitioned into the upper phase, whereas the unliganded receptor as well as the isolated alpha, and especially the beta and gamma chains of the receptor, preferentially partition into the lower detergent phase. Chromatography of IgE and of the subunits of the receptor on a hydrophobic support showed that the beta and gamma chains have a considerably greater hydrophobic surface than the alpha chains or IgE. These results indicate that the distribution of a protein in the two phases of phase-separated Triton X-114 is not an all-or-none effect based upon whether it binds detergent or not. Rather, it reflects the overall balance between the hydrophobic and hydrophilic properties of the protein's surface.

Animals↗
PubMed1983

Analysis of the rate-limiting step in a ligand-cell receptor interaction: the immunoglobulin E system.

Theory predicts that the kinetics of simple interactions between a ligand and a receptor bound on the surface of a cell will be affected by the occupancy of receptors on the same cell. In a diffusion-limited reaction the effect will be on the rate of dissociation but not on the rate of association until the cell is virtually saturated with ligand. If the rate of reaction is not diffusion limited, then the opposite holds; i.e., the forward velocities will be proportional to the concentration of vacant receptors, but the reverse reactions will not be. We examined the kinetics of reaction between immunoglobulin E (IgE) and its receptor and clearly demonstrated that the reaction is not diffusion controlled. The substantial (congruent to 30-fold) increase in the forward rate constant observed for the reaction of IgE with solubilized receptors as opposed to cell-bound receptors is therefore not an artifact of calculation. Since the reverse rate constants show little difference, we postulate that the presence of other surface components (rather than conformational differences in the receptor) affects the reaction with the cells. As an aid to the analysis, the theory has been extended so that not only the rate constants but also the entire course of the reaction of ligand with cell receptors can be predicted for diffusion-limited vs. non-diffusion-limited interactions.

Animals↗
PubMed1982

Phospholipids stabilize the interaction between the alpha and beta subunits of the solubilized receptor for immunoglobulin E.

The cell-surface component (alpha) which binds monomeric immunoglobulin E with high affinity is associated with a second polypeptide (beta) in the plasma membrane. The latter component tends to dissociate during purification of the alpha chain from detergent extracts of cells, even at neutral pHs and physiological ionic strengths. We now report that the interaction of alpha and beta can be stabilized by maintaining an appropriate phospholipid to detergent ratio. Under such conditions, other discrete components reproducibly copurify with the alpha and beta chains. These results suggest that the subunits of this membrane protein--or the interaction of it with other constituents in the cell--may be stabilized in ways not observed with ordinary soluble proteins.

Animals↗
PubMedDate not supplied

Importance of sulfation of gastrin or cholecystokinin (CCK) on affinity for gastrin and CCK receptors.

We investigated the importance of sulfation of gastrin or cholecystokinin (CCK) on influencing their affinity for gastrin or CCK receptors by comparing the abilities of sulfated gastrin-17 (gastrin-17-II), desulfated gastrin-17 (gastrin-17-I), CCK-8 and desulfated CCK-8 [des(SO3)CCK-8] to interact with CCK or gastrin receptors on guinea pig pancreatic acini. For inhibiting binding of 125I-gastrin to gastrin receptors, gastrin-17-II (Kd 0.08 nM) greater than CCK-8 (Kd 0.4 nM) greater than gastrin-17-I (Kd 1.5 nM) greater than des(SO3)CCK-8 (Kd 28 nM). For inhibiting binding of 125I-Bolton Hunter-labeled CCK-8 to CCK receptors the relative potencies were: CCK-8 much greater than des(SO3)CCK-8 = gastrin-17-II greater than gastrin-17-I. Each peptide interacted with both high and low affinity CCK binding sites. The relative abilities of each peptide to interact with high affinity CCK receptors showed a close correlation with their abilities to cause half-maximal stimulation of enzyme secretion. These results demonstrate that, in contrast to older studies, sulfation of both CCK and gastrin increase their affinities for both gastrin and CCK receptors. Moreover, the gastrin receptor is relatively insensitive to the position of the sulfate moiety, whereas the CCK receptor is extremely sensitive to both the presence and exact position of the sulfate moiety.

Amylases↗
PubMedDate not supplied

Characterization of the bombesin receptor on mouse pancreatic acini by chemical cross-linking.

Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of 125I-GRP to and in stimulating amylase release from mouse pancreatic acini. In the present study we used 125I-GRP and chemical cross-linking techniques to characterize the mouse pancreatic BN receptor. After binding of 125I-GRP to membranes, and incubation with various chemical cross-linking agents, cross-linked radioactivity was analyzed by SDS-PAG electrophoresis and autoradiography. With each of 4 different chemical cross-linking agents, there was a single broad polypeptide band of Mr 80,000. Cross-linking did not occur in the absence of the cross-linking agent. Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN. Dose-inhibition curves for the ability of BN or NMB to inhibit binding of 125I-GRP to membranes or cross-linking to the 80,000 polypeptide demonstrated for both that BN was 15-fold more potent than NMB. The apparent molecular weight of the cross-linked polypeptide was unchanged by adding dithiothreitol. N-Glycanase treatment reduced the molecular weight of the cross-linked peptide to 40,000. The present results indicate that the BN receptor on mouse pancreatic acinar cell membranes resembles that recently described on various tumor cells in being a single glycoprotein with a molecular weight of 76,000. Because dithiothreitol had no effect, this glycoprotein is not a subunit of a larger disulfide-linked structure.

Amidohydrolases↗