Evidence that gastrin 34 is preferentially released from the human duodenum.
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Biomedical subjects
Publications and source records attributed to J B Jansen.
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The effect of intravenously administered calcitonin and secretin on bombesin-stimulated serum gastrin and gastric acid secretion was studied on 7 volunteers. Secretin G.I.H. (1 C.U./kg per h) and calcitonin (0.5 I.U./kg per h) significantly (P less than 0.05) inhibited the serum gastrin and gastric acid responses to bombesin-14 (90 pmol/kg per h). Inhibition of gastrin release could not fully account for the inhibition of gastric acid secretion.
The effect of intravenous somatostatin on bombesin-stimulated serum gastrin and gastric acid secretion was studied in 5 healthy subjects. Somatostatin, 100 ng/kg/min, significantly inhibited serum gastrin and gastric acid responses to infusion of bombesin-tetradecapeptide in a dose of 2.5 ng/kg/min. Inhibition of gastrin release could not fully account for the inhibition of gastric acid secretion. Since both bombesin and somatostatin are present in the antrum of man, interrelations between these peptides might be involved in gastrin release from the antrum.
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To test the hypothesis, based on studies in healthy man and dog, that patients with impaired digestion due to severe pancreatic insufficiency have impaired postprandial cholecystokinin (CCK) secretion that can be improved by the addition of pancreatic enzymes, we have studied plasma CCK responses to a test meal with and without addition of pancreatic enzymes in 10 patients with pancreatic insufficiency and steatorrhea, in 8 patients with chronic pancreatitis without steatorrhea, and in 6 healthy subjects. The patients with steatorrhea had a significantly (P less than 0.001) lower integrated plasma CCK response to the meal (177 +/- 23 pM.150 min) than the healthy subjects (468 +/- 41 pM.150 min), while patients with chronic pancreatitis without steatorrhea had an intermediate integrated postprandial CCK secretion (327 +/- 101 pM.150 min). Addition of pancreatic enzymes to the meal significantly augmented the integrated CCK response in both the patients with steatorrhea to 483 +/- 72 pM.150 min (P less than 0.01) and in those without steatorrhea to 480 +/- 85 pM.150 min (P less than 0.05). These values were not significantly different from those in the healthy subjects (521 +/- 86 pM.150 min). Integrated CCK secretion in the three groups during bombesin infusion was similar (patients with steatorrhea 134 +/- 23 pM.20 min, patients without steatorrhea 131 +/- 33 pM.20 min, and healthy subjects 146 +/- 28 pM.20 min), indicating a normal capacity to secrete CCK in response to a humoral stimulus. These data are in agreement with the suggestions from previous studies that digestion of nutrients by pancreatic enzymes plays an important role in the regulation of plasma CCK secretion after feeding.
The present study was undertaken to characterize molecular forms of cholecystokinin (CCK) in human fat-stimulated plasma by Sephadex G50 column chromatography followed by radioimmunoassays employing 3 different region-specific antibodies. CCK was extracted and concentrated from plasma of healthy subjects by adsorption to SEP-PAK C18 cartridges and from plasma of gastrectomized patients by addition of 96% ethanol. Antibody 1703 binds to carboxy-terminal CCK-peptides containing at least 14 amino acid residues, antibody T204 to sulfated carboxy-terminal CCK-peptides and antibody 5135 to carboxy-terminal forms of CCK and gastrin. Four molecular forms of CCK were consistently demonstrated; peak I eluted in the void volume and comprised 1.8-10.2% of CCK-immunoreactivity, peak II eluted between the void volume and the CCK-33/39 standard and comprised 9.8-21.6%, peak III eluted at the position of the CCK-33/39 standard and comprised 42.4-55.4%, and peak IV eluted between the CCK-33/39 and CCK-14 standards and comprised 25.4-40.1% of CCK immunoreactivity. Since these 4 molecular forms reacted to all 3 CCK-antibodies it is likely that they contain the sulfated tyrosyl and carboxy-terminal regions of CCK and, therefore, possess biological activity.
To determine whether exogenous cholecystokinin (CCK) inhibits endogenous CCK release, cholecystokinin-8S (CCK-8S) was infused intravenously during continuous intraduodenal stimulation of endogenous CCK by a meal. CCK was measured in plasma by 2 region-specific radioimmunoassays employing antibodies T204 and 1703. AB T204 binds to carboxy-terminal CCK peptides containing the sulphated tyrosyl region, including CCK-8S, and AB 1703 to carboxy-terminal CCK peptides containing at least 14 amino acid residues. Meal-stimulated plasma CCK concentrations remained elevated during the entire infusion period. CCK-8S infusion further increased meal-stimulated plasma CCK concentrations, when measured with AB T204, while meal-stimulated plasma CCK concentrations were not suppressed by CCK-8S infusion, when measured with AB 1703. It is concluded that meal-stimulated endogenous CCK release is not affected by the effects of intravenously administered CCK-8S. These data suggest that autocrine feedback regulation of CCK release is not operative in man.
Magnetic resonance, CT, and ultrasound findings are described for a vipoma of the pancreas with hepatic metastases in a patient with Verner-Morrison syndrome and multiple endocrine neoplasia I.
The CT and magnetic resonance (MR) findings in 13 patients with advanced Zollinger-Ellison syndrome are described. In eight patients (62%) one or more primary tumors were found with both methods. All patients with proven liver metastases (n = 7) were identified by MR. Computed tomography was positive in six of these patients. Three patients with lymph node metastases were identified on CT and MR and one patient had bone metastases. Computed tomography and MR were inferior to selective arteriography in the detection of multiple lesions of the pancreas in a patient with multiple endocrine neoplasia-I syndrome. On the T1-weighted MR images, the primary tumors demonstrated no consistency with regard to their signal intensity relative to the adjacent pancreatic parenchyma. All gastrinomas had an increased relative signal intensity on the T2-weighted images with the exception of a calcified tumor. Liver and lymph node metastases had a low signal intensity on the T1-weighted images and an increased signal intensity on the T2-weighted images. The signal intensity of primary tumors and metastases was independent of size. In conclusion, MR was able to detect abnormalities based on its outstanding lesion/normal tissue contrast, whereas CT diagnosis was based mostly on contour distortion. For the current technique, MR is considered at least equal to CT.
OBJECTIVE: The imaging features of somatostatinoma are described in four patients. MATERIALS AND METHODS: Four patients, ranging in age from 24 to 57 years, with somatostatinoma were examined. Ultrasonography (US) and CT were performed in all four patients; MRI and angiography were performed in three patients. RESULTS: Three patients had a tumor in the pancreas and one in the papilla major. In two cases there were metastases in the liver, and one had bone and lymph node metastases. Pancreatic tumor and metastases were equally well detected by CT and MRI. One tumor in the tail of the pancreas was initially missed by US. Pancreatic tumor and metastases were echo poor. Angiography showed one vascular and one avascular tumor in the pancreas. Chronic obstructive pancreatitis was seen on CT and MRI in the patient with the tumor in the papilla major. Angiography and US failed to demonstrate this tumor; CT and MRI showed the tumor in retrospect. Primary tumor and metastases are of low signal intensity on T1-weighted imaging and increased signal intensity on T2-weighted imaging. CONCLUSION: Somatostatin-producing endocrine tumors are mainly located in the pancreas but can also be present in extrapancreatic organs such as the duodenum and papilla of Vater resulting in chronic obstructive pancreatitis. Duodenal somatostatinomas are associated with von Recklinghausen neurofibromatosis. Radiologic and MRI features of somatostatinomas resemble those of other neuroendocrine tumors. Radiological techniques and MRI often fail to demonstrate the tumors in the duodenum. The diagnosis in cases of duodenal localization can be established by endoscopic techniques.
OBJECTIVE: Our goal was assessment of the preoperative staging of rectal carcinoma with MR with double surface coil, MR with endorectal coil, and intrarectal ultrasound (IUS) as correlated with histopathologic findings. MATERIALS AND METHODS: Fifteen patients with rectal carcinoma had preoperative evaluation using intrarectal ultrasound (all 15 patients), MR with double surface coil alone (6 patients), and MR with double surface coil combined with endorectal surface coil (9 patients). The results of the preoperative staging were correlated with the histopathologic findings. RESULTS: IUS correctly staged the depth of bowel wall invasion in 10 of 15 patients, understaged 4, and overstaged 1. MRI correctly staged 10 of 15 patients. Without the endorectal surface coil, three of six were correct, and with endorectal surface coil seven of nine. MR with the endorectal surface coil is able to show the rectal wall in more detail than the double surface coil. CONCLUSION: Endorectal surface coil MRI provides increased detail of the rectal wall, leading to better delineation of its different layers. This may lead to better staging results than with other MR techniques. The results with endorectal MRI probably equal those of IUS for staging small tumors in the rectal wall. MR with the double surface coil gives additional information about tumor spread in more advanced cases.
BACKGROUND: Parenteral lipid emulsions are suspected of suppressing the immune function. However, study results are contradictory and mainly concern the conventional long-chain triglyceride emulsions. METHODS: Polymorphonuclear leukocytes were preincubated with parenteral lipid emulsions. The influence of the lipid emulsions on the production of oxygen radicals by these stimulated leukocytes was studied by measuring chemiluminescence. Three different parenteral lipid emulsions were tested: long-chain triglycerides, a physical mixture of medium- and long-chain triglycerides, and structured triglycerides. Structured triglycerides consist of triglycerides where the medium- and long-chain fatty acids are attached to the same glycerol molecule. RESULTS: Stimulated polymorphonuclear leukocytes preincubated with the physical mixture of medium- and long-chain triglycerides showed higher levels of oxygen radicals (p < .005) and faster production of oxygen radicals (p < .005) compared with polymorphonuclear leukocytes preincubated with long-chain triglycerides or structured triglycerides. Additional studies indicated that differences in results of various lipid emulsions were not caused by differences in emulsifier. The overall production of oxygen radicals was significantly lower after preincubation with the three lipid emulsions compared with controls without lipid emulsion. CONCLUSIONS: A physical mixture of medium- and long-chain triglycerides induced faster production of oxygen radicals, resulting in higher levels of oxygen radicals, compared with long-chain triglycerides or structured triglycerides. This can be detrimental in cases where oxygen radicals play either a pathogenic role or a beneficial one, such as when rapid phagocytosis and killing of bacteria is needed. The observed lower production of oxygen radicals by polymorphonuclear leukocytes in the presence of parenteral lipid emulsions may result in immunosuppression by these lipids.
BACKGROUND: To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. METHODS: Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. RESULTS: Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). CONCLUSIONS: LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.
BACKGROUND: Most postoperative patients lose net protein mass, which reflects loss of muscle tissue and organ function. Perioperative parenteral nutrition may reduce the loss of protein, but in general, with conventional lipid emulsions a waste of protein still remains. METHODS: We compared the effects on nitrogen balance of an emulsion containing structured triglycerides, a new type of synthesized triglycerides, with an emulsion of a physical mixture of medium- and long-chain triglycerides as part of parenteral feeding in moderately catabolic patients. The first 5 days after placement of an aortic prosthesis patients received total parenteral nutrition (TPN) providing 0.2 g of nitrogen per kg body weight per day; energy requirement was calculated using Harris and Benedict's equation, adding 300 kcal per day for activity. Twelve patients were treated with the structured triglyceride emulsion and 13 patients with the emulsion of the physical mixture of medium- and long-chain triglycerides. The design was a randomized, double-blind parallel study. RESULTS: In the patients who completed the study, the mean cumulative nitrogen balance over the first 5 postoperative days was -8+/-2 g in 10 patients on the structured triglyceride emulsion and -21+/-4 g in 9 patients on the emulsion of the physical mixture of medium- and long-chain triglycerides; the mean difference was 13 g of nitrogen (95% confidence interval 4 to 22, p = .015) in favor of the structured triglyceride emulsion. On the first postoperative day serum triglyceride and plasma medium-chain free fatty acid levels increased less during infusion of the structured triglyceride emulsion than with the physical mixture emulsion. CONCLUSIONS: The parenteral structured triglyceride emulsion improves the nitrogen balance and is cleared faster from the blood, compared with the emulsion of the physical mixture of medium- and long-chain triglycerides, in moderately catabolic patients.
During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction.
BACKGROUND: The use of medium-chain triglycerides in diets is limited by the frequent occurrence of diarrhea or crampy abdominal pain. Because these symptoms may result from an accelerated transit time induced by medium-chain triglycerides, we investigated the effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on small-bowel transit time in 10 healthy subjects. METHODS: Small-bowel transit time was measured by the lactulose hydrogen breath test after intraduodenal administration of lactulose. RESULTS: Intraduodenal administration of 20 mmol of long-chain triglycerides per hour for 90 minutes did not alter small-bowel transit time compared with control (77 +/- 11 minutes vs 77 +/- 10 minutes, respectively), whereas intraduodenal infusion of an equimolar dose of medium-chain triglycerides significantly accelerated small-bowel transit time (59 +/- 6 minutes) compared with long-chain triglycerides and control (p < .05). In six individuals, small-bowel transit time was shorter during the administration of medium-chain triglycerides compared with control, and three of these subjects experienced abdominal symptoms. Plasma cholecystokinin levels increased significantly (p < .05) during the administration of long-chain triglycerides, from 2.6 +/- 0.3 pmol/L to a maximum of 4.3 +/- 0.6 pmol/L. No significant alterations were observed in plasma cholecystokinin levels during administration of medium-chain triglycerides or in the control experiment. CONCLUSIONS: Although it significantly increases cholecystokinin secretion, the intraduodenal infusion of long-chain triglycerides does not affect small-bowel transit time, whereas the infusion of medium-chain triglycerides accelerates small-bowel transit time, independent of cholecystokinin.