Cholecystokinin receptor occupation and cholecystokinin-induced calcium mobilization in the early phase in rat pancreatic acini.

We examined receptor occupation, calcium mobilization and amylase release for cholecystokinin octapeptide (CCK-8) within a 3-min incubation period at 37 degrees C using dispersed acini from rat pancreas. Analysis of competitive binding inhibition data obtained after a 3-min incubation revealed the presence of only a single class of CCK receptors, while two classes of CCK receptor, i.e., high-affinity and low-affinity CCK receptors, were detected when binding reached a steady-state after a 60-min incubation. The IC50 of CCK receptors calculated from the 3-min binding data was 19.0 +/- 0.5 nM (mean +/- S.D.), close to the Kd of the low-affinity CCK receptors determined by equilibrium binding studies. Exposure of fura-2-loaded acini to 10-1000 pM CCK-8 caused an immediate and dose-dependent increase in [Ca2+]i followed by a gradual decrease in [Ca2+]i. The CCK-stimulated amylase release after 3 min of incubation was biphasic; amylase release increased over the dose range of 3-300 pM CCK-8, peaked at 300 pM CCK-8 and decreased with supramaximal concentrations of CCK-8. Our data suggest that occupation of the low-affinity, but not the high-affinity, CCK receptors is more directly associated with calcium mobilization and subsequent stimulation of amylase release in rat pancreatic acini.

Episodic fluctuation in serum intact parathyroid hormone concentration in men.

To evaluate the temporal features of physiological fluctuation in serum PTH concentration, we sampled peripheral blood at 4-min intervals for 24 h from five normal men (32.8 yr; range, 26-40 yr) and measured serum PTH levels using a two-site immunoradiometric assay with the exquisite sensitivity and specificity for human PTH-(1-84) (intact PTH). The resultant 24-h time series of serum intact PTH levels were assessed by contemporary techniques in chronophysiology for rhythmic and episodic peak detection. Cosinor analysis disclosed a significant circadian rhythm in serum intact PTH concentrations in all five men, with the mean circadian amplitude and acrophase of 7.2 +/- 4.4 ng/L and 2305 +/- 401 h, respectively (mean +/- SD; n = 5). No apparent fixed ultradian periodicity was found by autocorrelation and spectral analyses. Evaluation of episodic intact PTH pulsatility by Cluster analysis revealed 23.0 +/- 4.4 discrete PTH pulses/24 h (P less than 0.01 vs. signal-free noise), which occurred at an interpulse interval of 61.6 +/- 11.1 min. The average duration of a serum intact PTH peak was 42.8 +/- 7.3 min, and its mean incremental amplitude was 12.6 +/- 1.3 ng/L, which corresponded to a 31.8 +/- 5.2% increase above the preceding nadir. Discrete PTH peaks were separated by nonpulsatile valleys which lasted for 17.9 +/- 4.4 min. Cross-correlation between the time series of serum intact PTH and whole blood ionized calcium (Ca2+) was at its maximum (-0.5) at concurrent time points in three subjects, while significant positive correlation between serum intact PTH and simultaneous serum inorganic phosphorus concentrations was observed in four of five subjects. There was no apparent correlation between the levels of serum intact PTH and serum magnesium. Our data show that serum levels of intact PTH, the only biologically active form of PTH in the blood, is characterized by a significant circadian periodicity, spontaneous episodic pulsatility with distinct peak properties, and a significant temporal coupling with Ca2+ and inorganic phosphorus concentrations. We conclude that PTH secretion, as judged by the temporal pattern of serum intact PTH levels, is pulsatile in normal men.

Antitumor effect of transcatheter oily chemoembolization for hepatocellular carcinoma assessed by computed tomography: role of iodized oil.

The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82 patients with unresectable hepatocellular carcinoma (HCC) by computed tomography more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered to 40 cases. No significant differences were found in the patient background characteristics between the DOE-treated group and the EOE-treated group. Tumor regression of more than 50% of the product of two dimensions was observed in 26 DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No difference in antitumor effect was observed between DOE and EOE, although a sufficient dose per tumor volume would be required to manifest an antitumor effect on hepatocellular carcinoma.

FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors.

UNLABELLED: We previously reported that grading of GLUT-1 glucose transporter expression was related closely to FDG accumulation in FDG PET in human cancers. But in this strong GLUT-1 expression group, there was an enormous range of standardized uptake values (SUVs) within them. METHODS: To evaluate other factors determining the FDG PET uptake, FDG PET was performed in 36 preoperative patients (mean age 62.0 yr) suspected of having pancreatic tumors, including 33 malignant and 3 benign neoplastic tumors. FDG uptake at 50 min after injection of 185 MBq 18F-FDG with > 5 hr fasting condition was semiquantitatively analyzed as SUVs. The GLUT-1 expression was studied by immunohistochemistry of paraffin sections from these tumors after the operation using the antiGLUT-1 antibody. The number of tumor cells within a 5- x 5-mm square was counted manually using x200 magnification photographs and was graded immunohistochemically as strong, weak or negative. RESULTS: In all 36 cases there were 3 cases of GLUT-1 negative, 8 of GLUT-1 weak positive and 25 of GLUT-1 strong positive. In all cases, the total number of tumor cells had no significant value for SUVs. Among 33 GLUT-1 positive cases, the number of GLUT-1 positive tumor cells correlated significantly with SUVs (p < 0.01). Only in 25 strong grade cases, the number of GLUT-1 strong positive tumor cells had a more significant value for SUVs (p < 0.005). Computational multivariate analysis using multiple regression for SUVs was performed evaluating the five variables as follows: tumor size, GLUT-1 immunohistochemical grading, number of total tumor cells, number of total GLUT-1 positive tumor cells and number of GLUT-1 strong positive cells. This analysis revealed that only the variable, the number of GLUT-1 strong positive cells, had a significant regression coefficient for SUVs (standard regression coefficient = 0.855, p < 0.0001). CONCLUSION: These data indicate that GLUT-1 expression plays an essential role in higher FDG accumulation in pancreatic tumor FDG PET, and the cellularity has a significant influence on SUVs only in the condition of GLUT-1 strong positive expression.

[MR angiography in the evaluation of endoscopic injection sclerotherapy for esophago-gastric varices].

We evaluated the utility of magnetic resonance angiography (MRA) for the detection of esophago-gastric varices and assessment of their therapeutic response to endoscopic injection sclerotherapy (EIS). MRA was performed in a total of 12 patients with esophago (E)-gastric (G) varices (V) (9 EV and 3 GV patients) both before and two-weeks after EIS. 25-35 horizontal images were obtained during single breath holding and data were reconstructed by using the two dimension time of flight method. MRA detected varicose lesions in all GV patients and in 7 of 8 EV patients of the grades F2 or higher. Varicose lesion in grade F1 EV patients were initially undetectable before EIS but became evident on MRA after EIS. The portal collaterals were equally well displayed by MRA and the superior mesenteric arteriography at its portogram phase. MRA and endoscopy were concordant for the disappearance or persistence of varicose lesions after EIS. We conclude that MRA is useful for the detection of esophago-gastric varices and other portal collaterals. MRA provides a non-invasive and workable technique in evaluation of patients with esophago-gastric varices undergoing EIS.

[Analysis with immunoreactive CCKs and bioactive CCKs in rat duodenum and brain].

We extracted immunoreactive CCKs from rat duodenum and brain. We fractionated these samples by gel-filtration and analyzed with immunoreactivity and bioactivity of each fraction. 1) Elution profile of CCKs in duodenum and brain was well corresponding to that of bioactive CCKs. 2) Contents of CCKs determined by both RIA and Bioassay in each fraction were well correlated with each other. 3) Apparent molecular weights of CCKs of duodenum calibrated in column chromatography were approximately 2200, 1000 and 800. 4) Apparent molecular weight of CCK of brain seemed to be 1000.

Endotoxemia in patients on hemodialysis.

We examined endotoxins and limulus amebocyte lysate-reactive material (LAL-RM) in serum from 87 patients on hemodialysis, using the conventional chromogenic limulus test (CCLT) and a new specific endotoxin assay with factor G-free LAL (endotoxin-specific test: EST). All patients with regenerated cellulose dialyzers had increased CCLT values, whereas the EST values were not higher than in controls. This discrepancy can be explained by the LAL-RM which is cellulose-derived and cross-reacts with LAL via factor G. Using EST for measurements of endotoxin, 6 patients out of 87 had pathological endotoxemia and all of these patients were associated with either cirrhosis, infection, or malignancy. Some patients who had no complications showed fever before or during dialysis, but they did not have high endotoxin levels. EST is useful for the diagnosis of endotoxemia in patients on hemodialysis because of the presence of LAL-RM in serum. Endotoxemia is rare in patients on hemodialysis, if they are not associated with infection, cirrhosis, or other complications.

Cholecystokinin-induced regulation of muscarinic receptor on dispersed pancreatic acini.

We have examined the effect of cholecystokinin octapeptide (CCK-8) on the ability of carbamylcholine (carbachol) to inhibit binding of 3H-N-methylscopolamine (3H-NMS) to muscarinic receptors on dispersed acini from rat pancreas. Carbachol bound to muscarinic receptors on rat dispersed pancreatic acini with two different Kd values. EC50 value for the stimulation of amylase secretion by carbachol was well compatible to the calculated Kd value of high affinity binding site of carbachol, suggesting that high affinity binding sites were mainly involved in the secretory response. Simultaneous addition of CCK-8 decreased the ability of carbachol to inhibit binding of 3H-NMS to acini due to an apparent disappearance of high affinity binding site of carbachol. The effective range of concentrations of CCK-8 for such a receptor regulation, as well as the time course of CCK-8 effect, were in good agreement with those for the restriction of carbachol-induced amylase secretion by CCK-8. These findings suggest that the restriction of carbachol-stimulated amylase secretion by CCK-8 is mainly a result of the disappearance of high affinity binding site of muscarinic receptor as a result of CCK-8 administration.

Cholecystokinin downregulates receptors for vasoactive intestinal peptide and secretin in rat pancreatic acini.

We examined the effect of cholecystokinin (CCK) on the receptors for vasoactive intestinal peptide (VIP) and secretin in rat pancreatic acini. CCK decreased the specific binding of 125I-VIP and 125I-secretin by 42 and 51%, respectively. This CCK-induced inhibition was caused by an apparent decrease in the capacity of high-affinity binding sites of VIP and secretin receptors. CR 1409, a specific antagonist of CCK, abolished CCK-induced binding inhibition, whereas 12-O-tetradecanoylphorbol-13-acetate, A23187, and cycloheximide did not affect the binding of the radioligands. Both N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (Bt2cGMP) and nitroprusside inhibited the specific binding of 125I-VIP. This inhibition, however, was because of an apparent decrease in the capacity of low-affinity binding sites on VIP receptors. CCK-induced downregulation of VIP and secretin receptors was associated with the diminished acinar response to VIP or secretin-induced adenosine 3',5'-cyclic monophosphate accumulation and amylase secretion, whereas neither Bt2cGMP nor nitroprusside affected VIP-induced amylase secretion. Data suggest that CCK-induced downregulation is mediated by the initial interaction of CCK with CCK receptors followed by some postreceptor process, which appears unrelated to protein kinase C, calcium mobilization, decrease in protein synthesis, or cellular cGMP increases. This downregulation, at least in part, accounts for CCK-induced restricted stimulation of amylase secretion by VIP and secretin.

The usefulness of laparoscopy-assisted distal gastrectomy in comparison with that of open distal gastrectomy for early gastric cancer.

BACKGROUND: The technique of laparoscopy-assisted distal gastrectomy (LADG) was developed for early gastric cancer, but its feasibility and the associated clinical outcome remain unclear. METHODS: We reviewed 24 patients who underwent LADG (LADG group) and 35 patients who underwent traditional open distal gastrectomy (ODG group) for early gastric cancer in our hospital, and compared the clinical data of the two groups. RESULTS: The clinical and pathological backgrounds of the patients in the two groups were similar. The duration of surgery was not significantly different between the two groups, but the blood loss in the LADG group was significantly less than that in the ODG group. The number of removed lymph nodes was not significantly different between the two groups. The times to the first passing of flatus, first walking, and the restarting of oral intake; the length of hospital stay; and the duration of epidural analgesia were significantly shorter in the LADG group. The morbidity rate in the LADG group was lower than that in the ODG group. CONCLUSIONS: LADG is a safe and minimally invasive surgical technique, after which we can expect a faster recovery.

Hepatic neoplasms: effects of transcatheter arterial embolization on coagulation and fibrinolysis.

Forty-eight patients with hepatic malignancy (47 with hepatocellular carcinoma, one with metastatic colon carcinoma), who underwent transcatheter arterial embolization (TAE) for treatment of hepatic neoplasms, were investigated to determine the effects of TAE on coagulation and fibrinolysis. TAE was followed by a significant decrease in the platelet count (P less than .001); a prolongation of prothrombin time (P less than .001); an early increase in levels of fibrinopeptide A (P less than .01), fibrinopeptide B beta-15-42 (P less than .001), and fibrin(ogen) degradation products (P less than .001); and a delayed increase in the fibrinogen level (P less than .001), without a significant prolongation of the activated partial thromboplastin time. In the three patients who developed disseminated intravascular coagulation (DIC) after TAE, a reduction of both the platelet count and fibrinogen level occurred significantly earlier and in a more severe form than in the other patients without DIC; this reduction preceded the onset of the characteristic symptoms of DIC. Data suggested that close monitoring of platelet count and fibrinogen level is important for early detection of DIC following TAE.

Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma.

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.