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Biomedical subjects

Junichi Sakagami

Publications and source records attributed to Junichi Sakagami.

14 recordsLinked to original sources

Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats.

OBJECTIVES: Prior studies have indicated that endogenous or exogenous cholecystokinin (CCK) induces transient acinar cell proliferation at about 24 hours after its stimulation. The aims of the present study were to determine the time point when the administration of the CCK-A-receptor antagonist loxiglumide had its maximal suppressive effect on the proliferation of pancreatic acinar cells and to investigate the effects of loxiglumide on the cell cycle time of pancreatic acinar cells during transient acinar cell proliferation induced by endogenous or exogenous CCK. METHODS: Eight-week-old Wistar rats were divided into the following groups: preadministration of loxiglumide (40 mg/kg) intravenously at 120, 60, and 0 minutes before endogenous CCK stimulation induced by a single oral administration of camostat (50 mg/kg) or exogenous CCK stimulation by a subcutaneous injection of CCK-8 (6 g/kg body weight). For the controls, intravenous saline was used instead of loxiglumide (n = 7 in each group). The proliferative activity of pancreatic acinar cells at 24 hours after CCK stimulation and the cell cycle time of these proliferating pancreatic acinar cells were studied using an immunohistochemical technique. RESULTS: The most significant suppression of the proliferation of the acinar cells was observed in those groups which received loxiglumide 60 minutes before CCK stimulation (P < 0.016), but preadministration of loxiglumide had no effect on the cell cycle time of the proliferating acinar cells (not significant). CONCLUSION: CCK antagonist loxiglumide is expected as an excellent clinical applicable agent for acute pancreatitis. Previous researches suggest that CCK is an aggravating factor during the acute phase of acute pancreatitis, but CCK may be a healing factor during the recovery period. From the results of the present study, it can be said that the excess chronic administration of CCK antagonists during the acute phase of acute pancreatitis may prevent any regrowth of pancreatic cells during the healing period of acute pancreatitis.

Animals↗

Endoscopic resection for the diagnosis of visceral Kaposi's sarcoma.

Kaposi's sarcoma is an uncommon neoplasm that occasionally involves the gastrointestinal tract in immunosuppressed individuals. Infection with human herpes virus 8 is known to be necessary for developing all forms of Kaposi's sarcoma. We report a renal transplant recipient who developed visceral Kaposi's sarcoma 18 months after the transplantation. In Oriental countries, the incidence of Kaposi's sarcoma is extremely low, and this is the first case of Kaposi's sarcoma arising from a transplant recipient in Japan. Standard forceps biopsies of the gastric lesions failed to make the correct diagnosis. However, endoscopic resection successfully led to the correct diagnosis of Kaposi's sarcoma and herpes simplex virus 8 infection as well. This is the first report of a patient with visceral Kaposi's sarcoma who underwent endoscopic resection that reliably confirmed histological diagnosis and the viral genome at the same time.

Endoscopy, Digestive System↗

Solid pseudopapillary tumor as a possible cause of acute pancreatitis.

CONTEXT: Acute pancreatitis is not commonly seen in the first presentation of pancreatic neoplasms. Solid pseudopapillary tumor as a cause of acute pancreatitis has not yet been reported. This is the first report of acute pancreatitis resulting from solid pseudopapillary tumor. CASE REPORT: We report the case of a 21-year-old female who presented with a sudden onset of severe abdominal pain associated with elevated serum pancreatic enzyme concentration. The initial diagnosis was acute pancreatitis. However, subsequent ultrasonography and computed tomography showed an abdominal mass in the tail of the pancreas, retroperitoneal fluid and left pleural effusion. There was scarce pain relief even with large doses of analgesics. A distal pancreatectomy was then performed and a final diagnosis of solid pseudopapillary tumor was made histologically. The surrounding pancreatic tissue was characterized as hemorrhagic edematous pancreatitis. CONCLUSIONS: Solid pseudopapillary tumor is generally known as a slow-growing pancreatic neoplasm with few, if any, symptoms. However, solid pseudopapillary tumors should be kept in mind as a possible cause of acute pancreatitis, especially in cases of non-alcoholic young women having an acute pancreatitis attack.

Acute Disease↗

Increased QT dispersion in patients with alcoholic pancreatitis.

OBJECTIVES: Increased dispersion of the QT interval has been proposed to be a novel marker for increased risk of ventricular arrhythmia and sudden cardiac death. This study examined whether QT dispersion is affected in patients with alcoholic pancreatitis. METHODS: We measured the QT interval, corrected QT interval, activation recovery interval, activation time, recovery time, and their respective dispersions in 3 age- and gender-matched groups: patients with alcoholic pancreatitis [age, 58.9 +/- 11.8 years; male/female (M/F), 33/3], patients with alcohol dependence (age, 59.3 +/- 8.9 years; M/F, 33/4), and a healthy control group (age, 55.8 +/- 8.8 years; M/F, 33/3). RESULTS: The QT dispersions in patients with alcoholic pancreatitis (62.4 +/- 19.9 milliseconds; P < 0.001) or alcohol dependence (58.2 +/- 19.6 milliseconds; P < 0.001) were significantly greater than in the control group (41.4 +/- 13.3 milliseconds). Similarly, the corrected QT dispersions in patients with alcoholic pancreatitis (68.5 +/- 22.8 milliseconds; P < 0.001) or alcohol dependence (65.3 +/- 23.6 milliseconds; P < 0.001) were significantly greater than in the control group (42.8 +/- 13.2 milliseconds). Both QT dispersion and QTc dispersion were longer in patients with alcoholic pancreatitis than those with alcohol dependence (P = 0.011 and P = 0.039, respectively). Simple linear regression analysis of the relationship between the RR and QT intervals revealed that the regression lines for patients with alcoholic pancreatitis and alcohol dependence were almost parallel. However, the slope of the regression line for the control group was significantly greater (P < 0.05) than for the other 2 lines. CONCLUSION: The findings demonstrate increased QT and QTc dispersions in patients with either alcoholic pancreatitis or alcohol dependence. The QT dispersion and QTc dispersion were longer in patients with alcoholic pancreatitis than those with alcohol dependence.

Arrhythmias, Cardiac↗

[Role of apoptosis in severe acute pancreatitis].

The role of apoptosis in a severe acute pancreatitis is recently given the most attention, but it is hardly known in a clinical study. We show three assumptions between apoptosis and the pathophysiological mechanisms of severe acute pancreatitis in this paragraph. First, the apoptosis of pancreatic acinar cell might prevent from a worsening in acute pancreatitis due to diminish leakage of pancreatic enzyme and extension of inflammation. Secondly, impairment cellular immunity due to peripheral lymphocyte apoptosis might be linked to the development of subsequent infectious complications in acute pancreatitis. Third, apoptosis in various major organs might be involved in the mechanism of multiple organs failure in acute pancreatitis. These findings might lead the new development in the therapeutic strategy of acute pancreatitis.

Acute Disease↗

The effect of steroid pulse therapy on the development of acute pancreatitis induced by closed duodenal loop in rats.

BACKGROUND: The aim of the present study was to evaluate the effect of a high dose of methylprednisolone (MP) on the development of acute pancreatitis (AP) in rats induced by closed duodenal loop (CDL). METHODS: Pancreas web weight, volume of ascites, hematocrit, serum amylase activity, concentrations of interleukin (IL)-1beta and IL-6, organ blood flow in both the pancreas and the kidney, and histological findings of the pancreas were studied 6 h after the induction of AP. RESULTS: The intravenous administration of MP (30 mg/kg body weight) significantly reduced the increase in pancreas web weight, volume of ascites, hematocrit, serum amylase activity, concentrations of IL-1beta and IL-6, histological edema, and necrosis observed in CDL pancreatitis. The administration of MP also apparently improved both the pancreatic and the renal blood flow. CONCLUSIONS: The present results suggest that these cytokines influence at least the progression of AP, and that the mechanism by which MP pulse therapy inhibits the development of AP partly involves the inhibition by MP of the release of the cytokines.

Acute Disease↗

Ultrasonographic splanchnic arterial flow measurement in severe acute pancreatitis.

INTRODUCTION: Duplex ultrasonographic technology is now capable of detecting flow signals in the various splanchnic vessels and calculating the concomitant flow velocities using fast-Fourier transformation. AIM: To use Doppler sonography to investigate how splanchnic hemodynamics vary during the early stage of severe acute pancreatitis. METHODOLOGY: Six patients with severe acute pancreatitis (age, 59.0 +/- 6.57 years; four men, two women) and seven with mild to moderate acute pancreatitis (age, 60.1 +/- 7.41 years; five men, two women) were examined with Doppler sonography immediately after disease onset. The maximum velocity, minimum velocity, mean velocity, pulsatility index, and resistive index were determined from the Doppler spectra from the proper hepatic artery, celiac artery, and superior mesenteric artery. We also examined 15 healthy subjects (age, 59.3 +/- 4.60 years; 10 men, five women) as controls. RESULTS: The maximum velocity of the proper hepatic artery in patients with severe acute pancreatitis was significantly higher than that in patients with mild to moderate acute pancreatitis (p = 0.011) and in control subjects (p = 0.0047). Similarly, significant increases in both the minimum velocity and the mean velocity of the proper hepatic artery were observed in patients with severe acute pancreatitis. Neither pulsatility index nor resistive index of the proper hepatic artery showed a significant difference among the three groups. There were no significant differences among the three groups with respect to the flow velocity of the superior mesenteric artery. In contrast, the pulsatility index of the superior mesenteric artery in patients with severe acute pancreatitis was significantly lower than that in patients with mild to moderate acute pancreatitis (p = 0.0058) or in control subjects (p = 0.0024). For patients with acute pancreatitis, a significant inverse correlation was obtained between the maximum velocity of the proper hepatic artery and the pulsatility index of the superior mesenteric artery (r = -0.658, p = 0.0145). CONCLUSION: The increase in the hepatic arterial flow velocity and the decrease in the superior mesenteric arterial pulsatility index may represent early events of the severe type of acute pancreatitis.

Acute Disease↗

Relation between morphologic changes in the main pancreatic duct and exocrine pancreatic function after a secretin test.

INTRODUCTION: Because pancreatic exocrine function testing methods are problematic, both imaging and functional tests are important in the diagnosis of chronic pancreatitis. AIM: To evaluate the usefulness of ultrasonographic monitoring of the main pancreatic duct after a secretin test. METHODOLOGY: A total of 70 subjects (30 control subjects, 26 patients with probable chronic pancreatitis, and 14 patients with definite chronic pancreatitis) were selected. The main pancreatic duct diameters were measured serially after an injection of secretin (100 IU/body). The relation between the magnitude of the duct dilation and exocrine pancreatic function on the secretin test was evaluated. RESULTS: The main pancreatic duct dilated immediately after a bolus injection of secretin, showed a peak after 2-5 minutes, and recovered gradually. The response curve of the definite group had a flatter pattern than that of the other groups. For the maximal to basal duct diameter ratio, statistically significant differences were found between the control and definite groups and between the control and probable groups. In addition, the ratio correlated significantly with the maximal bicarbonate concentration and secretory volume on the secretin test. CONCLUSIONS: The results of the current study indicate that exocrine pancreatic function and the morphologic changes of the main pancreatic duct are significantly related. Dynamic ultrasonographic findings may reflect pancreatic function; consequently, this test may be a useful tool in the diagnosis of chronic pancreatitis.

Adult↗

Molecular cloning and characterization of chymopasin, a novel serine protease from rat pancreas.

INTRODUCTION: Pancreas secretes many enzymes for food digestion into the pancreatic juice. We cloned a novel serine protease, chymopasin, from rat pancreas. AIMS: To know the localization of this enzyme in the pancreas and to analyze the enzymatic characteristics. METHODOLOGY: We cloned chymopasin cDNA using 3' and 5' RACEs. Northern blot and in situ hybridization were used to study the expression of this enzyme. Recombinant chymopasin protein produced by was analyzed by Western blot using specific antibody, and its enzymatic characteristics were examined using commercially available synthetic substrates, fibrin and gelatin. RESULTS: The open reading frame of rat chymopasin consisted of 792 bp encoding 264 amino acid residues. The deduced amino acid sequence contained the essential catalytic triad characteristic of the serine protease family. There was no putative N-glycosylation site. The amino acid sequence of rat chymopasin showed 54.5% identity to rat chymotrypsin B. Northern blot analysis showed that the transcript was strongly expressed in the pancreas. In situ hybridization with digoxigenin-labeled cRNA probe showed that the positive signals were observed in the acinar cells, but not in the islet or duct cells. Chymopasin protein was detected in the pancreas homogenate and bile-pancreatic juice. Further, cerulein stimulated the secretion of rat chymopasin into bile-pancreatic juice. CONCLUSION: These results suggested that rat chymopasin might be a digestive enzyme secreted from the acinar cells. From the enzyme assay using synthetic substrates, the purified recombinant chymopasin expressed in showed chymotrypsin-like activity. In addition, rat recombinant chymopasin showed fibrinolytic and gelatinolytic activities. These results suggested a role in the pathogenesis of pancreatic damage.

Amino Acid Sequence↗