|
1. |
Postnatal Development of the Rat Exocrine Pancreas. I. Alterations in High‐ and Low‐Affinity Cholecystokinin Receptors and Enzyme Secretion |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 325-334
Shangguo Tang,
Satti Beharry,
Peter Durie,
Preview
|
PDF (925KB)
|
|
摘要:
We tested the hypothesis that postnatal alterations in cholecystokinin (CCK) receptors are associated with developmental changes in enzyme secretory response. We used simultaneous measurements of CCK receptor binding and amylase release in pancreatic acini isolated from rat pups at various ages (1, 2, 5, 6, 18, and 36 days). CCK receptor binding was analyzed using the LIGAND program. The affinity of the high- affinity state increased postnatally at 18 and 36 days (p< 0.05); the capacity of the high-affinity state also increased at 2 days (p< 0.05), then declined sequentially up to 36 days. The affinity of the low-affinity state increased postnatally reaching statistical significance at 5 days; the capacity of the low-affinity state increased twofold at 2 days, reaching statistical significance at 5 days (p< 0.05); this was followed by a slight decrease at 36 days. At 1 day postnatally a small amylase response occurred (p< 0.05), but no dose-dependent response was observed. A significant CCK dose-dependent secretory response occurred at all other ages. Maximal amylase release was highest at 18 days (p< 0.05). CCK doses required to stimulate maximal amylase release were 20, 2, 1, 0.2 and 0.4 nMat 2, 5, 6, 18, and 36 days, respectively. The receptor occupancy rates for high- and low- affinity states decreased sequentially between 2 and 18 days of age, when maximal amylase release occurred. These data suggest that more spare receptors become available with increasing postnatal age. We conclude that postnatal alterations of both high- and low-affinity states of CCK receptors in pancreatic acini are associated with developmental changes in enzyme secretory response to CCK. An increase in the affinity of high- affinity state and the capacity of the low-affinity state may enhance acinar sensitivity to CCK.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
2. |
Postnatal Development of the Rat Exocrine Pancreas. II. Effects of Protein‐Calorie Malnutrition on Amylase Secretion and CCK Receptor Binding |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 335-344
Shangguo Tang,
Satti Beharry,
Peter Durie,
Preview
|
PDF (866KB)
|
|
摘要:
Malnutrition induces pancreatic atrophy and intracellular derangement, but its effects on cholecystokinin (CCK) receptors and the CCK-induced secretory response remain unclear. We used a rodent model to study the developmental effects of protein-calorie malnutrition on exocrine pancreatic function. Simultaneous experiments evaluated postnatal alterations in CCK-induced amylase response and receptor binding of pancreatic acini. At all postnatal ages, somatic and pancreatic weight of the malnourished rats was significantly below age-matched controls (p< 0.01). The malnourished rats showed a higher secretory response to CCK at 1 day of age and increased acinar sensitivity at 2 days. Maximal amylase secretion was significantly higher at 5 and 18 days (p< 0.05), but remained similar to that of the age-matched controls at 36 days. CCK receptor binding showed no significant changes at 1 and 2 days postnatally in comparison with controls. At 5 and 18 days, the affinity of the high-affinity state showed a twofold increase, while the capacity of the high-affinity state decreased by 40-55%. At the same time, the affinity of the low-affinity state increased significantly (p< 0.05), but the capacity of the low-affinity state was essentially unchanged. The acinar sensitivity of malnourished rats was consistently reduced between 5 and 36 days, which coincided with a reduction in spare receptors in the malnourished rats. In conclusion, the increased amylase secretory response at 1 and 2 days of age may be due to an adaptive response of endocrine function to maternal metabolic stress. The increased affinities of CCK receptors at 5 and 18 days may be associated with a higher secretory responsiveness, while the decreased spare receptors may contribute to a reduction in the acinar sensitivity. These results demonstrate that malnutrition induces changes in CCK binding and its secretory response.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
3. |
Change of Pancreatic Enzymes, Pancreatic Stone Protein (PSP), and Plasma α2‐Macroglobulin‐Trypsin Complex‐like Substance (MTLS) in the Activation of Pancreatic Juice |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 345-349
Masanori Kato,
Shinobu Hayakawa,
Satoru Naruse,
Motoji Kitagawa,
Hiroshi Ishiguro,
Yasuyuki Nakae,
Tetsuo Hayakawa,
Preview
|
PDF (431KB)
|
|
摘要:
To characterize the activation of pancreatic zymogens (trypsinogen, chymotrypsinogen, and proelastase 1) in acute pancreatitis, we studied the activation of pancreatic juice with porcine enteropeptidase in vitro, and then enzymatic activities and the generation of pancreatic stone protein (PSP) S1form in pancreatic juice were investigated. Further, we determined immunoreactive trypsin, immunoreactive elastase 1, PSP, and α2-macroglobulin-trypsin complex-like substance (MTLS) levels in plasma to which the activated juice was added. In the present report, we demonstrate that the plasma MTLS level reflected the activation of pancreatic trypsinogen in pancreatic juice. Further, the generation of PSP S1form was found at an early stage of activation. Therefore, the plasma MTLS level and the generation of PSP S1form may offer new diagnostic information on the amounts of activated proteases and subsequently on the severity of acute pancreatitis.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
4. |
Different Changes in High‐Energy Phosphates in Alcoholic Acute Pancreatitis and Taurocholate Acute Pancreatitis in Rats Using NMR Spectroscopy at 2.0 T |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 350-357
Marco Siech,
Michael Davis,
Hans Beger,
Preview
|
PDF (910KB)
|
|
摘要:
We studied the pancreatic high-energy phosphates in two models of acute pancreatitis using31P nuclear magnetic resonance (NMR) in rats for the first time in vivo. Alcoholic pancreatitis was induced by acute ethanol intoxication and an obstruction-hyperstimulation mechanism. Taurocholate pancreatitis was generated by intraparenchymal administration of 1 ml of 1–10% taurocholate-Na+. In addition to the obligate control groups, a simple ischemia experiment was performed. The high-energy phosphates were monitored by31P NMR spectroscopy at 2.0 T. Additionally, by means of a scoring system, the quality and quantity of pathomorphologic parameters were quantified after 24 h.31P spectra acquired after injection of taurocholate showed an increase in inorganic phosphate with a concomitant decrease in ATP levels, similar to pancreatic ischemia. This irreversible decrease was accompanied histologically by severe pancreatic hemorrhage. After induction of alcoholic acute pancreatitis a reversible decrease in ATP was occasionally seen. Even when alcoholic pancreatitis had been fully established at 24 h, the31P NMR spectrum was normal in all animals. In conclusion, depletion of high-energy phosphates seems to occur as a result of pancreatic cell death rather than being a cause of pancreatic necrosis. For the first time we applied in vivo NMR in the rat pancreas to study the time course in acute pancreatitis.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
5. |
Islet Amyloid Polypeptide inPsammomys obesus(Sand Rat)Effects of Nutritionally Induced Diabetes and Recovery on Low‐Energy Diet or Vanadyl Sulfate Treatment |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 358-366
A. Leckström,
E. Ziv,
E. Shafrir,
P. Westermark,
Preview
|
PDF (4481KB)
|
|
摘要:
We investigated the possible relationship between islet amyloid polypeptide (IAPP) and the hyperinsulinemia and/or hyperglycemia that is seen in the desert-adapted gerbilPsammomys obesus, when the animal is transferred from a low-energy (LE) diet to a high-energy (HE) diet. The effects of vanadyl sulfate and transition from a HE to a LE diet on the diabetic state of thePsammomyswere also studied.Psammomysmaintained on a LE diet, showing normoinsulinemia and normoglycemia (group A), were used as controls. IAPP and insulin immunoreactivity in the islets of Langerhans was studied using the peroxidase-antiperoxidase technique and plasma levels of the two hormones were determined by radioimmuno- assays. The islet immunoreactivity of both IAPP and insulin was significantly weaker in the hyperinsulinemic and hyper- glycemicPsammomys(group C) compared to group A. Transfer to a LE diet resulted in complete recovery of the IAPP- and insulin-staining pattern to that seen in group A [group A—Rec (nutrition)]. The plasma IAPP levels of the group C animals were not significantly higher than in group A, while after vanadyl sulfate treatment the IAPP levels and IAPP/insulin ratios remained significantly higher [group A—Rec (vanadyl)]. At the same time the circulating levels of glucose and insulin were restored to normal. Conclusively, islet IAPP and insulin immunoreactivity disappeared and reappeared in parallel inPsammomystransferred to a HE diet and back to a LE diet. Furthermore, vanadyl sulfate treatment of the hyperinsulinemic and hyperglycemic animals normalized circulating glucose and insulin levels, but not IAPP levels, possibly due to a negative feedback effect of IAPP on insulin release.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
6. |
Altered Expression of Insulin‐like Growth Factor II Receptor in Human Pancreatic Cancer |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 367-373
Toshiyuki Ishiwata,
Uwe Bergmann,
Marko Kornmann,
Martha Lopez,
Hans Beger,
Murray Korc,
Preview
|
PDF (3452KB)
|
|
摘要:
The insulin-like growth factor-II (IGF-II) receptor (IGF-IIR) is a single-chain transmembrane protein identical to the mannose-6-phosphate receptor. In the present study we examined IGF-IIR expression in normal and cancerous human pancreatic tissues. In the normal pancreas, moderately strong IGF-IIR immunoreactivity was present in the cytoplasm of islet cells, and mild cytoplasmic immunoreactivity was evident occasionally in ductal and acinar cells. Some ductal cells also exhibited nuclear IGF-IIR immunoreactivity. In the pancreatic cancers, regions of strong IGF-IIR immunoreactivity were present in the duct-like cancer cells within the tumor mass, often exhibiting nuclear localization. Expression of IGF-IIR mRNA in the cancer cells was confirmed by in situ hybridization. By comparison with normal pancreatic tissues, 7 of 12 pancreatic cancers exhibited a 5.6-fold increase in IGF-IIR mRNA levels, whereas in 3 cancers the IGF-IIR transcript was below the level of detection. Furthermore, all six tested cultured human pancreatic cancer cell lines expressed the IGF-IIR mRNA transcript. Our data indicate that IGF-IIR is over expressed in a significant number of human pancreatic cancers, where it has a tendency to localize in the nucleus, and raise the possibility that IGF-IIR may contribute to the pathobiology of pancreatic cancer.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
7. |
Detection of Mutant K‐rasin Dissected Paraaortic Lymph Nodes of Patients with Pancreatic Adenocarcinoma |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 374-378
Nobuhisa Ando,
Akimasa Nakao,
Shuji Nomoto,
Shin Takeda,
Tetsuya Kaneko,
Tsuyoshi Kurokawa,
Toshiaki Nonami,
Hiroshi Takagi,
Preview
|
PDF (524KB)
|
|
摘要:
In this study, we attempted to detect K-raspoint mutations by means of two-stage polymerase chain reaction/ restriction fragment length polymorphism (PCR/RFLP) to diagnose micrometastases in paraaortic lymph nodes of patients with pancreatic adenocarcinoma. Main carcinoma tissues and corresponding lymph nodes in the paraaortic region were obtained from 15 patients who underwent extended radical surgery including the wide dissection of lymph nodes and who were diagnosed as lymph node negative by routine histological examination. DNA was extracted from the tissue specimens, and PCR/RFLP analysis was used to detect K-rasoncogene mutations at codon 12. Thirteen of the primary tumors were found to have K-rasmutations. In eight of the 13 cases, 42 of the 101 lymph nodes showed K-raspoint mutations in the paraaortic lymph nodes. These results suggested that PCR/ RFLP analysis is potentially highly sensitive for the detection of micrometastases in lymph nodes and that it may be useful in reaching an accurate assessment of the lymphatic dissemination of pancreatic adenocarcinoma at the molecular level.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
8. |
Inhibition of Growth and Invasive Activity of Human Pancreatic Cancer Cells by a Farnesyltransferase Inhibitor, Manumycin |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 379-383
Osamu Kainuma,
Takehide Asano,
Masayuki Hasegawa,
Takashi Kenmochi,
Toshio Nakagohri,
Yoshiharu Tokoro,
Kaichi Isono,
Preview
|
PDF (409KB)
|
|
摘要:
The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-rasmutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-rasgene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-typeras.Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
9. |
Intraislet Regulation of Pancreatic Polypeptide Secretion in the Isolated Perfused Rat Pancreas |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 384-391
Robert Kleinman,
Ronald Gingerich,
Gordon Ohning,
John Bradley,
Helen Wong,
Edward Livingston,
John Walsh,
F. Brunicardi,
Preview
|
PDF (739KB)
|
|
摘要:
The present study is to determine if intraislet insulin or somatostatin regulate pancreatic polypeptide (PP) secretion in the isolated perfused rat pancreas by infusing insulin or somatostatin antisera. Isolated rat panereata were stimulated with either 16.7 mMglucose (G) alone, G with antisomatostatin antibody (G + SA), or G with antiinsulin antibody (G + IA). G inhibited PP secretion −22 ± 9.5 pMbelow basal, a decrease of 9 ± 6.3% (n= 6;p= NS), G + IA inhibited PP secretion −10 ± 27.2 pMbelow basal, a decrease of 20 ± 15% (n= 7,p= NS), and G + SA stimulated PP secretion 18 ± 7.1 pMabove basal, an increase of 26 ± 5% (n= 6;p< 0.05). G stimulated insulin secretion 3,144 ± 210 pMabove basal (n= 6,p<0.05), and G + SA stimulated insulin secretion 2,695 ± 195 pMabove basal (n= 7;p< 0.05 vs. baseline,p= NS vs. G alone). G stimulated C-peptide secretion 886 ± 175 pMabove basal (n= 6;p< 0.05), G + SA stimulated C-peptide secretion 847 ± 102 pMabove basal (n= 7;p< 0.05,p= NS vs. G alone), and G + IA stimulated C-peptide secretion 834 ± 93 pMabove basal (n= 7;p< 0.05,p= NS vs. G alone). These data demonstrate that infusion of SA results in significant stimulation of PP secretion during high-G infusion, whereas IA has no effect. Infusions of SA or IA at the doses used have no effect on G-stimulated insulin or C-peptide secretion. This suggests that intraislet somatostatin may be an inhibitory regulator of PF secretion in the isolated perfused rat pancreas.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
10. |
Acute Interstitial Pancreatitis in Rats Induced by Dibutyltin Dichloride (DBTC)Pathogenesis and Natural Course of Lesions |
|
Pancreas,
Volume 15,
Issue 4,
1997,
Page 392-401
J. Merkord,
L. Jonas,
H. Weber,
G. Kroning,
H. Nizze,
G. Hennighausen,
Preview
|
PDF (2295KB)
|
|
摘要:
Dibutyltin dichloride (DBTC; 6 mg/kg body weight, i.v.) induced acute interstitial pancreatitis in rats. The course of the pancreatitis was examined within 28 days by light and electron microscopy as well as by pathobiochemistry (amylase, lipase, alkaline phosphatase, and bilirubin in serum; tin concentration in biliopancreatic juice, tissue, and concretions). The pathogenesis of the DBTC-induced pancreatitis in rats was studied by different experimental designs (in intact animals, after bile duct ligation, after surgical bypass of the bile duct). DBTC caused toxic necrosis of the biliopancreatic duct epithelium, which is then shed into the duct and forms obstructing plugs in the distal common bile duct. Interstitial pancreatitis occurred during the first 4 days, accompanied by significantly increased activities of serum α-amylase and lipase. After 7 days extensive infiltration of the pancreatic interstitium with mononuclear cells was observed. Twenty-eight days after administration of DBTC one-third of the rats showed periductal and interstitial fibrosis as well as an active inflammatory process in the pancreas. The findings suggest a twofold pathogenesis of the DBTC-induced pancreatitis: first, the cytotoxic effects on the biliopancreatic duct epithelium lead to epithelial necrosis with obstruction of the duct, subsequent cholestasis, and interstitial pancreatitis; and second, the hematogenic DBTC effects cause direct injury of pancreatic cells (mitochondrial damage, autophagy, cell necrosis) followed by interstitial edema and inflammation. Both processes lead to this special type of DBTC-induced acute pancreatitis with a tendency to a chronic course, when the obstruction of the duct and cholestasis persist.
ISSN:0885-3177
出版商:OVID
年代:1997
数据来源: OVID
|
|