摘要:

This prospective study aimed to pinpoint acute pancreatic patients who are at a higher risk of clinical deterioration. Once identified, they can be given more costly intensive-care therapy or transferred promptly to hospitals with specialized equipment. Our study included 217 patients with acute pancreatitis. All of them underwent computed tomography within 72 h of admission. Initial organ failure was defined according to the Atlanta classification (arterial po2, ≥60 mm Hg; serum creatinine, >2 mg/dl after rehydration). Forty-two (19%) of the 217 patients had initial organ failure, and 13 31%) of these deteriorated (i.e., 10 of them needed artificial ventilation, and three, dialysis treatment). Deterioration of initial organ failure was significantly more frequent in alcohol-than in non-alcohol-induced acute pancreatitis (p= 0.005). One hundred seventy-five (81%) patients had no initial organ failure, and 12 (7%) of these deteriorated. All needed artificial ventilation, and two of them dialysis treatment also. There was no significant correlation between etiology and deterioration in these patients. Patients with alcohol-induced acute pancreatitis and initial organ failure represented a major group at risk and should be closely monitored or transferred to specialized units, whereas patients without initial organ failure have a lower risk of later developing organ failure and usually do not need intensive care.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The activation of the kallikrein-kinin system is thought to be one of the pathophysiologic mechanisms in acute pancreatitis. A radioimmunoassay for human urinary tissue kallikrein was developed and used to measure tissue kallikrein peritoneal exudate and plasma from 48 patients with severe acute pancreatitis. All patients were treated with intraperitoneal lavage. One group (n= 22) received high doses of the protease inhibitor aprotinin (aprotinin group), and the other group, saline (control group). Levels of kallistatin in peritoneal exudates and plasma were measured with an enzyme immunoassay. A large increase in tissue kallikrein was observed in the peritoneal exudate, which declined in both groups after multiple lavages. Complexing of liberated tissue kallikrein with kallistatin was evidenced by gel filtration in both peritoneal exudates and plasma in both groups. The decrease in kallistatin observed in both peritoneal exudate and plasma is therefore regarded as being due not only to repeated lavage, but also to true consumption of the binding protein. Some of the liberated tissue kallikrein in the peritoneal fluid and plasma was complexed to aprotinin. In the control group, six patients were operated on because of pancreatic necrosis, compared with none in the aprotinin group. The levels of tissue kallikrein in the lavage fluid were lower in the control group, but this was the result of the very low tissue kallikrein values in the six patients operated on for pancreatic necrosis. Levels of kallistatin in plasma and peritoneal exudate in these six patients were lower on the day of admission compared with the other patients, and the plasma levels continued to be lower during the first week. Large amounts of tissue kallikrein were found to be released into the peritoneal exudates in acute pancreatitis. Lavages effectively cleared the released tissue kallikrein. The tissue kallikrein was complexed to kallistatin, whereas in the aprotinin group, also to aprotinin both in plasma and in peritoneal fluid. The partitioning of kallikrein between the two inhibitors was the result of the interaction between enzyme and inhibitors and the turnover of the complexes formed. The low admission levels of kallistatin in the six patients operated on because of pancreatic necrosis suggest that kallistatin may act as an early marker of severity in acute pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Patients with acquired immunodeficiency syndrome (AIDS) can develop biliary and pancreatic disorders, like sclerosing cholangitis and acute pancreatitis. Chronic pancreatic changes are rare and only poorly described. In this study, we report our endoscopic retrograde cholangiopancrea-tography (ERCP) findings in 20 patients with AIDS, focusing on pancreatographic changes. ERCP findings from 20 patients with advanced disease were analyzed. Patients with history of chronic alcoholism were ruled out. ERCP findings were correlated to the coexistence of an opportunistic infection and the taking of antiviral therapies. Bile duct and pancreatic duct abnormalities were observed in 11 (55%) of 20 and seven (37%) of 19 patients, respectively. Bile duct lesions were mainly sclerosing cholangitis, and chronic pancreatic alterations consisted of side-branch involvement (n= 4), multiple and diffuse strictures of the main duct (n= 1), and diffuse dilatation of the main pancreatic duct (n= 2). The presence of an opportunistic infection was correlated with sclerosing cholangitis but not with chronic pancreatic changes. Similarly, there was no association between the finding of an abnormal cholangiogram and the presence of pancreatic alterations. This population of patients with AIDS had a significant proportion (37%) of chronic pancreatic ductal changes, which do not seem to be related to morphologic alterations and/or opportunistic infections of the biliary tract.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Fas ligand (Fas-L) is a key molecule in normal immune development, homeostasis, modulation, and function. Recent reports suggested that tumor cells can evade immune attack by killing lymphocytes through expressing Fas-L on the tumor cell surface. The expression of Fas-L has been demonstrated in pancreatic cancer cell lines and in tissues. The messenger RNA (mRNA) and protein expression of Fas-L was investigated in four pancreatic cancer cell lines and 19 human pancreatic duct cell carcinomas (PDCs) by reverse transcrip-tion-polymerase chain reaction (RT-PCR) and immunohisto-chemistry, respectively. In addition, coculture assay of Fas-L and Fas-expressing PANC-1 cells and Fas-sensitive Jurkat cells was performed. Fas-L mRNA expression was observed in all four cell lines as well as in 10 PDC tissues, and the protein expression was frequently detected in the PDC tissues (16 of 19 cases). The coculture experiments showed that PANC-1 cells induced apoptosis of Jurkat cells, whereas the PANC-1 cells themselves and Jurkat cells cultured without the presence of PANC-1 showed few apoptotic changes. These findings suggest that Fas-L may play an important role in the ability of PDCs to escape from immune surveillance through the induction of apoptosis in tumor-attacking lymphocytes. The frequent expression of Fas-L in PDCs may partly explain the notorious biologic behavior of PDCs.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Islet amyloid polypeptide (IAPP) and insulin are co-stored and generally secreted in parallel; however, studies have demonstrated that the IAPP/insulin molar secretory ratio may be altered in response to certain stimuli. Because we previously demonstrated that intraislet somatostatin is an inhibitory regulator of basal insulin secretion in the isolated perfused human pancreas, this study was designed to determine the relative influence on the regulation of IAPP versus insulin secretion. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors with continuous perfusion of a modified Krebs media with the glucose level maintained at constant 3.9 mM. Intraislet somatostatin was immunoneutralized by the infusion of either a highly sensitive monoclonal somatostatin antibody (SAb) or its FAb fragment (SFAb). Sequential test periods separated by basal periods were performed by infusion of either of the following: glucose, SAb, SFAb, or appropriate controls. IAPP/insulin molar secretory ratio decreased by 33% in response to infusion of either SAb or the SFAb, respectively (p <0.01), and decreased by 67% in response to glucose infusion (p<0.01). An alteration of the IAPP/insulin secretory ratio is seen in response to infusion of exogenous glucose or in response to the neutralization of intraislet somatostatin.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar ge-notypic properties. By using an automated DNA sequencer, a K-rasmutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-rasmutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42, XY, add(3) (pl 1.2), der(7) t(7;12) (p22;ql2), -10, -12, add (14)(pl l), -18, add (20)(ql3), -22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a combination of bryostatin 1 and gemcitabine and a combination of spongistatin and gemcitabine produced remissions in only one of seven mice. From these results, we conclude that (a) this is the first study illustrating that clonal characteristics of primary pancreatic tumors remained unchanged when implanted in mice and as a permanent cell line grown in vitro; and (b) there is a synergistic effect between gemcitabine and selected marine products tested in this study, which is more apparent in the gemcitabine and auristatin-PE combination. The results of this preliminary study suggest that these agents should be explored clinically in the treatment of pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Variations in cancer cell adhesion to extracellular matrix (ECM) proteins might underlie an enhanced metastatic potential. ECM binding is mediated by cell-adhesion molecules, the membrane expression of which might be influenced by soluble mediators, such as cytokines. The aims of our study were to ascertain whether epidermal growth factor (EGF), transforming growth factor β1 (TGF-β1), interleukin 1α (IL-1α), or interleukin 1β (IL-1β) can modify MIA PaCa 2 (pancreatic cancer cell line) and CAPAN-1 (metastatic pancreatic cancer cell line) adhesion to fibronectin, laminin, or type I collagen, and whether these cytokines can shift the membrane expression of the hyaluronic acid receptor (CD44). EGF significantly enhanced MIA PaCa 2, but not CAPAN-1, adhesion to fibronectin, laminin, and type I collagen. TGF-β1 reduced MIA PaCa 2 adhesion to type I collagen, but enhanced CAPAN-1 adhesion to fibronectin and laminin. IL-1α was found to enhance MIA PaCa 2 adhesion to fibronectin, while reducing adhesion to type I collagen, whereas IL-1β reduced the adhesion to laminin. IL-1α enhanced CAPAN-1 adhesion to laminin in a dose-dependent manner; IL-1β slightly increased the adhesion of these cells to laminin at low dosage, and to type I collagen at high dosage. Both IL-1α and IL-1β reduced CD44 membrane expression of MIA PaCa 2, while TGF-β1 increased the percentage of CD44-positive CAPAN-1 cells. We suggest that the effects on cell adhesion induced by different cytokines depend on the status of the target pancreatic cancer cell. EGF and, in part, IL-1α can favor nonmetastatic pancreatic cancer cell adhesion to ECM, possibly favoring tumor spread. Metastatic cells seem to lose the responsiveness to EGF, while becoming hyperresponsive to IL-1α. TGF-β1 might exert an antidiffusive effect on primary, and a prodiffusive effect on metastatic pancreatic cancer cells. Only IL-1α, IL-1β, and TGF-pi seem to influence CD44 membrane expression. All the results presented in this study were obtained in vitro, and in vivo studies are needed to verify whether the studied cytokines can favor or counteract pancreatic cancer spread.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Transforming growth Factor-β (TGF-β) bind to the type II TGF-P receptor (TβRII), which then heterodimer-izes with the type I TGF-β receptor (TβRI), thereby initiating a signaling cascade. TGF-β are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although TβR II also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized TβR II expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with TβR II messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, TPRII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p<0.01) in TβRII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of TβRII and the levels of two invasion-promoting genes, plasminogen-activator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed TβRII had a significantly shorter survival period than did patients whose cancers expressed low levels of TβRII. It is suggested that TβRII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We aimed to devise a method of preparing the pancreas for in vitro study that would provide tissue that is viable and functional for 24 h, with preservation of integral functional cell-membrane structures. Pancreata of NIH Swiss mice were excised, gently insufflated with media, and carefully snipped into portions of <0.5 mm. Snips were incubated in cell culture for 0, 8, 24, and 48 h, with viability measured by 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyltetrazolium bromide (MTT) assay and amylase production quantified after stimulation with cerulein. Recombinant tumor necrosis factor-α (TNF-α) was added to cell culture, and apoptosis demonstrated by Hoechst staining at 0, 24, and 48 h. At 0, 8, and 24 h, pancreatic snips were determined to be viable by MTT assay. They also were functional with intact cell-membrane apparatuses at these same time points, as evidenced by amylase production in response to a cholecystokinin analogue. We were able to induce apoptosis with TNF-α ligand in these pancreatic snips in support of viability and overall cellular function. We conclude that the snip method provides an effective in vitro pancreatic model. Acinar cells are viable and functional for ≥24 h, with evidence that their cell-surface receptors are preserved in their operational state.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The acute effects of kidney bean (Phaseolus vulgaris) E2L2lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and a-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (≤90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats withL-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID