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Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection. 抗icam -1和抗lfa -1单克隆抗体对小鼠胰岛移植排斥反应的预防作用。
K Arai, M Sunamura, Y Wada, M Takahashi, M Kobari, K Kato, H Yagita, K Okumura, S Matsuno

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

在小鼠胰岛移植模型中,利用针对细胞间粘附分子-1 (ICAM)-1/白细胞功能相关抗原1 (LFA-1)的阻断单克隆抗体(mab)检测了这些分子的免疫抑制潜力。将ICR小鼠离体胰岛移植到链脲霉素诱导的糖尿病C57BL/6小鼠肾荚膜下间隙。移植后立即以100微克/只/天的剂量给予抗体,持续3或7天。在未治疗的小鼠中,胰岛移植物在16天内发生排斥反应,但单独使用抗icam -1单抗(KAT-1)、单独使用抗lfa -1单抗(KBA)或两种单抗治疗可显著延长移植物的存活时间。特别是,KAT-1和KBA在7天的疗程中显著延长了88%的受体,并诱导了100天以上的移植物无限期存活。逆转录聚合酶链式反应(RT-PCR)分析同种异体胰岛移植物中细胞因子转录物的表达。在KAT-1和KBA处理的小鼠中,未检测到Th1细胞因子(白细胞介素2 [IL-2]和干扰素γ [ifn - γ])的转录本,但Th2细胞因子(IL-4和IL-10)的表达增强并持续超过140 d。相比之下,Th1细胞因子在未处理的小鼠移植物中主要表达。这些结果表明,抗icam -1和/或抗lfa -1单克隆抗体通过提示Th2偏差可能延长小鼠胰岛移植存活。
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引用次数: 33
alpha-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation. 胰腺产生甲胎蛋白的腺癌,呈局灶性肝样分化。
S Tanno, T Obara, T Fujii, T Izawa, Y Mizukami, Y Saitoh, H Ura, Y Kohgo

We report a rare case of pancreatic carcinoma producing alpha-fetoprotein (AFP), showing focal hepatoid differentiation in metastatic lymph nodes. A 65-yr-old female was admitted because of abdominal pain. The serum AFP was measured at 16,170 ng/mL. Radiological examinations revealed a mass measuring 6 cm in diameter in the body and tail of the pancreas. A right supraclavicular lymphadenopathy was found and biopsied. Light microscopy showed a tumor consisting of a portion of a hepatoid area and well-differentiated adenocarcinoma, which was suggestive of a hepatoid adenocarcinoma. Immunohistochemical analysis showed that the tumor cells expressed AFP, alpha 1-antitrypsin (AT) and albumin. Although the pathological diagnosis of the primary pancreatic tumor was not obtained, this appears to be the first case of hepatoid adenocarcinoma of the pancreas.

我们报告一例罕见的胰腺癌产生甲胎蛋白(AFP),显示局灶肝样分化转移淋巴结。一名65岁女性因腹痛入院。测定血清AFP浓度为16170 ng/mL。放射学检查显示胰腺体和尾部有直径6厘米的肿块。发现右侧锁骨上淋巴结病变并行活检。光镜显示肿瘤由部分肝样区和高分化腺癌组成,提示肝样腺癌。免疫组化分析显示,肿瘤细胞表达AFP、α 1-抗胰蛋白酶(AT)和白蛋白。虽然原发胰腺肿瘤的病理诊断尚未获得,但这似乎是胰腺肝样腺癌的第一例。
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引用次数: 28
Human pancreatic leiomyosarcoma (PZX-7) growing as a serially transplantable xenograft in immunosuppressed mice. 人类胰腺平滑肌肉瘤(PZX-7)在免疫抑制小鼠体内作为连续移植的异种移植物生长。
A Zalatnai, J Bocsi, T Csákány, T Fekete, J Lásztity

Background: Several human leiomyosarcoma xenografts have been established, but pancreatic smooth muscle sarcomas have never been serially transplanted and investigated.

Method: Immunosuppression of CBA/CA mice was achieved by thymectomy, whole-body irradiation, and bone marrow reconstruction. Tumor fragments were subcutaneously implanted from a Grade III pancreatic leiomyosarcoma and serially passaged for more than 24 mo. The xenografted tumors were characterized by morphological, morphometrical, biochemical, and flow cytometric methods.

Results: The tumor has retained its characteristic morphology and no further differentiation occurred. The mitotic counts and the amount of the connective tissue all remained constant. The calculated volume doubling time was 11.3 d. Immunohistochemically, the tumor proved to be p53-negative, but the strong expression of the bcl-2 remained as a constant feature throughout successive transplantations. The DNA index and the proliferation indices did not change significantly with the time (mean DI: 1.65, range: 1.561-1.70; mean PI: 17.9%, range: 15.3-20.7%). Lactose dehydrogenase (LDH) isoenzyme electrophoresis evidenced a retained human pattern of the tumor even after 32 mo of transplantations.

Conclusion: The first human pancreatic leiomyosarcoma xenograft (PZX-7) growing in immuno-suppressed mice is described and characterized.

背景:已经建立了几种人类平滑肌肉瘤异种移植,但胰腺平滑肌肉瘤从未被连续移植和研究过。方法:采用胸腺切除、全身照射、骨髓重建等方法对CBA/CA小鼠进行免疫抑制。从III级胰腺平滑肌肉瘤皮下植入肿瘤碎片并连续传代超过24个月。异种移植肿瘤通过形态学,形态计量学,生化和流式细胞术方法进行表征。结果:肿瘤保持其特征形态,未发生进一步分化。有丝分裂计数和结缔组织的数量都保持不变。计算的体积倍增时间为11.3 d。免疫组织化学结果表明,肿瘤为p53阴性,但bcl-2的强表达在连续移植过程中保持不变。DNA指数和增殖指数随时间变化不显著(平均DI: 1.65,范围:1.561 ~ 1.70;平均PI: 17.9%,范围:15.3-20.7%)。乳糖脱氢酶(LDH)同工酶电泳证明,即使在移植32个月后,肿瘤仍保留人类模式。结论:描述了首例在免疫抑制小鼠体内生长的人胰腺平滑肌肉瘤异种移植瘤(PZX-7)。
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引用次数: 1
Massive intraperitoneal bleeding from tryptic erosions of the splenic vein. Another cause of sudden deterioration during recovery from acute pancreatitis. 脾静脉胰蛋白酶侵蚀导致大量腹腔内出血。急性胰腺炎恢复期突然恶化的另一个原因。
C H Müller, U Lahnert, A Schafmayer, P G Lankisch

Acute bleeding is a rare, but frequently fatal complication of pancreatitis. Bleeding into the gastrointestinal tract may occur owing to gastric or duodenal erosions, peptic ulcers, or varices in the esophagus, stomach, or colon following splenic vein thrombosis, or intraperitoneally from eroded vessels in pancreatic pseudocysts or expanding pseudoaneurysms. We report a novel case of massive intraperitoneal bleeding owing to tryptic erosions of the splenic vein in a patient recovering from acute pancreatitis. Diagnosis of the bleeding was made by ultrasound and ultrasound-guided blood aspiration. The source of the bleeding was identified intraoperatively, and a left-sided pancreatectomy and a splenectomy were performed.

急性出血是胰腺炎的一种罕见但经常致命的并发症。胃肠道出血的发生可能是由于胃或十二指肠糜烂、消化性溃疡、脾静脉血栓形成后食管、胃或结肠静脉曲张,或胰腺假性囊肿或扩张的假性动脉瘤的血管被侵蚀引起的腹腔内出血。我们报告一个新的病例大量腹腔内出血由于胰蛋白酶侵蚀脾静脉的病人从急性胰腺炎恢复。经超声及超声引导下吸血诊断出血。术中确定出血的来源,并进行了左侧胰腺切除术和脾切除术。
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引用次数: 15
Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini Consensus Conference. 诊断,客观评估严重程度,和管理急性胰腺炎。圣托里尼共识会议。
H G Beger, R Isenmann
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引用次数: 214
The potential for gene therapy in pancreatic cancer. 胰腺癌基因治疗的潜力。
M J Humphreys, W Greenhalf, J P Neoptolemos, P Ghaneh

Pancreatic cancer is highly aggressive and is a leading cause of cancer death in the Western world. Currently, there is no effective treatment for this disease; resection is only available to a small fraction of patients and has a marginal effect on overall survival rates. Chemotherapy and radiation also have very limited effects on patient survival. There is clearly a need for new approaches to treatment of such an aggressive disease. Gene therapy is of potential use in the treatment of cancer, and all currently available strategies are discussed with relevance to pancreatic cancer. A key to such strategy is specific delivery and selective gene expression in target cells. Current approaches include replacement of tumor suppressor genes, the use of antisense (AS) oligonucleotides, gene-directed enzyme prodrug therapy (GDEPT), and immunotherapy. The scene is now set for the next phase of development in clinical trials.

胰腺癌具有很强的侵袭性,是西方世界癌症死亡的主要原因。目前,这种疾病没有有效的治疗方法;切除仅对一小部分患者有效,对总生存率的影响很小。化疗和放疗对患者生存的影响也非常有限。显然,需要新的方法来治疗这种侵袭性疾病。基因治疗在癌症治疗中具有潜在的用途,目前所有可用的策略都与胰腺癌相关进行了讨论。这种策略的关键是在靶细胞中特异性递送和选择性基因表达。目前的方法包括替代肿瘤抑制基因、使用反义寡核苷酸(AS)、基因导向酶前药物治疗(GDEPT)和免疫治疗。现在已经为下一阶段的临床试验做好了准备。
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引用次数: 22
Proximal migration of transanastomotic pancreatic stent following pancreaticoduodenectomy and pancreaticojejunostomy. 经吻合口胰腺支架在胰十二指肠切除术和胰空肠吻合术后的近端移位。
B J Ammori, C M White

Background: The use of catheters to stent the pancreaticojejunal anastomosis following pancreaticoduodenectomy is practiced by some surgeons. Their long-term effects in this setting, however, remain unknown.

Methods: A 60-yr-old woman underwent a potentially curative pylorus preserving pancreaticoduodenectomy for Stage I ampullary carcinoma. Roux-en-Y pancreaticojejunostomy was constructed over a short stent. She presented 4 yr later with abdominal pain, steatorrhea, and weight loss. Computed tomography revealed a stent within the proximal pancreatic duct, with gross upstream ductal dilatation and parenchymal features of chronic pancreatitis.

Results: Laparotomy revealed no disease recurrence. The stent, removed through a jejunotomy, was occluded. On-table pancreatogram demonstrated a 3-cm proximal duct stricture. Drainage was achieved with a lateral pancreaticojejunostomy (modified Puestow procedure). Recovery was uneventful, with clinical recovery of pancreatic exocrine function at 6 mo follow-up.

Conclusion: Proximal migration of transanastomotic pancreatic stent with subsequent development of chronic pancreatitis is a potential complication following pancreaticoduodenectomy. It can be managed effectively with stent removal and a lateral pancreaticojejunostomy.

背景:一些外科医生在胰十二指肠切除术后采用导管支架进行胰空肠吻合术。然而,它们在这种情况下的长期影响尚不清楚。方法:一名60岁的妇女因I期壶腹癌接受了保留幽门的胰十二指肠切除术。Roux-en-Y胰空肠吻合术在短支架上构建。4年后出现腹痛、脂肪漏和体重减轻。计算机断层扫描显示近端胰管内的支架,有明显的上游胰管扩张和慢性胰腺炎的实质特征。结果:剖腹探查无疾病复发。通过空肠切开术取出支架,并将其闭塞。表上胰图显示近端胰管狭窄3厘米。采用外侧胰空肠吻合术(改良的Puestow手术)引流。术后恢复顺利,随访6个月胰腺外分泌功能恢复。结论:经吻合口胰腺支架近端移位并发慢性胰腺炎是胰十二指肠切除术后的潜在并发症。它可以通过支架移除和外侧胰空肠吻合术有效地处理。
{"title":"Proximal migration of transanastomotic pancreatic stent following pancreaticoduodenectomy and pancreaticojejunostomy.","authors":"B J Ammori,&nbsp;C M White","doi":"10.1007/BF02925969","DOIUrl":"https://doi.org/10.1007/BF02925969","url":null,"abstract":"<p><strong>Background: </strong>The use of catheters to stent the pancreaticojejunal anastomosis following pancreaticoduodenectomy is practiced by some surgeons. Their long-term effects in this setting, however, remain unknown.</p><p><strong>Methods: </strong>A 60-yr-old woman underwent a potentially curative pylorus preserving pancreaticoduodenectomy for Stage I ampullary carcinoma. Roux-en-Y pancreaticojejunostomy was constructed over a short stent. She presented 4 yr later with abdominal pain, steatorrhea, and weight loss. Computed tomography revealed a stent within the proximal pancreatic duct, with gross upstream ductal dilatation and parenchymal features of chronic pancreatitis.</p><p><strong>Results: </strong>Laparotomy revealed no disease recurrence. The stent, removed through a jejunotomy, was occluded. On-table pancreatogram demonstrated a 3-cm proximal duct stricture. Drainage was achieved with a lateral pancreaticojejunostomy (modified Puestow procedure). Recovery was uneventful, with clinical recovery of pancreatic exocrine function at 6 mo follow-up.</p><p><strong>Conclusion: </strong>Proximal migration of transanastomotic pancreatic stent with subsequent development of chronic pancreatitis is a potential complication following pancreaticoduodenectomy. It can be managed effectively with stent removal and a lateral pancreaticojejunostomy.</p>","PeriodicalId":73464,"journal":{"name":"International journal of pancreatology : official journal of the International Association of Pancreatology","volume":"25 3","pages":"211-5"},"PeriodicalIF":0.0,"publicationDate":"1999-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02925969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21317630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 30
Acute pancreatitis secondary to 5-aminosalicylic acid therapy in a patient with ulcerative colitis. 溃疡性结肠炎患者5-氨基水杨酸治疗继发急性胰腺炎1例。
E Adachi, K Okazaki, Y Matsushima, H Seno, K Uchida, H Nakase, C Kawanami, T Nakamura, T Chiba

Therapy with oral 5-aminosalicylic acid (5-ASA) for ulcerative colitis has been reported to be effective and safe. We describe a case of biochemically proven mild acute pancreatitis occurring after 9 d of oral 5-ASA therapy for ulcerative colitis. A hypersensitivity mechanism seemed to be involved in the development of pancreatitis probably owing to erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for early diagnosis of pancreatitis in patients with ulcerative colitis receiving 5-ASA administration. This is the first report of acute pancreatitis developed by oral 5-ASA therapy for the treatment of ulcerative colitis in the literature of Japan.

口服5-氨基水杨酸(5-ASA)治疗溃疡性结肠炎已被报道是有效和安全的。我们描述了一个生物化学证明轻度急性胰腺炎发生后9天口服5-ASA治疗溃疡性结肠炎。过敏机制似乎与胰腺炎的发展有关,可能是由于药物的不稳定的全身吸收。我们建议对接受5-ASA治疗的溃疡性结肠炎患者进行临床和生化监测,以早期诊断胰腺炎。这是日本文献中首次报道通过口服5-ASA治疗溃疡性结肠炎引起急性胰腺炎。
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引用次数: 23
The "two-hit" pathogenetic concept of chronic pancreatitis. 慢性胰腺炎的“双重打击”发病概念。
R W Ammann, P U Heitz, G Klöppel
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引用次数: 0
Different patterns in immunoreactive anionic and cationic trypsinogen in urine and serum in human acute pancreatitis. 急性胰腺炎患者尿和血清中免疫反应性阴离子和阳离子胰蛋白酶原的不同模式。
U Petersson, S Appelros, A Borgström

Background: Acute pancreatitis (AP) results in elevated concentrations of trypsinogen (T) isoenzymes in serum. Immunoreactive anionic trypsinogen in urin (irAT/u) is elevated in AP, and has recently been proposed as a rapid diagnostic instrument and severity predictor. These results have not been confirmed by other groups, and irAT/u has not been further characterized. The concentration of immunoreactive cationic trypsinogen in urine (irCT/u) and the serum irAT/irCT ratio in AP have not been extensively examined.

Methods: Levels of irAT and irCT were studied in urine and serum from 50 AP patients and in urine from 41 non-AP patients. Severity was assessed according to the Atlanta classification. irAT/u was characterized by gel filtration.

Results: Gel filtration revealed only AT in the urine. Highly significant differences in irAT/u were seen between AP/non-AP (p < 0.0001) and mild/severe disease (p = 0.0012). The irAT/irCT ratio in serum changed from normal 0.8 to 1.3 in AP.

Conclusions: IrAT and only traces of irCT were found in the urine in AP. IrAT/u was higher in AP than in other acute abdominal disorders (non-AP) and also higher in severe than in mild AP. IrAT in serum (irAT/s) increased proportionally more than irCT/s in AP, but did not discriminate mild from severe forms. High levels of irAT/u in some non-AP cases and a wide range in AP cases make the clinical value of the test questionable.

背景:急性胰腺炎(AP)导致血清中胰蛋白酶原(T)同工酶浓度升高。尿中免疫反应性阴离子胰蛋白酶原(irAT/u)在AP中升高,最近被认为是一种快速诊断工具和严重程度预测因子。这些结果尚未得到其他研究小组的证实,irAT/u也未得到进一步的表征。尿中免疫反应性阳离子胰蛋白酶原浓度(irCT/u)和AP中血清irAT/irCT比值尚未广泛检测。方法:对50例AP患者和41例非AP患者尿液和血清中的irAT和irCT水平进行了研究。严重程度根据亚特兰大分级进行评估。采用凝胶过滤法对irAT/u进行表征。结果:凝胶过滤仅显示尿中有AT。在AP/非AP和轻度/重度疾病(p = 0.0012)之间,irAT/u有极显著差异(p < 0.0001)。结论:AP患者血清irAT/irCT比值由正常的0.8变为1.3。结论:AP患者尿液中有irAT和微量irCT。AP患者的irAT/ u高于其他急性腹部疾病(非AP),重度AP患者高于轻度AP。血清irAT (irAT/s)比例高于重度AP患者的irCT/s,但不区分轻、重度AP。在一些非AP病例中,irAT/u的水平很高,而在AP病例中,irAT/u的范围很广,这使得该测试的临床价值值得怀疑。
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引用次数: 27
期刊
International journal of pancreatology : official journal of the International Association of Pancreatology
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