EUS-guided portal vein catheterization and pressure measurement in an animal model: a pilot study of feasibility

BACKGROUND: The extrahepatic portal vein is inaccessible to direct catheterization. METHODS: Because EUS can readily image the portal vein, the feasibility of EUS-guided portal vein catheterization by using a 22-gauge needle was studied in 7 normal pigs and 14 pigs in which portal hypertension was induced (7/14 anticoagulated). RESULTS: Catheterization was not possible by EUS or transhepatic methods in, respectively, 3 and 5 animals. One anticoagulated animal had a small amount of periduodenal bleeding as a result of EUS catheterization. The mean normal portal vein pressure (1 standard deviation) as determined by EUS and transhepatic methods was, respectively, 20.3 (4) mm Hg and 20.4 (2) mm Hg. Injection of polyvinyl alcohol particles increased the portal vein pressure by 10.2 (11.59) mm Hg. There was a close correlation under all conditions between the mean portal vein pressures obtained by EUS and transhepatic catheterization (r=0.91). CONCLUSIONS: EUS-guided portal vein catheterization appears to be feasible in an animal model and provides accurate pressure measurements.     

Characterization of mutations in ATP8B1 associated with hereditary cholestasis

Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened.     

Polyethylene glycol versus low-ionic-strength solution in pretransfusion testing: a blinded comparison study

BACKGROUND: Polyethylene glycol (PEG) has been shown to potentiate antigen-antibody reactions. STUDY DESIGN AND METHODS: To investigate the utility of PEG in pretransfusion testing, a blinded comparison study of PEG and a low-ionic-strength additive solution (LISS) was conducted. A total of 500 patient samples were tested in parallel with reagent antibody-detection cells using blind-coded PEG and LISS potentiators. RESULTS: In 34 (34%) of 100 samples with known antibodies in the Rh, Kell, Duffy, Kidd, and MNS systems, PEG antiglobulin reactions were stronger (total score, 382) than LISS antiglobulin reactions (total score, 216), and in 66 cases (66%), they were equal to those of LISS. Of 400 samples without detectable antibodies, 384 were negative with PEG and LISS, and 16 were positive in PEG tests and negative in LISS. Seven of the 16 were clinically important antibodies (D, 1; E, 3; Fya, 1; Jka; 1; Jkb, 1), and four were clinically benign antibodies (Le(a), 2; McCc, 1; Sda, 1). Five of the 16 demonstrated inconclusive PEG reactions, for a false-positive rate of 5 in 400 (1.3%). Of the 500 samples, none was negative in PEG tests and positive in LISS (0% false-negative rate). CONCLUSION: Although PEG demonstrates a relatively high false-positive rate, PEG is more sensitive than LISS in detecting clinically significant antibodies.     

三叶因子与胃黏膜保护的研究进展

三叶因子家族是一群主要由胃肠道黏液细胞分泌的小分子多肽.其共同特征为均含一特殊的P结构域及三叶状结构.这种稳定的结构使三叶因子家族具有明显的抗蛋白酶水解、酸消化及耐热特性,因而能在消化道复杂的环境中保持生物活性.目前在哺乳动物体内发现的有pS2/TFF1、SP/TFF2和ITF/TFF3三种,它们具有黏膜保护与修复、肿瘤抑制、信号传导、调节细胞凋亡等功能.本文阐述了三叶因子家族发现的历史,并初步探讨了其作用.同时也对三叶因子受体这一热点的研究现状进行总结.     

Cystic Lesions of the Pancreas

Opinion statement Pancreatic cystadenomas are a group of benign, premalignant, and malignant cystic tumors of the pancreas. Serous cystadenomas are benign lesions that often do not require surgical excision unless they are complicated by bleeding, obstruction, or pain. Mucinous cystadenomas are premalignant lesions that may be surgically excised if there is a concern regarding malignant degeneration. However, it may be difficult to predict the timing and risk of malignant change. Also, it is controversial whether all mucinous cystadenomas should be resected. Cystadenocarcinomas should be surgically managed if they are resectable, that is, there is no evidence of metastatic disease. Intraductal papillary mucinous tumors share many features with mucinous cystadenomas. However, intraductal papillary mucinous tumors arise from the pancreatic duct and are often associated with a dilated pancreatic duct. These lesions are often managed with surgical resection, including total pancreatectomy for diffuse lesions with evidence of localized malignancy.     

Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues

To increase transgenic production of granulocyte-macrophage colony- stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA) were transfected into cells in culture or animals using particle-mediated gene-transfer technology. Normal peripheral blood mononuclear cells accumulated 20- fold greater levels of GM-CSF mRNA and secreted comparably greater amounts of cytokine after transfection with hGM-AUGUA expression vectors versus hGM-AUUUA. hGM-AUGUA mRNA was fivefold more stable (t 1/2 = 95 minutes) than hGM-AUUUA mRNA (t 1/2 = 20 minutes), accounting for elevated steady-state levels. Transfection site extracts and serum samples obtained 24 hours after gene transfer of hGM-AUGUA cDNA into mouse skin contained greater than 32 ng/mL and 650 pg/mL of GM-CSF protein, respectively, compared with 0.33 ng/mL and less than 8 pg/mL for hGM-AUUUA cDNA. GM-CSF produced from mGM-AUGUA cDNA transfected into rat abdominal epidermis induced a profound neutrophil infiltrate. These data suggest a novel strategy for enhanced production of biologically active cytokines by normal cells after in vivo gene transfer.     

Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.