Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.     

Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss

The pathogenesis of progressive bile duct loss in primary biliary cirrhosis remains unclear. In this study, the involvement of cellular senescence of biliary epithelial cells was examined in liver tissue samples from patients with primary biliary cirrhosis (n = 33), and compared with control diseased and normal livers (n = 83). In addition, cellular senescence was induced by oxidative stress in cultured mouse biliary epithelial cells. Biliary epithelial cells in small bile ducts in primary biliary cirrhosis, especially those in patients presenting with chronic non-suppurative cholangitis, frequently expressed senescence-associated beta-galactosidase, and senescence-associated p16(INK4) and p21(WAF1/CIP). In contrast, senescence-associated markers were rarely expressed in small bile ducts in control livers. The infiltration of myeloperoxidase-positive inflammatory cells into biliary epithelial cell layers was closely associated with the cellular senescence of biliary epithelial cells in early-stage PBC. Cellular senescence of cultured mouse biliary epithelial cells was induced by treatment with H2O2 via the p38MAPK-dependent pathway and nitric oxide-augmented H2O2-induced cellular senescence. Oxidative stress- and nitric oxide-mediated cellular senescence may be involved in bile duct lesions, which are followed by progressive bile duct loss in primary biliary cirrhosis.     

数值模拟鼻甲的切除对鼻腔内气体流场的影响

量化研究鼻腔结构的变化对鼻腔内气体流场分布的影响.通过CT图像对鼻腔结构进行三维重建并用有限元方法对气体流场进行数值分析.对重建的鼻腔模型的一侧,分别去掉部分中鼻甲和部分下鼻甲并用有限元方法再次进行数值分析,将得到的结果与原始模型进行比较.观察气体流场分布的变化,在两侧鼻腔的流量分布均有变化,在去掉部分鼻甲的一侧流场和气压的分布也有所改变.通过数值模拟,我们量化的显示了鼻腔结构的变化对鼻腔内气体流场分布的影响.     

Expansion of human nasal chondrocytes on macroporous microcarriers enhances redifferentiation

Articular cartilage has a limited capacity for self-repair. To overcome this problem, it is expected that functional cartilage replacements can be created from expanded chondrocytes seeded in biodegradable scaffolds. Expansion of chondrocytes in two-dimensional culture systems often results in dedifferentiation. This investigation focuses on the post-expansion phenotype of human nasal chondrocytes expanded on macroporous gelatin CultiSpher G microcarriers. Redifferentiation was evaluated in vitro via pellet cultures in three different culture media. Furthermore, the chondrogenic potential of expanded cells seeded in polyethylene glycol terephthalate/ polybuthylene terephthalate (PEGT/PBT) scaffolds, cultured for 14 days in vitro, and subsequently implanted subcutaneously in nude mice, was assessed.

Chondrocytes remained viable during microcarrier culture and yielded doubling times (1.07±0.14 days) comparable to T-flask expansion (1.20±0.36 days). Safranin-O staining from pellet culture in different media demonstrated that production of GAG per cell was enhanced by microcarrier expansion. Chondrocyte–polymer constructs with cells expanded on microcarriers contained significantly more proteoglycans after subcutaneous implantation (288.5±29.2 μg) than those with T-flask-expanded cells (164.0±28.7 μg). Total collagen content was similar between the two groups.

This study suggests that macroporous gelatin microcarriers are effective matrices for nasal chondrocyte expansion, while maintaining the ability of chondrocyte differentiation. Although the exact mechanism by which chondrocyte redifferentiation is induced through microcarrier expansion has not yet been elucidated, this technique shows promise for cartilage tissue engineering approaches.     

肝外胆管梗阻病变MSCT曲面重建胆管成像与MRCP的比较研究

目的比较多层螺旋CT（MSCT）曲面重建（CPR）胆管成像与磁共振胰胆管成像（MRCP）对肝外胆管梗阻病变的诊断价值。方法66例经B超检查提示有肝外胆管梗阻病变的患者，采用单次激发快速自旋回波（SSFSE）序列，行MRCP检查，同期采用10mm层厚层距，使用血管对比剂，行MSCT增强扫描，将门静脉期图像采用2．5mm层厚、1．25mm层距重建，获得轴面源像（ASI），数据传输至图像工作站，作CPR胆管成像。比较CPR胆管成像、MRCP对肝外胆管梗阻病变的定位、定性诊断价值。结果CPR胆管成像、MRCP成功率为100％；CPR胆管成像、MRCP均对肝外胆管梗阻部位做出明确诊断，定位诊断率为100％；CPR胆管成像、MRCP定性诊断率分别为95．5％和80．9％。结论CPR胆管成像、MRCP对肝外胆管梗阻病变均能明确定位，CPR胆管成像定性诊断率明显高于MRCP，CPR胆管成像显示胆管及其周围病变与扩张胆管的关系更直观。     

原发性胆汁性肝硬化基因易感性的研究进展

原发性胆汁性肝硬化（PBC）是一种由自身免疫机制介导的慢性进行性胆汁淤积性肝脏疾病。近年来，其发病率逐年增长，研究表明谷胱甘肽S转换酶（GST）、细胞毒性T淋巴细胞相关抗原4（CTLA-4）、血管内皮细胞一氧化氮合成酶（eNOS）、人类白细胞分化抗原（HLA）、IL-10、细胞角蛋白19（CK19）、甘露糖结合凝集素（MBL）、IL-1、TNF-α基因以及x染色体关联的基因等可能与PBC相关。我对与PBC易感性相关的基因的研究进展进行综述，为今后的研究提供一定的依据。     

Peripheral hepatolithiasis incidentally found at autopsy

Summary Hepatolithiasis is a common disease in East Asia though very rare in the West. Four cases of hepatolithiasis in which calculi were incidentally found in the peripheral branches of the intrahepatic biliary tree at autopsy are described and compared with hepatolithiasis involving the major branches of the intrahepatic biliary tree. These four cases were all elderly, three patients were male and one female. The calculi were brown pigment stones in each case, as seen in the major branch type. The stone-containing ducts showed mild fibrosis and glandular proliferation with inflammatory changes in three cases; these changes were marked in the fourth case. The hepatic parenchyma around the stone-containing ducts was atrophic or collapsed in all four cases. The major branches of the intrahepatic biliary tree as well as the extrahepatic tree failed to show findings suggestive of bacterial infections or biliary anomalies. These data suggest that brown pigment stones develop primarily in the peripheral ducts in the liver. It remains uncertain whether the peripheral type eventually progresses to the major type or not.     

Expression of alpha-amylase isoenzymes and trypsin by the proliferating epithelium of large intrahepatic bile ducts and intrahepatic peribiliary glands in hepatolithiasis

The expression of alpha-amylase isoenzymes (pancreatic and salivary) and trypsin by the epithelium of large intrahepatic bile ducts and peribiliary glands was examined immunohistochemically in hepatolithiasis ( n = 22), extrahepatic biliary obstruction ( n = 20) and normal liver ( n = 22). Hepatolithiasis was associated with marked proliferation of bile duct cells and peribiliary glands. Expression of pancreatic and salivary amylase was observed in the proliferating bile duct cells and peribiliary glands of all livers, and trypsin was found in 68% of the livers. In extrahepatic biliary obstruction, proliferation of the biliary epithelium was less marked, but expression of amylase isoenzymes was observed in all livers and trypsin was found in 50%. All normal livers showed expression of amylase isoenzymes in large intrahepatic bile ducts, septal bile ducts and peribiliary glands, and trypsin was found in 73%. The density of enzyme-containing acini was highest in hepatolithiasis, intermediate in extrahepatic biliary obstruction and lowest in normal liver. These results show that the proliferating biliary epithelium in hepatolithiasis contains amylase isoenzymes and trypsin and that biliary epithelium retains the ability to produce these enzymes after proliferation, suggesting that a large amount of amylase isoenzymes and trypsin may be secreted into the bile ducts in hepatolithiasis. These enzymes may play an important role in the pathophysiology of hepatolithiasis.     

The enigma of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease characterized by a striking predominance in female patients (with most cases diagnosed between ages 40 and 60 yr) as well as serum auto-antibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and, ultimately, liver cirrhosis and failure (1). The precise mechanisms leading to selective destruction of biliary epithelial cells lining intrahepatic bile ducts are still unknown, although numerous immunomediated pathways have been proposed. Genetic background appears to be important in determining susceptibility to the disease (2), but no clear association with alleles in the major histocompatibility complex has been identified. Molecular mimicry either by infections (3) or xenobiotics (4) has been proposed to be capable of breaking tolerance in genetically predisposed individuals, thus leading to onset of PBC. This article describes and discusses the available data regarding the immunomediated pathogenesis of PBC (with particular attention to auto-antibodies and autoreactive T-cells) and presents the recent evidence indicating a role for either xenobiotic chemicals or novel infectious agents in the induction of the disease.     

Mechanism of slowing of mucociliary transport induced by SO2 exposure

Responses of nasal mucociliary transport mechanisms to exposure to 6 ppm SO₂ were studied in chickens in vivo. This model takes advantage of the natural cleft palate which exposes the mucociliated base of the nasal septum. Exposure to 6 ppm SO₂ decreased the mucociliary transport rate along the base of the nasal septum. The minimum force required to move an iron particle along this area of mucous membrane by use of a magnetic field in vivo increased significantly after SO₂ exposure, while the minimum force required to move an iron particle on a pool of mucus collected from the same chicken and tested in vitro showed no change after SO₂ exposure. The elastic recoil distance of mucus was measured both in vivo and in vitro. The in vivo recoil distance decreased significantly after SO₂ exposure, while SO₂ exposure did not change recoil distance in vitro. It is proposed that exposure of chickens to SO₂ results in the formation of multiple points of adhesion of strands of mucus between the acinar gland cells and the emergent extracellular mucus or adhesion of a mucous blanket to the cilia, causing mucociliary transport to be retarded or static.