Our understanding of the biology of malaria parasite liver stages is limited because of the lack of efficient in vitro systems that support the exo-erythrocytic (EE) development of the parasite. We report the development of a new hepatocyte line (HC-04) from normal human liver cells. The HC-04 cells have proliferated in hormone-free medium for more than 200 passages. The cells were hyperdiploid, resembled liver parenchymal cells, and synthesized major liver-specific proteins and enzymes. Using Plasmodium falciparum and P. vivax sporozoites harvested from salivary glands of infected mosquitoes, we showed that HC-04 cells supported the complete EE development of these two most prevalent human malaria parasites. The EE parasites attained full maturation as shown by their infectivity to human erythrocytes. The infection rates of the liver cells were estimated to be 0.066% and 0.041% for P. falciparum and P. vivax, respectively. As the first human hepatocyte line known to support complete EE development of both P. falciparum and P. vivax, HC-04 will provide an experimental model that can be used for studying the biology of liver stage malaria parasites.
Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men worldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues and matched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5% of tumor tissues but not detected in matched nontumor tissues. However, TOP2A gene amplification was not observed in both tumor and matched nontumor tissues. TOP2A overexpression was significantly associated with HCC tumor tissues (P < 0.001), hepatitis B surface antigen (HBsAg) in the serum (P = 0.004), and Ki-67 (P = 0.038) but not with age, tumor size, alpha-fetoprotein, TP53, and copy number of TOP2A gene and chromosome 17 centromere. In conclusion, TOP2A overexpression in HCC was not secondary to gene amplification. In addition, neither HER2 amplification nor overexpression could be used as prognostic and predictive marker in HCC.
Right-lobe graft has been used most frequently for living donor liver transplantation in adult patients; however, some donors cannot donate their right lobe (according to the Healey and Scroy's terminology) because the remaining residual liver would be too small. A recent study suggested the possibility of right posterior segment graft in these donors. The purpose of this study was to evaluate the feasibility of right lobe or right posterior segment graft with a volumetric analysis. Liver volumetry by computed tomography was performed in 155 consecutive donors, and the volume of each liver segment was calculated. To confirm the reliability of volumetric examination, the estimated graft volume and the actual weight were compared. The average volume ratios of the lefi lateral segment, lefi medial segment, caudate lobe, right anterior segment, and right posterior segment were 17%, 14%, 2%, 37%, and 30%, respectively. In 39 donors (25%), the volume ratio of the right lobe was over 70%. Of Tokyo, However, right lobectomy could impose a higher surgical risk on donors, as reflected by the volume of the residual liver mass. Furthermore, not all donors can provide their right lobe. Fan and associates* concluded that safe donation was possible only when the estimated residual liver volume was over 30%. Although it should be considered an important criterion to maintain donor safety, the proportion of donors whose right lobe volume ratio is over 70% remains unclear.Recently, to overcome this problem, the right posterior segment graft was introduced as an alternative liver graft.5 However, its feasibility remains obscure because nobody knows with acceptable probability whether the right posterior segment can provide a larger mass than the lefi lobe.To resolve these questions, volumetric analysis of each liver segment was performed. The estimated liver segment volume and actual graft weight were compared to confirm the reliability of volumetric examination. Materials and MethodsBetween January, 1996 and December, 2001, 155 LDLT procedures were performed at Tokyo University Hospital under approval of the Ethics Committee. The recipients consisted of 68 children (younger than 18 years of age) and 85 adults (1 8 years old or more). The patients ranged in age from 8 months to 64 years (mean, 27 years) with body weights ranging from 6 to 99 kg (mean, 39 kg).The underlying condition was biliary atresia in 65, primary biliary cirrhosis in 30, liver cirrhosis for hepatitis with or without hepatocellular carcinoma in 2 l , fulminant hepatic failure in nine, metabolic disorders in seven, and other conditions in 2 1.The remaining two patients underwent retransplantation for graft failure.The donors consisted of 78 parents, 36 children, 20 siblings, 12 spouses, grandmothers, uncles, nieces, and nephews in two, each, and one cousin. The donors ranged in age from 20 to 63 years (mean, 37 years) and weighed from 42 to 90 kg (mean, 61 kg). Segments harvested included left lateral segment (n = 35), extended lefi lateral segment (n = 15), ...
Hepatic artery aneurysm (HAA) is a rare vascular complication, but has a high mortality rate in liver transplant recipients. This study reports the precipitating factors, clinical manifestation, pre-operative diagnosis, related micro-organism, management, and outcome, in a series of HAAs that developed after adult orthotopic liver transplantation (OLT). Data on the primary disease as well as on the above were obtained from a prospective database, and all case records were reviewed. There were eight (0.5%) HAAs in 1,575 adult cadaveric OLTs between 1982 and March 2001. All were pseudo-aneurysms around the native hepaticartery (HA) anastomosis, and all occurred in whole-organ OLTs. There were three types of clinical presentations: sudden hypotension (n = 4), gastrointestinal (GI) bleeding (n = 2), and abnormal liverfunction tests (LFTs) (n = 2). The majority (n = 7) presented within the first 2 months (median: 27.5 days, range: 12-760 days) following OLT. A pre-operative diagnosis of HAA was not determined in five cases. The sensitivity of abdominal ultrasound scan (USS), computed tomography (CT) scan and angiography for detection of HAAs was 3 of 5, 1 of 2 and 3 of 4, respectively. Micro-organisnis could be identified in six patients (bacteria n = 4 and fungi n = 3). All patients underwent urgent operations (excision of HAA in six and ligation in two cases). Immediate reconstruction of the HA was carried out, two different methods being used: repair of native arteries (n = 2) and arterial conduit (interposition n = 3 and aortic conduit n = 2). Two patients died peri-operatively, two died within 2 months, and the remaining four patients are alive at between 8.6 and 12.8 years after repair. HAA following OLT is unpredictable in its presentation, and the sensitivity of clinical and radiological detection is low. A high index of suspicion is required, and urgent surgery with immediate revascularisation and use of appropriate antibiotic/anti-fungal agents is recommended.
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