Elevated Resistive Index in the Hepatic Artery as a Predictor of Fulminant Hepatic Failure in Patients with Acute Viral Hepatitis: A Prospective Study Using Doppler Ultrasound

To assess the sensitivity and specificity of the resistive index of the hepatic artery, which is related to the vascular resistance of the artery, for the prediction of fulminant hepatic failure, we performed Doppler ultrasonography examinations on the hepatic arteries of 72 patients with acute viral hepatitis (25 of whom developed fulminant hepatic failure and 47 of whom recovered without developing fulminant hepatic failure) as well as the hepatic arteries of age- and sex-matched controls. The mean resistive index of the hepatic arteries in patients who developed fulminant hepatic failure was significantly larger than that of patients who recovered without developing fulminant hepatic failure (P < 0.01). When a resistive index cutoff level of 0.74 was used, an 84% sensitivity and a 94% specificity were obtained for the prediction of fulminant hepatic failure. An elevated resistive index of the hepatic artery may be useful for predicting the patient's clinical outcome and determining the need for a liver transplantation in patients with acute viral hepatitis.     

Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection

Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P =.001) and scope (14/36 vs. 4/36 pools, P =.002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = -0.51, P =.049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs. 2.5% recovered, P =.002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence.     

Follow-up studies of Hokkaido residents with Kawasaki disease

OBJECTIVES: Sixteen national surveys of Kawasaki disease in Japan from 1970 to 2000 have identified a total of 169,117 patients with Kawasaki disease. Based on that figure, 8,460 residents of Hokkaido probably have a history of Kawasaki disease. It is also estimated that almost 270 Hokkaido residents would have Kawasaki disease-related coronary artery disease. We underwent follow-up studies of Hokkaido residents > or = 15 years with Kawasaki disease. METHODS: We mailed a questionnaire to the departments of internal medicine, cardiology or cardiovascular surgery inquiring about the health status of patients with Kawasaki disease at 451 hospitals with 20 or more beds in Hokkaido. RESULTS: We obtained replies from 185 hospitals (41.0%). Only 11 hospitals(5.9%) reported experience of patients with Kawasaki disease(with or without coronary artery disease) at hospital follow-up. Detailed patient histories for 60 patients from 7 hospitals were obtained: Twenty patients had Kawasaki disease complicated with coronary artery disease, whereas 40 patients had a history of Kawasaki disease and no present coronary artery disease. Thirty-seven patients without coronary artery disease were followed up at one hospital. The 60 patients were aged from 15 to 36 years. Thirty-nine patients(65%) were in the 15 to 20 year age bracket. Coronary aneurysms were recognized in 25 patients(24 males and 1 female) with Kawasaki disease(41.7%) at the onset of the disease. Twenty patients had an aneurysm(s) in the left main trunk and/or the left anterior descending artery, and 13 patients in the right coronary artery. There was a history of myocardial infarction in four patients (6.7%) and nine patients(15.0%) still suffered from angina pectoris. Aortocoronary bypass surgery was performed in one patient, whereas two patients required percutaneous coronary intervention. CONCLUSIONS: Our study suggests that the majority of Hokkaido residents with Kawasaki disease(with or without coronary artery disease) are not being followed up at area hospitals. The characteristics of patients who were followed up included age < or = 20 years, male sex and the presence of severe coronary artery disease other than circumflex involvement.     

Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short‐term ethanol perfusion in the rat

Abstract: Background/Aims: The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O₂^·?) release into the hepatic sinusoids during short‐term exposure to ethanol. Methods: The rat liver was perfused continuously with ethanol (a substrate for alcohol dehydrogenase) or tert‐buthanol (not a substrate for alcohol dehydrogenase) for 20 min at a final concentration of 40 mM. In order to detect O₂^·? production, MCLA (2‐methyl‐6‐[p‐methoxyphenyl]‐3,7‐dihydroimidazo[1,2‐a]pyrazin‐3‐one), a Cypridina luciferin analogue, was simultaneously infused and MCLA‐enhanced chemiluminescence was measured. The effects of gadolinium chloride (GdCL₃) (a suppressor of Kupffer cells (KCs)), staurosporine (ST) (an inhibitor of serine–threonine kinases, including protein kinase C), diphenyleneiodonium chloride (DPI) (an inhibitor of NADPH oxidase), ibuprofen (IB) (an inhibitor of cyclooxygenase) and 4‐methylpyrazole (4MP) (an inhibitor of ethanol metabolism) on the ethanol‐induced chemiluminescence were also evaluated. Sites where O₂^·? could be released were determined by histochemical detection of nitro blue tetrazolium reduction. Results: Both ethanol and tert‐buthanol rapidly caused O₂^·? release. GdCL₃ suppressed the ethanol‐induced O₂^·? release by 61%. Staurosporine and DPI, but neither IB nor 4‐MP, also significantly inhibited the ethanol‐induced O₂^·? release. In the histochemical examination, ethanol‐stimulated liver showed blue formazan precipitate on both sinusoidal endothelial cells (SECs) and Kupffer cells (KCs), whereas the GdCl₃‐pretreated liver had the precipitate only on SECs. Conclusions: This study shows that ethanol itself stimulates both SECs and KCs to release O₂^·? via activation of NADPH oxidase probably involving protein kinase C (PKC).     

Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome

JAK3 mutations have been reported in transient myeloproliferative disorder (TMD) as well as in acute megakaryoblastic leukaemia of Down syndrome (DS-AMKL). However, functional consequences of the JAK3 mutations in TMD patients remain undetermined. To further understand how JAK3 mutations are involved in the development and/or progression of leukaemia in Down syndrome, additional TMD patients and the DS-AMKL cell line MGS were screened for JAK3 mutations, and we examined whether each JAK3 mutation is an activating mutation. JAK3 mutations were not detected in 10 TMD samples that had not previously been studied. Together with our previous report we detected JAK3 mutations in one in 11 TMD patients. Furthermore, this study showed for the first time that a TMD patient-derived JAK3 mutation (JAK3(I87T)), as well as two novel JAK3 mutations (JAK3(Q501H) and JAK3(R657Q)) identified in an MGS cell line, were activating mutations. Treatment of MGS cells and Ba/F3 cells expressing the JAK3 mutants with JAK3 inhibitors significantly decreased their growth and viability. These results suggest that the JAK3 activating mutation is an early event during leukaemogenesis in Down syndrome, and they provide proof-of-principle evidence that JAK3 inhibitors would have therapeutic effects on TMD and DS-AMKL patients carrying activating JAK3 mutations.     

中文大学生版Buss-Perry攻击性量表的修订与信效度分析

目的:引进Buss-Perry攻击性量表(BPAQ),并在大学生群体中进行修订,用来测量我国大学生的攻击性水平.方法:在不同行政区域的9所综合型大学抽取1722名在校大学生.对样本编号后,奇数组(n =864)被用于探索性因素分析以确认因子结构;偶数组(n=858)被用于对所得维度进行验证性因素分析.用大学生社会技能量表(ChUSSI)和羞涩量表(RCBS)为效标.抽取其中一所大学的165名学生于初评后2周进行重测.结果:通过探索性因素分析,得到由敌意、身体攻击、冲动、易怒性4个分量表(共22个项目)构成的中文大学生版Buss-Perry攻击性量表(CC-BPAQ);验证性因素分析显示数据拟合良好(GFI=0.917,AGFI=0.896,CFI=0.899,RMSEA=0.059);CC-BPAQ的敌意、身体攻击和易怒性分量表得分与ChUSSI得分呈负相关(r=-0.23、-0.19、-0.20,均P＜0.01),CC-BPAQ的4个分量表得分均与RCBS得分呈正相关(r=0.45、0.21、0.11、0.32,均P＜0.01).总量表的内部一致性Cronbach α系数为0.89,4个分量表的α系数为0.73 ～0.85;总量表的重测信度为0.91,4个分量表的重测信度为0.75 ～0.80.结论:修订后的中文大学生版Buss-Perry攻击性量表具有良好的信度和效度,可以用于大学生的攻击性测量.     

Thermo-driven self-assembly of a PEG-containing amphiphile in a bilayer membrane

Self-assembly of lipid molecules in a plasma membrane, namely lipid raft formation, is involved in various dynamic functions of cells. Inspired by the raft formation observed in the cells, here we studied thermally induced self-assembly of a synthetic amphiphile, bola-AkDPA, in a bilayer membrane. The synthetic amphiphile consists of a hydrophobic unit including fluorescent aromatic and aliphatic components and hydrophilic tetraethylene glycol chains attached at both ends of the hydrophobic unit. In a polar solvent, bola-AkDPA formed aggregates to show excimer emission. In a lipid bilayer membrane, bola-AkDPA showed intensified excimer emission upon increase of its concentration or elevation of the temperature; bola-type amphiphiles containing oligoethylene glycol chains likely tend to form self-assemblies in a bilayer membrane triggered by thermal stimuli.

A synthetic multi-block amphiphile containing oligoethylene glycol chains formed a self-assembly in a bilayer membrane triggered by thermal stimuli.     

Vascular evaluation using transabdominal ultrasound for gallbladder polyps

Journal of Medical Ultrasonics - Ultrasound (US) is a cost-effective and noninvasive procedure without radiation exposure, with real-time evaluation and high spatial resolution. Although it is...