Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis

Background/Aims

We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.

Methods

Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.

Results

The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.

Conclusions

The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.     

Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia.

INTRODUCTION: Protein kinase CK2 is implicated in cellular proliferation and transformation. However, the clinical and biological significances of CK2 have not been elucidated in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: We evaluated the biological significances of catalytic subunit of CK2 (CK2alpha) expression in leukemia cell lines and primary leukemic blasts obtained from AML patients. RESULTS: In this study, the expression of CK2alpha was elevated in a substantial proportion of AML. In AML patients with normal karyotype, the disease-free survival and overall survival rates were significantly lower in the CK2alpha-high compared with the CK2alpha-low AML cases (P=0.0252 and P=0.0392, respectively). An induced overexpression of CK2alpha increased the levels of Ser473 phosphorylated (p)-Akt/protein kinase B (PKB), p-PDK1, pFKHR, p-BAD, Bcl-2, Bcl-xL, Mcl-1, and XIAP. Treatment of U937 cell line and primary AML blasts with selective CK2 inhibitor, tetrabromobenzotriazole or apigenin, reduced the levels of these molecules in a dose-dependent manner. CK2alpha small interfering RNA treatment also resulted in a down-regulation of p-Akt/PKB and Bcl-2 in U937 cells. Apigenin-induced cell death was preferentially observed in the CK2alpha-high leukemia cell lines, HL-60 and NB4, which was accompanied by cytoplasmic release of SMAC/DIABLO and proteolytic cleavage of procaspase-9, procaspase-3, procaspase-8, and poly(ADP)ribose polymerase. An induced overexpression of CK2alpha potentially enhanced the sensitivity of U937 cells to the apigenin-induced cell death. Apigenin-induced cell death was significantly higher in CK2alpha-high AML compared with CK2alpha-low AML (P<0.0001) or normal bone marrow samples (P<0.0001). CONCLUSION: These findings strongly suggest protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in AML.     

Delayed maturation of interstitial cells of Cajal in meconium obstruction

Background/Purpose: The etiology of meconium obstruction without cystic fibrosis is unclear. Interstitial cells of Cajal (ICC) function as pacemakers in gut motility and may play a role in the pathophysiology of the disease. Methods: The ICC were examined by immunohistochemical staining with anti-c-kit antibody in the bowel walls of 6 neonates who had meconium obstruction without cystic fibrosis, and the results were compared with specimens from normal neonates (n = 2). Results: Six patients underwent ileostomy between 2 and 15 days after birth, and 5 of them presented with microcolon. Ganglion cells were present in the ileum and colon. Whereas ICC were evenly distributed in the control specimens, they were not seen at the time of ileostomy in the colons of 2 patients, and the other 4 showed scanty distribution in muscle layers. However, ileum showed normal distribution of ICC in all patients. The ileostomies were closed between 39 and 104 days of age, and the ICC distribution was changed to a normal pattern in the colons of all 6 patients. Their bowel movements were restored to normal after closure. Conclusion: The findings of this study suggest that delayed maturity of ICC may be a cause of meconium obstruction without cystic fibrosis.     

联合免疫阻断乙肝病毒母婴垂直传播及其母乳喂养安全的临床研究

0引言 乙肝病毒(HBV)可垂直传播感染新生儿,在实行免疫预防程序后,婴儿通过产程和产后感染HBV的途径得到了有效的控制,但HBV宫内感染难以阻断[1],是形成慢性乙肝的主要途径和原因. 阻断HBV母婴传播是控制乙肝流行及预防HBV相关肝病的关键[2]. 寻找有效阻断HBV母婴垂直传播的预防措施已成为世界上控制乃至消灭乙肝的关键课题. 我们用乙肝免疫球蛋白(HB immunoglobulin,HBIG)联合乙肝疫苗(Hbvac)治疗,有效地阻断HBV宫内传播,同时对应用联合免疫的产妇母婴喂养的有关问题进行分析.     

Human lung fluke Paragonimus heterotremus: differential diagnosis between Paragonimus heterotremus and Paragonimus westermani infections by EITB

The specificity of three major polypeptides (35, 33 and 32.5 kD) from Paragonimus heterotremus antigens prepared from ether-extracted adult worms was tested against sera from heterologous infections as well as against P. westermani -infected sera. Only the 35 kD polypeptide was not present, its antigenic determinant being bound to the antibodies from all P . westermani -infected cases. Its cross-reactivity against various sera from heterologous helminthiases and other lung infections showed that it is not bound to these antigenic polypeptides. These major bands cannot be detected by Concanavalin A detector. Our research encourages the pattern (35, 33 and 32.5 kD) of immunoblot reactions for the diagnosis of P. heterotremus infections; the 35 kD antigen is specific for corresponding species and able to differentiate infections between both species of Paragonimus .     

Feasibility of baculovirus-expressed recombinant 10-kDa antigen in the serodiagnosis of Taenia solium neurocysticercosis

Bacterially expressed recombinant 10-kDa protein of Taenia solium metacestode (TsM) was previously found to be reliable in the diagnosis of active stage neurocysticercosis (NCC) by immunoblotting but not by ELISA. In this study, we evaluated the diagnostic feasibility of detecting eukaryote-expressed recombinant 10-kDa protein of TsM by ELISA (rTsM10-ELISA) in the serum and cerebrospinal fluid (CSF) from NCC patients. In 45 cases of active NCC, 91.1 and 97.8% cases showed positive reactions for serum and CSF by rTsM10-ELISA. ELISA employing the crude cyst fluid antigen (CF-ELISA) also revealed a similar result. Negligible cross-reactions were observed in serum samples from control subjects and from subjects with other helminthic diseases by rTsM10-ELISA (5/139 cases, 3.6%). By contrast, CF-ELISA demonstrated a high degree of cross-reactivity (24/139, 17.3%) especially from those patients with alveolar and cystic echinococcoses. The overall sensitivity and specificity of rTsM10-ELISA were 94.3 and 96.4%; and those of CF-ELISA were 95.7 and 84.5%, for serum and CSF, respectively. Antibody responses to rTsM10 were detected as early as 3 months after experimental infection of T. solium eggs in pigs. Our results show that ELISA with rTsM10 could be highly applicable in the serodiagnosis of NCC from early stage of infection.     

Activation of c-Jun N-terminal kinase is required for neurite outgrowth of dopaminergic neuronal cells

Recent studies indicate that activation of stress-activated protein kinases may be implicated in a broad range of biological activities including differentiation. To directly examine whether stress-activated protein kinases are involved in neuronal differentiation, we utilized retinoic acid-induced and spontaneous models of neurite outgrowth in dopaminergic neurons. Here, we show that retinoic acid-induced neurite outgrowth in MN9D dopaminergic neuronal cells was accompanied by activation of c-Jun N-terminal kinase but not p38. Consequently, cotreatment with a specific inhibitor of c-Jun N-terminal kinase or overexpression of c-Jun N-terminal kinase-binding domain of c-Jun N-terminal kinase-interacting protein-1 blocked retinoic acid-induced neurite outgrowth. In primary cultures of dopaminergic neurons, the extent of neurite outgrowth increased spontaneously in a time-dependent manner. When these cultures were treated with a specific inhibitor of c-Jun N-terminal kinase, the total extent of neurites, the primary neurite length and the number of neurites per cell were suppressed significantly. Thus, our data indicate that the c-Jun N-terminal kinase signal seems to play an important role during morphological differentiation in cultured dopaminergic neurons.     

Evaluation of cell proliferation in ear and lymph node using BrdU immunohistochemistry for mouse ear swelling test

The mouse ear swelling test (MEST) was developed as an alternative to guinea pig models for measuring the contact sensitization potential. However, the MEST relies on the quantitative measurement of ear swelling by micrometer as the means of determining the endpoint. The purpose of this study was to investigate the possibility of using cell proliferation in the ear and lymph node by bromodeoxyuridine (BrdU) immunohistochemistry as a reliable marker for MEST. Female Balb/c mice were treated by the topical application of various sensitizers, 2,4-dinitrochlorobenzene (DNCB), toluene diisocyanate (TDI) and α-hexylcinnamaldehyde (HCA) and an irritant, sodium lauryl sulfate (SLS) following the protocol of MEST. The proliferation of cells in the ear and auricular lymph node was analyzed by BrdU incorporations into cells. There were significant increases in the cell proliferations of the ear and auricular lymph node in mice treated with DNCB and TDI compared to the vehicle control. All allergens and the irritant were correctly identified by the MEST using BrdU immunohistochemistry of lymph node responses. The standard MEST assay showed positive results in the case of the strong sensitizers, DNCB and TDI. However, HCA and SLS were not correctly identified in the ear swelling assay. These results suggest that the measurement of cell proliferation in the auricular lymph node using BrdU immunohistochemistry could provide a reliable marker for MEST.     

Benzo[c]phenanthridine alkaloids fromCorydalis incisa

Six benzo[c]phenanthridine alkaloids, corynoline (1), acetylcorynoline (2), corynoloxine (3), luguine (4), 6-oxocorynoline (5), and 12-hydroxycorynoloxine (6) were isolated from the aerial parts of Corydalis incisa, and 6 was isolated for the first time from nature. The structure was elucidated by NMR techniques.