CLASSICAL HODGKIN AND REED-STERNBERG CELLS DEMONSTRATE A NON-CLONAL IMMATURE B LYMPHOID LINEAGE: EVIDENCE FROM A SINGLE CELL ASSAY AND IN SITU HYBRIDIZATION

Hodgkin and Reed-Sternberg (H & RS) cells are generally considered to be the neoplastic cells of Hodgkin's disease (HD), however such cells are only found in a minority of the lesions. Recently in a few studies on HD, the clonality of H & RS cells was examined, using a single-cell polymerase chain reaction (PCR) examination. To clarify the lineage and clonality of H & RS cells, we performed single cell PCR and in situ hybridization (ISH), and nine cases of classical HD were thus studied. By ISH, the immunoglobulin J chain, and the |gk and |gl light chain were rarely expressed in the H & RS cells, however, no T-cell markers could be detected. The expression of the recombination activating genes (RAG-1, 2) could be determined in the H & RS cells. We isolated CD30+ H & RS cells, CD3+ T cells and CD20+ B cells from suspended materials using a mechanical sorter. We performed single cell PCR in a sorted individual cell, to amplify the complementarity determining region of the Ig heavy chain (IgH) gene and T-cell receptor γ chain (TCR γ) gene. In all cases, TCR γ could be frequently amplified in the T cells, but was only rarely amplified in the H & RS and B cells. In contrast, the IgH was frequently amplified in the H & RS and B cells, but not in the T cells. In addition, the PCR production of the H & RS cells all showed different lengths. The results therefore support the polyclonal nature and immature B lymphoid cell origin of H & RS cells.     

Evolution of prognostic factors in hepatocellular carcinoma in Japan

Aliment Pharmacol Ther 31 , 407–414

Summary

Background The surveillance of hepatocellular carcinoma (HCC) has become prevalent, and the modalities for its treatment have improved. Aim To understand the changes that occur in the characteristics and prognostic factors of HCC with time. Methods Newly diagnosed HCC patients were divided into two groups; patients treated before 31 December 2000 (n = 504), and after 1 January 2001 (n = 746), and their clinical backgrounds and prognostic factors were analysed. Results The number of patients negative for both Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibody (HCVAb) increased with time (NBNC‐HCC). The size of HCC decreased in patients who were positive for HBsAg (B‐HCC) or HCVAb (C‐HCC), whereas no difference was observed in NBNC‐HCC. The patient survival of C‐HCC improved; however, no difference was detected for NBNC‐HCC. In multivariate analysis, low albumin, high aspartate aminotransferase (AST), ascites, large tumour size, multiple tumour number and high alpha‐fetoprotein were risk factors for survival before 2000, whereas the presence of HBsAg was additionally selected as a good prognostic factor and AST was excluded after 2001. Conclusions The prognostic factors as well as clinical background of HCC changed with time, and the presence of HBsAg was found to be an additional good prognostic factor after 2001.     

Disulfide bond-forming reaction using a dimethyl sulfoxide/aqueous HCl system and its application to regioselective two disulfide bond formation

Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cystine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.     

Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.     

HIGH ACTIVITY OF CYCLIC 3'',5''-NUCLEOTIDE PHOSPHODIESTERASE IN SERA OF PATIENT WITH PHAEOCHROMOCYTOMA

Our previous observations that serum cyclic 3',5'-nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP-PDE) and cyclic GMP phosphodiesterase (cyclic GMP-PDE) activities were measured at a low substrate concentration. Serum cyclic AMP-PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushing's syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP-PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP-PDE in the target organ and the soluble cyclic AMP-PDE may leak into blood vessels from target organs.     

X‐ray Radiation Causes Electromagnetic Interference in Implantable Cardiac Pacemakers

Background: X‐rays are not thought to cause electromagnetic interference (EMI) in implantable cardiac pacemakers. However, x‐ray radiation during computed tomography (CT) scanning has been reported to cause EMI in some implantable cardiac pacemakers. The objectives of this study were to identify the location within the pacemakers where x‐ray radiation causes EMI and to investigate the association of EMI with the x‐ray radiation conditions. Methods: We verified the location where x‐ray radiation caused EMI using a CT scanner and conventional radiographic x‐ray equipment. An inhibition test and an asynchronous test were performed using five types of implantable cardiac pacemakers. Results: X‐ray radiation inhibited the pacing pulses of four types of implantable cardiac pacemakers when the body of each implantable cardiac pacemaker, containing a complementary metal‐oxide semiconductor (CMOS), was scanned using a CT scanner. We confirmed that x‐ray‐induced EMI depends on the x‐ray radiation conditions, that is, the tube voltage, tube current, x‐ray dose, and direction of x‐ray radiation, as well as the sensing thresholds of the implantable cardiac pacemakers. Conclusions: X‐ray radiation caused EMI in some implantable cardiac pacemakers, probably because the CMOS component was irradiated. The occurrence of EMI depended on the pacemaker model, sensing threshold of the pacemaker, and x‐ray radiation conditions. (PACE 2010; 33:1174–1181)     

基于体素的牙种植体及颌骨的有限元建模

目的 为开发包含应力分析的牙种植PISA软件系统搭建有限元自动建模平台。方法 首先利用VTK技术由患者的CT图像建立3D实体模型并进行可视化;然后根据颌骨特点进行种植体的选型、定位并重新采样;最后通过将体素转换为8节点的正六面体单元来建立有限元几何模型;骨组织的材料属性值由节点的灰度值直接计算得到。结果 针对目前临床应用最多的骨内种植体,建立了适合牙种植体及颌骨特点的基于体素的有限元自动建模方法,能在几分钟内得到准确反映患者个体真实几何信息和骨材料状态的体素有限元模型。结论 本文建立的方法使得在临床利用有限元应力分析对种植牙手术进行术前预测、评价成为可能。该方法也可用于微结构的有限元建模。