Splenectomy for Severe Intestinal Bleeding Caused by Portal Hypertensive Enteropathy After Pediatric Living-Donor Liver Transplantation: A Report of Three Cases

Background

The incidence of portal vein thrombosis after pediatric living-donor liver transplantation (LDLT) is reported to be higher than that after deceased-donor or adult liver transplantation. Portal vein thrombosis can cause portal hypertension and related complications, including portal hypertensive gastropathy or portal hypertensive enteropathy (PHE). PHE, in particular, can lead to severe intestinal bleeding, which is extremely difficult to treat. However, the pathogenesis of and appropriate treatment for PHE are not clearly defined, especially after pediatric LDLT.

Sendai Virus and a Unified Model of Mononegavirus RNA Synthesis

Vesicular stomatitis virus (VSV), the founding member of the mononegavirus order (Mononegavirales), was found to be a negative strand RNA virus in the 1960s, and since then the number of such viruses has continually increased with no end in sight. Sendai virus (SeV) was noted soon afterwards due to an outbreak of newborn pneumonitis in Japan whose putative agent was passed in mice, and nowadays this mouse virus is mainly the bane of animal houses and immunologists. However, SeV was important in the study of this class of viruses because, like flu, it grows to high titers in embryonated chicken eggs, facilitating the biochemical characterization of its infection and that of its nucleocapsid, which is very close to that of measles virus (MeV). This review and opinion piece follow SeV as more is known about how various mononegaviruses express their genetic information and carry out their RNA synthesis, and proposes a unified model based on what all MNV have in common.     

Inactivated Sendai virus particle upregulates cancer cell expression of intercellular adhesion molecule‐1 and enhances natural killer cell sensitivity on cancer cells

We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ‐E) has multiple anticancer effects, including induction of cancer‐selective cell death and activation of anticancer immunity. The HVJ‐E stimulates dendritic cells to produce cytokines and chemokines such as β‐interferon, interleukin‐6, chemokine (C‐C motif) ligand 5, and chemokine (C‐X‐C motif) ligand 10, which activate both CD8⁺ T cells and natural killer (NK) cells and recruit them to the tumor microenvironment. However, the effect of HVJ‐E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated. In this study, we found that HVJ‐E induced the production of intercellular adhesion molecule‐1 (ICAM‐1, CD54), a ligand of lymphocyte function‐associated antigen 1, in several cancer cell lines through the activation of nuclear factor‐κB downstream of retinoic acid‐inducible gene I and the mitochondrial antiviral signaling pathway. The upregulation of ICAM‐1 on the surface of cancer cells increased the sensitivity of cancer cells to NK cells. Knocking out expression of ICAM‐1 in MDA‐MB‐231 cells using the CRISPR/Cas9 method significantly reduced the killing effect of NK cells on ICAM‐1‐depleted MDA‐MB‐231 cells. In addition, HVJ‐E suppressed tumor growth in MDA‐MB‐231 tumor‐bearing SCID mice, and the HVJ‐E antitumor effect was impaired when NK cells were depleted by treatment with the anti‐asialo GM1 antibody. Our findings suggest that HVJ‐E enhances NK cell sensitivity against cancer cells by increasing ICAM‐1 expression on the cancer cell surface.     

Glycoproteins of representative paramyxoviruses: isolation and antigenic analysis using a zwitterionic surfactant.

A new method for the isolation of biologically active envelope antigens from paramyxo- and myxoviruses was developed using a zwitterionic detergent Empigen BB. Essentially complete recovery of hemagglutinin and sialidase from representative paramyxoviruses (PMY, NDV, and Sendai virus) and influenza virus X7 was achieved. The glycoproteins (HN and F) of PMY were purified in a DEAE-Bio-Gel A column equilibrated with bicarbonate buffer containing Empigen, Polyacrylamide gel electrophoresis analysis of pooled HN fractions revealed one band, indicating that it is a common glycoprotein. Gels of pooled F-enriched fractions revealed three bands corresponding to LGP, HN, and F. Gels of PMY virus revealed six polypeptides, and they have been tentatively designated L, LGP, HN, F, NP, and M. LGP, a large glycoprotein, was not detected in gels of NDV and Sendai virus. It has been proposed that LGP may consist of a complex of F. Antiserum was prepared against purified HN and it was found to be monospecific. The antiserum inhibited both hemagglutination and enzyme activities of PMY, which is in support of the hemagglutinin and sialidase of PMY being associated with a common glycoprotein. By enzyme inhibition analysis of PMY, NDV, and Sendai virus, it was shown that the enzymes of these viruses are antigenically distinct. The methods described for the isolation and purification of PMY glycoproteins may be useful for the preparation of myxo- and paramyxovirus subunit vaccines.     

Sterile alpha motif containing domain 9 is involved in death signaling of malignant glioma treated with inactivated Sendai virus particle (HVJ‐E) or type I interferon

Malignant glioma is one of the most aggressive cancers. For the development of effective therapeutic strategies against such malignant diseases, elucidation of molecular targets is necessary. We found that inactivated Sendai virus particle (HVJ‐E) induced extensive cell death in the human glioblastoma cell line U251MG. Intradermal U251MG tumors were more effectively suppressed by HVJ‐E than interferon (IFN)‐β. From microarray analysis of gene expression in U251MG cells treated with HVJ‐E, we focused on the up‐regulation of sterile alpha motif containing domain 9 (SAMD9) gene. The expression of the SAMD9 gene was induced by administration of recombinant human IFN‐α, ‐β or ‐γ. The up‐regulation of the SAMD9 gene by HVJ‐E treatment was abrogated by IFN receptor blocking antibody or JAK inhibitor treatment. When SAMD9 expression was knocked down by RNA interference, apoptotic cell death induced by HVJ‐E was blocked in U251MG cells. Suppression of SAMD9 using SAMD9 siRNA also inhibited IFN‐β‐induced death in U251MG cells with a small, but significant, difference to control groups. However, overexpression of the SAMD9 gene failed to induce significant cell death in U251MG cells. Thus, SAMD9 could be a key molecule to control cancer cell death by HVJ‐E or IFN‐β treatment.     

家兔病毒性发热模型的研制

应用仙台病毒使家兔呼吸道感染,引起家兔发热,平均体温可升高1℃以上,可制备病毒性发热 模型。安乃近可使其体温下降至正常水平。     

Sendai virus particles carrying target virus glycoproteins for antibody induction

Induction of antibodies targeting viral glycoproteins is a key for the development of a vaccine against enveloped virus infection. Glycoproteins on the virion exhibiting native multimer structure may be a good immunogen to present antibody epitopes, but it is often difficult to prepare immunogenic inactivated virions. Preparation of soluble glycoprotein multimers has been attempted, while virus-like particles carrying target glycoproteins can be a more immunogenic antigen. In the present study, a target glycoprotein-embedded Sendai virus (SeV) particle was developed for induction of anti-virus antibodies. We constructed a chimeric antigen, HIV-1 EnvF, consisting of HIV-1 Env ectodomain and SeV F transmembrane-cytoplasmic domain, which was shown to be efficiently incorporated into the SeV virion. EnvF was recognized by anti-HIV-1 broadly-neutralizing monoclonal antibodies (bnAbs) including 35O22 that targets an Env trimer-dependent epitope. Analysis revealed that HIV-1_AD8 EnvF can mediate viral entry into the cells, which is inhibited by anti-HIV-1 bnAbs and HIV-1 entry inhibitors, suggesting that the EnvF exhibits an HIV-1 Env native-like functional structure to present bnAb epitopes. Immunization of mice with replication-defective SeVs expressing HIV EnvF and non-infectious SeV particles (NVP) carrying HIV EnvF efficiently induced anti-HIV Env antibodies. HTLV-1 EnvF also showed the potential to efficiently induce anti-HTLV-1 Env antibodies. These results indicate that SeV particles carrying EnvF can be a promising vaccine platform for induction of antibodies targeting enveloped virus glycoproteins.     

超声波均质化对仙台病毒ELISA测试中抗原稳定性的影响

目的研究超声波均质化(homogenization)处理对于仙台病毒在ELISA测试中抗原稳定性的影响。方法对BHK-21细胞内扩增培养的仙台病毒通过差速离心,富集后使用超声波做均质化处理,和未处理的病毒分别包被酶标板,使用标准免疫小鼠血清和SPF小鼠血清对包被平板进行测试,比较样品测试孔间测量数据的变异率。结果对免疫血清做梯度稀释,各梯度样品在未经超声处理仙台病毒抗原包被ELISA检测中测量值的变异率在1.97%～6.02%之间;在经超声处理仙台病毒抗原包被ELISA检测中测量值的变异率在0.53%～2.26%之间;SPF血清测量值的变异率均高于免疫血清;所有样品在经超声处理的病毒抗原包被ELISA检测中测量值的变异率均较小。结论超声波处理有效的提高了仙台病毒抗原的均质性,在ELISA测试中提高了抗原的稳定性。     

Lysosomal enzymes in human tear fluid collected by filter paper strips

Protein concentrations and lysosomal enzyme activities in tear fluid collected by filter paper strips were studied. The magnitude of the wetted area on the filter paper did not affect the apparent protein concentration in the tear fluid. Lysosomal enzyme activities in tear fluid were higher than those in serum. The pH and enzyme activity curves in tear fluid were similar to those in serum. The optimal pH of acid phosphatase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and alpha-D-mannosidase in tear fluid were determined.