Hiroko Nishida

Japanese intercultural communication competence and cross-cultural adjustment

Abstract This study explores the relationship between language and communication skills and patterns of success and failure in the cross-cultural adjustment of Japanese university students. Seven interpersonal communication skills which were selected by Ruben and Kealey as important to cross-cultural adjustment were examined: empathy, respect, role behavior flexibility, orientation to knowledge, interaction posture, interaction management, and tolerance for ambiguity. Besides these skills, language was taken into consideration as a major component influencing Japanese intercultural communication. The behavioral assessment method developed by Ruben was utilized to measure communicative performance and behaviors of Japanese university students who visited the United States for 4 weeks for their English training. In order to assess the language skills of these individuals, listening, speaking, structure and written expression, and vocabolary and reading comprehension skills were measured. At the end of their stay in the United States, the dimensions of culture shock, psychological adjustment, and interactional effectiveness were examined. Comparisons of pre- and post-test measures indicated that six out of the seven communication behaviors observed in the Japanese students did not predict success or failure in adjustment to the United States. Only ambiguity tolerance yielded correlation with culture shock. However, speaking and listening skills were closely correlated with interactional effectiveness.

CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells

Although cancer stem cells (CSCs) have been recently identified in myeloid leukemia, published data on lymphoid malignancy have been sparse. T-acute lymphoblastic leukemia (T-ALL) is characterized by the abnormal proliferation of T-cell precursors and is generally aggressive. As CD34 is the only positive-selection marker for CSCs in T-ALL, we performed extensive analysis of CD markers in T-ALL cell lines. We found that some of the tested lines consisted of heterogeneous populations of cells with various levels of surface marker expression. In particular, a small subpopulation of CD90 (Thy-1) and CD110 (c-Mpl) were shown to correlate with stem cell properties both in vitro and in transplantation experiments. As these markers are expressed on hematopoietic stem cells, our results suggest that stem cell-like population are enriched in CD90+/CD110+ fraction and they are useful positive-selection markers for the isolation of CSCs in some cases of T-ALL.

CD9 correlates with cancer stem cell potentials in human B-acute lymphoblastic leukemia cells

Cancer stem cell (CSC) theory suggests that only a small subpopulation of cells having stem cell-like potentials can initiate tumor development. While recent data on acute lymphoblastic leukemia (ALL) are conflicting, some studies have demonstrated the existence of such cells following CD34-targeted isolation of primary samples. Although CD34 is a useful marker for the isolation of CSCs in leukemias, the identification of other specific markers besides CD34 has been relatively unsuccessful. To identify new markers, we first performed extensive analysis of surface markers on several B-ALL cell lines. Our data demonstrated that every B-ALL cell line tested did not express CD34 but certain lines contained cell populations with marked heterogeneity in marker expression. Moreover, the CD9(+) cell population possessed stem cell characteristics within the clone, as demonstrated by in vitro and transplantation experiments. These results suggest that CD9 is a useful positive-selection marker for the identification of CSCs in B-ALL.

Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia

Although the prognosis of acute lymphoblastic leukemia (ALL) has improved considerably in recent years, some of the cases still exhibit therapy-resistant. We have previously reported that CD9 was expressed heterogeneously in B-ALL cell lines and CD9(+) cells exhibited an asymmetric cell division with greater tumorigenic potential than CD9(-) cells. CD9(+) cells were also serially transplantable in immunodeficient mice, indicating that CD9(+) cell possess self-renewal capacity. In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell (CSC) properties. In patient sample, CD9 was expressed in the most cases of B-ALL cells with significant correlation of CD34-expression. Gene expression analysis revealed that leukemogenic fusion proteins and Src family proteins were significantly regulated in the CD9(+) population. Moreover, CD9(+) cells exhibited drug-resistance, but proliferation of bulk cells was inhibited by anti-CD9 monoclonal antibody. Knockdown of CD9 remarkably reduced the leukemogenic potential. Furthermore, gene ablation of CD9 affected the expression and tyrosine-phosphorylation of Src family proteins and reduced the expression of histone-deubiquitinase USP22. Taken together, our results suggest that CD9 links to several signaling pathways and epigenetic modification for regulating the CSC properties of B-ALL.

Nuclear localization of CD26 induced by a humanized monoclonal antibody inhibits tumor cell growth by modulating of POLR2A transcription.

CD26 is a type II glycoprotein known as dipeptidyl peptidase IV and has been identified as one of the cell surface markers associated with various types of cancers and a subset of cancer stem cells. Recent studies have suggested that CD26 expression is involved in tumor growth, tumor invasion, and metastasis. The CD26 is shown in an extensive intracellular distribution, ranging from the cell surface to the nucleus. We have previously showed that the humanized anti-CD26 monoclonal antibody (mAb), YS110, exhibits inhibitory effects on various cancers. However, functions of CD26 on cancer cells and molecular mechanisms of impaired tumor growth by YS110 treatment are not well understood. In this study, we demonstrated that the treatment with YS110 induced nuclear translocation of both cell-surface CD26 and YS110 in cancer cells and xenografted tumor. It was shown that the CD26 and YS110 were co-localized in nucleus by immunoelectron microscopic analysis. In response to YS110 treatment, CD26 was translocated into the nucleus via caveolin-dependent endocytosis. It was revealed that the nuclear CD26 interacted with a genomic flanking region of the gene for POLR2A, a subunit of RNA polymerase II, using a chromatin immunoprecipitation assay. This interaction with nuclear CD26 and POLR2A gene consequently led to transcriptional repression of the POLR2A gene, resulting in retarded cell proliferation of cancer cells. Furthermore, the impaired nuclear transport of CD26 by treatment with an endocytosis inhibitor or expressions of deletion mutants of CD26 reversed the POLR2A repression induced by YS110 treatment. These findings reveal that the nuclear CD26 functions in the regulation of gene expression and tumor growth, and provide a novel mechanism of mAb-therapy related to inducible translocation of cell-surface target molecule into the nucleus.

Blockade of CD26 signaling inhibits human osteoclast development

Bone remodeling is maintained by the delicate balance between osteoblasts (OBs) and osteoclasts (OCs). However, the role of CD26 in regulating bone remodeling has not yet been characterized. We herein show that CD26 is preferentially expressed on normal human OCs and is intensely expressed on activated human OCs in osteolytic bone alterations. Macrophage‐colony stimulating factor (M‐CSF) and soluble receptor activator of NF‐κB ligand (sRANKL) induced human OC differentiation, in association with CD26 expression on monocyte‐macrophage lineage cells. CD26 expression was accompanied by increased phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK), which is crucial for early human OC differentiation. The humanized anti‐CD26 monoclonal antibody, huCD26mAb, impaired the formation and function of tartrate‐resistant acid phosphatase (TRAP)/CD26 positive multi‐nucleated (nuclei > 3) OCs with maturation in the manner of dose‐dependency. It was revealed that huCD26mAb inhibits early OC differentiation via the inactivation of MKK3/6, p38 MAPK and subsequent dephosphorylation of microphthalmia‐associated transcription factor (mi/Mitf). These inhibitions occur immediately after RANKL binds to RANK on the human OC precursor cells and were demonstrated using the OC functional assays. huCD26mAb subsequently impaired OC maturation and bone resorption by suppressing the expression of TRAP and OC fusion proteins. In addition, p38 MAPK inhibitor also strongly inhibited OC formation and function. Our results suggest that the blockade of CD26 signaling impairs the development of human functional OCs by inhibiting p38 MAPK‐mi/Mitf phosphorylation pathway and that targeting human OCs with huCD26mAb may have therapeutic potential for the treatment of osteolytic lesions following metastasis to alleviate bone destruction and reduce total skeletal‐related events (SREs).

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 ± 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm2) in a native blood sample in vitro. The mean ± SD occlusion time was 154.8 ± 64.7 s (men, 153.4 ± 64.2 s and women, 165.4 ± 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = −0.242, P = 0.0055) and von Willebrand factor antigen (r = −0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = −0.177, P = 0.0365), hemoglobin (r = −0.191, P = 0.0245) and hematocrit (r = −0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.

Primary isolated bone marrow diffuse large B-cell lymphoma with the initial presentation as severe thrombocytopenia, successfully treated with chemotherapy: a case report and review of the literature

Secondary bone marrow involvement of non-Hodgkin’s lymphoma (NHL) is relatively common. However, primary isolated bone marrow involvement in NHL, successfully treated without any relapse, is quite rare, except in several leukemia/ lymphoma cases which are considered to primarily involve the bone marrow. We here report a case of primary bone marrow diffuse large B cell lymphoma (PBML/DLBCL), in which the patient presented a prolonged high-grade fever and systemic purpura due to severe thrombocytopenia, which was successfully treated with systemic chemotherapy and remains in complete remission (CR) at 2.5 years after the initial diagnosis. Review of 53 cases of PBML/DLBCL presented in the literature suggests that the prognosis for this eternity is unfavorable, but rituximab-based therapeutic strategies, including autologous stem cell transplantation are promising for improving their outcomes.

Optic nerve involvement of Waldenström’s macroglobulinemia: with autopsy findings

Abstract Waldenström’s macroglobulinemia (WM) is an indolent chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma (LPL), characterized by a proliferation of plasmacytoid lymphocytes and the production of monoclonal IgM. Although, peripheral neurologic complications commonly occurs due to hyperviscosity in WM, central nervous system (CNS) involvement is very rare. Herein, we present the case of a 67-year-old man who initially presented with progressive visual loss and was diagnosed as WM/LPL with a very aggressive clinical course. He underwent chemotherapy with high dose methotrexate (MTX) plus cytarabine (Ara-C). However, he died and findings of a subsequent autopsy revealed the presence of lymphoplasmacytoid cells in the optic nerve.

Primary isolated bone marrow diffuse large B cell lymphoma with long-term complete remission

Secondary bone marrow involvement of non-Hodgkins lymphoma (NHL) is relatively common. However, primary isolated bone marrow involvement in NHL which was successfully treated and remains in complete remission (CR) for a long-term duration without any relapse is extremely rare. We herein report a patient of primary bone marrow diffuse large B cell lymphoma (PBML/DLBCL) who presented a prolonged high-grade fever and systemic purpura due to severe thrombocytopenia. The patient was successfully treated with systemic chemotherapy by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and remains in CR at 8 years after the initial diagnosis. Review of the literature in PBML/DLBCL cases are also shown.