-
[show abstract]
[hide abstract]
ABSTRACT: We report an unusual case of T-cell lymphoma presenting as ascites. A 72-year-old HIV-negative woman was admitted to our hospital
for abdominal discomfort associated with increasing abdominal girth over the course of 1 month. Physical examination showed
a tense and distended abdomen and edema of the lower extremities. There was no hepatosplenomegaly or lymphadenopathy. A computed
tomographic scan of the abdomen and chest showed massive ascites and pleural effusions, but there was no evidence of tumor
masses or lymph node enlargement. The cytospin prepared from the peritoneal fluid was hypercellular and composed of a population
of monotonous, large cells containing fine chromatin. No herpesvirus-8 (HHV-8) DNA was detected by polymerase chain reaction
in the cells. Immunohistochemistry showed the neoplastic cells to be CD3+, CD4-, CD7+, CD8-, CD34-, CD56-, and TCR-αβ+. Repeated cytogenetic studies showed common abnormalities of del(1) (p11p22), +i(7)(q10), and t(11;14)(q23;q11). The morphologic
and immunologic findings were suggestive of peripheral T-cell lymphoma (PTCL), unspecified. This case suggests that some PTCLs
with clonal chromosomal aberrations can exhibit peculiar serosal spreading in the absence of HHV-8 infection.
International Journal of Hematology 04/2012; 74(4):442-446. · 1.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The origin of Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin’s disease, has long remained controversial. Dendritic
cells (DCs) are highly specialized antigen-presenting cells that have the unique capacity to prime naive T cells, and they
may be progenitors of RS cells in a population of Hodgkin’s disease cells. In this study, the KM-H2 cell line, previously
established from a patient with Hodgkin’s disease of mixed cellularity, was reevaluated for its cellular derivation, particularly
in terms of DCs. KM-H2 cells were demonstrated to carry the newly proposed DC-associated molecules fascin, CD83, and DEC-205,
as well as costimulatory molecules such as CD40, CD80, and CD86. In addition, KM-H2 cells were shown to be able to potently
stimulate peripheral blood T cells and to have the strong endocytotic activity of fluorescein isothiocyanate—dextran. On the
other hand, KM-H2 cells were shown to have variable-diversity-joining recombination of the immunoglobulin H gene, although
they did not express any subclasses of immunoglobulin and they were negative for CD79a and CD79b. In addition, KM-H2 cells
produced the messenger RNA of thePax-5 gene.These findings lead to a hypothesis that KM-H2 cells originated from the cells that had differentiated through the possible
common DC—B-cell progenitors along the newly proposed pathway.
International Journal of Hematology 04/2012; 73(2):236-244. · 1.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Adult-onset Still’s disease (AOSD) is a rheumatoid disorder characterized by high fever, polyarthritis, leukocytosis, hyperferritinaemia,
and mild liver involvement. We describe the case of a patient with AOSD with severe liver dysfunction. His serum levels of
interleukin-10 and 18 showed a similar trend to his disease activity. Drug lymphocyte stimulation tests were positive for
three drugs in the patient. Hypercytokinaemia was controlled by plasma exchange therapy.
Modern Rheumatology 04/2012; 18(4):407-410. · 1.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We previously described a unique procedure for the collection of bone marrow cells (BMCs) using a perfusion method (PM). In cynomolgus monkeys, this method resulted in lower contamination with T cells (<10%). Here, we performed PM on a poor mobilizer lymphoma patient. We confirmed the safety of the intra-bone marrow injection of saline to collect the BMCs. The collected BMCs showed minimal contamination with T cells (<15%) and red blood cells (RBCs) (<4%) from the peripheral blood. It took a total of only 30 min to collect the BMCs. Moreover, transfusion of RBCs was unnecessary. There were no relevant post-operative side effects except for self-limiting pain at the sites of collection, and the patient was able to walk around the hospital after the operation.
International journal of hematology 06/2011; 93(6):822-4. · 1.17 Impact Factor
-
Roberto Lande,
Dipyaman Ganguly,
Valeria Facchinetti,
Loredana Frasca,
Curdin Conrad,
Josh Gregorio,
Stephan Meller,
Georgios Chamilos,
Rosalie Sebasigari,
Valeria Riccieri,
Roland Bassett,
Hideki Amuro, Shirou Fukuhara,
Tomoki Ito,
Yong-Jun Liu,
Michel Gilliet
[show abstract]
[hide abstract]
ABSTRACT: Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease.
Science translational medicine 03/2011; 3(73):73ra19. · 7.80 Impact Factor
-
Yuichi Katashiba,
Rie Miyamoto,
Akira Hyo,
Keiko Shimamoto,
Naoko Murakami,
Makoto Ogata,
Ryuichi Amakawa,
Muneo Inaba,
Shosaku Nomura, Shirou Fukuhara,
Tomoki Ito
[show abstract]
[hide abstract]
ABSTRACT: Dendritic cells (DCs) are initiators of innate immunity and acquired immunity as cells linking these two bio-defence systems through the production of cytokines such as interferon-α (IFN-α) and interleukin-12 (IL-12). Nucleic acids such as DNA from damaged cells or pathogens are important activators not only for anti-microbial innate immune responses but also in the pathogenesis of IFN-related autoimmune diseases. Plasmacytoid DCs are regarded as the main effectors for the DNA-mediated innate immunity by possessing DNA-sensing toll-like receptor 9 (TLR9). We here found that double-stranded DNA (dsDNA) complexed with lipotransfectants triggered activation of human monocyte-derived DCs (moDCs), leading to the preferential production of IFN-α but not IL-12. This indicates that myeloid DCs also function as supportive effectors against the invasion of pathogenic microbes through the DNA-mediated activation in innate immunity. The dsDNA with lipotransfectants can be taken up by moDCs without co-localization of endosomal LAMP1 staining, and the dsDNA-mediated IFN-α production was not impaired by chloroquine. These findings indicate that moDC activation by dsDNA does not involve the endosomal TLR pathway. In contrast, single-stranded RNA (ssRNA) stimulated moDCs to secrete IL-12 but not IFN-α. This process was inhibited by chloroquine, suggesting an involvement of the TLR pathway in ssRNA-mediated moDC activation. As might be inferred from our findings, myeloid DCs may function as a traffic control between innate immunity via IFN-α production and acquired immunity via IL-12 production, depending on the type of nucleic acids. Our results provide a new insight into the biological action of myeloid DCs underlying the DNA-mediated activation of protective or pathogenic immunity.
Immunology 02/2011; 132(2):165-73. · 3.32 Impact Factor
-
Naoki Wada,
Junichiro Ikeda,
Yumiko Hori,
Shigeki Fujita,
Hiroyasu Ogawa,
Toshihiro Soma,
Haruo Sugiyama, Shirou Fukuhara,
Akihisa Kanamaru,
Masayuki Hino,
Yuzuru Kanakura,
Eiichi Morii,
Katsuyuki Aozasa
[show abstract]
[hide abstract]
ABSTRACT: According to previous reports, the frequency of Epstein-Barr virus (EBV) positivity in diffuse large B-cell lymphoma is higher in East Asia (approximately 9%) than in Western countries. The presence of the EBV genome was examined in diffuse large B-cell lymphoma patients registered with the Osaka Lymphoma Study Group (OLSG) in Osaka, Japan, situated in East Asia. The EBV-positive rate was examined with in situ hybridization (ISH) in 484 immunocompetent diffuse large B-cell lymphoma patients registered with OLSG. The male-to-female ratio was 1.29, with ages ranging from 16 to 95 (median, 68) years. ISH with EBV-encoded small RNAs (EBER) probes revealed positive signals in the nuclei of tumor cells: the frequency of positively stained cells among all tumor cells was almost none in 458 cases, 5-10% in 5, 10-20% in 5, 20-50% in 11, and >50% in 5. When the frequency was >20% or >50%, the EBV-positive rate in the present series (3.3% or 1.0%) was rather similar to that reported in Western cases. Careful evaluation of patient backgrounds, including age distribution, type of lymphomas, exclusion of immunocompromised patients, and establishment of definite criteria for EBV positivity (>20%, >50%, or almost all tumor cells) are essential in comparing geographical differences.
Journal of Medical Virology 02/2011; 83(2):317-21. · 2.82 Impact Factor
-
Yuichi Katashiba,
Rie Miyamoto,
Akira Hyo,
Keiko Shimamoto,
Naoko Murakami,
Makoto Ogata,
Ryuichi Amakawa,
Muneo Inaba,
Shosaku Nomura, Shirou Fukuhara,
Tomoki Ito
[show abstract]
[hide abstract]
ABSTRACT: Dendritic cells (DCs) are initiators of innate immunity and acquired immunity as cells linking these two bio-defence systems through the production of cytokines such as interferon-α (IFN-α) and interleukin-12 (IL-12). Nucleic acids such as DNA from damaged cells or pathogens are important activators not only for anti-microbial innate immune responses but also in the pathogenesis of IFN-related autoimmune diseases. Plasmacytoid DCs are regarded as the main effectors for the DNA-mediated innate immunity by possessing DNA-sensing toll-like receptor 9 (TLR9). We here found that double-stranded DNA (dsDNA) complexed with lipotransfectants triggered activation of human monocyte-derived DCs (moDCs), leading to the preferential production of IFN-α but not IL-12. This indicates that myeloid DCs also function as supportive effectors against the invasion of pathogenic microbes through the DNA-mediated activation in innate immunity. The dsDNA with lipotransfectants can be taken up by moDCs without co-localization of endosomal LAMP1 staining, and the dsDNA-mediated IFN-α production was not impaired by chloroquine. These findings indicate that moDC activation by dsDNA does not involve the endosomal TLR pathway. In contrast, single-stranded RNA (ssRNA) stimulated moDCs to secrete IL-12 but not IFN-α. This process was inhibited by chloroquine, suggesting an involvement of the TLR pathway in ssRNA-mediated moDC activation. As might be inferred from our findings, myeloid DCs may function as a traffic control between innate immunity via IFN-α production and acquired immunity via IL-12 production, depending on the type of nucleic acids. Our results provide a new insight into the biological action of myeloid DCs underlying the DNA-mediated activation of protective or pathogenic immunity.
Immunology 09/2010; 132(2):165 - 173. · 3.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although Bacillus Calmette-Guérin (BCG) has historically emerged as a potent adjuvant in cancer immunization through dendritic cell (DC) activation, the efficacy of its antitumor effect has been limited. Therefore, the strategy of adjuvant therapy using BCG needs to be improved by adding enhancers. Here we found that thymic stromal lymphopoietin (TSLP) acts as an enhancer for the BCG-mediated antitumor effect. While BCG-stimulated DCs induced CD8(+) T cell production of IFN-gamma without strong cell expansion, TSLP-stimulated DCs induced robust CD8(+) T cell expansion without high quantities of IFN-gamma production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8(+) T cells that produced a large amount of IFN-gamma with a potent cytolytic activity related to granzyme B expression. Our data suggest that TSLP is a good adjuvant to enhance the BCG-mediated cytotoxic T cell effect through DC activation, and provide a functional basis for a novel strategy for antitumor immune-based therapy.
Clinical Immunology 08/2010; 136(2):205-16. · 4.05 Impact Factor
-
Naoki Wada,
Masaharu Kohara,
Junichiro Ikeda,
Yumiko Hori,
Shigeki Fujita,
Masaya Okada,
Hiroyasu Ogawa,
Haruo Sugiyama, Shirou Fukuhara,
Akihisa Kanamaru,
Masayuki Hino,
Yuzuru Kanakura,
Eiichi Morii,
Katsuyuki Aozasa
[show abstract]
[hide abstract]
ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) involving spinal epidural space (SEDLBCL) is relatively rare, constituting 1.8% of DLBCLs in Osaka, Japan. The aim of this study was to analyze SEDLBCL cases for their clinical and histopathologic findings, including an association with Epstein-Barr virus (EBV) and immunohistochemical characteristics. We analyzed the clinicopathologic findings of 27 SEDLBCL cases. They consisted of 16 males and 11 females, their age ranging from 37-86 years (median 64 years). Eight patients had stage I disease, 3 had stage II, 5 had stage III, and 11 had stage IV. Based on the staining pattern for anti-CD10, bcl-6, and MUM-1, the cases were categorized into 17 cases of the germinal center B-cell (GCB) type and nine of the non-GCB type. There was a 4%-positive rate for EBV in the tumor cells. When compared to nodal DLBCL, the frequency of patients with a high performance status (PS) is higher in SEDLBCL. Compared to the DLBCL of the central nervous system (CNS), the frequency of cases with high stage, 2 or more extranodal lesions, high international prognostic index (IPI), and GCB-type is higher in SEDLBCL. There were no significant differences in the histologic features between SEDLBCL and nodal/CNS DLBCL. Univariate analysis revealed that advanced stage was an unfavorable factor for overall survival (P=0.060). SEDLBCL is different from nodal and CNS DLBCL, but an association with EBV is unlikely in every group.
Pathology - Research and Practice 07/2010; 206(7):439-44. · 1.21 Impact Factor
-
Chihiro Yamazaki,
Rie Miyamoto,
Katsuaki Hoshino,
Yuri Fukuda,
Izumi Sasaki,
Masuyoshi Saito,
Hironori Ishiguchi,
Takahiro Yano,
Takahiro Sugiyama,
Hiroaki Hemmi,
Takashi Tanaka,
Eri Hamada,
Takeshi Hirashima,
Ryuichi Amakawa, Shirou Fukuhara,
Shosaku Nomura,
Tomoki Ito,
Tsuneyasu Kaisho
[show abstract]
[hide abstract]
ABSTRACT: Understanding dendritic cell (DC) subset functions should lead to the development of novel types of vaccine. Here we characterized expression of XC chemokine receptor 1 (XCR1) and its ligand, XCL1. Murine XCR1 was the only chemokine receptor selectively expressed in CD8alpha(+) conventional DCs. XCL1 was constitutively expressed in NK cells, which contribute to serum XCL1 levels. NK and CD8(+) T cells increased XCL1 production upon activation. These expression patterns were conserved in human blood cells, including the BDCA3(+) DC subset. Thus, in human and mice, certain DC subsets should be chemotactic towards NK or activated CD8(+) T cells through XCR1.
Biochemical and Biophysical Research Communications 07/2010; 397(4):756-61. · 2.48 Impact Factor
-
Hideki Amuro,
Tomoki Ito,
Rie Miyamoto,
Hiroyuki Sugimoto,
Yoshitaro Torii,
Yonsu Son,
Naoto Nakamichi,
Chihiro Yamazaki,
Katsuaki Hoshino,
Tsuneyasu Kaisho,
Yoshio Ozaki,
Muneo Inaba,
Ryuichi Amakawa, Shirou Fukuhara
[show abstract]
[hide abstract]
ABSTRACT: Statins, which are used as cholesterol-lowering agents, have pleiotropic immunomodulatory properties. Although beneficial effects of statins have been reported in autoimmune diseases, the mechanisms of these immunomodulatory effects are still poorly understood. Type I interferons (IFNs) and plasmacytoid dendritic cells (PDCs) represent key molecular and cellular pathogenic components in autoimmune diseases such as systemic lupus erythematosus (SLE). Therefore, PDCs may be a specific target of statins in therapeutic strategies against SLE. This study was undertaken to investigate the immunomodulatory mechanisms of statins that target the IFN response in PDCs.
We isolated human blood PDCs by flow cytometry and examined the effects of simvastatin and pitavastatin on PDC activation, IFNalpha production, and intracellular signaling.
Statins inhibited IFNalpha production profoundly and tumor necrosis factor alpha production modestly in human PDCs in response to Toll-like receptor ligands. The inhibitory effect on IFNalpha production was reversed by geranylgeranyl pyrophosphate and was mimicked by either geranylgeranyl transferase inhibitor or Rho kinase inhibitor, suggesting that statins exert their inhibitory actions through geranylgeranylated Rho inactivation. Statins inhibited the expression of phosphorylated p38 MAPK and Akt, and the inhibitory effect on the IFN response was through the prevention of nuclear translocation of IFN regulatory factor 7. In addition, statins had an inhibitory effect on both IFNalpha production by PDCs from SLE patients and SLE serum-induced IFNalpha production.
Our findings suggest a specific role of statins in controlling type I IFN production and a therapeutic potential in IFN-related autoimmune diseases such as SLE.
Arthritis & Rheumatism 07/2010; 62(7):2073-85. · 7.87 Impact Factor
-
Naoto Nakamichi,
Naoki Wada,
Masaharu Kohara, Shirou Fukuhara,
Haruo Sugiyama,
Hiroyasu Ogawa,
Masayuki Hino,
Akihisa Kanamaru,
Yuzuru Kanakura,
Eiichi Morii,
Katsuyuki Aozasa
[show abstract]
[hide abstract]
ABSTRACT: Lymphoproliferative disorder (LPD) with polymorphous composition of proliferation (polymorphous LPD), containing large lymphoid cells together with small lymphocytes, plasma cells, macrophages, and/or eosinophils, is found in individuals with immunodeficiency conditions. Clinicopathological findings in 19 cases of polymorphous LPD registered with the Osaka Lymphoma Study Group, Osaka, Japan, were analyzed; they represented 0.4% of the registered cases. In six cases, there was a history of rheumatoid arthritis; five of them had received immunosuppressive agents. There were no acquired immunodeficiency syndrome cases or organ transplant recipients. Southern blotting and/or polymerase chain reaction (PCR)-based clonality analysis revealed monoclonal B cell and T cell proliferation in eight and six cases (B- and T-LPD), respectively, and polyclonality in one. In B-LPD, there was polymorphous proliferation, containing large B-lymphoid cells, while medium-to-large T lymphoid cells with occasional eosinophilic infiltration were seen in T-LPD. Epstein-Barr virus (EBV) was detected in three of eight B-LPD, four of six T-LPD, and one of one polyclonal LPD. The prognosis was not favorable; the 3-year overall survival rate was 49.7 +/- 17.3%. Thus, polymorphous LPD is relatively rare in Japan and is a heterogeneous disease with monoclonal proliferation of B or T cells; additionally, it is occasionally EBV-associated, and behaves as an aggressive lymphoma.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2010; 456(3):269-76. · 2.49 Impact Factor
-
Rie Miyamoto,
Tomoki Ito,
Shosaku Nomura,
Ryuichi Amakawa,
Hideki Amuro,
Yuichi Katashiba,
Makoto Ogata,
Naoko Murakami,
Keiko Shimamoto,
Chihiro Yamazaki,
Katsuaki Hoshino,
Tsuneyasu Kaisho, Shirou Fukuhara
[show abstract]
[hide abstract]
ABSTRACT: Plasmacytoid dendritic cells (pDCs) play not only a central role in the antiviral immune response in innate host defense, but also a pathogenic role in the development of the autoimmune process by their ability to produce robust amounts of type I interferons (IFNs), through sensing nucleic acids by toll-like receptor (TLR) 7 and 9. Thus, control of dysregulated pDC activation and type I IFN production provide an alternative treatment strategy for autoimmune diseases in which type I IFNs are elevated, such as systemic lupus erythematosus (SLE). Here we focused on IkappaB kinase inhibitor BAY 11-7082 (BAY11) and investigated its immunomodulatory effects in targeting the IFN response on pDCs.
We isolated human blood pDCs by flow cytometry and examined the function of BAY11 on pDCs in response to TLR ligands, with regards to pDC activation, such as IFN-alpha production and nuclear translocation of interferon regulatory factor 7 (IRF7) in vitro. Additionally, we cultured healthy peripheral blood mononuclear cells (PBMCs) with serum from SLE patients in the presence or absence of BAY11, and then examined the inhibitory function of BAY11 on SLE serum-induced IFN-alpha production. We also examined its inhibitory effect in vivo using mice pretreated with BAY11 intraperitonealy, followed by intravenous injection of TLR7 ligand poly U.
Here we identified that BAY11 has the ability to inhibit nuclear translocation of IRF7 and IFN-alpha production in human pDCs. BAY11, although showing the ability to also interfere with tumor necrosis factor (TNF)-alpha production, more strongly inhibited IFN-alpha production than TNF-alpha production by pDCs, in response to TLR ligands. We also found that BAY11 inhibited both in vitro IFN-alpha production by human PBMCs induced by the SLE serum and the in vivo serum IFN-alpha level induced by injecting mice with poly U.
These findings suggest that BAY11 has the therapeutic potential to attenuate the IFN environment by regulating pDC function and provide a novel foundation for the development of an effective immunotherapeutic strategy against autoimmune disorders such as SLE.
Arthritis research & therapy 01/2010; 12(3):R87. · 4.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report a case of acute mixed-lineage leukemia, as seen in a 65 year-old female with MLL gene amplification and biallelic loss of wild type p53 gene. The diagnosis was based on the findings that her bone marrow (BM) blasts expressed cytoplasmic CD3 (cyCD3), B-lineage antigens and myeloid antigens accompanied by clonal rearrangements of IgH gene. The BM blasts consisted of small-sized peroxidase-negative blasts (97%) and large-sized peroxidase-positive blasts (3%). The BM blasts showed a complex "karyotype," including dic(17;20) (p11;q11), -5 and add (11q23). Add (11q23) abnormality was found in sideline karyotypes as well as the stemline abnormality of dic(17;20) (p11;q11). For the p53 gene, which is located at 17p13, fluorescence in situ hybridization analysis showed the loss of one of two p53 alleles. Furthermore, polymerase chain reaction-single-strand conformation polymorphism and following nucleotide sequencing showed that the p53 gene was mutated at codon 215, leading to an amino acid substitution from Ser to Arg. For the MLL gene, southern blot analysis showed that the MLL gene locus was amplified but not rearranged at its breakpoint cluster region, which is usually rearranged in balanced translocations with many partner genes. These findings suggest that MLL gene amplification may in this case be based on the genetic instability caused by the preceding biallelic loss of the wild type p53 gene.
Journal of Clinical and Experimental Hematopathology 01/2010; 50(1):51-8.
-
[show abstract]
[hide abstract]
ABSTRACT: A 28-year-old man had a 1-year history of hemoptysis. Consequently, he underwent a medical examination. A right pleural effusion, left hydropneumothorax, and multiple pulmonary nodular shadows were found on chest radiography. During a detailed interview, he reported that the hemoptysis began after eating "kejang" (a raw crab preparation) with a friend a year previously. His peripheral blood eosinophil count and serum IgE level were elevated. In addition, ova were detected in the sputum and bilateral pleural effusion. Morphological examination of the ova and immunoserological examination led to the diagnosis of Paragonimus westermani infection. The pleural effusion could be partially drained, and his symptoms and radiographic results showed improvement after treatment with Praziquantel administered at a dose of 75 mg/(kg x day) for 3 days. After one month, he and his friend ate seasoned raw crabs, Paragonimus was diagnosed in his friend. This case suggests that on encountering a paragonimus infection, everyone who ate food prepared in the same kitchen should be contacted because of possible infection with paragonimus.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 12/2009; 47(12):1131-4.
-
Naoki Wada,
Junichiro Ikeda,
Masaharu Kohara,
Hiroyasu Ogawa,
Masayuki Hino, Shirou Fukuhara,
Akihisa Kanamaru,
Haruo Sugiyama,
Yuzuru Kanakura,
Eiichi Morii,
Katsuyuki Aozasa
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to clarify whether diffuse large B-cell lymphoma (DLBCL) with a high number of epithelioid histiocytes (DLBCL-EH) could have distinctive clinicopathological characteristics. Clinicopathological findings in 22 cases with DLBCL-EH and, as a control, 96 cases with ordinary type of DLBCL were analyzed. There were ten men and 12 women with ages ranging from 38 to 91 (median, 64) years. The primary site was lymph node in 16 cases, extranodal organs in three, and unknown in three. Stage of disease was I in five cases, II in three, III in nine, and IV in five. Histologically, there was a diffuse proliferation of large lymphoid cells admixed with numerous clusters of epithelioid histiocytes sprinkling throughout the lesions. Immunohistochemically, the large lymphoid cells were CD20(+), CD15(-), and CD3(-) and positive for CD10, bcl-6, and MUM1 in nine (41%), eight (36%), and 12 (55%) of 22 cases, respectively. Epstein-Barr virus positive rate was higher in DLBCL-EH (23.8%) than that in ordinary DLBCL (4.5%; P<0.05). Clonality analysis revealed monoclonal bands in all of the examined 20 cases with DLBCL-EH. Multivariate analysis revealed the prominent epithelioid reaction to be an independent factor for favorable prognosis. These findings suggest that DLBCL-EH could be a specific morphological variant of DLBCL associated with a better prognosis.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2009; 455(3):285-93. · 2.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We assessed the role of platelet activation markers (PMPs, Annexin V and CD62P on activated platelets), cytokines (IL-1 β, IL-4, IL-6, IFN- γ, GM-CSF, and TNF α), and soluble factors (sIL-2R, TM, sHLA-1, β2-m sVCAM-l, sPECAM-1, sP-selectin and sE-selectin) in vascular damage related to SLE. There were differences in the levels of PMPs and platelet activation markers between the SLE patients and controls (PMPs: 493±82 vs. 328±36, p<0.05; plt-CD62P; 8.5%±1.2 % vs. 4.6%±0.7 %, p<0.05; plt-Annexin V: 11.3%±2.1 % vs. 4.9%±0.6 %, p<0.01). There were no differences in the levels of IFN- y between the groups. However, the levels of IL-11β IL-4, IL-6, GM-CSF, TNF α, and soluble factors were higher in the SLE patients than in the controls. The levels of IL-4, IL-6, p2-m, sIL-2R, sVCAM-1, sP-selectin, and sE-selectin in SLE patients with elevated sTM levels were higher than those in the SLE patients without elevated sTM levels. On the other hand, elevations of s[L-2R, sVCAM-l, and sP-selectin were not found in patients with Behcet disease or rheumatoid arthritis. The levels of platelet CD62P, platelet annexin V, and PMP were significantly elevated in high-sTM patients. These findings suggest the possibility that activated platelets and cytokines participate in the pathogenesis of SLE in patients with elevated sTM levels.
07/2009; 33(2):85-94.
-
Clinical and Applied Thrombosis/Hemostasis 03/2009; 15(1):123-4. · 1.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ABCG2 is a transporter preferentially expressed in a primitive subpopulation of cells and recently reported as a surviving factor for trophoblasts. To date, manner of ABCG2 expression in lymphoid tissues is not known. Immunohistochemically, strong ABCG2 expression was found in a small proportion of plasma cells mainly located in the interfollicular space of lymphoid tissues. The number of ABCG2-high plasma cells increased in interleukin-6- (IL-6) rich lesions, such as Castleman's disease of plasma cell type. Plasma cells are subjected to endoplasmic reticulum (ER) stress when excess proteins are synthesized, and IL-6 stimulates protein synthesis. Therefore, the effect of IL-6 and ER stress on ABCG2 expression in plasma cells was examined. The expression level of ABCG2 increased by treatment with either IL-6 or ER stress inducers, and further increased with both. The promoter analysis revealed that the effect of IL-6 and ER stress inducers was mediated through the site overlapping XBP-1 and HIF-1 binding sequences. Knocked-down of ABCG2 by siRNA or ABCG2 inhibitor reduced plasma cell viability under ER stress. These suggest that ABCG2 is a surviving factor for plasma cells. To our knowledge, this is the first study reporting the effect of ER stress on ABCG2 expression.
Laboratory Investigation 02/2009; 89(3):327-36. · 3.64 Impact Factor
