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Masatoshi Tateno

Publications and source records attributed to Masatoshi Tateno.

16 recordsLinked to original sources
PubMed2005

Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients.

PURPOSE: Nasal natural killer (NK)/T-cell lymphoma is associated with EBV and has distinct clinical and histologic features. However, little is known about its genetic features. In this study, we examined the genes expressed by SNK-6 and SNT-8 cells, which were established from nasal NK/T-cell lymphomas, and found that interleukin (IL)-9 was specifically expressed in these two cell lines. EXPERIMENTAL DESIGN: cDNA array was used to examine the genes expressed by SNK-6 and SNT-8 cells. Expression of IL-9 and IL-9 receptor was investigated by reverse transcription-PCR, ELISA, and flow cytometry. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunohistologic staining and ELISA were used to examine IL-9 expression in biopsies and sera from patients, respectively. RESULTS: In cDNA array, expression of IL-9 mRNA was much higher in SNK-6 and SNT-8 cells than in NK-92 cells from non-nasal NK-cell lymphoma and peripheral blood mononuclear cells from healthy volunteers. Furthermore, IL-9 was specifically expressed by SNK-6 and SNT-8 cells but not by other NK-cell, NK-like T-cell, and T-cell lymphoma/leukemia cell lines. IL-9 receptor was also expressed on the surfaces of SNK-6 and SNT-8 cells. An IL-9-neutralizing antibody inhibited the growth of these two cell lines, whereas recombinant human IL-9 enhanced their growth. Most significantly, IL-9 was present in biopsies and sera from patients with this lymphoma. CONCLUSIONS: These results suggest that IL-9 plays an important role in nasal NK/T-cell lymphoma possibly via an autocrine mechanism.

Autocrine Communication↗
PubMed2005

Defining MHC class II T helper epitopes for WT1 tumor antigen.

The product of Wilms' tumor gene 1 (WT1) is overexpressed in diverse human tumors, including leukemia, lung and breast cancer, and is often recognized by antibodies in the sera of patients with leukemia. Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy. In order to carry out an effective peptide-based cancer immunotherapy, MHC class II-restricted epitope peptides that elicit anti-tumor CD4(+) helper T lymphocytes (HTL) will be needed. In this study, we analyzed HTL responses against WT1 antigen using HTL lines elicited by in vitro immunization of human lymphocytes with synthetic peptides predicted to serve as HTL epitopes derived from the sequence of WT1. Two peptides, WT1(124-138) and WT1(247-261), were shown to induce peptide-specific HTL, which were restricted by frequently expressed HLA class II alleles. Here, we also demonstrate that both peptides-reactive HTL lines were capable of recognizing naturally processed antigens presented by dendritic cells pulsed with tumor lysates or directly by WT1+ tumor cells that express MHC class II molecules. Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine. Because HTL responses to TAA are known to be important for promoting long-lasting anti-tumor CTL responses, the newly described WT1 T-helper epitopes could provide a useful tool for designing powerful vaccines against WT1-expressing tumors.

Antigen Presentation↗
PubMed2005

Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, TARP.

PURPOSE: T cell-based immunotherapy via the in vitro or in vivo expansion of prostate tumor-associated antigen (TAA)-specific T lymphocytes is one of the most promising therapeutic approaches to treat prostate cancer. T-cell alternate reading frame protein (TARP) is a mitochondrial protein that is specifically expressed in prostate epithelial cells. We have done experiments aimed at identifying helper T lymphocyte (HTL) epitopes for TARP for the design of T cell-based immunotherapy for prostate cancer. EXPERIMENTAL DESIGN: Dendritic cells from normal donors were pulsed with synthetic peptides derived from TARP, which were predicted to serve as HTL epitopes. These dendritic cells were used to stimulate CD4(+) T cells in vitro to trigger HTL responses against TARP. T-cell responses to these peptides were also studied with lymphocytes from prostate cancer patients. RESULTS: The two peptides, TARP(1-14) and TARP(14-27), were shown to elicit effective in vitro HTL responses using lymphocytes from both normal volunteers and prostate cancer patients. Peptide TARP(1-14)-reactive HTLs were found restricted by HLA-DR53 and could recognize naturally processed protein antigen derived from tumor cells, which was presented by autologous dendritic cells. Most significantly, stimulation with peptide TARP(14-27) generated four HTL lines restricted by HLA-DR1, HLA-DR9, HLA-DR13, and HLA-DR15, some of which capable of recognizing naturally processed antigens presented by dendritic cell or directly by TARP-positive tumor cells. CONCLUSIONS: Our results show that TARP constitutes a TAA that can be recognized by tumor-reactive HTL. The newly described TARP epitopes could be used to optimize and improve T-cell epitope-based immunotherapy against prostate and other tumors expressing TARP.

Antigen Presentation↗
PubMed2005

CD56/NCAM-positive Langerhans cell sarcoma: a clinicopathologic study of 4 cases.

This report concerns the clinicopathologic features of 4 patients with CD56/neural cell adhesion molecule (NCAM)-positive Langerhans cell sarcoma (LCS). Three of the patients were elderly, between 59 and 62 years of age at presentation, and the other was 35 years old. The presenting symptoms included fever, bone pain, and weakness. The patients shared some clinical findings, such as multiorgan involvement of lymph nodes, skin, lung, bone marrow, and spleen. LCS carries a poor prognosis, and 3 of the patients died of the disease within several years of presentation despite multiagent chemotherapy and radiotherapy. Of special interest is that all of the cases showed CD56 expression on the tumor cells in addition to expression of CD1a, S100beta, and langerin, the presence of which suggests derivation from Langerhans cells. For control, CD56 was also examined in 8 cases of Langerhans cell histiocytosis (LCH), a single-system unifocal or multifocal disease, and the results of staining of the tumor cells were negative. Our findings indicated that CD56 may be a clinically relevant biologic marker for predicting an intractable course of Langerhans cell neoplasms, although it is often difficult to draw a definite morphologically-based distinction between LCS and LCH.

Adult↗
PubMed2004

Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein.

PURPOSE: Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative disorder and is resistant to chemotherapy, the establishment and enhancement of T-cell immunity to HTLV-I through the development of therapeutic vaccines could be of value. Thus, the identification of HTLV-I epitopes for both CD8(+) and CD4(+) T cells should facilitate the development of effective vaccines. Although numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized by CD4(+) helper T cells against this virus have been described. EXPERIMENTAL DESIGN: Synthetic peptides prepared from several regions of the HTLV-I envelope (Env) sequence that were predicted to serve as helper T-cell epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro helper T-cell responses using lymphocytes from normal volunteers. RESULTS: The results show that the HTLV-I-Env(317-331), and HTLV-I-Env(384-398)-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15, respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a consequence, secrete lymphokines. In addition, HTLV-I Env(196-210)-reactive helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+ lymphoma cells and recognize naturally processed antigen derived from killed HTLV-I+ lymphoma cells, which was presented to the helper T cells by autologous antigen-presenting cells. CONCLUSIONS: The present findings hold relevance for the design and optimization of T-cell epitope-based immunotherapy against HTLV-I-induced diseases such as ATLL.

Algorithms↗
PubMed2004

Neuronal calcium sensor protein visinin-like protein-3 interacts with microsomal cytochrome b5 in a Ca2+-dependent manner.

Visinin-like protein-3, which is one of the neuronal calcium sensors, has been shown to be mainly expressed in cerebellar Purkinje cells, but cellular function of this protein has not yet been elucidated. We examined the tissue distribution of murine visinin-like protein-3 transcripts using real-time reverse transcription-PCR. Visinin-like protein-3 mRNA was found to be expressed in peripheral tissues. Particularly, the expression of the transcript in the thymus was significantly higher than in other peripheral tissues. In addition, B6RVTC1 thymoma cells robustly expressed visinin-like protein-3 mRNA. To identify a target protein of visinin-like protein-3, we performed a pull-down experiment using glutathione S-transferase-tagged visinin-like protein-3 and two-dimensional electrophoresis. We demonstrated that microsomal cytochrome b(5) was a Ca(2+)-dependent binding partner of visinin-like protein-3. In a co-immunoprecipitation experiment, it was observed that hippocalcin, as well as visinin-like protein-3, could interact with cytochrome b(5). Furthermore, we confirmed that the sequence Val(114)-Tyr(127) at the C-terminal tail of cytochrome b(5) is the minimal structural requirement for binding to visinin-like protein-3. In addition, the loop His(19)-His(25) at the N terminus of visinin-like protein-3 is essential for binding to cytochrome b(5). Microsomal cytochrome b(5) was also shown to be a potential activator of cytochrome P450. The present findings raise the possibility that visinin-like protein-3 may link Ca(2+) signaling to the machinery of microsomal monooxygenase complex composed of cytochrome b(5), cytochrome P450, and some reductases. This report provides the first evidence of an interaction between visinin-like protein-3 and microsomal cytochrome b(5).

Amino Acid Sequence↗
PubMed2004

Multiple elastofibromas.

Elastofibroma is an uncommon fibroelastic tumor or tumorlike process that usually occurs between the scapula and the chest wall of elderly patients. This condition is rarely reported in the dermatologic literature, because it infrequently arises in the skin or within the subcutaneous tissue. We present a 78-year-old man with 15 separate subcutaneous nodules on the buttocks and upper extremities together with bilateral subscapular nodules. All specimens taken from different lesions were histologically confirmed as elastofibromas. As far as we know, this case with 17 distinct elastofibromas demonstrates the largest number ever reported in a single patient. Although the pathomechanism of the occurrence of multiple elastofibromas is unknown, it should be included in the differential diagnosis of multiple subcutaneous nodules.

Aged↗
PubMed2004

Decreased expression of retinoid X receptor isoforms in human thyroid carcinomas.

Retinoid X receptors (RXRs) are ligand-inducible transcription factors that belong to the superfamily of nuclear hormone receptors. Because RXRs heterodimerize with thyroid hormone receptor, retinoic acid receptor, vitamin D(3) receptor, and peroxisome proliferator-activated receptor, they play central roles in regulating a number of signaling pathways. To understand the roles of RXRs in human thyroid carcinogenesis, we have investigated the immunohistochemical expression of RXRs in normal and neoplastic thyroid tissues. Whereas nontumorous human thyroid cells exhibited distinct nuclear staining for the RXRs, thyroid carcinomas showed decreased nuclear expression of all three RXR isoforms. In particular, some thyroid carcinoma cells showed intense RXR-alpha cytoplasmic staining accompanied by decreased immunoreactivity in their nuclei. This subcellular localization of RXR-alpha was confirmed by Western blot analysis, which showed both lower nuclear expression levels of RXR-alpha and a cytosolic presence of RXR-related protein in neoplastic regions. We present here, for the first time, the histological distribution of each RXR protein (alpha, beta, and gamma) in human thyroid follicular cells. In addition, we found that the nuclear expression of RXRs was lower in thyroid carcinomas than in normal tissue. The differential expressions of these RXRs in thyroid carcinomas might be implicated in the pathogenesis of thyroid cancers.

Blotting, Western↗
PubMed2004

Squamous metaplasia mimicking papillary carcinoma in the upper urinary tract.

We experienced a case of squamous metaplasia mimicking papillary urothelial cell carcinoma in the upper urinary tract. A 69-year-old woman, who complained of gross hematuria and intermittent left flank dull pain underwent nephrectomy with the clinical diagnosis of papillary urothelial carcinomas in the left upper urinary tract according to positive split urine cytology and tumorous filling defects of contrast media by the abdominal CT scan. Pathological diagnosis was squamous metaplasia and concomitant foreign body granuloma. Those changes were judged due to a tiny calculus in the ureter. Our presented case implies that a tiny calculus can cause the metaplastic change in the urothelial epithelium and the combination of radiographical and cytological diagnoses would not be enough to lead the correct diagnosis and the definitive surgical treatment against protruding lesions in the upper urinary tract requires more reliable diagnostic modalities.

Aged↗
PubMed2003

Identification of naturally processed helper T-cell epitopes from prostate-specific membrane antigen using peptide-based in vitro stimulation.

PURPOSE: There is growing evidence that CD4(+) helper T lymphocytes (HTLs) play an essential role in the induction and long-term maintenance of antitumor CTL responses. Thus, approaches to develop effective T-cell-based immunotherapy should focus in the stimulation of both CTLs and HTLs reactive against tumor-associated antigens. The present studies were performed with the purpose of identifying HTL epitopes for prostate-specific membrane antigen (PSMA) for the optimization of vaccines for prostate cancer. EXPERIMENTAL DESIGN: Synthetic peptides from regions of the PSMA sequence that were predicted to serve as HTL epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro HTL responses in lymphocytes from normal volunteers. RESULTS: Our results show that 4 peptides from PSMA were effective in eliciting HTL responses. Moreover, HTL reactive to 3 of the 4 peptides were capable of reacting with naturally processed antigen in the form of freeze/thaw lysates or apoptotic cells produced from PSMA-positive LNCaP tumor cell lines. CONCLUSIONS: Human HTLs are capable of effectively recognizing epitopes derived from PSMA. The information presented here should facilitate the design of improved vaccination strategies for prostate cancer.

Animals↗
PubMed2003

Modulation of hepatic granulomatous responses by transgene expression of DAP12 or TREM-1-Ig molecules.

DAP12 (also known as KARAP) is a novel ITAM-bearing transmembrane adapter molecule that is expressed on the cell surface of natural killer cells, monocytes, dendritic cells, and macrophages. Several myeloid cell-specific DAP12-associating receptors, such as TREM receptor family, SIRP-beta1, and MDL-1 have been identified. The in vivo function of DAP12 and its associating molecules in inflammation has remained primarily unknown. To investigate DAP12 signaling during chronic inflammation, we constructed two adenoviral gene transfer vectors to express FLAG/DAP12 (Ad-FDAP12) and the extracellular domain of mouse TREM-1 and the Fc portion of human IgG1 (Ad-TREM-1 Ig), respectively, and observed their modulatory activities in a mouse model of hepatic granulomatous inflammation elicited by zymosan A. Mice were injected with zymosan A intravenously and 24 hours after zymosan A, they were injected with Ad-FDAP12 or Ad-TREM-1 Ig. Zymosan A-induced hepatic granuloma formation peaked at day 7 and markedly declined by day 10. Although adenoviral-mediated DAP12 gene transfer did not enhance granuloma formation by day 7, it sustained and enhanced granuloma formation beyond day 7. However, an anti-FLAG monoclonal antibody used to potentiate the signaling of adenoviral-derived DAP12, enhanced granuloma formation at day 7. In sharp contrast to the effect by Ad-FDAP12, transgene expression in the liver of soluble form of extracellular domain of TREM-1 as an antagonist of DAP12 signaling, remarkably inhibited zymosan A-induced granuloma formation at all time points examined. Our findings thus suggest that both DAP12 and TREM-1 are involved in the development of granulomatous responses in the liver.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[The chimerism and GVT effects on murine mini-transplantation model].

We established a murine mini-transplantation model to examine chimerism and graft versus tumor effects(GVT) using with C57BL/6(donor) and(C57BL/6 x BALB/c) (CBF1) (recipient) combination and a IgE producing plasmacytoma cell clone (B53) of BALB/c origin. The chimerism and graft versus tumor effects(GVT) were observed. Two experimental groups were prepared. One is mini-transplantation group (G2): recipients irradiated with 200 rad were inoculated with B53 cells, along with donor cells, the other is bone marrow transplantation group(G4): recipients irradiated with 800 rad were inoculated with B53, along with donor cells. The full chimera was observed one week after transplantation in G4, but that was seen 3 week after transplantation. The GVT effects were observed in both groups. However, GVT effects on G4 is stronger than that on G2 in pathological findings and serum IgE level.

2,4-Dinitrophenol↗
PubMed2002

Anti-CD95-induced lethality requires radioresistant Fcgamma RII+ cells. A novel mechanism for fulminant hepatic failure.

The Jo2 anti-mouse CD95 monoclonal antibody induces lethality in mice characterized by hepatocyte death and liver hemorrhage. Mice bearing a defect in Fas expression or in the Fas-mediated apoptotic pathway are resistant to Jo2. Here we show that FcgammaRII knockout mice or mice with monoclonal antibody-blocked FcgammaRII are also resistant to Jo2. The critical FcgammaRII(+) cells are radioresistant and could not be reconstituted with splenic cells. Death of sinusoidal lining cells and destruction of sinusoids were observed, consistent with the characteristic liver hemorrhage and the selective FcgammaRII expression in sinusoidal lining cells but not hepatocytes. Hemorrhage developed coincident with hepatocyte death and the sharp rise of serum alanine aminotransferase and alanine aminotransferase. Invariably, moribund mice showed severe liver hemorrhage and destruction of sinusoids. The data demonstrate a novel mechanism by which the destruction of liver sinusoids, induced by the Jo2-mediated co-engagement of Fas and FcgammaRII, leads to severe hemorrhage and lethal fulminant hepatitis.

Alanine Transaminase↗
PubMed2002

CD4+ T-cells from peripheral blood of a patient with psoriasis recognize keratin 14 peptide but not 'homologous' streptococcal M-protein epitope.

Psoriasis has been recognized as an immunologically mediated inflammatory skin disease that has been associated with group A, beta-haemolytic streptococcal infections. Notably cross-reactive autoimmune mechanism, which is mediated by T cells reacting to epitopes that are common to streptococcal M-protein and keratin, has been proposed in psoriasis. In order to investigate this possibility, peptides corresponding to M-protein and human epidermal keratin, which share some amino acid sequence between them, were synthesized and tested for their ability to stimulate T-cells of patients with psoriasis. Among five cases examined, we isolated a CD4(+) T-cell line that recognized the type I keratin (K14)(p168-181) when it was presented by the patient's HLA-DR molecules from a single psoriatic patient, whose MHC allele was HLA-A2/A26, -B27/B16, -DR4/DR8, -DQ8. Further analysis disclosed that the critical peptide recognized by the T-cell line was 10-mer keratin(p171-180) (DLRNKILTAT). However, corresponding M6 protein with homology to K14 did not stimulate the T-cell response and no evidence for cross-reactivity was obtained. The K14-responsive T cell line produced IFN-gamma, but little IL-4 when stimulated with irradiated autologous PBMC pulsed with this peptide. Thus, the finding that human epidermal keratin peptide is immunogenic in a psoriasis patient may provide the evidence that T lymphocytes play an important role in the pathogenesis of psoriasis as an autoimmune disorder participated with Th1 like cells. However, the keratin-responsive T cell line was detected in only one of five cases of psoriasis examined, suggesting that such T cell line appears to be not so popular in psoriatic patients. No evidence for cross-reactivity to streptococcal M protein also suggests that the contribution of streptococci may simply be inducing proliferation of various repertoire of T cells (including K14-responsive T cells) possibly through a superantigen-dependent process.

Antigens, Bacterial↗
PubMed2002

A novel animal model of thymic tumour: development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene.

The pX region encodes a major product of human T lymphocyte virus type I (HTLV-I) that has been implicated previously in tumour formation. To investigate the pathogenesis of pX gene in lymphoid tissues, we established a series of novel transgenic rats carrying the pX gene under the control of a rat lymphocyte-specific protein tyrosine kinase (p56lck) proximal promoter. The transgene was constructed with the -269 to +26 region of a rat p56lck proximal promoter and the pX cDNA, and was microinjected into fertilized ova of Fischer 344/jcl female rats. Six transgenic lines from 114 pups were established. Integration and expression of the transgene were detected by polymerase chain reaction (PCR) and Southern hybridization or by reverse transcriptase-PCR, northern hybridization, and immunostaining. Thymic tumours with lethal expansion occurred in 4 of 6 transgenic lines. The tumour consisted of spindle shaped cells. Immunohistochemical and ultra-structural analysis characterized the tumour cells to as epithelial cell type, and in the tumour arose in the medulla. Therefore, the tumour is classified into predominantly epithelial and spindle cell of medullary thymoma (type A of the new World Health Organization classification), as based on the human classification. Tumor occurrence increased in proportion to levels of the pX transcription in the thymus, for each line, and sex distinction was evident regarding rates related to tumour expansion. The transgenic rat model described here is suitable as a model for analysing tumorigenesis in epithelial thymoma occurring in humans.

Animals↗