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Makoto Suzuki,
Kenji Shiraishi,
Ayami Eguchi,
Koei Ikeda,
Takeshi Mori,
Kentaro Yoshimoto,
Yasuomi Ohba,
Tatsuya Yamada, Takaaki Ito,
Yoshifumi Baba,
Hideo Baba
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ABSTRACT: Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino-genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various malignancies. The aim of the present study was to assess the precise methylation levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC) using a pyrosequencing assay. Methylation of all regions was examined in 56 primary NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2, MAL and IGFBP7 were measured before and after treatment with a demethylating agent. Methylation of these genes was also examined in 9 lung cancer cell lines using RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values, were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features. The hypermethylation of all genes was well correlated with changes in expression. The methylation level and frequency of MAL were significantly higher in smokers and in patients without EGFR mutations. Through accurate measurement of methylation levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. Analysis of the methylation profiles of these genes may, therefore, provide novel opportunities for the therapy of NSCLCs.
Oncology Reports 01/2013; · 1.84 Impact Factor
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ABSTRACT: Nucleostemin (NS) has been reported as essential for stem and cancer cell proliferation. To investigate the significance of NS in oral squamous cell carcinomas (OSCCs), we examined NS expression in neoplastic tissue of the tongue and in OSCC cell lines. Nucleostemin expression in the histological samples showed positive correlation with Ki-67 expression. Furthermore, NS expression was associated with cellular proliferation in OSCC cell lines using siRNA, which upregulated p27, a cyclin-dependent kinase inhibitor. Regarding OSCC differentiation, NS expression did not influence cornification or oral epithelial differentiation markers such as involucrin and cytokeratin19. Thus, NS is widely expressed in normal and neoplastic oral epithelial tissues, and is likely a marker of proliferation.
Cancer Science 03/2011; 102(7):1418-23. · 3.33 Impact Factor
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Yusuke Tomita,
Katsunori Imai,
Satoru Senju,
Atsushi Irie,
Mitsuhiro Inoue,
Yuki Hayashida,
Kenji Shiraishi,
Takeshi Mori,
Yataro Daigo,
Takuya Tsunoda, Takaaki Ito,
Hiroaki Nomori,
Yusuke Nakamura,
Hirotsugu Kohrogi,
Yasuharu Nishimura
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ABSTRACT: The present study attempted to identify a useful tumor-associated antigen (TAA) for lung cancer immunotherapy and potential immunogenic peptides derived from the TAA. We focused on cell division cycle 45-like (CDC45L), which has a critical role in the initiation and elongation steps of DNA replication, as a novel candidate TAA for immunotherapy based on a genome-wide cDNA microarray analysis of lung cancer. The CDC45L was overexpressed in the majority of lung cancer tissues, but not in the adjacent non-cancerous tissues or in many normal adult tissues. We examined the in vitro and in vivo anti-tumor effects of cytotoxic T-lymphocytes (CTL) specific to CDC45L-derived peptides induced from HLA-A24 (A*24:02)-positive donors. We identified three CDC45L-derived peptides that could reproducibly induce CDC45L-specific and HLA-A24-restricted CTL from both healthy donors and lung cancer patients. The CTL could effectively lyse lung cancer cells that endogenously expressed both CDC45L and HLA-A24. In addition, we found that CDC45L (556) KFLDALISL(564) was eminent in that it induced not only HLA-A24 but also HLA-A2 (A*02:01)-restricted antigen specific CTL. Furthermore, the adoptive transfer of the CDC45L-specific CTL inhibited the growth of human cancer cells engrafted into immunocompromised mice. These results suggest that these three CDC45L-derived peptides are highly immunogenic epitopes and CDC45L is a novel TAA that might be a useful target for lung cancer immunotherapy.
Cancer Science 01/2011; 102(4):697-705. · 3.33 Impact Factor
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ABSTRACT: We investigated whether implantation of an ansa cervicalis nerve (ACN)-muscle pedicle into the thyroarytenoid (TA) muscle is efficacious in the presence of partial recurrent laryngeal nerve (RLN) innervation.
We studied a total of 36 rats. Twelve of the rats served as positive and negative control animals. In the remaining 24 rats, the left RLN was transected, a 1-mm piece of nerve was removed, and the stumps were abutted in silicone tubes (STs), inducing partial RLN regeneration. Twelve of the ST-treated rats underwent this procedure alone, and the other 12 rats had a nerve-muscle pedicle (NMP) implanted into the left TA muscle 5 weeks after ST treatment. At 15 weeks, reinnervation was assessed by histologic evaluation of the TA muscle and by electromyography with stimulation of the RLNs and ACNs.
The muscle area, the number of nerve terminals, the number of acetylcholine receptors, and the ratio of nerve terminals to acetylcholine receptors were significantly greater (p < 0.05) in the NMP group than in the ST group. Electromyography elicited TA muscle compound action potentials upon stimulation of the RLNs and ACNs.
In rats, NMP implantation is efficacious for reducing atrophic changes in the TA muscle in the presence of partial RLN innervation.
The Annals of otology, rhinology, and laryngology 12/2010; 119(12):823-9. · 1.05 Impact Factor
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ABSTRACT: TRAIL is known to play a pivotal role in the inhibition of autoimmune disease. We previously demonstrated that administration of dendritic cells engineered to express TRAIL and myelin-oligodendrocyte glycoprotein reduced the severity of experimental autoimmune encephalomyelitis and suggested that CD4(+)CD25(+) regulatory T cells (Tregs) were involved in mediating this preventive effect. In the current study, we investigated the effect of TRAIL on Tregs, as well as conventional T cells, using TRAIL-deficient mice. Upon induction of experimental autoimmune encephalomyelitis, TRAIL-deficient mice showed more severe clinical symptoms, a greater frequency of IFN-γ-producing CD4(+) T (Th1) cells, and a lower frequency of CD4(+)Foxp3(+) Tregs than did wild-type mice. In vitro, conventional T cells stimulated by bone marrow-derived dendritic cells (BM-DCs) from TRAIL-deficient mice showed a greater magnitude of proliferation than did those stimulated by BM-DCs from wild-type mice. In contrast, TRAIL expressed on the stimulator BM-DCs enhanced the proliferative response of CD4(+)CD25(+) Tregs in the culture. The functional TRAILR, mouse death receptor 5 (mDR5), was expressed in conventional T cells and Tregs upon stimulation. In contrast, the decoy receptor, mDc-TRAILR1, was slightly expressed only on CD4(+)CD25(+) Tregs. Therefore, the distinct effects of TRAIL may be due to differences in the mDc-TRAILR1 expression or the signaling pathways downstream of mouse death receptor 5 between the two T cell subsets. Our data suggest that TRAIL suppresses autoimmunity by two mechanisms: the inhibition of Th1 cells and the promotion of Tregs.
The Journal of Immunology 10/2010; 185(9):5259-67. · 5.79 Impact Factor
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ABSTRACT: Transcriptional function of cyclin D1, whose deregulation is frequently observed in human cancers, has been suggested to contribute to cancer formation. In the present study, we show that cyclin D1 protein inhibits RUNX3 activity by directly binding to it and interfering with its interaction with p300 interaction in lung cancer cells. Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively regulates cyclin-dependent kinase (cdk) inhibitor p21 expression. These transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation. We propose that cyclin D1 provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells. Since RUNX3 plays tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1 function may be critical for neoplastic transformation of the epithelial cells in which RUNX3 regulates proliferation.
Biochemical and Biophysical Research Communications 09/2010; 400(3):426-31. · 2.48 Impact Factor
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Mitsuhiro Inoue,
Satoru Senju,
Shinya Hirata,
Yoshiaki Ikuta,
Yuki Hayashida,
Atsushi Irie,
Michiko Harao,
Katsunori Imai,
Yusuke Tomita,
Takuya Tsunoda,
Yoichi Furukawa, Takaaki Ito,
Yusuke Nakamura,
Hideo Baba,
Yasuharu Nishimura
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ABSTRACT: To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2K(d)-restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2K(d)-binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1(143-151) (DYIGPCKYI) and SPARC-A24-4(225-234) (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy.
International Journal of Cancer 09/2010; 127(6):1393-403. · 5.44 Impact Factor
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ABSTRACT: To establish bromodeoxyuridine (BrdUrd)/iododeoxyuridine (IdUrd) double immunostaining for thick sections of epoxy resin-embedded tissues, young hamsters received intra-peritoneal injections of IdUrd and BrdUrd 3 hr and 1 hr before sacrifice, respectively. The intestines were fixed with phosphate-buffered 4% paraformaldehyde and embedded in an Epon-Araldite mixture. The epoxy resin was removed completely by a sodium methoxide/benzene/methanol solution. This epoxy resin removal method was effective for BrdUrd/IdUrd immunostaining using a mono-specific antibody for BrdUrd (Br-3) and a bi-specific antibody for BrdUrd and IdUrd (IU-4), followed by the ABC complex method. Epoxy sections stained with these antibodies showed clear localization of nuclei incorporating the two thymidine analogues with precise morphology of labeled cells. Furthermore, ultrastructural observation of thin sections adjacent to thick sections immunostained for BrdUrd/IdUrd confirmed the cell type and ultrastructural features of cells labeled with these thymidine analogues.
07/2009; 70(4):169-174.
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ABSTRACT: Nerve-muscle pedicle (NMP) implantation was effective in the recovery from atrophic changes in long-term denervated thyroarytenoid (TA) muscle. Re-innervation occurred via the transferred nerve. However, the effectiveness of the NMP method may decline with increasing duration of denervation.
To evaluate the effects of NMP implantation on long-term denervated rat TA muscle.
Wistar rats (n=105) were divided into two groups in which the left recurrent laryngeal nerve (RLN) was transected without (DNV group) or with (NMP group) subsequent NMP implantation, and subgroups of each group were formed depending on the period after RLN transection (immediate to 48 weeks). In the DNV subgroups, we histologically assessed the area of muscle and the number of neuromuscular junctions. In the NMP subgroups, we performed electromyographic, videolaryngoscopic, and histologic assessments. The muscle area and muscle action potentials were evaluated by comparing the treated and untreated sides. The ratio of the number of nerve terminals to that of acetylcholine receptors was also assessed.
The TA muscle area was significantly larger in most of the NMP subgroups compared with the DNV subgroups. Muscle action potentials were present in all NMP animals. All histologic and physiologic assessments revealed degradation as the denervation period in the five NMP subgroups.
Acta oto-laryngologica 01/2009; 129(12):1486-92. · 0.98 Impact Factor
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ABSTRACT: The α subunit of a GTP-blndlng protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemlcal method. Positive immunostaining for the α subunit of Go (Goα) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Goα-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Goα confirmed that Goα-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Goα is unclear in normal and neoplastic lung tissues, but Goα is a useful marker of neuroendocrine cells and neoplasms of the lung.
Pathology International 12/2008; 46(6):393 - 398. · 1.62 Impact Factor
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ABSTRACT: An animal model in which the human immune system can be reconstituted is necessary to study acquired immunity in vivo. We report here a novel model, the NOD/SCID/JAK3(null) mouse, for the human immune system's development. Newborn mice transplanted with human cord blood CD34(+) cells intrahepatically, developed human T and B cells, and myeloid and plasmacytoid dendritic cells. The T and B cells had a naïve to memory phenotype, and included plasma cells. The human acquired immune system can be reconstituted from CD34(+) cells in NOD/SCID/JAK3(null) mice. This model is a powerful tool for the study of human immunity.
International journal of hematology 12/2008; 88(5):476-82. · 1.17 Impact Factor
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ABSTRACT: To determine the effects of long-term denervation on the rat thyroarytenoid (TA) muscle and neuromuscular junctions.
A quantitative histologic assessment of the TA muscle after long-term denervation.
Thirty Wistar rats were euthanized 10, 18, 26, 42, and 58 weeks after left recurrent laryngeal nerve resection. The areas of the entire muscle and individual muscle fibers were evaluated using hematoxylin-eosin staining, and neuromuscular junctions were detected by immunohistochemistry. Changes after denervation were evaluated by comparing the treated (T) and untreated (U) sides (T/U ratio). The ratio of the number of nerve terminals (NTs) to that of acetylcholine receptors (AChRs) (NT/AChR ratio) was also assessed.
The average T/U ratio for the entire muscle area of the denervation groups ranged between 61.1% and 72.5% and did not differ significantly. Similarly, the T/U ratios for the individual muscle fiber area ranged between 45.0% and 51.9%, and the differences were not significant. The T/U ratio of AChRs at 58 weeks (35.3 +/- 20.2%) was significantly lower than that at 10 weeks (76.3 +/- 9.0%; P < .01). The NT/AChR ratios ranged between 30.3% and 35.6% and did not differ significantly among the denervation groups.
The entire TA muscle area, individual muscle fiber area, and NT/AChR ratio did not decrease with long-term denervation. Thus, the TA muscle may retain an ability to receive regenerating nerve axons. However, the ability of the TA muscle to receive nerve axons may deteriorate after an excessively long denervation period because the T/U ratio of AChRs decreased with long-term denervation.
The Laryngoscope 07/2008; 118(7):1318-23. · 1.75 Impact Factor
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ABSTRACT: To evaluate the effects of short-term denervation on the kinetics of satellite cells (SCs) and myocytes in the rat thyroarytenoid (TA) muscle using immunohistochemistry for a myogenic regulatory factor, MyoD, and a cell proliferation marker, Ki-67.
Quantitative immunohistochemical assessment of MyoD and Ki-67 expression in SCs and myocytes after denervation.
The left recurrent laryngeal nerve (RLN) was transected in 15 adult Wistar rats, which were sacrificed 1, 3, or 7 days after the treatment (n = 5, each group). Fluorescein immunostaining was used to visualize the localization of MyoD+ and Ki-67+ SCs in combination with M-cadherin immunostaining for detection of SCs. We examined the temporal changes of the ratios of MyoD+ and Ki-67+ SCs for all of the counted muscle fibers and M-cadherin+ cells in both the denervated and the contralateral control TA muscle.
On the denervated side, the TA muscle contained 3.8 +/- 0.4% MyoD+ SCs and 1.3 +/- 0.4% Ki-67+ SCs. Of the SCs, 22.6 +/- 2.2% were MyoD+, and 14.5 +/- 4.4% were Ki-67+, whereas SCs on the control side did not express these markers.
In the rat TA muscle, denervation induces SC activation, and some SCs enter the cell cycle, whereas others are involved in the differentiation process. The number of activated SCs is relatively small compared with all M-cadherin+ SCs. Therefore, SCs might be good targets for a therapy to prevent TA muscle atrophy after RLN paralysis.
The Laryngoscope 12/2007; 117(11):2063-7. · 1.75 Impact Factor
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ABSTRACT: Gastric lesions result from an imbalance between aggressive and defensive factors. Indirect lines of evidence suggest that heat shock proteins (HSPs) induced by various aggressive factors provide a major protective mechanism. In this study, we compared gastric ulcerogenic response in wild-type mice and in those lacking heat shock factor 1 (HSF1), a transcription factor for hsp genes. The severity of gastric lesions induced by ethanol or hydrochloric acid was worsened in HSF1-null mice. Immunoblotting, real-time reverse transcription-polymerase chain reaction, immunohistochemical analysis, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed that the ethanol administration up-regulated gastric mucosal HSPs, in particular HSP70, in an HSF1-dependent manner, and more apoptotic cells were observed in the gastric mucosa of HSF1-null mice than in wild-type mice. In contrast, other parameters governing the gastric ulcerogenic response, including gastric acid secretion, gastric mucosal blood flow, and prostaglandin E(2) levels, were not significantly affected by the absence of the hsf1 gene. Geranylgeranylacetone (GGA), a clinically used antiulcer drug with HSP-inducing activity, suppressed ethanol-induced gastric lesions in wild-type mice but not in heat shock factor 1 (HSF1)-null mice. The results suggest that the aggravation of irritant-induced gastric lesions in HSF1-null mice is due to their inability to up-regulate HSPs, leading to apoptosis. It is also suggested that the HSP-inducing activity of GGA contributes to the drug's antiulcer activity. This study provides direct genetic evidence that HSPs, after their HSF1-dependent up-regulation, confer gastric protection against the irritant-induced lesions.
Molecular Pharmacology 05/2007; 71(4):985-93. · 4.88 Impact Factor
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ABSTRACT: Cytokines have been implicated in the progression of acetaminophen (APAP)-induced acute liver injury. Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling by inhibiting the JAK-STAT pathway, but their role in APAP hepatotoxicity is unknown. In this present study, we attempted to explore the role of SOCS3 in T cells in APAP-induced liver injury. Mice with a cell-specific overexpression of SOCS3 in T cells (SOCS3Tg, in which Tg is transgenic) exhibited exaggerated hepatic injury after APAP challenge, as evidenced by increased serum alanine aminotransferase levels, augmented hepatic necrosis, and decreased survival relative to the wild-type mice. Adaptive transfer of SOCS3Tg-CD4(+) T cells into T and B cell-deficient RAG-2(-/-) mice resulted in an exacerbated liver injury relative to the control. In SOCS3Tg mice, hepatocyte apoptosis was enhanced with decreased expression of antiapoptotic protein bcl-2, whereas hepatocyte proliferation was reduced with altered cell cycle-regulatory proteins. Levels of IFN-gamma and TNF-alpha in the circulation were augmented in SOCS3Tg mice relative to the control. Studies using neutralizing Abs indicated that elevated IFN-gamma and TNF-alpha were responsible for the exacerbated hepatotoxicity in SOCS3Tg mice. Activation of STAT1 that is harmful in liver injury was augmented in SOCS3Tg hepatocytes. Alternatively, hepatoprotective STAT3 activation was decreased in SOCS3Tg hepatocytes, an event that was associated with augmented SOCS3 expression in the hepatocytes. Altogether, these results suggest that forced expression of SOCS3 in T cells is deleterious in APAP hepatotoxicity by increasing STAT1 activation while decreasing STAT3 activation in hepatocytes, possibly through elevated IFN-gamma and TNF-alpha.
The Journal of Immunology 04/2007; 178(6):3777-85. · 5.79 Impact Factor
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ABSTRACT: Gap junction intercellular communication (GJIC) is considered to play roles in regulation of homeostasis, development and differentiation of many tissues. In the present study, using reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR, we examined expression of Connexins (Cx26, 32, 37, 40, 43 and 45) in the normal lung and lung tumors of mice to determine whether their expressions change during lung tumorigenesis. Cx26, 32 and 40 were expressed similarly in the normal lung tissue and tumors with smaller size (0.5-1.5mm) though expression of Cx32 and 40 decreased in tumors with larger size (>2.5mm). Cx26 was undetectable in larger size tumors. Cx37 and 45 were expressed in both normal lung and larger size tumors but no expression was seen in smaller size tumors. Cx43 was similarly detectable in normal lung, smaller size tumor and larger size tumor, but western blotting showed that Cx43 was phosphorylated during lung tumorigenesis. Thus, it is likely that alteration of expression of these Cx may be involved in expression of the neoplastic phenotype.
Cancer Letters 03/2007; 246(1-2):224-9. · 4.24 Impact Factor
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ABSTRACT: Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling by inhibiting the JAK-STAT signal transduction pathway, but their role in innate immunity remains to be investigated. In the present study, we demonstrate that overexpression of SOCS5 in T cells augments innate immunity during septic peritonitis induced by cecal ligation and puncture (CLP). Mice with a cell-specific overexpression of SOCS5 in T cells (SOCS5 transgenic (Tg)) were resistant to the lethality relative to the wild-type (WT) mice. This was most likely due to the enhanced innate immunity in SOCS5Tg mice, as bacterial burden in SOCS5Tg mice was significantly lower than WT mice. Accumulation of neutrophils and macrophages was augmented in SOCS5Tg mice, an event that was accompanied by increased peritoneal levels of IL-12, IFN-gamma, and TNF-alpha. In vitro bactericidal activities of macrophages and neutrophils were enhanced in SOCS5Tg mice. Both neutrophils and macrophages from WT mice adopted enhanced bacterial killing activity when cocultured with CD4+ T cells from SOCS5Tg mice, relative to CD4+ T cells from WT mice. Adoptive transfer of SOCS5Tg-CD4+ T cells into T- and B cell-deficient RAG-2(-/-) mice resulted in augmented leukocyte infiltration and increased peritoneal levels of IL-12, IFN-gamma, and TNF-alpha after CLP, as compared with the controls. Furthermore, CLP-induced bacterial burden in RAG-2(-/-) mice harboring SOCS5Tg-CD4+ T cells was significantly reduced relative to the controls. These findings provide evidence that intervention of SOCS5 expression in T cells affects innate immunity, which highlight a novel role of T cells during sepsis.
The Journal of Immunology 01/2007; 177(12):8650-7. · 5.79 Impact Factor
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ABSTRACT: Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno-serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case.
Pathology International 12/2006; 56(11):674-7. · 1.62 Impact Factor
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ABSTRACT: To evaluate the effects of the nerve-muscle pedicle (NMP) method on the rat thyroarytenoid (TA) muscle after transection of the recurrent laryngeal nerve (RLN).
Quantitative histologic assessment of the TA muscle after NMP implantation.
Thirty-six Wistar rats were divided into two groups: animals subjected to transection of the left RLN alone (DNV group) and animals subjected to transection of the left RLN followed by immediate transplantation of a NMP flap containing the sternohyoid (SH) muscle and ansa cervicalis nerve branch (NMP group). Animals were killed 2, 4, and 10 weeks after the treatments. The TA muscle stained with hematoxylin-eosin was evaluated quantitatively. The pre- and postsynaptic structures of the neuromuscular junction (NMJ) in the TA muscle were analyzed histochemically. The myosin heavy chain (MyHC) isoforms were evaluated using immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR).
In the NMP group, the TA muscle fiber recovered to almost normal at 10 weeks, and the ratio of the number of synaptophysin-positive nerve terminals to that of alpha-bungarotoxin-positive acetylcholine receptors recovered to 79.8 +/- 11.8% (P < .05, compared with the control). Immunohistochemistry and the RT-PCR method after laser capture microdissection revealed the expression of MyHC isoforms type 2B and type 2A; the latter was detected in the SH muscle but not in the normal or denervated TA muscle.
The NMP method was effective for recovering from the atrophic changes of the TA muscle after transection of the RLN. This was attributed to successful reinnervation by reconstruction of the NMJ, which might change MyHC isoform expression.
The Laryngoscope 06/2006; 116(6):1027-32. · 1.75 Impact Factor
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ABSTRACT: An effective clearance of microbes is crucial in host defense during infection. In the present study, we demonstrate that CC chemokine receptor 8 (CCR8) skews innate immune response during septic peritonitis induced by cecal ligation and puncture (CLP). CCR8 was expressed in resident peritoneal macrophages and elicited leukocytes during CLP in the wild-type CCR8+/+ mice. CCR8-/- mice were resistant to CLP-induced lethality relative to CCR8+/+ mice, and this resistance was associated with an augmented bacterial clearance in CCR8-/- mice. In vitro, peritoneal macrophages from CCR8-/- mice, but not neutrophils, exhibited enhanced bactericidal activities relative to those from CCR8+/+ mice. Upon stimulation with the bacterial component LPS, elevated levels of superoxide generation, lysosomal enzyme release, and nitric oxide generation, effector molecules for bacterial killing were detected in CCR8-/- macrophages relative to CCR8+/+ macrophages. In addition, CCR8-/- macrophages produced significantly higher levels than CCR8+/+ macrophages of several cytokines and chemokines known to augment bactericidal activities of leukocytes that include TNF-alpha, IL-12, macrophage-derived chemokine (MDC/CCL22), macrophage inflammatory protein (MIP)-2, and KC. Altogether, these results indicate that CCR8 may have a negative impact on host defense during septic peritonitis, providing a new paradigm for the role of CCR8 in innate immunity.
The FASEB Journal 03/2006; 20(2):302-4. · 5.71 Impact Factor
