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Biomedical subjects

Tetsuya Yamamoto

Publications and source records attributed to Tetsuya Yamamoto.

At least 55 records · Page 3Linked to original sources
PubMed2005

DNA identification of the pathogen of candidal aspiration pneumonia induced in the course of oral cancer therapy.

Aspiration of oropharyngeal bacteria and fungi is occasionally suspected in patients with pneumonia. A patient with oral carcinoma underwent chemoradioimmunotherapy and, about 4 weeks from the start of the therapy, the patient suffered from severe oral mucositis induced by chemoradiotherapy, and candidal pneumonia was subsequently induced. The candidal pneumonia was insufficiently improved by potent antifungal drugs, taking a lethal course. Randomly amplified polymorphic DNA analysis and DNA sequence examination of strains isolated from the oral cavity 1 week before the onset of pneumonia and autopsied lung revealed the identity of both strains as Candida albicans, and the DNA analysis supported aspiration of oral Candida. These results indicate that the pathogen of the pneumonia, C. albicans, was aspirated from the oral cavity and that oral Candida is easily aspirated and becomes the pathogen of pneumonia.

Aerosols↗
PubMed2005

Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells.

The transcriptional factor hypoxia-inducible factor-1 (HIF-1) plays an important role in solid tumor cell growth and survival. Overexpression of HIF-1alpha has been demonstrated in many human tumors and predicts a poor response to chemoradiotherapy. We examined the HIF-1alpha-induced survival pathways in human oral squamous cell carcinoma cell (OSCC) lines. The results showed that forced expression of HIF-1alpha suppressed hypoxia-induced apoptosis of OSCC lines by inhibiting cytochrome c release from mitochondria. Overexpression of HIF-1alpha inhibited the generation of reactive oxygen species (ROS), elevation of intracellular Ca(2+) concentration, reduction of mitochondrial membrane potential, and cytosolic accumulation of cytochrome c, which resulted in the inactivation of caspase-9 and caspase-3. In addition, antiapoptotic Bcl-2 and Bcl-X(L) levels were increased and pro-apoptotic Bax and Bak levels were decreased in the HIF-1alpha-overexpressing OSCC line. Overexpression of HIF-1alpha also increased the levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK). These findings indicate that HIF-1alpha prevents apoptotic cell death through two mechanisms, including inhibition of cytochrome c release and activation of Akt and ERK.

Apoptosis↗
PubMed2005

Tissue type plasminogen activator facilitates NMDA-receptor-mediated retinal apoptosis through an independent fibrinolytic cascade.

PURPOSE: To investigate the association between apoptosis and the fibrinolytic system in retinal cell damage. METHODS: Tissue type plasminogen activator-deficient (tPA(-/-)), urokinase type plasminogen activator-deficient (uPA(-/-)), plasminogen activator inhibitor-1-deficient (PAI-1(-/-)), alpha2 antiplasmin-deficient (alpha2 AP(-/-)) mice, and their wild-type counterparts were used. Retinal cell damage was induced by intravitreal injection of the excitotoxin N-methyl-d-aspartate (NMDA). The TdT-dUTP terminal nick-end labeling (TUNEL) method was used to examine retinal cell damage. RESULTS: tPA(-/-) mice were resistant to retinal cell damage caused by administration of NMDA, and PAI-1(-/-) mice were more injured than their wild-type. No significant difference was observed between uPA(-/-) or alpha2 AP(-/-) and their wild-type mice. CONCLUSIONS: The results strongly suggest that endogenous tPA, but not uPA acts as a facilitator in NMDA-induced retinal cell damage, and that its mechanism may not be associated with cleavage of plasminogen into plasmin in the fibrinolytic cascade.

Animals↗
PubMed2005

Autoimmune thyroid disease (Graves' disease and hashimoto's thyroiditis) in two patients with Crohn's disease: case reports and literature review.

An increased prevalence of the association between autoimmune thyroid diseases and ulcerative colitis has been suggested, however, not with Crohn's disease, as only 7 cases of thyroid disease coexisting with Crohn's disease have been reported. Herein, we describe 2 patients with Crohn's disease complicated with Graves' disease or autoimmune thyroiditis, and also review other cases with those complications. Some immunological processes are suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.

Adult↗
PubMed2005

[Difference of optic disc topography between a low-tension group and a high-tension group in normal-tension glaucoma patients].

PURPOSE: Glaucomatous visual field loss and optic disc damage differ by intraocular pressure (IOP) levels. In this study, we compared the optic disc topography in the high-tension group and the low-tension group in normal-tension glaucoma (NTG). METHOD: We selected NTG patients with mean deviation (MD) > or = -10.00 dB and the highest recorded IOP of < 14 mmHg or > or = 17 mmHg without glaucoma treatment. We classified NTG eyes into the following two groups: 1) a low-tension group with the highest recorded IOP of < 14 mmHg, 2) a high-tension group with the highest recorded IOP of > or = 17 mmHg. The optic disc parameters in the low-tension group eyes were compared with those in the high-tension group eyes using a Heidelberg Retina Tomograph. RESULTS: Nineteen eyes of nineteen patients were selected for each group. The cup/disc area ratio in the global sector, and the rim volume in the nasal sector of the low-tension group had deteriorated more than in the high-tension group. CONCLUSIONS: The disc topography is different between the low-tension group and the high-tension group in the nasal sector, suggesting that different pathogenetic mechanisms exist in the optic disc damage in NTG.

Aged↗
PubMed2004

Physical and functional interactions between STAP-2/BKS and STAT5.

Signal-transducing adaptor protein family of proteins (STAPs), which currently contains two members, are proposed to be adaptor molecules because of their pleckstrin homology (PH) and Src-homology 2 (SH2)-like domains. STAP-1 has been shown to interact with STAT5 and the tyrosine kinase Tec. With regard to STAP-2/BKS functions, immunoprecipitation experiments and intracellular stainings revealed STAP-2/BKS binds STAT5 in several types of cells. Mutational studies revealed that the PH- and SH2-like domains of STAP-2/BKS interacted with the C-terminal region of STAT5. STAP-2/BKS and STAT5 were found to constitutively co-localize in the cytoplasm of resting cells, but STAP-2/BKS was found to dissociate upon STAT5 phosphorylation, suggesting a role in regulating signaling of STAT5. The physiological role of these interactions is not fully understood, but in studies of overexpression of STAP-2/BKS, cytokine-induced tyrosine phosphorylation and transcriptional activation of STAT5 was diminished. In addition, thymocytes from STAP-2/BKS-deficient mice showed the enhanced interleukin-2-dependent cell growth. Taken together, STAP-2/BKS is an additional modulator of STAT5-mediated signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14.

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.

Caspase 14↗
PubMed2004

Enhancement of sodium borocaptate (BSH) uptake by tumor cells induced by glutathione depletion and its radiobiological effect.

Sodium borocaptate (BSH) is widely used for boron neutron capture therapy (BNCT) of brain tumors. However, the mechanism of uptake by the tumor remains unclear. We investigated the sulfhydryl moiety of this compound. Down regulation of glutathione (GSH) by buthionine sulfoximine in cultured cells resulted in increase of BSH uptake (7.9-36.5%) compared to the control group and consequently the cytocidal effect of neutron irradiation also increased. On the other hand, the radiation caused damage by gamma-ray irradiation was suppressed when BSH uptake increased. These findings suggested that modulation of GSH enhanced the effect of B (n, alpha) reaction and the protective effect of secondary gamma-ray in BNCT.

Animals↗
PubMed2004

Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage.

To investigate the role of tissue plasminogen activator (tPA) in retinal damage, tPA-deficient and wild-type mice were employed. Two different retinal neuron insult models were used in the present study. One is an excitotoxin-treated retinal model, created by direct intravitreal injection of glutamate analogs, NMDA or kainic acid (KA), and the other is an ischemia-reperfusion model induced by transient elevation of intraocular pressure. TdT-dUTP terminal nick-end labeling (TUNEL) method was used to examine the retinal cell nuclear damage. The number of TUNEL-positive cells in ganglion cell layer (GCL) and inner nuclear layer (INL) in tPA-deficient mice after low-, but not high-dose NMDA was significantly less compared to wild type. In contrast, neither intravitreal KA or transient ischemia produced significant difference in retinal damage in tPA vs. wild-type mice. These data show that tPA-deficient mice are resistant to retinal damage by intravitreal injection of NMDA, and indicate that tPA plays a role in the retinal cell damage induced by excitotoxins, especially NMDA.

Animals↗
PubMed2004

The RING domain of PIASy is involved in the suppression of bone morphogenetic protein-signaling pathway.

Bone morphogenetic proteins (BMPs) play central roles in differentiation, development, and physiologic tissue remodeling. Recently, we have demonstrated that a protein inhibitor of activated STAT, PIASy, suppresses TGF-beta signaling by interacting with Sma and MAD-related protein 3 (Smad3). In this study, we examined a PIASy-dependent inhibitory effect on BMP signaling. PIASy expression was induced by BMP-2 stimulation and suppressed BMP-2-dependent Smad activity in hepatoma cells. Furthermore, BMP-2-regulated Smads directly bound to PIASy. We also demonstrated that the RING domain of PIASy played an important role in PIASy-mediated suppression of Smad activity. We here provide evidence that the inhibitory action of PIASy on BMP-regulated Smad activity was due to direct physical interactions between Smads and PIASy through its RING domain.

Blotting, Northern↗
PubMed2004

Molecular-scale observation of formation of nuclei in soap-free polymerization of styrene.

To clarify the mechanism of the nucleation process in the soap-free polymerization of styrene in water, the polymerization process of styrene mainly at a temperature 46 degrees C was investigated on a molecular scale using an atomic force microscope (AFM) as well as a scanning electron microscope (SEM) and a dynamic light scattering apparatus (DLS). A cationic initiator was employed to make polymerized styrene adsorb electrostatically on the negatively charged mica plate with molecular-scale smoothness, and the mechanism was estimated from their AFM measurements in situ in water. The following was found. There exist two streams to produce PSL particles in the polymerization: one is the polymerization in monomer droplets fragmented by mixing from the main monomer reservoir floating above the solution, and the other is the polymerization of monomers dissolved in the solution by initiators. The former is normally neglected or not recognized because of the small contribution. The latter is the main production process of PSL particle, which is investigated in detail on a molecular scale, and a possible mechanism was proposed.

Journal Article↗
PubMed2004

Fragmented DNA transport in dendrites of retinal neurons during apoptotic cell death.

Movement of fragmented DNA in dendrites of retinal neurons during the apoptotic cell death was investigated. The time-course of the movement of fragmented DNA in dendrites of retinal neurons undergoing apoptotic cell death induced by intravitreal N-methyl-d-aspartate (NMDA) injection were examined by in situ terminal dUTP-biotin nick end labeling of DNA fragments (TUNEL) method and fluorescence DNA detection technique by 4',6-diamidino-2-phenylindole (DAPI). The inhibitory effect of axoplasmic transport inhibitor, vincristine was also tested on the NMDA-induced fragmented DNA transport. The movement of fragmented DNA from apoptotic nuclei toward peripheral ends of the dendrites of the retinal neurons was clearly demonstrated. The transport of fragmented DNA, but not fragmentation per se, was completely inhibited by the co-administration of vincristine.

Animals↗
PubMed2004

Physical and functional interactions between Daxx and TSG101.

Daxx has been reported to mediate the Fas/JNK-dependent signals in the cytoplasm. However, several evidences have suggested that Daxx is located mainly in the nucleus and functions as a transcriptional regulator. Recently, we identified DMAP1, a TSG101-interacting protein as a Daxx binding partner by yeast two-hybrid screening. TSG101 has been shown to act as transcriptional co-repressor of nuclear hormone receptors. Here we examined whether TSG101also interacts with Daxx directly. The association of Daxx and TSG101 was confirmed using co-expressed tagged proteins. The interaction regions in both proteins were also mapped, and the cellular localization of the interaction was examined. TSG101 formed a complex with Daxx through its coiled-coil domain and co-localized in the nucleus. Furthermore, TSG101 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. These results provide the novel molecular interactions between Daxx and TSG101, which establish an efficient repressive transcription complex in the nucleus.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Cross-talk between endocrine-disrupting chemicals and cytokine signaling through estrogen receptors.

STAT3 mainly acts as a signal transducer of IL-6 family cytokines and transcriptionally activates specific target genes. STAT3 has also been demonstrated to mediate cellular transformation and is found in numerous cancers. Endocrine-disrupting chemicals (EDCs) are a diverse group of chemicals that bind to estrogen receptors (ERs), mimic estrogenic actions, and may have adverse effects on human health. In our previous study, we demonstrated that estrogens suppressed the STAT3-mediated transcription activity through ERs. In this study, we examined the effects of EDCs on STAT3-mediated signaling through ERs. Surprisingly, some of EDCs enhanced STAT3-mediated transcription activity through ERs. This finding strongly suggests that EDCs may play an important role in the endocrine functions by mimicking cytokine activity by stimulating STAT3 actions through ERs.

Cell Line, Tumor↗
PubMed2004

Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1.

Daxx has been shown to play an essential role in type I IFN-alphabeta-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify how Daxx regulates B cell development, we examined Daxx interacting partners by yeast two-hybrid screening. DNA methyltransferase 1 (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact with Daxx. The interaction regions in both proteins were mapped, and the cellular localization of the interaction was examined. Both Daxx and DMAP1 formed a complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx protected protein degradation of DMAP1 in vivo. These results provide the novel molecular link between Daxx and DNMT1, which establishes a repressive transcription complex in the nucleus.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Involvement of NF-kappaB in TGF-beta-mediated suppression of IL-4 signaling.

Control of immune response requires the coordinated integration of both stimulatory and inhibitory factors. Therefore, the cross-talk of different signaling pathways is critical in providing an integrated cellular response to multiple external signals. Both interleukin-4 (IL-4) and transforming growth factor (TGF-beta) are pleiotropic cytokines and play critical roles in controlling immune responses. For example, IL-4 mediates important pro-inflammatory functions in asthma including induction of the IgE isotype switch and expression of vascular cell adhesion molecules. Whereas, TGF-beta is secreted from B, T, and dendritic cells as well as macrophages, and negatively regulates their proliferation, differentiation, and activation by other cytokines. In this study, we examined the effect of TGF-beta on IL-4 signaling using B cells as well as embryonic kidney cells. TGF-beta inhibited IL-4-induced IgG1 production and gene expression of germline epsilon transcripts in B cells. In embryonic kidney cells, TGF-beta signals suppressed IL-4-induced transcription, when we monitored using germline epsilon promoter DNA. Furthermore, activation of NF-kappaB resulted in a resistance to TGF-beta-mediated suppression of IL-4 signaling. These results indicate that TGF-beta-mediated regulation of IL-4 signaling may act by targeting NF-kappaB signaling.

Animals↗
PubMed2004

Oxidized low-density lipoprotein autoantibodies in patients with primary gout: effect of urate-lowering therapy.

BACKGROUND: Uric acid is a strong scavenger of reactive oxygen species, which are known to contribute to the development of atherosclerosis, while the incidence of atherosclerotic diseases is rather high in patients with gout. Among the established risk factors for atherosclerosis, oxidized LDL is believed to play a major role in its development and progression. Allopurinol and its active metabolite, oxypurinol, have been suggested to possess an antioxidant ability to scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The objective of this work was to determine the degree of LDL oxidation in gout and the effect of allopurinol on LDL oxidation. METHODS: Age-matched male patients with primary intercritical gout and healthy male adults were included in the study. The serum concentrations of oxidized LDL autoantibodies and total antioxidant status were measured using an enzyme immunoassay. RESULTS: Serum concentrations of oxidized LDL autoantibodies were significantly higher in patients with gout than the control subjects (p < 0.05) and were significantly decreased after allopurinol treatment (p < 0.05), but not by benzbromarone treatment, in spite of the similar concentrations of uric acid and total antioxidant status in serum following their separate administration. CONCLUSIONS: Although the exact mechanism remains unclear, increased serum concentrations of oxidized LDL may play a role in the high incidence of coronary artery disease in gout. In addition, allopurinol may be more preferable to benzbromarone for treatment of gout in light of its inhibitory action toward LDL oxidation.

Allopurinol↗