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Akihiko Ito

Publications and source records attributed to Akihiko Ito.

At least 19 recordsLinked to original sources
PubMed2006

Direct interaction between nerves and mast cells mediated by the SgIGSF/SynCAM adhesion molecule.

Accumulating evidence has so far indicated that cross-talk between the nervous and immune systems plays a pivotal role in the pathophysiology of various diseases. As a prototypic demonstration of neuro-immune systems, the interaction between nerves and mast cells has been examined intensively. Anatomically, mast cells are often located in close proximity to nerves. Functionally, both cells communicate with each other in a bi-directional manner. Substance P released from nerves and proteases and cytokines from mast cells have proved to be important mediators in such communication. On the other hand, the molecules involved in membrane-membrane contacts between nerves and mast cells were largely unknown. In 2003, both cells were found to express the identical adhesion molecule, named SynCAM (synaptic cell adhesion molecule) or SgIGSF (spermatogenic immunoglobulin superfamily). Since SgIGSF/SynCAM binds homophilically, its involvement in nerve-mast cell interaction was examined in vitro. Superior cervical ganglia expressed SgIGSF/SynCAM along their neurites. Adhesion to these neurites of mast cells lacking SgIGSF/SynCAM was poor, and this was normalized by ectopic expression of SgIGSF/SynCAM. Moreover, SgIGSF/SynCAM-expressing mast cells were more competent in communicating with the neurites. Further understanding of the adhesion molecule-dependent interaction will be expected to open a new avenue in the field of neuro-immune cross-talk.

Animals↗
PubMed2006

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Acetaminophen↗
PubMed2006

Simultaneous measurement of temperature and chemical species concentrations with a holographic interferometer and infrared absorption.

What is believed to be a new technique that allows for the simultaneous measurement of 2D temperature and chemical species concentration profiles with high spatial resolution and fast time response was developed and tested successfully by measuring a thin layer of fuel vapor created over a volatile fuel surface. Normal propanol was placed in an open-top rectangular container, and n-propanol fuel vapor was formed over the propanol surface in a quiescent laboratory environment. An IR beam with a wavelength of 8-13 mum emitted from a heated plate and a He-Ne laser beam with a wavelength of 632 nm were combined and passed through the n-propanol vapor layer, and both beams were absorbed by the vapor layer. The absorption of the IR beam was recorded by an IR camera, and the He-Ne laser was used to form a holographic interferogram. Two-dimensional temperature and propanol vapor concentration profiles were, respectively, determined by the IR absorption and the fringe pattern associated with the holographic interferogram. This new measurement technique is a significant improvement over the dual wavelength holographic interferometry that has been used previously to measure temperature and fuel concentration, and it is ready for application under different types of fire and flame conditions.

Journal Article↗
PubMed2006

Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma.

BACKGROUND: The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS: The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS: The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index > or = 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS: TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.

Aged↗
PubMed2006

Increased expression of connexin 26 in the invasive component of lung squamous cell carcinoma: significant correlation with poor prognosis.

Reduced expression of connexins (Cxs), gap junction proteins, is frequently reported in malignant cell lines and tumors, whereas recent studies suggested that C x 26, a subtype of Cxs, might help tumor cells acquire malignant phenotypes. To examine this suggestion in the clinical setting, 50 lung squamous cell carcinomas (SCCs) were stained with the anti-C x 26 antibody. No C x 26-specific signals were detectable in 34 tumors (group I; 68%), whereas the remaining 16 were judged positive for C x 26 (group II; 32%). In 14 tumors of group II, C x 26-specific signals were detected not in all SCC cells but in SCC cells facing the tumor stroma or capsule, in which the signals were localized on the plasma membrane. Involved lymph nodes of group-II patients often contained metastatic foci consisting of all C x 26-positive cells. The proportion of C x 26-positive to C x 26-negative SCC cells in the metastatic nodes was larger than that in the corresponding primary tumors. C x 26-positive SCC cells seemed to be more invasive and metastatic than negative ones. Consistently, the 5-year cancer-specific survival rate of group-II patients was significantly lower than that of group-I patients (12.5 vs 38.9%; P=0.0391). Multivariate analysis demonstrated that C x 26 expression (P=0.0448) as well as pathological stage (P=0.0338) and vascular invasion (P=0.0191) were independent, significant prognostic predictors. These results suggest that C x 26 may represent an essential effector for controlling the biological aggressiveness of lung SCC tumor.

Biomarkers, Tumor↗
PubMed2006

Human lung mast cells adhere to human airway smooth muscle, in part, via tumor suppressor in lung cancer-1.

Mast cells infiltrate the airway smooth muscle (ASM) of patients with asthma, an event which is likely to be a key factor in the development of this disease. Adhesion is a fundamental mechanism facilitating cellular cross-talk. We have examined whether human lung mast cells (HLMC) and ASM adhere, and have also examined the mechanism involved. Primary cultures of HLMC and confluent human ASM were cocultured for 30 min, then nonadherent HLMC were removed by centrifugation. HLMC adhered avidly to ASM monolayers (mean +/- SEM adhesion 43.2 +/- 1.2%, n = 41). Adhesion was increased to 58.8 +/- 2.7% by 1 mM Mn2+ (p = 0.015), and was reduced by EDTA and EGTA to 20.5 +/- 1.5% and 21.0 +/- 1.3%, respectively (p < 0.0001). Adhesion-blocking Abs for ICAM-1, VCAM-1, CD18, and the alpha4 and beta1 integrins had no effect on HLMC adhesion. HLMC expressed tumor suppressor in lung cancer-1 (TSLC-1) and blocking this reduced adhesion from 38.5 +/- 4.8% to 28.3 +/- 3.7% (p = 0.004, n = 7). ASM did not express TSLC-1, indicating that TSLC-1 acts as a heterophilic adhesion molecule. In summary, HLMC adhere avidly to ASM in part via TSLC-1 and in part via an as-yet-undefined Ca2+-dependent pathway. This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells.

Asthma↗
PubMed2006

Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus.

Claudins are transmembrane proteins that seal tight junctions, bind with peripheral protein zonula occludens (ZO)-1, and are known to play an important role in several normal tissues and cancers. However, the role of claudin-1 and claudin-7 expressions in esophageal squamous cell carcinoma remains to be clarified. In the present study, we confirmed the expressions of claudin-1, claudin-7, and ZO-1 in the prickle cell layer of the normal human esophageal squamous epithelium. The expressions of claudin-1 and claudin-7 at the invasive front of the esophageal squamous cell carcinoma were analyzed immunohistochemically to clarify their role in tumor progression. Reduced expression of claudin-7 at the invasive front of the esophageal cancer was significantly associated with the depth of invasion (P = .004), stage (P = .038), lymphatic vessel invasion (P = .001), and lymph node metastasis (P = .014). In contrast, significant association was not detected between claudin-1 expression and clinicopathologic factors except for histologic differentiation of the tumor (P = .0029). Comparison of claudin-7 expression at the invasive front of the primary tumor and its corresponding metastatic lymph nodes revealed significant reduction in claudin-7 expression in the metastatic lymph nodes (P = .007). These results suggest that the reduced expression of claudin-7 at the invasive front of esophageal squamous cell carcinoma may lead to tumor progression and subsequent metastatic events. Thus, claudin-7 can be a novel marker for the prediction of lymph node metastasis.

Aged↗
PubMed2006

Molecular mechanisms of mast cell development.

Mast cells are progeny of multipotential hematopoietic stem cells (MHSCs). MHSCs commit to the mast cell lineage in the bone marrow, and the mast cell-committed progenitors leave the bone marrow, migrate in blood, invade connective or mucosal tissue, and then proliferate and differentiate to connective tissue-type or mucosal mast cell. GATA-1, GATA-2, and PU.1 transcription factors seem to be involved i the commitment to mast cells, and MITF, a basic helix-loop-helix leucine zipper-type transcription factor, seems to be involved in the migration, phenotypic expression, and survival of mast cells. KIT ligand (KITL) is the most important cytoline for development of mast cells, and KIT is the receptor of KITL. Tissues of loss-of-function mutants of KIT, KITL, or MITF are deficient in mast cells.

Animals↗
PubMed2006

Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer.

Overexpression of the enhancer of zeste homolog 2 (EZH2) protein, a known repressor of gene transcription, has been reported to be associated with biological malignancy of prostate cancer and several other cancers. The purpose of this study was to examine the expression of EZH2 and analyze its relationship with the clinicopathological features of human gastric cancers. Expression levels of EZH2 mRNA and protein were examined in 13 gastric cancer cell lines and in 83 surgically removed human gastric cancer tissues. Immunohistochemical analysis of the 83 tissue samples and corresponding non-cancerous gastric mucosa showed that EZH2 was more highly expressed in the cancerous than in the non-cancerous tissues, and the expression levels of EZH2 were highly correlated with tumor size, depth of invasion, vessel invasion, lymph node metastasis and clinical stages. Univariate analysis of survival rate calculated by the Kaplan-Meier method revealed that gastric cancer patients with high-level EZH2 expression had poorer prognosis than those expressing no or low levels of EZH2 (P = 0.0271). These findings suggest that overexpression of EZH2 may contribute to the progression and oncogenesis of human gastric cancers, and thus immunohistochemical study of EZH2 expression may serve as a new biomarker for predicting the prognosis of gastric cancers.

Aged↗
PubMed2006

Medicinal carbon tablets for treatment of acetaminophen intoxication: adsorption characteristics of medicinal carbon powder and its tablets.

Adsorption characteristics of medicinal carbon powder (JP 14) for acetaminophen were examined at 37 degrees C using conventional incubation in an attempt to obtain an effective oral dosage form. Hydroxypropyl cellulose (HPC) and maltitol (MT), being able to act as a binding agent, were tested as additives. Tablets of medicinal carbon were produced by the wet granulation method. The rate and extent of adsorption of the medicinal carbon powder were roughly similar in water, JP 14 1st fluid (pH 1.2) and JP 14 2nd fluid (pH 6.8). The relationship between concentrations of free and adsorbed acetaminophen indicated that the adsorption followed the Langmuir mode. The maximal adsorption of acetaminophen in water was 0.219 g per gram medicinal carbon powder, little influenced by the addition of MT, but slightly reduced by the addition of HPC. The tablet prepared using MT as a binding agent displayed a favorable hardness and adequate disintegration time. The tablet showed good adsorption potential for acetaminophen, though the adsorption rate and extent of the tablet were reduced to some extent as compared with powder.

Acetaminophen↗
PubMed2006

Evaluation of binders in the preparation of medicinal carbon tablets by wet granule compression.

Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that can be easily taken. The MC tablets were made by the wet granule compression method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was used as a model drug. The binders were evaluated in terms of formability of the granules and tablets, their strength, disintegration of the tablets, and their effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules at a fairly low concentration, but more MT was needed to obtain the strong granules. The tablets could be formed only when using MT at 120% (w/w) of the MC amount. The tablet displayed good hardness and rapid disintegration. The adsorption potential was not affected by CMC-Na, and slightly prevented by MT. However, the adsorption ability of MC was lowered more with the increase in HPC. The granules and tablets exhibited similar adsorption potentials, which were a little lower than that of MC suspended in MT aqueous solution. Similar adsorption characteristics were also observed in a real drug, acetaminophen. It is suggested that the MC tablets prepared by the wet granule compression using MT as a binder should be useful as a compact dosage form of MC.

Adjuvants, Pharmaceutic↗
PubMed2006

RECS1 is a negative regulator of matrix metalloproteinase-9 production and aged RECS1 knockout mice are prone to aortic dilation.

BACKGROUND: RECS1 is a mechanical stress responsive gene and RECS1 knockout (KO) mice (older than 14 months) are prone to cystic medial degeneration (CMD). The present study was designed to assess whether RECS1 KO mice have altered gelatinase (matrix metalloproteinase (MMP)-2 and MMP-9) levels and whether they are prone to aortic dilation. METHODS AND RESULTS: Aortic and plasma gelatinase levels in RECS1 KO and wild-type (WT) mice were assessed by gelatin zymography and Western blot analysis. Pro-MMP-9 (in the aorta), neutrophil gelatinase-associated lipocalin/MMP-9 complex (NGAL-MMP-9, in plasma), and active-MMP-9 protein levels were more abundant in KO mice throughout adulthood compared with WT mice. Aortic MMP-2, aortic MMP-9, and plasma MMP-9 activation increased with age, even though the aortic pro-MMP-9, plasma NGAL-MMP-9, aortic and plasma pro-MMP-2 production decreased: this was true both for the WT and KO animals. Aortic pro-MMP-2, aortic active-MMP-2, and plasma pro-MMP-2 protein levels were higher in the aged KO mice, but they were lower in the young KO mice than those in WT mice. Thoracic aortic dilation was observed only in the aged KO mice. In situ zymographic experiments confirmed that the increased aortic gelatinase activities were associated with CMD and aortic dilation observed in the aged KO mice. CONCLUSIONS: RECS1 negatively regulates aortic MMP-9 production and knocking out RECS1 induces susceptibility to aortic dilation as well as CMD in the aged mice. The present study suggests that RECS1 plays protective roles in vascular remodeling. We speculate that inhibiting unfavorable deposition and extracellular matrix degradation are both important for prevention and treatment of aneurysms.

Aging↗
PubMed2006

RECS1 deficiency in mice induces susceptibility to cystic medial degeneration.

RECS1 is a novel shear stress-responsive gene that encodes a protein putatively forming seven-span transmembrane domains. We reports here that mouse RECS1 (mRECS1) transcripts is detected in most tissues except for thymus, spleen and testis. The putative cytoplasmic N-terminus of mRECS1 has a high content of proline (23%) and glycine (12%) residues, contains one PPXY motif, multiple PXXP motifs and one overlapping P(T/S)AP and PPXY motif (P(T/S)APPXY). The PPXY motif lies within one potential PEST sequence (PEST score: +7.65). We prepared anti-RECS1 polyclonal antibody and found by western blot analysis that the mRECS1 protein in the lung and aorta was detected as a 34.4 kDa band. However, one shifted 58 kDa band or three shifted bands (48, 69, 82 kDa) were detected in the heart or the liver, respectively. Since northern blot detected only one species of mRECS1 mRNA in heart and liver tissues, as well as other tissues (approximately 2.2 kb), these differences in molecular weight seem to be due to posttranslational modification. Biochemical fractionation and RECS1-GFP fusion protein revealed that RECS1 localizes at the endosomal/lysosomal membranes in the cytoplasm. To understand the function of RECS1 in the body, we made RECS1 knockout (KO) mice and found that RECS1 KO mice (older than 14 months) are prone to cystic medial degeneration (CMD). Taken together, we conclude that RECS1 is an endosomal/lysosomal membrane protein which plays protective roles in vascular remodeling.

Amino Acid Sequence↗
PubMed2005

Sildenafil as adjunct therapy to high-dose epoprostenol in a patient with pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease is refractory to medical treatment and is generally associated with a poor prognosis. Treatment with vasodilators, such as prostacyclin, of patients with PVOD is controversial because of concerns regarding hemodynamic deterioration. Although a preferential pulmonary vasodilatory effect of a specific phosphodiesterase-5 inhibitor, sildenafil, has recently been reported in patients with primary pulmonary hypertension, little information is available regarding the effect of sildenafil on patients with pulmonary veno-occlusive disease. In the present case, remarkable improvement of hemodynamics and of clinical course was produced by adjunctive use of oral sildenafil in association with intravenous high-dose epoprostenol. These findings suggest that sildenafil may be a therapeutic option in the medical treatment of pulmonary veno-occlusive disease.

Adult↗
PubMed2005

The spermatogenic Ig superfamily/synaptic cell adhesion molecule mast-cell adhesion molecule promotes interaction with nerves.

Nerve-mast cell interaction is involved in both homeostatic and pathologic regulations. The molecules that sustain this association have not been identified. Because synaptic cell adhesion molecule (SynCAM), alternatively named spermatogenic Ig superfamily (SgIGSF), is expressed on both nerves and mast cells and because it binds homophilically, this molecule may be a candidate. To examine this possibility, mast cells with or without SgIGSF/SynCAM were cocultured with superior cervical ganglion neurons that express SgIGSF/SynCAM, and the number of mast cells attached to neurites was counted. The attachment of mast cells with SgIGSF/SynCAM, i.e., bone marrow-derived mast cells (BMMC) from wild-type mice, was inhibited dose-dependently by blocking Ab to SgIGSF/SynCAM. Mast cells without SgIGSF/SynCAM, i.e., BMMC from microphthalmia transcription factor-deficient mice and BMMC-derived cell line IC-2 cells, were defective in attachment to neurite, and transfection with SgIGSF/SynCAM normalized this. When the nerves were specifically activated by scorpion venom, one-quarter of the attached IC-2 cells mobilized Ca(2+) after a few dozen seconds, and ectopic SgIGSF/SynCAM doubled this proportion. At points of contact between neurites and wild-type BMMC, SgIGSF/SynCAM was locally concentrated in both neurites and BMMC. SgIGSF/SynCAM on mast cells appeared to predominantly mediate attachment and promote communication with nerves.

Animals↗
PubMed2005

A B56 regulatory subunit of protein phosphatase 2A localizes to nuclear speckles in cardiomyocytes.

Protein phosphatase 2A (PP2A) is widely distributed in heart tissues, yet its precise cellular functions are poorly understood. This study is based on the notion that PP2A action is governed by interactions of the core enzyme with B targeting/regulatory subunits. The subcellular localizations of two B subunits, B56alpha and B56gamma1, were assessed using adenovirus-driven expression of epitope-tagged (hemagglutinin, HA) in cultured neonatal and adult rat ventricular myocytes. Confocal imaging revealed that HA-B56alpha was excluded from the nucleus and decorated striated structures, whereas HA-B56gamma1 was principally found in the nucleus. Precise immunolabeling studies showed that B56gamma1 was concentrated in intranuclear structures known as nuclear speckles, macromolecular structures that accumulate transcription and splicing factors. Western blot analyses revealed that overexpression of either B subunit had no effect on the levels of other PP2A subunits in cultured neonatal cardiac cells. However, overexpression of only B56gamma1 increased whole cell PP2A activity by 40% when measured in cell extracts. Finally, B56gamma1 did not alter global gene expression or expression of hypertrophic gene markers such as alpha-skeletal actin. However, morphometric analyses of confocal images revealed that B56gamma1 alters the dynamic assembly/disassembly process of nuclear speckles in heart cells. These studies provide new insight into mechanisms of PP2A targeting in the subnuclear architecture in cardiomyocytes and into the role of this phosphatase in nuclear signaling.

Amino Acid Sequence↗