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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 19 recordsLinked to original sources
PubMed2007

TRPA1.

The TRPA1 protein has up to 18 N-terminal and presumed cytoplasmic ankyrin repeats followed by the six membrane spanning and single pore-loop domains characteristic of all TRPs. In mice, TRPA1 is almost exclusively expressed in nociceptive neurons of peripheral ganglia and in all the mechanosensory epithelia of inner ear. In nociceptive neurons, TRPA1 mediates the response to the proalgesic bradykinin as well as the response to pungent irritants found in mustards and garlic, and probably also to those found in cinnamon and tear gas. The channel properties of TRPA1 are discussed and compared to those of sensory transducers. TRPA1 is well conserved across the animal kingdom, with likely orthologs from human to nematode, which suggest an ancestral role for this channel, probably in sensation.

Animals↗
PubMed2006

Keyword extraction, ranking, and organization for the neuroinformatics platform.

Brain-related researches encompass many fields of studies and usually involve worldwide collaborations. Recognizing the value of these international collaborations for efficient use of resources and improving the quality of brain research, the International Neuroinformatics Coordinating Facility (INCF) started to coordinate the effort of establishing neuroinformatics (NI) centers and portal sites among the different participating countries. These NI centers and portal sites will serve as the conduit for the interchange of information and brain-related resources among different countries. In Japan, several NI platforms under the support of NIJC (NI Japan Center) are being developed with one platform called, Visiome, already operating and publicly accessible at "http://www.platform.visiome.org". Each of these platforms requires their own set of keywords that represent important terms covering their respective fields of study. One important function of this predefined keyword list is to help contributors classify the contents of their contributions and group related resources. It is vital, therefore, that this predefined list should be properly chosen to cover the necessary areas. Currently, the process of identifying these appropriate keywords relies on the availability of human experts which does not scale well considering that different areas are rapidly evolving. This problem prompted us to develop a tool to automatically filter the most likely terms preferred by human experts. We tested the effectiveness of the proposed approach using the abstracts of the Vision Research Journal (VR) and Investigative Ophthalmology and Visual Science Journal (IOVS) as source files.

Animals↗
PubMed2006

A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion.

We herein describe a 4-year-old boy who after being treated for pneumonia showed an abnormal shadow at the hilus of the right lung on chest X-rays with continued inflammatory findings in his laboratory data. CT and MR investigations suggested the existence of a neoplasm at that site. An open biopsy was thus performed for a definite diagnosis. The histological findings and the expression of TPM3-ALK fusion gene confirmed a diagnosis of an inflammatory myofibroblastic tumor. A right upper and middle lobectomy including the tumor was thus performed for a complete resection. In addition to the histological diagnosis, the detection of the tumor specific fusion gene provided objective evidence in making a diagnosis.

Anaplastic Lymphoma Kinase↗
PubMed2006

Treatment of post-dialytic orthostatic hypotension with an inflatable abdominal band in hemodialysis patients.

The purpose of this study was to ascertain whether abdominal compression with an inflatable abdominal band, a device we developed, improved post-dialytic orthostatic hypotension (OH) in hemodialysis (HD) patients. Twenty-five chronic HD patients with intractable post-dialytic OH were recruited. Post-HD changes in systolic blood pressure (DeltaSBP) in the supine and standing positions were compared in the patients, measured with or without the use of the band. The study showed DeltaSBP after HD without the band was significantly greater than that measured before HD (-36.1+/-18.2 vs -13.1+/-16.8 mm Hg; P<0.0001). DeltaSBP after HD with the band was reduced significantly in comparison to DeltaSBP after HD without the band (-19.4+/-21.2 vs -36.1+/-18.2 mm Hg; P<0.002). Use of the band did not cause an elevation in SBP in the supine position (149.0+/-29.6 vs 155.4+/-25.7 mm Hg); however, it did increase SBP upon standing (129.6+/-27.3 vs 117.2+/-22.6 mm Hg; P<0.05). Eight patients in whom an increase in SBP of 25 mm Hg or more was achieved with the band were classified as responders. Ejection fraction was significantly higher (76.4+/-11.1 vs 61.9+/-13.6%; P<0.02) and atrial natriuretic peptide concentration significantly lower (27.9+/-22.0 vs 68.9+/-47.5 pg/ml; P<0.02) in responders than in non-responders. We conclude that the abdominal band was effective for overcoming post-dialytic OH, without elevating supine SBP in some patients.

Abdomen↗
PubMed2006

The usefulness of a continuous administration of tirapazamine combined with reduced dose-rate irradiation using {gamma}-rays or reactor thermal neutrons.

We clarified the usefulness of the continuous administration of tirapazamine (TPZ) in combination with reduced dose-rate irradiation (RDRI) using gamma-rays or reactor thermal neutrons. Squamous cell carcinoma (SCC) VII tumour-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. Then, they received a single intraperitoneal injection or 24 h continuous subcutaneous infusion of TPZ in combination with conventional dose-rate irradiation (CDRI) or RDRI using gamma-rays or thermal neutrons. After irradiation, the tumour cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumour cells was determined using tumours that were not pre-treated with BrdU. The sensitivity of both total and Q cells, especially of Q cells, was significantly reduced with RDRI compared with CDRI. Combination of TPZ increased the sensitivity of both populations, with a slightly more remarkable increase in Q cells. Furthermore, the continuous administration of TPZ raised the sensitivity of both total and Q cell populations, especially the former, more markedly than the single administration, whether combined with CDRI or RDRI using gamma-rays or thermal neutrons. From the viewpoint of solid tumour control as a whole, including intratumour Q-cell control, the use of TPZ, especially when administered continuously, combined with RDRI, is useful for suppressing the reduction in the sensitivity of tumour cells caused by the decrease in irradiation dose rate in vivo.

Animals↗
PubMed2006

Localization and ontogeny of damage-induced neuronal endopeptidase mRNA-expressing neurons in the rat nervous system.

Neuropeptides are crucial mediators in nervous and endocrine systems. Processing and degradation, the major regulatory mechanisms, of enzymes are essential for the control of these peptidergic intercellular signaling systems. Damage-induced neuronal endopeptidase (or endothelin converting enzyme-like1), a member of the neprilysin family, has recently been identified as an M13 zinc metalloprotease. Damage-induced neuronal endopeptidase mRNA expression is strikingly restricted to neurons, and is remarkably induced in response to various types of neuronal injuries, although its function and substrate remain unknown. To clarify the role of damage-induced neuronal endopeptidase, we examined the localization and ontogeny of damage-induced neuronal endopeptidase mRNA expression in the rat nervous system using in situ hybridization. Damage-induced neuronal endopeptidase mRNA was detected at embryonic day 12, and its expression restricted to the ventral region of the neural tube. Subsequently, expression was also apparent in primordia of the striatum, hypothalamus, and cranial motor nuclei during neural development. This specific distribution was relatively maintained in the adult brain, although expression levels became weaker. Expression of damage-induced neuronal endopeptidase was absent in the cerebral cortex, hippocampus, and cerebellum. In addition to prominent expression in CNS, intestinal and sensory ganglia and retina demonstrated transient intense damage-induced neuronal endopeptidase mRNA expression during the embryonic period that then declined, and disappeared after birth. The results indicated that damage-induced neuronal endopeptidase might play an important role in embryonic neural development, in particular in peripheral ganglia derived from the neural crest, and in some neurons originating from the basal plate such as the hypothalamus and cranial motor neurons.

Age Factors↗
PubMed2006

Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity.

The efficient clearance of toxic bile acids such as lithocholic acid (LCA) requires drug-metabolizing enzymes. We therefore assessed the influence of pregnenolone 16alpha-carbonitrile (PCN) treatment on LCA-induced hepatotoxicity and disposition of LCA metabolites using female farnesoid X receptor (FXR)-null and wild-type mice. Marked decreases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and hepatic tauroLCA (TLCA) concentrations were found in LCA-fed wild-type mice co-treated with PCN. Whereas induction of Cyp3a and hydroxysteroid sulfotransferase (Sult2a) proteins was observed in FXR-null and wild-type mice, clear increases in biliary 3alpha-sulfated TLCA but not total 6alpha-hydroxy LCA (taurohyodeoxycholic acid and hyodeoxycholic acid) were only observed in PCN-treated wild-type mice. Biliary 3alpha-sulfated TLCA output rate was increased 7.2-fold, but accounts for only 4.2% of total bile acid output rate in LCA and PCN-co-treated wild-type mice. Total 3alpha-sulfated LCA (LCA and TLCA) was, however, the most abundant bile acid component in faeces suggesting that efficient faecal excretion of biliary 3alpha-sulfated TLCA through escape from enterohepatic circulation. FXR-null mice, which have constitutively high levels of the Sult2a protein, were fed a diet supplemented with 1% LCA and 0.4% dehydroepiandrosterone (DHEA), a typical Sult2a substrate/inhibitor. The faecal total 3alpha-sulfated bile acid excretion was reduced to 62% of FXR-null mice fed only the LCA diet. Hepatic TLCA concentration and serum AST activity were significantly higher in FXR-null mice fed DHEA and LCA diet than in FXR-null mice fed the LCA diet or DHEA diet. These results suggest that hepatic formation of 3alpha-sulfated TLCA is a crucial factor for protection against LCA-induced hepatotoxicity.

Animals↗
PubMed2006

Expression of granulysin in polymyositis and inclusion-body myositis.

BACKGROUND: Granulysin, a recently defined cytolytic molecule, is expressed in cytotoxic T cells and natural killer cells in a similar way to perforin, which is reported to have a major role in the pathogenesis of polymyositis and inclusion-body myositis (IBM). OBJECTIVE: To clarify the role of granulysin in polymyositis and IBM. METHODS: The expression of granulysin and perforin was examined by double staining with CD8, CD4 and CD56 in endomysial infiltrating cells and autoinvasive cells in muscle biopsy specimens of 17 patients with polymyositis (6 steroid resistant and 11 steroid responsive) and of 7 patients with IBM. RESULTS: Similar to perforin, granulysin was expressed in CD8, CD4 or CD56 cells in patients with polymyositis and IBM. The ratio of cells double positive for granulysin and CD8 to all CD8 cells at endomysial sites was notably higher in steroid-resistant polymyositis than in steroid-responsive polymyositis and IBM. CONCLUSION: Granulysin expression in CD8 cells seems to be correlated with steroid resistance in polymyositis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2006

An immunohistological study of the integration at the bone-tendon interface after reconstruction of the anterior cruciate ligament in rabbits.

We studied bone-tendon healing using immunohistochemical methods in a rabbit model. Reconstruction of the anterior cruciate ligament was undertaken using semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were performed at one, two, four and eight weeks after the operation. The expression of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the bone-tendon interface was very similar to that in the endochondral ossification. Some of the type-III collagen in the outer layer of the graft, which was deposited at a very early phase after the operation, was believed to have matured into Sharpey-like fibres. However, remodelling of the tendon grafted into the bone tunnel was significantly delayed when compared with this ossification process. To promote healing, we believe that it is necessary to accelerate remodelling of the tendon, simultaneously with the augmentation of the ossification.

Animals↗
PubMed2006

Positron-emission tomography of brain regions activated by recognition of familiar music.

BACKGROUND AND PURPOSE: We can easily recognize familiar music by listening to only one or 2 of its opening bars, but the brain regions that participate in this cognitive processing remain undetermined. We used positron-emission tomography (PET) to study changes in regional cerebral blood flow (rCBF) that occur during listening to familiar music. METHODS: We used a PET subtraction technique to elucidate the brain regions associated with the recognition of familiar melodies such as well-known nursery tunes. Nonmusicians performed 2 kinds of musical tasks: judging the familiarity of musical pieces (familiarity task) and detecting deliberately altered notes in the pieces (alteration-detecting task). RESULTS: During the familiarity task, bilateral anterior portions of bilateral temporal lobes, superior temporal regions, and parahippocampal gyri were activated. The alteration-detecting task bilaterally activated regions in the precunei, superior/inferior parietal lobules, and lateral surface of frontal lobes, which seemed to show a correlation with the analysis of music. CONCLUSION: We hypothesize that during the familiarity task, activated brain regions participate in retrieval from long-term memory and verbal and emotional processing of familiar melodies. Our results reinforced the hypothesis reported in the literature as a result of group and case studies, that temporal lobe regions participate in the recognition of familiar melodies.

Adult↗
PubMed2005

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

Adenoma↗
PubMed2005

Human artificial chromosome (HAC) vector provides long-term therapeutic transgene expression in normal human primary fibroblasts.

Human artificial chromosomes (HACs) segregating freely from host chromosomes are potentially useful to ensure both safety and duration of gene expression in therapeutic gene delivery. However, low transfer efficiency of intact HACs to the cells has hampered the studies using normal human primary cells, the major targets for ex vivo gene therapy. To elucidate the potential of HACs to be vectors for gene therapy, we studied the introduction of the HAC vector, which is reduced in size and devoid of most expressed genes, into normal primary human fibroblasts (hPFs) with microcell-mediated chromosome transfer (MMCT). We demonstrated the generation of cytogenetically normal hPFs harboring the structurally defined and extra HAC vector. This introduced HAC vector was retained stably in hPFs without translocation of the HAC on host chromosomes. We also achieved the long-term production of human erythropoietin for at least 12 weeks in them. These results revealed the ability of HACs as novel options to circumvent issues of conventional vectors for gene therapy.

Cells, Cultured↗
PubMed2005

Calcified intervertebral disc herniation in a child with myelopathy treated with laminoplasty.

STUDY DESIGN: Case report. OBJECTIVE: To describe a case of pediatric calcified intervertebral disc herniations at the cervical-thoracic junction surgically treated with laminoplasty. METHODS: A 13-year-old girl with calcified intervertebral disc herniations at C7/Th1 and Th1/2 causing myelopathy was performed with laminoplasty . RESULTS: Postoperative course was without complication, and the neurologic examination returned to a completely normal state at 5 years to date after surgery. CONCLUSIONS: Laminoplasty produced an excellent result and is a consideration for treatment of similar cases of calcified intervertebral disc herniation.

Calcinosis↗
PubMed2005

Prediction of oral clearance from in vitro metabolic data using recombinant CYPs: comparison among well-stirred, parallel-tube, distributed and dispersion models.

Intrinsic clearances (CLint-HLM-total) for the metabolism of NE-100, metoprolol, clarithromycin (CAM), lornoxicam and tenoxicam were predicted from in vitro data with recombinant cytochorme P450s (CYPs) using relative activity factor (RAF) and then compared with CLint-HLM observed in human liver microsomes (HLM). The predicted CLint-HLM-total correlated well with the observed CLint-HLM in HLM. When oral clearances (CLoral) of low-clearance drugs such as metoprolol, CAM, lornoxicam and tenoxicam were predicted from the in vitro data using four physiological models (well-stirred, parallel tube, distributed and dispersion models), the predicted CLoral corresponded well with the observed CLoralin vivo and were similar among the four models. For a high-clearance drug, the predicted CLoral of NE-100 in extensive CYP2D6 metabolizers (EMs) was substantially different between individual models, although the predicted CLoral in a poor metabolizer of CYP2D6 (PMs) was similar. The CLoral ratio of NE-100 between the EMs and the PMs predicted from the dispersion model, which leads to a reliable prediction for the high-clearance drug, was 48.4, but the ratio decreased depending on the increase of the NE-100 plasma concentration. The results suggest that the CLoral decrease in the EMs is caused by saturation of NE-100 metabolism mediated by CYP2D6 and is based on increases in plasma NE-100 concentrations dependent on the dose of NE-100. The study suggests that the RAF and the in vitro-in vivo scaling approaches are useful for predicting CLoral from in vitro data with recombinant CYPs without using HLM and hepatocytes.

Administration, Oral↗
PubMed2005

The usefulness of continuous administration of hypoxic cytotoxin combined with mild temperature hyperthermia, with reference to effects on quiescent tumour cell populations.

To evaluate the usefulness of continuous administration of hypoxic cytotoxins in terms of targeting acute hypoxia in solid tumours and the significance of combination with mild temperature hyperthermia (MTH) (40 degrees C, 60 min), the cytotoxic effects of singly or continuously administered tirapazamine (TPZ) and TX-402 were examined in combination with or without MTH in vivo. Further, the effects were also analysed on total (=proliferating (P)+quiescent (Q)) and Q cell populations in solid tumours with the method for selectively detecting the Q cell response. C3H/He mice bearing SCC VII tumours received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days to label all P cells. The tumour-bearing mice then received a single intra-peritoneal injection or 24 h continuous subcutaneous infusion of hypoxic cytotoxin, TPZ or TX-402, with or without MTH. On the other hand, to detect the changes in the hypoxic fraction (HF) in the tumours by MTH, another group of mice with or without MTH received a series of test doses of gamma-rays while alive or after tumour clamping. After each treatment, the tumour cells were isolated and incubated with a cytokinesis blocker (=cytochalasin-B) and the micronucleus (MN) frequency in cells without BrdU labelling (=Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total tumour cells was determined from the tumours that were not pre-treated with BrdU. The sensitivity to TX-402 was slightly higher than that to TPZ in both total and Q tumour cells. Continuous administration elevated the sensitivity of both total and Q cells, especially total cells. MTH raised the sensitivity of Q cells more remarkably than that of total cells in both single and continuous administrations. It was thought to be probably because of the higher dose distribution of hypoxic cytotoxin in intermediately hypoxic areas derived mainly from chronic hypoxia through MTH. From the viewpoint of tumour control as a whole including both total and Q tumour cells, the continuous administration of hypoxic cytotoxin combined with MTH may be useful for sensitizing tumour cells in vivo.

Animals↗
PubMed2005

Increase in killer-specific secretory protein of 37 kDa in bronchoalveolar lavage fluid of allergen-challenged patients with atopic asthma.

BACKGROUND: Atopic asthma is linked to a T-helper type 2 dominated pathogenesis, but there is increasing evidence of Th1/Tc1-mediated processes in the aetiopathology of asthma. Killer-specific secretory protein of 37 kDa (Ksp37) is expressed in cytotoxic lymphocytes, selectively in the effector subsets of CD8+- and CD4+ T lymphocytes and in CD16+/CD56dim natural killer cells and gamma/delta T cells. This effector cell-specific expression of Ksp37 and its coexpression with perforin suggest that Ksp37 might be involved in processes mediated by cytotoxic cells. OBJECTIVE: We hypothesize that Ksp37 could indicate the involvement of cytotoxic lymphocytes in the pathogenesis of atopic asthma, and investigated Ksp37 concentration in bronchoalveolar lavage fluid (BALF) collected 10 min, 18, 42 or 162 h after segmental allergen provocation and in serum of patients with atopic asthma (n=25). METHODS: Ksp37 concentrations in BALF and serum were detected by ELISA. Flow cytometric analysis was used to assess numbers and cell subsets in BALF. RESULTS: Ksp37 increased significantly in BALF 10 min, 18 and 42 h, but not 162 h after allergen challenge compared with saline-challenged controls, while Ksp37 serum levels did not change significantly at all time-points. In addition, the increase in Ksp37 concentrations in BALF correlated with the corresponding numbers of lymphocytes. CONCLUSIONS: We conclude that Ksp37 level increased in BALF 10 min, 18 and 42 h after allergen challenge but not in peripheral blood. Our findings suggest that segmental allergen challenge in asthma is associated with an increase in Ksp37 concentrations in BALF and an influx of potentially cytotoxic T lymphocytes into the lungs.

Adolescent↗
PubMed2005

MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

Adult↗