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Biomedical subjects

K Komura

Publications and source records attributed to K Komura.

At least 19 recordsLinked to original sources

Seasonal variations in 228Ra/226Ra ratio within coastal waters of the Sea of Japan: implications for water circulation patterns in coastal areas.

In this study, low-background gamma-spectrometry was used to determine the (228)Ra/(226)Ra ratio of 131 coastal water samples from various environments around Honshu Island, Japan (mainly around Noto Peninsula) at 1-3 month intervals from April 2003 until September 2005. Spatial variation in (228)Ra/(226)Ra ratios was also assessed by analyzing 34 coastal water samples from five areas within the Sea of Japan during May and June 2004. The (228)Ra/(226)Ra ratio of coastal water from all sites around Noto Peninsula shows seasonal variation, with minimum values during summer ((228)Ra/(226)Ra=0.7) and maximum values during autumn-winter ((228)Ra/(226)Ra=1.7-2). This seasonal variation is similar to that recorded for coastal water between Tsushima Strait and Noto Peninsula. The measured lateral variation in (228)Ra/(226)Ra ratios within coastal water between Tsushima Strait and Noto Peninsula is only minor (0.5-0.7; May-June 2004). Coastal waters from two other sites (Pacific shore and Tsugaru Strait, north Honshu) show no clear seasonal variation in (228)Ra/(226)Ra ratio. These measured variations in (228)Ra/(226)Ra ratio, especially the temporal variations, have important implications for seasonal changes in patterns of coastal water circulation within the Sea of Japan.

Environmental Monitoring↗

Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy.

OBJECTIVE: Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). METHODS: Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. RESULTS: Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. CONCLUSIONS: This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

Adult↗

Regulation of local and metastatic host-mediated anti-tumour mechanisms by L-selectin and intercellular adhesion molecule-1.

Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including L-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of L-selectin or combined loss of L-selectin and ICAM-1. In both situations, the combined loss of L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour.

Animals↗

Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.

OBJECTIVE: To determine serum levels of monocyte chemotactic protein-3 (MCP-3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum MCP-3 levels from 69 patients with SSc were examined by ELISA. RESULTS: Serum MCP-3 levels were raised in patients with SSc (n = 69) compared with healthy controls (n = 28). Patients with diffuse cutaneous SSc (n = 36) had higher levels of serum MCP-3 than those with limited cutaneous SSc (n = 33). Patients with raised MCP-3 levels had pulmonary fibrosis and decreased vital capacity (VC) more often than those with normal MCP-3 levels. MCP-3 levels correlated positively with the extent of skin fibrosis, and inversely with %VC and carbon monoxide transfer factor (Tlco) in patients with SSc. CONCLUSION: MCP-3 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that MCP-3 may have a role in the development of fibrosis in SSc.

Adolescent↗

A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease.

BACKGROUND: The transforming growth factor-beta (TGF-beta) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-beta receptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT share several symptoms, including telangiectasia. OBJECTIVE: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. METHODS: Serum sEndoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. RESULTS: Serum sEndoglin levels were significantly elevated in patients with lcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with lcSSc. CONCLUSION: Abnormal expression/function of endoglin may be linked to lcSSc-specific manifestations.

Adolescent↗

Increased cutaneous T-cell-attracting chemokine levels in sera from patients with systemic sclerosis.

OBJECTIVE: We sought to assess serum cutaneous T-cell-attracting chemokine (CTACK) levels and CTACK expression levels in skin from patients with systemic sclerosis (SSc), and determine whether serum CTACK levels correlate with clinical features in SSc patients. METHODS: Serum samples were obtained from 73 SSc patients, 32 patients with systemic lupus erythematosus and 26 patients with dermatomyositis. Serum CTACK levels were determined by enzyme-linked immunoabsorbent assay. CTACK mRNA expression in sclerotic skin was assessed by real-time reverse transcription-polymerase chain reaction. RESULTS: Serum CTACK levels were significantly increased in patients with diffuse cutaneous SSc (dSSc; n=32) and those with limited cutaneous SSc (lSSc; n=41) compared with normal controls (n=31; P<0.05 and P<0.0005, respectively). The presence of calcinosis and muscle involvement was more frequently detected in SSc patients with elevated CTACK levels (P<0.05 and P<0.05, respectively). Elevated C-reactive protein levels were also observed more frequently in SSc patients with increased CTACK levels (P<0.05). CTACK mRNA expression levels in the sclerotic skin of SSc patients were augmented. In a longitudinal study, serum CTACK levels were generally decreased during the follow-up. CONCLUSIONS: The increased serum CTACK levels and enhanced skin CTACK expression in SSc patients suggest that CTACK is related to the inflammation associated with SSc.

Adult↗

Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water circulation patterns in coastal areas of the Noto Peninsula, Japan.

To examine water circulation patterns of coastal water, 72 seaweed (Sargasso) samples and 27 coastal water samples were collected from coastal areas of the Noto Peninsula, Japan, during the period from December 1998 to June 2002. The (228)Ra and (226)Ra activities of those samples were measured by low-background gamma-ray spectrometry. There was a wide range of activities of (228)Ra (0.5-2Bq/kg-fresh) and (226)Ra (0.5-1.2Bq/kg-fresh) in the Sargasso samples. The (228)Ra/(226)Ra activity ratio of Sargasso samples exhibited seasonal variation with minimum values in June ((228)Ra/(226)Ra= approximately 1) and maximum values in December (1.5-2.5), which was mainly governed by changes in (228)Ra activity. It is also notable that the seasonal variation of the (228)Ra/(226)Ra ratio of Sargasso is in approximate agreement with that of the ambient coastal water. Sargasso samples appear to have retained the (228)Ra/(226)Ra ratio of the ambient coastal waters, and the temporal variations in that ratio provide insight into seasonal changes in water circulation in the Noto Peninsula coastal area.

Environmental Monitoring↗

Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To determine serum levels of soluble cytotoxic T-lymphocyte associated molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30 SSc patients were analysed (follow-up 2.1-7.0 yr). RESULTS: Serum sCTLA-4 levels were elevated in dSSc patients compared with normal controls (n = 41), lSSc patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients with elevated sCTLA-4 levels had a shorter disease duration and more frequent presence of digital pitting scars, contracture of phalanges, diffuse pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC) than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not improve in two of six dSSc patients with high sCTLA-4 levels throughout the follow-up, while the remaining four patients showed improvement of skin sclerosis. CONCLUSION: These results suggest that sCTLA-4 correlates with disease severity and activity of SSc and that sCTLA-4 plays a role in immunological abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well as T-cell responses by interfering with B7-CTLA-4 interactions that induce negative signals in T and B cells.

Antigens, CD↗

Measurements of 60Co in spoons activated by neutrons during the JCO criticality accident at Tokai-mura in 1999.

Neutron activated items from the vicinity of the place where the JCO criticality accident occurred have been used to determine the fluence of neutrons around the facility and in nearby residential areas. By using underground laboratories for measuring the activation products, it is possible to extend the study to also cover radionuclides with very low activities from long-lived radionuclides. The present study describes gamma-ray spectrometry measurements undertaken in a range of underground laboratories for the purpose of measuring (60)Co more than 2 years after the criticality event. The measurements show that neutron fluence determined from (60)Co activity is in agreement with previous measurements using the short-lived radionuclides (51)Cr and (59)Fe. Limits on contamination of the samples with (60)Co are evaluated and shown to not greatly affect the utility of neutron fluence determinations using (60)Co activation.

Chromium Radioisotopes↗

Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.

Autoantibodies↗

Autoantibodies to a collagen-specific molecular chaperone, heat-shock protein 47, in systemic sclerosis.

Heat-shock proteins are highly conserved and immunogenic proteins, which may be involved in the initiation and perpetuation of autoimmune diseases. Heat-shock protein 47 (HSP47) is expressed by collagen-secreting cells such as fibroblasts and serves as a collagen-specific molecular chaperone that plays a crucial role in collagen metabolism. Abnormal collagen accumulation and autoimmunity are characteristics of systemic sclerosis (SSc). We determined the presence and prevalence of autoantibodies to HSP47 in patients with SSc and also in tight-skin (TSK/+) mice, an animal model for SSc. Anti-HSP47 autoantibodies were present in SSc patients with a frequency of 26%, while patients with systemic lupus erythematosus, those with dermatomyositis, those with keloid and healthy subjects did not have anti-HSP47 antibodies. IgG1 and IgG2 were the major Ig isotypes of the autoantibodies. Patients positive for anti-HSP47 had a significantly shorter duration of disease than those who were negative. Anti-HSP47 autoantibodies were also positive in 79% of TSK/+ mice. Thus, autoantibodies to HSP47 were present in the sera from SSc patients as well as those from TSK mice, and may be associated with the pathogenesis of SSc.

Adolescent↗

Autoantibodies against phosphatidylserine-prothrombin complex in patients with systemic sclerosis.

OBJECTIVE: To determine the frequency and clinical association of antiphosphatidylserine-prothrombin complex (PS/PT) antibody (Ab) in systemic sclerosis (SSc). METHODS: Anti-PS/PT IgG Ab was examined by enzyme linked immunosorbent assay (ELISA) in 112 patients with SSc. Thirty three healthy volunteers and 30 patients with systemic lupus erythematosus (SLE) were also investigated as controls. RESULTS: Anti-PS/PT Ab was detected in 18/112 (16%) patients with SSc and 10/30 (33%) patients with SLE, whereas it was not detected in any normal controls. Anti-PS/PT Ab was more frequently detected in patients with SSc with peripheral ischaemia and lung disease (pulmonary fibrosis and pulmonary hypertension) than in patients with SSc without the Ab. However, anti-PS/PT Ab was not associated with the severity of skin sclerosis. Importantly, two patients were negative for both lupus anticoagulant and Ab against cardiolipin beta(2)-glycoprotein I complex among six anti-PS/PT Ab positive patients with SSc and a thromboembolic episode. CONCLUSIONS: Anti-PS/PT Ab is associated with thromboembolism, peripheral ischaemia, and lung involvement in some patients with SSc. Examination of this Ab may be useful to recognise the risk of thromboembolism in patients with SSc.

Adult↗

Elevated levels of circulating CD44 in patients with systemic sclerosis: association with a milder subset.

OBJECTIVE: To determine serum levels of soluble CD44 (sCD44), one of the adhesion molecules that regulate the migration of leucocytes, and clinical associations of these levels in patients with systemic sclerosis (SSc). METHODS: Serum sCD44 levels were examined by enzyme-linked immunosorbent assay. RESULTS: Serum sCD44 levels were elevated in SSc patients compared with normal controls. Serum sCD44 levels were higher in patients with limited cutaneous SSc than in those with diffuse cutaneous SSc. Patients with elevated sCD44 levels had pulmonary fibrosis less frequently than those with normal sCD44 levels. Serum sCD44 levels remained elevated during the follow-up in almost all patients with elevated levels at their first visit, whereas they remained normal in all patients with normal levels. CONCLUSION: Elevated sCD44 levels were associated with a relatively mild subset of SSc. These results suggest that CD44 could be a potential therapeutic target in SSc.

Adolescent↗

The Golgi apparatus of goblet cells in the mouse descending colon: three-dimensional visualization using a confocal laser scanning microscope.

The three-dimensional structure of the Golgi apparatus was studied in goblet cells in lectin-stained sections of the mouse descending colon by using a confocal laser scanning microscope. In the lower part of the crypt, the Golgi apparatus formed a dome- or globe-like structure in the supranuclear region. The wall of the dome had some holes, one of which usually faced toward the nucleus and others toward the apical cytoplasm. Mucous granules seemed to be initially released into the interior of the dome and transported toward the apical cytoplasm through the holes. In the upper part of the crypt, on the other hand, the Golgi apparatus formed a cup- or funnel-like structure with a larger opening toward the cell apex and a smaller opening toward the nucleus. A large mass of mucous granules occupied the inside of the cup to the apical cytoplasm. It is thought that the accumulation of mucous granules enlarges holes at the ceiling of the dome to form a large opening, which makes the configuration of the Golgi apparatus cup-shaped.

Animals↗

Aryl hydrocarbon receptor/dioxin receptor in human monocytes and macrophages.

Aryl hydrocarbon receptor (AhR) belongs to the bHLH/PAS transcription factor family and is activated by various polycyclic or halogenated aromatic hydrocarbons, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC). In the present study, we showed that in U937 cells and human macrophages AhR, with its partner cofactor Arnt, is expressed and CYP1A1 mRNA expression is induced in the presence of AhR ligand 3MC. Moreover, we showed that AhR, associating with Arnt, binds to target DNA sequences and activates transcription. Since part of AhR is activated into DNA binding species in the absence of exogenous ligand and competitive AhR antagonist alpha-naphthoflavone inhibits this activation process with reducing CYP1A1 mRNA expression levels, the presence of endogenous ligand is indicated.

Benzoflavones↗

Radiochemical approach to the JCO criticality accident in Tokai-mura, 1999--an overview of the radiochemistry group.

A few days after the JCO criticality accident in Tokai-mura, a collaborating scientific investigation group was organized to evaluate the environmental impact of the accident. The group consisted of two groups: an environmental research group (radiochemistry group) and a biological research group. This paper overviews the scientific activity of the former group based on 6 sampling campaigns conducted at the JCO campus, Tokai-mura and Naka-machi. Some of the topical results and our remaining tasks concerning the JCO accident are discussed.

Environment↗

Activation of soil and chemical reagents exposed to the neutrons released by the JCO criticality accident in Tokai-mura.

Specific activities (Bq/g-element) of residual neutron-induced radionuclides by the JCO criticality accident were measured for soil, concrete block and chemical reagent samples collected in the JCO campus. Induced radionuclides such as 24Na, 46Sc, 54Mn, 59Fe, 60Co, 65Zn, 82Br, 122Sb, 134Cs and 140La were detected in the samples, depending on the ground distance from the accident point and the sampling date. Apparent thermal, epi-thermal and fast neutron fluences, which reached the sample at each point, were roughly estimated from the specific activities and cross sections of the target nuclides taken from a literature. The present data are believed to be important as validation data for a three-dimensional neutron transport model calculation.

Construction Materials↗