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Biomedical subjects

K Mitsuishi

Publications and source records attributed to K Mitsuishi.

At least 19 recordsLinked to original sources
PubMed2005

The squamous cell carcinoma antigens as relevant biomarkers of atopic dermatitis.

BACKGROUND: Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13. OBJECTIVE: We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD. METHOD: We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients. RESULTS: SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-gamma or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity. CONCLUSIONS: Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity.

Adult↗
PubMed2004

Dynamic profile calculation of deposition resolution by high-energy electrons in electron-beam-induced deposition.

The effect of the accelerating voltage of incident electrons on the resolution of electron-beam-induced deposition was investigated by a dynamic Monte Carlo profile simulator which includes the electron scattering in the already grown deposit structure. By simulating the deposition at two different accelerating voltages of 20 and 200 kV with an idealistic zero-diameter incident probe on a bulk substrate, it was revealed that the smaller size structures were attainable by 200 keV than by 20 keV. The effect of the substrate was also argued by comparing the above results with the simulation results obtained for a point-like starting substrate. Surprisingly, the shapes of the deposits grown on bulk substrates were reproduced well by the simulations starting from point-like substrates indicating the small effect of the substrate on the shape of deposits.

Journal Article↗
PubMed2004

Observation of nanometer-Xe clusters embedded in Al crystals.

The structure of Xe precipitates with sizes in several nanometers embedded in Al is known to be stable and its structure is well confirmed. But knowledge about the structure of Xe precipitates with nanometer sizes is very limited. There are difficulties in observing such small structures embedded in a crystalline matrix. An off-Bragg condition is used to observe diffraction patterns, dark-field, and high-resolution transmission electron microscopy images. The structure of Xe precipitates with sizes of about 2 nm and smaller is observed and confirmed. They are in an fcc structure and their orientation relationship with the Al matrix is similar to that of larger crystalline Xe precipitates or in an undefined structure. The lattice spacing or atomic distance in such nanometer-sized Xe precipitates is smaller than those of larger Xe precipitates embedded in Al matrix. There is a trend that as the size becomes smaller, the precipitates are more likely to have an undefined structure.

Aluminum↗
PubMed2004

Application of transmission electron microscopes to nanometre-sized fabrication by means of electron beam-induced deposition.

Electron beam-induced deposition was carried out using a scanning transmission electron microscope with a field emission gun to fabricate nanometre-sized structures. A small amount of a metal-organic gas was introduced near the substrate in the microscope chamber, and focused electron beams were irradiated. Two- and three-dimensional structures were fabricated by scanning the beam position. The minimum line width of the freestanding structures was 8 nm at a constant gas flux used. This line width of 8 nm is considered to be achieved by employing a high accelerating voltage, which leads to a small probe size, and the optimum scanning speed.

Imaging, Three-Dimensional↗
PubMed2004

Structure of nanometre-sized Xe particles embedded in Al crystals.

The structure and lattice parameters of Xe particles about 1 nm to about 6 nm in size embedded in Al were investigated with off-Bragg condition high-resolution transmission electron microscopy. An Xe particle about 1 nm in size had different structural properties from those 2-6 nm in sizes. Some 1-nm Xe particles had an face-centred cubic (f.c.c.) structure with the same orientation as the Al matrix, whereas others of the same size had a non-f.c.c. structure. The lattice parameters of a 1-nm f.c.c. Xe particle were about 20% smaller than the average value obtained from electron diffraction, i.e. the particle was compressed by about 80%. The lattice parameters of Xe crystals about 2 nm to about 6 nm in size were almost the same as those obtained from diffraction results. One of the reasons for the extra compression seen with a 1-nm Xe particle is the increase in pressure inside an Xe particle with decreasing particle size.

Journal Article↗
PubMed2004

Possible mechanisms of gender bias in SLE: a new hypothesis involving a comparison of SLE with atopy.

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males, and numerous investigations of this gender bias have been performed from several perspectives. Sex hormones, particularly estrogens, may be significant in causing the gender discrepancy. This article discusses the possible importance of estrogens in regulating the expression of and responsivity to autoantigens in SLE and in atopic disorders, which are associated with hyperreactivity to exogenous antigens. Estrogens seem to play an important role in the overexpression of endogenous autoantigens, such as human endogenous retroviruses (HERV), and this may be related to the existence of a gender bias in the incidence of SLE but not atopy.

Antibody Formation↗
PubMed2003

In situ observation of the formation of Fe3O4 in Fe4N (001) due to electron irradiation.

gamma(')-Fe4N was subjected to electron irradiation with the dose rate of 6.8 x 10(23)e m(-2) s(-1) in a 400 kV transmission electron microscope. The first in situ observation of the formation of Fe3O4 (O) on Fe4N (gamma(')) with the orientation relationship of [100](O) parallel [100](gamma(')) and <001>(O) parallel <001>(gamma(')) has been made inside the microscope with the basic column vacuum of (5-6) x 10(-5) Pa. A mechanism is proposed involving the electron-stimulated dissociation of Fe-N chemical bonds, desorption of nitrogen from the surface, adsorption of oxygen to the surface, and the oxidization of excessive metallic iron on the surface.

Journal Article↗
PubMed2003

Layer-doubling method in ADF-STEM image simulation.

A layer-doubling method developed in LEED calculation is applied to the ADF-STEM image simulation. This approach makes it possible to simulate image intensities of systems having a repeated slab structure, such as embedded precipitates or defects, with a much higher efficiency because it does not require the diagonalization of repeated slabs. As a simple example of this method, channeling effects are calculated for a system with embedded crystalline displaced slabs for various different slab thicknesses.

Journal Article↗
PubMed2002

Transforming growth factor-beta1 suppresses atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Atopic dermatitis is a chronic, relapsing inflammatory disorder characterized by pruritic and eczematous skin lesions. Transforming growth factor (TGF)-beta1 has been implicated in the suppression of inflammatory responses. OBJECTIVE: The purpose of this study is to determine whether TGF-beta1 suppresses skin lesions in a mouse model of atopic dermatitis. METHODS: We used the NC/Nga strain of mice as an in vivo model of atopic dermatitis. The effects of exogenous TGF-beta1 on atopic dermatitis-like skin lesions in NC/Nga mice were evaluated clinically, histologically and immunologically. RESULTS: Subcutaneous injection of recombinant TGF-beta1 macroscopically suppressed eczematous skin lesions in NC/Nga mice associated with reduced serum immunoglobulin E (IgE) levels. Histological analysis showed that TGF-beta1 significantly inhibited the infiltration of inflammatory cells such as mast cells and eosinophils into the skin of NC/Nga mice. Spontaneous interferon (IFN)-gamma production from splenocytes of NC/Nga mice was down-regulated by the treatment with TGF-beta1 and neutralizing antibody against IFN-gamma inhibited skin lesions in NC/Nga mice. The inhibitory effect of TGF-beta1 on the skin lesions lasted at least 1 week after cessation of the treatment. CONCLUSION: These findings indicate that TGF-beta1 suppressed atopic dermatitis-like skin lesions in NC/Nga mice at least in part through down-regulation of IFN-gamma. These results suggest that TGF-beta1 may have a therapeutic potential for atopic dermatitis.

Animals↗
PubMed2001

High-angle annular dark-field STEM observation of Xe nanocrystals embedded in Al.

High-angle annular dark-field scanning transmission electron microscope (HAADF-STEM) observation of Xe precipitates embedded in crystalline membranes has been made using electron probes of atomic dimensions and HAADF-STEM images of Xe precipitates qualitatively different from conventional TEM observation results have been obtained. Multislice-based HAADF-STEM simulation has been made and it has been revealed that the intensity of images of Xe atoms at positions displaced from Al matrix columns decreases rapidly as the thickness increases. Even in a thin specimen, the off-site Xe atoms of the precipitate at deep locations, were not observable. Therefore, different images are expected for specimens of different thicknesses or depths of these precipitates. These results indicate that the observation of precipitates in crystalline membranes requires some care.

Journal Article↗
PubMed2001

New scheme for calculation of annular dark-field STEM image including both elastically diffracted and TDS waves.

A new scheme of calculation of high-angle annular dark-field STEM image, capable of including both elastically diffracted and thermal diffuse scattering waves, has been presented by a combination of Pennycook's and Nakamura's methods. The new scheme has been demonstrated for image simulations of Si(011) as functions of thickness, defocus values and detector angles. In the present method, the TDS electron intensities are treated in the same way as in Pennycook's method, having a clear physical picture of its origin and reflecting the atom configuration in the systems. For the case of Si(011), it has been confirmed that at the detector angle of 60 to 160 mrad, which is usually applied, the image becomes highly incoherent, and even the image formed only from SOLZ beams becomes incoherent at the detector angle. At a low detector angle, however, the image has coherent features indicating the necessity of a simulation for individual systems.

Journal Article↗
PubMed2001

Establishment and characterization of a murine mast cell line derived from NC/Nga mice.

A cell line, termed NCJ, was established from the bone marrow-derived mast cells (BMMCs) of NC/Nga mice that are mouse models for atopic dermatitis. NCJ cells expressed FcepsilonRI and c-kit and showed a metachromasia of the granules with a toluidine blue-positive and safranin-negative staining pattern that is characteristic for immature-type mast cells. Interestingly, NCJ cells showed proliferation independent of IL-3, which was associated with constitutive phosphorylation of Raf-1 and Erk kinases. Although NCJ cells had several characteristics of mast cells, we failed to detect FcepsilonRI-mediated beta-hexosaminidase release and its histamine content. These findings indicated that NCJ cells represented a mast cell line with an immature phenotype and the ability to proliferate in the absence of mast cell growth factors. NCJ cells might thus be useful to study the molecular basis of mast cell proliferation.

Animals↗
PubMed2000

[The effect of suplatast tosilate on immunological parameters for the patients with atopic dermatitis].

A dose of 300 mg/day of suplatast tosilate was administered to one hundred one cases of atopic dermatitis for eight weeks, and the severity scores, peripheral blood eosinophil count, total serum IgE levels, plasma eosinophil cationic protein (ECP) levels, and other immunological parameters before and after the trial were observed and comparatively examined. The results are as follows: 1) Temporary improvements were found in the scores of severity and itchiness on all evaluated skin regions (face, limbs, and trunk). These scores decreased significantly for all observation periods at two, four, six and eight weeks after administration of suplatast tosilate compared with those before the administration (p < 0.01). 2) There was no sign of adverse effects on the drug. In the blood tests, one patient displayed elevated levels of GPT and another showed elevated total bilirubin. In the urine test (qualitative test), one case with positive urinary protein was observed. 3) Clinical examinations including assessment of the immunologic parameters were conducted at an average of 8.68 +/- 0.36th week. The peripheral blood eosinophil count, the percentage of eosinophil, and plasma ECP levels significantly diminished compared with those before administration, but no significant difference was found in total serum IgE levels and LDH levels. 4) The subjects were divided into two groups, one in which the clinical scores were improved by more than five and another with scores of less than five (including worsening), and the fluctuation of the immunological parameters (values before and after administration of the drug) of the two groups were compared. As a result, a significant difference was observed in the plasma ECP levels (p = 0.02) and peripheral blood eosinophil count (p = 0.091), but no difference was observed in total serum IgE levels and LDH levels. From the above mentioned results, the high efficacy and safety of suplatast tosilate in the treatment of severe atopic dermatitis were confirmed. At the same time, a decrease in the peripheral blood eosinophil count and the serum ECP levels were observed, suggesting the possibility that these values could be used as indices of the severity of atopic dermatitis.

Adult↗
PubMed1999

IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis.

IgE hyperproduction frequently observed in patients with atopic dermatitis (AD) may greatly contribute to the pathogenesis of AD, but its mechanisms are still unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered from AD-like skin lesions with elevation of plasma IgE levels. We investigated mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of BALB/c mice. Although there was no difference in the expression of CD40 on B cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells, which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells isolated from PBMC of AD patients with high serum IgE levels, JAK3 was constitutively phosphorylated at the tyrosine residue, and its phosphorylation was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and patients with AD.

Aluminum Hydroxide↗
PubMed1999

NC/Nga mice: a mouse model for atopic dermatitis.

Atopic dermatitis (AD) is a common pruritic disease that occurs primarily in infancy and childhood. AD is characterized by itching and the patient having an individual or family history of atopic diseases. Although AD is also frequently associated with elevated serum IgE levels and with common environmental factors contributing to its pathogenesis, the etiology of AD is still unknown. We examined NC/Nga mice (NC mice) that showed AD-like skin lesions with aging as a possible mouse model for AD. NC mice were maintained under conventional (Conv) or specific pathogen-free (SPF) conditions. Clinical symptoms, serum IgE levels and histopathology of the skin were compared between these 2 groups, and we explored their application as a model of human AD. It was found that the skin lesions of inbred NC mice were clinically and histologically very similar to human AD when the mice were raised under Conv conditions, but not under SPF conditions, and we assumed that some kinds of environmental factors might trigger AD-like signs and symptoms in NC mice. To further investigate the pathophysiology and treatment of AD, a suitable animal model is absolutely required, and NC mice are very useful for this purpose.

Aging↗
PubMed1997

[Study of preoperative combination therapy with UFT + CDDP in patients with gastric and colorectal cancer--concomitant effects based on the thymidylate synthase inhibitory rat].

UNLABELLED: The subjects were 39 patients with gastric cancer and 44 patients with colorectal cancer divided into a group administered 400 mg/day of UFT orally for 2 weeks preoperatively (UFT group) and a group administered 400 mg/day of UFT as well as 40 mg/m2 (i.v.) of cisplatin (CDDP) by drip infusion once concomitantly (UFT + CDDP group). The thymidylate synthase (TS) inhibitory rate was measured in resected specimens and lymph nodes, and the concomitant effects of UFT and CDDP were investigated. RESULTS: 1) The TS inhibitory rate in tumor tissue showed no significant difference between the two groups. 2) The TS inhibitory rate of metastasized lymph nodes was higher in UFT + CDDP group than in the UFT group in gastric cancer patients (p < 0.05). The TS inhibitory rate by lymph node metastasis in patients with gastric cancer or colorectal cancer was significantly higher in metastasized lymph nodes than in non-metastasized lymph nodes in the UFT + CDDP group (p < 0.05 for gastric cancer, p < 0.05 for colorectal cancer). These results indicated that concomitant use of UFT and CDDP appeared to be more effective against metastasized lymph nodes, especially in cases of gastric cancer, than against the primary tumor focus.

Administration, Oral↗
PubMed1995

[UFT/CDDP preoperative chemotherapy for progressive gastric cancer--histological antitumor effects and thymidylate synthase inhibition rate].

Pre-operative chemotherapy with concomitant use of UFT and CDDP (UFT: oral administration of 400 mg/day for 2 weeks till one day before operation, CDDP, one intravenous drip of 40 mg/m2 one week before operation) was used for 24 untreated cases of advanced stomach cancer diagnosed as resectable pre-operatively, and the histological antitumor effect analyzed in dissected preparation and the thymidylate synthase inhibition rate (TSIR: %) in tumor tissue were examined. The average administration dose of CDDP was 61.1 mg/body, and the average total administration dose of UFT was 5.0 g/body. The histological antitumor effect was grade 0 in 8 cases (33.3%), grade 1a in 10 cases (41.7%), grade 1b in 5 cases (20.8%), and grade 2 in 1 case (4.2%). TSIR in tumor tissue was under 10% in 2 cases (9.1%); over 10% and under 20% in 4 cases (18.2 %); over 20% and under 30% in 6 cases (27.3%); over 30% and under 40% in 5 cases (22.7%); over 40% and under 50% in 3 cases (13.6%); over 50 % in 2 cases (9.1%), and not measurable in 2 cases, with the average of 29.0%. The correlation was observed between histological anti-tumor effect and TSIR in tumor tissue (p < 0.05). These results suggest the possibility that the anti-tumor effect can be estimated at the in vivo level from measurement of TSIR in tumor tissue.

Adult↗