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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 145 records · Page 8Linked to original sources

[Two cases of spinal epidural lipomatosis].

Two cases of spinal epidural lipomatosis (SEL) were reported. Patient 1 was on oral corticosteroid and patient 2 was obese and had prostate cancer. Patient 1 was a 45-year-old man diagnosed as sarcoid myelopathy at C 5/6 vertebral body levels and had been placed on oral corticosteroid therapy for 14 months. He showed spastic paraplegia, hypesthesia below C 4 level with distal dominancy and dysesthesia below Th 6 level. MRI revealed epidural lipomatosis from Th 3 to Th 9 vertebral bodies, which presented high in T 1 weighted image (WI) and T 2 WI, and non-signal in STIR image. On axial image spinal cord was compressed by this mass. Patient 2 was a 73-year-old man with spastic paraplegia, and superficial and deep sensory disturbances below Th 6. He had been obese (BMI 26.1) upon admission. He was diagnosed as prostate cancer with bone metastasis. On MRI of the thoracic spine revealed epidural mass of high in T 1 WI and T 2 WI, and non-signal in STIR image. SEL is a rare condition known as hyperplasia of normal fat tissue in epidural space which sometimes compresses the spinal cord or spinal nerve roots resulting in neurologic deficit. SEL should be kept in mind as having possible neurologic complications in obese patients or ones on long term steroid therapy.

Aged↗

A newly designed underwater antenna and its application to underwater radio-telemetry for measuring electroencephalographic activity from the rainbow trout freely swimming in natural environments.

A novel underwater antenna (which we named an 'aquaerial') for telemetering the biological signals from freely swimming fish in freshwater natural environments is presented. It is designed for receiving a 90-100 MHz carrier wave and consists of plural unit receiving antennas (UAs). The plural UAs are placed underwater to cover the area where the target fish carrying the transmitter is swimming. The UAs are equally spaced and have a directional coupling amplifier to supply the signals received to the coaxial cable. The optimal length of the UA was found to be 16.5 cm (a half wavelength in water) and optimal spacing was 2 m (one wavelength along coaxial cable) when 95 MHz was used as the carrier frequency. Using this 'aquaerial', long-term monitoring of EEG signals from the olfactory bulb of the rainbow trout (Oncorhynchus mykiss) swimming freely in natural environments was achieved.

Animals↗

[Triamcinolone Acetonide Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of triamcinolone acetonide was examined for preparation of the "Triamcinolone Acetonide Reference Standard (Control 981)". The analytical data obtained were: melting point, 289 degrees C (decomposition); UV spectrum, lambda max of 238 nm; IR spectrum, same as that of the Triamcinolone Acetonide Reference Standard (Control 834); optical rotation, [alpha]D20 = +106.8 degrees; thin-layer chromatography, no impurities detected; high-performance liquid chromatography, total amount of impurities less than 0.4%; loss on drying, 1.3%; assay by HPLC, 100.1%. Based on the above results, the raw material was authorized as the Triamcinolone Acetonide Reference Standard (Control 981) of the National Institute of Health Sciences.

Government Agencies↗

[Triamcinolone Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of triamcinolone was examined for preparation of the "Triamcinolone Reference Standard (Control 981)". The analytical data obtained were: melting point, 246 degrees C (decomposition); UV spectrum, lambda max of 239 nm and specific absorbance in methanol at 289 nm of 394; IR spectrum, specific absorptions at 3462, 1716, 1659, 1615, 1604, 1132 and 1061 cm-1; optical rotation, [alpha]D20 = +69.7 degrees; high-performance liquid chromatography, five impurities detected and amount of each impurity estimated to be less than 0.6% and total amount of impurities less than 1.4%; loss on drying, 0.24%. Based on the above results, the raw material was authorized as the Triamcinolone Reference Standard (Control 981) of the National Institute of Health Sciences.

Government Agencies↗

[Digoxin Reference Standard (Control 991) of National Institute of Health Sciences].

The raw material of digoxin was examined to prepare a "Digoxin Reference Standard". The analytical data obtained were: optical rotation, [alpha](20)D = + 11.7 degree; loss on drying, 0.008%, infrared spectrum, the same as that of the Digoxin Reference Standard (Control 807); high-performance liquid chromatography, several impurities detected and the total amount estimated to be about 0.31%, assay by spectrophotometry, 100.1%. Based on the above results, the candidate material was authorized as the Digoxin Reference Standard (Control 991) of the National Institute of Health Sciences.

Digoxin↗

[Lanatoside C Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of lanatoside C was examined for preparation of the "Lanatoside C Reference Standard". The analytical data obtained were: melting point, 247.4 degree C; optical rotation, [alpha]20(D) = + 34.0 degree, loss on drying, 6.93%; infrared spectrum, the same as that of the Lanatoside C Reference Standard (Control 784); thin-layer chromatography, two impurities detected; high-performance liquid chromatography, several impurities detected and the total amount estimated to be about 1.26%; assay by spectrophotometry, 103.0%. Based on the above results, the candidate material was authorized as the Lanatoside C Reference Standard (Control 981) of the National Institute of Health Sciences.

Government Agencies↗

[Glycyrrhizic Acid Reference Standard (Control 991) of National Institute of Health Sciences].

The raw material of glycyrrhizic acid examined for preparation of the "Glycyrrhizic Acid Reference Standard". The analytical data obtained were: UV spectrum: Lambda max, 251 nm; specific absorbance (E (1%) 1cm) in ethanol at 251 nm, 146; IR spectrum, specific absorptions at 1716,1656, 1215, and 1170 cm-1; and the spectrum of raw material was consistent with that of Standard (Control 941). Also, thin-layer chromatography, no impurities detected; high-performance liquid chromatography, three impurities detected. The amount of each impurity was estimated at less than 0.1%, and the total amount of impurities was less than 0.2%. Based on the above results, the candidate material was authorized as the Glycyrrhizic Acid Reference Standard (Control 991) of the National Institute of Health Sciences.

Glycyrrhizic Acid↗

[Tocopherol Succinate Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of tocopherol succinate was tested for preparation of the "Tocopherol Succinate Reference Standard (Control 981)". The analytical data obtained were: infrared spectrum same as that of the Tocopherol Succinate Reference Standard (Control 8510); specific absorbance, E(1%)1 cm (286 nm) = 40.7; thin-layer chromatography, no impurities detected until 50.0 microgram; high-performance liquid chromatography (HPLC),three impurities detected and amount of tocopherol succinate estimated to be 98.2%, loss on drying, 0.19%, assay by HPLC, 101.7%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 981).

Government Agencies↗

[Fluocinolone Acetonide Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of fluocinolone acetonide was examined for preparation of the "Fluocinolone Acetonide Reference Standard (Control 981)". The analytical data obtained were: melting point, 271.5 degree C; UV spectrum, Lambda max of 237.0 nm and specific absorbance in ethanol at 237 nm of 359.3; IR spectrum, same as that of the Fluocinolone Acetonide Reference Standard (Control 904); optical rotation, [alpha]20(D) = + 102.8; thin-layer chromatography, no impurities detected; high-performance liquid chromatography, one impurity detected and total amount estimated to be about 0.17%; loss on drying, 0.29%; assay by HPLC, 100.9%. Based on the above results, the raw material was authorized as the Fluocinolone Acetonide Reference Standard (Control 981) of the National Institute of Health Sciences.

Fluocinolone Acetonide↗

[Fluocinonide Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of fluocinonide was examined for preparation of the "Fluocinonide Reference Standard (Control 981)". The analytical data obtained were: UV spectrum, lambda max of 237.4 nm; IR spectrum, same as that of the Fluocinonide Reference Standard (Control 841); optical rotation, [alpha]20(D) = + 84.4 degree, thin-layer chromatography, one impurity detected; high-performance liquid chromatography, three impurities detected and total amount estimated to be about 0.20%; loss on drying, 0.15%; assay by HPLC, 99.6% Based on the above results, the raw material was authorized as the Fluocinonide Reference Standard (Control 981) of the National Institute of Health Sciences.

Fluocinonide↗

Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat1 fibroblasts expressing insulin receptors.

Shc is phosphorylated on Tyr-239/240 and/or Tyr-317, which serves as a docking site for Grb2. To clarify the relative involvement of Shc Tyr-239/240 and Tyr-317 in insulin-induced mitogenesis, we generated expression vectors for Y317F (1F)-Shc, Y239/240F (2F)-Shc, and Y239/240/317F (3F)-Shc, and stably transfected them into Rat1 fibroblasts expressing insulin receptors (HIRc). Insulin-induced Shc phosphorylation and subsequent association with Grb2 was enhanced in wild-type (WT)-Shc cell. In contrast, insulin-stimulated Shc phosphorylation and Shc.Grb2 association were significantly decreased in 1F-Shc and 3F-Shc cells, while these were only slightly affected and almost comparable in 2F cells compared with those in parental HIRc cells. The kinetics of MAP kinase activation closely paralleled the kinetics of Shc phosphorylation and Shc.Grb2 association. Thus, insulin stimulation of MAP kinase activation occurred more rapidly in WT-Shc cells, and the activation was delayed in 1F-Shc and 3F-Shc cells, while it was comparable in 2F-Shc cells compared with that in HIRc cells. Furthermore, WT-Shc cells displayed enhanced sensitivity to insulin stimulation of thymidine incorporation. Importantly, the sensitivity was significantly decreased in 1F-Shc and 3F-Shc cells, while it was almost comparable in 2F-Shc cells compared with that in HIRc cells. These results indicate that Shc Tyr-317 is more predominant insulin-induced phosphorylation site than Tyr-239/240 for coupling with Grb2 leading to MAP kinase activation and mitogenesis in Rat1 fibroblasts.

Adaptor Proteins, Signal Transducing↗

Induction of thymocyte apoptosis by Ca2+-independent protein kinase C (nPKC) activation and its regulation by calcineurin activation.

Glucocorticoids appear to participate in apoptosis of unselected CD4(+)CD8(+) thymocytes. Activation of Ca2+-independent novel protein kinase C (nPKC) precedes glucocorticoid-induced thymocyte apoptosis, while proper levels of Ca2+-dependent protein kinase C (cPKC) and calcineurin activities contribute to rescue thymocytes. To clarify the role of nPKC in thymocyte apoptosis, murine thymocytes were stimulated with the diterpene diester, ingenol 3, 20-dibenzoate (IDB). IDB induced selective translocation of nPKC-delta, -epsilon, and -theta and PKC-mu from the cytosolic fraction to the particulate fraction and induced morphologically typical apoptosis through de novo synthesis of macromolecules. The apoptosis was also induced by thymeleatoxin, a diterpene ester, at relatively high concentrations that induced translocation of cPKC, nPKC-theta, and PKC-mu. The IDB- or thymeleatoxin-induced death was inhibited by non-isoform-selective PKC inhibitors, but not by their structural analogs with weak PKC-inhibitory activity or the selective inhibitor of cPKC and PKC-mu, Gö 6976. The death was also inhibited by calcium ionophore ionomycin at concentrations within a narrow range. The range corresponded to the concentration range that contributes to the inhibition of glucocorticoid-induced apoptosis. The antiapoptotic effect was canceled by the immunosuppressant FK506 but not by rapamycin. These results indicate that activation of nPKC, especially nPKC-theta, induces apoptosis in thymocytes and that calcineurin activation regulates the apoptosis.

Animals↗

Progressive aphemia in a patient with Pick's disease: a neuropsychological and anatomic study.

We describe a patient with progressive aphemia with agrammatism that was later overlaid with buccofacial apraxia and pseudobulbar palsy. Pathological findings were consistent with those of classic Pick's disease with argyrophilic inclusions and neuronal achromasia, except for restricted cortical atrophy in the frontal operculum posterior to the pars opercularis (Brodmann Area 44). In addition, major neuronal loss was confined to the premotor cortex and the anterior half of the precentral gyrus (Area 6), which apparently explained the aphemia. The present case demonstrated that classic Pick's disease can show quite limited cortical atrophy in a patient who clinically presents with progressive aphemia. Also, our patient differed from the progressive non-fluent aphasia patients reported as having Pick's disease, who were all Pick variants, revealing that classic Pick's disease can be included in the spectrum of progressive aphasia syndrome.

Aphasia, Broca↗

Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex.

Mitochondrial cytochrome bc1 complex performs two functions: It is a respiratory multienzyme complex and it recognizes a mitochondrial targeting presequence. Refined crystal structures of the 11-subunit bc1 complex from bovine heart reveal full views of this bifunctional enzyme. The "Rieske" iron-sulfur protein subunit shows significant conformational changes in different crystal forms, suggesting a new electron transport mechanism of the enzyme. The mitochondrial targeting presequence of the "Rieske" protein (subunit 9) is lodged between the two "core" subunits at the matrix side of the complex. These "core" subunits are related to the matrix processing peptidase, and the structure unveils how mitochondrial targeting presequences are recognized.

Amino Acid Sequence↗

A role of calcineurin in coreceptor regulation during differentiation of Cd4+Cd8+ T cells.

The immunosuppressant FK506 inhibits thymocyte positive selection. Calcineurin, a FK506-sensitive Ca2+/calmodulin-dependent protein phosphatase, is presumed to be involved in this event without direct evidence. We have previously shown that moderate stimulation of CD4(+)CD8(+) thymocytes with a combination of the calcium ionophore ionomycin and phorbol myristate acetate mimics positive selection events including downregulation of CD8 expression. Moderate stimulation of a CD4(+)CD8(+) T cell line with the same combination of drugs also induced specific downregulation of CD8 expression. FK506 inhibited the CD8 downregulation in both cell types. The T cell line was transfected with an expression vector encoding an active form of calcineurin. The transfectans remained CD4(+)CD8(+), but became CD4(+)CD8(-) or CD4(+)CD8(low) upon stimulation with phorbol myristate acetate alone. The extent of the CD8 downregulation was correlated with the expression level of the mutant calcineurin. These results suggest that the calcium signal for the CD8 downregulation is mainly delivered through calcineurin activation.

Animals↗

Involvement of heat shock protein 90 in the degradation of mutant insulin receptors by the proteasome.

We previously reported three families with type A insulin-resistant syndrome who had mutations, either Asp1179 or Leu1193, in the kinase domain of the insulin receptor. The extreme insulin resistance of these patients was found to be caused by the decreased number of insulin receptors on the cell surface, due to the intracellular rapid degradation (Imamura, T., Takata, Y., Sasaoka, T., Takada, Y., Morioka, H., Haruta, T., Sawa, T., Iwanishi, M., Yang, G. H., Suzuki, Y., Hamada, J., and Kobayashi, M. (1994) J. Biol. Chem. 269, 31019-31027). In the present study, we first examined whether these mutations caused rapid degradation of unprocessed proreceptors, using the exon 13 deleted mutant insulin receptors (DeltaEx13-IR), which were accumulated in the endoplasmic reticulum as unprocessed proreceptors. The addition of Asp1179 or Leu1193 mutation to DeltaEx13-IR caused accelerated degradation of the unprocessed DeltaEx13-IR in the transfected COS-7 cells. Next, we tested whether these mutant receptors were degraded by the proteasome. Treatment with proteasome inhibitors Z-Leu-Leu-Nva-H (MG-115) or Z-Leu-Leu-Leu-H (MG-132) prevented the accelerated degradation of these mutant receptors, resulting in increased amounts of the mutant receptors in the COS-7 cells. Essentially the same results were obtained in the patient's transformed lymphocytes. Finally, we found that these mutant receptors bound to heat shock protein 90 (Hsp90). To determine whether Hsp90 played an important role in the accelerated receptor degradation, we examined the effect of anti-Hsp90 antibody on the mutant receptor degradation. The microinjection of anti-Hsp90 antibody into cells prevented the accelerated degradation of both Asp1179 and Leu1193 mutant insulin receptors. Taken together, these results suggest that Hsp90 is involved in dislocation of the mutant insulin receptors out of the endoplasmic reticulum into the cytosol, where the mutant receptors are degraded by the proteasome.

Animals↗