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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 109 records · Page 6Linked to original sources

Introduction to endoscopic mucosal resection.

The advent of videoendoscopes showed the very minute details of the gastrointestinal tract. Three American and five Japanese endoscopists who are experts and founders in their original EMR for the entire gastrointestinal tract were invited. All of them have tremendous experience with EMR. One can appreciate the technique and pitfalls of EMR through their data analyses based on a large number of cases. In western countries, early esophageal cancers arising from Barrett's esophagus seem to be the most likely candidates for EMR. It is hoped that these techniques aid the reader's endoscopic practice and provide a better quality of life to patients.

Digestive System Neoplasms↗

Neuroradiologic findings in focal cortical dysplasia: histologic correlation with surgically resected specimens.

PURPOSE: We investigated the neuroradiologic characteristics of focal findings of surgically resected specimens obtained from 47 patients with focal cortical dysplasia (FCD). METHODS: Forty cases were detected by magnetic resonance imaging (MRI), and two cases were detected only by single-photon emission computed tomography (SPECT), but five cases could not be detected before operation. RESULTS: MRI revealed abnormal gyri and sulci in 34 patients (pachygyric in 18, polymicrogyric in 10, both in six), and blurring of the gray matter-white matter junction in 29 (72%) patients. Signal abnormalities were found in 36 (90%) patients, in the gray matter in 32, with white matter in 30, and at the gray matter-white matter junction in 13. Moreover, peculiar patterns of abnormal signals in the white matter were recognized, including remarkably abnormal subcortical signals of T2 hyperintensity and T1 hypointensity adjacent to the dysplastic cortex in 15 cases, high radiated T2 signals extending from the ependymal surface of the lateral ventricle to the overlying cortex in 11 cases, and widespread abnormal signals in the white matter with gray matter involvement in four cases. Histologically, these abnormal signals corresponded to various degrees of dyslamination and morphologic abnormalities of neurons and glial cells in the gray matter, and to dysmyelination, ectopic clustering of dysplastic neurons, glial proliferation, and necrotic change in the white matter. Regional cerebral blood flow SPECT showed interictal hypoperfusion in 29 (62%) of the 47 patients, interictal hyperperfusion in two, and ictal hyperperfusion in 28 of the 34 patients associated with FCD. [123I]iomazenil SPECT demonstrating the distribution of central benzodiazepine receptors showed low accumulations localized spatially corresponding to the epileptogenic foci associated with FCD in seven of eight patients. CONCLUSIONS: These results demonstrate that neuroimaging reflects various structural and functional changes closely related to epileptogenesis in FCD.

Adolescent↗

Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers.

Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastrointestinal malignancies, and it is thought that high levels of syndecan-1 correlate with the maintenance of epithelial morphology and inhibition of invasiveness. In our study, we characterized the expression of syndecan-1 in normal, chronic pancreatitis and primary and metastatic human pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines expressed syndecan-1 mRNA and protein at variable levels. In addition, these cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues markedly over-expressed syndecan-1 mRNA in comparison with both chronic pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6-fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression between early and advanced tumors. By in situ hybridization and immunohistochemistry, syndecan-1 expression was evident at relatively low levels in the ductal cells and less frequently in acinar cells of the normal pancreas. In chronic pancreatitis, syndecan-1 was present at low to moderate levels in areas with atrophic acinar cells and ductular complexes. In contrast, in pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in the majority of the cancer cells within the tumor mass and also in metastatic lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal malignancies (esophageal, gastric, colon and liver cancers) were not significantly different from the levels observed in the corresponding normal samples. Together, our findings suggest that syndecan-1 expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies.

Adenocarcinoma↗

p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.

Through direct cloning of p53 binding sequences from human genomic DNA, we have isolated a novel gene, designated p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), whose expression is inducible by wild-type p53. Ectopically expressed p53AIP1, which is localized within mitochondria, leads to apoptotic cell death through dissipation of mitochondrial A(psi)m. We have found that upon severe DNA damage, Ser-46 on p53 is phosphorylated and apoptosis is induced. In addition, substitution of Ser-46 inhibits the ability of p53 to induce apoptosis and selectively blocks expression of p53AIP1. Our results suggest that p53AIP1 is likely to play an important role in mediating p53-dependent apoptosis, and phosphorylation of Ser-46 regulates the transcriptional activation of this apoptosis-inducing gene.

Adenocarcinoma↗

Expression of GAP-43 and SCG10 mRNAs in lateral geniculate nucleus of normal and monocularly deprived macaque monkeys.

We performed nonradioactive in situ hybridization histochemistry (ISH) in the lateral geniculate nucleus (LGN) of the macaque monkey to investigate the distribution of mRNA for two growth-associated proteins, GAP-43 and SCG10. GAP-43 and SCG10 mRNAs were coexpressed in most neurons of both magnocellular layers (layers I and II) and parvocellular layers (layers III-VI). Double-labeling using nonradioactive ISH and immunofluorescence revealed that both GAP-43 and SCG10 mRNAs were coexpressed with the alpha-subunit of type II calcium/calmodulin-dependent protein kinase, indicating that both mRNAs are expressed also in koniocellular neurons in the LGN. We also showed that GABA-immunoreactive neurons in the LGN did not contain GAP-43 and SCG10 mRNAs, indicating that neither GAP-43 nor SCG10 mRNAs were expressed in inhibitory interneurons in the LGN. GABA-immunoreactive neurons in the perigeniculate nucleus, however, contained both GAP-43 and SCG10 mRNAs, indicating that both mRNAs were expressed in inhibitory neurons in the perigeniculate nucleus, which project to relay neurons in the LGN. Furthermore, to determine whether the expression of GAP-43 and SCG10 mRNAs is regulated by visual input, we performed nonradioactive ISH in the LGN and the primary visual area of monkeys deprived of monocular visual input by intraocular injections of tetrodotoxin. Both mRNAs were downregulated in the LGN after monocular deprivation for 5 d or longer. From these results, we conclude that both GAP-43 and SCG10 mRNAs are expressed in the excitatory relay neurons of the monkey LGN in an activity-dependent manner.

Animals↗

Identification of fractalkine, a CX3C-type chemokine, as a direct target of p53.

Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and cytotoxic T cells. Using the differential display method for examining gene expression in p53-defective cells transfected by adenovirus containing wild-type p53, we observed that fractalkine was induced by ectopic expression of p53. An electrophoretic mobility shift assay showed that a potential p53-binding site present in the promoter of the fractalkine gene could bind to p53 protein. Moreover, a heterogeneous reporter assay indicated that this promoter sequence possessed p53-dependent transcriptional activity. The strong induction of fractalkine when p53 protein was expressed by a wild-type transgene in p53-defective cells brought to light a novel role for p53; that is, potential elimination of damaged cells by the host immune response system through transcriptional regulation of fractalkine. Our results imply a pivotal role of p53 in immunosurveillance to prevent cells from undergoing malignant transformation.

Adenoviridae↗

cDNA cloning, expression, and functional characterization of PI31, a proline-rich inhibitor of the proteasome.

The primary structure of PI31, a protein inhibitor of the 20 S proteasome, was deduced by cDNA cloning and sequencing. The human protein has a calculated molecular weight of 29,792, a value in excellent accord with 31,000, as estimated by SDS-polyacrylamide gel electrophoresis for purified bovine PI31, and is not similar to any other protein in current data bases. PI31 is a proline-rich protein, particularly within its carboxyl-terminal half where 26% of the amino acids are proline. Wild-type PI31 and various truncation mutants were expressed in Escherichia coli and purified to homogeneity. Recombinant wild-type PI31 displayed structural and functional properties similar to those of PI31 purified from bovine red blood cells and inhibited the hydrolysis of protein and peptide substrates by the 20 S proteasome. Analysis of truncation mutants demonstrated that proteasome inhibition was conferred by the carboxyl-terminal proline-rich domain of PI31, which appears to have an extended secondary structure. Inhibition of the 20 S proteasome by PI31 involved formation a proteasome-PI31 complex. In addition to its direct inhibition of the 20 S proteasome, PI31 inhibited the activation of the proteasome by each of two proteasome regulatory proteins, PA700 and PA28. These results suggest that PI31 plays an important role in control of proteasome function, including that in ubiquitin-dependent pathways of protein degradation.

Amino Acid Sequence↗

Unaltered endothelium-dependent modulation of contraction in the pulmonary artery of hypertensive rats.

Involvement of endothelium-derived nitric oxide (EDNO) in alpha-adrenoceptor agonist-induced contractile responses was studied in isolated pulmonary arteries from Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). In the presence of propranolol, noradrenaline-induced contraction was potentiated by endothelium removal or by N(G)-nitro-L-arginine (L-NOARG). The magnitude of the potentiation was independent of the noradrenaline concentration. L-NOARG also shifted the concentration-response curves for phenylephrine and methoxamine to the left and upward. Contractile responses to 2-amino-5,6,7,8, -tetrahydro-6-ethyl-4H-oxazolo-(5,4-d)-azepine-dihydrochloride (BHT-933) and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK-14304) were augmented by L-NOARG in a concentration-dependent manner. There were no differences in the effects of L-NOARG on the contractile responses to alpha-adrenoceptor agonists between the preparations from WKY and SHRSP. Endothelium-dependent relaxation in response to acetylcholine was not impaired in the preparations from SHRSP when compared with those from WKY. These observations suggest that the contractile responses to the alpha(1)-adrenoceptor agonists were depressed mainly by basally released EDNO, while the responses to the alpha(2)-adrenoceptor agonists were depressed mainly by EDNO released in response to alpha(2)-adrenoceptor stimulation. The comparable influence of the endothelium on the alpha-adrenoceptor agonist-induced contractions in the pulmonary arteries from WKY and SHRSP, which were markedly different from other arteries, could be explained by the unaltered endothelium-dependent relaxation in the preparations from SHRSP.

Adrenergic alpha-Agonists↗

Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1.

BRCA2, a gene responsible for inherited susceptibility to breast cancer in a number of families, is thought to be critical for replication and repair of DNA during S-phase. To elucidate the physiological functions of BRCA2, we used a yeast two-hybrid system to screen for proteins that could associate with BRCA2. Here we report interaction of BRCA2 with a mitotic checkpoint protein, hBUBR1, and its phosphorylation by hBUBR1 in vitro. After cotransfection of BRCA2 and hBUBR1 expression vectors into the COS7 cell line, both proteins were stained together in the nuclei of cells whose spindle fibers were disrupted, but not in undamaged cells. Treatment with vincristine, which disrupts microtubules, significantly increased expression of both hBUBR1 and BRCA2 in the MCF7 cells. The results suggest that BRCA2 protein might be involved in a mitotic checkpoint in vivo after it has been phosphorylated by hBUBR1.

Animals↗

Specific and chemoselective multi-alpha-arylation reaction of benzoylformic acid with or without decarbonylation in P(2)O(5)-MsOH and related acidic media

In P(2)O(5)-MsOH, or related acidic media, benzoylformic acid (1) undergoes three types of di- or mono-alpha-arylation reactions with or without decarbonylation ((1) decarbonylative alpha, alpha-diarylation, yielding triarylmethanols 6, (2) decarbonylative alpha-monoarylation, giving benzophenone derivatives 7, and (3) alpha,alpha-diarylation without decarbonylation, affording diarylated carboxylic acids 5) and one simple decarbonylation, without arylation, to form benzoic acid (8), instead of the conventional Friedel-Crafts acylation type reaction. The product ratios are governed by the capability of the acidic medium to form mixed anhydrides with carboxylic acids and the ability of the arenes to accept electrophiles.

Journal Article↗

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats.

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.

Adrenergic alpha-Agonists↗

Probing bulk states of correlated electron systems by high-resolution resonance photoemission

Electron correlations are known to play an important role in determining the unusual physical properties of a variety of compounds. Such properties include high-temperature superconductivity, heavy fermion behaviour and metal-to-insulator transitions. High-resolution photoelectron spectroscopy (PES) provides a means of directly probing the electronic states (particularly those near the Fermi level) in these materials, but the short photoelectron mean free paths (< or = 5 A) associated with the low excitation energies conventionally used (< or = 120 eV) make this a surface-sensitive technique. Now that high-resolution PES is possible at much higher energies, with mean free paths as long as 15 A (ref. 6), it should become feasible to probe the bulk electronic states in these materials. Here we demonstrate the power of this technique by applying it to the cerium compounds CeRu2Si2 and CeRu2. Previous PES studies of these compounds revealed very similar spectra for the Ce 4f electronic states, yet it is expected that such states should be different owing to their differing degrees of hybridization with other valence bands. Our determination of the bulk Ce 4f electronic states of these compounds resolves these differences.

Journal Article↗

A role of glutamate in drug-induced ototoxicity: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate in the guinea pig cochlea.

The time course of the changes in perilymphatic glutamate was determined during the application of kanamycin and ethacrynic acid, which are known to damage the hair cells in the inner ear. For the continuous recording of glutamate, the microdialysis technique combined with an enzyme-linked fluorometric assay was used. In guinea pigs receiving a loading dose of 800 mg/kg of kanamycin subcutaneously followed 3 h later by an i.v. injection of 40 mg/kg of ethacrynic acid, a marked glutamate release was clearly found about 2 h after the injection of ethacrynic acid. Injection of kanamycin or ethacrynic acid alone did not produce any change in the perilymphatic glutamate. The morphological changes induced by the administration of both drugs indicated that the collapsing hair cells might release glutamate into the perilymphatic space. The present findings provide additional evidence that glutamate acts as an aggravating factor in aminoglycoside-induced ototoxicity.

Animals↗

Inhibition of A beta fibril formation and A beta-induced cytotoxicity by senile plaque-associated proteins.

A beta neurotoxicity is generally believed to require A beta fibril formation. The prevention of A beta fibril formation thus seems to be a promising strategy for the treatment of AD. Recent studies have shown senile plaque-associated proteins such as laminin to have an inhibitory effect on both A beta40 and A beta42 fibril formation in vitro. In the present study, we thus investigated whether or not midkine (MK) and alpha2-macroglobulin (alpha2M), both of which are also senile plaque-associated proteins like laminin, affect A beta fibril formation and A beta-induced cytotoxicity. The present study demonstrated that both MK and alpha2M inhibit both A beta fibril formation and A beta-induced cytotoxicity in PC12 cells. The confirmation of the present results based on in vivo experiments is called for in future studies to clarify whether or not senile plaque-associated proteins such as MK and alpha2M can be a model for therapeutic agents in the treatment of AD.

Alzheimer Disease↗

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Adenocarcinoma↗

Relation between thymidylate synthase expression and survival in colon carcinoma, and determination of appropriate application of 5-fluorouracil by immunohistochemical method.

BACKGROUND: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied. METHODS: Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup. RESULTS: Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439). CONCLUSIONS: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.

Antimetabolites, Antineoplastic↗

Rotational acetabular osteotomy for severely dysplastic acetabulum.

The operative procedures chosen for arthrosis with severe acetabular dysplasia vary among orthopaedic surgeons. We operated on 250 hips using the rotational acetabular osteotomy (RAO) method of Ninomiya and Tagawa [8]. In this report, we describe the technique of RAO and the results of this procedure in patients with severely dysplastic hips. Among the 250 hips, there were 6 which were classified as Severin group V. In those hips, the CE angle was less than 0 degrees, and the femoral head showed superolateral subluxation. After acetabular osteotomy with straight and curved osteotomes, smooth inferolateral rotation could be done in all cases. At the latest follow-up symptoms were improved remarkably, especially pain. Radiographically, adequate coverage of the femoral head was achieved and joint congruence improved in all 6 hips.

Acetabulum↗