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Biomedical subjects

T Matsui

Publications and source records attributed to T Matsui.

At least 685 records · Page 38Linked to original sources

Molecular cloning and expression of a novel adhesion molecule, SC1.

SC1, an integral membrane glycoprotein of 100 kd, is uniquely and transiently expressed on spinal cord motoneurons early in development and appears in peripheral neurons and several other tissues during development. SC1 has been purified by immunoaffinity techniques, and SC1 cDNA clones have been obtained by screening an E4 chick embryo phage expression library with a rabbit polyclonal antibody produced against purified SC1. The deduced protein sequence of 588 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The sequence is most similar to MUC18, reported as a tumor progression marker in human melanoma. Transfection of SC1 cDNA into mammalian cells leads to cell surface expression of SC1 antigen and a subsequent increase in cell-cell adhesion. SC1 molecules bind to each other via a homophilic adhesion mechanism, independently of calcium or magnesium ions. SC1 may have a role in lateral motor column formation or neurite growth or fasciculation.

Activated-Leukocyte Cell Adhesion Molecule↗

Phorbol 12,13-diacetate-induced contraction of the canine basilar artery: role of protein kinase C.

The pharmacological and biochemical mechanisms of contractile responses to the protein kinase C (PKC) activator phorbol-12,13-diacetate (PDA) were investigated in canine basilar arteries. In the normal medium, PDA elicited a strong, dose-related, and slow-developing sustained contraction. Among the constrictors examined, including serotonin, prostaglandin F2 alpha, and endothelin, only PDA yielded contractions in a Ca2(+)-free medium. In both media, the PDA-induced contractions were virtually inhibited by either staurosporine, H-7, or quinacrine, while neither neurotransmitter blockades nor R24571 (calmidazolium) exerted significant effects. In addition, it was shown that 8-bromocyclic GMP, but not 8-bromocyclic AMP, markedly curtailed the PDA-induced contractions. Biochemical analysis, furthermore, showed that PDA induced increased phosphorylations of 27- and 96-kDa and proteins other than the myosin light chain (MLC) 20-kDa protein. Thus, the present results open up a novel mechanism of sustained cerebral artery contractions, where PKC activation rather than Ca2+/calmodulin/MLC system plays a key role that is regulated both by phospholipase A2 and by cyclic GMP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Possible role of protein kinase C-dependent smooth muscle contraction in the pathogenesis of chronic cerebral vasospasm.

In the present study, we investigate the possible role of protein kinase C (PKC)-dependent smooth muscle contraction in cerebral vasospasm following subarachnoid hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of chronic vasospasm was angiographically confirmed on day 7 in the basilar artery, which was exposed via the transclival approach. The artery was superfused with aerated Krebs-Henseleit solution containing various agents, and the subsequent changes in the basilar artery diameter were recorded by successive angiography. The preexisting spasm was not ameliorated by local application of neurotransmitter antagonists (atropine, methysergide, phentolamine, and diphenhydramine), calmodulin inhibitors (R24571 and W-7), or a calcium antagonist, nicardipine. However, the application of PKC inhibitors such as H-7 and staurosporine induced significant dilation of the artery. In another experiment, an intrinsic PKC activator, 1,2-diacylglycerol (DAG), in the basilar artery, the CSF, and the cisternal clot of beagles exposed to two hemorrhages was measured on days 1, 2, 4, 7, and 14 using the DAG kinase method. On days 2, 4, and 7, the DAG content of the basilar artery showed a significant and prolonged increase (150-190% of control), whereas it was unchanged on days 1 and 14. Throughout the experimental period, there was a significant linear correlation between the DAG content and the angiographical diameter of the basilar artery. The above results indicate that SAH leads to an increase in the DAG level within the cerebral artery through an as yet unknown mechanism and that subsequent activation of the PKC-dependent contractile system participates in the occurrence of chronic vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Mixed lymphocyte-autologous tumor cell reaction in hematological malignancies--effect of interferon-beta and correlation with the expression of MHC class I antigen on tumor cells.

The mixed lymphocyte-autologous tumor cell reaction (MLTR) was performed in 15 patients with hematological malignancies. Lymphocyte proliferative response and generation of cytotoxic cells against autologous tumor cells were evaluated and as was the effect of interferon-beta (IFN-beta) (750 IU/ml). Lymphocytes from patients during complete remission had sufficient functions in mixed lymphocyte culture with normal lymphocytes. Tumor cells stimulated allogeneic lymphocytes, although to a generally lesser extent as compared with remission lymphocytes from the same patients. Increased [3H]TdR uptake was observed in 5 patients and was suppressed by the addition of IFN-beta. Autologous tumor cell kill activity was induced by MLTR in 3 patients; IFN-beta-enhanced killing activity was present in these patients as well as in 3 other patients. Tumor cells from the 3 patients with positive autologous tumor cell kill activity had almost the same stimulating capacity as lymphocytes. The expression of MHC class I antigen and IFN-beta-enhanced expression was observed in all tumor cells studied by indirect immunofluorescence. These data suggest that some factors on tumor cells, in addition to MHC class I antigen, participate in the generation of cytotoxic cells against autologous tumor cells and its enhancement by IFN-beta.

Cytotoxicity, Immunologic↗

Protein deficiency suppresses bone resorption in sheep based on a short-term in vivo bone model.

Six sheep were fed protein-deficient and control diets for 40 d for each diet in a crossover design. Each sheep was intramuscularly injected with 120 pmol.d-1.kg body wt-1 of 1,25-dihydroxycholecalciferol during the last 7 d of each dietary period. Approximately 100 mg of bone powder was implanted on the abdominal muscle on d 21 and d 28 of each dietary period. Plaques induced by the bone powder were harvested 12 d after the implantation. Tartrate-resistant acid phosphatase (TR-ACP) activity was lower and the number of multinucleated cells was smaller in plaques of animals during the protein-deficient period than during the control period. The administration of 1,25-dihydroxycholecalciferol increased the activity of TR-ACP and the number of multinucleated cells during both dietary treatments. However, TR-ACP activity was still lower and the cell number was still smaller during the protein-deficient period than during the control period when they were injected with 1,25-dihydroxycholecalciferol. These results suggest that protein deficiency reduces the activity of osteoclastic cell induction. The suppressive effect of protein deficiency on the induction and the activity of osteoclastic cells is not related to the action of 1,25-dihydroxycholecalciferol.

Animals↗

Cavernous lymphangioma of the breast: case report with electron microscopic and immunohistochemical investigations.

A rare case of cavernous lymphangioma of the breast in a 16-year-old Japanese girl was investigated by light and electron microscopies, and immunohistochemistry. The patient, who had a soft breast tumor measuring 16 x 14 cm, had undergone a tumorectomy two years after she noticed the tumor. Histologically, the tumor was composed of numerous narrow spaces containing amorphous fluid lined with a monolayer of endothelial cells. Abundant collagen fibers and numerous fibroblasts were found beneath the endothelium. Histological findings confirmed a diagnosis of lymphangioma of the breast. Immunohistochemically, the endothelium showed negative immunoreaction for factor VIII-related antigen, but the discontinuous basal lamina was positive for laminin. Ultrastructurally, numerous microfilaments and pinocytotic vesicles were found in the cytoplasm of the endothelial cells, and intermediate junctions were recognized between adjacent cells. In addition, a discontinuous basal lamina was seen beneath the endothelium. Electron microscopic and immunohistochemical investigations are thus useful in confirming a diagnosis of cavernous lymphangioma of the breast.

Adolescent↗

Adult T-cell leukemia/lymphoma with gastric lesions. Report of three cases.

We describe three cases of adult T-cell leukemia/lymphoma (ATL) with malignant cell infiltration into the stomach. Case 1, a 63-year-old man, had a large ulcerative lesion on the lesser curvature of the upper stomach. Case 2, a 44-year-old man, had an irregular depressed lesion simulating a IIc-type early gastric cancer on the posterior wall of the mid portion of the stomach. Case 3, a 58-year-old man, had multiple irregular depressed lesions on the lesser curvature of the lower part of the stomach. In all cases, histologic examinations of the biopsy specimens confirmed ATL-cell infiltration into the stomach. In cases 1 and 2, repeated roentgenographic and endoscopic examinations revealed the characteristic changes of the gastric lesions over the course of time.

Adult↗

Febrile convulsions in northern Japan: a quantitative and qualitative analysis of EEG and clinical findings.

In an attempt to describe the characteristics of febrile convulsions (FC) 133 children with a history of FC were checked neurologically at health centers in northern Japan. Using categorical data from principal component analysis, family history of FC, recurrence and body temperature prior to convulsion, EEG disorders, exogenous factors, age at onset as the principal components were extracted. A quantitative and qualitative analysis of EEG showed that children with FC had more paroxysmal and basic abnormalities, that the rate of appearance of theta wave was more common and of alpha wave was less common, and that mean values of frequency ranges of theta and alpha wave ranges together were significantly lower in the background activity than those of control group children.

Cerebral Cortex↗

A role for fibroblast growth factor in oligodendrocyte development.

The differentiation of oligodendrocyte-type 2 astrocyte (O-2A) glial progenitor cells into myelin-forming oligodendrocytes is influenced by several polypeptide growth factors. Exposure of O-2A progenitors to basic fibroblast growth factor (bFGF) promotes their sustained proliferation, blocks their differentiation, and maintains both a high level of platelet-derived growth factor (PDGF) alpha-receptors and PDGF sensitivity. Exposure to PDGF, in contrast, promotes only a limited number of cell divisions prior to their differentiation and triggers progenitor cell migration. In the continued presence of bFGF the cells have a stellate morphology with short processes. Upon addition of PDGF these stellate cells become bipolar with long processes, and on removal of PDGF their morphology reverts back to stellate. Thus the phenotype of O-2A progenitor cells in response to these growth factors is plastic. Our studies suggest that bFGF (or a related ligand) in the CNS may sensitize O-2A progenitors to PDGF and thereby initiate their ability to migrate into white matter tracts prior to the onset of myelination.

Amino Acid Isomerases↗

Deletion or substitution within the alpha platelet-derived growth factor receptor kinase insert domain: effects on functional coupling with intracellular signaling pathways.

The tyrosine kinase domains of the platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1)/c-fms receptors are interrupted by kinase inserts (ki) which vary in length and amino acid sequence. To define the role of the ki in the human alpha PDGF receptor (alpha PDGFR), we generated deletion mutants, designated alpha R delta ki-1 and alpha R delta ki-2, which lacked 80 (710 to 789) and 95 (695 to 789) amino acids of the 104-amino-acid ki region, respectively. Their functional characteristics were compared with those of the wild-type alpha PDGFR following introduction into a naive hematopoietic cell line, 32D. Biochemical responses, including PDGF-stimulated PDGFR tyrosine phosphorylation, phosphatidylinositol (PI) turnover, and receptor-associated PI-3 kinase activity, were differentially impaired by the deletions. Despite a lack of any detectable receptor-associated PI-3 kinase activity, 32D cells expressing alpha R delta ki-1 showed only partially impaired chemotactic and mitogenic responses and were capable of sustained proliferation in vitro and in vivo under conditions of autocrine stimulation by the c-sis product. 32D transfectants expressing the larger ki deletion (alpha R delta ki-2) showed markedly decreased or abolished biochemical and biological responses. However, insertion of the highly unrelated smaller c-fms (685 to 750) ki domain into alpha R delta ki-2 restored each of these activities to wild-type alpha PDGFR levels. Since the CSF-1R does not normally induce PI turnover, the ability of the c-fms ki domain to reconstitute PI turnover in the alpha R delta ki-2 transfectant provides evidence that the ki domain of the alpha PDGFR does not directly couple with this pathway. Taken together, all od these bindings imply that their ki domains have evolved to play very similar roles in the known signaling functions PDGF and CSF-1 receptors.

Animals↗

Effects of 250 and 500 Hz tone exposure on the inner ear of guinea pigs as determined by electrophysiological techniques.

The electrophysiological study of cochlear microphonics (CM), whole nerve action potential (AP) and endocochlear potential (EP) were examined. (1) With the extension of the exposure time of 500 Hz tone, a decrease of CM maximum output voltage in test frequency from 2 to 6 kHz was observed. (2) N1 potential of AP decreased very significantly by 500 Hz tone exposure. (3) A very pronounced decrease of the absolute value of the negative potential of the EP in 500 Hz exposure was seen.

Action Potentials↗

Therapeutic trial of hematological disorders with intermittent administration of high-dose 1-alpha-hydroxyvitamin D3.

Aplastic anemia and myelodysplastic syndrome were successfully treated with an intermittent administration of high-dose 1 alpha-hydroxy-vitamin D3, an active analogue of 1,25-dihydroxyvitamin D3. This effect was considered to be through the differentiation-inducing and immunomodulatory actions of 1,25-dihydroxyvitamin D3. The only adverse effect was hypercalciuria which was controllable by decreasing the dose.

Adult↗

Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm.

We previously suggested that activation of the protein kinase C-mediated contractile system may participate in the occurrence of chronic cerebral vasospasm. In the present study, we compared segments of normal beagle basilar arteries in vitro with segments of arteries undergoing chronic vasospasm to determine the responsiveness to various agonists such as serotonin, prostaglandin F2 alpha, and phorbol 12,13-diacetate as well as to external Ca2+. We also compared the effects of W-7 (a calmodulin inhibitor), nicardipine (a calcium channel blocker), and H-7 (a protein kinase C inhibitor) on the spontaneous tonus of arterial segments stabilized at a resting tension of 3 g. Compared with normal segments, the responsiveness to each agonist in segments undergoing vasospasm was essentially unchanged whereas the the responsiveness to external Ca2+ was significantly decreased (p less than 0.001). In segments undergoing vasospasm the decrease in resting tension induced by W-7 was markedly diminished (p less than 0.01), that induced by nicardipine was unchanged, and that induced by H-7 was significantly increased (p less than 0.01). Our results indicate that spontaneous tonus due to activation of the protein kinase C system is significantly augmented in segments undergoing vasospasm. Thus this system, rather than the Ca2+/calmodulin system, appears to play a major role in the occurrence of chronic vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Bovine undifferentiated alveolar rhabdomyosarcoma and its differentiation in xenotransplanted tumors.

At necropsy, a 7-year-old Holstein cow, clinically diagnosed via rectal palpation as having malignant abdominal neoplasia was found to have many metastatic tumors of various sizes in the abdominal and thoracic cavities and in the liver, lung, kidney, adrenal, uterus, and lymph nodes. These tumors were examined by histologic and immunohistochemical methods using anti-human myoglobin, anti-bovine myoglobin, and anti-desmin sera. Tumors were diagnosed as undifferentiated alveolar rhabdomyosarcomas. The tumors in the abdominal and thoracic cavities differed histologically from the metastases in organs. The former tumors consisted of only undifferentiated cells, most of which did not stain positively for desmin or myoglobin. The metastatic tumors contained a few rhabdomyoblastic cells that stained positively for desmin and myoglobin. Tumors tissues from the cow were transplanted and propagated through six passages in athymic nude mice. After one passage, the transplanted tumor histologically resembled those from the abdominal serosa and consisted of cells with scanty cytoplasm with an alveolar arrangement. Cells from this tumor stained positively for desmin and negatively for myoglobin. After two passages through nude mice, tumor cells were of two distinct histologic types: those cells with scanty cytoplasm and elongated cells with plentiful eosinophilic cytoplasm. Both of these cells stained positively for both desmin and myoglobin. After six passages, cross striations were detected in neoplastic cells by electron microscopy. These findings illustrate that a highly undifferentiated bovine rhabdomyosarcoma, in which most of the cells in the original tumor lacked desmin and myoglobin, became better differentiated and stained positively for desmin and myoglobin after serial transplantation in nude mice.

Abdominal Neoplasms↗

Two platelet-derived growth factor receptors in vascular smooth muscle cells.

Distinct genes encode alpha and beta PDGF receptors which differ in their abilities to be triggered by three dimeric forms of the PDGF molecules. By use of a strategy involving introduction of expression vectors for alpha and beta PDGF receptor cDNA into the cells originally lacking these receptors, we demonstrated that each receptor was able to couple independently with mitogenic signal transduction pathways inherently present in these cells. Moreover, both receptors were capable of inducing a readily detectable chemotactic response. The vascular smooth muscle cells which express both types of PDGF receptors are mitogenic and chemotactic for PDGFs. Moreover, the alpha receptor is the preferred receptor for platelet PDGF-AB as well as the PDGF-AA isoform which is ubiquitously produced in many cells forming atherosclerotic plaques including macrophages, endothelial cells and even arterial smooth muscle cells. Our results indicated that the availability of specific PDGF isoforms and the relative expression of each receptor gene product appear to be major determinants of the PDGF response. An understanding of the mechanisms by which the expression of PDGF and their receptors on vascular smooth muscle cells are regulated will give greater insights as to how these gene products are involved in atherosclerosis.

Arteriosclerosis↗

Extracellular ATP stimulates steroidogenesis in bovine adrenocortical fasciculata cells via P2 purinoceptors.

Effects of ATP and other purine derivatives on steroidogenesis in primary cultured bovine adrenocortical fasciculata cells were examined. At concentrations higher than 1 microM, ATP showed a potent stimulative effect on the cortisol production of the cells. The potency order of the steroidogenic effect of the tested purine derivatives was ATP greater than ADP much greater than adenosine much greater than AMP. alpha,beta-Methylene ATP had no stimulative effect on the steroidogenesis at concentrations as high as 1 mM. Theophylline did not antagonize the steroidogenic effect of ATP. These results suggest that bovine adrenocortical fasciculata cells possess the P2y purinoceptors that are linked to steroidogenesis.

Adenosine↗

Amyloidosis of the small intestine: findings on double-contrast radiographs.

The appearance of the small intestinal mucosa on double-contrast barium examinations was studied in 26 patients with proved intestinal amyloidosis. Findings included innumerable fine granular densities 1-3 mm in diameter (16 patients), multiple nodular densities 3-4 mm in diameter (four patients), multiple polypoid protrusions 4-10 mm in diameter (three patients), irregularities of Kerckring folds (12 patients), and multiple erosions (eight patients). The multiple nodular densities and erosions disappeared after the patients were treated with total parenteral nutrition. The other abnormalities remained unchanged on follow-up examinations. Our results indicate that double-contrast radiographic findings of the small intestine in patients with amyloidosis include mucosal abnormalities that vary according to the pathologic type of amyloid deposition.

Amyloidosis↗