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Biomedical subjects

S Yamamura

Publications and source records attributed to S Yamamura.

At least 91 records · Page 5Linked to original sources

[Necrotizing sarcoid granulomatosis diagnosed by video thoracoscopic lung biopsy].

A 28-year-old woman was admitted to our hospital because of chest pain. A chest roentgenogram and a chest computed tomogram revealed many nodular shadows on both sides. Examinations of specimens obtained by and by transbronchial lung biopsy during fiberoptic bronchoscopy were not diagnostic, and therefore video thoracoscopic lung biopsy was done. The lung lesion was characterized by aggregates of epithelioid cell granulomas, along with granulomatous and necrotizing angitis. We therefore diagnosed necrotizing sarcoid granulomatosis, and began to administer prednisolone. The nodular shadows disappeared within four weeks. In this case video thoracoscopic lung biopsy was useful in the diagnosis of necrotizing sarcoid granulomatosis in the lung.

Adult↗

Extrathymic differentiation of resident T cells in the joints of mice with collagen-induced arthritis.

Murine collagen-induced arthritis (CIA) is known as a T cell-mediated autoimmune disease, although autoantibodies are also suspected to be associated with the onset of the disease. To determine the origin of such T cells in the joints of mice with CIA, their phenotypic properties as well as those of T cells in other immune organs were examined in DBA/1 mice. Since a significant number of mononuclear cells (MNC) was also yielded by the joints of normal DBA/1 mice, the properties of these T cells were examined in parallel. When CIA was induced by an intradermal injection of type II collagen at the base of the tail, the numbers of MNC yielded by the regional lymph nodes and the foot joints were doubled. Interestingly, regardless of the onset of CIA, the joints were always comprised of unique T cell populations, including IL-2(R)alpha- beta+ T cells, gammadelta T cells, CD8alpha+ beta- cells, and CD44+ L-selectin- cells. All these properties coincide with those of extrathymic T cells in liver and intestine. In the case of gammadelta T cells in joints, Vgamma and Vdelta usages were unique and different from those in the other organs. More importantly, Vgamma and Vdelta usages in gammadelta T cells in the joints of normal mice and in those of mice with CIA were essentially the same. Taken together with the expression of recombination-activating gene-1 and -2 mRNAs by MNC in mice with CIA, these findings raise the possibility that the joints have their own resident T cells that are extrathymically generated in situ.

Animals↗

Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes show serious side effects such as damage to the gastroduodenal mucosa and dysfunction of the liver. Although many investigators have focused on some types of leukocytes, a comprehensive study concerning all types of leukocytes, especially recently identified extrathymic T cells, remains to be done. When mice were treated with an intraperitoneal injection of indomethacin (50 or 300 microg/mouse), the number of thymocytes decreased while the number of MNC in various peripheral organs increased. This increase in MNC was due mainly to the increase in the numbers of granulocytes and extrathymic T cells. Reflecting thymic atrophy, the proportion of thymus-derived T cells distributed in the periphery decreased. The use of other NSAIDs revealed that granulocytosis seen in the periphery arose from a selective activation of myelomonocytic cells in the bone marrow. Some functional experiments using the Ca2+ influx, iNOS mRNA expression, and autoreactive cytotoxicity as indicators suggested that granulocytes and extrathymic T cells were in activated states not only in number but also in function. Since both granulocytes and extrathymic T cells become cytotoxic effectors against self-tissues or self-cells when overactivated, these activated leukocytes may be intimately related to the etiology of the tissue damage inducible by NSAIDs (i.e., adverse drug reaction).

Animals↗

Level of myelopoiesis in the bone marrow is influenced by intestinal flora.

Mice were orally given kanamycin (50 mg/day/ mouse) for 1 or 2 weeks. Almost all bacteria in the intestine were eliminated within a week. In parallel with this elimination, the level of granulocytes in the bone marrow decreased from 41 to 31%. Since the total number of bone marrow cells decreased as well (up to one-third), the decrease in the level of granulocyte generation in the bone marrow was substantial. Kanamycin is not absorbed from the intestine into the body; namely, it does not have a direct effect on the bone marrow. It is speculated that the interaction of granulocytes or epithelial cells with intestinal bacteria accelerates the production of free radicals and superoxids, some cytokines, or unknown factors and that such substances then stimulate the generation of granulocytes in the bone marrow. The present results suggest that intestinal flora and other resident bacteria are important for maintaining the level of myelopoiesis in the bone marrow.

Animals↗

Sphingosine-1-phosphate inhibits actin nucleation and pseudopodium formation to control cell motility of mouse melanoma cells.

Sphingosine-1-phosphate (Sph-1-P), the initial product of sphingosine (Sph) catabolism, has been reported to inhibit motility of mouse melanoma B16/F1 and other types of cells at very low concentrations (10-100 nM). Sph-1-P (100 nM-1 microM) inhibited pseudopodium formation by blocking polymerization and reorganization of actin filaments in newly formed pseudopodia, and reduced F-actin by approximately 25% in F1 cells. A pyrene-labeled actin nucleation assay revealed that Sph-1-P (100 nM) inhibits actin nucleation mediated by F1 cell plasma membranes. These results suggest that Sph-1-P interacts with molecules associated with actin nucleation to inhibit reorganization of pseudopodium formation and cell motility.

Actins↗

Role of protein kinase C in attachment, spreading, and migration of human endothelial cells.

Attachment, spreading, and migration of vascular endothelial cells (EC) are necessary for angiogenesis, reendothelialization of an injured artery, or seeding of a prosthetic graft. However, little is known about the signaling pathways that mediate these effects. Protein kinase C (PKC) is a ubiquitous intracellular messenger which we have previously shown to be necessary for EC proliferation (Kent et al., 1995, Circ. Res. 77, 231-238). In this study, we investigate whether activation of PKC is necessary for EC attachment, spreading, and migration. Using human umbilical vein EC, we found that direct activation of PKC with the phorbol ester phorbol 12-myristate-13-acetate enhanced all three processes. Inhibition of PKC by the selective agent, chelerythrine, markedly diminished the ability of EC to attach, spread, and migrate. Depletion of intracellular PKC by downregulation (prolonged exposure of EC to phorbol ester) reduced EC attachment and migration; however, downregulation had no effect on endothelial spreading. PKC is a family of isotypes, each of which may control specific cellular functions. By Western blotting, we identified PKC alpha, beta, delta, epsilon, eta, theta, and zeta isotypes in human EC. Downregulation led to a significant reduction in the quantity of PKC alpha and epsilon. These data demonstrate that activation of PKC is both necessary and sufficient for attachment, spreading, and migration of human EC. An isotype of PKC that is susceptible to downregulation (either alpha and/or epsilon) is at least partially responsible for attachment and migration. Pharmacological activation of PKC may be used as a method to enhance reendothelialization.

Alkaloids↗

Inflammatory reaction in chondroblastoma.

OBJECTIVE: The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. DESIGN: We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. RESULTS: In all cases, MR imaging showed marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. CONCLUSION: We propose that these inflammatory reactions of chondroblastomas are important signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor.

Adolescent↗

Structure-activity relationship of lepidimoide and its analogues.

The structure-activity relationship of lepidimoide and its analogues was investigated by means of the Amaranthus caudatus L. hypocotyl elongation test. In addition, the activities of alpha-D-galacturonic acid and L-(+)-rhamnose, which are component sugars of lepidimoide, were also studied. The carboxylic acid free type of lepidimoide showed growth-promoting activity as high as the original lepidimoide (sodium type). The acetylated compound showed considerably higher activity than lepidimoide, whereas the methylated lepidimoide did not show any activity. The hydroxylated lepidimoide without a double bond in the C-4,5 position showed lower activity. The sugar alcohol type of lepidimoide [2-O-(alpha-D-glucopyranosyl)-L-rhamnose] showed the highest activity in all the compounds studied. alpha-D-Galacturonic acid, L-(+)-rhamnose and their mixtures, which are component sugars of lepidimoide, exhibited only slight or no activity, respectively. D-Glucose and the mixture of D-glucose and L-(+)-rhamnose were also slightly active or inactive. These data suggest that the active sites in the chemical structure of the lepidimoide are the uronic acid derivative bearing an alpha,beta-unsaturated carboxylate bonded to rhamnose via an alpha-glucoside linkage and a double bond in the C-4,5 position in the uronic acid.

Carbohydrate Sequence↗

Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways.

BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs). Three isotypes of PDGF (BB, AB, and AA) have been identified; each of these isotypes may have differing effects on the behaviour of vascular SMCs. In this study we evaluated the influence of PDGF isotypes on proliferation and migration of human venous SMCs and explored the signaling pathways through which these effects are mediated. METHODS: Proliferation was measured by a 72-hour assay of cell number, and migration was evaluated by a 4-hour microchemotaxis assay. The effects of PDGF isotypes on the activities of the signaling proteins mitogen-activated protein kinase (MAP-K), p 125 focal adhesion kinase (p125FAK), and tensin were measured by immunoprecipitation of these proteins and subsequent phosphorylation on myelin basic protein (in MAP-K) and Western blotting with antiphosphotyrosine (in tensin and p125FAK). RESULTS: All three isotypes stimulated SMC proliferation (PDGF-BB > AB > AA). PDGF-BB and -AB, but not -AA, stimulated chemotaxis. All three isotypes activated MAP-K with an intensity that corresponded to their proliferative effects. PDGF-BB and -AB tyrosine phosphorylated tensin and p125FAK, whereas PDGF-AA had no effect on either of these proteins. CONCLUSIONS: For human vascular SMCs the physiologic effects and the signaling pathways that mediate these effects are specific for each of the three PDGF isotypes. These data also suggest an association between MAP-K and SMC proliferation and between the proteins, p125FAK and tensin, and migration.

Calcium-Calmodulin-Dependent Protein Kinases↗

Extracellular matrix proteins are potent agonists of human smooth muscle cell migration.

PURPOSE: Extracellular matrix proteins can stimulate smooth muscle cell (SMC) migration by three distinct mechanisms: chemokinesis (nondirected migration in the presence of soluble protein), chemotaxis (directed migration toward soluble protein), and haptotaxis (directed migration toward insoluble, substrate-bound protein). This study investigates the effects of four prevalent extracellular matrix proteins (collagen types I and IV, fibronectin, and laminin), and platelet-derived growth factor (PDGF) on haptotaxis, chemotaxis, and chemokinesis of human SMCs. The role of large guanosine triphosphate-binding proteins (G-proteins) in the signaling mediating these effects is also evaluated. METHODS: Human saphenous vein SMCs were used in all migration studies. Chemokinesis, chemotaxis, and haptotaxis to each of the matrix proteins were measured and compared with PDGF through the use of a 48-well microchemotaxis chamber. The role of G-proteins in matrix-induced SMC migration was studied with the modulators of G-protein function, cholera and pertussis toxins. RESULTS: For all matrix proteins the relative strength of the various stimuli for migration was haptotaxis > chemotaxis > chemokinesis (p < 0.05). For all three stimuli collagen I and IV produced the most significant migration followed by fibronectin > PDGF-AB > laminin (p < 0.05). Pertussis toxin completely inhibited chemotaxis and partially inhibited haptotaxis by laminin but did not affect migration by other matrix proteins, whereas cholera toxin abolished migration in response to all four matrix proteins. CONCLUSION: Matrix proteins, with the exception of laminin, provide a more significant stimulus for SMC locomotion than does the prototypical agonist, PDGF-AB. Of the three mechanisms by which migration can be stimulated, haptotaxis elicits the most profound effect. The importance of G-proteins as second messengers for migration varies with each matrix protein and with the mechanism of stimulation.

Cell Movement↗

Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. I. Producing strain, fermentation, isolation, and biological activities.

New protein farnesyltransferase inhibitors, andrastins A-C, have been discovered in the cultured broth of Penicillium sp. FO-3929. Andrastins extracted from broth supernatant were purified by silica gel chromatography, ODS chromatography and HPLC. The IC50 of andrastins A, B, and C against protein farnesyltransferase were 24.9, 47.1, and 13.3 microM, respectively.

Alkyl and Aryl Transferases↗

Giant cell-rich osteosarcoma: a case report.

This report discusses a rare case of giant cell-rich osteosarcoma. The patient, a 19-year-old male, was diagnosed with a metadiaphyseal osteolytic lesion when he consulted a local doctor complaining of motion pain without swelling. Radiography revealed a geographic osteolytic lesion, cortical thinning and ballooning without obvious cortical destruction. However, a fine onion skin-like periosteal reaction was observed on the lateral side of the femur. The transitional none was narrow and endosteal scalloping was also noted. Needle biopsied material clearly showed nuclear atypism of the stromal tumor cells with numerous osteoclast-like giant cells. Using a combination of pathological examination, radiography, computed tomography (CT) and magnetic resonance imaging (MRI), a diagnosis of giant cell-rich osteosarcoma was reached. After chemotherapy, resection and limb salvage surgery with an autogeneous autoclaved bone graft, a vascularized fibular graft were performed, and the patient has shown excellent limb function without local recurrence or distant metastasis during the past 72 months.

Adult↗

Solid variant of an aneurysmal bone cyst (giant cell reparative granuloma) of the 3rd lumbar vertebra.

A 9-year-old girl with a solid variant of an aneurysmal bone cyst in the 3rd lumbar vertebra showed a good response to low-dose radiation as the only treatment. The solid variant of aneurysmal bone cyst is thought to be a reactive response to intraosseous hemorrhage and is also called giant cell reparative granuloma or giant cell reaction. These lesions in the jaw and the short tubular bones of the hands and feet frequently recur after surgery. Aneurysmal bone cysts of the spine also show a fairly high recurrence rate after incomplete resection or radiation therapy. However, 7 previous cases of the solid variant of aneurysmal bone cyst in the spine and this case did not show recurrence after a mean follow-up period of 45 months. This difference in behaviour suggests that the solid variant should be recognized before surgery as being distinct from conventional aneurysmal bone cysts, especially in the spine.

Bone Cysts, Aneurysmal↗

Proliferating cell nuclear antigen staining as a prognostic indicator in soft-tissue malignant fibrous histiocytoma.

To determine the value of proliferating cell nuclear antigen (PCNA) staining as a prognostic indicator in soft-tissue malignant fibrous histiocytoma (MFH), we studied 27 patients who underwent resection including an adequately wide margin but without chemotherapy. The survival rate of patients with a lesion in which less than 70% of the cells was positively stained was significantly higher (P < 0.01) than of those with more than 70% positive staining. Twenty-two patients (81.5%) evidenced disease-free survival (mean follow-up period 4.6 years), 1 patient was alive with disease, and 4 (14.8%) died of the disease with lung or lymph node metastasis. In all 4 patients who died, PCNA staining was over 70% positive. In 2 of them, an increase in the number of PCNA-positive cells was observed after repeated recurrence. We conclude that PCNA is a useful prognostic indicator which provides a quantitative measure of the grade of malignancy in MFH patients who receive operative treatment without chemotherapy.

Adolescent↗

Antiallergic dimeric prenylbenzoquinones from Ehretia microphylla.

The ethyl acetate-soluble portion of the MeOH extract of Ehretia microphylla showed inhibitory activity on exocytosis in antigen-stimulated rat basophils. The bioassay-guided separation of this fraction afforded five biologically active compounds. By means of chemical and spectroscopic methods, the structures of these compounds, which include microphyllone, a unique dimeric prenylbenzoquinone, and its congeners, were elucidated.

Allergens↗

Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction.

Activation of the PDGF receptor on human arterial smooth muscle cells (SMC) induces migration and proliferation via separable signal transduction pathways. Sphingosine-1-phosphate (Sph-1-P) can be formed following PDGF receptor activation and therefore may be implicated in PDGF-receptor signal transduction. Here we show that Sph-1-P does not significantly affect PDGF-induced DNA synthesis, proliferation, or activation of mitogenic signal transduction pathways, such as the mitogen-activated protein (MAP) kinase cascade and PI 3-kinase, in human arterial SMC. On the other hand, Sph-1-P strongly mimics PDGF receptor-induced chemotactic signal transduction favoring actin filament disassembly. Although Sph-1-P mimics PDGF, exogenously added Sph-1-P induces more prolonged and quantitatively greater PIP2 hydrolysis compared to PDGF-BB, a markedly stronger calcium mobilization and a subsequent increase in cyclic AMP levels and activation of cAMP-dependent protein kinase. This excessive and prolonged signaling favors actin filament disassembly by Sph-1-P, and results in inhibition of actin nucleation, actin filament assembly and formation of focal adhesion sites. Sph-1-P-induced interference with the dynamics of PDGF-stimulated actin filament disassembly and assembly results in a marked inhibition of cell spreading, of extension of the leading lamellae toward PDGF, and of chemotaxis toward PDGF. The results suggest that spatial and temporal changes in phosphatidylinositol turnover, calcium mobilization and actin filament disassembly may be critical to PDGF-induced chemotaxis and suggest a possible role for endogenous Sph-1-P in the regulation of PDGF receptor chemotactic signal transduction.

Actin Cytoskeleton↗