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Biomedical subjects

M Shimamura

Publications and source records attributed to M Shimamura.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Effects of interelectrode separation in sensory nerve conduction studies].

Sensory nerve action potentials (SNAPs) obtained by conventional sensory nerve conduction studies are greatly influenced by the distance between exploring and reference electrodes. Changes in SNAPs were investigated in 12 healthy median nerves using the orthodromic and antidromic sensory nerve conduction studies with 1-cm, 2-cm, 3-cm, 4-cm, and 5-cm of interelectrode distances. Peak-to-peak (orthodromic) or baseline-to-peak (antidromic) amplitudes and durations between the positive peaks were measured and each value was expressed as a ratio to the recording of 1-cm of interelectrode distance. SNAPs with maximum amplitude were obtained by more than 3-cm of interelectrode distance. Duration of SNAP was increased by an increase of interelectrode distance. Change in amplitude along with the interelectrode distance was larger in the orthodromic method than in the antidromic method. Contrariwise, change in duration was larger in the antidromic method. SNAPs with long duration had a gently sloping configuration, and each peak tended to be indistinct. So, 3-cm of active and reference interelectrode separation should be recommended in performing sensory nerve conduction studies between wrist and finger, because maximum amplitude and clear visualization of peaks are available.

Action Potentials↗
PubMed1998

The proteasome is involved in angiogenesis.

The proteasome is a recently identified intracellular protease whose catalytic active site is a threonine residue and has been shown to play key roles in a variety of important intracellular events, including cell cycle progression, the antigen-presenting pathway, and apoptosis. However, its biological significance in multicellular organisms is still largely unknown because of lack of experimental systems for its study. Here we verified potential involvement of the proteasome in angiogenesis using lactacystin, a specific proteasome inhibitor. Lactacystin treatment resulted in almost complete prevention of in vivo neovascularization in the developing chick embryo chorioallantoic membrane. It also inhibited vascular endothelial tube formation on Matrigel, a model for in vitro angiogenesis, in a concentration-dependent fashion. Moreover, it prevented production of plasminogen activator, an important protease responsible for induction of angiogenesis, by endothelial cells, which correlated well with its suppression of intracellular proteasome activity. Our studies suggest that the proteasome operates in the process of angiogenesis, a phenomenon essential in important physiological and pathological settings.

Acetylcysteine↗
PubMed1998

Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouches.

Whether spinorphin, an endogenous regulator of enkephalin-degrading enzymes, plays a role in an anti-inflammatory action was examined, using a mouse air-pouch assay as a model of acute inflammation. Repeated intravenous administration (6 times) of spinorphin every hour significantly suppressed carrageenan-induced polymorphonuclear neutrophil (PMN) accumulation, an indicator of inflammation (3.21+/-0.95 x 10[6] cells vs 8.92+/-0.96 x 10[6] cells, 10mg/kg spinorphin-treated vs saline-treated group, n=5, P<0.01) at 6 hr. The combination of spinorphin and leuhistin (2 mg/kg, i.v.), a specific inhibitor of aminopeptidase N (APN), markedly suppressed the PMN accumulation induced by carrageenan (1.11+/-0.17 x 10[6] cells, 88% inhibition compared to the saline-treated group, n=5, P<0.01). This inhibition was less than, but comparable to that of dexamethasone (30 mg/kg/one shot, i. v.), a representative anti-inflammatory drug. These results indicate that spinorphin may be an endogenous anti-inflammatory regulator, its inhibitory activity being modulated by APN.

Aminopeptidases↗
PubMed1998

[Mediastinal neurilemmoma originating in the right phrenic nerve: a case report].

We report on a 31-year-old man with a mediastinal neurilemmoma originating in the right phrenic nerve. The patient was admitted because of abnormal chest X-ray shadows observed during a routine checkup. A preoperative diagnosis of bronchial cyst in the mediastinum was made. The tumor was resected by video-assisted thoracic surgery. It was 3 x 4 x 3 cm in size, weighted 15 g, and originated in the right phrenic nerve. The histopathologic diagnosis was mediastinal neurilemmoma. Only 14 cases have been reported in the Japanese literature.

Adult↗
PubMed1997

Inhibitory effects of spinorphin, a novel endogenous regulator, on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils.

To characterize the inflammatory effect of spinorphin, an endogenous peptide purified from bovine spinal cord, its effects on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated human neutrophils (PMNs) in vitro were examined. At 10 microM, spinorphin significantly inhibited chemotaxis by FMLP-stimulated PMNs. Spinorphin at 100 microM also inhibited both O2- generation and exocytosis of beta-glucuronidase and collagenase by FMLP-stimulated PMNs. The mechanisms by which spinorphin inhibits these PMN functions were examined further. Spinorphin markedly suppressed the binding of FML[3H]P to its receptor on PMNs, as observed in a binding assay. However, other neuropeptides that were examined (angiotensin II and substance P) had no effect on FML[3H]P binding, suggesting the possibility that spinorphin plays a specific role in the inhibition of the binding between FMLP and its receptor. The suppression of FMLP binding also caused a decrease of the FMLP-induced intracellular calcium concentration [Ca2+]i, which acts as a second messenger leading to PMN functions. These results suggest that spinorphin may be a new endogenous inflammation-regulatory peptide that modulates the interaction of FMLP with its receptor.

CD13 Antigens↗
PubMed1997

Molecular evidence from retroposons that whales form a clade within even-toed ungulates.

The origin of whales and their transition from terrestrial life to a fully aquatic existence has been studied in depth. Palaeontological, morphological and molecular studies suggest that the order Cetacea (whales, dolphins and porpoises) is more closely related to the order Artiodactyla (even-toed ungulates, including cows, camels and pigs) than to other ungulate orders. The traditional view that the order Artiodactyla is monophyletic has been challenged by molecular analyses of variations in mitochondrial and nuclear DNA. We have characterized two families of short interspersed elements (SINEs) that were present exclusively in the genomes of whales, ruminants and hippopotamuses, but not in those of camels and pigs. We made an extensive survey of retropositional events that might have occurred during the divergence of whales and even-toed ungulates. We have characterized nine retropositional events of a SINE unit, each of which provides phylogenetic resolution of the relationships among whales, ruminants, hippopotamuses and pigs. Our data provide evidence that whales, ruminants and hippopotamuses form a monophyletic group.

Animals↗
PubMed1997

Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.

NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.

Animals↗
PubMed1997

Lack of directed V alpha 14-J alpha 281 rearrangements in NK1+ T cells.

NK1.1+ T cells are an unusual subset of TCR alpha beta cells distinguished by their highly restricted V beta repertoire and predominant usage of an invariant V alpha 14-J alpha 281 chain. To assess whether a directed rearrangement mechanism could be responsible for this invariant alpha chain, we have analyzed V alpha 14 rearrangements by polymerase chain reaction and Southern blot in a panel of cloned T-T hybrids derived from thymic NK1.1+ T cells. As expected a high proportion (17/20) of the hybrids had rearranged V alpha 14 to J alpha 281. However, V alpha 14-J alpha 281 rearrangements always occurred on only one chromosome and were accompanied by other V alpha-J alpha rearrangements (not involving V alpha 14) on the homologous chromosome. These data argue that rigorous ligand selection rather than directed rearrangement is responsible for the high frequency of V alpha 14-J alpha 281 rearrangements in NK1.1+ T cells.

Animals↗
PubMed1997

Design, synthesis, and biological activity of anti-angiogenic hypoxic cell radiosensitizer haloacetylcarbamoyl-2-nitroimidazoles.

We designed, synthesized, and evaluated haloacetylcarbamoyl-2-nitroimidazoles, including chloro (KIN-1800, TX-1835, and TX-1836) and bromo derivatives (TX-1844, TX-1845, and TX-1846), as potential hypoxic cell radiosensitizers with antiangiogenic activities. To establish biological function owing to the haloacetylcarbamoyl group in the side-chain, we compared their in vitro radiosensitizing activities with those of their parent 2-nitroimidazoles without haloacetylcarbamoyl groups: misonidazole (MISO), TX-1831, and TX-1832, respectively. Both tert-butoxy substituted derivatives. TX-1835 and TX-1845, were more potent radiosensitizers than TX-1831. The p-tert-butylphenoxy-substituted derivatives, TX-1836 and TX-1846, and the methoxysubstituted derivatives, KIN-1800 and TX-1844, were stronger radiosensitizers than TX-1832 and MISO. We examined the anti-angiogenic activities of these 2-nitroimidazole derivatives containing haloacetylcarbamoyl group by the rat lung endothelial (RLE) cell proliferation assay and chick embryo chorioallantoic membrane (chick CAM) angiogenesis assay and showed that haloacetylcarbamoyl-2-nitroimidazoles were more potent angiogenic inhibitors than the corresponding desacetylcarbamoyl-2-nitroimidazoles. The in vivo chick CAM angiogenesis assay showed that the strong bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, were the strongest angiogenic inhibitors among them. We concluded that the bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, are promising as anti-angiogenic hypoxic cell radiosensitizers.

Adenosine Triphosphate↗
PubMed1997

Potent and subtype-selective CCK-B/gastrin receptor antagonists: 2,4-dioxo-1,5-benzodiazepines with a plane of symmetry.

A series of CCK-B/gastrin receptor antagonists, 2,4-dioxo-1,5-benzodiazepine derivatives with a plane of symmetry, were designed, synthesized, and evaluated for antagonistic activity. Structure-activity relationship studies revealed that carbonylmethyl groups at both N-1 and N-5 positions and hydrophilic groups, such as the carboxyl group on the benzene ring attached to the ureido group at the C-3 position, brought about potent affinity and subtype selectivity for CCK-B/gastrin receptors. Several compounds showed excellent in vivo inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats.

Animals↗
PubMed1997

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗
PubMed1997

Inhibition of angiogenesis by rhizoxin, a microbial metabolite containing two epoxide groups.

Previous studies by our and other groups have shown that microbial products containing more than one epoxide group, including eponemycin, radicicol, depudecin and AGM-1470, exhibits anti-angio-genic activity in an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. Based on these findings, rhizoxin, a microbial metabolite that contains two epoxide groups and exhibits anti-tubulin activity, was tested for anti-angiogenic activity in a CAM assay system. Rhizoxin caused dose-dependent inhibition of embryonic angiogenesis, the ID50 value being 2 ng (3.2 pmol) per egg. In addition, this compound (2 mg/kg i.p.) significantly suppressed neovascularization induced by M5076 mouse tumor cells in a mouse dorsal air sac assay system, compared to the vehicle alone (P < 0.05). These results indicate that rhizoxin is a novel inhibitor of angiogenesis, and that is has potential as a new therapeutic agent for cancer.

Animals↗
PubMed1997

Synthesis of a new potent anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedroxyprogesterone acetate [FMPA]).

A new anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedoroxyprogesterone acetate [FMPA, 9] was synthetized in a 10-step sequence. FMPA (9) had about two orders of magnitude stronger anti-angiogenic activity than medroxyprogesterone acetate (MPA), as estimated in a bioassay involving chorioallantoic membranes of growing chick embryos.

Animals↗
PubMed1996

Potent inhibition of angiogenesis by wortmannin, a fungal metabolite.

Wortmannin ([1S-(1 alpha, 6b alpha, 9a beta, 11 alpha, 11b beta)]-11-(acetyloxy)-1,6b,7,8,9a,10,11,11b-octahydro-1- (methoxymethyl)-9a, 11b-dimethyl-3 H-furo[4,3,2-de]indeno[4,5-h]-2-benzopyran-3,6,9-trione), a fungal metabolite that is as a selective inhibitor of phosphatidylinositol 3-kinase, was evaluated for its potential as an inhibitor of in vivo angiogenesis in a bioassay system involving growing chick embryo chorioallantoic membranes. It showed dose-dependent inhibitory activity against embryonic angiogenesis. This inhibition occurred at a dose as low as 1 ng (2.3 pmol) per egg and the ID50 value was 30 ng/egg. These findings suggest that wortmannin is a new angiogenesis inhibitor, and that it may be a lead antibiotic for a novel class of therapeutic agents for angiogenesis-dependent diseases like cancer, diabetic retinopathy and rheumatoid arthritis.

Allantois↗
PubMed1996

Effects of bezafibrate on ethanol oxidation in rats.

Bezafibrate is used to lower serum lipid levels in humans. Fibrate derivatives induce an enzyme participating in the beta-oxidation by peroxisomes. We gave ethanol (2 g/kg) orally to bezafibrate-treated (300 mg/kg) male rats of the Wistar strain. Blood ethanol levels were remarkably lower and ethanol elimination stood at 432.6 mg/kg/hr (control, 336.6 mg/kg/hr) in the bezafibrate group (p < 0.01). Blood acetate levels were conversely higher in the bezafibrate group. The fatty acid beta-oxidation activity of liver peroxisome in bezafibrate-treated, clofibrate-treated, or gamma-linolenic acid-treated rats for 4 days was assayed. The activity was 5.8-fold higher in rats given bezafibrate, 5.4-fold in the clofibrate (p < 0.01), and 2.0-fold in the gamma-linolenic acid (p < 0.05). Alcohol dehydrogenase and aldehyde dehydrogenase activity of cytosol in the liver was not induced by the hypolipidemic drugs, but aldehyde dehydrogenase activity in the liver homogenate was induced. From foregoing results, bezafibrate induced in the organism beta-oxidation by peroxisomes and increased H2O2 production, which led to augmented ethanol metabolism by catalase.

Acetates↗
PubMed1996

[Effects of kamikihi-to on ovariectomy-induced changes in behavior and circulation in rats].

The various symptoms that women experience in the climacteric period, such as flashing, depression, paresthesia and insomnia, have been termed the menopausal syndrome. Since Kamikihi-to (KMK) has been administered clinically for several of these symptoms, the effects of KMK were evaluated in a series of experiments using adult ovariectomized (OVX) rats. After surgery, KMK and other drugs were administered daily for 7 or 8 days until the experiments. OVX rats showed significantly higher electric shock thresholds, and KMK restored their sensitivity to electric shock in a dose-dependent manner. Furthermore, the latency of OVX rats in the step-through passive avoidance test was significantly shortened, and KMK prolonged the latency significantly. OVX rats showed a significantly decreased number of correct choices and an increased number of errors in the 8-arm radial maze task, and KMK normalized both of these parameters in a dose-dependent manner. The blood pressure of OVX rats was significantly increased, and KMK improved the blood pressure levels. These findings suggest that KMK might be useful for treatment of the menopausal syndrome, and it is considered that the improvements induced by KMK are due to other actions, such as normalization of the central nervous system, rather than sex hormones.

Animals↗
PubMed1996

[Chest wall reconstruction after the resection of primary chest wall tumors].

Between April 1983 and June 1994, we performed chest wall reconstructions on 9 patients (7 males and 2 females) out of 27 all of whom underwent the radical resection for the primary chest wall tumors. Histological diagnosis of tumors included 6 chondrosarcomas, 1 Ewing's sarcoma, 1 plasmacytoma and 1 giant cell tumor. Six lesions were located on the rib and 3 on the sternum. For the materials for reconstruction of the chest wall use a polyethylene plate in 2 patients, a Marlex mesh in 5 patients and a Marlex mesh with a methyl methacrylate utilizing the sandwich method in 2 patients. The polyethylene plate proved to be satisfactory for maintaining stability of the chest wall. However, our experience using this plate showed intensive foreign body reactions, and discovering these we have not use the polyethylene plate. Marlex mesh had an affinity with human tissue and was very easy to use and produced no complications. We use Marlex mesh for flat surfaces on the anterior or posterior chest wall. Marlex mesh and methyl methacrylate utilizing the sandwich method, combined the solidity and shaping of methyl methacrylate with the benefit such as easy fixation and excellent incorporation of the mesh.

Adult↗