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Biomedical subjects

S Koyama

Publications and source records attributed to S Koyama.

At least 55 records · Page 3Linked to original sources

Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in bovine retinal endothelial cells.

Recent studies have shown that angiopoietins (Angs) and their receptor, Tie2, play a role in vascular integrity and neovascularization. The renin-angiotensin system has been hypothesized to contribute to the development of diabetic retinopathy. In this study, we investigated the effect of angiotensin II (AII) on Ang1 and Ang2 expression in cultured bovine retinal endothelial cells (BRECs). AII stimulated Ang2 but not Ang1 mRNA expression in a dose- and time-dependent manner. This response was inhibited completely by angiotensin type 1 receptor (AT1) antagonist. AII increased the transcription of Ang2 mRNA, but did not change the half-life. Protein kinase C (PKC) inhibitor completely inhibited AII-induced Ang2 expression, and the mitogen-activated protein kinase (MAPK) inhibitor also inhibited it by 69.4+/-15.6%. In addition, we confirmed the upregulation of Ang2 in an AII-induced in vivo rat corneal neovascularization model. These data suggest that AII stimulates Ang2 expression through AT1 receptor-mediated PKC and MAPK pathways in BREC, and AII may play a novel role in retinal neovascularization.

Angiopoietin-1↗

[The usefulness of intra-operative angiography during off-pump CABG].

BACKGROUND: Recently OPCAB has become more and more common in CABG, although one problem of OPCAB like the quality of anastomosis has not been solved yet. We discussed the usefulness of intra-operative angiography during OPCAB. METHODS: During March 1997-July 2000, 55 patients underwent OPCAB (including 35 MIDCAB cases) in our institute. Graft flow and anastomosis were examined by intra-operative or immediate post-operative angiography. RESULTS: Immediate postoperative angiography was performed in 22 MIDCAB cases. In 15 cases an excellent graft flow without stenosis could be confirmed, in 7 cases the native LAD was so small, which caused a poor flow of the LITA and three cases needed additional PTCA because of anastomosis stenosis. Intra-operative angiography was done in 9 MIDCAB and 17 OPCAB. As a result, re-anastomosis was performed in one case of MIDCAB because of severe anastomosis stenosis, one case of OPCAB had confirmed poor flow because of a small LAD, but in 24 cases an excellent graft flow could be seen on time. In 2 cases OPCAB was combined with PTCA to achieve complete revascularization. CONCLUSIONS: Intra-operative angiography is a useful strategy to confirm the surgical results quickly in OPCAB (included MIDCAB). Using such a strategy, combination of OPCAB and PTCA as a new approach for complete revascularization can be performed safe and smooth.

Aged↗

Methotrexate stimulates lung fibroblasts and epithelial cells to release eosinophil chemotactic activity.

OBJECTIVE: To determine if methotrexate (MTX) induces human lung fibroblast (HFL-1) and epithelial (BEAS 2B) cell lines to release eosinophil chemotactic activity (ECA). METHODS: HFL-1 and BEAS 2B cell supernatant fluids were evaluated for ECA by a blind well chamber technique. RESULTS: HFL-1 and BEAS-2B cells released ECA in a dose and time dependent manner in response to MTX. Partial characterization revealed that ECA was partly heat labile, trypsin sensitive, and ethylacetate extractable. Thus the culture supernatant fluids were evaluated for known eosinophil chemotactic factors. Although several were released constitutively, granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly increased in response to MTX from both cell types. Consistent with these observations, ECA from both cell types was inhibited by GM-CSF antibodies. CONCLUSION: These data suggest that lung fibroblasts and epithelial cells may modulate eosinophil recruitment into the lung by releasing ECA in response to MTX.

Antibodies↗

[A case of a multiple sclerosis with severe perifocal edema].

We present a case of tumoral multiple sclerosis in a 66-year-old male and emphasize two clinical features: (1) Multiple well-demarcated massive enhanced lesions except for the central area, which was accompanied with severe perifocal edema, occurred within the cerebral hemispheres and should be strongly considered in the diagnosis of mass lesions. The patient underwent partial removal of the mass lesion. The initial histopathological diagnosis of the surgical specimen was astrocytoma grade II. (2) Multiple lesions disappeared completely for one and half months after starting medication using steroid. The reexamination of the surgical specimen was compatible with that of multiple sclerosis. Again, half a month after remission, multiple enhanced lesions without perifocal edema developed in the cerebral and cerebellar hemisphere. The difficulty of the initial diagnosis of multiple sclerosis with severe perifocal edema was discussed, based on our experience.

Aged↗

Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into the tympanic cavity.

Tinnitus is an otological symptom that is encountered often, yet its treatment is difficult. If tinnitus is of cochlear origin, a reasonable assumption is that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic infusion of a local anesthetic (4% lidocaine) to anesthetize the inner ear was conducted in a patient suffering from tinnitus. Transtympanic infusion of 4% lidocaine was performed as a treatment for cochlear tinnitus, and its efficacy was investigated. The overall efficacy rate for the 292 patients with 369 affected ears was 81%. In the investigation of the treatment results in cases of different underlying ear diseases, the efficacy rate was high for tinnitus accompanying sudden deafness and labyrinthine vertigo. However, vestibular symptoms, such as vertigo and nausea, developed after lidocaine infusion. No permanent side effects were noted. Lidocaine infusion is thought to be a useful treatment option for tinnitus and should be considered before surgical treatment. Inner ear anesthesia into the tympanic cavity has been carried out in patients who had cochlear tinnitus and in whom conservative methods of therapy, such as oral medication, had proved unsuccessful. This treatment method is useful as a local therapy for cochlear tinnitus.

Anesthetics, Local↗

Presynaptic 5-HT3 receptor-mediated modulation of synaptic GABA release in the mechanically dissociated rat amygdala neurons.

Nystatin-perforated patch recordings were made from mechanically dissociated basolateral amygdala neurons with preserved intact native presynaptic nerve terminals to study the mechanism of 5-HT3 receptor-mediated serotonergic modulation of GABAergic inhibition. The specific 5-HT3 agonist mCPBG (1 microM) rapidly facilitated the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and this facilitation desensitized within 1 min. Tropisetron (30 nM), a specific 5-HT3 antagonist, blocked the mCPBG effect. mCPBG augmented mIPSC amplitude. However, no direct postsynaptic serotonergic currents were evoked by mCPBG. Neither GABA-evoked current amplitude nor the kinetics of individual GABAergic mIPSCs were affected by mCPBG. Therefore, the augmentation is unlikely to be due to postsynaptic effects evoked by mCPBG. At higher concentrations mCPBG produced shorter-duration facilitation of miniature events. While mCPBG increased the mIPSC frequency in calcium-containing solution with Cd2+, this increase was absent in Ca2+-free external solution. It appears that the Ca2+ influx through voltage-dependent calcium channels was not as crucial as that through 5-HT3 receptors for synaptic GABA release. When two pulses of mCPBG (each 1 microM, 1 min) were given, the response to the second pulse elicited full recovery when the interval between pulses was at least 9 min. Protein kinase A (PKA) activation by 8-Br-cAMP (300 microM) shortened and PKA inhibition by Rp-cAMP (100 microM) prolonged the recovery time. PKA activity did not affect the time course of fast desensitization. Our results suggest that a 5-HT3-specific agonist acts on presynaptic nerve terminals facilitating synaptic GABA release without postsynaptic effects. The facilitation requires calcium influx through presynaptic 5-HT3 receptors. PKA modulates the recovery process from desensitization of presynaptic 5-HT3 receptor-mediated regulation of synaptic GABA release.

Amygdala↗

The masking effect in foreign speech sounds perception revealed by neuromagnetic responses.

The backward masking effect on non-native consonants by a following vowel was examined using neuromagnetic responses to synthesized speech sounds. Native speakers of Japanese were presented with sequences of frequent (85%) and infrequent (15%) speech sounds (/ra/ and /la/ respectively, no /l/ /r/ contrast in Japanese language). The duration of the stimuli was 110 ms in a short session and 150 ms in a long session. In the short session, the stimuli were terminated in the course of the transition from the consonant to the vowel to diminish the masking effect from the vowel part. A distinct magnetic counterpart of mismatch negativity (MMNm) was observed for the short session, whereas a smaller MMNm was observed for the long session.

Adult↗

Presynaptic modulation of synaptic gamma-aminobutyric acid transmission by tandospirone in rat basolateral amygdala.

Nystatin-perforated patch recordings were made from mechanically dissociated neurons (in which functional native presynaptic nerve terminals are preserved), isolated from the basolateral amygdala regions to investigate the effects of tandospirone on gamma-aminobutyric acidergic (GABAergic) inhibition. Two types of neurons, ovoid-shaped and pyramidal-shaped neurons, were obtained from the basolateral amygdala nuclei and the electrophysiological characteristics of these two types of neurons supported the morphological classification of these isolated neurons. From the ovoid-shaped neurons, bicuculline-sensitive GABA(A)ergic miniature inhibitory postsynaptic currents (miniature IPSC) were recorded in the presence of tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphovaleric acid (DL-AP5). Tandospirone (10 microM) reversibly and continuously inhibited the GABAergic miniature synaptic events to 66.3+/-2.1% of control (P<0.01, n=17) without affecting the miniature IPSC amplitude (104.0+/-3.1% of control, n=17). The similar inhibition of miniature IPSC frequency was mimicked by a specific 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 1 microM), and the effects of tandospirone were prevented in the presence of a specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190, 1 microM). Activation of 5-HT1A receptors by 8-OH-DPAT (1 microM) evoked no direct postsynaptic effects in enzyme-treated isolated basolateral amygdala neurons, suggesting that tandospirone acts at presynaptic 5-HT1A receptors. Furthermore, this presynaptic inhibition by tandospirone was prevented after treatment with a pertussis toxin-sensitive GTP-binding protein (G-protein) inhibitor, N-ethylmaleimide (at 3 microM for 5 min). In conclusion, in the basolateral amygdala nuclei, tandospirone activated presynaptic 5-HT1A receptors on the GABAergic nerve terminals projecting to ovoid-shaped neurons and inhibited synaptic GABA transmission via G-proteins.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Regulation of complex formation of POB1/epsin/adaptor protein complex 2 by mitotic phosphorylation.

RalBP1 and POB1, the downstream molecules of small GTP-binding protein Ral, are involved in receptor-mediated endocytosis together with Epsin and Eps15. The regulation of assembly of the complex of these proteins was examined. RalBP1, POB1, Epsin, and Eps15 formed a complex with alpha-adaptin of AP-2 in Chinese hamster ovary cells, but the formation was reduced in mitotic phase. RalBP1, POB1, Epsin, and Eps15 were all phosphorylated in mitotic phase. The phosphorylated forms of POB1 and Epsin were recognized by the antibody MPM2, which is known to detect mitotic phosphoproteins. POB1 and Epsin were phosphorylated by p34(cdc2) kinase in vitro. Their phosphorylation sites (Ser(411) of POB1 and Ser(357) of Epsin) were determined. Phosphorylated Epsin and Epsin(S357D) formed a complex with alpha-adaptin less efficiently than wild type Epsin. Although the EH domain of POB1 bound directly to Epsin, phosphorylation of Epsin inhibited the binding. Furthermore, Epsin(S357D) but not Epsin(S357A) lost the effect of Epsin on the insulin-dependent endocytosis. These results suggest that phosphorylation of Epsin in mitotic phase inhibits receptor-mediated endocytosis by disassembly of its complex with POB1 and alpha-adaptin.

Adaptor Proteins, Vesicular Transport↗

Reactive nitrogen and oxygen species attenuate interleukin- 8-induced neutrophil chemotactic activity in vitro.

Peroxynitrite, formed by the reaction between nitric oxide and superoxide, has been shown to induce protein nitration, which compromises protein function. We hypothesized that peroxynitrite may regulate cytokine function during inflammation. To test this hypothesis, the neutrophil chemotactic activity (NCA) of interleukin-8 (IL-8) incubated with peroxynitrite was evaluated. Peroxynitrite attenuated IL-8 NCA in a dose-dependent manner (p < 0.01) but did not significantly reduce NCA induced by leukotriene B(4) or complement-activated serum. The reducing agents, dithionite, deferoxamine, and dithiothreitol, reversed and exogenous L-tyrosine abrogated the peroxynitrite-induced NCA inhibition. Papa-NONOate [N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1, 2-dialase or sodium nitroprusside, NO donors, or a combination of xanthine and xanthine oxidase to generate superoxide did not show an inhibitory effect on NCA induced by IL-8. In contrast, small amounts of SIN-1, a peroxynitrite generator, caused a concentration-dependent inhibition of NCA by IL-8. Consistent with its capacity to reduce NCA, peroxynitrite treatment reduced IL-8 binding to neutrophils. Nitrotyrosine was detected in the IL-8 incubated with peroxynitrite by enzyme-linked immunosorbent assay. These findings are consistent with nitration of tyrosine by peroxynitrite with subsequent inhibition of IL-8 binding to neutrophils and a reduction in NCA and suggest that oxidants may play an important role in regulation of IL-8-induced neutrophil chemotaxis.

Chemotaxis, Leukocyte↗

Increased sinusoidal pressure is associated with early liver weight gain in ischemia-reperfusion injury in isolated perfused rat liver.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation. This could be caused by an increase in sinusoidal pressure, a determinant of hepatic transvascular fluid movement. We determined the role of sinusoidal pressure, assessed by triple vascular occlusion pressure (P(to)), in the I/R injury in isolated rat livers perfused with leukocyte-free diluted blood bivascularly via the portal vein and hepatic artery. MATERIALS AND METHODS: Ischemia was induced at room temperature by occlusion of either the inflow lines of the hepatic artery and portal vein (the open outflow group, n = 10) or both the inflow and the outflow (hepatic venous) lines (the closed outflow group, n = 10) for 1 h, followed by 1-h reperfusion in a recirculating manner. RESULTS: Liver weight in both groups increased biphasically after reperfusion; the initial peak occurred at 3 min and the second peak at 60 min. Immediately after reperfusion, P(to) peaked, followed by a gradual decline. The initial weight increase in groups combined was significantly and positively correlated with an increase in P(to) (r = 0.716, P = 0.0002), but the second peak was independent of P(to). Liver injury, assessed by perfusate levels of hepatic enzymes and reduced bile flow rate, was observed at 60 min after reperfusion in both groups. CONCLUSIONS: These findings suggest that increased sinusoidal pressure contributes to only the early liver weight gain after reperfusion in isolated perfused rat livers. The late weight gain may be presumably due to liver injury.

Animals↗

Seventeen-year follow-up of massive osteolysis of the scapula.

A 14-year-old boy with massive osteolysis of the right scapula was treated by irradiation with a total dose of 58 Gy, using cobalt 60 (2 Gy per fraction) in 1983 and 1984. Histopathology in a biopsy specimen revealed hemangiomatosis associated with few osteoclasts and a lining of oval or spindle-shaped endothelial-like cells. The osteolysis has been interrupted since the last irradiation. In January 2000, 17 years after the initial treatment, the patient is working as a public officer, and shows no clinical signs of postradiation sarcoma. Radiographs show a residual scapula with sclerotic margin, associated with marked hypoplasia and atrophy of the right humerus. Ranges of motion of the right shoulder are 100 degrees on anterior elevation, 40 degrees on posterior elevation, and 70 degrees on abduction. The patient experiences no problems in daily living, except for difficulty in lifting.

Adolescent↗

Tissue culture of the deep-sea bivalve Calyptogena soyoae.

Tissue culture for the deep-sea clam Calyptogena soyoae (C. soyoae) has been examined. Mantle tissue was cultured in Dulbecco's modified Eagle medium that was prepared using artificial seawater supplemented with fetal bovine serum (FBS) and the body fluid of C. soyoae. The mantle cells were viable in culture for at least 13 days at 4 degrees C and atmospheric pressure on a polylysine-coated dish, although no cells attached in the body fluid-free culture medium. It was found that mantle cells synthesized DNA and seemed to proliferate under atmospheric conditions.

Animals↗

p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1.

p33/ING1s (the growth inhibitor ING1 and candidate tumor suppressor ING1) are key players in the suppressive pathways for human tumorigenesis. We analyzed their complete transcripts, primary structures, and expression. The results led us to discover two novel and related alternatively spliced transcripts encoding p24/ING1-ALT1 and p47/ING1-ALT2. They share C-terminal residues with the candidate tumor suppressors p33/ING1. The candidate tumor suppressors p33/ING1 and p24/ING1-ALT1 were coexpressed in a variety of fetal and adult human tissues, but p47/ING1-ALT2 was minimally expressed.

Adult↗

Hemispheric lateralization in an analysis of speech sounds. Left hemisphere dominance replicated in Japanese subjects.

Evoked magnetic responses to speech sounds [R. Näätänen, A. Lehtokoski, M. Lennes, M. Cheour, M. Huotilainen, A. Iivonen, M. Vainio, P. Alku, R.J. Ilmoniemi, A. Luuk, J. Allik, J. Sinkkonen and K. Alho, Language-specific phoneme representations revealed by electric and magnetic brain responses. Nature, 385 (1997) 432-434.] were recorded from 13 Japanese subjects (right-handed). Infrequently presented vowels ([o]) among repetitive vowels ([e]) elicited the magnetic counterpart of mismatch negativity, MMNm (Bilateral, nine subjects; Left hemisphere alone, three subjects; Right hemisphere alone, one subject). The estimated source of the MMNm was stronger in the left than in the right auditory cortex. The sources were located posteriorly in the left than in the right auditory cortex. These findings are consistent with the results obtained in Finnish [R. Näätänen, A. Lehtokoski, M. Lennes, M. Cheour, M. Huotilainen, A. Iivonen, M.Vainio, P.Alku, R.J. Ilmoniemi, A. Luuk, J. Allik, J. Sinkkonen and K. Alho, Language-specific phoneme representations revealed by electric and magnetic brain responses. Nature, 385 (1997) 432-434.][T. Rinne, K. Alho, P. Alku, M. Holi, J. Sinkkonen, J. Virtanen, O. Bertrand and R. Näätänen, Analysis of speech sounds is left-hemisphere predominant at 100-150 ms after sound onset. Neuroreport, 10 (1999) 1113-1117.] and English [K. Alho, J.F. Connolly, M. Cheour, A. Lehtokoski, M. Huotilainen, J. Virtanen, R. Aulanko and R.J. Ilmoniemi, Hemispheric lateralization in preattentive processing of speech sounds. Neurosci. Lett., 258 (1998) 9-12.] subjects. Instead of the P1m observed in Finnish [M. Tervaniemi, A. Kujala, K. Alho, J. Virtanen, R.J. Ilmoniemi and R. Näätänen, Functional specialization of the human auditory cortex in processing phonetic and musical sounds: A magnetoencephalographic (MEG) study. Neuroimage, 9 (1999) 330-336.] and English [K. Alho, J. F. Connolly, M. Cheour, A. Lehtokoski, M. Huotilainen, J. Virtanen, R. Aulanko and R.J. Ilmoniemi, Hemispheric lateralization in preattentive processing of speech sounds. Neurosci. Lett., 258 (1998) 9-12.] subjects, prior to the MMNm, M60, was elicited by both rare and frequent sounds. Both MMNm and M60 sources were posteriorly located in the left than the right hemisphere.

Adult↗