Search PubMed⌕ Search

Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 217 records · Page 12Linked to original sources

Effect of docosahexaenoic acid on smooth muscle cell functions.

There is increasing evidence that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders, including hypertension. Docosahexaenoic acid (DHA), may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study is to clarify the in vitro effect of DHA on cultured smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca2+ metabolism, which are involved in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on cell growth or on cell hypertrophy induced by angiotensin II as measured by flow cytometry. DHA had no stimulatory effect on interleukin-1beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP, but rather slightly inhibited it. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in intracellular Ca2+ concentration induced by angiotensin II, but not by thapsigargin. This was due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results indicate that DHA specifically suppresses Ca2+ mobilization into smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.

Animals↗

Heparin inhibits human coronary artery smooth muscle cell migration.

Heparin, an anticoagulant, has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies, but the clinical trials of heparin in coronary balloon angioplasty have been negative. The current study, therefore, examined the effect of heparin on basal or stimulated migration by serum and platelet-derived growth factor (PDGF)-BB in cultured human coronary artery smooth muscle cells (SMCs) by Boyden's chamber method. In addition, the reversibility of the heparin effect on human coronary artery SMC migration was examined. Fetal calf serum (FCS) and PDGF-BB stimulated SMC migration in a concentration-dependent manner. Heparin in moderate to high concentration (10 to 100 U/mL) exhibited concentration-related inhibition of FCS- and PDGF-BB-stimulated SMC migration; however, a low concentration (1 U/mL) of heparin had no inhibitory effects. Heparin also had weak inhibitory effects on nonstimulated SMC migration. The SMCs that were exposed to a high concentration (100 U/mL) of heparin for 6 hours were capable of migrating after a short lag period of removal of heparin from the culture medium. These SMCs also showed recovery of responses to FCS and PDGF-BB by migrating significantly greater than the nonstimulated level. Furthermore, heparin-containing medium did not contain detached cells. These results indicate that heparin inhibits human coronary artery SMC migration, especially when stimulated by FCS or PDGF-BB, and that this inhibitory effect of heparin is reversible and not simply a function of killing cells.

Anticoagulants↗

Cervical hemangioblastoma with a past history of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) with a spinal origin is a rare clinical entity. The most common source of SAH is an arteriovenous malformation. Only six cases of spinal hemangioblastomas causing SAH have been reported. CASE DESCRIPTION: This 48-year-old man had experienced severe headache 12 years earlier, which was diagnosed as SAH by computed tomography (CT) scan and lumbar puncture. However, cerebral angiography could not detect either aneurysm or arteriovenous malformation. Thereafter, he spent an uneventful life until he was incidentally diagnosed with a cervical tumor on magnetic resonance imaging (MRI) study for Meniere's disease. The tumor was situated at the cervicomedullary junction, and fed by the left vertebral artery. Histologic findings of the tumor showed features typical of hemangioblastoma. CONCLUSIONS: We describe a case of cervical spinal extramedullary hemangioblastoma with a past history of SAH. In our case, the SAH of 12 years ago perhaps occurred from the cervicomedullary junction hemangioblastoma. Since the etiology of SAH could not be detected at the first angiography, not only follow-up reangiography, but also MRI of the spinal cord and spinal angiography could have played an important role.

Cerebellar Neoplasms↗

Determination of isatin, an endogenous monoamine oxidase inhibitor, in urine and tissues of rats by HPLC.

1. We have previously identified isatin as one of the endogenous monoamine oxidase (MAO) inhibitors in the urine and the brain of stroke-prone spontaneously hypertensive rats (SHRSP), using gas chromatography-mass spectrometry (GC-MS). 2. In this study, we attempted to develop a convenient assay to determine isatin using high performance liquid chromatography with an ultraviolet detector (HPLC-UV). The standard curve for authentic isatin was linear at a range from 2 to 20 nmol per ml. The coefficient of variance was within 3% for both intra-assay and inter-assay. The sensitivity was 20 pmol per 10 microl of urine sample. 3. Isatin concentration correlated significantly and positively with endogenous MAO activity (tribulin-like activity) in both urine (r=0.924, P<0.001) and kidney extracts (r=0.862, P<0.01). There was a significant difference in urinary isatin between Wistar Kyoto rats (WKY) and SHRSP. Oral administration of isatin increased urinary isatin concentration and systolic blood pressure in WKY. 4. Determination of isatin using HPLC-UV may be useful for elucidating role of isatin in various conditions of stress and disease.

Animals↗

Effects of granisetron and its combination with dexamethasone on cisplatin-induced delayed emesis in the ferret.

1. Granisetron and its combination with dexamethasone for the treatment of delayed emesis following cisplatin (CDDP) administration were investigated using ferrets. 2. CDDP-induced emesis was significantly inhibited in both the granisetron group and the combined granisetron and dexamethasone group during the acute and delayed phase in terms of total emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly increased as compared with the CDDP control group. 4. 5-Hydroxytryptamine (5-HT) level was increased in the ileum and the 5-hydroxyindole acetic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemetic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination with dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase.

Animals↗

Patterns of uterine enhancement with helical CT.

OBJECTIVE: The purpose of this study was to evaluate the enhancement characteristics of the normal uterine body and cervix using dynamic contrast-enhanced helical CT. METHODS: Thirty-eight women scheduled for pelvic CT for non-gynecologic malignancies underwent dynamic contrast-enhanced helical CT of the pelvis. Data acquisition was during the arterial phase (30-45 s after the start of injection), the parenchymal phase (90-120 s after the start of injection), and delayed phase (3-9 min after the start of injection). The images were evaluated by four radiologists for the pattern of myometrial and cervical enhancement. Correlation was made with the age and menstrual status of the patients. RESULTS: In the uterine body, three types of enhancement were observed. Type 1 enhancement, seen in 16 patients (42%), was characterized by the visualization of a subendometrial zone of enhancement, 30-120 s after the start of injection. Eight of these patients also showed an enhancing zone in the outer myometrium. Both zones were transitory, and in all cases, the uterus became homogeneous in the delayed phase. This pattern was seen predominantly in premenopausal women with a mean age of 34 years. Type 2 enhancement, seen in 17 cases (45%), was defined by the absence of subendometrial enhancement in the early phase. Enhancement was either diffuse from the outset or originated in the outer myometrium. This pattern was seen nearly equally in premenopausal and postmenopausal women with a mean age of 40 years. Type 3 enhancement was seen in five postmenopausal patients (13%) with a mean age of 53 years and was characterized by faint diffuse enhancement. In the cervix, a zonal pattern of enhancement defining inner and outer stroma was seen in 23 patients (61%). Fifteen patients were premenopausal and eight were postmenopausal. CONCLUSION: In this study, we have shown a transitory zonal distribution of the contrast in the myometrium and cervix using dynamic contrast-enhanced helical CT. The demonstration of these patterns is not constant and depends on individual variables. Of these, the menopausal status and/or age of the patient appear to be most important. While CT is not the primary imaging modality to evaluate the uterus, knowledge of these normal findings might help when confronted with unusual uterine enhancement during routine studies obtained with spiral CT.

Adult↗

Conserved Ser residues in the basic region of the bZIP-type transcription factor HBP-1a(17): importance in DNA binding and possible targets for phosphorylation.

HBP-1a(17) is representative of a group of plant bZIP-type transcription factors which includes HBP-1a proteins and G-box-binding factors. We found kinase activity in wheat nuclear extract that phosphorylated HBP-1a(17). Experiments using recombinant HBP-1a(17) derivatives as substrates revealed that all three of the Ser residues in the basic region, Ser-261, Ser-265, and Ser-269, were phosphorylated in a Ca(2+)-stimulated manner. DNA-binding analysis of mutants with a Ser-to-Glu change, prepared to mimic the phosphorylated proteins, indicated that introduction of a negative charge at position 265 or 269 prevents HBP-1a(17) from binding DNA not only in the homodimer of mutants but also in heterodimers with a wild-type protein. It is therefore suggested that the phosphorylation regulates the function of HBP-1a(17) at least at the level of DNA binding. Since Ser-265 and Ser-269 are highly conserved among the plant bZIP-type factors known to date, a common Ca(2+)-mediated regulatory mechanism may exert an effect on the bZIP-type factors through phosphorylation of these conserved Ser residues.

Amino Acid Sequence↗

Changes in the structure of sleep spindles and delta waves on electroencephalography in patients with nocturnal enuresis.

OBJECTIVE: To evaluate the mechanism of the dysfunction of arousal in patients with Type I and Type IIa enuresis. PATIENTS AND METHODS: The numbers of sleep spindles and delta waves were analysed during electroencephalography in 19 patients with enuresis (17 male, two female, mean age 9.7 years, range 8-14). RESULTS: In four patients with Type I enuresis, who awoke spontaneously and remained dry as a result of urinary sensation, the numbers of sleep spindles and delta waves diminished gradually and finally disappeared just before the patients awoke completely. In the remaining nine patients with Type I enuresis, there was no decrease in the number of sleep spindles and delta waves, and enuresis occurred without the subjects awakening. In the six patients with Type IIa enuresis, there was no arousal reaction or generation of sleep spindles on urination while asleep. CONCLUSIONS: An immaturity in the function of the thalamus might be a cause of the arousal dysfunction in patients with Type I enuresis. In Type IIa enuresis, a possible abnormal or immature arousal mechanism in the pons or the lower tract may be responsible.

Adolescent↗

Dynamics of hepatitis C viremia following interferon-alpha administration.

Knowledge of the dynamics of hepatitis C virus (HCV) in vivo is important for elucidation of its pathogenesis and the establishment of therapeutic guidelines. The aim of this study was to obtain kinetic information about virus load following interferon-alpha (IFN-alpha) administration. Serial serum HCV core protein and HCV RNA levels were measured. IFN-alpha exponentially reduced serum HCV levels. The mean (+/-SD) viral half-life was 7.0 +/- 2.6 h in HCV core protein assay and 7.2 +/- 3.1 h in HCV RNA assay on the first day of therapy. This initial rapid decrease was followed by a slower decrease in serum HCV levels thereafter. Thus, the biphasic reduction in virus load during IFN-alpha therapy was demonstrated.

Adult↗

Human large luteal cells in the menstrual cycle and early pregnancy express leukotriene A4 hydrolase.

Leukotriene (LT) A4 hydrolase (EC3.3.2.6) converts LTA4 to LTB4 which shows a chemotactic activity to leukocytes. To investigate the involvement of LTB4 in human corpus luteum (CL) function, the localization of LTA4 hydrolase in human ovarian tissues was examined by immunohistochemistry with a rabbit polyclonal antibody against LTA4 hydrolase. The enzyme was weakly expressed on granulosa cells of the follicles. After ovulation, the intensity of LTA4 hydrolase on large luteal cells increased and was highest in the midluteal phase. High expression was also observed in the CL of early pregnancy. In theca interna and small luteal cells, LTA4 hydrolase was weakly detected in all developmental stages. Immunoblot analysis demonstrated that the molecular mass of LTA4 hydrolase expressed in CL was 62 kDa, and confirmed that LTA4 hydrolase expression increased during CL formation and remained high in early pregnancy. The sequence encoding mRNA of LTA4 hydrolase, which was isolated from CL and amplified by polymerase chain reaction, was shown to be identical to the previously reported one. Immunocytochemistry showed that LTA4 hydrolase expression in cultured granulosa cells increased over 4 days in vitro and was enhanced by human chorionic gonadotrophin treatment. These expression profiles of LTA4 hydrolase suggest the involvement of LTB4 in luteal cell function during CL formation and early pregnancy.

Adolescent↗

Effect of the endothelin family of peptides on human coronary artery smooth-muscle cell migration.

The migration of coronary artery medial smooth-muscle cells (SMCs) is one of the key events in the process of intimal thickening in coronary atherosclerotic lesions. The objectives of the present study were to determine whether any of the three isoforms of endothelin (ET), ET-1, ET-2, and ET-3, or an intermediate form of ET, big ET-1, induces migration of human coronary artery SMCs, and to investigate the possible interaction of ET peptides and well-known migration-stimulatory factors, platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II), on SMC migration by the Boyden's chamber method. None of the ET peptides alone induced SMC migration between 10(-9) and 10(-7) mol/L. In contrast, ET-1 and ET-2 significantly induced SMC migration in the presence of low concentrations of PDGF-BB (0.5 ng/mL) or Ang II (10(-9) mol/L), although ET-3 was less active (ET-1 = ET-2 > ET-3). In contrast, big ET-1 was without significant activity on PDGF-BB-or Ang II-induced SMC migration. The potentiation of SMC migration by ET peptides was clearly inhibited by the ETA receptor antagonist BG-123 in a concentration-dependent manner. These results suggest that the ET family of peptides, especially ET-1 and ET-2, can induce human coronary artery SMC migration in combination with PDGF-BB or Ang II, probably via ETA receptors. Taken together with the finding that the concentrations of ET, PDGF-BB and Ang II are locally increased at sites of endothelial injury, this indicates that ET may be an initial stimulus for human coronary artery medial SMC recruitment during coronary atherosclerosis, possibly in combination with PDGF-BB or Ang II.

Angiotensin II↗

Heparin suppresses cyclosporine-induced endothelin-1 synthesis in rat endothelial cells.

Cyclosporine stimulates vasoconstrictor endothelin-1 (ET-1) synthesis. This study examined the effect of heparin on cyclosporine-induced ET-1 synthesis in Wistar rat aortic endothelial cells in culture. Cyclosporine (0.01-5 mumol/L) stimulated ET-1 mRNA expression in a dose-dependent manner. A nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA) (10(-5) mol/L), did not affect cyclosporine-induced ET-1 mRNA expression. Heparin (1-20 U/ml) suppressed cyclosporine-induced ET-1 mRNA expression in a dose-dependent manner. The inhibitory effect of heparin was blunted in the presence of either L-NMMA (10(-5) mol/L) or calmodulin inhibitors such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) (5 x 10(-5) mol/L) or calmidazolium (5 x 10(-5) mol/L) in the presence of the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (0.1 mmol/L). These results suggest that heparin suppresses cyclosporine-induced ET-1 mRNA expression via both NO- and calmodulin-dependent pathways.

Animals↗

Suppression of endothelin-3-induced nitric oxide synthesis by triglyceride in human endothelial cells.

Reduced endothelium-derived nitric oxide (NO) production characterizes several vascular diseases. This study examined the effect of triglyceride on NO production induced by endothelin-3 (ET-3) in cultured human umbilical vein endothelial cells. Triglyceride-rich human plasma obtained after a high-carbohydrate diet with white wine was used in an ex vivo study. The plasma triglyceride fraction was found to consist of large amounts of palmitic and oleic acids detected by gas-liquid chromatography. Therefore, the effect of synthetic tripalmitin and triolein emulsion on NO production was also examined. ET-3 stimulated NO and guanosine 3',5'-cyclic monophosphate production and increased cytosolic Ca2+ levels in the endothelial cells (ECs). After incubation of the ECs with the triglyceride-rich plasma for 2 h, these responses to ET-3 were ameliorated in a triglyceride concentration-dependent manner (50-200 mg/dl). A synthesized emulsion of tripalmitin (100 mg/dl) and triolein (100 mg/dl) also blunted the responses to ET-3. Neither endothelial constitutive NO synthase mRNA expression nor its protein level was affected by treatment with triglycerides. These results suggest that triglyceride suppresses ET-3-induced NO synthesis in human ECs by inhibiting cytosolic Ca2+ elevation.

Blotting, Northern↗

Power Doppler sonography for hepatocellular carcinoma: factors affecting the power Doppler signals of the tumors.

AIMS/BACKGROUND: A recent advancement in Doppler ultrasonography (US) is power Doppler for detecting low-velocity blood flow at the microvascular level with angle independence. The present study was performed to characterize the factors contributing to the power Doppler signals of hepatocellular carcinoma (HCC). METHOD: Correlation of Doppler signals of HCC in 114 patients with 178 HCC nodules was analyzed in relation to the findings of CT and angiography, tumor characteristics (size, echo pattern, and histological differentiation of tumor), viral markers and severity of liver disease. RESULTS: The sensitivity of power Doppler US was superior to that of CT and angiography (each p<0.05; McNemar's test). The detection rate of power Doppler signal was significantly higher in tumors with diameter > or =2 cm (vs <2 cm in diameter), and with low/mixed echo pattern (vs high echo appearance), and with moderately/poorly differentiated HCC (vs well-differentiated HCC). Univariate analysis revealed that echo pattern, tumor size and histological differentiation of HCC in addition to CT and angiographic findings were significant. Multivariate analysis showed that tumor size and differentiation were significant. CONCLUSION: These results indicate that tumor characteristics play an important role in power Doppler signals and that these could be assessed by the presence or absence of power Doppler signals.

Angiography↗

Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes.

Previous studies have demonstrated that ethanol and volatile anesthetics inhibit the function of some metabotropic (G protein-coupled) receptors, including the 5-hydroxytryptamine2 and muscarinic cholinergic receptors. The metabotropic glutamate receptors (mGluRs) show little sequence homology with most other metabotropic receptors and are important modulators of synaptic transmission in the mammalian central nervous system. It was of interest to determine drug actions on these receptors, and we investigated the effects of ethanol, halothane, the anesthetic compound F3 (1-chloro-1,2,2-trifluorocyclobutane), and the nonanesthetics F6 (1,2-dichlorohexafluorocyclobutane) and F8 (2,3-chlorooctafluorobutane) on the function of mGluR1 and mGluR5 expressed in Xenopus laevis oocytes. Halothane, F3, and ethanol inhibited mGluR5-induced Ca(2+)-dependent Cl- currents, yet pharmacologically relevant concentrations of these compounds had little effect on the glutamate-induced currents in the oocytes expressing mGluR1. F6 had inhibitory effects on both receptors, and F8 did not affect either mGluR1 or mGluR5 function. The protein kinase C (PKC) inhibitor GF109203X enhanced the glutamate-induced current, and the PKC activator phorbol-12-myristate-13-acetate inhibited this current in the oocytes expressing mGluR5, but these compounds had little effect on mGluR1 function. GF109203X abolished the inhibitory effects of halothane, F3, and ethanol on mGluR5s. Conversely, the phosphatase inhibitor calyculin A prolonged the action of halothane and ethanol. Furthermore, mutation of a PKC consensus site (Ser890) of mGluR5 abolished the inhibitory effects of halothane, F3, and ethanol. These results suggest that ethanol and volatile anesthetics inhibit mGluR5 because they promote PKC-mediated phosphorylation.

Anesthetics, Inhalation↗

[Signal transduction of serotonin release from enterochromaffin cells in mouse ileal crypts].

Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered to be regulated by multiple receptor-mediated mechanisms, little is known about the signal transduction in EC cells. We investigated the effects of adrenoceptor stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in organ bath were perfused with a buffered solution. Released 5-HT was measured using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by moderate pipetting. Intracellular calcium dynamics were analyzed by digital video-imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a transient elevation of intracellular calcium in some EC cells. The effect of NE (1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM significantly induced an increase in intracellular calcium concentration. NE-induced intracellular calcium dynamics was not significantly affected by timolol, Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT release from ileal EC cells is mediated predominantly via alpha 2-, but not beta-adrenoceptors, by a mechanism dependent on elevation of intracellular calcium concentration.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

[A molecular mechanism for supersensitization of adenylyl cyclase system in cloned opioid receptor-transfected cells following sustained opioid treatment].

Chronic opioid treatment has been shown to develop supersensitization of adenylyl cyclase (AC) system or cAMP overshoot. In this study, we investigated the molecular mechanism of supersensitization of AC system using CHO cells expressing one of the cloned mu-, delta- and kappa-opioid receptors. In naive cells, acute treatment with an opioid agonist, but not antagonist, suppressed forskolin-stimulated cAMP accumulation. In the cells sustainedly (4 hr) treated with the agonist, the challenge by antagonist induced the cAMP overshoot over the naive level (supersensitization of AC system), but had no effect on GTPase activity. This supersensitization of AC system was not affected by pretreatment with cycloheximide, a protein synthesis inhibitor, or various protein kinase inhibitors (H7, H8, H89 and staurosporine). On the other hand, pretreatment with pertussis toxin blocked both inhibition of AC activity by acute agonist treatment and development of supersensitization of AC system. To examine an involvement of the interaction between G protein and AC in the supersensitization of AC system, we used CHO cells coexpressing the opioid receptor and some chimeric G alpha proteins between G alpha i2 and G alpha q. The results revealed that a specific region of G alpha i2, which is responsible for the interaction with AC, is closely related to the supersensitization. In addition, the supersensitization of AC system was induced by sustained muscarinic agonist treatment in CHO cells expressing the cloned m2 or m4 muscarinic receptor, suggesting this phenomenon is common to the members of the Gi-coupled receptor superfamily. In conclusion, these findings suggest that the development of supersensitization of AC system is attributed to a continuous inhibition of AC by G alpha i, but not to continuous activations of the Gi-coupled receptor and G protein themselves.

Adenylyl Cyclases↗