PubMed Health⌕ Search

Biomedical subjects

Y Ito

Publications and source records attributed to Y Ito.

At least 19 recordsLinked to original sources
PubMed2007

Long-term treatment with TGFbeta1 impairs mechanotransduction in bovine aortic endothelial cells.

BACKGROUND AND PURPOSE: Vascular endothelial cells play a role in the physiological response to mechanical stress. Transforming growth factor beta1 (TGFbeta1) induces morphological changes in endothelial cells, and this may alter their mechanosensitive responses. The aim of this study was to examine the effects of TGFbeta1 on hypotonic stress (HTS)-induced responses in bovine aortic endothelial cells (BAECs). EXPERIMENTAL APPROACH: Cultured BAECs were treated with 3 ng ml(-1) TGFbeta1 for 24 h (24h-TGFbeta1) or 7 days (7d-TGFbeta1). Cytosolic actin fibres were stained with rhodamine-phalloidin. Intracellular Ca2+ concentration was measured using fura2. Tyrosine phosphorylation and RhoA expression were assessed by Western blotting. Expression of RhoA mRNA was assessed by real-time PCR. KEY RESULTS: BAECs developed pseudopod-like processes within 24 h and showed a fibroblast-like appearance after 7 days. HTS induced Ca2+ transients via endogenous ATP release in both control and 24h-TGFbeta1 BAECs but not in 7d-TGFbeta1 BAECs. We have previously shown that HTS-induced ATP release is mediated by sequential activation of RhoA and tyrosine kinases. The basal amount of membrane-bound RhoA was significantly lower in 7d-TGFbeta1 than in 24h-TGFbeta1 or control BAECs. HTS increased the membrane-bound RhoA to the same fractional level in 24h-TGFbeta1 and control BAECs, but its net maximal amount was significantly lower in 7d-TGFbeta1. HTS-induced downstream signals of RhoA activation, i.e. the tyrosine phosphorylation of FAK and paxillin, were markedly suppressed in 7d-TGFbeta1 BAECs. CONCLUSIONS AND IMPLICATIONS: These results indicate that long-term treatment with TGFbeta1 does not impair mechanoreception in BAECs but impairs mechanotransduction by affecting RhoA membrane translocation.

Actins↗
PubMed2007

Microbleeds on gradient-echo T2(*)-weighted MR images from patients with multiple simultaneous intracerebral haemorrhages.

BACKGROUND: Multiple simultaneous intracerebral haemorrhages (ICH) occur rarely and the mechanism remains unknown. In this report, we compare several clinical factors of multiple haemorrhages, including microbleeds, with single intracerebral haemorrhages and discuss a potential explanation for their occurrence. METHODS: One hundred and ninety consecutive patients with intracerebral haemorrhage who were admitted within 24 hours after onset from January 2003 to November 2005 were included in the study. Several clinical factors, including the number of microbleeds on gradient-echo T2(*)-weighted magnetic resonance images, were compared between patients with single and multiple haemorrhages. FINDINGS: Computed tomography scans revealed that nine patients had multiple intracerebral haemorrhages. In all cases, five or more microbleeds were revealed on T2(*)-weighted magnetic resonance images. This was significantly higher than the number of microbleeds in patients with single intracerebral haemorrhage (p < 0.05). Systolic blood pressure on admission was > or =200 mmHg in seven of the nine patients and was higher than in patients with a single haemorrhage (p = 0.05). CONCLUSIONS: Elevated blood pressure induced by an initial haemorrhage was speculated to be the result of secondary haemorrhages in some patients with multiple microbleeds. Thus, strict blood pressure control may help to prevent the occurrence of multiple haemorrhages.

Adult↗
PubMed2006

A review of 227 cases of small papillary thyroid carcinoma.

AIMS: To review differences in biological aggressiveness, clinical behaviors or selected surgical treatments between the PMC and the slightly larger PTC of 1.0<T<or=2.0 cm. METHODS: Two hundred and twenty-seven cases of papillary thyroid carcinoma not larger than 2.0 cm, diagnosed and treated at the Kuma Hospital, Kobe, Japan, with a 10-year follow-up from 1992 to 2003, were reviewed. RESULTS: The small PTCs demonstrated excellent outcomes, and persistent/recurrent disease was identified in only nine patients (4%). None of the patients died of the disease. A multivariate analysis revealed that massive extrathyroidal extension at presentation was the only independent prognostic factor for locoregional recurrence. Subdivision into PMCs and slightly larger tumors (1<T<or=2 cm) did not affect the excellent outcomes, but the patients in the latter subgroup received more lymph node surgery and displayed more aggressive clinico-histological features such as higher rates of extrathyroidal extension, lymph node metastasis, loss of polarity, invasive growth pattern and loss of cohesiveness. CONCLUSIONS: Small PTC not larger than 2.0 cm could be considered as favorable a prognosis as PMC.

Adenocarcinoma, Papillary↗
PubMed2006

Ruptured intracranial aneurysm following gamma knife surgery for acoustic neuroma.

A-63-year-old woman underwent gamma knife surgery (GKS) for acoustic neuroma. Six years later, she suffered sudden onset of severe headache followed by a disturbance of consciousness and subarachnoid haemorrhage due to a ruptured aneurysm originating from the distal anterior inferior cerebellar artery. The aneurysm was not located at a branching site and was included within the radiation field. The aneurysm was treated by endovascular embolization, and now, 15 months later, the patient has recovered satisfactorily. This is the first report of aneurysm formation following GKS for acoustic neuroma.

Basilar Artery↗
PubMed2006

Actions of ZD0947, a novel ATP-sensitive K+ channel opener, on membrane currents in human detrusor myocytes.

BACKGROUND AND PURPOSE: ATP-sensitive K+ channels (K(ATP) channels) play important roles in regulating the resting membrane potential of detrusor smooth muscle. Actions of ZD0947, a novel KATP channel opener, on both carbachol (CCh)-induced detrusor contractions and membrane currents in human urinary bladder myocytes were investigated. EXPERIMENTAL APPROACH: Tension measurements and patch-clamp techniques were utilized to study the effects of ZD0947 in segments of human urinary bladder. Immunohistochemistry was also performed to detect the expression of the sulphonylurea receptor 1 (SUR1) and the SUR2B antigens in human detrusor muscle. KEY RESULTS: ZD0947 (> or = 0.1 microM) caused a concentration-dependent relaxation of the CCh-induced contraction of human detrusor, which was reversed by glibenclamide. The rank order of the potency to relax the CCh-induced contraction was pinacidil > ZD0947 > diazoxide. In conventional whole-cell configuration, ZD0947 (> or = 1 microM) caused a concentration-dependent inward K+ current which was suppressed by glibenclamide at -60 mV. When 1 mM ATP was included in the pipette solution, application of pinacidil or ZD0947 caused no inward K+ current at -60 mV. Gliclazide (< or =1 microM), a selective SUR1 blocker, inhibited the ZD0947-induced currents (Ki = 4.0 microM) and the diazoxide-induced currents (high-affinity site, Ki1 = 42.4 nM; low-affinity site, Ki2 = 84.5 microM) at -60 mV. Immunohistochemical studies indicated the presence of SUR1 and SUR2B proteins, which are constituents of KATP channels, in the bundles of human detrusor smooth muscle. CONCLUSIONS AND IMPLICATIONS: These results suggest that ZD0947 caused a glibenclamide-sensitive detrusor relaxation through activation of glibenclamide-sensitive KATP channels in human urinary bladder.

ATP-Binding Cassette Transporters↗
PubMed2006

The actions of azelnidipine, a dihydropyridine-derivative Ca antagonist, on voltage-dependent Ba2+ currents in guinea-pig vascular smooth muscle.

BACKGROUND AND PURPOSE: Although azelnidipine is used clinically to treat hypertension its effects on its target cells, Ca2+ channels, in smooth muscle have not been elucidated. Therefore, its effects on spontaneous contractions and voltage-dependent L-type Ca2+ channels were investigated in guinea-pig portal vein. EXPERIMENTAL APPROACH: The inhibitory potency of azelnidipine on spontaneous contractions in guinea-pig portal vein was compared with those of other dihydropyridine (DHP)-derived Ca antagonists (amlodipine and nifedipine) by recording tension. Also its effects on voltage-dependent nifedipine-sensitive inward Ba2+ currents (IBa) in smooth muscle cells dispersed from guinea-pig portal vein were investigated by use of a conventional whole-cell patch-clamp technique. KEY RESULTS: Spontaneous contractions in guinea-pig portal vein were reduced by all of the Ca antagonists (azelnidipine, Ki = 153 nM; amlodipine, Ki = 16 nM; nifedipine, Ki = 7 nM). In the whole-cell experiments, azelnidipine inhibited the peak amplitude of IBa in a concentration- and voltage-dependent manner (-60 mV, Ki = 282 nM; -90 mV, Ki = 2 microM) and shifted the steady-state inactivation curve of IBa to the left at -90 mV by 16 mV. The inhibitory effects of azelnidipine on IBa persisted after 7 min washout at -60 mV. In contrast, IBa gradually recovered after being inhibited by amlodipine, but did not return to control levels. Both azelnidipine and amlodipine caused a resting block of IBa at -90 mV. Only nifedipine appeared to interact competitively with S(-)-Bay K 8644. CONCLUSIONS AND IMPLICATIONS: These results suggest that azelnidipine induces long-lasting vascular relaxation by inhibiting voltage-dependent L-type Ca2+ channels in vascular smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2006

Sustained contraction and loss of NO production in TGFbeta1-treated endothelial cells.

BACKGROUND AND PURPOSE: Transforming growth factor beta1 (TGFbeta1) is generated in atherosclerotic and injured vessel walls. We examined whether the endothelial-to-mesenchymal transdifferentiation induced by TGFbeta1 affects endothelial functions. EXPERIMENTAL APPROACH: Bovine aortic endothelial cells (BAECs) were treated with 3 ng ml(-1) TGFbeta1 for 7 days. Contraction of TGFbeta1-treated BAECs was assessed by collagen gel contraction assay. Protein expression and phosphorylation were assessed by Western blotting. Intracellular Ca2+ concentration and NO production were measured using fura2 and DAF-2, respectively. KEY RESULTS: TGFbeta1-treated BAECs showed dense actin fibers and expressed smooth muscle marker proteins; they also changed into smooth muscle-like, spindle-shaped cells in collagen gel cultures. ATP (10 microM) induced a gradual contraction of collagen gels containing TGFbeta1-treated BAECs but not of gels containing control BAECs. ATP-induced contraction of TGFbeta1-treated BAECs was not reversed by the removal of ATP but was partially suppressed by a high concentration of sodium nitroprusside (1 microM). TGFbeta1-treated BAECs showed sustained phosphorylation of myosin light chain in response to ATP and low levels of basal MYPT1 expression. ATP-induced Ca2+ transients as well as eNOS protein expression were not affected by TGFbeta1 in BAECs. However, ATP-induced NO production was significantly reduced in TGFbeta1-treated BAECs. Anti-TGFbeta1 antibody abolished all of these TGFbeta1-induced changes in BAECs. CONCLUSIONS AND IMPLICATIONS: Mesenchymal transdifferentiation induced by TGFbeta1 leads to sustained contraction and reduced NO production in endothelial cells. Such effects, therefore, would not be beneficial for vascular integrity.

Animals↗
PubMed2006

A case of a large retroperitoneal liposarcoma presenting as an incarcerated inguinal hernia.

We report a rare case of retroperitoneal liposarcoma developing within an incarcerated inguinal hernia. A 53-year-old man presented to our hospital with left inguinal mass. Preoperative computed tomography revealed an intraabdominal huge mass, and a clinical diagnosis of liposarcoma. Physical findings except for the inguinal mass and laboratory examination, including tumor markers (CEA, CA19-9), were within normal range. Intraoperatively, the mass was incarcerated in the inguinal canal and involved the left testis. We performed a radical tumor resection, including a left orchiectomy. The resected specimen measured 45 x 30 cm and weighed 7,510 g. Histopathologically, the tumor was diagnosed as a well-differentiated liposarcoma, and originated from retroperitoneum. We did not undergo adjuvant therapy in consideration of histopathological subtype and curable surgical treatment. The patient is well and shows no evidence of recurrence four months after the operation.

Drainage↗
PubMed2006

Comparative studies of AJG049, a novel Ca2+ channel antagonist, on voltage-dependent L-type Ca2+ currents in intestinal and vascular smooth muscle.

BACKGROUND AND PURPOSE: Antagonists of Ca2+ channels reduce contraction of intestinal smooth muscle but also affect vascular smooth muscle. We have therefore examined the effects of AJG049, a newly synthesized antagonist for regulation of gut motility, on voltage-dependent L-type Ca2+ channels, in vascular and intestinal smooth muscle, comparing AJG049 with two other Ca2+ channel antagonists, verapamil and diltiazem. EXPERIMENTAL APPROACH: Affinities of AJG049 for various types of voltage-dependent Ca2+ channels were examined by binding studies. Effects of AJG049 on voltage-dependent inward Ca2+ (or Ba2+) currents (ICa or IBa) in dispersed smooth muscle cells from guinea-pig ileum, colon and mesenteric artery were measured using conventional whole-cell configurations. KEY RESULTS: In binding studies, AJG049 showed a high affinity for the diltiazem-binding site of L-type Ca2+ channels. In whole-cell configuration, AJG049 suppressed ICa in ileal myocytes, with concentration-, voltage-and use-dependencies. AJG049 shifted the steady-state inactivation curve of ICa to the left. The order of potency to inhibit ICa in ileal myocytes was AJG049>verapamil>diltiazem. AJG049 also suppressed IBa in guinea-pig mesenteric arterial myocytes, showing concentration- and voltage-dependencies and the potency order for this action was also AJG049>verapamil>diltiazem. For the relative ratio of Ki values between ileal and mesenteric arterial myocytes, the order was AJG049>diltiazem>>verapamil. CONCLUSIONS AND IMPLICATIONS: These results show that AJG049 inhibits L-type Ca2+ channels mainly through the diltiazem-binding site(s). From our results, AJG049 showed a little selectivity for these Ca2+ channels in intestinal smooth muscle.

Animals↗
PubMed2006

Seasonal variations of acute massive submacular haemorrhage associated with age-related macular degeneration.

AIMS: To determine whether there is a seasonal variation in the onset of acute, massive submacular haemorrhage associated with age-related macular degeneration. METHODS: Sixty eyes of 59 patients diagnosed between April 1998 and March 2005, were studied retrospectively. For each patient, the month and season of onset of the submacular haemorrhage and the mean monthly ambient temperature in Nagoya were analysed. Any history of systemic hypertension was also recorded, and the seasonal variations were also investigated in hypertensive and non-hypertensive groups. RESULTS: The number of cases peaked in winter with a trough in summer, and this seasonal variation was significant (Roger's R = 12.03, p<0.01). The monthly incidence was inversely correlated with the temperature (Spearman's rank correlation coefficient r = 0.89, p<0.01). The seasonal variations were significant in the hypertensive group but not in the non-hypertensive group. CONCLUSION: The considerable seasonal variations suggests that the mechanism for the haemorrhage is strongly correlated with the systemic blood pressure.

Acute Disease↗
PubMed2006

RUNX3 protein is overexpressed in human basal cell carcinomas.

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Blotting, Western↗
PubMed2006

The use of colour Doppler imaging in the diagnosis of retinal detachment.

DESIGN: Prospective study. PURPOSE: To evaluate real-time duplex colour Doppler examination with colour and pulse Doppler ultrasonography (US) (colour Doppler imaging (CDI)) for detection of the retinal detachment from membranous structures in the posterior segment. MATERIALS AND METHODS: In 33 consecutive patients with ophthalmoscopically invisible eyes (34 eyes), CDI was performed to detect the presence or absence of retinal detachment. The diagnostic criterion for retinal detachment was whether or not spectral waveforms were detected in membranous structures with colour and pulse Doppler US. In all cases, the absence or presence of retinal detachment was confirmed by surgery. RESULTS: In 27 of 34 eyes, membranes and/or opacities were observed in the vitreous cavity with CDI. In 12 of these 27 eyes, blood flow in those structures was detected by CDI. In all of these 12 eyes, retinal detachment was confirmed at surgery, and in 14 of the 15 eyes in which blood flow was not detected by CDI, absence of retinal detachment was confirmed at surgery. When a diagnosis confirmed by surgery was used as the definitive finding, CDI had a sensitivity of 92.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 93.3%, and an accuracy in the detection of retinal detachment from membranes and/or opacities in the vitreous cavity of 96.3%. CONCLUSION: Real-time duplex colour Doppler examination with colour and pulse Doppler US (CDI) is a noninvasive method useful for the detection of retinal detachment from vitreous opacity and/or membrane in the posterior segment.

Adolescent↗
PubMed2006

v-Src requires Ras signaling for the suppression of gap junctional intercellular communication.

Cell transformation by v-Src causes suppression of gap junctional intercellular communication (GJIC). Although tyrosine phosphorylation of connexin43 (Cx43), a gap junctional component, appears to be necessary for the suppression, involvement of other signaling remains unclear. We investigated the role of Ras signaling in the suppression of GJIC by v-Src. Conditional expression of either S17N Ras or mtGap1m dramatically recovered GJIC in v-Src-transformed cells. Although expression of S17N Ras or mtGap1m substantially decreased the levels of active Ras, tyrosine phosphorylation of cellular proteins including Cx43 remained unchanged. Similarly, treatment of v-Src-transfomed cells with a Ras farnesyltransferase inhibitor, manumycin A, restored GJIC, whereas tyrosine phosphorylation of Cx43 remained unchanged. Thus, these results strongly suggest that, in addition to Cx43 phosphorylation, constitutive activation of Ras signaling is required for the suppression of GJIC by v-Src.

Animals↗
PubMed2006

Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain.

Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Pharmacokinetic and pharmacodynamic studies following oral administration of erythropoietin mucoadhesive tablets to beagle dogs.

Oral administration of mucoadhesive tablets containing erythropoietin (EPO) and an absorption enhancer Labrasol was studied in rats and dogs. Mucoadhesive tablets were prepared using Sylysia 550 holding the absorption enhancer and Carbopol 974P as a mucoadhesive agent. Mucoadhesive tablets were covered with a water-insoluble backing layer made of cellulose acetate and a pH-sensitive covering layer made of Eudragit L/Eudragit S. Tablet was administered into the rat jejunum at EPO dose of 100 IU/kg and serum samples were collected for 6h. Serum EPO level was analysed with a standard ELISA procedure. After administration, rats showed a maximum serum EPO level of C(max) 70.6 +/- 8.9 mIU/ml. Oral administration of a single tablet containing 100 IU/kg EPO to beagle dogs showed a C(max) of 24.6 +/- 4.1. When EPO dose was increased to 500 IU/kg and the number of tablets was also increased to 5, the C(max) was 54.8 +/- 9.0 mIU/ml. However, when EPO, 100 IU/kg dose was divided into five tablets, the C(max) was 15.5 +/- 1.8 mIU/ml. In the absence of absorption enhancer, the C(max) was 35.8 +/- 3.8 with 500 IU/kg dose distributed among five tablets. Pharmacodynamic studies were carried out following oral administration of mucoadhesive tablets for 6 consecutive days at an EPO dose of 500 IU/kg. Whole blood samples were collected and percent circulating reticulocytes were counted using Miller technique. The increase in percent circulating reticulocytes was found to be 1.7% on day 8 following oral administration. As a control study, EPO was administered by i.v. route at a dose of 300 IU/kg for 3 consecutive days and the percent circulating reticulocytes were counted. Mucoadhesive tablets showed promising results as an oral drug delivery system for protein therapeutics.

Acrylates↗
PubMed2006

Fetal pleuroamniotic shunting for bronchopulmonary sequestration with hydrops.

Bronchopulmonary sequestration (BPS), a non-functional pulmonary tissue mass, when complicated by fetal hydrops, carries a high risk of perinatal mortality. However, a limited number of cases of BPS complicated by fetal hydrops with an informative clinical course have been reported. We report here on three cases of BPS complicated by fetal hydrothorax and hydrops that were successfully treated by pleuroamniotic shunting, which should be considered as a treatment option for fetal hydrothorax and hydrops associated with BPS.

Adult↗