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T Kita

Publications and source records attributed to T Kita.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prediction of acute left main coronary artery obstruction by 12-lead electrocardiography. ST segment elevation in lead aVR with less ST segment elevation in lead V(1).

OBJECTIVES: We sought to determine the electrocardiographic (ECG) features associated with acute left main coronary artery (LMCA) obstruction. BACKGROUND: Prediction of LMCA obstruction is important with regard to selecting the appropriate treatment strategy, because acute LMCA obstruction usually causes severe hemodynamic deterioration, resulting in a less favorable prognosis. METHODS: We studied the admission 12-lead ECGs in 16 consecutive patients with acute LMCA obstruction (LMCA group), 46 patients with acute left anterior descending coronary artery (LAD) obstruction (LAD group) and 24 patients with acute right coronary artery (RCA) obstruction (RCA group). RESULTS: Lead aVR ST segment elevation (>0.05 mV) occurred with a significantly higher incidence in the LMCA group (88% [14/16]) than in the LAD (43% [20/46]) or RCA (8% [2/24]) groups. Lead aVR ST segment elevation was significantly higher in the LMCA group (0.16 +/- 0.13 mV) than in the LAD group (0.04 +/- 0.10 mV). Lead V(1) ST segment elevation was lower in the LMCA group (0.00 +/- 0.21 mV) than in the LAD group (0.14 +/- 0.11 mV). The finding of lead aVR ST segment elevation greater than or equal to lead V(1) ST segment elevation distinguished the LMCA group from the LAD group, with 81% sensitivity, 80% specificity and 81% accuracy. A ST segment shift in lead aVR and the inferior leads distinguished the LMCA group from the RCA group. In acute LMCA obstruction, death occurred more frequently in patients with higher ST segment elevation in lead aVR than in those with less severe elevation. CONCLUSIONS: Lead aVR ST segment elevation with less ST segment elevation in lead V(1) is an important predictor of acute LMCA obstruction. In acute LMCA obstruction, lead aVR ST segment elevation also contributes to predicting a patient's clinical outcome.

Acute Disease↗
PubMed2001

Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus.

Chronic treatment with dopamine D2 blockers in schizophrenic patients has been proposed as one of the causes of polydipsia and water intoxication, but this conclusion is still controversial. To investigate the relationship between dopamine D2 blockers and these syndromes, we designed a behavioral and neurochemical study using hyperosmotic stimulation in the supraoptic nucleus (SON) by microdialysis after chronic treatment with haloperidol in rats. Animals were injected with haloperidol decanoate (20 mg/kg, i.m.) or sesame oil at 2-week intervals for 8 successive weeks. During the 7th week, water-intake was increased 30-60 min after the hyperosmotic stimulation in both groups, but more so in haloperidol-treated animals compared to that in the control group. Moreover, arginine vasopressin (AVP) was released by the hyperosmotic stimulation in SON, but was not significantly different between groups. In addition, striatal dopamine levels 3-4 days after the microdialysis study showed a significant decrease in the haloperidol-treated animals. These results suggest that chronic treatment with haloperidol enhances water-intake produced by hyperosmotic stimulation in the SON but does not increase AVP levels in dialysates following hyperosmotic stimulation. Thus, these symptoms may be mediated by dopaminergic systems in brain.

Animals↗
PubMed2001

Gas6 induces mesangial cell proliferation via latent transcription factor STAT3.

Mesangial cell proliferation is essential for the pathogenesis and progression of glomerular disease. Previously, we showed that Gas6 plays a pivotal role in mesangial cell proliferation in vitro and in vivo. In the present study, we identified downstream targets of Gas6 signaling to examine the role in mesangial cell proliferation in vitro and in vivo. We found that Gas6 tyrosine phosphorylates STAT3 (signal transducers and activators of transcription) with concomitant translocation to the nucleus and induces STAT3-dependent transcriptional activation in cultured mesangial cells. Expressing dominant negative STAT3 inhibited Gas6-mediated transcriptional activation of STAT3 and abolished Gas6-induced mesangial cell proliferation. In a model of mesangial proliferative glomerulonephritis, STAT3 is phosphorylated in mesangial cells, and its phosphorylation peaks at day 8 after the injection of anti-Thy1.1 antibody. Inhibition of Gas6 by warfarin and the extracellular domain of its receptor, Axl, abolished phosphorylation of STAT3 in vivo. Thus, our in vitro and in vivo findings indicate that autocrine growth factor Gas6 induces mesangial cell proliferation via latent transcription factor STAT3. Therefore, STAT3 might be a new therapeutic target for kidney disease induced by mesangial proliferation.

Animals↗
PubMed2001

Number, origins, and chemical types of rat pallidostriatal projection neurons.

The dorsal globus pallidus (GP) receives major inputs from the dorsal neostriatum (Str), the subthalamic nucleus (STN) and the dorsal thalamus. The GP projects to multiple basal ganglia nuclei. One of the GP projection sites is the Str. The pallidostriatal projection has been considered minor. However, several recent studies have suggested that this projection is heavier than previously thought and that it might play a significant role in controlling the activity of the Str. To reveal more details of this projection, we examined the number of GP neurons that participated in the projection, their origins in the GP and their immunoreactivity for the calcium binding protein parvalbumin (PV), by using a combination of Fluoro-Gold (FG) retrograde labeling and immunohistochemical methods. Immunostaining for the calcium binding protein calbindin-28K (CaBP) was used to identify the CaBP-poor sensorimotor and CaBP-rich associative Str regions and the corresponding CaBP-poor middle, CaBP-rich border, and the caudomedial GP regions. The CaBP-poor dorsolateral Str region occupies a small portion of the Str, whereas the CaBP-poor middle GP region occupies a large portion of the GP. The immunostaining for neuron-specific nuclear protein (NeuN) was used to visualize neurons that were immunonegative for FG or PV. Cell counts revealed that the middle GP region contained a higher density of neurons and also a higher percentage of PV-positive neurons than the border and caudomedial regions of the GP. These observations suggested that the GP is involved more in sensorimotor function than associative function. Approximately 40% of neurons in the CaBP-poor middle GP region project to the CaBP-poor part of the dorsolateral Str. Approximately 30% of the neurons in both the CaBP-rich border and the caudomedial GP regions project to the CaBP-rich Str region. More than 40% of the pallidostriatal neurons in CaBP-poor middle GP region are PV-positive, whereas most of those in CaBP-rich GP regions are PV-negative. It was estimated from the cell count data that most of the PV-negative neurons in all three regions of the GP project to the Str. The results indicate that the sensorimotor and associative territories of the Str have reciprocal projections between corresponding territories of the GP. The involvement of a large number of GP neurons suggested that the pallidostriatal projection should be taken into account in the analysis of functional roles of the basal ganglia.

Animals↗
PubMed2001

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) supports cell adhesion to fibronectin.

Lectin-like oxidized lipoprotein receptor-1 (LOX-1) is a specific receptor for atherogenic oxidized low density lipoprotein (OxLDL) which belongs to the scavenger receptor family. In the present report, we show that LOX-1 can also support cell adhesion to fibronectin (FN) in a divalent cation-independent fashion. CHO-K1 cells stably expressing bovine LOX-1 (BLOX-1-CHO), but not untransfected CHO-K1 cells, can adhere to FN-coated plates, but not to collagen-coated plates, in the presence of EDTA. BLOX-1-CHO adhesion to FN-coated plates can also be suppressed by scavenger receptor ligands, such as OxLDL, polyinosinic acid (poly I), and dextran sulfate, but not by native LDL, acetylated LDL, polycytidylic acid (poly C), or chondroitin sulfate. Cultured bovine aortic endothelial cells can similarly adhere to FN-coated plates, which was inhibited by OxLDL, poly I, and dextran sulfate in the presence of EDTA. LOX-1 may play an important role in cell adhesion to FN in an integrin-independent manner.

Animals↗
PubMed2001

Identification of protein kinase Calpha as an essential, but not sufficient, cytosolic factor for Ca2+-induced alpha- and dense-core granule secretion in platelets.

Upon activation, platelets release many active substances. Here, we have analyzed the mechanism governing Ca(2+)-induced secretion of von Willebrand factor stored in alpha-granules and 5-hydroxytryptamine in dense-core granules in permeabilized human platelets. Both secretions were dependent on ATP and cytosol. An essential factor for both granule secretions was purified from rat brain cytosol and identified to be protein kinase Calpha (PKCalpha) by partial amino acid sequencing. Purified PKCalpha efficiently stimulated both secretions in the presence of cytosol, whereas PKCalpha alone did not support the secretion of either type of granules, suggesting that PKCalpha is not a sufficient factor. Finally, in human platelet cytosol fractionated by a gel filtration column, the stimulatory activity for dense-core granule secretion paralleled with the concentration of PKC, suggesting that PKC could also be such a stimulatory factor in platelet cytosol. Thus, we identified PKCalpha as an essential, but not sufficient, cytosolic factor for the Ca(2+)-induced secretions of both alpha- and dense-core granules in platelets.

Adenosine Triphosphate↗
PubMed2001

Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions.

At tight junctions (TJs), claudins with four transmembrane domains are incorporated into TJ strands. Junctional adhesion molecule (JAM), which belongs to the immunoglobulin superfamily, is also localized at TJs, but it remains unclear how JAM is integrated into TJs. Immunoreplica electron microscopy revealed that JAM showed an intimate spatial relationship with TJ strands in epithelial cells. In L fibroblasts expressing exogenous JAM, JAM was concentrated at cell-cell adhesion sites, where there were no strand-like structures, but rather characteristic membrane domains free of intramembranous particles were detected. These domains were specifically labeled with anti-JAM polyclonal antibody, suggesting that JAM forms planar aggregates through their lateral self-association. Immunofluorescence microscopy and in vitro binding assays revealed that ZO-1 directly binds to the COOH termini of claudins and JAM at its PDZ1 and PDZ3 domains, respectively. Furthermore, another PDZ-containing polarity-related protein, PAR-3, was directly bound to the COOH terminus of JAM, but not to that of claudins. These findings led to a molecular architectural model for TJs: small aggregates of JAM are tethered to claudin-based strands through ZO-1, and these JAM aggregates recruit PAR-3 to TJs. We also discuss the importance of this model from the perspective of the general molecular mechanisms behind the recruitment of PAR proteins to plasma membranes.

Animals↗
PubMed2001

Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice.

BACKGROUND: The vascular smooth muscle cell (VSMC) is the central cell component involved in the fibroproliferative response in atherogenesis. As the lesion advances, VSMCs migrate from the media into the subendothelial space, thereby forming fibrous plaque lesions. Platelet-derived growth factor (PDGF) has been known to be a potent chemoattractant and mitogen for SMCs, but the pathophysiological role of the 2 PDGF receptors, receptor-alpha (PDGFR-alpha) and receptor-beta (PDGFR-beta) in atherogenesis is poorly understood. To clarify this problem, we prepared antagonistic rat monoclonal antibodies, APA5 and APB5, against murine PDGFR-alpha and PDGFR-beta, respectively. METHODS AND RESULTS: Apolipoprotein E-deficient mice were fed a high-fat diet containing 0.3% cholesterol from 6 weeks of age and subjected to injection with 1 mg/d IP of either antibody from 12 to 18 weeks every other day. In the mice injected with APB5, the aortic atherosclerotic lesion size and the number of intimal VSMCs were reduced by 67% and 80%, respectively, compared with the control mice injected with irrelevant rat IgG. In contrast, the mice that received APA5 showed only minimal reduction of lesion size, and a large number of VSMCs were observed in the intima. In the intima of advanced lesions, APB5 immunolabeled VSMCs, whereas APA5 could detect VSMCs mainly in the media. CONCLUSIONS: These results indicate that PDGFR-beta plays a significant role in formation of fibrous atherosclerotic lesions and that regulation of the signal transduction through PDGFR-beta could affect atherogenesis in mice.

Animals↗
PubMed2001

Monocyte chemoattractant protein 1 causes differential signalling mediated by proline-rich tyrosine kinase 2 in THP-1 cells.

Monocyte chemoattractant protein 1 (MCP-1) has a crucial role in atherogenesis and inflammation. However, MCP-1-mediated signalling pathways in monocytes have not been fully elucidated. In the present study we investigated the role of tyrosine kinases such as proline-rich tyrosine kinase 2 (Pyk2) in MCP-1-mediated signal transduction in the monocytic cell line THP-1. Pyk2 was tyrosine phosphorylated very quickly after stimulation with MCP-1. We found that Lyn, Shc and paxillin were also tyrosine phosphorylated by MCP-1. We examined the association of these molecules by immunoprecipitation and immunoblot analysis. The association of Pyk2 with Lyn was dependent on stimulation with MCP-1 and on tyrosine phosphorylation of Pyk2. Phosphorylation of p38 was also dependent on tyrosine phosphorylation of Pyk2. However, the association of Pyk2 with paxillin and Grb2 was not affected by stimulation with MCP-1. Phosphorylation of ERK (extracellular-signal-regulated protein kinase) was not affected by overexpression of kinase-negative Pyk2. Our results indicate that Pyk2 forms a complex with paxillin, Grb2 and Lyn in THP-1 cells. However, Pyk2 is not always involved in MCP-1-mediated signalling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2001

LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria.

Adhesion of bacteria to vascular endothelial cells as well as mucosal cells and epithelial cells appears to be one of the initial steps in the process of bacterial infection, including infective endocarditis. We examined whether lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), a member of scavenger receptor family molecules with C-type lectin-like structure, can support adhesion of Gram-positive and Gram-negative bacteria. Chinese hamster ovary-K1 (CHO-K1) cells stably expressing LOX-1 can support binding of FITC-labeled Staphylococcus aureus and Escherichia coli, which was suppressed by poly(I) and an anti-LOX-1 mAb. Adhesion of these bacteria to LOX-1 does not require divalent cations or serum factors and can be supported under both static and nonstatic conditions. Cultured bovine aortic endothelial cells (BAEC) can also support adhesion of FITC-labeled S. aureus, which was similarly suppressed by poly(I) and an anti-LOX-1 mAb. In contrast, binding of FITC-labeled E. coli to BAEC was partially inhibited by the anti-LOX-1 mAb, and poly(I) did not block FITC-labeled E. coli adhesion to BAEC, but, rather, enhanced it under a static condition. TNF-alpha increased LOX-1-dependent adhesion of E. coli, but not that of S. aureus, suggesting that S. aureus adhesion to BAEC may require additional molecules, which cooperate with LOX-1 and suppressed by TNF-alpha. Taken together, LOX-1 can work as a cell surface receptor for Gram-positive and Gram-negative bacteria, such as S. aureus and E. coli, in a mechanism similar to that of class A scavenger receptors; however, other unknown molecules may also be involved in the adhesion of E. coli to BAEC, which is enhanced by poly(I).

Animals↗
PubMed2001

Presence of multiple HIV type 1 subtypes among mothers and children in Japan.

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.

Amino Acid Sequence↗
PubMed2001

Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis.

Transmigration of monocytes to the subendothelial space is the initial step of atherosclerotic plaque formation and inflammation. Integrin activation and chemotaxis are two important functions involved in monocyte transmigration. To delineate the signaling cascades leading to integrin activation and chemotaxis by monocyte chemoattractant protein-1 (MCP-1), we have investigated the roles of MAPK and Rho GTPases in THP-1 cells, a monocytic cell line. MCP-1 stimulated beta1 integrin-dependent, but not beta2 integrin-dependent cell adhesion in a time-dependent manner. MCP-1-mediated cell adhesion was inhibited by a MEK inhibitor but not by a p38-MAPK inhibitor. In contrast, MCP-1-mediated chemotaxis was inhibited by the p38-MAPK inhibitor but not by the MEK inhibitor. The inhibitor of Rho GTPase, C3 exoenzyme, and a Rho kinase inhibitor abrogated MCP-1-dependent chemotaxis but not integrin-dependent cell adhesion. Further, C3 exoenzyme and the Rho kinase inhibitor blocked MCP-1-dependent p38-MAPK activation. These data indicate that ERK is responsible for integrin activation, that p38-MAPK and Rho are responsible for chemotaxis mediated by MCP-1, and that Rho and the Rho kinase are upstream of p38-MAPK in MCP-1-mediated signaling. This study demonstrates that two distinct MAPKs regulate two dependent signaling cascades leading to integrin activation and chemotaxis induced by MCP-1 in THP-1 cells.

CD18 Antigens↗
PubMed2001

Small GTPase Rho regulates thrombin-induced platelet aggregation.

Platelets play essential roles in hemostasis and thrombosis by aggregating with each other. However, the molecular mechanism governing platelet aggregation is not yet fully understood. Here, we established an assay system using platelets permeabilized with streptolysin-O to analyze mechanism of the thrombin-induced aggregation, focusing upon a controversial issue in the field whether small GTPase Rho regulates the aggregation. Incubation of the permeabilized platelets with Rho GDP-dissociation inhibitor, an inhibitory regulator for Rho family GTPases, extracted Rho family proteins extensively from the plasma and intracellular membranes, and inhibited the thrombin-induced aggregation. Incubation of the permeabilized platelets with botulinum exoenzyme C3, which specifically inhibits Rho function by ADP-ribosylating it, abolished the thrombin-induced aggregation. Thus, Rho is involved in thrombin-induced aggregation of platelets.

ADP Ribose Transferases↗
PubMed2001

Vortex-lattice phases of superfluid (3)He in rapid rotation.

Superfluid 3He in the angular velocity of 0.01 Omega(c2) < or = Omega < or = Omega(c2) is studied theoretically, where Omega(c2) is the upper critical field of order (1 - T/T(c)) x 10(7) rad/s. Five different phases have been found in the pressure-Omega plane. Especially, it is shown that the A-phase-core vortex experimentally found in the B phase originates from Schopohl's polar state at Omega(c2) via an A-phase mixed-twist lattice with polar cores and the normal-core lattice of Ohmi, Tsuneto, and Fujita [Prog. Theor. Phys. 70, 647 (1983)].

Journal Article↗
PubMed2001

Epithelioid leiomyosarcoma of the uterine cervix.

BACKGROUND: Leiomyosarcomas with an epithelioid appearance arising in the uterine cervix are extremely rare neoplasms. We present a case of triple uterine cancer containing cervical epithelioid leiomyosarcoma. CASE: A 72-year-old Japanese woman, gravida 1, para 1, 55 years in menopause, visited her local doctor due to atypical bleeding and the endometrial smear was suspect for malignancy. She was referred to our hospital. Endometrial curettage revealed endometrioid adenocarcinoma, G1, with a fragment of sarcomatous tumor. A total hysterectomy with bilateral salpingo-oophorectomy was performed. The histological findings revealed triple uterine cancer consisting of endometrial adenocarcinoma, cervical epithelioid leiomyosarcoma, and cervical squamous cell carcinoma. CONCLUSION: This extremely rare case of triple uterine cancer containing cervical epithelioid leiomyosarcoma is the first report, to the best of our knowledge.

Aged↗
PubMed2001

Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis.

Proliferation of mesangial cells is a hallmark of glomerular disease, and understanding its regulatory mechanism is clinically important. Previously, we demonstrated that the product of growth arrest-specific gene 6 (Gas6) stimulates mesangial cell proliferation through binding to its cell-surface receptor Axl in vitro. We also showed that warfarin and the extracellular domain of Axl conjugated with Fc portion of human IgG1 (Axl-Fc) inhibit mesangial cell proliferation by interfering the Gas6/Axl pathway in vitro. In the present study, therefore, we examined in vivo roles of Gas6 and Axl in an experimental model of mesangial proliferative glomerulonephritis induced by the injection of anti-Thy1.1 antibody (Thy1 GN). In Thy1 GN, expression of Gas6 and Axl was markedly increased in glomeruli, and paralleled the progression of mesangial cell proliferation. Administration of warfarin or daily injection of Axl-Fc inhibited mesangial cell proliferation, and abolished the induction of platelet-derived growth factor-B mRNA and protein in Thy1 GN. Moreover, the anti-proliferative effect of warfarin was achieved at lower concentrations than those in routine clinical use. These findings indicate that the Gas6/Axl pathway plays a key role in mesangial cell proliferation in vivo, and could be a potentially important therapeutic target for the treatment of renal disease.

Animals↗
PubMed2001

A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis.

OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong inhibitory effects on mesangial cell proliferation in vitro. In the present study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis. Both OCT and 1,25(OH)(2)D(3) significantly inhibited mesangial cell proliferation, the degree of glomerulosclerosis, and albuminuria at day 8 compared to the disease control group. The OCT-treated group showed normal calcium levels but the 1,25(OH)(2)D(3)-treated group showed higher levels. The disease control group showed a marked increase of type I and type IV collagens, and alpha-smooth muscle actin (alpha-SMA) compared to the normal group. The treatment of OCT or 1,25(OH)(2)D(3) significantly reduced the expression of these proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly higher levels of type I and type IV collagens, and alpha-SMA at day 8 compared to normal rats. Treatment with OCT or 1,25(OH)(2)D(3) inhibited the mRNA expressions of type I and type IV collagens, as well as that of alpha-SMA. These data demonstrate that OCT inhibits mesangial cell proliferation and extracellular matrix expansion with a low calcemic activity. Disease control rats showed significantly increased levels of transforming growth factor-beta1 protein in the glomeruli, but treatment with OCT or 1,25(OH)(2)D(3) markedly reduced this expression. The levels of mRNA in glomeruli were also consistent with these protein levels. Therefore, the suppressive effect of OCT may be mediated by inhibition of transforming growth factor-beta1. The present results suggest that OCT has potential for use in therapeutic strategy for the treatment of glomerulonephritis without inducing hypercalcemia.

Actins↗