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N Sakai

Publications and source records attributed to N Sakai.

At least 109 records · Page 6Linked to original sources
PubMed2001

[Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis].

The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.

Adult↗
PubMed2001

Expression of CD44 in synovium of rabbits with chronic arthritis induced by immunization with Escherichia coli.

OBJECTIVE: To investigate the expression of CD44 and its role in experimental chronic arthritis in rabbits. METHODS: Rabbits were immunized with Escherichia coli 0:14 for short (4 mo) and long (8-10 mo) periods. Immunohistochemical staining was performed on knees, using anti-CD44 antibodies. RESULTS: Lymphocyte infiltration in the synovium was found in 30.0% of rabbits after short term immunization, and the rate increased to 58.3% after longterm immunization. CD44 was present in synovial lining cells in 30.0% of rabbits after short term immunization, and it increased significantly (p < 0.05) after longterm immunization (66.7%). CD44 was also observed in lymphocytes in knee synovium after longterm immunization (25.0%). CONCLUSION: CD44 in lining cells might play a role in promoting chronic arthritis in rabbits immunized with E. coli.

Animals↗
PubMed2001

[Two cases of Chlamydia psittaci infection occurring in employees of the same pet shop].

We report here 2 cases of psittacosis in a pet shop. In the first case, a 44-year-old male was admitted with fever, and a chest radiograph showed an infiltration shadow in the right lower lung. One day later, a colleague of the first patient, a 42-year-old man, developed fever and was admitted. In this patient, chest radiography revealed an infiltration shadow in the left lower lung. Both patients had mild liver dysfunction. The serum titer of a complement fixation (CF) test against Chlamydia psittaci was elevated fourfold in the first case and sixteen-fold in the second on the analysis of paired acute- and convalescent-phase serum specimens. Clinical symptoms and abnormal laboratory data were attenuated by the administration of minocycline for 2 weeks. Since both patients worked in same pet shop and since some parakeets at the shop had died, we speculated that the psittacosis had originated from these birds.

Adult↗
PubMed2000

Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein.

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport, a protective system against atherosclerosis. CETP, as well as plasma phospholipid transfer protein, belongs to members of the lipid transfer/lipopolysaccharide-binding protein (LBP) gene family, which also includes the lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein. Although these four proteins possess different physiological functions, they share marked biochemical and structural similarities. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with a marked hyperalphalipoproteinemia (HALP). Two common mutations in the CETP gene, intron 14 splicing defect and exon 15 missense mutation (D442G), have been identified in Japanese HALP patients with CETP deficiency. The deficiency of CETP causes various abnormalities in the concentration, composition, and functions of both HDL and low density lipoprotein. Although the pathophysiological significance of CETP in terms of atherosclerosis has been controversial, the in vitro experiments showed that large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Epidemiological studies in Japanese-Americans and in the Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have shown an increased incidence of coronary atherosclerosis in CETP-deficient patients. The current review will focus on the recent findings on the molecular biology and pathophysiological aspects of plasma CETP, a key protein in reverse cholesterol transport.

Animals↗
PubMed2000

Increased phospholipase D2 activity during hypoxia-induced death of PC12 cells: its possible anti-apoptotic role.

During hypoxic incubation (1% O2) of PC12 cells, the PLD activity was transiently increased within 12h, followed by a gradual decrease. In the in vitro assay, the increased PLD activity was independent of GTPgammaS required for PLD1 or of oleic acid for PLD(OA), suggesting the activation of PLD2. The level of PLD2 protein showed no change up to 12h but a gradual decrease after 24 h. Pretreatment of cells with S. chromofuscus PLD resulted in inhibition of hypoxia-induced apoptotic cell death. In contrast, 1-butanol, but not 2-butanol, potentiated cell death. Moreover, the number of apoptotic cells significantly reduced in PC12 cells over-expressing PLD2. These results raise the possibility that PLD2 activation may play an anti-apoptotic role in hypoxia-induced cell death.

1-Butanol↗
PubMed2000

K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid.

The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation.

Administration, Oral↗
PubMed2000

Enhancement of the spin-dependent effect of pi/2-angle Compton scattering using elliptically polarized synchrotron radiation.

Noticeable enhancement of the spin-dependent Compton scattering intensity in right-angle scattering has been achieved by using high-energy X-rays having elliptical polarization. A promising momentum resolution of better than 0.4 atomic units for Compton-profile measurements is firmly predicted by means of an ordinary Ge solid-state detector when the scattering-angle divergence at 90 degrees is crucially restricted. It is pointed out that the angle between a scattering vector and the direction of sample magnetization can be chosen as 90 degrees without seriously weakening the spin-dependent effect. Comparison is made between 274 keV and 122 keV experiments.

Journal Article↗
PubMed2000

Importance of protein kinase C targeting for the phosphorylation of its substrate, myristoylated alanine-rich C-kinase substrate.

We visualized the translocation of myristoylated alanine-rich protein kinase C substrate (MARCKS) in living Chinese hamster ovary-K1 cells using MARCKS tagged to green fluorescent protein (MARCKS-GFP). MARCKS-GFP was rapidly translocated from the plasma membrane to the cytoplasm after the treatment with phorbol ester, which translocates protein kinase C (PKC) to the plasma membrane. In contrast, PKC activation by hydrogen peroxide, which was not accompanied by PKC translocation, did not alter the intracellular localization of MARCKS-GFP. Non-myristoylated mutant of MARCKS-GFP was distributed throughout the cytoplasm, including the nucleoplasm, and was not translocated by phorbol ester or by hydrogen peroxide. Phosphorylation of wild-type MARCKS-GFP was observed in cells treated with phorbol ester but not with hydrogen peroxide, whereas non-myristoylated mutant of MARCKS-GFP was phosphorylated in cells treated with hydrogen peroxide but not with phorbol ester. Phosphorylation of both MARCKS-GFPs reduced the amount of F-actin. These findings revealed that PKC targeting to the plasma membrane is required for the phosphorylation of membrane-associated MARCKS and that a mutant MARCKS existing in the cytoplasm can be phosphorylated by PKC activated in the cytoplasm without translocation but not by PKC targeted to the membrane.

Animals↗
PubMed2000

Subtype-specific translocation of diacylglycerol kinase alpha and gamma and its correlation with protein kinase C.

We examined the translocation of diacylglycerol kinase (DGK) alpha and gamma fused with green fluorescent protein in living Chinese hamster ovary K1 cells (CHO-K1) and investigated temporal and spatial correlations between DGK and protein kinase C (PKC) when both kinases are overexpressed. DGKalpha and gamma were present throughout the cytoplasm of CHO-K1 cells. Tetradecanoylphorbol 13-acetate (TPA) induced irreversible translocation of DGKgamma, but not DGKalpha, from the cytoplasm to the plasma membrane. The (TPA)-induced translocation of DGKgamma was inhibited by the mutation of C1A but not C1B domain of DGKgamma and was not inhibited by staurosporine. Arachidonic acid induced reversible translocation of DGKgamma from the cytoplasm to the plasma membrane, whereas DGKalpha showed irreversible translocation to the plasma membrane and the Golgi network. Purinergic stimulation induced reversible translocation of both DGKgamma and alpha to the plasma membrane. The timing of the ATP-induced translocation of DGKgamma roughly coincided with that of PKCgamma re-translocation from the membrane to the cytoplasm. Furthermore, re-translocation of PKCgamma was obviously hastened by co-expression with DGKgamma and was blocked by an inhibitor of DGK (R59022). These results indicate that DGK shows subtype-specific translocation depending on extracellular signals and suggest that PKC and DGK are orchestrated temporally and spatially in the signal transduction.

Animals↗
PubMed2000

Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Tokyo Joshi-Idai Asthma Research Group.

BACKGROUND: Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma. METHODS: 85 patients with moderate to severe asthma taking high doses (> or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists. FINDINGS: Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group. INTERPRETATION: Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed.

Administration, Inhalation↗
PubMed2000

Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells.

Ceramide has recently been regarded as a potential mediator of apoptosis. In the present study, the effects of Bcl-2 and Bax on the ceramide-mediated apoptotic pathways were examined in glioma cells overexpressing Bcl-2 or Bax. Etoposide, cisplatin and tumor necrosis factor-alpha induced apoptosis of C6 rat glioma cells which was associated with ceramide formation due to activation of neutral sphingomyelinase, followed by release of mitochondrial cytochrome c into the cytosol and activation of caspases-9 and -3. The growth of C6 cells stably overexpressing either Bcl-2 or Bax was almost equal to that of the vector-transfected cells. Bax overexpression enhanced etoposide-induced apoptosis through acceleration of cytochrome c release and caspases activation. However, Bax had no effect on ceramide formation. Similar findings were obtained in C6 cells and U87-MG human glioblastoma cells which were transiently overexpressed with Bax. In contrast, Bcl-2 overexpression resulted in a retardation of the apoptotic process via prevention of cytochrome c release and caspases activation, and ceramide formation was also blocked when Bcl-2 was highly overexpressed in glioma cells. In addition, transient overexpression of Bcl-xL also exerted inhibitory effects on ceramide formation and apoptotic cell death induced by etoposide. These results indicate that Bax promotes apoptosis regardless of ceramide formation and that Bcl-2 or Bcl-xL prevents ceramide formation by repressing neutral sphingomyelinase as well as ceramide-induced cytochrome c release. Oncogene (2000) 19, 3508 - 3520

Animals↗
PubMed2000

Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry.

An expeditious route to synthetic lysobisphosphatidic acid S,S-1, its enantiomer, and regioisomers is reported. Synthetic difficulties concerning lipid stability and stereochemistry are bypassed using a phosphite triester approach in combination with multiple silyl protection. Spectroscopic studies evidence that acyl group migration in S,S-1 is accelerated by nonpolar solvents and inhibited by pyridine.

Biochemistry↗
PubMed2000

Identification of a GPI-anchored type HDL-binding protein on human macrophages.

To identify the HDL3-binding proteins on human macrophages, we examined the involvement of GPI-anchored protein in the binding of HDL3, and tried to purify HDL3-binding protein. From membrane fractions of macrophages, we obtained 80- and 130-kDa HDL3-binding proteins by ligand blotting. Treatment of macrophages with phosphatidylinositol-specific phospholipase C (PI-PLC) significantly decreased the specific HDL3-binding in a dose-dependent manner. Furthermore, treatment with mannosamine, which blocks GPI-anchor formation, decreased specific HDL3-binding in a dose-dependent manner. PI-PLC treatment released from the cells the proteins with an M(r) of 80 kDa, which could also bind HDL3. PI-PLC as well as mannosamine treatment markedly reduced cholesterol efflux from macrophages in association with the decreased HDL-binding. Using HDL3-affinity chromatography, we purified 80-kDa GPI-anchored type HDL3-binding protein. In summary, we demonstrate the implication of 80-kDa GPI-anchored protein in the binding of HDL3 to human macrophages, which might have some role in reverse cholesterol transport.

Binding Sites↗
PubMed2000

Giant Artificial Ion Channels Formed by Self-Assembled, Cationic Rigid-Rod beta-Barrels We thank Dr. E. Buck (Warner Instrument Corp., Hamden, CT) and R. Marclay (University of Geneva) for installation of a BLM workstation, Dr. E. Buck for BLM instructions, A. Pinto, J.-P. Saulnier, the group of Prof. Gülaçar, and Dr. H. Eder for NMR, MS, and elemental analyses, respectively (University of Geneva), and the Swiss NSF and Suntory Institute for Bioorganic Research (SUNBOR Grant) for financial support.

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Journal Article↗
PubMed2000

cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.

Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.

Animals↗
PubMed2000

On the electrostatics of cell-membrane recognition: from natural antibiotics to rigid push-pull rods.

The question why pore-forming, alpha-helical natural antibiotics are not toxic is discussed within the general context of the interaction of electrostatically asymmetric "nanorods" with neutral, anionic, and polarized bilayer membranes. We suggest that simplification of the structural complexity of natural systems will be necessary to ultimately define the involved subtle balance between constructive and destructive electrostatic interactions.

Amino Acid Sequence↗