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Biomedical subjects

M Naito

Publications and source records attributed to M Naito.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effect of bioflavonoids on vincristine transport across blood-brain barrier.

Several grapefruit juice bioflavonoids, including quercetin, are reported to stimulate P-glycoprotein-mediated drug efflux from cultured tumor cells. To see whether these bioflavonoids alter the permeation of vincristine across the blood-brain barrier, we conducted experiments with cultured mouse brain capillary endothelial cells (MBEC4 cells) in vitro and ddY mice in vivo. The steady-state uptake of [3H]vincristine by MBEC4 cells was decreased by 10 microM quercetin, but increased by 50 microM quercetin. Similarly, the in vivo brain-to-plasma concentration ratio of [3H]vincristine in ddY mice was decreased by coadministration of 0.1 mg/kg quercetin, but increased by 1.0 mg/kg quercetin. Kaempferol had a similar biphasic effect on the in vitro uptake of [3H]vincristine. Other aglycones tested (chrysin, flavon, hesperetin, naringenin) increased [3H]vincristine uptake in the 10-50 microM range, and glycosides (hesperidin, naringin, rutin) were without effect. We then addressed the mechanism of the concentration-dependent biphasic action of quercetin. Verapamil, a P-glycoprotein inhibitor, inhibited the efflux of [3H]vincristine from MBEC4 cells, while 10 microM quercetin significantly stimulated it. The uptake of [3H]vincristine by MBEC4 cells was increased by inhibitors of protein kinase C, but decreased by phorbol 12-myristate-13-acetate (PMA), as well as by 10 microM quercetin. The phosphorylation level of P-glycoprotein was increased in the presence of 5 microM quercetin or 100 nM PMA, but decreased by the protein kinase C inhibitor H7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine, 30 microM). We conclude that low concentrations of quercetin indirectly activate the transport of [3H]vincristine by enhancing the phosphorylation (and hence activity) of P-glycoprotein, whereas high concentrations of quercetin inhibit P-glycoprotein. Our results indicate that patients taking drugs which are P-glycoprotein substrates may need to restrict their intake of bioflavonoid-containing foods and beverages, such as grapefruit juice.

3-O-Methylglucose↗
PubMed2000

The domains of human fibronectin mediating the binding of alpha antigen, the most immunopotent antigen of mycobacteria that induces protective immunity against mycobacterial infection.

We have recently shown that alpha antigen (alpha-Ag), the immunodominant antigen of mycobacteria, has a novel fibronectin (FN)-binding motif that is unique among mycobacteria [Naito, Ohara, Matsumoto and Yamada (1998) J. Biol. Chem. 273, 2905-2909]. In this study, we examined the domains of human FN that interacted with alpha-Ag. Fragments of FN generated by either proteolysis or recombinant DNA techniques were compared for their ability to bind to alpha-Ag. Fragments containing either the C-terminal heparin-binding domain or the central cell-binding domain consistently bound to alpha-Ag. The fragment of the C-terminal heparin-binding domain, upon mutation that resulted in the loss of its heparin-binding activity, could not bind with alpha-Ag. These findings suggested that the mutated site, i.e. the main heparin-binding site of FN, was also the principal site for binding to alpha-Ag. The alpha-Ag-binding domains of FN could bind whole mycobacterial bacilli, suggesting that these two domains are important contributors to mycobacterial infection.

Antigens, Bacterial↗
PubMed2000

Smooth muscle cell outgrowth stimulated by fibrin degradation products. The potential role of fibrin fragment E in restenosis and atherogenesis.

This study is based on the observation that deposition of thrombus within the arterial wall and on its surface is a consistent response to the vascular injury of angioplasty and of angioplasty lesions at risk of rapid restenosis. Mitogenic activity is stimulated by fibrin degradation products in extracts of human atherosclerotic plaques and plasmin digests of fibrin, and this has been attributed to products that include fibrin fragment E. The effect of human fibrin degradation products on smooth muscle outgrowth from rabbit aortic medial explants now has been explored in culture. Every batch of fibrin degradation products was first tested on the in vivo chick chorioallantoic membrane model for the ability to stimulate cell proliferation, including angiogenesis as shown previously. Increasing concentrations of fibrin degradation products were stimulated significantly earlier and with greater outgrowth of smooth muscle cells than controls, up to an optimum at 92 microg/mL fibrin degradation products. The effect of fibrin degradation products was blocked by the prior admixture of a specific antifragment E antiserum, but not by an antifragment D antiserum. Purified commercial fibrinogen E is inactive, but when treated with thrombin to resemble fibrin E it stimulated smooth muscle cell outgrowth, and this was not seen with comparable dosages of fragment D. We propose that fibrin degradation products, in particular fibrin fragment E, provide an abundant in situ early initiator of smooth muscle cell migration and proliferation in restenosis and atherogenesis.

Angioplasty↗
PubMed2000

Molecular cloning and functional analysis of apoxin I, a snake venom-derived apoptosis-inducing factor with L-amino acid oxidase activity.

We previously purified apoxin I, an apoptosis-inducing factor with L-amino acid oxidase (LAO) activity, from Western diamondback rattlesnake venom. To determine the primary structure of apoxin I, we cloned its cDNA. The amino acid sequence showed that apoxin I has an FAD binding domain and shares homology with L-amino acid oxidase (LAO) from Neurospora crassa, human monoamine oxidase B, and mouse interleukin 4-induced F1G1 protein. The full-length apoxin I has an N-terminal signal sequence that is processed in mature apoxin I in venom. When the apoxin I gene was transfected into human 293T cells, the recombinant protein was expressed in the cells, and a significant amount of apoxin I was secreted into the medium. The secreted recombinant apoxin I protein showed LAO and apoptosis-inducing activity, but the recombinant protein in the cells did not, suggesting that maturation and secretion of the apoxin I protein is needed for its activity. Treating the transfected cells with tunicamycin inhibited the secretion and LAO activity of the recombinant apoxin I. In addition, deleting the amino-terminal region flanking the signal sequence, the FAD-binding domain and the carboxy-terminal region abolished the secretion and LAO activity of the recombinant proteins. These results indicate that in order for apoxin I to become active, these regions and posttranslational modification, such as N-glycosylation, are required.

Amino Acid Oxidoreductases↗
PubMed2000

Inhibition of multiplication of Mycobacterium leprae in mouse foot pads by recombinant Bacillus Catmette-Guérin (BCG).

Immunization of mice with recombinant Mycobacterium bovis Bacillus Calmette-Guérin (rBCG) which over-produces a putative protective antigen candidate, the A component of antigen 85 complex (Ag85A), reduced the multiplication of Mycobacterium leprae in the foot pads of mice. The inhibition by this rBCG (rBCG/85A) was more evident than that with parental BCG. Repeated rBCG/85A immunization significantly could reduce M. leplae multiplication in mice. This is first report of rBCG to control mycobacterial infection in animal model. Therefore, rBCG technique may be useful for the development of a more effective mycobacteria vaccine.

Acyltransferases↗
PubMed2000

Utility of blasts with a clear halo around the nucleolus as a predictive indicator for disease progression in patients with myelodysplastic syndromes and aplastic anemia.

This study was designed to evaluate the utility of blasts with a clear halo around their nucleoli (BCHN) as a predictive indicator of disease progression in myelodysplastic syndromes (MDSs) and aplastic anemia (AA). Bone marrow aspirates from 75 patients with MDSs and 18 with AA were fixed in 95% ethanol solution or 10% neutral formalin and stained with the Papanicolaou method. BCHNs were detected in 57 of 75 patients with MDSs and in 10 of 18 AA patients. Disease progression was restrictedly observed in 17 patients with MDSs who had BCHNs at onset and in 1 patient with AA. The proportion of BCHNs increased with disease progression in these 16 of 17 patients with MDSs. The presence of BCHNs at onset and the increase in proportion of BCHNs during the clinical course of MDSs were significant indications for predicting disease progression.

Anemia, Aplastic↗
PubMed2000

Role of macrophage scavenger receptor in endotoxin shock.

Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages, including CD14 and macrophage scavenger receptor class A types I and II (MSR-A), and stimulates macrophages to release various inflammatory mediators. MSR-A recognizes a broad range of polyanionic ligands such as chemically modified lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic acid of Gram-positive bacteria, suggesting a role in host defence. In this study, mice lacking MSR-A were used to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A(-/-)) mice bound less remarkably to LPS than those from wild-type (MSR-A(+/+)) mice and the binding activity of MSR-A(+/+) macrophages to LPS was reduced by the addition of an anti-MSR-A antibody. Clearance of LPS in serum was retarded in MSR-A(-/-) mice after intraperitoneal administration of LPS. LPS-induced expression of cytokines in the liver was similar in MSR-A(+/+) and MSR-A(-/-) mice, but levels of interleukin (IL)-1beta expression and serum IL-1beta were lower in MSR-A(-/-) mice. Administration of large doses of LPS resulted in a higher mortality of MSR-A(+/+) mice and pretreatment with an IL-1 receptor antagonist reduced the mortality. Thus, MSR-A-mediated macrophage activation plays a negative role in protecting mice from endotoxin shock by enhancing IL-1beta production by macrophages.

Animals↗
PubMed2000

Temperament and Character Inventory (TCI) as predictors of depression among Japanese college students.

To examine the predictive power of Cloninger's psychobiology model of depression, 167 Japanese college students were studied on two occasions, with an interval of approximately three months. At Time 1 (T1), the Temperament and Character Inventory (TCI) and Self-rating Depression Scale (SDS) were distributed. At Time 2 (T2), the SDS was distributed again. The T2 SDS score was positively correlated with Harm Avoidance and negatively correlated with Reward Dependence and Self-directedness at T1. However, after controlling for the T1 SDS score, the T2 SDS score was predicted only by T1 Self-directedness. These data suggest that lower Self-directedness can be predictive of depression, whereas higher Harm Avoidance and lower Reward Dependence are state-dependent.

Adult↗
PubMed2000

Analysis of the significance of the measurement of acceleration with respect to lateral laxity of the anterior cruciate ligament insufficient knee.

The purpose of this study was to assess dynamically the lateral thrust of anterior cruciate ligament (ACL) insufficient knees, and from the findings determine any relationship between ACL insufficiency and the later development of osteoarthritis (OA). We investigated 80 knees in 40 patients awaiting ACL reconstruction and 25 knees of 25 patients, which had undergone ACL reconstruction. An acceleration sensor was fixed to the anterior tibial tubercle and this 'acted' in two directions--medial lateral and perpendicular. The peak value of the lateral acceleration immediately after heel strike was significantly greater in the ACL insufficient knees when compared to their opposite normal knees. When the periods from injury were compared, the lateral thrust of the injured side after 3 years or more was significantly greater than in the first 3 years. There was no significant difference between the normal knees and the ACL reconstructed knees. The results indicated that the lateral acceleration peak value was significantly greater in the ACL insufficient knees than in their opposite normal knees.

Acceleration↗
PubMed2000

Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus.

Although cyclosporin A and tacrolimus are used clinically as potent immunosuppressants, there have been reports of neurotoxicity and encephalopathy. A possible mechanism is that these drugs damage the blood-brain barrier (BBB), inducing dysfunction and increased permeability, and are then able to enter the brain. We studied the cytotoxicity of cyclosporin A and tacrolimus, focused on apoptosis induction, using an immortalized cell line established from BALB/c mouse cerebral microvessel endothelial cells (MBEC4). We found that these two drugs induced cell shrinkage, chromatin condensation and DNA fragmentation, which are characteristics of apoptosis. Our data suggest that the induction of apoptosis on the brain capillary endothelial cells may be at least partly involved in the occurrence of immunosuppressant-induced encephalopathy.

Animals↗
PubMed2000

Mode of action of sesame lignans in protecting low-density lipoprotein against oxidative damage in vitro.

We investigated the antioxidant properties of sesaminol, a major component of sesame oil, on the oxidative modification of human low-density lipoprotein (LDL) in vitro. Sesaminol inhibited the Cu2+-induced lipid peroxidation in LDL in a concentration-dependent manner with an IC50 36.0 +/- 10.0 nM. Sesaminol was a more effective scavenger than either alpha-tocopherol or probucol in reducing the peroxyl radicals derived from 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in aqueous solution. In addition, as determined by the secondary products of lipid peroxidation identified by using immunochemical methods, sesaminol completely inhibited the formation of 4-hydroxy-nonenal (4-HNE)- and malondialdehyde (MDA)-adducts in a concentration-dependent manner. Probucol and alpha-tocopherol at the same concentration exhibited a lesser inhibitory effect. Our findings suggest that sesaminol is a potentially effective antioxidant that can protect LDL against the oxidation.

Antioxidants↗
PubMed2000

Involvement of glial cells in cyclosporine-increased permeability of brain endothelial cells.

1. To test whether astrocytes participate in cyclosporine-induced dysfunction of the blood-brain barrier, we examined the effects of cyclosporine on the permeability of the mouse brain endothelial (MBEC4) cells cocultured with C6 glioma cells, each cell layer placed on the top and bottom of the insert membrane, respectively. 2. The presence of C6 cells remarkably aggravated cyclosporine-increased permeability of MBEC4 cells to sodium fluorescein. 3. In light of these findings, the possibility that astroglial cells could contribute to the occurrence of cyclosporine-induced dysfunction of the blood-brain barrier triggering neurotoxicity should be considered.

Animals↗
PubMed2000

Fibronectin-binding proteins secreted by Mycobacterium avium.

Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Fibronectin is an extracellular matrix protein and is a virulence factor for several extracellular pathogenic bacteria binding to mucosal surfaces. We investigated the fibronectin (FN)-binding proteins in the culture filtrate of M. avium by two-dimensional electrophoresis (2DE). Proteins in Sauton medium of M. avium after 3 weeks were separated by 2DE. The proteins were blotted onto polyvinylidene difluoride membrane and incubated with FN. FN-binding proteins were detected by Western blotting using anti-FN antibody. FN bound to five spots (33 kDa, 32 kDa, 31 kDa, 30 kDa and 25 kDa). N-terminal amino acids of these were determined. The 33 kDa spot corresponded to antigen 85 (Ag 85) C. The 32 and 31 kDa spots were either Ag 85 A or Ag 85 B. The 30 kDa spot corresponded to Ag 85 B of M. avium. The 25 kDa spot corresponded to MPA51 (M. avium MPB51). Thus, FN bound exclusively to the Ag 85 complex and MPA51.

Amino Acid Sequence↗
PubMed2000

Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice.

BACKGROUND/AIMS: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony-stimulating factor (M-CSF/CSF-1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M-CSF to lipopolysaccharide (LPS)-induced cytokine expression and neutrophil infiltration in the liver. METHODS: We investigated the effects of LPS administration in M-CSF-deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT-PCR. Neutrophil infiltration in the liver was also examined. RESULTS: After LPS administration, cytokine production and expression of LPS receptors, such as CD14 and scavenger receptor class A (MSR-A), were induced at lower levels in op/op mice than those in littermate mice. Neutrophil infiltration in the liver of op/op mice did not differ significantly from that of littermate mice. Anti-IL-8 receptor homologue and anti-C5a receptor antibody reduced the number of infiltrating neutrophils. CONCLUSIONS: These findings indicate that deficient macrophage activation following LPS injection in op/op mice is associated with decreased expression of CD14 and MSR-A in the liver. Thus, M-CSF plays a critical role in LPS-induced macrophage activation but does not exert a dominant role in neutrophil infiltration in the liver.

Animals↗
PubMed2000

Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy.

The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

Animals↗
PubMed2000

Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor.

Macrophage-colony-stimulating factor (M-CSF) regulates the survival, proliferation and differentiation of the mononuclear phagocyte lineage. Osteopetrotic (op/op) mice defective in producing functional M-CSF were used in order to investigate the role of M-CSF on the development of microglia and brain macrophages and the expression of scavenger receptor (SR). Adult op/op and littermate mice at 10-47 weeks of age were investigated by immunohistochemistry with a panel of monoclonal antibodies (F4/80, Mac-1, anti-major histocompatibility complex (MHC) class II and anti-SR), electron microscopy and reverse transcriptase-polymerase chain reaction (RT-PCR). Microglia were weakly immunolabeled with F4/80 and Mac-1 in op/op and littermate mice, but the number of microglia in op/op mice was reduced in the cerebrum, cerebellum and brainstem compared with that of normal littermates. The numbers of Mac-1-positive microglia in op/op mice was 39% (pons) and 30% (cerebellar cortex) lower than that in normal littermates (P<0.05). In addition, the microglia cell processes in op/op mice were often shorter than those in control mice. In op/op and littermate mice, both MHC class II and SR were present in perivascular cells and macrophages of the leptomeninx and choroid plexus. Ultrastructurally, perivascular cells appeared to be immature, since their cytoplasm was narrow and contained few inclusion bodies compared with those of control mice. Reverse transcriptase-polymerase chain reaction showed a weak expression for SR mRNA in the brains of op/op mice as well as littermate mice. These results indicate that microglia are partly dependent on M-CSF for their proliferation and differentiation and that M-CSF has no significant effect on the expression of SR in the physiological brain. The study also suggests that M-CSF affects the maturation of perivascular cells at the ultrastructural level.

Animals↗
PubMed2000

The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis.

BACKGROUND/PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) was assessed in the diagnosis of cholestatic liver disease in infants. METHODS: ERCP was performed in 50 infants who had prolonged cholestasis. Their ages ranged from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to 6.7 kg (mean, 4.7 kg). Incomplete visualization of the biliary tree or visualization of only the pancreatic duct was followed by exploratory laparotomy. In those in whom the biliary tree was visualized completely, the caliber of the bile duct was compared with that of the pancreatic duct. RESULTS: ERCP was completed in 43 patients (success rate, 86%) without complications. In the 7 patients in whom ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory laparotomy. The other patient had congenital biliary dilatation (CBD). In 29 of the 43 patients, the biliary tree was seen partially or only the pancreatic duct was visualized. These patients had BA diagnosed by laparotomy. Complete visualization of the biliary tree was obtained in 14 patients. Of these, 9 had neonatal hepatitis (NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD. In all of the patients with NH, cholestasis improved spontaneously. The 2 patients with PIBLD had biopsy-proven disease. The caliber of the bile duct was larger than that of the pancreatic duct in NH. This relationship was not observed in PIBLD. CONCLUSIONS: ERCP is safe in infants. It is useful in the diagnosis of prolonged cholestasis.

Cholangiopancreatography, Endoscopic Retrograde↗