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Biomedical subjects

M Nagamine

Publications and source records attributed to M Nagamine.

At least 19 recordsLinked to original sources

Effect of fluoride-releasing adhesive system on decalcified dentin.

The aim of this study was to evaluate the effect of fluoride-releasing adhesive systems on human decalcified dentin in vitro. Two fluoride-releasing adhesive systems, Reactmer bond (RB, Shofu) and ABF (AF, Kuraray), an experimental system, and a commercial adhesive system without fluoride release, SE bond (SE, Kuraray), were used in this study. The amount of fluoride release from adhesive in deionized water was measured every week for 10 weeks. Class V cavities were prepared on extracted human pre-molars and decalcified dentin was promoted by using a bacterial caries induction system at the cavity floor. The cavities preserving decalcified dentin were restored with resin composite (AP-X, Kuraray) after treatment by each adhesive system. The specimens without treatment by adhesive system and restoration were used for control. The specimens with restoration were then incubated for 4 weeks at 37 degrees C, 100% humidity. Microradiographs of the specimens showed that the radiopacities of the decalcified dentin layers in RB and AF groups with fluoride release were significantly higher than those in SE or control groups without fluoride release. This result suggested that the fluoride-releasing adhesive systems enhanced mineralization of decalcified dentin.

Bicuspid↗

Inhibition of artificial secondary caries by fluoride-releasing adhesives on root dentin.

Fluoride-releasing materials can be expected to inhibit the secondary caries. The aim;of this study was to evaluate the effect of fluoride-releasing adhesives on inhibition of secondary caries in outer and wall lesions. Two commercial fluoride-releasing adhesives, Reactmer bond (RB) and One-up bond F (OB), and a commercial adhesive without fluoride release, Mac-bond II (MB), were used prior to placement of restorative materials without fluoride release, Lite-fil II A (LF) and Estelite (EL), and a fluoride-releasing restorative material, Reactmer paste (RP). Class V cavities prepared on extracted human premolars were restored with various combinations of the materials: MB/EL, OB/EL, RB/LF and RB/RP. The restored teeth were incubated in bacterial medium containing sucrose with Streptoccus mutans for 14 days. Microradiographs of specimens showed no wall lesions in all groups and an acid-resistant layer adjacent to the restoration in the caries-like lesion. OB/EL, RB/LF and RB/RP groups showed thicker layers than the MB/EL group. The RB/RP group formed the shallowest outer lesion among all groups. These results indicate that fluoride-releasing adhesives are effective in the prevention of wall lesions but exhibit little outer lesion inhibition. Therefore, combined restoration using a fluoride-releasing adhesive and fluoride-releasing restorative material should be selected to inhibit secondary caries.

Analysis of Variance↗

The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection.

The UL41 gene product (vhs) of herpes simplex virus (HSV) is packaged in the virion, and mediates host protein synthesis shutoff at the early stage of the virus replication cycle. In order to clarify the role of vhs in virus replication and virulence, we isolated a completely UL41-deficient mutant (the VRDelta41 strain) and its revertant (the VRDelta41R strain). In the mouse encephalitis model, the replication of strain VRDelta41 was inhibited after 2 days post-infection, resulting in low virulence, by gamma-ray-sensitive cells such as lymphocytes and/or neutrophils. The result suggested that some cytokines, produced in VRDelta41-inoculated brains, activate and induce the migration of gamma-ray-sensitive cells to the infection site. Therefore, cytokines produced by HSV-1-infected human cells were screened, and potent inductions of interleukin (IL)-1beta, IL-8 and macrophage inflammatory protein-1alpha by VRDelta41 infection were observed. Moreover, the VRDelta41 strain showed 20- and 5-fold higher sensitivity to interferon-alpha and -beta compared to the wild-type strain, respectively. These results indicate that one important role of vhs in vivo is evasion from non-specific host defence mechanisms during primary infection through suppression of cytokine production in HSV-infected cells and reduction of the anti-HSV activity of interferon-alpha and -beta.

Animals↗

Rapid phenotypic characterization method for herpes simplex virus and Varicella-Zoster virus thymidine kinases to screen for acyclovir-resistant viral infection.

A rapid phenotypic screening method for herpes simplex virus (HSV) and varicella-zoster virus (VZV) thymidine kinase (TK) genes was developed for monitoring acyclovir-resistant viruses. This method determines the biochemical phenotype of the TK polypeptide, which is synthesized in vitro from viral DNA using a procedure as follows. The TK gene of each sample virus strain is amplified and isolated under the control of a T7 promoter by PCR. The PCR products are transcribed with T7 RNA polymerase and translated in a rabbit reticulocyte lysate. Using this method, enzymatic characteristics and the size of the TK polypeptides encoding HSV and VZV DNA were defined in less than 2 days without virus isolation. The assay should be a powerful tool in monitoring drug-resistant viruses, especially in cases in which virus isolation is difficult.

Acyclovir↗

Comparison of polymorphism of thymidine kinase gene and restriction fragment length polymorphism of genomic DNA in herpes simplex virus type 1.

The polymorphism of the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) was analyzed and was compared with the restriction fragment length polymorphism (RFLP) of the whole genome to evaluate the relative efficiency of the TK gene as a potential probe for identification and discrimination of HSV-1. The effectiveness of using the polymorphism of the TK gene in classifying HSV-1 strains was comparable to that of RFLP analysis of 66 sites, suggesting that TK gene sequencing may have important applications in epidemiological studies of HSV-1.

DNA, Viral↗

[A study on stress processes for college students during semester-end examinations].

The present study examined individual differences in psychological and physiological stress responses to the same stressor. In Study 1, psychological stress responses were assessed at three time periods: four weeks before, the day before, and the middle day of the semester-end examination period (N = 69). Both stress coping and MPI were assessed once during the study. In Study 2, 15 subjects were exposed to the same psychological stressor in an experiment to measure heart rate. The stressors were memorization of material relevant to the examination (Test 1), and mental calculation irrelevant to the examination (Test 2). Subjects were divided into 2 groups on the basis of their Study 1 psychological stress response scores: the low stress group (LS, N = 10) and the high stress group (HS, N = 5). The results of Study 1 and Test 1 of Study 2 suggested that there were significant differences between LS and HS in stress responses. These findings were discussed in light of cognitive appraisal and controllability of time. Further studies are needed to clarify the aspect of time span in cognitive appraisal.

Adolescent↗

[The role of daunorubicin in induction therapy for adult acute myeloid leukemia].

The relationship between the total dose of daunorubicin (DNR) in induction therapy and the treatment outcome were evaluated based upon individualized doses of DNR during induction therapy for patients with acute myeloid leukemia(AML). Ninety-two previously untreated adult AML patients admitted to our hospital were analyzed for the dose of DNR required for complete remission (CR), the CR rate, disease-free survival (DFS) and overall survival (OS). The induction therapy consisted of DNR (40 mg/m2/d, i.v., from D 1 until the marrow was hypoplastic), Ara-C, prednisolone, and/or 6-thioguanine. Eighty-three out of 92 patients were assessable. Sixty-three patients entered CR (76%), of whom 52 attained CR with the first course of induction therapy. The 10-year DFS and OS rates were 31.2% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120-480 mg/m2), which was not influenced by initial WBC count, or FAB type. These results indicate that when the dose is linked to the observed tumor response, the optimal dose of DNR in the induction therapy is around 280 mg/m2 (40 mg/m2 x 7 times), which is higher than the conventional dose of 40-60 mg/m2 for 3 days. The higher dose of DNR in the induction therapy for adult AML should be selected when the feasibility of a new drug is evaluated in a randomized trial.

Adolescent↗

Binding characteristics of [3H]DAA1106, a novel and selective ligand for peripheral benzodiazepine receptors.

Here, we investigated the binding characteristics of [3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]DAA1106), a potent and selective ligand for peripheral benzodiazepine receptors, in mitochondrial fractions of the rat brain. [3H]DAA1106 bound to the mitochondrial fraction of the rat brain in a saturable manner. The dissociation constant (Kd) and maximal number of binding sites (Bmax) obtained from Scatchard plot analysis of the saturation curve of [3H]DAA1106 binding were 0.12 +/- 0.03 nM and 161.03 +/- 5.80 fmol/mg protein, respectively. [3H]DAA1106 binding to mitochondrial preparations of the rat cerebral cortex was inhibited by several peripheral benzodiapine receptor ligands, and DAA1106 was the most potent inhibitor in inhibiting [3H]DAA1106 binding among the peripheral benzodiazepine receptor ligands we tested. The binding of [3H]DAA1106 was not affected by several neurotransmitter-related compounds, including adrenoceptor, gamma-aminobutyric acid (GABA), dopamine, 5-hydroxytryptamine (5-HT), acetylcholine, histamine, glutamate and central benzodiazepine receptor ligands even at a concentration of 10 microM. In the cerebral cortex of rhesus monkeys, DAA1106 and 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) potently inhibited [3H]DAA1106 binding, while 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydrobenzo[e][1,4]diazepin -2-one (Ro5-4864) did not. The highest [3H]DAA1106 binding was observed in the olfactory bulb, followed by the cerebellum. In autoradiographic studies, practically the same results were obtained, in that the highest binding of [3H]DAA1106 was in the olfactory bulb. Potent labeling was also noted in ventricular structures such as the choroid plexus. Thus, [3H]DAA1106 is a potent and selective ligand for peripheral benzodiazepine receptors and should prove useful for elucidating the physiological relevance of events mediated through peripheral benzodiazepine receptors.

Acetamides↗

Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106.

Receptor binding and behavioral profiles of N-(4-chloro-2-phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (DAA1097) and N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), novel, selective agonists for the peripheral benzodiazepine receptor (PBR) were examined. DAA1097 and DAA1106 inhibited [3H]PK 11195 binding to crude mitochondrial preparations of rat whole brain, with IC50 values of 0.92 and 0.28 nM. Likewise, DAA1097 and DAA1106 inhibited [3H]Ro 5-4864 binding to the same mitochondrial preparation, with IC50 values of 0.64 and 0.21 nM. In contrast, DAA1097 and DAA1106 did not inhibit [3H]-flunitrazepam, the central benzodiazepine receptor (CBR) ligand, binding to membranes of rat whole brain (IC50>10,000nM). Oral administration of DAA1097 and DAA1106 had anxiolytic effects in the mouse light/dark exploration test and in the rat elevated plus- maze test. Oral administration of DAA1106, diazepam and buspirone but not DAA1097 significantly increased sleeping time in hexobarbital-induced anesthesia in mice. The order of potency of potentiation of hexobarbital anesthesia was diazepam> buspirone> DAA1106> DAA1097. Oral administration of DAA1097 and DAA1106 but not diazepam and buspirone did not affect spontaneous locomotor activity in mice. These findings indicate that DAA1097 and DAA1106 are PBR selective ligands with potent anxiolytic-like properties, in laboratory animals.

Acetamides↗

A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.

NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.

Animals↗

In vivo receptor occupancy of NRA0045, a putative atypical antipsychotic, in rats.

We have previously reported that (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045) is a novel antipsychotic agent with affinities for dopamine D4, 5-hydroxytryptamine 2A (5-HT2A) and alpha1 receptors. In the present study, in vivo receptor occupancy of 5-HT2A, alpha1, dopamine D2 and D3 receptors by NRA0045 was assessed, based on in vivo and ex vivo receptor binding, and findings were compared to reference antipsychotic drugs (haloperidol, risperidone, clozapine). Intraperitoneal administration of haloperidol highly occupied the dopamine D2 receptor in the striatum and nucleus accumbens, and alpha1 adrenoceptors in the frontal cortex. Occupation of the 5-HT2A receptor in the frontal cortex and the dopamine D3 receptor in the nucleus accumbens and islands of Cajella was moderate. By contrast, atypical antipsychotics such as risperidone and clozapine dose-dependently occupied the 5-HT2A receptor in the frontal cortex, with moderate to negligible occupancy of the D2 receptor in the striatum and the nucleus accumbens. Clozapine and risperidone also occupied the alpha1 adrenoceptor in the frontal cortex, and clozapine did not occupy the dopamine D3 receptor. As seen with other atypical antipsychotics, intraperitoneal administration of NRA0045 dose-dependently occupied the 5-HT2A receptor and the alpha1 adrenoceptor in the frontal cortex, while it was without effect on dopamine D2 and D3 receptors in the striatum, nucleus accumbens and islands of Cajella. Thus, the strong occupancy of 5-HT2A and alpha1 receptors is involved in the pharmacological action of NRA0045.

Animals↗

Release and recharge of fluoride by restorative materials.

This study investigated the release and recharge of fluoride by restorative materials. Resin-modified glass ionomers (RGIs), polyacid-modified composite resins (PMCRs) and resin composite containing fluoride were used for comparison of fluoride release. Non-fluoride-releasing resin composite was used as a control. The amounts of fluoride release from RGIs and PMCRs remarkably increased in the citrate-phosphate acid buffer compared with distilled water. The amounts of fluoride recharged in RGIs increased with the concentration of NaF solution, but those of PMCRs exposed to all concentrations of NaF solutions were less than 1.5 ppm. Neither resin composite containing fluoride and non-fluoride-releasing resin composite gave any evidence of recharge. RGIs and PMCRs affected by acid buffer solution could not recharge much fluoride even if they were immersed in the 1000 ppmF NaF solution. The results suggested that the matrix of RGIs and PMCRs functioned as a reservoir of fluoride, but the functions were lost by acid attack.

Adsorption↗

Inhibition of carious lesions in vitro around gallium alloy restorations by fluoride releasing resin-ionomer cement.

A new fluoride releasing resin-ionomer cement was used for bonding of gallium alloy restorations in vitro. Etching, priming, and fluoride releasing resin-ionomer cement were used in the experimental group (ARG), prior to placement of the gallium alloy restorations. Three different controls were used: gallium alloy only (G), no etching, fluoride releasing resin-ionomer cement, gallium alloy (RG), etching, priming, non-fluoride cement and gallium alloy (ACG). The mean shear bond strengths of ARG group to enamel and dentin were higher than those of the three control groups. Artificial secondary caries lesions around the restorations in the experimental group and the control groups were produced, using a strep. mutans culture. The microradiographs were examined for presence of a caries inhibition zone near the restoration. Caries inhibition zones were clearly detected around RG and ARG, but not around G and ACG. The results indicate that the fluoride releasing resin-ionomer cement provided good adhesion and caries inhibition in enamel and dentin.

Adhesiveness↗

Influence of filler content and gap dimension on wear resistance of resin composite luting cements around a CAD/CAM ceramic inlay restoration.

We investigated the influence of filler content and gap dimension on the wear resistance of composite luting cement around CAD/CAM ceramic inlay restorations. Experimental hybrid dual-cured composite luting cements containing 60, 70, 72, 74 and 80 wt% of silanated barium-silica fillers were used for cementing CAD/CAM ceramic inlay into the cavity. The specimens involving inlay-cement-tooth interfaces were subjected to a three-body wear test. The relation between the interfacial gap dimension and wear loss was also investigated using 60, 70 and 80 wt% filled cements. The cements containing more than 70 wt% filler presented significantly higher wear resistance than 60 wt% filled cement. There was a positive linear relationship between gap dimension and wear loss, and the inclination of the regression line decreased with increasing filler content. These results indicated that the higher filler content of the cement increased the wear resistance and this desirable influence appeared more remarkably in the wider horizontal gap dimension.

Analysis of Variance↗

Nucleotide sequence of thymidine kinase gene of sequential acyclovir-resistant herpes simplex virus type 1 isolates recovered from a child with Wiskott-Aldrich syndrome: evidence for reactivation of acyclovir-resistant herpes simplex virus.

Recurrent acyclovir (ACV)-resistant (ACV-r) herpes simplex virus type 1 (HSV-1) infections occurred in a patient with Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency syndrome composed of three clinical characteristics of immunodeficiency, thrombocytopenia, and an eczematous dermatitis. The patient had severe and recurrent ACV-r herpes simplex and was treated with vidarabine in a satisfactory manner from 1993 to 1997. During the 4-year observation period, two ACV-sensitive (ACV-s) HSV-1 isolates and five ACV-r HSV-1 isolates were recovered. The nucleotide sequence of the thymidine kinase (TK) gene from these sequential ACV-r isolates was compared with the ACV-s isolates. A single nucleotide deletion of cytosine (C) from homopolymer stretch of four C residues between nucleotide 1061 and 1064 of the open reading frame was found in all ACV-r isolates. No other differences were observed in the TK nucleotide sequence between ACV-s and ACV-r isolates. The TK nucleotide sequences of the two ACV-s isolates were identical to each other and those of the five ACV-r isolates were identical to one another. These results suggest that the ACV-r HSV-1 might have derived from the ACV-s strain in the patient body and that TK-associated ACV-r HSV-1 can reactivate from latency.

Acyclovir↗

In vivo receptor labeling of peripheral benzodiazepine receptor by ex vivo binding of [3H]PK11195.

In vivo receptor labeling of the peripheral benzodiazepine receptor was investigated using ex vivo binding of [3H]-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carb ox-amide ([3H]PK11195). In autoradiographic studies, high level specific binding of [3H]PK11195 was observed in the olfactory bulb. Intravenous administration of PK11195 dose-dependently (0.03-3 mg/kg) inhibited ex vivo binding of [3H]PK11195 in the olfactory bulb. Likewise, N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), a newly identified peripheral benzodiazepine receptor-specific ligand, dose-dependently (0.1-100 mg/kg) reduced ex vivo binding of [3H]PK11195, when administered intraperitoneally. In contrast, clonazepam, a central benzodiazepine receptor-specific agonist, had negligible effects on ex vivo binding of [3H]PK11195. We propose that the ex vivo receptor binding technique we used will facilitate determination of in vivo receptor occupancy of the peripheral benzodiazepine receptor.

Animals↗

Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.

PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION: These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.

Adolescent↗