Biomedical subjects

H Aoki

Publications and source records attributed to H Aoki.

At least 19 recordsLinked to original sources

PubMed2006

Precipitation of octacalcium phosphates on artificial enamel in artificial saliva.

The natural saliva samples were collected from 30 Japanese men and women aged between 20 and 30, and the inorganic components in the saliva were analyzed chemically. Artificial saliva (AS) was prepared based on the chemical analysis using chemical reagents. The calcium/phosphate molar ratio of the AS was 0.28 with pH=7.0. Artificial enamel (AE) was prepared by sintering hydroxyapatite powder at 1,200 degrees C. The AE was placed in the AS at 37 degrees C. XRD, SEM and EDX investigated precipitation on the AE. The precipitation was always identified as being OCP. As decrease in the pH of the surface of the AE and increase in the concentration of phosphate ions were observed by chemical analysis, it was concluded that the OCP occurs by the pH decrease and phosphate ion concentration increase on the surface of AE.

Adult↗

PubMed2006

A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo.

Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in a variety of cancer types, including malignant gliomas. STAT3 is activated by phosphorylation of a tyrosine residue, after which it dimerizes and translocates into the nucleus. There it regulates the expression of several genes responsible for proliferation and survival at the transcriptional level. A selective inhibitor of STAT3 phosphorylation, AG490, has been shown to inhibit growth and induce apoptosis in some cancer cell types. However, although AG490 routinely shows in vitro anticancer activity, it has not consistently demonstrated an in vivo anticancer effect in animal models. Here, we have tested WP1066, a novel inhibitor structurally related to AG490 but significantly more potent and active, against human malignant glioma U87-MG and U373-MG cells in vitro and in vivo. IC(50) values for WP1066 were 5.6 muM in U87-MG cells and 3.7 muM in U373-MG cells, which represents 18-fold and eightfold increases in potency, respectively, over that of AG490. WP1066 activated Bax, suppressed the expression of c-myc, Bcl-X(L) and Mcl-1, and induced apoptosis. Systemic intraperitoneal administration of WP1066 in mice significantly (P<0.001) inhibited the growth of subcutaneous malignant glioma xenografts during the 30-day follow-up period. Immunohistochemical analysis of the excised tumors revealed that phosphorylated STAT3 levels in the WP1066 treatment group remained inhibited at 3 weeks after the final WP1066 injection, whereas tumors from the control group expressed high levels of phosphorylated STAT3. We conclude that WP1066 holds promise as a therapeutic agent against malignant gliomas.

Antineoplastic Agents↗

PubMed2006

Change in the cross-sectional area of a patellar tendon graft after anterior cruciate ligament reconstruction.

The purpose of this study was to clarify the change in the cross-sectional area (CSA) of a patellar tendon graft after anterior cruciate ligament (ACL) reconstruction, and its relationship with postoperative knee laxity. Forty patients (25 men and 15 women) were included in this study. Intraoperative CSA measurements were performed with an instrumented areamicrometer, while a magnetic resonance imaging (MRI) evaluation was utilized for the assessment postoperatively. For intraoperative measurement, the average CSA of a 10-mm wide patellar tendon graft was 32.3 +/- 7.0 mm2, while the average CSA measured at follow-up (mean: 14.8 months) was 48.8 mm2, showing a significant mean increase ratio of 49.4%. This value corresponded to 115% of the native ACL. The average CSA measured in 30 patients at 6 months was 49.7 mm2, almost equal to the value at the final follow-up (49.8 mm2) in the same patient group. Among potentially influential factors, postoperative notch width (available space for the ACL graft) had significant correlation with the CSA of the graft at follow-up. Finally, both intra- and postoperative CSA values did not correlate with postoperative knee laxity, indicating that a bigger graft does not guarantee a better laxity.

Adolescent↗

PubMed2006

Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells.

The mammalian target of rapamycin (mTOR) plays a central role in regulating the proliferation of malignant glioma cells, and mTOR-specific inhibitors such as rapamycin analogs are considered as promising therapy for malignant gliomas. However, the efficacy of mTOR inhibitors alone in the treatment of patients with malignant gliomas is only modest, potentially because these agents rather than acting as mTOR kinase inhibitors instead interfere with the function of only mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not perturb all mTOR functions. The purpose of this study was to determine whether global inhibition of the mTOR molecule enhances the antitumor effect of rapamycin on malignant glioma cells. We showed that rapamycin induced autophagy and that inhibition of autophagy by small interfering RNA (siRNA) directed against autophagy-related gene Beclin 1 attenuated the cytotoxicity of rapamycin in rapamycin-sensitive tumor cells, indicating that the autophagy was a primary mediator of rapamycin's antitumor effect rather than a protective response. Exogenous expression of an mTOR mutant interfering with its kinase activity markedly enhanced the incidence of rapamycin-induced autophagy. Moreover, silencing of mTOR with siRNA augmented the inhibitory effect of rapamycin on tumor cell viability by stimulating autophagy. Importantly, not only rapamycin-sensitive malignant glioma cells with PTEN mutations but also rapamycin-resistant malignant glioma cells with wild-type PTEN were sensitized to rapamycin by mTOR siRNA. These results indicate that rapamycin-induced autophagy is one of the agent's antitumor effects and that silencing or inhibiting mTOR kinase activity could enhance the effectiveness of rapamycin.

Autophagy↗

PubMed2006

Dissolution behavior and in vitro evaluation of sputtered hydroxyapatite films subject to a low temperature hydrothermal treatment.

Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency sputtering. Some of the as-sputtered films were hydrothermally recrystallized at 110 degrees C. In immersion tests, the as-sputtered film completely dissolved after 2 days in a culture medium, whereas the thickness of hydrothermally treated films increased with an increase in immersion period, reaching a thickness of 127% after a period of 4 weeks. The proliferation and alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblast-like cells on the as-sputtered and hydrothermally treated films were investigated, and the cell morphology was also observed using scanning electron microscopy. The proliferation of MC3T3-E1 cells on the as-sputtered films was suppressed, whereas proliferation on the hydrothermally treated films was comparable to that on control and titanium substrate. The suppression of cell proliferation is associated with an increase in pH of the culture medium caused by dissolution of the as-sputtered film. After a 96-h culture time, the ALP activity of the cells on the hydrothermally treated film was higher than that on the control, titanium substrate, and as-sputtered film samples. From scanning electron microscopic observations, it was found that the MC3T3-E1 cells on the hydrothermally treated films were elongated and had established more intricate filopodia networks with each other, which were also observed for MC3T3-E1 cells on the as-sputtered films after a period of 24 h.

Animals↗

PubMed2006

Molecular localization of a ribosome-dependent ATPase on Escherichia coli ribosomes.

We have previously isolated and described an Escherichia coli ribosome-bound ATPase, RbbA, that is required for protein synthesis in the presence of ATP, GTP and the elongation factors, EF-Tu and EF-G. The gene encoding RbbA, yhih, has been cloned and the deduced protein sequence harbors two ATP-motifs and one RNA-binding motif and is homologous to the fungal EF-3. Here, we describe the isolation and assay of a truncated form of the RbbA protein that is stable to overproduction and purification. Chemical protection results show that the truncated RbbA specifically protects nucleotide A937 on the 30S subunit of ribosomes, and the protected site occurs at the E-site where the tRNA is ejected upon A-site occupation. Other weakly protected bases in the region occur at or near the mRNA binding site. Using radiolabeled tRNAs, we study the stimulating effect of this truncated RbbA on the binding and release of different tRNAs bound to the (aminoacyl) A-, (peptidyl) P- and (exit) E-sites of 70S ribosomes. The combined data suggest plausible mechanisms for the function of RbbA in translation.

Adenosine Triphosphatases↗

PubMed2006

Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway.

A substantial number of neural stem cells (NSCs) continue to proliferate and generate neurons in the central nervous system throughout life. Ionizing radiation, an important adjuvant therapy for glioma patients, may damage NSCs and cause neuronal deficits, such as cognitive dysfunction and memory impairment. However, the precise mechanism of radiation effects on death and differentiation of NSCs remains largely unknown. Here, we found that radiation induced apoptosis in NSCs via the mitochondrial pathway, upregulating the ratio of Bax to Bcl-2 and releasing cytochrome c into the cytoplasm. Radiation also inhibited neuronal differentiation of NSCs by 50%. Of the three stress-associated mitogen-activated protein kinases (MAPKs), only c-Jun NH(2)-terminal kinase (JNK) was activated in NSCs after radiation. Interestingly, JNK inhibition by the specific inhibitor SP600125 rescued NSCs from apoptosis and improved neuronal differentiation. Furthermore, we examined whether radiation directly inhibits neuronal differentiation or not. Radiation did not affect the promoter activity of NeuroD, a basic helix-loop-helix transcription factor that regulates the expression of neuronal differentiation markers. Radiation induced more apoptosis in NeuroD-positive cells than NeuroD-negative cells. We concluded that radiation activates JNK and induces apoptosis, especially in neural progenitor cells, resulting in the inhibition of neurogenesis. Our findings raise the possibility that JNK inhibition has therapeutic potential in protecting NSCs from the adverse effects of radiation.

Animals↗

PubMed2006

No evidence to indicate topographic dependency on bone formation around cp titanium implants under masticatory loading.

In vitro studies have proved the topographic dependency upon osteogenesis on titanium plate by investigating the cell-adhesion, -shape, -proliferation, -differentiation, ALP activity and osteocalcin production of osteogenic stem cells, MG36, MC3T3-E1 and wild strains of bone formative cells from animal and human. However, this in vivo study on bone growth around cp titanium dental implants under masticatory loading did not demonstrate significant difference among the different surface roughness in the range of Ra 0.4-1.9 microm, Rz 2.8-11.2 microm, Rmax 3.6-28.1 microm and Sm 2.9-41.0 microm, which was estimated by measuring the bone contacts, bone occupancies and bone bonding strengths at the implant/bone marrow interface. It is revealed that the topographic dependency on the osteogenetic activity is apt to be covered with wide variation in bone healing potential under the clinical condition with functional biting load.

Animals↗

PubMed2006

Preparation of germanium apatite and its cytotoxicity.

Germanium apatite was synthesized via the solid-state reaction between GeO(2) and (NH(4))(3)PO(4). The synthesized materials were characterized using XRD, and thermal analysis was carried out using TG-DTA. Ge(2)P(2)O(7) was preferentially produced at temperatures between 300-900 degrees C, and at temperatures above 1000 degrees C, germanium apatite (Ge(5)O(PO(4))(6), GeAp) was synthesized. In solubility tests, 0.36% and 0.65% of Ge ions were liberated from GeAp powder in distilled water at 37 and 80 degrees C after four weeks, respectively. A GeAp aqueous solution maintained at 37 degrees C was strongly acidic with a pH=1.67 after four weeks. The growth rate of human adult gingival fibroblast cells in a medium that included GeAp, HA, and GeO(2) was investigated. The growth rate of the cells in a 0.1 mg/ml GeAp medium was almost the same as that in the control. The cell growth was restricted in a 1.0 mg/ml GeAp medium, whereas the cell growth in a pH-adjusted 1.0 mg/ml GeAp medium at pH=7.60 was higher than that in non-adjusted medium at pH = 7.06.

Apatites↗

PubMed2006

Effect of a thin HA coating on the stress/strain distribution in bone around dental implants using three-dimensional finite element analysis.

Three-dimensional finite element analysis was performed for thin hydroxyapatite (HA) coated and titanium dental implants to study the effects on stress/strain distribution in the mandible with application of axial and oblique loads. The implants were of screw and cylinder types. With an axial load, the maximum equivalent bone stresses in the titanium implants were 21.5 and 29.0 MPa for the cylinder and screw types respectively, and the stress and strain distributions differed. For the cylinder type, the highest stress was located at the implant base, and for the screw type, it was located at the top edge of the first thread within the cortical bone. For the HA-coated cylinder and screw implants, the maximum equivalent bone stresses were 7.1 and 7.2 MPa respectively. The stress and strain distributions were similar, and the highest stress was located on the upper side of the cortical bone around the implant neck for both implants. Of the implants examined, the screw type HA-coated implant had the most uniform stress distribution in bone.

Anisotropy↗

PubMed2006

Bone response to titanium implants coated with thin sputtered HA film subject to hydrothermal treatment and implanted in the canine mandible.

Hydroxyapatite (HA) was coated onto titanium implants using radio frequency magnetron sputtering. The HA films were crystallized in an autoclave tube using low temperature hydrothermal treatment. The average film thickness on the implant was 1.1 microm. HA-coated and pure-titanium implants were inserted into canine mandibles for up to 24 weeks. Forty-eight implants were placed in eight beagles. After 2, 4, 12 and 24 weeks, implants were retrieved and prepared for histological observation, and the HA film thickness was determined using energy-dispersive X-ray spectroscopy. Light microscopy revealed that, after two weeks, the bone response to the HA-coated implants was much better than to the pure titanium implants, and osteoblasts were observed at the bone-implant interface. After four weeks, the screw threads of the HA-coated implants were almost completely covered with bone. The HA film thickness rapidly decreased up to four weeks of implantation, then gently decreased, reaching 0.40+/-0.03 microm at the upper region of the implant after 12 weeks. That indicates that about 80% of the HA film had dissolved after 12 weeks of implantation. The rate of decrease in the HA film thickness was greater with increasing implant depth.

Animals↗

PubMed2005

Pressure-induced superconductivity in noncentrosymmetric heavy-fermion CeRhSi3.

We report the pressure-induced superconductivity in the noncentrosymmetric heavy-fermion CeRhSi3. The superconductivity emerges above about 12 kbar even though the antiferromagnetic ordering persists. Furthermore, another anomaly is observed in the superconducting phase. The anomalous magnetic field-temperature phase diagram with a high upper critical field suggests that an unconventional superconductivity is realized in CeRhSi3.

Journal Article↗

PubMed2005

IgM secretion and absorption in the materno-fetal interface of a viviparous teleost, Neoditrema ransonneti (Perciformes; Embiotocidae).

We investigated maternal IgM secretion in the ovary and the absorption of IgM by fetuses in a viviparous fish, Neoditrema ransonneti (Embiotocidae). Serum IgM, whose molecular weight was approx. 820k, was purified by two steps of gel filtration chromatography. Immunohistochemistry and Western blotting revealed that IgM was secreted from the epithelia of the ovigerous lamellae of pregnant females into ovarian cavity fluid. The IgM-secreting activity of ovigerous folds showed notable changes according to the reproductive stage. In fetuses, IgM was absorbed as macromolecules by enterocytes of the hypertrophied hindgut. IgM in the fetal blood was also demonstrated, although its concentration remained low during gestation. These findings suggest that IgM was transported from the maternal tissues to embryos via a unique pathway in N. ransonneti.

Animals↗

PubMed2005

Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells.

Histone deacetylase (HDAC) inhibitors have both apoptotic and differentiating effects on various tumor cells. However, the mechanisms underlying the effect of HDAC inhibitors remain unclear. In this study, we investigated the function of anti-proliferative effects of HDAC inhibitors, N-butyric acid and trichostatin A, on human malignant glioma cell lines, U251-MG and D54. MTT assay showed a dose-dependent inhibition of cellular proliferation in both cell lines. Cell cycle analysis revealed increased sub-G1 population in both lines, and G1 arrest only in U251-MG cells. Induction of apoptosis was also supported by the occurrence of DNA fragmentation in tumor cells treated with HDAC inhibitors. Furthermore, caspase inhibition assay indicated that HDAC inhibitor-induced apoptosis was caspase-dependent. Neither mitochondrial membrane potential nor the expression of caspase-9 was changed by treatment with HDAC inhibitors, suggesting the possibility that HDAC inhibitor-induced apoptosis was not mediated by the mitochondrial cell death pathway. On the other hand, immunoblot assay confirmed increased expression of caspase-8 in both lines, and elevation of p21 but not p27 protein in U251-MG cells following HDAC inhibitor treatment. Taken together, the HDAC inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis with or without p21-mediated G1 arrest in human malignant glioma cells.

Apoptosis↗

PubMed2005

[Operative decision for acute type A aortic dissection; ascending aorta or arch replacement].

Operative technique of acute type A aortic dissection remains controversial. We adopted the strategy to replace the aortic arch only when the entry of the dissection was found in the aortic arch, or atherosclerotic arch aneurysm existed. The purpose of the current study was to elucidate the feasibility of the ascending aorta and hemiarch replacement and to follow the fate of the patent false lumen distal to the anastomosis after surgery. Nineteen patients operated from 2000 to 2004 were included in this study. Ascending or hemiarch replacement were performed in 15/19 (78.9%) patients. The early mortality rate was 10.5% (2/19). The causes of death included major brain infarction and rupture of the descending aortic aneurysm 25 +/- 23 days after surgery. Thrombosed distal false lumen of the thoracic aorta was observed in 60% (9/15) of patients of De Bakey type I dissection. Thus our strategy for acute type A aortic dissection including entry closure and the ascending or hemiarch replacement is a reasonable option especially for the elderly patients in acute phase. Our results also indicated that the thrombosis of the false lumen distal to the anastomosis can be expected and the enlargement of the distal aorta is minimal.

Adult↗

PubMed2005

[Atrial fibrillation after isolated coronary bypass surgery].

Postoperative atrial fibrillation (Af) remains a significant source of morbidity after coronary artery bypass grafting (CABG). Prophylactic therapy with beta-adrenergic blockers or amiodarone hydrochloride is reported to reduce the incidence of Af. We studied the incidence of Af retrospectively and considered the risk factors for it. Ninety-three patients who underwent isolated CABG from April 2003 to March 2004 are included in this study. Postoperative Af was observed in 22 (25%) patients. Ten of them were operated on off-pump procedure, and 14 had any type of beta-adrenergic blockers preoperatively. The mean age of the group of postoperative Af is 69.7 +/- 9.2 years old (older than the non-Af group: 65.5 +/- 10 years old, p = 0.087). And the preoperative left atrial size was larger in the Af group than in the non-Af group (43.4 +/- 6.1 versus 40.6 +/- 5.4mm, p = 0.064) Major embolic complication occurred in only 1 (1.1%) patient of non-Af group. We observed postoperative Af in 25% of patients after CABG. Older age and larger left atrial size may relate to the incidence of Af, and appropriate anticoagulant therapy and medication of beta-blockers are important for the patients who have such risk factors.

Adrenergic beta-Antagonists↗

PubMed2004

Evolution of spin and field dependences of the effective mass with pressure in CeIn(3).

We have studied the field and spin dependences of the effective masses in CeIn3 as a function of pressure via the de Haas-van Alphen (dHvA) effect. The effective mass increases with the field at pressures up to about 10 kbar and then decreases with the field. The spin direction of the dominant dHvA oscillation is likely to be reversed across the same pressure. The dHvA frequency changes significantly at the pressure P(c) for the antiferromagnetic quantum critical point and two neighboring pressures P2 and P4 below and above P(c). The spin and field dependences rapidly diminish across P(c) and finally disappear above P4. These observations are discussed in conjunction with relevant observations and theories.

Journal Article↗

PubMed2004

Components and fractions for differently bound water molecules of dipalmitoylphosphatidylcholine-water system as studied by DSC and 2H-NMR spectroscopy.

Differently bound water molecules of dipalmitoylphosphatidylcholine (DPPC)-H2O system were investigated with differential scanning calorimetry (DSC). According to a method previously reported by us, the ice-melting DSC curves of the DPPC-H2O samples of varying water contents were deconvoluted into multiple components, and the ice-melting enthalpies for the individual deconvoluted components were used to estimate average molar ice-melting enthalpies for freezable interlamellar and bulk waters, respectively. With these average molar ice-melting enthalpies, the numbers of differently bound water molecules of the DPPC-H2O system were calculated at varying water contents and were used to construct a water distribution diagram of this system. Furthermore, to evaluate the reliability of the present DSC deconvolution method, 2H-NMR T1 measurements of DPPC-2H2O system were carried out at 5 degrees C of the gel phase temperature, and components and fractions for differently bound water (2H2O) molecules were estimated from the analysis of nonexponential magnetization recovery curves.

1,2-Dipalmitoylphosphatidylcholine↗