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Biomedical subjects

K Ito

Publications and source records attributed to K Ito.

At least 19 recordsLinked to original sources

Blood permeability of a novel ceramic scaffold for bone morphogenetic protein-2.

A functionally graded apatite (fg-HAp) with body fluid permeability was developed from bovine bone. The tissue reaction of fg-HAp and its efficacy as a scaffold for recombinant human bone morphogenetic protein-2 (BMP-2) were evaluated histomorphometrically, and a component of permeable fluid into the fg-HAp was analyzed by immunoblotting assay. The fg-HAp block (27 mm(3)) combined with and without BMP-2 (5 microg) was implanted subcutaneously in 4-week-old Wistar rats. Histological examination showed that the surface and bulk degradations of the fg-HAp proceeded extensively and giant cells appeared on the fg-HAp at 2 weeks. Body fluid permeation was found inside the fg-HAp, and the fluid component was immunopositive for albumin. In addition, albumin was detected as a main component among proteins collected from the in vivo implanted fg-HAp. The bioabsorption of the fg-HAp was accelerated as BMP-2-induced bone matured. Histomorphometrical analysis at 4 weeks in the BMP-2/fg-HAp implant showed 59.0% in the total volume of bone and marrow. These results indicate that fg-HAp is an innovative, bioabsorbable bioceramic with fluid permeability characteristic, and may become a biointegrated scaffold for bone engineering.

Albumins↗

A comparison of root surface instrumentation using two piezoelectric ultrasonic scalers and a hand scaler in vivo.

BACKGROUND AND OBJECTIVE: This study compared the effectiveness of two piezoelectric ultrasonic scalers and a hand scaler for subgingival scaling and root planing in vivo. MATERIAL AND METHODS: Fifteen patients with advanced periodontal disease and with teeth scheduled for extraction were selected for this study. Three experimental groups of 10 teeth each were treated with one of two piezoelectric ultrasonic scalers [Vector scaler and Enac scaler] or with a hand scaler. Instrumentation was continued until the root surface felt hard and smooth to an explorer tip. The root surface characteristics after instrumentation were examined using scanning electron microscopy, and the amount of remaining calculus, roughness and loss of tooth substance were estimated using the remaining calculus index and roughness loss of tooth substance index. RESULTS: The remaining calculus index did not differ significantly among the three groups. The roughness loss of tooth substance index was significantly lower for the Vector scaler and Enac scaler groups than for the hand scaler group and also differed significantly between the Vector scaler and Enac scaler groups. CONCLUSION: This study suggests that the Vector scaler produces a smooth root surface with minimal loss of tooth substance. It is a reasonable choice for gentle periodontal maintenance treatment.

Dental Calculus↗

Interbreath-hold reproducibility of lung tumour position and reduction of the internal target volume using a voluntary breath-hold method with spirometer during stereotactic radiotherapy for lung tumours.

The purpose of this study was to evaluate the interbreath-hold reproducibility of the tumour (gross tumour volume, GTV) position and relative reduction of the internal target volume (ITV) using a voluntary breath-hold method with a spirometer in a clinical setting of stereotactic radiotherapy (SRT) for lung tumours 11 patients with 14 lung tumours were enrolled in this study. CT scans were performed once at the free breathing phase and five times at the breath holding phase before the first treatment day. Patients held their breath at the end-expiration phase under spirometer-based monitoring. All GTVs were delineated by a physician and the GTV centroid was calculated automatically. To evaluate the interbreath-hold reproducibility of the tumour position, we measured the distance of three dimensions (craniocaudal, CC; left-right, LR; anteroposterior, AP) and vectors between the GTV centroid and bony landmark. The reproducibility was defined as the average of the differences between the GTV centroid and bony landmark from the second to fifth CT scans with regard to that from the first CT scans. We also evaluated the relative reduction of ITV between the free breathing and breath-holding phase. The interbreath-hold reproducibility of the tumour position was 1.3+/-1.3 mm, 1.4+/-1.8 mm, 2.1+/-1.6 mm and 3.3+/-2.2 mm in CC, LR and AP directions and vectors, respectively. ITV at the breath-holding phase was significantly smaller than that at the free breathing phase (P<0.01). In conclusion, the voluntary breath-hold method with a spirometer is feasible, with relatively good reproducibility of the tumour position for SRT in the clinical setting.

Aged↗

Role of the simultaneous enhancement of NMDA and dopamine D1 receptor-mediated neurotransmission in the effects of clozapine on phencyclidine-induced acute increases in glutamate levels in the rat medial prefrontal cortex.

Clozapine (CLZ) can improve both the positive and negative symptoms of treatment-resistant schizophrenia (TRS), which does not respond to typical antipsychotics. This suggests that elucidation of the pharmacological mechanism for CLZ could lead to further clarification of the pathophysiology of TRS. This study examined the effects of CLZ on phencyclidine (PCP)-induced hyperlocomotion and on the acute increases in glutamate levels that occur in the medial prefrontal cortex (mPFC) in order to test the hypothesis that CLZ effect is associated with the simultaneous enhancement of N-methyl-D: -aspartate (NMDA) and dopamine D(1) receptor-mediated neurotransmission. CLZ effect on PCP-induced hyperlocomotion and increases in glutamate levels were examined by using behavioral rating scores and in vivo microdialysis, respectively. CLZ and haloperidol (HAL) dose-relatedly attenuated PCP-induced hyperlocomotion, and concentration-relatedly blocked PCP-induced acute increases in glutamate levels in the mPFC, with the decrease in saline-induced locomotor activity induced by CLZ being much weaker than that induced by HAL. CLZ also blocked, in a dose-related manner, acute increases in glutamate levels in the mPFC that were induced by local perfusion with a competitive NMDA receptor antagonist, CPP, in this region. Although an enhanced blocking effect of the sub-threshold concentration of NMDA perfusion on PCP-induced acute increases in glutamate levels in the mPFC was noted after co-perfusion with a dopamine D(1) receptor agonist, SKF-38393, perfusion with SKF-38393 did not reverse the CLZ blocking of PCP-induced increases in glutamate levels. Therefore, CLZ may block PCP-induced acute increases in glutamate levels in the mPFC by an enhancement of the NMDA receptor-mediated neurotransmission that is not accelerated by an enhanced dopaminergic transmission via dopamine D(1) receptors. This blocking effect may partially explain the CLZ-induced attenuation of PCP-induced hyperlocomotion.

Analysis of Variance↗

Down-regulation of an inhibitor of cell growth, transmembrane protein 34 (TMEM34), in anaplastic thyroid cancer.

PURPOSE: Ansaplastic thyroid cancer (ATC) is one of the most lethal malignancies, but the carcinogenic mechanism of ATC has not been clarified. Recently, we performed a cDNA microarray analysis and identified transmembrane protein 34 (TMEM34) that down-regulated in anaplastic thyroid cancer cell lines (ACL)s as compared to normal thyroid tissues. METHODS: To investigate the role of TMEM34 in ATC carcinogenesis, we examined expression levels of TMEM34 in ACLs as well as differentiated thyroid cancers (DTC)s and normal human tissues. To explore the effect of TMEM34 in ATC development, cell-growth assays with KTA2 cells were performed. RESULTS: Expression of TMEM34 was down-regulated in all 11 ACLs, as compared to either normal thyroid tissues or cell lines derived from papillary or follicular thyroid cancers. TMEM34 was expressed ubiquitously in normal human tissues tested. Transfection of TMEM34 into KTA2 cells led to inhibition of cell growth. CONCLUSIONS: Our findings suggest that TMEM34 might be a tumor suppressor gene, associated with the development of ATC from DTC.

Carcinoma↗

Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial.

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.

Adult↗

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer.

PURPOSE/OBJECTIVE: To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). METHODS AND MATERIALS: We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. RESULTS: Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%. The 2-year local control rate was 85.7%. Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. CONCLUSIONS: Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed.

Aged↗

Experimental investigation of core-valence double photoionization.

Core-valence double photoionization has been observed in Ne atoms and N2 molecules using a magnetic-bottle time of flight spectrometer. The multielectron coincidence data sets give complete information on the energy correlations between all emitted electrons, which supports a detailed description of the core-valence double photoionization processes including direct spectroscopy of the core-valence doubly ionized states, the final states populated by their Auger decay and details of the dynamics of core-valence double photoionization for selected states.

Journal Article↗

Prediction of collagen orientation in articular cartilage by a collagen remodeling algorithm.

OBJECTIVE: Tissue engineering is a promising method to treat damaged cartilage. So far it has not been possible to create tissue-engineered cartilage with an appropriate structural organization. It is envisaged that cartilage tissue engineering will significantly benefit from knowledge of how the collagen fiber orientation is directed by mechanical conditions. The goal of the present study is to evaluate whether a collagen remodeling algorithm based on mechanical loading can be corroborated by the collagen orientation in healthy cartilage. METHODS: According to the remodeling algorithm, collagen fibrils align with a preferred fibril direction, situated between the positive principal strain directions. The remodeling algorithm was implemented in an axisymmetric finite element model of the knee joint. Loading as a result of typical daily activities was represented in three different phases: rest, standing and gait. RESULTS: In the center of the tibial plateau the collagen fibrils run perpendicular to the subchondral bone. Just below the articular surface they bend over to merge with the articular surface. Halfway between the center and the periphery, the collagen fibrils bend over earlier, resulting in a thicker superficial and transitional zones. Near the periphery fibrils in the deep zone run perpendicular to the articular surface and slowly bend over to angles of -45 degrees and +45 degrees with the articular surface. CONCLUSION: The collagen structure as predicted with the collagen remodeling algorithm corresponds very well with the collagen structure in healthy knee joints. This remodeling algorithm is therefore considered to be a valuable tool for developing loading protocols for tissue engineering of articular cartilage.

Algorithms↗

RUNX3 protein is overexpressed in human basal cell carcinomas.

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Blotting, Western↗

Positronium formed by recombination of positron-electron pairs in polymers.

In nonpolar polymers, positronium (Ps) is dominantly formed by fast intraspur reactions of the energetic positron, but its formation is partially contributed by recombination of weakly bound Mott-Wannier-like positron-electron pairs and is susceptible to electric field and positron irradiation induced perturbations. The average initial energy of para-Ps (p-Ps) formed by recombination is found to be about half the energy of ordinary p-Ps dominantly formed by the fast intraspur reactions.

Journal Article↗

Relationship between development of cross-sensitization to MK-801 and delayed increases in glutamate levels in the nucleus accumbens induced by a high dose of methamphetamine.

RATIONALE: The present study hypothesized that delayed increases in extracellular glutamate (Glu) levels in the nucleus accumbens (NAC), induced by a high dose of methamphetamine (METH), can result in some functional changes of excitatory amino acid receptors, developing behavioral cross-sensitization to a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. OBJECTIVES: The present study aims to examine whether two different doses of METH (2.5 and 1.0 mg/kg) induce different effects on the development of cross-sensitization to MK-801. To clarify the mechanisms for development and expression of cross-sensitization to MK-801, we measured extracellular Glu and dopamine (DA) levels in the NAC at METH injections in a treatment period and at MK-801 injection after a 12-day withdrawal period. MATERIALS AND METHODS: METH- or MK-801-induced changes in Glu and DA levels and in locomotion were measured using in vivo microdialysis and infrared sensor, respectively. RESULTS: METH, at only 2.5 mg/kg, produced delayed increases in Glu levels and developed behavioral cross-sensitization to MK-801 (0.2 mg/kg). MK-801 (0.2 mg/kg) induced delayed increases in Glu levels in the NAC, but this time course was not completely consistent with MK-801-induced enhanced hyperlocomotion. During this time course, MK-801 (0.2 mg/kg) did not induce any changes in DA levels. CONCLUSIONS: These results suggest that METH-induced, at 2.5 mg/kg, delayed increases in Glu levels are necessary for development of behavioral cross-sensitization to MK-801, but not METH. The enhanced locomotion-inducing effect of MK-801 might be related to some functional changes in excitatory amino acid receptors such as NMDA and DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid in the NAC.

Animals↗

Valproate blocks high-dose methamphetamine-induced behavioral cross-sensitization to locomotion-inducing effect of dizocilpine (MK-801), but not methamphetamine.

RATIONALE: Our group has recently shown that methamphetamine (METH) (2.5 mg/kg) induced delayed increases in glutamate (Glu) levels in the rat nucleus accumbens (NAC), and that its repeated administration leads to behavioral cross-sensitization to a selective uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801). OBJECTIVES: The present study aims to examine whether valproate (VPA) would inhibit the delayed increases in Glu levels and prevent METH (2.5 mg/kg)-induced behavioral cross-sensitization to MK-801 (0.2 mg/kg). MATERIALS AND METHODS: We examined the effects of post-treated VPA (50 mg/kg) on METH (2.5 mg/kg)-induced delayed increases in Glu levels. We injected VPA (50 mg/kg) at 120 min after each METH (2.5 mg/kg, once every other day, total of five times) administration and measured locomotor activity induced by challenge with MK-801 (0.2 mg/kg) or METH (0.15 mg/kg) after sufficient withdrawal period. Finally, we measured locomotion induced by MK-801 (0.2 mg/kg) after pretreatment of a competitive NMDA receptor antagonist, CPP (30 mg/kg). Effects of VPA on extracellular Glu levels were examined by using in vivo microdialysis. Locomotor activity was measured by using an infrared sensor. RESULTS: VPA administered 120 min after METH injection had no effect on METH-induced hyperlocomotion, and inhibited METH-induced delayed increases in Glu levels. Repeated VPA administration prevented METH-induced behavioral cross-sensitization to MK-801, but not sensitization to METH. MK-801-induced hyperlocomotion was enhanced when pretreated with the competitive NMDA receptor antagonist, CPP. CONCLUSIONS: These results suggest that VPA inhibits high-dose METH-induced delayed increases in Glu levels to prevent development of behavioral cross-sensitization to an NMDA antagonist, but not sensitization to METH.

Animals↗

Antiapoptotic function of 17AA(+)WT1 (Wilms' tumor gene) isoforms on the intrinsic apoptosis pathway.

The WT1 gene is overexpressed in human primary leukemia and a wide variety of solid cancers. The WT1 gene is alternatively spliced at two sites, yielding four isoforms: 17AA(+)KTS(+), 17AA(+)KTS(-), 17AA(-)KTS(+), and 17AA(-)KTS(-). Here, we showed that 17AA(+)WT1-specific siRNA induced apoptosis in three WT1-expressing leukemia cell lines (K562, HL-60, and Kasumi-1), but not in WT1-non-expressing lymphoma cell line (Daudi). 17AA(+)WT1-specific siRNA activated caspase-3 and -9 in the intrinsic apoptosis pathway but not caspase-8 in the extrinsic one. On the other hand, 17AA(-)WT1-specific siRNA did not induce apoptosis in the three WT1-expressing cell lines. The apoptosis was associated with activation of proapoptotic Bax, which was activated upstream of the mitochondria. Constitutive expression of 17AA(+)WT1 isoforms inhibited apoptosis of K562 leukemia cells induced by apoptosis-inducing agents, etoposide and doxorubicin, through the protection of mitochondrial membrane damages, and DNA-binding zinc-finger region of 17AA(+)WT1 isoform was essential for the antiapoptotic functions. We further studied the gene(s) whose expression was altered by the expression of 17AA(+)WT1 isoforms and showed that the expression of proapoptotic Bak was decreased by the expression of 17AA(+)KTS(-)WT1 isoform. Taken together, these results indicated that 17AA(+)WT1 isoforms played antiapoptotic roles at some points upstream of the mitochondria in the intrinsic apoptosis pathway.

Apoptosis↗

Immobility reduces muscle fiber necrosis in dystrophin deficient muscular dystrophy.

Duchenne/Becker muscular dystrophy is a progressive muscle disease, which is caused by the abnormality of dystrophin. Spina bifida is characterized by paralysis of the feet, with most of the upper extremities not being affected. We report here on the first case of Becker muscular dystrophy coinciding with spina bifida. The muscle biopsy specimens of the patient showed dystrophic changes in upper extremities, but clearly less in lower extremities. The results show that the restriction of excessive exercise is important for dystrophin deficiency disease.

Child, Preschool↗

A preliminary study on the relationship between stimulated saliva and periodontal conditions in community-dwelling elderly people.

OBJECTIVES: The purpose of this study was to explore the relationship between flow rate and spinnbarkeit of stimulated whole saliva and periodontal conditions in healthy elderly people. METHODS: Three hundred and fifty-five dentate subjects aged 76 years were included. The pocket probing depth (PD), attachment level (AL), and bleeding on probing (BOP) were measured. Stimulated whole saliva was collected and the salivary flow rate (SFR) was calculated. Then, salivary spinnbarkeit (SS) was immediately measured. RESULTS: The mean SFR and SS were 1.44 ml/min and 1.91 mm, respectively. SFR was not significantly related to each periodontal parameter. On the other hand, subjects with SS 2.00 mm exhibited a significantly higher mean PD (p<0.05), % of sites with PD>or=4mm (p<0.05), mean AL (p<0.01), % of site with AL>or=4mm (p<0.05) and % of sites with AL>or=6mm (p<0.01) than subjects in the other three groups (one-way ANOVA). In the logistic regression analysis, the factors significantly associated with the highest quintile of PD>or=4mm were: the low salivary flow and the high salivary spinnbarkeit (OR 3.84), current smokers (OR 5.08), cleaning interdental spaces rarely/never (OR 2.12), and frequent BOP (OR 5.20). CONCLUSION: These findings suggest that high salivary spinnbarkeit in addition to a low salivary flow rate might be a high risk for periodontal disease in elderly people.

Activities of Daily Living↗

Regulation of human lung epithelial cell numbers by diesel exhaust particles.

Particulate air pollution is associated with respiratory morbidity and has cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined. When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP (5-200 microg.mL-1) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 microg.mL-1) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G0/1 arrest. DEP also reduced the increase in apoptotic cells, as defined by double expression of annexin V/PI, observed after serum starvation (from 28.35 to 15.46%). The antioxidants, N-acetylcysteine (NAC; 33 mM) and AEOL10113 (10-100 microM), the N-terminal c-jun kinase inhibitor, SP600125 (33 microM), and nuclear factor-kappaB inhibitor, SN50 (33 microM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G0/1 and increase in cells in the S and G2/M phases. Expression of p21CIP1/WAF1 mRNA and protein seen with serum starvation was reduced by DEP. In conclusion, diesel exhaust particles prevented serum starvation-led decreases in A549 epithelial cells by inducing cell cycle progression and preventing apoptosis, processes involving oxidative stress, inhibition of p21CIP1/WAF1 expression and stimulation of N-terminal c-jun kinase and nuclear factor-kappaB. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.

Apoptosis↗