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Biomedical subjects

I Nishimura

Publications and source records attributed to I Nishimura.

At least 19 recordsLinked to original sources
PubMed2006

Genes differentially expressed in titanium implant healing.

Bone generation occurs around titanium implants; however, its underlying mechanisms are unknown. We hypothesized that molecular determinants distinct from those undertaking normal bone healing regulate osseointegration. Using differential display-polymerase chain-reaction in the male rat model, we isolated 3 genes that are differentially expressed in bone healing with implants, but not in osteotomy healing. A homology search indicated that these 3 genes are apolipoprotein E, prolyl 4-hydroxylase alpha-subunit, and an unknown transcript. Differential expression of these genes was remarkable during early healing stages up to week 2, and accelerated with rough acid-etched surfaces compared with machined surfaces. The differential expression was confirmed in the female rats, with enhanced expression for the acid-etched surfaces. The osseointegration-unfavorable condition created by gonadal estrogen deficiency reduced the level of differential expression. This study provides evidence that selected gene transcripts are induced by titanium implants under regulatory control strongly associated with the nature of osseointegration.

Acid Etching, Dental↗
PubMed2005

Three-dimensional computer-aided design based design sensitivity analysis and shape optimization of the stem using adaptive p-method.

The number of stem designs for total hip arthroplasty is increasing, and occasionally design changes have yielded unexpected clinical results. At present, we are not able to clearly identify which parameter of the stem is most important, and the optimum value of many parameters. The goals of this study were to identify which parameter is most important, to understand the effect of design change, and to find the optimum stem shape. For this purpose, we used adaptive p-method together with three-dimensional computer-aided design software program for the design sensitivity analysis (DSA) and shape optimization of the stem. The results suggested that increasing the lateral and medial width of the distal cross-section together with decreasing the medial-lateral width and the medial radius of the distal cross-section from the default value would lead to a decrease in the largest maximum principal stress of the distal cement. The medial width of middle cross-section, however, was not so simple. The result of DSA suggested that decreasing this parameter from the default value decreased the stress in the distal cement, but the optimum shape was obtained by increasing this parameter. The method used in this study will assist our engineers and surgeons in the process of modifying and optimizing the stem design.

Arthroplasty, Replacement, Hip↗
PubMed2002

Ovariectomy hinders the early stage of bone-implant integration: histomorphometric, biomechanical, and molecular analyses.

Postmenopausal osteoporosis is a contributing factor to alveolar bone atrophy associated with tooth loss in the elderly. The use of dental titanium implants has been increasingly adapted to treat these edentulous patients. This study examines whether female gonadal hormone deficiency interferes with the critical integration process between bone and implants. Two types of experimental titanium implants with acid-treated surfaces were placed in the femurs of ovariectomized (ovx) and sham-operated control rats: T-cell implants with a hollow chamber for histomorphometric and steady-state mRNA expression assays, and unthreaded cylindrical implants for biomechanical push-in tests. At week 2, less bone area was found in the ovx-implant group (p = 0.0495) than in the sham-implant group. The implant push-in test showed that the ovx-implant group had approximately half of the withstanding value of the sham-implant group (p = 0.009). However, these differences between the ovx and sham groups became diminished at week 4. Total RNA samples were examined by a reverse transcriptase-polymerase chain reaction assay for col1a1, col3a1, bone sialoprotein (bSP) II, osteonectin, osteopontin, osteocalcin, integrin beta1 and integrin beta3. In untreated bones and in created bone defects without implant placement, ovx did not affect the steady-state levels of the mRNAs tested. When implants were placed, significant upregulation of these genes was observed in the sham-implant group; however, only osteocalcin and integrins were upregulated in the ovx-implant group. The results suggest a biphasic effect of female gonadal hormone deficiency that may temporarily interfere with the early implant-tissue integration process, and which may be associated with a failure to upregulate a selected set of bone extracellular matrix genes. Once established, however, functional bone-implant integration can be achieved even in ovx rats.

Animals↗
PubMed2002

Cell death induced by a caspase-cleaved transmembrane fragment of the Alzheimer amyloid precursor protein.

The Alzheimer amyloid precursor protein (APP) is a transmembrane protein whose abnormal processing is associated with the pathogenesis of Alzheimer's disease. Activated caspases cleave APP and generate its carboxyl-terminally truncated fragment (APPdeltaC31). We have previously reported that overexpression of wild-type APP induces caspase-3 activation and apoptosis in postmitotic neurons. We now report that APPdeltaC31 potentially plays pathophysiological roles in neuronal death. Adenovirus-mediated overexpression of wild-type APP695 induced activation of caspase-3 and accumulation of APPdeltaC31 in postmitotic neurons derived from human NT2 embryonal carcinoma cells, whereas an APP mutant lacking the Abeta(1-20) region induced neither caspase-3 activation nor APPdeltaC31 generation. Inhibition of caspase-3 suppressed the generation of APPdeltaC31 in APP-overexpressing neurons. Forced expression of APPdeltaC31 induced apoptotic changes of neurons and non-neuronal cells, but failed to activate caspase-3. The cytotoxicity of APPdeltaC31 was also dependent on the Abeta(1-20) region. These results suggest that accumulation of wild-type APP activates neuronal caspase-3 to generate APPdeltaC31 that mediates caspase-3-independent cell death.

Adenoviridae↗
PubMed2002

Molecular cloning of wound inducible transcript (wit 3.0) differentially expressed in edentulous oral mucosa undergoing tooth extraction wound-healing.

Tooth extraction is the most commonly prescribed ablation surgery in dentistry and results in the formation of edentulous mucosa. Although the edentulous mucosa serves as the critical interfacial tissue for removable and implant-assisted prostheses, the structure and physiology of this wound-induced tissue are largely uninvestigated. We addressed the hypothesis that tooth extraction activates the expression of a unique set of genes in healing edentulous mucosa. Using the Differential Display Polymerase Chain Reaction and 5' Rapid Amplification of cDNA Ends protocols, we isolated overlapping cDNAs encoding a 3.0-kb-long mRNA, Wound Inducible Transcript, 3.0 (wit 3.0). In situ hybridization demonstrated that wit 3.0 was primarily expressed by the fibroblasts associated with tooth extraction wound-healing. Appearing to generate from the wit 3.0 gene, two alternative transcripts presented, encoding 215-(wit 3.0 alpha) and 253-(wit 3.0 beta) amino-acid-long peptides with the characteristics of an intracellular molecule. Analysis of these data may provide new clues to the molecular mechanism of edentulous mucosa formation.

Amino Acid Sequence↗
PubMed2001

In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector.

Ischemic white matter lesions have been reported in rats after bilateral common carotid ligation (BCAL). Previously, comparing normotensive rats (WKY) with spontaneously hypertensive rats (SHR), we too found that sustained moderate ischemia with spontaneous hypertension accelerated the formation of ischemic white matter lesions. In this study, we explored the feasibility of gene therapy for lesioned white matter by means of an adenovirus vector expressing a reporter gene, LacZ. Using sham-operated and hypoperfused SHR as well as sham-operated and hypoperfused WKY, we demonstrated that (i) adenovirus vectors could deliver a foreign gene into oligodendrocytes and astrocytes in the cerebral white matter; (ii) the transduction efficiency was most effective in SHR after BCAL; and (iii) the level of alpha(V)-integrin was significantly correlated with adenoviral transduction efficiency.

Adenoviridae↗
PubMed2001

Development of the Baylor Gyro permanently implantable centrifugal blood pump as a biventricular assist device.

The Baylor Gyro permanently implantable centrifugal blood pump (Gyro PI pump) has been under development since 1995 at Baylor College of Medicine. Excellent results were achieved as a left ventricular assist device (LVAD) with survival up to 284 days. Based on these results, we are now focusing on the development of a biventricular assist device (BVAD) system, which requires 2 pumps to be implanted simultaneously in the preperitoneal space. Our hypothesis was that the Gyro PI pump would be an appropriate device for an implantable BVAD system. The Gyro PI 700 pump is fabricated from titanium alloy and has a 25 ml priming volume, pump weight of 204 g, height of 45 mm, and pump diameter of 65 mm. This pump can provide 5 L/min against 100 mm Hg at 2,000 rpm. In this study, 6 half-Dexter healthy calves have been used as the experimental model. The right pump was applied between the infundibular of the right ventricle and the main pulmonary artery. The left pump was applied between the apex of the left ventricle and the thoracic descending aorta. As for anticoagulation, heparin was administered at the first postoperative week and then converted to warfarin sodium from the second week after surgery. Both pump flow rates were controlled maintaining a pulmonary arterial flow of less than 160 ml/kg/min for the sake of avoidance of pulmonary congestion. Blood sampling was done to assess visceral organ function, and the data regarding pump performance were collected. After encountering the endpoint, which the study could not keep for any reasons, necropsy and histopathological examinations were performed. The first 2 cases were terminated within 1 week. Deterioration of the pump flow due to suction phenomenon was recognized in both cases. To avoid the suction phenomenon, a flexible conduit attached on the inlet conduit was designed and implanted. After using the flexible inflow conduit, the required power and the rotational speed were reduced. Furthermore, the suction phenomenon was not observed except for 1 case. There was no deterioration regarding visceral organ function, and pulmonary function was maintained within normal range except for 1 case. Even though the experimental animal survived up to 45 days with the flexible inflow conduit, an increase in power consumption due to thrombus formation behind the impeller became a problem. Lower rotational speed, which was probably produced by the effectiveness of the flexible inflow conduit, was speculated to be one of the reasons. And the minimum range of rotational speed was 1,950 rpm in these 6 BVAD cases and the previous 3 cases of LVAD. In conclusion, 6 cases of BVAD implantation were performed as in vivo animal studies and were observed up to 45 days. The flexible inflow conduit was applied in 4 of 6 cases, and it was effective in avoiding a suction phenomenon. The proper rotational speed of the Gyro PI 700 pump was detected from the viewpoint of antithrombogenicity, which is more than 1,950 rpm.

Animals↗
PubMed2001

The sphericity of the bearing surface in total hip arthroplasty.

This study evaluated the sphericity of bearing surfaces in total hip arthroplasty. The out-of-roundness of metal femoral heads, the inner surface of polyethylene liners, and commercially available ball bearings was measured. The hip prostheses were obtained directly from the manufacturers. The sphericity of the bearing surfaces was significantly inferior to that of the ball bearings. The sphericity of the femoral head on the sagittal plane was inferior to that on the transverse plane. Several significant differences were found among different manufacturers. The sphericity of the femoral head on the sagittal plane and that of polyethylene significantly improved in 1999 and 2000 compared with those in 1995. Further improvement is desirable, however, because good sphericity is expected to prolong the functional performance of the prosthesis after total hip arthroplasty.

Analysis of Variance↗
PubMed2001

Push-out strength of hydroxyapatite coated by sputtering technique in bone.

Hydroxyapatite was coated with 1 microm thickness on titanium columns of a length of 10 mm, an outer diameter of 4.0 mm by radio frequency magnetron sputtering. The hydroxyapatite coating titanium columns were implanted in the diaphysis of femora of 3 adult dogs, and push-out test was carried out after 2, 4 and 12 weeks of implantation using a testing machine. The interface of bone/column was observed histologically after the test. At 12 weeks the push-out strengths of coating and non-coating columns were 3.5 and 1 MPa, respectively. Histological observation indicated a formation of thin connective tissue with 5-30 microm thickness at the interface of the bone/column. No inflammation was observed during the implantation periods.

Animals↗
PubMed2000

Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein.

To elucidate the mechanism of neuronal death in Alzheimer's disease, we investigated the effects of overexpression of wild-type Alzheimer amyloid precursor protein (APP) on neuronal cells and glial cells in vivo. When an APP695-expressing adenovirus was injected into the dorsal hippocampal region, a number of neurons in remote areas were positively stained with anti-APP monoclonal antibody, and underwent severe degeneration from 3 to 7 days after viral inoculation. Most degenerating neurons were immunopositive with both APP and activated caspase-3, but some neurons that expressed activated caspase-3 were not expressing APP from 7 to 14 days after virus injection. In the neighborhood of the degenerating neurons, activated microglia/macrophages, which were identified by the phenotypic marker C3bi receptor (CD11b/c; OX-42), were observed, and some of them appeared to phagocytose the caspase-3-immunopositive degenerating neurons. In addition to microglia/macrophages, infiltrating leukocytes expressing CD45 or CD4 were also detected. These results suggest that the increased accumulation of APP induced not only caspase-3-mediated death machinery, but also inflammatory responses including microglial activation. These inflammatory responses might cause further neurodegeneration through the alternative pathway that might activate the caspase-3-mediated death machinery without APP expression.

Adenoviridae↗
PubMed2000

Low stray ELF magnetic field exposure system for in vitro study.

An exposure facility for wide application to cell exposure to an ELF (extremely low frequency) magnetic field was developed. It is suitable for conducting experiments under a high-intensity, variable-frequency magnetic field, on the biological effects of the ELF magnetic field in an in vitro study. The exposure system consists of Merritt's 4-square coil as a basic component to generate the required magnetic field intensity of 10 mT at 50 Hz with spatial field uniformity less than +/-3% in a 400 mm cube. Concentric compensation coils are adopted to eliminate the effects of stray fields on sham (control) samples in the vicinity of the exposure system. The uniformity of the magnetic field in the exposure coil, the increase in the power supply capacity due to the existence of compensation coils, and the stray field estimation were investigated carefully. After fabricating the system, performance tests were carried out and all the characteristics were found to be satisfactory. In addition, the ideal configuration for a concentric coil system was proposed.

Animals↗
PubMed2000

Reduction of polyethylene wear by concave dimples on the frictional surface in artificial hip joints.

For the purpose of reduction of polyethylene wear generated in artificial hip joints, concave dimples were formed on the surface of the metal femoral head by electrical discharge etching with the constant diameter of 0.5 mm, pitch of 1.2 mm, and depth of 0.1 mm. Using a hip joint simulator, the total amount of polyethylene wear was 7.2 mg in the concave-patterned condition and 23.1 mg in the nonpatterned condition. The reasons for the reduction of polyethylene wear by the concave pattern may be i) a reduction of abrasive wear by providing escape dimples for wear particles and ii) an improvement in the lubricity on the frictional surface by the supply of lubricant that is stored in dimples.

Friction↗
PubMed2000

Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems.

Novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems were designed and synthesized to provide J-111,347 (1a) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Staphyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b). which showed improved safety profiles and retained broad-spectrum antibacterial activities.

Animals↗
PubMed2000

Effect of osseointegrated implants on the coordination of masticatory muscles: a pilot study.

STATEMENT OF PROBLEM: The neuromuscular network of masticatory function is, in part, coordinated with afferent information provided by the periodontal ligament (PDL). Osseointegrated implant-supported prostheses lack this PDL-derived proprioceptive feedback mechanism. PURPOSE: This pilot study was designed to address the hypothesis that implant patients acquire different patterns of functional coordination. Patients with implant-supported prostheses were characterized in regard to masticatory muscle tenderness and fatigue as well as changes in the coordinated activities of masticatory muscles during chewing and maximal occluding force. Results were compared with those of patients with natural teeth and interpreted to assess the functional outcome of implant therapy. MATERIAL AND METHODS: Fifty-seven volunteers (25 partially edentulous patients restored with implantsupported fixed prostheses; 32 control patients) were evaluated. A comprehensive set of clinical examinations was performed, including occlusal analysis and examination of masticatory muscle and TMJ. EMG recordings of 5 volunteers from each group were further evaluated. EMG activities of the masseter and anterior temporalis were recorded during habitual chewing and voluntary maximal occluding force. RESULTS: There were essentially no differences in the clinical evaluations between volunteers in the implant and control groups and no significant alterations in the masticatory muscle coordination for habitual chewing. During the maximal occluding force measurement, EMG recordings revealed a unique masticatory muscle coordination pattern in the implant group with a tendency to activate the working and nonworking side muscles simultaneously. CONCLUSION: Patients with implant-supported prostheses appeared to be well adapted to perform habitual masticatory functions. However, during a nonhabitual function such as maximal occluding force, our pilot data revealed a less coordinated masticatory muscle activity in the implant patients.

Adaptation, Physiological↗
PubMed2000

Biomechanical evaluation of osseous implants having different surface topographies in rats.

Biomechanical and biological factors can co-dependently influence the establishment of implant-tissue integration; thus, concurrent evaluation of these factors should provide a better understanding of osseointegration. This study aimed to establish and validate an in vivo rat model frequently used in molecular/cellular biology for implant biomechanical studies. We tested the hypotheses that the implant push-in test assesses the degree of osseointegration by the breakpoint load at the implant-tissue interface and that it sensitively differentiates between the effects of different implant surface topographies. The implant push-in test, which produces a consistent load-displacement measurement, was used to test miniature cylindrical titanium implants placed at the distal edge of the adult rat femur. The push-in test values obtained at each post-implantation healing point (weeks 0, 2, 4, and 8) significantly increased in a time-dependent manner. The implant surface after the push-in test was associated with remnant tissues containing host-derived elements, such as calcium, phosphate, and sulfate. In this model, acid-etched implants (average roughness, 0.159 microm) showed significantly greater push-in test values than did turned implants (average roughness, 0.063 microm) throughout the experimental period (p < 0.0001). These results support the validity of the push-in test in rats, which may be used as a rapid and sensitive biomechanical assay system for implant osseointegration research.

Analysis of Variance↗
PubMed2000

Collagen XII mutation disrupts matrix structure of periodontal ligament and skin.

Collagen XII has been postulated to organize the extracellular matrix (ECM) architecture of dense connective tissues such as the periodontal ligament (PDL) and skin. The objective of this study was to test this hypothesis in transgenic mice carrying a dominant interference mutation of collagen XII. The truncated alpha1(XII) collagen minigene construct MXIINC3(-), driven by the mouse alpha2(I) collagen promoter, was prepared and used to generate transgenic mouse lines. The PDL matrix fibers of molar teeth lost the ordered architecture characteristic of ligament tissue without noticeable inflammation. Cellular cement appeared to be disrupted at the PDL insertion. By confocal laser scanning microscopy, the PDL of transgenic mice demonstrated swollen and irregularly arranged collagen fibers associated with internal porosity. The skin of transgenic mice revealed the lack of matrix fiber structure in the papillary dermis. These results indicated that the dominant interference mutation of collagen XII disorganized the ECM architecture of PDL and skin.

Animals↗
PubMed2000

Crystal chemistry of hydroxyapatite deposited on titanium by sputtering technique.

Crystalline hydroxyapatite (HA) powder was coated on titanium substrate by radio frequency (RF) magnetron sputtering. The coating was homogeneous thin film and the thickness was 1microm. Crystallinity of the HA coating was low and Ca/P ratio was high as 3.0. Particle sizes were 40 to approximately 100 nm, and the crystallite size was calculated by 30 to approximately 50 nm using an X-ray diffractometry (XRD) and a transmission electron microscopy (TEM). When the coating was heated at 800 degrees C for 1 h, the low crystalline HA grew up crystalline HA, and a diffraction pattern of CaO appeared. When the coating was immersed in pH 7.4 of bovine serum for 1 week, c-axis of HA increased.

Animals↗