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Biomedical subjects

T Sakai

Publications and source records attributed to T Sakai.

At least 145 records · Page 8Linked to original sources
PubMed2001

Comparisons of intraosseous graft healing between the doubled flexor tendon graft and the bone-patellar tendon-bone graft in anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon (FT) graft and the bone-patellar tendon-bone (BPTB) graft in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY: Randomized trial. METHODS: A biomechanical and histologic study was conducted with 24 adult beagle dogs. Bilateral ACL reconstructions were performed in each animal. Autogenous doubled FT and BPTB grafts were used for the left and right knees, respectively. Each end of the 2 grafts was tethered with a polyester suture to a screw post with a washer. The animals were then allowed unrestricted activities in their cages. Eight animals were killed at 3, 6, and 12 weeks, respectively. RESULTS: Histologically, the FT graft was anchored to the tunnel wall with newly formed collagen fibers resembling Sharpey's fibers by 12 weeks. These fibers were more abundant in the anterior (ventral) gap than in the posterior (dorsal) gap. In the BPTB graft, the bone plug was anchored with newly formed bone at 3 weeks, although osteocytes in the plug trabeculae were necrotic for 12 weeks. Degeneration of the tendon-bone junction in the plug progressed at 6 weeks. Tensile testing showed that the weakest site was different not only between the 2 grafts but also between the observation periods. In the FT graft, the weakest site was the graft-wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks. In the BPTB graft, the weakest site was the graft-wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks. The ultimate failure load of the FT graft was significantly inferior (45.8%) to that of the BPTB graft at 3 weeks (P =.021). At 6 weeks, the load of the FT graft was 85% that of the BPTB graft without a significant difference (P =.395). CONCLUSIONS: As to the clinical relevance, the fixation device chosen for soft-tissue fixation appears to be more important than comparing it to the BPTB graft, although this has yet to be conclusively proven.

Animals↗
PubMed2001

A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high-dose daily interferon alfa plus ribavirin and intravenous twice-daily treatment with interferon beta.

Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of antiviral mechanisms by analyzing HCV dynamics in PBMC. To address potential molecular differences associated with distinct antiviral regimens, we studied HCV dynamics in both serum and PBMC in 44 patients with HCV genotype 1b and high viral load who were randomly assigned to the following 4 different treatment groups: 1) combination therapy with 6 MU daily of interferon alfa 2b (IFN-alpha2b) plus 800 mg of ribavirin; 2) monotherapy with 6 MU daily of IFN-alpha2b; 3) monotherapy with twice-daily intravenous administration with 3MU of IFN-beta; and 4) monotherapy with daily intravenous administration with 6 MU of IFN-beta. HCV-RNA levels were measured serially using highly sensitive real-time detection polymerase chain reaction (PCR). HCV dynamics in both the serum and PBMC showed a "biphasic" pattern. The exponential decay slopes of the second phase were significantly higher in the combination or twice-daily dosing regimen groups compared with groups 2 or 4 (0.10 +/- 0.08 vs. 0.02 +/- 0.09 or 0.16 +/- 0.09 vs. 0.02 +/- 0.04 day(-1); P <.05 or P <.0005, respectively). Moreover, the viral half-lives in the second phase were significantly shorter in these groups (73.2 +/- 42.5 vs. 240.1 +/- 120.7 or 56.0 +/- 44.6 vs. 361.6 +/- 293.5 hours; P <.05 or P <.05, respectively). Additionally, the slope of HCV decline in PBMC tended to be higher in the combination regimens, as compared with monotherapy. Taken together, our data on HCV dynamics provide molecular insight into utilization of combination or twice-daily dosing regimens to increase rates of sustained viral eradication of HCV.

Adult↗
PubMed2001

Lack of noninvasive markers of ventricular repolarization inhomogeneity in patients with idiopathic ventricular tachyarrhythmia.

Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.

Adult↗
PubMed2001

Effects of tetrahydrobiopterin on ataxia in Machado-Joseph disease may be based upon the theory of 'cerebellar long-term depression'.

We previously verified the effectiveness of tetrahydrobiopterin (BH4) on the ataxia in Machado-Joseph disease (MJD; SCA3 [spinocerebellar ataxia type 3]) as one of the most common types of dominantly inherited spinocerebellar ataxias. We hypothesized as to the pharmacological mechanism of BH4 that on the basis of 'cerebellar long-term depression' theory, BH4 may exert its actions at the levels of soluble guanylate cyclase in the Purkinje cells and of nitric oxide synthase in the granule cells. If cerebellar long-term depression is the case as the theoretical basis of BH4, it will open a new page of therapeutic strategy for spinocerebellar ataxias.

Biopterins↗
PubMed2001

Congenital central hypoventilation syndrome associated with Hirschsprung's disease: mutation analysis of the RET and endothelin-signaling pathways.

Three cases of congenital central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HSCR) were examined with respect to their genomic DNA on the coding region of the receptor tyrosine kinase (RET) and the endothelin-B receptor (EDNRB). No causative mutations for the disease were detected, but one polymorphism was observed in exon 11 of the RET proto-oncogene. In cases with CCHS, HSCR occurs with a high incidence, and this disease complex has been described as neurocristopathy due to aberrations in neural crest cell proliferation, differentiation or migration during the early fetal period. Both the RET and EDNRB may play important roles in the modulation of neurocristopathies; however, further systemic studies in a large population of patients and control subjects are necessary for elucidating the pathogenesis of this disorder.

Child↗
PubMed2001

The fate of a tissue-engineered cardiac graft in the right ventricular outflow tract of the rat.

OBJECTIVE: The synthetic materials currently available for the repair of cardiac defects are nonviable, do not grow as the child develops, and do not contract synchronously with the heart. We developed a beating patch by seeding fetal cardiomyocytes in a biodegradable scaffold in vitro. The seeded patches survived in the right ventricular outflow tract of adult rats. METHODS: Cultured fetal or adult rat heart cells (1 x 10(6) cells) were seeded into a gelatin sponge (15 x 15 x 1 mm), and the cell number was expanded in culture for 1 or 3 weeks, respectively. The free wall of the right ventricular outflow tract in syngeneic adult rats was resected and repaired with either unseeded patches or patches seeded with either fetal or adult cardiomyocytes (n = 10 for each group). The patches were examined histologically over a 12-week period. RESULTS: A significant inflammatory reaction was noted in the patch at 4 weeks as the scaffold dissolved. At 12 weeks, the gelatin scaffold had completely dissolved. Both types of the seeded cells were detected in the patch with 5-bromo-2'-deoxyuridine staining, and they maintained their continuity. Unseeded patches had an ingrowth of fibrous tissue. The patches became thinner between the fourth and the twelfth weeks in unseeded (P =.003), fetal (P =.0001), and adult (P =.07) cardiomyocyte groups as the scaffold dissolved. The control patch, but not the cell-seeded patches, was thinner than the normal right ventricular outflow tract. The endocardial surface area of each patch was covered with endothelial cells identified by factor VIII staining. CONCLUSIONS: A gelatin patch was used to replace the right ventricular outflow tract in syngeneic rats. The seeded cells survived in the right ventricular outflow tract after the scaffold dissolved 12 weeks after implantation. In addition, the unseeded patches encouraged the ingrowth of fibrous tissue as the scaffold dissolved and the patches remained completely endothelialized.

Absorbable Implants↗
PubMed2001

Angiogenesis by endothelial cell transplantation.

PURPOSE: Myocardial angiogenesis may improve regional perfusion and perhaps function after cardiac injury. We evaluated the effect of endothelial cell transplantation into a myocardial scar on angiogenesis and ventricular function, as an alternative to angiogenic gene or protein therapy. METHODS AND RESULTS: A transmural myocardial scar was created in the left ventricular free wall of rat hearts by cryoinjury. Allogeneic aortic endothelial cells were injected into the scar 2 weeks after cryoinjury. A cluster of transplanted cells was identified at the site of injection 1 day and 1 week after transplantation, but not after 2 weeks. The size of this cluster of transplanted cells decreased as vascular density in the transplanted scar tissue increased with time. Six weeks after transplantation, vascular density was significantly greater in transplanted hearts than in control hearts. Regional blood flow, by microsphere analysis, was greater in the transplanted rats. Systolic and diastolic ventricular function was similar between groups. In a second series of experiments, syngeneic aortic endothelial cells labeled with bromodeoxyuridine were transplanted 2 weeks after cryoinjury. Vascular density in the transplanted scar was greater than in controls. Labeled transplanted endothelial cells were identified forming part of the newly developed blood vessels. No difference in vascular density was found between allogeneic and syngeneic cell transplantation. Vascular endothelial growth factor was not expressed at greater levels in the transplanted cells or the myocardial scar. CONCLUSION: Transplanted endothelial cells stimulated angiogenesis, were incorporated into the new vessels, and increased regional perfusion in myocardial scar tissue, but did not improve global function in this cryoinjury rat model.

Animals↗
PubMed2001

Osteoblastic response to osteoarthrosis of the hip does not predict outcome of cementless cup fixation: 79 patients followed for 5-11 years.

We evaluated the influence of osteoblastic response to osteoarthrosis of the hip on the outcome of cementless acetabular cup after 91 total hip replacements in 79 patients. Of the 91 hips, 23 were atrophic, 37 normotrophic, and 31 hypertrophic, according to Bombelli's criteria. There were no clinical or radiographic differences among the three groups at the final follow-up (average 7 (5-11) years), when stable bone growth had been achieved by all of the acetabular cups in patients with the atrophic type, 35/37 of the normotrophic type, and all the hypertrophic type. Revision of the acetabular cup was performed on 1 hip of the normotrophic type, in connection with severe polyethylene liner wear and progressive osteolysis.

Adult↗
PubMed2001

Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V(alpha)14 NKT cells.

A novel lymphocyte, NKT cells bearing an invariant V(alpha)14 antigen receptor, specifically recognizes alpha-galactosylceramide (alpha-GalCer) exclusively presented by mouse CD1d (mCD1d). However, the precise molecular interaction remains unclear. For the basis of functional analyses, a docking model of alpha-GalCer with the crystal structure of mCD1d was constructed. Possible residues involved in the alpha-GalCer--mCD1d interaction were found to be Arg79, Glu83 and Asp80 for carbohydrate recognition, and Asp153 for interaction with the amide group on the fatty acyl chain. The alpha-GalCer-presenting ability of various transfectants expressing mutant mCD1d was completely abrogated if a single amino acid mutation was induced at positions 79, 80, 83 or 153, suggesting that the polar amino acids above the F' pocket are crucial for alpha-GalCer presentation to activate V(alpha)14 NKT cells. The possibility that Glu83 is a contact site for the NKT cell receptor is also discussed.

Amino Acids↗
PubMed2001

Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice.

Prior to the activation of CD4 (+) T cells, exogenous proteins must be digested by endo/lysosomal enzymes in antigen-presenting cells (APC) to produce antigenic peptides that are able to be presented on class II molecules of the MHC. Studies described here inspect the functional significance of cathepsin L inhibition for antigen processing and T (h) 1/T (h) 2 differentiation in experimental leishmaniasis. We first demonstrated using in vitro systems that cathepsin L is one of the candidate endo/lysosomal enzymes in processing of soluble Leishmania antigen (SLA) and that its specific inhibitor, CLIK148, modulated the processing of SLA. BALB/c mice are known to be susceptible to infection with Leishmania major. Interestingly, treatment of BALB/c mice with CLIK148 exacerbated the infection by enhancing the development of SLA-specific T (h) 2-type response such as production of IL-4 and generation of T (h) 2-dependent specific IgE/IgG1 antibodies. Moreover, addition of CLIK148 in incubation of a SLA-specific CD4 (+) T cell line with APC up-regulated the production of IL-4. However, CLIK148 did not exert any direct influence on the function of T cells themselves. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APC, resulting in the potentiation of T (h) 2-type immune responses and thus leading to exacerbation of the infection. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.

Adjuvants, Immunologic↗
PubMed2001

In vitro refolding of porcine pepsin immobilized on agarose beads.

Since in vitro refolding of pepsin has long been attempted without success, it has been suspected that pepsin has no intrinsic refolding ability. In the present study, in order to eliminate unfavorable intermolecular interactions bringing about aggregation and autoproteolysis, we immobilized pepsin onto agarose beads. This technique enabled us to search extensively for appropriate refolding conditions without limitation of the refolding period. Renaturation of immobilized pepsin was observed exclusively at pH 3-5. This process was extremely slow and reached equilibrium after 300 h. Sixty percent of the proteolytic activity was recovered at pH 5. Addition of salts raised the recovery to 80% but had no significant effect on the refolding rate, suggesting that the salts mainly stabilize the native state of pepsin. This is the first report on the successful in vitro refolding of pepsin.

Animals↗
PubMed2001

Analysis of survivorship after total hip arthroplasty using a ceramic head.

To determine the clinical efficacy of an alumina ceramic head, 119 cemented total hip arthroplasties in 97 patients using an alumina head coupled with ethylene oxide gas sterilized polyethylene were reviewed. Eighty-two patients (101 hips) with greater than 10 years followup were evaluated clinically and radiographically (range, 10-17.6 years), and 97 patients (119 hips) were evaluated for survivorship analysis (range, 0.6-17.6 years). The average functional hip scores according to Merle d'Aubigné and Postel improved from 8.6 preoperatively to 15.0 at the final followup, and 57 patients (64 hips) had no pain. The average polyethylene wear rate was 0.15 mm/year (range, 0.04-0.34 mm/year). Patients with polyethylene wear greater than 3 mm showed significantly higher rates of acetabular loosening. Fifteen-year survival rates (with 95% confidence intervals) with radiographic evidence of aseptic loosening as the end point were 46.8% +/- 13.4% in acetabular components and 91.9% +/- 6.6% in femoral components. Fifteen-year survival rates of hip arthroplasties with revision because of aseptic loosening as the end point were 75.3% +/- 10.2% and 97.9% +/- 3.0%, respectively. Results of the current study suggest that using an alumina head instead of a metal head may not be beneficial when coupled with ethylene oxide gas sterilized polyethylene.

Adult↗
PubMed2001

Crystallization and preliminary X-ray analysis of a novel pectolytic enzyme, polymethoxygalacturonase SX1 from Trichosporon penicillatum.

A novel pectolytic enzyme, polymethoxygalacturonase SX1 from Trichosporon penicillatum, with a molecular weight of 36 kDa was crystallized by the hanging-drop vapour-diffusion method using polyethylene glycol 1000 as a precipitant. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 165.6, b = 61.0, c = 48.7 A, beta = 93.1 degrees. The calculated V(M) based on one molecule per asymmetric unit was 3.40 A(3) Da(-1). A native data set was collected to 2.08 A resolution from a crystal on a Cu Kalpha rotating-anode X-ray source. A molecular-replacement solution was obtained using the program AMoRe and the structure of endopolygalacturonase II from Aspergillus niger as a model.

Crystallization↗
PubMed2001

Three-dimensional finite element simulation of a piezoelectric vibrator under gyration.

A three-dimensional finite element modeling is applied to the characteristic evaluation of the piezoelectric gyroscopes. The Coriolis' effect is incorporated with the three-dimensional finite element code that we have already developed. There is no limitation for the vibrational modes and the direction of the gyratory axis. The piezoelectric thin plate gyroscope in plane vibration is again considered for the demonstration. The solution characteristics are compared with those of the two-dimensional modeling and also with the experimental results. Reasonable agreement is achieved. The application is then extended to a bimorph-type gyroscope vibrating out of plane, which is only numerically considered for another example of demonstration. The examination shows that, with this configuration, not only the rotation but also the gyratory axis can be detected in the three-dimensional space.

Journal Article↗
PubMed2001

Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response.

During infection, parasites evade the host immune system by modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility complex class II molecules or secrete cytokine-like molecules. However, it is not clear whether helminths disturb the immune responses of their hosts by controlling the antigen-processing pathways of the hosts. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode, Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin family 2, consists of 144 amino acids and is secreted as a 14-kDa mature form. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also greatly suppressed in rNbCys-treated mice. Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected by rNbCys treatment, OVA-specific IgE was preferentially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by lysosomal cysteine proteases from the spleens of mice. Mice with anti-nippocystatin antibodies became partially resistant to infection with N. brasiliensis. Based on these findings, N. brasiliensis appears to skillfully evade host immune systems by secreting nippocystatin, which modulates antigen processing in antigen-presenting cells of hosts.

Amino Acid Sequence↗
PubMed2001

Bone scintigraphy for osteonecrosis of the knee in patients with non-traumatic osteonecrosis of the femoral head: comparison with magnetic resonance imaging.

OBJECTIVE: To determine whether technetium bone scintigraphy (BS) is useful for screening of non-traumatic osteonecrosis of the knee (ONK), which was a major affected site, secondary to the femoral head, among multiple osteonecrosis, in patients with non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A total of 214 knee joints in 107 patients with ONFH were evaluated by BS and a comparison made with magnetic resonance imaging (MRI). ONK was classified into five sites, including the femoral condyles (ONFC), distal femoral metaphysis (ONFM), tibial plateau (ONTP), proximal tibial metaphysis (ONTM), and patella (ONP). RESULTS: Based on the diagnosis by MRI, ONK was detected in 103 knees of 62 patients (48%). ONFC was most common (86 knees, 40%), ONFM (15%), followed by ONTM (10%), ONP (3%), and ONTP (0.9%). Sensitivity, specificity, and accuracy of BS for ONFC detection were 63%, 71%, and 68%, respectively. When the ONFC lesions on the coronal views of MRI were large or medium sized and occupied two thirds, or the entire anteroposterior joint surface on the sagittal views, the sensitivity of BS for ONFC detection increased to 89% (34/38 knees). The sensitivity of BS for ONFM, ONTM, and ONP detection was 3%, 0%, and 0%, respectively, but these lesions showed a low likelihood of collapse. CONCLUSION: BS is useful for screening large ONK in patients with ONFH given that 89% of patients with ONFC who had a high risk of collapse of the knee were identified.

Adolescent↗