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Biomedical subjects

Yasuo Takeuchi

Publications and source records attributed to Yasuo Takeuchi.

At least 19 recordsLinked to original sources

Elevated IgG titers to periodontal pathogens related to Buerger disease.

BACKGROUND: Periodontal pathogens were frequently detected in the occluded arteries of Buerger disease patients, hence we hypothesized that the infection from periodontal pathogens may be associated with Buerger disease. METHODS: We investigated periodontal status using various clinical parameters and serum IgG antibody levels against T. denticola, P. gingivalis, A. actinomycetemcomitans and P. intermedia in nineteen Buerger disease patients and fifteen control subjects. The results were statistically analyzed. RESULTS: The prevalence of periodontitis and the percentages of probing sites with PD> or =4 mm and CAL> or =4 mm were significantly higher in the patient group (P<0.001, P=0.016, and P<0.001, respectively). Patients had significantly higher serum IgG titers against T. denticola, P. gingivalis and A. actinomycetemcomitans (P=0.002, P=0.039, and P=0.011, respectively). CONCLUSIONS: This study provides evidence for possible implications of periodontitis in Buerger disease.

Aggregatibacter actinomycetemcomitans↗

Anti-CD40L monoclonal antibodies can replace anti-CD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism.

BACKGROUND: We have previously demonstrated that xenogeneic bone marrow engraftment and donor-specific tolerance can be induced in mice receiving anti-CD4, -CD8, -Thy-1.2, and -NK1.1 monoclonal antibodies (mAbs) on Days -6 and -1, 3 Gy total body irradiation (TBI), and 7 Gy thymic irradiation on Day 0, followed by injection of T-cell depleted (TCD) rat bone marrow cells. We have recently demonstrated that anti-CD40L mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance in an allogeneic combination. METHODS: We investigated the ability of anti-CD40L mAb to promote mixed xenogeneic chimerism and donor-specific tolerance in B6 mice receiving anti-CD8, -Thy1.2 and -NK1.1 mAbs and 3 Gy TBI followed by TCD bone marrow transplantation (BMT) from F344 rats. RESULTS: Administration of anti-CD4 mAb in this model could be completely replaced by one injection of anti-CD40L mAb. Evidence for deletional tolerance was obtained in mixed chimeras prepared with this anti-CD40L-based regimen. However, anti-NK1.1 and anti-Thy1.2 mAb could not be replaced by anti-CD40L mAb. CONCLUSIONS: These results demonstrate that anti-CD40L in combination with xenogeneic BMT can tolerize preexisting peripheral and intrathymic CD4 cells to xenoantigens. However, anti-CD40L does not prevent NK cell and/or gammaDelta cell-mediated rejection of xenogeneic bone marrow.

Animals↗

Crystallization and preliminary X-ray analysis of enoyl-acyl carrier protein reductase (FabK) from Streptococcus pneumoniae.

The enoyl-acyl carrier protein (ACP) reductase from Streptococcus pneumoniae (FabK; EC 1.3.1.9) is responsible for catalyzing the final step in each elongation cycle of fatty-acid biosynthesis. Selenomethionine-substituted FabK was purified and crystallized by the hanging-drop vapour-diffusion method at 277 K. The crystal belongs to space group P2(1), with unit-cell parameters a = 50.26, b = 126.70, c = 53.63 A, beta = 112.46 degrees . Diffraction data were collected to 2.00 A resolution using synchrotron beamline BL32B2 at SPring-8. Two molecules were estimated to be present in the asymmetric unit, with a solvent content of 45.1%.

Bacterial Proteins↗

Characteristics of polyclonal anti-human nephrin antibodies induced by genetic immunization using nephrin cDNA.

BACKGROUND: Nephrin is an essential protein for maintaining the normal structure of the podocyte foot process and the glomerular filtration barrier. To analyse the mechanism of proteinuria and treatment of nephrotic syndrome, we produced and characterized polyclonal anti-human nephrin antibodies using a newly developed genetic immunization technique. METHODS: An expression vector with full-length or fragmented cDNA of human nephrin protein was administered to female Lewis rats once a week for 12 weeks using a gene-gun method. Antibody production against different fragments of nephrin protein was then analysed by ELISA, Western blot analysis, immunoprecipitation and FACS analysis. We also analysed recognition of native nephrin protein using immunohistochemistry and electron microscopy, and conducted a functional analysis of in vitro clustering of nephrin protein. RESULTS: Serum anti-nephrin antibody titers reached a maximum level at 8 or 12 weeks. Four of five antibodies induced with cDNA of five different Ig-like motif fragments showed antigen-specific binding to Escherichia coli and produced recombinant human nephrin protein. Only two of these four antibodies, plus one antibody induced by full-length human nephrin protein cDNA, bound to solubilized native nephrin protein. These three IgG antibodies, subclasses IgG1, IgG2a and IgG2b, showed fine granular staining along the glomerular basement membrane of normal human glomeruli and clustering of human nephrin protein on plasma membranes of HEK293 cells. CONCLUSIONS: We successfully produced polyclonal anti-human nephrin antibodies by genetic immunization using nephrin cDNA. These new antigen-specific polyclonal antibodies will be useful for functional analysis and tissue staining of native nephrin protein.

Animals↗

Noninvasive assessment of off-pump coronary artery bypass surgery by 16-channel multidetector-row computed tomography.

BACKGROUND: Sixteen-channel multidetector-row computed tomography (MDCT), with higher spatial and temporal resolution, enables noninvasive visualization of images with reduced motion artifact and breath-holding time. We compared images of 16-channel MDCT and selective bypass graft angiography among patients who had off-pump coronary artery bypass graft surgery. METHODS: The study, conducted from April 2003 to March 2004, involved 42 patients who underwent off-pump coronary artery bypass graft surgery. Samples yielded a total of 96 arterial grafts, 5 vein grafts. Sixteen-channel MDCT (LightSpeed Ultra 16; GE Healthcare, Milwaukee, Wisconsin) was performed on each patient using 500-ms or 600-ms rotation time, 0.625-mm slice thickness, and mean scanning time of approximately 24 seconds. RESULTS: If several sequential anastomoses in one graft existed, each was calculated as a separate graft. Selective bypass graft angiography yielded a patency rate of 97% (155 of 160). Multidetector-row computed tomography enabled detection of 143 of 155 patent grafts and all 5 occluded grafts visualized by selective bypass graft angiography (100% sensitivity and 93% specificity for graft occlusion after exclusion of grafts not evaluated by MDCT). In 149 graft anastomoses of 143 patent grafts viewed by MDCT, 2 significant stenoses were detected by both selective bypass graft angiography and MDCT. Twelve distal anastomoses were not evaluated by MDCT because of metallic clip artifacts. Evaluation possible graft anastomoses were 92%. Sensitivity and specificity for significant stenosis after exclusion of graft anastomoses not evaluated by MDCT were 100% and 99%, respectively. CONCLUSIONS: High-quality 16-channel MDCT images allowed detection of graft occlusion and significant stenosis of graft anastomosis after off-pump coronary artery bypass graft surgery, demonstrating an alternative tool less invasive than selective bypass graft angiography to assess grafts after surgery.

Adult↗

Experimental assessment of the drainage capacity of small silastic chest drains.

Recently, flexible fluted small silicone drains have been used widely as chest drains after cardiac surgery. Despite the clinical advantages of using smaller silastic chest drains over conventional chest tubes, an experimental comparison of the drainage capacity between these two drain tubes has not yet been performed. The drainage capacity of 19F silicone drains and 28F conventional tubes was tested. In an in vitro study, both tubes were set in a water bath and drained at a pressure of 10 mm Hg. In an in vivo study, the drains were inserted into the hemithorax in 8 adult pigs. Blood was infused at 20 mL x min(-1) into both chest cavities and the tubes were drained at 15 cm H(2)O for 30 min. In the in vitro study, the drainage capacity of the conventional chest tube was 9-times higher than that of the smaller silicone drain (103.8 vs. 11.6 L x hr (-1)). However, in the in vivo study, there was no difference in drainage capacity between the two different tubes over time. This experiment demonstrated that the smaller silastic chest drain has sufficient drainage capacity, almost identical to the conventional chest tube, in the clinical setting.

Animals↗

Early angiographic results of multivessel off-pump coronary artery bypass grafting.

OBJECTIVES: Recently off-pump coronary artery bypass grafting (CABG) is being widely used for coronary revascularization. However, there is some evidence that off-pump surgery increases the risk of recurrent angina and the need for reintervention, suggesting poor graft quality or incomplete revascularization. We describe our experience to demonstrate the feasibility of multiple coronary revascularization in off-pump CABG (OPCAB). PATIENTS AND METHODS: From January 2002 to March 2003, 168 patients underwent OPCAB at our institute. In 16 of them, 6 to 9 vessels were revascularized in each patient. There were 14 males and 2 females with a mean age of 66 years (47 to 74 years). All patients had triple-vessel disease. Ten patients received in situ arterial grafts only which were harvested with the skeletonization technique using an ultrasonic scalpel. We used the Starfish heart positioner to expose lateral, posterior, and inferior walls of the heart with minimal hemodynamic compromise. RESULTS: All patients were discharged from the hospital without any serious complications. Postoperative angiography was performed in 87.5% within 1 month after operation. The patency rate was 96.6%. CONCLUSION: These results indicate that complete revascularization can be achieved in OPCAB in patients with diffuse coronary arterial disease. Complete revascularization with in situ arterial conduits only is technically feasible and yields a high early graft patency, even in the off-pump situation.

Aged↗

Early regulation of CD8 T cell alloreactivity by CD4+CD25- T cells in recipients of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral deletion of donor-reactive CD8+ T cells, precluding a role for sustained regulation.

While acquisition of regulatory function by CD4+CD25- T cells has been reported following antigenic stimulation, "naturally occurring" regulatory CD4+ T cells (Treg) are believed to express CD25. We examined the mechanisms involved in peripheral CD8 T cell tolerance by induction of mixed chimerism using non-myeloablative conditioning with low-dose (3 Gy) total body irradiation and anti-CD154 antibody. Recipient CD4+ T cells were initially required for the induction of CD8 cell tolerance, but were not needed beyond 2 weeks. Depletion of CD25+ Treg prior to bone marrow transplantation and blockade of IL-2 with neutralizing antibody did not impede tolerance induction. Tolerance was dependent on CTLA4, but not on IFN-gamma. In C57BL/6 mice containing a fraction of 2C TCR transgenic CD8+ T cells, which recognize the MHC class I alloantigen Ld, induction of chimerism with L(d+), but not Ld-, bone marrow cells led to deletion of peripheral 2C+ CD8+ cells within 1 week in peripheral blood and spleen. Complete deletion required the presence of recipient CD4+ T cells. Thus, a novel, rapid form of regulation by CD4+CD25- T cells permits initial CD8 T cell tolerance in this model. Rapid peripheral deletion of donor-specific CD8 T cells precludes an ongoing requirement for CD4 T cell-mediated regulation.

Animals↗

Concise synthesis of dl-febrifugine.

Racemic compound (1) of the antimalarial agents febrifugine (d-1) was synthesized using an stereoselective Michael reaction of an omega-amidoenone (5) which was prepared by the Wittig reaction of piperidinediol (7).

Antimalarials↗

Single-vessel revascularization with minimally invasive direct coronary artery bypass: minithoracotomy or ministernotomy?

STUDY OBJECTIVES: To compare the early outcome in patients who underwent off-pump single-vessel revascularization of the left anterior descending coronary artery (LAD) using two different approaches of minimally invasive direct coronary artery bypass grafting (MIDCAB): left anterior small thoracotomy (LAST) and lower ministernotomy. DESIGN: A retrospective analysis of the medical records on length of the skin incision, total operation time, duration of mechanical ventilation, blood transfusion rate, ICU stay, postoperative wound pain, and morbidities. PATIENTS: Thirty-two patients who underwent MIDCAB with the left internal thoracic artery to the LAD for single-vessel disease were studied. LAST was performed in 16 patients, and ministernotomy was performed in 16 patients. For the ministernotomy approach, the lower half of the sternum was split without transverse division, which we called the lower-end sternal splitting (LESS) approach. Postoperative pain was evaluated using a face-rating scale (scale, 1 to 6). RESULTS: There were no significant differences between the two groups in length of the skin incision, duration of mechanical ventilation, and ICU stay. Total operation time was shorter in the LESS group than in the LAST group (p < 0.05). No patients received a blood transfusion in either group. Atrial fibrillation developed in one patient in the LAST group and two patients in the LESS group. Early graft potency was 94% in the LAST group and 100% in the LESS group (p = 0.48). In the LAST group, subcutaneous emphysema developed in three patients and superficial wound dehiscence developed in two patients, but these complications were not observed in the LESS group (p < 0.05). Postoperative pain was significantly higher in the LAST group up to postoperative day 7 (p < 0.05). CONCLUSIONS: Although LAST is the most commonly used approach for MIDCAB, wound complications and postoperative pain with this technique are not insignificant compared with the lower ministernotomy approach.

Aged↗

Anaphylaxis to aprotinin in fibrin sealant.

A 50-year-old man with chronic otitis media was admitted to our hospital for investigation of lung cancer. He had received repeated instillations of fibrin sealant (Bolheal) in myringoplasty 7 times over 12 months. During the lower lobectomy, soon after fibrin sealant was applied to seal bronchopleural fistulas, systolic blood pressure decreased to 60 mmHg. Treatment with epinephrine and dopamine was required until his condition improved 2 days later. The specific IgE antibody was detected for the solution for fibrinogen and factor XIII containing bovine aprotinin. Cross-reactivity between purified aprotinin and the solution was noted by competitive ELISA inhibition tests.

Anaphylaxis↗

Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L.

Treatment with a single injection of anti-CD40L (CD154) monoclonal antibody (mAb) and fully mismatched allogeneic bone marrow transplant (BMT) allows rapid tolerization of CD4+ T cells to the donor. The addition of in vivo CD8 T-cell depletion leads to permanent mixed hematopoietic chimerism and tolerance. We now describe two approaches that obviate the requirement for CD8 T-cell depletion by rapidly tolerizing recipient CD8 T cells in addition to CD4 cells. Administration of donor-specific transfusion (DST) to mice receiving 3 Gy total body irradiation (TBI), BMT and anti-CD40L mAb on day 0 uniformly led to permanent mixed chimerism and tolerance, compared with only 40% of mice receiving similar treatment without DST. In the absence of DST, moving the timing of 3 Gy TBI to day -1 or day -2 instead of day 0 led to rapid (by 2 weeks) induction of CD8+ cell tolerance, and also permitted uniform achievement of permanent mixed chimerism and donor-specific tolerance in recipients of anti-CD40L and BMT on day 0. These nontoxic regimens overcome CD8+ and CD4+ T-cell-mediated alloresistance without requiring host T-cell depletion, permitting the induction of permanent mixed chimerism and tolerance.

Animals↗

The distribution of periodontopathic bacteria among Japanese children and their parents.

OBJECTIVE AND BACKGROUND: It is not well known how periodontopathic bacteria colonize in the oral cavity during childhood. The purpose of this study was to investigate the distribution of periodontopathic bacteria in oral cavities of children and their parents and the relationship between the bacterial findings and clinical parameters. METHODS: Fifty-six children (mean age: 8.3 +/- 3.5, range: 1-15 years), including 15 with deciduous dentition, 26 with mixed dentition and 15 with permanent dentition, and their parents participated in this study. Whole saliva and dental plaque of the children and whole saliva of their parents were collected for detection of seven species of periodontopathic bacteria (Actinobacillus actinomycetemcomitans, Tannerella forsythensis (Bacteroides forsythus), Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Treponema denticola) using the polymerase chain reaction method. Clinical parameters including simplified Oral Hygiene Index and Papillary-Marginal-Attachment Index were recorded for the children and their accompanied parents. RESULTS: The detection frequencies of T. forsythensis, C. rectus, P. nigrescens, T. denticola, A. actinomycetemcomitans and P. gingivalis in the oral cavities of children were 42.9%, 94.6%, 42.9%, 48.2%, 1.8% and 8.9%, respectively. T. forsythensis, P. gingivalis and T. denticola were detected more frequently in the saliva of parents (54.8%, 54.8%, 88.1%, respectively) than in the saliva of children (25.5%, 7.3%, 41.8%, respectively). Different detection frequencies of P. nigrescens were found among the oral cavities of children with deciduous, mixed and permanent dentitions. In mixed dentition, females harbored T. forsythensis more frequently than males did. Children who harbored T. forsythensis, P. intermedia, P. nigrescens and T. denticola showed high scores for oral debris measurement by simplified Oral Hygiene Index. T. forsythensis, P. intermedia and P. nigrescens were detected more frequently in children whose parents were positive for these pathogens than in children whose parents were negative. CONCLUSIONS: High plaque retention seems to promote the colonization of periodontal pathogens in the oral cavities of children. T. forsythensis, P. intermedia and P. nigrescens were detected more frequently in the oral cavities of children whose parents already harbored these bacteria. Familial transmission of these bacteria is suggested.

Adolescent↗

Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity.

Bone marrow transplantation from diabetes-resistant strains with complete replacement of the recipient immune system by the allogeneic donor has led to tolerance to donor islets and cure of diabetes in a mouse model of type 1 diabetes. However, the ability to tolerize host T-cells of diabetic NOD mice is unknown. We demonstrate that nonmyeloablative conditioning achieves mixed hematopoietic chimerism across major histocompatibility complex (MHC) barriers in spontaneously diabetic NOD mice. This conditioning preserves alloreactive and autoreactive diabetogenic host NOD T-cells, but when mixed chimerism was established, diabetic NOD mice accepted donor-type allogeneic islet grafts and were cured of diabetes, despite a significant recipient T-cell contribution. Furthermore, induction of mixed chimerism permitted acceptance of NOD islet grafts, demonstrating reversal of autoimmunity. Allogeneic bone marrow transplantation was critical for tolerization of diabetogenic and alloreactive host T-cells. Thus, mixed hematopoietic chimerism induces tolerance to donor islets and reverses established autoimmunity in diabetic NOD mice.

Animals↗