Biomedical subjects

Yoshinobu Sato

Publications and source records attributed to Yoshinobu Sato.

At least 19 recordsLinked to original sources

PubMed2006

Increase of CD4+ CD25+ regulatory T-cells in the liver of patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The immune response to tumor-specific antigens is typically unable to control the growth and spread of malignant cells. Accumulating evidence indicates that the suppressive effects of CD4+ CD25+ regulatory T-cells are at least partially responsible for the failure of immune-mediated elimination of tumor cells. METHODS: We have studied 25 patients with hepatocellular carcinoma (HCC). The liver tissues with HCC were separated into the marginal region of tumor (peri-tumor region) and the non-tumor region distant from the tumor. CD4+ CD25+ T-cells were quantified in the blood and the liver by flow cytometry and immunohistochemistry, and their effect on T-cell proliferation and activation was determined. RESULTS: We found a significant increase in both the proportion and absolute numbers of CD4+ CD25+ T-cells in the peri-tumor regions, but not in unaffected areas (9.5 +/- 4.5 vs. 4.6 +/- 2.8%, P = 0.011). CD4+ CD25+ T-cells isolated from peri-tumor regions displayed phenotype markers characteristic of regulatory T-cells, and expressed Foxp3 mRNA. CD8+ T-cells in peri-tumor regions were inversely proportional to CD4+ CD25+ T-cells in the same region (P < 0.001). Moreover, isolated CD4+ CD25+ T-cells inhibited autologous CD8+ T-cell proliferation. CONCLUSIONS: Our results suggest that CD4+ CD25+ T-cells in the marginal region of HCC may play a critical role in controlling CD8+ cytotoxic T-cell activity and, thereby, contribute to the progression of HCC.

Adult↗

PubMed2006

Anergic lymphocytes generated by blocking CD28 and ICOS pathways in vitro prolong rat cardiac graft survival.

Regulatory cells may play a pivotal role in inducing and maintaining transplantation tolerance. We investigated the mechanism of anergic lymphocytes with regulatory cell potential generated in vitro by ICOS and CD 28 co-stimulatory blockades as a source of cellular therapy for treating allograft rejection. Anergic lymphocytes were generated by a mixed lymphocyte reaction consisting of DA splenocytes as the stimulator and Lewis splenocytes as the responder in the presence of anti-ICOS mAb and rCTLA-4I g. Immunoregulatory effects of these lymphocytes were evaluated by secondary MLR and using other various stimulations. DA heart was transplanted into 7.5 Gy-irradiated Lewis rat after intravenous administration of these cells and/or Lewis spleen lymphocytes. We observed that these lymphocytes were not only anergic to alloantigen and polyclonal stimulations but also exhibited regulative activity to inhibit the alloreactive T-cell response. Our adoptive transfer studies revealed that irradiated recipients that received both anergic lymphocytes and naIve Lewis lymphocytes had significantly prolonged DA cardiac graft survival (mean 17.5 days) compared with a group that received Lewis lymphocytes alone (mean 10.8 days). Furthermore, some of the recipients accepted the graft indefinitely after receiving anergic lymphocytes alone (>100 days). These results demonstrated that anergic lymphocytes with regulatory activities can be generated through blocking co-stimulatory signals, CD 28 and ICOS, simultaneously in vitro, and may advance a new immunomodulatory strategy for preventing allorejection in organ transplantation.

Abatacept↗

PubMed2006

Shear stress induces hepatocyte PAI-1 gene expression through cooperative Sp1/Ets-1 activation of transcription.

Partial hepatectomy causes hemodynamic changes that increase portal blood flow in the remaining lobe, where the expression of immediate-early genes, including plasminogen activator inhibitor-1 (PAI-1), is induced. We hypothesized that a hyperdynamic circulatory state occurring in the remaining lobe induces immediate-early gene expression. In this study, we investigated whether the mechanical force generated by flowing blood, shear stress, induces PAI-1 expression in hepatocytes. When cultured rat hepatocytes were exposed to flow, PAI-1 mRNA levels began to increase within 3 h, peaked at levels significantly higher than the static control levels, and then gradually decreased. The flow-induced PAI-1 expression was shear stress dependent rather than shear rate dependent and accompanied by increased hepatocyte production of PAI-1 protein. Shear stress increased PAI-1 transcription but did not affect PAI-1 mRNA stability. Functional analysis of the 2.1-kb PAI-1 5'-promoter indicated that a 278-bp segment containing transcription factor Sp1 and Ets-1 consensus sequences was critical to the shear stress-dependent increase of PAI-1 transcription. Mutations of both the Sp1 and Ets-1 consensus sequences, but not of either one alone, markedly prevented basal PAI-1 transcription and abolished the response of the PAI-1 promoter to shear stress. EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress. In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1.

Animals↗

PubMed2006

Proposal for internet-based Digital Dental Chart for personal dental identification in forensics.

A dental chart is very useful as a standard source of evidence in the personal identification of bodies. However, the kind of dental chart available will often vary as a number of types of odontogram have been developed where the visual representation of dental conditions has relied on hand-drawn representation. We propose the Digital Dental Chart (DDC) as a new style of dental chart, especially for open investigations aimed at establishing the identity of unknown bodies. Each DDC is constructed using actual oral digital images and dental data, and is easy to upload onto an Internet website. The DDC is a more useful forensic resource than the standard types of dental chart in current use as it has several advantages, among which are its ability to carry a large volume of information and reproduce dental conditions clearly and in detail on a cost-effective basis.

Forensic Dentistry↗

PubMed2006

Longitudinal quantitative evaluation of lesion size change in femoral head osteonecrosis using three-dimensional magnetic resonance imaging and image registration.

It remains controversial whether some lesions of femoral head osteonecrosis regress during the natural course of the disease. With image registration, accurately matched image sets of the same subject can be acquired at different times. We applied image registration to evaluate lesion size change and assessed accuracy and usefulness compared to volume measurements and a conventional method. We also investigated whether lesions regress with this technique and with volume measurements. Baseline and 1 year minimum follow-up scans were conducted on 25 patients (31 hips) without radiological evidence of collapse. A three-dimensional (3D) spoiled gradient recalled echo sequence was used in the coronal direction (slice thickness = 2 mm; slice pitch = 1 mm). Size change was evaluated on all contiguous pairs of matched images after image registration. As a conventional method, coronal images (slice thickness = 5 mm) were reconstructed, and size change was evaluated on the five representative coronal slices. Evaluation with the conventional method identified eight lesions with apparent reduction; assessments using image registration and volume measurements identified three lesions, all within a year of initial steroid treatment and remaining at ARCO stage I at follow up. Evaluation of lesion size change using image registration was comparable to volume measurements. Inaccurate estimation of lesion size change due to mismatching of slice planes can be excluded. We demonstrated that some early lesions detected less than a year after initial steroid treatment can show size reduction with image registration as well as with volume measurements.

Adolescent↗

PubMed2006

Management of major portosystemic shunting in small-for-size adult living-related donor liver transplantation with a left-sided graft liver.

PURPOSE: We investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver. METHODS: Five patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 +/- 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated. RESULTS: The portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH(2)O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH(2)O to 258 mmH(2)O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl. CONCLUSIONS: We recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.

Age Factors↗

PubMed2006

Present status and perspectives of bioartificial kidneys.

Currently, hemodialysis is not adequate as a renal replacement therapy because it provides intermittent treatment and does not provide the metabolic function of renal tubules. The next generation of artificial kidney should replace intermittent hemodialysis with continuous hemofiltration and provide the full metabolic function of renal tubules. The current decade has witnessed the development of bioartificial kidneys using artificial membranes and renal tubular epithelial cells. Active transport and metabolic functions were confirmed in the confluent monolayers of tubular cells on artificial membranes. Bioartificial kidneys have succeeded in improving the prognosis of patients with multiple organ dysfunction, presumably by lowering plasma cytokine levels in patients. For successful treatment of chronic renal failure using bioartificial kidneys, it is necessary to overcome some technical hurdles such as improving the antithrombogenic properties of the surface of artificial membranes and prolonging the function of renal tubule cells on an artificial membrane. Transfection of functional protein genes into renal tubule cells enables bioartificial tubule devices to increase their transport capacity and metabolic functions such as digoxin secretion and water transport. The development of wearable roller pumps is also essential for the clinical application of a continuous treatment system.

Biomedical Research↗

PubMed2006

Noninvasive method using multidetector CT for calculating the relative blood supply ratio of duplicated renal arteries in renal donors.

PURPOSE: The aim of this study was to evaluate the correlation between the renal artery cross-sectional area measured by multidetector computed tomography (MDCT) and the nephrogram area calculated by renal arteriography in potential living renal donors with duplicated renal arteries. MATERIALS AND METHODS: Medical records of 18 patients with duplicated renal arteries who underwent both MDCT angiography and renal arteriography between 2001 and 2003 were retrospectively reviewed. All 20 kidneys were evaluated. Renal artery cross-sectional areas were measured using the workstation to which the CT data were transferred; the nephrogram areas on the digitized angiographic images were calculated using public domain software. Bland-Altman analysis was performed to compare the cross-sectional area ratio of the accessory arteries to the main renal arteries, with the ratios obtained from the nephrogram areas calculated from the arteriograms. RESULTS: The mean cross-sectional areas of the accessory and main renal arteries were 6.78 and 20.9 mm2, respectively. The ratio of the nephrogram areas calculated from the arteriograms ranged from 0.094 to 0.809. Bland-Altman analysis showed no significant difference. CONCLUSION: It is possible to predict the supply volume of accessory renal arteries by measuring the cross-sectional area of the accessory and main renal arteries in potential living renal donors.

Adult↗

PubMed2006

Video-assisted living donor hemihepatectomy through a 12-cm incision for adult-to-adult liver transplantation.

OBJECTIVES: There has been remarkable progress in recent technical innovations for laparoscopic hepatectomy. However, a laparoscopic procedure rarely has been indicated for donation of the liver in living-related liver transplantation (LRLT). Here, we described the technique and the outcome of video-assisted donor hepatectomy (VADH) for adult-to-adult LRLT. METHODS: For 13 donors in adult-to-adult LRLT, 3 types of major hepatectomy--right hemihepatectomy (3), and left hemihepatectomy, with or without the caudate lobe (10)--were performed through video-assisted procedures; surgical manipulation via ports or via a 12-cm incision and viewing through a laparoscope or through incision were combined and used. RESULTS: VADH was completed in 13 donors, with a median operation time of 363 +/- 33 minutes and a median blood loss of 302 +/- 191 mL. No complications specific to video-assisted procedures, postoperative bile leak, or bleeding were observed. The restoration of the liver function was smooth, and the use of an analgesic (median: 1.2 times) was reduced, compared with the historical control (median: 3.8 times) that underwent a standard donation of the liver. Currently, all donors are healthy and have returned to their previous activities. The grafts have been functioning well, excluding 3 recipients who succumbed to serious complications unrelated to the video-assisted procedure. CONCLUSION: We have shown a new method of VADH through a 12-cm laparotomy for adult-to-adult LRLT. This technique is as feasible as standard open donor hepatectomy, with less pain and with improved postoperative symptoms.

Adult↗

PubMed2006

Present status and perspective of the development of a bioartificial kidney for chronic renal failure patients.

A bioartificial tubule device was applied for the treatment of 10 acute renal failure and multiple organ failure patients by Humes et al. A bioartificial kidney for chronic renal failure patients, however, has never been applied. In order to develop a bioartificial kidney for preventing and treating long-term complications of maintenance dialysis patients, we have to overcome difficulties such as antithrombogenic issue of hemofilters and development of long functioning tubule devices in the context of economical and easy treatment. Continuous hemofilters should modify with an antithrombogenic material on the inner surfaces of membranes to get more hemocompatible characteristics. We are developing an antithrombogenic continuous hemofilter coating with methacryloyloxyethyl phosphorylcholine polymer which will mimic phospholipid layers of human cell membrane on the inner surface of a hemofilter. The transportability of H2O, Na+, and glucose of bioartificial tubule devices using polysulfone hollow fiber modules and porcine proximal tubular epithelial cells LLC-PK1 were evaluated using two kinds of circuits of different medium inside and outside of the cell-attached hollow fiber membrane. Transport of H2O, Na+, and glucose were significantly increased when 2.5 g/dL of albumin was added, and plateaued on the eight day and then decreased thereafter until the 13th day. Transfection of a specific gene into human tubular epithelial cells might be required to keep contact inhibition in order to maintain a confluent monolayer for longer duration.

Animals↗

PubMed2006

Computer-assisted spherical osteotomy with a curved-bladed Tuke Saw.

Techniques for spherical osteotomy, such as rotational acetabular osteotomy, can help orthopaedic surgeons correct bony deformities and remove spherical acetabular components. Curved chisels are used during a spherical osteotomy, but they require skill and have a potential risk of damaging blood vessels or nerves. In order to perform a precise, quick and safe spherical osteotomy, we have developed a novel computer-assisted surgical tool using a vibrating bone saw, the Tuke Saw, with a curved blade that operates under the guidance of an optical navigation system. In this study, the accuracy and ease of use of this curved-bladed Tuke Saw in spherical osteotomy were examined in comparison with the conventional curved chisel. Using these surgical tools, hemispherical osteotomies were performed on rectangular parallelepiped Sawbones blocks and rotational acetabular osteotomies were performed on cadaveric pelves. The distance error with the curved-bladed Tuke Saw was significantly smaller than that with the curved chisel, and the procedure time with the Tuke Saw was approximately half that with the chisel. It can thus be concluded that the curved-bladed Tuke Saw is more accurate and easier to use than the conventional curved chisel.

Acetabulum↗

PubMed2005

Augmentation of heme oxygenase-1 expression in the graft immediately after implantation in adult living-donor liver transplantation.

Heme oxygenase (HO)-1 is a cytoprotective protein and has recently been identified as a graft survival gene. However, there are little data currently available regarding the expression of HO-1 in human living-related liver transplantation. This is the first report that HO-1 expression is increased in small-for-size liver allografts. We performed biopsies of the graft liver and donor liver left in six patients at four time points during the procedure and studied HO-1 expression by reverse-transcriptase polymerase chain reaction and immunohistochemistry. HO-1 mRNA was expressed at a low level in steady-state liver tissue but was strongly expressed after perfusion of the graft liver. HO-1 expression increased in nonparenchymal cells in the human graft liver. The number of HO-1 positive cells increased threefold by the end of liver transplantation. This study suggests that ischemia-reperfusion injury and excessive shear stress secondary to portal hypertension might augment HO-1 expression in the graft liver.

Female↗

PubMed2005

Assessment of the three-dimensional relationship of the ossific nuclei and cartilaginous anlagen in congenital clubfoot by 3-D MRI.

PURPOSE: Radiographic measurement is the usual method used to objectively determine the extent of a congenital clubfoot deformity. Although radiographs have been used clinically to estimate the size and location of tarsal bones through measurements of the ossific nuclei, it is not clear to what extent these relationships are actually reflected in these measurements. So, we used a 3-D MRI system that could more objectively estimate sizes and positional relationships. MATERIAL AND METHOD: We evaluated 5 patients with unilateral congenital clubfoot deformity. Magnetic resonance imaging was performed of both feet using 1.5-T magnet. Based on the resulting magnetic resonance imaging volume data, a three-dimensional surface bone model was reconstructed by the Marching Cubes method. We used this model to perform a comparative analysis of the volume and volume ratio of each cartilaginous anlage and ossific nucleus, the length of the talus and the calcaneus, and the position of the center of gravity of ossific nuclei within the cartilaginous anlagen. We measured the relationship between the ossific nuclei and cartilaginous anlagen in the talus and calcaneus of patients with unilateral clubfoot deformity. RESULT: In clubfeet talus volume was reduced by 20.1% and calcaneal volume was reduced by 15.7%. Furthermore, the volume of the talar ossific nucleus was reduced by 42.6% and that of the calcaneal ossific nucleus was reduced by 12.1%. The length of the clubfoot talus was 8.2% shorter than normal, and that of the calcaneus was 4.8% shorter. CONCLUSION: The assessment technique presented herein was shown to be useful in ascertaining the various pathological characteristics associated with clubfoot.

Calcaneus↗

PubMed2005

[Development of three-dimensional kinematic analysis system for artificial knee implants using X-ray fluoroscopic imaging].

To achieve quantitative assessment of 3D dynamic motion of artificial knee implants under clinical conditions, we developed a 3D kinematic analysis system using X-ray fluoroscopic imaging. The 3D pose-estimation technique for knee implants was built on a 2D/3D registration algorithm, which determines the spatial pose for each femoral and tibial component from the knee implant contours and computer-assisted design (CAD) models of the implant. In order to validate the accuracy of the 3D pose estimation and the system, computer simulation and in vitro tests were performed using images of knee implants taken in 10 different poses with respect to X-ray focus. Computer simulation tests showed that the root mean square errors (RMSE) for all variables were less than 1.0 mm 1.0 degrees. In vitro tests showed that the RMSE for translation perpendicular to the X-ray image plane was about 1.5 mm, while the accuracy of the remaining two translational and three rotational variables was found to be sufficient for analyzing knee kinematics. Computation time in 3D pose estimation was then obtained in less than 30 seconds for each frame. In clinical application, dynamic movement in deep knee bending was quantitatively analyzed, and the feasibility and effectiveness of the system was demonstrated.

Algorithms↗

PubMed2005

Application of 3D-MR image registration to monitor diseases around the knee joint.

PURPOSE: To estimate the accuracy and consistency of a method using a voxel-based MR image registration algorithm for precise monitoring of knee joint diseases. MATERIALS AND METHODS: Rigid body transformation was calculated using a normalized cross-correlation (NCC) algorithm involving simple manual segmentation of the bone region based on its anatomical features. The accuracy of registration was evaluated using four phantoms, followed by a consistency test using MR data from the 11 patients with knee joint disease. RESULTS: The registration accuracy in the phantom experiment was 0.49+/-0.19 mm (SD) for the femur and 0.56+/-0.21 mm (SD) for the tibia. The consistency value in the experiment using clinical data was 0.69+/-0.25 mm (SD) for the femur and 0.77+/-0.37 mm (SD) for the tibia. These values were all smaller than a voxel (1.25 x 1.25 x 1.5 mm). CONCLUSION: The present method based on an NCC algorithm can be used to register serial MR images of the knee joint with error on the order of a sub-voxel. This method would be useful for precisely assessing therapeutic response and monitoring knee joint diseases; normalized cross-correlation; accuracy.

Algorithms↗

PubMed2005

Usefulness of three-dimensional multidetector-row CT images for preoperative evaluation of tumor extension in primary breast cancer patients.

PURPOSE: Usefulness of three dimensional (3D) multidetector-row CT (MDCT) images for preoperative evaluation of tumor extension was studied in primary breast cancer patients. METHODS: 3D-MDCT tumor images of 143 tumors in 143 patients with primary breast cancer were created with the volume rendering method. The transverse tumor size (TS) and vertical tumor size (VS) were then measured in an anterior-posterior view of the 3D-MDCT images. The pathological tumor size was determined according to a map of the tumor spread prepared by pathologists using multi-sliced (3-5 mm intervals) surgical specimens and compared with the tumor size on 3D-MDCT images. RESULTS: First, the optimal method for creating 3D-MDCT tumor images was determined for the first 40 patients (learning set), resulting in a fairly good correlation of tumor size on 3D-MDCT images with pathological tumor size (r = 0.983 for TS and r = 0.958 for VS). We then carried out a validation study on the next 103 patients (validation set). The 3D-MDCT tumor size's strong correlation with the pathological tumor size demonstrated a high rate of accuracy (r = 0.974 for TS and r = 0.977 for VS). Subset analyses according to histological type showed that correlation coefficients were r = 0.979 for TS and r = 0.981 for VS of invasive ductal carcinomas (n = 88), r = 0.948 for TS and r = 0.970 for VS of ductal carcinomas in situ (n = 10), and r = 0.984 for TS and r = 0.976 for VS of invasive lobular carcinomas (n = 5). CONCLUSION: 3D-MDCT images can assess breast cancer tumor extension highly accurately, and thus seems to be useful for planning the extent of resection in breast conserving surgery.

Adult↗

PubMed2005

Application of three-dimensional magnetic resonance image registration for monitoring hip joint diseases.

The purpose of this study was to estimate the accuracy of a method in which three-dimensional (3D) magnetic resonance (MR) volume registration is used for monitoring hip joint disease. Data were analyzed using a normalized cross-correlation (NCC) algorithm involving a user-selected 3D box including the proximal femur. Most of the femoral head was not included in the 3D box because it can become deformed during the course of disease. The accuracy of registration around the femoral head was evaluated using five phantoms and clinical MR data of 17 patients with hip joint disease. In the phantom experiment, registration accuracy was evaluated using four fiducial markers attached to the femoral head. In the experiment using clinical data, registration accuracy was evaluated using a landmark in the femoral head. The registration accuracy in the phantom and clinical experiment was 0.43+/-0.18 mm (S.D.) and 1.12+/-0.46 mm (S.D.), respectively. The former is a value less than half the minimum dimension of a voxel (1.25 x 1.25 x 1.0 mm). Although the latter is slightly larger than the minimum dimension of a voxel, actual errors would be smaller because of the uncertainty in landmark localization. In conclusion, the present method based on an NCC algorithm can be used to accurately register serial MR images of the femoral heads with an error on the order of a voxel. We believe that this method is sufficiently accurate for monitoring hip joint diseases.

Algorithms↗

PubMed2005

Hepatic natural killer and natural killer T cells markedly decreased in two cases of drug-induced fulminant hepatic failure rescued by living donor liver transplantation.

The human liver contains significant numbers of innate immune cells, such as natural killer (NK) cells and natural killer T (NKT) cells, which express both T-cell receptors and NK-cell receptors simultaneously. It has been suggested that the innate immune system plays a crucial role in the liver. In this report, the distribution of NK and NKT cells in the liver and peripheral blood of two patients with drug-induced fulminant hepatic failure (FHF) who had undergone living donor liver transplantation was examined. In both the liver and peripheral blood, the proportions of NK and NKT cells markedly decreased compared with those in healthy donors. It was also revealed that, unlike murine NKT cells, human CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is one of the important costimulatory molecules on T cells. Additionally, the residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28 than in controls. This result suggests that NKT cells might be more activated in FHF. Although the accumulation of further cases is required, it is suggested that both NK and NKT cells might be involved in hepatic injury in FHF.

Adult↗