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Eiichi Sato

Publications and source records attributed to Eiichi Sato.

At least 19 recordsLinked to original sources
PubMed2007

Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C.

PURPOSE: To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. METHODS: Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. RESULTS: Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. CONCLUSIONS: RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.

Adult↗
PubMed2006

In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines.

Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice resulted in the regression of established NY-ESO-1-expressing tumors. Intratumoral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1-specific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimurium type III secretion system is a promising novel strategy for cancer vaccine development.

Animals↗
PubMed2006

Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection.

The pathophysiological significance of matrix metalloproteinases (MMPs) in aortic dissection remains poorly understood. The purpose of the present study is to clarify the significance of MMPs in aortic dissection. The activities and distributions of MMP-2, membrane-type 1-MMP (MT1-MMP), and MMP-9 were evaluated by gelatin zymography, immunohistochemistry, and in situ hybridization in 29 patients and seven autopsy cases. To assess if these MMPs are related to a tissue remodeling process, we compared the expression of these MMPs with that of type I procollagen and platelet-derived growth factor receptor beta chain (PDGF Rbeta). Patients were divided into three groups based on histological findings: acute, intermediate, and healed groups. The most remarkable changes were observed in the intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima, organizing thrombus, and the adventitia. These expression patterns were essentially coupled with those of type I procollagen mRNA and PDGF-Rbeta protein. The association of MMP-2, MT1-MMP, type I procollagen, and PDGF-Rbeta suggests that MMP-2 and MT1-MMP could be involved not only in the degradation of aortic tissue but also in tissue remodeling, which may be associated with the healing process.

Aged↗
PubMed2006

Prediction of ambulation prognosis in the elderly after hip fracture.

We investigated the factors influencing ambulation prognosis after hip fracture in the elderly patient and examined whether it is possible to predict the ambulation status upon hospital discharge at the time of admission. Two hundred and five patients aged 60 or older with a hip fracture who were ambulant before injury were studied. The patients were divided into two groups according to their ability to walk at the time of discharge from hospital: the ambulatory group and the non-ambulatory group. We assessed the value of various predictive factors. At discharge, 136 patients (66.3%) were ambulatory while 69 patients (33.7%) were non-ambulatory. Factors significantly affecting walking ability at discharge were: (1) age, (2) dementia, (3) residence before injury, (4) anaemia, (5) electrolyte abnormality, (6) abnormal chest X-ray, and (7) chronic systemic disease. Each patient was scored on the basis of the above factors (1=yes, 0=no), and the total was used as the predictive score. The mean score was significantly higher (p<0.0005) in the non-ambulatory group. It is possible to predict ambulation prognosis after hip fracture using our scoring system at the time of admission.

Aged↗
PubMed2006

Association between systemic arterial stiffness and age-related macular degeneration.

BACKGROUND: A number of epidemiological studies suggest that age-related macular degeneration (AMD) and cardiovascular disease share the same risk factors. Systemic arterial stiffness is a clear indicator of cardiovascular disease. We investigated whether there is an association between directly measured systemic arterial stiffness and the presence of AMD. METHODS: We used a SphygmoCor 2000 system to noninvasively measure two indicators of the systemic arterial stiffness, the arterial pulse wave velocity (PWV) and the central aortic blood pressure waveform, from which the augmentation pressure is determined. We studied 50 patients with AMD (12 men, 38 women, aged 60 to 91 years, mean 77 years) and 11 age-matched control subjects (3 men, 8 women, aged 66 to 92 years, mean 75 years). All study subjects received a complete ophthalmic examination including digital fundus photography. All of the patients with AMD were classified as stage 3 or worse in at least one eye according to the AREDS system. RESULTS: Pulse wave velocity was significantly higher in the patients with AMD (8.2+/-1.1 m/s, mean +/- SD) compared with controls (7.1+/-0.8 m/s, p=0.0025), indicating increased arterial stiffness. There was no significant difference in PWV in AMD patients with and without choroidal neovascularization. There was no association between PWV and the presence of hypertension in either the patients or the controls. The central aortic augmentation pressure was significantly higher in the AMD patients than in the controls (p=0.040), also indicating increased arterial stiffness. CONCLUSIONS: Patients with AMD have increased systemic arterial stiffness compared with age-matched controls. Treatments aimed at preventing or reversing systemic arterial stiffness may also be effective in preventing the onset or slowing the progression of AMD.

Aged↗
PubMed2006

Glycoprotein A34, a novel target for antibody-based cancer immunotherapy.

To identify novel, tissue-restricted cell surface proteins in cancer which can serve as targets for antibody-based diagnostics and therapeutics, a translated version of the expressed sequence tag database (tblastn) was mined for transcripts with similarity to the glycoprotein A33 (GPA33) colon cancer antigen. A novel human transcript, termed A34, was identified which encoded a putative cell surface protein, GPA34, which is approximately 30% identical to GPA33 and other members of the junctional adhesion molecule (JAM) family. Conventional end-point and quantitative real-time RT-PCR showed that A34 mRNA expression is highly tissue-restricted, as it is expressed predominantly in stomach and testis. A34 mRNA was also detected in 6/19 (31%) gastric cancers, 8/16 (50%) esophageal carcinomas, and 4/17 (23%) ovarian cancers, but not in lung, breast or colon carcinomas. A murine monoclonal antibody (mAb A34) was generated to the extracellular domain of the A34 protein and used to biochemically and immunohistochemically characterize the A34 antigenic system. The mAb A34 specifically recognized glycoproteins ranging in apparent size from 55-70 kDa, present in normal gastric mucosa and in COS-7 cells transfected with A34 cDNA. Of 31 different normal tissues examined by immunohistochemistry, GPA34 protein expression was detected primarily in normal stomach mucosa and testicular germ cells, and in the tumor cells of 5/17 (29%) gastric cancers, 7/11 (63%) esophageal cancers, and 2/21 (9%) ovarian cancers, in agreement with gene expression results. The A34 antigen and monoclonal antibody may be of considerable value for immunotherapy of different types of cancer.

Amino Acid Sequence↗
PubMed2006

Effect of systemic administration of simvastatin on retinal circulation.

OBJECTIVE: To investigate the effect of systemic administration of simvastatin on the retinal circulation. METHODS: The effects of systemic administration of simvastatin on the retinal circulation after 90 minutes and after 7 days were studied in a placebo-controlled, double-masked, clinical trial among 12 healthy men. We used laser Doppler velocimetry to measure vessel diameter and blood velocity and calculated the blood flow in retinal arteries and veins. We also measured the intraocular pressure and the plasma nitrite/nitrate levels, the stable end products of nitric oxide metabolism. RESULTS: There were no significant changes in any retinal circulatory parameters at 90 minutes after administration of simvastatin. Daily administration of simvastatin for 7 days significantly increased blood velocity and blood flow in retinal arteries and veins but did not significantly change vessel diameter. The intraocular pressure significantly decreased at 90 minutes and at 7 days after administration of simvastatin. Simvastatin also significantly increased the plasma nitrite/nitrate levels. CONCLUSION: Simvastatin induced an increase in blood velocity and blood flow in retinal arteries and veins, increased the plasma nitrite/nitrate levels, and decreased the intraocular pressure, probably through the increase in nitric oxide.

Administration, Oral↗
PubMed2006

In vivo evaluation of the improved MCMS-0102 pacemaker with a rapid pacing mode for induction of experimental heart failure in animals.

The MCMS-0102 cardiac pacemaker for rapid ventricular pacing to induce heart failure in animals has been improved in terms of miniaturization and performance. To determine the performance of the new MCMS-0102, six devices were implanted in beagle dogs, and two of these devices were reimplanted for continued pacing in a total of eight beagle dogs. The hearts were paced at 260 beats per minute for 4 weeks (P group: n = 8). The hemodynamic status of the P group was examined and compared with nonpaced dogs (NP group: n = 8). The neurohumoral status of the P group was evaluated before and after rapid pacing. Stable operation of the six devices during rapid pacing was confirmed using the telemetry system. Postmortem examinations revealed features similar to clinical heart failure characterized by massive ascites, pleural effusion, cardiomegaly, and liver congestion in all the paced dogs. Cardiac output was 1.1 +/- 0.2 l/min in the NP group and 0.5 +/- 0.1 l/min in the P group (P < 0.0001). The left atrial pressure and the central venous pressure of the P group and the NP group were 23 +/- 6 versus 6 +/- 2 mmHg (P < 0.0001) and 10 +/- 3 versus 4 +/- 3 mmHg (P < 0.001), respectively. In the paced dogs, plasma renin activity increased from 0.5 +/- 0.4 to 8.5 +/- 7.4 ng/ml/h (P < 0.05) and atrial natriuretic peptide levels increased from 69 +/- 41 to 229 +/- 72 pg/ml (P < 0.001). The improved MCMS-0102 was successfully implanted in beagle dogs and it succeeded in inducing the congestive heart failure model.

Animals↗
PubMed2006

Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation: first histologically confirmed case.

The present case involves unique enteritis forming multiple ulcers associated with Epstein-Barr virus (EBV). A 57-year-old man had undergone a reduced intensity allogeneic stem cell transplantation for a relapse of multiple myeloma following sequential autologous peripheral blood stem cell transplantation. The ileum, resected for massive melena, showed multiple irregular ulcers with occasional cobblestone-like appearance. There was inflammation including numerous plasma cells in the ulcer bases and surrounding areas, where many EBV-infected plasma cells were detected by double staining with EBV-encoded small RNA-1 (EBER-1) in situ hybridization and CD79a, while EBV-infected epithelial cells were not noted. The number of EBER-1-positive cells in the ileum (mucosa, 1451 cells/mm(2); submucosa, 465 cells/mm(2)) was much larger than in control samples (malignant lymphoma or leukemia after allogeneic stem cell transplantation, n = 4, range 0-113 cells/mm(2); malignant lymphoma after chemotherapy, n = 14, range 0-0.89 cells/mm(2); colon cancer, n = 12, range 0-3.5 cells/mm(2)). In the mucosa near the ulcers, EBER-1-positive cells often surrounded and involved the glandular epithelium, forming lymphoepithelial-like lesions. The histological findings differ from post-transplant lymphoproliferative disorders or intestinal thrombotic microangiopathy, and this is the first case of EBV-associated enteritis with ulcers characterized by numerous plasma cells and lymphoepithelial-like lesions after stem cell transplantation.

CD79 Antigens↗
PubMed2005

Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer.

In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer.

Adult↗
PubMed2005

Combined use of SLO microperimetry and OCT for retinal functional and structural testing.

BACKGROUND: This study compared SLO microperimetry scotoma size measurements with the sizes of lesions assessed with OCT in the areas of scotoma. METHODS: SLO microperimetry was performed on eight patients to assess the location and extent of scotoma areas. An SLO microperimetry master image was used to localize the scotoma areas in the real time OCT fundus image and to center OCT cross scans on the areas of scotoma. The sizes of the morphological changes measured by OCT were compared with the scotoma size measurements. RESULTS: In each patient, OCT revealed a morphological change located in the area of scotoma. Scotoma sizes ranged from 465 to 3180 microm horizontally and from 570 to 2550 microm vertically. The corresponding lesion sizes ranged from 461 to 2660 microm horizontally and from 523 to 2282 microm vertically. The average difference between SLO and OCT measurements was 2.4% horizontally and 4.9% vertically. There were significant correlations between horizontal and vertical SLO and OCT measurements (Horizontal: R (sq)=0.955, P<0.0001; Vertical: R (sq)=0.898, P=0.0003). CONCLUSION: SLO microperimetry scotoma size measurements and OCT lesion size measurements are similar to each other. Combining retinal functional testing with morphological testing provides information about the underlying causes of scotoma.

Female↗
PubMed2005

Accumulation of CCR5+ T cells around RANTES+ granulomas in Crohn's disease: a pivotal site of Th1-shifted immune response?

Immunological abnormalities are implicated in the pathogenesis of inflammatory bowel disease (IBD), that is, Crohn's disease and ulcerative colitis. In particular, Crohn's disease is considered to be a T helper type 1 (Th1)-shifted disease. Chemokines and their receptors are involved in various immune responses including Th1- and Th2 responses. In this study, we analyzed chemokines and their receptors by immunohistochemistry, using frozen sections derived from 33 patients with Crohn's disease and 24 with ulcerative colitis. In inflamed mucosa, small mononuclear cells predominantly expressed CCR5 and CXCR3, the receptors selectively expressed on Th1 cells, without significant differences between Crohn's disease and ulcerative colitis. We then focused on the noncaseating granulomas that are characteristic of Crohn's disease. Granuloma cells, observed in all the layers of intestinal tissues, were positive for RANTES/CCL5 protein along their cell membranes. Lymphocytes surrounding granulomas were mostly CCR5+ and CXCR3+ T cells with CD4+ and CD8+ cells at similar frequencies. Granuloma cells were positive for RANTES mRNA by in situ hybridization. By contrast, lymphoid aggregates in Crohn's disease and lymphoid follicles in the normal intestinal mucosa were characterized by abundant B cells, a predominance of CD4+ T cells over CD8+ T cells, and low frequencies of cells expressing CCR5 or CXCR3. Together with the notion that granuloma cells are possible antigen-presenting cells, our results suggest that the noncaseating granulomas could be one of the crucial sites of Th1-shifted immune responses in Crohn's disease.

Adolescent↗
PubMed2005

Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison with other melanocyte differentiation markers.

PNL2 is a novel monoclonal antibody, which has recently been introduced as an immunohistochemical reagent to stain melanocyte and tumors derived thereof. In the present study, we analyzed the immunoreactivity of this mAb in various normal tissues, melanocytic nevi, primary and metastatic melanoma, nonmelanocytic tumors, including histologic mimickers of melanoma as well as angiomyolipoma, and multiple cell lines derived from different tumors types. We used several tissue microarray panels as well as selected conventional sections from tissue blocks. For metastatic melanoma, immunoreactivity for PNL2 was compared with A103 (Melan-A/MART-1), T311 (tyrosinase), HMB45 (gp100), and D5 (MITF). Positive staining with PNL2 was found in normal melanocytes and neutrophils, but no other normal cell type. Among melanocytic lesions, both benign nevi as well as primary malignant melanomas, especially epithelioid variants thereof, were commonly immunopositive. Only 1 of 13 desmoplastic melanomas reacted with PNL2. PNL2 showed high sensitivity for metastatic melanoma (87%). In comparison, 82% of metastatic melanomas were positive for A103, 76% for HMB45, 92% for T311, and 84% for D5. The combined use of all five reagents minimized the number of immunonegative cases. None of the selected nonmelanocytic tumors (carcinomas or soft tissue neoplasms) was positive for PNL2 in this series except for angiomyolipomas and chronic myeloid leukemias and 1 single case of a malignant peripheral nerve sheath tumor with heterologous differentiation (malignant Triton tumor). Despite its reactivity with neutrophils, PNL2 appears to be a valuable supplementary reagent for the diagnosis of melanocytic tumors.

Antibodies, Monoclonal↗
PubMed2005

Compact monochromatic flash x-ray generator utilizing a disk-cathode molybdenum tube.

The high-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -50 to -70 kV by a power supply, and the electric charges in the condensers are discharged to an x-ray tube after closing gap switches in the surge generator with a trigger device. The x-ray tube is a demountable diode, and the turbo molecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Clean molybdenum Kalpha lines are produced using a 20 microm-thick zirconium filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. At a charging voltage of -70 kV, the instantaneous tube voltage and current were 120 kV and 1.0 kA, respectively. The x-ray pulse widths were approximately 70 ns, and the generator produced instantaneous number of Kalpha photons was approximately 3 x 10(7) photons/cm2 per pulse at 0.5 m from the source of 3.0 mm in diameter.

Animals↗
PubMed2005

Relationship between the parameters of retinal circulation measured by laser Doppler velocimetry and a marker of early systemic atherosclerosis.

PURPOSE: To examine the relation between intima-media thickness (IMT) in the common carotid artery, which is generally recognized as a marker of early atherosclerosis, and retinal circulatory parameters. METHODS: The vessel diameter and blood velocity of retinal arterioles were measured with laser Doppler velocimetry (LDV) in 33 patients with coronary artery disease (CAD), because they were thought to have general atherosclerosis. The retinal blood flow (RBF) and wall shear rate (WSR), an index of wall shear stress in retinal vessels, were calculated from the two parameters. The carotid IMT was evaluated with B-mode ultrasonography. RESULTS: The patients were divided into two groups: those with an IMT >0.70 mm and those with an IMT < or =0.70 mm. The blood velocity, WSR, and upstroke time in the retinal arterioles were significantly higher in the group with an IMT >0.70 mm compared with the group with an IMT < or =0.70 mm. There were no significant differences in vessel diameter and RBF between the groups. Positive correlations were found between the carotid IMT and blood velocity (r = 0.51, P = 0.002) and WSR (r = 0.60, P = 0.0001). Multiple regression analysis showed that the retinal WSR and blood velocity correlated independently with the IMT in patients with CAD. CONCLUSIONS: The present findings from this pilot study suggest that the retinal circulatory parameters measured by LDV may be associated with systemic atherosclerosis. These results support recent studies showing an association between retinal microvascular changes and cardiovascular disease.

Aged↗
PubMed2004

IFN-gamma enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.

We compared monocyte-derived dendritic cells and transforming growth factor-beta1-induced Langerhans-like cells (LCs) for their capacity to cross-present exogenous NY-ESO-1 protein/antibody immune complexes to an NY-ESO-1-specific CD8+ T cell clone. In contrast to dendritic cells, LCs were not able to cross-present NY-ESO-1 to the T cell clone constitutively but did so after treatment with IFN-gamma. Remarkably, this IFN-gamma-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. Rather, IFN-gamma acted at least in part by potentiating the maturation of otherwise refractory LCs, enabling in turn exogenous antigen to reach the processing machinery. This model of conditional cross-presentation establishes an original level of action for IFN-gamma as an effective immune modulator and supports the use of IFN-gamma in protein vaccination strategies targeting LCs.

Amino Acid Sequence↗
PubMed2004

Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception.

Neurotensin (NT) is a neuropeptide that induces a wide range of biological activities including hypothermia and analgesia. Such effects are mediated by the NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in specific NT functions remains unknown. To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM). The mutant and control mice were subjected to the examination of thermal nociception, and in the hot plate test, a significant alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1-deficient or wild-type control mice. Latencies of tail flick and hind paw licking of the mutant mice were not affected compared to control mice. These results suggest that Ntsr2 has an important role in thermal nociception compared to Ntsr1, and that these mutant mice may represent a useful tool for the development of analgesic drugs.

Animals↗