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Shigeru Sato

Publications and source records attributed to Shigeru Sato.

52 records · Page 3Linked to original sources
PubMed2003

Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis.

Multiple sclerosis (MS) is considered to be an autoimmune disease mediated by T cells reactive with Ags in the CNS. Therefore, it has been postulated that neuroantigen-reactive T cells bearing particular types of TCRs are expanded clonally during the course of the disease. However, there is a controversy with regard to the TCR usage by T cells associated with the development of MS. By the use of complementarity-determining region 3 spectratyping analysis that is shown to be a useful tool for identification of pathogenic TCR in autoimmune disease models, we tried to demonstrate that spectratype was T cells bearing particular types of TCR are activated in MS patients. Consequently, it was found that Vbeta5.2 were often oligoclonally expanded in peripheral blood of MS patients, but not of healthy subjects. Sequence analysis of the complementarity-determining region 3 region of spectratype-derived TCR clones revealed that the predominant TCR clone was different from patient to patient, but that similar results were obtained in a patient examined at different time points. More importantly, examination of cerebrospinal fluid T cells and longitudinal studies of PBLs from selected patients revealed that Vbeta5.2 expansion was detectable in the majority of patients examined. These findings suggest that Vbeta5.2 spectratype expansion is associated with the development of MS and that TCR-based immunotherapy can be applicable to MS patients if the TCR activation pattern of each patient is determined at different stages of the disease.

Adolescent↗
PubMed2003

Chronic effects of ethanol on cultured myocardial cells: ultrastructural and morphometric studies.

Ultrastructural alterations of the myocardium due to chronic ethanol exposure were investigated using an in vitro system-mouse ventricular myocardial cells in a monolayer culture, which were spontaneously and synchronously contracting-by chronic exposure to 12.5, 50, and 200 mM ethanol for up to 21 days. Morphometric analyses revealed that exposure to 12.5 mM ethanol for 14 days induced an increase in the number of residual bodies, which are lysosomes containing electron-dense, amorphous materials. Some cells exposed to 50 mM ethanol for 14 days contained an accumulation of glycogen granules, increasing in inverse proportion to the mitochondrial volume. The volumetric proportion of myofibrils on day 14 decreased as the ethanol dose became lower, and was in proportion to large and giant mitochondria within the limits of three ethanol groups. Dose-dependent increases in the size and volumetric proportion of mitochondria were observed after the 14-day exposure; at a low dose (12.5 mM) mitochondria of usual size tended to increase, whereas at a high dose (200 mM) giant mitochondria increased. Coincidentally with this mitochondrial increase or gigantism, all ethanol groups showed higher beat rates than the control. Consequently, it is most likely that chronic 14-day exposures to these three ethanol doses remodel the cellular function of the in vitro myocardium in different ways; the 200-mM dose induced mitochondrial hypertrophy, an adaptive response to switch myocardial energy metabolism over to some special one; the 50-mM dose was a boundary dose; and the 12.5-mM dose mostly mimicked the chronic in vivo administration of ethanol and induced slightly degenerative alterations-increased residual bodies and lysosomes, decreased myofibrils and lowered mitochondrial respiratory function.

Animals↗
PubMed2003

Ultrastructural changes elicited by a non-ablative wrinkle reduction laser.

BACKGROUND AND OBJECTIVES: Cosmeceuticals, chemical peels and collagen injections are used to rejuvenate skin, but none of these methods is effective or permanent. Recently, laser resurfacing has been found to be effective, but the incidence of side effects is relatively high. Two years ago, the non-ablative wrinkle reduction laser (N-Lite, ICN Photonics, UK) was developed, and there have been several reports about its clinical effectiveness. In this study, we have investigated ultrastructural changes elicited by exposure to the N-Lite laser. STUDY DESIGN/MATERIALS AND METHODS: Eight adult volunteers were recruited for this study. They were treated with the N-Lite laser and 3-mm skin punch biopsies were obtained 3 hours, 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks after the laser exposure. These specimens were examined by electron microscopy. RESULTS: Three hours after the laser therapy, the capillaries showed endothelial cell edema with hemostasis and marked edema was observed around them. Neutrophils, monocytes and mast cells were observed in the extravascular dermis. These acute dermal inflammatory changes were observed until 1 week after the laser treatment. Two weeks after the laser treatment, the capillaries showed an almost normal structure, and dermal edema was not observed around them. New elastic fibers and collagen fibers had increased around the capillaries. Four weeks after the laser treatment, interstitial fibrosis was observed around the capillaries. CONCLUSIONS: N-Lite laser irradiation leads to interstitial fibrosis, especially around the capillaries, 4 weeks after the laser irradiation.

Adult↗
PubMed2003

Identification of an electron densification of the glomerular basement membrane in renal biopsy specimens.

Ultrastructural examination of renal biopsy specimens is often necessary to establish a diagnosis. We have noted, in some renal biopsies, that normal-appearing glomerular basement membrane (GBM) shows an electron densification. The aim of this study was to describe this phenomenon and assess the degree of its occurrence. We reviewed ultrastructural pathology records of 153 renal biopsy patients with special reference to the careful examination of the electron micrographs. Of these, 28 cases (18%) showed a definite and homogeneous electron densification of normal-appearing GBM in the glomeruli. The pathological diagnosis in these cases was IgA nephropathy in 15, minimal change nephrotic syndrome in 6, interstitial nephritis in 3, membranoproliferative glomerulonephritis in 2, and nephritis of Henoch-Schonlein purpura and membranous nephropathy in 1 case each. In addition, frequent deposition of IgG without C3 in the GBM (86%) and glomerular endothelial cell edema (96%) were observed. No apparent correlation could be ascertained between the presence of the electron densification and pathological diagnosis. It is suggested that electron densification of the GBM may be caused by the penetration of some electron-dense materials into the GBM as a result of an abnormality in the glomerular filtration barrier and that this could be considered as a sign of altered properties of the lamina densa.

Adolescent↗
PubMed2003

Use of oolong tea extract (OTE) for elastin staining and enhancement in ultrathin sections.

To assess the usefulness of oolong tea extract (OTE) staining for connective tissue observation, we examined the visceral pleural mesothelium of rat lung by transmission electron microscope. Four kinds of electron microscopic staining methods (routine, tannic acid, OTE in distilled water, and OTE in 0.1 M phosphate buffer) were compared to determine the most suitable method for electron microscopic observation of ultrathin sections. Elastin (elastic laminae) was selectively stained by tannic acid and both water and buffered OTE. Except for elastin, connective tissue and cell ultrastructures were also electron enhanced by tannic acid and both water and buffered OTE staining. However, using water OTE, the electron-dense filaments (10-12 nm in diameter) were obscured. In tannic acid staining, the unit membranes of the visceral pleural mesothelial cells were weaker as compared with routine and buffered OTE stains. Thus, the buffered OTE staining method is a highly useful technique for connective tissue observation and electron-enhanced staining in transmission electron microscopic preparations.

Animals↗
PubMed2003

Cloning and functional analysis of ascidian Mitf in vivo: insights into the origin of vertebrate pigment cells.

The microphthalmia-associated transcription factor (Mitf) is a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) transcription factor essential for the development and function of all melanin-producing pigment cells in vertebrates. To elucidate the evolutionary history of Mitf and the antiquity of its association with pigment cells, we have isolated and characterized HrMitf, a sole member of the Mitf-TFE bHLH-ZIP subfamily in the ascidian Halocynthia roretzi. Maternal HrMitf mRNA is detected in the fertilized egg and in the animal hemisphere from 4-cell stage through the gastrula stage. From the neurula through the early tailbud stage, HrMitf is preferentially expressed in the pigment-lineage cells that express the lineage-specific melanogenesis genes tyrosinase (HrTyr) and Tyrp. Overexpression of HrMitf induced ectopic expression of HrTyr enzyme activity in mesenchymal cells where the same enzyme activity was induced by overexpression of HrPax3/7, suggesting that a part(s) of the Pax3-Mitf-tyrosinase gene regulatory cascade seen in vertebrate melanocytes is operative during ascidian embryogenesis. We also show HrMitf and mouse Mitf-A, a Mitf isoform abundantly expressed in pigmented epithelial cells, share similar functional characteristics. These results suggest antiquity of the association of the Mitf-TFE subfamily with pigment cells and may support the idea that acquisition of multiple promoters (isoforms) by an ancestral Mitf gene has allowed the evolution of multiple pigment cell types.

Amino Acid Sequence↗
PubMed2003

Interferon-alpha significantly reduces cerebrospinal fluid CD4 cell subsets in HAM/TSP.

We, for the first time, analyzed T cell and natural killer (NK) cell subsets in the cerebrospinal fluid (CSF) in nine patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) treated with interferon-alpha (IFN-alpha). The CD4/CD8 ratio in CSF was significantly lower after the therapy, which is mainly attributable to the significant reduction in CD4+ cells, especially CD25+CD4 and CD45RO+CD4 cell subsets. Meanwhile, NK, natural T and NKT cell subsets in the CSF remained unchanged. There was no CSF lymphocyte subset significantly associated with the clinical efficacy of IFN-alpha in this small-scale study, and more patients should be analyzed to ascertain the link.

Aged↗
PubMed2003

Isolation and developmental expression of tyrosinase family genes in Xenopus laevis.

The tyrosinase family of genes in vertebrates consists of three related members encoding melanogenic enzymes, tyrosinase (Tyr), tyrosinase-related protein-1 (TRP-1, Tyrp1) and tyrosinase-related protein-2 (Dct, TRP-2, Tyrp2). These proteins catalyze melanin production in pigment cells and play important roles in determining vertebrate coloration. This is the first report examining melanogenic gene expression in pigment cells during embryonic development of amphibians. Xenopus provides a useful experimental system for analyzing molecular mechanisms of pigment cells. However, in this animal little information is available not only about the developmental expression but also about the isolation of pigmentation genes. In this study, we isolated homologues of Tyr, Tyrp1 and Dct in Xenopus laevis (XlTyr, XlTyrp1, and XlDct). We studied their expression during development using in situ hybridization and found that all of them are expressed in neural crest-derived melanophores, most of which migrate through the medial pathway, and in the developing diencephalon-derived retinal pigment epithelium (RPE). Further, XlDct was expressed earlier than XlTyr and XlTyrp1, which suggests that XlDct is the most suitable marker gene for melanin-producing cells among them. XlDct expression was detected in migratory melanoblasts and in the unpigmented RPE. In addition, the expression of XlDct was detected in the pineal organ. The sum of these studies suggests that expression of the tyrosinase family of genes is conserved in pigment cells of amphibians and that using XlDct as a marker gene for pigment cells will allow further study of the developmental mechanisms of pigment cell differentiation using Xenopus.

Amino Acid Sequence↗
PubMed2003

[Acceleration of ATP-induced contraction in the obstructed bladder of the rat].

BACKGROUND: Detrusor instability is one of the most common problems in patients with lower urinary tract obstructive diseases, such as benign prostatic hyperplasia. Adenosine triphosphate (ATP) has been associated as a neuronal component in the detrusor instability. MATERIALS AND METHODS: Ninety-six female Splague-Dawley rats were studied. Outflow obstructions were created by ligature of the urethra over which a catheter was placed. Changes in the bladder capacity, and an isovolumetric contractile response to pharmacologic antagonists were studied in the obstructed rats for a period of from one day to four weeks. RESULTS: The bladder capacity of rats obstructed for four weeks increased significantly. Maximum bladder contraction pressure with the use of atropine medication was inhibited in 60 percent and, 30 percent of in the control group, respectively. The inhibitory effect of the maximum bladder contraction pressure by the pyridoxalphosphate-6-azophenyl-2', 4'-disulphonate (PPADS) dosage after the atropine dosage was not recognized it in the control group, but the effect was recognized powerfully in the obstructed group. CONCLUSION: In the obstructed bladder rat, strong rise of the bladder contraction by P2X receptor with a lower urinary obstruction was accepted, and that result reflects positively. Therefore, it was guessed that the result was an end of the compensatory mechanism of unstable bladder.

Adenosine Triphosphate↗
PubMed2002

Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1.

Myotonic dystrophy 1 (DM1) is the most common inherited neuromuscular disease in adults. The disorder, characterized by myotonia, muscle wasting and weakness, cataract, insulin resistance, and mental impairment, is caused by the expansion of an unstable CTG repeat located in the 3' untranslated region of DMPK. The repeat expansion suppresses the expression of the homeobox gene SIX5. We describe here an experimental system to identify downstream transcriptional targets of mouse Six5 in order to elucidate the role of SIX5 in the pathogenesis of DM1 and development. By overexpressing a constitutively active Six5 (VP16-Six5wt) using adenovirus-mediated gene transfer in P19 cells and subsequent expression profiling using cDNA arrays, 21 genes, whose expression level increased by the treatment, were identified as potential target genes. Genes expressed in the somites, skeletal muscles, brain and meninges comprised the majority, suggesting the role of Six5 in the development and function of mesodermal tissues and brain. We provide evidence that Igfbp5 encoding a component of IGF signaling is a direct Six5-target. Moreover, the overall expression level of Igfbp5 was decreased in Six5-deficient mouse fibroblasts, and the response of human IGFBP5 to MyoD-induced muscle conversion was altered in cells of DM1 patients. Our results not only identify Six5 as an activator that directs Igfbp5 expression but also suggest that reduced SIX5 expression in DM1 might contribute to specific aspects of the DM1 phenotype.

Adenoviridae↗
PubMed2002

[Rapidly growing renal angiomyolipoma during pregnancy with tumor thrombus into the inferior vena cava: a case report].

A case of renal angiomyolipoma rapidly growing during pregnancy with tumor thrombus into the inferior vena cava is reported. Angiomyolipoma in a 31-year-old woman was incidentally found by ultrasonography. CT scan revealed a fat-containing tumor in the right kidney with 4 cm in diameter. The patient was followed at outpatient clinic without any treatment. Fifteen months later, the post-delivery follow-up CT scan showed that tumor size had grown up to 11 cm in diameter. Although laparoscopic right nephrectomy was tried, open transperitoneal right nephrectomy was performed because the tumor thrombus extending into the inferior vena cava was found during the laparoscopic procedure. Pathological diagnosis was angiomyolipoma of the kidney. There are several reports that indicate angiomyolipoma grows rapidly during pregnancy. Our case demonstrates that careful follow-up is required for angiomyolipoma in women with possible conception and delivery.

Adult↗
PubMed2002

[Early results in the initial 15 cases of laparoscopic radical prostatectomy in Akita University Medical Center].

We herein report our experience and early results of laparoscopic radical prostatectomy in 15 cases of localized prostate cancer (11 T1c and 4 T2a tumors) performed between March 2000 and October 2001. The operative procedure was almost identical to the Montsouris technique. Conversion to the open procedure was required only in the first case because of a widely opened bladder neck that involved the ureteral orifice. No severe intraoperative or postoperative complications were observed. The mean operating time and blood loss was 383 minutes and 640 ml including intraoperative urine, respectively. Only one patient required blood transfusion. All 14 patients with a successful procedure could take fluid and walk freely on postoperative day 1. Twelve (86%) of the 14 patients could take food on postoperative day 1 and a Foley catheter was successfully removed on day 6 to 8 in 12 (86%) cases. Histologically, positive surgical margin was observed in 5 (33%) cases and all of them were considered non-organ confined (pT3 or more). Without adjuvant hormonal therapy, biochemical (PSA) failure was observed in 5 (36%) cases (median follow-up period: 11 months). Continence has been well maintained in 12 patients with no need for a pad by 3 months postoperatively and 2 patients are using only 1 pad/day for caution's sake. In terms of early postoperative recovery, intraoperative blood loss and maintenance of continence, laparoscopic radical prostatectomy may give a satisfactory result. Although long-term follow-up is required to assess disease control and maintenance of sexual function, laparoscopic radical prostatectomy may become an alternative for the treatment of organ-confined prostate cancer.

Aged↗
PubMed2002

[Pathogenesis of optic-spinal MS].

We reviewed the clinical and immunological features of optic-spinal multiple sclerosis (OSMS), or relapsing neuromyelitis optica. OSMS has collected much attention as to whether it is a distinct entity from conventional MS (CMS). However, OSMS plus minor cerebral and brainstem/cerebellar involvement and the later conversion into CMS had been a diagnostic dilemma. To overcome such problems and delineate the features of OSMS, we analyzed 'Pure OSMS' with which patients had only relapsing optic neuritis and myelitis clinically and consistently normal brain MRI during 5 years or longer follow-ups. As a result, we found that this type of MS was characterized by a definite female preponderance and negative oligoclonal IgG bands (OB), although 'Pure OSMS' was heterogeneous with regards to the clinical severity and HLA class II alleles. Previously reported immunological data in OSMS include negative OB and no elevation of IL-10 or matrix metalloproteinase-9 in the cerebrospinal fluid (CSF) during relapses. In addition, we recently demonstrated that the CCR5+ Th1 cell subset in CSF during relapses, which significantly increased in CMS, remained low in OSMS. These unique clinical and immunological findings probably relate to fundamental differences in the pathogeneses of OSMS and CMS and deserve further characterization.

Female↗