S Okada

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (187)691.41 Total impact

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    ABSTRACT: The long-term effectiveness of zonisamide (ZNS) was evaluated in 11 patients with West syndrome (7 symptomatic) who had cessation of spasms with ZNS monotherapy. During the follow-up period (24 to 79 months, mean = 53 months), this response was maintained in 7 patients (3 symptomatic, relapse rate = 36%), including 2 children in whom ZNS was successfully discontinued. No serious adverse reactions were noted. ZNS may be both effective and well tolerated for the treatment of West syndrome.
    No preview · Article · Jun 2002 · Neurology
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    ABSTRACT: Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.
    Full-text · Article · Apr 2002 · Bone Marrow Transplantation
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    ABSTRACT: We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.
    No preview · Article · Jul 2001 · Bone Marrow Transplantation
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    ABSTRACT: To assess the involvement of vascular endothelial cell activation and damage in stem cell transplantation (SCT)-related complications, such as acute and chronic GVHD and thrombotic microangiopathy (TMA), we investigated the changes in serum levels of soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) in SCT. The soluble form of intercellular adhesion molecule-1 (sICAM-1) was also analyzed. In patients with acute GVHD (grades II-IV), serum levels of sE-selectin and sICAM-1 increased around onset of GVHD (day 30). While the increase of sE-selectin levels was transient, sICAM-1 levels remained high until day 60. In patients with extensive chronic GVHD, sVCAM-1 as well as sE-selectin levels significantly increased. The appearance of clinical symptoms was preceded by elevations of sVCAM-1 and sE-selectin levels on day 60, and sICAM-1 levels on days 30 and 60. For the analysis of TMA, to exclude the influence of GVHD, serum levels were measured in auto-SCT patients. Around the onset of TMA, sVCAM-1 and sE-selectin levels significantly increased in patients with TMA without an increase of sICAM-1 levels. These findings support the notion that activation and injury of endothelium are commonly involved in the pathogenesis of acute and chronic GVHD and TMA.
    No preview · Article · Jun 2001 · Bone Marrow Transplantation
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    ABSTRACT: Human herpesvirus-6 (HHV-6) and -7 were analyzed in 25 and 18 patients with allogeneic (allo) and autologous (auto) stem cell transplantation (SCT), respectively, by weekly examination of viral DNA in peripheral mononuclear cells using semiquantitative PCR and serologic tests up to 12 weeks after SCT. HHV-6 DNA was detected in 29.6% and 27.9% of samples after allo- and auto-SCT, respectively. The proportions of HHV-6-DNA-positive samples increased in week 3 and 4 after allo-SCT, and in week 1 to 3 after auto-SCT. The frequency of HHV-7 DNA detection, however, was higher after auto-SCT (24.7%) than allo-SCT (12.8%) (P 10(2) copies of HHV-6 DNA (/10(5) cells) on two consecutive occasions were allo-SCT recipients and three showed clinical episodes. Conversely, three of five patients with continuous reactivation of HHV-7 were auto-SCT recipients. Thus, the frequencies of HHV-6 and -7 DNA detection showed an inverse relationship comparing allo- and auto-SCT, suggesting a different mechanism may regulate HHV-6 and -7 reactivation.
    Full-text · Article · Jun 2001 · Bone Marrow Transplantation
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    Y Wani · K Notohara · C Tsukayama · S Okada
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    ABSTRACT: We performed an immunohistochemical analysis of 2 major DNA mismatch repair proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected specimens, as well as 30 samples from non-cancerous livers. In well-differentiated HCCs, the immunoreactivity for these antigens was well preserved, and the staining intensity was stronger compared to the surrounding liver tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the expression of both of these antigens was reduced. Moreover, in 41 tumors of differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively, contained a less-differentiated area with a reduced number of immunoreactive cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue were well immunostained for both hMLH1 and hMSH2. We confirmed in this series that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that it might play a role in tumor progression.
    Preview · Article · May 2001 · Acta medica Okayama
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    ABSTRACT: We report an 11-year-old girl who presented with episodes of hyperkalemia during the period of recovery, from hemolytic uremic syndrome (HUS) induced by Shiga toxin-producing Escherichia coli. She developed moderate azotemia but continued to pass urine. However, hyperkalemia was observed on days 11 and 25 of clinical course, although hemolysis and renal insufficiency had recovered by that time. Nafamostat mesilate (NM), continuously infused to relieve thrombotic microangiopathy, may have elevated serum potassium level by decreasing urinary potassium excretion. However, a direct effect of Shiga toxin on distal nephron segments was also suggested. Hyperkalemia should be considered in patients with Shiga toxin-associated HUS, not only in the acute phase but also in the recovery period.
    No preview · Article · Mar 2001 · Clinical and Experimental Nephrology
  • T Tokuhisa · M Hatano · S Okada · T Fukuda · I Kunimasa
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    ABSTRACT: Abstract Antigen-reactive B cells in the spleen of mice immunized with T cell-dependent antigens generate antibody-producing foci in periarteriolar lymphoid sheaths (PALS) or migrate into follicles to form germinal centers. Germinal center B cells clonally expand, have somatic hypermutation in IgV-region genes, are selected by apoptosis on the basis of antigen-specific signals, and differentiate to memory B cells. Two transcription factors (Bcl6 and c-Fos) in B cells play a critical role in the development of germinal centers. (1) Bcl6 is highly expressed in germinal center B cells, and defects in B cells perturb the formation of germinal centers but not that of PALS-associated foci, indicating the essential role of Bcl6 in the differentiation. (2) Overexpression of c-Fos in germinal center B cells induces apoptosis and perturbs the formation of memory B cells. Overexpression of Bcl-2 cannot rescue c-Fos-induced apoptosis in germinal center B cells. Since c-Fos is induced in mature B cells which have reacted with antigens, and clonal deletion of self-reactive B cells is insensitive to overexpression of Bcl-2, c-Fos may play a causal role in the clonal deletion of germinal center B cells. Thus, these factors provide a unique opportunity to investigate the molecular mechanisms of memory B cell development.
    No preview · Article · Mar 2001 · Modern Rheumatology
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    ABSTRACT: McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.
    No preview · Article · Feb 2001 · Journal of Bone and Mineral Metabolism
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    S Kojima · M Hatano · S Okada · T Fukuda · Y Toyama · S Yuasa · H Ito · T Tokuhisa
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    ABSTRACT: Bcl6 protein has been detected in testicular germ cells, mainly spermatocytes, of normal mice, but its physiological role is largely unknown. The number of spermatozoa in the cauda epididymis of adult Bcl6-deficient (Bcl6-/-) mice is lower than that of Bcl6+/+ mice. We have found numerous apoptotic spermatocytes at the metaphase I stage with induction of Bax protein in adult Bcl6-/- testes. Developmentally, the incidence of germ cell apoptosis of Bcl6-/- mice was similar to that of Bcl6+/+ mice until six weeks of age and increased after eight weeks of age. The incidence of apoptosis in heterozygous Bcl6+/- mice was also higher than that of Bcl6+/+ mice. Since the activated form of p38 MAP kinase was detected in spermatocytes of adult Bcl6-/- mice, the germ cell apoptosis may be induced by stressors. Treatment of testes of adult Bcl6+/+ mice with a mild hyperthermia resulted in germ cell apoptosis predominantly in metaphase I spermatocytes with induction of Bax protein and activation of p38 MAP kinase and this apoptosis mimics that in adult Bcl6-/- mice. Thus, Bcl6 may play a role as a stabilizer in protecting spermatocytes from apoptosis induced by stressors.
    Preview · Article · Feb 2001 · Development
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    ABSTRACT: The proximal promoter of lck directs gene expression exclusively in T cells. To investigate the developmental regulation of the lck proximal promoter activity and its relationship to T cell lineage commitment, a green fluorescence protein (GFP) transgenic (Tg) mouse in which the GFP expression is under the control of the proximal promoter of lck was created. In the adult GFP-Tg mice, >90% of CD4(+)CD8(+) and CD4(+)CD8(-) thymocytes, and the majority of CD4(-)CD8(+) and CD4(-)CD8(-) [double-negative (DN)] thymocytes were highly positive for GFP. Slightly lower but substantial levels of expression of GFP was also observed in mature splenic T cells. No GFP(+) cells was detected in non-T lineage subsets, including mature and immature B cells, CD5(+) B cells, and NK cells, indicating a preserved tissue specificity of the promoter. The earliest GFP(+) cells detected were found in the CD44(+)CD25(-) DN thymocyte subpopulation. The developmental potential of GFP(-) and GFP(+) cells in the CD44(+)CD25(-) DN fraction was examined using in vitro culture systems. The generation of substantial numbers of alphabeta and gammadelta T cells as well as NK cells was demonstrated from both GFP(-) and GFP(+) cells. However, no development of B cells or dendritic cells was detected from GFP(+) CD44(+)CD25(-) DN thymocytes. These results suggest that the progenitors expressing lck proximal promoter activity in the CD44(+)CD25(-) DN thymocyte subset have lost most of the progenitor potential for the B and dendritic cell lineage. Thus, progression of T cell lineage restriction in the earliest thymic population can be visualized by lck proximal promoter activity, suggesting a potential role of Lck in the T cell lineage commitment.
    Full-text · Article · Jan 2001 · International Immunology
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    ABSTRACT: To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.
    No preview · Article · Nov 2000 · American Journal of Surgical Pathology
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    ABSTRACT: We report a 5-year-old boy with juvenile myelomonocytic leukemia (JMML) which relapsed after an allogeneic bone marrow transplant who was successfully treated with interferon-alpha (IFN-alpha). One year after starting the therapy, he remains clinically well and in complete remission while continuing treatment with IFN-alpha and bestatin. Although the precise mechanism by which remission was induced is uncertain, a GVL effect combined with a direct antileukemia effect of IFN-alpha may be responsible. Further assessment of the role of IFN-alpha in relapsed JMLL patients is warranted.
    Full-text · Article · Oct 2000 · Bone Marrow Transplantation
  • S. Okada · M. Hatano · T. Tokuhisa
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    ABSTRACT: The proto-oncogene c-fos is transiently expressed in various kinds of cells except for macrophages (Mφ) by external stimuli, and works as a component of AP-1. Murine peritoneal Mφ and Mφ like cell line, RAW 264 constitutively expressed c-fos mRNA, which produce nitric oxide (NO) by external stimuli and fall into apoptosis. To investigate the role of c-fos in Mφ, we used transgenic mice carrying the c-fos gene under the control of the interferon-α/β inducible Mx-promoter (Mx-c-fos). By the stimulation in IFN-γ and LPS, c-fos expression was down-regulated within one hour after stimulation after transient up-regulation and returned to the previous level after 6 hours. Inducible nitric oxide synthase (iNOS) expression was observed after the down-regulation of c-fos. Over-expression of the c-fos in the Mx-c-fos mice derived Mφ inhibited iNOS mRNS expression and NO production whereas the IL-1 and IL-6 production were not inhibited, indicated that down-regulation of c-fos is needed for the iNOS expression. Luciferase assay revealed c-fos suppressed NF-IL-6 dependent iNOS promoter activity. As NF-IL-6 is known to be a strong activator of iNOS and make heterodimer with c-fos, c-fos may suppress iNOS expression not by AP-1 complex but by neutrization of NF-IL-6 activity. These results suggest that constitutively expressed c-fos may inhibit the accidental expression of iNOS expression and works as the stabilizer of Mφ.
    No preview · Article · Jul 2000 · Experimental Hematology
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    ABSTRACT: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.
    Preview · Article · Apr 2000 · European Journal of Endocrinology
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    ABSTRACT: Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of glucose-6-phosphatase (G6Pase) that is expressed in the liver, kidney, and intestinal mucosa. Clinical manifestations include short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. To elucidate a spectrum of the G6Pase gene mutations and their frequencies, we analyzed mutations in 51 unrelated Japanese patients with GSD-Ia. The most prevalent mutation was g727t, accounting for 88 of 102 mutant alleles examined, followed by R170X mutation, which accounted for 6 mutant alleles, and R83H mutation which was observed in 3 mutant alleles. In addition, 3 different, novel mutations, IVS1-1g<a, Gly122-to-Asp (G122D) and His179-to-Pro (H179P), were identified. We were able to detect "ectopically" transcribed G6Pase-mRNA in Epstein-Barr virus-transformed lymphoblastoid cells and observed aberrant mRNA splicing associated with the g727t and IVS1-1g<a mutations. To our knowledge, this is the first report that ectopic expression can be utilized for the characterization of GSD-Ia mutations. Our findings suggest that a screening for the g727t, R170X, and R83H mutations by simple DNA-based diagnostic methods can detect 95% of the G6Pase mutant alleles in Japanese patients with GSD-Ia, and remaining mutations can be identified and characterized by the direct sequencing of genomic DNA and/or the analysis of ectopically expressed mRNA. The noninvasive molecular diagnosis for GSD-Ia may ultimately replace the conventional means of enzymatic diagnosis that requires liver biopsy.
    No preview · Article · Mar 2000 · American Journal of Medical Genetics
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    ABSTRACT: Background. To clarify the pathophysiological features associated with phosphate depletion in hypophosphatemic (Hyp) mice, we examined the effect of extracellular phosphate on parathyroid hormone (PTH)-stimulated adenosine 3′,5′-cyclic monophosphate (cAMP) production in the proximal convoluted tubules (PCT). Methods. PTH-Stimulated cAMP production and ATP content were determined by radioimmunoassay and luciferin-luciferase chemiluminescence methods, respectively. Results. The level of cAMP stimulated by PTH at an extracellular phosphate concentration of 0.78 mM was lower in the Hyp mice than in normal mice. The PTH-stimulated cAMP production in the Hyp mice was increased when the extracellular phosphate concentration was raised. In contrast, an increase in extracellular phosphate did not affect the PTH-stimulated cAMP production in the normal mice. Although the ATP content of the PCT was not different between the normal and Hyp mice immediately after microdissection, after 60 min of incubation, it had decreased to a greater extent in Hyp mice than in the normal animals. Raising the extracellular phosphate concentration from 0.78 to 2.3 mM prevented the decrease in ATP content in Hyp mice, and the intracellular ATP content then became comparable to that in the normal control. Conclusions. These results suggest that ATP content in the PCT tended to be decreased in Hyp mice by a decreased phosphate supply and that the blunted effect of PTH on cAMP production in these mice is due to ATP depletion.
    No preview · Article · Feb 2000 · Clinical and Experimental Nephrology
  • K Imai · T Mano · K Shimono · H Ueda · T Okinaga · K Yanagihara · Z Li · S Okada

    No preview · Article · Feb 2000 · No to hattatsu. Brain and development
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    T Ogino · Y Ma · T A Than · M Omori · S Okada
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    ABSTRACT: Monochloramine derivatives are physiological oxidants produced by activated neutrophils. We report the effects of chemically prepared monochloramine (NH2Cl) on Fas-induced apoptosis in Jurkat T cells. When the cells were pretreated with NH2Cl (20-70 microM), subsequent addition of apoptosis-inducing anti-Fas antibody resulted in a synergistic enhancement of apoptosis. Treatment of NH2Cl (50-70 microM) alone resulted in a slight but definite apoptosis. Caspase activities, as measured by DEVD and IETD cleavage activities, were also elevated synergistically by NH2Cl + anti-Fas antibody stimulation. Moreover, a broad caspase inhibitor, Z-VAD-fmk, almost completely inhibited the apoptosis induced by NH2Cl and/or anti-Fas antibody. Fas expression on the Jurkat cell surface was not affected by the NH2Cl treatment. After 3 h of NH2Cl treatment, when the apoptosis was beginning to increase, the cells showed cytochrome c release from mitochondria, proteolytic activation of caspase 9, and poly (ADP-ribose) polymerase cleavage, regardless of Fas stimulation. Z-VAD-fmk almost completely inhibited this poly (ADP-ribose) polymerase cleavage, but not cytochrome c release. By contrast, Fas stimulation alone resulted in neither cytochrome c release nor caspase 9 activation at 3 h, and the increase in the DEVD cleavage activity and apoptosis became evident at later time points. These results suggested that NH2Cl enhanced Fas-induced apoptosis through the cytochrome c release and caspase 9 activation at the early stage of apoptosis. Chloramines derived from acute inflammation may modify immune reactions, such as cell-mediated cytotoxicity and some autoimmune diseases, by the enhancement of Fas-induced apoptosis.
    Full-text · Article · Feb 2000 · Journal of Leukocyte Biology
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    A Honda · M Shima · S Onoe · M Hanada · T Nagai · S Nakajima · S Okada
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    ABSTRACT: A rare case of botryoid Wilms tumor is presented. The main clinical manifestations were persistent low-grade fever, malaise, and proteinuria associated with microhematuria. Ultrasonography revealed an echogenic mass in the right kidney, and a contrast-enhanced mass was found in the dilated collecting system by contrast-enhanced computed tomography. The surgically resected tumor was a polypoid, light-yellow, glistening mass that occupied a large part of the renal pelvis and originated from the pelvicaliceal wall. Part of the tumor extended to the proximal ureter, resulting in hydronephrosis in the involved kidney. No parenchymal lesion was observed. Microscopic examination revealed epithelial, stromal, and blastemal components, which indicated Wilms tumor. Infection had occurred in the hydronephrotic kidney, which presumably had caused the major presenting symptoms. The prognosis of our patient and previously reported cases of botryoid Wilms tumor was good compared with that of typical Wilms tumor, since the botryoid type can be detected at an early stage.
    Preview · Article · Feb 2000 · Pediatric Nephrology

Publication Stats

4k Citations
691.41 Total Impact Points


  • 2001-2002
    • Osaka City University
      • Department of Pediatrics
      Ōsaka, Ōsaka, Japan
  • 1998-2002
    • Osaka Medical Center and Research Institute for Maternal and Child Health
      Izumi, Ōsaka, Japan
  • 2000-2001
    • Chiba University
      • Department of Developmental Genetics
      Tiba, Chiba, Japan
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States
  • 1996-2001
    • Okayama University
      • • Department of Pathology and Oncology
      • • Medical School
      Okayama, Okayama, Japan
  • 1983-2001
    • Osaka University
      • • Graduate School of Medicine
      • • Division of Pediatrics
      • • Department of Medical Genetics
      • • Radiation Oncology
      Suika, Ōsaka, Japan
  • 1999
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki-ken, Japan
  • 1997
    • The Jikei University School of Medicine
      • Department of Pediatrics
      Edo, Tokyo, Japan
  • 1995-1997
    • Kanagawa University
      • Faculty of Engineering
      Yokohama, Kanagawa, Japan
  • 1994
    • National Center of Neurology and Psychiatry
      Кодаиры, Tōkyō, Japan
  • 1989-1992
    • Kyoto University
      Kioto, Kyōto, Japan
  • 1990
    • Fukushima Medical University
      • Department of Pediatrics
      Hukusima, Fukushima, Japan
  • 1983-1985
    • Shiga University of Medical Science
      • Department of Pediatrics
      Ōtu, Shiga Prefecture, Japan