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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 73 records · Page 4Linked to original sources
PubMed2001

Monoclonal antibody (5F3) defining renal cell carcinoma-associated antigen disialosyl globopentaosylceramide (V3NeuAcIV6NeuAcGb5), and distribution pattern of the antigen in tumor and normal tissues.

Renal cell carcinoma (RCC) has been characterized by high expression of three types of disialogangliosides: two based on lacto-series type 1 structure (disialosyl Lc(4), GalNAc disialosyl Lc(4)), the other based on globo-series structure (disialosyl globopentaosylceramide; disialosyl Gb5). The present study established a mAb, 5F3, directed to disialosyl Gb5. 5F3 was established after immunization with RCC cell line ACHN. The major disialoganglioside antigen isolated from ACHN cells, showing specific reactivity with 5F3, was characterized unequivocally as disialosyl Gb5 (V(3)NeuAcIV(6)NeuAcGb5) by identification of the core structure as globopentaosylceramide (Gb5) after enzymatic and acid hydrolysis, and by 2-dimensional (1)H-NMR spectroscopy. 5F3 does not react with monosialosyl Gb5 (V(3)NeuAcGb5), Gb5, or any lacto-series structures. 5F3 strongly stained 19 of 41 cases of primary RCC tissue. It reacted with proximal tubules (but not distal tubules) of kidney, microglial cells of cerebrum and cerebellum, goblet cells of stomach and intestine, smooth muscle of various organs. It did not react with parenchymatous cells of various organs, except for kidney epithelia and prostate stroma. Immunostaining of RCC tissue by mAb 5F3, in combination with staining by other antibodies directed to globo-series and lacto-series structures, has prognostic significance in defining metastatic potential of RCC.

Antibodies, Monoclonal↗
PubMed2001

Identification of MICA alleles with a long Leu-repeat in the transmembrane region and no cytoplasmic tail due to a frameshift-deletion in exon 4.

MHC class I chain-related gene A (MICA) is located close to HLA-B gene and expressed in epithelial cells. The MICA gene is reported to be highly polymorphic as are the classical class I genes. To further assess the polymorphism in the MICA gene, we analyzed a total of 60 HLA-homozygous cells for the sequences spanning exons 2-6. In the analysis, four new MICA alleles were identified and six variations were recognized in exon 6. MICA*017, which was identified in three HLA-B57 homozygous cells (DBB, DEM and WIN), differed from MICA*002 in exon 3 and had a guanine deletion at the 3' end of exon 4. MICA*015 identified in an HLA-B45 homozygous cell (OMW) also had the same deletion that causes a frameshift mutation resulting in complete change of the transmembrane region and premature termination in the cytoplasmic tail; these alleles have a long hydrophobic leucine-rich region instead of the alanine repeat in the transmembrane region and terminate at the second position in the cytoplasmic domain. The frameshift deletion was found only in HLA-B45- or -B57-positive panels tested, suggesting a strong linkage disequilibrium between the deletion and B45 or B57. MICA*048, which was different in exon 5 from MICA*008, was identified in an HLA-B61 homozygous cell (TA21), while MICA*00901 identified in HLA-B51 homozygous cells (LUY and KT2) was distinguished from MICA*009 by exon 6.

Base Sequence↗
PubMed2001

Establishment of gingival epithelial cell lines from transgenic mice harboring temperature sensitive simian virus 40 large T-antigen gene.

We established two gingival epithelial cell lines (GE1 and GE6), originating from transgenic mice harboring the temperature-sensitive simian virus 40 large T-antigen gene. GE1 and GE6 grew at a permissive temperature (33 degrees C) in a pavement arrangement and solely formed multilayers that exhibited morphological features similar to those of the stratified oral epithelium, with neither the use of stromal equivalents nor feeder layers. Both GE cells underwent apoptosis at a non-permissive temperature (39 degrees C). Characteristic keratin peptides, keratin 4 and 13, for mucosal epithelium were obviously expressed in the suprabasal cells, and keratohyalin granules and involucrin were present in the surface flat cells in the multilayered culture. Keratin 10 (one of the markers for higher keratinized gingival epithelium) was rarely found in some uppermost cells, and filaggrin (a component of keratohyalin granules) appeared sparsely in uppermost desquamating cells in the older cultures. These observations indicated that GE1 and GE6 cells exhibited the phenotype characterizing nonkeratinized sulcular epithelium, which possessed the potency undergoing keratinization in such highly stratified cultures as oral gingival epithelium. GE cells increased the expression levels of mRNA of interleukin-1beta and tumor necrosis factor alpha by the stimulation of lipopolysaccharide and extracellular substances of oral streptococci. The GE cell lines thus could serve as an excellent experimental system for further studies on the physiology of gingival epithelium and corresponding diseases, such as periodontal disease, epithelial hyperplasia, and gingival tumors.

Animals↗
PubMed2001

Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose-dependent manner.

We previously reported that abnormal copper release from mutated Cu, Zn-superoxide dismutase (SOD1) proteins might be a common toxic gain-of-function in the pathogenesis of familial amyotrophic lateral sclerosis (FALS) [Ogawa et al. (1997) Biochem. Biophys. Res. Commun., 241, 251-257.]. In the present study, we first examined metallothioneins (MTs), known to bind copper ions and decrease oxidative toxicity, and found a twofold increase in MTs in the spinal cord of the SOD1 transgenic mice with a FALS-linked mutation (G93A), but not in the spinal cord of wild-type SOD1 transgenic mice. We then investigated whether the clinical course of FALS mice could be modified by the reduced expression of MTs, by crossing the FALS mice with MT-I- and MT-II-deficient mice. FALS mice clearly reached the onset of clinical signs and death significantly earlier in response to the reduction of protein expression. These results indicated that the copper-mediated free radical generation derived from mutant SOD1 might be related to the degeneration of motor neurons in FALS and that MTs might play a protective role against the expression of the disease.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Stabilization of mutant Cu/Zn superoxide dismutase (SOD1) protein by coexpressed wild SOD1 protein accelerates the disease progression in familial amyotrophic lateral sclerosis mice.

Transgenic mice carrying familial amyotrophic lateral sclerosis (FALS)-linked mutant Cu/Zn superoxide dismutase (SOD1) genes such as G93A (G93A-mice) and G85R (G85R-mice) genes develop limb paresis. Introduction of human wild type SOD1 (hWT-SOD1) gene, which does not cause motor impairment by itself, into different FALS mice resulted in different effects on their clinical courses, from no effect in G85R-mice to acceleration of disease progression in G93A-mice. However, the molecular mechanism which causes the observed difference, has not been clarified. We hypothesized that the difference might be caused by the stability of mutant SOD1 proteins. Using a combination of mass spectrometry and enzyme-linked immunosorbent assay, we found that the concentration of G93A-SOD1 protein was markedly elevated in tissues of transgenic mice carrying both G93A- and hWT-SOD1 genes (G93A/hWT-mice) compared to that in G93A-mice, and also found that the concentration of G93A-SOD1 protein had a close relation to the disease duration. The concentration of metallothionein-I/II in the spinal cord, reflecting the degree of copper-mediated oxidative stress, was highest in G93A/hWT-mice, second in G93A-mice, and normal in the mice carrying hWT-SOD1 gene. These results indicated that the increase of G93A-SOD1 protein was responsible for the increase of oxidative stress and disease acceleration in G93A/hWT-mice. We speculate that coexpression of hWT-SOD1 protein is deleterious to transgenic mice carrying a stable mutant such as G93A-SOD1, because this mutant protein is stabilized by hWT-SOD1 protein, but not to transgenic mice carrying an unstable mutant such as G85R-SOD1, because this mutant protein is not stabilized by hWT-SOD1.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Absence of BAT-26 instability in gastric intestinal metaplasia.

BAT-26 instability, a sensitive marker for the high-frequency microsatellite instability (MSI-H) phenotype, was analyzed in samples of gastric cancer and in adjacent intestinal metaplastic mucosae. Although all MSI-H gastric cancer samples showed BAT-26 instability, as assessed using 12 dinucleotide microsatellite markers, BAT-26 instability was not found in the adjacent intestinal metaplastic mucosa in any of the samples.

Genetic Markers↗
PubMed2001

Interferon-gamma is required for lupus nephritis in mice treated with the hydrocarbon oil pristane.

BACKGROUND: Although the precise mechanisms leading to lupus nephritis remain obscure, both TH1 and TH2 cytokines have been implicated. The present study examined the roles of interleukin (IL)-4 and interferon-gamma (IFN-gamma) in a novel inducible form of lupus that develops in non-autoimmune mice treated with the hydrocarbon oil pristane. METHODS: BALB/c IL-4 or IFN-gamma deficient mice (IL-4 -/-, IFNgamma -/-) and wild type controls (+/+) received either pristane or phosphate-buffered saline (PBS) IP. Serial sera were analyzed for anti-DNA/chromatin, anti-RNP/Sm, and total immunoglobulin levels. Proteinuria was measured and kidneys were examined by direct immunofluorescence and light microscopy. RESULTS: Renal disease did not develop in pristane-treated IFN-gamma -/- mice, as assessed by the absence of capillary immune deposits, glomerular pathology and proteinuria whereas IL-4 -/- mice developed renal disease similar to +/+ mice. Production of IgG anti-single stranded DNA and anti-chromatin antibodies was abrogated in IFN-gamma -/- mice. In contrast, these autoantibodies were produced at similar or higher frequencies and levels by IL-4 -/- versus wild-type mice. The frequency of anti-nRNP/Sm was markedly reduced in IFN-gamma -/- mice. IL-4 deficiency had little effect on the production of anti-DNA/chromatin and anti-nRNP/Sm. CONCLUSIONS: IFN-gamma is essential for the induction of nephritis and anti-DNA/chromatin following pristane exposure in BALB/c mice, suggesting that genetic or environmental factors influencing TH1-TH2 balance could be an important determinant of renal disease in lupus.

Animals↗
PubMed2001

Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters.

BACKGROUND: Oxidative stress during hemodialysis is thought to promote the progression of vascular complications in hemodialysis patients. The protective role of vitamin E as a lipophilic antioxidant against oxidative stress has been widely investigated. Here we investigated the effects of a vitamin E-coated regenerated cellulose hollow fiber dialyzer (CL-EE) on oxidative stress compared with a polysulfone hollow fiber (CL-PS). METHODS: For at least three months before beginning the protocol, 10 nondiabetic (NDM) patients (70.0 +/- 7.5 years; 6 males and 4 females) and 8 diabetic (DM) patients (65.0 +/- 7.4 years; 4 males, 4 females) were dialyzed with CL-PS. After that, we treated all of the patients with CL-EE for six months. Malondialdehyde (MDA), advanced glycation end products (AGEs), and 8-hydroxydeoxyguanosine (8-OHdG) were monitored as biomarkers for oxidative stress at the start and then at one, three, and six months into treatment with CL-EE. RESULTS: Serum MDA, AGE, and 8-OHdG levels increased after the hemodialysis with CL-PS. The increase of the biomarkers was completely prevented by a single use of CL-EE. Long-term hemodialysis with CL-EE for six months significantly reduced the basal levels of the oxidant markers at one month for AGE and at six months for 8-OHdG in both DM and NDM patients. Serum MDA was reduced in only DM patients at three months. The improvement of the oxidative stress with CL-EE was more prominent in the DM patients. CONCLUSIONS: Long-term treatment with CL-EE efficiently improves the oxidative stress associated with hemodialysis and potentially reduces dialysis complications due to oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) is a clinically and genetically heterogeneous disease of the sarcomere. Molecular genetic studies have shown that familial HCM involves mutations in 8 different genes that encode proteins of the myofibrillar apparatus. METHODS: We thoroughly searched these genes to find the mutations in 38 probands of unrelated families with familial HCM. RESULTS: We found a novel missense mutation that resulted in Ala57Gly amino acid substitution of the ventricular essential myosin light chain (vMLC1) gene in two unrelated Korean families with familial HCM and one Japanese patient. The mutated site is located in the putative helix-loop-helix region (named EF-hand domain) of the calcium-binding site that is highly conserved in vMLC1 isoforms across the various species. The phenotype of this mutation in the affected families is a classic asymmetric septal hypertrophy, and the disease penetrance in genotyped members older than 18 years is 78%. In one Korean family a 42-year-old woman and two brothers (34 and 38 years old) with the mutation had fully expressed the disease, but two sisters (39 and 29 years old) with the mutation had no phenotypic expression of HCM. CONCLUSIONS: Ala57Gly mutation in the vMLC1 gene may exhibit the classic form of familial HCM and widely different penetration of the disease phenotype in the family members with mutation, especially in women.

Adult↗
PubMed2001

Treatment of recurrent auricle pseudocyst with intralesional injection of minocycline: a report of two cases.

Pseudocyst of the auricle (PCA) is characterized by asymptomatic and fluctuant swelling of the external ear and frequent relapses despite various therapeutic approaches. We describe two patients with recurrent PCA who were successfully treated with intralesional injection of 1 mg/mL of minocycline hydrochloride (minocycline), 2 or 3 times at 2-week intervals. Intralesional injection of minocycline may be a new therapeutic choice for conservative management of PCA, especially in recurrent cases. The mechanisms of minocycline action that may have led to reduction of the cystic lesions are discussed.

Adolescent↗
PubMed2001

Four cases of meningeal hemangiopericytoma treated with surgery and radiotherapy.

We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation.

Adult↗
PubMed2001

Two patients with N3 bladder cancer successfully treated by internal iliac arterial infusion chemotherapy and irradiation: case reports.

The prognosis of patients with bladder cancer with pelvic lymph node metastasis is poor, and only 30% of them have been reported to achieve 5- and 10-year survival rates. Prognosis of the patients with pelvic lymph node metastasis larger than 5 cm (N3) is especially poor. and no patient has been reported to have survived more than 3 years. The authors report the successful treatment of two patients with pelvic N3 bladder cancer by internal iliac arterial infusion chemotherapy combined with whole-pelvis irradiation.

Aged↗
PubMed2001

Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice.

The authors previously reported that mRNA for macrophage inflammatory protein-1alpha (MIP-1 alpha), a member of the CC chemokines, was expressed in glial cells after focal cerebral ischemia in rats. However, the function of chemokines in the ischemic brain remains unclear. Recently, viral macrophage inflammatory protein-II (vMIP-II), a chemokine analogue encoded by human herpesvirus-8 DNA, has been demonstrated to have antagonistic activity at several chemokine receptors. In the present study, the effects of vMIP-II and MIP-1alpha on ischemic brain injury were examined in mice to elucidate the roles of chemokines endogenously produced in the ischemic brain. Intracerebroventricular injection of vMIP-II (0.01-1 microg) reduced infarct volume in a dose-dependent manner when examined 48 hours after 1-hour middle cerebral artery occlusion followed by reperfusion. However, 1 microg MIP-1alpha increased infarct volume in the cortical region. These results supported the possibility that chemokines endogenously produced in the brain are involved in ischemic injury, and that chemokine receptors are potential targets for therapeutic intervention of stroke.

Animals↗
PubMed2001

Activation of inositol 1,4,5-trisphosphate receptor is essential for the opening of mouse TRP5 channels.

We studied the opening mechanism of Ca(2+)-permeable channels formed with mouse transient receptor potential type 5 (mTRP5) using Xenopus oocytes. After stimulation of coexpressed muscarinic M(1) receptors with acetylcholine (ACh) in a Ca(2+)-free solution, switching to 2 mM Ca(2+)-containing solution evoked a large Cl(-) current, which reflects the opening of endogenous Ca(2+)-dependent Cl(-) channels following Ca(2+) entry through the expressed channels. The ACh-evoked response was not affected by a depletion of Ca(2+) store with thapsigargin but was inhibited by preinjection of antisense oligodeoxynucleotides (ODNs) to G(q), G(11), or both. The mTRP5 channel response was also induced by a direct activation of G proteins with injection of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). The ACh- and GTP gamma S-evoked responses were inhibited by either pretreatment with a phospholipase C inhibitor, U73122, or an inositol-1,4,5-trisphosphate (IP(3)) receptor inhibitor, xestospongin C (XeC). An activation of IP(3) receptors with injection of adenophostin A (AdA) evoked the mTRP5 channel response in a dose-dependent manner. The AdA-evoked response was not suppressed by preinjection of antisense ODNs to G(q/11) or U73122 but was suppressed by either preinjection of XeC or a peptide mimicking the IP(3) binding domain of Xenopus IP(3) receptor. These findings suggest that the activation of IP(3) receptor is essential for the opening of mTRP5 channels, and that neither G proteins, phosphoinositide metabolism, nor depletion of the Ca(2+) store directly modifies the IP(3) receptor-linked opening of mTRP5 channels.

Acetylcholine↗
PubMed2001

Detection of hypermethylation of the p16(INK4A) gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus.

BACKGROUND/AIM: Inactivation of the p16(INK4A) (p16) tumour suppressor gene by promoter region hypermethylation has been demonstrated not only in many types of tumours, including hepatocellular carcinoma (HCC), but also in early preneoplastic lesions in the lung, colon, oesophagus, and pancreas. The aim of this study was to examine the methylation status of the p16 promoter in pre- and/or non-neoplastic liver diseases. PATIENTS/SUBJECTS/METHODS: The methylation status of p16 was evaluated in 22 HCC, 17 cirrhosis, 17 chronic hepatitis, nine primary biliary cirrhosis (PBC), eight autoimmune hepatitis, seven drug induced liver disease, six fatty liver, and three normal liver tissues using methylation specific polymerase chain reaction (MSP). p16 protein expression was also examined by immunohistochemical staining. RESULTS: Methylation of the p16 promoter was detected in HCC (72.7%, 16/22) and also in cirrhosis (29.4%, 5/17) and chronic hepatitis (23.5%, 4/17), all of which were positive for hepatitis B or C virus infections. Methylation was not detected in any of the other samples. All methylation positive HCC, cirrhosis, and chronic hepatitis samples showed loss of p16 expression, and a significant correlation was found between methylation and loss of expression. Analysis of serial samples from individual patients with methylation positive HCC revealed that loss of p16 expression with promoter methylation occurred in 18 of 20 patients at the stage of chronic hepatitis without clinically detectable carcinoma. CONCLUSIONS: Our results suggest that methylation of the p16 promoter and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful in the follow up of patients with a high risk of developing HCC, such as those with hepatitis B or C viral infections.

Adult↗
PubMed2001

Steroid pulse therapy combined with tonsillectomy in IgA nephropathy associated with diabetes mellitus.

Ten patients with biopsy-confirmed IgA nephropathy associated with diabetes mellitus underwent dietary weight control and three courses of intravenous pulses of methylprenisolone followed by prednisolone for 6-12 months and tonsillectomy. The average length of the follow-up period was 47.8 (range 30-96) months. As compared with pretreatment values, hematuria, proteinuria, body mass index, and hemoglobin A(1c) were significantly improved after treatment. There were no significant differences with regard to blood pressure and glycemic blood glucose control. There was no worsening of diabetic retinopathy and nephropathy. During steroid pulse therapy, the patients who were treated with insulin needed a higher dosage of insulin; after steroid pulse therapy, the dosage returned to baseline. Even patients with IgA nephropathy and diabetes mellitus could be treated with combined therapy and showed beneficial responses, it they succeeded in reducing body mass index.

Adult↗
PubMed2001

New compound heterozygous mutation in the CYP17 gene in a 46,XY girl with 17 alpha-hydroxylase/17,20-lyase deficiency.

BACKGROUND: 17alpha-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17alpha-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads. RESULTS: In the present study, we analyzed the CYP17 gene in a Japanese patient with 17alpha-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17alpha-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17alpha-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17alpha-hydroxylase and 17,20-lyase activities. CONCLUSIONS: Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17alpha-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17alpha-hydroxylase/17,20-lyase deficiency.

Adrenal Hyperplasia, Congenital↗