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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 127 records · Page 7Linked to original sources

Cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum.

PURPOSE: The aim of this study was to clarify whether cyclooxygenase-2 and cyclooxygenase-1 is expressed in hyperplastic polyps and serrated adenomas. METHODS: Forty-nine serrated adenomas and 25 hyperplastic polyps were immunostained using anticyclooxygenase-2 and anticyclooxygenase-1 antibodies. Cyclooxygenase-2 and cyclooxygenase-1 expression was investigated in all specimens. RESULTS: Cyclooxygenase-2 was expressed in dysplastic glands in the majority of serrated adenomas. Thirty-five of 49 (71.4 percent) serrated adenomas exhibited moderate to intense cyclooxygenase-2 immunoreactivity, and 8 of 25 hyperplastic polyps (32 percent) showed weak to moderate cyclooxygenase-2 immunoreactivity. Cyclooxygenase-1 immunoreactivity was very weak in all the hyperplastic polyps and serrated adenomas. CONCLUSIONS: These results suggest that cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum. Cyclooxygenase-2 inhibitors will reduce the incidence of serrated adenomas.

Adenoma↗

Estrogen receptor-mediated cross-talk with growth factor signaling pathways.

Estrogen (E2) palys critical roles in the development of tumors in female reproductive organs. Development of most breast cancers is dependent on E&sub2; in most cases. Most E&sub2; actions are considered to be exerted through two subtypes of Estrogen receptors (ERs), ERalpha and ERbeta. ERs belong to the nuclear receptor superfamily, and act as ligand-inducible transcription factors to activate transcription of a particular set of the target genes. Ligand-bound ER recruits at least two distinct classes of coactivator complexes. In estrogen-dependent breast cancer, growth factors are shown to often act synergisticaly with E&sub2;, and the breast cancer often become resistant to treatment of estogen antagonists. However, the molecular basis of this coupled regulation of growth factor and ER-mediated signaling and hormone-resistance are largely unknown. We have previously shown that MAP (mitogen-activated protein) kinase (MAPK) activated by growth factors phosphorylates and potentiates the N-terminal transactivation function (AF-1), indicating a possible molecular mechanism of a novel cross-talk between two signalings (Kato et al, 1995). Furthermore, we have identified a coactivator that specifically interacts with ER alpha AF-1 (Endoh et al, 1999). In this review, this cross-talk is discussed in terms of the transactivation function of ERs and their coactivators.

Animals↗

Childhood subarachnoid hemorrhage associated with fibromuscular dysplasia.

A rare case of childhood subarachnoid hemorrhage (SAH) is reported. A 5-year-old boy presented with SAH. A cerebral angiogram showed obstruction of the first segment of the left anterior cerebral artery (A1). The A1 was surgically trapped to prevent rebleeding. Proliferation of myofibroblasts was revealed in the intima of the A1. Cerebral infarction appeared in the territory of the left middle cerebral artery (MCA) on day 2 after onset of SAH, and the patient suffered a second SAH on day 26. The second angiogram showed stenosis and a saccular aneurysm in the left MCA. A second surgery, neck clipping of the aneurysm, was needed. The multiple arterial lesions and histological findings indicated that the SAHs and the infarction were caused by the dissecting aneurysm affected with fibromuscular dysplasia (FMD). Intracranial FMD is mainly detected in children and causes cerebral ischemia and bleeding. Surgical treatment of childhood SAH should be discretely chosen with due consideration for FMD.

Aortic Dissection↗

Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy.

Fatal infantile mitochondrial cytopathy associated with a C3303T mutation in the mitochondrial tRNA(Leu(UuR)) gene has been reported clinically, biochemically and genetically. Here we have analyzed the percentage of this mutation in various autopsied tissues, and also in single muscle fibers using a micromanupulator, to evaluate the correlation between the pathology and heteroplasmic condition using polymerase chain reaction/restriction fragment length polymorphism. A 5-month-old Japanese girl was admitted to our hospital showing generalized muscle weakness, hepatomegaly, and cardiomegaly with lactic acidosis, and died at 6 months of age. Skeletal muscle showed severe degenerating myopathy found to be full of ragged-red fibers (RRFs), an increased number of lipid droplets, and severe cytochrome c oxidase (COX) deficiency. Microscopically hepatocytes showed massive accumulation in lipid droplets, and the heart muscle showed a network pattern suggesting metabolic cardiomyopathy. The activities of respiratory chain enzyme complex I and complex IV in the skeletal muscle were significantly decreased to 23.4% and 5.0%, respectively, of the control value. The percentage of C3303T mutation in the patient tissues were variable, and ranged from 25% in the pancreas to 99% in the spinal cord. By single fiber analysis, the percentages of C3303T mutation in RRFs with COX negative (group 1; 42.4+/-7.0) and with COX positive (group 2; 58.2+/-5.8) were significantly higher than in non RRFs with normal COX staining (group 3; 10.7+/-6.3) (both P>0.001). Our patient showed a fatal infantile form of encephalopathy, myopathy and cardiomyopathy associated with widely distributed C3303T mutation in all of somatic cells.

DNA Mutational Analysis↗

Copper chaperone for superoxide dismutase co-aggregates with superoxide dismutase 1 (SOD1) in neuronal Lewy body-like hyaline inclusions: an immunohistochemical study on familial amyotrophic lateral sclerosis with SOD1 gene mutation.

The copper chaperone for superoxide dismutase (CCS) interacts with Cu/Zn-binding superoxide dismutase 1 (SOD1) specifically and delivers copper to SOD1. To determine the role of the CCS-SOD1 interaction in the pathogenesis of SOD1-mutated familial amyotrophic lateral sclerosis (FALS) patients, we produced an affinity-purified rabbit antibody against CCS and investigated the immunohistochemical localization of both CCS and SOD1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of two FALS patients with a two-base pair deletion at codon 126 in the SOD1 gene and three FALS patients with an Ala to Val substitution at codon 4. The LBHIs in anterior horn cells from the five FALS patients showed identical immunoreactivities for CCS: the reaction product deposits with the antibody against CCS were generally restricted to the periphery of the core and halo-type LBHIs. The localizations of the immunoreactivities for CCS and SOD1 were similar in the inclusions: both CCS and SOD1 colocalized in neuronal LBHIs in the five mutant SOD1-linked FALS patients. Our results suggest that the specific interaction and aggregation of CCS-SOD1 (probably CCS-mutant SOD1) in SOD1-mutated FALS patients may amplify the formation of inclusions and emphasize a more marked mutant SOD1-mediated toxicity.

Adult↗

Temporospatial relationship between the expressions of superoxide dismutase and nitric oxide synthase in the developing human brain: immunohistochemical and immunoblotting analyses.

To clarify a significant relationship between superoxide dismutase (SOD) and nitric oxide synthase (NOS) in the developing human brain temporospatially, we demonstrate immunohistochemical expression of Cu/Zn-binding SOD1 (SOD1), Mn-containing SOD2 (SOD2), neuronal NOS (nNOS), inducible NOS (iNOS), and nitrotyrosine in human brains from 13 weeks of gestation to 2 years after birth. The immunoreactivities of both SOD1 and SOD2 were detected in fetal neuroblasts at 13 weeks' gestation, as well as mature neurons at the age of 2 years. By contrast, nNOS neurons could be recognized only at 28 and 33 weeks of gestation in the cerebrum, and only at 15, 18, and 23 weeks of gestation in the brain stem. No significant immunoreactivity for iNOS or nitrotyrosine was detected in any type of cell in any region during any stage examined. Immunoblotting analysis using frontal tissue homogenates at 15, 28, 40 weeks of gestation and 18 months of age revealed single band corresponding to SOD1 molecular weight, observed at all stages examined; a single band compatible with the nNOS molecular mass was detected only at the 28th week of gestation. Together with the fact that nitric oxide (NO) plays a potential role in neuronal differentiation, and that large amounts of NO have cytotoxicity from the reaction of NO with superoxide anions, our data suggested that the expressions of both SOD1 and SOD2, as scavengers of superoxide anions, were maintained from an early developmental stage to prepare stage-specific nNOS expression for a potential differentiation role and to elude NO cytotoxicity.

Aging↗

An ocular cat-scratch disease patient positive for cytoplasmic anti-neutrophil cytoplasmic antibody.

BACKGROUND: We report a case of ocular cat-scratch disease with permanent vision reduction in a patient who was cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) positive. METHODS: Case report and review of the literature. RESULTS: While taking steroids and antibiotics, a 52-year-old man with uveitis associated with cat-scratch disease developed retinal vein occlusion and a macular exudate. His final visual acuity was poor because of residual macular degeneration and optic atrophy. Serum C-ANCA increased and decreased in parallel with ocular inflammatory activity. CONCLUSION: C-ANCA is an indicator of vasculitis and may be useful as an indicator of severe cat-scratch disease.

Ampicillin↗

Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations.

BACKGROUND: This study was designed to compare genetic differences in single-nucleotide polymorphisms of the S-mephenytoin 4'-hydroxylation (CYP2C19) gene among four Asian populations. METHODS: Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis of CYP2C19 was conducted in Japanese, Chinese, Thai, and Vietnamese populations. All genotype frequencies were analyzed. Wild-type homozygote and wild-type heterozygote genotypes were extensive proton pump inhibitor (PPI) metabolizers. Mutant-type heterozygote and mutant-type homozygote genotypes were poor PPI metabolizers. RESULTS: No significant differences in CYP2C19 phenotype, calculated based on genotype frequencies, (P > 0.05) were found among the four populations. CONCLUSIONS: Many factors, including CYP2C19 polymorphisms, affect the success rate of Helicobacterpylori eradication with PPI-based therapy. We suspect that CYP2C19 polymorphisms may not be the main factor associated with differences among these four Asian populations in the success rates of H. pylori eradication with PPI-based therapy.

Adolescent↗

Association of the interleukin-1 beta genetic polymorphism and gastric cancer risk in Japanese.

BACKGROUND: Helicobacter pylori infection is associated not only with gastroduodenal ulcers but with the development of gastric cancer. Interleukin-1 beta (IL-1 beta) is a potent inhibitor of gastric secretion. The -31 C-to-T base transition in the intron of this gene has been reported to be involved in carcinogenic changes within the stomach, especially in H. pylori-infected individuals. METHODS: In this study, the -511 T-to-C polymorphism in the IL-1 beta gene was investigated in 669 patients with gastric diseases. RESULTS: The allelic frequencies of the C allele, which indicates low acid secretion and is a component of a supposedly high-risk genotype for gastric cancer, were 0.48 in H. pylori-negative noncancer controls, 0.52 in H. pylori-positive noncancer controls, 0.57 in subjects with chronic active gastritis (CAG) with H. pylori, 0.58 in subjects with intestinal metaplasia (IM) or CAG without H. pylori, and 0.52 in gastric cancer patients. Significant differences among the groups were observed between the IM or CAG without H. pylori group and the gastric cancer group and between the IM or CAG without H. pylori group and the H. pylori-negative noncancer control group (P < 0.05). CONCLUSIONS: The IL-1 beta-511 genetic polymorphism was not associated with gastric cancer in a multistep carcinogenesis model. However, in view of the results for the IM or CAG without H. pylori group, the presence of the C allele may also indicate a risk of mucosal atrophy of the stomach in the Japanese population.

Genotype↗

A 13C-urea breath test in children with helicobacter pylori infection: assessment of eradication therapy and follow-up after treatment.

PURPOSE: Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. METHODS: Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. RESULTS: Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. CONCLUSIONS: The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

Adolescent↗

Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X.

Patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.

Amino Acid Metabolism, Inborn Errors↗

Successful in vitro generation of Epstein-Barr virus-specific cytotoxic T lymphocytes from severe chronic active EBV patients.

Severe chronic active Epstein-Barr virus (EBV) infection (SCAEBV) is a rare but life-threatening disorder. Poor cytotoxic activity against the virus is widely believed to contribute to the development of this disease. We wished to determine whether it is possible to generate autologous EBV-specific cytotoxic T cells (CTLs) in vitro that can be infused back into the patient to treat his/her viremia. To do this, we first had to establish autologous EBV-transformed B cells (EBCL) as antigen-presenting cells, which is known to be difficult to do with B cells from SCAEBV patients. In one patient, the standard method of incubating B cells with EBV-containing B95-8 supernatant was sufficient. In a second patient, however, the B cells apoptosed too rapidly in culture to permit transformation. However, apoptosis could be blocked by the presence of CD40 ligand-transfectant cells, and EBV transformation was successful when performed with this transfectant. Indicating a native immune response to EBV, peripheral blood lymphocytes from both patients proliferated in response to autologous EBCL. Furthermore, patient T cells had higher frequencies of IFN-gamma-producing CD8 cells after stimulation with autologous EBCL than sero-positive healthy controls. EBV-specific CTLs could be generated from both patients after repeated stimulation with autologous EBCL. These CTL lines were predominantly composed of CD4+ cells, and autologous EBCL killing was largely inhibited by an antibody against HLA-DR. These findings support the possibility of adoptive immune therapy to treat SCAEBV patients.

3T3 Cells↗

Glycemic control and lens transparency in patients with type 1 diabetes mellitus.

PURPOSE: To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS: Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS: The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION: Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.

Adult↗

A case of multiple sclerosis with granulomatous uveitis in Japan--use of the antilipoarabinomannan (LAM)-B test in differential diagnosis.

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in both eyes. The diagnosis of tuberculosis was suspected because of a positive tuberculin skin test. However, a further examination by an anti-LAM-B antibody test excluded active tuberculosis. Her clinical findings were thought most likely to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION: We should consider the possibility of multiple sclerosis as the underlying origin in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody titer may be useful in the differential diagnosis of granulomatous uveitis.

Administration, Topical↗

Anterior capsular contraction after cataract surgery in vitrectomized eyes.

PURPOSE: To assess the contraction of continuous curvilinear capsulorhexis after cataract surgery in eyes with past pars plana vitrectomy. METHODS: In a prospective study, 16 eyes of 16 patients underwent phacoemulsification and implantation of a foldable acrylic intraocular lens after pars plana vitrectomy. Eyes after intensive or repeated vitrectomy were not included. Twenty eyes of 19 patients served as age-matched controls. Aqueous flare intensity was measured using the laser flare-cell meter 1 year after surgery. The area of anterior capsular opening (ACO) was determined by diaphanoscopy using the anterior eye segment analysis system EAS-1000 at 1 day and 1 year postoperatively. RESULTS: There was no significant difference in the mean ACO area between the vitrectomy and control groups both at 1 day and 1 year postoperatively. Aqueous flare intensity 1 year after surgery was slightly higher in the vitrectomy group, but the difference was not statistically significant. CONCLUSION: Eyes after simple vitrectomy are not at a higher risk of ACO contraction following cataract surgery.

Aged↗

Fluoride concentrations at and near the neonatal line in human deciduous tooth enamel obtained from a naturally fluoridated and a non-fluoridated area.

This study sought to obtain a precise profile of fluoride concentrations at and near the neonatal line in deciduous incisors and canines from the naturally fluoridated area (1.0--1.3 parts/10(6) F in drinking water) of West Hartlepool and the non-fluoridated area (less than 0.1 parts/10(6) F in drinking water) of Leeds in England. An abrasive microsampling method was used to determine the distribution of fluoride and phosphorus concentrations. The profile of fluoride concentrations in 100-microm layers before and after the neonatal line, that is, in the prenatal and postnatal enamel, were significantly higher in teeth from the fluoridated than non-fluoridated areas. It was concluded that the fact that the fluoride concentrations were about the same prenatally and postnatally in deciduous enamel obtained from the fluoridated and non-fluoridated areas indicates that fluoride enters the prenatal deciduous enamel and that it is transferred through the placenta.

Calcium↗

Technology for recovering phosphorus from incinerated wastewater treatment sludge.

A bench-top study of phosphorus-recovering technology from ash associated with incinerated wastewater (sewage) treatment sludge was conducted by adding sulfuric acid to ashes for the elution of phosphorus. With the exception of lead, which is insoluble in sulfuric acid, when the pH of the ash fell below 2.0, phosphorus and various heavy metals in the ash were extracted. The study found that, when alkalis were added to adjust the pH of the ash extract to 4.0, phosphorus was subsequently recovered via filtration. Furthermore, when alkalis were added to adjust the pH to 10, the recovery of various heavy metals was observed. In addition, disposal of the remaining solution (wastewater), which consists of a relatively low concentration of salts, is not considered to be a significant issue since it is within wastewater discharge standards and has been found to be useful as an acid-treating substance.

Conservation of Natural Resources↗

The efficient generation of CD83 positive immunocompetent dendritic cells from CD14 positive acute myelomonocytic or monocytic leukemia cells in vitro.

The ability of leukemic cells to differentiate to mature dendritic cells (DCs) was investigated in six acute myelomonocytic or monocytic leukemia cases. It was found that CD14 positive cells were more efficiently changed to CD83 positive mature typed DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) compared with CD14 negative cells. Such leukemia derived DCs expressed a sufficient level of costimulatory molecules (CD80 and CD86), and were shown to be monoclonal based on an the X-inactivation analysis. They also stimulated not only allo- but auto-T lymphocytes, which thereafter became cytotoxic T lymphocytes (CTLs).

Adult↗