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Biomedical subjects

S Hosono

Publications and source records attributed to S Hosono.

At least 19 recordsLinked to original sources
PubMed2007

Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.

Twist is a transcription factor that regulates the expression of tumour suppressors such as E-cadherin. We examined the distribution and expression of Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical significance. Paraffin sections from EOC tissues (n=82) were immunostained with Twist antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics staging, histological type, tumour grade, preoperative value of CA125, peritoneal cytology, volume of ascites and residual tumour after cytoreductive surgery. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were negative for Twist immunoexpression, and 33 (40.2%) were positive immunoexpression. When categorized into negative vs positive expression, Twist was not associated with any of the clinicopathological parameters examined. However, positive Twist expression significantly predicted poorer OS and PFS when compared with negative expression (P<0.0001). In the multivariate analyses, positive Twist expression was the only independent prognostic factor for survival in this study (P<0.0001). Positive Twist expression seems to be a useful marker in patients with EOC likely to have an unfavourable clinical outcome.

Blotting, Western↗
PubMed2001

High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the foundation of powerful complex trait and pharmacogenomic analyses. The availability of large SNP databases, however, has emphasized a need for inexpensive SNP genotyping methods of commensurate simplicity, robustness, and scalability. We describe a solution-based, microtiter plate method for SNP genotyping of human genomic DNA. The method is based upon allele discrimination by ligation of open circle probes followed by rolling circle amplification of the signal using fluorescent primers. Only the probe with a 3' base complementary to the SNP is circularized by ligation. RESULTS: SNP scoring by ligation was optimized to a 100,000 fold discrimination against probe mismatched to the SNP. The assay was used to genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput format. Assay directly from genomic DNA eliminates the need to preamplify the target as done for many other genotyping methods. The sensitivity of the assay was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the assay can detect a single molecule of the circularized probe. CONCLUSIONS: Compatibility with homogeneous formats and the ability to assay small amounts of genomic DNA meets the exacting requirements of automated, high-throughput SNP scoring.

Journal Article↗
PubMed2001

Effect of vibration on auditory organ systems in low-birth weight infants treated with high-frequency oscillatory ventilation: 5 year outcome.

BACKGROUND: To determine the effects of vibration exposure caused by high-frequency oscillatory ventilation (HFOV) on the auditory organ systems in low-birth weight (LBW) infants. METHODS: Between 1989 and 1990, 30 LBW infants who received assisted ventilation with HFOV (n = 14) or conventional mechanical ventilation (CMV; n = 16) in the level III neonatal intensive care unit at Tokyo Metropolitan Ohtsuka Hospital were enrolled in this study. The effects of vibration exposure on the auditory system structures were investigated with auditory brainstem responses (ABR) at 37-41 weeks of postconceptional age and at 6, 12, 18 and 24 months of age until they passed and follow-up studies were performed at least until 5 years of age. RESULTS: All infants enrolled in the study survived at discharge and one (7.1%) infant in the HFOV group and two (12.5%) in the CMV group failed the initial ABR test, but there were no significant differences between the two groups. Auditory brainstem response abnormalities were still observed in one infant in the HFOV group at 6 months of age, but this child died at 9 months of age because of meningitis. In contrast, in the CMV group, one patient passed the ABR test at 6 months of age, but another remained abnormal at 5 years of age. One of three infants with ABR abnormalities at 6 months of age had neurologic sequelae at 5 years of age and one of 28 infants who passed the initial ABR test was detected with cerebral palsy. No patients with hearing loss were clinically detected at 5 years of age. CONCLUSIONS: The results of the serial ABR examinations and the 5 year follow-up studies suggest that vibration exposure caused by HFOV may not increase the adverse effects on the auditory system in LBW infants.

Audiometry, Evoked Response↗
PubMed2001

Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy.

BACKGROUND: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. METHODS: Fifty-eight infants (gestational age 39.4 +/- 1.4 weeks; birth weight 3,245 +/- 435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. RESULTS: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40 +/- 0.19, 0.41 +/- 0.20 and 0.43 +/- 0.20 microg/dL, respectively. CONCLUSIONS: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic.

Albumins↗
PubMed2001

Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus.

BACKGROUND: To evaluate the effects of an increase in glucose infusion rate of 2 mg/kg per min from the basal infusion rate on the prevention of hypoglycemia in very low-birthweight (VLBW) infants, following indomethacin therapy for patent ductus arteriosus (PDA). METHODS: Forty VLBW infants with PDA were given indomethacin 0.2 mg/kg intravenously up to three doses. In 15 of the 40 infants (supplemented group: between April 1995 and March 1996) the glucose infusion rate was increased in 2 mg/kg per min increments from the basal rate just before the initial indomethacin administration, compared with 25 historical control infants who received a fixed glucose infusion rate during the first 12 h after the initial dose. We evaluated the changes in blood glucose levels and glucose infusion rates in both groups. RESULTS: In the control group 11 of 25 (44%) infants had a blood glucose value below 40 mg/dL between 12 and 60 h (mean 32.7 h). In contrast only two out of 15 infants in the supplemented group reached the glucose level below 40 mg/dL between 72 and 96 h but both two were light-for-dates infants (defined as birthweight below the 10th percentile for gestational age on the standard intrauterine growth curve). Blood glucose values in the supplemented group were significantly higher than those in the control group between 12 and 96 h. However, glucose infusion rates were similar before and between 72 and 96 h. CONCLUSIONS: This retrospective study shows that an increase in glucose infusion rate of 2 mg/kg per min, in addition to the pre-existing stable maintenance glucose intake, might prevent against the occurrence of unexpected hypoglycemia in VLBW infants following indomethacin therapy.

Blood Glucose↗
PubMed2000

E-cadherin is a WT1 target gene.

The WT1 tumor suppressor gene encodes a transcription factor that can activate and repress gene expression. Transcriptional targets relevant for the growth suppression functions of WT1 are poorly understood. We found that mesenchymal NIH 3T3 fibroblasts stably expressing WT1 exhibit growth suppression and features of epithelial differentiation including up-regulation of E-cadherin mRNA. Acute expression of WT1 in NIH 3T3 fibroblasts after retroviral infection induced murine E-cadherin expression. In transient transfection experiments, the human and murine E-cadherin promoters were activated by co-expression of WT1. E-cadherin promoter activity was increased in cells overexpressing WT1 and was blocked by a dominant negative form of WT1. WT1 activated the murine E-cadherin promoter through a conserved GC-rich sequence similar to an EGR-1 binding site as well as through a CAAT box sequence. WT1 produced in vitro or derived from nuclear extracts bound to the WT1-response element within the murine E-cadherin promoter, but not the CAAT box. E-cadherin, a gene important in epithelial differentiation and neoplastic transformation, represents a downstream target gene that links the roles of the WT1 in differentiation and growth control.

3T3 Cells↗
PubMed1999

WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts.

The WT1 tumor suppressor gene, implicated in hereditofamilial and sporadic Wilms' tumor, is required for normal renal development and is up-regulated during the mesenchymal-epithelial transition. NIH3T3 fibroblasts overexpressing WT1 were less proliferative, larger in size and more firmly attached to tissue culture plastic, suggesting an alteration of their state of differentiation. These cells were studied in vivo by subcutaneous injection into nude mice. The resulting tumors exhibited epithelioid histopathology and formed desmosome-like structures. Molecular analyses of these WT1 expressing fibroblasts grown in culture and in nude mice revealed significant alterations in the expression of many kidney epithelial markers. These studies indicate that WT1 expression can initiate features of a program of epithelial differentiation consistent with a prominent role for WT1 in the mesenchymal epithelial transition that occurs during renal development. Through this work we identified a number of novel target genes for the WT1 transcription factor, including uvomorulin, integrin alpha8 and perlecan, and suggest that WTI may activate the IGF-II gene, also implicated in the development of Wilms' tumor.

3T3 Cells↗
PubMed1999

Successful transcutaneous arterial embolization of a giant hemangioma associated with high-output cardiac failure and Kasabach-Merritt syndrome in a neonate: a case report.

We describe the case of a patient with a neonatal giant cutaneous hemangioma with high-output cardiac failure and Kasabach-Merritt syndrome and successfully treated with transcutaneous arterial embolization aimed at controlling severe congestive heart failure and consumption coagulopathy. A patient was admitted to the neonatal care unit on the first day of age because of a large hemangioma on his right lateral chest wall and respiratory distress, associated with cardiac failure resulting from arteriovenous shunting. On the second day of age the platelet count decreased to 5.7 x 10(4)/microliter and fibrinogen level was 85 mg/dl. The values of prothrombin time and activated partial thromboplastin time were prolonged. Intravenous predonisone therapy was started immediately, but bleeding tendency was getting worse and the evidence of congestive heart failure persisted. On the third day the patient then underwent embolization of feeding arteries with microcoils. The cardiac failure and thrombocytopenic coagulopathy had improved significantly without complications. We conclude that transcutaneous arterial embolization is an effective and safe treatment in this neonate and should be considered for the treatment of control high-output cardiac failure and coagulopathy in infants with hemangioma and Kasabach-Merritt syndrome.

Cardiac Output, High↗
PubMed1999

Reduction in blood glucose values following indomethacin therapy for patent ductus arteriosus.

PURPOSE: To evaluate the effects of indomethacin on blood glucose values in premature infants with patent ductus arteriosus (PDA). METHODS: Twenty-five very low birthweight infants with PDA were given 0.2 mg/kg, i.v., indomethacin for up to three doses. We examined the relationship between blood glucose values and glucose infusion rate before and after indomethacin therapy. RESULTS: There was a significant reduction in blood glucose values between 12 and 96 h following i.v. indomethacin therapy. Eleven of 25 infants (44%) had blood glucose values below 40 mg/dL between 12 and 60 h (mean 32.7 h) after the initial dose. Although the glucose infusion rate during the first 12 h was constant (3.56 +/- 0.98 mg/kg per min), the blood glucose values decreased from 96 +/- 32 mg/dL at the starting point to 75 +/- 29 mg/dL at 12 h (P < 0.05). The maximum blood glucose reduction was 51.6 +/- 34.7 mg/dL and the maximum blood glucose reduction rate was 50.4 +/- 20.2%. CONCLUSIONS: The results suggest that blood glucose values should be measured at least every 6 h for 72 h until they stabilize in order to prevent unexpected hypoglycemia.

Cardiovascular Agents↗
PubMed1998

An evaluation of infants' growth in the Kingdom of Nepal.

BACKGROUND: The His Majesty's Government/Japan International Cooperation Agency Primary Health Care Project began in April 1993 in collaboration with the Saitama Prefectural Government, for the purpose of improving the health status of the people in model districts of the Kingdom of Nepal. Growth monitoring is one of the basic methods that defines the health and nutritional status of children. METHODS: Anthropometric indices were measured in 759 children in the Bhaktapur district. We used the World Health Organization prototype growth chart and national growth standard for Japanese children (1990) to analyze the growth data. RESULTS: We found that the average bodyweight growth curve of children up to 4 months of age followed the 50th percentile reference curve. For children of 5-12 months of age, there was a delay in bodyweight gain and the growth curve reached the 3rd percentile curve. For children more than 1 year old, the growth curve moved below the third percentile curve. Catch-up growth did not occur before the children reached 5 years of age. The main causes of catch-up growth being hampered were chronic undernutrition and inadequate nutritional balance. CONCLUSIONS: As this was the first opportunity to evaluate infant growth in this district, the first important consequence of the results was to analyze the causes of growth faltering and failure-to-thrive in Nepalese children. Even more important, was the need to give appropriate counseling on improving feeding and other health-related practices, and the most important consequence of all was to instruct Nepalese health workers that utilizing the growth charts is an integral part of health care.

Anthropometry↗
PubMed1997

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗
PubMed1997

Myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibodies -- related scleroderma renal crisis treated with double-filtration plasmapheresis.

A 46-year-old female patient who was diagnosed with systemic sclerosis (SSc) developed rapidly progressive renal failure without elevation of blood pressure or plasma renin concentration. Renal biopsy revealed necrotizing crescentic glomerulonephritis (pauci-immune type) and the myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA) titer was found to be elevated to 669 EU/ml. Methylprednisolone (MP) pulse therapy followed by prednisolone (PSL) and mizoribine (MZR) did not suppress the progression of renal failure. Therefore, we started double-filtration plasmapheresis (DFPP) which effectively removed MPO-ANCA and prevented renal failure despite the relatively low dose of immunosuppressive agents.

Acute Kidney Injury↗
PubMed1996

Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the Bacillus subtilis genome containing the skin element and many sporulation genes.

As part of the Bacillus subtilis genome sequencing project, we have determined a 283 kb contiguous sequence from 210 degrees to 232 degrees of the B. subtilis genome. This region contains the 48 kb skin element which is excised during sporulation by a site-specific recombinase. In this region, 310 complete ORFs and one tRNA gene were identified: 66 ORFs have been sequenced and characterized previously by other workers, e.g. acc, ans, bfm, blt, bmr, comE, comG, dnaK, rpoD and sin operons; cwiA, gpr and lysA genes; many sporulation genes and operons, spo0A, spoIIA, spoIIM, spoiiP, spoIIIA, spoIIIC, spoIVB, spoIVCA, spoIVCB and spoVA, etc. The products of 84 ORFs were found to display significant similarity to proteins with known function in data banks, e.g., proteins involved in nucleotide metabolism, lipid biosynthesis, amino acid transport (ABC transporter), phosphate-specific transport, the glycine cleavage system, the two-component regulatory system, cell wall autolysis, ferric uptake and sporulation. However, the functions of more than half of the ORFs (52%, 160 ORFs) are still unknown. In the skin element containing 60 ORFs, 32 ORFs (53%) encode proteins which have significant homology to gene products of the B. subtilis temperate phage phi 105 and/or the defective phage PBSX.

Bacillus subtilis↗
PubMed1995

The transcriptional effect of WT1 is modulated by choice of expression vector.

The WT1 Wilms' tumor suppressor gene encodes a zinc finger transcription factor which plays a critical role in renal and genitourinary development. The WT1 protein was reported to both activate and repress transcription. We found that the transcriptional effect of WT1 on the Egr1 promoter could be modulated by the use of expression vectors containing different promoters. WT1 activated the Egr1 promoter when expression of WT1 was driven by the Rous sarcoma virus promoter. In contrast, a cytomegalovirus (CMV) promoter-containing WT1 expression vector repressed the Egr1 promoter. However, WT1 activated transcription of a simple test promoter, EGR3tkCAT, regardless of the expression vector used. Co-transfection of the parental CMV-based vector strongly depressed the basal activity of the Egr1-CAT reporter, suggesting that the CMV promoter competes with the Egr1 promoter for transcription factors or co-factors which may be required for activation by WT1. In support of this hypothesis, WT1 was converted from an activator to a repressor by co-transfection of an excess of the parental CMV-based vector. These results provide an important caveat to the interpretation of co-transfection studies and confirm the bi-functional nature of the WT1 transcription factor.

Animals↗
PubMed1995

Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes.

Despite the extensive molecular information on serum-derived human hepatitis B viruses (HBV), liver-derived replicative HBV genomes have remained largely uninvestigated. We have examined the sequences of the entire core antigen (nucleocapsid) of liver-derived HBVs in 15 different hepatoma patients. Bona fide mutations, rather than subtype polymorphism, have been identified based on the high-frequency occurrence of structural differences from wild type at the highly evolutionarily conserved positions, instead of at the positions known to contain genetic heterogeneity among different isolates from different geographic locations. The distribution of these naturally occurring mutations of HBV core gene appears to be nonrandom and is found predominantly within three major (I, IV, and V) and four minor domains (II, III, VI, and VII). In general, domain IV mutations correlate with domain V mutations. The replicative HBV DNAs tend to accumulate a higher number of mutated core domains than the integrated HBV DNAs. At the domain level, there is no significant difference in HBV core mutation frequencies between the liver tumors and the adjacent nontumorous livers. Strikingly, domains I, III, and V coincide with three major known T cell epitopes within the core protein in acute and chronic hepatitis B patients. Furthermore, these domains coincide with HLA class II-restricted T cell epitopes, rather than with the conventional HLA class I-restricted epitopes of cytotoxic T lymphocytes. Our results support the hypothesis that HBV core antigen variants can accomplish immunoevasion via accumulated escape mutations. In addition, they also provide a potential molecular explanation for the maintenance of persistent infection of human hepatitis B virus in chronic carriers.

Adult↗
PubMed1995

The tumor suppressor gene WT1 inhibits ras-mediated transformation.

Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.

3T3 Cells↗