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Biomedical subjects

S Takano

Publications and source records attributed to S Takano.

At least 91 records · Page 5Linked to original sources

Circadian variation in skin blood flow responses to passive heat stress.

To examine whether there is a circadian variation in skin blood flow response to passive heat stress and maximal skin blood flow, which was measured by local warming to 42 degrees C for 45 min, we studied six men at an ambient temperature of 28 degrees C at four different times of day [0400-0700 (morning), 1000-1300 (daytime), 1600-1900 (evening), and 2200-0100 hours (night)], each time of day being examined on separate days. Heat stress at rest was performed by immersing the legs below the knee in hot water (42 degrees C) for 60 min. The esophageal temperature (Tes) at rest was significantly higher in the evening than in the morning. The maximal skin blood flow (SkBFmax) on both sites, back and forearm, did not show a significant difference among the four times of day. The variation in Tes thresholds for cutaneous vasodilation to heat stress was similar to the circadian rhythm in resting Tes. The relationship of the percentage of SkBFmax (%SkBF) with Tes was significantly lower in the morning than in the evening. The results suggest that the maximal skin blood flow during local warming does not show variation over the day, but the sensitivity of vasodilation to passive heat stress shows a circadian variation.

Adult↗

Elevated levels of mortalin expression in human brain tumors.

We have performed immunohistochemical studies of mortalin in normal and tumor human brain sections. In normal brain sections, the expression was seen mainly as being confined to neurons. Normal astrocytes showed undetectable expression of this unique member of the heat shock 70 protein family. Three grades of astrocyte tumors (low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma), however, showed an increasing number of mortalin-positive cells. Other types of brain tumors, such as meningiomas, neurinomas, pituitary adenomas, and metastases, also showed elevated levels of mortalin expression compared to those in the normal brain. Mortalin has earlier been reported to have differential intracellular distribution in normal and transformed cells in vitro. Therefore, we substantiated the present study with immunofluorescence localization of the protein in normal and glioblastoma cells. The observations indicated that the tumors might be expressing a nonpancytosolic mortalin. An increase in number of mortalin-positive cells with malignant progression of brain tumors and its correlation with Ki-67 (a cell proliferation marker)-positive cells further suggested an involvement of nonpancytosolic mortalin(s) in malignant transformation of cells in vivo.

Animals↗

Thirteen-week subchronic toxicity study of thiamphenicol in F344 rats.

A 13-week subchronic toxicity study of thiamphenicol (TAP) was performed in F344 rats. The minimum lethal dose was estimated to be greater than 10 g/kg body weight, when a single dose of 4-10 g/kg of TAP was given orally. In the subchronic toxicity study, groups of 12 F344 rats of each sex were given solutions containing 0 (control), 125, 250 and 500 ppm of TAP as their drinking water ad libitum for 13 weeks. Body weight gain was significantly suppressed in both sexes of the 250 and 500 ppm groups. Slight suppression of erythropoiesis was observed in the highest-dose group along with slightly reduced spermatogenesis in the testes of the males. In addition, spermatogranulomas were found in the epididymis of both middle- and highest-dose groups. The no observed adverse effect level (NOAEL) was concluded to be 125 ppm (daily doses of 9.0 mg/kg in males and 11.6 mg/kg in females). From the above described results, doses of 250 and 125 ppm were selected as appropriate for a 2-year carcinogenicity study.

Animals↗

Expression analysis of mortalin, a unique member of the Hsp70 family of proteins, in rat tissues.

We have investigated the expression of mortalin in rat tissues by Northern analysis, RNA in situ hybridization, and immunohistochemical studies. By Northern assay, the highest level of expression was detected in brain, heart, and skeletal muscle followed by lung, liver, and kidney, and the least level of expression was detected in testis and spleen. RNA in situ and immunohistochemical studies showed that mortalin expression is significantly higher in upper nondividing layers than in the lower basal layers of skin, in neurons and nerve fibers than in surrounding glial cells in brain, in cardiomyocytes than in nonmyocytes in heart, and in interstitial secretory tissue than in germinating follicles in ovary. Such tissue- and cell-specific expression patterns of mortalin coordinates with its earlier reported antiproliferative function in normal cells. However, a deregulation of the expression is observed in rat brain tumor along with the detection of nonpancytosolic mortalin in rat glioma cell line C6. The study suggests that mortalin is involved in pathways that regulate division capacities of cells in vivo.

Animals↗

Undectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype.

PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mismatch repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary nonpolyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples. MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of the hMLH1 gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product.

Adaptor Proteins, Signal Transducing↗

Circadian variation of sweating responses to passive heat stress.

The aim of present study was to examine whether sweating responses to passive heat stress change with the circadian rhythm of internal temperature. Six men had their legs immersed in water at 42 degrees C for 60 min in an ambient temperature of 28 degrees C on four separate days. Experiments were conducted at four different times [06.00 h (morning), 12.00 h (daytime), 18.00 h (evening) and 24.00 h (night)]. We measured oesophageal temperature (Toes), mean body temperature (Tb), local sweating rate (msw) on the forehead, back, forearm and thigh, the densities of activated sweat gland (ASG) on the back, forearm and thigh, and the frequency of sweat expulsion per minute (Fsw) which has been suggested to represent central sudomotor activity. Sweat gland output (SGO) on each site was calculated by dividing msw by ASG. ASG was significantly higher on the forearm than on the back and thigh, and SGO was significantly lower on the forearm than on the back and thigh. However, ASG and SGO did not significantly change over the day. Tb and Toes thresholds for the onset of sweating showed a significant change with both the temperature rhythms at rest prior to each procedure, while the slopes of the relationships Fsw-Tb and msw-Fsw showed no significant difference over the day. We suggest that the circadian variation of sweating response to passive heat stress is regulated by a central sudomotor mechanism rather than by sweat gland function.

Adult↗

Determination of ascorbic acid in human vitreous humor by high-performance liquid chromatography with UV detection.

PURPOSE: Ascorbic acid (AA) accumulates in vitreous at a concentration several times higher than in plasma. It has been suggested that AA may serve as an antioxidant that protects ocular tissues from free radical attack. There are many reports about the concentration of AA in ocular tissues. However, AA in adult human vitreous humor has not been determined. We measured concentrations of AA from pathologic human vitreous samples and compared the results. METHODS: AA was measured by high-performance liquid chromatography (HPLC) with UV detection. Human vitreous humor was collected from patients undergoing pars plana vitrectomy. RESULTS: AA was quantified in vitreous humor of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), macular hole (MH), idiopathic premacular fibrosis (PMF), and Terson syndrome (Terson). The concentrations of AA were 120.9 +/- 36.3 micrograms/ml (mean +/- SD), 129.8 +/- 36.6, 311.5 +/- 126.7, 446.9 +/- 154.2 and 406.0 +/- 22.0, respectively. There was no significant difference between the PDR and the PVR groups (unpaired t-test). Patients with PDR and PVR showed significantly lower concentrations of AA than those with MH, PMF, and Terson (p < 0.01). CONCLUSIONS: These findings suggest that increased oxidative stress may be produced in the ocular tissues of eyes with PDR and PVR, and AA appears to be consumed (oxidized) in performing its protective role.

Ascorbic Acid↗

Effect of growth hormone on fatty liver in panhypopituitarism.

A 17 year old boy was admitted because of short stature and hepatomegaly. He was diagnosed with panhypopituitarism and fatty liver. The fatty liver improved, not with hydrocortisone or levothyroxine treatment, but with growth hormone administration. The fatty liver in this patient was attributable to a growth hormone deficient state.

Adolescent↗

[Comparison of three methods for quantitative measurement of hepatitis C virus].

Three assays for measuring hepatitis C virus(HCV) were compared with regard to sensitivity and correlations. The methods included were the Roche Amplicor HCV Monitor test(PCR), the branched DNA signal amplification assay(b-probe), and the serum concentration of HCV core protein measured by the sandwich FEIA (Core-Ag). Also, HCV serotypes were determined by the enzyme-linked immunosorbent assay. Testing 105 consecutive HCV-RNA positive samples showed that the PCR was the most sensitive assay(100% quantifiable), followed by the Core-Ag(82.4%) and the b-probe(75.3%). The values obtained by each method correlated well in serotype 1, whereas some discordance was noted in serotype 2 cases. Also, serotype 2 samples were less quantifiable particularly by b-probe assay than serotype 1 samples. These points have to be considered in quantification of serum HCV levels by currently available these three methods.

Biomarkers↗

Possible existence of platelet aggregation inhibitor(s) in a gas-phase extract of cigarette smoke.

Present study demonstrated an existence of anti-aggregation factor(s) in water-soluble extract of a gas-phase of cigarette smoke, and studied chemical characteristics of the factor(s) evaluating its inhibitory potency on platelet aggregation of human and rabbit platelets. The water-soluble extract was prepared by passing mainstream smoke of one cigarette through a Cambridge glassfiber filter and then bubbling it through 1 ml of water. The inhibitory effects were similar in both human and rabbit platelets with the final concentrations of 1 to 5% of the aqueous extract, and were also non-specific irrespective of types of agonists such as collagen, arachidonic acid, STA2 (a stable analogue of thromboxane A2), ADP or nor-adrenaline. The inhibitory effect of water-soluble extract on platelet aggregation were not affected by treatment of the extract by erythrocytes, indicating that the factor(s) was different from the one that is adsorbed by hemoglobin, such as superoxide radicals, nitric oxide (NO), nitrogen oxides (Nox), hydrogen peroxide (H2O2), carbon monoxide (CO), aldehydes, trace elements (Cd2+, Cu2+) or carcinogenic nitrosocompounds. The inhibitor(s) was stable in acidic condition under 4 degrees C but unstable in basic condition under room temperature. The anti-platelet factor(s) was retained on a reversed phase chromatography column, and eluted with 50 to 60% methanol. The substance(s) was also adsorbed by H+ and OH- form ion exchange columns, but not by Cl- form, suggesting that the substance is both basic and acidic but not so strong as to be absorbed by Cl- form column. These facts suggest that the anti-platelet substance(s) in the water extract of cigarette smoke seems to be moderately non polar, both acidic and basic in water and not adsorbed by hemoglobin.

Animals↗

Establishment and characterization of two cultured cell lines derived from malignant rhabdoid tumors of the kidney.

Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of childhood. Its histogenesis is unclear, and it is highly resistant to multimodality therapy. To elucidate the origin and the oncogenetic potential of RTK, we investigated the characteristics of 2 newly established RTK cell lines, SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not exhibit contact inhibition and exhibited intermediate filaments, a specific marker for RTK. These cells possess the characteristics of mesenchymal cells based on their positive reactions with anti-vimentin and anti-laminin antibodies and their negative reactions with anti-keratin and anti-desmin antibodies. The karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(11)(pter-p13::p12-qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers examined, SWT-2 released tissue polypeptide antigen into the culture supernatant. No rearrangement or amplification of the myc and ras oncogenes or of the p53 tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were expressed in both cells. Our data suggest that these 2 cell lines may be useful in identifying the oncogenetic pattern of RTK.

Antineoplastic Agents↗

Structural studies of the proton-translocating NADH-quinone oxidoreductase (NDH-1) of Paracoccus denitrificans: identity, property, and stoichiometry of the peripheral subunits.

The proton-translocating NADH-quinone oxidoreductase (NDH-1) of Paracoccus denitrificans is composed of at least 14 unlike subunits and contains one FMN and at least five EPR-detectable iron-sulfur clusters. The 14 subunits are designated NQO1 through NQO14. The expression and partial characterization of the NQO4, -5, and -6 subunits have been performed. The NQO4, -5, and -6 subunits were individually expressed in Escherichia coli. The NQO4 subunit was expressed in both the cytoplasmic phase and membrane fraction, the NQO5 subunit in the cytoplasmic phase only, and the NQO6 subunit in the membrane fraction only. The NQO4 and NQO5 subunits were purified from cytoplasmic phase. Neither subunit contains non-heme iron or acid-labile sulfide, suggesting that the NQO4 or NQO5 subunit is not an iron-sulfur subunit. The antibodies against the NQO4, -5, and -6 subunits cross-reacted with their counterpart subunits in bovine heart complex I. The NQO4, -5, and -6 subunits in membrane-bound P. denitrificans NDH-1 were extracted by treatment at alkaline pH ( > or = 10) or with chaotropes (NaBr, Nal, and urea), suggesting that these subunits are localized in the peripheral part (not in the membrane sector) of the enzyme complex similar to the NQO1, -2, and -3 subunits. In addition, the subunit stoichiometry of NQO1 through -6 of the membrane-bound P. denitrificans NDH-1 has been determined by radioimmunoassays. There is 1 mol each of the NQO1 through -6 subunits per mol of the P. denitrificans NDH-1.

Amino Acids↗

Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients.

Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytoma, low grade astrocytoma, meningioma, malignant lymphoma, and metastatic brain tumor as well as normal brain. Although VEGF concentration of the serum was not correlated with that of the tissue, VEGF concentrations of glioblastoma cyst fluid were 200-300-fold higher than those of serum in the patients. VEGF concentration in the tumors was significantly correlated with the vascularity measured by counting vessels stained with von Willebrand factor antibody. VEGF protein localized to the cytoplasm of tumor cells and vasculature in gliomas, predominantly in the peripheral microvessel "hot spots" as well as around the necrosis in glioblastomas. VEGF immunopositivities were well reflected with VEGF concentration determined by ELISA. VEGF ELISA demonstrated time-dependent increase of the VEGF concentration in the serum-free conditioned medium of various glioma cell lines. The conditioned medium with high VEGF concentration induced endothelial cell migration. These observations suggest that VEGF represents a useful marker and measurable element of glioblastoma angiogenesis. The measurement of VEGF concentration by ELISA in tumor and tumor cyst fluid may allow for the assessment of vascularity in gliomas.

Adult↗

PRL-1, a protein tyrosine phosphatase, is expressed in neurons and oligodendrocytes in the brain and induced in the cerebral cortex following transient forebrain ischemia.

Protein tyrosine phosphorylation is thought to play an important role in the regulation of neural function. We reported previously that CL100, a cytoplasmic type protein tyrosine phosphatase (PTP), was induced after transient forebrain ischemia. In the present study, changes in the mRNA levels after ischemia of PRL-1, a cytoplasmic type PTP and immediate-early gene similar to CL100, was examined. In situ hybridization histochemistry showed that PRL-1 mRNA was expressed in normal adult rats in neurons and oligodendrocytes in widespread regions including the cerebral cortex, hippocampus and cerebellum. PRL-1 mRNA was expressed in the developing brains on embryonic days 15 and 19 and postnatal day 1. Northern blot analysis showed that PRL-1 mRNA was induced from 6 h to 9 h after reperfusion in the cerebral cortex of postischemic rats. These findings suggest that PRL-1 plays a role in neurons and oliogodendrocytes, and that expression of PRL-1 mRNA is regulated by a mechanism different from those of other immediate-early genes such as c-fos and c-jun.

Animals↗

Prospective assessment of donor blood screening for antibody to hepatitis C virus by first- and second-generation assays as a means of preventing posttransfusion hepatitis.

In November 1989, the Japanese Red Cross began screening blood donors for the hepatitis C virus antibody (anti-HCV) by first-generation assay and high-titer hepatitis B virus core antigen antibody. A significant reduction in the incidence of acute posttransfusion hepatitis was reported; however, the incidence still ranged from 2 percent to 4 percent. The Red Cross changed to the second-generation assay in February 1992, the objective being the complete elimination of potential posttransfusion hepatitis. The aim was to elucidate the advantage of second-generation assay as a blood-donor screening test. The incidence of posttransfusion hepatitis after the introduction of second-generation assay was compared with that before the introduction of the first-generation assay and with that during its use. The incidence of posttransfusion hepatitis was 9.6 percent (216/2,240) before anti-HCV-s donor screening. It was 3.7 percent (24/655) and 0.9 percent (3/326) after the introductions of the first- and second-generation hepatitis C virus (HCV) assays, respectively (chi (2) = 50.0, P < .01). Blood-donor screening by second-generation anti-HCV provided a significant benefit compared with the first-generation assay.

Adult↗

Case report: mucin-producing cystic neoplasm of the pancreas with onset in childhood.

Mucin-producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle-aged and elderly people. In the present report, a case of a 21-year-old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.

Adult↗