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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 145 records · Page 8Linked to original sources

Mutagenic activity of surface soil and quantification of 1,3-, 1,6-, and 1,8-dinitropyrene isomers in soil in Japan.

To clarify the mutagenic potential of nonagricultural surface soil in Japan, 110 soil samples were collected from five geographically different areas between November 1996 and March 1997, and organic extracts of the soil samples were examined by the Ames/Salmonella assay. Most of the soil extracts showed mutagenicity toward both strains TA98 and TA100 in the presence and/or absence of a mammalian metabolic activation system (S9 mix), suggesting that surface soil is largely contaminated with environmental mutagens. Soil samples collected at Hekinan, Kobe, and Osaka were highly mutagenic toward both strains, and their potencies toward TA98 without S9 mix were extremely high, inducing more than 12 000 revertants per gram of soil. On the other hand, soil samples from Muroran showed strong mutagenicity toward TA100 with S9 mix. Furthermore, 1, 3-dinitropyrene (DNP), 1,6-DNP, and 1,8-DNP in soil samples collected at 10 sampling sites in three metropolitan areas were quantified by fluorometric detection of the corresponding diaminopyrene isomers using high-performance liquid chromatography (HPLC). Three DNP isomers were detected in all soil samples, and the amounts of 1,3-, 1,6-, and 1,8-DNP isomers in the soil samples were 12-3270, 14-5587, and 13-6809 pg/g, respectively. The gross amount of three DNP isomers in surface soil collected at Hekinan was more than 10 ng per gram of soil. The highest contribution ratios of DNP isomers to the mutagenicity of soil extracts were observed for the samples collected at Osaka, and the total of the contribution ratios of three DNP isomers was about 50%. These results suggest that surface soil is largely contaminated with mutagenic compounds and that DNP isomers are one class of major mutagenic and carcinogenic compounds contaminating surface soil.

Air Pollutants↗

Dietary restriction initiated late in life can reduce mitochondrial protein carbonyls in rat livers: western blot studies.

Life long dietary restriction has a variety of beneficial effects such as retarding the age-related decline of physiological functions as well as the onset of diseases, thus prolonging the life span of experimental animals. In the present work we investigated the effect of DR initiated late in life on rats regarding oxidative modifications of liver mitochondrial proteins in terms of generation of carbonyl moieties by western blot using antibodies against dinitrophenylhydrazones after the reaction of the proteins with dinitrophenylhydrazine. Protein carbonyls in mitochondria of 30-month-old animals increased by about 55% as compared with their 10-month-old counterparts. Every-other-day feeding initiated at the age of 26.5 months and continued for 3.5 months resulted in the decrease of the carbonyls to the level of the ad libitum fed young animals. Our findings suggest that DR initiated late in life can have a beneficial effect by reducing the accumulated oxidative damage in mitochondrial proteins.

Aging↗

The efficacy of biochemical markers in patients with ossification of posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum levels of carboxyterminal propeptide of type I collagen (PICP), osteocalcin (OC), carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in patients with ossification of posterior longitudinal ligament of the spine (OPLL) and age-matched control subjects. OBJECTIVES: To evaluate the efficacy of these biochemical markers of the patients with OPLL. SETTING: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. METHODS: Spot urine and blood samples were obtained from 20 healthy males aged 45 - 78 (mean+/-SD; 63. 0+/-11.5) and 22 male patients with OPLL aged 46 - 77 (mean+/-SD; 59. 9+/-8.8), and serum levels of PICP, OC, ICTP and urinary levels of Pyr and Dpyr were measured. RESULTS: There were no significant difference in age, serum PICP, OC, ICTP, urinary Pyr and Dpyr levels between OPLL and control group. CONCLUSION: Neither bone formation nor bone resorption was accelerated in the patients with OPLL.

Aged↗

Telomerase activity in peripheral blood for diagnosis of hepatoma.

BACKGROUND: Telomerase activity may be used as a molecular marker for the detection of circulating hepatoma cells in blood of patients with hepatoma. METHODS: Telomerase activity in peripheral blood from hepatocellular carcinoma (HCC) patients was assessed by using a highly sensitive and non-radioisotope telomerase polymerase chain reaction (PCR) ELISA. Initially, tissue telomerase activity was measured in the hepatoma and non-tumour portions by using PCR ELISA within the same specimen, to compare its sensitivity with the conventional telomeric repeat amplification protocol (TRAP) method. Second, telomerase activity was measured in the peripheral blood obtained from patients with HCC, patients with chronic liver disease and in healthy controls. RESULTS: Of the 17 HCC patients, telomerase activity was found to be positive in 14 (82%) by using TRAP and 15 (88%) by using PCR ELISA, indicating that PCR ELISA is a reliable tool for the measurement of telomerase activity. By using the Telomerase PCR ELISA assay, telomerase activities in the peripheral blood of 20 HCC patients was 1.65 +/- 0.78 units. This was significantly greater than the results obtained for 20 chronic liver disease patients (0.43 +/- 0.36 units) and 20 healthy controls (0.39 +/- 0.14 units; P < 0.0001).When the arbitrary cut-off level was set at 0.7 units (maximum value of healthy controls + 0.1), the positive frequency of telomerase activity was 25% for chronic liver disease and 80% for HCC patients (sensitivity 80%, specificity 75%). Among the HCC patients, high telomerase activity in the peripheral blood was shown at stage III HCC with vascular invasion (2.10 +/- 0.62 units, n = 9). This was significantly higher than patients at stage II of HCC (1.28 +/- 0.72 units, n = 11, without vascular invasion; P = 0.012). CONCLUSION: These results suggest that peripheral blood telomerase activity, which may reflect haematogenous micrometastasis, is potentially a practical diagnostic/predictive marker of HCC.

Biomarkers, Tumor↗

Differential diagnosis of obstructive sleep apnea syndrome patients and snorers using cephalograms.

Severe snoring is thought by many to be an early stage of obstructive sleep apnea syndrome (OSAS), but the anatomical relation between snoring and OSAS, if any, has remained unclear. To compare the morphology of the airway between snorers and OSAS patients for possible similarities, we conducted a cephalometric analysis of Japanese OSAS patients (n=10), habitual snorers (n=10), and non-snoring controls (n=50). There was no significant difference in SNB (the angle formed by the sella, nasion and point B) between OSAS patients and the control subjects. Obstructive sleep apnea syndrome patients tended to have an anteriorly positioned maxilla, and an anteroposterior misalignment between the maxilla and mandible. There was also a tendency toward skeletal openbite. Both OSAS patients and snorers had large tongues and large soft palates, thus causing constriction of the airway with resultant smaller airway diameter and smaller airway surface area. Significant differences between OSAS patients and snorers were found in thickness and length of soft palate surface area, and thickness, length, and position of the hyoid bone. These results suggest that cephalographic measurements may be of considerable use in determining the seriousness of a patient's condition.

Adult↗

Major hepatic resection may suppress the growth of tumours remaining in the residual liver.

Little is known as to how hepatectomy is associated with the growth of hepatic tumours, which may reside in the remaining liver after curative resection for hepatocellular carcinoma. Using an intra-hepatic tumour implantation model in rats, the effects of hepatectomy on tumour growth in the remaining liver were investigated. On post-operative day 7, the tumour weight in the remaining liver following 30% hepatectomy was 0.321+/-0.058 g (mean +/- SD) which was significantly greater than that (0.245+/-0.040 g) in sham operations (P<0.05). However, the tumour weight (0.156+/-0.067 g) in the remaining liver following 60% hepatectomy was significantly lower than that in sham animals (P< 0.005). The number of TdT-mediated dUTP nick-end labelling (TUNEL) positive tumour cells was significantly increased in 60% hepatectomy as compared with the sham and 30% hepatectomy group. The mRNA expression of TGF-beta1, TNF-alpha and Fas in the tumour portion of 60% hepatectomy, was higher than that in 30% hepatectomy group. Plasma levels of TGF-beta1 were inversely correlated with intra-hepatic tumour weights. These results suggest that major hepatic resection may lead to an increased induction of apoptosis for the remaining hepatic tumour.

Animals↗

Phosphorylation of mitogen-activated protein kinase cascade during early embryo development in the mouse.

The mitogen-activated protein kinase (MAPK) cascade is one of the most important signal transduction pathways that regulate the cell cycle in somatic cells. The present study examined the phosphorylation states of components in the MAPK cascade, Raf-1, MEK-1, and extracellular signal regulated kinases (ERKs), which are activated by mitogens, throughout early mouse embryo development and in cultured somatic cells generally. In somatic cells, Raf-1 and MEK-1 were phosphorylated at M-phase and dephosphorylated during interphase. ERKs were not phosphorylated at any stage during the cell cycle. These results were similar to previous findings for the first and second cell cycles of early mouse embryos. In contrast, after the four-cell stage, not only ERKs, but also Raf-1 and MEK-1, were not phosphorylated at any stage during the cell cycle in mouse early embryos. These results suggest that the MAPK cascade in mouse embryos is regulated by the same mechanism as in somatic cells before the two-cell stage, and that regulation is changed to an embryo-specific mechanism after the four-cell stage.

3T3 Cells↗

Mitogen-activated protein kinase, ERK1/2, is essential for the induction of vascular endothelial growth factor by ionizing radiation mediated by activator protein-1 in human glioblastoma cells.

Vascular Endothelial Growth Factor (VEGF)/Vascular Permeability Factor plays an important role in angiogenesis and cell proliferation of cancer cells. Glioblastoma cells are most malignant and show resistance to radiation therapy inducing VEGF to cause angiogenesis and brain edema. In the present study, the regulatory mechanism of the expression of VEGF by ionizing radiation was studied in three human glioblastoma cells. Induction of VEGF mRNA by ionizing radiation was dependent on dose and incubation time. Activator protein-1 (AP-1) was activated by 10 Gy of ionizing radiation in 1 h in T98G glioblastoma cells on an electrophoretic mobility shift assay. We constructed chimeric genes containing various regions of the VEGF promoter gene and the coding region for chloramphenicol acetyltransferase (CAT) and transiently transfected them to T98G cells. CAT assay with the VEGF promoter gene containing an AP-1 site demonstrated that the promoter activity of the VEGF gene was enhanced by ionizing radiation. Immunological analysis of the activity of mitogen-activated protein kinase, ERK1/2, showed that this activity is up-regulated by ionizing radiation. These results suggest that ERK1/2 pathway is involved in the up-regulation of VEGF expression ionizing radiation mediated by AP-1, which may lead to further neovascularization and proliferation of glioblastoma cells resistant to radiation therapy.

Blotting, Northern↗

Irreversible extrusion of the first loop facing the matrix of the bovine heart mitochondrial ADP/ATP carrier by labeling the Cys(56) residue with the SH-reagent methyl methanethiosulfonate.

The effect of the SH-reagent methyl methanethiosulfonate (MMTS) on the ADP/ATP carrier of bovine heart mitochondria was studied under various conditions. MMTS labeled predominately Cys(56) in the first loop facing the matrix (loop M1), and the labeling inhibited ADP transport via the carrier. The transport inhibition was found to be due to fixation of the carrier in the m-state conformation. MMTS labeling was suggested not to affect ADP binding to its major binding site. These features were the same as those of another commonly used SH-reagent, N-ethylmaleimide (NEM). Although the van der Waals volume of the non-hydrogen-bondable methylthio group of MMTS is much smaller than that of the ethylsuccinimide group of NEM, modification of Cys(56) inhibited the interconversion between the m- and c-state conformation. The mechanism by which MMTS inhibited the transport activity is discussed in terms of stabilization of conformation of the loop M1.

Adenosine Diphosphate↗

Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse.

Recent findings in animals emphasize that experimental ischemic brain damage can be strikingly reduced by estrogen: however, the neuroprotective mechanisms are not well understood. It was hypothesized that estrogen signaling via cognate estrogen receptors (ERs) within the vasculature is an important aspect of cerebral ischemic protection in the female brain, in part by amplifying intraischemic cerebral blood flow (CBF). In the present study, the hypothesis that chronic treatment with the pure ER antagonist ICI182,780 (ICI) would increase ischemic brain damage by a blood flow-mediated mechanism was investigated. Adult C57B1/6J mice were pretreated with either subcutaneous ICI (100 microg/day) or oil/ethanol vehicle for 1 week before 2 hours of middle cerebral artery occlusion (MCAO) and 22 hours of reperfusion. End-ischemic regional CBF was evaluated in additional cohorts using [14C]iodoantipyrine autoradiography. Infarction volume as measured by cresyl violet histology was greater in the striatum of ICI-treated females (70 +/- 3% of contralateral striatum vs. 40 +/- 12% in vehicle-treated females). Cortical injury was not enhanced relative to control animals (39 +/- 6% of contralateral cortex in ICI group vs. 27 +/- 8% in vehicle-treated group). Physiologic variables and ischemic reduction of the ipsilateral cortical laser-Doppler flow signal were similar between groups. Further, ICI treatment did not alter end-ischemic cortical or striatal CBF. The deleterious effect of ICI was limited to females, as there were no differences in stroke damage or CBF between male treatment groups. These data suggest that estrogen inhibits ischemic brain injury in striatum of the female by receptor-mediated mechanisms that are not linked to preservation of intraischemic CBF.

Animals↗

[The efficacy of influenza vaccine among geriatric inpatients].

To investigate the efficacy of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titer for the three types of influenza viruses were measured and the influenza infection rate was determined serologically in geriatric inpatients. Influenza vaccination was done for inpatients. For patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once or twice, and the number of injections were determined randomly. Influenza vaccine was injected twice to those had not received influenza vaccine in the previous year. Serum samples were collected from 166 vaccinated and 104 unvaccinated patients before and after 1996/1997 influenza season. In the vaccinees who had been vaccinated the previous year, 56 patients were injected once and 58 patient were injected twice. Fifty-two patients had not been vaccinated the previous year. Serologically diagnosed influenza infection rate in the 104 unvaccinated patients was 16.3% for influenza A/H3N2 and 8.7% for influenza B. The infection rate was 3.0% for influenza A/H3N2 and 0.6% for influenza B in the 166 vaccinated patients. The infection rates were significantly lower in the vaccinees than in the unvaccinated patients (p < 0.001 with A/H3N2 and p < 0.01 with B). There was no significant difference in the infection rate among the three vaccinated groups. These results suggest that the influenza vaccination had significant protective efficacy for influenza infection in the elderly. Prior vaccination did not diminish the efficacy of the influenza vaccine. The efficacy of a single influenza vaccine injection was equivalent to that of two injection.

Aged↗

Isolation of tannin-degrading lactobacilli from humans and fermented foods.

Lactobacilli with tannase activity were isolated from human feces and fermented foods. A PCR-based taxonomic assay revealed that the isolates belong to Lactobacillus plantarum, L. paraplantarum, and L. pentosus. Additional studies on a range of Lactobacillus species from established culture collections confirmed that this enzymatic activity is a phenotypic property common to these three species.

Animals↗

TT virus infection in nonhuman primates and characterization of the viral genome: identification of simian TT virus isolates.

Newly discovered TT virus (TTV) is widely distributed in human populations. To understand more about the relationship between TTV and its hosts, we tested 400 sera from various nonhuman primates for the presence of TTV DNA by PCR assay. We collected serum samples from 24 different species of nonhuman primates. TTV DNA was determined by PCR with primers designed from the 5'-end region of the TTV genome. Nucleotide sequencing and phylogenetic analysis of viral genomes were also performed. TTV DNA was detected in 87 of 98 (89%) chimpanzees and 3 of 21 (14%) crab-eating macaques. Nucleotide sequences of the PCR products obtained from both animals were 80 to 100% identical between two species. In contrast, the sequences differed from TTV isolates in humans by 24 to 33% at the nucleotide level and 36 to 50% at the amino acid level. Phylogenetic analysis demonstrated that all TTV isolates obtained from simians were distinct from the human TTV isolates. Furthermore, TTV in simians, but not in humans, was classified into three different genotypes. Our results indicate that TTV in simians represents a group different from, but closely related to, TTV in humans. From these results, we tentatively named this TTV simian TTV (s-TTV). The existence of the s-TTV will be important in determining the origin, nature, and transmission of human TTV and may provide useful animal models for studies of the infection and pathogenesis of this new DNA virus.

Amino Acid Sequence↗

Effect of lithium carbonate on the enhancement of serotonin 2A receptor elicited by dexamethasone.

The purpose of this study was to investigate whether chronic dexamethasone (Dex) administration induces serotonin (5-HT) 2A receptor supersensitivity and if chronic lithium carbonate (Li) administration contributes to the normalization of 5-HT2A receptor supersensitivity induced by Dex in rat brain. We investigated the effects of a 14-day administration of Dex and/or Li on changes in body weight (BW), on plasma corticosterone levels, on plasma lithium levels, on 5-HT2A receptor binding sites, and on (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI)-induced wet dog shake (WDS), which is mediated by 5-HT2A receptor in rats. Dex significantly reduced the BW of rats. Li did not have any effect on BW gain and did not prevent the BW loss induced by Dex. The plasma corticosterone levels of rats treated with Dex were too low to be detected. Li did not have any effect on corticosterone levels and did not prevent the decrease in the corticosterone levels induced by Dex. Six hours after the last treatment, the plasma lithium levels of rats treated with Li were significantly higher than those of rats treated with Dex/Li. Chronic Dex administration resulted in a significant increase in the density (B(max)) of the 5-HT2A receptor without a significant change in the affinity (K(d)). The increase in the B(max) induced by Dex was not prevented by chronic combined treatment with Dex and Li. Chronic Dex administration potentiated the WDS, and this increase was prevented by chronic combined treatment with Dex and Li. Chronic Li administration did not have any effect on WDS. These results indicate that chronic Li administration may improve the supersensitivity of the 5-HT2A receptor elicited by chronic Dex administration without decreasing the density of the 5-HT2A receptor, and the effect of Li was also independent of hypothalamo-pituitary-adrenal axis function.

Animals↗

Temporal sequence of response to unilateral GPi pallidotomy of motor symptoms in Parkinson's disease.

The present study was performed to determine the temporal sequence of the response to unilateral MRI/microelectrode-guided pallidotomy of each cardinal symptom in Parkinson's disease (PD). For this purpose, we performed a quantitative assessment of motor functions in 19 patients with PD at several time points up to 6 months following surgery. We here report that although all the motor signs were significantly improved 6 months after pallidotomy, the temporal sequence of tremor response was different from those of other symptoms.

Aged↗

A new approach to antiplatelet therapy: inhibitor of GPIb/V/IX-vWF interaction.

Evidence has been presented that the interaction between von Willebrand factor (vWF) and its platelet membrane receptor, the GPIb/V/IX complex, plays an important role in the pathogenesis of arterial thrombosis. A monoclonal antibody against the A1 domain of vWF has been shown to inhibit thrombus formation in the animal model of arterial thrombosis. Based upon these findings, a new approach to treating arterial thrombosis has been proposed by intervening in the interaction between vWF and platelet.

Acetates↗