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Biomedical subjects

A Sakamoto

Publications and source records attributed to A Sakamoto.

At least 55 records · Page 3Linked to original sources

Duration or disadvantage? Exploring nativity, ethnicity, and health in midlife.

OBJECTIVES: This study examined nativity as a risk factor for poor physical and emotional health for an ethnically diverse population making the transition into retirement. The authors addressed whether the health disadvantage observed for immigrants lessens with increased time spent in the country (supporting theories of assimilation) or increases with duration of residence (supporting theories of cumulative disadvantage). METHODS: The sample was drawn from Waves 1 and 2 of the Health and Retirement Study (HRS), an in-depth economic, social, and health database of persons in midlife and beyond. The analyses were restricted to 9,912 native-born and 1,031 foreign-born individuals. RESULTS: The data revealed that after socioeconomic factors were controlled, foreign-born individuals were at higher risk of poor emotional health than their native-born counterparts. Although aging immigrants displayed worse health than the native-born population, this disadvantage was mediated by duration of residence (young age at migration) and socioeconomic incorporation. DISCUSSION: These findings extend our understanding of nativity and duration as risk factors for poor physical and emotional health. Immigrants may overcome the nativity disadvantages found for emotional distress with increased duration of residence, but the pattern becomes more complicated with the inclusion of race and Hispanic ethnicity.

Affective Symptoms↗

A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction.

UNLABELLED: Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent mechanical hyperalgesia and allodynia. CCI is widely known as a model of neuropathic pain, and many studies using this model have been reported. Recently, c-fos has been used as a neural marker of pain, and various studies have assessed the relationship between hyperalgesia and c-fos expression in the lumbar spinal cord. In this study, we examined the role of a prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) in a rat CCI model. EP1 receptor antagonist (EP1-ra) oral administration from day 8 to day 14 significantly reduced hyperalgesia and allodynia in the three pain tests on day 15. EP1-ra treatment from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V-X compared with saline treatment. A single dose of EP1-ra treatment on day 8 significantly reduced hyperalgesia and allodynia at 1 h and 2 h after administration, but the efficacy was not observed at 24 h. We conclude that EP1-ra treatment may be useful for hyperalgesia and allodynia and that EP1 receptor mechanisms are involved in the maintenance of c-fos gene expression induced by nerve injury. IMPLICATIONS: We examined whether a prostaglandin E2 receptor subtype EP1 receptor antagonist abrogates neuropathic pain induced by chronic constriction injury model in rats. The EP1 receptor antagonist significantly reduced hyperalgesia, allodynia, and c-fos positive cells. These findings suggested that EP1 receptor antagonists may have a role in treatment of neuropathic pain.

Animals↗

Functional expression in Escherichia coli of low-affinity and high-affinity Na(+)(Li(+))/H(+) antiporters of Synechocystis.

Synechocystis sp. strain PCC 6803 has five genes for putative Na(+)/H(+) antiporters (designated nhaS1, nhaS2, nhaS3, nhaS4, and nhaS5). The deduced amino acid sequences of NhaS1 and NhaS2 are similar to that of NhaP, the Na(+)/H(+) antiporter of Pseudomonas aeruginosa, whereas those of NhaS3, NhaS4, and NhaS5 resemble that of NapA, the Na(+)/H(+) antiporter of Enterococcus hirae. We successfully induced the expression of nhaS1, nhaS3, and nhaS4 under control of an Na(+)-dependent promoter in Escherichia coli TO114, a strain that is deficient in Na(+)/H(+) antiport activity. Inverted membrane vesicles prepared from TO114 nhaS1 and TO114 nhaS3 cells exhibited Na(+)(Li(+))/H(+) antiport activity. Kinetic analysis of this activity revealed that nhaS1 encodes a low-affinity Na(+)/H(+) antiporter with a K(m) of 7.7 mM for Na(+) ions and a K(m) of 2.5 mM for Li(+) ions, while nhaS3 encodes a high-affinity Na(+)/H(+) antiporter with a K(m) of 0.7 mM for Na(+) ions and a K(m) of 0.01 mM for Li(+) ions. Transformation of E. coli TO114 with the nhaS1 and nhaS3 genes increased cellular tolerance to high concentrations of Na(+) and Li(+) ions, as well as to depletion of K(+) ions during cell growth. To our knowledge, this is the first functional characterization of Na(+)/H(+) antiporters from a cyanobacterium. Inverted membrane vesicles prepared from TO114 nhaS4 cells did not have Na(+)/H(+) antiport activity, and the cells themselves were as sensitive to Na(+) and Li(+) ions as the original TO114 cells. However, the TO114 nhaS4 cells were tolerant to depletion of K(+) ions. Taking into account these results and the growth characteristics of Synechocystis mutants in which nhaS genes had been inactivated by targeted disruption, we discuss possible roles of NhaS1, NhaS3, and NhaS4 in Synechocystis.

Amino Acid Sequence↗

Immunoreactivity of p53, mdm2, and p21WAF1 in dedifferentiated liposarcoma: special emphasis on the distinct immunophenotype of the well-differentiated component.

Alteration of the p53/mdm2 pathway has been reported in the well-differentiated liposarcoma (WDLS)/dedifferentiated liposarcoma (DDLS) group. We investigated the immunoreactivity of p53, mdm2, and p21WAF1, along with the MIB-1-labeling index (MIB-1-LI) in 21 WDLS and 21 DDLS cases, to clarify the association of these markers with the morphologic changes and the biological factors responsible for the aggressiveness of DDLS. Within DDLS, p53 and p21WAF1 expression and mdm2 overexpression were significantly more prevalent in the dedifferentiated (DD) components than in the well-differentiated (WD) components. The mdm2 overexpression and p21WAF1 expression was significantly associated with sclerosing liposarcomas in both WDLS and the WD components of DDLS. There was no significant difference in the immunoreactivity of p53, mdm2, or p21WAF1 or MIB-1-LI between WDLS and the WD components of DDLS. An association was found between p53 expression and mdm2 overexpression in the WD group (comprising WDLS and WD components of DDLS) and in the DD group, significantly so in the WD group. Notably, this correlation was found in the subtype of sclerosing liposarcoma but not in that of lipoma-like liposarcoma. Within DDLS, the clinical outcome of the nonaccessible soft tissue (non-AST: comprising retroperitoneum and mediastinum) group was significantly worse than that of the accessible soft tissue (AST: comprising extremities, buttocks, axilla, and scrotum) group; however, the immunophenotypes of p53, mdm2, and p21WAF1 and the MIB-1-LI showed no correlation with survival in the AST group alone, in the non-AST group alone, or in the 2 together. This study suggests that the immunoreactivity of p53, mdm2, and p21WAF1 is associated with the morphologic changes, but not with the biological factors responsible for the aggressiveness of DDLS.

Adult↗

Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of isoflurane.

The adenosine triphosphate-dependent potassium (K(ATP)) channel has been proposed to play an important role in the cardioprotective effect of isoflurane (ISO). However, the question of whether the K(ATP) channel, sarcolemmal or mitochondrial is the main contributor to the effect has not been clarified. The major aim of the present study was to determine whether or not the mitochondrial potassium channel was a site of action for ISO. Whether there was an acute "memory phase", in which drugs were not detected in the tissues, but the protective effect still remained in the ischemic preconditioning (IP) -like effect of ISO was also investigated. Dangling participle isolated rat hearts, a 20-min normothermic nonperfused phase was maintained to produce a global ischemia. Under these ischemic conditions, the effects of ISO, sodium 5-hydroxydecanoate (5HD: a selective mitochondrial K(ATP) channel antagonist), and ISO combined with 5HD on cardiac performance were examined. To all these four groups, (non-treated group, ISO group, 5HD group and ISO plus 5HD group, n=6 each) drugs were given for 30 min. After 10 min of drug-free perfusion (pre-ischemia restabilization period), 20 min of ischemia followed. Then the cardiac performance and the creatine kinase (CK) release during the reperfusion period were tested. In the non treated group and 5HD group, cardiac performance was stable during the treated period and pre-ischemia the restabilization period. In the ISO group and ISO plus 5HD group, heart rate (HR), left ventricular (LV) systolic pressure, and LV maximum rate of development of tension (dP/dtMax) during the drug-treated period became gradually and linearly worse. However, these values were the same as in the non-treated group and 5HD group at the end of the pre-ischemia restabilization period. So 5HD itself had no hemodynamic effect; nor did it have any influence on the actions of ISO. At the end of the pre-ischemia restabilization period, the significant hemodynamic differences among the groups diminished and ISO was not detected in the solution. In the post-reperfusion period, except for the ISO group, (non treated group, 5HD group and ISO plus 5HD group) cardiac performances were drastically decreased. ISO significantly ameliorated the dysfunction of cardiac output, LV systolic pressure and LV+dP/dtMax. The CK level in the coronary effluent during reperfusion was also significantly reduced by ISO. 5HD completely inhibited these cardiac effects of ISO. Activation of the adenosine triphosphate sensitive mitochondrial potassium channel is involved in the cardioprotective effect of ISO, and the action of this agent has an acute"memory phase" like ischemic preconditioning.

Adenosine Triphosphate↗

H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis.

Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma.

Adult↗

[The productivity of electronic brainstorming: a comparison of three systems with a control].

Some studies have indicated that the brainstorming in a computer-mediated meeting can be effective. Accordingly, an experiment was conducted to investigate relative effectiveness of three electronic brainstorming systems, compared with a control, and find cognitive variables that mediated its effectiveness. One hundred undergraduate women, in groups of four, participated in the experiment. The number and quality of unique ideas generated by electronic brainstorming groups of three presentation systems: random, sequential, and sequence-emphasized, were compared with those of a nominal group. Results indicated that the three brainstorming groups were higher than the control, in terms of originality of generated ideas. Also, the possibility was suggested that pleasure in task performance mediated the originality effect of electronic brainstorming.

Cognition↗

Selective reduction and recovery of invariant Valpha24JalphaQ T cell receptor T cells in correlation with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To study the regulatory role of CD4-CD8- double-negative (DN) invariant T cell receptor (TCR) Valpha24JalphaQ T cells, a human counterpart of murine NK 1 + T cells, in the autoimmune process of systemic lupus erythematosus (SLE). METHODS: We carried out a 2 step frequency analysis of DN Valpha24JalphaQ T cells in patients with SLE before and after prednisolone therapy; the frequency of DN Valpha24+ T cells was determined by 3 color FACS analysis and subsequently the frequency of Valpha24JalphaQ rearrangement among DN Valpha24+ T cells was determined by sequencing. RESULTS: DN Valpha24+ T cells were significantly increased in patients with active SLE compared to healthy subjects. In healthy subjects, invariant Valpha24JalphaQ TCR dominated in DN Valpha24+ T cells at a high frequency (93-100%). However, the invariant Valpha24JalphaQ TCR was not detected in DN Valpha24+ T cells from patients with active SLE, and instead 2 to 9 Jalpha genes other than the invariant JalphaQ were oligoclonally expanded in the patients. In inactive SLE induced by prednisolone therapy, the invariant Valpha24JalphaQ TCR could be detected in DN Valpha24+ T cells from all the patients and dominated in most of the patients. Further, oligoclonally expanded Valpha24+ clones other than the invariant JalphaQ gene in active disease states were significantly decreased by prednisolone therapy. CONCLUSION: The selective reduction of DN invariant Valpha24JalphaQ T cells is related to the disease progression of SLE, while DN TCR Valpha24 T cells other than Valpha24JalphaQ T cells constitute autoaggressive T cells in SLE.

Adult↗

C(2)-Symmetric bis-sulfoxide: A novel chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols

A new heterocyclic compound, C(2)-symmetric bis-sulfoxide 1, has been found to be an efficient chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal fission. Both (R,R)- and (S,S)-1 are readily synthesized with high optical purity via asymmetric oxidation of 1, 5-benzodithiepan-3-one (2). After acetalization of meso-1,2-diols 6a-e and a mono-TMS ether 6f with this chiral auxiliary 1, the resulting acetals 7a-f were subjected to base-promoted acetal fission upon treatment with potassium hexamethyldisilazide (KHMDS) followed by acetylation or benzylation to give the desymmetrized diol derivatives 8a-f with high diastereoselectivity. The chiral auxiliary 1 is readily removed by acid-promoted hydrolysis and can be recovered without a loss in enantiomeric excess.

Journal Article↗

Control of homeostasis of CD8+ memory T cells by opposing cytokines.

Memory T cells maintain their numbers for long periods after antigen exposure. Here we show that CD8+ T cells of memory phenotype divide slowly in animals. This division requires interleukin-15 and is markedly increased by inhibition of interleukin-2 (IL-2). Therefore, the numbers of CD8+ memory T cells in animals are controlled by a balance between IL-15 and IL-2.

Animals↗

Prognostic value of the preserved expression of the E-cadherin and catenin families of adhesion molecules and of beta-catenin mutations in synovial sarcoma.

This study addresses the immunohistochemical expression of the E-cadherin and catenin families and mutations of the beta-catenin gene detected by PCR-SSCP in synovial sarcoma. Immunohistochemical analysis was performed for 72 cases, with follow-up data available on 62. The prognostic value of the expression of these proteins was evaluated. Reduced immunoreactivity for E-cadherin and alpha-catenin was significantly correlated with a poor survival rate (p=0.0040 and 0.0053, respectively). According to multivariate analysis, low AJC stage (stages I and II: p<0.0001), the preservation of alpha-catenin expression (p=0.0001), and a low necrotic rate (<50%: p=0.0139) were independent favourable prognostic factors. Widespread aberrant staining of beta-catenin protein within cytoplasm and/or nuclei was observed in 28 cases (38.9%) and was significantly correlated with poor survival (p=0.0122). In addition, there was a trend towards a correlation between widespread aberrant staining of beta-catenin and the MIB-1 labelling index (p=0.0535). Mutational analysis of exon 3 of the beta-catenin gene was performed for 49 cases. Nucleotide sequencing analysis revealed that four (8.2%) contained point mutations (three in codon 32, GAC to TAC; one in codon 37, TCT to TTT). Survival data were available for three out of four cases with beta-catenin mutations; two of these patients died within 1 year (died of disease at 6 and 11 months, respectively). These results suggest that E-cadherin and alpha-catenin undertake important roles as intercellular adhesion molecules; their preserved expression is associated with a better overall survival rate in synovial sarcoma and may have prognostic value. Abnormal levels of beta-catenin, with or without mutation, could contribute to the development and progression of synovial sarcoma, through increasing the proliferative activity of the tumour cells.

Cadherins↗

Degradation of the metal-cyano complex tetracyanonickelate (II) by Fusarium oxysporum N-10.

A fungus with the ability to utilize a metalcyano compound, tetracyanonickelate (II) ¿K2[Ni (CN)4]; TCN¿, as its sole source of nitrogen was isolated from soil and identified as Fusarium oxysporum N-10. Both intact mycelia and cell-free extract of the strain catalyzed hydrolysis of TCN to formate and ammonia and produced formamide as an intermediate, thereby indicating that a hydratase and an amidase sequentially participated in the degradation of TCN. The enzyme catalyzing the hydration of TCN was purified approximately ten-fold from the cell-free extract of strain N-10 with a yield of 29%. The molecular mass of the active enzyme was estimated to be 160 kDa. The enzyme appears to exist as a homotetramer, each subunit having a molecular mass of 40 kDa. The enzyme also catalyzed the hydration of KCN, with a cyanide-hydrating activity 2 x 10(4) times greater than for TCN. The kinetic parameters for TCN and KCN indicated that hydratase isolated from F. oxysporum was a cyanide hydratase able to utilize a broad range of cyano compounds and nitriles as substrates.

Amino Acid Sequence↗

Plasma total glutathione concentrations in epileptic patients taking anticonvulsants.

Glutathione plays an important role in protecting cells against oxidative damage as a free radical scavenger. Since several anticonvulsants have been associated with decreased intrahepatic glutathione levels, we investigated plasma concentrations of total glutathione (including reduced and oxidized forms, tGSH=GSH+GSSG) in 45 epileptic patients taking anticonvulsant drugs. Plasma tGSH concentrations were significantly lower than in controls in patients treated with carbamazepine or phenytoin monotherapy, or with multiple drugs. Plasma tGSH concentrations in patients treated with valproic acid and in patients treated with phenobarbital did not differ significantly from those in controls. In no patient group was a significant correlation evident between duration of treatment or drug concentration and plasma tGSH concentration. No significant differences in plasma total cysteine concentrations were found between any patient group and controls. We conclude that some anticonvulsant drugs can lower plasma tGSH levels, reflecting treatment-related oxidative stress.

Adolescent↗

Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma.

The hepatocyte growth factor (HGF)/c-MET signaling system plays an important role in the carcinogenesis of various organs. We investigated the expression of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic parameters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and SYT-SSX fusion gene was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 concordant frozen materials. Twenty-one of 69 (30.4%) tumors showed positive reaction for c-MET, whereas 22 tumors (31.9%) were positive for HGF. In 10 cases, co-expression of HGF and c-MET was observed; however, there was no significant correlation between HGF and c-MET expression. HGF expression was correlated with female patients, large tumors (more than 5 cm), the presence of rhabdoid cells, low frequency of mast cells (<20/10 HPF), high nuclear grade (grade III), and high American Joint Committee (AJC) stage (III and IV). Conversely, c-MET expression was only correlated with large tumors. However, the coexpression of HGF and c-MET was significantly correlated with large tumor size, the existence of rhabdoid cells, and high AJC stage. Both the expression of HGF and the co-expression of HGF and c-MET showed a significantly high MIB-1 LI and were correlated with poor prognosis according to univariate analysis. Multivariate Cox analysis showed that high AJC stage, the expression of HGF, and a high MIB-1 LI (12.0>) independently had a negative impact on overall survival. In 22 frozen material cases evaluated by both IHC and RT-PCR, a statistically significant correlation was found between the 2 techniques. SYT-SSX fusion transcripts were detected in all 22 cases. Three tumors had SYT-SSX2 fusion transcripts, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET paracrine signaling may contribute to tumorigenesis and progression in synovial sarcoma.

Adult↗

Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin.

The histological differentiation of thyroid carcinoma is known to correlate with prognosis. Ras oncogene mutations, which have been identified in various human cancers, have been suspected playing an important role in carcinogenesis and tumor progression. The purpose of this study was to clarify the mechanism of thyroid tumor progression, focusing on ras oncogenes. We examined ras mutations using nested polymerase chain reaction (PCR) and direct sequencing methods. The ras oncogene product was also examined immunohistochemically. Our results indicated that the incidence of ras mutations correlated with the histological differentiation of thyroid cancer. Three poorly differentiated carcinomas showed a higher rate of ras mutations than did 17 well-differentiated counterparts. Hot spots were not identified except for a relative accumulation of the N-ras gene at codon 61. There was a correlation between the immunoreactivity of the ras oncogene product and ras mutation, although the immunoreactivity of ras-p21 did not correlate with the histological differentiation. Mutation of the ras gene seemed to be one of the important events in the progression from well-differentiated carcinoma to poorly differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗

Minor cardiac troponin T release in patients undergoing coronary artery bypass graft surgery on a beating heart.

OBJECTIVES: To determine whether and to what extent coronary artery bypass graft (CABG) surgery without extracorporeal circulation is associated with cardiac troponin T (TnT) release. DESIGN: Prospective study. SETTING: A single university hospital. PARTICIPANTS: Twenty-three patients scheduled for minimally invasive CABG surgery. Sixteen patients received one coronary anastomosis, and seven received two. INTERVENTIONS: TnT and creatine kinase-MB (CK-MB) levels were determined immediately before induction of anesthesia (baseline) and at 0, 12, and 24 hours after surgery. Hemodynamic measurements were made, and 5-lead electrocardiograms with continuous automated ST-segment trends were analyzed. MEASUREMENTS AND MAIN RESULTS: All patients had a good cardiac outcome. Median cumulative coronary artery occlusion time was 27 minutes (range, 10 to 49 minutes). TnT levels were undetectable in 91.3% of patients at baseline when a detection limit of 0.01 ng/mL was employed. TnT and CK-MB showed significant elevations at 12 and 24 hours versus baseline. Postoperatively, TnT was detectable in 91.3% of patients, and 17.4% suffered minor myocardial damage, as evidenced by an abnormal increase in TnT greater than 0.2 ng/mL, excluding those exhibiting myocardial infarction. ST segment changes developed in seven patients, persisting for 13.0 minutes (range, 9.5 to 15.8 minutes) and disappearing immediately after coronary artery clamp release. There were no significant correlations between cumulative coronary occlusion time and peak TnT or CK-MB levels. CONCLUSIONS: TnT was detected after surgery in most patients, and significant TnT levels indicative of myocardial injury (>0.2 ng/mL) were detected in only 17% of patients, probably as a result of brief periods of coronary artery occlusion.

Adult↗