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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 91 records · Page 5Linked to original sources

Mössbauer study of the reaction of laser-evaporated iron atoms with nitrogen molecules in low-temperature argon matrices.

Reaction products of laser-evaporated iron atoms with nitrogen molecules were investigated using a low-temperature matrix isolation technique. The products observed in the Mössbauer spectra were FeNNN, Fe(NN), and Fe(NN)2, isolated in argon matrices. Yields of the species changed, depending on the concentration of nitrogen in the matrix. A product assigned to Fe(NN)6 was obtained in a pure nitrogen matrix. Infrared spectra and molecular orbital calculations of the products support these findings.

Journal Article↗

Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.

We analyzed retrospectively the relationship between coagulation profile, and either hepatic function or hemodynamics, in patients who had undergone a Fontan-type procedure, comparing them, first, with a control group of 12 patients without significant hemodynamic abnormality, and, second, with a group of 14 patients who had not undergone a Fontan procedure, but whose mean right atrial pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30 patients submitted to the Fontan-type operation. Prothrombin time, and factor XIII, were significantly lower in those who had undergone the Fontan procedure than in the other groups. Those submitted to the Fontan operation also had lower levels of protein C than controls, and their levels of plasminogen were lower than the patients with high right atrial pressure. Both aspartate aminotransferase and alanine aminotransferase were higher in those undergoing the Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in these patients was higher than in the control group. Mean right atrial pressure was highest in those undergoing the Fontan procedure, while cardiac index was lowest. Prothrombin time was correlated to some extent with aspartate aminotransferase, mean right atrial pressure, and cardiac index. Protein C correlated with both aspartate aminotransferase and mean right atrial pressure, while factor XIII correlated with alanine aminotransferase, mean right atrial pressure, and cardiac index. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic function, correlated significantly with mean right atrial pressure. In those who had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics, in the absence of a right sided pumping chamber, may predispose to subclinical hepatic dysfunction, leading to selective disturbances of protein synthesis.

Adolescent↗

Primary Ewing's sarcoma/peripheral primitive neuroectodermal tumor at the vertex of the skull with elevated serum carcinoembryonic antigen: case report.

A primary Ewing's sarcoma arising in the skull is relatively rare. Although a small number of case reports noted elevated carcinoembryonic antigen (CEA) in patients with primary central nervous system (CNS) neoplasms, there is no report of Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET) with elevated serum levels of CEA. A 7-year-old boy who had episodes of headache and vomiting had noticed a solid mass in the vertex of the head. Imaging studies revealed a large intra- and extracranial tumor at the vertex of the skull. Hematological examination demonstrated high serum levels of CEA: 91.09 ng/ml. The patient initially underwent an embolization of the bilateral middle meningeal arteries with Gelfoam particles. One week later, the patient was operated on and a subtotal resection of the tumor was performed. On histopathological and molecular genetic examination, the tumor was diagnosed as a Ewing's sarcoma/peripheral PNET. Immunohistochemical study showed strongly positive staining for CEA in the tumor cells. The serum level of CEA was normalized at 0.83 ng/ml after the tumor was removed and the boy underwent radiotherapy and 3 courses of chemotherapy. This is the first reported case of a primary Ewing's sarcoma/peripheral PNET at the vertex of the skull with elevated serum CEA.

Carcinoembryonic Antigen↗

Isolated noncompaction of the ventricular myocardium: ultrafast computed tomography and magnetic resonance imaging.

This study was undertaken to evaluate the feasibility of ultrafast computed tomography (CT) and magnetic resonance imaging (MRI) for anatomical and pathophysiological diagnosis of isolated noncompaction of the left ventricular myocardium (INVM) compared with other imaging modalities including thallium myocardial imaging. Six patients, three sets of siblings, ranging in age from 13 to 18 years, were included in this study. Two-dimensional echocardiograms revealed numerous prominent trabeculations and deep intertrabecular recesses in one or more ventricular wall segments in all cases. Thallium-201 myocardial imaging disclosed a hypoperfusion area corresponding to the zones where noncompacted ventricular myocardium was localized. Ultrafast CT showed early defects of varying degrees and rate enhancement of the noncompacted ventricular myocardium, implying fibrosis in this area. MRI disclosed inner zones of noncompacted myocardium distinguishable from thin outer zones of compacted myocardium. T2-weighted imaging revealed high intensity areas at the apex of the left ventricle, suggesting disturbed microcirculation due to fibrosis, thrombus formation, and hypokinesis. Cine MRI revealed hypokinesis of the noncompacted ventricular wall during the cardiac cycle. In conclusion, ultrafast CT and MRI provide high-resolution imaging of noncompacted myocardium, and also pathophysiological details regarding this rare disease.

Adolescent↗

Genetic structure of spatial and verbal working memory.

Working memory (WM) encompasses both short-term memory (storage) and executive functions that play an essential role in all forms of cognition. In this study, the genetic structure of storage and executive functions engaged in both a spatial and verbal WM span task is investigated using a twin sample. The sample consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages 16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship between WM and cognitive ability is confirmed (r = 0.26-0.44). Individual differences in WM storage and executive functions are found to be significantly influenced by genes, with heritability estimates all moderately high (43%-49%), and estimates for cognitive ability comparable to previous studies (65%). A large part of the genetic variance in storage and executive functions in both spatial and verbal modalities is due to a common genetic factor that accounts for 11% to 43% of the variance. In the reduced sample, this common genetic factor accounts for 64% and 26% of the variance in spatial and verbal cognitive ability, respectively. Additional genetic variance in WM (7%-30%) is due to modality specific factors (spatial and verbal) and a storage specific factor that may be particularly important for the verbal modality. None of the variance in cognitive ability is accounted for by the modality and storage genetic factors, suggesting these may be specific to WM.

Adult↗

Covariance structure of neuroticism and agreeableness: a twin and molecular genetic analysis of the role of the serotonin transporter gene.

The Revised NEO Personality Inventory domains of Neuroticism and Agreeableness are considered factorially distinct despite several intercorrelations between these domains. The genetic correlation, an index of the degree to which these intercorrelations are caused by genetic influences, was estimated using data from 913 monozygotic and 562 dizygotic volunteer twin pairs from Canada, Germany, and Japan. The serotonin transporter gene, 5-HTTLPR, was assayed in a sample of 388 nontwin sibling pairs from the United States to determine the contribution of the serotonin transporter locus to the covariation between the Neuroticism and Agreeableness scales. In all four samples, genetic influences contributed to the covariance of Neuroticism and Agreeableness, with the serotonin transporter gene accounting for 10% of the relationship between these domains.

Adult↗

Epidemiology of suicidal ideation and help-seeking behaviors among the elderly in Japan.

This study offers an analysis of the elderly (over 65 years of age) among a general community population in terms of the percentages of: (i) persons with recurring thoughts of death and/or of committing suicide, and (ii) people who have consulted others, including medical professionals, with regard to these problems. Among 433 elderly over the age of 65 in one community in a town in Aomori Prefecture, 358 agreed to participate in the project. Forty-four participants (12.3%) responded that they had either 'thoughts of death' or 'thoughts of suicide', and these thoughts had continued for more than 2 weeks in 12 participants (3.4%). Only 15 of the 44 suicidal elderly responded that they had consulted someone about their problems. Although there are many elderly people exhibiting a subclinical depressive state with recurring thoughts of death or thoughts of suicide, the number of people who consult family members, professionals, or others is very low. This suggests the importance of community networking through educational activities so that people can more readily talk to and support one another.

Aged↗

Growth fractions of human renal cell carcinoma defined by monoclonal antibody Ki-67. Predictive values for prognosis.

BACKGROUND: We used immunohistochemical techniques to elucidate the role of growth fractions of renal cell carcinoma in the clinicopathology of the condition and patient survival. METHODS: Fifty-two fresh-frozen nephrectomy specimens were immunostained with Ki-67 monoclonal antibody. Ki-67 indexes were determined to examine the relationship between tumor size, grade, stage and survival curve. This study included 43 men and nine women with the mean age 58.4 +/- 11.7 years, who had been followed up for 39 +/- 25 months. RESULTS: The Ki-67 index ranged from 0.6 to 14.1%, averaging 4.6 +/- 5.8%. It was 2.8 +/- 2.4% in tumors <5 cm, 4.7 +/- 3.6% in tumors > or =5 cm and 7.1 +/- 9.0% in tumors > or =10 cm. The Ki-67 index of grades 1, 2 and 3 tumors was 2.3 +/- 1.1%, 3.3 +/- 2.7% and 12.0 +/- 10.4%, respectively. Grade 3 tumors had a significantly higher Ki-67 index than grade 1 or grade 2 tumors. There was no correlation between the Ki-67 index and tumor stage. Patients with a Ki-67 index < 5.6% had a better prognosis than those with an index > 5.6% (P=0.029). However, multivariate analysis demonstrated that tumor size (P=0.034) and grade (P=0.038) were higher in hazard ratio than the Ki-67 index. CONCLUSIONS: Most renal cell carcinomas had low growth fractions. Although a high Ki-67 index should indicate a poor prognosis, Ki-67 did not correlate to metastasis. We believe it is necessary to investigate the factors, other than growth potential, that affect metastasis.

Adult↗

Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer.

OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.

Aged↗

Generation of a constitutively active fragment of PKN in microglia/macrophages after middle cerebral artery occlusion in rats.

PKN is a fatty acid- and Rho-activated serine/threonine kinase, which has a catalytic domain highly homologous to that of protein kinase C (PKC). Recent studies have demonstrated that PKN is proteolytically cleaved after apoptotic stimulation and then a constitutively active 55-kDa fragment is generated. However, the role of the 55-kDa fragment are poorly understood. Adult Sprague-Dawley (SD) rats underwent middle cerebral artery occlusion (MCAO), and the temporal and spatial changes in the fragmentation of PKN and of PKC delta were examined by immunoblotting. No proteolytic fragment of PKC delta (about 40 kDa) was detected. The 55-kDa fragment of PKN appeared transiently from 3 days after MCAO at the ipsilateral normal cortex. At the boundary zone of infarction, the 55-kDa fragment was markedly induced from day 5 then peaked on day 21 and persisted until day 28. Analysis of anti-phosphoserine immunoprecipitates with an anti-PKN antibody revealed phosphorylation of the 55-kDa band. Double staining for PKN and Ox42 was used to examine the source of the 55-kDa fragment. PKN immunoreactivity was significantly increased in Ox42-positive cells (microglia/hematogenous macrophages). No DNA laddering and only a few terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were observed on day 14 in despite of the high level appearance of the 55-kDa band. These results suggest that the constitutively active 55-kDa fragment of PKN does not contribute to apoptosis, but may contribute to a function of microglia/macrophages.

Animals↗

Papillon-Lefèvre syndrome: mutations and polymorphisms in the cathepsin C gene.

The Papillon-Lefèvre syndrome, inherited in an autosomal recessive pattern, manifests with palmoplantar keratoderma and early, destructive periodontitis. Recently, mutations in the gene encoding cathepsin C have been disclosed in a limited number of families with Papillon-Lefèvre syndrome. We have examined two multiplex families with Papillon-Lefèvre syndrome, and evaluated the gene encoding cathepsin C for mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all seven exons and flanking intronic sequences, followed by direct nucleotide sequencing. This strategy identified two missense mutations, W39S and G301S, affecting highly conserved amino acid residues within the cathepsin C polypeptide. The affected individuals were homozygotes whereas heterozygous carriers of the mutations were clinically unaffected, confirming the recessive nature of the mutations. Addition of these cathepsin C gene mutations into the expanding Papillon-Lefèvre syndrome mutation database allows further development of genotype/phenotype correlations towards understanding this severe genodermatosis.

Cathepsin C↗

Clinical evaluation of human telomerase catalytic subunit in bladder washings from patients with bladder cancer.

PURPOSE: We examined the expression of mRNA of human telomerase reverse transcriptase (hTERT), a catalytic subunit of the telomerase complex, in bladder washings as a tumor marker for the detection of bladder cancer. MATERIALS AND METHODS: Bladder washings were obtained from 63 patients. We examined the expression of hTERT mRNA by the nested reverse transcription-polymerase chain reaction (RT-PCR) method and also measured the relative expressions of hTERT mRNA and beta(2)-microglobulin (beta(2)-MG) in these samples by RT-PCR analysis. Correlations between the relative expression of hTERT mRNA and clinical features were analyzed. We also compared the sensitivity of this assay with that of urinary cytology. RESULTS: By nested RT-PCR, we detected three false-positive cases (11%) in the control group. Therefore, the relative expression values of hTERT mRNA and beta(2)-MG correlated strongly with tumor size, but not with multiplicity or histologic grade. When the cut-off value of the expression was fixed at 0.27%, the sensitivity and specificity of this assay were 74% and 93%, respectively. This assay was more sensitive than urinary cytology for the detection of bladder cancer. CONCLUSION: These results suggest that the relative expression of hTERT mRNA in bladder washings is useful in screening for bladder cancer. Relative expression is of assistance in diagnosing bladder cancer.

Biomarkers, Tumor↗

Loss of p73 induction in a cisplatin-resistant bladder cancer cell line.

BACKGROUND: Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. METHODS: To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2. RESULTS: The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells. CONCLUSION: These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.

Antineoplastic Agents↗

Prospective and randomized comparison of combined androgen blockade versus combination with oral UFT as an initial treatment for prostate cancer.

OBJECTIVE: This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. METHODS: A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. RESULTS: A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values <40 ng/ml showed a good indication for this endocrine chemotherapy. CONCLUSION: This endocrine chemotherapy was confirmed to be tolerable and significantly effective in the delay of disease progression, which leads to longer survival in patients with prostate cancer.

Aged↗

PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family.

PKNbeta is a novel isoform of PKNalpha, which is one of the target protein kinases for the small GTPase Rho. By yeast two-hybrid screening of a human embryonic kidney 293 cell cDNA library with the PKNbeta linker region containing proline-rich motifs as a bait, clones encoding Graf (GAP for Rho Associated with Focal adhesion kinase) and a novel Graf-related protein, termed Graf2, were isolated. The full length of Graf2 contains a putative PH domain, a RhoGAP domain, and an SH3 domain as well as Graf. Northern and Western blot analyses demonstrated that Graf2 is expressed in several tissues, with the highest expression in skeletal muscle. Recombinant Graf2 exhibited GTPase-activating activity toward the small GTPase RhoA and Cdc42Hs, but not toward Rac1, in vitro. The SH3 domains of Graf and Graf2 purified from Escherichia coli bound directly to PKNbeta. Graf or Graf2 was co-immunoprecipitated with PKNbeta in COS-7 cells transiently transfected with Graf or Graf2 and PKNbeta expression constructs. The catalytically active form of PKNbeta phosphorylated Graf and Graf2 in vitro. The interplay of PKNbeta and the GTPase-activating proteins, Graf and Graf2, may offer a novel mechanism regulating the Rho-mediated signaling.

Amino Acid Sequence↗

Cloning and expression of human anti-tumor necrosis factor-alpha monoclonal antibodies from Epstein-Barr virus transformed oligoclonal libraries.

Peripheral blood was obtained from a healthy human volunteer and transformed with Epstein-Barr virus (EBV). This produced an oligoclonal cell library in culture medium that was screened by ELISA for anti-human tumor necrosis factor-alpha (TNFalpha) activity. RNA from two positive clones was applied to RT-PCR using antibody-specific primers, and the light (kappa and lambda) and heavy chain genes (gamma and mu) were cloned into the plasmid vector pFab1-His2. The antibodies produced in Escherichia coli as Fab fragments were assayed for anti-TNFalpha activity utilizing ELISA. Two IgG1/kappa anti-TNFalpha antibodies and two IgM/kappa anti-TNFalpha antibodies were isolated. DNA sequence analysis showed that the VL and VH gene families of IgM and IgG were the same. Both the antibodies showed almost the same activity on ELISA-testing. Ten clones randomly selected from light (kappa and lambda) and heavy (gamma and mu) chain genes in the oligoclonal cell library 1D5 were sequenced, and each gene (kappa, lambda, gamma, and mu) was found to be composed of one to three different genes. These data support the conclusion that the cell clone is oligoclonal at the molecular level.

Amino Acid Sequence↗