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Biomedical subjects

Y Nagai

Publications and source records attributed to Y Nagai.

At least 19 recordsLinked to original sources
PubMed2006

Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats.

AIMS/HYPOTHESIS: We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP-delta and leads to the induction of the chemokine (C-C motif) ligand 2 gene (Ccl2, also known as MCP-1) expression in aortas. METHODS: Hyperinsulinaemia was induced by feeding rats a high-fructose diet. CCL2 production was analysed by ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by quantitative RT-PCR. The binding of C/EBP-beta to Ccl2 was assessed by chromatin immunoprecipitation (ChIP) assay. RESULTS: Insulin at a concentration of 10 nmol/l significantly stimulated the expression of Cebpb, Cebpd and Ccl2 mRNAs, depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knock-down of C/EBP-beta with siRNA abolished the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt/protein kinase B, a downstream effector of PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%, respectively, compared with those of control-fed rats. The induction Ccl2 mRNA expression in the aortas was significantly correlated with the expression of Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated binding of C/EBP-beta to the 5' upstream region of Ccl2 in the aortas from fructose-fed rats. CONCLUSIONS/INTERPRETATION: These findings clearly indicate the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation-related protein, observed in the hyperinsulinaemic state, which may initiate the process of atherosclerosis.

Animals↗
PubMed2006

Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp.

This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type patients in response rates (78 vs 14%, P = 0.0017), and MST (15.4 vs 11.1 months, P = 0.0135). A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259, P = 0.036). This research showed the need for screening for EGFR mutations in NSCLC patients.

Adult↗
PubMed2006

Arteriographic evaluation of vascular changes of the extremities in patients with systemic sclerosis.

BACKGROUND: Although digital ulcerations frequently occur in patients with systemic sclerosis (SSc), there have been few reports on the macrovascular involvement. OBJECTIVES: To evaluate the macrovascular involvement in patients with SSc exhibiting digital ulceration or gangrene. METHODS: Transfemoral catheter arteriography of the upper and/or lower extremities was performed in eight patients (one man and seven women, age range 42-71 years) with SSc exhibiting digital ulceration or gangrene. The background of the patients, such as autoantibody profiles and vascular risk factors including smoking habits, was also investigated. RESULTS: Macrovascular involvement was detected in seven of eight patients. In three of seven patients who underwent arteriography of the upper extremity, occlusion was limited to the digital arteries. Obliteration of the ulnar artery and superficial palmar arch was detected in three of seven patients, and the radial artery in one patient. Only one of five patients who underwent arteriography of the lower extremity showed the occlusion limited to digital arteries of the foot. Occlusion of the posterior tibial artery, dorsalis pedis artery and arcuate artery was detected, each in one patient. Two patients showed occlusion of the plantar arch. Overall, the occlusion of arteries proximal to the digits was demonstrated in four of eight patients. Three of the four patients were positive for antitopoisomerase-1 antibody and had diffuse cutaneous SSc (dcSSc) with multiple skin ulcers or gangrene. CONCLUSIONS: Macrovascular involvement as detected with arteriography is not rare in SSc patients with digital ulceration or gangrene. Moreover, the vascular occlusion proximal to the digits seemed to be frequent in antitopoisomerase-1 antibody-positive dcSSc patients with multiple skin ulcers or gangrene.

Adult↗
PubMed2006

Brain site-specific gene expression analysis in Alzheimer's disease patients.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is characterized by a progressive loss of higher cognitive functions. The brain of an individual with AD exhibits extracellular senile plaques (SPs) of aggregated amyloid-beta peptide (Abeta) and intracellular neurofibrillary tangles (NFTs). Given the critical role of neuronal transport of both proteins and organelles, it is not surprising that perturbation of microtubule-based transport may play a major role in the pathogenesis of AD. MATERIALS AND METHODS: We used the cDNA subtraction methodology and in vitro neural cell culture analyses to study the meaning of the brain site-specific gene expression pattern in cerebral tissue obtained from AD patients and also from control subjects at autopsy. RESULTS: We observed that cytoskeleton-associated proteins were down-regulated in AD subjects. We also noted an altered expression of the microtubule-associated protein 1B (MAP1B), the heat-shock protein (HSP)-90 (a key chaperone molecule), the tripartite motif-containing proteins (TRIM)-32/37 (an anti apoptotic enzyme with ubiquitin-protein ligase activity) and the Reticulon-3 (a modulator of the amyloid-precursor-protein (APP) cleavage) in AD brains. Additional molecular- and cell-biological studies revealed that small interfering RNA (siRNA)-mediated down-regulation of MAP1B expression leads to neuronal cell death in vitro. CONCLUSION: Altered expression of MAP1B, HSP90, TRIM32/37 and Reticulon-3 provides new clues by which the ubiquitin-proteasome-, the protein-chaperon- and the APP-processing systems are disturbed in AD, thus, leading to neuritic amyloid plaques and neurofibrillary tangles.

Aged↗
PubMed2006

Assessment of efficacy of a live oral poliovirus vaccine for virulent Sabin-like poliovirus 1 strains in Japan.

Virulent Sabin-like poliovirus (VSLP) was isolated from river and sewage waters between October 1993 and September 1995 in Toyama Prefecture, Japan (Yoshida et al., Lancet 356, 1461-1463, 2000). In this study, to assess the possibility of an epidemic of poliomyelitis caused by a VSLP in Japan under the current vaccination policy of administration of live attenuated oral poliovirus vaccine (OPV), we determined titers of serum neutralizing antibodies to poliovirus 1 (PV-1) strains Sabin (vaccine strain), Mahoney (wild-type strain) and G4-12 (VSLP) in various groups of residents of Toyama Prefecture, Japan. The seropositivity and geometric mean neutralizing antibody titers against these strains in the individuals who obtained two doses of OPV were 99.1%, 94.5% and 95.5%, respectively, and 564, 186 and 194, respectively. Although the antibody titers to G4-12 were lower compared with those to Sabin, these results indicate that the OPV vaccination policy in Japan has been effective in preventing poliomyelitis caused by VSLPs. These results also suggest that (i) an epidemic of poliomyelitis caused by a VSLP has not occurred in Japan due to herd immunity, and (ii) the possibility of reemergence of VSLPs will be prevented if sufficient herd immunity is acquired immediately after completion of the OPV vaccination in accordance with the poliomyelitis eradication program.

Adolescent↗
PubMed2005

Self-energy correction to momentum-density distribution of positron-electron pairs.

Positron two-dimensional angular correlation of annihilation radiation (2D ACAR), i.e., the 2D projection of the electron momentum densities sampled by positron, in Si is employed to verify the prediction of the density functional theory within the local-density approximation (LDA). Carefully conducted test shows that the LDA introduces small but definite discrepancies to the 2D-ACAR anisotropies. Self-energy calculation using the GW method indicates that density-fluctuation contributes anisotropic momentum-density correction and thus improves the agreement between theory and experiment. These results provide valuable annotations to the arguments concerning the accuracy and validity of the LDA and GW schemes.

Journal Article↗
PubMed2004

The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes.

BACKGROUND: During ICSI, we occasionally observe pronucleus sized translucent vacuoles. We investigated why these vacuoles occur and determined the effect on pregnancy outcome. METHODS: Translucent vacuole-positive oocytes and the corresponding cohort were examined by transmission electron microscopy (TEM) and histochemical staining with DiI and ER-Tracker. Stimulation methods, hormonal levels, patients' condition and grade of transferred embryos were compared between vacuole-positive and vacuole-negative cycles. RESULTS: By TEM, we confirmed that the vacuoles were tubular-type smooth endoplasmic reticulum clusters (sERCs). Numerous small sERCs were also observed in the oocytes from the same cohort. Veeck's grades of transferred embryos were higher in sERC-positive cycles and fertilization rate was similar to those of sERC-negative cycles. However, in sERC-positive cycles, significantly lower pregnancy and higher biochemical pregnancy rates were shown. Serum estradiol levels on the day of hCG administration were significantly higher in sERC-positive cycles. CONCLUSIONS: The presence of sERCs is associated with lower chances of successful pregnancy, even in sERC-negative oocytes from the same cohort that are transferred along with the sERC-positive oocytes. High estradiol levels could be one of the causes of sERC formation.

Cohort Studies↗
PubMed2004

Characterizing the new transcription regulator protein p60TRP.

Active cell death ('apoptosis' or 'programmed cell death') is essential in the development and homeostasis of multicellular organisms and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death might be implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using bioinformatics-, Western-blotting-, yeast-two-hybrid-system-, polymerase chain reaction (PCR)-, and fluorescence microscopy-analyses, we demonstrate here that the neuroprotective protein p60TRP (p60-transcription-regulator-protein) is a basic helix-loop-helix (bHLH) domain-containing member of a new protein family that interacts with the Ran-binding-protein-5 (RanBP5) and the protein-phosphatase-2A (PP2A). The additional findings of its influence on NNT1 and p48ZnF (new-neurotrophin-1, p48-zinc-finger-protein)-signaling and its down-regulation in the brain of AD subjects point to a possible pivotal role of p60TRP in the control of cellular aging and survival.

Aged↗
PubMed2004

Accessory genes of the paramyxoviridae, a large family of nonsegmented negative-strand RNA viruses, as a focus of active investigation by reverse genetics.

The Paramyxoviridae, a large family of nonsegmented negative-strand RNA viruses, comprises several genera each containing important human and animal pathogens. They possess in common six basal genes essential for viral replication and, in addition, a subset of accessory genes that are largely unique to each genus. These accessory genes are either encoded in one or more alternative overlapping frames of a basal gene, which are accessed transcriptionally or translationally, or inserted before or between the basal genes as one or more extra genes. However, the question of how the individual accessory genes contribute to actual viral replication and pathogenesis remained unanswered. It was not even established whether they are dispensable or indispensable for the viral life cycle. The plasmid-based reverse genetics of the full-length viral genome has now come into wide use to demonstrate that most, if not all, of these putative accessory genes can be disrupted without destroying viral infectivity, conclusively defining them as indeed dispensable accessory genes. Studies on the phenotypes of the resulting gene knockout viruses have revealed that the individual accessory genes greatly contribute specifically and additively to the overall viral fitness both in vitro and in vivo.

Animals↗
PubMed2004

Brain activity relating to the contingent negative variation: an fMRI investigation.

The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention, yet its functional neuroanatomical basis is poorly understood. We used functional magnetic resonance imaging (fMRI) with simultaneous EEG and recording of galvanic skin response (GSR) to investigate CNV-related central neural activity and its relationship to peripheral autonomic arousal. In a group analysis, blood oxygenation level dependent (BOLD) activity during the period of CNV generation was enhanced in thalamus, somatomotor cortex, bilateral midcingulate, supplementary motor, and insular cortices. Enhancement of CNV-related activity in anterior and midcingulate, SMA, and insular cortices was associated with decreases in peripheral sympathetic arousal. In a subset of subjects in whom we acquired simultaneous EEG and fMRI data, we observed activity in bilateral thalamus, anterior cingulate, and supplementary motor cortex that was modulated by trial-by-trial amplitude of CNV. These findings provide a likely functional neuroanatomical substrate for the CNV and demonstrate modulation of components of this neural circuitry by peripheral autonomic arousal. Moreover, these data suggest a mechanistic model whereby thalamocortical interactions regulate CNV amplitude.

Adult↗
PubMed2004

Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function.

We examined neural activity related to modulation of skin conductance level (SCL), an index of sympathetic tone, using functional magnetic resonance imaging (fMRI) while subjects performed biofeedback arousal and relaxation tasks. Neural activity within the ventromedial prefrontal cortex (VMPFC) and the orbitofrontal cortex (OFC) covaried with skin conductance level (SCL), irrespective of task. Activity within striate and extrastriate cortices, anterior cingulate and insular cortices, thalamus, hypothalamus and lateral regions of prefrontal cortex reflected the rate of change in electrodermal activity, highlighting areas supporting transient skin conductance responses (SCRs). Successful performance of either biofeedback task (where SCL changed in the intended direction) was associated with enhanced activity in mid-OFC. The findings point to a dissociation between neural systems controlling basal sympathetic tone (SCL) and transient skin conductance responses (SCRs). The level of activity in VMPFC has been related to a default mode of brain function and our findings provide a physiological account of this state, indicating that activity within VMPFC and OFC reflects a dynamic between exteroceptive and interoceptive deployment of attention.

Adult↗
PubMed2004

Binary and ternary textures containing higher-order spatial correlations.

A quantitative method is presented for creating a large number of classes of binary (256) and ternary (7.62 x 10(12)) textures. The binary textures are presented as black and white (contrasts -1 and 1). The ternary textures have three levels: black, white and the mean luminance gray (contrasts -1, 0 and 1). The ternary patterns in particular display a wide variety of properties, including depth cues from disparity and lighting. Given the very large number of ternary patterns, we present guidelines and analytical methods for selecting sets of textures with particular image qualities and/or nonlinear relationships between pixels. The second- and third-order correlation functions of several thousand examples were examined to reveal patterns that are functionally isotrigon with other textures and or with uniformly distributed noise patterns.

Contrast Sensitivity↗
PubMed2004

Generation of a recombinant Sendai virus that is selectively activated and lyses human tumor cells expressing matrix metalloproteinases.

Malignant tumor cells often express matrix metalloproteinases (MMPs) at a high level to enable their dissemination and metastasis. Sendai virus (SeV), a nonsegmented negative strand RNA virus, spreads in the target tissues in vivo via cleavage activation of the viral fusion glycoprotein by a tissue-specific, trypsin-like enzyme. By deleting the viral matrix protein, we previously generated a recombinant SeV that does not bud to mature virions, but is highly fusogenic and spreads extensively from cell to cell in a trypsin-dependent manner. Here, we changed the tryptic cleavage site of the fusion glycoprotein of this virus to a site susceptible to MMPs. The resulting recombinant virus was no longer activated by trypsin but spread efficiently in cultured cells supplemented with MMP2 or MMP9 and in human tumor cell lines expressing these MMPs. Furthermore, the virus spread extensively in tumor cells xenotrasplanted to nude mice without disseminating to the surrounding normal cells, leading to the inhibition of the tumor growth in the mice. These results demonstrate the selective targeting and killing of human tumor cells by recombinant SeV technology and greatly advance the reemerging concept of oncolytic virotherapy, which currently appears to rely largely upon a natural preference of certain viruses for cancer cells.

Animals↗
PubMed2003

Mechanical compression of the extracranial vertebral artery during neck rotation.

Using duplex ultrasonography (US), the authors showed compression of the extracranial vertebral artery (ECVA) during neck rotation in 5.0% of 1,108 patients. Age (per 10-year increase, OR 0.80, 95% CI 0.67 to 0.96), vessel diameters (per 0.5-mm diameter increase, OR 0.63, 95% CI 0.51 to 0.79), and symptoms upon neck rotation (OR 4.01, 95% CI 1.35 to 11.9) were associated with vessel compression. In one case, SPECT revealed decreased cerebral perfusion of the hindbrain during rotation. ECVA US is useful in identifying vessel compression, especially in patients with symptoms on neck rotation.

Aged↗
PubMed2003

Comparative gene identification-94--a pivotal regulator of apoptosis.

Apoptosis is an active form of cell death that is carried out by proteins that are designed to kill the cell during normal mammalian development and tissue homeostasis. Cell death by apoptosis comprises a sequence of events leading to the activation of caspases which execute the fragmentation of the cellular protein and DNA leading to disintegration of the cell. This physiological neuronal apoptosis allows the nervous system to eliminate excess neurons. In addition, apoptotic cell death occurs in a variety of neuronal degeneration such as Alzheimer's disease. Here we describe second mitochondria-derived activator of caspases/Diablo as a new interacting protein of CGI-94 (comparative gene identification-94) which itself is probably involved in degenerative processes of Alzheimer's disease. Our findings that CGI-94 interacts with second mitochondria-derived activator of caspases/Diablo, inhibits nerve growth factor-induced neurite outgrowth and that its neuronal expression leads to cell death point to its pivotal role in the control of cellular survival. In conclusion, CGI-94 appears to be involved in processes of neuronal degeneration.

Animals↗