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N Nagai

Publications and source records attributed to N Nagai.

At least 19 recordsLinked to original sources
PubMed2001

Decreases in blood perfusion of the anterior cingulate gyri in Anorexia Nervosa Restricters assessed by SPECT image analysis.

BACKGROUND: It is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics. METHODS: The subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated. RESULTS: SPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups. CONCLUSIONS: These findings suggest that some localized functions of the ACCare possibly relevant to the psychopathological aspects of AN-R.

Anorexia Nervosa↗
PubMed2001

Depletion of circulating alpha(2)-antiplasmin by intravenous plasmin or immunoneutralization reduces focal cerebral ischemic injury in the absence of arterial recanalization.

In the absence of arterial recanalization, thrombolytic agents induce a dose-related extension of focal cerebral ischemic injury (FII) in experimental animals. However, FII is smaller in mice lacking alpha(2)-antiplasmin (alpha(2)-AP), the physiologic inhibitor of plasmin, suggesting its depletion might reduce FII in the absence of reperfusion. Therefore, the effect of human plasmin (Pli), human miniplasmin (mPli), and an Fab fragment neutralizing murine alpha(2)-AP (Fab-4H9) on FII after middle cerebral artery (MCA) ligation was studied in mice and in hamsters. In BALB/c mice, the median FII after 24 hours was 28 microL (range, 20-34) (n = 10) with saline and 23 microL (range, 17-26) (n = 9) with a single bolus of 0.07 mg Pli, given after MCA ligation (P =.010), which reduced alpha(2)-AP to 44% and fibrinogen from 0.75 to 0.44 g/L. FII was 20 microL (range, 13-26) (n = 6, P =.025) with 0.2 mg mPli and was 24 microL (range, 20-27) (n = 6, P =.020) with 1.7 mg Fab-4H9. Neuronal atrophy and reduction of laminin immunoreactivity were comparably observed in the infarct area after saline and Pli. In hamsters, a single bolus injection of 1 mg Pli, after MCA ligation, depleted alpha(2)-AP and fibrinogen and reduced FII at 24 hours from 20 microL (range, 9.9-38) (n = 6) to 7.0 microL (range, 0.44-31) (n = 7, P =.032). Thus, reduction of circulating alpha(2)-AP, with a single bolus of plasmin or of a neutralizing antibody fragment, significantly reduced FII after MCA ligation in mouse and hamster models, suggesting that, provided these observations can be extrapolated to human beings, transient depletion of circulating alpha(2)-AP might reduce ischemic stroke in the absence of reperfusion.

Animals↗
PubMed2001

Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.

The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level obtained in the presence of both oleic acid and insulin. This attenuation by bezafibrate and enhancement by troglitazone required the presence of both oleic acid and insulin. It is interesting that PAI-1 expression was affected so differently by these two PPAR activators.

Bezafibrate↗
PubMed2001

Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma.

Chromosome rearrangements involving 12q15 are frequently observed in a variety of human mesenchymal tumors. The high mobility group protein gene HMGIC has been identified as the target involved in these rearrangements. Uterine leiomyomas frequently use chromosome band 14q24 as a translocation partner to HMGIC. Recent studies within the chromosome 14 breakpoint region in cell lines carrying t(12;14)(q15;q23-24) revealed that RAD51L1, a member of the RAD51 recombination gene family, is the HMGIC partner. Using RT-PCR, we screened a panel of 81 uterine leiomyomas removed from 30 women for rearrangement between RAD51L1 and HMGIC. This is the first molecular analysis in which primary tumors have been examined for the RAD51L1/HMGIC transcripts. The chimeric transcripts were identified from two cases in which exon 7 of the RAD51L1 gene is fused in frame to either exon 2 or exon 3 of the HMGIC gene. These transcripts encode fusion proteins containing RAD51L1 nucleotide binding domains and the HMGIC protein lacking the N-terminal AT hook motifs. The detection of the RAD51L1/HMGIC fusion in primary tumors adds to the accumulating evidence implicating this fusion in a proportion of uterine leiomyoma patients.

Adult↗
PubMed2001

The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors.

Angiotensin 1-7 has been recently claimed the active member of the angiotensins' family. In the present study we compared the effect of angiotensin II and angiotensin 1-7 on the concentration of dopamine, serotonin, epinephrine, and norepinephrine and some of their metabolites in the rat hypothalamus, where the levels of angiotensins are particularly high. Intracerebroventricular injection of angiotensin II, but not angiotensin 1-7, time-dependently elevated the levels of both epinephrine (p < 0.05) and norepinephrine (p < 0.05) in the hypothalamus and both effects could be prevented by intracerebroventricular injection of either AT(1) (candesartan), AT(2) (PD123319) or AT(1-7) (A-779) receptor antagonist. Neither angiotensin II nor angiotensin 1-7 produced any changes in the level of dopamine, dihydroxyphenylacetic acid, homovanilic acid, serotonin, 5-hydroxyindoleacetic acid, or tryptophan at any time point in comparison with the control groups. However, AT(1) but not AT(2) receptor blockade, unmasked the stimulatory effect of angiotensin 1-7 on dopamine concentration in the hypothalamus. Thus, angiotensin II and its active metabolite angiotensin 1-7 regulate selectively, albeit differentially, adrenergic, noradrenergic and dopaminergic systems in the hypothalamus, the effects that involve AT(1), AT(2) and AT(1-7) angiotensin receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women.

OBJECTIVES: We sought to evaluate the relationship between the angiotensin-converting enzyme (ACE) genotype and the change in forearm vasoreactivity in response to a three-month course of oral estrogen in postmenopausal women. BACKGROUND: The ACE genotype is a known predictor of the response to an ACE inhibitor drug; however, it is not clear whether it can modify the effect of estrogen replacement therapy (ERT) on endothelial function in postmenopausal women. METHODS: Fifty-five postmenopausal women received 0.625 mg of conjugated equine estrogen daily for three months. Forearm blood flow (FBF) was measured by strain-gauge plethysmography. RESULTS: Twenty-one, 25 and 9 patients had the insertion/deletion (ID), II and DD genotypes, respectively. Plasma ACE activity was significantly higher at baseline in patients with either the DD or ID genotype than in those with the II genotype (p < 0.05). A significant decrease in plasma ACE activity with ERT was seen in the ID and II genotypes (p < 0.05), but not in the DD genotype. There were no significant differences in the FBF responses to reactive hyperemia at baseline between the three groups. Estrogen replacement therapy did not alter the FBF response to reactive hyperemia in the DD genotype (4.0 +/- 1.3%), although ERT significantly increased the FBF response in the ID and II genotypes (32.6 +/- 7.5% and 30.6 +/- 6.5%, respectively; p < 0.05). Forearm blood flow after administration of sublingual nitroglycerin did not change over three months in any of the three groups. CONCLUSIONS: These findings suggest that the effect of ERT in postmenopausal women on forearm endothelial function may be determined in part by the genotype of the ACE gene.

Administration, Oral↗
PubMed2001

Quantitation of epidermal growth factor receptor gene amplification by competitive polymerase chain reaction in pre-malignant and malignant oral epithelial lesions.

Abnormal amplification of epidermal growth factor receptor (EGFR) gene has been reported widely in various human tumors. However, the status of amplification of this gene in the process of carcinogenesis is not clearly defined. We used competitive polymerase chain reaction (PCR) to study whether EGFR gene is amplified and the degree of amplification in pre-malignant and malignant oral epithelial lesions, and also examined the relationship between EGFR gene aberration and the development of squamous cell carcinoma (SCC). Genomic DNA was extracted from paraffin sections of 17 cases of oral epithelial dysplasia (ED), four cases of carcinoma in situ (CIS), and 20 cases of untreated primary SCC. The extracted DNA was subjected to competitive PCR to amplify EGFR gene. Amplification of the EGFR gene was observed in three cases (17%) of ED, one case of CIS and four cases (20%) of SCC. In cases showing EGFR gene amplification, the degree of amplification was low in ED and CIS cases, whereas it was extremely high in SCC cases. These results suggest that amplification of EGFR gene occurs in the relatively early stage of the development of oral SCC. However, a high level of EGFR gene accumulation probably plays an important role in the progression to invasive cancer.

Carcinoma in Situ↗
PubMed2001

Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland.

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 was assessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair et al. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P =.007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neural invasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P <.0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P =.031, relative risk = 5.5) and low p27 expression (P =.012, relative risk = 5.2) were risk factors for worse disease-free survival. Low p27 expression (P =.015, relative risk = 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis. These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland.

Adolescent↗
PubMed2001

Are DNA ploidy and epidermal growth factor receptor prognostic factors for untreated ovarian cancer? A prospective study.

To identify prognostic factors for untreated ovarian cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a prospective series of 40 patients with ovarian cancer and 7 patients with borderline malignant ovarian tumor followed up for 5 years or more (median, 77 months). The frequency of aneuploid cells was 53.8% (21/39) in ovarian cancer and 14.3% (1/7) in borderline malignancy. There was no significant association between DNA ploidy and the clinicopathologic findings, in which aneuploid ovarian cancer was more common among advanced tumors. The S-phase fraction and P.I. value were higher in the patients with aneuploid tumors (p = 0.076). EGFR expression was detected in 76.9% (30/39) of ovarian cancers and 42.9% (3/7) of borderline malignant ovarian tumors, and the mean EGFR level was 5.8 +/- 12.1 (range: 0-49.5) and 28.3 +/- 71.1 (range: 0-189.4) fmol/mg protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I., and clinicopathologic findings analyzed. The 5-year survival rate in patients with aneuploid tumors was significantly worse in patients with ovarian cancer (p = 0.0165, log-rank test). No significant relationship was shown between P.I., EGFR expression, and 5-year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not associated with the risk of death (p = 0.5917, p = 0.9924, and p = 0.6840, respectively), although clinical stage shows a significant relationship (p = 0.0027). Our data showed that DNA ploidy is significantly related to the prognosis by univariate analysis, but DNA ploidy, P.I., and EGFR expression were not independent prognostic factors for the untreated ovarian cancer.

ErbB Receptors↗
PubMed2001

Tissue-type plasminogen activator is involved in the process of neuronal death induced by oxygen-glucose deprivation in culture.

Effect of tissue-type plasminogen activator (tPA) on oxygen-glucose deprivation (OGD) was studied in cultured cortical neurons prepared from tPA gene knockout (tPA-KO) and wild-type (Wt) mice. Three hours of OGD induced 45% and 23% of neuronal death in Wt and tPA-KO mice, respectively. Neuronal death in tPA-KO mice was increased to 42% by additional tPA. Six hours of OGD induced 80% and 40% of neuronal death in Wt and tPA-KO mice, respectively, whereas the addition of tPA increased to 62% in tPA-KO mice. These results suggest that tPA is directly involved in the process of neuronal death induced by ischemia-mimic stress without involving vascular or circulatory components.

Animals↗
PubMed2001

Evolution of the periodicity and the self-similarity in DNA sequence: a Fourier transform analysis.

Fourier transform analysis was applied to elucidate the periodical and self-similar properties in the DNA sequences mainly of beta-globin genes in different species, and the evolutionary change in those properties was then investigated. Map patterns of a two-dimensional DNA walk showed that the stretches of exons are significantly shorter than those of introns, suggesting that the evolution of exons is driven by natural selection, whereas that of introns is generated by unknown internal rules. Using a monomer analysis, we obtained the power spectra of four different bases, A, G, C, and T, in DNA sequences. Periodicities in the short- (2 to 10 base pairs [bp]), medium- (10 to 50 bp) and long-range order (50 to 300 bp) of beta-globin gene sequences could be observed, and power spectral densities of these periodicities were increased with evolution. These results suggest the existence of the internal rules in the occurrence of the synonymous and nonsynonymous substitutions in the sequences, the destabilization of the interaction between DNA and histone protein, and the stabilization of the chromatin structure, respectively. Moreover, 1/f(alpha) analysis of the power spectra (log-log plot) in the far long-range region (160 to 16,000 bp) suggested the increase in the self-similarity (the fractal structure) of DNA sequences with evolution. A general trend of the increase in a 3 bp periodicity with evolution might be functionally related to the CAG trinucleotide repeat diseases such as Huntington chorea, where a marked periodicity of 3 bp could be observed. Fourier transform analysis applied to a DNA sequence offers a great new avenue for extracting information on the evolution of a DNA sequence.

Animals↗
PubMed2001

Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas.

Reduced expression of a cyclin-dependent kinase inhibitor, p27, has been reported to be associated with poor prognosis in several human cancers. The aim of this study was to investigate the potential role of p27 in ovarian cancer development and progression. Immunohistochemical expression of p27 was determined using 117 epithelial ovarian tumor tissues and 8 normal ovaries. p27 mRNA expression was examined by semi-quantitative PCR amplification using 26 ovarian cancer samples. Nuclear staining of p27 was commonly observed in the normal ovarian surface epithelium and the epithelial cells of germinal inclusion cysts. Positive p27 staining rates were significantly higher in serous adenomas (p=0.006) and in serous LMP tumors (p=0.013) than that in serous carcinomas (Fisher's exact test). In serous ovarian cancers, positive p27 staining rate was significantly higher in early stage (stage1/2) than that in advanced stage (stage 3/4) diseases (p=0.030, Fisher's exact test). Log-rank testing showed that negative p27 expression significantly correlates with poor survival in serous ovarian cancer patients (p=0.041). Considerable levels of p27 mRNA were detected in all ovarian cancer samples examined. These results suggest that the underexpression of p27 caused by post-translational mechanism may contribute to the development and progression and result in poor prognosis of serous ovarian cancers.

Cell Cycle Proteins↗
PubMed2001

[Two cases of digitalis toxicity with reversible and severe decrease of visual acuity].

BACKGROUND: We performed electrophysiologic tests on two patients with digitalis toxicity who first had photophobia and xanthopsia and revealed reversible reduced visual acuity and binocular central scotoma. CASES: The patients were a 72-year-old male and a 54-year-old male who had symptoms of digitalis toxicity. FINDINGS: The corrected visual acuity was severely decreased during digitalis toxicity, 0.02 oculus dexter (OD) and 0.1 oculus sinister (OS) in case 1 and 0.04 OD and 0.2 OS in case 2. But visual acuity recovered as the blood levels of digitalis decreased to the normal level and the corrected visual acuity was 0.7 OD and 0.8 OS in case 1 and 0.8 OD and 0.9 OS in case 2. We recorded 30 Hz-flicker electroretinogram (ERG), single flash ERG, photopic ERG, and scotopic ERG when digitalis blood levels were elevated and normal. Decreased amplitudes of 30 Hz-flicker ERG and photopic ERG suggested that photoreceptor function was disturbed at digitalis toxicity and cone dysfunction was more severely disturbed than rod dysfunction. CONCLUSION: 30 Hz-flicker ERG, as well as electrocardiogram and digitalis blood level, is a relatively convenient and useful measure of digitalis toxicity. It is necessary consiler toxicity when severe visual dysfunction is observed in patients with digitalis therapy.

Aged↗
PubMed2001

[A case of renal oncocytoma with synchronous contralateral renal cell carcinoma].

A case of bilateral, synchronous renal cell carcinoma and oncocytoma is reported. The patient was a 70-year-old woman. Computed tomographic scan revealed bilateral low density masses, which had a diameter of approximately 4 cm (right kidney), and 2.5 cm (left kidney). We suspected bilateral renal cell carcinomas, and performed, right nephrectomy and left enucleation of the tumor. Pathological diagnosis was right renal cell carcinoma and left oncocytoma. To our knowledge only 5 previous cases of renal cell carcinoma associated with oncocytoma have been reported in Japan. Two cases were metachronous and three cases were unilateral and synchronous. This is the first reported case of bilateral, synchronous renal cell carcinoma and oncocytoma.

Adenoma, Oxyphilic↗
PubMed2001

[Analysis of factors related to the high incidence of tuberculosis in the city of Wakayama--analysis according to age groups, and sputum test results].

Over the last 20 years, the decrease in the incidence of Tuberculosis (TB) in Japan has slowed down. As of 1999, the incidence rate was 34.6 per 100,000 population in Japan, which was higher than that of the other developed countries, and the incidence rate in the city of Wakayama, one of the prefectural capital cities in Japan, during the same period was 42.9 per 100,000 population. We investigated the causes of this high incidence rate of TB in Wakayama City according to the analysis by age groups and sputum test results when patients are newly registered. Comparing our data during the period from 1.1.1998 to 12.31.1999 with data during the same period in the whole country and the rest of Wakayama Pref., the following results were obtained. Observing by age-groups, the incidence of TB in Wakayama City as well as in the rest of Wakayama Pref. and in the whole country was highest in the age-group above 70 years of age, though the rate of Wakayama City was significantly higher (146.2 per 100,000 population) than that in the rest of Wakayama Pref. (98.5 per 100,000 population) and that in the whole country (90.3 per 100,000 population). Furthermore, the incidence rate of cases diagnosed as TB without bacteriological proof in Wakayama City (57.1 per 100,000 population) was significantly higher than that of the whole country (33.7 per 100,000 population). Therefore, we concluded that one of the causes of high incidence of TB in Wakayama City was due to inappropriate method of diagnosing TB. More extensive use of sputum examination and strict evaluation of cases without bacteriological proof are desirable to increase the accuracy of TB diagnosis in Wakayama City.

Adolescent↗
PubMed2000

Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis.

Triple helix formation of procollagen after the assembly of three alpha-chains at the C-propeptide is a prerequisite for refined structures such as fibers and meshworks. Hsp47 is an ER-resident stress inducible glycoprotein that specifically and transiently binds to newly synthesized procollagens. However, the real function of Hsp47 in collagen biosynthesis has not been elucidated in vitro or in vivo. Here, we describe the establishment of Hsp47 knockout mice that are severely deficient in the mature, propeptide-processed form of alpha1(I) collagen and fibril structures in mesenchymal tissues. The molecular form of type IV collagen was also affected, and basement membranes were discontinuously disrupted in the homozygotes. The homozygous mice did not survive beyond 11.5 days postcoitus (dpc), and displayed abnormally orientated epithelial tissues and ruptured blood vessels. When triple helix formation of type I collagen secreted from cultured cells was monitored by protease digestion, the collagens of Hsp47+/+ and Hsp47+/- cells were resistant, but those of Hsp47-/- cells were sensitive. These results indicate for the first time that type I collagen is unable to form a rigid triple-helical structure without the assistance of molecular chaperone Hsp47, and that mice require Hsp47 for normal development.

Animals↗
PubMed2000

Previous exposure to footshock stress attenuates nicotine-induced serotonin release in rat striatum during the subsequent stress.

We have analyzed the effects of chronic or repeated footshock stress on the release of serotonin (5-hydroxytryptamine: 5-HT) in the striatum of rats that received nicotine by using a microdialysis technique. Neither local infusion of nicotine alone nor stress application alone changed 5-HT release. Local infusion of 1 mM nicotine to the striatum, however, significantly increased 5-HT release in the striatum to 145.9 +/- 30.8 pg/dialysate during simultaneous stress application. These increases of extracellular 5-HT release induced by the combination of nicotine and stress application were also observed in rats that had received daily chronic footshock. However, the previously administered footshock induced the reduced release of 5-HT from the striatum to 33.5 +/- 8. 6 (repeated footshock) and 10.0 +/- 3.6 pg/dialysate (daily footshock) when footshock was given together with nicotine infusion. These results suggest that previous exposure to stress attenuated the nicotine-induced 5-HT release in the striatum during the subsequent stress.

Animals↗