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Biomedical subjects

Kenjiro Kikuchi

Publications and source records attributed to Kenjiro Kikuchi.

At least 55 records · Page 3Linked to original sources
PubMed2004

Small cell lung cancer cells express EGFR and tyrosine phosphorylation of EGFR is inhibited by gefitinib ("Iressa", ZD1839).

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ("Iressa", ZD1839) has demonstrated anti-tumor activity in non-small cell lung cancer (NSCLC) and has been approved in over 20 countries. NSCLC has been reported to express high levels of EGFR. However, gefitinib appears to be more effective against adenocarcinoma than squamous cell carcinoma, the latter expressing more EGFR. In the present study, we evaluated the effect of gefitinib against the small cell lung cancer (SCLC) cell lines NCI-H82, NCI-H209, NCI-H510, NCI-H526 and NCI-H660. SCLC has been reported to express a low to undetectable level of EGFR. We compared the effects of gefitinib between cell lines with detectable and undetectable EGFR expression. First, we evaluated expression levels of EGFR and HER2/neu by Western blotting and immunoprecipitation respectively; EGFR protein was detected in two of the five SCLC cell lines, whereas HER2/neu was not detected in any. Next, we analyzed expression levels of phosphorylated ERK1/2 and compared these results with EGFR (HER-1/ErbB1) and HER2/neu (ErbB2) expression levels, as EGFR conducts signals through Ras-Raf-MAPK pathway; gefitinib inhibited phosphorylation of ERK1/2 by EGF addition in cell lines with detectable and undetectable EGFR expression. These data suggest that gefitinib is potentially effective against cancers with low EGFR expression such as SCLC.

Antineoplastic Agents↗
PubMed2004

[Secondary nephrotic syndrome due to cardiovascular disease].

Cardiovascular diseases ralely evoke nephrotic syndrome. Especially hypertensive renal disease (nephroscrelosis) and renovascular hypertension occasionally may lead to nephrotic syndrome. We reported a case of nephrotic syndrome with renovascular hypertension successfully treated with candesartan. In eldery patients cardiovascular diseases are appeared. It is very important for clinicians to detect the mechanism of nephrotic syndrome caused by cardiovascular diseases.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

[Effects of calcium channel blockers in atherosclerosis and cardiovascular event and oxidative vascular damage].

Ca antagonists are relevant therapeutic tool for patients with hypertension. The effects of Ca antagonists against oxidative vascular damage and followed atherosclerosis were elucidated in various experimental model accompanied with the vasodilatative effects of Ca antagonists by blocking the L-type Ca channel. The beneficial effects of Ca antagonists in cardiovascular disease have been demonstrated in several clinical trials, as we demonstrated the beneficial effect of Ca antagonist in the incidence of cardiovascular event in Japanese patients with coronary disease. In patient with diabetes mellitus, the cardiovascular disease was also caused by the mechanism involved with the increase in oxidative stress in blood vessels and related factors such as advanced glycation endproducts, protein kinase C and insulin resistance. The beneficial effects of Ca antagonists in cardiovascular disease in patients with diabetes mellitus have been demonstrated in several clinical trials, may be dependent on the effect of Ca antagonist against the oxidative stress in the setting of hyperglycemia.

Animals↗
PubMed2003

Prevalence of multiple sclerosis in Asahikawa, a city in northern Japan.

Twenty-two years after the first survey, a follow-up study was performed on the prevalence of multiple sclerosis (MS) in Asahikawa, a city in northern Japan. The crude prevalence of MS rose from 2.5/100,000 (in 1975) to 10.2/100,000 (in 2002). The clinical diagnosis was established using the Poser diagnostic criteria, and the degree of physical disability was determined using the Expanded Disability Status Scale (EDSS). The distribution of patients according to the clinical form of MS was 65% with relapsing-remitting MS, 19% with secondary chronic progressive MS and 16% with the primary chronic progressive forms of MS. Symptoms at onset in the present study less often affected optic nerves (3%) than previously reported in Japan and was more like that seen in western MS series. Although prevalence of MS increase four-fold in Japan over the last two decades, it remains uncertain whether this apparent increase is real or reflects better ascertainment.

Adolescent↗
PubMed2003

Thromboxane A2 regulates vascular tone via its inhibitory effect on the expression of inducible nitric oxide synthase.

BACKGROUND: Circulatory failure in sepsis arises from vascular hyporesponsiveness, in which nitric oxide (NO) derived from inducible NO synthase (iNOS) plays a major role. Details of the cross talk between thromboxane (TX) A2 and the iNOS-NO system, however, remain unknown. We intended to clarify the role of TXA2, via the cross talk, in vascular hyporesponsiveness. METHODS AND RESULTS: We examined cytokine-induced iNOS expression and NO production in cultured vascular smooth muscle cells (VSMCs) and cytokine-induced hyporesponsiveness of the aorta from mice lacking the TXA2 receptor (TP-/- mice). The cytokine-induced iNOS expression and NO production observed in wild-type VSMCs were significantly augmented in TP-/- VSMCs, indicating an inhibitory effect of endogenous TXA2 on iNOS expression. Furthermore, in indomethacin-treated wild-type VSMCs, U-46619, a TP agonist, inhibited cytokine-induced iNOS expression and NO production in a concentration-dependent manner, effects absent from TP-/- VSMCs. In an ex vivo system, the cytokine-induced hyporesponsiveness of aortas to phenylephrine was significantly augmented in TP-/- aorta but was almost completely canceled by aminoguanidine, an iNOS inhibitor. Accordingly, cytokine-induced NO production was significantly higher in TP-/- aorta than in wild-type aorta. Moreover, U-46619 significantly suppressed lipopolysaccharide-induced NO production in vivo only in wild-type mice. CONCLUSIONS: These results suggest that TXA2 has a protective role against the development of vascular hyporesponsiveness via its inhibitory action on the iNOS-NO system under pathological conditions such as sepsis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

The diagnostic and prognostic relevance of human telomerase reverse transcriptase mRNA expression detected in situ in patients with nonsmall cell lung carcinoma.

BACKGROUND: The objectives of this study were to evaluate the diagnostic and prognostic relevance of human telomerase reverse transcriptase (hTERT) detected in situ in patients with nonsmall cell lung carcinoma (NSCLC) and to investigate the possible correlations between hTERT mRNA in NSCLC and the patients' clinicopathologic features, including survival. METHODS: hTERT mRNA was detected by in situ hybridization in 146 samples from patients with NSCLC. The signal intensity of hTERT mRNA expression was evaluated by two independent observers. The expression level was defined subjectively as strong, moderate, or weak. RESULTS: hTERT mRNA was detected mainly in the cytoplasm of tumor cells. It was detected in the cytoplasm of 100% of samples from patients with NSCLC but was not detected in normal lung tissue, except in activated lymphocytes. There was a significant correlation between hTERT mRNA expression and pathologic tumor status, pathologic disease stage (pStage), and Ki-67 labeling index. There was no significant correlation between hTERT mRNA expression and age, gender, pathologic lymph node status (pN), histology, or tumor differentiation. The 5-year survival rates for patients with strong and moderate hTERT mRNA expression levels were 46.9% and 77.9%, respectively; the difference was statistically significant (P = 0.0001). A multivariate analysis of survival using a stepwise procedure revealed that hTERT mRNA expression, pN status, pStage, and age were statistically significant prognostic factors (P = 0.0029, P = 0.0012, P = 0.0237, and P = 0.0496, respectively). CONCLUSIONS: The findings suggested that hTERT mRNA expression may be useful for the diagnosis of NSCLC and also may be an independent prognostic factor for patients with NSCLC.

Adult↗
PubMed2003

Inhaled nitric oxide modifies left ventricular diastolic stress in the presence of vasoactive agents in heart failure.

Nitric oxide (NO) inhalation therapy has been widely used in several diseases with pulmonary hypertension. However, application of NO inhalation therapy remains controversial in heart failure. Cardiovascular effects of inhaled NO (iNO) were evaluated in dogs before and after induction of heart failure with and without infusion of vasoactive agents. iNO did not affect the baseline left ventricular (LV) function or the response to isoproterenol in control conditions or heart failure induced by procainamide. Pulmonary vascular resistance was significantly decreased by iNO in heart failure with infusion of vasoactive agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO in heart failure in the presence of infusion of vasoactive agents independent of their types; either the vasodilating agents of acetylcholine and nitroglycerin or the vasoconstricting agents of norepinephrine and angiotensin-II. The end-diastolic LV dimension and wall stress were also significantly increased by iNO, however, those at end systole were not affected. These results suggested that NO inhalation therapy reduced pulmonary vascular resistance, whereas in the presence of additional stress of vasoactive agents, it increased LV preload and end-diastolic wall stress in heart failure.

Acetylcholine↗
PubMed2003

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by 123I-BMIPP SPECT and 99mTc-tetrofosmin electrocardiographically gated SPECT.

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.

Adolescent↗
PubMed2003

Improved accuracy in estimation of left ventricular function parameters from QGS software with Tc-99m tetrofosmin gated-SPECT: a multivariate analysis.

UNLABELLED: The purpose of this study was to verify whether the accuracy of left ventricular parameters related to left ventricular function from gated-SPECT improved or not, using multivariate analysis. METHODS: Ninety-six patients with cardiovascular diseases were studied. Gated-SPECT with the QGS software and left ventriculography (LVG) were performed to obtain left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). Then, multivariate analyses were performed to determine empirical formulas for predicting these parameters. The calculated values of left ventricular parameters were compared with those obtained directly from the QGS software and LVG. RESULTS: Multivariate analyses were able to improve accuracy in estimation of LVEF, EDV and ESV. Statistically significant improvement was seen in LVEF (from r = 0.6965 to r = 0.8093, p < 0.05). Although not statistically significant, improvements in correlation coefficients were seen in EDV (from r = 0.7199 to r = 0.7595, p = 0.2750) and ESV (from r = 0.5694 to r = 0.5871, p = 0.4281). CONCLUSION: The empirical equations with multivariate analysis improved the accuracy in estimating LVEF from gated-SPECT with the QGS software.

Adolescent↗
PubMed2003

Roles of calcineurin and calcium/calmodulin-dependent protein kinase II in pressure overload-induced cardiac hypertrophy.

Calcineurin and calcium/calmodulin-dependent protein kinase (CaMK) II have been suggested to be the signaling molecules in cardiac hypertrophy. It was not known, however, whether these mechanisms are involved in cardiac hypertrophy induced by pressure overload without the influences of blood-derived humoral factors, such as angiotensin II. To elucidate the roles of calcineurin and CaMK II in this situation, we examined the effects of calcineurin and CaMK II inhibitors on pressure overload-induced expression of c-fos, an immediate-early gene, and protein synthesis using heart perfusion model. The hearts isolated from Sprague-Dawley rats were perfused according to the Langendorff technique, and then subjected to the acute pressure overload by raising the perfusion pressure. The activation of calcineurin was evaluated by its complex formation with calmodulin and by its R-II phosphopeptide dephosphorylation. CaMK II activation was evaluated by its autophosphorylation. Expression of c-fos mRNA and rates of protein synthesis were measured by northern blot analysis and by 14C-phenylalanine incorporation, respectively. Acute pressure overload significantly increased calcineurin activity, CaMK II activity, c-fos expression and protein synthesis. Cyclosporin A and FK506, the calcineurin inhibitors, significantly inhibited the increases in both c-fos expression and protein synthesis. KN62, a CaMK II inhibitor, also significantly prevented the increase in protein synthesis, whereas it failed to affect the expression of c-fos. These results suggest that both calcineurin and CaMK II pathways are critical in the pressure overload-induced acceleration of protein synthesis, and that transcription of c-fos gene is regulated by calcineurin pathway but not by CaMK II pathway.

Animals↗
PubMed2003

Alterations in penicillin binding protein gene of Streptococcus pneumoniae and their correlation with susceptibility patterns.

Penicillin binding protein (pbp) gene alterations of 328 clinical isolates of Streptococcus pneumoniae were examined for a correlation with their antibiotic-resistance. The frequency of penicillin G (PEN-G) resistance was determined to clarify susceptibility to several antibiotics, namely PEN-G, ampicillin, sulbactam/ampicillin, cefozopram, panipenem (PAPM), clarithromycin (CLR), azithromycin (AZM) and levofloxacin (LVX). Oligonucleotide primers for three pbp genes (pbp1a, pbp2x and pbp2b) were used to detect mutations in pbp. Of the strains, 25.9% were classified as Pen-Gs, 68.0% as Pen-Gir and 6.1% as Pen-Gr. The polymerase chain reaction product for wild-type pbp1a was found in 185 isolates, that for wild-type pbp2x was found in 66 isolates and that for wild-type pbp2b was found in 213 isolates. None of these three genes was detectable in 100 isolates while all of them were detected in 64 isolates (1aw/2xw/2bw). Of those 64 isolates with 1aw/2xw/2bw, the minimum inhibitory concentration (MIC) of PEN-G was < or =0.06 mg/l for 54 isolates and 0.12 mg/l for 10 isolates. Of the 272 strains for which the MIC of PAPM was < or =0.03 mg/l, there were 85 Pen-Gs, 184 Pen-Gir and three Pen-Gr isolates. Three strains for which the MIC of LVX was > or =4.0 mg/l included one Pen-Gs and two Pen-Gir isolates. The MICs of CLR correlated significantly with those of AZM. The MIC of CLR was > or =1 mg/l for 216 isolates, and the MIC of AZM was > or =1 mg/l for 244 of them. These data suggested that PAPM may be effective against S. pneumoniae infection, although acquisition of resistance should be considered. LVX also seemed to be effective against S. pneumoniae.

Aminoacyltransferases↗
PubMed2003

A case of a short-coupled variant of torsades de Pointes with electrical storm.

This case report describes a short-coupled variant of Torsades de Pointes with a characteristic ECG pattern consisting of a prominent J wave in leads V3-V6, in which an electrical storm was evoked with autonomic receptor stimulation and a blockade test. The patient's frequent VF attacks were triggered by short-coupled premature ventricular contractions with a right bundle branch block morphology and left-axis deviation, and were suppressed by deep sedation followed by a combination therapy using verapamil and mexiletine. Interestingly, with the use of those drugs, the prominent J wave diminished. The mechanism underlying this syndrome is discussed.

Electrocardiography↗
PubMed2003

Collapsin response mediator protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat.

The rat collapsin response mediator protein-2 (CRMP-2) is a member of CRMP family (CRMP-1-5). The functional consequence of CRMP-2 during embryonic development, particularly in neurite elongation, is relatively understood; however, the role in nerve regeneration is unclear. Here we examined the role of CRMP-2 during nerve regeneration using rat hypoglossal nerve injury model. Among the members, CRMP-1, CRMP-2, CRMP-5 mRNA expressions increased after nerve injury, whereas CRMP-3 and CRMP-4 mRNA did not show any significant change. In the N1E-115 cells, CRMP-2 has the most potent neurite elongation activity among the CRMP family members. In dorsal root ganglion (DRG) organ culture, CRMP-2 overexpression by adenoviral vector demonstrated substantial neurite elongation. On the other hand, CRMP-2 (DeltaC381), which acts as a dominant negative form of CRMP-2, inhibited neurite formation. Collectively, it would be plausible that CRMP-2 has potent nerve regeneration activity after nerve injury. We therefore examined whether CRMP-2 overexpression in the injured hypoglossal motor neurons accelerates nerve regeneration. A retrograde-tracer, Fluoro-Gold (FG), was used to evaluate the number of reprojecting motor neurons after nerve injury. CRMP-2-overexpressing motor neurons demonstrated the accelerated reprojection. The present study suggests that CRMP-2 has potent neurite elongation activity in nerve regeneration in vivo.

Animals↗
PubMed2003

Effect of beta-adrenoceptor antagonist and angiotensin-converting enzyme inhibitor on hypertension-associated changes in adenylyl cyclase type V messenger RNA expression in spontaneously hypertensive rats.

Adenylyl cyclase (AC) messenger RNA (mRNA) expression is decreased in failing hearts. Diminished expressions are accompanied by desensitization of beta-adrenergic signal transduction. Factors contributing to such changes in mRNA expression for the major myocardial isoform AC V are not well established. To assess the contributions of hypertension, left ventricular hypertrophy (LVH), the renin-angiotensin-aldosterone system (RAS), and the sympathetic nervous system to these changes, ventricular expression of AC V mRNA was measured at different ages in spontaneously hypertensive rats (SHRs). In addition, the effects on them of angiotensin-converting enzyme inhibitor and beta-adrenoceptor antagonists were determined. Prior to quantitative Northern blotting at ages 5, 9, or 12 weeks, hemodynamic and morphologic variables were measured in SHRs and Wistar-Kyoto rats (WKYs). The SHRs and WKYs were treated with an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg/d), or a beta(1)-adrenoceptor antagonist, atenolol (100 mg/kg/d), for 8 weeks preceding Northern analysis. Myocardial AC V mRNA expression increased from 5-12 weeks in both SHRs and WKYs. Expression of AC V mRNA in SHRs increased somewhat less than in WKYs at 9 weeks and significantly less at 12 weeks. This was accompanied by development of LVH and hypertension in SHRs. Blood pressure and left ventricular weight relative to body weight were markedly decreased by enalapril and were moderately decreased by atenolol. Expression of AC V mRNA in SHRs at 12 weeks was normalized equally by enalapril and atenolol to the level of WKYs. Thus AC V mRNA expression increases are blunted in the early stages of LVH in SHRs under the influences of beta(1)-adrenergic signal transduction and the RAS.

Adenylyl Cyclases↗
PubMed2003

Cervical and intracranial atherosclerosis and silent brain infarction in Japanese patients with coronary artery disease.

PURPOSE: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). METHODS: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. RESULTS: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). CONCLUSIONS: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.

Adult↗
PubMed2003

Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction.

The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-beta-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion.

Aged↗