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Kensuke Kawasaki

Publications and source records attributed to Kensuke Kawasaki.

16 recordsLinked to original sources
PubMed2007

Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231).

Some kinds of breast cancer cell lines, similar to several types of solid tumors, express epidermal growth factor receptor (EGFR). However, gefitinib, an EGFR tyrosine kinase inhibitor, is not effective for all these cell lines. Similarly, taxane is effective for many of the cell lines, although some, such as the multidrug-resistant MCF7/ADR cell line, show taxane-resistance. Here, we examined the growth inhibitory effect of combination treatment with gefitinib and taxane on the breast cancer cell lines MDA-MB-231 (EGFR-positive) and MCF7/ADR (EGFR- and HER2-positive). To estimate the combined effect, a Combination Index was calculated for each cell line. The combination of gefitinib and taxane showed a strong synergistic effect on MCF7/ADR cells, but an invitro additive-antagonistic effect on MDA-MB-231 cells. Similarly, the combination treatment showed a significantly increased tumor inhibitory effect on MCF7/ADR xenografts, but not on MDA-MB-231 xenografts. Regarding the mechanism of the synergistic effect, Western blotting analysis revealed that taxane activated the EGFR-Akt pathway in MCF7/ADR cells but not in MDA-MB-231. To determine the optimal sequential administration of gefitinib and taxane for MCF7/ADR cells, we used flow cytometry to analyze the cell cycle and apoptosis; finding that taxane treatment followed by gefitinib produced a higher rate of G2 arrest and apoptosis than gefitinib treatment followed by taxane. These results suggest gefitinib overcomes the drug-resistance of these cells, thereby increasing the effects of taxane on MCF7/ADR cells. Further, activation of the EGFR-Akt pathway by taxane is related to this synergistic effect.

Animals↗
PubMed2006

The significance of 123I-BMIPP delayed scintigraphic imaging in cardiac patients.

BACKGROUND: Earlier studies have not fully investigated the significance of radionuclide planar imaging in cardiac patients using the fatty acid analogue 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP). OBJECTIVES: This study was to clarify the effectiveness of 123I-BMIPP in assessing the heart-to-mediastinum ratio (H/M) and myocardial washout rate (WR) in patients with heart disease. METHODS: Myocardial 123I-BMIPP imaging was performed in 33 patients (20 with chronic heart failure [CHF] and 13 with stable angina pectoris [AP]) and 11 control subjects. Myocardial 123I-BMIPP planner images were obtained 30 min (early image) and 4 h (delayed image) after tracer injection. The left ventricular ejection fraction (LVEF) was measured by quantitative gated single photon emission computed tomography. The concentration of plasma brain natriuretic peptide (BNP) was measured before the scintigraphic study. RESULTS: (1) Delayed H/M was much lower in CHF than in AP (1.93 +/- 0.37 vs. 2.21 +/- 0.38, p < 0.05) and controls (vs. 2.47 +/- 0.38, p < 0.001). (2) The WR in CHF and AP were higher than the WR in controls (39.8 +/- 12.7% and 38.7 +/- 11.1 vs. 27.9 +/- 10.2%, p < 0.01 and p < 0.05, respectively). (3) In all subjects, LVEF was correlated with delayed H/M (r = 0.39, p < 0.01). And, the BNP was correlated with both the WR (r = 0.36, p < 0.05) and delayed H/M (r = - 0.29, p = 0.05). CONCLUSION: These data strongly suggest that the delayed H/M and myocardial WR of 123I-BMIPP enhances the assessment of the myocardial fatty acid metabolism disorders in patients with heart disease in both masked and unmasked conditions.

Aged↗
PubMed2006

Gender difference in the level of high-density lipoprotein cholesterol in elderly Japanese patients with coronary artery disease.

OBJECTIVE: High-density lipoprotein cholesterol (HDLC) levels are known to be reduced in the metabolic syndrome, but the HDLC profile of elderly patients with coronary artery disease (CAD) has not been well characterized. This study investigated the gender difference of HDLC levels in elderly Japanese patients with CAD. METHODS: Serum lipid data were analyzed retrospectively to assess sex-related differences of the lipid profile, and to evaluate the effects of pharmacotherapy or physical exercise on hyperlipidemia. PATIENTS: A total of 163 elderly (> or = 65 years) outpatients with CAD (128 men aged 70.6+/-5.2 years and 35 women aged 74.1+/-6.0 years [mean+/-SD]) were investigated. RESULTS: The mean total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and triglyceride (TG) levels were similar in men and women, while the mean HDLC level was significantly higher in women than men (58.3+/-18.1 vs. 50.3+/-13.5 mg/dL; p=0.0064). The HDLC level was not significantly influenced by oral lipid-lowering therapy or regular exercise in either sex. However, women without lipid-lowering therapy had significantly higher HDLC levels than men with (p=0.0312) or without (p=0.0338) lipid-lowering therapy, while women performing regular exercise had significantly higher HDLC levels than men with (p=0.0047) or without (p<0.001) regular exercise. CONCLUSION: Elderly women with CAD have higher HDLC levels relative to their postmenopausal state than those of men with CAD. Low HDLC levels, unlike in men, may not be a major risk factor for CAD in elderly women.

Aged↗
PubMed2006

Proteasome inhibitor bortezomib increases PTEN expression and enhances trastuzumab-induced growth inhibition in trastuzumab-resistant cells.

PTEN (phosphatase and tension homolog deleted on chromosome 10) has been shown to be inactivated in a wide range of cancers and the role of this gene product is associated with the suppression of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway in many cancers. Recently, some reports demonstrated that the degree of PTEN expression could predict trastuzumab chemosensitivity in ErbB2-overexpressing breast cancer. Here, we demonstrate the possible involvement of a proteasome inhibitor (PS341) in PTEN expression and elucidate the influence of PI3K/Akt, one of the main cascades of the ErbB2 downstream pathway, and discuss the role of the proteasome inhibitors in trastuzumab resistance. ErbB2-overexpressing SKBR3 human breast cancer cells and trastuzumab-resistant SKBR3/R cells were analyzed in this study. We show that the expression of phosphorylated Akt was highly increased in trastuzumab-resistant cells, although the expression of PI3K, phosphorylated PI3K and non-phosphorylated Akt was unchanged in comparison with wild-type SKBR3 cells. However, following treatment with PS341, the level of phosphorylated Akt was decreased in a dose-dependent manner. Conversely, the level of PTEN was increased in the same fashion. PS341 showed sufficient cytotoxicity in resistant cells in combination with trastuzumab and the efficacy of trastuzumab was inclined to be better in resistant cells under PS341 treatment. Remarkable activity of Akt was observed in trastuzumab-resistant SKBR3 breast cancer cells and this phenomenon could be associated with the decreased expression of PTEN. The proteasome inhibitor PS341 could increase the level of PTEN and inhibit the downstream pathway of ErbB2, interfering with phosphorylation of Akt.

Antibodies, Monoclonal↗
PubMed2006

Use of multifocal visual evoked potential tests in the objective evaluation of the visual field in pediatric epilepsy surgery.

OBJECT: To evaluate objectively the visual fields of patients with pediatric epilepsy who are uncooperative with perimetry and in whom postoperative visual field deficits are expected, the authors investigated the usefulness of the multifocal visual evoked potential (VEP) method. METHODS: Normal waves in multifocal VEP were determined in 21 healthy children (21 eyes) 6 to 15 years of age (mean 11.4 years). Responses from eight sites in each child were divided into four quadrants (superior and inferior temporal and superior and inferior nasal). In each quadrant, two response waves were grouped and averaged. The peak latency and amplitude at approximately 100 msec were used for assessment. In three cases involving patients with epilepsy, multifocal VEP measurements were also recorded and compared with the peak latency and amplitude in the healthy children. In these children, no significant differences were observed in the peak latency of amplitude among four quadrants using one-way analysis of variance. In each patient, multifocal VEP tests showed abnormal waves in the quadrant corresponding to the lesion demonstrated in neuroradiological images. This result was useful in the treatment of choice and the postoperative evaluation. CONCLUSIONS: Multifocal VEP tests can be useful in evaluating the visual field of children objectively. They can also be valuable in assessing preoperative visual field defects and revealing changes in the visual field after treatment.

Adolescent↗
PubMed2006

[Clinical application of multifocal visual evoked potentials in children with epilepsy caused by intracranial disease].

PURPOSE: We investigated whether visual field defects could be objectively evaluated using multifocal visual evoked potential(m-VEP) in two children with epilepsy caused by intracranial disease in whom it was difficult to measure the visual field. METHODS: To determine normal waves in m-VEP, recording was performed using a visual evoked response imaging system(VERIS)Junior Science program (Mayo, Aichi, Japan) in 20 healthy children (20 eyes); peak latency and amplitude were used for assessment. In the two children with epilepsy, m-VEPs were recorded, and compared with the results of static perimetry or the lesions observed by Magnetic Resonance Imaging (MRI). RESULTS: In the 20 healthy children, there was no significant difference in the peak latency or amplitude among 4 quadrants by one-way analysis of variance. m-VEP in the children with epilepsy showed abnormal waves, corresponding to the visual field defects in the static perimetry or the lesions observed by MRI. CONCLUSIONS: Objective evaluation of visual field defects using m-VEP may be useful in children with epilepsy caused by intracranial disease in whom kinetic/static perimetry as a subjective examination is difficult.

Brain Diseases↗
PubMed2005

Reversible ventricular dysfunction takotsubo cardiomyopathy.

BACKGROUND: Recently, many cardiologists have recognized the existence of a rapidly reversible form of heart failure of unknown origin characterized by a takotsubo-shaped, dyskinetic left ventricle on left ventriculography. AIM: To determine the detailed clinical features of takotsubo cardiomyopathy. METHODS: Thirteen elderly patients (11 women and 2 men with a mean age of 75.3 years) who had normal coronary arteries and takotsubo-like left ventricular dysfunction were prospectively enrolled in this study. RESULTS: Cardiac enzymes did not increase significantly, but the mean plasma norepinephrine level was very high on admission (0.98 microg/l). Coronary angiography revealed normal coronary arteries in all patients, but left ventriculography showed apical akinesis combined with basal hyperkinesis, i.e., a takotsubo (Japanese octopus fishing pot)-shaped ventricle. Left ventricular wall motion normalized within a mean of 16.9 hospital days in 12 patients, but 1 patient died of acute renal failure on hospital day 7. Cardiac events did not recur during a follow-up period of 0.5 to 5 years. CONCLUSION: Takotsubo cardiomyopathy seems to be a new type of acute heart failure, which generally has a good prognosis and does not recur. Myocardial damage by catecholamine overload, adrenoceptor hypersensitivity, and changes of catecholamine dynamics due to stress may cause this condition.

Aged↗
PubMed2005

A child with epilepsy in whom multifocal VEPs facilitated the objective measurement of the visual field.

PURPOSE: We investigated whether visual field defects can be objectively evaluated by using multifocal visual evoked potential (multifocal VEP) in children with epilepsy in whom it is difficult to measure the visual field. METHODS: First, to determine normal waves in multifocal VEP, recording was performed by using a VERIS Junior Science (Mayo, Aichi, Japan) in 21 healthy children (21 eyes) consisting of 12 boys and nine girls aged 6 to 15 years (mean age, 11.4 years). Responses from eight sites in each subject were divided into four quadrants (superior and inferior temporal quadrants and superior and inferior nasal quadrants). In each quadrant, two response waves were grouped and averaged; peak latency and amplitude were used for assessment. In a child with epilepsy in whom kinetic or static perimetry was impossible, multifocal VEPs were recorded and compared with the peak latency and amplitude in the healthy subjects. RESULTS: In the 21 healthy children, no significant differences were observed in the peak latency or amplitude among four quadrants by one-way analysis of variance. Multifocal VEPs in the child with epilepsy showed abnormal waves in the right hemivisual field, which corresponded to the lesion observed with magnetic resonance imaging. CONCLUSIONS: The objective evaluation of visual field defects by using multifocal VEP may be useful in children with epilepsy in whom kinetic/static perimetry as a subjective examination is difficult.

Adolescent↗
PubMed2005

Long-term follow-up of a patient with Kawasaki disease and coronary aneurysm associated with asymptomatic thrombosis: a case report.

A 20-year-old male was first diagnosed with Kawasaki disease at age 2 years 9 months. Coronary angiography in the acute phase revealed coronary aneurysms, so chronic antiplatelet therapy was initiated with aspirin and ticlopidine. The patient was asymptomatic and was followed up. Stress myocardial imaging showed asymptomatic myocardial ischemia at age 20 years. Coronary angiography was performed, and revealed 99% occlusion of the right coronary artery and collateral circulation from the left coronary artery. Occlusion was attributed to coronary aneurysm thrombosis. Much remains unknown about the long-term prognosis in patients with coronary aneurysm associated with Kawasaki disease. Asymptomatic children who are followed up sometimes develop ischemic heart disease as young adults. This case highlights the need for long-term follow-up in patients with Kawasaki disease and coronary aneurysms.

Adult↗
PubMed2004

Hydronephrosis due to ureteral endometriosis treated by transperitoneal laparoscopic ureterolysis.

Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 43-year-old multiparous woman who suffered from periodic left loin pain in the terminal period of her menstruation. Excretory urogram demonstrated left hydronephrosis and hydroureter and obstruction of the lower left ureter just inferior to the left sacroiliac joint without urolithiasis. An enhanced computed tomography scan showed soft tissue density mass around the left ureter at the level of the stenosis. She underwent transperitoneal laparoscopic ureterolysis and adhesiotomy of the left ureter under the diagnosis of ureteral endometriosis. Because blueberry spots were clearly observed on the pelvic brim, the fibrous tissue surrounded the ureter was removed with peritoneal bleeding spots. Histological examination of the surrounding tissue confirmed the ectopic endometriosis. Even though retroperitoneoscopy is frequently used for ureteral lesion, transperitoneal laparoscopy has an advantage for resection of ectopic endometriosis surrounding the ureter.

Adult↗
PubMed2004

Congenital absence of the left circumflex coronary artery associated with acute myocardial infarction: a case report.

Among the congenital anomalies of the coronary arteries, a left circumflex artery (LCX) defect is extremely rare. A 49-year-old man who developed an acute anterior infarction underwent coronary angiography, which revealed complete occlusion of the left main trunk, but the territory usually supplied by the LCX had been perfused by the superdominant right coronary artery. Treatment of the left main trunk by percutaneous coronary intervention produced a favorable result. Accurate evaluation of the principal vessels and the extent of compensatory perfusion is important when diagnosing ischemic heart disease accompanied by anomalous coronary arteries and for choosing the best treatment modality.

Arteries↗
PubMed2004

Left ventricular rupture associated with Takotsubo cardiomyopathy.

A 70-year-old woman was admitted to the hospital with chest discomfort after quarreling with her neighbors. Electrocardiography revealed ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6. Coronary angiography demonstrated normal arteries, but left ventriculography showed apical akinesis and basal hyperkinesis. Takotsubo cardiomyopathy was diagnosed on the basis of these characteristic findings. The creatine kinase and creatine kinase-MB concentrations were elevated at admission and reached maximum levels 6 hours after admission. The plasma level of brain natriuretic peptide was 10.7 pg/mL (reference range, <18.4 pg/mL) on the first hospital day. ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6 persisted at 72 hours after admission. On the third hospital day, sudden rupture of the left ventricle occurred, and despite extensive resuscitation efforts, the patient died. Takotsubo cardiomyopathy presents in a manner similar to that of acute myocardial infarction, but ventricular systolic function usually returns to normal within a few weeks. To our knowledge, this is the first reported case of fatal left ventricular rupture associated with takotsubo cardiomyopathy. We suggest that takotsubo cardiomyopathy may be a newly recognized cause of sudden cardiac death.

Aged↗
PubMed2002

Relationship between infarction location and size to QT dispersion in patients with chronic myocardial infarction.

The relationship between the location and size of an infarction and QT dispersion was investigated in 84 Japanese patients with chronic myocardial infarction (54 with anteroseptal infarction and 30 with inferior infarction). The control group consisted of 23 subjects without ischemic heart disease (13 normal subjects and 10 hypertensive patients). Corrected QT dispersion (maximum corrected QT interval minus minimum corrected QT interval: QTc dispersion), was significantly larger in the anterior infarction group than in the control group (69.9+/-21.5 msec vs 53.0+/-17.6 msec), while the inferior infarction group showed no significant difference from control subjects. QTc dispersion was significantly greater in the patients with large anterior infarcts than in those with small anterior infarcts (80.5+/-20.5 msec vs 61.9+/-18.8 msec). In patients with chronic myocardial infarction, QT dispersion is influenced by the infarct location and size. Accordingly, interpretation of QT dispersion data should take these factors into consideration.

Electrocardiography↗
PubMedDate not supplied

Volume phase transition of bovine vitreous body in vitro and determination of its dynamics.

The phase equilibrium property and structural and dynamical properties of bovine vitreous body was studied by macroscopic observation of swelling behavior and dynamic light scattering under various conditions. It was found that the vitreous body collapses into a compact state isotropically or anisotropically depending on the external conditions. The vitreous body collapses while maintaining the shape when the pH (</= 4) and the concentration of calcium ions (</= 1 mol/L) are changed, whereas it collapses along the orbital axis in a mixed solvent of methanol and water. From observations of the dynamics of light scattered by the vitreous body, intensity autocorrelation functions that revealed two independent diffusion coefficients, D(fast) = 7.8 +/- 1.5 x 10 (- 8) cm(2)/s and D(slow) = 3.8 +/- 0.60 x 10 (-9) cm(2)/s, were obtained. The diffusion coefficients were found to be statistically independent of position within a focal depth range of 1-1.5 mm. Divergent behavior in the measured total scattered light intensities and diffusion coefficients was observed as the concentration of calcium ion approached the critical threshold, 1 mol/L. Namely, a slowing down of the dynamic modes accompanied by increased "static" scattered intensities was observed. The divergent behavior in the scattered light intensities and diffusion coefficients was reversible. This is indicative of the occurrence of a phase transition upon calcium ion concentration.

Animals↗
PubMedDate not supplied

Biocompatibility of polyvinylalcohol gel as a vitreous substitute.

Polyvinylalcohol (PVA) hydrogel cross-linked by gamma irradiation was assessed as a possible vitreous substitute. From a series of experiments, rise of intraocular pressure and inflammatory changes in the vitreous cavity after operation were observed in some cases. Crab-eating macaques were used for this experiment. PVA gels were injected into vitreous cavity after vitrectomy and followed clinically by opthalmoscopy, tonometry, fundus photography, electroretinogram (ERG), chemotaxis, and flare cell meter. Histopathologic examination by light and electron microscopy was performed after 3 months. As a result, there were no significant changes in ophthalmoscopic findings. No abnormal rising of intraocular pressure (IOP) was recognized. ERG did not show meaningful amplitude weakness. From the photon counting of flare cell meter, significant break of blood-aqueous barrier and blood-retinal barrier was not observed. Histopathologic examination revealed that all layers of the retina were intact and no loss of tissue was evident. However, in PVA gel-injected eyes, some vacuolations of the inner retina were found in some specimens. To conclude, PVA gel was well tolerated in these experiments. The gel with a network similar to the vitreous body showed the best biocompatibility, though it is necessary to investigate the biocompatibility for the long-term. PVA gel is a good candidate for a vitreous substitute.

Animals↗