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K Ishikawa

Publications and source records attributed to K Ishikawa.

At least 91 records · Page 5Linked to original sources
PubMed2001

Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice.

Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.

Animals↗
PubMed2001

Effect of added NaHCO3 on the basic properties of apatite cement.

Alternation of a composition of set apatite cement (AC) from carbonate-free apatite (CO3-free AP) to carbonate apatite (CO3-AP) may accelerate replacement of the set AC with bone because CO3-AP can be dissolved much faster than CO3-free AP in the weak acidic solution produced by osteoclasts. In this investigation, NaHCO3 was added to the AC component and the effects of added NaHCO3 on cement-setting behavior and on set mass were studied as an initial step for the fabrication of AC, which can be replaced with bone faster than current AC. When NaHCO3 was added to AC, the resultant set mass contained CO3. Although not all CO3 was incorporated in the set AC, the amount of CO3 incorporated into the set AC increased with the amount of added NaHCO3. Powder X-ray diffraction analysis and Fourier transform infrared spectrometer measurements revealed the formation of B-type CO3-AP. The setting time measured in an incubator at 37 degrees C and 100% relative humidity slowed from 30 to 45 min, indicating that NaHCO3 has an inhibitory effect on AP formation. The diametral tensile strength of the set AC decreased significantly with the addition of NaHCO3. Scanning electron microscopic observation revealed that fine crystals were formed in the set AC when NaHCO3 was added to AC. As a result, the crystallinity indices of the set AC measured using X-ray diffraction and Fourier transform infrared spectroscopy decreased with an increase in the amount of added NaHCO3. The dissolution rate of set AC in weak acid, pH 5.5, increased with the amount of added NaHCO3. We concluded that the formation of B-type CO3-AP and the resulting faster dissolution of set AC in weak acidic solution is preferable for the faster replacement of set AC with bone even though the decreased diametral tensile strength value is a shortcoming.

Apatites↗
PubMed2001

In vitro resorption of three apatite cements with osteoclasts.

To evaluate the replacement of apatite cement (AC) with bone, osteoclasts were incubated for 48 h on the surface of three AC types: conventional AC (c-AC), fast-setting AC (fs-AC), and anti-washout AC (aw-AC), using sintered apatite (AP) and cortical bone as control materials. We found osteoclasts attached to the surface of AC and osteoclastic resorption pits after 48 h of incubation for all experimental AC types. In contrast, no resorption pit was observed on the surface of sintered AP although osteoclasts were attached to the surface of sintered AP. There was no significant difference among the types of AC with respect to the resorption area, but the resorption areas were only approximately 1% of that on the surface of cortical bone. We concluded, therefore, that ACs could be replaced with bone regardless of the type but that it takes extensive time for the ACs to be completely replaced with bone.

Animals↗
PubMed2001

Myocardial damage and left ventricular dysfunction in patients with and without persistent negative T waves after Q-wave anterior myocardial infarction.

Persistent T-wave inversions during the chronic stage of Q-wave myocardial infarction (MI) indicate the presence of a transmural infarction with a fibrotic layer pathologically. The aim of the present study was to examine the relation between left ventricular (LV) damage and changes in polarity of the T waves from the acute to chronic phase in patients with Q-wave anterior wall MI. We studied 140 patients with persistent T-wave inversions in leads with Q waves (negative T-wave group) and 158 patients with positive T waves (positive T-wave group) at 12 months after anterior MI. In the positive T-wave group, the precordial T waves reverted from a negative to a positive morphology < 3 months after MI in 21 patients (3 M-positive T-wave subgroup), 3 to 6 months in 52 patients (6 M-positive T-wave subgroup), and 6 to 12 months in 75 patients (12 M-positive T-wave subgroup). Ten patients had persistent positive T waves without initial T-wave inversion (persistent positive T-wave group). Wall motion index and LV dimension were higher and the wall thickness for the infarct area and LV ejection fraction were lower in the negative T-wave than in the positive T-wave groups, except the persistent positive T-wave group in the chronic stage (p < 0.0001). Wall motion in the infarcted area improved over the course of 1 year in the 3 M-, 6 M-, and 12 M-positive T-wave subgroups (p < 0.0001), but not in the persistent positive T-wave group. Among the patients with T-wave inversions after admission, those who had persistent negative T waves after 12 months had worse LV function. In patients with initial T-wave inversion, earlier normalization of the precordial T waves was associated with greater improvement in LV function. Patients with persistent positive T waves without initial negative T waves had poorer recovery of LV function than patients with persistent negative T waves. We conclude that the presence of inverted T waves in leads with abnormal Q waves 12 months after MI and the time required for T-wave normalization can be used to assess the degree of LV dysfunction.

Aged↗
PubMed2001

A new coronary artery disease index of treadmill exercise electrocardiograms based on the step-up diagnostic method.

Treadmill exercise electrocardiography (ECG) is one of the most common noninvasive methods for detecting ischemic heart disease. However, this method has problems due to false-positive and false-negative results in a significant number of patients. The aim of this study was to determine whether the diagnostic accuracy of treadmill exercise ECG for detecting significant coronary stenosis can be improved by employing a step-up diagnostic method using multiple diagnostic indicators. We studied 273 consecutive patients (mean age, 56 +/- 9 years; 190 men and 83 women) without a history of myocardial infarction who underwent treadmill exercise ECG and coronary angiography for ischemic chest pain. Of these, 146 patients had no significant coronary stenosis, 61 had single-vessel disease, 56 had multivessel disease, and 10 patients had left main truncus disease. A multivariate logistic regression analysis was used to select 3 treadmill exercise electrocardiographic parameters that were independent predictors of the presence or absence of significant coronary stenosis: exercise-induced maximum ST-segment depression, QT dispersion immediately after exercise, and Athens QRS score. Significant coronary stenosis was diagnosed with a sensitivity of 84% and a specificity of 90% when a step-up diagnostic method using these 3 indicators was employed. These results were better than those obtained for each indicator alone (exercise-induced maximum ST-segment depression: sensitivity, 66%, and specificity, 73%; QT dispersion immediately after exercise [> or =60 ms positive]: sensitivity, 76%, and specificity, 86%; and Athens QRS score [< or =5 mm positive]: sensitivity, 72%, and specificity, 72%). We conclude that this step-up diagnostic method, using multiple diagnostic indicators, is a clinically useful predictor of the presence or absence of significant coronary stenosis.

Aged↗
PubMed2001

Prognosis following acute myocardial infarction in patients with ST-T abnormalities on electrocardiograms obtained before myocardial infarction.

BACKGROUND: Many studies have examined the relationship between prognosis after myocardial infarction (MI) and electrocardiographic (ECG) findings at the time of or after the onset of MI. However, little work has been done concerning the association between ECG findings obtained before the onset of MI (pre-MI) and the prognosis after MI. HYPOTHESIS: The study was undertaken to determine whether ST-T segment and T-wave morphology on pre-MI ECGs provides useful information for prognosis after acute MI. METHODS: Pre-MI ECGs of 212 patients recorded within the 6-month period before MI were studied for the presence of high-voltage R waves, ST-segment depression, and negative T waves. The Kaplan-Meier method and multivariate analysis were used to determine the relationship between these ECG findings and in-hospital cardiac death. RESULTS: In-hospital cardiac death occurred in 32 (15.1%) patients. The in-hospital mortality rate was 38.5% (5/13) for the patients with high-voltage R waves, 54.5% (6/11) for patients with ST-segment depression, and 45.6% (15/33) for patients with negative T waves. The in-hospital mortality rate was 13.6% (27/199) for patients without high-voltage R waves, 12.9% (26/201) for patients without ST-segment depression, and 9.5% (17/179) for those without negative T waves. Multivariate analysis identified age and negative T waves as independent risk factors for cardiac death, with a hazard ratio for negative T waves of 3.1. CONCLUSION: Negative T waves on pre-MI ECGs represent an independent predictor of in-hospital cardiac death in patients with MI.

Age Factors↗
PubMed2001

Myocardial bridging of the left anterior descending coronary artery in acute inferior wall myocardial infarction.

BACKGROUND: We observed marked myocardial bridging of the left anterior descending coronary artery (LAD) in the acute stages of inferior wall myocardial infarction (MI) in a group of patients who developed shock despite successful reperfusion of the infarct-related lesion (IRL). HYPOTHESIS: The purpose of this study was to elucidate the clinical significance of myocardial bridging in patients with inferior wall MI and shock. METHODS: The study group consisted of 53 patients with single-vessel disease of the right coronary artery, who underwent coronary angiography for acute inferior wall MI. Clinical characteristics, coronary angiographic findings, and left ventricular function during the chronic phase were compared between the patients who developed shock (the shock group) and those who did not (the non-shock group). In addition, a multiple logistic analysis was performed to identify independent predictors of shock in patients with acute inferior wall MI. RESULTS: Reperfusion of the IRL was obtained in all 53 patients. The incidence of myocardial bridging of the LAD, the incidence of right ventricular MI, the peak creatine phosphokinase (CPK-MB). the pulmonary capillary wedge pressure, and the prevalence of pulmonary congestion seen on chest roentgenogram were significantly higher in the shock group than in the non-shock group. Myocardial bridging (p = 0.0018), right ventricular MI (p = 0.0374), and peak CPK-MB (p = 0.0189) were identified as independent predictors of shock in acute inferior wall MI. CONCLUSION: This study suggests that myocardial bridging plays a role in left ventricular function in the acute stage of inferior wall MI.

Adult↗
PubMed2001

Continuous long-term dosing with oral slow-release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction.

BACKGROUND: In the short term, isosorbide dinitrate (ISDN) is considered to be therapeutically effective. The long-term effects of treatment with slow-release ISDN are less clear. HYPOTHESIS: The study was undertaken to investigate the effects of continuous, long-term dosing with oral slow-release ISDN on the incidence of cardiac events in patients with healed myocardial infarction (MI). The study was carried out in accordance with the intention-to-treat principle. METHODS: In all, 1.102 in- and outpatients, of either gender, with healed MI were randomly divided into groups treated with ISDN (n = 470) and not treated with ISDN (n = 632). Patients in the ISDN group received a continuous regimen of 20 mg of oral, long-acting ISDN three times a day, after meals. The mean observation period was 15.0 +/- 18.5 months. The primary endpoints were nonfatal and fatal recurrent MI, death from congestive heart failure, and sudden death. RESULTS: There were no significant differences in the baseline characteristics of the patients in the ISDN and no-treatment groups; nevertheless, significantly more patients in the ISDN group experienced cardiac events. In the ISDN group, 35 patients (7.4%) experienced cardiac events during the observation period, versus only 28 patients (4.4%) in the no-treatment group (p < 0.05; odds ratio 1.74; 95% confidence interval 1.04-2.90). CONCLUSION: Continuous long-term dosing with oral, slow-release ISDN does not reduce and probably increases the incidence of cardiac events among patients with healed MI.

Administration, Oral↗
PubMed2001

Cross-checking of nanoelectrospray ionization mass spectrometry and computer simulation for the evaluation of the interaction strength of non-covalently bound enkephalins in solution.

Nanoelectrospray ionization mass spectrometry (nanoESI-MS) and computer simulation were applied to the characterization of non-covalent interactions of [Leu5]-enkephalin (LE) and its optical isomers, [D-Tyr1, Leu5]-enkephalin (Y-LE), [D-Phe4, Leu5]-enkephalin (F-LE) and [D-Tyr1, D-Phe4, Leu5]-enkephalin (YF-LE). The dimer formation tendencies of the optical isomers of LE were evaluated by nanoESI-MS using quadruply deuterated LE (H2N-Tyr-(2,2-d2)Gly-(2,2-d2)Gly-Phe-Leu-COOH, d4-LE) as an internal standard. The relative interaction strengths of the optical isomers of LE were estimated to be Y-LE < F-LE < LE < YF-LE. Geometry optimization calculations were performed for interactions in vacuo and in water using a semi-empirical SCF method (PM3). The initial coordinate of the dimer structure of LE was taken from that obtained from single-crystalline x-ray diffraction analysis. Estimates of the interaction strengths of the dimer complexes were based on the heats of formation of a dimer complex (Hd) and the corresponding monomers (Hm) using the equation DeltaH = Hd - 2Hm. The values of DeltaH obtained from the calculations for interactions in water decreased in the order Y-LE > F-LE > LE > YF-LE. Since the smaller values of DeltaH correspond to stronger interactions between peptides, the results from computer simulations were qualitatively consistent with those obtained from the nanoESI experiments. The possibility of cross-checking these independent techniques was demonstrated using medium-sized molecules of biological importance. The agreement of the results from the two techniques suggested that nanoESI experiments, at least qualitatively, reflected the relative interaction strengths of non-covalently bound enkephalins in aqueous solution.

Computer Simulation↗
PubMed2001

Novel growth factor supporting survival of murine primordial germ cells: evidence from conditioned medium of ter fetal gonadal somatic cells.

The ter (teratoma, chromosome 18) mutation causes a deficiency of primordial germ cells (PGCs) in ter/ter embryos from the ter congenic mouse strain at 8.0 days post coitum (dpc). In order to analyse the function of the ter gene, here we examined effects of conditioned medium (CM) from 14.5 dpc testicular and ovarian somatic cells of +/+, +/ter, or ter/ter genotype on mouse PGCs "mixed-cultured" with own somatic cells on feeder cells. The results showed that +/+ and +/ter CM supported survival in 9.5 and 11.5 dpc ICR PGCs but ter/ter CM did not rescue TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)-positive apoptosis in the PGCs though it did not affect 5-bromo-2-deoxyuridine incorporation in PGCs. This supportive substance in +/+ CM, not ter/ter CM, was characterized as soluble, heat labile, and larger than 30 kDa. We also found that several known growth factors for PGCs and their receptors were expressed in ter/ter testes as well as +/+ testes, suggesting the ter function is independent. Thus, it was concluded that fetal gonadal somatic cells express a novel PGC growth factor (designated as TER Factor) supporting survival of PGCs not somatic cells and that the PGC deficiency in ter/ter testes is caused by a loss of this factor.

Animals↗
PubMed2001

Determination of reduced, protein-unbound, and total concentrations of N-acetyl-L-cysteine and L-cysteine in rat plasma by postcolumn ligand substitution high-performance liquid chromatography.

A high-performance liquid chromatographic assay was developed for the quantitative determination of the sulfur-containing amino acids N-acetyl-L-cysteine (NAC) and L-cysteine (Cys) in rat plasma. The thiols were separated by reverse-phase ion-pair chromatography, and the column eluent was continuously mixed with an iodoplatinate-containing solution. The substitution of sulfur of the thiol compound with iodide was quantitatively determined by measuring changes in the absorption at 500 nm. The low-molecular-weight disulfides and mixed disulfide conjugates of thiols with proteins were entirely reduced to the original reduced compounds by dithiothreitol. By reducing these two types of disulfides separately during sample pretreatment, the reduced, protein-unbound, and total thiol concentrations could also be determined. Validation testing was performed, and no problems were encountered. The limit of detection was approximately 20 pmol of thiol on the column. The present method was used to measure the plasma concentrations of NAC and Cys in the rat after a bolus intravenous administration of NAC, focusing on disulfide formation. The binding of NAC to protein through mixed disulfide formation proceeds in a time-dependent and reversible manner. Moreover, this "stable" covalent binding might limit total drug elimination, while the unbound NAC is rapidly eliminated. Consequently, the analytical method described in this study is very useful for the determination of plasma NAC and Cys, including disulfide conjugates derived from them.

Acetylcysteine↗
PubMed2001

Evaluation of liver regeneration using the L-[1-13C]methionine breath test.

BACKGROUND: We examined the relationship between changes in the liver weight/body weight percentage, amount of hepatic tissue total DNA, and the results of the [1-(13)C]methionine ((13)Cmet) breath test during hepatic regeneration in a rat model of 70% hepatectomy, to assess their usefulness for evaluating hepatic regeneration. MATERIALS AND METHODS: Male Wistar rats (230-290 g) were subjected to 70% hepatectomy under anesthesia with Nembutal. One, 2, 3, 7, and 14 days postoperatively, 40 mg/kg (13)Cmet was intravenously injected into the femoral vein, and the increase in exhaled (13)CO(2) (Delta(13)CO(2)) was measured for 15 min. Simple laparotomy was performed in control rats. Following the breath test, the regenerated liver was removed and weighed. The amount of DNA was determined. RESULTS: The correlation coefficients (r) between liver weight/body weight (LW/BW) and results of the (13)Cmet breath test, and between DNA and results of the (13)Cmet breath test were 0.892 and 0.800, respectively. CONCLUSIONS: The (13)Cmet breath test is considered to be very useful for assessing liver regeneration, and total (13)CO(2) output over 15 min in the (13)Cmet breath test graph seems to be an effective indicator for evaluating liver regeneration.

Animals↗
PubMed2001

[1-(13)C] breath test of galactose and fructose for quantitative liver function.

BACKGROUND: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of [1-(13)C]fructose or [1-(13)C]galactose. MATERIALS AND METHODS: Under nembutal anesthesia, 100 mg/kg of [1-(13)C]fructose or [1-(13)C]galactose was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 120 min. Then, 30, 70, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. A breath test was conducted 20 min after laparotomy. We examined the correlation of a single point (13)CO(2) level (SP) every 5 min until 30 min, and at 45 and 60 min with liver wt/body wt (LW/BW) (%). RESULTS: In the control group and all groups undergoing hepatectomy, the [1-(13)C]fructose breath test graph reached a plateau level at about 25 min. In the control group, the [1-(13)C]galactose breath test graph reached a plateau level, but in all groups undergoing hepatectomy a plateau level was not reached during measurement. The correlation coefficient between SP(5) after [1-(13)C]fructose administration and LW/BW was the highest, 0.656 (P = 0.0017). The correlation coefficient between SP(25) after [1-(13)C]galactose administration and LW/BW was the highest, 0.923 (P < 0.0001). CONCLUSION: In the breath test with intravenously administered [1-(13)C]fructose, hepatopathy could not be quantitatively evaluated accurately. However, hepatopathy could be quantitatively evaluated accurately by measuring SP(25) in the breath test with intravenously administered [1-(13)C]galactose over a short period.

Animals↗
PubMed2001

Intraoperative radiation therapy for curatively resected rectal cancer.

PURPOSE: Intraoperative radiotherapy has been used for local control of locally advanced rectal cancer. The aim of this study was to investigate the efficacy of intraoperative radiotherapy for curatively resected rectal cancer. METHODS: Between 1982 and 1998, intraoperative radiotherapy was administered in combination with curative resection in 78 patients with adenocarcinoma of the middle or lower third of the rectum (intraoperative radiotherapy group). Sixty-two of the patients had received preoperative radiotherapy with 20 Gy. Intraoperative radiotherapy was performed by a new strategy in which an electron beam was administered as uniformly as possible to the entire dissected surface of the pelvis. Retrospective comparisons were made with 248 patients treated by surgery alone during the same period (non-intraoperative radiotherapy group). RESULTS: The differences in tumor stage or surgical procedures between the two groups were not statistically significant. Survival, disease-free survival, and local recurrence-free survival in the intraoperative radiotherapy group were significantly more favorable than in the non-intraoperative radiotherapy group (P = 0.01, P = 0.04, and P = 0.02). Differences in survival were observed in Stage II patients but not in Stage I or Stage III patients. The local failure rate was 2.6 percent in the intraoperative radiotherapy group and 11.3 percent in the non-intraoperative radiotherapy group, and the difference was significant (P = 0.02). The distant metastasis rate was 18.0 percent in the intraoperative radiotherapy group and 19.5 percent in the non-intraoperative radiotherapy group, and the difference was not significant. There was a significantly higher rate of wound infection in the intraoperative radiotherapy group, but no infections were serious. CONCLUSIONS: In patients with adenocarcinoma of the middle or lower third of the rectum, intraoperative radiotherapy to the entire dissected surface of the pelvis reduced local recurrence in Stage II and Stage III patients and improved survival in Stage II patients.

Adenocarcinoma↗
PubMed2001

Change in signal intensity on MRI of fat in the head of markedly emaciated patients.

The amount of fat in various parts of the body decreases in emaciated patients, but responds differently to disease processes. The order of disappearance of fat in various parts of the head has rarely been studied with MRI. We imaged ten patients with anorexia nervosa and one cachectic patient with a psychiatric disorder with a 1.5 T imager. Signal intensities of bone marrow of the skull, subcutaneous tissue, and orbits were assessed on T1- and T2-weighted images, and correlated with the body mass index (BMI) and haemoglobin concentration (Hb). On T1-weighted images, five patients (BMI 15.6-17.8 kg/m2, mean 16.6 kg/m2; Hb 10.1-14.2 g/dl, mean 13.8 g/dl) showed the normal pattern of fat. One (BMI 13.6 kg/m2, Hb 10.4 g/dl) lost the high signal of bone marrow, but high signal of subcutaneous tissue and the orbits was preserved. High signal from bone marrow and subcutaneous tissue disappeared in three patients (BMI 11.5-13.5 kg/m2, mean 12.5 kg/m2; Hb 7.9-9.7 g/dl, mean 8.7 g/dl), but orbital high signal was preserved. The remaining two patients (BMI 9.3 and 13.5 kg/m2, mean 11.5 kg/m2; Hb 7.6 and 8.9 g/dl, mean 8.3 g/dl) showed complete loss of high signal from fat in the head. The order of disappearance of fat (bone marrow, subcutaneous fat, then orbits) correlated with both BMI and Hb. Atrophy of bone marrow was demonstrated on T2-weighted images in five patients with BMI 13.5 kg/m2 or less, and Hb 9.7 g/dl or less.

Adipose Tissue↗
PubMed2001

MRI in essential primary cutis verticis gyrata.

We report MRI findings in four patients with essential primary cutis verticis gyrata (CVG). The patients were all men, aged 49-81 years (mean 65 years). They had no symptoms related to this rare scalp condition, preceding scalp disease or associated systemic disease. Coronal images showed a characteristic corrugated appearance of the thickened scalp at the vertex, diagnostic of CVG. Neuroradiologists should be aware of this condition.

Aged↗