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M Koda

Publications and source records attributed to M Koda.

At least 37 records · Page 2Linked to original sources

Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process.

Dynamic process of apoptosis has not been elucidated in adult rat cardiomyocytes. Soluble Fas ligand (0.1 microg/ml) in the presence of actinomycin D (0.05 microg/ml) induced apoptosis in cultured adult rat cardiomyocytes, as documented by activated caspase-3, DNA fragmentation, and apoptotic ultrastructure. In the present model, we observed 60 adult cardiomyocytes with a normal rod shape under a real-time videomicroscope continuously for 48 hours. Seventeen cells (28%) were unchanged and 7 cells (12%) showed oncosis (so-called necrosis) in which no beating was evident. In the remaining 36 cells (apoptosis, 60%), a slow beating (17 +/- 3/min) was initiated 16 +/- 1 hours later. Approximately 1 hour later, the rod cells showed long-axial shortening as bone- or club-like, or square-shaped, accompanied with faster beating rates (35 +/- 7/min). In 29 cells (type A1 and A2), marked shrinkage occurred; the cellular shape became almost completely round with a smooth surface and the beating ceased 3.0 +/- 0.4 hours later. Then, smooth budding appeared 0.6 +/- 0.2 hours later. Apoptotic bodies were found in 8 cells 10 +/- 4 hours later (type A1, 13%) but not in 21 cells (type A2, 35%). In the other 7 cells (type A3, 12%), the cell surface became rough 8 +/- 3 hours later and the beating ceased. Maximal beating rate was greatest in type A1 (72 +/- 26/min) and greater in type A2 (29 +/- 5/min) than in type A3 (10 +/- 2/min). Electron microscopy confirmed apoptotic ultrastructure even in the cardiomyocytes with bone-, club-like, or square shapes, suggesting that type A3 as well as A1 and A2 is also under apoptotic process. A caspase inhibitor, zVAD.fmk, blocked beating, apoptotic morphology, and DNA fragmentation, indicating these depended on caspase activation. In the caspase-dependent apoptotic process of cultured adult cardiomyocytes, beating and the following deformity of the cellular edges were the initial signs and the rate of beating was related with the subsequent three different processes of apoptosis.

Animals↗

Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C: a pilot study.

The aim of the present study is to evaluate whether interferon alpha (IFNalpha) therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C. Forty patients were enrolled in this study. They had solitary, small HCC</=3 cm in diameter, underlying chronic hepatitis C, and were </=70 years old. Of the patients, 18 were treated with IFNalpha for 6 months after the treatment of HCC, and 22 patients who did not receive IFNalpha therapy were used as controls. Six (33%) patients in the IFN group showed sustained response. The incidence of local recurrence was not different in the IFN and non-IFN groups (6 vs. 9%). The cumulative incidences of distant recurrence in the non-IFN and IFN groups were 9 and 6% at 1 year, 27 and 11% at 2 years, 63 and 18% at 3 years, 76 and 28% at 4 years, and 82 and 28% at 5 years; they were significantly different (P<0.01). Six (27%) patients in the non-IFN group died from the progression of HCC, but all IFN-treated patients were alive (P<0.05). The pilot study demonstrates that IFNalpha therapy after the curative treatment of small HCC can inhibit intrahepatic recurrence in the remnant liver and improve the prognosis of hepatitis C virus-related HCC.

Journal Article↗

Comparison of clinical laboratory liver tests between asymptomatic HBV and HCV carriers with persistently normal aminotransferase serum levels.

We examined the clinicopathological state in asymptomatic hepatitis C virus (HCV) carriers with persistently normal aminotransferase serum levels in comparison with asymptomatic hepatitis B virus (HBV) carriers. The findings showed that the thymol turbidity test (TTT) values and zinc sulfate turbidity test (ZTT) values were significantly higher in asymptomatic HCV carriers than in asymptomatic HBV carriers, whose values were within the normal limits. Multivariate analysis showed that the independent predictor of serum TTT and ZTT levels was the HCV infection. In clinical state, simple and cheap tests such as TTT and ZTT are useful for mass screening to detect HCV carriers in medical check-ups of healthy workers.

Journal Article↗

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases.

BACKGROUND AND AIM: Cerebral hemodynamic derangement is well known in patients with liver cirrhosis. The advent of transcranial Doppler enables a non-invasive observation of cerebral hemodynamics. To evaluate the clinical usefulness we examined cross-sectionally and longitudinally cerebral hemodynamic parameters in patients with cirrhosis. METHODS: The subjects of the cross-sectional study were 117 patients with cirrhosis, 15 patients with chronic hepatitis and 25 healthy controls. The longitudinal study included 26 cirrhotic patients without encephalopathy, and 27 cirrhotic patients with encephalopathy. The pulsatility and resistive indices of the right middle cerebral artery were used as parameters of cerebral hemodynamics. RESULTS: Cerebral pulsatility and resistive indices were significantly higher in patients with cirrhosis (1.05 +/- 0.23, P < 0.0001 and 0.63 +/- 0.07, P < 0.0001, respectively) than in the controls (0.75 +/- 0.11 and 0.55 +/- 0.05, respectively) and patients with chronic hepatitis (0.81 +/- 0.11 and 0.52 +/- 0.05, respectively). Cerebral pulsatility and resistive indices were significantly related with the severity of liver cirrhosis. Patients with encephalopathy had higher cerebral pulsatility and resistive indices than patients without encephalopathy. In the longitudinal studies, cerebral pulsatility and resistive indices were changed in parallel with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices were significantly correlated with the blood ammonia level and serum levels of bilirubin and albumin. CONCLUSION: These cross-sectional and longitudinal studies showed that cerebral vascular resistance indices measured by using transcranial Doppler were increased in association with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices are real-time and useful parameters to assess and monitor cirrhotic patients.

Aged↗

Diagnostic value of serum type IV collagen test in comparison with platelet count for predicting the fibrotic stage in patients with chronic hepatitis C.

BACKGROUND AND AIM: The serum type IV collagen test is now used as a diagnostic aid for the detection of liver fibrosis and cirrhosis. Recently, a platelet count has been reported to be a useful marker for assessing the fibrotic stage in chronic hepatitis C. The aim of this study was to compare the usefulness of the serum type IV collagen test and platelet count for diagnosing the fibrotic stage in chronic hepatitis C patients. METHODS: The diagnostic values were assessed by the use of receiver operating characteristic (ROC) analysis in 165 patients with chronic hepatitis C, with the exception of those patients with cirrhosis. RESULTS: The serum type IV collagen level increased, and the platelet count decreased significantly with the progression of fibrosis staging. As judged from ROC curves, the serum type IV collagen test was more useful than the platelet count for differentiating moderate or severe fibrosis from no or mild fibrosis. At a cut-off value of 110 ng/mL, the serum type IV collagen test had an overall diagnostic accuracy of 75%, while at a cut-off value of 16 x 10(4)/mm(3), the platelet count had a diagnostic accuracy of 70%. The serum type IV collagen test and platelet count were similar in differentiating severe fibrosis from no, mild or moderate fibrosis. Both serum type IV collagen (at a cut-off value of 130 ng/mL) and platelet count (at a cut-off value of 14 x 10(4)/mm(3)) had a diagnostic accuracy of 73%. CONCLUSION: The serum type IV collagen test was slightly superior to the platelet count for assessing the fibrotic stage in patients with chronic hepatitis C.

Adult↗

Changes in esophageal variceal pressure after transcatheter arterial embolization for hepatocellular carcinoma.

BACKGROUND AND STUDY AIM: The aim of this study was to investigate the influence of transcatheter arterial embolization on esophageal variceal pressure and portal hemodynamics. PATIENTS AND METHODS: Out of 18 cirrhotic patients with hepatocellular carcinoma, 12 underwent transcatheter arterial embolization and the remaining six patients underwent angiography alone as a control. We examined esophageal variceal pressure with an endoscopic pneumatic pressure sensor and portal blood flow with Doppler ultrasonography immediately before and 3 days after transcatheter arterial embolization or angiography. RESULTS: Angiography alone did not influence esophageal variceal pressure or portal blood flow. Transcatheter arterial embolization resulted in an increase in variceal pressure in five (42%) of the 12 patients and in a marked increase in portal blood flow in eight (88.9%) of nine patients, although no change in the endoscopic variceal findings was observed after transcatheter arterial embolization. The change in esophageal variceal pressure did not correlate with the change in portal blood flow. We could not find predictive factors for the elevation of variceal pressure after transcatheter arterial embolization. CONCLUSION: Our study demonstrated that transcatheter arterial embolization resulted in an increase in esophageal variceal pressure in about half of the patients, bearing little relation to portal hemodynamic parameters.

Aged↗

Red blood cell status in alcoholic and non-alcoholic liver disease.

Macrocytosis is most commonly associated with vitamin B(12) and folic acid deficiency, followed by alcoholism, liver disease, and other pathologic conditions. We studied the red cell and vitamin status in 423 consecutive patients with various liver diseases, including 31 with acute viral hepatitis (AVH), 105 with chronic hepatitis (CH), and 134 with alcoholic liver disease (ALD), who consisted of 84 with non-cirrhotic alcoholic liver disease (NCALD) and 50 with alcoholic liver cirrhosis (ALC), 60 with non-alcoholic liver cirrhosis (NALC), and 93 with hepatocellular carcinoma (HCC). The mean corpuscular volume (MCV) and red cell distribution width (RDW) were significantly higher in patients with ALD and NALC, and among them macrocytosis occurred more frequently in patients with ALC. Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development of macrocytic anemia. In ALD, the MCV was significantly correlated with the estimated alcohol consumption and inversely correlated with the serum folic acid level, which, however, was often maintained within the normal range in patients with macrocytic ALC. After abstinence from alcohol, the MCV and RDW were reduced significantly and were associated with an increasing serum folic acid level. This suggests that macrocytic anemia was a common feature of alcoholic and non-alcoholic liver cirrhosis and that alcohol abuse and folic acid deficiency play a secondary role in macrocytosis.

Adult↗

Proton magnetic resonance spectroscopy for assessment of human body composition.

BACKGROUND: The usefulness of magnetic resonance spectroscopy (MRS)-based techniques for assessment of human body composition has not been established. OBJECTIVE: We compared a proton MRS-based technique with the total body water (TBW) method to determine the usefulness of the former technique for assessment of human body composition. DESIGN: Proton magnetic resonance spectra of the chest to abdomen, abdomen to pelvis, and pelvis to thigh regions were obtained from 16 volunteers by using single, free induction decay measurement with a clinical magnetic resonance system operating at 1.5 T. The MRS-derived metabolite ratio was determined as the ratio of fat methyl and methylene proton resonance to water proton resonance. The peak areas for the chest to abdomen and the pelvis to thigh regions were normalized to an external reference (approximately 2200 g benzene) and a weighted average of the MRS-derived metabolite ratios for the 2 positions was calculated. TBW for each subject was determined by the deuterium oxide dilution technique. RESULTS: The MRS-derived metabolite ratios were significantly correlated with the ratio of body fat to lean body mass estimated by TBW. The MRS-derived metabolite ratio for the abdomen to pelvis region correlated best with the ratio of body fat to lean body mass on simple regression analyses (r = 0.918). The MRS-derived metabolite ratio for the abdomen to pelvis region and that for the pelvis to thigh region were selected for a multivariate regression model (R = 0.947, adjusted R(2) = 0.881). CONCLUSION: This MRS-based technique is sufficiently accurate for assessment of human body composition.

Adipose Tissue↗

Apoptosis, rather than oncosis, is the predominant mode of spontaneous death of isolated adult rat cardiac myocytes in culture.

A number of isolated adult cardiomyocytes dies within a few days of culture and the mode of death has recently been suggested to be apoptosis, based on its association with the appearance of DNA fragmentation. However, morphological evidence is still lacking and precise analysis, including quantification, has not been performed. Adult rat ventricular cardiomyocytes isolated by enzymatic dissociation were incubated for 7 days in a serum-free medium (the rapid attachment model) and after various incubation periods, both attached and floating cells were counted and classified based on combined criteria of morphology and membrane permeability (dye exclusion): type 1, rod cells with intact membranes; type 2, non-rod cells with intact membranes; and type 3, non-rod cells with ruptured membranes. The number of both rod-shaped and dye-excluding cells decreased with the incubation period. After 7 days culture, the number of residual cells decreased to 12% of the initial value. Electron microscopy identified type 1 cells as viable, type 2 cells as viable or apoptotic, and type 3 as undergoing oncosis (primary necrosis) or secondary post-apoptotic necrosis. Ultrastructural morphometry revealed that oncotic cell death occurred predominantly during the early phase of culture whereas the more abundant apoptotic cell death occurred throughout the culture period. In conclusion, although both apoptotic and oncotic death occur in the natural course of adult rat cardiomyocytes in short-term culture, apoptosis is more predominant. Because of the high incidence of spontaneous cell death predominantly via apoptosis, this information is important for the interpretation of studies using this cell type in culture.

Animals↗

Proliferating activity in oral dysplastic leasions and squamous cell carcinomas.

The aim of the study was the quantitative analysis of AgNORs in oral squamous cell carcinomas as well as in dysplastic epithelial changes accompanied and not accompanied by oral squamous cell carcinomas. AgNOR proteins were visualized in histological slides using silver impregnation technique according to D. Ploton. In each sample 100 cell nuclei were assessed. The study used 54 cases of proliferating oral epithelial changes divided into 3 groups: group I consisting of 13 cases of dysplastic lesions not accompanied by oral squamous cell carcinomas; group II (a total of 18 cases) containing dysplastic lesions situated in the vicinity of oral carcinomas and group III (23 cases) with oral squamous cell carcinomas. Statistically significant differences were found between groups with mild dysplasia and groups with severe dysplasia as well as squamous cell carcinomas. Statistical analysis did not show any differences in the number of AgNORs between squamous cell carcinomas and epithelial lesions with severe dysplasia. Our results demonstrate that the analysis of AgNORs expression can serve only as an additional parameter to evaluate the potential of malignant transformation.

Cell Division↗

PCNA and P53 expression in relation to clinicopathological features of oral papilloma.

Although papilloma is the most frequent benign epithelial tumour of oral cavity, its biological potential for malignant transformation is still to be evaluated. The aim of the study was to correlate PCNA and P53 expression in 55 oral papillomas with some clinicopathological variables. The tissue samples were stained with H+E and by immunohistochemistry for PCNA and P53 protein. Staining patterns were assessed semiquantitatively and correlated with each other and grade of tumour epithelial dysplasia, tumour size, localization well patient age and sex. PCNA immunostaining was positive 43 (78%) oral papillomas. P53 immunohistochemical reaction was positive in 38 (69%) out of 55 epithelial tumours. Positive relationship between PCNA and P53 expression was observed as well as between PCNA immunostaining and grade of epithelial dysplasia. There was no statistically significant relationships between PCNA, P53 immunohistochemical positivity and papilloma size, site, patient age and sex. The results of this study suggest that immunohistochemical P53 overexpression is valuable marker of early neoplastic transformation and together with PCNA are presumed predictors for malignant transformation of oral papillomas.

Adult↗

Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma.

BACKGROUND: Percutaneous ethanol injection therapy has been used widely for small hepatocellular carcinoma. This study was undertaken to determine factors predictive of local recurrence or new nodular recurrence in patients with small hepatocellular carcinoma treated with percutaneous ethanol injection. METHODS: The authors studied 73 nodules treated with percutaneous ethanol injection in 49 patients with small hepatocellular carcinoma. The usefulness of predictive factors for recurrence was assessed with the Kaplan-Meier method. The clinicopathologic variables examined included age, gender, Child-Pugh classification, number of tumors (single vs. multiple), tumor size, degree of tumor differentiation, ultrasonographic findings such as peripheral hypoechoic band (so-called 'halo'), intratumoral echo pattern, tumor staining on enhanced computed tomography, combination therapy with transcatheter arterial embolization, and serum alpha-fetoprotein level. RESULTS: The local recurrence rates were 19%, 27%, 33%, 33%, and 33%, respectively, and the new nodular recurrence rates were 19%, 51%, 74%, 83%, and 83%, respectively, at 1, 2, 3, 4, and 5 years after percutaneous ethanol injection therapy. The frequency of local recurrence was associated with the histologic differentiation of more than moderately differentiated (P < 0.001), presence of a sonographic halo (P < 0. 005), an intratumoral heterogeneous echo pattern (P < 0.001), and positive tumor staining on enhanced computed tomography (P < 0.01). Multivariate analysis showed that the presence of a halo and an intratumoral heterogeneous echo pattern were the most important variables for predicting local recurrence. The frequency of new nodular recurrences was related to the presence of multiple tumors (P < 0.01) and a high serum alpha-fetoprotein level (P < 0.001). Multivariate analysis showed that a high serum alpha-fetoprotein level was a reliable predictor of new nodular recurrence. CONCLUSIONS: This study showed that the presence of a halo and an intratumoral echo pattern on ultrasonography were useful predictors for local recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma, and that a high serum alpha-fetoprotein level was associated with a higher frequency of new nodular recurrences.

Adult↗

Measurement of relative fat content by proton magnetic resonance spectroscopy using a clinical imager.

The aim of this study was to determine the applicability of a proton magnetic resonance (MR) spectroscopy-based technique using a clinical 1.5-T MR imager for assessment of relative fat content. Proton MR spectra were obtained from a trunk phantom and 23 volunteers using a single free induction decay measurement. The ratios of fat methyl and methylene proton resonance to the water proton resonance were compared with the ratio of oil weight to water weight for the phantom, and with the ratio of body fat to lean body mass estimated by bioelectrical impedance analysis for the human subjects. Good linear relationships were found between the MR metabolite ratio and the ratio of oil weight to water weight (r = 0.9989), and the ratio of body fat to lean body mass (r = 0.9169). This MR spectroscopy-based technique is sufficiently accurate and may be applicable to assessment of human body composition.

Adipose Tissue↗

Renovascular resistance assessed by color Doppler ultrasonography in patients with chronic liver diseases.

BACKGROUND AND AIMS: Renal arterial vasoconstriction is known to be related to renal hemodynamic derangement in patients with liver cirrhosis. Using color Doppler ultrasonography in patients with chronic liver diseases, abnormal resistance in the renal artery was examined non-invasively both cross-sectionally and longitudinally to clarify the relationship between renal vascular resistance and liver function to neurohumoral factors. METHODS: The study comprised 118 patients with cirrhosis, 23 patients with chronic hepatitis, and 35 healthy controls. Pulsatility and resistive indices that were derived from renal artery velocity analysis were used as parameters of renal arterial resistance. RESULTS: Both the pulsatility and resistive indices were significantly higher in cirrhotic patients (1.29 +/- 0.37, P < 0.001 and 0.69 +/- 0.07, P < 0.001, respectively) compared to controls (1.00 +/- 0.12 and 0.62 +/- 0.05, respectively) and compared to patients with chronic hepatitis (0.97 +/- 0.13 and 0.60 +/- 0.05, respectively). Both indices showed significant correlation with increased Child-Pugh grade. Each correlated significantly with plasma renin activity and plasma aldosterone and norepinephrine levels. Multivariate analysis of the relationship between neurohumoral factors and renal arterial resistance disclosed that plasma renin activity was a significant independent predictor. The longitudinal change in pulsatility index, resistive index and neurohumoral factors were examined in the cirrhotic patients who were followed-up for longer than 6 months. Pulsatility and resistive indices increased according to the deterioration of liver function and the changes in both indices were closely related to the change in plasma renin activity. CONCLUSIONS: Pulsatility index and resistive index as measured by color Doppler ultrasonography were closely related to the severity of cirrhosis and to the levels of neurohumoral factors, especially plasma renin activity, in this cross-sectional and longitudinal study. Therefore, they are useful indices for assessing renal hemodynamics in patients with cirrhosis.

Adult↗

Comparison between the air displacement method and dual energy x-ray absorptiometry for estimation of body fat.

Air displacement plethysmography (ADP) is a method for the determining percent body fat (%BF) using the two-compartment model, in which the body is partitioned into body-fat mass and fat-free mass (FFM). Although this model assumes a constant density of FFM as 1.10 g/ml, its density may depend upon the bone mineral content (BMC) and total body water (TBW) which vary with age, gender, and race/ethnicity. This study compared %BF determined from ADP (ADP%BF) with %BF obtained by dual-energy x-ray absorptiometry (DXA%BF), and also investigated the effects of BMC, TBW, and other factors on its value. The subjects were 721 female and male Japanese aged 40 to 79 years. Body density was measured by ADP and %BF was calculated using Brozek et al's equation. BMC and body-fat volume were measured using DXA, and TBW was measured by multifrequency bioelectrical impedance. A series of anthropometric measurements was taken. Although ADP%BF was highly correlated with DXA%BF (female: r = 0.89, male: r = 0.90) (p < 0.001), ADP%BF differed significantly from DXA%BF (female: -1.30 +/- 0.14% (mean +/- s.e.m.), male: 1.22 +/- 0.13%) (p < 0.001). The difference in %BF (ADP%BF-DXA%BF) was negatively associated with BMC/FFM but not with TBW/FFM in both genders. The difference in %BF was also positively correlated with waist circumference. Considering previous studies, this result may be explained by the underestimation of DXA%BF, rather than by the overestimation of ADP%BF. In conclusion, ADP may be a useful method to measure %BF. However, BMC should be taken into consideration. Furthermore, DXA%BF may be underestimated in people with large waists.

Absorptiometry, Photon↗

Antiplatelet action of losartan involves TXA2 receptor antagonism but not TXA2 synthase inhibition.

Various AT1 receptor antagonists including losartan are known to inhibit human platelet activation by antagonising TXA2/PGH2 receptors (TP receptors). Presently, we check a hypothesis that losartan, an imidazole derivative in contrast with valsartan, a non-imidazole compound, may inhibit human platelet activation also through inhibition of TXA2 synthesis. Inhibitory action of losartan (2-n butyl-4-chloro-5-hydroxymethyl-1-beta(2'-(1H-tetrazol-5yl)biphenyl-4-yl)methyl] imidazole), its active metabolite EXP 3174 (2-n-butyl-4-chloro-1-beta (2-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]imidazole-5-carboxylic acid) and valsartan ((S)-N-valeryl-N-(beta2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]valine), on collagen-induced platelet aggregation and TXA2 generation was compared to effects achieved by each compound on U46619-induced aggregation in aspirinized platelets. Losartan and aspirin inhibited collagen-induced platelet aggregation with approximately the same potency, whereas EXP 3174 and valsartan showed much weaker antiplatelet effects. Interestingly, losartan, EXP 3174 and valsartan displayed similar potencies as inhibitors of U46619-induced aggregation in asprinized platelets as in collagen-induced aggregation in non-aspirinized platelets. None of the above three AT1 antagonists, up to a concentration of 300 microM, did influence collagen-induced TXA2 synthesis in human platelets. In conclusion, antiplatelet effects of AT1 antagonists, irrespective of the presence or absence of non-condensed imidazole in their chemical structure, involve antagonism of TP receptors but not inhibition of TXA2 synthesis in platelets.

Antihypertensive Agents↗