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T Ohtake

Publications and source records attributed to T Ohtake.

At least 55 records · Page 3Linked to original sources

Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular carcinoma and hepatoma cell lines.

We investigated the expression and genomic alteration of nm23-H1 (which encodes a nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs) and four hepatoma cell lines. The expression of nm23-H1 protein was significantly reduced in HCCs with intrahepatic metastasis (72%) compared with expression in HCCs without intrahepatic metastasis (38%). However, in two of three HCCs examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated carcinoma) revealed marked reduction of nm23-H1 protein compared with two other hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12 HCCs examined. No point mutation in the coding region of the nm23-H1 gene was observed in any of the 12 HCCs or the four hepatoma cell lines. These findings suggest that: (i) the expression of nm23-H1 protein is inversely associated with high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may occasionally occur at both the transcriptional and post-transcriptional levels in HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.

Adult↗

Impaired myocardial vasodilation during hyperemic stress with dipyridamole in hypertriglyceridemia.

OBJECTIVES: This study sought to investigate the specific role of hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest flow ratio (MDR). BACKGROUND: Reduced MDR has been reported in hypercholesterolemic patients without evidence of ischemia. However, the specific role of hypertriglyceridemia in MDR has not been studied. METHODS: Fifteen nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched control subjects were studied. Myocardial blood flow (MBF) during dipyridamole administration and baseline MBF in hypertriglyceridemic patients and control subjects were measured using positron emission tomography and nitrogen-13 ammonia, after which the MDR was calculated. RESULTS: Baseline MBF (ml/min per 100 g heart weight) in hypertriglyceridemic patients (mean +/- SD 73.6 +/- 24.1) did not differ significantly from that in control subjects (81.6 +/- 37.2). MBF during dipyridamole loading in hypertriglyceridemic patients (198 +/- 106) was significantly reduced compared with that in control subjects (313 +/- 176, p < 0.05), as was the MDR (2.71 +/- 1.07 vs. 3.73 +/- 1.14, respectively, p < 0.05). Spearman rank-order correlation analysis showed a significant relation between plasma triglyceride concentration and MDR (r = -0.466, asymptotic SE 0.157, p = 0.0125); however, no such significant relation was seen between total plasma cholesterol concentration and MDR (r = -0.369, asymptotic SE 0.130, p = 0.059). CONCLUSIONS: Impaired myocardial vasodilation was suggested in hypertriglyceridemic patients without symptoms and signs of ischemia.

Adult↗

Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases.

4-Hydroxy-2-nonenal (HNE) is one of the major components of lipid peroxidation product and has been shown to react with proteins to form HNE-protein adducts. HNE-protein adducts are relatively stable and can be used as a marker of radical-mediated cellular damage. We report herein the immunohistochemical analysis of HNE-protein adducts in human alcoholic liver diseases using a specific monoclonal antibody HNEJ-2. Cytoplasm of hepatocytes and bile duct epithelia was positively stained for HNE-protein adducts, and the nucleus was negligibly stained. The immunohistochemical intensity of hepatocytes was classified into three groups: strong, moderate, and faint staining. Strong staining was found in 43% of alcoholic liver diseases and in 4% of viral liver diseases. Hepatocytes of alcoholic liver diseases contained a higher amount of HNE-protein adducts than those of viral liver diseases, and the difference was statistically significant (p = 0.005; chi2 test). Semiquantitative analysis of the histological intensities of HNE-protein adducts and iron indicated a significant positive correlation (p = 0.084; Spearman's rank correlation). The localization of HNE-protein adducts and iron in hepatocytes appeared to be identical. These data suggested the correlation between HNE-protein adducts and iron. Our results indicate that HNE-protein adducts, a marker of oxidative stress-induced damage, are increased in human alcoholic liver damage, and that hepatic siderosis may act on the production of free radicals.

Aldehydes↗

Altered intrahepatic pathway of para-umbilical vein in portal hypertension.

The object of this study was to determine the frequency and characteristics of altered paraumbilical vein in the hepatic parenchyma, developed from portal hypertension, using computed tomography (CT). Two hundred and ninety-two patients who presented with portal hypertension from 1986 to 1996 were studied retrospectively. The pathway of the dilated para-umbilical vein was demonstrated by contrast-enhanced CT. Thirty-one (11%) patients had a dilated para-umbilical vein arising from the left portal vein into the falciform ligament. In 24 (77%) of these patients, the para-umbilical vein followed the expected route, passing through the fissure of ligamentum teres hepatis. The remaining seven patients (23%) displayed the unusual pathway, with the vein arising from the left branch of the portal vein and passing into the hepatic parenchyma. In these seven patients, four had one collateral vein, and three patients had two collateral veins in the liver parenchyma. The dilated para-umbilical vein frequently passes through the hepatic parenchyma in patients with portal hypertension.

Adult↗

A patient with thrombotic microangiopathy accompanied by glomerular subendothelial electron dense deposits.

A 50-year-old woman presented with thrombocytopenia, microangiopathic hemolytic anemia, and nephrotic syndrome. Although a high level of circulating immune complexes, mild hypocomplementemia, and the antinuclear antibody also were present, the criteria for collagen disease were not fulfilled. Renal biopsy demonstrated a typical thrombotic microangiopathy (TMA) involving glomeruli. There also were electron-dense deposits located just beneath the original glomerular basement membrane in the dilated subendothelial space, thought to be immune complexes following positive IgG, C1q and C3 staining on an immunofluorescent study. Corticosteroid therapy rapidly ameliorated her hematologic abnormalities and proteinuria and normalized the immunologic data. These findings strongly suggest that the TMA in this patient was induced by immune complex-associated mechanisms.

Biopsy↗

Altered myocardial vasodilatation in patients with hypertriglyceridemia in anatomically normal coronary arteries.

Reduced myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported. However, the status of MVD in hypertriglyceridemics has not yet been clarified. The aim of this study was to investigate whether MVD is impaired in patients with hypertriglyceridemia without overt coronary stenosis. Twenty-three hypertriglyceridemics (10 normocholesterolemic hypertriglyceridemics [HTGs] and 13 mixed combined hyperlipidemics [MCHLs]) and 13 age-matched controls were studied. All patients were proven to have more than one normal coronary artery, as diagnosed by coronary angiography, and those segments that were perfused by anatomically normal coronary arteries were used in the study. Myocardial blood flow (MBF) during dipyridamole (DP) loading and baseline MBF were measured by using positron emission tomography and [13N]ammonia, after which MVD was calculated. Baseline MBF (mL.min(-1).100 g(-1)) was comparable among HTG (76.0+/-26.1), MCHL (77.0+/-26.1), and controls (80.3+/-38.5). However, MBF during DP loading was significantly lower in MCHL (159+/-52.5) than in control subjects (292+/-166, P<.01), while it was comparable in HTG (202+/-104) and controls. MVD was significantly reduced in both HTG (2.70+/-1.09, P<.05) and MCHL (2.07+/-.70, P<.01) compared with controls (3.73+/-1.14). MVD in MCHLs tended to be reduced compared with that in HTGs, but the difference was statistically insignificant (P=.08). There was a significant relationship between MVD and both plasma triglycerides (r=-.47, P<.01) and plasma total cholesterol (r=-.55, P<.01). When controls and HTGs were combined, the relationship between MVD and plasma total triglycerides became more prominent (r=-.55, P<.05), and the significant relationship between cholesterol level and MVD disappeared. Multivariate regression analysis has revealed that the triglyceride level (F=5.2, P<.05) was independently related to MVD (r=.69, P<.01). In conclusion, MVD was reduced in hypertriglyceridemics in anatomically normal coronary arteries. Hypertriglyceridemia is an independent factor for this abnormality.

Aged↗

Hyperglycemia rather than insulin resistance is related to reduced coronary flow reserve in NIDDM.

To clarify if coronary flow reserve (CFR) is related to insulin resistance or hyperglycemia in normotensive NIDDM, myocardial blood flow (MBF) at baseline and during dipyridamole loading were measured with 13N-ammonia positron-emission tomography. CFR was significantly reduced in NIDDM patients compared with age-matched control subjects. CFR in patients with well-controlled NIDDM was significantly higher than in those with poorly controlled NIDDM, whereas insulin resistance was comparable between the two groups. CFR in NIDDM patients was not related to the degree of insulin resistance. CFR correlated significantly with average fasting glucose concentration and average HbA1c, but not with insulin resistance, age, lipid parameters, or blood pressure. In conclusion, control of blood glucose concentration rather than insulin resistance is most likely related to the reduced CFR in NIDDM.

Adult↗

[Analysis of cerebral blood flow SPECT imaging on standard brain atlas in patients with dementia of Alzheimer type].

Statistical parametric map (SPM) has been developed by Friston et al. to analyze focal changes in rCBF induced by brain activation. This automated and objective approach has the potential of being applied to SPECT image data sets. This study evaluated an automated analysis of brain SPECT imaging in patients with dementia of Alzheimer type (DAT) using SPM95. Seventeen patients with clinically diagnosed moderate to severe DAT and nine normal control subjects were studied. The SPECT device used was a triple-headed rotation gamma camera GCA9300A/HG. All images were transformed into the standard anatomical space of the stereotactic brain atlas of Talairach and Tournoux, and then smoothed. Statistical analysis was made between DAT and normal control groups. SPM analysis of SPECT images revealed that the parieto-temporal areas and posterior cingulate gyrus of both cerebral hemispheres were significantly decreased in DAT patients compared to normal controls. In conclusion, SPM analysis of SPECT images proved to be useful in the evaluation of abnormal perfusion areas of demented patients.

Aged↗

Organ-specific insulin resistance in patients with noninsulin-dependent diabetes mellitus and hypertension.

UNLABELLED: Abnormal heart and skeletal muscle glucose metabolism in diabetes or essential hypertension has been demonstrated. However, the role of hypertension in heart and skeletal muscle glucose utilization in diabetes has not been clarified yet. METHODS: We compared heart and skeletal muscle glucose utilization using PET and the whole-body glucose disposal rate (GDR) during insulin clamping in 9 patients with noninsulin-dependent diabetes mellitus (NIDDM) and essential hypertension and 11 patients with NIDDM without hypertension to examine the effect of hypertension on heart and skeletal muscle glucose utilization. Results also were compared with those for 8 asymptomatic healthy control participants. RESULTS: Skeletal muscle glucose utilization rate was comparable between hypertensive NIDDM patients (61.2 +/- 55.5 micromol x min(-1) x kg(-1)) and normotensive NIDDM patients (50.9 +/- 25.2 micromol x min(-1) x kg(-1)) but was significantly reduced in both groups compared with control subjects (94.2 +/- 57.3 micromol x min(-1) x kg(-1)), as was the GDR (25.2 +/- 11.3 and 24.0 +/- 7.5 micromol x min(-1) x kg(-1)), respectively, for patients compared with 38.5 +/- 11.5 micromol x min(-1) x kg(-1) for control participants). However, the myocardial glucose utilization (MGU) rate was significantly reduced in NIDDM patients without hypertension (389 +/- 185 micromol x min(-1) x kg(-1)) than in those with hypertension (616 +/- 86.4 micromol x min(-1) x kg(-1), p < 0.01). Multivariate stepwise regression analysis has shown that MGU was significantly correlated with systolic blood pressure and plasma free fatty acid concentration. CONCLUSION: Whole-body insulin resistance was observed in NIDDM patients independent of hypertension. The MGU rate may have different properties to oppose insulin resistance than glucose utilization of skeletal muscle in hypertensive patients with NIDDM.

Case-Control Studies↗

[The review of myocardial positron emission computed tomography and positron imaging by gamma camera].

To measure myocardial blood flow, Nitrogen-13 ammonia. Oxygen-15 water, Rubidium-82 and et al. are used. Each has merit and demerit. By measuring myocardial coronary flow reserve, the decrease of flow reserve during dipyridamole in patients with hypercholesterolemia or diabetes mellitus without significant coronary stenosis was observed. The possibility of early detection of atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is measured by Fluorine-18 fluorodexyglucose (FDG), and it is considered as useful for the evaluation of myocardial viability. We are using FDG to evaluate insulin resistance during insulin clamp in patients with diabetes mellitus by measuring glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has been measured by 11C-palmitate, but absolute quantification has not been performed. Recently the method for absolute quantification was reported, and new radiopharmaceutical 18F-FTHA was reported. Oxygen metabolism has been estimated by 11C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or cardiac transplantation was evaluated. Imaging of positron emitting radiopharmaceutical by gamma camera has been performed. Collimator method is clinically useful for cardiac imaging of viability study.

Coronary Circulation↗

Evaluation of glomerular filtration rate by camera-based method in both children and adults.

UNLABELLED: We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.

Adult↗

[Stepwise analysis of cerebral blood flow SPECT imaging on standard brain atlas in patients with dementia of Alzheimer's type].

Statistical parametric mapping (SPM) has been developed by Friston et al. to analyze focal changes in regional cerebral blood flow (rCBF) induced by brain activation. This automated and objective approach has the potential of being applied to single photon emission computed tomography (SPECT) image data sets. This study evaluated an automated analysis of N-isopropyl-p[123I]iodoamphetamine SPECT (123I-IMP) imaging in patients with dementia of Alzheimer's type (DAT) using statistical parametric mapping '95 (SPM'95). Eighteen patients with clinically diagnosed mild to severe DAT who were classified into two groups and ten normal control subjects were studied. The SPECT device used was a triple-headed rotation gamma camera. All images were transformed into the standard anatomical space of the stereotaxic brain atlas of Talairach and Tournoux, and then smoothed. Statistical analyses were made between severe DAT, mild DAT and normal control groups. SPM analysis of 123I-IMP SPECT images revealed that the parietotemporal association areas and posterior cingulate gyri of both cerebral hemispheres were significantly decreased in CBF in mild DAT group compared to normal controls. In comparison of DAT groups, the right hippocampal area and basal forebrain were significantly decreased in CBF in severe DAT group. In conclusion, these results obtained by SPM analysis of SPECT images suggested that the right hippocampal area and basal forebrain followed the parietotemporal association areas and posterior cingulate gyri in the reduction of the rCBF in patients with DAT.

Aged↗

CAG repeat length and disease duration in Machado-Joseph disease: a new clinical classification.

To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.

Adult↗