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Biomedical subjects

T Ohtake

Publications and source records attributed to T Ohtake.

At least 73 records · Page 4Linked to original sources
PubMed1997

Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus.

OBJECTIVES: We analyzed myocardial flow reserve (MFR) in patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia. BACKGROUND: Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM. METHODS: Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated. RESULTS: Baseline MBF in patients with NIDDM ([mean +/- SD] 74.0 +/- 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 +/- 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 +/- 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 +/- 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 +/- 0.85; control subjects: 3.8 +/- 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 +/- 0.84) compared with women with NIDDM (3.18 +/- 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 +/- 0.80) and medication therapy groups (2.76 +/- 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = -0.55, p < 0.01) and fasting plasma glucose concentration (r = -0.57, p < 0.01) but not age or lipid fractions. CONCLUSIONS: Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.

Blood Glucose↗
PubMed1997

Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer's disease.

Apolipoprotein E (ApoE) epsilon4 allele is established to be a risk factor for the development of late-onset Alzheimer's disease (AD) which is associated with increased frequency of senile plaques and extent of amyloid angiopathy. In a recent report, we demonstrated that ApoE epsilon4 dosage correlates with an increase in A beta1-40 but not A beta1-42/43-immunoreactive plaques. In the present study, we sought to confirm this relationship at a biochemical level by using a sensitive ELISA to measure the amounts of A beta1-42/43 and A beta1-40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE epsilon4 allele correlated significantly with cortical A beta1-40 levels, while levels of A beta1-42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A beta1-40 may play a key role in the pathogenesis of late-onset sporadic AD.

Aged↗
PubMed1997

Role of age as a prognostic factor in breast cancer.

The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or II breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.

Adult↗
PubMed1997

Flow characteristics of soft-tissue vascular anomalies evaluated by direct puncture scintigraphy.

Soft-tissue vascular anomalies such as haemangioma and vascular malformation are treated by surgical resection, arterial embolization or sclerotherapy. Because the effect of sclerotherapy, i.e. the percutaneous injection of sclerosing agents, depends on intralesional haemodynamics, estimation of flow characteristics of soft-tissue vascular anomalies is essential when determining appropriate patient management. However, lesions are at present divided into only two groups: high flow and low flow. We have developed a new method, direct puncture scintigraphy, to evaluate in detail the haemodynamics of vascular anomalies under conditions simulating sclerotherapy. Twenty-six soft-tissue vascular anomalies in 21 patients were studied. After 30 MBq of technetium-99m Sn colloid was injected percutaneously into the intravascular space of the lesion, dynamic imaging was performed for 5 min. A time-activity curve for the lesion was generated, with the infiltrated activity on injection subtracted. A monoexponential curve was fitted to the declining phase of the time-activity curve, and mean vascular transit time (MTT) was obtained. The lesions were classified into high-flow and low-flow lesions based on radionuclide angiography with intravenous injection of 99mTc-labelled red blood cells, and estimates of MTT in the two groups were compared. The imaging procedures were carried out with no major complications, and broad intralesional diffusion of 99mTc-Sn colloid was achieved in most lesions. The high-flow lesions (six lesions) had a short MTT, ranging from 1.6 to 3.4 s, while the low-flow lesions (20 lesions) had a longer MTT, with no overlap between the groups. MTT showed a wide range in low-flow lesions: it was less than 30 s in six lesions and more than 10 min in five other lesions. Direct puncture scintigraphy provides a quantitative indicator of the flow characteristics of soft-tissue vascular anomalies, and may aid in determining treatment strategies for patients with vascular anomalies.

Adolescent↗
PubMed1997

Effect of deadtime loss on quantitative measurement of cerebral blood flow with technetium-99m hexamethylpropylene amine oxime.

Deadtime count loss may cause error in quantitative measurements with a gamma camera. We evaluated the effect of deadtime loss on the measurement of cerebral blood flow (CBF). Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was performed in 20 patients. A reference source was placed on the periphery of the detector to monitor deadtime loss, and CBF was calculated based on the data of radionuclide angiography with and without deadtime correction. In ten patients injected with 1110 MBq of the tracer, the CBF value without correction was 9.9%+/-1.8% higher than that with correction. This shows that deadtime loss may cause significant overestimation. The difference between CBF values obtained with and without correction was smaller in ten patients with an injected dose of 370 MBq (3.0%+/-1.2%). These results suggest a substantial effect of deadtime loss on CBF as measured by radionuclide angiography and 99mTc-HMPAO.

Adolescent↗
PubMed1997

Abnormal calcium metabolism in myotonic dystrophy as shown by the Ellsworth-Howard test and its relation to CTG triplet repeat length.

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by peculiar clinical features. Its molecular basis is the unstable expansion of a CTG triplet repeat in the gene encoding myotonin protein kinase (Mt-PK), the nucleotide sequence of which has extensive homology to the cyclic AMP (cAMP)-dependent protein kinase gene. Extensive efforts have been made to clarify the signal transduction pathway in which the responsible gene operates, but confirming evidence has yet to be obtained. Because some symptoms in DM are similar to those in hypoparathyroidism, we divided 24 DM patients into two groups on the basis of their serum calcium levels; Group 1, those with normocalcemia (11 patients), and group 2, those with hypocalcemia (13 patients). The highly sensitive parathyroid hormone (HS-PTH) plasma levels in group 1 were within normal limits, whereas those in group 2 were abnormally high. Laboratory findings for the group 2 patients resembled those for pseudohypoparathyroidism (PHP), whereas those for group 1 patients were normal. The Ellsworth-Howard (EH) test was used to determine which type of PHP the group 2 patients belonged to. Both the phosphaturic (delta P) and urinary cAMP (UcAMP) responses were estimated. The delta P responses in group 2 were significantly lower than those in group 1, but their UcAMP responses did not differ. This is evidence that group 2 patients had PHP type II, whereas group 1 patients were normal. We also investigated whether the disease severity differed between the groups. Cataracts, ectopic calcifications, and ossifications, which are associated with PHP, were more frequent in group 2. In addition, the mean IQ in that group was significantly lower. Clinically, the group 2 signs agreed well with those of PHP, whereas for group 1 there was only a slight similarity. These results are additional evidence that the patients in group 2 have abnormal calcium metabolism, the abnormality being in the postadenylate cyclase-cAMP pathway in the renal tubular cells. The degree of (CTG)n expansion, the so-called expanded DNA fragment (EF) size, was determined by standard Southern blot analysis. The allelic EF sizes in both groups were greater than in the healthy controls. Moreover, those in group 2 were significantly longer than those in group 1. We therefore investigated whether EF size is correlated with the serum calcium and plasma PTH levels, the delta P responses in the EH test, and IQ. All these items were significantly correlated with EF size. Our findings show that the expanded DNA fragment size in DM is correlated with the degree of abnormal calcium metabolism.

Adolescent↗
PubMed1997

Roles of reactive oxygen species and antioxidant enzymes in murine daunomycin-induced nephropathy.

We evaluated the roles of reactive oxygen species and intrinsic antioxidant enzymes in the development of daunomycin (DM)-induced nephropathy in mice. A single dose of DM (20 mg/kg intravenously) induced proteinuria by day 7 and the nephrotic syndrome by day 14 in DM-sensitive strain (A/J) but not in DM-resistant strain (C57BL/6J) (B6). Renal cortical lipid peroxide levels in the A/J mice significantly increased at days 2, 4, and 7 after DM injection, whereas no increase was observed in the B6 mice. The resistance to DM in B6 mice was associated with higher activities in renal cortical superoxide dismutase and glutathione peroxidase. The administration of superoxide dismutase or of dimethylthiourea significantly suppressed the DM-induced proteinuria in the A/J mice. Four days of superoxide dismutase or dimethylthiourea administration suppressed the proteinuria. These findings suggested that murine DM-nephropathy appeared to be mediated by reactive oxygen species and that intrinsic antioxidant enzyme activities may play an important role in the susceptibility to DM-induced nephropathy in mice.

Albuminuria↗
PubMed1997

Retrograde degeneration and colchicine protection of basal forebrain cholinergic neurons following hippocampal injections of an immunotoxin against the P75 nerve growth factor receptor.

Intracerebroventricular injection of 192 IgG antibody against the p75LNGFR rat low affinity nerve growth factor receptor conjugated with saporin, a ribosome inactivating protein, has been shown to destroy the p75LNGFR-expressing cholinergic neurons of the basal forebrain. We injected this immunotoxin into the hippocampus and studied its retrograde effect upon the cholinergic neurons of the medial septum and the vertical limb of the diagonal band of Broca. Seven days after injection, there was a nearly total depletion of cholinergic axons within the hippocampus. This depletion was associated with a marked and significant decrease in the number of cholinergic neurons of the ipsilateral medial septum and the vertical limb of the diagonal band of Broca. At longer survival times, these changes were more pronounced. Parvalbumin-positive, GABAergic neurons within the same areas of the basal forebrain were not affected by immunotoxin injections. Injections of saporin alone had no effect upon cholinergic neurons. Simultaneous injection of colchicine with the immunotoxin resulted in a significant reduction of retrograde degeneration of cholinergic neurons and relative preservation of hippocampal cholinergic axons. These observations suggest that 192 IgG-saporin is transported retrogradely from the hippocampus to the cholinergic neurons in the medial septum and the vertical limb of the diagonal band of Broca and provide a model for retrograde degeneration of basal forebrain cholinergic neurons following cortically based toxic-pathologic processes.

Animals↗
PubMed1997

Hemodynamic and endocrine responsiveness to mental arithmetic task and mirror drawing test in patients with essential hypertension.

To evaluate the reactivity to psychological stress in patients with essential hypertension we investigated hemodynamic and endocrinologic changes during a mental arithmetic task (MAT) and a mirror drawing test (MDT) in 10 hypertensive subjects. Hemodynamic changes were assessed continuously using an ambulatory radionuclide cardiac detector. There were significant increases in systolic blood pressure (deltaSBP: +37.8 +/- 11.1 and +41.0 +/- 9.4 mm Hg during MAT and MDT, respectively, P < .01) and diastolic blood pressure (deltaDBP: +17.5 +/- 3.1 and +21.2 +/- 3.9 mm Hg, P < .01) and in heart rate (deltaHR: +17.1 +/- 5.3 and +12.5 +/- 2.9 beats/min, P < .01) during both tasks in association with an increase in cardiac output (CO). The plasma levels of norepinephrine and epinephrine increased during both the MAT (deltaNE: +0.074 +/- 0.022 ng/mL, P < .01; deltaEP: +0.068 +/- 0.025 ng/mL, P < .01) and the MDT (deltaNE: +0.067 +/- 0.034 ng/mL, P < .01; deltaEP: +0.030 +/- 0.011 ng/mL, .05 < P < .1). Although the deltaNE was similar in response to the MAT and MDT, the deltaEP during the MDT tended to be less than half the deltaEP during the MAT (.05 < P < .10). The deltaEP was positively correlated with the deltaDBP and the deltaCO during both tasks and with the deltaSBP and the deltaHR during the MAT. These findings suggest that MAT- and MDT-induced increases in BP were attributable mainly to an increase in CO, possibly as the result of stimulation of the sympathoadrenomedullary system. However, the sympathoadrenomedullary system appeared to be more closely associated with the hemodynamic responses during the MAT than during the MDT.

Adrenocorticotropic Hormone↗
PubMed1997

Ultrastructural background of albuminuria in rats with passive Heymann nephritis.

BACKGROUND: Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria. METHODS: The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats. RESULTS: Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups. CONCLUSIONS: Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.

Albuminuria↗
PubMed1997

Effect of angiotensin II on arteriovenous shunting assessed by hepatic arterial perfusion scintigraphy.

Angiotensin II (AT II) has been reported to improve drug delivery in intraarterial chemotherapy for hepatic tumors. We studied the effect of this agent on arteriovenous (AV) shunting in the liver. Eleven patients with hepatic tumors and an indwelling catheter in the hepatic artery underwent hepatic arterial perfusion scintigraphy with and without AT II infusion. At baseline, following the administration of technetium-99m macroaggregated albumin (Tc-99m MAA) through the catheter, static images of the upper abdomen and whole-body anterior and posterior images were obtained. Two to 14 days later, AT II was infused via the catheter one minute prior to Tc-99m MAA injection, and imaging was performed in the same way as the baseline study. Visual interpretation of the static images showed improvement of drug delivery to the hepatic tumors in eight of 11 patients and no changes in the remaining patients. The percent injected dose in the lungs assessed quantitatively using the whole-body images increased in all patients, suggesting enhancement of AV shunt flow. It was concluded that intraarterial infusion of AT II increases AV shunting in the liver with better targeting to hepatic tumors.

Adult↗
PubMed1997

Metabolism of technetium-99m-L,L-ethyl cysteinate dimer in rat and cynomolgus monkey tissue.

UNLABELLED: Technetium-99m-L,L-ethyl cysteinate dimer (99mTc-ECD) is thought to be hydrolyzed in the brain by an enzyme and to be trapped as a hydrophilic product. We investigated the characteristics of the enzymatic system that metabolizes 99mTc-ECD. METHODS: In 50 mM phosphate buffer (pH 7.4), 99mTc-ECD was incubated with various concentrations of homogenates of rat tissues (blood, liver and brain) or cynomolgus monkey tissues (blood, liver, cerebral gray matter, cerebral white matter and cerebellar gray matter), and the metabolic rates were assessed. Inhibition studies were performed using diisopropyl fluorophosphate, eserine and p-chloromercuribenzoate as inhibitors. The metabolic rates in the brain homogenates of rat and monkey were measured at various levels of pH, ranging from 6.6 to 7.6. Technetium-99m-L,L-ethyl cysteinate dimer metabolism was also examined in the presence of purified enzymes. RESULTS: In both species, the metabolic rate was high in liver tissue, intermediate in brain tissue and low in blood. The rate in cerebral gray matter of cynomolgus monkey was higher than those in rat brain, monkey cerebral white matter and monkey cerebellar gray matter. All substances used as inhibitors depressed 99mTc-ECD metabolism, and the response was different among tissues. Reduction in pH induced slight decreases in metabolic rate. Hydrophilic conversion of 99mTc-ECD was observed after incubation with porcine liver carboxylesterase. CONCLUSION: These results support the hypothesis that the hydrophilic conversion of 99mTc-ECD is mediated by enzymes. It is also suggested that various enzymes catalyze the hydrolysis of 99mTc-ECD and that the enzymatic system that metabolizes 99mTc-ECD is different between tissues and between species.

Acetylcholinesterase↗
PubMed1997

[Typical normal cases and normal cases with abnormal image pattern in every myocardial SPECT radiopharmaceutical].

Working group of cardiac nuclear medicine was made as a Japanese part of society of international cardiac nuclear medicine under the cooperation between Japanese society of nuclear medicine and Japanese society of cardiology. We investigated typical normal cases and normal cases with abnormal image pattern in every myocardial SPECT radiopharmaceutical as one of the research activity of working group. From 11 faculties, 16 T1 cases, 14 BMIPP cases, 8 MIBG cases, 8 MIBI cases and 14 tetrofosmin cases were submitted as typical normal cases, and 12 T1 cases, 5 BMIPP cases, 12 MIBG cases, 10 MIBI cases and 5 tetrofosmin cases were submitted as normal cases with abnormal image pattern. We summarized the condition of SPECT data acquisition of each faculties. And we added the discussion from literature about how to discriminate normal cases with abnormal image pattern from abnormal cases. In MIBG, patterns of typical normal cases and normal cases with abnormal image pattern were slightly different from other 4 pharmaceuticals. In other 4 pharmaceuticals, diaphragmatic attenuation, breast attenuation, apical thinning and others were presented as normal cases with abnormal image pattern.

3-Iodobenzylguanidine↗
PubMed1997

[Characterization of antibodies against core, NS3, NS4, NS5 region of hepatitis C virus in patients with hepatitis C].

Third-generation screening assays for HCV antibodies were recently developed, in which a mixture of recombinant antigens from four different regions of the viral protein (core, NS3, NS4, NS5) was used. We reported the analytical performance and clinical usefulness of a third-generation counting immunoassay (RANREAM HCV) with PAMIA 30 (Toa Medical Electronics Inc., Kobe). In the present study, we investigated a modified assay of RANREAM HCV to detect region-specific antibody by using single antigen from four different regions, and studied response pattern of HCV antibodies and region-specific antibody in the patients with HCV infection. HCV antibodies of the seroconversion panel serum samples (BBI, USA) measured by RANREAM HCV were greatly coincident with those obtained by Ortho RIBA 3.0. The region-specific assay of serial sera from the patient with acute hepatitis revealed that anti-core antibody was produced at the initial stage of infection. In 165 patients with chronic hepatitis, pattern of region-specific antibody was different from case to case, although anti-NS3 and anti-core antibodies seemed to be predominant. The change of pattern was not observed for at least one year. All 2 cases who achieved complete remission with interferon showed low serum titer of anti-core antibody, in contrast to partial or non remission patients in which the level of anti-core antibodies was low in 6 of 16 cases.

Hepatitis C↗
PubMed1996

Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis.

BACKGROUND: Reduced coronary flow reserve (CFR) in hypercholesterolemic patients without evidence of ischemia has been reported. However, it remains uncertain whether this abnormality occurs without overt coronary atherosclerosis. This study aimed to clarify whether CFR is impaired even in anatomically normal coronary arteries in hypercholesterolemic patients and to compare CFR between familial hypercholesterolemic (FH) patients and secondary hypercholesterolemic (SH) patients. METHODS AND RESULTS: Twenty-two patients with hypercholesterolemia (11 FH, 11 SH) and 11 control subjects were studied. Baseline myocardial blood flow (MBF) and MBF during dipyridamole loading were measured in segments perfused by angiographically normal coronary arteries with the use of positron emission tomography and 13N-ammonia, and CFR was calculated. Baseline MBF (mL/min per 100 g heart wt) in FH (81.3 +/- 31.4) and SH (70.0 +/- 20.7) patients was not different from that in control subjects (75.0 +/- 34.9). However, MBF during dipyridamole loading was significantly lower in FH patients (129 +/- 19.1) than in control subjects (322 +/- 174, P < .01) and SH patients (210 +/- 71.2, P < .01). CFR in FH patients (1.59 +/- 0.41) was also significantly lower compared with both control subjects (4.22 +/- 1.42, P < .01) and SH patients (3.00 +/- 0.96, P < .01). CFR in SH patients was also significantly lower than that in control subjects (P < .05). CFR correlated significantly with both plasma total cholesterol (r = .67, P < .01) and LDL cholesterol concentrations (r = .69, P < .01). CONCLUSIONS: CFR was decreased even in anatomically normal coronary arteries in hypercholesterolemic patients. This abnormality was more prominent in FH patients.

Blood Pressure↗
PubMed1996

Simple method to quantify myocardial glucose metabolism from MB ratio in myocardial FDG PET.

To provide a simple means of quantifying myocardial glucose metabolism, we tried to estimate the K complex (KC) from the myocardium to background ratio (MB ratio), which was obtained with a single static FDG scan and single venous sampling. In 48 fasting subjects and 74 subjects under oral glucose loading or insulin clamp, the reference KC was obtained from Patlak analysis by using an input function. We compared the reference KC with the MB ratio at 35 min 45 sec, 45 min 45 sec, and 55 min 45 sec, and with the FDG uptake index (FUI) reported by Tamaki. The correlation between KC and each index was very close during fasting (r = 0.97, 0.98, 0.98 and 0.97, respectively n = 48), and clinically acceptable during oral glucose loading and insulin clamp (r = 0.92, 0.91, 0.90 and 0.93, respectively n = 74). The average differences between the reference KC and KC estimated from the simple method were 13%, 10%, 8%, and 13%, respectively, during fasting, and 15%, 14%, and 16%, respectively, during oral glucose loading and insulin clamp. Both the MB ratio and FDG uptake index can be used for the simple estimation of myocardial glucose metabolism not only during fasting but also during oral glucose loading and insulin clamp, although the MB ratios at 45 min and at 55 min were slightly better than MB that at 35 min and the FDG uptake index during fasting.

Adult↗
PubMed1996

Use of whole-body imaging using Tc-99m RBC in patients with soft-tissue vascular lesions.

We investigated the usefulness of whole-body imaging as an adjunct to spot imaging in soft-tissue vascular lesions, such as hemangiomas and vascular malformations. Spot imaging of the known lesion and whole-body imaging were performed 1-3 hours after the injection of Tc-99m RBC in 42 patients with soft-tissue vascular lesions. Whole-body imaging was considered to be useful in only two patients, who had multiple distant occult lesions in addition to large known lesions. It was suggested that the routine addition of whole-body imaging is not cost effective in patients with soft-tissue vascular lesions, although it may be beneficial for detecting occult lesions in patients with hemangiomas.

Adolescent↗