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A Waki

Publications and source records attributed to A Waki.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased mitochondrial DNA deletion in the brain of SAMP8, a mouse model for spontaneous oxidative stress brain.

Oxidative stress is considered to be closely correlated with degenerative brain abnormalities. In this study, the plausibility of a SAMP8 strain mouse showing memory deterioration and short life span as an oxidative stress brain model was evaluated. Mitochondrial DNA deletions were detected using polymerase chain reaction (PCR) as cumulative spontaneous oxidative stress. In the 4-8-week-old SAMP8 brain, multiple mitochondrial DNA (mtDNA) deletions were already found and the contents were significantly higher than those of SAMR1 or ddY controls. Enzyme activity studies indicated that electron transport was disturbed at the lower site of the chain and the electronegativity of the upper site might be increased, a cause of radical production and therefore oxidative stress.

Aging↗
PubMed1998

Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiography technique using rat living brain slices.

To demonstrate the preference of lactate over glucose as an energy substrate in normal brain tissue under normoxic condition, the dynamic changes in glucose uptake by lactate loading were investigated in living rat brain slices using a positron autoradiography technique. Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution containing 10 mM glucose at 36 degrees C. During incubation, serial two-dimensional imaging of [18F]FDG uptake in the slices was constructed on the imaging plates. Lactate loading (20 mM) reversibly suppressed the [18F]FDG accumulation up to 80 min. Compared with the pre-loading and the unloaded control values, [18F]FDG uptake was suppressed to 25-45% in cerebral regions and 6-7% in cerebellum. The lactate concentration in the surrounding medium decreased after lactate loading. Hence brain tissue preferentially uses lactate over glucose under normoxic and euglycemic condition.

Animals↗
PubMed1998

Neural networks for generation and suppression of alpha rhythm: a PET study.

To study neuronal activities that influence the generation of the alpha rhythm, we used positron emission tomography and simultaneous recording of the electroencephalogram (EEG) in normal volunteers and under passive conditions. A negative correlation between regional cerebral blood flow and alpha power was found in the occipital cortex, consistent with the visual modality-specific reactivity of the alpha rhythm. A positive correlation was found in the pons, midbrain, hypothalamus, amygdala, the basal prefrontal cortex, insula and the right dorsal premotor cortex. Neuronal activities of the brain stem and limbic system that are positively correlated with alpha power may provide an anatomical basis for studies of the relationship between emotional state and brain rhythm in health and disease.

Adult↗
PubMed1998

Non-invasive estimation of the net influx constant using the standardized uptake value for quantification of FDG uptake of tumours.

To reduce the variability of the standardized uptake value (SUV) which is widely used to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake by neoplasms, net influx constant (Ki) was derived from SUV. The relationship Ki=SUV.kp.V0, where kp is the plasma clearance rate and V0 is the initial distribution volume of FDG, was utilized. A total of 71 plasma input functions were measured up to 60 min after intravenous injection of FDG in 55 patients and were analysed to obtain kp and V0. SUV and V0 were calculated based on either body weight or body surface area. To validate the Ki estimation, another group of eight patients with squamous cell carcinoma of the head and neck was included. Parametric images of the net influx constant were obtained by Patlak graphical analysis of dynamic positron emission tomography (PET) data and measured plasma input function. V0 based on body weight was 0.1627+/-0.0329 (ml/g) and showed a weak negative correlation with body weight (y=0.23356-0.00138x, r=0.591). V0 based on body surface area was 5540+/-871 (ml/m2) and had no significant correlation with body weight. kp at 50 min post injection was 0. 03272+/-0.00243 (1/min), and had no correlation with the plasma glucose concentration. A highly significant positive correlation was noted between true Ki and estimated Ki based on both body weight (y=0.0033+1.0371x, r2=0.897), and body surface area (y=0.0033+1. 0351x, r2=0.926). Ki, a better indicator of FDG uptake by tumour than SUV, is derivable non-invasively. Quantification of FDG uptake by Ki will aid standardization of diagnostic criteria of FDG PET oncology.

Carcinoma, Squamous Cell↗
PubMed1998

The effect of neuronal perturbation on the uptake of [18F]2-fluoro-2-deoxy-D-glucose in brain slices of the rat.

The positron-emitting radionuclide 18F was used to label 2-fluoro-2-deoxy-D-glucose producing [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), and subsequently applied to sagittally-sectioned brain slices of the rat to evaluate the activity of neurons for up to 7 h in living brain slices. The amount of [18F]FDG uptake, which is proportional to the activity of neurons, was monitored every 20 min in five representative brain regions: frontal cortex, caudate-putamen, thalamus, hippocampus and cerebellum. The uptake of [18F]FDG linearly increased with time in these areas, showing constant glucose utilization. The rate of uptake was reversibly decreased by tetrodotoxin (TTX) regardless of brain region, but some uptake was insensitive to TTX. There was a tendency for the uptake to be decreased in Ca2+-free, 5 mM Mg2+ (2 mM EGTA) solution, suggesting some remaining functional synapses. Thus in sagittally-sectioned brain slices, most glucose metabolism is dedicated to neuronal firings and some metabolism to synaptic activities and to other functions of neurons and glial cells. When Cd2+ was applied to brain slices at 0.1-1 mM, the curve of [18F]FDG uptake irreversibly declined, indicating its toxic effect rather than its blocking action of transmitter release at synapses. The cerebellum was the most sensitive to Cd2+, and the caudate-putamen was the least sensitive. The present method, therefore, can be also used as a rapid examination system for checking neurotoxicity of substances.

Action Potentials↗
PubMed1998

Intracellular metabolism of 99mTc-d,l-HMPAO in vitro: a basic approach for understanding the hyperfixation mechanism in damaged brain.

The mechanism of technetium-99m-labeled d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) hyperfixation in damaged brain was elucidated using in vitro metabolic studies. Among the subcellular fractions of mouse brain homogenate, the mitochondrial fraction showed dominant metabolic activity with respect to 99mTc-HMPAO, followed by the cytosolic fraction. The metabolic activity of the mitochondrial fraction was enhanced by heat and detergent treatment, being proportional to the leakage of thiol (SH) compound(s) from the granules. The leaked SH compound(s) had a higher metabolic activity than glutathione, a well-known reductant in cells. 99mTc-HMPAO might be metabolized by mitochondrial SH compound(s) exhibiting strong reductant activity, and hyperfixation might be an indication of mitochondrial damage of the brain.

Animals↗
PubMed1998

The importance of glucose transport activity as the rate-limiting step of 2-deoxyglucose uptake in tumor cells in vitro.

Glucose transporter (GLUT) expression and hexokinase activity are thought to be related to high [18F]-fluorodeoxyglucose (FDG) uptake in tumor cells, but their relative importance is still unknown. To determine which is the predominant factor in FDG uptake in tumor cells, cultured tumor cell lines and a normal cell line were studied in vitro with respect to 2-deoxyglucose (DG) uptake, hexokinase activity, and the initial uptake rate of 3-O-methylglucose (3-O-MG) transport, which is generally accepted as indicating the amount of GLUT expressed on the plasma membrane. In 16 types of tumor cells and one fibroblast cell line, DG uptake was assessed for 60 min, the initial uptake rate of 3-O-MG transport was measured for 1 min, and total hexokinase activity, including that in the mitochondrial fraction, was determined. Across all 16 tumor cell lines, there was a significant correlation between DG uptake and 3-O-MG transport (p = 0.0012, F test), but not between DG uptake and hexokinase activity. Hexokinase activity of the tumor cells was comparable to that of the human fibroblast cells in the exponential growth phase. Most tumor cells showed higher DG uptake and 3-O-MG transport than the human fibroblast cells. The results suggest that DG uptake of cultured tumor cells is governed by GLUT expression, which may be a distinct characteristic of the neoplastic process.

3-O-Methylglucose↗
PubMed1998

Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements--a PET study.

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.

Adult↗
PubMed1998

Glucose transporter protein-independent tumor cell accumulation of fluorine-18-AFDG, a lipophilic fluorine-18-FDG analog.

UNLABELLED: Fluorine-18-fluorodeoxyglucose (FDG) is used clinically for tumor diagnosis, but its mechanism of accumulation in tumor cells is complicated because two factors, glucose transporter protein (GLUT) and hexokinase, govern [18F]FDG uptake directly. We selected a lipophilic [18F]FDG analog, 1,3,4,6-tetra-acetyl-2-[18F]-2-deoxy-D-glucose ([18F]AFDG), to regulate the effects of hexokinase and evaluated its characteristics in an in vitro cell culture system. METHODS: Fluorine-18-AFDG was synthesized by the method used to produce [18F]FDG, as an intermediate of [18F]FDG. Fluorine-18-AFDG uptake study was performed with LS180 tumor cells, and its metabolites were also investigated by thin-layer chromatography. To evaluate the relationship between [18F]AFDG and GLUT, we also examined [18F]AFDG uptake in the presence of cytochalasin B or with increased medium glucose concentration. The effects of lowered temperature (4 degrees C) on [18F]AFDG uptake were also investigated. RESULTS: Fluorine-18-AFDG (lipophilicity: octanol/water = 3.5) uptake was 3.3-fold higher than that of [18F]FDG. Metabolic analysis showed that [18F]AFDG was extremely stable in the incubation medium but was quickly hydrolyzed and metabolized to 2-fluoro-[18F]-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6P) in tumor cells. Fluorine-18-FDG-6P accounted for approximately 45% of the total radioactivity after a 60-min incubation of [18F]AFDG. Incubation with 50 microM cytochalasin B did not affect [18F]AFDG uptake. In medium with double the control glucose level, [18F]FDG uptake was decreased by about 50%, but [18F]AFDG uptake was not affected. Fluorine-18-AFDG uptake and [18F]FDG-6P production did not show saturation and increased linearly with addition of a 10-fold higher concentration of [18F]AFDG. Lowered incubation temperature caused decreased [18F]AFDG uptake due to reduced [18F]FDG-6P production. CONCLUSION: Fluorine-18-AFDG rapidly penetrated the cell membrane as a result of its high lipophilicity and was metabolized to [18F]FDG-6P within cells. Fluorine-18-AFDG was thus characterized as "GLUT-independent [18F]FDG."

Cytochalasin B↗
PubMed1998

Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors.

UNLABELLED: To determine whether PET could help differentiate malignant from benign thyroid tumors, 18F-fluorodeoxyglucose (FDG) accumulation and 201Tl scintigraphy were examined relative to histological diagnosis. METHODS: Nodular thyroid lesions in 11 patients were evaluated before surgical resection. Static PET scanning with 370 MBq FDG was done for 20 min (from 40 to 60 min postinjection) in all patients, and standardized uptake values (SUVs) in these lesions were calculated. In addition, eight patients were evaluated with dynamic PET scan up to 60 min postinjection, and the lesions were further evaluated using graphical analysis. Thallium-201 delayed images were visually evaluated in 10 patients. RESULTS: Four of 11 nodules were well-differentiated papillary carcinoma, another five were benign follicular adenomas, one was a multinodular goiter and another a case of chronic thyroiditis that was proved not to contain a nodule. Time-activity curves of FDG uptake showed different patterns in malignant and benign tumors. In the malignant tumors, FDG uptake increased with time after the tracer injection. By contrast, FDG uptake in benign tumors gradually decreased. With use of a cutoff value of 5.0 mg/ml for SUV and 10 microl x min(-1) x ml(-1) for Kc (K complex value determined using the linear fitting of the time-activity curve of FDG accumulation), all of the four malignant nodules and the six benign nodules were separated correctly. Chronic thyroiditis had high SUV in the malignant range. Of the four patients with thyroid carcinoma, the delayed 201Tl images revealed a slightly higher or equal uptake to background activity. In a patient with chronic thyroiditis, the delayed 201Tl images revealed diffuse accumulation higher than background activity. CONCLUSION: FDG-PET is superior to 201Tl in differentiating malignant from benign tumors. Both SUVs and Kc values were useful indexes for this discrimination. Although careful evaluation is needed for chronic inflammatory lesions, this technique appears to be useful in evaluating thyroid nodules.

Adenoma↗
PubMed1998

Coregistration of FDG PET and MRI of the head and neck using normal distribution of FDG.

UNLABELLED: For better localization of head and neck structures by PET with 2-(18)F-2-deoxy-D-glucose (FDG), direct incorporation of anatomical information from MRI by the coregistration of FDG PET and MRI without external markers is proposed. METHODS: Seventeen patients with neoplasms and 16 normal subjects who had both FDG PET and MRI were studied. First, the three-dimensional normal distribution of FDG was evaluated, and then the structures of the head and neck regions with normal distribution patterns of FDG were used as internal markers for the coregistration of PET and MRI. The effectiveness of the coregistration was evaluated using focal neoplasms that were identified by both PET and MRI as fiducial internal markers. RESULTS: The normal structures selected as internal landmarks for coregistration were the tonsils, salivary glands, mucosal layers of the oral cavity and pharynx, spinal cord, inferior portion of the frontal lobe, cerebellum and nasal turbinates. These structures were more easily observed in sagittal or coronal sections than in transaxial sections. All primary neoplasms were delineated by PET, whereas 4 were missed by MRI. Thirteen primary tumors and 7 cervical lymph node metastases coregistered well, with a center-of-mass distance of <2 mm, whereas 10 lymph node metastases were slightly misregistered, with a center-of-mass distance of 7.8+/-6.5 mm (mean+/-s.d.), probably due to differences in neck positions. CONCLUSION: Normal distribution of FDG uptake in the head and neck regions delineated by multidirectional sections is important for effective coregistration of FDG PET with MRI.

Aged↗
PubMed1997

Role of the supplementary motor area and the right premotor cortex in the coordination of bimanual finger movements.

To obtain a better understanding of the cortical representation of bimanual coordination, we measured regional cerebral blood flow (rCBF) with 15O-labeled water and positron emission tomography (PET). To detect areas with changes of rCBF during bimanual finger movements of different characteristics, we studied 12 right-handed normal volunteers. A complete session consisted of three rest scans and six scans with acoustically paced (1 Hz) bimanual, mirror, or parallel sequential finger movements. Activation of the right dorsal premotor area (PMd) extending to the posterior supplementary motor area (SMA) was significantly stronger during the parallel movements than during the mirror sequential movements (p < 0.05, at cluster level with correction for multiple comparisons). To determine whether these cortical areas truly represented bimanual coordination, a different group of nine normal volunteers was studied with a different task. Subjects performed acoustically paced (2 Hz) abduction-adduction movements of the index finger, making right only, left only, and bimanual mirror and parallel movements. Activation of the posterior SMA and right PMd was significantly greater during the parallel movements than during the bimanual mirror movements or the unimanual movements of either hand (p < 0.01, with anatomical constraint). Thus, the posterior SMA and right PMd appear to be related to the bimanual coordination of finger movements.

Adult↗
PubMed1997

Effects of antitumor agents on 3H-2-deoxyglucose uptake in tumor cells and their relationship with the main targets of the antitumor agents.

To investigate the effects of antitumor drugs on 3H-2-deoxyglucose (DG) uptake in tumor cells, we performed DG uptake studies of the short-term treatment of four kinds of antitumor drugs in a cell culture system. The antitumor drugs adriamycin (ADM) and cisplatin (cDDP), which affect on DNA synthesis, did not greatly affect DG uptake, but DG uptake was lowered by antitumor drugs, actinomycin D (AcD) and cycloheximide (CHX), which target the gene expression system. To investigate the mechanism of DG uptake changes, we also tested the effects of some glucose metabolic inhibitors on DG uptake. An inhibitor of glycolytic flow (iodoacetate) lowered DG uptake whereas mitochondrial inhibition increased DG uptake. These results on the inhibition of glucose metabolism indicated that there were two types of factors affecting DG uptake directly; one affects glycolysis and the other affects oxidative phosphorylation. The two antitumor drugs with effects on gene expression were thought to act by the former. The effects of the drug treatments for tumors on DG uptake could be divided into three groups; glycolysis inhibition, mitochondrial inhibition and no relation to glucose metabolism. With the further observations of FDG uptake changes based on this prediction, the biochemical relationship between treatment effects and FDG uptake changes will be clarified.

2,4-Dinitrophenol↗
PubMed1997

Delayed enhancement of myocardial FDG uptake on glucose loading FDG-PET in NIDDM patient.

We report a case of delayed enhancement of myocardial FDG uptake in NIDDM patient after oral glucose loading. A 65-year-old man who had a past history of NIDDM received FDG-PET examination during fasting and glucose loading. In neither condition, was an accumulation of FDG in the myocardium, and myocardial blood flow was normal. An oral glucose tolerance test (OGTT) was performed to find the best time for FDG injection and 3 hours after loading, the serum insulin concentration was increased significantly. When the interval between glucose loading and the injection of FDG was set at 3 hours, enhancement of myocardial FDG uptake was demonstrated. To know the best time for the FDG injection in advance is thought to be important in obtaining better image quality and interpreting the myocardial viability when FDG-PET examination during glucose loading is performed in NIDDM patients.

Aged↗
PubMed1997

Radioiodinated alpha-p-iodophenyl-N-tert-butylnitrone as a radical detecting agent in vivo.

For in vivo detection of unstable radical species, a novel radioiodinated radical trapping agent, alpha-p-iodophenyl-N-tert-butylnitrone (IPBN), was designed based on the plausible characteristics of alpha-p-hydroxy-m-iodophenyl-N-tert-butylnitrone (HIPBN). Both compounds are iodinated analogs of alpha-phenyl-N-tert-butylnitrone (PBN), but the latter showed low stability in vivo. The present compound IPBN was easily prepared and labeled with radioiodine. It showed very stable characteristics in vitro as well as in vivo, but was easily metabolized and retained at sites of superoxide production.

Animals↗
PubMed1997

Reassessment of FDG uptake in tumor cells: high FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production.

To determine appropriate use of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and 3H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

Adenosine Triphosphate↗
PubMed1997

Transient increase in glycolytic metabolism in cultured tumor cells immediately after exposure to ionizing radiation: from gene expression to deoxyglucose uptake.

The transient change in uptake of deoxyglucose (DG) and expression of glycolysis-associated gene products in cultured tumor cells (LS180 human colon adenocarcinoma cells) immediately after single-dose X irradiation were examined to acquire basic data for use in the early assessment of tumor responses to radiation treatment by position emission tomography. An increase in accumulation of DG was found 3-5 h postirradiation. Inhibitors of both mRNA and protein synthesis and glycoprotein transport suppressed the increase in accumulation of DG to the control level. Both the glucose transporter-1 mRNA expression and the enzymatic activity of hexokinase in the cells were significantly elevated in conjunction with high DG accumulation. These findings indicate that the transiently elevated glucose metabolism occurred via processes at the levels of gene expression. These transient tumor cell responses might be useful for the early assessment of radiation damage.

Colonic Neoplasms↗