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Biomedical subjects

A Waki

Publications and source records attributed to A Waki.

50 records · Page 3Linked to original sources

Quantification of regional cerebral blood flow with continuous infusion of technetium-99m-ethyl cysteinate dimer.

UNLABELLED: We propose a new method to quantify regional cerebral blood flow (rCBF) with continuous infusion of 99mTc-ethyl cysteinate dimer (ECD) and dynamic SPECT. METHODS: Thirteen subjects were studied. Seven subjects had SPECT and PET studies, and the other six subjects were involved in the measurement of blood clearance of 99mTc-ECD. During constant infusion of 99mTc-ECD (740 MBq) over 10 min, dynamic SPECT scans were obtained every 1 min by means of a triple-head rotating SPECT camera. Intermittent arterial blood sampling with octanol extraction was performed every 1 min to estimate the arterial input function. Influx constant (Ku) obtained by Gjedde-Patlak graphical plot method was compared with rCBF measured by PET using 15O CO2 steady state method. In order to simplify the procedure, arterial input function in each subject was estimated by calibration of the arterial blood sampled at the end of the scan to the standard arterial input function estimated from the blood clearance rate in six subjects. RESULTS: Ku was linearly correlated with rCBF (Ku = 0.09 + 0.62 rCBF, r = 0.85, p < 0.05). Ku calculated with the estimated input function (Ku') and rCBF also demonstrated a linear relationship (Ku' = 0.05 + 0.65 rCBF, r = 0.84, p < 0.05). CONCLUSION: The proposed method with one-point arterial sampling is a simple, clinically feasible tool for quantitative measurement of rCBF with 99mTc-ECD.

Adult↗

[Basic studies on the 111In labeled antisense oligonucleotide for tumor imaging].

Antisense oligonucleotide labeled with short lived radionuclide has been proposed as a radiopharmaceutical for the detection of abnormal gene expression. In this study, plausibility of 32P or 111In labeled oligonucleotide was basically evaluated using c-erbB-2 protooncogene mRNA as a model target. In cell uptake studies, sequence specific accumulation of 32P-oligonucleotide was found in the cells with c-erbB-2 mRNA expression, but not control cells, indicating the basic possibility of antisense strategy. Synthesis of 111In labeled isothiocyanobenzyl-EDTA (IBE)-oligonucleotide could be performed, but some problems were found in purification step. Stability of 111In-IBE-oligonucleotide was high when compared with that of 32P-oligonucleotide, and in vivo biodistribution data might indicate that 111In-IBE-oligonucleotide was plausible for tumor imaging.

Animals↗

Activation of silent MDR1 genes in revertant cells by fusion with multidrug-resistant cells.

We isolated revertant and resistant clones from multidrug-resistant K562/ADM cells and evaluated the expression of P-glycoprotein and the DNA copy number of MDR1. The 9 revertant clones contained 2- to 26-fold DNA copies of MDR1; however, they expressed an extensively decreased P-glycoprotein compared with K562/ADM, while the 10 multidrug-resistant clones contained 4- to 48-fold DNA copies, and the expression level of P-glycoprotein was dependent on the copy number of MDR1 DNA. The decreased expression of P-glycoprotein in the revertants was not due only to the loss of the copy number of MDR1 DNA. To elucidate the mechanism of P-glycoprotein expression decrease in the revertants, a revertant clone (R1-5) was fused with a multidrug-resistant clone (A2-1) or with a drug-sensitive clone isolated from K562. Compared with K562 clone, the A2-1 contained 32-fold MDR1 DNA copies and showed 131-fold resistance to Adriamycin. The revertant clone R1-5 contained 26-fold MDR1 DNA copies but expressed only 5% the P-glycoprotein of A2-1 cells and showed only 2-fold resistance to Adriamycin. For selection of intraspecific hybrids, a neomycin-resistant or a blasticidin S-resistant gene was introduced into clones by electroporation of pSV2neo or pSV2bsr. The introduction of these resistant genes did not alter the copy number or expression of MDR1 in the clones. Hybrid cells between R1-5bsr and A2-1neo were found to express 136 +/- 15% of the P-glycoprotein of A2-1 cells evaluated by quantitive flow cytometry. These hybrid cells contained 41- to 48-fold MDR1 copies and showed the multidrug-resistant phenotype, such as decrease of rhodamine123 accumulation and 120- to 210-fold resistance to Adriamycin (compared with K562), indicating that the 'silent' MDR1 genes in the revertant clone R1-5 were activated by cell fusion with an MDR clone. R1-5bsr x K562neo hybrids were found to contain 8- to 11-fold MDR1 copies and there was no increase in P-glycoprotein expression as compared with R1-5.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Differential aging pattern of cerebral accumulation of radiolabeled glucose and amino acid in the senescence accelerated mouse (SAM), a new model for the study of memory impairment.

Using an accelerated senescence-prone model mouse strain, SAMP8, with spontaneously occurring age-related deficits in learning and memory, cerebral glucose and amino acid accumulation were investigated to study the metabolic abnormalities in relation to age. The findings were compared with those in an accelerated senescence-resistant mouse strain, SAMR1, without deterioration of ability in learning and memory. [14C]-2-Deoxyglucose accumulation in the SAMP8 brain was normal at 1 month of age but decreased from 2-3 months of age onwards. In contrast, tyrosine accumulation was unchanged from 1 to 5 months of age. The impairment of memory in the SAMP8 at 2-3 months of age corresponded with the decrease in [14C]-2-deoxyglucose accumulation, but was not related to Tyr. This animal model may help provide new information on the metabolic changes in aging.

Aging↗

Visualization of the cervical spinal cord with FDG and high-resolution PET.

PURPOSE: Our aim was to evaluate the visibility of the cervical spinal cord with [18F]2-fluoro-2-deoxyglucose (FDG) and a high-resolution PET scanner and to quantify the glucose utilization by the cervical cord. METHOD: Twenty-one normal subjects and three cervical myelopathy patients were studied. The visibility of the cervical spinal cord in sagittal and coronal sections was evaluated. The metabolic rate of glucose (MRGlu) and standardized uptake value (SUV) of FDG in the cord were calculated. RESULTS: The entire cervical spinal cord was clearly visualized in 57% of the subjects: the upper cord in 81%, the middle cord in 73%, and the lower cord in 57%. The MRGlu of the normal cord was 1.93 +/- 0.37 mg/100 g/min. SUV was constant across all the vertebral levels and negatively correlated with subject age. In the myelopathy patients, the SUV of the entire cervical cord was lower than in the age-matched normal subjects. CONCLUSION: These preliminary results indicate that the cervical spinal cord can be visualized as a normal structure in routine head and neck PET imaging and that FDG-PET may provide quantitative information about spinal cord disorders.

Adult↗

Activation patterns of covert word generation detected by fMRI: comparison with 3D PET.

PURPOSE: The aim of our study was to compare the activation patterns of higher cognitive function detected by functional MRI (fMRI) with those by H2(15)O positron emission tomography (PET). METHOD: Activation studies with both modalities were performed in six normal volunteers with identical covert word generation tasks and statistical analysis. For PET, each subject had five rest scans and five task scans at 10 min intervals. fMRI was performed with a 1.5 T magnet using T2*-weighted echo planar sequences. Each scanning session consisted of two rest and two task periods of 30 s each, alternating rest and task. RESULTS: In group analysis, the activation patterns on both PET and fMRI were similar, whereas the deactivation patterns differed, presumably due to the noise of fMRI. In single-subject analysis, PET showed fewer activated areas and fMRI showed more areas of activation than in group analysis. CONCLUSION: fMRI has an advantage over 3D PET in its better signal-to-noise ratio for detecting change in neuronal activity for higher brain function.

Adult↗

Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography.

To investigate age-related changes in cerebral energy production, we compared senescence-accelerated prone mice (SAMP8) as an animal model of accelerated aging and senescence-accelerated resistant mice (SAMR1) as a control. Considering that the cerebral glucose metabolic rate (CMRglc) at the time of O(2) deprivation and 2,4-dinitrophenol (DNP) loading would reflect anaerobic glycolytic capacity and mitochondrial function, respectively, we investigated dynamic changes in CMRglc before and after loading with these perturbations. Fresh brain slices were incubated with [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [(18)F]FDG uptake in these slices were obtained on the imaging plates. The fractional rate constant (=k(3)*) of [(18)F]FDG proportional to the CMRglc was evaluated by applying the Gjedde-Patlak graphical method to the image data. The k(3)* value before the hypoxic perturbation in all of the brain sites analyzed was higher in SAMP8 than SAMR1 in both the 2- and 10-month-old groups. With O(2) deprivation, k(3)* values were higher without site specificity in the 2-month-old SAMP8 than in 2-month-old SAMR1, whereas in 10-month-old mice, there was no significant difference between the two groups. In contrast, with DNP loading, while no significant difference was noted between 2-month-old SAMP8 and 2-month-old SAMR1, in 10-month-old mice, the SAMP8 group showed lower values in certain regions than SAMR1 mice. These results suggest that in the brain tissue of SAMP8, a marked transient enhancement of anaerobic glycolytic capacity in the 2-month-olds and a decrease in mitochondrial function in the subsequent period occur, as a result of which glucose metabolism appears to be enhanced in both the 2- and 10-month-old groups compared to SAMR1 mice.

Age Factors↗