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T Mukai

Publications and source records attributed to T Mukai.

At least 271 records · Page 15Linked to original sources

Polymorphism for the number of tandemly multiplicated glycerol-3-phosphate dehydrogenase genes in Drosophila melanogaster.

A 26-kilobase-pair region encompassing the sn-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase, EC 1.1.1.8) locus in Drosophila melanogaster from two natural populations in Japan was surveyed by restriction mapping. Both tandem duplications and triplications in this region were found in both populations. Detailed analysis of 86 chromosome 2 lines revealed restriction site and allozyme polymorphisms in the transcriptional unit: two restriction sites and the allozymes [fast (F) or slow (S)] were polymorphic among both duplication-bearing chromosomes and those carrying the standard sequence. This finding suggests recurrent recombination and/or gene conversion in this 5-kilobase-pair region. The differences observed for restriction site and allozyme haplotypes among the triplicated sequence both within and between populations, together with the distribution in natural populations, suggest a relatively recent ancestry of the triplication events and an independent origin in respective populations. Such events may represent the process of the formation of multigene families [compare Ohta, T. (1987) Genetics 115, 207-213]. Finally, the evolution of this type of polymorphism is discussed.

Animals↗

Glucose metabolism and rate constants in Alzheimer's disease examined with dynamic positron emission tomography scan.

Glucose metabolic rate constants in patients with Alzheimer's disease were analyzed using dynamic positron emission tomography with [18-F] fluoro-2-deoxyglucose (FDG). The cerebral metabolic rate of glucose (CMRG) was calculated using obtained rate constants, as well as the autoradiographic method. The half-life and distribution volume of FDG between the blood and the brain tissue were also calculated from obtained metabolic rate constants. The most severely affected metabolic step was the phosphorylation of glucose in the parietotemporal regions. The distribution volume of FDG showed no remarkable deviation from normal controls, while the half-life of FDG was found to be longer in the parietal and temporal regions. The CMRG from rate constants and that from the autoradiographic method showed no remarkable differences.

Alzheimer Disease↗

Synthesis and aldose reductase-inhibitory activity of benzo[b]furan derivatives possessing a carboxymethylsulfamoyl group.

Various benzo[b]furan derivatives with a carboxymethylsulfamoyl group were prepared and evaluated for aldose reductase-inhibitory potency. Most of the compounds displayed significant inhibitory activities (IC50, 10(-8)-10(-7) M). Among the test compounds, the compounds having a carboxymethylsulfamoyl group at the 3- or 4-position exhibited the greatest inhibitory potency. Structure-activity trends of the tested compounds are discussed.

Aldehyde Reductase↗

Temporal changes in accumulation of N-isopropyl-p-iodoamphetamine in human brain: relation to lung clearance.

Temporal changes in brain uptake of 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) were studied by means of a multi-detector single photon emission computed tomography (SPECT) scanner. Serial dynamic SPECT scan was performed for 50 min following an i.v. bolus injection of IMP in 30 patients with various neurologic diseases. In 18 of them the radioactivity in the lung was also recorded by a single probe detector during the serial dynamic SPECT scan. Brain activity showed a gradual increase after the injection of IMP, reaching 63 +/- 7% of the maximum activity at 5 min and 90 +/- 5% at 20 min. The lung clearance showed a large variation among the individual cases; 29 to 72% (52 +/- 11%) of the initial peak activity at 20 min and 22 to 57% (41 +/- 9%) at 50 min after the injection. A significant positive correlation was observed between the clearance half-time in the lung and the time to reach 90% of the maximum activity in the brain (r = 0.86, p less than 0.001). These results suggested that brain uptake of IMP is influenced by the lung clearance and the optimum time to start SPECT data acquisition using a conventional rotating gamma camera system is 20 min after the injection.

Adult↗

Distribution of Gm allotypes among the three populations of the Miyako Islands in Okinawa.

Serum samples from 738 unrelated individuals of three populations in the Miyako Islands were tested for twelve Gm allotypes to investigate the variability of phenotypes and haplotypes. Nine phenotypes observed in these populations as well as mainland Japanese could be explained by the presence of the four Gm haplotypes, ag, axg, ab3st, and afb1b3. A good agreement was obtained in the samples of each populations between the observed and expected frequencies on the basis of the Hardy-Weinberg equilibrium of phenotypes. These populations showed remarkable heterogeneities with one another on the basis of Gm haplotype frequency analysis. Moreover they exhibited no homogeneities with the Ryukyuans nor with the mainland Japanese. Homogeneity was found between the Ainu and the people in Ueno village but not in the other two locations. However, Gm xg haplotype, only detected in the Ainu, was not found in Ueno. These may imply a racial relationship between the Ainu and the inhabitants in Miyako in the remote past. However, there is no certainty that both of Ainu and the people in Ueno derived from the same origin, or that genetic drift due to endogamy in this village took place. The Gm phenotype and haplotype frequencies observed in Miyako show that they belong to the northern mongoloid group characterized by a high frequency of Gm ag and an extremely low frequency of Gm afb1b3. It is therefore reasonable to assume that they came from northern Asia as well as mainland Japanese.

Asian People↗

Regional dynamics of N-isopropyl-(123I)p-iodoamphetamine in human brain.

Regional cerebral dynamics of N-isopropyl-(123I)p-iodoamphetamine (IMP) in the human brain were studied using a multi-detector single photon emission computed tomography (SPECT) scanner in 35 subjects both normal and with a variety of neurological conditions. Distribution of IMP in the brain was also compared with regional cerebral blood flow (CBF) measured by positron emission tomography (PET) in 15 of these 35 cases. A significant regional difference in temporal changes of radioactivity was observed among normal brain structures. A rapid increase with early washout of the tracer was shown in the cerebellum and the occipital cortex, while the basal ganglia revealed a relatively slow increase and prolonged retention, indicating the regional difference in extraction and/or retention of IMP among the cerebral tissues. In cases with unilateral hypoperfusion, the percentage of the activity in the lesion to that in the contralateral normal cortex on the early SPECT was correlated well with that on CBF measured by PET (r = 0.870, p less than 0.001). However, the contrast on the SPECT image decreased with time after injection; 84.0 +/- 7.4% on the SPECT at 5-20 min scan, 87.6 +/- 7.6% at 35-50 min scan and 96.2 +/- 6.3% at 5 hr scan. In a case with a brain tumor having high blood flow documented by PET, increased accumulation of IMP was observed in the tumor on the early images obtained within 20 min followed by a rapid washout. These findings suggested altered extraction and/or retention of IMP in normal and diseased tissues, and these factors should be considered for the assessment of distribution and redistribution of IMP.

Alzheimer Disease↗

Quantitative analysis of regional wall motion by gated myocardial positron emission tomography: validation and comparison with left ventriculography.

Electrocardiographically gated positron emission tomography (ECG-gated PET) with [13N] ammonia was used to assess regional myocardial wall motion of left ventricle (LV) based on a nongeometric method in nine healthy volunteers and 16 patients with coronary artery disease (CAD). Three transverse sections (upper, middle, and lower) with 16-mm intervals at end-diastole (ED) and end-systole (ES) were analyzed. The LV wall was divided into eight segments with every 30 degrees from septal wall to lateral wall. Based on circumferential profile analysis, the percent count increase [( ES count - ED count) divided ED count x 100) in each segment was analyzed as an index of regional wall motion. In the study of normal controls, the percent count increase was the lowest (32.9 +/- 7.2%) at septal wall of the lower slice and the highest (72.8 +/- 26.5%) at lateral wall of the upper slice (p less than 0.01). In five normal controls, the percent count increase was compared with the percent systolic wall thickening analyzed by magnetic resonance imaging, and a good correlation was observed (r = 0.84). In the study of patients with CAD, the percent count increase was compared with wall motion assessed by left ventriculography (LVG). The percent count increase significantly decreased as wall motion on LVG worsened. In addition, the value in normal controls tended to be higher than that in the segments with normal wall motion in patients with CAD. Thus, quantitative analysis of regional wall thickening was feasible by ECG-gated PET, which should be useful for combined analysis of regional function, perfusion and metabolism in patients with CAD.

Adult↗

The structure of brain-specific rat aldolase C mRNA and the evolution of aldolase isozyme genes.

The cDNA clones for rat aldolase C mRNA having the nearly complete length were isolated from a rat brain cDNA library and sequenced. The nucleotide sequence of pRAC2-1, a cDNA clone having the largest cDNA insert, indicates that the cDNA is composed of a 105-base-pair 5'-noncoding sequence, a 1089-base-pair coding-sequence and a 382-base-pair 3'-noncoding sequence. The amino acid sequence of aldolase C deduced from a possible open reading frame was composed of 362 residues having a relative molecular mass of 39,164 excluding the initiating methionine, one amino acid shorter than aldolases A and B. The length of aldolase c mRNA was 1750 residues, somewhat longer than that of the aldolase A and B transcripts. The aldolase C mRNA was distributed mainly in the brain, some in ascites hepatoma and fetal liver. Comparison of the amino acid sequences of rat aldolase C with those for rat aldolase A and B [Joh et al. (1985) Gene 39, 17-24; Tsutsumi et al. (1984) J. Biol. Chem. 259, 14572-14575], which have been determined previously, shows the existence of highly conserved stretches of amino acid among the three isozymic forms throughout their sequences. The extent of the homology between aldolases A and C is 81%, while those between aldolases A and B, and B and C are 70%, respectively. The analysis of amino acid substitution among aldolases A, B and C from several species suggests that the isozyme genes diverged much earlier than animal species appeared and that the aldolase C gene has evolved from the aldolase A gene after aldolase A and B genes diverged.

Amino Acid Sequence↗

Dynamic positron emission tomography with 13N-ammonia in liver tumors.

Dynamic positron emission tomography (PET) of the liver tumor was performed with a whole body multi slice PET device and 13N-ammonia. Sixteen patients with hepatocellular carcinoma (HCC) and seven patients with metastatic liver tumor were studied. In 12 of 16 patients with HCC, in which cases rich tumor vessels and dense tumor stain were proven by hepatic angiography, the tumors showed remarkable uptake of 13N-ammonia from the first scan, whereas the radionuclide accumulation was more gradual in the other part of the liver, and high tumor to liver ratio (T/L ratio) (2.62 +/- 1.09) was observed in the 1st scan, so that the tumor was clearly visualized by high contrast. However, HCC with poor blood supply from the hepatic artery or central necrosis of the tumor were demonstrated as low T/L ratio. In seven cases with metastatic liver tumor, the accumulation of 13N-ammonia was also lower than the normal liver throughout the scan. The results suggested that hepatic arterial blood flow of the liver tumors can be assessed with dynamic PET, which may provide valuable information for the characterization of tumors as well as for the evaluation of the treatment.

Ammonia↗

Measurement of arterial time-activity curve by monitoring continuously drawn arterial blood with an external detector: errors and corrections.

Accurate description of the arterial time-activity curve (ATAC) is of paramount importance in quantitative determination of the regional cerebral blood flow (rCBF) using positron tomography following bolus i.v. injection of 0-15 labeled water. Frequent manual sampling from an arterial catheter does not permit sampling in less than 5-sec intervals and runs the risk of missing the arrival time or the peak count. A continuous ATAC monitoring system has been developed. This system consists of a single bismuth germinate detector in a lead shield and a constant-flow aspirator. The arterial blood was drawn continuously from a catheter within the brachial artery into an extended tube and its activity was monitored by the detector as the detector time-activity curve (DTAC). Comparison with the manual sampling from the contralateral brachial artery in the same run revealed that the DTAC differed from the manual sampling not only in delayed arrival but also in the shape of the curve, which was dispersed because of viscosity and the width of the detector field of view. However, deconvolution of DTAC using the experimentally obtained system step response provided an accurate arterial time course, which successfully filled in the gaps of the manual sampling. Moreover, water and blood showed different dispersion in the step response, suggesting that the system function should be determined using blood or a fluid of similar hydrodynamic nature.

Arteries↗

A new subtraction method for obtaining myocardial perfusion images with oxygen-15 water and positron emission tomography.

The myocardial positron emission tomograms which are obtained during the perfusion phase following bolus injection of O-15 water (H2(15)O) intravenously require subtraction of the blood pool activity overlaid upon the myocardium. Subtraction has been carried out using the blood pool images obtained in the same position following single inhalation of O-15 labeled carbon monoxide gas (C15O). However, because a difference in activity exists between the left ventricular (LV) cavity and the right ventricular (RV) cavity, simple subtraction of the LV cavity activity using C15O blood pool images induced significant over-subtraction in the right-side heart including the interventricular septum and RV wall. We developed a new method, "two-component subtraction," in which the C15O blood pool images were decomposed into the right-side and left-side components using the early phase images of the H2(15)O dynamics under the assumption that the whole activity of that phase was distributed in the right-side heart homogeneously. Thus we subtracted the blood pool spillover from RV and LV separately. This method provided myocardial perfusion images of high quality which were well correlated with N-13 ammonia images.

Heart↗

SPECT with [99mTc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization.

In order to validate the use of technetium-99m-d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a "linearization algorithm" to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p less than 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

Adult↗

Scatter correction in SPECT using non-uniform attenuation data.

Quantitative assessment of activity levels with SPECT is difficult because of attenuation and scattering of gamma rays within the object. To study the effect of attenuation and scatter on SPECT quantitation, phantom studies were performed with non-uniform attenuation. Simulated transmission CT data provided information about the distribution of attenuation coefficients within the source. Attenuation correction was performed by an iterative reprojection technique. Scatter correction was done by convolution of the attenuation-corrected image and an appropriate filter. The filter characteristics depended on the attenuation and activity measurement at each pixel. The scatter correction could compensate completely for the 28% scatter component from a line source, and the 61% component from a thick, extended source. Accuracy of regional activity ratios and the linearity of the relationship between true radioactivity and the SPECT measurement were both significantly improved by these corrections. The present method is expected to be valuable for the quantitative assessment of regional activity.

Models, Structural↗

[Aldolase deficiency].

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Anemia, Hemolytic, Congenital Nonspherocytic↗