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T Mukai

Publications and source records attributed to T Mukai.

At least 163 records · Page 9Linked to original sources

[Parametric images of central-type benzodiazepine receptor binding and ligand transport by two SPECT scans of 123I-iomazenil: relative quantification without blood data].

Parametric images of intrasubject distribution of the central-type benzodiazepine receptor binding and ligand transport were determined from two SPECT images after an intravenous bolus injection of 123I-iomazenil in six healthy volunteers and five patients by using a table look-up procedure based on a 3-compartment, 2-parameter kinetic model. Individual arterial input functions were estimated by calibrating a standardized input function with the injected dose to avoid blood sampling. The parametric images without blood data provided the same information as those determined by using measured arterial input function. A simulation study suggested that this method gave relatively small error as long as true receptor binding and ligand transport did not differ from each other in a large extent. The present method may be practical in clinical settings.

Biological Transport↗

Measurement of regional cerebral blood flow with copper-62-PTSM and a three-compartment model.

UNLABELLED: We evaluated quantitatively 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied. METHODS: We performed both 15O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve. RESULTS: Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62Cu-PTSM can be analyzed by the three-compartment model with negligible K4. Using this model, K1-K3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K1-K3. The influx rates (Ki) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62Cu-PTSM and 150-water studies demonstrated excellent correlation. CONCLUSION: The results suggest the potential feasibility of quantitation of cerebral perfusion with 62Cu-PTSM accompanied by dynamic PET and simple arterial sampling.

Brain↗

Unusual findings in a fatal case of poisoning with chromate compounds.

An interesting case of acute poisoning by chromate compounds is reported. A 51-year-old man committed suicide by ingesting a fatal dose of sodium chromate solution. He unexpectedly lost consciousness 6 h after the ingestion and died approximately 20.5 h later. An examination of the blood showed noticeable hepatic damage and thrombocytopenia. The postmortem examination revealed extensive bleeding in the alimentary tract and a severe hepatic lesion due to hepatocellular necrosis. However, the renal disorder was unusually light in the microscopic and clinical findings. Moreover, the renal lesion was observed mainly in the distal tubules instead of the proximal tubules which is more typical in cases of acute poisonings by diverse heavy metals including chromium. The patient's death was assumed to have been caused by circulatory collapse due to internal bleeding and the direct toxicity of chromate compounds with hepatic malfunction and possibly disseminated intravascular coagulation (DIC).

Chemical and Drug Induced Liver Injury↗

The MEF2B homologue differentially expressed in mouse embryonal carcinoma cells.

The MEF2 gene family encodes a MADS-box transcription factor which regulates expression of many muscle-specific genes. We examined the expression of the MEF2 genes in mouse embryonal carcinoma P19 cells before and after in vitro muscle differentiation induced by dimethyl sulfoxide (DMSO). At least three different MADS/MEF2 domains (MEF2A, 2B and 2D) were isolated from P19 cells with the MOPAC technique (mixed oligonucleotides primed amplification of cDNA). Although two of the MADS/MEF2 domain sequences were identical to those of human MEF2A and MEF2D, another domain sequence was similar but not identical to that of human MEF2B. While the transcription of MEF2A and MEF2D was up-regulated during differentiation of P19 cells, the MEF2B homologue was abundantly transcribed in undifferentiated P19, F9 and ES cells and down-regulated in adult heart, skeletal muscle or brain, suggesting that the murine MEF2B homologue might have a function distinct from other members of the MEF2 gene family in embryogenesis and development.

Amino Acid Sequence↗

Cloning and mapping of the U2af1-rs2 gene with a high transmission distortion in interspecific backcross progeny.

We have cloned and analyzed the mouse U2af1-rs2 gene based on its sequence similarity to the imprinted gene U2af1-rs1 (SP2). Sequence analysis of this U2af1-rs2 cDNA revealed that it contained an open reading frame encoding a protein of 462 amino acid residues. The predicted amino acid sequence showed 72.7 and 35.8% identity to the U2af1-rs1 and U2 small nuclear ribonucleoprotein auxiliary factor, respectively. Interspecific backcross analysis showed this gene to map to the distal region of the X chromosome and also indicated that there was significant distortion of transmission ratio of the U2af1-rs2 allele in the backcrossed progeny from (C57BL/6J x Mus spretus)F1 females mated to Mus spretus males.

Amino Acid Sequence↗

Allele-specific methylation and expression of an imprinted U2af1-rs1 (SP2) gene.

The mouse U2af1-rs1(SP2) gene, which was cloned by a two-dimensional genome scanning method, is expressed exclusively from the paternally inherited chromosome. This gene has significant similarity to U2AF and located in chromosome 11, of which maternal duplication/paternal deficiency results in a small body. In this report, we cloned genomic U2af1-rs1(SP2) and found its promoter was methylated in a maternal-allele-specific manner. This allelic methylation was not established in parental gametes, but established between 1.5 d.p.c. and 12.5 d.p.c. on the contrary, the allele-specific expression occurred in the two-cell stage when transcription initiates. Absence of the methylation of the upstream region in this stage indicates that methylation is not necessary for inactivation of the expression.

Alleles↗

Identification of the major capsid protein gene of human herpesvirus 7.

Two human herpesvirus 6 (HHV-6) open reading frames were identified with significant amino acid similarity to UL86 (major capsid protein, MCP) and UL85 of human cytomegalovirus (HCMV) in human herpesvirus 7 (HHV-7) genes. The predicted lengths of the complete HHV-7 MCP and the HCMV-UL85 open reading frames were 1344 and 293 amino acids with estimated molecular weights of approximately 153 and 33 kDa, respectively. Computer analysis showed that the amino acid of HHV-7 MCP was 61% identical to the MCP of HHV-6 variants A and B, 28% to HCMV. These results suggest that HHV-7 is more closely related to HHV-6 than to HCMV.

Adult↗

On the evolution of dust in the solar vicinity.

The analysis of interplanetary dust shows that the majority of particles in out-of-ecliptic regions comes from comets and also that near solar dust, in the ecliptic regions, results most probably largely from comets. The intense radiation flux in the solar vicinity is expected to cause strong modifications in the material composition and surface structure of interplanetary dust particles and hence the analysis of near solar dust provides interesting insights into the evolution of meteoritic, especially cometary materials. Because of the lack of in-situ measurements our present knowledge concerning these processes derives from remote sensing, i.e. observations of the solar F-corona. In particular these are observations of albedo, polarization and colour temperature given in terms of average particle properties. For example the analysis of near infra-red F-corona data points to the existence of a strong component of irregularly structured silicate particles, most probably of cometary origin. The data may indicate a subsequent sublimation of different particles or different constituents of the particles. Here we compare particle properties derived from F-corona observations with model calculations of single particle properties and discuss perspectives of future analysis of cometary dust in the interplanetary cloud.

Cosmic Dust↗

Radiolabeled metabolites of proteins play a critical role in radioactivity elimination from the liver.

We have recently reported that the behavior of radiolabeled metabolites in the liver appears to be responsible for the hepatic radioactivity levels after administration of protein radiopharmaceuticals. To better understand the role played by radiolabeled metabolites in hepatic radioactivity levels, two benzyl-EDTA derivatives rendering different radiolabeled metabolites, 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA) and 1-[p-(5-maleimidopentyl)aminobenzyl]ethylenediaminetetraacetic acid (ECMS-Bz-EDTA), were selected as bifunctional chelating agents (BCAs), and 111In labeling of galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) was performed. Biodistribution of radioactivity in mice and subcellular distribution of radioactivity in hepatocytes were then compared. After accumulation in hepatic parenchymal cells, NGA-EMCS-Bz-EDTA-111In rendered a faster elimination rate of radioactivity from the liver than NGA-SCN-Bz-EDTA-111In. Although each 111In-NMA exhibited a delayed elimination rate of radioactivity from the liver compared to the 111In-NGA counterpart, NMA-EMCS-Bz-EDTA-111In showed faster elimination rate of radioactivity than NMA-SCN-Bz-EDTA-111In. Analyses of radioactivity excreted in feces and urine and remaining in the liver indicated that both BCAs rendered mono-amino acid adducts as the major radiolabeled metabolites (cysteine-EMCS-Bz-EDTA-111In and lysine-SCN-Bz-EDTA-111In), which were generated in both cell types of the liver within 1 h postinjection. Subcellular distribution of radioactivity indicated that the radioactivity was copurified with lysosomes. These results demonstrate that although in vivo stability of radiometal chelates is essential, the biological properties of the radiolabeled metabolites generated after lysosomal proteolysis in hepatocytes play a critical role in radioactivity elimination from the liver.

Animals↗

Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse.

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it a tumour suppressor candidate. Several types of childhood tumours including Wilm's tumour, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting. Here, as a first step towards elucidating the genesis of human cancers in this region, we showed that a mouse homologue of p57KIP2 is genomically imprinted. The paternally inherited allele is transcriptionally repressed and methylated. This murine gene maps to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14-18).

Adrenal Cortex Neoplasms↗

Transfer of dietary sulphamonomethoxine and sulphadimethoxine into various tissues of laying hens.

1. Sulphamonomethoxine (SMM) or sulphadimethoxine (SDM) were fed to laying hens at a dietary concentration of 400 mg/kg. Concentrations (mg/kg) of SMM and SDM in the blood, kidney, liver, ovary, muscle and adipose tissue, collected at 4, 8, 16 and 24 h after the start of feeding, were determined by HPLC. 2. The relationships between the sulphonamide concentrations (mg/kg) in the tissues and times (h) after the start of the feeding were analysed statistically. 3. Dietary SMM and SDM were transferred throughout the whole body, and concentrations in all tissues became constant 8 h after the start of feeding. 4. Among the 6 tissues examined the constant values (mg/kg) of both SMM and SDM were highest in the kidney and were lowest in adipose tissue. 5. With the exception of adipose tissue, the values of SDM in the tissues were statistically greater than those of SMM.

Adipose Tissue↗

Parents' contributions to children's knowledge and attitudes regarding AIDS: another look.

Attempted to determine, using a sample of students in Grades 3, 5, and 7, whether parent-child communication about AIDS and parent knowledge of AIDS predict children's knowledge, social attitudes, and worry regarding AIDS, partially replicating tests by Sigelman, Derenowski, Mullaney, and Siders (1993) of main effects, interaction, and potentiation models of parent-child socialization. Most parents had talked to their children about AIDS but many were susceptible to myths about HIV transmission. Child age was the strongest predictor of accurate knowledge and positive attitudes, but gender, ethnicity, and parent education also made modest contributions. Consistent with the potentiation model, parent knowledge of common transmission myths predicted child knowledge of those same myths (and willingness to interact with individuals who have AIDS as well) only when parent-child communication about AIDS was relatively extensively (and only when child rather than parent reported it). Findings suggest that both the quantity and quality of parental messages must be considered by socialization researchers but that parents may not be the primary socializers of knowledge and attitudes regarding AIDS and other health issues.

Acquired Immunodeficiency Syndrome↗

Copy-dependent and position-independent expression of rat aldolase A gene.

In order to understand the molecular mechanisms of the temporal and spatial differences of gene expression in higher organisms, rat aldolase A gene carrying two distinct promoters was introduced into fertilized eggs and the resulting transgenic mice were analyzed. The transgene expression is tissue-specific and is developmentally regulated. In addition, the expression is regulated in a copy-dependent manner irrespective of where the transgene is integrated, suggesting that a mechanism excluding the effect of the integration site exists within the transgene itself. To explore the conformational change of this gene in the genome, the DNase I hypersensitive sites of the gene were examined. Three sites (DHS-1,2, and 3) were identified upstream and downstream of the gene and these sites were retained in the transgene as well as in the gene observed endogenously.

Animals↗

Cyclic change in 3 alpha-hydroxysteroid dehydrogenase in rat ovary during the estrous cycle.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) activity and content in the rat ovary were measured at various stages of the estrous cycle, and the enzyme protein in the ovary was localized by immunohistochemistry. The cyclic change of ovarian 3 alpha-HSD activity towards 5 alpha-dihydrotestosterone (5 alpha-DHT) as a substrate was characterized by two peaks. The first peak occurred at 0800 h on proestrus; then the reductase activity decreased and reached its minimum at 2000 h on proestrus. Thereafter, it gradually increased, reaching the second peak (170% of the value at 2000 h on proestrus) at noon of estrus. Quantitative analysis by immunoblotting revealed that the alteration in 3 alpha-HSD content in the rat ovary during the estrous cycle was essentially similar to that in 5 alpha-DHT reductase activity. Changes in the reductase activities towards 5 alpha-androstane-3,17-dione and 5 alpha-DHT and in the dehydrogenase activity towards androsterone in the ovary were entirely different from those in the 5 alpha-DHT reductase activity and 3 alpha-HSD content; on the other hand, the change in carbonyl reductase activity towards p-nitroacetophenone was similar to changes in 5 alpha-DHT reductase activity and 3 alpha-HSD content. Therefore, p-nitroacetophenone may be a useful substrate, instead of 5 alpha-DHT, for detection of 3 alpha-HSD activity at a high sensitivity, since the p-nitroacetophenone reductase activity was 10-fold higher than the 5 alpha-DHT reductase activity. The enzyme was primarily localized in the granulosa cells and CL cells. At 2000 h on proestrus, however, the overall intensity of immunostaining in the granulosa cells of the Graafian follicles was markedly diminished. In addition, immunoreactivity in the CL cells at 0800 h on estrus was observed only in the cells outlining the CL in some cases.

3-Hydroxysteroid Dehydrogenases↗

Carcinosarcomas of the esophagus.

Two cases of carcinosarcoma of the esophagus are reported. Both were polypoid tumors occurring in the middle of the intrathoracic esophagus. The tumors were predominantly composed of spindle-shaped sarcoma cells with some squamous cell carcinomas (SCC). One tumor showed many bizarre giant cells with filamentous materials in the cytoplasm. Microscopical examination of both tumors revealed transition from SCC to sarcoma cells. Immunohistochemically, the spindle-shaped sarcoma cells in both tumors displayed a strongly positive immunoreaction to alpha-smooth muscle actin, as did the bizarre giant cells of one tumor to sarcomeric actin. SCC and a few spindle-shaped sarcoma cells near the SCC showed a positive immunoreaction to cytokeratin. Electron microscopy revealed that the spindle-shaped cells had many myofilaments with dense bodies and that the bizarre giant cells had sarcomere structures with Z-bands in their cytoplasm. These findings indicate that both tumors were carcinosarcomas of SCC and myogenic sarcoma. We considered that sarcoma cells might originate in SCC, representing its metaplastic differentiation, or that both SCC and sarcoma might originate in a pluripotent stem cell.

Aged↗

[Arterial oxygen saturation monitoring of sleeping infants by pulse-oximeter--effect of sleeping position on arterial oxygen saturation in infants].

Monitoring of the arterial oxygen saturation (SaO2) in two sleeping infants was reported. They were a couple of female twins and had grown up normally after admission to NICU (Neonatal Intensive Care Unit) for a month. We investigated their SaO2 with the puls-oximeter at the terms between the 2nd and the 10th month. There was no significant difference between SaO2 in prone positions (n = 29) and that in supine positions (n = 30). In the infant with the sniffing conditions, however, SaO2 in prone positions seemed to be slightly lower than that in the healthy conditions. The slightly low SaO2 would give no effects on the healthy infants, but it may cause ALTE (Apparent Life Threatening Event) or death from SIDS (Sudden Infant Death Syndrome) to some infants who are not in good health and/or who are prone to get into ALTEA or SIDS. Especially, in the sniffing condition with hyperthermia, as the oxygen dissociation curve sifts to right and SaO2 degradation appears easily, sudden infant death may be possible to happen in prone position.

Blood Gas Analysis↗

Simple quantification of benzodiazepine receptor binding and ligand transport using iodine-123-iomazenil and two SPECT scans.

UNLABELLED: The feasibility of simplified procedures for the quantification of benzodiazepine receptor binding using [123I]iomazenil and SPECT was assessed. METHODS: Six normal male volunteers were studied. Following intravenous injection of 111 MBq [123I]iomazenil, serial dynamic SPECT scanning was performed for 120 min and the concentration of lipophilic compounds in the arterial plasma was determined by chloroform extraction. Kinetic parameters were estimated by a curve-fitting procedure using the following four models: three-compartment, four-parameter (K1-k4) (3C4P), three-compartment, three-parameter (fixed K1/k2) (3C3P), three-compartment, two-parameter (fixed K1/k2 and k4) (3C2P) and two-compartment, two-parameter (K1 and k2) (2C2P). Kinetic parameters were also calculated by a table look-up procedure with 3C2P using only two SPECT data acquisitions. Parametric images were generated based on the same procedure. RESULTS: In all models, the curve-fitting procedure gave similar outcomes for ligand transport (K1) and receptor density parameters (i.e., binding potential or distribution volume). The 3C4P parameters showed significant correlation between k2 and k3, while 3C3P did not show such a correlation, suggesting the stability of 3C3P. The 3C2P provided parameters essentially identical to those with the 3C3P, indicating the suitability of this model, while 2C2P gave similar distribution volume but obviously low K1. CONCLUSION: Table look-up procedures based on the 3C2P model permit quantification of benzodiazepine receptor binding using [123I]iomazenil with two SPECT scans. This method may be of clinical value in the diagnosis of various diseases.

Adult↗

Ultra-high resolution SPECT system using four pinhole collimators for small animal studies.

UNLABELLED: We describe a newly developed ultra-high resolution SPECT system using four pinhole collimators for small animal studies. METHODS: The system utilizes a clinical four-head SPECT scanner with specially designed pinhole collimators. Four types of pinholes with different configurations were designed with different effective aperture sizes (1.0, 2.0 and 4.0 mm) and rotating radii (40 mm and 50 mm). The distance from the axis of rotation to the scintillator was fixed to 180 mm. A filtered backprojection algorithm was used to reconstruct SPECT images after fanbeam-to-parallel-beam data conversion. RESULTS: The system provided a reconstructed spatial resolution of 1.65 mm (FWHM) and sensitivity of 4.3 kcps/microCi/ml with the best type of pinholes, respectively. The 99mTc-HMPAO SPECT image in rat studies clearly visualized small brain structures, and the left ventricular myocardium and cardiac cavity were clearly separated with 99mTc-MIBI. Dynamic SPECT imaging of rat brain with [123I]iomazenil was also feasible. CONCLUSION: This ultra-high resolution SPECT system can be used to measure the regional distribution of radiolabeled tracers in small animals in vivo and may play a significant role in the development of new radiopharmaceuticals and in studies of various disease models using living animals.

Animals↗