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Biomedical subjects

T Mukai

Publications and source records attributed to T Mukai.

At least 199 records · Page 11Linked to original sources

Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and linearization based on permeability-surface area product model.

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.

Adult↗

Discriminated release of a hippurate-like radiometal chelate in nontarget tissues for target-selective radioactivity localization using pH-dependent dissociation of reduced antibody.

UNLABELLED: To achieve high and selective target radioactivity localization by monoclonal antibodies (Mabs) labeled with metallic radionuclides, the discriminated release of a hippurate-like radiometal chelate in nontarget tissues was performed using chemically modified Mabs. METHODS: The disulfide bonds of a Mab against osteogenic sarcoma (OST7, IgG1) were reduced and 67Ga chelate of succinyldeferoxamine (SDF) was conjugated proximal to the Mab molecule via an ester bond with exposed thiol groups (67Ga-DFO-MESS-redOST7), which would impair esterase access to the ester bond of 67Ga-DFO-MESS-redOST7 due to the steric interference induced by bulky antibody molecule, stabilizing the ester bond in plasma and on the target cell's surface. Gallium-67-SDF was also conjugated to OST7 via an ester bond with 2-iminothiolane to render the ester bond in a position distal from the OST7 molecule (67Ga-DFO-MESS-IT-OST7). RESULTS: Although SDS-PAGE analyses of 67Ga-DFO-MESS-redOST7 showed a partial cleavage of its disulfide bonds, size-exclusion HPLC and cell binding assays indicated that the IgG structure and immunoreactivity of this conjugate were preserved in a neutral buffer and plasma of the systemic circulation. CONCLUSION: The present radiochemical design of an antibody utilizing pH-dependent dissociation would constitute a promising approach in establishing selective target radioactivity localization by Mabs.

Animals↗

[Neuropathological study of battered child syndrome: eight autopsy cases].

The term "battered-child syndrome" was coined by Kempe in 1962. The morphology of brain lesions in abused children is rarely reported in Japan. This clinicopathological entity in the central nervous system is characterized by retinal hemorrhages, subdural and subarachnoid hemorrhage. However, reports on microscopic findings of intracerebral lesion are fewer than those on macroscopic findings of scalp, skull and intracranial cavity. This study was performed on 8 cases of battered children who were autopsied. They consisted of six female and two male infants. The age ranged from one week to four years old. The causes of the injuries were shaking in four cases, throwing in three cases, dropping in two cases and strangling in one case, mostly in combination. CT scans were examined for three cases. CT scan revealed acute cerebral swelling and acute subdural hematoma with interhemispheric blood clot in three cases and multiple low density area in one case. Evacuation of the subdural hematoma and external decompression was performed in one case. The survival period from injury to death was one day in four cases, and 2, 3, 9 and 41 days in the others. In the gross anatomical findings there are many excoriations and bruises of the face and scalp in five cases, widespread subcutaneous hematoma in all cases and skull fracture in only two cases. The brain weight was exceedingly heavier than normal brain weight by age in five cases. In the macroscopic findings, there were marked cerebral swelling and cerebral herniation in all cases, traumatic subarachnoid hemorrhage in six cases, and thin widespread acute subdural hematoma with interhemispheric clot in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Axons↗

A new imprinted gene cloned by a methylation-sensitive genome scanning method.

We cloned a new imprinted gene by searching for parental-origin-specific CpG methylations using methylation-sensitive two-dimensional genome scanning method. This gene encodes a putative 51 kDa protein with significant similarity to U2 small nuclear ribonucleoprotein auxiliary factor small subunits, an essential mammalian splicing factor, and is located on mouse chromosome 11, of which maternal duplication/paternal deficiency results in a small body.

Amino Acid Sequence↗

Human tissue factor pathway inhibitor (TFPI) gene: complete genomic structure and localization on the genetic map of chromosome 2q.

Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. We have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5' noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 59 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline gamma-polypeptide locus CRYGP1(p5G1).

Base Sequence↗

Distribution of polymorphic gene duplication at the Gpdh locus in natural populations of Drosophila melanogaster.

The glycerol-3-phosphate dehydrogenase (GPDH, E.C. 1.1.1.8) gene of Drosophila melanogaster contains a tandem duplication of a 4.5-kb-long DNA fragment. Survey of the Gpdh gene region by the Southern blot analysis revealed the following features of this gene duplication: (1) The duplication was not observed in chromosome lines that carry In(2L)t, a cosmopolitan chromosomal inversion in this species. The duplication and the inversion are in linkage disequilibrium. (2) The duplication is polymorphic in the Japan and US natural populations examined. Its frequency is 0.26 on an average in In(2L)t-free chromosomes. (3) Triplication is absent or has not become frequent in the populations surveyed. Possible evolutionary factors of this duplication polymorphism are discussed.

Alleles↗

Successful resection of a recurrent leiomyosarcoma of the pulmonary trunk.

We successfully performed a total resection of the pulmonary artery trunk and replaced it with an equine pericardial xenograft roll in a patient with a recurrent leiomyosarcoma. We believe, based on anatomic and embryologic principles, total rather than partial resection of the pulmonary artery trunk should be the treatment of choice for primary leiomyosarcomas of the pulmonary artery.

Aged↗

A type of incompatibility between genes and their genetic background inducing decrease in heterozygote viability approximately equal to that of homozygotes, found in a natural population of Drosophila.

In the Osaka population of Drosophila melanogaster, we found an incompatibility between second chromosomes and their genetic backgrounds, where a decrease in the average viability of heterozygotes in the foreign genetic background relative to that of the native one (A'/A = 0.889) was about equal to that in non-lethal homozygotes (C'/C = 0.874). This feature is different from that of the incompatibility found in the Ishigakijima population, where little difference in average viabilities of heterozygotes between the native and foreign backgrounds was found, whereas in mean non-lethal homozygotes viabilities a large decrease was seen. This feature is supposed to be induced by the P-M hybrid dysgenesis, as strong P-transposase activity was shown in this population with the GD sterility test. Although a property similar to that of the Osaka population had been detected in the Katsunuma population, an increased frequency of the lethal-carrying chromosomes had been found in the foreign genetic background relative to the native one, and was not seen in the Osaka population.

Animals↗

Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection.

Human herpesvirus-7 (HHV-7), which is a newly identified human herpesvirus with an unknown pathologic role, was isolated from a 5-year-old boy suffering from fever, hepatosplenomegaly and pancytopenia. Although the clinical course was similar to that of chronic active Epstein-Barr virus infection, no viruses other than HHV-7 were isolated. This finding raises the possibility that HHV-7 played a pathogenic role in the present patient.

Child, Preschool↗

The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene.

The rat aldolase A gene contains two alternative promoters and two alternative first exons. The distal promoter M is expressed at a high level only in skeletal muscle. Previous in vitro transfection studies identified the region from -202 to -85 as an enhancer that is responsible for dramatic activation during the differentiation of chicken primary myoblasts. This enhancer contains an A/T-rich sequence resembling the MEF-2 motif, which is an important element of muscle enhancers and promoters. In this study, we demonstrate that the MEF-2 sequence is essential but not sufficient for the activity of the enhancer. Another region required for the activity was recognized by a nuclear factor, tentatively named MAF1. MAF1 was found in both muscle cells and nonmuscle cells, and MAF1 from both cell types was indistinguishable by gel retardation and DNase I footprint experiments. The sequence required for MAF1 binding is very similar to the MEF-3 motif, which is an element of the skeletal muscle-specific enhancer of the cardiac troponin C gene. Because MAF1 and MEF-3 are closely related in both recognition sequence and distribution, MAF1 and MEF-3 probably represent the same nuclear factor which may play an important role in muscle gene transcription. Thus, the muscle-specific induction of the aldolase A gene is governed by muscle-specific MEF-2 and existing MEF-3 (MAF1).

Animals↗

Detection of enteroviral genome and its significance in cardiomyopathy.

Myocarditis is an important disease that can lead to dilated cardiomyopathy (DCM). Using the polymerase chain reaction (PCR), we examined whether viral genomes were present specifically in the hearts of viral myocarditis or DCM patients in our autopsy series and compared the results with their clinicopathological features. We applied three different criteria of myocarditis to fully describe the histological features. The presence of a viral genome was detected by PCR but was not specific in DCM or myocarditis. PCR might be helpful in the diagnosis of viral myocarditis, when combined with other clinical information.

Adult↗

Spontaneous mutation rates in null and band-morph mutations of enzyme loci in Drosophila melanogaster.

Spontaneous mutations were accumulated for a total of 1,678,388 allele-generations in several hundred replicate second chromosome lines. These lines were compared of a Cy chromosome and one of three different lethal bearing chromosomes from natural populations. Electrophoretic mobility and/or activity change was screened for seven enzyme loci. Forty-four null mutations were detected, but no band-morph mutations were observed. There is significant variation in null mutation rate among enzyme loci and among lethal chromosomes. This may be attributable to differences in the distribution of transposable elements among the lines. The band-morph mutation rate is pooled with previous results and becomes 7.48 x 10(-7) with a 95% confidence limit of 2.04 x 10(-7) to 1.91 x 10(-6) per locus per generation. Similarly, the pooled null mutation rate becomes 1.30 x 10(-5) with 95% confidence limit of 1.15 x 10(-5) to 1.52 x 10(-5) per locus per generation.

Animals↗

[Effect of dynamic cardiomyoplasty on the left ventricular function and hemodynamics in chronic canine models].

This study was undertaken to examine the effect of cardiac assist and left ventricular function after dynamic cardiomyoplasty (DCMP). In the first group (GI) of 10 mongrel dogs DCMP was drived immediately after wrapping both ventricles by latissmus dorsi muscle flap (LDMF). In the second group (GII) of 10 mongrel dogs DCMP was derived over 6 weeks after production of DCMP for achievement of complete adhesion between LDMF and myocardium. In the both groups, aortic pressure, cardiac output, left ventricular systolic pressure, and ejection fraction of the left ventricle were significantly increased by DCMP driving (p < 0.001). But left ventricular systolic pressure was remarkably increased in GII compared with that of GI (21.2 +/- 10.2% versus 14.0 +/- 9.6%, p < 0.001), and end diastolic pressure of the left ventricle was apparently decreased in GII (61.6 +/- 42.3% p < 0.05). Thus, satisfactory results were recognized that cardiac assist for left ventricular function was enhanced after completion of adhesion between myocardium and LDMF. Echocardiography in GII demonstrated that left ventricular systolic dimention was significantly decreased from 33.8 +/- 1.0 mm to 27.6 +/- 1.2 mm (p < 0.001). Thus, left ventricular fractional shortening was significantly increased from 24.0 +/- 2.4% to 38.0 +/- 2.6% (p < 0.001). However, left ventricle end-diastolic dimention was not changed even during DCMP driving. So disturbance in left ventricular function during diastole could not be recognized. In conclusion, especially after adhesion of both muscles of LDMF and myocardium, effect of cardiac assist was remarkably enhanced, and disturbance of diastolic function of the left ventricle could not be observed.

Animals↗

[Effect of dynamic cardiomyoplasty on coronary arterial blood flow].

We investigated whether or not dynamic cardiomyoplasty adversely affected coronary arterial blood flow (CABF) through compression of the coronary arteries by muscular contraction during systole and incomplete relaxation of the skeletal muscle flap during diastole. Dynamic cardiomyoplasty was performed in 20 mongrel dogs using a left latissimus dorsi muscle flap, paced synchronously with the R wave of the electrocardiogram. A Doppler catheter (3 F in diameter) was placed in the left main trunk of the coronary artery to analyze the instantaneous changes of coronary arterial blood flow velocity by fast Fourier transformation analysis. We compared both systolic and diastolic properties during assisted versus unassisted cardiac cycles by calculating the peak velocity and the time velocity integrate (TVI). A significant enhancement of systolic CABF was recognized by increases in the systolic peak velocity (26.5 +/- 29.2%) and TVI (20.2 +/- 38.6%). The improved systolic CABF was consistent with an increase in systolic aortic pressure (15.5 +/- 4.3%) and stroke volume (42.8 +/- 11.2%). CABF was also enhanced in diastole because a significant increase of diastolic peak velocity (4.4 +/- 9.4%) and TVI (11.0 +/- 16.7%) was observed. Enhancement of diastolic CABF was associated with the augmentation of cardiac function and the reduction of left ventricular end-diastolic pressure. It could be concluded that CABF was increased by the enhancement of cardiac function as a result of dynamic cardiomyoplasty leading to an increase of cardiac output and aortic pressure and a decrease of left ventricular end-diastolic pressure.

Animals↗

[Statistical observations on the cases of unnatural deaths examined at our department during the past 10 years].

Medicolegal evaluation of 1495 cases of unnatural death of last 10 years was carried out in our department and the data so obtained were statistically analysed. The cases consisted of 260 inspections, 865 judicial autopsies and 370 administrative autopsies. The most frequent category was death from diseases followed by suicide, homicide, traffic accidents, other accidents and self originated accidents. In homicide cases, sharp objects were mainly used. Six cases of accident of scuba diving were included within the group of 28 cases of drowning of self originated variety. Although Okinawa is subtropical 12 cases of death by accidental hypothermia were found. Gangland fight using rifles cost 7 lives, 2 policemen, a high school student and 4 members of locally originated gangsters during last 18 months. Cardiac insufficiency was the most common of sudden unexpected death cases that complied with the data of Tokyo and Osaka. Death from alimentary disorder in Okinawa was 1.5 times more frequent than that in Tokyo and Osaka and liver disorder accounted for about 41%. The 68 cases of death from suckling contained 10 SIDS cases. Complication of medical treatment was encountered in 9 cases during the past 10 years.

Adolescent↗

Genomic analysis of human hepatocellular carcinomas using Restriction Landmark Genomic Scanning.

Restriction Landmark Genomic Scanning (RLGS) was used to examine the multiple alterations of genomic DNAs that occur in association with transformation and development of malignancy in primary hepatocellular carcinoma (HCC). Genomic DNAs from HCC and its normal counterpart were cleaved by the restriction enzyme NotI, radiolabeled at the cleavage sites, and then size-fractionated by two-dimensional electrophoresis using HinfI as the second cleavage enzyme. About 2000 spots were recognized, whose position and intensity reflect the locus and the copy number of the corresponding restriction sites. Using this system in combination with micromanipulation of HCC to eliminate possible carry-over of nonmalignant cells, we detected six spots that were decreased in intensity in common to three different HCCs, along with five that were intensified spots. In addition, several spots showed changes that were nonoverlapping among different tumors.

Carcinoma, Hepatocellular↗