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Biomedical subjects

T Mukai

Publications and source records attributed to T Mukai.

At least 289 records · Page 16Linked to original sources

[Indications and problems of endoscopic treatment for gastrointestinal tract cancers, with special reference to early gastric cancer].

We carried out a clinicopathologic and endoscopic investigation of the relationship between the presence/absence of lymph node or distant metastasis and several crucial factors using resected specimens of early gastric cancer, and concluded that endoscopic treatment was indicated for four types of early gastric cancer: 1) type IIa less than 2 cm in size, 2) focal cancer, 3) so called "gastritis-like" early cancer less than 2 cm in size and 4) polypoid type with mucosal involvement. Up to now, cases of early gastric cancer have been treated by polypectomy, strip biopsy and laser endoscopy. Residual cancer cells were found in 10 out of 20 resected cases. In 2 out of 54 cases followed up for more than one year without any surgical treatment, cancer cells were discovered by biopsy. The effectiveness rate was estimated to be 84% (62/74). Endoscopic treatment was able to provide high efficiency for early gastric cancer of the above types. Causes of ineffectiveness were a lesion more than 2 cm in size, vertical invasion of the lesion into the submucosa and the location of a lesion in a difficult area such as the prepylorus or the cardia.

Aged↗

Molecular gene mapping of human aldolase A (ALDOA) gene to chromosome 16.

Mapping of human aldolase A (ALDOA) gene was performed by molecular hybridization techniques using a panel of human-mouse cell hybrids and sorted fractions of human metaphase chromosomes besides in situ hybridization. For the purpose, three kinds of DNA probes derived from the coding region (probe-1), the 3' noncoding region (probe-2), and the coding and 3' noncoding regions (probe-3) of human aldolase A cDNA clone, pHAAL116-3, were selectively employed. The results of RNA and DNA blot analyses indicated that the human ALDOA gene is located on chromosome 16. The in situ hybridization experiment also indicated that the ALDOA gene was localized to 16q22-q24.

Animals↗

RNA processing by RNase III is involved in the synthesis of Escherichia coli polynucleotide phosphorylase.

The synthesis of Escherichia coli polynucleotide phosphorylase (PNPase) was examined in a mutant strain defective in the RNA processing enzyme RNase III (Rnc-). We found that the specific activity and the synthesis rate of PNPase were increased in the Rnc- strain by more than three times that in an Rnc+ strain. Such increased synthesis of PNPase was not observed in a mutant strain transformed with a plasmid carrying the rnc+ gene. Quantitative analysis of RNA showed that the transcripts from the pnp gene, which encodes PNPase, were degraded more slowly in the Rnc- strain than in the Rnc+ strain. These results indicate that processing of the transcripts by RNase III is intimately involved in controlling the expression of pnp by affecting the stability of its messenger RNA.

DNA Restriction Enzymes↗

Repressor of P elements in Drosophila melanogaster: Cytotype determination by a defective P element carrying only open reading frames 0 through 2.

The P element is a type of transposable element in Drosophila melanogaster. Characteristics of the syndrome of "hybrid dysgenesis" are due to transposition of P elements, and the molecular mechanism for regulation of this transposition has been unknown. In this study a Q strain (which carries only defective P elements in its genome but still is able to repress the transposition of complete P elements although defective in transposase activity) was used to determine the structure of the P element with this repressor (or P cytotype-determining) domain. Examination of the cytotype and structure of the P elements of particular strains with reduced copy number of P elements showed that the P element with a repressor domain was defective, being deleted between bases 1991 and 2448. This region corresponds to most of the third intron [between open reading frame (ORF) 2 and ORF 3] as well as half the ORF 3 of an intact P element. Therefore ORF 3 was deemed to be unnecessary for repressor production.

Journal Article↗

Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation.

Fructose-1,6-bisphosphate aldolase A (fructose-bisphosphate aldolase; EC 4.1.2.13) deficiency is an autosomal recessive disorder associated with hereditary hemolytic anemia. To clarify the molecular mechanism of the deficiency at the nucleotide level, we have cloned aldolase A cDNA from a patient's poly(A)+ RNA that was expressed in cultured lymphoblastoid cells. Nucleotide analysis of the patient's aldolase A cDNA showed a substitution of a single nucleotide (adenine to guanine) at position 386 in a coding region. As a result, the 128th amino acid, aspartic acid, was replaced with glycine (GAT to GGT). Furthermore, change of the second letter of the aspartic acid codon extinguished a F ok I restriction site (GGATG to GGGTG). Southern blot analysis of the genomic DNA showed the patient carried a homozygous mutation inherited from his parents. When compared with normal human aldolase A, the patient's enzyme from erythrocytes and from cultured lymphoblastoid cells was found to be highly thermolabile, suggesting that this mutation causes a functional defect of the enzyme. To further examine this possibility, the thermal stability of aldolase A of the patient and of a normal control, expressed in Escherichia coli using expression plasmids, was determined. The results of E. coli expression of the mutated aldolase A enzyme confirmed the thermolabile nature of the abnormal enzyme. The Asp-128 is conserved in aldolase A, B, and C of eukaryotes, including an insect, Drosophila, suggesting that the Asp-128 of the aldolase A protein is likely to be an amino acid residue with a crucial role in maintaining the correct spatial structure or in performing the catalytic function of the enzyme.

Anemia, Hemolytic, Congenital↗

The genetic structure of natural populations of Drosophila melanogaster. XX. Comparison of genotype-environment interaction in viability between a northern and a southern population.

In order to examine the operation of diversifying selection as the maintenance mechanism of excessive additive genetic variance for viability in southern populations in comparison with northern populations of Drosophila melanogaster, two sets of experiments were conducted using second chromosomes extracted from the Ogasawara population (a southern population in Japan) and from the Aomori population (a northern population in Japan). Chromosomal homozygote and heterozygote viabilities were estimated in eight kinds of artificially produced breeding environments. The main findings in the present investigation are as follows: (1) Significant genotype-environment interaction was observed using chromosomes extracted from the Ogasawara population. Indeed, the estimate of the genotype-environment interaction variance for heterozygotes was significantly larger than that of the genotypic variance. On the other hand, when chromosomes sampled from the Aomori population were examined, that interaction variance was significant only for homozygotes and its value was no more than one quarter of that for the chromosomes from the Ogasawara population. (2) The average genetic correlation between any two viabilities of the same lines estimated in the eight kinds of breeding environments for the chromosomes sampled from the Ogasawara population was smaller than that for the chromosomes from the Aomori population both in homozygotes and in heterozygotes, especially in the latter. (3) The stability of heterozygotes over homozygotes against fluctuations of environmental conditions was seen in the chromosomes from the Ogasawara population, but not from the Aomori population. (4) From the excessive genotype-environment interaction variance compared with the genotypic variance in heterozygotes, it was suggested for the chromosomes from the Ogasawara population that the reversal of viability order between homozygotes took place in some environments at the locus level. On the basis of these findings, it is strongly suggested that diversifying selection is operating in a southern population of D. melanogaster on some of the viability polygenes which are probably located outside the structural loci, and the excessive additive genetic variance of viability in southern populations is maintained by this type of selection.

Alleles↗

Human aldolase B gene: characterization of the genomic aldolase B gene and analysis of sequences required for multiple polyadenylations.

The chromosomal gene encoding human aldolase B was isolated. The gene is composed of nine exons interrupted by eight introns and spans 15 kb, and a single copy of it occurs per haploid human genome. The initiation of transcription occurs at three different sites. Two minor sites, m1 and m2, start at 49 and 21 nucleotides, respectively, upstream from the major site, M. The gene also carries poly(A) addition signals at two different sites, thereby another two distinct mRNA species are produced. We examined the sequences required for mRNA 3'-end formation in this gene carrying multiple poly(A) addition sites. By constructing deletion mutants as to the region distal to the poly(A) addition site and then assaying through transfection into COS-1 cells, we demonstrated that 8 nucleotides distal to the site of poly(A) addition is sufficient for proximal polyadenylation, but is not sufficient for distal polyadenylation.

Animals↗

A case of pancreatic cancer with liver metastasis which responded to chemotherapy.

A case of pancreatic cancer with liver metastasis is reported, in which chemotherapy had a marked effect, with the responses clearly documented. The patient was a 59-year-old male who experienced epigastric pain in February 1985, upper gastrointestinal X-ray examination revealing extragastric compression by the pancreas. He visited the National Cancer Center Hospital, Tokyo, in April 1985 and the diagnosis of pancreatic cancer with liver metastasis was made using the imaging procedures of ultrasonography, computed tomograph scanning and endoscopic retrograde cholangiopancreatography as well as by biochemical and serological tests. At the time a 5 cm tumor was palpable in the middle upper abdomen. The patient was treated with Cis-diaminedichloro platinum, tegafur, and 5-fluorouracil, successively, and the abdominal tumor gradually diminished, finally becoming impalpable. The response was evaluated as one of partial responses (PR) by ultrasonography, and the improvement substantiated by computed tomography and tumor markers.

Cisplatin↗

Expression of three mRNA species from a single rat aldolase A gene, differing in their 5' non-coding regions.

The complete nucleotide sequence of the rat aldolase A isozyme gene, including the 5' and 3' flanking sequences, was determined. The gene comprises ten exons, spans 4827 base-pairs and occurs in a single copy per haploid rat genome. The genomic DNA sequence was compared with those of three species of rat aldolase A mRNA (mRNAs I, II and III) that have been found to differ from each other only in the 5' non-coding region and to be expressed tissue-specifically. It revealed that the first exon (exon M1) encodes the 5' non-coding sequence of mRNA I, while the second exon (exon AH1) encodes those of mRNAs II and III and the following eight exons (exons 2 to 9) are shared commonly by all the mRNA species. These results allowed us to conclude that mRNA I and mRNAs II, III were generated from a single aldolase A gene by alternative usage of exon M1 or exon AH1 in addition to exons 2 to 9. S1 nuclease mapping of the 5' ends of their precursor RNAs suggested that these three mRNA species were transcribed from three different initiation sites on the single gene.

Animals↗

Tissue-specific expression of rat aldolase A mRNAs. Three molecular species differing only in the 5'-terminal sequences.

Three species of aldolase A mRNA (mRNAs I, II, and III) only differing in the structure of the 5'-terminal noncoding region were detected in rat tissues. The cDNA clones for mRNAs II and III were prepared from ascites hepatoma AH60C and sequenced. The mRNA II is 1393 nucleotides long excluding poly(A) tail, while the mRNA III is 1440 nucleotides long, some 50 nucleotides longer than the mRNA II. The mRNAs II and III differ in the sequence between -25 and the 5' termini from the previously reported skeletal muscle aldolase A mRNA (mRNA I, 1343 nucleotides long). By contrast, the residual 5' noncoding sequence (-24 to -1) and the coding and 3' noncoding sequences are common to all the mRNAs. By dot spot hybridization and S1 mapping the distribution of these mRNAs in the various tissues was determined. The mRNA I appears exclusively in a skeletal muscle and some in heart and hepatoma AH60C, whereas the mRNAs II and III appear more or less in all the tissues examined, implying that their appearances are under tissue-specific control. Furthermore, partial nucleotide sequence analysis of the fetal liver aldolase A mRNA supports that aldolase A mRNA that reappeared in hepatoma is really a resurgence of the gene product expressed in the fetus.

Amino Acid Sequence↗

Asynchronous filling in ischemic heart disease and hypertrophic cardiomyopathy.

A multigated blood-pool study was performed to assess regional and global emptying and filling in 16 patients with hypertrophic cardiomyopathy (HCM), 43 patients with ischemic heart disease (IHD), and 14 controls. The regional volume curve was fitted using second-order harmonics in the Fourier series, while the global left-ventricular volume curve was fitted using third-order harmonics. As asynchronous indices, the standard deviations (SD) in distribution histograms of time to end-systole (TES), time to peak ejection (TPE), and time to peak filling (TPF) were obtained in the left ventricle. In patients with IHD, the TPF-SD was higher (14.4 +/- 11.3 degrees) than the TES-SD (7.8 +/- 5.1 degrees) and TPE-SD (8.1 +/- 5.9 degrees), suggesting the presence of asynchronous filling. In patients with HCM, the TPF-SD was also higher (11.6 +/- 11.1 degrees) than the TES-SD (3.5 +/- 2.4 degrees) and TPE-SD (6.2 +/- 4.4 degrees). The phase delay was localized in the anteroseptal or apical region in all 5 HCM patients with abnormal wall motion, while it corresponded with the region of abnormal wall motion in the patients with IHD. The TPF-SD was inversely correlated with the left-ventricular ejection fraction (r = -0.46), peak filling rate (r = -0.50), and the ratio of peak filling rate to peak ejection rate (r = -0.52), suggesting that asynchronous filling is related to global diastolic disturbance. We conclude that asynchronous filling is often present in patients with IHD and HCM, and that our technique can be used to obtain a quantitative assessment of regional asynchronous emptying and filling in these diseases.

Adult↗

[Asynchronous wall motion in patients with ischemic heart disease assessed by higher-order harmonics of the Fourier series].

To assess regional cardiac function in patients with ischemic heart disease (IHD), multigated blood-pool studies using higher-order harmonics of the Fourier series were performed for 14 normal persons and 37 patients with IHD. IHD was further divided into IHD (I) (EF greater than or equal to 50%) and IHD (II) (EF less than 50%). A pixel-by-pixel volume curve was simulated using second order harmonics of the Fourier series to create functional images of the following parameters: time to endosystole (TES), peak ejection rate (PER), time to PER (TPE), peak filling rate (PFR), and time to PFR (TPF). TES (SD), TPE (SD), and TPF (SD) were calculated as the standard deviations of left ventricular (LV) histograms of each phase, representing indexes of asynchronous wall motion. An LV volume curve was simulated using third order harmonics to calculate PFR, PFR/PER, and TPF/TPE, representing indexes of diastolic function. TES (SD) was abnormal in 10 cases (50%), and TPE (SD) was abnormal in seven cases (35%) of IHD (II). On the contrary, TPF (SD) was abnormal in three cases (18%) of IHD (I) and 15 cases (75%) of IHD (II), indicating that diastolic asynchronous indexes are more sensitive than systolic asynchronous indexes in detecting IHD. IHD (I) and IHD (II) showed lower PFR (2.32 +/- 0.55, 1.64 +/- 0.46 EDV/sec) and lower PFR/PER (0.84 +/- 0.15, 0.68 +/- 0.26) than those in normals (3.25 +/- 0.98 EDV/sec, 0.99 +/- 0.19), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

Attenuation and processing of RNA from the rpsO-pnp transcription unit of Escherichia coli.

Ribosomal protein S15 and polynucleotide phosphorylase of E. coli are encoded by two adjacent genes, rpsO and pnp, respectively. Analysis of in vivo transcripts from these two genes shows that they are within the same operon (S15 operon). By correlating the 5' and 3' ends of their in vivo transcripts with the DNA sequence, we have identified several features of the operon structure. These features include a promotor upstream from rpsO, an attenuator downstream from rpsO and an RNA processing site between these two genes.

Chromosome Mapping↗