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Biomedical subjects

K Mita

Publications and source records attributed to K Mita.

At least 19 recordsLinked to original sources

Evolutionarily conserved structure of the 3' non-translated region of a Chinese hamster polyubiquitin gene.

From a V79 Chinese hamster genomic library, we isolated a clone containing a polyubiquitin gene (designated as CHUB1), and determined its nucleotide sequence. The coding region of the CHUB1 gene consisted of five direct repeats of the ubiquitin unit with no spacer, followed by a single tyrosine residue. Northern hybridization analysis with a synthesized probe specific to the 3' non-translated region of the CHUB1 gene revealed that it codes for a 1.8 kb mRNA. An evident homology to the human polyubiquitin gene UbB and the chicken UbI gene was observed in the region corresponding to the full extent of the mature mRNA sequence, suggesting that these three genes belong to a common polyubiquitin gene subfamily, and that the sequence in the 3' non-translated region of the CHUB1 gene is unique to this subfamily.

Amino Acid Sequence

Essential role of duplications of short motif sequences in the genomic evolution of Bombyx mori.

The Bombyx fibroin gene has a discrete mosaic structure of various repetitive sequences, which may have evolved through various repeating arrangements. Detailed sequence analysis of the fibroin gene containing coding and noncoding regions revealed that the whole sequence could be arranged as an array of short repetitive sequences. A portion of the intron of the fibroin gene is one of interspersed repetitive elements. We cloned a 1.5-kb DNA fragment of the Bombyx genome that contains interspersed elements homologous to the intron sequence. Sequence comparison between the intron and the 1.5-kb fragment shows that partial duplication has frequently occurred in evolutionary progress, and the resultant repetitive blocks of short motif sequences are abundant in the genome. These facts suggest that tandem duplication of the short motif sequence is an important rearrangement in genomic evolution of the fibroin gene.

Animals

Spontaneous rupture of hepatocellular carcinoma: an approach with delayed hepatectomy.

Two cirrhotic patients with ruptured hepatocellular carcinoma (HCC), presenting with hemoperitoneum, were successfully treated by elective hepatectomy. Both of these patients, a 67-year-old female and a 76-year-old male, had first been taken to other primary hospitals by ambulance due to hypovolemic shock. They were then found to have a mass of approximately 5 cm in the cirrhotic liver. In the initial management, however, neither any direct hemostasis by surgery nor indirect measures such as transcatheter hepatic arterial embolization were performed in either case. Instead, conservative treatment consisting mainly of fresh blood and plasma transfusions were continued for more than a month until the liver function stabilized. In both hepatectomies, the use of a microwave tissue coagulator resulted in minimal intra-operative blood loss and an appreciably excellent post-operative course. These cases point to the effectiveness of a "wait and see" policy for selected patients with ruptured HCC.

Aged

Essential factors determining codon usage in ubiquitin genes.

Ubiquitin is ubiquitous in all eukaryotes and its amino acid sequence shows extreme conservation. Ubiquitin genes comprise direct repeats of the ubiquitin coding unit with no spacers. The nucleotide sequences coding for 13 ubiquitin genes from 11 species reported so far have been compiled and analyzed. The G + C content of codon third base reveals a positive linear correlation with the genome G + C content of the corresponding species. The slope strongly suggests that the overall G + C content of codons of polyubiquitin genes clearly reflects the genome G + C content by AT/GC substitutions at the codon third position. The G + C content of ubiquitin codon third base also shows a positive linear correlation with the overall G + C content of coding regions of compiled genes, indicating the codon choices among synonymous codons reflect the average codon usage pattern of corresponding species. On the other hand, the monoubiquitin gene, which is different from the polyubiquitin gene in gene organization, gene expression, and function of the encoding protein, shows a different codon usage pattern compared with that of the polyubiquitin gene. From comparisons of the levels of synonymous substitutions among ubiquitin repeats and the homology of the amino acid sequence of the tail of monomeric ubiquitin genes, we propose that the molecular evolution of ubiquitin genes occurred as follows: Plural primitive ubiquitin sequences were dispersed on genome in ancestral eukaryotes. Some of them situated in a particular environment fused with the tail sequence to produce monomeric ubiquitin genes that were maintained across species. After divergence of species, polyubiquitin genes were formed by duplication of the other primitive ubiquitin sequences on different chromosomes. Differences in the environments in which ubiquitin genes are embedded reflect the differences in codon choice and in gene expression pattern between poly- and monomeric ubiquitin genes.

Amino Acid Sequence

Advantages of triple therapy with mizoribine, cyclosporine and prednisolone over other types of triple and/or double therapy including cyclosporine for renal transplantation.

Mizoribine (Mz) is an analogue of azathioprine (Az) with less hepatotoxicity, being extensively used as immunosuppressant in place of the latter agent especially in Japan. However, careful comparative studies of mizoribine (Mz), cyclosporine (Cy), and prednisolone (Pr) versus azathioprine (Az), Cy and Pr or Cy and Pr in renal allotranspalnt patients have not been reported. Retrospectively we compared triple therapy with Mz, Cy, and Pr (group I, n = 50) to triple therapy with Az, Cy and Pr (group II, n = 13) and/or double therapy with Cy and Pr (group III, n = 11) in one-haplotype-identical living related renal transplantations performed between Oct. 1984 through March 1989. Initial and maintenance doses of Cy in groups I and II were largely two thirds of those in group III. Patient and graft survival rates at 3 years in each group are 100% and 92% (group I), 100% and 91% (group II), and 91% and 82% (group III). There were no statistical differences in patient and graft survival rates between these three groups. The incidences of miscellaneous complications were the same in the groups. Bone marrow suppression, however, was significantly less in group I than in group II (P less than 0.005). Cy related nephrotoxicity was apparently less in groups I and II than in group III. Estimated US $5,000 in a year can be saved by immunosuppressive treatment in a patient of group I as compared to a patient in group III. Therefore, we conclude that triple therapy with Mz, Cy and Pr is superior to those with Az, Cy and Pr, and/or double therapy with Cy and Pr.

Cyclosporine

Assessment of daily physical activity levels of severely disabled persons using heart rate series.

Daily physical activity levels of severely disabled persons were assessed by means of a statistical analysis of their heart rate during a 24-h period. A non-Gaussian probability density function of the heart rate was calculated and separated into two levels of heart rate distributions, i.e. a relatively lower heart rate for basic daily activity and a relatively higher heart rate relating to vigorous activity. Disabled persons with low ambulatory ability showed daily activity levels similar to normal subjects in the length of time and the level of the heart rate. Their daily activity satisfied their needs for maintaining good health. However, more prolonged vigorous activity in daily living was necessary to improve cardiovascular fitness. For severely disabled persons without ambulatory ability, almost all of the heart rates during daily activity were categorized into the lower heart rate distribution. Their low level of physical activity may lead to a serious decrease in cardiovascular function with its attendant risk of cardiopulmonary disease.

Activities of Daily Living

Non-stationary analysis of electromyographic activity prior to a ballistic voluntary contraction.

The electromyogram (EMG) in a ballistic voluntary action of muscle after a slight sustained contraction shows a short period of decrease or disappearance of the activity prior to the onset of phasic discharge. The EMG of elbow extensor (triceps brachii) prior to phasic discharge was analyzed as a non-stationary stochastic process. The distribution of the EMG amplitude began to change from 100 ms before the phasic discharge. The statistical test showed that the EMG activity became non-Gaussian from 30 to 50 ms before the phasic discharge. The standard deviation of the EMG showed a decreasing tendency from 80 to 100 ms prior to the phasic discharge. The statistical evidence for the EMG depression was also confirmed in fourth and sixth order coefficients of the orthogonal expansion of the probability density function. These results suggested that the EMG process profoundly changed its statistical characteristics just before the phasic discharge.

Action Potentials

Statistical approach for the estimation of daily physical activity levels using the probability density function of heart rate.

An investigation was undertaken into the statistical properties of heart rate during daily physical activity. The probability density function of the heart rate was estimated using the Gram-Charlier series. In addition, the probability density was separated into two Gaussian distributions: relatively low and relatively high heart rates. The former appeared to correspond to the metabolic rate associated with basic daily living and the latter appeared to be associated with more active physical activity of the type necessary to sustain or elevate the level of physical fitness. The higher heart rate distribution of five subjects occupied 8.72 +/- 2.15% of a period of waking. The validity of the statistical approach was confirmed with fractional estimation error of 1.22 +/- 0.62%.

Heart Rate

[Clinical studies on 228 renal transplants].

We studied patient survival and graft survival rates by dividing 228 renal transplants into seven groups according to their immunosuppressive regimen and the degree of histocompatibility. Both patient survival and graft survival rates of HLA identical sibling (Id Sib), living related transplantation with cyclosporin (CYA), transplantation with donor-specific transfusion and anti-lymphocyte globulin (DST.ALG) and cadaveric transplantation with cyclosporin (CYA.Cad) groups were better than those of living related transplantation with ALG, without DST (ALG), living related transplantation with azathioprine and steroid (Non-DST.Non-ALG) and cadaveric transplantation without cyclosporin (Conv.Cad) groups. The incidence and severity of acute rejection were lower in Id Sib, CYA, DST.ALG and CYA.Cad groups than in other groups. The incidence of infections was the highest in Conv.Cad group and that of fatal infections was higher in ALG, Non-DST.Non-ALG and Conv.Cad groups than in other groups. These results indicated that acute rejection and infection were two important factor that influenced the survival rates of these patients. Up to now, the graft survival rate of CYA.Cad group has been much improved as compared to that of Conv.Cad group and was better than those of ALG and Non-DST.Non-ALG groups. The fact urges us to promote more cadaveric renal transplantation in our country by virtue of ciclosporin.

Adult

Identification of a novel class of elastase isozyme, human pancreatic elastase III, by cDNA and genomic gene cloning.

By using porcine elastase I cDNA as a probe, we have isolated two different but closely related cDNAs encoding elastase-like proteases from a human pancreatic cDNA library. The amino acid sequences deduced from the cloned cDNA sequences showed 56-61% identity with those of both pancreatic elastases I and II, similar to the homology between elastases I and II. The active form of the elastase-like proteases appeared to be composed of 242 amino acids and preceded by a signal peptide and propeptide of 28 amino acids. Dot blot analysis of various tissue mRNAs demonstrated that the genes for the cloned cDNAs are expressed at a high level only in the pancreas. In addition, sequence analysis of the cloned genomic genes corresponding to one of the cDNAs showed that they are members of the elastase gene family. These results indicate that the two enzymes encoded by the cDNAs should be classified into a third class of elastase isozyme. Therefore, we designated them as human pancreatic elastases IIIA and IIIB. They strongly resembled cholesterol-binding pancreatic protease, suggesting that they may possess not only a digestive function but also function(s) related to cholesterol metabolism or transport in the intestine.

Amino Acid Sequence