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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 253 records · Page 14Linked to original sources

Physical training and fasting erythrocyte activities of free radical scavenging enzyme systems in sedentary men.

Effects of 10 weeks of physical training on free radical scavenging enzyme systems in erythrocytes were investigated in 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. Their maximum oxygen uptake and 12 min walk-run performance increased significantly after training. Of the antioxidant enzyme systems examined in the erythrocytes, both catalase activity and concentration and total glutathione reductase (GR) activity also showed significant increases following the training. The erythrocyte GR activity coefficient also increased significantly. These results suggest that chronic aerobic exercise increases riboflavin requirements and has some positive effects on antioxidative processes.

Adolescent↗

Expression of tissue-specific genes in transgenic mice.

The ability to introduce cloned genes into mouse germ line has been used for analyzing cis-acting DNA sequences involved in tissue-specific and developmental regulation of the introduced gene. Using this system we have attempted to produce a transgenic mouse model for human dominantly inherited disease, familial amyloidotic polyneuropathy. Recently the mutant transthyretin gene which is considered to be responsible for this disease has been cloned and well characterized at molecular level. We have produced transgenic mice by microinjecting human mutant gene. Amyloid deposition was observed in the mucosa of alimentary tract and renal glomeruli, suggesting that this approach is successful in establishing the mouse model for human genetic disease. In addition, these experiments suggest that the expression of the mutant gene is regulated normally during developmental process and that the cause of adult onset is not due to the dysregulation of this gene expression.

Amyloidosis↗

Effect of physical training on immunoreactive gamma-glutamyltransferase in human plasma.

The effects of 10-week physical training on both the activity and concentration of gamma-glutamyltransferase (gamma-GT) in plasma were investigated on 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. The maximal oxygen uptake (Vo2max) and 12-min field performance increased significantly after training, from 43.5 and 2,683.7 to 48.1 ml.kg-1.min-1 and 2,931.1 m, respectively. After training the resting plasma gamma-GT concentration decreased to half, whereas the gamma-GT activity did not vary substantially. The training did not affect the response to the Vo2max test of either concentration or activity of gamma-GT. These results may suggest that plasma gamma-GT concentration is useful as an index of the extent of physical training.

Adolescent↗

No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D.

A 31-year-old female patient with xeroderma pigmentosum (XP) XP43KO was assigned to complementation group D by the cell-fusion complementation methods. Cultured XP43KO cells from our patient had the defective DNA repair phenotype showing a residual level of ultraviolet (UV)-induced unscheduled DNA synthesis (45% of normal) and an eightfold higher sensitivity to 254-nm UV killing, compared with normal cells. The phototest on the patient revealed the delayed maximum reaction to UV-B-induced erythema and lower minimal erythema doses at 290- and 300-nm monochromatic wavelengths. However, the XP43KO patient showed no apparent neurologic abnormalities and rather mild or moderate skin lesions at the age of 31 years, although DNA repair deficiency in XP43KO cells from our patient fell into the range of group D cells.

Adult↗

Tissue-specific and developmental expression of human transthyretin gene in transgenic mice.

To analyze the regulation of transthyretin gene expression we have produced transgenic mice by microinjecting cloned human transthyretin genes into fertilized eggs of C57BL/6 mice. The 7.6-kilobase (kb) human transthyretin gene containing about 500 base pairs (bp) in the upstream region was used for microinjection. Seven out of nine transgenic mice had detectable amounts of human transthyretin in serum when analyzed by enzyme-linked immunosorbent assay. Transthyretin mRNA was detected in liver and yolk sac but not in other tissues including brain. The amount of mRNA was variable among transgenic mice and was about one-tenth of mouse endogenous transthyretin mRNA. Human and mouse transthyretin mRNAs were detected in liver of fetus and yolk sac at 13 days of gestation and unlike yolk sac the level of mRNA in liver increased gradually during development and reached the maximum at around 17 days of gestation. Human transthyretin was associated with mouse transthyretin to form tetramers as judged from the dilution curve of enzyme-linked immunosorbent assay and the spur formation in Ouchterlony assay.

Animals↗

Metastatic brain tumour and fibrinopeptides.

Tumour growth essentially requires fibrin formation and fibrinopeptide A (FPA) is liberated into the circulation of fibrin formation. In the present study, a possible elevation of serum FPA level was examined in patients with metastatic brain tumour. A significant elevation of serum FPA level was shown in all 6 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. It was extremely high in 2 patients with rapidly growing tumour. However, such a significant elevation was not shown in 3 cancer patients without brain metastasis or in 1 patient with a huge meningioma. This suggests the possibility that the presence of metastatic brain tumour could be detected by measuring FPA in blood drawn form the internal jugular vein. This also suggests the tendency that elevation of serum FPA is higher in patients with more rapidly growing tumour. Infusion of urokinase into the internal carotid artery resulted in an elevation of serum fibrinopeptide B beta (1)15-42 (FPB beta) in 5 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. This suggests that urokinase could induce fibrinolysis in the tumour tissue, though this remains in conclusive because of the lack of complete controls.

Adult↗

The mode of hepatitis B virus DNA integration in chromosomes of human hepatocellular carcinoma.

Nineteen DNA samples that carry integrated hepatitis B virus (HBV) DNA were isolated from seven independent human hepatomas by molecular cloning, and their structures were determined. The results, combined with reported data, were analyzed so that one can obtain insights into the mechanisms of integration of this virus DNA and possible rearrangements that occur subsequently. The distribution of DNA junctions along the virus genome suggests that there are recombination-proficient regions. Thus, about half of the integrants were the Coh type, viz., one of their virus-cell DNA junctions fell within the so-called cohesive end region that lies between two 11-bp direct repeats (DR1 and DR2) in the virus genome where transcription and replication of the genome are initiated. All the integrated virus genomes were defective at least in one site around the cohesive end region, particularly within the X gene. The recombination-proficient regions are used not only for formation of virus-cell but also of virus-virus junctions. Neither virus nor cell DNA show unique sequences at the junctions, and targets for integration lie on many different chromosomes.

Base Sequence↗

Molecular genetics of familial amyloidotic polyneuropathy.

We established a diagnosis of familial amyloidotic polyneuropathy (FAP) based on DNA and demonstrated a direct link between prealbumin gene mutation and FAP. The individuals with FAP, so far examined, were heterozygous for the prealbumin gene, carrying one normal and one mutant gene. To investigate the molecular pathogenesis of FAP, we isolated a normal prealbumin gene (7 kb in length) and also a mutant prealbumin gene associated with FAP. We compared their nucleotide sequences and found that they matched except for a single-base substitution present in the second exon. In an effort to construct mouse model systems for the FAP, we developed strains of transgenic mice carrying human mutant prealbumin genes.

Amyloidosis↗

Methylation of hepatitis B virus DNA and liver-specific suppression of RNA production in transgenic mouse.

Three lines of transgenic mice carrying hepatitis B virus (HBV) DNA were produced. In a pSHB1BB transgenic mouse carrying one copy of BamHI fragment of HBV with a deletion of Bg/II-Bg/II fragment, no RNA transcription was observed. Transgenic mice that had integrated either one or three tandem copies of HBV DNA produced RNA in various tissues except liver. However, neither initiation nor termination of transcription occurred at the correct place. Hepatitis B surface antigen and hepatitis B e antigen were not detectable in these transgenic mice. HBV DNA was methylated at all CCGG sequences, which might have resulted in aberrant RNA production. In two out of five transgenic mice HBV DNA was integrated into the Y chromosome. Although the frequency is unusually high, the mechanism is not known yet.

Animals↗