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Biomedical subjects

N Sugawara

Publications and source records attributed to N Sugawara.

At least 19 recordsLinked to original sources
PubMed1992

Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.

In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu concentrations increased in 7 regions, in particular, significantly so in the striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn concentration were not found in any region. The Fe concentration increased in cortex and olfactory lobes. The three LEC groups showed a very high concentration of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared to the other two LEC groups. These results suggest that the increase of the cerebral Cu concentration is closely related to the inherently abnormal Cu metabolism and then to the changes of Cu metabolism from about 13 weeks after birth.

Animals↗
PubMed1992

The effects of aluminum ingestion on intestinal cadmium absorption, lipid peroxidation and alkaline phosphatase activity.

Consumption of dietary aluminum (A1, 2000 or 4000 ppm) for 1 month did not influence mouse body weight. In order to estimate an absorption of cadmium (Cd) from the gastrointestinal tract, mice were intubated twice every 24 h with Cd (CdCl2). In the A1-supplemented mice, Cd absorption increased rather than decreased. Intestinal Cd and metallothionein concentrations were increased by the A1 supplement. Intestinal alkaline phosphatase activity and lipoperoxide concentrations were also enhanced by A1 ingestion. Of course, intestinal A1 concentration was at a high level in the A1-supplemented groups. However, A1 accumulation was not observed in the liver. The increase of Cd absorption may be due to an abnormality of the gut wall caused by the A1. Our results suggest that A1 is not inert for animals, even though A1 absorption is poor.

Administration, Oral↗
PubMed1992

Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis.

The Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day-old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later.

Animals↗
PubMed1992

Characterization of double-strand break-induced recombination: homology requirements and single-stranded DNA formation.

In the yeast Saccharomyces cerevisiae, a double-strand chromosome break created by the HO endonuclease is frequently repaired in mitotically growing cells by recombination between flanking homologous regions, producing a deletion. We showed that single-stranded regions were formed on both sides of the double-strand break prior to the formation of the product. The kinetics of the single-stranded DNA were monitored in strains with the recombination-deficient mutations rad52 and rad50 as well as in the wild-type strain. In rad50 mutants, single-stranded DNA was generated at a slower rate than in the wild type, whereas rad52 mutants generated single-stranded DNA at a faster rate. Product formation was largely blocked in the rad52 mutant. In the rad50 rad52 double mutant, the effects were superimposed in that the exonucleolytic activity was slowed but product formation was blocked. rad50 appears to act before or at the same stage as rad52. We constructed strains containing two ura3 segments on one side of the HO cut site and one ura3 region on the other side to characterize how flanking repeats find each other. Deletions formed preterentially between the homologous regions closest to the double-strand break. By varying the size of the middle ura3 segment, we determined that recombination initiated by a double-strand break requires a minimum homologous length between 63 and 89 bp. In these competition experiments, the frequency of recombination was dependent on the length of homology in an approximately linear manner.

Base Sequence↗
PubMed1992

Risk of leukemia among participants of gastric mass screening survey in Japan: a population-based, case-control study.

To assess the risks of leukemia for individuals participating in a gastric mass screening program using barium photofluorographic examination in Japan, a population-based, case-control study was carried out. The histories of participation in the last 10 years of 79 leukemia cases diagnosed between 1978 and 1985 and twofold controls matched for sex, age (+/- 5 years), and residence were investigated using the records of the gastric mass screening program. The odds ratio of any type of leukemia for those participating at least once in the last 10 years was 1.09 (95% confidence interval, 0.61-1.96) and that of myeloid type was 0.88 (95% confidence interval, 0.38-2.27). Even when the histories of the preceding 5 years were ignored, no significant excess risks were found among patients with any type and myeloid type of leukemia. These results suggest that there is insufficient evidence to support the positive association between the incidence of leukemia and participation in gastric mass screening. The limitations and implications of this analysis are discussed.

Adult↗
PubMed1992

Copper metabolism in new mutant Long-Evans cinnamon (LEC) rats causing hereditary hepatitis: gastrointestinal absorption and distribution of radioisotopic copper (64Cu).

Long-Evans cinnamon (LEC) rats 60 days old showed a concentration of 127.7 +/- 10.9 micrograms/g of Cu in the liver, compared to 1.6 +/- 0.1 micrograms/g in Fischer rats 60 days old. At 2 hr after an oral injection of 64Cu, total retention of 64Cu in the whole blood, liver and kidneys was 16.8 +/- 3.4% of the dose in LEC rats, compared to 13.1 +/- 1.3% in Fischer rats. The recovery rates of retained-64Cu in the livers in LEC and Fischer rats were 82% and 59%, respectively. More than 90% and about 60% of hepatic 64Cu existed in the cytosol fraction in LEC and Fischer rats, respectively. Furthermore, more than 90% of the cytosolic 64Cu was found as MT in LEC rats. In Fischer rats, this proportion was about 60%. In the duodenum mucosal cytosol fraction from LEC rats, about 50% of 64Cu was bound to metallothionein (MT) protein. In Fischer rats, this proportion was less than 20%. When a 64Cu compound was intraperitoneally injected, 70% and only 15% were recovered in the liver 20 hr after the injection in LEC and Fischer rats, respectively. Furthermore, LEC rats showed very low 64Cu activity in the serum, and their duodenal activities were slightly low compared to Fischer rats. These results suggest that the gross accumulation of hepatic Cu is mainly due to deficient excretion of Cu from the liver.

Animals↗
PubMed1991

Copper metabolism in the LEC rat: involvement of induction of metallothionein and disposition of zinc and iron.

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5 +/- 21.6 micrograms/g liver) than in Fischer rats (5.2 +/- 0.1 microgram/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.

Animals↗
PubMed1991

Gastrointestinal absorption of Cd-metallothionein and cadmium chloride in mice.

CdCl2 or Cd-metallothionein (MT) (6 micrograms Cd with 2.25 muCi (83.25 KBq) 109Cd) was given orally to mice, which were sacrificed at 30 min and 2 h after intubation. Although 109Cd in Cd-MT was excreted rapidly into the urine, its absorption was found to be significantly less than that of CdCl2. The poor absorption was due to a decrease of Cd-MT uptake into the intestine. Cadmium chloride taken up into the mucosa could stimulate MT synthesis even 30 min after its intubation. However, the percentage of MT-bound Cd in the Cd of intestinal supernatants was lower with CdCl2 (62% at 30 min and 2 h) than with Cd-MT (78% and 84% at 30 min and 2 h, respectively). These results suggest that the transport mode of lumenal Cd-MT to mucosal cells is different from that of lumenal CdCl2. Lumenal Cd-MT is probably internalized into intestinal cells in an intact form. Furthermore, the Cd-MT may pass through the basolateral membrane in this form. This hypothesis was supported by the different distributions of Cd in the liver and kidney after Cd-MT and CdCl2 intubations.

Animals↗
PubMed1991

Cost-effectiveness analysis of screening for colorectal cancer in Japan.

To clarify the best cost-effective screening strategy for colorectal cancer in Japan, the cost-effectiveness ratio was compared among six currently performed procedures. The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. In the screening by the immunological fecal occult blood test (FOBT), a comparison between the one- and two-day fecal collection methods indicated that the latter was more cost-effective than the former. A comparison was also made on the four workup methods: barium enema (BE) alone, a combination of BE and sigmoidoscopy (BE + SIG), total colonoscopy (TCF) alone, and a combination of BE and TCF (BE + TCF). The cost-effectiveness ratio was the lowest in the method using TCF alone, followed by those based on BE alone and BE + TCF, and the highest in the BE + SIG method. The superiority of TCF alone strategy was stable over a range of estimates such as the sensitivity of diagnostic tests, the probability of complications due to TCF, etc. It is concluded that a combination of the two-day FOBT and TCF yields the best cost-effectiveness.

Barium Sulfate↗
PubMed1991

Cost-effectiveness analysis of screening for gastric cancer in Japan.

Cost-effectiveness analysis of gastric cancer screening in Japan was performed, and the cost-effectiveness ratio was compared with that of colorectal cancer screening. The analytical model was the same as that adopted in our previous study on colorectal cancer screening (Tsuji et al. 1991). The results indicated that the cost per case-fatality prevented by colorectal cancer screening was 5.5 and 2.7 times more expensive for males and females, respectively, than that by gastric cancer screening. The age of the population influenced the cost-effectiveness of screening programs. The cost-effectiveness ratio in gastric cancer screening became negative among males older than the age of 65 years, suggesting that the total cost for prevention and control of deaths by gastric cancer in these age populations is saved by the screening program.

Adult↗
PubMed1991

Copper metabolism in LEC rats aged 30 and 80 days old: induction of Cu-metallothionein and status of zinc and iron.

In 30- and 80-day-old LEC rats, hepatic Cu and Cu-metallothionein (MT) concentrations were much higher than those in control Fischer rats. The gross deposition was accompanied with enhancements of Zn and Fe concentrations. In LEC rats, more than half of the hepatic Cu was located in the cytosol fraction. Most of cytosolic Cu was bound to MT. In organs other than the liver, sharp depositions of Cu were not found. Both groups of LEC rats showed significantly low serum Cu concentrations and ceruloplasmin activity. The great accumulation of hepatic Cu with the increase of age is due to the inherent depression of the release of Cu from the liver. The deposition may be closely related to the onset of the sudden hepatitis observed in LEC rats.

Aging↗
PubMed1991

Harmful effect of administration of copper on LEC rats.

When four male LEC rats aged 80 days old were given 3.0 mg/kg of Cu once every day for 3 days, all rats showed severe jaundice, and two of them died within 48 hr after the final dose. In Fischer rats given Cu, jaundice or death was not found. With the injection of Cu, the Cu metabolism of Fischer and LEC rats showed different responses. In particular, the concentration of hepatic Cu increased only slightly in LEC rats. Furthermore, LEC rats did not respond to the release of ceruloplasmin to the blood and of Cu to the bile. These results suggest that Cu was very dangerous for LEC rats because of its gross accumulation over the level of homeostasis.

Animals↗
PubMed1991

Distribution of Cu and induction of Cu-metallothionein in mice treated with Cu-nitrilotriacetic acid.

Slightly higher levels of copper were incorporated into the liver in copper-nitrilotriacetic acid (Cu-NTA)-treated mice than in CuSO4-treated mice. There was no difference in the distribution of Cu in hepatic subfractions between the two groups. In the cytosol fraction, however, metallothionein (MT) was significantly decreased in the Cu-NTA-treated mice. Excretion of Cu from liver to bile and blood was not changed in the two groups. The poor induction of MT by Cu-NTA supports the possibility that the compound is more harmful than CuSO4.

Animals↗
PubMed1990

The metabolic effect of carbon monoxide on the heart.

The acute effects of carbon monoxide (CO) on cardiac metabolism at the mitochondrial level were investigated. Rats were exposed to 4% CO for 4 minutes in a closed chamber. Immediately after exposure, hearts were removed and frozen with a precooled clamp. Blood from the thoracic cavity was sampled for analysis. Gas analysis of arterial blood taken from the abdominal aorta demonstrated severe hypoxia with oxygen partial pressure less than 20 mmHg, metabolic acidosis and reduced pH value. There were no significant changes in the plasma level of glucose and non esterified fatty acids (NEFA). In the myocardium, ATP levels decreased significantly, and concomitantly, a significant increase in the plasma uric acid level was observed. Although no significant change was observed in short chain acyl carnitine, free carnitine levels decreased to one fourth of the control value. Long chain acylcarnitine increased 11-fold. Coenzyme Q9 (CoQ9) level decreased significantly, but there was no significant change in Coenzyme Q10 (CoQ10).

Adenosine Triphosphate↗
PubMed1990

Concentration in, and binding of several metals by myelin from mice.

There was no significant difference between 6 and 28 week old mice, in the concentration of some elements, Zn, Cu, Fe and Mg in whole brain and myelin. Ca was found at a high level in myelin, compared to the whole brain. The binding activity of two neurotoxic metals, Cd and Mn to the myelin was not changed by ageing. However, the binding of some metals was different. In particular, Zn and Pb showed high values. Lipid peroxide (LPO) used as an index of age-associated changes did not increase in the brain of the 28-week-old group. However, testicular and cardiac LPO increased significantly in the 28-week-old mice than in the 6-week-old mice. At least, judging from the LPO concentration, it seems that the age-associated changes of the brain were not yet found in the 28-week-old mice.

Adenosine Triphosphatases↗
PubMed1990

[The analysis of peripheral blood lymphocyte subsets in patients with Epstein Barr virus induced hepatitis].

Both humoral and cell-mediated immunity to Epstein Barr virus related antigen have recently been reported and are thought to be important for the generation of Epstein Barr virus induced human diseases. For this reason, to study immunological features in Epstein Barr virus induced hepatitis (EBH), we studied the ratio of various immunocompetent cells in peripheral blood and compared them to that of healthy control and acute hepatitis (disease control). We found that a significant elevation of CD8+ CD11- cells existed in EBH patients (48.9 +/- 18.3% in EBH, 17.0 +/- 6.9% in AH and 13.6 +/- 7.0% in healthy control) and atypical lymphocytes which are frequently observed in EBH belong to CD8+ CD11- cells. Regarding the study of surface expression of activated T cell markers, we found that these CD8+ cells also expressed HLA-DR antigen on their cell surface. Furthermore, the percentage of CD8+ CD11- cells returned to normal level with the recovery of their liver function. From these results, we can assume that activated CD8+ CD11- cells may have an important roles in generation of EBH.

Adult↗