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Biomedical subjects

S Kamiyama

Publications and source records attributed to S Kamiyama.

At least 37 records · Page 2Linked to original sources

Demonstration of a new mouse mammary tumor virus locus in the genome of the mammary tumor prone strain SHN mouse.

Until this report, there have been no detailed analyses of the mouse mammary tumor virus (MMTV) loci in the mammary tumor prone strain SHN. Using a probe, which hybridizes to the env sequence of MMTV, Southern blotting of genomic DNA from the brain after digestion with EcoRI revealed 5 endogenous proviruses: Mtv-1 (4.5kb), Mtv-2 (11 kb), Mtv-8 (6.7kb), Mtv-17 (8.3kb) and a newly-found 6.5-kb fragment. F1-hybrid mice (C3H/He female x SHN male) also possessed the 6.5-kb fragment. Thus, we conclude that the 6.5-kb fragment is unique to SHN mice. Genomic DNA from mammary tumors of SHN mice showed MMTV insertions, suggesting that activation of an oncogene(s) occurred in this strain.

Animals↗

Electrophoresis of phosphoglycerate kinase-2 to determine testicular damage induced by ethylene glycol monomethyl ether and sterility associated with chromosomal abnormality.

Phosphoglycerate kinase (PGK, EC 2.7.2.3), which is expressed specifically in sperm and spermatids, is an enzyme in the Embden-Meyerhof pathway that converts glucose to pyruvate. We developed an electrophoresis method to determine relative PGK-2 quantity and applied it to evaluate spermatogenesis activity. In the ethylene glycol monomethyl ether (EGME)-induced testicular toxicity, relative PGK-2 quantity had not decreased until 4 weeks of exposure. Mean relative PGK-2 quantities, defined as PGK-2 quantity over PGK-1 quantity in a pooled spleen sample (+/- SD) were: 1.43 +/- 0.32 for control animals (N = 10); 1.67 +/- 0.24 for the group exposed at 500 mg/kg for 5 days (N = 6); 1.85 +/- 0.58 for the group exposed at 500 mg/kg for 2 weeks (N = 6); 0.09 +/- 0.06 for the group exposed at 500 mg/kg for 4 weeks (N = 6); not detectable in animals exposed at 500 mg/kg for 5 weeks (N = 7); 0.208 +/- 0.103 for the group exposed at 250 mg/kg for 5 weeks (N = 6); and 1.35 +/- 0.38 for the group exposed at 125 mg/kg for 5 weeks (N = 6). These relative quantities showed a good correlation with sperm/spermatid counts (r = 0.823, p less than 0.01) and histological findings. These findings suggest that EGME has toxicity on primary spermatocytes and spermatogonia. In the case of sterility associated with a chromosomal abnormality (chromosomal translocation between chromosome X and 16), relative PGK-2 quantity was not detected in any of the seven adult (12 weeks of age) mice, although many primary spermatocytes were detected by histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence of clonal proliferation of hepatocytes after carbon-tetrachloride-induced hepatic injury in PGK-1 mosaic mice.

During aging processes, the liver is exposed continuously to both endogenous and exogenous chemicals which result in various degrees of hepatic damage. Hepatocytes maintain mitotic potential so that damaged cells are replaced by proliferation of selected clones of cells. Changes in the clonality after hepatic damage were investigated using carbon tetrachloride (CCl4) as a model hepatotoxin. The changes in clonality were determined by the alteration of the electrophoretic patterns of the allozyme, phosphoglycerate kinase-1A/1B (PGK-1A/1B), the locus of which is on the X-chromosome. In mammalian females random inactivation of one of the two X-chromosomes, of either paternal or maternal origin, are known to result in phenotype mosaicism. Heterozygous female (PGK-1a/1b) mice were obtained by crossing female (PGK-1b/1b) and male (PGK-1a/-) C3H/He mice. Liver samples were collected from these mice 5 days before (by biopsy) and 18 days after dosing with CCl4 (1 ml/kg, i.p.). Quantitative evaluation of the electrophoretic bands showed significant changes (percent change more than 7.2%, P less than 0.01) in the relative PGK-1A activity in 4 out of 10 cases. In one mouse a remarkable change, from 83.0 to 59.2%, was observed. Thus we concluded that selective hepatocyte proliferation occurs after cellular damage. We speculated that this process may play an important role in the aging of the liver.

Aging↗

Effects of energy restriction on mouse mammary tumor virus mRNA levels in mammary glands and uterus and on uterine endometrial hyperplasia and pituitary histology in C3H/SHN F1 mice.

We investigated the effects of energy restriction on the pituitary-ovarian axis and on a hormone responsive gene, the mouse mammary tumor virus (MMTV). Female C3H/SHN F1-hybrid mice, known to display a high incidence of mammary tumors, ate an energy-restricted diet (48 kcal/wk) or a control diet (95 kcal/wk) beginning at the time of weaning. By 67 wk of age, 12 of 32 mice in the control group, but none of the 33 mice in the energy-restricted group, had developed mammary tumors. Six tumor-free mice from each group were studied in detail at 67 wk of age. All six tumor-free control mice, but none of the six energy-restricted mice, showed uterine endometrial hyperplasia at autopsy. Mice subjected to energy restriction did not display an estrous cycle. The average levels of MMTV mRNA in mammary glands and uteri were strongly reduced by energy restriction. MMTV mRNA levels in mammary glands from control mice were two orders of magnitude lower than those in mammary tumors. Energy restriction lowered the percentage of pituitary mammatropes and suppressed proliferation of mammatropes with advancing age. Energy restriction thus appeared to inhibit endometrial hyperplasia and to decrease MMTV production at the mRNA level in the mammary glands and in the uterus. These effects may be a consequence of hormonal changes originating at the pituitary-ovarian axis.

Animals↗

Structure and pulmonary toxicity relationship on O,O-dimethyl S-alkyl phosphorothioate esters.

The structure-pulmonary toxicity relationship was investigated using three different O,O,S-trimethylphosphorothioate (OOS-TMP) analogues, which is known to induce a typical mortality pattern (delayed death) and pulmonary injury; O,O-dimethyl S-ethyl (OOS-DMEP), O,O-dimethyl S-propyl (OOS-DMPP), and O,O-dimethyl S-butyl (OOS-DMBP) phosphorothioates. The mortality pattern in rats dosed with OOS-DMEP was similar to the "delayed death" pattern: the LD50s in rats for OOS-DMEP decreased dramatically from more than 200 mg/kg within 24 hr to 41.1 (males) or 13.8 (females) mg/kg 7 days after treatment while the LD50s in rats for OOS-DMPP and OOS-DMBP did not. Histopathological examinations revealed that OOS-DMEP induced pulmonary oedema and bleeding at a dose of 1/2 LD50 by 72 hr after dosing while the other two compounds did not. Thus, it was concluded that OOS-DMEP induces pulmonary injury, thereby eliciting the "delayed death" mortality pattern.

Animals↗

[Contamination of urban air in a snowy district with 1-nitropyrene and particulate matter during the winter].

Nitroarenes, potent rodent carcinogens, have attracted much attention as environmental contaminants. Recently, simultaneous exposure to dust have been found to potentiate tumorigenicity of nitroarenes in rats (14). We hypothesized that inhabitants of northwestern Japan may be exposed to such substances in winter. First, we sought to develop a sensitive yet time saving method to determine nitroarene concentrations in airborne particulate matter. The method developed used a high-performance liquid chromatograph equipped with a fluorescence detector. By on-column catalytic reduction, using silica coated with platinum and rhodium, 1-nitropyrene (1-NP), 1,3-dinitropyrene, 1,6-dinitropyrene, and 1,8-dinitropyrene were effectively reduced to their amino derivatives which were easily detectable with the fluorescence detector. The lowest detectable limits found using the present method were on the order of picograms for individual compounds. Subsequently, we sought to determine the concentrations of nitroarenes using the new method on airborne particulate matter during the period from November to April. Samples were collected at sampling sites on road with high-volume air samplers for 24 hours or 72 hours in four different rural areas in Iwate Prefecture. At one location in the city of Morioka, samples were collected at the height of 25 m from the ground. Among the four nitropyrenes mentioned above, only 1-NP was detected in the samples. The concentrations of 1-NP and airborne particulates changed significantly in all examined areas in parallel with the rise and fall of the frequencies of studded tire use. The highest 1-NP and airborne particulate concentrations were 1.210 pg/m3 and 1,291 micrograms/m3, respectively, being recorded at the busiest road in Kitakami. In contrast, the lowest values were 38 to 66 pg/m3 for 1-NP and 54 to 94 micrograms/m3 for airborne particulates in Morioka, being recorded in November and April, respectively. The mutagenicities of extracts of airborne particulate matter showed similar trends. Thus, exposure situations with high concentrations of dust and 1-NP were confirmed to occur in Iwate. Finally, the risk posed by 1-NP in airborne particulate matter was estimated using the equation proposed by Cuddihy and McClellan (37) and was found to range from 3.12 x 10(-2) to 24.2 x 10(-2) lung cancer/year/10(6) people. Although the estimated risk due to 1-NP is relatively small, further surveillance is highly recommended in those areas since heavy dust exposure also occurs there.

Air Pollutants↗

[Experimental glomerulonephritis induced by Coxsackie B4 virus in mice--glomerular changes associated with intermittent viral inoculations].

It has been considered that viruses may be implicated in the genesis and progression of glomerular diseases. Several experimental and clinical studies have reported nephritogenecity of Coxsackie (Cox.) B4 virus infection. So in order to elucidate glomerulopathy of intermittent Cox. B4 virus infection, one-month-old Swiss albino mice were inoculated intravenously with purified Cox. B4 virus, 3 x 10(7) TCD50, once a month, and then were sacrificed from 4 to 9 mo. of age (from 3 to 8 times inoculation) at one month after final inoculation. Virological assay of neutralization titer (NT) of sera and histological study of the kidneys were performed. The results were as follows: 1) NT of sera was 1:16 at 4 mo. of age and gradually elevated to 1:256 at 8 and 9 mo. of age. 2) Light microscopy revealed PAS-positive mesangial deposits that were increased by degrees and marked showing hemispherically. Several glomeruli had GBM alteration, mesangial sclerosis and crescent formation with interstitial inflammatory response. 3) By immunofluorescence, IgG, IgA, and Cox. B4 viral antigen were stained in mesangial pattern and its intensity were increased in proportion to the number of inoculations. These results demonstrated that intermittent intravenous inoculation with Cox. B4 virus in mice produces virus mediated immune complex type glomerulonephritis closely resembling those in human chronic glomerulonephritis with mesangial immune deposits.

Animals↗

Caloric restriction perturbs the pituitary-ovarian axis and inhibits mouse mammary tumor virus production in a high-spontaneous-mammary-tumor-incidence mouse strain (C3H/SHN).

Dietary restriction (DR) retards aging and extends maximum life span. It is also known to decrease the incidence of hormone-dependent tumors. In the present investigation, we focussed primarily on the influence of DR on the pituitary-ovarian axis, and subsequently on gene expression of the mouse mammary tumor virus. F1 females from the mating of SHN female and C3H male mice were used in this study, since these hybrids display a very high incidence of mouse mammary tumors. The mice weaned at 3 weeks were raised on either a calorically-restricted diet (DR: 50 kcal/week; N = 5) or on a control diet (C: 95 kcal/week N = 5) for 5 weeks. Three C57BL/6J Jcl ad libitum-fed female mice, 8 weeks of age, were used as reference animals since this strain has a very low incidence of mammary tumors. The mean cellular contents of prolactin (PRL) and growth hormone (GH) in the pituitary, as determined by immunohistochemistry, were found to be reduced in mice raised on the DR diet. The decrease in the mean cellular content of PRL (50% of the mean control value) was accompanied by a decrease in the number of lactotrophs (17% of the mean value of control diet mice). However, the decrease in cellular content of GH (53% of the mean control value) was not accompanied by a decrease in the number of somatotrophs (no. of somatotrophs in DR = 103% of mean control value). Histologically, ovaries from DR mice showed many growing and atretic follicles, with few corpora lutea. In contrast, both control-diet and reference (C57BL/6J Jcl) mice showed two or three corpora lutea per ovarian section. In accordance with this finding, DR mice had not established stable estrus cycles by 8 weeks of age, in contrast to both control-diet and reference mice. Since caloric restriction has been shown to decrease mammary tumor virus (MMTV) gene expression, MMTV production was investigated by electron microscopy to confirm the validity of our experimental conditions. In DR or reference C57BL/6J Jcl mice, MMTV particles were rarely found in the mammary gland samples, but were always found in samples from control mice. The development of mammary glands, as indicated by the number of villi or the development of the rough endoplasmic reticulum, was delayed in DR mice. Thus, it was concluded that caloric restriction decreases the number of lactrotrophs, inhibits ovulation and delays mammary gland development. This immature status is considered to be due to perturbations in the pituitary-ovarian axis by caloric restriction.

Animals↗

A new analytical method for stereoisomers of methamphetamine and amphetamine and its application to forensic toxicology.

We have developed a rapid and sensitive high-performance liquid chromatographic method for the determination of low concentrations of the stereoisomers of methamphetamine (MAMP) and the demethylated metabolite, amphetamine (AMP). The acetyl derivatives of the stereoisomers (d and l-form) of MAMP and AMP smuggled by gangsters or extracted from biological specimens (hair) of drug addicts were clearly separated on two stereoisomer-analytical columns (Chiralcel OB and OJ, Daicel Ind. Co., Japan) connected in series at 50 degrees C. The mobile phase was a mixture of n-hexane and isopropanol (9:1, v/v) and the UV detector was set at 220 nm. The practical limit of sensitivity for the analysis was 62.5 ng of the stereoisomers of MAMP and AMP. Our analytical method for MAMP and AMP in human hair is very useful for the diagnosis of abuse of the drug. The determination of the d/l ratio of MAMP and AMP (the fingerprint of MAMP and AMP) is applicable to the investigation of smuggling routes of these drugs.

Amphetamine↗

Forensic toxicologic analysis of methamphetamine and amphetamine optical isomers by high performance liquid chromatography.

Optical isomers (d and l) and racemic compounds (dl) of methamphetamine (MAMP) and amphetamine (AMP), and biologic materials including those substances, could be analyzed by high performance liquid chromatography. Examining the temperature for the analysis, 40 degrees C was the optimal condition in the reproducibility of separated MAMP-isomers. The reproducibility at the temperature did not vary significantly. The measured values of optical isomers were 0.116 +/- 0.012, 1.082 +/- 0.070 and 8.984 +/- 0.136 for the mixing ratios (l/d) of 0.111, 1.000, and 9.000, respectively. The detection limit for both d- and l-isomers was 25 ng. The analytic result of hair specimens from two stimulant abusers by the present method indicates that they contained only d-MAMP and d-AMP, which is believed to have the strongest pharmacologic effect among the optical isomers of MAMP. The coefficient of variation in the analysis of five replicate standards, prepared by adding 1,000 ng each of racemate MAMP and AMP to hair, was less than 4%. The measured value against l/d = 1.000 was 1.040 +/- 0.040 in MAMP and 0.980 +/- 0.030 in AMP. The detection limit for both racemate MAMP and AMP accumulated in hair was 250 ng. The analysis of the optical isomers by our method would contribute to identifying the smuggling routes or the illicit method.

Amphetamine↗

Cancer patterns among Koreans in Japan, Koreans in Korea and Japanese in Japan in relation to life style factors.

Cancer incidences for major sites were compared among Koreans in Osaka, Japan, Koreans in Korea and Japanese in Osaka by calculating standardized proportional incidence ratios (SPIR's), in addition to updating the findings on cancer mortality experiences of Koreans and Japanese in Osaka reported before. Compared with Japanese, Koreans in Osaka had significantly higher mortality rates from cancers of the esophagus, liver and lung in males, and liver in females. Mortality rates among Koreans in Osaka were significantly lower for stomach cancer in both sexes and for breast cancer in females. Compared with Korean counterparts in the homeland, Koreans in Osaka had a reduced risk for cancers of the stomach in males and the uterus in females. On the other hand, an elevated risk was observed for cancers of the esophagus, colon, liver and lung among Korean males in Osaka and for cancers of the colon and liver among Korean females in Osaka. The risk for cancer of the breast in females was similar among Koreans in the host and home countries. These different cancer patterns among Koreans in the host and home countries and Japanese are discussed in relation to their life styles, such as smoking, drinking and dietary habits, which have been investigated by means of questionnaire surveys.

Adult↗

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants in high- and low-risk areas for stomach cancer in northern Japan.

Three samples of 24-h urine were collected from each of 104 inhabitants of high-risk (Akita) and low-risk (Iwate) areas for stomach cancer in northern Japan, according to the following protocols: (i) when they were undosed, (ii) after ingestion of proline three times a day and (iii) after ingestion of proline together with vitamin C three times a day. These samples were analysed for N-nitrosamino acids, nitrate and chloride ion as indices of the exposure. The median values of N-nitrosoproline (NPRO) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA) excreted in the urine of undosed subjects were not different between the two areas; however, that of N-nitrosothiazolidine 4-carboxylic acid (NTCA) was significantly higher in subjects of the high-risk area. Salt intake, estimated from the level of chloride ion in the urine, did not differ in two areas. After intake of proline, the NPRO level increased significantly only in subjects of the high-risk area, but not in those of the low-risk area; intake of vitamin C inhibited this increase of NPRO and lowered the levels of other nitrosamino acids only in the high-risk subjects. In contrast, the urinary level of nitrate was higher in subjects of the low-risk area than in those of the high-risk area; nitrate levels were found to correlate well with the amounts of vegetables consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗