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Biomedical subjects

A Koizumi

Publications and source records attributed to A Koizumi.

At least 19 recordsLinked to original sources
PubMed1992

Specific inhibition of pituitary prolactin production by energy restriction in C3H/SHN female mice.

Pituitaries were excised from control (C; 95 kcal/week) or energy restricted (ER; 48 kcal/week) female mice of 2, 3, 7, and 18 months of age. The total RNA and relative actin mRNA amounts in the pituitary were significantly greater in C than in ER mice both at 7 and 18 months. Prolactin (PRL) mRNA, standardized with actin mRNA, was significantly less in ER mice of 7 (50%) and 18 (51%) months of age than in age-matched controls, suggestive of specific inhibition of PRL mRNA transcription. Pituitary RNA and actin mRNA increased from 7 to 18 months in C mice but not in ER mice. Similarly, mean pituitary volumes increased between 2 and 18 months in C mice but not in ER mice. PRL mRNA, standardized with actin mRNA, did not change in either C or ER mice 7-18 months of age. All examined C mice of 3, 7, and 18 months of age had estrous cycles but none of the ER mice of the same ages. After 1 month of ER, the pituitary volumes and serum insulin concentrations in 2-month-old female mice were reduced. Thus net reduction of PRL mRNA per pituitary by ER is attributable to decreases in pituitary size and specific inhibition of PRL production, both of which may be due to low estrogen and insulin levels.

Actins↗
PubMed1992

alpha-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice.

alpha-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD50 in mice and conducted histopathological examinations. The 6-day LD50 was found to be 199 mg/kg with 95% confidence limits of 126-314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.

Animals↗
PubMed1992

Mitotic activity in mice is suppressed by energy restriction-induced torpor.

We monitored core body temperature by telemetry in energy-restricted (201 kJ/wk) and control (397 kJ/wk) C57BL/6 and SHN/C3H F1 mice to determine whether torpor may be involved in the suppression of mitotic activities resulting from energy restriction. The energy restriction regimen employed inhibited the development of cancer and greatly extended longevity in both these mouse strains. Male and female C57BL/6 mice subjected to energy restriction from 4 wk of age and tested at 3 mo of age became torporific (body temperature less than 31 degrees C) at ambient air temperatures of 20-22 degrees C, whereas control animals stayed euthermic (greater than 35 degrees C). Energy restriction also induced torpor in 3- and 13-mo-old SHN/C3H F1 female mice, whereas 3-, 13- and 24-mo-old control mice were euthermic. Energy restriction decreased mitotic activities to approximately 30% of control values in both jejunum and epidermis in 3-mo-old female C57BL/6 mice maintained at 20-22 degrees C. However, this suppression of mitotic activities was antagonized by housing the energy-restricted mice at 30 degrees C for 2 wk, indicating that torpor plays a substantial role in suppressing mitotic activities in energy-restricted mice.

Animals↗
PubMed1992

Hemorrhagic myocardial infarction after reperfusion detected by X-ray CT--experimental and clinical study.

The purpose of this study was to determine whether computed tomography (CT) can detect hemorrhagic infarction occurring after intracoronary thrombolytic therapy (ICT) for acute myocardial infarction (AMI). In an experimental study, 12 dogs underwent 2-4 h of left anterior descending artery (LAD) occlusion, followed by reperfusion, and infusion of contrast material into the LAD. After CT examination, the heart was cut into transverse sections. A good correlation was obtained between the CT-enhanced area and the hemorrhagic area in the sliced heart section (r = 0.895, p less than 0.001). In a clinical study, we applied CT immediately after ICT in 25 patients with AMI. In 13 of 25 patients, the CT showed post-ICT myocardial enhancement areas. To evaluate the relationship of the enhancement areas shown by CT to the viability of the myocardium, we compared enhancement areas by CT with the corresponding perfusion defect areas of Thallium-201 imaging (SPECT) one month later. There was no significant correlation between the enhancement areas and perfusion defect areas (r = 0.38, p greater than 0.1). The SPECT defect areas were consistently smaller than the CT enhancement areas. These results indicate that CT can detect hemorrhage into the myocardium after ICT, and that after ICT half the AMI patients showed hemorrhagic infarction. However, hemorrhage did not cause complete deterioration of the myocardium.

Adult↗
PubMed1992

A skin-specific MMTV provirus is stably transmitted by horizontal transmission.

Mouse mammary tumor virus (MMTV) is a retrovirus with a life cycle that remains to be elucidated. In establishing Mtv-4 congenic mice, an extra copy of the MMTV provirus was found specifically in the skin of both sexes of SHN mice but not in C3H/He mice. This extra copy was not, however, found in other normal tissues such as brain, lung, liver, spleen, kidney, uterus, testis, and mammary glands from SHN or C3H/He mice. In the skin of SHN mice, an 11-kb DNA fragment, which approximates in size to the entire MMTV genome, was detected in undigested high-molecular weight DNA. This unique MMTV provirus was shown to be transmitted horizontally from SHN mice to exogenous-MMTV-free C3H/He mice through nursing. The virus is thus concluded to be exogenous. Clusters of MMTV type A particles were found in sebaceous glands by electronmicroscopic examination. The present findings indicates that exogenous MMTV may be stably maintained in the skin as an unintegrated provirus during its life cycle.

Animals↗
PubMed1991

Stable Lyonization of X-linked pgk-1 gene during aging in normal tissues and tumors of mice carrying Searle's translocation.

We investigated whether age-dependent reactivation of a repressed X-linked gene occurs. Subjects were female mice, carrying the X-autosomal translocation, T(X;16)16H (Searle's translocation). The mice were also heterozygous, for the X-linked gene coding for phosphoglycerate kinase (T16H pgk-1b/+ pgk-1a and pgk-1a was selectively repressed in these mice (McMahon and Monk, 1983). An electrophoretic method was applied to determine the PGK-1 allozyme patterns in blood, bone marrow, brain, gastrointestinal tract, liver, heart, spleen, and uterus (including tumor tissues when found). Samples were collected from mice of three different ages: 2 months (n = 4), 11 to 12 months (n = 10), or 18 to 21 months (n = 15). The lowest detection limit of the relative cellular population expressing the PGK-1A allozyme was found to be 2%, which was sensitive enough to detect the reported reactivation ratio (more than 10% of cells in a lower power microscopic field). We could not detect PGK-1A activity in any organ, including tumors in any age group, leading to the conclusion that reactivation of the repressed pgk-1a gene did not occur during aging.

Aging↗
PubMed1991

Experimental evidence for the possible exposure of workers to hexachlorobenzene by skin contamination.

The absorption of dermally applied 14C-hexachlorobenzene (14C-HCB; ranging from 2.5 to 2.6 mg/4 cm2) was investigated in the rat. The absorbed portion increased from 1% at six hours to 9.7% at 72 hours after dosing and blood concentrations of 14C increased linearly with time. The rate of absorption was 3.51 (SD 0.81) micrograms/h/4 cm2 and the absorption constant 1.40 (SD 0.33) x 10(-3)/h. Washing with soap at six hours after dosing removed 34% of the dose and decreased absorption by 50% in the next 66 hours. Finally, the compartment model, which incorporated the absorption constant, simulated the time profile of HCB kinetics in blood, and that of cumulative excretion in rats. The model with the absorption constant for the rat was then scaled up for a 70 kg worker, whose exposure was assumed to be exclusively dermal. A rough dermal contamination, which corresponds to the tentative HCB critical blood concentration of 200 ppb, was calculated for different simulated biological half lives. It was 18.2 mg for 100, 5.02 mg for 365, and 2.56 mg for 730 day half lives. The study indicates that dermal contamination can be a source of HCB body burden, and that personal hygiene, such as taking a shower and hand washing is likely to have a profound influence on the body burden of HCB.

Animals↗
PubMed1991

[On the mechanisms of retardation of aging and inhibition of mammary tumorigenesis by energy restriction in SHN/C3H F1 female mice].

Although it has long been known that energy restriction (ER) inhibits tumors and retards aging in rats and mice, its mode of action remains unknown. In rodents, ER alters the rate of age-related changes in physiological indices. Thus, it affects a broad array of age-sensitive parameters. However, present evidence does not indicate which parameters are primary contributors to the deceleration of aging. Compared to fasting or short-term underfeeding, little is known about the metabolic effects of long-term, life-prolonging ER. We thus investigated the effects of ER on hepatic enzyme activities, including drug-metabolizing enzymes and antioxidant enzymes such as superoxide dismutase and catalase. The catalase activity was found to be higher in ER mice than in control mice both at 12 and 24 months of age. In accord with the high catalase activity, lipid peroxidation in liver was much less in ER mice than in age matched control mice. beta-Naphthoflavone, known to induce P-450 related enzymes and xanthine oxidase, was given (ip) to increase lipid peroxidation. The ER was found to inhibit lipid peroxidation after beta-naphthoflavone treatment. It was, therefore, concluded that long-term life-prolonging ER increases antioxidant defence, supporting indirectly the free radical theory of aging. It is well known that ER delays puberty in rodents and has a profound influence on serum hormone levels, including those of prolactin (PRL) and thyroid hormones. However, it remains unknown how these effects are produced by ER. We therefore investigated the effects of ER on the islets of Langerhans in the pancreas and on the pituitary-ovarian axis. In the islets of Langerhans, ER was found to increase the density of alpha-cells significantly both in 11- and 67-week-old mice. In the pituitary gland in ER mice, the cellular density of PRL-producing cells diminished significantly while that of growth-hormone-producing cells did not. One of the modes of action of ER on the endocrine system is thus concluded to be mediated by changing cellular population. Since ER decreased PRL-producing cells and PRL plays a key role in mammary tumorigenesis, we investigated whether ER decreased the gene expression of mouse mammary tumor virus (MMTV) in SHN/C3H mice. The SHN strain, which was found to have a new MMTV provirus locus, mtv-4, was used in the study.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1990

[Frequency of psychiatric patients visiting non-psychiatrist's outpatient clinic and its correlates].

To examine the frequency of psychiatric patients who visit outpatient clinic of non-psychiatrists in Japan, a mailed questionnaire survey was conducted of 200 non-psychiatrists randomly selected from the 703 registered members of the Kawasaki-city Medical Association, Kanagawa prefecture. Responses from 124 or 62% were received and data for 112 male respondents were analyzed. 1) The median number of psychiatric patients treated per month by respondents was 4, and the median proportion of the total outpatients that were psychiatric patients was 0.7%. 2) Sixty-one internists saw significantly greater numbers and proportions of psychiatric patients than the other 51 doctors. 3) The internists saw a higher proportion of mild anxiety, depression, alcohol-drug dependency and psychosomatic problems among all psychiatric patients than did other doctors. 4) For the internists a significant inverse correlation was observed between the total number of outpatients and the proportion of psychiatric patients. This was the result of a group of physicians who saw a relatively small number of outpatients but had a higher proportion of psychiatric patients among outpatients.

Adult↗
PubMed1989

Immature alveolar/blood barrier and low disaturated phosphatidylcholine in fetal lung after intrauterine exposure to O,O,S-trimethylphosphorothioate.

Intrauterine exposure to the potent lung toxicant OOS-TMP was found to result in neonatal lethality attributed to immature lungs (Koizumi et al. 1988). The present study was initiated to investigate biological/pathological profiles of such pulmonary immaturity. OOS-TMP was given p.o. to five pregnant female Sprague-Dawley rats on gestation day (G) 19 at 2.5, 7 or 20 mg/kg. Control (N = 6) or pair-fed dams (N = 5: pair-fed to 20 mg/kg dams) received 2 ml/kg corn oil. On G 22, fetuses were delivered by Cesarean section. The biochemical maturity of lungs was assessed by glycogen content and production of disaturated phosphatidylcholine (DSPC), a major component of pulmonary surfactant. Mean DSPC content was significantly lower in fetuses from dams dosed at 7 or 20 mg/kg while mean glycogen concentration, in contrast, was 3- to 6-fold higher in those fetuses than fetuses from control or pair-fed dams. Pathological examination revealed that in fetuses delivered from dams dosed at 7 mg/kg or 20 mg/kg, glycogen-rich cuboidal epithelial cells completely covered the terminal air space and alveolar/blood barriers stayed at the poorly developed stage. The stage of the pulmonary development in those fetuses was similar to those in fetuses on G19. Therefore it was concluded that intrauterine exposure to OOS-TMP delayed pulmonary development, thereby causing respiratory failure after birth.

Animals↗
PubMed1989

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↗