Biomedical subjects

A Maekawa

Publications and source records attributed to A Maekawa.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of cobalamin on the allergic response in mice.

Cyanocobalamin, deoxyadenosylcobalamin and methylcobalamin were separately administered to mice sensitized with the ovalbumin antigen to investigate the allergic response. The serum IgE and pulmonary histamine concentrations were significantly lower in all cobalamin (Cbl)-administered groups. The production of interleukin (IL)-2 and IL-4 in splenocytes was also lower in all Cbl-administered groups. These results show that Cbls were effective in mitigating allergic reactions and IL-2 production. CD3+ CD28+ (CD28 is an accessory molecule related to IL-2 production) and CD4+ CD28+ in splenocytes were higher in all the Cbl-administered groups. However, CD3+ CD28-, CD4+ CD28- and CD5+ CD25- (CD25: IL-2 R alpha/p55) were lower in the Cbl-administered groups. In addition, Cbl specifically inhibited the cellular phosphorylation of tyrosine induced by ovalbumin sensitization. These results indicate that the signal in a cell by CD 28 was restrained by Cbl. We infer that Cbl administration significantly reduced the IL-2 concentration, and secondarily the IL-4, IgE and histamine concentrations.

Animals↗

PubMed2000

[A case report of Binswanger type encephalopathy manifested after coronary artery bypass grafting].

A 68-year-old man showed signs of dementia after undergoing triple CABG with cardiopulmonary bypass. Brain CT revealed widespread atrophy and lucency in white matter without any sign of stroke. No critical stenosis in cervical vessels was found in duplex scanning. He kept politeness well, but had severe memory impairment. These findings were characteristic of Binswanger type encephalopathy which must have been latent preoperatively. This disease is caused by ischemic damage in brain stem and white matter due mainly to atherosclerotic micro cerebrovasculopathy, and highly related to hypertension. We have to be aware of intracranial cerebrovascular disease when assessing the risk of brain damage in candidates for CABG.

Aged↗

PubMed1999

Hepatotoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice.

It has been reported that flumequine (FLU) induces hepatic tumors in mice when given orally for 18 months. We investigated possible underlying mechanisms using a two-stage mouse hepatocarcinogenesis model. After initiation with a single intraperitoneal injection of 100 mg/kg body weight diethylnitrosamine (DEN) or saline, male CD-1 mice were given 4000 ppm FLU in the diet or 500 ppm phenobarbital (PB) in drinking water for 9, 19, 24 or 30 weeks. Toxicity, evidenced by centrilobular swollen and polar hepatocytes with fatty droplets, infiltration of inflammatory cells and increased numbers of mitosis in hepatocytes, was apparent in the livers of mice treated with FLU at all time points, but its severity declined towards the termination. FLU did not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2 as assessed immunohistochemically, while positive expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes of both DEN + FLU and FLU groups compared with the relevant controls. In animals given PB, eosinophilic swelling of hepatocytes was prominent, and the hepatocytes showed strongly positive reactions for CYP 1A1 and 3A2. Altered cell foci were induced in the livers of FLU-treated animals both with and without DEN initiation, especially the former, and their development paralleled the degree of hepatic toxicity. These results suggest that FLU hepatocarcinogenicity in mice is dependent on hepatotoxic damage and consequently increased cell proliferation. Oxidative damage to DNA may also be a crucial factor.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.

Adenocarcinoma↗

PubMed1999

Estrogen receptor mRNA in uteri of normal estrous cycling and ovariectomized rats by in situ hybridization.

Biological effects of estrogen are mediated via its binding to the estrogen receptor (ER), the contents of its protein and mRNA varying during the estrous cycle. In the present study, the ERalpha mRNA expression in different cell components of the uterus was investigated in normal estrous cycling rats using nonisotopic in situ hybridization. Additionally, ovariectomized (OVX) rats treated with 17beta-estradiol (E2: 5 microg/kg, sc injection daily) were also investigated to clarify the effects of exogenous E2. At proestrus and diestrus, and especially the former, the luminal and glandular epithelial (LE and GE) cells were strongly positive, along with stromal cells beneath the luminal epithelium. At estrus, the expression was slightly diminished in LE cells, but almost completely lacking in GE cells. At metestrus, positive signals appeared again in GE cells. In the myometrium, ER mRNA was demonstrated to be constantly positive in all estrous cycle stages. OVX rat uteri underwent marked atrophy, but ER mRNA still remained in all cell types. After 2 consecutive days of E2 treatment, markedly increased intensity was observed, especially in LE and GE cells. The uteri of OVX rats treated with E2 for 14 days, however, showed slightly diminished expression, whereas the serum concentration of E2 was comparable to that in rats after 2 days. These results provide evidence that cell-type specific patterns of ER mRNA expression characterize the uteri of both normal estrous cycling rats and OVX rats after estrogen treatment.

Animals↗

PubMed1999

K-ras point mutations in spontaneously occurring endometrial adenocarcinomas in the Donryu rat.

The Donryu rat has been found to have a high incidence of spontaneous uterine endometrial carcinomas. Moreover the histologic findings, biological nature and pathogenesis of these rat tumors appear similar to those in humans. To determine if the incidence of H- and K-ras gene mutations in these rat tumors is similar to that in human endometrial cancers, we isolated DNA samples from 2 atypical hyperplasias, 5 simple or complex hyperplasia without atypia, 9 adenocarcinomas and 7 histologically normal tissues, amplified exons 1 and 2 of the H- and K-ras genes by PCR and hybridized the products with allele specific oligonucleotide probes. K-ras point mutations were observed in 1/2 of the atypical hyperplasia (codon 12: GGT-->GTT) and 3/9 of the carcinoma (codon 12: GGT-->GAT, GGT-->AGT, codon 61: CAA-->CAC), while they were not detected in 7 of the normal tissues and in 5 of the simple or complex hyperplasia without atypia. H-ras point mutations were not detected in any of these DNA samples. These frequencies in this rat model are similar to those in humans. The absence of K-ras mutations from simple and complex hyperplasia tissue samples suggests that these mutations are associated with cytological atypia. Our findings suggest that alterations in the K-ras gene may be one of the important initiating event in endometrial carcinogenesis in some of the Donryu rat, like the human.

Adenocarcinoma↗

PubMed1999

[Folic acid].

One-carbon derivatives of tetrahydrofolate, the coenzyme form of the vitamin folic acid, play a key role in DNA synthesis and cell replication, through their involvement in the biosynthesis of purine nucleotides and the amino acids. Although the most conspicuous symptom of folic acid deficiency is pernicius anemia, it has been observed that the lack of folate intake during the pregnancy induce the incidence of neural tube defects such as apina bifida. Recently, it has been reported that clinical progression of coronary heart disease and cerebral peripheral vascular disease occurred at a high rate in hyperhomocysteinemia with low folate content in plasma. Consequently, the nutritional importance of folate has been increasingly recognized.

Female↗

PubMed1998

Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen.

The effects of tamoxifen (TAM) on uterine carcinogenesis were investigated in female Donryu rats. The effects were initiated by a single intrauterine treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a dose of 20 mg/kg body weight via the vagina at 10 weeks of age. TAM tubes (cholesterol tubes containing 50% TAM) were implanted into the backs of the rats for 13 months (full TAM group) or for the second-half of this period (half TAM group). In the control group treated with ENNG alone, various proliferative lesions were induced in the uterine endometrium and the incidence of endometrial adenocarcinomas was about 30%. In contrast, the uteri in both TAM-treated groups showed severe atrophy and the incidences of uterine proliferative lesions were limited to a few endometrial hyperplasias in the half TAM group. Most of the vaginas in both TAM-treated groups showed mucification, while cornification was common in the vaginal epithelium of controls. The ovaries demonstrated similar atrophy with cystic follicles and no corpora lutea in all groups. Other estrogen responsive endocrine organs, such as the pituitaries and adrenals, were small in the TAM-treated groups. Serum estrogen levels in the TAM-treated groups were lower than in the control group but progesterone levels did not differ. These results indicated that TAM acts as an anti-estrogen on the adult rat uterus, inhibiting the development of endometrial adenocarcinomas initiated by ENNG.

Adrenal Glands↗

PubMed1998

Granular cell foci of the uterus in Donryu rats.

Eleven cases of uterine granular cell foci were observed in a total of 855 female Donryu rats. All the lesions were microscopical and focal or multifocal in nature, and composed of uniformly large cells with abundant granulated eosinophilic cytoplasm. Histopathologically, immunohistochemically and ultrastructurally they resembled granular cell tumours of the uterus reported in rats and mice. The development of granular cell foci may be the result of hormonal stimulation.

Adenocarcinoma↗

PubMed1998

Strain-differences in proliferative activity of uterine endometrial cells in Donryu and Fischer 344 rats.

Strain differences in proliferative activities of uterine endometrial cells were sequentially investigated in Donryu and Fischer 344 (F344) rats until 52 weeks of age. At 13 and 26 weeks of age, when all rats showed a normal estrous cycle, histological findings for the endometrium at each estrous stage were similar in both strains. Mitoses of epithelial cells were frequently observed during the proestrous and metestrous stages, and especially in the latter, but were very few in the estrous stage. The bromodeoxyuridine(BrdU)-labeling indices coincided with the histological findings, the results indicating a peak of cell proliferative activity in the metestrous stage. In Donryu rats, estrous cycle abnormalities increased age-dependently after 26 weeks of age, and almost all animals showed persistent estrus at 52 weeks of age. At 39 and 52 weeks of age, the rats showing persistent estrus displayed similar vaginal smears and histological findings to those of younger rats in the estrous stage, but the BrdU-labeling indices of epithelial cells were age-dependently increased. In contrast, vaginal smear of F344 rats indicated a normal estrous cycle at all ages, with no changes in BrdU-labeling being observed. Previously, we reported that the Donryu rat is a high incidence strain in terms of spontaneous development of endometrial adenocarcinomas, this being related to an age-dependent hormonal imbalance, characterized in particular by an increased estrogen/progesterone ratio. The F344 rat in contrast is a low incidence strain. The present results thus indicate that a constant high-level of proliferative activity of epithelial cells may play an important role, together with an age-related hormonal imbalance, in the spontaneous development of endometrial carcinomas in Donryu rats.

Adenocarcinoma↗

PubMed1998

Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres.

BACKGROUND: Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. RESULTS: ATF4-deficient mice exhibited severe microphthalmia. Although ATF4-deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4-deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens-specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. CONCLUSION: These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.

Activating Transcription Factor 4↗

PubMed1998

Dietary docosahexaenoic acid dose not promote lipid peroxidation in rat tissue to the extent expected from peroxidizability index of the lipids.

Docosahexaenoic acid (DHA) ingestion enhanced the susceptibility of rat liver and kidney to lipid peroxidation as a function of the dietary DHA level, but did not increase lipid peroxides as assessed by thiobarbituric acid (TBA) values to the level expected from the peroxidizability index of the tissue total lipids. This phenomenon was especially prominent in the liver. In the liver, the higher proportion of DHA in the non-phosphorus lipids might play an important role in lessening the susceptibility of the tissue to lipid peroxidation. In the brain and testis, on the other hand, lipid peroxide levels were decreased when DHA was given to the animals. In the testis, in particular, the proportion of DHA in total lipids was lowest among all tissues examined, even when a relatively high level of DHA had been ingested, and this could be related to the low lipid peroxide level. Therefore, the protection against lipid peroxidation differed from tissue to tissue, even from the viewpoint of the fatty acid composition of the tissue lipids. In addition, changes in the lipid peroxide levels of the liver, kidney, brain and testis, as assessed by TBA values, seemed to be associated with changes in the peroxidizability index of phosphatidylcholine (+cardiolipin) in each tissue.

Animals↗

PubMed1998

Sequential alterations in clinical biochemical indicators of renal function in 5/6 nephrectomized rats--basic study for renal toxicity using 5/6 nephrectomized rats.

It has been established that progression of renal lesions in 5/6 nephrectomized rats, in which the total right kidney was removed and two poles of the left kidney were excised surgically, and are used as an animal model of renal failure in man, can be morphologically divided into three stages. In the present study, for establishing a renal toxicity study using this animal model on the physiological side, changes of biochemical parameters were sequentially investigated in 20 male 5/6 nephrectomized Wistar rats until 26 weeks after nephrectomy. Creatinine clearance (CLcre) and water as well as electrolyte reabsorption (FRwater and FR Na, K, Cl) were reduced at weeks 2-4, then increased slightly from weeks 6 to 10, and reduced again thereafter. On the contrary, urinary protein was elevated throughout the experimental period, while albumin fraction was increased after week 2 and low-molecular tubular protein increased after week 6 by electrophoresis. Urinary LDH also demonstrated high levels throughout the observation period, but ALP only increased after week 18. The present study thus confirmed that renal function after 5/6 nephrectomy is indeed changed in three stages with clinical biochemical parameters, especially CLcre and FR Na, K, Cl being good indicators to distinguish the three stages of glomerular and tubular dysfunction, respectively. In addition, urinary protein-fractions by electrophoresis in this animal model were examined for the first time, proving useful approach to glomerular and tubular dysfunction.

Albumins↗

PubMed1998

Histochemical observation and cellular distribution of ascorbic acid in persimmon leaves.

This study was carried out to resolve the discrepancy of data for the proportion of ascorbic acid and dehydroascorbic acid in persimmon leaves at the final stage of the season and to clarify their cellular distributions using histochemical and biochemical techniques. Fresh persimmon leaves were collected and used on July 31, September 5 and October 7, 1996. Ascorbic acid and dehydroascorbic acid in subcellular fractions were determined by the HPLC method that was found to be the most reliable for separation. The percent of dehydroascorbic acid in the total leaves was found to be almost constant (between 32 and 37%) in all preparations tested. In all preparations, more than 90% of the ascorbic acid and dehydroascorbic acid was found in the soluble fraction. The histochemical detection of ascorbic acid and an electron micrograph of persimmon leaf cells showed that the reactive color, after the reduction of silver nitrate under acidic conditions, in the leaves of all three preparations was mainly found on the face side of columned-type palisade parenchyma cells where chloroplasts were not rich and large vacuoles were seen. On the inner side of the palisade parenchyma cells where chloroplasts were the richest, only weak color development was observed. This study demonstrates that the percent of dehydroascorbic acid in persimmon leaves did not exceed 40% at least until October 7. It also shows that in persimmon leaf cells, ascorbic acid is mainly localized in the cytosol of palisade parenchyma tissue cells where large vacuoles are seen.

Ascorbic Acid↗

PubMed1998

Serum C3 content in vitamin B(12)-deficient rats.

As a clue to clarifying the role of vitamin B12 (B12) in the function of the complement system, serum C3 content was determined in B12-deficient rats, and the effect of the administration of methylcobalamin (CH3-B12) on the serum C3 content was also studied. It was found that the serum C3 content in rats fed on a vitamin B12-deficient diet for 90 and 120 days significantly decreased compared with that in control rats. The administration of CH3-B12) restored the serum C3 content to control levels. The above results indicate that B12-deficiency depressed the serum C3 content and lowered humoral immunocompetence, and that these changes were ascribable to B12-deficiency.

Animals↗

PubMed1998

[A case of submitral left ventricular pseudoaneurysm following mitral valve replacement for infective endocarditis].

A 25-year-old female presented with high fever and dyspnea. She was diagnosed as infective endocarditis, severe mitral regurgitation, grade II A-V block and acute left heart failure We performed emergency mitral valve replacement. At operation, mitral ring abscess was found which was extended to submitral left ventricular wall. The abscess was excised and the defect of mitral annulus was repaired with Xenomedica patch. Left ventriography at 30 days after the operation showed a submitral left ventricular pseudoaneurysm (size: 30 x 26 x 33 mm) without evidence of infection. Further examinations showed that the aneurysm extended to the annulus of tricuspid valve through interatrial septum. About 1 year after the operation, she had paroxysmal atrial fibrillation due to right atrial overloading. We decided to perform reoperation. At reoperation, the ostium of the aneurysm was closed with a Xenomedica patch after taking off the prosthetic valve. It was very difficult to close the ostium because we could not see the submitral ventricular wall directly. Although postoperative course was good, she had complete A-V block necessitating permanent pacemaker.

Adult↗

PubMed1997

Thirteen-week subchronic toxicity study of thiamphenicol in F344 rats.

A 13-week subchronic toxicity study of thiamphenicol (TAP) was performed in F344 rats. The minimum lethal dose was estimated to be greater than 10 g/kg body weight, when a single dose of 4-10 g/kg of TAP was given orally. In the subchronic toxicity study, groups of 12 F344 rats of each sex were given solutions containing 0 (control), 125, 250 and 500 ppm of TAP as their drinking water ad libitum for 13 weeks. Body weight gain was significantly suppressed in both sexes of the 250 and 500 ppm groups. Slight suppression of erythropoiesis was observed in the highest-dose group along with slightly reduced spermatogenesis in the testes of the males. In addition, spermatogranulomas were found in the epididymis of both middle- and highest-dose groups. The no observed adverse effect level (NOAEL) was concluded to be 125 ppm (daily doses of 9.0 mg/kg in males and 11.6 mg/kg in females). From the above described results, doses of 250 and 125 ppm were selected as appropriate for a 2-year carcinogenicity study.

Animals↗

PubMed1997

Overexpression of PU.1 induces growth and differentiation inhibition and apoptotic cell death in murine erythroleukemia cells.

PU.1 is a member of the ets family of transcription factors and is expressed in Friend virus-induced murine erythroleukemia (MEL) cells as a consequence of proviral integration into the PU.1/Spi-1 locus. After induction of MEL cell differentiation by treatment with dimethylsulfoxide (DMSO), expression of the PU.1/Spi-1 gene decreased before induction of beta-globin gene expression. Overexpression of PU.1 by using a zinc-inducible expression plasmid in MEL cells resulted in unexpected growth inhibition of the transfectants. When PU.1-overexpressing transfectants were treated with DMSO, growth inhibition became much pronounced and apoptosis was induced. Expression of the beta-globin gene was not induced under this condition. Neither growth inhibition nor apoptosis was induced in MEL cells after expression of mutant PU.1 proteins with a deletion of the activation domain or the DNA-binding Ets domain irrespective of the presence of DMSO. Interestingly, beta-globin gene expression was not induced in the transfectants expressing the former mutant, whereas it was induced in those expressing the latter one in the presence of DMSO. These results indicate that overexpression of PU.1 in MEL cells results in growth and differentiation inhibition and, in conjunction with DMSO treatment, apoptotic cell death. These results also suggest that the activation domain and the Ets domain of PU.1 contribute differently to induction of these effects.

Animals↗