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Biomedical subjects

M Hayashi

Publications and source records attributed to M Hayashi.

At least 217 records · Page 12Linked to original sources
PubMed2001

Systemic and eosinophilic lesions in rats with spontaneous eosinophilia (mes rats).

The mes rat is from an inbred mutant colony of rats with spontaneous eosinophilia. In order to investigate the pathogenesis of the mes rat, the histopathology and hematology for 76 mes rats were examined at several weeks of age. Tissue eosinophilia developed at 8 weeks of age when the blood eosinophil was 500 cells per microliter or more. Subsequently, eosinophilia progressed with age, and splenic eosinophilopoiesis and erythropoiesis appeared simultaneously. Many inflammatory lesions were induced after 10 weeks of age when the blood eosinophils became 1,000 cells per microliter or more. Gastroenteritis and mesenteric lymphadenitis were seen in 44 of 47 (94%) and 31 of 47 (66%) rats, respectively, after 10 weeks of age. Aortitis that deteriorated with age was found in 19 of 39 (49%) rats after 12 weeks of age. Hepatic fibrosis was found in four rats that exhibited severe eosinophilia and anemia. These results are comparable to the features of a hypereosinophilic syndrome in humans and other animals.

Animals↗
PubMed2001

Accumulation of calcium in the arteries of Japanese monkey.

To examine whether the calcium accumulation in the arteries is related to the way of walk or not, the calcium contents were determined in various arteries of Japanese monkeys of quadrupedal walk by inductively coupled plasma-atomic emission spectrometry. Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. Age-related changes of the calcium content were examined in various monkey arteries. Significant relationships between age and calcium content were found in the arteries, such as the axillary, brachial, radial, subclavian, common carotid, common iliac, and femoral arteries, but not statistically in the thoracic and abdominal aortas, ulnar, external iliac, internal iliac, popliteal, and tibial arteries. The average contents of calcium were compared between the two groups of the monkeys below 14 yr and over 24 yr of age. Below 14 yr, the calcium content was a little higher in the arteries, such as the common, external and internal iliac, and femoral arteries than that of the other ones. Over 24 yr, the calcium content increased remarkably in the arteries, such as the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries. The calcium contents of the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries increased by more than two times over 24 yr compared with those below 14 yr. In a comparison between the calcium contents of the arteries in the anatomically corresponding regions of the upper and lower limbs, no statistically significant differences were found in the subjects over 24 yr as well as the subjects 2-29 yr of age. The calcium accumulation in the arteries of monkeys with aging was different from those in the arteries of humans, because in the case of human, a very high accumulation of calcium occurred in the arteries of the lower limb with aging in comparison with those in the upper limbs. Therefore, it is likely that different ways of walk or different species are partly affected in the calcium accumulation in the arteries with aging.

Aging↗
PubMed2001

Accumulation of magnesium as well as calcium and phosphorus in Japanese monkey arteries with aging.

To examine whether an accumulation of elements in the arteries with aging differs between human and animal, the authors investigated the relationships among element contents in the arteries of the Japanese monkeys. The Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. The aorta, common and external iliac, femoral, common carotid, subclavian, and axillary arteries were resected from the monkeys and element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were very high correlations between calcium and phosphorus contents, between calcium and magnesium contents, and between phosphorus and magnesium contents in all of the monkey arteries. In addition, significant correlations were found among the other element contents in some, but not all of the arteries. These results were consistent with the foregoing findings of the human arteries. It is likely that magnesium forms compounds with phosphorus or calcium in the monkey arteries.

Age Factors↗
PubMed2001

Hypertonic treatment inhibits radiation-induced nuclear translocation of the Ku proteins G22p1 (Ku70) and Xrcc5 (Ku80) in rat fibroblasts.

The effects of X irradiation and hypertonic treatment with 0.5 M NaCl on the subcellular localization of the Ku proteins G22p1 (also known as Ku70) and Xrcc5 (also known as Ku80) in rat fibroblasts with normal radiosensitivity were examined using confocal laser microscopy and immunoblotting. Although these proteins were observed mainly in the nuclei of human fibroblasts, approximately 80% of the intensities of immunofluorescence from both G22p1 and Xrcc5 was observed in the cytoplasm of rat fibroblasts. When the rat cells were X-irradiated with 4 Gy, the intensities of the fluorescence derived from G22p1 and Xrcc5 in the nuclei increased from 20% to 50% of the total cellular fluorescence intensity at 20 min postirradiation. No significant differences were observed between the total intensities of the cellular fluorescence from the proteins in unirradiated and irradiated rat fibroblasts. The results showed that the proteins were translocated from the cytoplasm to the nucleus in the rat cells after X irradiation. The nuclear translocation of the proteins from the cytoplasm was inhibited by hypertonic treatment of the cells with 0.5 M NaCl for 20 min, which inhibits the fast repair process of potentially lethal damage (PLD). When the rat cells were treated with 0.5 M NaCl immediately after X irradiation, the repair of DNA DSBs was inhibited. The surviving fraction was approximately 60% of that of irradiated cells that were not treated with 0.5 M NaCl. The surviving fraction increased with incubation time in the growth medium before treatment with NaCl. The proportions of the intensities of fluorescence from G22p1 in the nuclei of X-irradiated cells also increased from 20% to 50% with increasing interval between X irradiation and treatment with NaCl. These results suggest that nuclear translocation of G22p1 and Xrcc5 is important for the fast repair process of PLD in rat cells.

Active Transport, Cell Nucleus↗
PubMed2001

Peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that can be activated by xenobiotics and natural fatty acids. To assess the potential physiological activity of PPAR ligands on cardiac muscular cells, the effects of PPAR alpha agonist, WY-14,643, on both rat hearts and a rat cardiomyocyte cell line (H9c2 cells) were investigated. Male F344 rats were fed a diet containing WY-14,643 at a concentration of 100 ppm for 26 weeks. Cardiac muscular hypertrophy was revealed by morphometric analysis in which the diameter of the muscular fibers in WY-14,643-treated rats was larger than those of control rats. Using H9c2 cells in vitro, the protein content per cell was increased in a dose-dependent manner with the treatment of WY-14,643. The transcription of myosin light chain-2 (MLC-2), a parameter of myocardial hypertrophy, was increased in H9c2 cells transfected with the rat MLC-2/luciferase fusion gene by WY-14,643 as well as other peroxisome proliferators, clofibrate and di(2-ethylhexyl) phthalate. In addition, accumulation of myosin light chain protein was confirmed in H9c2 cells treated with WY-14,643 at 10 micrograms/ml for 7 days or more by immunohistochemistry. These results suggest that PPAR alpha ligands have a potential to regulate MLC-2, which is a contractile protein in cardiomyocytes and may play a part of role in the pathogenesis of cardiac hypertrophy.

Animals↗
PubMed2001

Gitelman's syndrome first diagnosed as Bartter's syndrome.

A 29-year-old man, who had been treated with potassium, spironolactone and indomethacin for over 9 years, was admitted because of nausea, vomiting, diarrhea and tetany manifestation. At the age of 20, he had been diagnosed as having Bartter's syndrome according to the criteria of the Japanese Ministry of Health and Welfare. Findings on admission were hypokalemia, hypomagnesemia and hypocalciuria. Renal distal fractional reabsorption rates of sodium, chloride and calcium were markedly decreased by administration of furosemide but there was no obvious change with administration of thiazide. These findings indicate that the patient had Gitelman's syndrome rather than Bartter's syndrome.

Adult↗
PubMed2001

Sarcoidosis with granulomatous interstitial nephritis: report of three cases.

Three cases of sarcoidosis with granulomatous interstitial nephritis are reported. Patients were all male and over 50 years of age. They simultaneously had evidence of multiorgan involvement of sarcoidosis including lung and skin and/or eye. In addition, distinct features were found in each case: a granulomatous infiltration mimicking unilateral renal tumor (case 1); renal insufficiency solely due to granulomatous interstitial nephritis (case 2); and renal insufficiency with calcemic nephropathy and granulomatous interstitial nephritis (case 3). Prednisolone therapy resulted in disappearance of the pseudotumor in case 1 and partial improvement of renal function in cases 2 and 3. In cases 2 and 3, however, plasma creatinine did not return to normal values and a second renal biopsy in case 2 demonstrated residual interstitial fibrosis and few granulomas, suggesting that steroid therapy did not achieve complete reversal of changes.

Aged↗
PubMed2001

Trauma sites and clinical features associated with acute hyperextension spinal cord injury without bone damage--relationship between trauma site and severity.

To elucidate whether a relationship exists between the site of trauma and severity of acute hyperextension spinal cord injury without bone damage, we examined the clinical features of 25 male and 10 female patients aged 13 to 88 years. None of the patients had vertebral damage such as fracture and dislocation. The site of impact was classified as the buccal, forehead, or mandibular region. The neurological findings were assessed according to Frankel's classification at admission and at follow up after 3 months or more to assess outcome. Eleven patients suffered trauma in the buccal region, one patient in Frankel's grade B, three in grade C, and seven in grade D at admission. All 11 of these patients showed an improvement of one grade or more to an outcome of C in one patient, D in one, and E in nine. Trauma occurred at the forehead region in 18 patients, four in grade B, 10 in grade C, and four in grade D. Improvement was seen at follow up by one grade or more to C in one patient, D in 10, and E in seven. Trauma occurred at the mandibular region in six patients, four in grade B and two in grade C. Four of these patients showed improvement of one grade or more to grade B in one, grade C in four, and grade E in one. Overall, seven patients had poor outcomes, five of whom suffered trauma to the mandibular region, indicating that impact to the mandibular region tends to have an unfavorable clinical outcome. Our findings indicate that the site of trauma greatly influences the severity of hyperextension spinal cord injury.

Adolescent↗
PubMed2001

Anterior ischemic optic neuropathy after combined ophthalmic artery embolization and craniofacial surgery--case report.

A 57-year-old man developed visual loss following craniofacial surgery for an inflammatory ethmoidal sinus mass. Surgery was preceded by endovascular occlusion of the ophthalmic artery distal to central retinal artery (CRA). Routine angiography obtained immediately after endovascular ophthalmic artery occlusion showed patency of the CRA. He complained of visual loss one day after craniofacial surgery (2 days after embolization). Repeat emergency angiography confirmed the patent CRA. Ophthalmic examination and fluorescein angiography showed that the visual loss was due to anterior ischemic optic neuropathy (AION). Preservation of the CRA is critical during ophthalmic artery embolization to avoid visual complications. Neurosurgeons should be aware of the possibility of AION as a complication of ophthalmic artery embolization.

Embolization, Therapeutic↗
PubMed2001

Response bias by neuroblastoma screening participation status and social desirability bias in an anonymous postal survey, Ishikawa, Japan.

OBJECTIVE: To examine response bias by neuroblastoma screening participation status in a population-based postal survey of parents in Ishikawa Prefecture, Japan. METHODS: The eligibility criteria for the study were: 1) parents whose infants were born in Ishikawa Prefecture between March 1997 and February 1998, and 2) of those parents who resided in the Prefecture in March 1999. Four-page questionnaires were mailed to one-third of screening participants (n = 2,886) and all the nonparticipants (n = 1,401). Questionnaires were anonymous, with no identifiers on the questionnaire. Colored papers were used for printing questionnaires to differentiate screening participation status. Response rates were calculated using demographic information on the infant registry as the denominator and demographic characteristics data from the returned questionnaire as the numerator. RESULTS: The response rate was 63% for participants and 33% for nonparticipants. The following factors were associated with lower response rates regardless of screening participation status: older maternal age (> or = 35 years), higher parity (> or = 4), nuclear family status, and mother having a full-time occupation. Approximately 20% of screening nonparticipants reported having participated in the screening. Place of residence, maternal age, and parity were associated with the percentage of incorrect reporting. CONCLUSION: Screening participation status was a major factor associated with low response rate, although some demographic characteristics were also predictive of low response rates. Incorrect reporting of screening participation among nonparticipants indicates a strong social desirability bias in this official survey in Japan.

Adult↗
PubMed2001

Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells.

Pancreatic islet cells express receptors and transporters for L-glutamate and are thus believed to use L-glutamate as an intercellular signaling molecule. However, the mechanism by which L-glutamate appears in the islets is unknown. In the present study, we investigated whether L-glutamate is secreted through exocytosis by alphaTC6 cells (clonal mouse pancreatic alpha-cells). An appreciable amount of L-glutamate was released from cultured cells after the addition of KCl or A23187 in the presence of Ca2+ and 10 mmol/l glucose in the medium. The KCl-induced glutamate release was significantly reduced when assayed in the absence of Ca2+ or when the cells were pretreated with EGTA-AM. The KCl-induced Ca2+-dependent glutamate release was inhibited approximately 40% by voltage-gated Ca2+ channel blockers, such as nifedipine at 20 micromol/l. The degree of KCl-induced Ca2+-dependent glutamate release was correlated with an increase in intracellular [Ca2+], as monitored by fura-2 fluorescence. Botulinum neurotoxin type E inhibited 55% of the KCl-induced Ca2+-dependent glutamate release, followed by specific cleavage of 25 kDa synaptosomal-associated protein. Furthermore, bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, inhibited 40% of the KCl-induced Ca2+-dependent glutamate release. Immunoelectronmicroscopy with antibodies against synaptophysin, a marker for neuronal synaptic vesicles and endocrine synaptic-like microvesicles, revealed a large number of synaptophysin-positive clear vesicles in cells. Digitonin-permeabilized cells took up L-glutamate only in the presence of MgATP, which is sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (a proton conductor) but insensitive to either oligomycin or vanadate. From these results, it was concluded that alphaTC6 cells accumulate L-glutamate in the synaptophysin-containing vesicles in an ATP-dependent manner and secrete it through a Ca2+-dependent exocytic mechanism. The Ca2+-dependent glutamate release was also triggered when cells were transferred in the medium containing 1 mmol/l glucose, suggesting that low glucose treatment stimulates the release of glutamate. Our results are consistent with the idea that L-glutamate is secreted by alpha-cells through Ca2+-dependent regulated exocytosis.

Adenosine Triphosphate↗
PubMed2001

The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation.

The cofactor of mitochondrial dehydrogenase complexes and potent antioxidant alpha-lipoic acid has been shown to lower blood glucose in diabetic animals. alpha-Lipoic acid enhances glucose uptake and GLUT1 and GLUT4 translocation in 3T3-L1 adipocytes and L6 myotubes, mimicking insulin action. In both cell types, insulin-stimulated glucose uptake is reduced by inhibitors of p38 mitogen-activated protein kinase (MAPK). Here we explore the effect of alpha-lipoic acid on p38 MAPK, phosphatidylinositol (PI) 3-kinase, and Akt1 in L6 myotubes. alpha-Lipoic acid (2.5 mmol/l) increased PI 3-kinase activity (31-fold) and Akt1 (4.9-fold). Both activities were inhibited by 100 nmol/l wortmannin. alpha-Lipoic acid also stimulated p38 MAPK phosphorylation by twofold within 10 min. The phosphorylation persisted for at least 30 min. Like insulin, alpha-lipoic acid increased the kinase activity of the alpha (2.8-fold) and beta (2.1-fold) isoforms of p38 MAPK, measured by an in vitro kinase assay. Treating cells with 10 micromol/l of the p38 MAPK inhibitors SB202190 or SB203580 reduced the alpha-lipoic acid-induced stimulation of glucose uptake by 66 and 55%, respectively. In contrast, SB202474, a structural analog that does not inhibit p38 MAPK, was without effect on glucose uptake. In contrast to 2-deoxyglucose uptake, translocation of GLUT4myc to the cell surface by either alpha-lipoic acid or insulin was unaffected by 20 micromol/l of SB202190 or SB203580. The results suggest that inhibition of 2-deoxyglucose uptake in response to alpha-lipoic acid by inhibitors of p38 MAPK is independent of an effect on GLUT4 translocation. Instead, it is likely that regulation of transporter activity is sensitive to these inhibitors.

3T3 Cells↗
PubMed2001

Body fatness and fat distribution as predictors of metabolic abnormalities and early carotid atherosclerosis.

OBJECTIVE: To test the hypothesis that intra-abdominal fat plays a primary role over general adiposity for metabolic abnormalities and atherosclerosis. RESEARCH DESIGN AND METHODS: We cross-sectionally studied 849 Japanese men aged 50.3 +/- 8.5 years (range 20-78) with BMI 23.5 +/- 2.9 kg/m(2). Intimal-medial thickness (IMT) of the carotid artery was measured by ultrasound. General adiposity was assessed by BMI. Waist circumference and waist-to-hip ratio (WHR) were used as a surrogate measure for abdominal fat. Abdominal subcutaneous fat area (ASF) and intra-abdominal fat area (IAF) were measured by computed tomography. Correlations between these measures and carotid IMT were analyzed. The interaction of generalized adiposity (BMI) and IAF in relation to metabolic variables, such as glucose tolerance, insulin resistance, and serum lipids, was also evaluated. RESULTS: BMI, waist circumference, WHR, ASF, and IAF were all correlated with carotid IMT. Adjustment for BMI eliminated the associations between IMT and waist circumference, ASF, and IAF. In contrast, WHR retained a significant correlation with IMT. BMI and IAF were associated with insulin resistance, glucose tolerance, HDL cholesterol, and blood pressure independently of each other. IAF was an independent correlate for serum triglyceride, but BMI was not. CONCLUSIONS: The primary importance of IAF over general adiposity for carotid atherosclerosis was not confirmed. Caution is recommended when using WHR as a measure of abdominal fat. The roles of IAF for metabolic abnormalities may be more limited than conventionally thought. BMI and WHR are simple and better clinical predictors for carotid atherosclerosis versus IAF.

Abdomen↗
PubMed2001

[Assessment of stage IIB lung cancer from the pathological factors].

In our experience, the prognosis of patients with pathological T3N0M0 lung cancer is generally poor, the 5-year survival rate being almost the same as that of patients with stage IIIA disease. Thus, we assessed patients with stage IIB disease by examining the pathological factors, lymphatic invasion, vessel invasion, histological type, differentiation, tumor size, and node dissection. Lymphatic invasion was found to be positive in 20 of 21 cases, patients with T3N0M0 lung cancer, and all of those with positive vessel invasion had a significantly poor prognosis. This indicates that positive lymphatic and vessel invasion could be a prognostic factor predicting a poor outcome. Patients with T3N0M0 lung cancer that are found to have this poor prognostic factor may not be diagnosed as having stage IIB disease.

Aged↗
PubMed2001

Reporter gene transgenic mice as a tool for analyzing the molecular mechanisms underlying experimental carcinogenesis.

Carcinogenic compounds are classified into 2 categories, genotoxic and non-genotoxic, which are basically judged from in vitro genotoxicity data. However, it is well documented that genotoxicants do not necessarily exert in vivo carcinogenicity in rodents, partly because of a discrepancy between in vitro and in vivo mutagenicities. Recently, transgenic animal models with reporter genes such as lacI, lacZ and gpt have been developed as a tool for assessing in vivo mutagenicity as well as carcinogenicity. In this article, data using lacI transgenic mice and gpt delta mice are presented and their application is discussed. In lacI transgenic mice, dimethylnitrosamine (DMN) treatment significantly increased lacI mutant frequency (MF) in the liver, kidenys and lungs, but not in other non-target organs. Repeated dose ip administration of DMN was more effective than single dose treatment in the induction of lacI MF. The spectrum of mutant plaques induced by DMN was characterized by deletions as well as GC to AT base transitions. The remaining mice receiving DMN proved to have liver adenomas at a high frequency after 78 weeks. Meanwhile, dietary 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) significantly increased lacI and gpt MFs in the liver and colon. The characteristic spectrum of mutant plaques induced by MeIQx was a GC to TA base transversion in both the lacI and gpt mutations. Our results thus strongly suggest that these reporter gene transgenic animal models could offer a useful tool for analyzing molecular mechanisms underlying experimental carcinogenesis and for assessing the carcinogenic risk of environmental chemicals.

Animals↗
PubMed2001

Mapping of QTLs associated with cytosolic glutamine synthetase and NADH-glutamate synthase in rice (Oryza sativa L.).

Ninety-eight backcross inbred lines (BC1F6) developed between Nipponbare, a japonica rice, and Kasalath, an indica rice were employed to detect putative quantitative trait loci (QTLs) associated with the contents of cytosolic glutamine synthetase (GS1; EC 6.3.1.2) and NADH-glutamate synthase (NADH-GOGAT; EC 1.4.1.14) in leaves. Immunoblotting analyses showed transgressive segregations toward lower or greater contents of these enzyme proteins in these backcross inbred lines. Seven chromosomal QTL regions for GS1 protein content and six for NADH-GOGAT protein content were detected. Some of these QTLs were located in QTL regions for various biochemical and physiological traits affected by nitrogen recycling. These findings suggested that the variation in GS1 and NADH-GOGAT protein contents in this population is related to the changes in the rate of nitrogen recycling from senescing organs to developing organs, leading to changes in these physiological traits. Furthermore, a structural gene for GS1 was mapped between two RFLP markers, C560 and C1408, on chromosome 2 and co-located in the QTL region for one-spikelet weight. A QTL region for NADH-GOGAT protein content was detected at the position mapped for the NADH-GOGAT structural gene on chromosome 1. A QTL region for soluble protein content in developing leaves was also detected in this region. Although fine mapping is required to identify individual genes in the future, QTL analysis could be a useful post-genomic tool to study the gene functions for regulation of nitrogen recycling in rice.

Biological Transport↗