Search PubMed⌕ Search

Biomedical subjects

M Yonezawa

Publications and source records attributed to M Yonezawa.

At least 19 recordsLinked to original sources
PubMed2006

The role of histone modifications in epigenetic transitions during normal and perturbed development.

Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. DNA methylation, histone modifications and variants, nucleosome remodeling and noncoding RNAs all contribute to the dynamic make-up of chromatin under distinct developmental options. In particular, the great diversity of covalent histone tail modifications has been proposed to be ideally suited for imparting epigenetic information. While most of the histone tail modifications represent transient marks at transcriptionally permissive chromatin, some modifications appear more robust at silent chromatin regions, where they index repressive epigenetic states with functions also outside transcriptional regulation. Under-representation of repressive histone marks could be indicative of epigenetic plasticity in stem, young and tumor cells, while committed and senescent (old) cells often display increased levels of these more stable modifications. Here, we discuss profiles of normal and aberrant histone lysine methylation patterns, as they occur during the transition of an embryonic to a differentiated cell or in controlled self-renewal vs pro-neoplastic or metastatic conditions. Elucidating these histone modification patterns promises to have important implications for novel advances in stem cell research, nuclear reprogramming and cancer, and may offer novel targets for the combat of tumor cells, potentially leading to new diagnostic and therapeutic avenues in human biology and disease.

Animals↗
PubMed2005

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

Adenoma↗
PubMed2004

Radioresistance in mammals induced by low-level chronic irradiation: modeling and experimental investigations.

Effects of chronic low-level preirradiation on radiosensitivity of mice is studied experimentally and by making use of the methods of mathematical modeling. The experiments show that a priming exposure to chronic internal irradiation can induce radioresistance in mice. The manifestation of this radioprotection effect is reduced mortality of preexposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic syndrome. Therefore, the theoretical investigation of the influence of preirradiation on radiosensitivity of mice is conducted by making use of the mathematical models that describe the dynamics of hematopoietic system in mice exposed to challenge acute irradiation following the chronic one. Modeling results show that the radioprotection effect of chronic low-level long-term (more than 1 mo) preirradiation on mice is caused by decreased radiosensitivity (radioresistance) of the granulocytopoietic system, which appeared at the level of one functional cell pool, blood granulocytes. In turn, the above-indicated state of radioresistance of the granulocytopoietic system is the consequence of hypercompensation of the radiation damage of this system resulting in relaxation to elevated concentrations of blood granulocytes and their nondividing and dividing bone-marrow precursors and in enhanced mitotic activity of the latter. Modeling results also indicate that the radiosensitization effect of chronic low-level short-term (less than 1 mo) preirradiation on mice is due to increased radiosensitivity of lymphopoietic, granulocytopoietic, and erythropoietic systems accompanied by increased or close to the normal level radiosensitivity of thrombocytopoietic system. In turn, increased radiosensitivity of above-noted hematopoietic lines is the consequence of an exhaustion of these cell systems. Modeling estimations of the duration of low-level chronic preexposures, which result in radioprotection and radiosensitization effects on mice, are in agreement with the relevant experimental data.

Animals↗
PubMed2003

Radioprotection effect of low level preirradiation on mammals: modeling and experimental investigations.

This paper is devoted to experimental and theoretical studies of low level preirradiation effects on radiosensitivity of mammals. It is shown experimentally that a priming exposure to a low dose can induce radioresistance in mice in two (early and late) periods after preirradiation. The manifestation of such effects is reduced mortality of preexposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic subsyndrome of the acute radiation syndrome. Therefore, proceeding from the radiobiological concept of critical system, the theoretical investigation of the influence of preirradiation on mammalian radiosensitivity is conducted by making use of the mathematical models of the vital body system, hematopoiesis. Modeling results obtained make it possible to elucidate the mechanisms of the radioprotection effect of low level priming irradiation on mammals. Specifically, the state of acquired radioresistance in mice is caused by reduced radiosensitivity of lymphopoietic and thrombocytopoietic systems in the early period and by reduced radiosensitivity of granulocytopoietic system, which is accompanied by slightly reduced or close to the normal level radiosensitivity of lymphopoietic system, in the late period after preirradiation. In turn, reduced radiosensitivity of above-noted hematopoietic lines is the consequence of hypercompensation of radiation damages of certain cell pools during the recovering processes running in these systems after priming irradiation. It is important to emphasize that the evaluations of the duration of the early and late periods of postirradiation radioresistance in mice, carried out on the basis of the modeling and experimental investigations, practically coincide. All this demonstrates the effectiveness of joint modeling and experimental investigations of such complicated radiobiological problems as acquired radioresistance.

Adaptation, Physiological↗
PubMed2002

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Adenocarcinoma↗
PubMed2001

Popliteal pseudoaneurysm simulating soft-tissue sarcoma: complication of osteochondroma resection.

Pseudoaneurysm complicating osteochondroma is extremely rare. We describe a pseudoaneurysm in the popliteal fossa of a 21-year-old man, occurring 5 years after apparently incomplete resection of an osteochondroma at that site. We found magnetic resonance imaging and magnetic resonance angiography to be of great diagnostic value. Resection of the pseudoaneurysm and anastomosis of the popliteal artery were successful, with no recurrence detected for almost 7 years since the operation.

Adult↗
PubMed2001

Results of surgery and radio-hyperthermo-chemotherapy for patients with soft-tissue sarcoma.

BACKGROUND: Between 1990 and 1999, we performed radio-hyperthermo-chemotherapy (RHC) in 44 patients with high-grade soft-tissue sarcomas of the limbs. METHODS: Radiotherapy involved the delivery of radiation at a dose of 2 Gy once daily on 16 days, to give a total dose of 32 Gy. Hyperthermia was conducted once a week, with a total of five sessions. Chemotherapy was performed by implanting a reservoir and administering cisplatin (3 mg/kg) three times, and pinorubin (an adriamycin derivative; 1 mg/kg) twice by intra-arterial infusion, at weekly intervals. These drugs were administered alternately during hyperthermia sessions. RESULTS: Tumor shrinkage was observed in 98% (43/44) of the patients. Of the 36 patients with M0 tumors, 30 were disease-free at final follow-up, 2 had no evidence of disease, 1 was alive with disease, and 3 had died of the disease. Amputation was required only in the first patient, and the affected limb was preserved in the other 43 patients. The surgical margin was wide in 9 patients and marginal in 29 patients, and intralesional excision was performed in 5 patients. There was recurrence in only 1 of the 44 patients. CONCLUSION: RHC is currently the most potent and relatively safe treatment method for high-grade soft-tissue sarcomas that is available clinically.

Adolescent↗
PubMed2001

A new treatment of aneurysmal bone cyst by endoscopic curettage without bone grafting.

Curettage and bone grafting are the accepted methods of treatment of aneurysmal bone cysts. Unfortunately, recurrence is common. We treated 4 patients with atypical aneurysmal bone cysts that lacked aneurysmal dilatation by endoscopic curettage without bone grafting. New bone formation and remodeling were observed in all patients. In the patients in whom the follow-up was longer than 30 months, there was no evidence of recurrence. Endoscopic curettage without bone grafting is a simple and effective treatment for aneurysmal bone cysts.

Adolescent↗
PubMed2001

Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation.

PURPOSE: Primary conditioning low dose irradiation suppresses the molecular responses against secondary challenge high dose irradiation; this phenomenon has been termed the radioadaptive response. The mechanism of the radioadaptive response is not yet clear. This study was undertaken to elucidate the radiation response of apoptosis in mouse spleen after whole-body irradiation. MATERIALS AND METHODS: The induction of apoptosis was analysed in the spleens of C57BL/6N mice after chronic irradiation with gamma-rays at 1.5 Gy (0.001 Gy/min for 25 h) followed by challenge irradiation with X-rays at 3.0Gy (1 Gy/min). RESULTS: Accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen 12 h after acute irradiation at a high dose-rate. However, it was found that there was significant suppression of the accumulation of p53 and Bax, and induction of apoptosis 12 h after challenge irradiation at 3.0Gy at a high dose-rate following chronic preirradiation at 1.5Gy at a low dose-rate. In addition, the combination of pre-irradiation at 1.5Gy at a high dose-rate and challenge irradiation at 3.0Gy at a high dose-rate could not suppress the accumulation of p53 and Bax or the induction of apoptosis. CONCLUSIONS: Chronic pre-irradiation at a low dose-rate suppressed Bax-mediated apoptosis. These findings suggest that the radioadaptive response in mouse spleen may be due to a suppression of p53-mediated apoptosis.

Adaptation, Physiological↗
PubMed2001

Long-term prognosis of acute aortic dissection with medical treatment: a survey of 263 unoperated patients.

Between 1973 and 1998, 263 patients with acute aortic dissection were medically treated only. They were divided into 4 groups: Stanford type A and B with open false lumen (open) or with early thrombosed false lumen (thrombosed). An event was defined as death by dissection or re-dissection. Gender, age, maximum diameter of dissected aorta and presence of shock at onset were examined as risk factors. In the open false lumen group, the presence of shock was associated with the event. During the chronic period, the diameter of the aorta was associated with prognosis in open type B dissection. The rate of event was higher in the open type A and B groups than in the thrombosed type A and B groups; however, there was no difference in the event-free rate between types A and B in patients surviving the acute period. The prognosis of medically treated dissecting aorta was not poor in patients with type B or with early thrombosed false lumen. The presence of shock at onset with open false lumen and the diameter of the aorta (> or =40 mm) in type B were significantly correlated with a poor prognosis.

Aged↗
PubMed2001

Tumor suppressor p53 response is blunted by low-dose radiation.

To estimate the effects of space radiation on health of space crews, we aimed to clarify whether g-ray-irradiation at a low-dose-rate interferes in a p53 centered signal transduction pathway induced by radiation in human cultured cells and CB-17 Icr+/+ mice. In vitro experiments, the human cultured squamous cell carcinoma cells (SAS/neo) were examined for cellular levels of p53 and Bax, and the incidence of apoptosis after irradiation at a low-dose-rate (1 mGy/min) or a high-dose-rate (1 Gy/min). It was found that challenging irradiation-induced apoptosis was depressed by chronic irradiation at 1.5 Gy for 25 h with the depression of p53 and Bax accumulation. In vivo experiments, a significant suppression of Bax and apoptosis induced by challenging irradiation at 3.0 Gy was observed when the mice were pre-irradiated chronically at 1.5 Gy for 25 h in the spleen of CB-17 Icr+/+ mice. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signaling and/or p53 stability.

Animals↗
PubMed2000

A new model of pulmonary superinfection with Aspergillus fumigatus and Pseudomonas aeruginosa in mice.

We have produced a new model of pulmonary super-infection with Aspergillus fumigatus and Pseudomonas aeruginosa in immunosuppressed mice. Male ICR mice were given an intratracheal inoculation of 4 x 10(5) conidia of A. fumigatus in agar beads, and were immunosuppressed with 100 mg/kg subcutaneous injections of cortisone acetate on days 7, 9, 12, 14, and 16 after inoculation. Twelve days after inoculation, with the agar beads, the mice were challenged with the intranasal instillation of 2 x 10(6) CFU of P. aeruginosa. The survival rates of superinfected, A. fumigatus-alone, P. aeruginosa-alone, and non-infected mice were 50%, 30%, 90%, and 100% 14 days after pseudomonal infection (26 days after inoculation of A. fumigatus), respectively. In the superinfected mice, both A. fumigatus and P. aeruginosa were detected more than 10 days after pseudomonal infection (22 days after inoculation of A. fumigatus). Histopathological examination revealed peribronchial necrosis around A. fumigatus hyphae and inflammation by P. aeruginosa. This infection model in mice would be useful for studying the pathogenesis of superinfection.

Animals↗
PubMed2000

Therapeutic effects of parenteral beta-lactam antibiotics on experimental otitis media caused by penicillin-resistant Streptococcus pneumoniae in guinea-pigs.

The therapeutic effects of parenteral beta-lactam antibiotics were evaluated in experimental acute otitis media caused by penicillin-resistant Streptococcus pneumoniae (PRSP) in guinea-pigs. Cefotaxime, ceftriaxone and piperacillin significantly reduced viable cell counts of PRSP in the middle ear at a dose of 50 mg/kg bd for 3 days (P < 0.01 compared with control). The therapeutic effects of cefotaxime, ceftriaxone and piperacillin were superior to those of cefotiam and ceftazidime. These therapeutic effects reflected both in vitro activity and pharmacokinetic properties of the drugs.

Animals↗
PubMed2000

Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.

OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.

Adenoma↗
PubMed2000

Descending aorta wall volume and coronary artery disease: a comparative study using enhanced computed tomography of the chest and coronary angiography.

The study examined the association between aortic wall volume (AWV) detected by enhanced computed tomography and coronary artery atherosclerosis observed on angiography. In 180 cases, AWV was measured as the total wall volume of a 7-cm portion of the descending thoracic aorta distal from the tracheal bifurcation. Coronary artery atherosclerosis was angiographically quantified by both Gensini score, in terms of the severity of coronary artery stenosis, and Extent score, in terms of the severity of coronary artery involvement. Mean AWV values between the patients with significant coronary artery stenosis and those without significant stenosis were 9.83+/-4.04 cm3 and 8.09+/-2.39 cm3, respectively (p<0.001). AWV was a significantly independent variable for significant coronary artery disease (p=0.0097) and an Extent score > or = 60 (p=0.0092). Calcification of AWV, however, was not associated with coronary atherosclerosis. The quantification of aortic atherosclerosis was useful for diagnosing coronary artery disease.

Aged↗
PubMed2000

Risk of colorectal cancer in patients with hematologic disease.

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.

Aged↗