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Biomedical subjects

M Takemoto

Publications and source records attributed to M Takemoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans.

It is of great interest and value to evaluate the systemic nitric oxide (NO) production rate in humans under various conditions. However, the currently available estimation methods are troublesome and time-consuming. We thus aimed at developing a simple method to estimate the basal systemic NO production rate in humans based on a steady-state analysis, i.e., a balance between the systemic NO production rate and the total nitrate elimination rate. Plasma nitrate concentrations of young healthy volunteers (n = 7 in group 1: n = 9 in group 2) were measured for 2 days. In group 1, all subjects had the same meals for 7 days prior to the plasma nitrate measurement. In group 2, all subjects were allowed free diets. The plasma nitrate concentrations were highly influenced by dietary nitrite/nitrate intake in both groups and reached the steady-state levels after 14-h fasting. Accordingly, the basal systemic NO production rates were estimated from the plasma nitrate concentrations after 14-h fasting (group 1, 630 +/- 37 nmol min(-1) = 0.78 +/- 0.03 micromol kg(-1) h(-1); group 2, 597 +/- 45 nmol min(-1) = 0.66 +/- 0.05 micromol kg(-1) h(-1), P = not significant vs group 1). These estimated values were comparable to the values obtained by other methods. In conclusion, the present estimation method with 14-h fasting using a single-compartment analysis was found to be a simple approach to quantitative evaluation and intra- and interindividual comparisons of the basal systemic NO production rates in humans.

Adult↗
PubMed2000

Diagnostic usefulness of diffusion-weighted magnetic resonance imaging in influenza-associated acute encephalopathy or encephalitis.

A magnetic resonance imaging (MRI) study was performed for a 20-month-old girl with an influenza type A infection who presented acute encephalopathy. Conventional MRI performed 8 days after the onset of encephalopathy, including T1-weighted, T2-weighted, and fluid-attenuated inversion recovery imaging, revealed only vague lesions in the right frontal, temporal, and parietal lobes. In contrast, diffusion-weighted imaging (DWI) then demonstrated the lesions much more intensively. On the 26th day, the lesions previously observed on DWI had become less discernible. The hyperintensity observed on DWI might reflect cytotoxic edema. Thus, DWI may be useful for evaluation of acute influenzal encephalopathy/encephalitis.

Acute Disease↗
PubMed2000

Microcapsulated parathyroid tissue in vitro.

Ideally, microcapsules will make it possible to transplant parathyroid tissue for allo- and xenotransplantation in hypoparathyroid patients. In this study, parathyroid tissues capsulated by polyelectrolyte complex were evaluated in vitro. Hormone secretion ability was significantly (P < 0.001) greater in sediment than in supernatant. There was no difference in hormone secretion ability between the parathyroid tissue thawed at room temperature and the tissue thawed in a bath at 37 degrees C. Both non-capsulated and capsulated parathyroid tissues were incubated for three weeks. The ability of capsulated parathyroid to secrete hormones in vitro was reduced gradually and disappeared within three weeks. There are still several problems to be solved before the clinical application of parathyroid allotransplantation using microcapsulation.

Cryopreservation↗
PubMed2000

Chronic inhibition of nitric oxide synthesis in rats increases aortic superoxide anion production via the action of angiotensin II.

OBJECTIVE: Chronic inhibition of nitric oxide (NO) synthesis by Nomega-nitro-L-arginine methyl ester (L-NAME) increases vascular tissue angiotensin II activity and oxidative stress in animals by incompletely understood mechanisms. In a rat model, we investigated the role of local angiotensin II activity in the pathogenesis of increased oxidative stress. DESIGN: We studied the aortas of control rats and others receiving L-NAME or L-NAME plus an angiotensin II type 1 receptor antagonist (CS-866). RESULTS: Administration of L-NAME for 7 days significantly increased superoxide anion (O2-) and both immunoreactivity and electrophoretically demonstrable activity of redox-sensitive transcription factors (NF-kappaB and AP-1). Treatment with the angiotensin II type 1 receptor antagonist prevented all of the above changes. The observed effects of the type 1 receptor antagonist was independent of the L-NAME-induced arterial hypertension. CONCLUSIONS: These findings suggest that chronic inhibition of NO synthesis may increase vascular oxidative stress and oxidative stress-sensitive signals via the action of angiotensin II mediated via type 1 receptors.

Angiotensin II↗
PubMed2000

Enhanced expression of osteopontin by high glucose. Involvement of osteopontin in diabetic macroangiopathy.

Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.

Animals↗
PubMed2000

Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis.

We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathways as well as hexosamine pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the staining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smooth muscle cells. OPN and PDGF synergistically activated focal adhesion kinase as well as extracellular signal-regulated kinase; this finding seems to explain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken together, our present results raise a possibility that OPN plays a role in the development of diabetic vascular complications.

Adult↗
PubMed2000

Interpolation of missing part of human follicle border on ultrasonic B-mode image by iterative revision.

In clinical infertility treatments, assessment of ovarian follicle growth by ultrasonography is important. In order to measure the geometrical characteristics of the human follicle, such as the area of the cross-sectional image and the volume inside the follicle, a method based on manual tracing of the follicle contour from the ultrasonic B mode image is widely used. However, the observable ultrasonic B mode images are sometimes imperfect and some parts of the follicle border are missing due to the existence of the acoustic shadow. In this paper, a method that interpolates the missing part of the follicle border from the known part is proposed. This method uses a priori information of the follicle, which is usually known in actual cases: (1) the follicle's surface is so smooth that its border is assumed to be a smooth closed curve; and (2) the position of the follicle's center is roughly predicted in advance in the ultrasonic B-mode image. In the proposed method, the missing part of the human follicle border is interpolated from the known part by applying an iterative revision so as to satisfy the smoothness condition of the follicle. This method is also applied to three-dimensional image reconstruction of the human follicle.

Algorithms↗
PubMed2000

Inhibition of in vitro fertilization of mouse gametes by sulfated sialic acid polymers.

The effect of sialic acid (N-acetyl neuraminic acid), sialic acid dimer, sialic acid polymers (colominic acid) and sulfated colominic acid on the activity of hyaluronidase, on the dispersion of cumulus cells by mouse sperm and on in vitro mouse fertilization (sperm penetration of zona pellucida) were evaluated. Bovine testicular hyaluronidase activity was significantly inhibited by colominic acid and sulfated colominic acid, but not by sialic acid and its dimer. The dispersion of cumulus cells from eggs by mouse sperm was also inhibited by colominic acid and sulfated colominic acid. In vitro fertilization of mouse gametes was inhibited by sulfated colominic acid. The IC50 value of sulfated colominic acid-induced inhibition of fertilization was 0.3 mg/ml (ca. 0.9 mM). The value changed from 0.9 mM for cumulus-surrounded egg to 1.5 mM for cumulus free-egg. On the other hand, colominic acid showed little or no inhibitory effect on mouse in vitro fertilization at 0.5 mg/ml (ca. 1.6 mM). This antifertility activity by sulfated colominic acid did not appear to be due to an effect on sperm motility or on the oocytes. These results suggest that (1) the cumulus cells surrounding the eggs were dispersed by sperm hyaluronidase, (2) hyaluronidase was inhibited by colominic acid and by sulfated colominic acid, (3) sulfated colominic acid inhibits sperm penetration of zona pellucida by the inhibition of hyaluronidase and/or some enzymes required for mouse gametes fertilization.

Animals↗
PubMed2000

Decrease of nitric oxide end-products during coronary circulation reflects elevated basal coronary artery tone in patients with vasospastic angina.

The aim of this study was to investigate the role of nitric oxide (NO) in the coronary circulation and its relation to basal coronary artery tone in patients with vasospastic angina (VSA). We evaluated the level of nitric oxide end-products (NOx; nitrite + nitrate) in coronary circulation blood using an HPLC-Griess system for nine patients with VSA and nine control patients. All of the patients with VSA experienced focal spasm in the proximal to middle segments of the left anterior descending coronary artery (LAD) in response to intracoronary injection of ergonovine maleate. The luminal diameter of the coronary artery was measured in each patient by quantitative coronary arteriography. Blood samples for NOx measurement were obtained from the coronary sinus (NOxV) and the ostium of the left coronary artery (NOxA). The NOx difference, calculated from the coronary venous-arterial difference in NOx, was close to zero for the control patients whereas it was clearly negative for the patients with VSA. In addition, the NOx difference in the patients with VSA showed a negative correlation with basal coronary artery tone (r = -0.91, p < 0.01) and a positive correlation with the dose of ergonovine required for spasm provocation (r = 0.77, p < 0.05). These results indicate that increased basal coronary artery tone and higher susceptibility to ergonovine in patients with VSA would be a consequence of coronary endothelial dysfunction as is indicated by NOx.

Adult↗
PubMed2000

An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation.

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.

Disease-Free Survival↗
PubMed1999

Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells.

Atherosclerotic vascular disease is a major complication of diabetic patients, and osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin, and azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase (the key enzyme of the hexosamine pathway), profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.

Animals↗
PubMed1999

Platelet-derived growth factor activates p38 mitogen-activated protein kinase through a Ras-dependent pathway that is important for actin reorganization and cell migration.

Members of the mitogen activated protein (MAP) kinase family, extracellular signal-regulated kinase, stress-activated protein kinase-1/c-Jun NH2-terminal kinase, and p38, are central elements that transduce the signal generated by growth factors, cytokines, and stressing agents. It is well known that the platelet-derived growth factor (PDGF) activates extracellular signal-regulated kinase, which leads to cellular mitogenic response. On the other hand, the role of the other MAP kinases in mediating the cellular function of PDGF remains unclear. In the present study, we have investigated the functional role of the other MAP kinases in PDGF-mediated cellular responses. We show that ligand stimulation of PDGF receptors leads to the activation of p38 but not stress-activated protein kinase-1/c-Jun NH2-terminal kinase. Experiments using a specific inhibitor of p38, SB203580, show that the activation of p38 is required for PDGF-induced cell motility responses such as cell migration and actin reorganization but not required for PDGF-stimulated DNA synthesis. Analyses of tyrosine residue-mutated PDGF receptors show that Src homology 2 domain-containing proteins including Src family kinases, phosphatidylinositol 3-kinase, the GTPase-activating protein of Ras, the Src homology 2 domain-containing phosphatase SHP-2, phospholipase C-gamma, and Crk do not play a major role in mediating the PDGF-induced activation of p38. Finally, the expression of dominant-negative Ras but not dominant-negative Rac inhibited p38 activation by PDGF, suggesting that Ras is a potent mediator in the p38 activation pathway downstream of PDGF receptors. Taken together, our present study proposes the existence of a Ras-dependent pathway for the activation of p38, which is important for cell motility responses elicited by PDGF stimulation.

Actins↗
PubMed1999

Rubinstein-Taybi syndrome: a girl with a history of neuroblastoma and premature thelarche.

A 7-year-old girl with Rubinstein-Taybi syndrome (RTS) who had a history of neuroblastoma and premature thelarche is reported. The neuroblastoma was detected at age 6 months on a nation-wide neuroblastoma screening program, surgically removed, and took a favorable clinical course with minimal therapy. She developed isolated breasts at age 6 years, had normal plasma levels of estradiol, follicular-stimulating hormone (FSH), and luteinizing hormone (LH), and showed a FSH-predominant pattern on the LH-releasing hormone stimulation test. In view of these findings, she was diagnosed to have premature thelarche. Premature thelarche may not be uncommon in girls with RTS.

Breast↗
PubMed1999

Increase in circulating levels of monocyte chemoattractant protein-1 with aging.

Monocyte chemoattractant protein-1 (MCP-1) is a member of chemokines with chemoattractant activity for monocytes, T cells, mast cells, and basophils. Precursor mRNA or protein was detected at high levels in the lesions of several diseases, such as pulmonary fibrosis, rheumatoid arthritis, atherosclerosis, and some types of tumors. The regulation of MCP-1 production and the role of this chemokine in pathophysiologic states, however, remain largely unknown. In this study, using an enzyme-linked immunosorbent assay (ELISA), we measured the circulating MCP-1 levels in 405 healthy Japanese subjects of various ages, eliciting a profound age-dependent MCP-1 increase. Multivariate regression analysis revealed that significant predictors of MCP-1 value for males were age (p = 0.033) and serum triglyceride (p = 0.039). For females, age was also a significant predictor (p = 0.00002). One possible explanation is that the plasma MCP-1 concentration might reflect the existence of atherosclerosis, although the plasma MCP-1 concentration from patients with coronary artery disease or cerebrovascular accidents appears not to differ from age-matched, disease-free controls. This is the first report linking an increase in a particular chemokine level with aging.

Adult↗
PubMed1999

The results of radiotherapy for T1 glottic cancers; influence of radiation beam energy.

We analyzed the influence of various parameters on the results of radiotherapy for T1 glottic cancer by assessing the outcomes of 60 patients with this cancer who received definitive radiotherapy between 1985 and 1994. Seven patients were treated with a cobalt-60 unit, and the other 53 with a linear accelerator (26 patients at 3-MV, 10 at 6-MV, and 17 at 10-MV). Of the 17 patients treated at 10-MV, 4 also received part of their treatment with a cobalt-60 unit. The total radiation dose ranged from 56 Gy to 70 Gy (mean, 61 Gy). The total radiation dose of 51 patients (85%) was 60 Gy. The factors found to influence local control were the strength of the radiation beam energy and whether or not there was gross tumor invasion of the anterior commissure. The local control rate was 71% in the patients treated with a 10-MV linear accelerator, 56% in those treated with a 6-MV linear accelerator and, 97% in those treated with a cobalt-60 unit or a 3-MV linear accelerator (P = 0.0173). The local control rate was 43% in the patients with gross anterior commissure invasion and 88% in those without (P = 0.0075). We conclude that low energy photon beams are more suitable for the treatment of early glottic cancers, especially if the lesion grossly invades the anterior commissure.

Aged↗
PubMed1999

A new experimental system for irradiating tumors in mice using a linear accelerator under specific pathogen-free conditions.

We developed a reliable system for the irradiation of xenografted tumors in mice which allows for accurate local irradiation under specific pathogen-free conditions. The system presented here consists of acrylic supports for mice and an acrylic box connected to a pump through 0.22 microns pore-sized filters. Mice with xenotransplanted tumors growing on their right hind legs were set on the supports and put into the box in a laminar flow hood. The tumors of 7 mice were irradiated simultaneously with X-rays of 6 and 10 MV generated by a linear accelerator at a dose rate of 3.1-4.7 Gy/min. The air was ventilated through filters during irradiation in the closed box. Microorganism tests confirmed that no bacteria entered or left the box. One of the significant characteristics of this setup is that it allows for irradiation under conditions of acute hypoxia, which is obtained using an integrated tourniquet. The dose variation among 7 tumors was less than 1%. The rest of the mouse's body was shielded effectively by a half-field technique and a lead block. As a result, the whole body dose for the mice was 0-4% of the total dose absorbed by the tumor. Due to the high dose rate and the ability to irradiate 7 mice simultaneously under specific pathogen-free conditions, this new system can be considered a time-saving and valuable tool for radiation oncology research.

Animals↗
PubMed1999

[Effects of aging and hyperlipidemia on plasma osteopontin level].

In order to elucidate a possible mechanism for accelerated atherogenesis as well as enhanced vascular calcification observed during the normal aging process, we measured plasma osteopontin (OPN) levels and examined their relation to aging and certain disease parameters. In all cases examined, no significant relation was found between the plasma OPN level and age, body mass index, blood pressure, plasma levels of glucose and insulin, serum levels of creatinine, triglyceride, and high density lipoprotein cholesterol. On the other hand, a significant negative correlation was found between the plasma OPN level and serum total cholesterol concentration (n = 78, r = -0.355, p = 0.0014). The serum level of low density lipoprotein (LDL) cholesterol, calculated by the formula of Friedewald, also showed a significant negative correlation to the plasma OPN level (n = 78, r = -0.301, p = 0.0075). In cases without diabetes mellitus and hypertension, a significant positive correlation was found between the plasma OPN level and age (n = 22, r = 0.445, p = 0.0378). It is postulated that OPN plays a negative regulatory role in the development of vascular calcification. Therefore, the observed negative relationship between the plasma OPN level and the serum levels of total cholesterol and LDL cholesterol, suggests a possibility that hypercholesterolemia facilitates vascular calcification by suppressing OPN synthesis. On the other hand, in non-diabetic and normotensive cases, the positive relationship between the plasma OPN level and age may reflect a defense mechanism against age-related increase of vascular calcification.

Aging↗