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Biomedical subjects

N Sakuma

Publications and source records attributed to N Sakuma.

At least 19 recordsLinked to original sources
PubMed2007

Mobile phone base station-emitted radiation does not induce phosphorylation of Hsp27.

An in vitro study focusing on the effects of low-level radiofrequency (RF) fields from mobile radio base stations employing the International Mobile Telecommunication 2000 (IMT-2000) cellular system was conducted to test the hypothesis that modulated RF fields act to induce phosphorylation and overexpression of heat shock protein hsp27. First, we evaluated the responses of human cells to microwave exposure at a specific absorption rate (SAR) of 80 mW/kg, which corresponds to the limit of the average whole-body SAR for general public exposure defined as a basic restriction in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. Second, we investigated whether continuous wave (CW) and Wideband Code Division Multiple Access (W-CDMA) modulated signal RF fields at 2.1425 GHz induced activation or gene expression of hsp27 and other heat shock proteins (hsps). Human glioblastoma A172 cells were exposed to W-CDMA radiation at SARs of 80 and 800 mW/kg for 2-48 h, and CW radiation at 80 mW/kg for 24 h. Human IMR-90 fibroblasts from fetal lungs were exposed to W-CDMA at 80 and 800 mW/kg for 2 or 28 h, and CW at 80 mW/kg for 28 h. Under the RF field exposure conditions described above, no significant differences in the expression levels of phosphorylated hsp27 at serine 82 (hsp27[pS82]) were observed between the test groups exposed to W-CDMA or CW signal and the sham-exposed negative controls, as evaluated immediately after the exposure periods by bead-based multiplex assays. Moreover, no noticeable differences in the gene expression of hsps were observed between the test groups and the negative controls by DNA Chip analysis. Our results confirm that exposure to low-level RF field up to 800 mW/kg does not induce phosphorylation of hsp27 or expression of hsp gene family.

Brain Neoplasms↗
PubMed2006

DNA strand breaks are not induced in human cells exposed to 2.1425 GHz band CW and W-CDMA modulated radiofrequency fields allocated to mobile radio base stations.

We conducted a large-scale in vitro study focused on the effects of low level radiofrequency (RF) fields from mobile radio base stations employing the International Mobile Telecommunication 2000 (IMT-2000) cellular system in order to test the hypothesis that modulated RF fields may act as a DNA damaging agent. First, we evaluated the responses of human cells to microwave exposure at a specific absorption rate (SAR) of 80 mW/kg, which corresponds to the limit of the average whole body SAR for general public exposure defined as a basic restriction in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. Second, we investigated whether continuous wave (CW) and Wideband Code Division Multiple Access (W-CDMA) modulated signal RF fields at 2.1425 GHz induced different levels of DNA damage. Human glioblastoma A172 cells and normal human IMR-90 fibroblasts from fetal lungs were exposed to mobile communication frequency radiation to investigate whether such exposure produced DNA strand breaks in cell culture. A172 cells were exposed to W-CDMA radiation at SARs of 80, 250, and 800 mW/kg and CW radiation at 80 mW/kg for 2 and 24 h, while IMR-90 cells were exposed to both W-CDMA and CW radiations at a SAR of 80 mW/kg for the same time periods. Under the same RF field exposure conditions, no significant differences in the DNA strand breaks were observed between the test groups exposed to W-CDMA or CW radiation and the sham exposed negative controls, as evaluated immediately after the exposure periods by alkaline comet assays. Our results confirm that low level exposures do not act as a genotoxicant up to a SAR of 800 mW/kg.

Cell Line↗
PubMed2006

Phosphorylation and gene expression of p53 are not affected in human cells exposed to 2.1425 GHz band CW or W-CDMA modulated radiation allocated to mobile radio base stations.

A large-scale in vitro study focusing on low-level radiofrequency (RF) fields from mobile radio base stations employing the International Mobile Telecommunication 2000 (IMT-2000) cellular system was conducted to test the hypothesis that modulated RF fields induce apoptosis or other cellular stress response that activate p53 or the p53-signaling pathway. First, we evaluated the response of human cells to microwave exposure at a specific absorption rate (SAR) of 80 mW/kg, which corresponds to the limit of the average whole-body SAR for general public exposure defined as a basic restriction by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. Second, we investigated whether continuous wave (CW) and wideband code division multiple access (W-CDMA) modulated signal RF fields at 2.1425 GHz induced apoptosis or any signs of stress. Human glioblastoma A172 cells were exposed to W-CDMA radiation at SARs of 80, 250, and 800 mW/kg, and CW radiation at 80 mW/kg for 24 or 48 h. Human IMR-90 fibroblasts from fetal lungs were exposed to both W-CDMA and CW radiation at a SAR of 80 mW/kg for 28 h. Under the RF field exposure conditions described above, no significant differences in the percentage of apoptotic cells were observed between the test groups exposed to RF signals and the sham-exposed negative controls, as evaluated by the Annexin V affinity assay. No significant differences in expression levels of phosphorylated p53 at serine 15 or total p53 were observed between the test groups and the negative controls by the bead-based multiplex assay. Moreover, microarray hybridization and real-time RT-PCR analysis showed no noticeable differences in gene expression of the subsequent downstream targets of p53 signaling involved in apoptosis between the test groups and the negative controls. Our results confirm that exposure to low-level RF signals up to 800 mW/kg does not induce p53-dependent apoptosis, DNA damage, or other stress response in human cells.

Amino Acid Sequence↗
PubMed2001

Cholesteryl ester transfer protein deficiency causes slow egg embryonation of Schistosoma japonicum.

In our attempt to discover a potential cause for accumulation of cholesteryl ester transfer protein (CETP) deficiency in Eastern Asia, we studied the association of CETP deficiency with pathogenesis of Schistosoma japonicum, a life-threatening parasite peculiar to this region. The eggs of S. japonicum showed slow embryonation when cultured in CETP-deficient human plasma. Restoration of CETP to the deficient plasma rescued it, while inhibition of CETP in normal plasma did not cause slow embryonation of the cultured eggs. The egg embryonation was also retarded in the liver but not in the intestine of wild-type mice in comparison to the CETP-transgenic mice. The granulomatous lesion around the parasite eggs in the liver was less in the wild-type than in the CETP-transgenic mice. Thus, CETP deficiency may act against Schistosomiasis japonica by retarding egg embryonation, a potential cause of liver granulomatosis. It does not seem directly due to the lack of CETP activity in plasma but to abnormal lipoprotein generated by chronic CETP deficiency.

Animals↗
PubMed2001

Metastasis of cervical esophageal carcinoma to the temporal bone--a study of the temporal bone histology.

A 49-year-old male developed left abducens nerve palsy as a result of metastatic spread of carcinoma of the cervical esophagus to Rouviere's node and infiltration of the petrous portion of the left temporal bone. Postmortem temporal bone histology revealed that cancer cells had invaded the greater superficial petrosal nerve (GPN), lesser superficial petrosal nerve, tensor tympani muscle (TTM) and the skin covering the anterior wall of the left external auditory meatus. These findings suggest that the carcinoma metastasized from the cervical esophagus to Rouviere's node and directly invaded the middle cranial fossa and then the temporal bone, and further infiltrated the middle ear via perineural invasion.

Carcinoma, Squamous Cell↗
PubMed2001

Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body, as well as the body's ability to exclude selectively other dietary sterols, are poorly understood. An average western diet will contain about 250-500 mg of dietary cholesterol and about 200-400 mg of non-cholesterol sterols. About 50-60% of the dietary cholesterol is absorbed and retained by the normal human body, but less than 1% of the non-cholesterol sterols are retained. Thus, there exists a subtle mechanism that allows the body to distinguish between cholesterol and non-cholesterol sterols. In sitosterolemia, a rare autosomal recessive disorder, affected individuals hyperabsorb not only cholesterol but also all other sterols, including plant and shellfish sterols from the intestine. The major plant sterol species is sitosterol; hence the name of the disorder. Consequently, patients with this disease have very high levels of plant sterols in the plasma and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. We previously mapped the STSL locus to human chromosome 2p21 and further localized it to a region of less than 2 cM bounded by markers D2S2294 and D2S2291 (M.-H.L. et al., manuscript submitted). We now report that a new member of the ABC transporter family, ABCG5, is mutant in nine unrelated sitosterolemia patients.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities.

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.

Arteriosclerosis↗
PubMed2001

Localized malignant mesothelioma of the pleura.

We describe a case of malignant pleural mesothelioma appearing as a solitary pleural tumor in a 56-year-old Japanese man with no history of exposure to asbestos. A chest radiograph revealed an isolated extrapulmonary mass in the left hemithorax. The patient underwent tumor resection, but the tumor later recurred on the contralateral pleura. The patient developed cerebral metastases and died 16 months after the initial surgery. The resected tumor was sessile with broad-based pleural attachment. Microscopically, the tumor was composed of interlacing fascicles of plump spindle cells intermixed with few polygonal cells. Most of the tumor cells showed positive immunoreactivity for cytokeratins (AE1 and AE3) and vimentin. Many of the tumor cells were positive for epithelial membrane antigen, and a few were positive for desmin. In contrast, the tumor cells were consistently negative for carcinoembryonic antigen, epithelial antigen BerEP4, calretinin, S-100 protein, neuron-specific enolase, muscle actin antigen HHF35, alpha-smooth muscle actin antigen and CD34. Ultrastructurally, the tumor cells had diffusely distributed cytoplasmic intermediate filaments, desmosome-like junctions, and a few microvilli. Some tumor cells contained cytoplasmic tonofilaments. Immunohistochemical and ultrastructural findings supported the mesothelial nature of the tumor, and led us to diagnose this tumor as a sarcomatoid localized malignant mesothelioma.

Brain Neoplasms↗
PubMed2001

Ascorbic acid protects against peroxidative modification of low-density lipoprotein, maintaining its recognition by LDL receptors.

Peroxidatively modified low-density lipoprotein (LDL) may contribute to atherosclerotic processes; therefore, protecting LDL against peroxidation may thus reduce or retard the progression of atherosclerosis. We have evaluated the protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification. The protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification were examined by measurement of concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via LDL receptor-mediated pathway. The measurement of concentration of lipid hydroperoxides in LDL showed that ascorbic acid inhibited peroxidative modification of LDL. Also, ascorbic acid preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. These findings indicate that ascorbic acid may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.

Adult↗
PubMed2000

Recurrence of Cushing's disease after long-term remission due to pituitary apoplexy.

We encountered a case with long-term remission of Cushing's disease due to pituitary apoplexy. The apoplexy of pituitary adenoma secreting adrenocorticotropin hormone was diagnosed by successive and timely magnetic resonance imaging when the symptoms of the patient were not yet severe and anterior pituitary dysfunction was only a transient reduction of growth hormone secretion. Seven years after the first episode of pituitary apoplexy, hypercorticism recurred, and pituitary magnetic resonance imaging showed a regrowth of the pituitary adenoma. A spontaneous remission of Cushing's disease without significant visual, neurologic or hormonal defects seems to be a much more common phenomenon than has been previously suggested. Cases with relapse after spontaneous remission of Cushing's disease are rare and the duration of remission in previous reports was within 5 years. We observed such a patient with a 7 year-remission caused by pituitary apoplexy. We consider that a careful long-term follow-up is required for patients with Cushing's disease whose remission was due to pituitary apoplexy.

Adenoma↗
PubMed1999

Antiaggregatory, antithrombotic effects of MS-180, a novel platelet glycoprotein IIb/IIIa receptor antagonist.

The antiaggregatory and antithrombotic effects of (S)-(-)-ethyl[6-[4-(morpholinoformimidoyl)benzamido]-3,4-dihydro-2 H-1-benzo-pyran-3-yl]acetate hydrochloride (MS-180), a novel platelet glycoprotein IIb/IIIa receptor antagonist, were investigated. Ma-HCl, (S)-(-)-[6-[4-(Morpholinoformimidoyl)benzamido]-3,4-dihydro-2H-1-b enzopyran-3-yl]acetic acid hydrochloride, the hydrochloride salt of Ma (active metabolite), inhibited the binding of fibrinogen to immobilized human glycoprotein IIb/III receptor with an IC50 value of 0.12+/-0.03 nM without affecting binding to either fibronectin or vitronectin receptors. In anesthetized guinea pigs, intraduodenal administration of MS-180 caused dose-dependent inhibition of both ADP- and collagen-induced ex vivo platelet aggregation. At the same dosages, occluded thrombus formation and platelet release reactions were also markedly suppressed. In anesthetized dogs, the bleeding time was prolonged slightly even when submaximal inhibition (< 90%) of ex vivo platelet aggregation was achieved following i.v. administration of Ma-HCl. Aspirin (100 mg/kg) prolonged the bleeding time to the same extent as MS-180 (1 mg/kg), although it suppressed only collagen-induced platelet aggregation. Therefore, MS-180 may be clinically useful for the treatment of thrombotic diseases.

Acetates↗
PubMed1999

Takayasu's arteritis accompanied with massive pericardial effusion--a case report.

A 40-year-old woman who had been treated for Takayasu's arteritis was admitted to the hospital with fever, fatigue, malaise, and severe chest pain. Computed tomography of the chest demonstrated massive pericardial effusion and bilateral pleural effusion. In laboratory data, the C-reactive protein was high at 22.0 mg/dL, and erythrocyte sedimentation rate was also high at 80 mm/hr. The diagnosis was pericarditis with a recurrence of the systemic inflammatory process of Takayasu's arteritis. The patient was treated with methylprednisolone pulse therapy. Her massive pericardial effusion disappeared without pericardiocentesis.

Adult↗
PubMed1999

[Differential diagnosis among reactive mesothelia, adenocarcinoma and malignant mesothelioma].

We tried to distinguish reactive mesothelia (RM), adenocarcinoma (AC), and malignant mesothelioma (MM) in the body fluid. Morphometrically, nuclear uneveness index (NUI) of the benign and neoplastic mesothelial cells was smaller than that of the adenocarcinoma cells. About N/C area ratio, that of reactive mesothelial cells was larger than that of two types of malignant cells (lung AC and MM). But that of gastric AC was the largest in all groups. Ultrastructurally, length to diameter ratio (LDR) of mesothelioma cells was statistically greater, and intermediate filaments of benign and malignant mesothelial cells were more abundant than that of AC. For immunohistochemical diagnosis, it was necessary to use appropriately the specific and sensitive markers for benign and malignant mesothelial cells, or AC cells in combination.

Adenocarcinoma↗
PubMed1998

Strong synergistic anti-peroxidative effects of HDL3 and ascorbic acid against copper-catalyzed LDL peroxidation.

The aim of this study was to investigate the effects of high density lipoprotein 3 (HDL3) and ascorbic acid (AsA) in combination on copper-catalyzed low density lipoprotein (LDL) peroxidation. LDL and HDL3 were isolated from sera of healthy volunteers. LDL protein, 200 microg/ml, was incubated in phosphate-buffered saline (PBS) containing 2.5 microM CuSO4 in the absence or presence of AsA, with HDL3 protein alone, or with coincubation of HDL3, 200 microg/ml, and AsA, 20 microg/ml, at 37 degrees C for up to 24 h. As a control, the same amount of control LDL protein was added to PBS. The protective effects of the HDL3 and AsA were examined by both electrophoresis and determination of the lipid hydroperoxide (LPO) level in each sample. The concentration of AsA was also measured in samples containing AsA. The coincubation of HDL3 and AsA exerts more powerful anti-peroxidative effects against copper-catalyzed LDL peroxidation, than either of these agents alone. In addition, AsA was retained in the media by the addition of HDL3. The findings suggest that there are strong synergistic anti-peroxidative effects of HDL3 and AsA and these two may act in concert in vivo to inhibit LDL peroxidation and thus exert an anti-atherosclerotic effect.

Antioxidants↗
PubMed1998

Fractional removal rate of fat emulsion (K2) remains to be low in APOE3/3 phenotype subjects with serum triglyceride level above 180mg/dl.

The relation between fractional catabolic rate (K2) of an intravenously injected fat emulsion, Intralipid, and the level of serum triglyceride (TG) was evaluated to cast light on TG-rich lipoprotein metabolism in 182 subjects who were homozygotes for the most common form of apoE3/3. Both normolipidemic individuals and primary hyperlipidemic patients were included. To assess the influence of variation in the apoE phenotype on fat emulsion metabolism, 25 subjects with the apoE 4/3 phenotype and 21 with apoE 3/2 phenotype were also evaluated. In the apoE 3/3 subjects, K2 decreased with increasing TG level up to 180mg/dl, but above 180mg/dl, K2 remained at a constant level. This TG value was therefore concluded to be a cut off beyond which the TG-dependent decrease in K2 disappeared. No apparent correlation between K2 and serum TG was observed in subjects with apoE 4/3 or 3/2 phenotypes. In subjects with TG above 180mg/dl, presumably both accelerated synthesis and limited removal are involved in the development of their hypertriglyceridemia. Since K2 demonstrated little change with increase of TG over 180mg/dl in apoE 3/3 subjects, we concluded that the capacity to catabolize fat emulsion reaches a kinetic saturation. The TG value of 180mg/dl may be a physiological significance. The relation between K2 and TG was specific in apoE 3/3, as it was not observed in subjects having apoE 4/3 or 3/2 phenotypes.

Adult↗
PubMed1998

Preparation of a monoclonal antibody specific for human stanniocalcin.

Stanniocalcin (STC) is a glycoprotein hormone that was first identified in fish, where it regulates the calcium level in the body fluid. The cDNA which encodes human STC has recently been reported but the function has not been completely elucidated. We have prepared a monoclonal antibody against human STC using an analogous peptide of the putative antigenic domain in human STC; it was conjugated with keyhole limpet hemocyanin (KLH). The monoclonal antibody specifically stained the distal convoluted tubules in human kidney which is a putative target organ of STC. The ELISA was established using the monoclonal antibody and recombinant human STC as a standard antigen. The monoclonal antibody prepared in this study provides a useful tool for clinical studies of STC in human.

Amino Acid Sequence↗
PubMed1998

alpha-tocopherol protects the peroxidative modification of LDL to be recognized by LDL receptors.

BACKGROUND: Peroxidatively modified low-density lipoprotein (LDL) may contribute to the atherosclerotic process; therefore, protecting LDL against peroxidation may reduce or retard the progression of atherosclerosis. We evaluated the effect of alpha-tocopherol on copper-catalyzed LDL peroxidative modification. METHODS: The protective effects of alpha-tocopherol on copper-catalyzed LDL peroxidative modification were examined by measurement of the concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via the LDL receptor-mediated pathway. RESULTS: The measurement of concentration of lipid hydroperoxides in LDL showed that alpha-tocopherol inhibited the peroxidative modification of LDL. Also, alpha-tocopherol preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. CONCLUSION: These findings indicate that alpha-tocopherol may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.

Adult↗