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N Sasaki

Publications and source records attributed to N Sasaki.

At least 19 recordsLinked to original sources
PubMed2006

The atypical antipsychotic clozapine impairs insulin secretion by inhibiting glucose metabolism and distal steps in rat pancreatic islets.

AIMS/HYPOTHESIS: Diabetogenic effects of some atypical antipsychotic drugs have been reported, although the mechanisms are not fully understood. We investigated the long-term effects of culturing isolated rat pancreatic islets with atypical antipsychotic clozapine. METHODS: Glucose- and non-glucose-stimulated insulin secretion, glucose metabolism and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in islets cultured with or without clozapine. RESULTS: Although acute incubation or 3-day culture with clozapine did not affect glucose-stimulated insulin secretion, clozapine suppressed glucose-stimulated insulin secretion by 53.2% at 1.0 micromol/l (therapeutic concentration) after 7 days of culture. Islet glucose oxidation and [Ca(2+)](i) elevation by high glucose were not affected after 3 days of culture, but clozapine significantly inhibited islet glucose oxidation, ATP production, and [Ca(2+)](i) elevation by high glucose after 7 days of culture. Moreover, 7 days of culture with clozapine inhibited insulin secretion stimulated by: (1) membrane depolarisation induced by high K(+); (2) protein kinase C activation; and (3) mastoparan at 16.7 mmol/l glucose under stringent Ca(2+)-free conditions. Elevation of [Ca(2+)](i) by high K(+)-induced membrane depolarisation was similar in control and clozapine-treated islets. Clozapine, a muscarinic blocker, acutely inhibited carbachol-induced insulin secretion, as did atropine, whereas after 7 days of culture atropine did not have the inhibitory effect shown by clozapine after 7 days. The impairment of glucose-stimulated insulin secretion recovered 3 days after the removal of clozapine treatment. CONCLUSIONS/INTERPRETATION: The present study demonstrated that the atypical antipsychotic drug clozapine directly impaired insulin secretion via multiple sites including glucose metabolism and the distal step in insulin exocytosis in a long-term culture condition. These mechanisms may be involved in the form of diabetes mellitus associated with atypical antipsychotic drugs.

Adenosine Triphosphate↗
PubMed2006

Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team.

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.

Adolescent↗
PubMed2006

Apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.

A five-year-old, male crossbreed rabbit was referred for acute caudal abdominal swelling. On physical examination, the rabbit was slightly depressed and showed an enlarged subcutaneous cyst in the caudal abdomen and an adjacent small, ulcerated solid mass. A drainage tube was placed in the cystic area, and surgical resection of the solid mass was performed. The histopathological diagnosis of the mass was apocrine adenocarcinoma. To the authors' knowledge, this report describes the first case of spontaneous apocrine adenocarcinoma of possible sweat gland origin in a male rabbit.

Adenocarcinoma↗
PubMed2006

Effect of CT acquisition parameters in the detection of subtle hypoattenuation in acute cerebral infarction: a phantom study.

BACKGROUND AND PURPOSE: We evaluated the effects of varying tube voltage, current per rotation, and section thickness on detectability of 2- and 4-Hounsfield unit (HU) differences on brain CT between normal and ischemic gray matter within 6 hours of ischemia onset, by using a low-contrast phantom. METHODS: The phantom with an attenuation of 36 HU corresponding to normal gray matter contained 2 sets of spheres (34 HU and 32 HU) corresponding to the early CT signs of ischemic brain and complete infarction, respectively. The reproducibility of the CT numbers and the contrast-to-noise ratio (CNR), defined as the CT number difference between the background (36 HU) and the spheres (34 HU or 32 HU) divided by the SD of the background CT number were measured. Five radiologists rated the phantom images for detection of the low-contrast spheres by visual inspection. RESULTS: The CT numbers were reproducible within 1 HU with a tube current of > or =150 mAs at 120 kVp. The CNRs for the 34- and 32-HU spheres were positively correlated with the tube voltage, tube current per rotation, and the section thickness. A CNR of 1.0 was obtained for the 34-HU sphere when scanning was conducted with a section thickness of 10 mm at 120 kVp and 700 mAs, or 135kVp and 450 mAs, respectively. A significant improvement of the accuracy of detection was found with increasing tube current, tube voltage per rotation, and section thickness. CONCLUSION: Our study indicated that the 2-HU hypoattenuation corresponding to the early CT sign of acute ischemic stroke can be detected by using appropriate parameter settings.

Acute Disease↗
PubMed2005

Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours.

We characterised cultured canine mammary gland adenocarcinoma cells by exhaustive step protein expression analysis to identify factors associated with tumour progression or metastasis of canine mammary gland tumour. Cultured adenocarcinoma cells derived from a total of 3 primary and 3 metastatic lesions from 3 dogs (CHMp/m, CIPp/m and CNMp/m, where CHM, CIP, and CNM indicate the 3 animals) were used in this study. The expression of 24 proteins reported to be related to tumourigenesis or malignancy of human breast cancers were examined by Western blot analysis using 24 antibodies. The expression of sialyl Lewis X [sLe(x)] was only observed in CHMm cells, which were derived from pleural effusion. This expression was further confirmed by immunohistochemistry. The levels of some factors, such as 14-3-3sigma, cyclinD1 and Rb, differed among cells or between the primary and metastatic cells in the pair. Though the difference in their expression was not consistent within the cells from primary and metastatic origin, this characterisation should provide useful information for further molecular analysis of these cultured cells. Since some of the factors, such as sLe(x), 14-3-3sigma, cyclinD1 and Rb, showed different levels of expression in the pair, these cultured cells might be meaningful tools for clarification of distant metastasis in canine mammary gland tumours.

14-3-3 Proteins↗
PubMed2005

Coat protein-independent cell-to-cell movement of bromoviruses expressing brome mosaic virus movement protein with an adaptation-related amino acid change in the central region.

The movement protein (MP) of Brome mosaic virus (BMV) depends on the coat protein (CP) to mediate the cell-to-cell movement of BMV and CCMV(B3a), a recombinant Cowpea chlorotic mottle virus (CCMV) expressing BMV MP. Previous studies identified gain-of-function mutations in the central region of BMV MP that enable CCMV(B3a) to adapt to a resistant host. This study demonstrates that all adaptation-related MPs can partially or almost fully mediate the cell-to-cell movement of CCMV(B3a) and BMV without CP. Based on these results, we discuss adaptation mechanisms of CCMV(B3a) and the role of the central region of MP in the determination of virus movement mode.

Adaptation, Physiological↗
PubMed2005

Salivary bisphenol-A levels detected by ELISA after restoration with composite resin.

Bisphenol-A diglycidylether methacrylate (Bis-GMA), which is synthesized from bisphenol-A (BPA), a compound with exogenous endocrine disrupter action, is widely used as a dental material. During clinical filling with sealants and composite resins, the compounds are solidified by polymerization and then used. However, it has been noted that unpolymerized monomers may become dissolved in saliva. In this study using a competitive ELISA system, we investigated the changes in the BPA concentration in saliva after restoration with composite resins. Commercial composite resins from nine companies were tested. Mixed saliva was collected from 21 subjects. Based on the dynamics of salivary BPA detected by this ELISA system, we concluded that several tens to 100 ng/ml of BPA were contained in saliva after filling teeth with composite resin but that sufficient gargling can remove it from the oral cavity. Our data suggest that sufficient gargling after treatment is important for risk management.

Benzhydryl Compounds↗
PubMed2005

Malate dehydrogenase activities are lower in some types of peripheral leucocytes of dogs and cats with type 1 diabetes mellitus.

The activities of the enzymes in the malate-aspartate shuttle were measured in peripheral leucocytes of spontaneous type 1 diabetic dogs and cats treated with insulin injections. In the diabetic dogs and cats, fasting plasma glucose concentrations were three- or fourfold greater than the control levels in spite of insulin injections and the activities of cytosolic malate dehydrogenase (MDH), one of pivotal enzymes in the malate-aspartate shuttle, were remarkably lower than the controls. Depressed expression of cytosolic MDH mRNA was confirmed by RT-PCR analysis in the diabetic animals. The cytosolic ratio of MDH/lactate dehydrogenase (LDH) activity (M / L ratio) in leucocytes of the diabetic animals was significantly lower than that of normal control animals. The smaller M / L ratio appeared to reflect depression of energy metabolism in the diabetic animals. Intrinsically lower and further decreased MDH activities may be factors that induce insulin resistance observed in diabetic cats.

Animals↗
PubMed2005

Distribution of new methylene blue injected into the caudal epidural space in cattle.

To investigate the distribution of solutions injected into the first intercoccygeal epidural space, 24 adult, standing cattle were randomly assigned to 5-, 10- and 20-mL groups and injected with 0.12% new methylene blue (NMB) in 0.9% saline. Ten heifers received 1 mL NMB solution/100 kg of body weight. There was a significant correlation between the injected volume and the number of cranially stained spinal segments in three adult cattle groups (correlation coefficient R2=0.46; P<0.0001). In three cattle, NMB solution did not distribute more than one spinal segment cranially from the injection site due either to fibrosis of the epidural tissue or to inadvertent intravenous administration into the epidural vein. The study showed that the larger the volume of solution injected, the greater the spread with increased individual variation. The results could form the basis for determining the volume of injection required and for evaluating the pharmacokinetics of anaesthetics used in caudal epidural anaesthesia.

Anesthesia, Epidural↗
PubMed2005

Two cases of feline malignant craniopharyngioma.

Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.

Animals↗
PubMed2004

Stable expression of foreign proteins in herbaceous and apple plants using Apple latent spherical virus RNA2 vectors.

Infectious cDNA clones of Apple latent spherical virus (ALSV)-RNA1 (pEALSR1) and -RNA2 (pEALSR2) were constructed using an enhanced 35S promoter. A viral vector was constructed from pEALSR2 by creating artificial protease processing sites by duplicating the Q/G protease cleavage site between 42KP and Vp25. Eight RNA2-derived vectors expressing GFP with varied sizes of duplications around the 42KP/Vp25 junction were constructed and tested for infectivity in Chenopodium quinoa. The results indicated that greater than five aa from the C-terminus of 42KP and N-terminus of Vp25 in duplication are necessary for systemic infection. In infected C. quinoa plants, GFP fluorescence was observed in both inoculated and upper leaves. Serial passages of the viruses derived from the above vectors in C. quinoa showed that the size of duplications affected the stability of the GFP gene. The version of the RNA2-vector (pER2L5R5GFP) with the shortest duplications and its silent mutant version could stably express GFP in leaves even after at least nine serial passages. ALSV-RNA2 vector has a capacity to maintain a DNA insert as long as 1300 bp because Apple chlorotic leaf spot virus movement protein (50KP) gene could be expressed in C. quinoa. Inoculation of a virus derived from pER2L5R5GFP to apple seedlings resulted in the expression of GFP fluorescence in uninoculated upper leaves, indicating that the vector is available for the expression of foreign genes in apple trees.

Blotting, Western↗
PubMed2004

Transient posttranslational up-regulation of telomerase activity during megakaryocytic differentiation of K562 cells.

Telomerase is active in immature somatic cells, but not in differentiated cells. However, the mechanism by which telomerase is regulated in relation to cell differentiation is not well understood. In this study, the human erythroid leukemia cell line K562 was induced to differentiate into megakaryocytes by TPA and into erythroid by STI571. The human acute myeloblastic leukemia cell line HL60 was also induced to differentiate into monocytes by TPA. Telomerase activity, the expression of human telomerase reverse transcriptase, hTERT, and the cell cycle were examined. TPA induced a transient increase in telomerase activity during the megakaryocytic differentiation while the message of hTERT decreased gradually throughout the same period. This suggests the existence of a regulatory mechanism other than transcription of hTERT. Cell cycle analysis revealed that cells in G(2)/M phase increased in number in accordance with the changes in telomerase activity. Pretreatment with PKC inhibitors inhibited the megakaryocytic differentiation, transient increase in telomerase activity, and G(2)/M arrest. These results suggest that PKC acts as a transient post-translational activator of telomerase during megakaryocytic differentiation.

Base Sequence↗
PubMed2004

Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma.

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.

Blotting, Western↗
PubMed2004

Is pigment epithelium-derived factor level in cerebrospinal fluid a promising biomarker for early diagnosis of Alzheimer's disease?

Alzheimer's disease (AD) is the most common cause of dementia in Western countries and in Japan. Early diagnosis and treatment is needed to slow down the degenerative process and dementia in AD. The main histopathological characteristics of AD are senile plaques and neurofibrillary tangles. Based on the disease pathology, numerous blood and cerebrospinal fluid (CSF) tests have been proposed for early detection of AD. However, there is no definite clinical method to determine in which patients with mild cognitive impairment will progress to AD with dementia. Since pigment epithelium-derived factor (PEDF) has been recently shown to protect various types of cells including neuronal cells against oxidative stress- or glutamate-induced injury through its anti-oxidative properties, we examined here the expression levels of PEDF in AD's brain. PEDF was found to have the strong immunoreactivity in cortical neurons and astrocytes in the brains of AD. Further, the distribution of PEDF proteins was good concordance with RAGE proteins, one of the receptors for amyloid beta peptides, which are involved in neuronal cell death and microglial activation in AD. These results suggest that PEDF overexpression may indicate a compensation mechanism to fight against neuronal cell injury in AD. Our present observations suggest that PEDF in CSF might reflect cerebral PEDF turnover and provide a means for monitoring neuronal perturbation induced by oxidative stress in the early stage of AD. Clinical use of CSF-PEDF as a biomarker for AD might enable more effective diagnosis and treatment of patients with this disorder.

Alzheimer Disease↗
PubMed2003

C60 molecular bearings.

An ultralubricated system is reported which confines a C60 monolayer between graphite plates. C60 molecules act as molecular bearings, assisted by the nanogears of six-membered carbon rings between C60 molecules and graphite, in which the mean dynamical frictional forces are zero up to a high load of 100 nanonewtons. A stick-slip rolling model with a step rotation of a C60 molecule is proposed. This ultralubricated system, very promising for the realization of nano- and micromachines, is expected to open a new field of molecular bearings.

Journal Article↗