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N Sakai

Publications and source records attributed to N Sakai.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characteristics of fulminant-type autoimmune hepatitis: an analysis of eleven cases.

BACKGROUND: Although a few adult cases of fulminant-type autoimmune hepatitis have been reported, their clinical features and prognosis have remained uncertain. AIM: To assess the clinical features and prognosis of patients with fulminant-type autoimmune hepatitis. METHODS: Eleven patients (10%) diagnosed with fulminant-type autoimmune hepatitis in accordance with the 1999 criteria of the International Autoimmune Hepatitis Group were analysed. RESULTS: All 11 patients were female, with a median age of 53 years. Five patients survived without liver transplantation, one received a liver transplantation, and five died without liver transplantation. Nine patients (82%) survived for 2 weeks or more following diagnosis, without liver transplantation. Except for the patient receiving a liver transplantation, serum total bilirubin levels measured during the clinical course were significantly higher in non-survivors than in survivors, although the accompanying serum alanine aminotransferase levels measured for the two groups were similar. Most significantly, serum total bilirubin levels in non-survivors worsened during days 8-15, while levels in survivors improved during the same period. CONCLUSIONS: The short-term prognosis for patients with fulminant-type autoimmune hepatitis may be good. However, patients whose serum total bilirubin levels worsen during days 8-15 should be considered for liver transplantation.

Adolescent↗
PubMed2006

Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that maintains the glomerular and peritubular capillary (PTC) network in the kidney. The soluble form of the VEGF receptor-1 (soluble fms-like tyrosine kinase 1 (sFlt-1)) is known to regulate VEGF activity by binding VEGF in the circulation. We hypothesized that VEGF may be beneficial for maintaining glomerular filtration barrier and vascular network in rats with progressive glomerulonephritis (GN). For blockade of VEGF activity in vivo, rats were transfected twice with plasmid DNA encoding the murine sFlt-1 gene into femoral muscle 3 days before and 2 weeks after the induction of antiglomerular basement membrane antibody-induced GN. Inhibition of VEGF with sFlt-1 resulted in massive urinary protein excretion, concomitantly with downregulated expression of nephrin in nephritic rats. Further, blockade of VEGF induced mild proteinuria in normal rats. Administration of sFlt-1 affected neither the infiltration of macrophages nor crescentic formation. In contrast, treatment of sFlt-1 accelerated the progression of glomerulosclerosis and interstitial fibrosis accompanied with renal dysfunction and PTC loss at day 56. VEGF may play a role in maintaining the podocyte function as well as renal vasculature, thereby protecting glomeruli and interstitium from progressive renal insults.

Animals↗
PubMed2006

Fast-scanning atomic force microscopy reveals the molecular mechanism of DNA cleavage by ApaI endonuclease.

Newly developed fast-scanning atomic force microscopy (AFM) allows the dissection of molecular events such as DNA-enzyme reactions at the single-molecule level. With this novel technology, a model is proposed of the DNA cleavage reaction by a type IIP restriction endonuclease ApaI. Detailed analyses revealed that ApaI bound to DNA as a dimer and slid along DNA in a one-dimensional diffusion manner. When it encountered a specific DNA sequence, the enzyme halted for a moment to digest the DNA. Immediately after digestion, the ApaI dimer separated into two monomers, each of which remained on the DNA end and then dissociated from the DNA end. Thus, fast-scanning AFM is a powerful tool to aid the understanding of protein structures and dynamics in biological reactions at the single-molecule level in sub-seconds.

Binding Sites↗
PubMed2005

Functional MRI detection of activation in the primary gustatory cortices in humans.

Magnetoencephalography (MEG) has recently revealed that the transitions between the parietal operculum (Pop) and the insula (area G) and the ventral end of the central sulcus (cs) were activated with the shortest latency by instrumental gustatory stimulation, which suggests that the location of the primary gustatory area is in these two regions. However, studies using other noninvasive brain-imaging methods such as positron-emission tomography or functional magnetic resonance imaging (fMRI) with manual application of tastants into the mouth have been unable to confirm this. The present study examined cortical activation by repetitive stimulation of the tongue tip with 1 M NaCl with a computer-controlled stimulator and used fMRI to detect it. In individual brains, activations were detected with multiple comparisons (false discovery rate) across the whole brain corrected (threshold at P < 0.05) at both area G and frontal operculum (Fop) in 8 of 11 subjects and at the rolandic operculum (Rop) in 7 subjects. Activations were also found at the ventral end of the cs (n = 3). Group analysis with random-effect models (multiple comparison using familywise error in regions of interest, P < 0.02) revealed activation at area G in both hemispheres and in the Fop, Rop, and ventral end of the cs on the left side. The present study revealed no activation on the gyrus of the external cerebral surface except for the Rop. Taking MEG findings into consideration, the present findings strongly indicate that the primary gustatory area is present at both the transition between the Pop and insula and the Rop including the gray matter within a ventral part of the cs.

Adult↗
PubMed2005

Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study.

Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.

Adult↗
PubMed2005

Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

OBJECTIVE: We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus. PATIENTS AND MEASUREMENTS: Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism. RESULTS: Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements. CONCLUSIONS: In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

Aged↗
PubMed2005

Fructooligosaccharide consumption improves the decreased dentin formation and mandibular defects following gastrectomy in rats.

OBJECTIVE: We examined the effects of fructooligosaccharides (FOS) consumption on gastrectomy-evoked osteopenia and disorders of dentin formation in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 28, 35-day old) were equally divided into two groups; sham-operated and gastrectomized, and sham-operation or total gastrectomy was performed. Four weeks after each surgery, the rats were divided into two sub-groups (n = 7 each); with or without 7.5% FOS-feeding for 6 weeks. Backscattered electron images of the mandibular sections were taken to calculate trabecular bone area, cortical bone area and total scan area. Thereafter, the dentin formation rate in maxilla were calculated using a fluorescent microscope. RESULTS: Trabecular bone area and cortical bone area in GX rats were markedly decreased. FOS-feeding significantly counteracted this reduction, but not to the level seen in sham-operated rats. Total scan area in gastrectomized groups was significantly decreased. The dentin formation rate was not statistically different among the groups, except the gastrectomized group. CONCLUSION: These results suggest that FOS consumption partially restored osteopenia and almost completely restored the reduction in dentin formation following gastrectomy in rats.

Animals↗
PubMed2005

Development of a novel microbial sensor with baker's yeast cells for monitoring temperature control during cold food chain.

A novel microbial sensor containing a commercial baker's yeast with a high freeze tolerance was developed for visibly detecting inappropriate temperature control of food. When the yeast cells fermented glucose, the resulting gas production triggered the microbial sensor. The biosensor was a simple, small bag containing a solution of yeast cells, yeast extract, glucose, and glycerol sealed up with multilayer transparent film with barriers against oxygen and humidity. Fine adjustment of gas productivity in the biosensor at low temperatures was achieved by changing either or both concentrations of glucose and yeast cells. Moreover, the amount of time that food was exposed to inappropriate temperatures could be deduced by the amount of gas produced in the biosensor. The biosensor was stable without any functional loss for up to 1 week in frozen storage. The biosensor could offer a useful tool for securing food safety by maintaining low-temperature control in every stage from farm to fork, including during transportation, in the store, and at home.

Biosensing Techniques↗
PubMed2004

Considerations in the surgical treatment of superior-wall type aneurysm at the proximal (M1) segment of the middle cerebral artery.

OBJECTIVE: To present our experience and analyze the risks of neck clipping for superior-wall type aneurysms of the proximal segment of the middle cerebral artery (M1-Sup aneurysm). METHODS: Of 14 patients with M1-Sup aneurysms, 4 suffered postoperative infarctions in the territory of the lenticulostriate arteries (LSA) or fronto-orbital arteries. We re-examined our intraoperative findings and clinical records in an effort to identify possible causes. RESULTS: The patency of the LSA was confirmed at the end of surgery in all 14 cases. We posit that temporary occlusion of the LSA by a permanent clip resulted in delayed obstruction of the LSA in 3 patients. Other possibilities we considered were relatively long temporary occlusion of the M1, slipping of the clips and twisting of the clip blades after release of the brain retractors. CONCLUSION: M1-Sup aneurysms are some of the most complicated aneurysms; they carry the risk of perforator injury during neck clipping. Surgical considerations to avoid perforator injury are discussed.

Adult↗
PubMed2004

p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis.

Although the p53 tumor-suppressor gene product plays a critical role in apoptotic cell death induced by DNA-damaging chemotherapeutic agents, human glioma cells with functional p53 were more resistant to gamma-radiation than those with mutant p53. U-87 MG cells with wild-type p53 were resistant to gamma-radiation. U87-W E6 cells that lost functional p53, by the expression of type 16 human papillomavirus E6 oncoprotein, became susceptible to radiation-induced apoptosis. The formation of ceramide by acid sphingomyelinase (A-SMase), but not by neutral sphingomyelinase, was associated with p53-independent apoptosis. SR33557 (2-isopropyl-1-(4-[3-N-methyl-N-(3,4-dimethoxybphenethyl)amino]propyloxy)benzene-sulfonyl) indolizine, an inhibitor of A-SMase, suppressed radiation-induced apoptotic cell death. In contrast, radiation-induced A-SMase activation was blocked in glioma cells with endogenous functional p53. The expression of acid ceramidase was induced by gamma-radiation, and was more evident in cells with functional p53. N-oleoylethanolamine, which is known to inhibit ceramidase activity, unexpectedly downregulated acid ceramidase and accelerated radiation-induced apoptosis in U87-W E6 cells. Moreover, cells with functional p53 could be sensitized to gamma-radiation by N-oleoylethanolamine, which suppressed radiation-induced acid ceramidase expression and then enhanced ceramide formation. Sensitization to gamma-radiation was also observed in U87-MG cells depleted of functional p53 by retroviral expression of small interfering RNA. These results indicate that ceramide may function as a mediator of p53-independent apoptosis in human glioma cells in response to gamma-radiation, and suggest that p53-dependent expression of acid ceramidase and blockage of A-SMase activation play pivotal roles in protection from gamma-radiation of cells with endogenous functional p53.

Apoptosis↗
PubMed2004

Molecular mechanisms of TNF-alpha-induced ceramide formation in human glioma cells: P53-mediated oxidant stress-dependent and -independent pathways.

The present study was designed to examine the roles of p53, reactive oxygen species (ROS), and ceramide, and to determine their mutual relationships during tumor necrosis factor (TNF)-alpha-induced apoptosis of human glioma cells. In cells possessing wild-type p53, TNF-alpha stimulated ceramide formation via the activation of both neutral and acid sphingomyelinases (SMases), accompanied by superoxide anion (O2-*) production, and induced mitochondrial depolarization and cytochrome c release, whereas p53-deficient cells were partially resistant to TNF-alpha and lacked O2-* generation and neutral SMase activation. Restoration of functional p53 sensitized glioma cells expressing mutant p53 to TNF-alpha by accumulation of O2-*. z-IETD-fmk (benzyloxycarbonyl-Ile-Glu-Thr-Asp fluoromethyl ketone), but not z-DEVD-fmk (benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethyl ketone), blocked TNF-alpha-induced ceramide formation through both SMases as well as O2-* generation. Caspase-8 was processed by TNF-alpha regardless of p53 status of cells or the presence of antioxidants. Two separate signaling cascades, p53-mediated ROS-dependent and -independent pathways, both of which are initiated by caspase-8 activation, thus contribute to ceramide formation in TNF-alpha-induced apoptosis of human glioma cells.

Apoptosis↗
PubMed2004

Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study.

OBJECTIVE: To examine (11)C-methyl methionine (MET) accumulation on positron emission tomographic (PET) imaging of glioblastoma multiforme to determine the distribution of metabolic abnormality compared with magnetic resonance imaging (MRI). METHODS: Contemporaneous MRI was superimposed on corresponding MET-PET images in 10 patients with newly diagnosed glioblastoma multiforme before treatment. Differences between the extended area of MET accumulation on PET imaging (MET area), the gadolinium (Gd) enhanced area on T1 weighted images (Gd area), and the abnormal high signal intensity area on T2 weighted images (T2-high area) were assessed. RESULTS: The MET area was larger than the Gd area and included the entire Gd area. The discrepancy in volume between the MET and Gd areas became greater with increasing tumour diameter. On average, 58.6% of the MET area was located within the Gd area, 90.1% within 10 mm outside the Gd area, 98.1% within 20 mm, and 99.8% within 30 mm. A newly developed Gd area had emerged in five of the 10 cases up to the time of study. In three of the five cases this was in the MET area even after complete surgical resection of the Gd area on the initial MRI; in the remaining two it originated in the residual Gd area after surgery. In all cases, the T2-high area was larger than the MET area. The MET area extended partly beyond the T2-high area in nine cases, and was completely within it in one. CONCLUSIONS: Glioblastoma multiforme cells may extend over the Gd area and more widely with increasing tumour size on Gd-MRI. The T2-high area includes the greater part of the tumour but not its entire area. The methods reported may be useful in planning surgical resection, biopsy, or radiosurgery.

Adult↗
PubMed2004

Elasto-plastic contact analysis of an ultra-high molecular weight polyethylene tibial component based on geometrical measurement from a retrieved knee prosthesis.

The wear phenomenon of ultra-high molecular weight polyethylene (UHMWPE) in knee and hip prostheses is one of the major restriction factors on the longevity of these implants. Especially in retrieved knee prostheses with anatomical design, the predominant types of wear on UHMWPE tibial components are delamination and pitting. These fatigue wear patterns of UHMWPE are believed to result from repeated plastic deformation owing to high contact stresses. In this study, the elasto-plastic contact analysis of the UHWMPE tibial insert, based on geometrical measurement for retrieved knee prosthesis, was performed using the finite element method (FEM) to investigate the plastic deformation behaviour in the UHMWPE tibial component. The results suggest that the maximum plastic strain below the surface is closely related to subsurface crack initiation and delamination of the retrieved UHMWPE tibial component. The worn surface whose macroscopic geometrical congruity had been improved due to wear after joint replacement showed lower contact stress at macroscopic level.

Aged↗
PubMed2003

Pre-medication with pronase reduces artefacts during endoscopic ultrasonography.

BACKGROUND: Gastric mucus usually induces artefacts during endoscopic ultrasonography. AIM: To investigate the effectiveness of pre-medication with the proteolytic enzyme, pronase, before endoscopic ultrasonography. METHODS: Out-patients scheduled for endoscopic ultrasonography were randomly assigned to oral pre-medication with the anti-foam agent, dimethylpolysiloxane, alone (treatment A; n = 29), with dimethylpolysiloxane plus sodium bicarbonate (treatment B; n = 29) or with dimethylpolysiloxane, sodium bicarbonate and pronase (treatment C; n = 29). All drinks were given about 10 min before the start of the procedure. After insertion of the endoscope, endoscopists recorded visibility scores before the procedure, imaging scores at endoscopic ultrasonography and the numbers of high-echo spots in the gastric cavity and on the gastric wall surface after the procedure. RESULTS: Pre-medication with pronase (treatment C) significantly reduced (both at P < 0.05) the visibility score (score 4, 46%) in comparison with that obtained for pre-medication without pronase (10% for both treatments A and B). Treatment with pronase significantly reduced (both at P < 0.05) the endoscopic ultrasonography score in the gastric cavity (score 4, 34%) in comparison with that found for treatments A (7%) and B (0%). It also significantly reduced (P < 0.05) the endoscopic ultrasonography score on the gastric wall surface (score 4, 14%) in comparison with that observed for treatment A (3%). The numbers of high-echo spots in the gastric cavity and on the gastric wall surface were significantly less (both at P < 0.001) for pre-medication with pronase (treatment C) than for pre-medication with treatments A and B. There were no complications associated with the solutions. CONCLUSIONS: Pre-treatment with pronase reduced the artefacts during endoscopic ultrasonography.

Artifacts↗
PubMed2003

Novel LPL mutation (L303F) found in a patient associated with coronary artery disease and severe systemic atherosclerosis.

BACKGROUND: Patients with lipoprotein lipase (LPL) deficiency had been generally thought to be spared accelerated atherosclerosis in spite of a marked elevation of plasma triglyceride levels. However, it has been recently reported that some heterozygous and homozygous LPL-deficient patients are associated with premature atherosclerosis. In this paper, we report a 55-year-old type I hyperlipidaemic patient with a novel missense mutation in the LPL gene. PATIENT AND RESULTS: The patient had suffered from coronary artery disease, abdominal aortic aneurysm, and stenoses of the bilateral renal arteries and superficial femoral arteries. Sequencing of the genomic DNA revealed that the patient was a homozygote for the mutation, a G to C transition at nucleotide position 1069 in the exon 6, resulting in an amino acid substitution of Phe for Leu303 (L303F). Approximately 6% and approximately 40% of normal LPL activity and LPL mass, respectively, were detected in the patient's postheparin plasma. An in vitro expression study demonstrated that COS7 cells transfected with L303F mutant cDNA produced a 40% amount of LPL protein in cell lysates compared with normal cDNA, but no protein was detected in the media. Lipoprotein lipase activity was completely absent in both lysates and media of the cells transfected with the mutant cDNA, suggesting that this mutation in the LPL gene results in the production of a functionally inactive protein. CONCLUSION: This case suggests that the LPL missense mutation (L303F), which impairs lipolysis but preserves the LPL mass, is proatherogenic.

Arteriosclerosis↗
PubMed2003

Delayed adverse reactions to iodinated radiographic contrast media after coronary angiography: a search for possible risk factors.

OBJECTIVE: The incidence of and risk factors for delayed adverse events (DAEs) that appear from 1 h to 7 days after injection of radiographic contrast media were investigated in patients who had undergone coronary angiography (CAG). METHODS: DAEs were monitored by questionnaire in 155 patients who received iomeprol. Isosorbide dinitrate was injected in every case. Risk factors for DAEs were analysed by a logistic regression model. RESULTS: Of 118 patients who returned questionnaires, 54 complained of DAEs, although no severe or fatal reactions occurred. Erythema, rash and nausea were frequent events. Female gender, total dose of isosorbide dinitrate <2 mg, and execution of acetylcholine provocation test were found to be the major risk factors, and the incidence of DAEs increased as the number of risk factors increased. CONCLUSION: Care should be taken when CAG is performed on female patients who undergo acetylcholine provocation tests and receive low-dose nitric oxide donor injections.

Aged↗