ACE activity in CSF of patients with mild cognitive impairment and Alzheimer disease.
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Aged↗
Biomedical subjects
K Furukawa
Publications and source records attributed to K Furukawa.
Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers.
Gangliosides GD3 and GD2 are specifically expressed in neuro-ectoderm-derived tumors, and are considered to play roles in the malignant properties of those cells. We analysed effects of small interfering (si) RNAs against GD3 synthase gene on the expression of ganglioside GD2 and biological phenotypes of human lung cancer cells expressing GD2. An siRNA could suppress the mRNA level of GD3 synthase gene even by single transfection, whereas repeated transfection was required to suppress GD2 expression on the cell surface. Significant reduction in the cell growth and invasion activity was observed in both lung cancer cell lines examined, when repeatedly transfected with the siRNA twice a week. DNA ladder formation was observed after third transfection, indicating the potent induction of apoptosis. Stable transfection of an RNAi expression vector with H1 RNA promoter was also examined. Transfectant cells with the RNAi expression vector showed almost equivalent suppression of GD2 expression and tumor properties in vitro. Furthermore, the stable transfectant cells showed slower cell growth than the control cells in severe combined immunodeficiency mice. These results suggested that siRNAs and/or RNAi expression vectors to generate siRNAs are promising approach to overcome human lung cancers.
Apoptosis↗
Phospho-regulation of human protein kinase Aurora-A: analysis using anti-phospho-Thr288 monoclonal antibodies.
Mammalian Aurora-A is related to a serine/threonine protein kinase that was originally identified by its close homology with Saccharomyces cerevisiae Ipl1p and Drosophila melanogaster aurora that are key regulators in the orchestration of mitotic events. The protein level of Aurora-A, its peak kinase activity during mitosis, and its activation have been attributed to phosphorylation. Here we show that this enzyme is an arginine-directed kinase and define its substrate specificity. We also found that Thr288 within the activation loop is a critical residue for activating phosphorylation events in vitro and that it is spatiotemporally restricted to a brief window at mitosis on duplicated centrosomes and on spindle microtubules proximal to the poles in vivo. Immunodepletion assays indicated that an upstream kinase(s) of Aurora-A might exist in mammalian cells in addition to autophosphorylation. Furthermore, human activated Aurora-A forms complexes with the negative regulator protein serine/threonine phosphatase type 1 (PP1) that was negatively phosphorylated on Thr320. Interestingly, phospho-specific Aurora-A monoclonal antibodies restrain Aurora-A kinase activity in vitro, providing further therapeutic avenues to explore.
Amino Acid Sequence↗
Portal systemic shunt through the renal vein.
BACKGROUND: Despite the semi-routine use of color Doppler sonography for evaluating portal circulation abnormalities, there is a relative paucity of detailed color Doppler findings of portal systemic (P-S) shunt through the renal vein (P-SR shunt). METHODS: We reviewed the color Doppler findings of 18 patients with P-SR shunt to determine its clinical significance and appropriate scanning techniques for diagnosing accurately P-SR shunt. RESULTS: The splenorenal shunt was imaged as a highly tortuous vessel at the splenic hilum, which then coursed backward behind the spleen. Splenic vein flow was reversed or very slow. The gastrorenal shunt originated from the splenic vein, coursed backward, and joined the left renal vein. Flow direction in the splenic vein was always hepatopetal. The P-S shunt through the right renal vein originated from duodenal or jejunal varices, coursed posterolaterally, and joined the right renal vein at the renal hilum. CONCLUSION: Familiarity with these color Doppler findings will help increase the diagnostic confidence of P-SR shunt by color Doppler sonography.
Adult↗
Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital.
BACKGROUND AND OBJECTIVES: We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years. STUDY DESIGN/MATERIALS AND METHODS: PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition. RESULTS: Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter. CONCLUSIONS: In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT.
Adult↗
Left hemianomia of musical symbols caused by callosal infarction.
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Aged↗
Development of single-stage nitrogen removal using anammox and partial nitritation (SNAP) and its treatment performances.
Single-stage Nitrogen removal using Anammox and Partial nitritation (SNAP) process was newly developed as an economical nitrogen removal process for ammonium rich wastewaters. The experimental studies for the evaluation of SNAP process were carried out using a novel biofilm reactor, in which hydrophilic net-type acryl fiber biomass carrier was applied. This SNAP reactor was operated under operational conditions of pH 7.5-7.7, 35 degrees C and DO 2-3 mg/L, and 60 to 80% of influent NH4-N was removed under loading rate of 0.48 kg-N/m3/d. Through the DNA analysis of the attached sludge, it was made clear that ammonium oxidizing bacteria (AOB) and anammox bacteria coexisted in the attach-immobilized sludge on the acryl fiber biomass carrier. Favorable conditions for the growth of anammox bacteria were created inside attach-immobilized nitrifying sludge. Two kinds of anammox bacteria and two kinds of AOB were detected in the SNAP sludge. Existence ratios of anammox and AOB were estimated to be 15% and 8.7%, respectively, based on the obtained clone numbers. This coexisting condition was confirmed by the FISH image of SNAP sludge and its confocal laser scanning microscope.
Ammonia↗
Risk factor analysis for ascending aorta and aortic arch repair using selective cerebral perfusion with open technique: role of open-stent graft placement.
AIM: The present study was designed to identify risk factors that may induce adverse outcome defined as permanent neurological dysfunction and mortality after aortic arch surgery using selective cerebral perfusion by logistic regression analysis and to reveal the role of open stent-graft placement. METHODS: One hundred and nineteen consecutive patients underwent ascending aorta and/or aortic arch operation with open technique between 1995 and 2005 were examined. Ascending aorta and/or hemiarch was replaced in 28 patients, total arch in 75 patients, and proximal or distal aortic arch replacement in 16 patients. Open stent-graft placement was used in 25 patients. RESULTS: The in-hospital mortality rate was 9.2%. Permanent neurological dysfunction occurred in 10 patients (8.4%). Thoracotomy (P=0.0331) and cardiopulmonary bypass time (P=0.0238) were significant risk factors for permanent neurological dysfunction. Preoperative shock (P=0.0266) was significant independent risk factor for mortality. Emergent operation (P=0.0454), thoracotomy (P=0.0232), and cardiopulmonary bypass time (P=0.0379) were significant independent risk factors for adverse outcome. The duration of selective cerebral perfusion was not associated with adverse outcome. Open stent-graft placement has no need of thoracotomy for aneurysm extending descending thoracic aorta and time variables concerning the operation were significantly shorter in the patients with open stent-graft placement than in patients with standard operation for total arch replacement. RESULTS: Thoracotomy was significant risk factor for adverse outcome after aortic arch repair using selective cerebral perfusion. Total arch replacement with open stent-graft placement can avoid the need of thoracotomy and reduce time variables concerning the operation to improve the surgical
Adult↗
Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides.
Gangliosides, sialic acid-containing glycosphingo-lipids, are enriched in the mammalian nervous system. Since mutant mice with disrupted beta1,4-N-acetylgalactosaminyl-transferase (GM2/GD2 synthase) were generated, there have been several studies on the pathology of the mutant mice, i.e. mild functional disorders and Wallerian degeneration in the peripheral nervous system. To further analyze the chronological alteration in the mutant mice, we examined the peripheral and CNS mainly with morphological approaches, such as electron microscopy and immunohistochemistry. Accordingly with the sensory dysfunction, neural degeneration, glial proliferation and synaptic remodeling in the dorsal horn of the spinal cord were found in adult mice. Thick astrocytic processes with densely packed glial filaments were extended among the neuropils and around blood vessels. Morphological changes in the synaptic vesicles and modes of synaptic contacts with central terminals were detected, suggesting synaptic remodeling following the degeneration. These results suggest that complex gangliosides are essential in the maintenance of integrity in architecture and function of the nervous system, lack of which results in neural degeneration in a sensory nerve-dominant manner.
Age Factors↗
Observation of B0-->pi0pi0.
We report the observation of the decay B0-->pi(0)pi(0), using a 253 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) collider. The measured branching fraction is B(B0-->pi(0)pi(0))=(2.3(+0.4+0.2)(-0.5-0.3))x10(-6), with a significance of 5.8 standard deviations including systematic uncertainties. We also make a measurement of the direct CP violating asymmetry in this mode.
Journal Article↗
Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.
OBJECTIVE: To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS). METHODS: The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barré syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10). CONCLUSIONS: C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.
Adult↗
[Castleman disease of the inter-lobar lymph node origin].
We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.
Adult↗
Evidence for direct CP violation in B0-->K+pi- decays.
We report evidence for direct CP violation in the decay B0-->K+pi(-) with 253 fb(-1) of data collected with the Belle detector at the KEKB e(+)e(-) collider. Using 275x10(6) BB pairs we observe a B-->K+/-pi(-/+) signal with 2140+/-53 events. The measured CP violating asymmetry is A(CP)(K+pi(-))=-0.101+/-0.025(stat)+/-0.005(syst), corresponding to a significance of 3.9sigma including systematics. We also search for CP violation in the decays B+-->K+pi(0) and B+-->pi(+)pi(0). The measured CP violating asymmetries are A(CP)(K+pi(0))=0.04+/-0.05(stat)+/-0.02(syst) and A(CP)(pi(+)pi(0))=-0.02+/-0.10(stat)+/-0.01(syst), corresponding to the intervals -0.05<A(CP)(K+pi(0))<0.13 and -0.18<A(CP)(pi(+)pi(0))<0.14 at 90% confidence level.
Journal Article↗
Observation of large CP violation and evidence for direct CP violation in B0-->pi(+)pi(-) decays.
We report the first observation of CP violation in B0-->pi(+)pi(-) decays based on 152x10(6) gamma (4S)-->BB decays collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. We reconstruct a B0-->pi(+)pi(-) CP eigenstate and identify the flavor of the accompanying B meson from its decay products. From the distribution of the time intervals between the two B meson decay points, we obtain A(pipi)=+0.58+/-0.15(stat)+/-0.07(syst) and S(pipi)=-1.00+/-0.21(stat)+/-0.07(syst). We rule out the CP-conserving case, A(pipi)=S(pipi)=0, at a level of 5.2 standard deviations. We also find evidence for direct CP violation with a significance at or greater than 3.2 standard deviations for any S(pipi) value.
Journal Article↗
Upper bound on the decay tau-->microgamma from the Belle detector.
We have performed a search for the lepton-flavor-violating decay tau-->microgamma using a data sample of 86.3 fb(-1) accumulated by the Belle detector at KEK. No evidence for a signal is seen, and we set an upper limit for the branching fraction of B(tau-->microgamma)<3.1 x 10(-7) at the 90% confidence level.
Journal Article↗
Measurements of the D(sJ) resonance properties.
We report measurements of the properties of the D(+)(sJ)(2317) and D(+)(sJ)(2457) resonances produced in continuum e(+)e(-) annihilation near sqrt[s]=10.6 GeV. The analysis is based on an 86.9 fb(-1) data sample collected with the Belle detector at KEKB. We determine the masses to be M(D(+)(sJ)(2317))=2317.2+/-0.5(stat)+/-0.9(syst) MeV/c(2) and M(D(+)(sJ)(2457))=2456.5+/-1.3(stat)+/-1.3(syst) MeV/c(2). We observe the radiative decay mode D(+)(sJ)(2457)-->D(+)(s)gamma and the dipion decay mode D(+)(sJ)(2457)-->D(+)(s)pi(+)pi(-) and determine their branching fractions. No corresponding decays are observed for the D(sJ)(2317) state. These results are consistent with the spin-parity assignments of 0(+) for the D(sJ)(2317) and 1(+) for the D(sJ)(2457).
Journal Article↗
[Novel strategy for thoracoabdomianl aortic aneurysm repair; intraoperative selective perfusion of the Adamkiewicz artery].
We report our method for delineating the Adamkiewicz artery using multidetector row computed tomography (MDCT) with selective perfusion using a distal perfusion cannula that is clinically available for off-pump coronary artery bypass (OPCAB). The tip of a distal perfusion catheter (Medtronic Quickflow, Minneapolis) designed for OPCAB was applicable for selective perfusion of the segmental arteries. The femoro-femoral venoarterial bypass was branched off into selective perfusion of the segmental arteries, using an independent roller pump and heat exchanger. Our method of visualization of the Adamkiewicz artery was MDCT scanning with injection of contrast medium directly into the proximal descending aorta: namely, "CT during aortography". Lower descending aorta to abdominal aorta (the range involving the aneurysm) was scanned in a cephalad-to-caudal direction using a detector collimation of 4 x 1.25 mm with a table speed of 9.4 mm/sec, pitch of 6, and image thickness of 1.25 mm. All images were reviewed on a workstation to investigate the continuity between the Adamkiewicz artery and its proximal segmental artery with paging, mulitplanar reformation and curved planar reformation. Distal perfusion cannulae of 2.0 mm in diameter were inserted into the respective intercostal arteries. 4-0 polyethylene sutures were placed to tourniquet the catheters. Segmental arteries were perfused with total flow of approximately 80 ml/min at a circuit pressure of 120 mmHg. Reattachment of the ninth intercostal arteries related to the Adamkiewicz artery was carried out. A total of 6 consecutive 6 patients with thoracoabdominal aortic aneurysm (TAAA) have undergone graft replacement by the methods described, since April 2002. All patients survived surgery without any neurological complications. This method is expected to minimize the ischemic time of the spinal cord and attenuate the reperfusion injury.
Aged↗
Granulation of Anammox microorganisms in up-flow reactors.
Experimental studies were performed to evaluate the feasibility of granulation of Anammox microorganisms for biomass retention in up-flow reactors. Two experimental studies, one using a 6.4-L lab-scale reactor with synthetic medium and the other using a 200-L pilot-scale reactor with half-nitrified reject water from a sludge digester were conducted. To enhance the granulation process, seed granules from a UASB reactor were added to both experimental reactors. Granulation of Anammox microorganisms was observed using both the synthetic medium and the reject water. The core of a large proportion of Anammox granules retained part of the original seed biomass. The Anammox granules had a slightly lower density than the seed granules from the UASB process, but the size and other physical properties were comparable. The successful granulation of the Anammox microorganisms led to a stable nitrogen removal performance. The maximum nitrogen removal rate of the lab-scale reactor was observed to be 2.9 kg/(m3 x d) after 173 days of operation and that of the pilot-scale reactor was 6.4 kg/(m3 x d) after 12 months of operation.
Biomass↗