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Biomedical subjects

Kenji Nakamura

Publications and source records attributed to Kenji Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Versatile roles of R-Ras GAP in neurite formation of PC12 cells and embryonic vascular development.

Ras GTPase-activating proteins (GAP) are negative regulators of Ras that convert active Ras-GTP to inactive Ras-GDP. R-Ras GAP is a membrane-associated molecule with stronger GAP activity for R-Ras, an activator of integrin, than H-Ras. We found that R-Ras GAP is down-regulated during neurite formation in rat pheochromocytoma PC12 cells by nerve growth factor (NGF), which is blocked by the transient expression of R-Ras gap or dominant negative R-ras cDNA. By establishing a PC12 subclone that stably expresses exogenous R-Ras GAP, it was found that NGF reduced endogenous R-Ras GAP but not exogenous R-Ras GAP, suggesting that down-regulation of R-Ras GAP occurs at the transcription level. To clarify the physiological role of R-Ras GAP, we generated mice that express mutant Ras GAP with knocked down activity. While heterozygotes are normal, homozygous mice die at E12.5-13.5 of massive subcutaneous and intraparenchymal bleeding, probably due to underdeveloped adherens junctions between capillary endothelial cells. These results show essential roles of R-Ras GAP in development and differentiation: its expression is needed for embryonic development of blood vessel barriers, whereas its down-regulation facilitates NGF-induced neurite formation of PC12 cells via maintaining activated R-Ras.

Animals↗
PubMed2006

Anionic hybrid threadlike micelle formation in an aqueous solution.

Novel anionic hybrid threadlike micelle formation was found in an aqueous solution of an anionic surfactant, sodium tetradecylsulfate (NaC(14)S), and partially quarternized polyelectrolyte at ca. 0.55, poly(N,N-diallyl-N-methylamine-ran-N,N-diallyl-N-ethyl-N-methylammonium bromide) (P(DAM/DAEMBr)). The system precipitated insoluble complexes at a composition of iso-electric points, forming long and stable hybrid threadlike micelles at a composition close to an iso-molar point between NaC(14)S and P(DAM/DAEMBr) in monomer units. Then, the system turned into transparent liquids and showed remarkable viscoelasticity due to entanglements between the formed anionic hybrid threadlike micelles.

Letter↗
PubMed2006

Threadlike micelle formation of anionic surfactants in aqueous solution.

We have investigated the formation of threadlike micelles consisting of anionic surfactants and certain additives in aqueous solution. Threadlike micelles long enough to be entangled with each other were formed in a clear aqueous solution of two anionic surfactants, sodium hexadecyl sulfate and sodium tetradecyl sulfate. These solutions also contained pentylammonium bromides or p-toluidine halides and exhibited remarkable viscoelasticity. Because the molar ratio of surfactants to cationic additives in these micelles seemed close to unity, they formed 1:1 stoichiometric complexes between surfactant anions and additive cations, as previously found in systems of cationic surfactants such as hexadecyltrimethylammonium bromide and sodium salicylate. The viscoelastic behavior of these anionic threadlike micellar systems was adequately described by a simple Maxwell element with a single relaxation time and strength, as in many similar cationic systems.

Journal Article↗
PubMed2006

Successful treatment of giant rectal varices by modified percutaneous transhepatic obliteration with sclerosant: Report of a case.

We present a female patient with continuous melena, diagnosed with rectal variceal bleeding. She had a history of esophageal varices, which were treated with endoscopic therapy. Five years after the treatment of esophageal varices, continuous melena occurred. Since colonoscopy showed that the melena was caused by giant rectal varices, we thought that they were not suitable to receive endoscopic treatment. We chose the modified percutaneous transhepatic obliteration with sclerosant, which is one of the interventional radiology techniques but a new clinical procedure for rectal varices. After the patient received this therapy, her condition of rectal varices was markedly improved.

Aged↗
PubMed2006

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.

Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.

Animals↗
PubMed2006

Development of an oral sustained release drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer.

A new oral sustained-release (SR) drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer (CP) has been proposed. This swelling polymer incorporation layer system, referred to as SPILA system, consists of core granules coated with a mixture of CP, water insoluble polymer, and water-soluble polymer (WP). Release profiles of metoprolol tartrate (ME) from SPILA system were pH dependent: drug release was slower in the medium of pH 1.2 than in the medium of pH 6.8 due to a coating layer with pH-dependent swelling polymer, CP. Lower C(max), longer T(max), longer MRT and higher AUC values were obtained following administration of SR granules based on SPILA system to beagle dogs compared with pH-independent SR granules having a coating layer without CP, while both SR granules provided similar in vitro release profiles. Moreover, using morphine hydrochloride (MO), in vitro and in vivo performances of the SPILA system were investigated. pH-dependency on the release profiles of MO from SPILA system was more evident when the amount of CP incorporated in SPILA system was increased. AUC and MRT values following administration of SR granules of MO with a coating layer containing 8% of CP to beagle dogs were 191 ng h/mL and 10.6 h respectively, while those following SR granules of MO with a coating layer containing 1% of CP to beagle dogs were 86.4 ng h/mL and 5.86 h, respectively. An important role of CP in the release-regulating layer of SPILA system for keeping the higher and more extended plasma levels of morphine free base was confirmed from the in vivo performance of SPILA system.

Acrylic Resins↗
PubMed2006

Possible role of scavenger receptor SRCL in the clearance of amyloid-beta in Alzheimer's disease.

Accumulation of beta-amyloid protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD), and Abeta-mediated pathogenesis could result from increased production of Abeta or insufficient Abeta clearance by microglia, astrocytes, or the vascular system. Cell-surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of Abeta; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C-type lectin (SRCL), a member of the scavenger receptor family containing coiled-coil, collagen-like, and C-type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild-type mouse brain, in a double transgenic mouse model of AD (Tg-APP/PS1), immunohistochemistry showed that SRCL was markedly induced in Abeta-positive astrocytes and Abeta-positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg-APP/PS1 temporal cortex. The presence of a large number of SRCL/Abeta double-positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg-APP/PS1 mice and AD patients suggests a role for SRCL in Abeta clearance. Moreover, CHO-K1 cells transfected with SRCL isoforms were found to bind fibrillar Abeta(1-42). These findings suggest that SRCL could be the receptor involved in the binding or clearing of Abeta by glial and vascular/perivascular cells in AD.

Adult↗
PubMed2006

Fluorine-18-fluorodeoxyglucose positron emission tomography for assessment of patients with unresectable recurrent or metastatic lung cancers after CT-guided radiofrequency ablation: preliminary results.

OBJECTIVES: We compared the diagnostic value of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with that of computed tomography (CT) following radiofrequency ablation (RFA) of inoperable recurrent or metastatic cancers in the lung. METHODS: Twelve patients (9 males and 3 females; 5 had recurrent lung cancer and the other 7 had metastatic nodules from a variety of primary cancers) were treated by RFA for 17 pulmonary nodules. FDG-PET was performed before and 2 months after RFA, and the mean standardized uptake value (SUV) was calculated. The response evaluation was based on the percent reduction relative to the baseline and the absolute values of SUV on FDG-PET performed at 2 months after RFA. We compared the response evaluations made based on findings of FDG-PET and CT at 2 and > or =6 months (mean 10.2) after RFA. RESULTS: The percent reduction in uptake at 2 months was significantly lower in nodules considered progressive (69.6 +/- 18.6%) than nonprogressive disease (38.7 +/- 12.5%; p < 0.01) based on CT findings at > or =6 months after RFA. The absolute SUV at 2 months was significantly higher in nodules considered progressive (2.61 +/- 0.75) than nonprogressive disease (1.05 +/- 0.67; p < 0.01) based on CT findings at > or =6 months post-RFA. CONCLUSION: Although our pilot study comprised few cases of various histopathological types of cancers in the lung, the results suggest that FDG-PET could predict regrowth on subsequent follow-up CT. Regrowth could be diagnosed earlier by FDG-PET than by CT, and nodules with residual uptake and with <60% reduction of uptake relative to baseline on FDG-PET at 2 months after ablation might require additional therapy.

Adult↗
PubMed2006

An animal model for type II endoleaks with use of a tsuzumi drum-shaped stent-graft.

PURPOSE: To create an animal model of type II endoleaks after endoluminal deployment of a specially designed stent-graft (SG). MATERIALS AND METHODS: Five swine were used. A tsuzumi drum-shaped SG consisting of a covered Z stent with its diameter narrowed at the center was deployed in the midthoracic aorta. In this way, a residual space (RS) was created between the aortic wall and the graft to simulate an aneurysm sac. A 5-F catheter was placed into the RS, and then aortography, RS angiography, and pressure measurements were performed. Follow-up was performed at 3 and 10 days after the procedure. Mean pressure indexes (MPIs) were calculated as the ratio of the mean RS pressure to the aortic pressure. Histologic examination was also performed. RESULTS: RSs with two or three pairs of intercostal arteries were successfully created in all cases. Aortography showed two type II endoleaks in five swine just after SG deployment and four type II endoleaks at 10 days. RS angiography showed circulation between the RS and the intercostal arteries in all cases. The mean MPI was 69.4% +/- 10.4% just after SG deployment and increased to 87.8% +/- 5.2% at 10 days. By gross examination, RS patency was retained. CONCLUSIONS: A swine model of type II endoleaks was successfully created endoluminally. This model does not require direct surgery to the aorta and its side branches and promises to be useful to study the mechanism of and therapy for type II endoleaks.

Angiography↗
PubMed2006

Local community intervention through depression screening and group activity for elderly suicide prevention.

This study aims to evaluate outcomes of a community-based program to prevent suicide among the elderly (>or=65 years old) using a quasi-experimental design with two neighboring references. During 1999-2004, the program including depression screening and group activity was conducted by the public health nurses in the Minami district (population 1685) of Nagawa town, rural Japan. Pre-post changes in the risk of completing suicide were estimated by the incidence rate ratios (IRR). The risk for Minami's elderly females was reduced by 74% (age-adjusted IRR, 0.26; 90% CI, 0.07-0.98) more than the historical trend, while there was no change in the risk of Minami's males and nor in the male or female references. The local intervention using public health nursing would be effective against suicide for elderly females without diffusing to the surroundings.

Aged↗
PubMed2006

18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided radiofrequency ablation on implanted VX2 lung tumors in rabbits.

UNLABELLED: The primary goals of this study were to investigate the behavior of normal lung tissues after radiofrequency ablation (RFA) and to determine the suitability of 18F-FDG PET, using a dedicated small-animal scanner, for monitoring the early therapeutic effects of RFA on VX2 lung tumors (VX2s) in rabbits. METHODS: Fourteen Japanese white rabbits with normal lungs underwent RFA, followed by 18F-FDG PET at 1 d and at 1, 2, 4, and 8 wk. In addition, 7 rabbits with untreated VX2s underwent 18F-FDG PET, and 13 rabbits with RFA-treated VX2s underwent 18F-FDG PET at 1 d (n = 7) or 1 wk (n = 6) after the treatment. RESULTS: After RFA of normal lungs, ring-shaped accumulations of 18F-FDG, which coincided with inflammation caused by ablation, were observed. The mean early- (40-60 min after injection) and delayed (100-120 min)-phase ablated lesion-to-muscle ratios were, respectively, 2.9 +/- 1.0 and 3.3 +/- 0.8 (1 d), 4.1 +/- 0.6 and 5.2 +/- 0.9 (1 wk), 4.1 +/- 1.0 and 5.3 +/- 1.5 (2 wk), 3.1 +/- 0.5 and 3.6 +/- 1.1 (4 wk), and 1.8 +/- 0.1 and 2.3 +/- 0.1 (8 wk). At 4 and 8 wk, the uptake was less than that at 1 and 2 wk (P < 0.05). VX2s showed mean tumor-to-muscle ratios of 6.6 +/- 2.1 and 8.6 +/- 3.3 at the early and delayed phases, respectively. For ablated tumors, the respective ratios were 0.8 +/- 0.4 and 1.1 +/- 0.7 (1 d) and 1.2 +/- 0.5 and 1.5 +/- 0.7 (1 wk). These values were significantly lower than those for nonablated tumors (P < 0.001). Histopathologic examination confirmed the absence of viable tumors. 18F-FDG accumulation around ablated tumors reflected thermally damaged normal tissues and was significantly lower than that of control VX2s (P < 0.01). CONCLUSION: Our data suggest that 18F-FDG PET is promising for evaluating the therapeutic response of lung malignancies to RFA: Accumulation of 18F-FDG in surrounding normal tissues appears to be time dependent, and the data suggest that, clinically, 18F-FDG PET should be performed 4 wk or more after RFA. Delayed-phase images seem to better distinguish tumor from inflammation than do early-phase images.

Animals↗
PubMed2006

[A case of bronchogenic cyst with elevated SLX levels in serum and cystic fluid].

A 27-year-old man was admitted with chest pain and cough in January 1999. Chest radiograph on admission showed a widened tracheal bifurcation. Computer tomography on admission showed a low density mass located at the tracheal bifurcation. Magnetic resonance imaging of the chest showed a well defined mass with isointensity on T1-weighted images, and high intensity on T2-weighted images. Laboratory data on admission showed mild inflammatory findings and a high level of Sialyl Lewis X-i antigen (SLX) in serum. Thoracotomy revealed a cystic mass and pathologically, the cyst wall was lined with bronchial epithelium which showed no malignancy. The level of SLX in the cystic fluid was elevated, and immunohistochemical staining of the cystic epithelium was positive for SLX. After resection of the cyst, the level of SLX in serum decreased. This represents a rare case of bronchogenic cyst with a high level of SLX in serum and cystic fluid.

Adult↗
PubMed2005

Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality.

By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10), which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development.

Animals↗
PubMed2005

Novel transcription factor zfh-5 is negatively regulated by its own antisense RNA in mouse brain.

Here, we report features of a novel transcription factor zfh-5, which we isolated from the mouse brain; in addition to the mRNA, the antisense strand of zfh-5 is also expressed in the developing brain, in a manner complementary to the expression of zfh-5 mRNA. Although most neurons express zfh-5 mRNA soon after their final mitosis, several types of neurons, such as the pyramidal and granule cells in the hippocampus, express the zfh-5 antisense RNA prior to the mRNA expression. Using gene-targeting approach, we showed that this antisense RNA has a negative regulatory role on the expression of zfh-5 mRNA. These observations suggest that, in specific types of neurons, the expression of zfh-5 is additionally regulated by a mechanism depending on this antisense RNA.

Animals↗
PubMed2005

Liquid-phase binding assay of alpha-fetoprotein using DNA-coupled antibody and capillary chip electrophoresis.

An immunoassay using DNA-coupled antibody for bound/free separation in a liquid-phase binding assay format is described. Anti-alpha-fetoprotein monoclonal antibody was conjugated with DNA, mixed with alpha-fetoprotein (AFP), and incubated, and then 1 muL of the mixture was applied to capillary electrophoresis on a microchip. The DNA molecule of the antibody-DNA conjugate and the DNA-conjugated immune complex peak were detectable fluorophotometrically using intercalator dye within 90 s, whereas the Alexa-labeled antibody was detected as a broad and slower migrating peak. The electrophoretic mobility of the immune complex could be optimized for resolution and sharpness by changing the length of the DNA coupled to the antibody. The detection limit of AFP was approximately 300 pM in a sample. This immunoassay method utilizing a liquid-phase binding assay format is simple and convenient for antigen measurements on microchips.

Antibodies↗
PubMed2005

Farnesylation of retinal transducin underlies its translocation during light adaptation.

G proteins are posttranslationally modified by isoprenylation: either farnesylation or geranylgeranylation. The gamma subunit of retinal transducin (Talpha/Tbetagamma) is selectively farnesylated, and the farnesylation is required for light signaling mediated by transducin in rod cells. However, whether and how this selective isoprenylation regulates cellular functions remain poorly understood. Here we report that knockin mice expressing geranylgeranylated Tgamma showed normal rod responses to dim flashes under dark-adapted conditions but exhibited impaired properties in light adaptation. Of note, geranylgeranylation of Tgamma suppressed light-induced transition of Tbetagamma from membrane to cytosol, and also attenuated its light-dependent translocation from the outer segment to the inner region, an event contributing to retinal light adaptation. These results indicate that, while the farnesylation of transducin is interchangeable with the geranylgeranylation in terms of the light signaling, the selective farnesylation is important for visual sensitivity regulation by providing sufficient but not excessive membrane anchoring of Tbetagamma.

Adaptation, Ocular↗