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Kaoru Yamada

Publications and source records attributed to Kaoru Yamada.

9 recordsLinked to original sources
PubMed2006

Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid beta-peptide by the liver.

PURPOSE: To identify the molecules responsible for amyloid beta-peptide (1-40) (Abeta(1-40)) uptake by the liver, which play a major role in the systemic clearance of Abeta(1-40). METHODS: The liver uptake index method was used to examine the mechanisms of Abeta(1-40) uptake by the liver in vivo. RESULTS: [125I]Abeta(1-40) uptake by the rat liver was concentration-dependent (50% saturation concentration = 302 nM). The inhibitory spectrum of Abeta fragments indicated that 17-24 in Abeta (LVFFAEDV) was the putative sequence responsible for hepatic Abeta(1-40) uptake. Receptor-associated protein (RAP) inhibited [125I]Abeta(1-40) uptake by 48%. RAP-deficient mice, in which low-density lipoprotein receptor-related protein 1 (LRP-1) expression was suppressed, showed a 46% reduction in [125I]Abeta(1-40) uptake by the liver. siRNA-mediated suppression of LRP-1 expression in the liver resulted in a reduction in [125I]Abeta(1-40) uptake by 64%. Both the expression of LRP-1 in the liver and the hepatic Abeta(1-40) uptake were significantly reduced in 13-month-old rats compared with 7-week-old rats. CONCLUSIONS: LRP-1 is the major receptor responsible for the saturable uptake of plasma free Abeta(1-40) by the liver. Reduction of LRP-1 expression will play a role in the age-related reduction in hepatic Abeta(1-40) clearance.

Age Factors↗
PubMed2005

Symbioimine and neosymbioimine, amphoteric iminium metabolites from the symbiotic marine dinoflagellate Symbiodinium sp.

Two amphoteric iminium metabolites, symbioimine (1) and neosymbioimine (2), were isolated from a cultivated symbiotic marine dinoflagellate Symbiodinium sp. Compounds 1 and 2 have a characteristic 6,6,6-tricyclic iminium ring structure and an aryl sulfate moiety. The plausible biogenetic pathway of 1 and 2 can be explained by an intramolecular Diels-Alder reaction followed by imine cyclization. Symbioimine (1) inhibited the differentiation of RAW264 cells into osteoclasts (EC50 = 44 microM), and significantly inhibited cyclooxygenase-2 activity at 10 microM. Thus, symbioimine is a potent anti-resorptive and anti-inflammatory drug.

Animals↗
PubMed2004

Symbioimine exhibiting inhibitory effect of osteoclast differentiation, from the symbiotic marine dinoflagellate Symbiodinium sp.

An amphoteric iminium metabolite, symbioimine (1), was isolated from a cultivated symbiotic marine dinoflagellate Symbiodinium sp. Its structure was deduced by spectroscopic analysis and X-ray crystallographic analysis. Symbioimine (1) has a characteristic 6,6,6-tricyclic iminium ring structure and an aryl sulfate moiety. The plausible biogenetic pathway of 1 can be explained by an intramolecular Diels-Alder reaction followed by imine cyclization. Symbioimine (1) inhibited the differentiation of RAW264 cells into osteoclasts, whereas its cell viability was not affected. Thus, symbioimine (1) is an antiresorptive drug candidate for the prevention and treatment of osteoporosis in postmenopausal women.

Animals↗
PubMed2004

[Post-traumatic high-flow priapism: a case report].

A 48-year-old man, who previously had normal erectile function, visited our hospital complaining of a painless erection that had persisted for 6 days. He had suffered perineal trauma in a traffic accident 9 days earlier. A diagnosis of post-traumatic high-flow priapism was suggested from the findings on penile blood gas analysis. Selective internal pudendal arteriography showed an arterial blush along the bilateral cavernous arteries. Subsequently, embolization of a cavernous fistula was performed with an autologous clot. However, the embolus was removed within a minute, so the procedure was repeated with Gelfoam. This patient had normal erectile function after 11 months, with no recurrence of priapism.

Accidents, Traffic↗
PubMed2003

Severe neutropenia with gelatinous bone marrow transformation in anorexia nervosa: a case report.

A 28-year-old woman with a history of anorexia nervosa was admitted with excessive weight loss, edema, and amenorrhea. She had lost 34% of her previous body weight within 2 years, and her body mass index was 12.3 kg/m(2). The leukocyte count on admission was 2150/microl and gradually decreased to 980/microl (neutrophils; 276/microl). Bone marrow biopsy disclosed gelatinous transformation with hypocellularity. After the patient was treated with intravenous nutritional support, the severe neutropenia improved to the level on admission. Hematological abnormalities seem to be common in anorexia nervosa, but severe neutropenia with gelatinous bone marrow transformation has rarely been reported.

Adult↗
PubMed2003

Phenotype correction of Fanconi anemia group A hematopoietic stem cells using lentiviral vector.

Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure due to defective stem cell function. FA patients' cells are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC), exposure to which results in cytogenetic aberrations and cell death. To date Moloney murine leukemia virus vectors have been used in clinical gene therapy. Recently, third-generation lentiviral vectors based on the HIV-1 genome have been developed for efficient gene transfer to hematopoietic stem cells. We generated a self-inactivating lentiviral vector expressing the FA group A cDNA driven by the murine stem cell virus U3 LTR promoter and used the vector to transduce side-population (SP) cells isolated from bone marrow of Fanconi anemia group A (Fanca) knockout mice. One thousand transduced SP cells reconstituted the bone marrow of sublethally irradiated Fanca recipient mice. Phenotype correction was demonstrated by stable hematopoiesis following MMC challenge. Using real-time PCR, one proviral vector DNA copy per cell was detected in all lineage-committed cells in the peripheral blood of both primary and secondary recipients. Our results suggest that the lentiviral vector transduces stem cells capable of self-renewal and long-term hematopoiesis in vivo and is potentially useful for clinical gene therapy of FA hematopoietic cells.

Animals↗
PubMed2003

Lentivirus vector purification using anion exchange HPLC leads to improved gene transfer.

Recombinant lentiviral vectors stably transduce both dividing and nondividing cells. Virus pseudotyping with vesicular stomatitis virus envelope G (VSV-G) protein broadens the host range of lentiviral vector and enables vector concentration by ultra-centrifugation. However, as a result of virus vector concentration, contaminating protein debris derived from vector-producing cell culture media is toxic to target cells and reduces the transduction efficiency. Here we report a new and rapid technique for purifying lentivirus vector using the strong anion exchange column that significantly improves gene transfer rates. We purified VSV-G pseudotyped self-inactivating lentivirus vector and obtained two protein elution peaks (Peak 1 and Peak 2) corresponding to transducing activity. Peak 1 viral particles were 4-8 times more effective in transducing target cells than Peak 2 or non-purified (pre-HPLC) viral particles. We used purified lentivirus vector expressing the human Fanconi anemia group A (FANCA) gene to transduce murine hematopoietic stem/progenitor cells. We observed a consistent 2- to 3-fold increase in gene transfer rates using Peak 1 purified virus compared with non-purified virus. We conclude that the purification method using the HPLC system provides the highly purified virus vector that reduces cell toxicity and significantly improves gene transfer in primary cells.

Animals↗