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Biomedical subjects

D Fujita

Publications and source records attributed to D Fujita.

14 recordsLinked to original sources
PubMed2003

Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells.

Prostaglandin (PG) E(2) is a known bone absorbing agent that acts on osteoblasts to facilitate osteoclastogenesis by increasing the secretion of RANKL. In the present study, we investigated the direct action of PGE(2) on osteoclastic progenitors that differentiate into TRAP-positive multinucleated cells. The hematopoietic stem cell obtained from murine bone marrow was purified by a Sephadex G-10 column, and cultured in the presence of CSF-1 and RANKL to facilitate cell differentiation. The introduction of low-density PGE(2) into the culture resulted in a drastic increase of TRAP-positive multinucleated cells, whereas the addition of high-density PGE(2) had the opposite effect. PCR analysis revealed increased level of EP3 mRNA in undifferentiated cells and reduced level after the development of osteoclast; EP1, EP2 and EP4 were constitutively expressed throughout the differentiation. Investigation of intracellular signaling verified that low-density PGE(2) suppressed PKA activity in undifferentiated cells, suggesting that PGE(2) acts on the osteoclastic cell lineage to facilitate cell differentiation by suppressing PKA in the presence of RANKL.

Animals↗
PubMed1999

A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling.

PP1 has previously been described as an inhibitor of the Src-family kinases p56(Lck) and FynT. We have therefore decided to use PP1 to determine the functional role of Src in platelet-derived growth factor (PDGF)-induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs). A synthetic protocol for PP1/AGL1872 has been developed, and the inhibitory activity of PP1/AGL1872 against Src was examined. PP1/AGL1872 potently inhibited recombinant p60(c-src) in vitro and Src-dependent tyrosine phosphorylation in p60(c-srcF572)-transformed NIH3T3 cells. PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs, as determined in the modified Boyden chamber, as well as PDGF-stimulated proliferation of HCASMCs. Surprisingly, in addition to inhibition of Src kinase, PP1/AGL1872 was found to inhibit PDGF receptor kinase in cell-free assays and in various types of intact cells, including HCASMCs. PP1/AGL1872 did not inhibit phosphorylation of the vascular endothelial growth factor receptor KDR (VEGF receptor-2; kinase-insert domain containing receptor) in cell-free assays as well as in intact human coronary artery endothelial cells. In line with the insensitivity of KDR, PP1/AGL1872 had only a weak effect on vascular endothelial growth factor-stimulated migration of human coronary artery endothelial cells. On treatment of cells expressing different receptor tyrosine kinases, the activities of the epidermal growth factor receptor, fibroblast growth factor receptor-1, and insulin-like growth factor-1 receptor were resistant to PP1/AGL1872, whereas PDGF alpha-receptor was susceptible, albeit to a lesser extent than PDGF beta-receptor. These data suggest that the previously described tyrosine kinase inhibitor PP1/AGL1872 is not selective for the Src family of tyrosine kinases. It is also a potent inhibitor of the PDGF beta-receptor kinase but is not a ubiquitous tyrosine kinase inhibitor. PP1/AGL1872 inhibits migration and proliferation of HCASMCs probably by interference with 2 distinct tyrosine phosphorylation events, creating a novel and potent inhibitory principle with possible relevance for the treatment of pathological HCASMC activity, such as vascular remodeling and restenosis.

3T3 Cells↗
PubMed1999

Obtaining an accepted Investigational New Drug application to operate an umbilical cord blood bank.

BACKGROUND: The residual blood left in the placenta, previously considered a biologic waste, contains sufficient hematopoietic stem and progenitor cells to consistently engraft at least a small recipient. Over the past several years, more than 500 HLA-matched, related and unrelated, allogeneic cord blood transplants have been performed. Consequently, public and private cord blood banks are being developed to meet future demands. Thus, the definition of a suitable and effective cord blood component needs to be critically defined. In February 1997, the US Food and Drug Administration (FDA) proposed that cord blood banks should operate under an Investigational New Drug (IND) license. STUDY DESIGN AND METHODS: Standard operating procedures were designed using standards from the Foundation for Accreditation of Hematopoietic and Cellular Therapy, the American Association of Blood Banks, and the National Marrow Donor Program and in accordance with current good manufacturing practices. The standard operating procedures were field-tested and submitted to the FDA. RESULTS: Issues of the utmost concern to the FDA dealt with transplant recipient outcome data collection, donor recruitment, sample tracking, the use of unlicensed materials, and the reporting of positive infectious disease results. After three attempts, an IND application was approved. CONCLUSIONS: To obtain approval of an IND application, cord blood banks need a set of standard operating procedures that describe cord blood collection, processing, freezing, and storage. Issues relating to potential cord blood recipient identification, cord blood shipping, and reporting of transplant recipient outcomes are also needed. The IND process provides an opportunity for outside reviewers to make suggestions that may be included in the standard operating procedures.

Blood Banks↗
PubMed1998

Martefragin A, a novel indole alkaloid isolated from red alga, inhibits lipid peroxidation.

Martefragin A (1), a novel indole alkaloid, was isolated from a red alga, Martensia fragilis, by repeated column chromatography. The structure of 1 was elucidated on the basis of spectral analysis of its methyl ester (2), including 1H- and 13C-NMR, 1H-1H correlation spectroscopy (COSY), and 13C-1H COSY. A single crystal X-ray analysis of the hydrochloride of 1 confirmed the assignment. Martefragin A (1) showed inhibitory activity on NADPH-dependent lipid peroxidation in rat liver microsomes. The IC50 values of 1, alpha-tocopherol and ascorbic acid were 2.8, 87 and 200 microM, respectively.

Alkaloids↗
PubMed1998

[Screening test by statistically reducing the number of the State-Trait Anxiety Inventory (STAI) items].

The purpose of the study is to find a method of mental examination which can be simply performed concurrently with physical examination during a regular check-up. On a regular check-up, the state-trait anxiety inventor (STAI) was administered to 264 construction workmen engaged in reconstruction work for the Hanshin Awaji Great Earthquake. Data on a total of 40 STAI items, i.e., 20 state anxiety (A-State) items and 20 trait anxiety (A-Trait) items were subjected to multiple regression analysis and five items were extracted from A-State and five from A-Trait items as a practical tool for a simple screening test. The contribution rates of the respective five items for the total score were 90.0% for A-State and 88.5% for T-State. The correlation coefficients, r, between predicted and observed values were 0.949 (p < 0.01) for A-State and 0.940 (p < 0.01) for A-Trait. Because of certain degrees of validity and reliability of each five-item system, it is considered that this method is useful as a simple screening test to roughly grasp the mental health of subjects and can be utilized for mental health care at offices.

Adult↗
PubMed1992

[Effect of cadmium on lipid components: relation of cadmium to thyroid hormone and growth hormone].

To clarify the relationship of cadmium (Cd), thyroid hormone (TH) and growth hormone (GH) to lipid components, 4-week-old SD rats were dosed orally with Cd (CdCl2) at a dose of 2.0 mg/kg body weight five times a week, orally with TH at a dose of 2.5 mg/kg body weight five times a week and subcutaneously with GH (somatotropin) at a dose of 1.0 IU/kg body weight three times a week, all for 4 weeks. As lipid components, the serum concentrations of triglycerides, free fatty acids, lipid peroxides and long-chain fatty acids were determined. We have devised a new method for determining the fatty acid composition in the femur using gas chromatography-mass spectrometry and made a simultaneous analysis of fatty acids, from myristic acid (C14:0) to cholesterol. The results of the present study led to the following conclusions. 1. Cd may inhibit lipogenesis by binding with SH of coenzyme A, thereby reducing the serum levels of free fatty acids and lipid peroxides. 2. When TH and Cd were administered in combination, the addition of Cd produced an inhibitory effect on lipid components, although TH given alone stimulated the lipid metabolism. Therefore, Cd and TH may have an interaction in lipid components. 3. When GH and Cd were administered in combination, Cd modulated the action of GH, which enhanced the effect of somatomedin on the lipid metabolism. The inhibitory effect of Cd on somatomedin activity via Zn was suggested. 4. A sex difference was found in the composition of fatty acids in blood. The males had higher proportions of palmitic acid (C16:0) and linoleic acid (C18:2), while the females had a higher proportion of arachidonic acid (C20:4). There was no sex difference in fatty acid composition in the femur. 5. It was confirmed that TH produced a peroxide of dehydrocholesterol, a precursor of vitamin D3, in the diaphysis of the femur in the increased metabolic state.

Animals↗
PubMed1989

Relationship of cadmium accumulation to zinc or copper concentration in horse liver and kidney.

The concentrations of Cd, Zn, Cu, and metallothionein (MT) in the liver, renal cortex, and renal medulla were determined in 24 male and 15 female younger thoroughbreds (age 27 to 97 months) and two old male horses (age 154 months and 190 months). High correlations were found between Zn and MT in the liver (partial correlation coefficient 0.836), between Cd and MT in the renal cortex (partial correlation coefficient 0.786), and between Cd and Zn in the renal cortex (partial correlation coefficient 0.675), while the correlation between Cd and MT in the liver was low (partial correlation coefficient 0.124). In the renal medulla, high correlations were found between Cd and Zn (partial correlation coefficient -0.631), between Zn and Cu (partial correlation coefficient 0.881), and between Cd and Cu (partial correlation coefficient 0.785). Therefore, in the liver, the MT concentration is the most highly correlated with the Zn concentration and is not correlated with the CD concentration unless artificially exposed to Cd. In the renal cortex, the MT and Cd concentrations are very highly correlated with each other. The Zn concentration is about 20 micrograms/g when the Cd concentration in the renal cortex is the lowest.

Animal Feed↗
PubMed1978

Genesis of a virus-transforming gene.

The gene src responsible for neoplastic transformation of fibroblasts by avian sarcoma viruses was apparently derived from highly conserved nucleotide sequences in the normal avian genome. The cellular homologue of src is unlinked to the genome of an endogenous virus in chicken cells and functions in an unknown manner during normal cell metabolism.

Alpharetrovirus↗