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Biomedical subjects

H Takayanagi

Publications and source records attributed to H Takayanagi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Modulation of osteoclast function by adenovirus vector-induced epidermal growth factor receptor.

We have explored the use of adenovirus vector-mediated gene transfer to introduce foreign genes into osteoclasts, terminally differentiated cells responsible for bone resorption. A replication-deficient adenovirus vector that contains a reporter gene encoding beta-galactosidase efficiently infected human osteoclast-like cells (OCLs) derived from human giant cell tumors and mouse OCLs formed in vitro. We then constructed an adenovirus vector carrying human epidermal growth factor receptor (EGFR) cDNA (Ax1CAhEGFR) and introduced the EGFR gene into mouse OCLs. Clear induction of EGF receptor was detected in Ax1CAhEGFR-infected OCLs (EGFR-OCLs) by immunocytochemistry and immunoblotting, and EGF stimulation induced rapid tyrosine phosphorylation of several proteins including EGF receptor itself. Large vacuoles appeared in EGFR-OCLs in response to EGF treatment, and pit-forming activity by EGFR-OCLs was dose-dependently suppressed by recombinant human EGF. In addition, survival of EGFR-OCLs was prolonged by EGF. No expression of EGF receptor or effects of EGF were observed in noninfected OCLs or control vector-infected OCLs. These results suggest that adenoviral vectors are useful for modulating osteoclast function by introducing foreign genes into osteoclasts and that they will be a good means of gene therapy of metabolic bone diseases.

Adenoviridae↗
PubMed1998

Overgrowth of the ischial tuberosity complicating femoral bone and muscle atrophy: implications for a delayed complication of malunited apophyseal avulsion fracture.

Delayed complications occurring several years after the fused avulsion of ischial tuberosity have rarely been reported. We present a patient with overgrowth of the ischial tuberosity who complained of knee pain associated with significant bone and muscle atrophy in the thigh, which occurred 10 years after the ischial injury. Reinforcement exercise of the hamstrings relieved the knee pain. Here, we emphasize that avulsion fractures of the ischial tuberosity can cause persistent disability and that patients with avulsion fracture of the ischial apophysis in the adolescent period should actively maintain the strength of the hamstrings, even after more than 1 decade.

Adult↗
PubMed1997

A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis.

Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.

Acid Phosphatase↗
PubMed1997

Ion-exchange high-performance liquid chromatographic separation of protein variants and isoforms on MCI GEL ProtEx stationary phases.

Protein variants and isoforms were successfully separated on MCI GEL ProtEx ion-exchange HPLC columns. There was no irreversible adsorption of proteins, and sample proteins were quantitatively recovered. Species variants of cytochrome c (bovine, horse and rabbit) were completely separated on a sulfopropyl (ProtEx-SP) stationary phase in a gradient system. Diethylaminoethyl (ProtEx-DEAE) phase was determined to be effective for the separation of human growth hormone and its deamidated isoforms. These characteristics of ProtEx stationary phases may be attributed both to particle uniformity and to hydrophillic surface coverage of the base polymeric material.

Animals↗
PubMed1996

An alternative access to a trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 19A.

A chemical synthesis has been achieved for beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-->3)-L-Rha, a trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 19A, by stepwise link-up of the suitably functionalized, constituent sugar units. A beta-selective glycosylation of trimethylsilylethyl glucoside having free 4-OH with 2-(benzoyloxyimino)-2-deoxyglycosyl bromide, followed by manno-selective hydroboration, N-acetylation, and functionalization of the anomeric center (1-OSE-->1-OH-->1-F), gave a key disaccharide donor, beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-->F. Ensuing glycosylation of an L-rhamnosyl acceptor with the donor substrate afforded, after deblocking, the target trisaccharide in 6.5% yield over 13 steps from D-glucose.

Carbohydrate Sequence↗
PubMed1996

Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. II. Structure elucidation and biosynthesis.

The structures of new protein farnesyltransferase inhibitors, andrastins A-C, were elucidated. The cyclopentane ring of andrastins exhibited keto-enol tautomerism, which made the structure hard to elucidate. Therefore, the structure of andrastin A was elucidated by INADEQUATE and 13C-13C couplings using 13C-labeled andrastin A. The absolute configuration of the p-bromobenzoyl derivative of andrastin A was elucidated by X-ray crystallographic analysis and its skeleton was shown to be ent-5 alpha,14 beta-androstane. The biosynthesis of andrastin A was also studied by the incorporation of 13C-labeled acetates. Though the andrastins had a common androstane skeleton, they were biosynthesized from a sesquiterpene and a tetraketide.

Alkyl and Aryl Transferases↗
PubMed1995

Kinetics and mechanism of photocycloaddition of deoxyuridines to 2,3-dimethyl-2-butene.

The mechanism of photocycloaddition of 2'-deoxyuridine (1a) and thymidine (1b) to 2,3-dimethyl-2-butene (Bu) in acetonitrile by UV irradiation has been studied. The reciprocal quantum yield for the cycloaddition increased linearly with reciprocal concentrations of Bu in acetonitrile to give limiting quantum yields at infinite concentration of Bu as 0.030 and 0.0096 for 1a and 1b, respectively. This shows that the cycloaddition proceeds in a two-step mechanism between the triplet state of 1 and Bu through biradical intermediates. Addition of cis-1,3-pentadiene quenched the reaction obeying the Stern-Volmer equation. The above quenching experiments and laser transient spectroscopy revealed that the triplet state of 1a reacts with Bu with much larger rate constant (1.3-1.6 x 10(9) M-1 s-1) than that of 1b (4-5 x 10(7) M-1 s-1) reflecting larger steric hindrance exerted in the reaction of 1b than that of 1a.

Alkenes↗
PubMed1995

Louisianins A, B, C and D: non-steroidal growth inhibitors of testosterone-responsive SC 115 cells. II. Physico-chemical properties and structural elucidation.

New non-steroidal growth inhibitors of testosterone-responsive SC 115 cells, louisianins A (MW: 189; C11H11NO2), B (MW: 191; C11H13NO2), C (MW: 173; C11H11NO) and D (MW: 173; C11H11NO) were isolated from the cultured broth of Streptomyces sp. WK-4028. Their structures were determined on the basis of spectroscopic data. The structure of louisianin A in particular was confirmed by X-ray crystallographic analysis. The four compounds commonly possess a unique pyrindine skeleton in the molecule.

5-alpha Reductase Inhibitors↗