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Biomedical subjects

S Matsunaga

Publications and source records attributed to S Matsunaga.

At least 73 records · Page 4Linked to original sources

Bioactive triterpenoids from the stem bark of Picea glehni.

Two new triterpenoids, 3 alpha-methoxyserrat-14-en-21 beta-yl formate (1), and 24-methylcycloartenone (2), were isolated from the stem bark of Picea glehni (Fr. Schm.) Masters together with three known triterpenoids, 3 alpha-methoxyserrat-14-en-21 beta-ol, 3 beta-methoxyserrat-14-en-21 beta-ol, and piceanonol A. Compounds 1, 2, and a synthetic sample, 3 alpha-methoxyserrat-13-en-21 beta-yl formate showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).

Antigens, Viral↗

GABA-Mediated inhibition between amacrine cells in the goldfish retina.

Retinal amacrine cells have abundant dendro-dendritic synapses between neighboring amacrine cells. Therefore an amacrine cell has both presynaptic and postsynaptic aspects. To understand these synaptic interactions in the amacrine cell, we recorded from amacrine cells in the goldfish retinal slice preparation with perforated- and whole cell-patch clamp techniques. As the presynaptic element, 19% of the cells recorded (15 of 78 cells) showed spontaneous tetrodotoxin (TTX)-sensitive action potentials. As the postsynaptic element, all amacrine cells (n = 9) were found to have GABA-evoked responses and, under perforated patch clamp, 50 microM GABA hyperpolarized amacrine cells by activating a Cl(-) conductance. Bicuculline-sensitive spontaneous postsynaptic currents, carried by Cl(-), were observed in 82% of the cells (64 of 78 cells). Since the source of GABA in the inner plexiform layer is amacrine cells alone, these events are likely to be inhibitory postsynaptic currents (IPSCs) caused by GABA spontaneously released from neighboring amacrine cells. IPSCs were classified into three groups. Large amplitude IPSCs were suppressed by TTX (1 microM), indicating that presynaptic action potentials triggered GABA release. Medium amplitude IPSCs were also TTX sensitive. Small amplitude IPSCs were TTX insensitive (miniature IPSCs; n = 26). All of spike-induced, medium amplitude, and miniature IPSCs were Ca(2+) dependent and blocked by Co(2+). Blocking of glutamatergic inputs by DL-2-amino-phosphonoheptanoate (AP7; 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2 microM) had almost no effect on spontaneous GABA release from presynaptic amacrine cells. We suggest that these dendro-dendrotic inhibitory networks contribute to receptive field spatiotemporal properties.

Action Potentials↗

Retinoid receptors and the induction of apoptosis in canine osteosarcoma cells.

Retinoids, all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis-RA), induced morphological changes and apoptosis-like cell death characterized by cell shrinkage, chromatin condensation and nuclear disintegration in three canine osteosarcoma cells, OOS, HOS and POS, at a concentration of 10(-5) M. Both retinoid receptors, RARs and RXRs, were identified in these cells. 9-cis-RA bound to both the RXRs and the RARs, whereas ATRA bound to only the RARs in these cells. Those results indicate that the induction of apoptosis in canine osteosarcoma cells may be mediated by the specific control of RARs and RXRs.

Alitretinoin↗

Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice.

OBJECTIVE: To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. ANIMALS: Forty-five 5-week-old female BALB/c nude mice. PROCEDURE: 1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. RESULTS: Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE: 9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs.

Alitretinoin↗

In vitro retinoid-induced growth inhibition and morphologic differentiation of canine osteosarcoma cells.

OBJECTIVE: To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells. SAMPLE POPULATION: 3 osteosarcoma cell lines established from osteosarcomas in dogs. PROCEDURE: Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted. RESULTS: In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies. CONCLUSION AND CLINICAL RELEVANCE: Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs.

Alitretinoin↗

Nonsurgically managed patients with degenerative spondylolisthesis: a 10- to 18-year follow-up study.

OBJECT: Controversy exists concerning the indications for surgery and choice of surgical procedure for patients with degenerative spondylolisthesis. The goals of this study were to determine the clinical course of nonsurgically managed patients with degenerative spondylolisthesis as well as the indications for surgery. METHODS: A total of 145 nonsurgically managed patients with degenerative spondylolisthesis were examined annually for a minimum of 10 years follow-up evaluation. Radiographic changes, changes in clinical symptoms, and functional prognosis were surveyed. Progressive spondylolisthesis was observed in 49 patients (34%). There was no correlation between changes in clinical symptoms and progression of spondylolisthesis. The intervertebral spaces of the slipped segments were decreased significantly in size during follow-up examination in patients in whom no progression was found. Low-back pain improved following a decrease in the total intervertebral space size. A total of 84 (76%) of 110 patients who had no neurological deficits at initial examination remained without neurological deficit after 10 years of follow up. Twenty-nine (83%) of the 35 patients who had neurological symptoms, such as intermittent claudication or vesicorectal disorder, at initial examination and refused surgery experienced neurological deterioration. The final prognosis for these patients was very poor. CONCLUSIONS: Low-back pain was improved by restabilization. Conservative treatment is useful for patients who have low-back pain with or without pain in the lower extremities. Surgical intervention is indicated for patients with neurological symptoms including intermittent claudication or vesicorectal disorder, provided that a good functional outcome can be achieved.

Activities of Daily Living↗

Immunolocalization of transforming growth factor-betas and their receptors in the intervertebral disk of senescence-accelerated mouse.

The temporal and spatial immunolocalization of TGF-betas and their receptors in the intervertebral disk of senescence-accelerated mouse (SAM) was examined to determine the biological roles played by TGF-betas and their receptors in the process of intervertebral disk degeneration. Ten male SAM and ICR mice aged 8, 24 or 50 weeks after birth were used for this experiment. Histological and immunohistochemical studies using specific antibodies for TGF-beta1, -beta2, -beta3, TbetaR-I, and TbetaR-II were performed. Intervertebral disks of SAM exhibited more degenerative changes than those of ICR mice. Expression of TGF-betas and TbetaRs in disk of SAM and ICR mice was observed at 8 weeks of age, and became weaker with aging. Our results suggest TGF-betas may play a role in the growth and maintenance of intervertebal disks.

Aging, Premature↗

[A case of malignant fibrous histiocytoma of mesocolon successfully resected after combined chemotherapy with epirubicin, CDDP and vincristine].

We experienced a case of MFH of the sigmoid mesocolon which was successfully resected after preoperative combined chemotherapy. A 66-year-old male underwent a laparotomy following a diagnosis of retroperitoneal tumor. The tumor had extensively invaded the surrounding tissue and an incisional biopsy was done. It was diagnosed as MFH histologically. Ten cycles of post-operative chemotherapy with doxorubicin were effective for a complete remission. However, the MFH reappeared at the same site after 2 years and 9 months. Three cycles of combined chemotherapy with epirubicin, CDDP and vincristine led to a regression of the tumor and no distant metastasis was found. The tumor was successfully resected with a negative surgical margin. It proved to be MFH of sigmoid mesocolon origin. The patient has been in good health for 7 years and 2 months after the second operation without further therapy. In cases of MFH such as the present in which the patient is sensitive to chemotherapy, neoadjuvant chemotherapy might be effective in allowing minimal surgery and offering a better quality of life.

Aged↗

The active digestion of uniparental chloroplast DNA in a single zygote of Chlamydomonas reinhardtii is revealed by using the optical tweezer.

The non-Mendelian inheritance of organelle genes is a phenomenon common to almost all eukaryotes, and in the isogamous alga Chlamydomonas reinhardtii, chloroplast (cp) genes are transmitted from the mating type positive (mt(+)) parent. In this study, the preferential disappearance of the fluorescent cp nucleoids of the mating type negative (mt(-)) parent was observed in living young zygotes. To study the change in cpDNA molecules during the preferential disappearance, the cpDNA of mt(+) or mt(-) origin was labeled separately with bacterial aadA gene sequences. Then, a single zygote with or without cp nucleoids was isolated under direct observation by using optical tweezers and investigated by nested PCR analysis of the aadA sequences. This demonstrated that cpDNA molecules are digested completely during the preferential disappearance of mt(-) cp nucleoids within 10 min, whereas mt(+) cpDNA and mitochondrial DNA are protected from the digestion. These results indicate that the non-Mendelian transmission pattern of organelle genes is determined immediately after zygote formation.

Animals↗

On topography and functionality in the B-D rings of cephalostatin cytotoxins.

Analogues 12'beta-hydroxycephalostatin 1 (9), 7'-deoxyritterazine G (10), and 14-epi-7'-deoxyritterazine B (11) were prepared via our protocol for unsymmetrical pyrazine synthesis. Cytotoxicity against human tumors was also determined for the first time for ritterazines, with femtomolar potency and a high correlation to cephalostatins observed. The SAR of these and related compounds provide insight into the importance of topography and certain chemical functionality in the B-D and B'-D' rings of cephalostatin type antineoplastics.

Antineoplastic Agents↗

Immunolocalization of bone morphogenetic protein and its receptors in degeneration of intervertebral disc.

STUDY DESIGN: Immunohistochemical study of expression and localization of bone morphogenetic protein (BMP)-2/4 and type I and II receptors on intervertebral disc. OBJECTIVES: To determine the biologic functions of BMPs and their receptors in the process of degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Biologic and pathologic processes in the cell during the degeneration of the intervertebral disc are as yet poorly understood. METHODS: The cervical spines of 15 male senescence-accelerated mice aged 8, 24, or 50 weeks were used for histologic and immunohistochemical examination of BMP-2/4 and BMP receptors IA, IB, and II. Immunostaining was performed with the avidin-biotin-peroxidase complex method. RESULTS: Degenerative change was recognized within intervertebral discs of senescence-accelerated mice aged 50 weeks. BMP-2/4 and its receptors were abundant in hyaline cartilaginous cells within the endplate of the vertebrae at 8 and 24 weeks of age. However, the expression of BMP-2/4 and its receptors moved from the hyaline cartilage of the endplate of the vertebrae to fibrous cells within the anulus and to the calcified cartilage at the site of enthesis of mice aged 50 weeks. CONCLUSIONS: BMP-2/4 and its receptors may play roles in degenerative change of intervertebral disc.

Aging↗

Genetic analysis of ossification of the posterior longitudinal ligament.

STUDY DESIGN: The human leukocyte antigen (HLA) haplotypes in families of patients with known ossification of the posterior longitudinal ligament (OPLL) were reviewed. OBJECTIVE: To clarify how genetic factors relate to the development of OPLL. SUMMARY OF BACKGROUND DATA: The association between genetic factors and the development of OPLL is still unknown. MATERIALS AND METHODS: The association between HLA haplotypes and OPLL was studied in families of 24 patients with OPLL. RESULTS: The prevalence of OPLL was higher in the siblings showing a higher share of identical HLA haplotypes: 10 (53%) of 19 with concurrence of two strands, and 5 (24%) of 21 with concurrence of one strand. Of 21 subjects who had no HLA haplotype identical with that in OPLL patients, only one showed evidence of OPLL. CONCLUSION: Genetic factors predispose toward the development of OPLL.

Aged↗

Strain on intervertebral discs after anterior cervical decompression and fusion.

STUDY DESIGN: An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. OBJECTIVES: To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. SUMMARY OF BACKGROUND DATA: There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. METHODS: Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. RESULTS: In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. CONCLUSIONS: Close attention should be paid to long-term biomechanical changes in the unfused segment.

Adult↗

Octa- and nonaprenylhydroquinone sulfates, inhibitors of alpha1,3-fucosyltransferase VII, from an Australian marine sponge Sarcotragus sp.

Alpha1,3-fucosyltransferase (Fuc TVII) is a key enzyme in the biosynthesis of selectin ligands. We have isolated two inhibitors of Fuc TVII from a marine sponge Sarcotragus sp. They were characterized as octa- and nonaprenylhydroquinone sulfates on the basis of spectral data. These compounds inhibited Fuc-TVII with IC50 values of 3.9 and 2.4 microg/mL, respectively.

Animals↗

The solution structures of calyculin A and dephosphonocalyculin A by NMR.

The NMR solution structure of calyculin A (1) in chloroform exhibits intramolecular interactions, resembling the original crystal structure. In methanol, calyculin A has the hydrogen bonding moieties solvent exposed. Dephosphonocalyculin A in chloroform resembles calyculin A in chloroform and the crystal structure of calyculin A. Dephosphonocalyculin A in methanol resembles calyculin A in methanol.

Animals↗

Theonellamide F, a Bicyclic Peptide Marine Toxin, Induces Formation of Vacuoles in 3Y1 Rat Embryonic Fibroblast.

: The effect of a marine bicyclic peptide, theonellamide F, on vacuole formation in exponentially growing 3Y1 rat embryonic fibroblasts was studied in comparison with the effect of monensin. Many abnormally large vacuoles appeared around the nucleus in the cells treated with 6 µM theonellamide F within 24 hours. Following prolonged treatment with this agent, the number of enlarged vacuoles increased. Such vacuoles accumulated many granules that showed Brownian movement. The effect of theonellamide F on the cells was more drastic in an amino-acid-deficient medium, in which all cells died within 1 hour at a 3-µM concentration of the agent. Theonellamide F probably affects cellular autophagy, inhibiting the degradation of the organelles and turnover of proteins. Monensin, a well-known Na(+) ionophore that disintegrates the Golgi apparatus, induced similar types of vacuole formation, although the vacuoles were localized in a region slightly distant from the nucleus. Monensin readily affected cell morphology, resulting in cell death. We propose that theonellamide F, like monensin, is a useful agent for investigating membrane structures in cells.

Journal Article↗