Biomedical subjects
Publications and source records attributed to S Yamamura.
A series of the oxanosine and carbocyclic oxanosine derivatives were synthesized to evaluate for their anti-HIV activity. Compound 1, 7 and 9 showed weak anti-HIV activities.
The enantiomerically pure synthesis of 9-[(2'S, 3'S)-bis(hydroxymethyl)thietan-1'-yl]adenine 2,3'-thio analog of oxetanocin A, was achieved via coupling of silylated 6-chloropurine and sulfoxide 16 under Pummerer reaction conditions.
Peritoneal dissemination has an unfavorable impact on the prognosis of pancreatic cancer, and a peritoneal dissemination model was created in hamsters by using an experimental pancreatic cancer to clarify its pathological characteristics. PGHAM-1, a cancer cell line we established from BOP induced pancreatic cancer in Syrian golden hamsters, was inoculated into the abdominal cavity of Syrian golden hamsters. After inoculation, sequential changes in the diaphragm, omentum, and parietal peritoneum, and the metastatic patterns of the PGHAM-1 cells were morphologically investigated by macroscopical, microscopical, and ultrastructural observation. The cancer cells were easily absorbed at the stomata in the diaphragm and milky spots in the omentum, which were absorptive lymphatic structures, and lymphatic metastasis occurred 4 days after inoculation. In the parietal peritoneum, however, the cancer cells attached to and proliferated on the parietal peritoneum where mesothelial cells had exfoliated and the basement membrane was exposed. This process was comparatively time-consuming, and metastasis occurred in the parietal peritoneum at 7 days after inoculation. This study suggested that there might be two patterns of peritoneal dissemination of hamster pancreatic cancer. One route is lymphatic metastasis via stomata in the diaphragm and milky spots in the omentum, and the other is direct metastasis on the parietal peritoneum; each metastasis forms independently.
Effects of DAC (doxifluridine (5'-DFUR), adriamycin (ADM), cyclophosphamide (CPA)) chemotherapy were evaluated in seven patients with advanced breast cancer. 5'-DFUR of 600 mg was orally daily, ADM of 40 mg/m2 was administered intravenously (bolus) at day 1 and CPA of 400 mg/m2 was administered intravenously (one shot) at day 1 and day 8. These were repeated as one cycle of 21 days. Two complete responses, three partial responses and two progressive diseases were obtained, and the response rate was 71% (95% confidence interval: 29-96%). The side-effects of more than grade 3 were observed in leucocytopenia (4/7), neutrocytopenia (6/7), anorexia (2/7), nausea or vomiting (2/7) and alopecia (6/7). These results suggest that DAC chemotherapy is a novel, attractive regimen for treatment of advanced breast cancer. The randomized clinical trial is required to elucidate the efficacy of 5-fluorouracil (5-FU) or its analogues and the significance of methods for their administration in management of patients with advanced breast cancer.
PURPOSE: In contrast with many analyses of surgical treatment for spinal metastases, there have been only a few recent well-documented publications assessing nonsurgical treatment. This paper is a study of the outcome of nonsurgical therapy for metastatic tumors of the spine. METHODS AND MATERIALS: One hundred and one patients with spinal metastases were treated with radiation therapy and/or chemotherapy without surgical intervention between 1990 and 1995, in prospective analysis, and had follow-up for more than 24 months. This study included 59 men and 42 women with a mean age of 61 years (range: 14 to 81). Mean follow-up periods were 11 months for patients dying of the disease and 53 months for the survivors. Neurological status, pain relief, functional improvement, and cumulative survival rate were assessed. RESULTS: Of the total treated, 67 patients (66%) were evaluated as being neurologically stable or improved after treatment. Pain relief was achieved in 67%, and 64% showed functional improvement. Primary lesion responsiveness to nonsurgical therapy influenced the survival, neurological recovery, pain control, and function. Neurological findings before therapy were useful in predicting ambulatory status after treatment. CONCLUSION: Nonsurgical treatment was often successful when primary tumors had responsiveness to radiation therapy and/or chemotherapy. We found this to be evident even when neurological deficits were found, particularly in lumbar spines. Spinal metastases of tumors with less responsiveness, unless patients were neurologically intact, responded poorly to therapy. Most of the patients who were successfully treated enjoyed relief lasting nearly until death. Their functional ability was limited by general debility, rather than by local tumor regeneration.
The presence of microdomains enriched in clustered glycosphingolipids (GSLs) at the surface of plasma membranes and liposome membranes, and their functional role in signal transduction, have been suggested by a series of observations, as follows: (1) GSL clusters (patches) are observed by electron microscopy; (2) microvesicles enriched in GSLs and other sphingolipids can be isolated as detergent-insoluble particles by sucrose density gradient ultracentrifugation: (3) such vesicles isolated from B16 melanoma cells contain > 90% of cellular GM3, > 90% of c-Src and Ras, approximately 50% of Rho, and approximately 20 percent of Fak, despite the fact that this vesicle fraction contains only 0.5% of total cellular protein (this fraction is termed "detergent-insoluble GSL-enriched microdomain" (DIGEM)); (4) GM3 in DIGEM can be coimmunoprecipitated with c-Src and Rho, indicating a close association of GM3 with these transducer molecules; (5) stimulation of GM3 in B16 melanoma cells by anti-GM3 antibody or by Gg3 results in change of signal transduction. Thus, GSLs, together with various transducer molecules present at DIGEM, may directly induce signal transduction rather than modulate or modify signal transduction created through receptors of growth factors or hormones as previously observed.
The enantiomerically pure synthesis of [(2'S, 3'S)-bis(hydroxymethyl)pyrrolidin-1-yl] thymine 17 and -adenine 20 was achieved via construction of the base on the 1-amino-pyrrolidine 15, and their anti-HSV-1 and -2, and anti-HIV-1 activities were evaluated.
Mouse melanoma B16 cells are characterized by the predominant presence of ganglioside GM3 and adhere to lactosylceramide- or Gg3-coated plates through interaction of GM3 with lactosylceramide or Gg3, whereby not only adhesion but also spreading and enhancement of cell motility occur (Kojima, N., Hakomori, S. (1991) J. Biol. Chem. 266, 17552-17558). We now report that the adhesion process is based essentially on a glycosphingolipid-enriched microdomain (GEM) at the B16 cell surface, since >90% of GM3 present in the original cells is found in GEM, and GEM is also enriched in several signal transducer molecules, e.g. c-Src, Ras, Rho, and focal adhesion kinase (FAK). GEM was isolated as a low density membranous fraction by homogenization of B16 cells in lysis buffer under two different conditions (i.e. buffer containing 1% Triton X-100, or hypertonic sodium carbonate without detergent), followed by sucrose density gradient centrifugation. A close association of GM3 with c-Src, Rho, and FAK was indicated by co-immunoprecipitation of GM3 present in GEM by anti-GM3 monoclonal antibody DH2, followed by Western blotting with antibodies directed to these transducer molecules. The following data indicate that GEM is a structural and functional unit for initiation of GM3-dependent cell adhesion coupled with signal transduction. 1) Tyrosine phosphorylation in FAK was greatly enhanced in B16 cells adhered to Gg3-coated plates but was minimal in cells adhered to GM3-coated, GlcCer-coated, or noncoated plates. 2) GTP loading on Ras and Rho increased significantly when cells were adhered to Gg3-coated plates, compared with GM3-coated, GlcCer-coated, or noncoated plates. Since Ras and Rho are closely associated with GM3 in GEM, cell adhesion/stimulation through GM3 in GEM may induce activation of Ras and Rho through enhanced GTP binding.
The effect of disaccharide lepidimoide on light-induced chlorophyll accumulation was studied in cotyledons of sunflower (Helianthus annuus L.) seedlings and detached cucumber (Cucumis sativus L.) cotyledons. From studies on the structure-activity relationships of lepidimoide, its analogs, and sucrose with respect to light-induced chlorophyll accumulation in the cotyledons of sunflower seedlings, both lepidimoide and the free carboxylic acid of lepidimoide (lepidimoic acid) showed the highest promoting activity, whereas the hydrogenated lepidimoide, which lacks a double bond in the C4, 5 position in uronic acid, showed lower activity than lepidimoide; however, sucrose exhibited very weak activity. These results suggest that lepidimoide acts as a new type of plant growth regulator, not simply as a carbon source providing energy. Lepidimoide promoted not only light-induced chlorophyll accumulation in sunflower cotyledons but also light-induced 5-aminolevulinic acid content, which is considered to be a rate-limiting step in chlorophyll biosynthesis. Lepidimoide with cytokinin stimulated the accumulation of chlorophyll and 5-aminolevulinic acid additively. In detached cucumber cotyledons, lepidimoide also promoted light-induced chlorophyll accumulation. These results indicate that lepidimoide, in cooperation with cytokinin, causes light-induced chlorophyll accumulation in the cotyledons of several dicot plant species by affecting the level of 5-aminolevulinic acid. Key Words. 5-Aminolevulinic acid accumulation-Chlorophyll accumulation-Cucumis sativus-Cytokinin-Helianthus annuus-Lepidimoic acid-Lepidimoide-Structure-activity relationship
We employed hydroxyapatite (HA) granules to enhance screw fixation in revision surgery of failed osteosynthesis with a compression hip screw system in an 83-year-old woman. After reduction of the fracture, the fracture site with a large bone defect was filled with HA granules, and osteosynthesis was accomplished with a double cannulated lag screw and plate system. We feel that this HA granule augmentation method may also be suitable for osteosynthesis in other osteoporotic fractures.
We describe the clinical course of a 16-year-old baseball player with a history of recurrent hematoma of the thigh. The lesion was aspirated percutaneously several times and curetted under the diagnosis of traumatic hematoma. Microscopical examination revealed massive hemorrhage, necrosis, and a small number of Ewing's sarcoma cells. He died of multiple metastases. With recurrent hematoma in the soft tissue, neoplastic lesions should be ruled out.
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From the leaves and roots of Polyscias fruticosa, eight new oleanolic acid saponins named polysciosides A to H were isolated together with three known saponins. The structures of the saponins were established by means of spectral data, particularly NMR, which included COSY, HSQC, HMBC, HOHAHA and ROESY techniques.
PURPOSE: Mitogen-activated protein kinase (MAPK) is a ubiquitous signaling protein that has been associated with cellular proliferation; however, its role in cellular migration has not been established. In this study, we investigate the role of MAPK in platelet-derived growth factor (PDGF)-induced migration and proliferation of human vascular smooth muscle cells (SMCs). METHODS: SMC migration was measured using a microchemotaxis assay (4 hours), and proliferation was assessed using 3H-thymidine uptake and cell counts. PD098059 was used as a specific noncompetitive inhibitor of MAPK activation. RESULTS: Coincubation of SMCs with PD098059 resulted in significant inhibition of PDGF-BB (5 ng/ml)-induced SMC chemotaxis and proliferation. The IC50 for both processes was approximately 10 mumol/L with complete inhibition at 50 mumol/L. Stimulation of SMCs with PDGF produced an early peak in MAPK activity followed by a plateau of activity that persisted for 24 hours. We hypothesized that variations in the temporal activation of MAPK might explain the action of this enzyme on these two disparate cellular events. By adding PD098059 at intervals after stimulation of SMCs with PDGF, we demonstrated an association between MAPK activity within the first 15 minutes and SMC migration, whereas MAPK activity between 1 and 4 hours was associated with SMC proliferation. CONCLUSIONS: MAPK activity is essential for both SMC migration and proliferation, and distinct phases of enzyme activation are required to stimulate these two discrete cellular events. Inhibition of this signaling protein may prove to be a useful method for preventing intimal hyperplasia.
The distribution of CD57+ T and CD56+ T cells in patients with RA was examined. In control osteoarthritis patients, these cells exist as a minor population in the peripheral blood. Our data show that in patients with RA, CD57+ T cell levels are elevated in peripheral blood, knee joint fluid, knee synovial membrane and bone marrow (BM), compared with peripheral blood of controls. CD57+ T cells are especially high in knee joint fluid and joint-adjacent BM, while CD56+ T cells show no such increase. CD57+ T cells contain a major population of CD8+ cells and higher proportions of CD4-8- cells and gammadelta T cells than do CD57- T cells. CD57+ T cells in peripheral blood and joint fluid increase with the duration of disease. Erythrocyte sedimentation rate (ESR) is inversely correlated with the proportion of CD57+ T cells in the joint fluid. Although RA frequently occurs in patients with CD3+57+ cell leukaemia, and some CD57+ T cells are likely to be involved in the onset of RA, we suggest that CD57+ T cells may rather suppress inflammation of RA, and other cellular components (e.g. granulocytes) may govern the severity of the inflammation of RA. These CD57+ T cells are probably generated extrathymically in the adjacent BM or joint space.
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The effects of thiopental on contraction, membrane potential and membrane ionic currents were studied in single canine left ventricular cells. Thiopental 10(-5) and 10(-4) mol/l reduced the cell-shortening from 7.02 +/- 0.64 microns to 5.66 +/- 1.39 and 3.48 +/- 0.64 microns respectively (mean +/- S.D., N = 10, 0.5 Hz). This effect was enhanced in higher (> 1.0 Hz) electrical stimulation frequencies. Also, thiopental decreased the plateau phase and shortened the duration of action potential. On the other hand, voltage clamp experiment revealed that thiopental 10(-6), 10(-5), and 10(-4) mol/l reduced peak Ca2+ current from 520 +/- 48 pA to 387 +/- 60 pA, 261 +/- 84 pA, and 84 +/- 36 pA respectively (mean +/- S.D., N = 8), and showed a use-dependent block of Ca2+ current. However, only a high dose of thiopental (10(-4) mol/l) inhibited the Na+ current. We conclude that the negative inotropic effect of thiopental on the heart is mediated mainly via inhibition of the Ca2+ current.
The objectives of this study were to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples prepared by spray-drying, and to demonstrate the applicability of thermal and water-vapour-adsorption techniques for studying the material. Amorphous UDCA was prepared by spray-drying a solution of the compound in a mixture of ethanol and dichloromethane. The amorphous material was characterized by powder X-ray diffraction, infrared (IR) spectroscopy, isothermal microcalorimetry, differential scanning calorimetry (DSC) and water-vapour adsorption. When the inlet-air temperature of the spray drier was increased beyond 140 degrees C, the intensity of X-ray diffraction peaks from crystalline UDCA decreased and the IR bands in the hydroxyl-stretching and carboxyl-stretching regions changed. Dissolution of intact and spray-dried samples of UDCA prepared at 60 and 100 degrees C was an endothermic process but the dissolution became exothermic with increasing inlet-air temperature. UDCA samples differing in crystallinity were obtained, depending on the inlet-air temperature. A good correlation was obtained between the heat of solution and the heat of crystallization determined from DSC peak area. A good correlation was also obtained between the heat of solution and the crystallinity determined by Ruland's method from X-ray diffraction patterns. The amount of water vapour adsorbed on UDCA samples increased with increasing inlet-air temperature, indicating hydrogen bonding between water molecules and the hydroxyl groups or the carboxyl groups of amorphous UDCA. These results indicate that measurement of adsorption of water vapour and thermal analysis can both be used to evaluate the crystallinity of solid substances.