Search PubMed⌕ Search

Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 163 records · Page 9Linked to original sources
PubMed2000

1Alpha-hydroxyvitamin D3 prevents the decrease of bone mineral density in lactating beagles.

We assessed the change of bone mineral density (BMD) in lactating beagles with dual energy X-ray absorptiometry (DXA) and the preventive effect of 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on the BMD. Beagles, two to five years old, were used for detecting the time course change of BMD. Since the coefficient of variation (CV(%)) on detecting lumber vertebral (L2-L4) and tibial BMD by DXA was about 0.5%, DXA was useful to detect the change of BMD in beagles. There was a marked decrease in vertebral BMD during lactational period in the control group. The BMD levels after weaning were found to reverse to the initial level at mating. The same tendency was observed in tibial BMD as vertebral BMD, though the BMD changes were not marked. Beagles were administered at a dose of 0.1 microg/kg of 1alpha(OH)D3 three times in a week, and it was found to suppress the decrease in vertebral BMD during the breast feeding period. Also, the administration of 1alpha(OH)D3 promoted the prevention of decreased BMD during lactation both in vertebrae and tibiae. Significant effects of 1alpha(OH)D3 administration on tibial BMD were not observed. No adverse effects, such as hypercalcemia and hypercalciuria, were observed during the experimental period. Therefore, DXA was useful for detecting the changes of BMD in lactating beagles and the change of BMD was marked in lumber vertebrae, which are rich in trabecular bone. The preventive effect of 1alpha(OH)D3 on the decrease of BMD during the lactation period was observed in beagles.

Absorptiometry, Photon↗
PubMed2000

Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen.

Although alfacalcidol has been widely used for the treatment of osteoporosis in certain countries, its mechanism of action in bone, especially in the vitamin D-replete state, remains unclear. Here we provide histomorphometric as well as biochemical evidence that alfacalcidol suppresses osteoclastic bone resorption in an ovariectomized rat model of osteoporosis. Furthermore, when compared with 17beta-estradiol, a representative antiresorptive drug, it is evident that alfacalcidol causes a dose-dependent suppression of bone resorption, and yet maintains or even stimulates bone formation, as reflected in increases in serum osteocalcin levels and bone formation rate at both trabecular and cortical sites. 17beta-Estradiol, which suppresses bone resorption to the same extent as alfacalcidol, causes a parallel reduction in the biochemical and histomorphometric markers of bone formation. As a final outcome, treatment with alfacalcidol increases bone mineral density and improves mechanical strength more effectively than 17beta-estradiol, with a more pronounced difference in cortical bone. We conclude that estrogens depress bone turnover primarily by suppressing bone resorption and, as a consequence, bone formation as well, whereas alfacalcidol "supercouples" these processes, in that it suppresses bone resorption while maintaining or stimulating bone formation.

Animals↗
PubMed2000

Experimental postoperative adjuvant chemotherapy by UFT using primary tumor amputation model.

We evaluated the postoperative adjuvant chemotherapy by UFT using the primary tumor amputation-pulmonary metastasis model. When Lewis lung carcinoma (LLC) primary tumors on the hind foot pad grew palpable, they were amputated on two different days. In experiment (A) (earlier amputation model), micrometastases were detected on the day of amputation only by the histopathological examination. In the experiment (B) (later amputation model), nodules could be determined even by necropsy. Long-term (60-day) consecutive administration of UFT (22 mg/kg/day), which produced no body weight loss, markedly prolonged the survival period in experiment (A) (ILS: over 118%), 1 of the 15 mice being cured. UFT had a relatively weak but significant effect (67% of ILS) in schedule (B). Using the same model, we examined the inhibitory effect of UFT (2-week administration) on the number of metastatic nodules. A significant decrease of metastatic nodules was observed by UFT with both amputation schedules, but its effect was superior with schedule (A). In the same model using Colon 26 PMF-15, UFT markedly prolonged the survival period of mice (150% of ILS) and significantly decreased the metastatic nodules (86% inhibition). The dose of UFT used was relatively low, and did not significantly inhibit the growth of large tumors. However, the sensitivity to the micrometastases was high. These findings suggest that the postoperative adjuvant chemotherapy by the long-term consecutive administration of UFT would be effective for clinical cancer especially in curatively resected cases.

Amputation, Surgical↗
PubMed2000

Effects of metal combinations on cytotoxicity evaluation using a dynamic extraction method.

The effects of metal combinations on cytotoxicity were examined following dynamic extraction by freely gyrating two spherical metals in a glass vessel. The cell viabilities of an Au alloy, a Ag-Pd-Au alloy and Ti were little affected by combinations among three metals. Cell viability ranged between 60 and 80% when precious alloys were in combination with Co-Cr or Ni-Cr alloys. Ti showed a clear difference in cell viability either in combination with Co-Cr or Ni-Cr alloys. The cell viability of the Ti/Co-Cr alloy combination was the same as that of precious alloys/Co-Cr or Ni-Cr alloy combinations. However, in an analogy with Co-Cr alloy/Ni-Cr alloy combination, the Ti/Ni-Cr alloy combination depressed the cell viability below 20%. This suggested that when new metals are to be used in combination with dissimilar metals, the cytotoxicity of the metals could be evaluated in extraction conditions using the mutual dynamic contact of dissimilar metals.

Analysis of Variance↗
PubMed2000

[Predictors of prognosis after angioplasty in the unprotected left main coronary artery].

OBJECTIVES: The short-term and long-term predictors of outcome after coronary angioplasty in the unprotected left main coronary artery were investigated. METHODS: The procedure was performed in 122 consecutive patients for de novo lesions without myocardial infarction in our hospital between April 1986 and October 1998, including 16 emergency cases. Procedures were directional coronary atherectomy (73 patients), balloon angioplasty (31 patients), and stent implantation (18 patients). There were 101 males and mean age was 68 +/- 10 years. Follow-up angiography was performed in 98% of discharged patients, and all patients were clinically followed up for more than 1 year. Clinical and angiographic predictors of in-hospital and long-term outcome were evaluated. RESULTS: The in-hospital mortality was 5.7% (7 of 122 patients). Multivariate analysis revealed that more patients were admitted as emergency cases (57% vs 10%, p = 0.0088), with left ventricular ejection fraction < or = 35% (57% vs 22%, p = 0.029) and renal failure (43% vs 3%, p = 0.0004) finally died. Mean follow-up period was 3.5 years. Estimated survival rate was 77.1%, and cardiac-death free survival rate was 81.0% at 5 years by the Kaplan-Meier method. Univariate analysis showed that the predictors of cardiac death were emergency angioplasty, renal failure, decreased left ventricular ejection fraction, multivessel disease and unstable angina and/or congestive heart failure. Cox's regression model showed that renal failure (p = 0.0004) and multivessel disease (p = 0.0075) were significant predictors of long-term prognosis. CONCLUSIONS: Renal failure was the strongest predictor of outcome after unprotected left main coronary artery angioplasty.

Aged↗
PubMed2000

Late onset systemic lupus erythematosus with lichen planus-like eruption and cardiac tamponade.

A 71-year-old Japanese woman is reported as a case of late onset systemic lupus erythematosus (SLE) with lichen planus (LP)-like eruption and cardiac tamponade. As an initial symptom, our patient had cutaneous lesions clinically and histologically resembling LP, and then the passage of time allowed for the development of additional criteria (lymphopenia, pericarditis) until the diagnosis of SLE could be made. Our case suggests that LP-like eruptions may be one of the unusual variations of late onset SLE and elderly patients with LP-like eruptions should be carefully followed until a final diagnosis can be clearly made.

Age Factors↗
PubMed2000

[Molecular therapy of muscular dystrophy].

Muscular dystrophy is a nosology for a group of hereditary muscle disorders characterized by progressive wasting and weakness of skeletal muscle, where degeneration of muscle fibers is detected by pathological examination. Since the causative gene of Duchenne muscular dystrophy (DMD), the most severe and abundant form of muscular dystrophy, the DMD gene, and its product dystrophin was isolated by positional cloning by Dr. Kunkel and his colleagues, the studies on molecular pathologies of muscular dystrophy has been extensively developed. The current therapeutic approaches of muscular dystrophy, such as DMD involves pharmacological suppression of the inflammatory and immure responses, which usually provides only modest and temporary beneficial effects. Future approaches depend on cell and gene therapy technology and will require different strategies, none of which are currently ready to enter clinical practice. These approaches involve the efficient, non-antigenic gene transfer for in vivo gene therapy, pharmacological upregulation of the synthesis of utrophin, a related protein that compensates for the loss of dystrophin, and myogenic stem cell transplantation. These approaches could be integrated each other and called as molecular therapy.

Animals↗
PubMed1999

Identification of EPS8 as a Dvl1-associated molecule.

Dishevelled (Dsh) is involved in both Wingless (Wg) and Frizzled (Fz) signaling pathways. To further determine the function of Dsh, we have performed yeast two-hybrid screening and isolated several genes encoding the molecules associated with the PDZ domain of Dvl1, one of the murine Dsh homologs. During the screening, we found that EPS8, which is a substrate for activated EGF receptor (EGFR), specifically interacted with Dvl1. This interaction was also confirmed in vitro. Through transfection studies, we observed the mutual action between Dvl1 and EPS8. Dvl1 was hyperphosphorylated in the presence of EPS8, whereas the tyrosine phosphorylation of EPS8 by activated EGFR was inhibited in the presence of Dvl1. Immunohistochemistry showed that Dvl1 and EPS8 expression overlap in particular tissues during organogenesis. These results indicate that interaction between Dvl1 and receptor tyrosine kinase signal plays certain roles in developmental events.

Acid Phosphatase↗
PubMed1999

Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.

Yeast Mre11 functions with Rad50 and Xrs2 in a complex that has pivotal roles in homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand break (DSB) repair pathways. Vertebrate Mre11 is essential. Conditionally, MRE11 null chicken DT40 cells accumulate chromosome breaks and die upon Mre11 repression, showing frequent centrosome amplification. Mre11 deficiency also causes increased radiosensitivity and strongly reduced targeted integration frequencies. Mre11 is, therefore, crucial for HR and essential in mitosis through its role in chromosome maintenance by recombinational repair. Surprisingly perhaps, given the role of Mre11 in yeast NHEJ, disruption of NHEJ by deletion of KU70 greatly exacerbates the effects of MRE11 deficiency, revealing a significant Mre11-independent component of metazoan NHEJ.

Animals↗
PubMed1999

Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation.

ATM is a member of the large phosphatidylinositol-3 kinase family and plays an important role in cellular response to DNA damage. To further define the physiological roles of ATM at the cellular level, we created an isogenic set of stable cell lines differing only in their ATM status from the chicken B cell line DT40 by targeted integration. These stable DT40 cell lines, as most of transformed chicken cell lines, do not express p53. However, ATM-/- DT40 cells displayed retarded cellular proliferation, defective G2/M checkpoint control and radio-resistant DNA synthesis. Furthermore, ATM-/- DT40 cells were sensitive to ionizing radiation and showed highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In addition, a slight but significant reduction in targeted integration frequency was observed in ATM-/- DT40 cells. These results suggest that ATM has multiple p53-independent functions in cell cycle checkpoint control and in maintenance of chromosomal DNA. These ATM deficient DT40 clones therefore provide a useful model system for analysing p53-independent ATM functions.

Animals↗
PubMed1999

Analysis of dyestuff degradation products by capillary electrophoresis.

Capillary electrophoresis (CE) with two different detection methods, mass spectrometry (MS) and UV absorption spectroscopy with photodiode array detection (UV/DAD), was used for the analysis of the degradation products of dyestuffs. We have studied wet oxidation with solid catalyst as the treatment method of wastewaters containing dyestuffs. When the Orange II (C.I. Acid Orange 7) solution was used as the model wastewater, treated solution contained unknown highly polar degradation products. We were able to determine the molecular masses of some products by CE-MS. From this clue, we tried to identify these products by CE-UV/DAD. By means of the comparison of the migration time and UV spectra of standard samples, three degradation products were identified. The separation of degradation products was successful within 15 min.

Coloring Agents↗
PubMed1999

Nitric oxide production by bronchoalveolar cells during allograft rejection in the rat.

BACKGROUND: We reported the increased nitric oxide (NO) level in exhaled air of rat lung transplant recipients during acute rejection (AR). The aim of this study was to determine the site and level of NO production in the rejected graft. METHODS: Rat lung transplantation was performed in isografts and allografts. RESULTS: In isografts, no AR and no significant increase in NO production was identified. In allografts, grades I-II of AR was seen on postoperative day (POD) 3 and grade III on POD 5. NO produced by BAL cells increased on both POD 3 (11.8+/-2.0 parts per billion [ppb]) and POD 5 (115.3+/-66.9 ppb). There was a highly significant correlation between the level of NO and the severity of AR (p=0.862, P<0.005). BAL cells from allografts expressed iNOS mRNA. Among them, macrophages, lymphocytes and neutrophils were immunostained for iNOS. CONCLUSION: NO produced by BAL cells was detected in the early stages of rejection. Therefore, it may serve as a sensitive indicator of AR in lung transplantation.

Animals↗
PubMed1999

Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation.

Alzheimer's amyloid precursor protein (APP), the precursor of beta-amyloid (Abeta), is an integral membrane protein with a receptor-like structure. We recently demonstrated that the mature APP (mAPP; N- and O-glycosylated form) is phosphorylated at Thr668 (numbering for APP695 isoform), specifically in neurons. Phosphorylation of mAPP appears to occur during, and after, neuronal differentiation. Here we report that the phosphorylation of mAPP begins 48-72 hr after treatment of PC12 cells with NGF and that this correlates with the timing of neurite outgrowth. The phosphorylated form of APP is distributed in neurites and mostly in the growth cones of differentiating PC12 cells. PC12 cells stably expressing APP with Thr668Glu substitution showed remarkably reduced neurite extension after treatment with NGF. These observations suggest that the phosphorylated form of APP may play an important role in neurite outgrowth of differentiating neurons.

Alzheimer Disease↗
PubMed1999

Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis.

KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A-/- embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at approximately 10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.

Animals↗
PubMed1999

Merkel cells are responsible for the initiation of taste organ morphogenesis in the frog.

Taste organs in the frog have a distinctive cell type located exclusively in the basal portion. In the same fashion as type III cells in mammalian taste buds, these basal cells show immunoreactivity for serotonin antibody. Further, these cells are morphologically similar to epidermal Merkel cells. To determine the significance of these serotonergic basal cells, we examined the early development of taste organs during metamorphosis of the frog by focusing on the origin and possible roles of serotonergic basal cells. For convenience of description, five stages of development (metamorphic stage to climax stages A-D) are defined. In the metamorphic stage, a few noninnervated Merkel cells appear at the upper layer of the lingual epithelium. No neuronal elements are seen in the epithelium at this stage. At climax stages A-B, immature fungiform papillae become discernible in the dorsal surface of the tongue, where the Merkel cells are located. Merkel cells then move downward and extend their cytoplasmic processes toward the basal lamina. These cells are identified by their intense immunoreactivity for serotonin. During the later stages, many nerve fibers in the subepithelial connective tissue approach the epithelium containing Merkel cells. At climax stages C-D, Merkel cells extend cytoplasmic processes along the basal lamina toward the center of the newly forming fungiform papillae. The morphology of these Merkel cells exactly coincides with that of serotonergic basal cells in adult taste organs. Profuse exocytotic release of dense-cored granules of Merkel cells toward the nerve fibers through the basal lamina is frequently seen in these stages. The present study indicates that serotonergic basal cells are derived from intraepithelial Merkel cells, which act as target sites for growing nerves and may be responsible for the initiation of taste organ morphogenesis.

Animals↗
PubMed1999

Application of capillary electrophoresis to the analysis of inorganic ions in environmental samples.

A comprehensive review is presented of the state-of-the-art of capillary electrophoresis for application to the analysis of inorganic species, mainly ions, in environmental samples. This brief review covers the developments principally in sensitivity and matrix interference for the determination of inorganic ions in the following samples: drinking, mineral, surface, and ground waters, rainwater, snow, seawater, brine and waste waters, aerosol, and others. References published mainly from 1995 to 1997 were summarized in this review.

Aerosols↗