Biomedical subjects
Publications and source records attributed to S Hashimoto.
FR191512, a novel polyphenolic compound, inhibited the infectivity of influenza A virus in Madin-Darby canine kidney (MDCK) cells in vitro. Furthermore, FR191512 showed good in vivo anti-influenza activity in a mouse model of intranasal infection with influenza A virus. The cytotoxic activity of FR191512 against MDCK cells was very weak.
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WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated separately from the culture mycelium of a fungal strain Aphanoascus fulvescens No. 14865. Spectroscopic analysis revealed that both WF14865A and B were composed of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or leucine. These compounds inhibited human cathepsins B and L with IC50 values in the range of 8.4 approximately 72nM in vitro. Though their in vitro properties were typical as trans-epoxysuccinyl type inhibitors, they exerted strong bone resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2 approximately 10 mg/kg.
FR901469 is a novel antifungal antibiotic produced by an unidentified fungus No.11243. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatography, and lyophilization. FR901469 is a white powder which melts at 182 approximately 187 degrees C and possesses the molecular formula C71H116N14O23. This compound has good water solubility. FR901469 inhibited the activity of 1,3-beta-glucan synthase from Candida albicans with an IC50 value of 0.05 microg/ml, and displayed greater inhibitory activity than other 1,3-beta-glucan synthase inhibitors such as, WF11899A, echinocandin B, aculeacin A, and papulacandin B.
FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.
Purpose: The purpose of this study was to evaluate the long-term results of percutaneous transluminal angioplasty (PTA) for stenosis and/or occlusion of dialysis shunts. Methods: One hundred thirty-nine stenosed or thrombosed dialysis shunts (99 native fistulae, 37 grafts) in 122 patients were treated by PTA. In 39 cases, additional PTA for restenosis was performed. In total, 230 PTAs were performed (1-10 PTA/shunt). Results: The initial success rate was 86% in cases without occlusion. In contrast, the success rate in cases with occlusion was 53%, significantly worse than in the cases without occlusion. In cases in which initial success was obtained, primary cumulative patency rates at 3, 6, and 12 months were 87%, 60%, and 40%, respectively. With repeat PTA, secondary cumulative patency rates at 3, 6, 12, and 24 months were 96%, 83%, 63%, and 55%, respectively. Patency of native fistulae was better than patency of grafts. There was no significant relationship between the anatomical location of the stenoses and the patency rates. Conclusion: PTA is an effective treatment for shunt stenosis; although primary patency after PTA is not sufficient, repeated PTA increases patency.
OBJECTIVES: The aim of this study is to clarify the operative situation of the supporting programs for social activity of the elderly by city, town, village governments in 1997. METHODS: We conducted a study of 3,255 of cities, towns and villages in Japan using a mailed questionnaire, which had been developed to assess the activities of supporting programs for social activity of the elderly. The questionnaire asks government officers whether they had each of the 33 programs in 1997. Each one of these programs belongs to one of the four different aspects of social activities: 1. employment, 2. social participation/volunteering, 3. education/training, 4. individual activities. For each program, the frequency of regions having the program were counted in total, as well as for each of four levels on governments scale: 1. ordinance-designated city, 2. city, 3. town, 4. village. The number of programs operated by the municipality were also evaluated. The main results were as follows One thousand six hundred (49.2%) of cities, towns and villages responded to our questionnaire. 1. Four programs, the promotion of clubs for elderly people, class/lecture meetings for the elderly, sporting events/athletic meetings for the elderly, and a respect-for-age congratulatory gift/money, were put into operation by over 80% of cities, towns and village governments. 2. The number of programs in total or for each of the three aspects of social activities except for social participation/volunteering tended to be high for the large scale governments. There were wide gaps in the number of programs among the regions even of the same level of the government scale. 3. The regions having supporting programs for employment consisted mainly of cities. Seventy-five percent of villages had no supporting program for employment. CONCLUSION: The operational situation of the supporting programs for social activity of the elderly by city, town, village governments was clarified. Furthermore, results obtained by this study can be used for self-assessment of operational situations by municipalities and can contribute to the activation of their supporting programs.
Adult respiratory distress syndrome (ARDS) characterized by permeability edema is observed in severe insults such as bacteremia sepsis. Interleukin (IL)-8, which chemoattracts and activates neutrophils, has been suggested to play an important role in the production of ARDS. Therefore, the inhibition of IL-8 production is an important strategy for the treatment of ARDS. Recent studies have revealed the role of p38 mitogen-activated protein (MAP) kinase in cytokine expression and the inhibition by a selective inhibitor of p38 MAP kinase activity of cytokine expression in a variety of cell types. However, little is known about the role of p38 MAP kinase in lipopolysaccharide (LPS)-induced IL-8 expression in pulmonary vascular endothelial cells and the effect of a selective p38 MAP kinase inhibitor on it. In the present study, we therefore attempted to clarify these issues. The results showed that LPS induced p38 MAP kinase phosphorylation and activity, and SB 203580 as a selective inhibitor of p38 MAP kinase activity inhibited p38 MAP kinase activity and IL-8 expression in LPS-stimulated pulmonary vascular endothelial cells. These results indicate that p38 MAP kinase regulates LPS-induced IL-8 expression in pulmonary vascular endothelial cells. Although it is currently not known whether SB 203580 is capable of producing beneficial effects on ARDS, a strategy of inhibiting p38 MAP kinase activity by a selective p38 MAP kinase inhibitor may apply to the therapy for ARDS.
PURPOSE: To determine whether nephron-sparing surgery is appropriate for patients with renal cell carcinoma (RCC) and a normal contralateral kidney. MATERIALS AND METHODS: We prepared whole-area histologic sections from 58 cases of RCC to examine the features of satellite tumor lesions (STLs), the proliferative potential of which was evaluated by counting argyrophilic nucleolar organizing regions (AgNORs). RESULTS: We found three types of microscopic lesions: STLs, adenomas, and dysplastic foci, the latter two of which appeared to be preneoplastic. Of the 58 cases, STLs were observed in 27 (47%) and either adenomas or dysplastic foci in 19 (33%). At least one of the three types of lesion was found in 37 cases (64%). No correlation was found between the incidence of STL and the size of the main tumor, but the incidence tended to be higher in lesions of higher grade or stage. The STLs were located >2 cm from the margin of the main tumor in 6 of the 27 cases (22%). The mean number of AgNORs per high-power field was 5.09 +/- 1.53 (SD) in the main tumors, 4.21 +/- 1.36 in the STLs, and 2.27 +/- 0.07 in the adenomas and dysplastic foci. CONCLUSIONS: These findings suggest that nephron-sparing surgery risks leaving STLs, which have considerable proliferative potential. Thus, nephron-sparing surgery must still be considered adventurous treatment in elective cases but can be recommended for patients who require nephron preservation.
Cholangiography is the most fundamental and reliable examination for diagnosis of the extent of bile duct carcinoma. Hepatic angiography is also informative for diagnosis of vascular invasion. However, an accurate understanding of three-dimensional biliary and vascular anatomy at the hepatic hilum is not easily gained by conventional cholangiography and angiography. We have performed three-dimensional cholangiography and angiography (3D-CG & AG) using rotational DSA (Advantx ACT) and a 3D spinning digital imaging system in 29 patients with hilar cholangiocarcinoma, etc. 3D-CG & AD provides clear three-dimensional visualization of the biliary tract and blood vessels affected by bile duct cancer, and useful information on optimal resection. Of 13 patients with hilar cholangiocarcinoma undergoing resection, curative resection was carried out in 11 (85%). 3D-CG & AG is considered to be an indispensable imaging modality for evaluation of the extent and staging of hilar cholangiocarcinoma.
OBJECTIVE: Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce chondrocyte apoptosis. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on chondrocyte apoptosis and NO production using an experimental osteoarthritis (OA) model. METHODS: Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into 3 groups. Four weeks after ACLT, the HA group started intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; the no injection group received no treatment. All ACLT knees were harvested at Week 9 and evaluated for OA severity. Culture supernatants of the cartilage were analyzed for nitrite concentration. Cartilage sections were analyzed by TUNEL for apoptosis and by immunohistochemistry for nitrotyrosine. RESULTS: OA in the HA group was less severe than the other 2 groups. The number of apoptotic chondrocytes was significantly lower in the HA group. HA injection did not influence NO production in cartilage. CONCLUSION: HA protects against chondrocyte apoptosis during the development of OA, while it may not have definite effects on NO production in the joints. These inhibitory effects of HA on chondrocyte apoptosis may play a role in its mechanism of action in chondroprotection.
Since 1991, we have performed stent placement for 35 iliac artery lesions in 31 patients. The etiologic diseases were atherosclerotic in 34 patients and traumatic dissection in one. The indications of placement were total occlusion in 3, late restenosis after angioplasty in 5, dissection in 5, and residual stenosis due to inadequate angioplasty in 21. We also performed direct stent placement for one traumatic dissection. The stents used were Wallstents in 10, Palmaz stents in 14, Strecker stents in 9, and Memotherm stents in 2 lesions. Follow-up was performed clinically or angiographically with measurement of the ankle/arm pressure index. Stent placement was successful in all cases, and relief or improvement of symptoms was achieved. The follow-up period ranged from 6-85 months (mean, 37.3 months). Late stent stenosis or occlusion occurred in 6 cases, among which 4 occluded lesions were successfully recanalized by thrombolytic therapy with angioplasty or second stent placement. In total, the primary patency rates were 88% and 77% at two and four years, respectively, while the secondary patency rates were 94% and 94%. In conclusion, metallic stent placement may offer extended application of intravascular treatment for iliac artery occlusive disease, and good long-term patency rates can be expected.
Dioxin-like and estrogenic activities were measured in a sediment core collected from Tokyo Bay using in vitro bioassays after fractionating sediment extracts into three fractions by florisil column chromatography. Target analytes including polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polycyclic aromatic hydrocarbons (PAHs) and nonylphenol (NP) were measured by gas chromatography-mass spectrometry (GC-MS) or high performance liquid chromatography (HPLC) techniques. NP concentrations were greater in surface sediments (0 to 12 cm) than those in sub-surface (12-30 cm). The maximum observed PCN concentration was 5 ng/g, whereas that of PCBs was 300 ng/g. Concentrations of PCBs in fraction 1 (F1) were not high enough to induce significant luciferase activities in H4IIE-luc cells. Significant dioxin-like activities were found in fractions 2 (F2) and 3 (F3). PAH concentrations were correlated with dioxin-like activities measured in F2. Compounds that contribute to the dioxin-like activities in F3 were not identified yet. Significant estrogenic activities were observed in F2 samples, which may be related to the presence of certain estrogenic PAHs. F3 samples were cytotoxic to MCF-7 cells and therefore their estrogenic potential could not be estimated.
Nasal carriage of MRSA is a significant risk-factor for the endogenous MRSA infection in immunocompromised patients. MRSA infection in ICU patients is thus mostly endogenous infection. To evaluate the impact of mupirocin use on the incidence of endogenous infection caused by MRSA in an intensive care unit, we prospectively treated all patients in the unit with mupirocin, 3 times daily for 3 days. This routine use of mupirocin led to eradication of nasal MRSA carriage in 81.8% of surveillance cultures and to a significant reduction in the total incidence of MRSA infection among MRSA carrier patients (0 episode in 11 patients) when compared to historical controls prior to the use of mupirocin (3 episodes in 7 patients). Mupirocin nasal ointment was significantly effective to prevent endogenous MRSA infection.
We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2-30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of 212.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.
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