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Biomedical subjects

H Tanino

Publications and source records attributed to H Tanino.

At least 19 recordsLinked to original sources

Three-dimensional computer-aided design based design sensitivity analysis and shape optimization of the stem using adaptive p-method.

The number of stem designs for total hip arthroplasty is increasing, and occasionally design changes have yielded unexpected clinical results. At present, we are not able to clearly identify which parameter of the stem is most important, and the optimum value of many parameters. The goals of this study were to identify which parameter is most important, to understand the effect of design change, and to find the optimum stem shape. For this purpose, we used adaptive p-method together with three-dimensional computer-aided design software program for the design sensitivity analysis (DSA) and shape optimization of the stem. The results suggested that increasing the lateral and medial width of the distal cross-section together with decreasing the medial-lateral width and the medial radius of the distal cross-section from the default value would lead to a decrease in the largest maximum principal stress of the distal cement. The medial width of middle cross-section, however, was not so simple. The result of DSA suggested that decreasing this parameter from the default value decreased the stress in the distal cement, but the optimum shape was obtained by increasing this parameter. The method used in this study will assist our engineers and surgeons in the process of modifying and optimizing the stem design.

Arthroplasty, Replacement, Hip↗

Differential expression of rat brain caspase family proteins during development and aging.

It is well recognized that caspases are essential effector molecules for carrying out apoptosis in eukaryotic cells. The expression of rat brain caspase family proteins (caspase-2, -3, -6, -7, -8, -9, 10) in development and aging was assessed using immunochemical detection. All of these caspases were expressed in the rat brain. Immunoblot analysis of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that cytosolic caspase-3, -7, -8, and -10 were highly expressed at E19, and decreased after birth. In contrast, cytosolic caspase-2, -6, and -9 were constitutively expressed from the early stages to 96 weeks of age. These results show that the expression of rat brain caspase family proteins is differentially regulated during the development and aging.

Aging↗

Differential subcellular localization of caspase family proteins in the adult rat brain.

The distribution of the caspase family (caspase-2, -3, -6, -7, -8, -9, -10) was assessed using immunochemical detection of subcellular fractions of 8-week-old rat brain tissues. The present study demonstrated that the relative protein level of caspase-2, -3, -6, -8 and -10 was highest in the soluble cytosolic fraction, while that for caspase-9 was highest in the nucleus. We also found that caspase-3 and -6 were present at high levels and caspase-2, -8 and -9 at moderate levels in the nerve endings fraction as well as in the soluble cytosolic fraction. These results suggest that rat brain caspases are differentially expressed in the subcellular fractions of the rat brain, and that caspases not only contribute to the regulation of neuronal death, but also to synaptic plasticity.

Animals↗

Resistant mechanisms of anthracyclines--pirarubicin might partly break through the P-glycoprotein-mediated drug-resistance of human breast cancer tissues.

Juliano and Ling initially reported the expression of a 170 kDa glycoprotein in the membrane of Chinese hamster ovarian cells in 1976, and named this glycoprotein P-glycoprotein (P-gp) based on its predicted role of causing "permeability" of the cell membrane. After much research on anthracycline-resistance, this P-gp was finally characterized as a multidrug-resistant protein coded by the mdr1 gene. Multidrug resistance associated protein (MRP) was initially cloned from H69AR, a human small cell-lung carcinoma cell line which is resistant to doxorubicin (DXR) but does not express P-gp. MRP also excretes substrates through the cell membrane using energy from ATP catabolism. The substrate of MRP is conjugated with glutathione before active efflux from cell membrane. Recently, membrane transporter proteins were re-categorized as members of "ATP-Binding Cassette transporter"(ABC-transporter) superfamily, as shown at http://www.med.rug.nl/mdl/humanabc.htm and http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html. A total of ABC transporters have been defined, and MDR1 and multidrug resistance associated protein 1 (MRP1) were reclassified as ABCB1 and ABCC1, respectively. Their associated superfamilies include 11 and 13 other protein, in addition to ABCB and ABCC, respectively. Lung resistance-related protein (LRP) is not a member of the superfamily of ABC transporter proteins, because it shows nuclear membrane expression and transports substrate between nucleus and cytoplasm. LRP was initially cloned from a non-small cell lung carcinoma cell line, SW1573/2R120 which is resistant to DXR, vincristine, etoposide and gramicidin D and does not express P-gp. The mechanisms of resistance remains unclear, and why some resistant cell lines express P-gp and others express MRP and/or LRP is likewise unclear.

ATP-Binding Cassette Transporters↗

The sphericity of the bearing surface in total hip arthroplasty.

This study evaluated the sphericity of bearing surfaces in total hip arthroplasty. The out-of-roundness of metal femoral heads, the inner surface of polyethylene liners, and commercially available ball bearings was measured. The hip prostheses were obtained directly from the manufacturers. The sphericity of the bearing surfaces was significantly inferior to that of the ball bearings. The sphericity of the femoral head on the sagittal plane was inferior to that on the transverse plane. Several significant differences were found among different manufacturers. The sphericity of the femoral head on the sagittal plane and that of polyethylene significantly improved in 1999 and 2000 compared with those in 1995. Further improvement is desirable, however, because good sphericity is expected to prolong the functional performance of the prosthesis after total hip arthroplasty.

Analysis of Variance↗

Alterations of phospholipase C isozymes in rat cerebral cortex through hyperoxia.

The effect of hyperoxia on the level of three phospholipase C (PLC) isozymes (beta1, gamma1, delta1) was assessed in the rat cerebral cortex. When the rats were exposed to 100% oxygen for 60 h, there was a significant reduction in the catalytic activity of low molecular weight phosphotyrosine phosphatase, which was susceptible to activity loss under oxidative stress. The result suggests that oxidative stress is induced in the rat cerebral cortex through hyperoxia. The protein levels of PLC-beta1 and -delta1 were significantly increased in the cerebral cortex where oxidative stress had been induced, although that of PLC-gamma1 was not altered. There was no significant difference in the total PLC activity of the cerebral cortex between hyperoxia and control rats. Using gel filtration chromatography, it was revealed that the PLC-beta1 activity in the cerebral cortex of the hyperoxia rats was higher than that in the control rats, but the PLC-delta1 activity in the former did not differ from that in the latter, despite an increase in the PLC-delta1 protein level. These findings suggest that the PLC-beta1 and -delta1 protein levels of brain tissues are increased by oxidative stress, and that the increased PLC-delta1 molecule is less active.

Aerobiosis↗

[A case of docetaxel-resistant breast cancer responsive to paclitaxel therapy].

A 73-year-old woman underwent docetaxel therapy for lung metastasis from breast cancer after having received CAF therapy. Because of the progressive disease due to secondary resistance to docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15 and 22, repeated every 6 weeks). The paclitaxel therapy brought about no adverse effects and a 51%-reduction in the size of the metastatic lung tumor (PR). Although the duration of the response to the paclitaxel therapy was limited to about one month due to progression of a brain metastasis, paclitaxel therapy may be effective against docetaxel-resistant breast cancer.

Aged↗

[Non-small cell lung cancer with liver metastasis responsive to gemcitabine--a case report].

A 56-year-old male patient underwent a right upper lobectomy and lymph node dissection for non-small cell lung cancer in March 1994. Multiple lung metastases in the right lung were found 45 months after the operation, and chemotherapy with docetaxel was administered. A liver metastasis was detected 11 months later, and it was refractory to docetaxel. Therefore, the patient was treated with cisplatin, mitomycin C and vinorelbine, which resulted in no change to the liver metastasis. He was next treated with gemcitabine, which resulted in a partial response of the liver metastasis. The adverse effects of gemcitabine were Grade 3 thrombocytopenia and Grade 2 neutropenia. The response duration for gemcitabine therapy was three months.

Adenocarcinoma↗

Activation of NADPH oxidase in Alzheimer's disease brains.

The present study is the first to show that superoxide (O(-)(2)) forming NADPH oxidase is activated in Alzheimer's disease (AD) brains by demonstrating the marked translocation of the cytosolic factors p47-phox and p67-phox to the membrane. In conjunction with a recent in vitro study showing that amyloid beta activates O(-)(2) forming NADPH oxidase in microglia, where these phox proteins are localized in this study, the present results suggest that, in AD, NADPH oxidase is activated in microglia, resulting in the formation of reactive oxygen species which can be toxic to neighboring neurons in AD.

Aged↗

Increase in phospholipase C-delta1 protein levels in aluminum-treated rat brains.

The effect of administration of aluminum to rats on the level of three phospholipase C (PLC) isozymes (beta1, gamma1, and delta1) was assessed in a variety of brain tissues. After exposure to aluminum, a statistically significant increase in malondialdehyde, an index of lipid peroxidation, was observed. In addition, there was a significant reduction in the catalytic activity of low molecular weight phosphotyrosine phosphatase, which loses its activity during oxidative stress. This suggests that oxidative stress is induced in brain tissues exposed to aluminum. The protein level of PLC-delta1, but not that of PLC-beta1 or -gamma1, was significantly increased in brains where oxidative stress had been induced. The total PLC activity in aluminum-treated rat brains was significantly higher than that in control brains. These results suggest that PLC-delta1 protein levels in brain tissues are increased by the induction of oxidative stress, giving an explanation for its up-regulation in Alzheimer's disease.

Aluminum↗

Bisphosphonate therapy for bone metastases from breast cancer: clinical results and a new therapeutic approach.

BACKGROUND: We evaluated the usefulness of bisphosphonate (BIS) monotherapy, the safety of rapid infusion of BIS and the efficacy of BIS-sequential therapy for bone metastases from breast cancer. PATIENTS AND METHODS: Twenty-nine patients with bone metastasis or invasion were treated with BIS monotherapy. Each BIS (pamidronate 30 mg, alendronate 10 mg, or incadronate 10 mg) was infused over 30 minutes every two weeks a median of 12 times. RESULTS: With BIS therapy, five patients (17%) showed partial response of the bone lesions, and eighteen patients (64%) had pain relief. Of the nine patients treated with BIS-sequential therapy, one (11%) showed a partial response of the bone metastases, three (33%) had pain relief, and one (11%) showed a decrease in the serum tumor marker level. CONCLUSION: BIS therapy is effective against bone metastases from breast cancer, and rapid infusion of BIS is both safe and convenient for patients. BIS-sequential therapy can be a unique therapeutic option in some cases.

Adult↗

[Efficacy of docetaxel for recurrent breast cancer: evaluation based on chemosensitivity test and clinical response].

We investigated the chemosensitivity of anticancer agents against primary (230 patients, 268 tumors) and recurrent breast cancer (40 patients, 51 tumors) using histoculture drug response assays (HDRA) of surgical specimens. Of the 40 recurrent breast cancer patients, 26 were pretreated with anthracycline. The efficacy of the agents was assessed according to an inhibition index of optical density detected by an ELISA reader. The inhibition rate of docetaxel against recurrent tumors was similar that against primary ones, although the rates of adriamycin, 5 fluorouracil, mitomycin and cisplatin against recurrent tumors were significantly lower than those against primary ones. The clinical response of docetaxel was also evaluated in ten patients with recurrent breast cancer. Of the ten patients with recurrent breast cancer, eight were pretreated with anthracycline, and seven showed a partial response. These results indicate that docetaxel is effective against recurrent breast cancer, even anthracycline-resistant breast cancer.

Antineoplastic Agents, Phytogenic↗

[Histoculture drug response assay on non-small cell lung cancer].

We examined the chemosensitivity of non-small cell lung cancer (NSCLC) tissues to CDDP, 5-FU, ADM, MMC, ETP and SN38 using histoculture drug response assay (HDRA). One-hundred and thirty surgical specimens from NSCLC patients who were not given preoperative chemotherapy were used. The inhibition indexes of CDDP, 5-FU, MMC, ADM, ETP and SN38 were 39.1 +/- 18.2%, 48.0 +/- 19.7%, 63.3 +/- 17.7%, 47.6 +/- 22.0%, 36.9 +/- 21.1%, and 37.9 +/- 25.2%, respectively. Inhibition indexes were above the cutoff level, i.e., 'judged sensitive,' in 40 cases (31.3%) for CDDP, 34 cases (27.4%) for 5-FU, 54 cases (44.3%) for MMC, 36 cases (33.0%) for ADM, 29 cases (29.8%) for ETP, and 34 cases (37.4%) for SN38, respectively. In almost one-third of patients, the inhibition indexes of all drugs were under cutoff levels. Correlations between in vitro chemosensitivity data and patient responses to chemotherapy were obtained from 16 evaluable patients, and a 44.4% true positive rate and a 100% true negative rate were observed. Our results with HDRA for NSCLC showed a high incidence of intrinsic multidrug resistance. HDRA may help doctors to avoid non-effective chemotherapy for NSCLC patients.

Adenocarcinoma↗

In Vitro and In Vivo Modulation of Growth Regulation in the Human Breast Cancer Cell Line MCF-7 by Estradiol Metabolites.

BACKGROUND: The natural estrogen 17 beta-estradiol (E2) functions as a potent tumor promoter during tumorigenic transformation of the mammary gland. From amongst the various pathways of E2 metabolism upregulation of C16 alpha-hydroxylation of E2 has been associated with carcinogenesis. In the present study in vitro and in vivo experiments were performed on estrogen receptor positive human breast cancer MCF-7 cells to examine whether the natural estrogen E2 and its metabolites 16 alpha-hydroxyestrone (16 alpha-OHE1) and 2-hydroxyestrone (2-OHE1)function as modulators of tumor cell growth. METHODS: An anchorage-independent growth assay was used for in vitro study bycounting the number of tri-dimensional colonies formed by MCF-7 cells suspendedin 0.33% agar. In vivo experiments examined the effect of implanting metabolitematerial pellets into female nude mice. RESULTS: In the anchorage-independent growth assay (AIG), continuous 14-day exposure to E2 and to 16 alpha-OHE1 at 200 ng/ml induced a 59.4% and a 105.9% increase (P= 0.001)respectively in the number of colonies of MCF-7 cells. Identical treatment with 2-OHE1, however, failed to increase AIG relative to that seen in the solvent treated control cultures. In the in vivo tumorigenicity assay, treatment of nude mice with 1.5 mg E2 or 16 alpha-OHE1 resulted in a 335.4% and a 384.1% increase (P< 0.0002) in tumor growth, while identical treatment with 2-OHE1 failed to exhibit any increase relative to the control group. CONCLUSION: These results suggest that the 16 alpha- and 2-hydroxylated metabolites of E2 may directly affect in vitro growth of MCF-7 cells via an autocrine mechanism and in vivo growth via paracrine mechanisms. Thus, E2-mediated growth regulation in MCF-7 cells may in part be due to distinct effects of specific E2 metabolites on the breast cancer cells.

Journal Article↗

Changes in caspase expression in Alzheimer's disease: comparison with development and aging.

Changes in caspase-2 and -3 protein levels in Alzheimer's disease (AD) brains were assessed in comparison with their expression in development and aging. The protein levels of caspase-2 and -3 were significantly increased in AD brains, caspase-2 in the particulate fraction and caspase-3 in both the cytosolic and particulate fractions, compared with controls. Immunoblot analysis of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that caspase-3 levels were high from E19 to 2 weeks, while caspase-2 remained high from 4 to 96 weeks, indicating that the expression of caspase-2 and -3 is differentially regulated during development and aging. These results suggest that caspase-2 and -3 are upregulated in AD and that the changes in AD are different from those observed in senescent brains.

Aged↗

Abundance of low molecular weight phosphotyrosine protein phosphatase in the nerve-ending fraction in the brain.

The distribution of low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in subcellular fractions of rat brain tissue was investigated by immunoblotting analysis using anti-LMW-PTP antibody. The enzyme was detected in the 105000 g precipitate in addition to the supernatant of brain homogenate, even after the precipitate was extensively washed, and was abundant in the particulate fraction of nerve endings. Nerve ending LMW-PTP was effectively solubilized by 1% Triton X-100 or 1% deoxycholate, though the enzyme was solubilized by thorough sonication. Two forms of LMW-PTP, designated as LMW-PTP-I and -II, were separated from the nerve ending-rich fraction by chromatofocusing. Nerve endings PTP-I and -II were different in molecular weight, isoelectric point and susceptibility to activators and inhibitors. The properties of nerve endings LMW-PTP-I and -II were similar to those of cytosolic LMW-PTP-I and -II. The abundance of LMW-PTP in nerve endings as well as in the cytosol suggests that this enzyme plays an important role in synaptic function.

Animals↗

[Docetaxel therapy against anthracycline resistant breast cancer].

To evaluate the efficacy of docetaxel therapy against anthracycline-resistant breast cancer, twenty patients were treated with docetaxel. Of the 20 patients pretreated with anthracycline, 17 were clinically anthracycline-resistant and the remaining three were refractory to anthracycline on histoculture drug response assay. Nine patients had loco-regional recurrence and 11 had distant +/- loco-regional recurrence. Docetaxel (49-60 mg/m2) was administered every 4 weeks, and was infused 1-13 times (median; 3 times). Of the 19 evaluable patients, eight (42%) showed partial response with the docetaxel therapy. Durations of the response ranged from 1 to 8 months (median; 4 months). Major adverse effects of the therapy were alopecia, neutropenia, and leucocytopenia. Hypersensitivity reaction was observed in one case. In addition, severe adverse effects such as grade 2 pneumonia and grade 4 diarrhea were found in one patient each. In conclusion, although the adverse effects are not negligible, docetaxel therapy is effective against anthracycline-resistant breast cancer.

Aged↗