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Biomedical subjects

Y Kano

Publications and source records attributed to Y Kano.

At least 91 records · Page 5Linked to original sources

Successful treatment of Schamberg's disease with pentoxifylline.

Three patients with Schamberg's disease were treated with pentoxifylline, 300 mg daily for 8 weeks. A significant response was observed within 2 to 3 weeks. One patient had recurrence after discontinuation of this treatment; but promptly responded to resumption of therapy. No adverse effects were noted in any patients. We investigated the expression pattern of adhesion molecules in relation to perivascular accumulation of lymphocytes in specimens obtained before and after treatment with pentoxifylline in these patients. Our results suggest that pentoxifylline exerts its therapeutic effects on Schamberg's disease at the level of T-cell adherence to endothelial cells and keratinocytes.

Adult↗

Adaptation of myoglobin in compensatory hypertrophied rat muscle.

This study investigated the time course change of myoglobin concentration ([Mb]) in skeletal muscle during muscle hypertrophy in rats. Seven groups of Wistar rats (n = 7 per group) were examined. Compensatory hypertrophy of the plantaris muscle was induced by the bilateral ablation of the medial and lateral heads of the gastrocnemius muscle, and the effect of compensatory hypertrophy on the [Mb] of the plantaris muscle was examined at 7, 21 and 42 days post-ablation. The [Mb] expressed as mg g(-1) wet muscle weight tended to decline at 7 days post-ablation (-12.1%) and returned to the control level by 42 days post-ablation, as did the muscle protein concentration. However, the [Mb] expressed as mg g(-1) protein weight was not significantly different between the ablation and control groups throughout the experimental period. The estimated value of absolute Mb content in the whole plantaris muscle was significantly increased by 28.4% (P < 0.01) at 42 days post-ablation compared with the age-matched controls. Therefore, the longer period of compensatory activity allowed the Mb to increase in its absolute content, although the [Mb] did not exceed the level of control muscle. The capacity of facilitated oxygen diffusion and oxygen storage by Mb in the muscle cells will not change even when muscle enlargement takes place.

Animals↗

Differences in clinical characteristics between Tourette syndrome patients with and without 'generalized tics' or coprolalia.

The purpose of this study is to examine whether there are differences in clinical characteristics between Tourette syndrome (TS) patients with and without 'generalized tics' (GT) which involve the entire body, and/or coprolalia. Subjects were 64 patients (55 males and 9 females, mean age, 17.4 +/- 7.2 years) who visited Tokyo University's outpatient clinic of neuropsychiatry from 1974 to 1993 and who met criteria for Tourette's disorder of DSM-III-R. Data on clinical characteristics, including tic symptoms and courses of their development, complications and developmental histories, treatment and severity, were collected by systematic chart review of all subjects. Tourette syndrome patients with 'generalized tics' tended to show multiple complex vocal tics more frequently than TS patients without GT. Tourette syndrome patients with coprolalia tended to show significantly higher rates of copropraxia, echolalia, and 'cleaning/washing' compulsion than did the TS patients without coprolalia. Tourette syndrome patients with both GT and coprolalia were classified as the severest group in terms of tic symptoms and social impairment. Tourette syndrome patients who had neither of these morbidities were classified into the mildest group in all aspects. Generalized tics and coprolalia seemed to indicate the severest end of the TS spectrum and seemed to be related with a need of intensive treatment.

Adolescent↗

Pharmacological properties of traditional medicines. XXIII. Searching for active compounds in the blood and bile of rats after oral administrations of extracts of sansohnin [symbol: see text].

We made a trial of searching for the bioactive substances from Sansohnin [symbol: see text]. The blood and bile of rats after the oral administration of extracts of Sansohnin were analyzed by three-dimensional high-performance liquid chromatography (3D-HPLC). In blood, spinosin and feruloyl spinosin were found after the oral administration of a butanol extract of Sansohnin. In bile, spinosin and feruloyl spinosin were also identified after the oral administration of a water extract of Sansohnin. Spinosin and feruloyl spinosin induced the prolongation of hexobarbital sleeping time in mice at doses of 50 and 100 mg/kg, respectively. We concluded that spinosin and feruloyl spinosin were the bioactive constituents of Sansohnin. It was assumed that spinosin and feruloyl spinosin circulated through the intestine and liver, therefore, these results will provide support for the sedative and hypnotic use of this crude drug in Oriental medicine.

Administration, Oral↗

Construction of Escherichia coli-Bifidobacterium longum shuttle vector transforming B. longum 105-A and 108-A.

A shuttle vector, pBLES100, was constructed by cloning a Bifidobacterium longum plasmid and a gene encoding spectinomycin adenyltransferase AAD(9) from Enterococcus faecalis into the Escherichia coli vector pBR322. Stable transformants with this plasmid were obtained with an efficiency of 2.2 x 10(4) transformants/microgram DNA or 6.9 x 10(-5) transformants/cell/microgram DNA under the optimal conditions of 10.0 kV/cm, 200 omega, and 25 microF, using B. longum 105-A harvested at late log phase of growth.

Bifidobacterium↗

The localized melting of mini-F origin by the combined action of the mini-F initiator protein (RepE) and HU and DnaA of Escherichia coli.

Replication of mini-F plasmids requires the initiator protein RepE, which binds specifically to four iterons within the origin (ori2), as well as some host factors that are involved in chromosomal DNA replication. To understand the role of host factors and RepE in the early steps of mini-F DNA replication, we examined the effects of RepE and the Escherichia coli proteins DnaA and HU on the localized melting of ori2 DNA in a purified in vitro system. We found that the binding of RepE to an iteron causes a 50 degrees bend at or around the site of binding. RepE and HU exhibited synergistic effects on the localized melting within the ori2 region, as detected by sensitivity to the single-strand specific P1 endonuclease. This opening of duplex DNA occurred around the 13mer of ori2, whose sequence closely resembles the set of 13mers found in the chromosomal origin oriC. Further addition of DnaA to the reaction mixture increased the efficiency of melting and appeared to extend melting to the adjacent AT-rich region. Moreover, DNA melting with appreciably higher efficiencies was observed with mutant forms of RepE that were previously shown to be hyperactive both in DNA binding in vitro and in initiator activity in vivo. We propose that the binding of RepE to four iterons of ori2 causes bending at the sites of RepE binding and, with the assistance of HU, induces a localized melting in the 13mer region. The addition of DnaA extends melting to the AT-rich region, which could then serve as the entry site for the DnaB-DnaA complex, much as has been documented for oriC dependent replication.

Bacterial Proteins↗

Preferential replication-dependent mutagenesis in the lagging DNA strand in Escherichia coli.

The mutation frequencies attributable to -1 frameshift or one-base substitution in the structural genes coding for resistance to chloramphenicol (Cm) and tetracycline (Tc) were followed over several cycles of DNA replication, and found to differ several-fold, depending on the orientation of the gene on the plasmid with respect to the direction of (unidirectional ColE1-type) replication. The mutation frequency was higher when the reporter gene was present in the plasmid in the same orientation as the direction of the origin, i.e., when the transcription template is the lagging daughter strand, than when the gene was inserted in the opposite orientation. This significant difference in reversion frequencies of genes with different polarities was demonstrated only for a brief period of cell growth (several cycles of replication) after induction of the dnaQ49 mutator, but was not observed when an increased number of replication cycles, was permitted, most probably due to fixation of the mutation into both strands. The mutated intermediate DNA which possesses a misaligned basepair in the Cm gene was demonstrated to be replicated into two progeny DNA molecules; one is the chloramphenicol-resistant (CmR) DNA synthesized from the template strand having the mutation and the other is the CmS DNA from the template strand without mutation. Our results suggest that replication-dependent mutagenesis may occur preferentially in the lagging strand.

Bacteriocin Plasmids↗

Effects of 13-hydroxy SM5887 in combination with other anticancer agents on human tumor cell lines.

A new anthracycline derivative, SM5887, in combination with commonly used anticancer agents was evaluated against T-cell leukemia MOLT-3 and human osteosarcoma MG-63 cell lines in culture. MOLT-3 and MG-63 cells were incubated with various concentrations of 13-hydroxy SM5887 (SM5887-OH, the active metabolite of SM5887) and other drugs for 3 and 4 days, respectively. Cell growth inhibition was determined by MTT assay. The antitumor effects of the drug combinations at 80% inhibitory concentration (IC80) were analyzed by the isobologram of Steel and Peckham. In MOLT-3 cells, SM5887-OH had additive effects with bleomycin, etoposide, doxorubicin, cisplatin, mitomycin-C, 4-hydroperoxy ifosfamide, 5-fluorouracil, cytarabine, and vincristine, whereas it had mainly protective (marked antagonistic) effects with methotrexate. In MG-63 cells, SM5887-OH had additive effects with bleomycin, etoposide, doxorubicin, cisplatin, mitomycin-C, 4-hydroperoxy ifosfamide; mainly subadditive (mild antagonistic) effects with 5-fluorouracil and cytarabine; and mainly protective (marked antagonistic) effects with vincristine and methotrexate. These findings suggest that SM5887 is suitable for simultaneous administration with bleomycin, etoposide, doxorubicin, cisplatin, mitomycin-C, or ifosfamide and not suitable for simultaneous administration with methotrexate. The effects of SM5887 in combination with 5-fluorouracil, cytarabine or vincristine may be variable, depending on cell lines. To find optimal combinations, further in vitro and in vivo studies of antitumor activity and toxicity appear to be warranted.

Animals↗

Augmentation of antitumor effect by combined administration with interleukin-2 and sizofiran, a single glucan, on murine EL-4 lymphoma.

The antitumor effect of the combined administration with recombinant human interleukin-2 (rIL-2) and sizofiran (SPG), a single glucan of Shizophyllum commune Fries, was studied in vivo in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The effect was evaluated by a) comparing the survival time of the mice, b) analysis of the intraperitoneal cell population in Giemsa-stained specimens, c) surface marker analysis of peritoneal exudative cells with flow cytometry, d) cytotoxic assay of cells against EL-4 and Yac-1 lymphoma, and e) elimination of some cell populations by monoclonal antibodies, to identify the antitumor-effector cells showing cytotoxic activity. The survival of mice given both rIL-2 and SPG was significantly longer than the control mice or those given SPG alone or rIL-2 alone. It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune-response cells in the peritoneal cavity such as T lymphocytes, NK cells, or macrophages, which might be effective in reducing lymphoma cells. The combination of rIL-2 and SPG administration appears to activate the antitumor-immune response at the tumor site more effectively than when either agent was administered alone.

Animals↗

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer.

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin 2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.

Adjuvants, Immunologic↗

Inhibitory effect of metastasis by combined administration with interleukin-2 and sizofiran, a single glucan--immunohistochemical study.

Innovations in methods of combined administration with other BRM or chemotherapeutic drugs have been discussed. We have reported that combined administration with recombinant interleukin-2 (rIL-2) and sizofiran (SPG) is effective in prolonging survival time of C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The immunomechanisms of the combined administration were clarified investigating the intraperitoneal cell population in the primary tumor site, especially the tumor infiltrating lymphocyte (TIL) quantitatively. In the present study, to clarify the antitumor effects of combined administration with rIL-2 and SPG on the metastatic sites, the immunomechanisms of the suppressive effects of combined administration on the metastasis were studied in EL-4 lymphoma cells intraperitoneally transplanted to mice. Inasmuch as EL-4 lymphoma shows rapid hepatosplenic metastasis, we studied the metastatic foci in the liver and the spleen semiquantitatively in investigating the histopathological and immunohistochemical findings of the metastatic foci, especially the TIL. The metastatic foci were stained by hematoxylin-eosin (HE) and monoclonal antibodies (L3T4, Lyt2, asialo GM1, Mac-1, and Ia). The combined administration resulted in: 1) fewer infiltrating tumor cells, 2) more lymphocytic infiltration, and 3) more antitumor effector cells (cytotoxic T cells: Lyt2 and natural killer cells: asialo GM1), macrophages (Mac-1), helper T cells (L3T4), and cells with MHC-class-II antigen (Ia) than did administration of rIL-2 alone or SPG alone, or no administration of these two at all. Combined administration with rIL-2 and SPG appears to activate antitumor-immune response at the metastatic site more effectively than when either agent is administered alone.

Animals↗

In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines.

The schedule-dependent interaction of paclitaxel and cisplatin was studied in four human carcinoma cell lines: non-small cell lung cancer, A549; breast cancer, MCF7; ovarian cancer, PA1; and colon cancer, WiDr cells. The cells were exposed simultaneously to the drugs for 24 h and sequentially to paclitaxel first for 24 h followed by cisplatin for 24 h, or vice versa, and then incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was then determined by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the IC80 level were analyzed by the isobologram method. On simultaneous exposure to paclitaxel and cisplatin, additive and subadditive (slight antagonistic) effects were observed in A549, MCF7, and PA1 cells, while sub-additive and protective (antagonistic) effects were observed in WiDr cells. On sequential exposure to paclitaxel first, followed by cisplatin, additive effects were observed in all cell lines. On sequential exposure to cisplatin first, followed by paclitaxel, additive effects were observed in PA1 cells, while additive, sub-additive, and protective effects were observed in A549, MCF7, and WiDr cells. These findings suggest that the interaction of paclitaxel and cisplatin is schedule- and cell line-dependent. The optimal schedule of this combination may be paclitaxel first followed by cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗

Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.

Adolescent↗

Schedule-dependent interaction between paclitaxel and 5-fluorouracil in human carcinoma cell lines in vitro.

We assessed the cytotoxic interaction between paclitaxel and 5-fluorouracil administered at various schedules against four human carcinoma cell lines, A549, MCF7, PA1 and WiDr. The cells were exposed simultaneously to paclitaxel and to 5-fluorouracil for 24 h or sequentially to one drug for 24 h followed by the other for 24 h, after which they were incubated in drug-free medium for 4 and 3 days respectively. In another experiment, the cells were exposed simultaneously to both agents for 5 days. Cell growth inhibition was determined by MTT reduction assay. The effects of drug combinations at IC80 were analysed by the isobologram. The cytotoxic interaction of paclitaxel and 5-fluorouracil was definitely schedule dependent. Simultaneous exposure to paclitaxel and 5-fluorouracil for 24 h showed mainly subadditive effects in A549, MCF7 and WiDr cell lines, whereas it showed additive effects in PA1 cells. Sequential exposure to paclitaxel followed by 5-fluorouracil showed additive effects in all cell lines. Sequential exposure to 5-fluorouracil followed by paclitaxel showed subadditive effects in A549, MCF7 and PA1 cells. Whereas it showed additive effects in WiDr cells. These findings suggest that maximum cytotoxic effects can be obtained when paclitaxel precedes 5-fluorouracil. Interestingly, the continuous (5-day) exposure to paclitaxel and 5-fluorouracil had additive effects in A549, PA1 and WiDr cells, indicating that the prolonged simultaneous administration of these agents may circumvent the antagonistic interaction produced by short-term simultaneous administration. These findings may be useful in clinical trials of combination chemotherapy with paclitaxel and 5-fluorouracil.

Antimetabolites, Antineoplastic↗

Time-course analyses of exercise-induced lesions in a patient with urticarial vasculitis.

Using immunoperoxidase techniques, we examined the histological changes of exercise-induced lesions of urticarial vasculitis over a 24 h period. At 3 h, endothelial swelling and an eosinophilic infiltrate was seen. Neutrophils were increased in number by 10 h. Typical leucocytoclastic vasculitis with red blood cell extravasation developed by 24 h. Maximal deposition of eosinophil peroxidase was at 10 h compared to significant neutrophil elastase deposits at 24 h. This demonstrates the importance of the eosinophil in the development of the lesions of urticarial vasculitis.

Exercise↗