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S Hara

Publications and source records attributed to S Hara.

At least 37 records · Page 2Linked to original sources
PubMed2002

Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer.

PURPOSE: The prognostic value of altered blood group factor and Lewis-related carbohydrate antigen expression in breast cancers has not been fully determined. METHODS: To this end, breast carcinoma samples from 87 radical mastectomy patients with primary cancer were analyzed by immunohistochemistry for the ABH factors, Le(a), sialyl Le(a), Le(x), and sialyl Le(x). RESULTS: It was found that ABH, Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens were expressed in 25 (21.8%), 26 (22.6%), 26 (22.6%), 36 (31.3%), and 37 specimens (32.2%), respectively. Tumors with lymph node metastasis expressed Le(x) or sialyl Le(x) antigens more frequently than those without lymph node metastasis ( P=0.0020 or P=0.039, respectively). The survival time of patient s after surgery was significantly shorter for those whose tumors expressed Le(x) or sialyl Le(x) than for those without Le(x)- or sialyl Le(x)-positive tumors ( P=0.0028 and P=0.0029, respectively). Cox's multiple regression analysis revealed that sialyl Le(x) expression was an independent prognostic factor for patient survival regardless of primary tumor (T factor) and lymph node (N factor) status (hazards ratio, 3.80). CONCLUSIONS: Thus, expression of sialyl Le(x) antigen in tumor cells is associated with poor prognosis in patients with breast cancer and must be considered in the design of future therapeutic trials.

ABO Blood-Group System↗
PubMed2002

Successful allogeneic blood stem cell transplantation for aplastic anemia in a patient with renal insufficiency requiring dialysis.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Adult↗
PubMed2002

Health-related quality of life after radical cystectomy for bladder cancer: a comparison of ileal conduit and orthotopic bladder replacement.

OBJECTIVE: To compare the health-related quality of life (HRQoL) after radical cystectomy in patients with an ileal conduit or an orthotopic neobladder. PATIENTS AND METHODS: The study included 85 men who underwent radical cystectomy for bladder cancer, comprising 48 with an orthotopic neobladder (26 with an ileal and 22 with a colon neobladder) and 37 with an ileal conduit. HRQoL was evaluated using the Short Form-36 survey containing 36 questions assessing eight aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The mean follow-up periods for patients with a neobladder (ileal and sigmoid) and with an ileal conduit was 45.9 (38.2 and 53.1, respectively) and 130.9 months, respectively. Scale scores were not affected by the duration of follow-up in either group. There was no significant difference in any scale scores between the neobladder and ileal conduit groups. However, general health and social functioning in both the neobladder and ileal conduit groups appeared to be significantly lower than those in the general population in the USA. Furthermore, patients with a colon neobladder had a significantly higher score for role-emotional functioning than those with an ileal neobladder, while there was no significant difference in the remaining seven scores between patients with ileal and colon neobladders. CONCLUSIONS: Six of the eight scales of HRQoL were favourable in both patients with a neobladder or an ileal conduit, and there was no significant difference between these groups. In addition, the HRQoL of patients with an orthotopic neobladder (except for role-emotional functioning) was unaffected by the segment of the intestine used for neobladder construction. Therefore, patients with both types of urinary diversion were generally satisfied with their overall health and quality of life.

Colon↗
PubMed2002

Calcium-sensing receptor gene polymorphism affects the parathyroid response to moderate hypercalcemic suppression in patients with end-stage renal disease.

AIM: The basic mechanism of secondary hyperparathyroidism is still unclear, but a change in Ca2+ sensing by parathyroid cells is possibly involved in this uremic complication. A rightward shift of the calcium set-point and an increase of the minimum secretion rate have been found in secondary hyperparathyroidism, indicating abnormal calcium sensing. METHODS: We evaluated the effect of calcium sensing receptor (CaR) gene polymorphism (codon G990R) on the response of the parathyroid gland to moderate hypercalcemic suppression in 77 ESRD patients on regular hemodialysis (HD using 2.5 mEq/l Ca2+ dialysate). All patients underwent an HD session with 3.0 mEq/l Ca2+ dialysate to suppress parathyroid hormone (PTH). Then we investigated the effect of CaR gene polymorphism on the parathyroid response to hypercalcemic stimulation. RESULTS: Patients were divided into 3 groups on the basis of genotype (GG = 33 patients (42.9%), GR = 39 patients (50.6%), RR = 5 patients (6.5%)). Baseline intact PTH levels in patients without the R allele were not significantly different from those in patients with the R allele (GG group, 181.4 +/- 31.1 pg/ml vs. GR and RR groups, 230 +/- 51.2 pg/ml: mean +/- SEM). The significant effect of moderate hypercalcemic suppression on the intact PTH level was observed in the GG group (p < 0.01) but not in the GR and RR groups, despite the identical increase in Ca2+. CONCLUSION: Our results suggest that CaR gene polymorphism (codon G990R) influences the responsiveness of the parathyroid gland to changes of extracellular Ca2+ in ESRD patients. The glands of patients with the GG genotype of the CaR gene may be more sensitive to extracellular Ca2+ changes.

Calcium↗
PubMed2002

Standard protocol for exchange of health-checkup data based on SGML: the Health-checkup Data Markup Language (HDML).

OBJECTIVES: To develop a health/medical data interchange model for efficient electronic exchange of data among health-checkup facilities. RESULTS: A Health-checkup Data Markup Language (HDML) was developed on the basis of the Standard Generalized Markup Language (SGML), and a feasibility study carried out, involving data exchange between two health checkup facilities. The structure of HDML is described. RESULTS: The transfer of numerical lab data, summary findings and health status assessment was successful. CONCLUSIONS: HDML is an improvement to laboratory data exchange. Further work has to address the exchange of qualitative and textual data.

Computer Communication Networks↗
PubMed2001

Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha.

Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS superfamily. Here we examined the expression of HIF-alpha subunit proteins in the human kidney and found that, in addition to HIF-1alpha and -2alpha, HIF-3alpha was also expressed. The sequence analysis revealed that, like mouse HIF-3alpha, human HIF-3alpha has high similarity with HIF-1alpha and -2alpha in the bHLH and PAS domains, but lacks structures for transactivation found in the C-terminus of HIF-1alpha and -2alpha. Furthermore, we performed reporter gene analysis and showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression. HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in the human kidney.

Amino Acid Sequence↗
PubMed2001

The analysis of heparin-protein interactions using evanescent wave biosensor with regioselectively desulfated heparins as the ligands.

Evanescent wave biosensor has been recently employed as a powerful tool for analyses of macromolecular interactions. In the present study, evanescent wave biosensor analysis was developed to analyze the heparin-protein interaction using as ligands a series of heparin derivatives regioselectively desulfated by chemical methods, particularly to evaluate the effect of each sulfate group of heparin. The method for immobilizing heparin on the cuvette of the evanescent wave biosensor equipment was optimized to obtain the high response required for accurate measurement. The best result was achieved when the amino group introduced at the reducing end of heparin was coupled with carboxymethyl dextran on the surface of the cuvette using glycolchitosan as a multivalent linker. The established system appeared to describe well the interactions of heparin with such proteins as acidic and basic fibroblast growth factors and tissue factor pathway inhibitor.

Biosensing Techniques↗
PubMed2001

Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo.

Sodium butyrate (NaBt), a physiologically occurring short-chain fatty acid, induces differentiation as well as apoptosis in numerous cell types, and this induction is partially regulated by Bcl-2 expression. The objectives of our study were to characterize the in vitro effects of NaBt and/or docetaxel on the growth, cell cycle and apoptosis of human bladder cancer cells, and to determine whether tumor growth in vivo is inhibited by isobutyramide, an orally bioavailable Bt analogue, and/or docetaxel by using Bcl-2-transfected human bladder cancer cell line KoTCC-1/BH and control vector only-transfected cell line KoTCC-1/C. NaBt caused a decrease in growth of both KoTCC-1/C and KoTCC-1/BH cells, however, its growth inhibitory effect was significantly greater in KoTCC-1/C cells. One mM NaBt resulted in G1 cell cycle arrest, accompanied by up-regulation of p21 (waf1/cip1) and down-regulation of cyclin D1 in KoTCC-1/C cells, whereas KoTCC-1/BH showed resistance to G1 cell cycle arrest. An amount of 5 mM NaBt induced apoptosis, accompanied by up-regulation of Bak in KoTCC-1/C cells but failed to induce apoptosis in KoTCC-1/BH cells despite substantial down-regulation of Bcl-2. Oral administration of isobutyramide significantly reduced the KoTCC-1/C tumor volume compared with the KoTCC-1/BH tumor volume in nude mice. Furthermore, docetaxel induced Bcl-2 phosphorylation in KoTCC-1/BH cells and combined treatment with isobutyramide and docetaxel synergistically inhibited the growth of KoTCC-1/BH cells both in vitro and in vivo. These findings suggest that isobutyramide therapy could be a novel therapeutic strategy for patients with bladder cancer if docetaxel is combined according to the Bcl-2 expression status.

Amides↗
PubMed2001

Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.

Although numerous chemotherapeutic agents have been evaluated for patients with advanced prostate cancer, none have demonstrated improved survival benefits. Here, in order to determine whether the efficacy of chemotherapy can be enhanced by changing the regimen, we evaluated the effect of the varied timing and dosage of chemotherapy in combination with androgen withdrawal on time to androgen-independent (AI) progression in the human androgen-dependent LNCaP tumour model. We first demonstrated the synergistic effect of mitoxantrone on induction of apoptosis in LNCaP cells maintained in the steroid hormone-depleted charcoal-stripped media (CSM) compared to those in the standard media. In addition, this synergy was most remarkable during the simultaneous treatment of LNCaP cells with mitoxantrone and CSM compared to the pre- or post-use of mitoxantrone with CSM. LNCaP tumour growth in athymic nude mice and their increase in serum PSA levels were significantly inhibited by the simultaneous injection of mitoxantrone with castration, compared to the administration of mitoxantrone 2 weeks before or after castration. The TUNEL staining revealed that apoptotic cell death was extensively induced in LNCaP tumours treated with simultaneous castration and mitoxantrone compared to tumours treated with the other schedules. Furthermore, nude mice bearing LNCaP tumours were injected with a total of 0.5 mg mitoxantrone divided into 2, 5 and 10 days, with the most significant therapeutic effect and delayed AI progression observed in mice given injection of mitoxantrone for 2 days. These findings suggest that this might be the optimal way to perform cytotoxic chemotherapy and androgen withdrawal simultaneously in patients with advanced prostate cancer and to administer chemotherapeutic agents at high dosage within short intervals.

Androgens↗
PubMed2001

Mn K-edge XMCD in Mn3MC (M=Zn and Ga) perovskite.

Mn3MC (M=Zn and Ga) perovskite has attracted interest because of a variety of magnetic phase transitions. In this work, we measure temperature and magnetic field dependence of X-ray magnetic circular dichroism (XMCD) at Mn K-edge and discuss effect of second constituent metal on the magnetic states of Mn atoms. The spectrum in Mn3ZnC is characterized by a dispersion-type profile. In Mn3GaC, intensity of the positive peak at the edge is drastically reduced. The difference originates in charge transfer from Zn or Ga to Mn atoms. Temperature and magnetic field variations of the Mn K-edge XMCD spectrum suggest that orbital magnetic moments are closely related to the magnetic phase transition.

Journal Article↗
PubMed2001

High-level expression of human acidic fibroblast growth factor and basic fibroblast growth factor in silkworm (Bombyx mori L.) using recombinant baculovirus.

A hybrid of Autographa californica nuclear polyhedrosis virus and Bombyx mori nuclear polyhedrosis virus, which is infectious to both Spodoptera frugiperda and Bombyx mori, was prepared in our previous study. Two recombinant hybrid baculoviruses, carrying cDNAs of human acidic and basic fibroblast growth factors, respectively, were successfully constructed in this study, for the large-scale production of human aFGF and bFGF using silkworm as host. These recombinant viruses were used to inoculate silkworm larvae. After the infection, the recombinant proteins were not found in the hemolymph. Such nonsecretion from cells has also been observed in the established insect cell lines, Sf21 and Tn-5. Tissue distribution analysis indicated that the expressed products were mainly located in fat body and the production of the recombinant aFGF and bFGF was maximal at around 80 h postinfection. Therefore, silkworm larvae infected with recombinant viruses were dissected and fat bodies were collected for the purification of recombinant aFGF and bFGF. The expression levels in both cases were estimated to be as high as approximately 600-700 microg per larva. Furthermore, the recombinant proteins were characterized and their biological activities were evaluated by in vitro bioassay using cell culture.

Adult↗
PubMed2001

The significance of bivariate cytokeratin and DNA flow cytometry in paraffin-embedded specimens of non-small cell lung cancer.

BACKGROUND: The presence of non-tumor cells inside cancer tissue is one of the causes of errors in cell cycle analysis by DNA flow cytometry. The recent establishment of bivariate cytokeratin and DNA flow cytometry has made feasible the accurate assessment of tumor proliferative activity. METHODS: Bivariate flow cytometry and immunohistochemistry examinations of paraffin-embedded specimens were performed in 92 patients with non-small cell lung cancer (NSCLC). Determination of the S-phase fraction by flow cytometry, with cytokeratin gating (CK-gated SPF) and without gating (ungated SPF), and the expression of proliferating cell nuclear antigen by immunohistochemistry (PCNA labeling index), were used to assess cancer cell proliferation. RESULTS: Two tumors had DNA histograms with a coefficient of variation of more than 8.0% and were excluded from the flow cytometric analysis. In DNA diploid tumors (n = 25), the ungated SPFs (8.7 +/- 3.6%) showed a lower distribution than the CK-gated SPFs (14.3 +/- 4.7%) (P < 0.0001). In DNA aneuploid tumors (n = 65), there was no difference in distribution between the ungated SPFs (15.0 +/- 8.3%) and the CK-gated SPFs (15.1 +/- 7.1%) (P = 0.94). The CK-gated SPF and the PCNA labeling index of an individual tumor had a good correlation (P < 0.0001), and this agreed with the result showing that DNA diploid and aneuploid tumors had equal proliferative activity (P = 0.64 and P = 0.63, respectively). CONCLUSION: The technique using CK-gating markedly improved the SPF measurement in DNA diploid tumors. This assessment showed no difference in proliferative activity between DNA diploid and aneuploid tumors in NSCLC. Bivariate cytokeratin and DNA flow cytometry is an accurate and objective method for cancer-specific analysis, and will surely be informative in clinical oncology.

Adult↗
PubMed2001

No parallel relationship between nitric oxide production and wet dog shakes susceptible to nitric oxide synthase inhibitors following systemic administration of paraquat in rats.

Shaking behavior, so-called wet dog shakes (WDS), in rats is characteristic behavior indicating morphine abstinence in morphine-dependence and central excitation in relation to seizures elicited by chemicals or electrical stimulation. We have found that paraquat (PQ), a nonselective herbicide, administered systemically to rats induces WDS in a dose-dependent manner. PQ-induced WDS are suppressed by nitric oxide (NO) synthase (NOS) inhibitors, but this suppression is not reversed by an NO precursor, L-arginine (L-Arg). The present study was performed to determine whether the NO system is associated with PQ-induced WDS in rats. A time-course study on the frequency of WDS for each 30-min period up to 120 min after PQ administration (70 mg/kg, s.c.) revealed that significant induction of WDS occurred during the first and second 30-min periods, that is within 60 min of PQ administration. A nonselective NOS inhibitor, Nomega-nitro-L-arginine (L-NA; 30 mg/kg, i.p.), reduced the frequency of the PQ-induced WDS during both of these periods, but the reduced frequency was not reversed by L-Arg (500 mg/kg, i.p.) in either period. Significant induction of WDS occurred when PQ (50 nmol) was administered directly into the ventral or dorsal hippocampus, but not when administered into the amygdala or the caudate putamen, indicating that the hippocampus plays an important role in PQ-induced WDS. The WDS after the administration of PQ into the dorsal hippocampus was significantly suppressed by pretreatment with L-NA (30 mg/kg, i.p.). The extracellular levels of nitrite (NO2-) and nitrate (NO3-), the oxidative products of NO, in the dorsal hippocampus determined by in vivo microdialysis, were stimulated after systemic PQ administration (70 mg/kg, s.c.) in urethane-anesthetized rats. The increases in extracellular NO2- and NO3- were inhibited by L-NA (30 mg/kg, i.p.), and this inhibition was partly reversed by L-Arg (500 mg/kg, i.p.). The increases in extracellular NO2- and NO3- in the dorsal hippocampus appeared 60 min after PQ administration, when the WDS had occurred and disappeared. These findings suggest that NO production in the hippocampus plays a minor role in PQ-induced WDS in rats and that the suppression of PQ-induced WDS by NOS inhibitors might be mediated though complex mechanisms in the brain.

Animals↗
PubMed2001

Central nervous system involvement in pyothorax-associated lymphoma: ring enhancement on CT scan.

A 71-year-old male was diagnosed as having pyothorax-associated lymphoma (PAL), a rare hematological malignancy associated with artificial pneumothorax for the treatment of pulmonary tuberculosis. Because of the low incidence, its clinical features have not been fully clarified. The PAL lesion in this patient disappeared after local radiotherapy and corticosteroid treatment. However, 8 months after the initial diagnosis, he developed a variety of neurological disorders and low-grade fever. Neither recurrence of the primary pulmonary lesion nor nodal enlargement was observed. Immediate magnetic resonance imaging of the brain revealed a ring-enhanced mass, suggesting a brain abscess. However, through a stereotactic biopsy of the brain lesion, infiltration of PAL cells was identified. The brain lesion rapidly enlarged despite intensive radiotherapy, and he finally died of lymphoma progression. This case demonstrates that PAL may progress as a type of extranodal lymphoma, and that brain lesions may produce a ring-enhanced pattern on computed tomography.

Aged↗
PubMed2001

Synergistic antitumor effect of ionomycin and cisplatin against renal cell carcinoma in vitro and in vivo.

Objectives. To characterize the synergistic antitumor effects of the calcium ionophore, ionomycin, and of cisplatin against human renal cell carcinoma cell line, ACHN, both in vitro and in vivo.Methods. The in vitro growth rate of ACHN after exposure to these compounds was measured, using the MTT assay. The apoptotic features in ACHN were evaluated by DNA ladder analysis and flow cytometric analysis. Bcl-2 and Bax expression levels in ACHN after treatment were examined by Western blot. The synergistic antitumor effects of ionomycin and cisplatin against the growth of established ACHN tumors in athymic nude mice were then tested.Results. The in vitro growth rate of ACHN was suppressed more by ionomycin and cisplatin in combination than by either alone. DNA ladder and fragmentation were more obvious when the cells were incubated with ionomycin and cisplatin together than with either reagent alone. Ionomycin treatment increased the expression level of Bax protein, whereas Bcl-2 expression was not influenced. Although an intraperitoneal injection of cisplatin or an intratumoral injection of ionomycin against subcutaneous ACHN tumors somewhat reduced tumorigenicity in nude mice, the effect was significantly enhanced by a combination of these drugs.Conclusions. The synergistic antitumor effects suggest that ionomycin-based therapy could be a novel therapeutic strategy with which to treat advanced renal cell carcinoma.

Animals↗
PubMed2001

Increased Fas ligand expression in the tumor tissue and serum of patients with testicular germ cell tumors with seminomatous elements.

OBJECTIVES: To measure the expression levels of Fas and Fas ligand (FasL) in testicular germ cell tumor (TGCT) and to determine whether the serum level of soluble FasL (sFasL) could be used as a marker for patients with TGCT. METHODS: The expression of Fas and FasL in 51 specimens obtained from patients with TGCT was examined by reverse transcriptase-polymerase chain reaction, and the results were confirmed by Western blot analysis. The serum levels of sFasL in 24 patients with TGCT were measured using an enzyme-linked immunosorbent assay system. RESULTS: Of 33 TGCT specimens that included seminomatous elements, Fas and FasL was expressed in 24 (73%) and 24 (73%), respectively. On the other hand, 10 (56%) and 2 (11%) specimens expressed Fas and FasL, respectively, in 18 TGCT specimens without seminomatous elements. Moreover, the serum levels of sFasL were significantly higher in patients with TGCT with a seminomatous element than in those without it. CONCLUSIONS: These results indicate that FasL is strongly expressed in tumor tissue and is present at high levels in the serum of patients with TGCT with a seminomatous element compared with those without it and that the serum levels of sFasL could be used as a novel diagnostic marker for TGCT with seminomatous elements.

Biomarkers, Tumor↗