Biomedical subjects

Hiroko Fujii

Publications and source records attributed to Hiroko Fujii.

7 recordsLinked to original sources

PubMed2006

C-reactive protein alters antioxidant defenses and promotes apoptosis in endothelial progenitor cells.

OBJECTIVE: C-reactive protein (CRP) has been suggested to participate in the development of atherosclerosis, in part, by promoting endothelial dysfunction and impairing endothelial progenitor cell (EPC) survival and differentiation. In the present study, we evaluated the effects of CRP on antioxidative enzymes, reactive oxygen species production, telomerase activity, and apoptosis in human circulating EPCs. METHODS AND RESULTS: EPCs, isolated from peripheral venous blood, were cultured in the absence or presence of native pentameric azide and lipopolysaccharide (LPS)-free CRP (0, 5, 15, and 20 microg/mL), N-acetylcysteine (NAC), hydrogen peroxide (H2O2) or monoclonal anti-CRP antibodies. Fluorescence-activated cell sorter (FACS) analysis was used for the measurement of intracellular H2O2 and superoxide (O2(-)) by loading cells with 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). Apoptosis was evaluated with Annexin V immunostaining and cytosolic cytochrome c expression. Western blot analysis was used for the determination of manganese superoxide dismutase (MnSOD) and glutathione peroxidase expression, and polymerase chain reaction enzyme-linked immunosorbent assay was used to assess telomerase activity. Incubation of EPCs with CRP caused a concentration dependent increase in reactive oxygen species (ROS) production and apoptosis, with an effect quantitatively similar to H2O2. This effect was attenuated during coincubation with NAC or anti-CRP antibodies. Furthermore, CRP altered EPC antioxidative enzyme levels, demonstrating a reduced expression of glutathione peroxidase and a significant increase in MnSOD expression. Transfection of EPCs with MnSOD-RNAi resulted in a reduction in CRP-induced ROS production, apoptosis, and telomerase inactivation. CONCLUSIONS: CRP, at concentrations known to predict cardiovascular events, may serve to impair EPC antioxidant defenses, and promote EPC sensitivity toward oxidant-mediated apoptosis and telomerase inactivation. These data further support a direct role of CRP in the development and/or progression of atherothrombosis.

Acetylcysteine↗

PubMed2006

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma].

AIM: We examined the efficacy and adverse effects of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) or THP-COP (pirarubicin, cyclophosphamide, vincristin, prednisone) in previously untreated old-old and extremely old patients with diffuse large B cell lymphoma (DLBCL). METHODS: Subjects were 13 initial DLBCL patients consisting of 7 men and 8 women with a median age of 79 years (range 75-91 years). These patients received CHOP or THP-COP plus 375mg/m2 rituximab intravenously given on the day before each cycle. The dose was adjusted depending on the patient's age and associated complications. Administration was performed for 6 to 8 cycles, whenever possible. RESULTS: Seven patients (54%) achieved a complete response (CR), 4 (31%) achieved a partial response (PR), 2 (15%) failed to respond. The 2-year survival rates were 62%. The CR rate and survival rate were higher than in patients previously treated with CHOP alone in our hospital, but there was no statistically significant difference. The most frequent adverse effect was bone marrow suppression, observed in 9 patients (69.2%). Adverse effects that seemed to be infusion reaction occurred in 4 patients (30.7%). These adverse effects related to infusion reaction disappeared by reducing or stopping rituximab. Four (30.7%) patients died and 3 of those died due to disease progression. One of those died 1.5 month after he began chemotherapy and the cause of death was unknown. CONCLUSION: This result suggested that both CHOP and THP-COP combined with rituximab were safe and effective for old-old and extremely old patients.

Aged↗

PubMed2006

[A case of myxoid liposarcoma in the right inguinal region: a case report].

We report a case of myxoid liposarcoma developed in the right inguinal region. A 45-year-old man visited our hospital with a chief complaint of painless right inguinal mass. He was diagnosed with right direct inguinal hernia for the first time and received a hernia repair. However, the size of the inguinal mass increased gradually after the operation. Then, the tumor was re-evaluated by imaging study such as ultrasonography, computed tomography and magnetic resonance imaging. A fatty mass 4.0 cm in diameter was demonstrated and the tumor was diagnosed as a liposarcoma preoperatively. In addition to the right high orchiectomy, surrounding fatty tissue was also removed at the time of the operation. Histological examination revealed a myxoid liposarcoma and the existence of several daughter regions outside the pseudo-capsule. Right spermatic cord and testis were intact. Postoperatively, he received 54 Gy dose of radiation therapy to right inguinal region for the prevention of the local recurrence of the disease.

Abdominal Neoplasms↗

PubMed2004

A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model.

OBJECTIVES: We investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation. BACKGROUND: The myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography. METHODS: Fourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD. RESULTS: In the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01). CONCLUSIONS: Myocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Animals↗

PubMed2003

Antiproliferative constituents from Umbelliferae plants VI. New ursane-type saikosaponin analogs from the fruits of Bupleurum rotundifolium.

The MeOH extract of the fruits of Bupleurum rotundifolium showed inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth (GI(50): 6.25 microg/ml). From this extract, 10 new ursane-type triterpene glycosides viz. three 3-O-triosides (called rotundifoliosides A, I, and J) of 13beta,28-epoxy-3beta,16alpha-dihydroxyurs-11-ene, two (G and H) of 13beta,28-epoxy-3beta,16alpha,23-trihydroxyurs-11-ene, two (E and F) of 13beta,28-epoxy-3beta,16alpha,21beta-trihydroxyurs-11-ene, two (B and C) of 3beta,11alpha,16alpha,28-tetrahydroxyurs-12-ene, and one (D) of 3beta,11alpha,28-trihydroxy-15alpha,16alpha-epoxyurs-12-ene were isolated in addition to 16 new oleanane-type triterpene glycosides (rotundiosides J-Y), echinocystic acid 3-O-sulfate and 3 known oleanane-type triterpene glycosides (rotundiosides A, F and G). The isolation, structures and antiproliferative activity of the new ursane-type triterpene glycosides against MK-1, human uterus carcinoma (HeLa), and murine melanoma (B16F10) cell lines are described with some comments on the structural requirements for their activity.

Animals↗

PubMed2002

[Relationship between aging and vitamin E].

We investigated the pathophysiological significance in biomembranes of the redox dynamics of Vitamin E (alpha-tocopherol) which is lipophilic radical scavenger related to aging or pathologic status such as non-insulin-dependent diabetes mellitus or primary hyperlipidemia. Vitamin E eliminates lipid peroxyl radicals by the peroxidation chain reaction of the membrane lipid, and it becomes Vitamin E radical. Furthermore, the Vitamin E radical becomes Vitamin E quinone which is an oxidic metabolite of Vitamin E. Therefore, it was needed to determine the alpha-tocopherol and alpha-tocopherolquinone simultaneously to evaluate the antioxidative status of alpha-tocopherol in biomembranes exactly. For this purpose, we developed the assay method for the simultaneous determination of the two substances using HPLC system. Then we applied this method to basic and clinical research. 1) For the simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone, highly-sensitive measurement system by HPLC-multiple coulometric ECD was developed. This system is useful to estimate the redox dynamics of alpha-tocopherol in biomembranes. 2) The utilization rate of alpha-tocopherol in the erythrocyte membrane of 10- to 120-week-old rats was significantly increased, whereas alpha-tocopherol uptake in the erythrocyte membrane decreased age-dependently. Furthermore, a significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of the erythrocyte membrane were seen with age. 3) There was a strongly significant positive correlation between age and the utilization rate of alpha-tocopherol in the erythrocyte membrane of healthy volunteers aged between 23 and 103. 4) The alpha-tocopherol uptake in erythrocyte membrane was significantly lower in elderly non-insulin-dependent diabetes mellitus patients (average 68.1 years old) than in healthy subjects (average 71.8 years old). 5) The utilization rate of alpha-tocopherol in erythrocyte membrane and the alpha-tocopherol uptake in erythrocyte membrane were significant lower in elderly patients with primary hyperlipidemia (average 74.1 years old) compared to healthy subjects (average 71.2 years old). These findings suggest that the redox dynamics of alpha-tocopherol in biomembranes should be investigated with special regard to the onset, aggravation and complications of several diseases or aging as a result of oxidative stress. In addition redox dynamics were suggested to be useful to evaluate the grade of aging.

Aged↗

PubMedDate not supplied

Mitochondrial control of cell death induction by sodium 5,6-benzylidene-L-ascorbate.

Previous studies have demonstrated the dramatic antitumor activity of sodium 5,6-benzylidene-L-ascorbate (SBA). However, the molecular mechanism of this antitumor action is unclear. We investigated the changes in the fine structures of a human submandibular gland carcinoma cell line, HSG, during the cell death induced by SBA. When HSG cells were incubated for 6 hours with non-cytotoxic concentrations of SBA, changes in the mitochondria, such as the disassembly of cristae and decrease in the electron density, were discrenible. At cytotoxic concentrations, the swelling and vacuolization of the mitochondria became apparent, while the nuclear architecture including the profile and ratio of heterochromatin and euchromatin and thickness of the nuclear membrane were intact. These data suggest that the mitochondria, not the nucleus, may be the target organelle of SBA, and support the ability of SBA to induce non-apoptotic cell death in HSG cells.

Antineoplastic Agents↗