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Biomedical subjects

H Fujii

Publications and source records attributed to H Fujii.

At least 343 records · Page 19Linked to original sources
PubMed1998

Significance of chromosomal alterations and mutations of the N-RAS and TP53 genes in relation to leukemogenesis of acute myeloid leukemia.

We examined chromosomes and mutations of the N-RAS and TP53 genes in 73 patients with acute myeloid leukemia (AML). Twenty-six patients showed a reciprocal chromosomal translocation or an inversion, and 34 patients showed only unbalanced aberrations. Balanced aberrations were predominantly detected in the AML patients who did not have myelodysplasia, preceding myelodysplastic syndrome, and a history of chemotherapy or radiation therapy. In contrast, unbalanced aberrations were more frequently seen in the patients with AML with trilineage myelodysplasia, AML transformed from MDS, and therapy-related AML. Twenty-two mutations of the N-RAS and TP53 genes were detected, and these mutations were frequently associated with unbalanced chromosomal aberrations. Furthermore, the spectrum of mutations was suggestive of an exposure to alkylating chemicals.

Acute Disease↗
PubMed1998

Ovarian dysgerminoma showing high serum levels and positive immunostaining of placental alkaline phosphatase and neuron-specific enolase associated with elevation of serum prolactin level.

We report a 35-year-old Japanese female patient with ovarian dysgerminoma showing elevated serum levels of placental alkaline phosphatase (PLAP), neuron-specific enolase (NSE) and prolactin (PRL). All elevated tumor markers improved dramatically after the removal of the tumor. Immunohistochemically examined, the tumor was stained positive for PLAP and NSE and negative for PRL. Our present case is the first report of dysgerminoma showing positive immunostaining for PLAP and NSE, and the association of high serum level of PRL followed by decrease accompanied by the tumor debulking.

Adult↗
PubMed1998

High transepidermal water loss induces fatty acid synthesis and cutaneous fatty acid-binding protein expression in rat skin.

Stratum corneum lipids (SCLs) are responsible for the water barrier function (WBF) of the skin in mammals. Recent studies have indicated that epidermal lipid synthesis might be regulated by WBF of stratum corneum and that cutaneous fatty acid-binding protein (C-FABP) plays an important role in fatty acid metabolism in epidermis. To clarify the regulatory mechanism of lipid synthesis, we assessed the effects of barrier disruption induced by either acetone treatment or linoleic acid deficiency on epidermal lipid synthesis in rat. Transepidermal water loss (TEWL) was measured with an evaporimeter before and after treatment. The time course of re-establishing SCLs was examined biochemically and histochemically and the expression of C-FABP in the epidermis was immunohistochemically examined. When the rat skin was covered with a vapor-impermeable membrane after the acetone treatment removing SCLs and inducing WBF disruption, the usual recovery of SCLs was blocked and TEWL was kept high by 24 h. In the uncovered area, rapid redeposition of SCLs within 24 h was found and associated with normal compositions of epidermal lipids including sphingolipids, free fatty acids and sterol and, immunohistochemically, C-FABP was very weakly expressed in epidermis at 0.5 and 2 h, and then strongly in the whole layers at 4 h, and returned to a normal pattern by 8 h. The epidermis of the covered rat skin was kept weak in C-FABP expression by 24 h. In the linoleic acid-deficient rats, TEWL did not increase and the expression pattern of C-FABP showed no notable change until 28 weeks after initiation of the diets, indicating that C-FABP expression may not be affected by altered essential fatty acid metabolism. These results suggest that increase of TEWL itself stimulates C-FABP expression, leading to activation of fatty acid metabolism.

Acetone↗
PubMed1998

Toxicity and efficacy of ifosfamide, carboplatin and etoposide (modified ICE) as a salvage chemotherapy in Japanese patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

The combination of ifosfamide, carboplatin and etoposide (modified ICE), was evaluated for its toxicity and activity in relapsed or refractory aggressive non-Hodgkin's lymphoma. Twenty patients, 14-69 years of age, with relapsed (19 cases) or refractory (one case) aggressive non-Hodgkin's lymphoma were treated with modified ICE therapy, consisting of ifosfamide 6 g/m2 (1.2 g/m2 day 1-5), carboplatin 400 mg/m2 (day 1) and etoposide 500 mg/m2 (100 mg/m2 day 1-5). The regimen was repeated at approximately 28-day intervals. All patients had undergone a doxorubicin-containing regimen before modified ICE therapy. Median total dose of previously received doxorubicin was 406 mg/m2 (range: 200-825 mg/m2). The median interval from diagnosis to modified ICE therapy was 9.4 months (range: 3.6-121 months). Two patients achieved CR and five achieved PR out of 16 patients with measurable lesions (response rate 43.8%; 95% confidence interval 19.0-68.6%). Median overall survival was 227 days (range: 41-552 days) from the start of modified ICE therapy. Myelosuppression was the most serious toxicity, namely 16 patients (80%) and 11 patients (55%) showed grade 4 neutropenia and grade 4 thrombocytopenia after the first course, respectively. Modified ICE therapy might be an active regimen with acceptable toxicity as a salvage chemotherapy in aggressive non-Hodgkin's lymphoma.

Adolescent↗
PubMed1998

A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix.

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthesized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, Rrev-COCH2CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (Rrev-COCH2CH2-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis.

Animals↗
PubMed1998

Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.

We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.

Animals↗
PubMed1998

Vaccination with B7-1+ tumor and anti-adhesion therapy with RGD pseudo-peptide (FC-336) efficiently induce anti-metastatic effect.

We have previously shown that expression of costimulatory ligand B7-1 on MHC class I+ tumor cells (B16-BL6 melanoma) resulted in marked reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice and led to induction of immunity to the challenge by the parental B7-1 negative tumor. Here we investigated the effectiveness of irradiated B7-1 transfected tumor cells as a vaccine on established tumor metastasis and whether or not expression of B7-1 molecule on tumor cells in combination with administration of anti-adhesion peptide FC-336 can augment the antimetastatic efficacy. Immunization with X-irradiated B7-1 transfectants after i.v. injection of B7-1- parental B16-BL6 cells was effective in inhibiting lung metastasis. We also found that vaccination with irradiated B7-1 transfectants after excision of primary tumor on day 21 resulted in significant inhibition of spontaneous lung metastasis by intrafootpad injection of viable parental B16-BL6 melanoma, as compared with the untreated control. However, immunizing twice with mock transfectants did not affect inhibition of spontaneous lung metastasis of wild-type tumors. On the other hand, multiple administration of a pseudo-peptide of RGD sequence (FC-336) after tumor inoculation inhibited spontaneous lung metastasis through the interference of tumor invasion, migration and adhesion. Combined treatment of B7-1 transfected tumor vaccine and anti-adhesive therapy with FC-336 led to the augmentation of the antimetastatic effect in both experimental and spontaneous metastasis models, as compared with either treatment alone. B7-1- and FC-336-mediated inhibition of tumor metastasis may be mediated by different mechanisms at various steps of metastasis, based on the regulation (promotion or inhibition) of tumor interaction with host cells and components.

Animals↗
PubMed1998

A phase I trial of docetaxel and 5-day continuous infusion of 5-fluorouracil in patients with advanced or recurrent breast cancer.

To determine the maximum-tolerated doses (MTDs), the dose-limiting toxicities (DLTs) and the recommended doses for further trials of docetaxel in combination with a 5-day continuous infusion of 5-fluorouracil (5-FU) in advanced or recurrent breast cancer patients who had been treated previously with at least one chemotherapeutic regimen, patients were treated with docetaxel as a 1-h infusion on day 1 followed by 5-FU as a continuous infusion on days 1 through 5 every 3-4 weeks. Three or six patients were assessed at the following escalating dose levels of docetaxel/5-FU per day: 40/150, 40/300, 50/300, 50/500 and 60/500 mg m(-2). Nineteen patients entered this trial, of whom 18 could be assessed for adverse event and therapeutic efficacy. The DLTs were neutropenia and diarrhoea. The MTDs were 60 mg m(-2) of docetaxel on day 1 and 500 mg m(-2) per day of 5-day continuous infusion of 5-FU. One of 18 patients achieved a complete response and eight achieved partial response (over all response rate: 50%). The recommended doses of docetaxel and 5-day continuous infusion of 5-FU for a phase II trial are 50 mg m(-2) and 500 mg m(-2) per day every 3 or 4 weeks.

Adult↗
PubMed1998

Propagation of various tooth impacts in the human body.

The purpose of this study was to investigate how far tooth impacts were propagated in the body and whether the propagation would be influenced by posture. The impacts were propagated to all recording sites on the head and neck of the 10 examinees tested. In the recordings on the limbs, even at the most distal site, the number of examinees detecting the vibration was seven out of nine examinees. These results showed that the impacts exerted on the tooth were propagated to distal sites of limbs through the bones and soft tissues and implied that the propagated vibration would influence the whole of the body. On the other hand, as the amplitude of propagated vibration was influenced by posture and recording site, the posture during jaw functioning appears to be important.

Acromion↗
PubMed1998

Autotransfusion supported by erythropoietin therapy in transurethral resection of the prostate.

We investigated the collection and transfusion of autologous blood after treatment with EPO in 68 BPH patients (including 10 controls) who were scheduled to undergo TUR-P. All patients received oral and/or intravenous iron supplements. Assessments were made based on the preoperative increase in blood hemoglobin levels including autologous blood predonation (deltaHb). The deltaHb in patients undergoing collection of 600 ml of blood were as follows: control group: -0.36 +/- 0.57 g/dl; EPO group, 9 x 3000 units intravenously: 1.15 +/- 0.83 g/dl; EPO group, 6 x 6000 units intravenously: 0.79 +/- 0.80 g/dl; EPO group, 3 x 12,000 units subcutaneously: 1.47 +/- 0.62 g/dl. In patients undergoing collection of 800 ml of blood, the results were as follows: EPO group, 3 x 12,000 units subcutaneously: 1.80 +/- 0.69 g/dl; EPO group, 3 x 24,000 units subcutaneously: 2.03 +/- 0.77 g/dl. All EPO-treated patients successfully underwent surgery using their own blood, and none of them required homologous transfusion. The increase of Hb was greater in the patients treated with EPO than in controls, allowing safe preoperative blood collection even in elderly patients. In patients with relatively severe BPH, homologous transfusion could be avoided and surgery was performed safely.

Aged↗
PubMed1998

Branched-chain alpha-keto acid dehydrogenase kinase content in rat skeletal muscle is decreased by endurance training.

The activity state of branched-chain alpha-keto acid dehydrogenase complex in skeletal muscle was elevated by running exercise in trained and untrained rats, but level of this elevation was significantly greater in the former than in the latter. To elucidate the mechanism of the training effect on the exercise-induced activation of the complex, a protein amount of branched-chain alpha-keto acid dehydrogenase kinase, which is responsible for inactivation of the complex by phosphorylation, in the muscle was measured by the Western blot analysis. Endurance training decreased the content of the kinase protein in the muscle by approximately 30%, suggesting that this decrease is involved in the mechanisms for greater activation of the complex by exercise in trained rats.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1998

Nitric oxide: prospects and perspectives of in vivo detection by L-band EPR spectroscopy.

This paper discusses, compares and evaluates various in vivo EPR methods of detection of nitric oxide (NO). In particular the various classes of agents are: Fe(II)-dithiocarbamate derivative complexes of MGD (N-methyl-D-glucamine dithiocarbamate) and DTCS [N-(dithiocarboxy)sarcosine], stable imidazolineoxy N-oxides and nitronyl N-oxides, and NO-sensitive chars. As a specific example direct, real-time, in vivo measurements of nitric oxide (NO) in mice are described with the water soluble metal chelator complex (MGD)2-Fe(II), as monitored at L-band EPR. The three-line EPR spectrum of [(MGD)2-Fe(II)-NO] was observed non-invasively in both control animals injected with the preformed product [(MGD)2-Fe(II)-NO] and from lipopolysaccharide (LPS) treated mice subsequently injected with (MGD)2-Fe(II) complex. The [(MGD)2-Fe(II)-NO] spectrum was markedly suppressed after administration of phenyl N-tert-butyl nitrone (PBN) prior to LPS injection as PBN inhibits the expression of inducible nitric oxide synthase (iNOS). When 15N-arginine was administered to LPS-treated mice, an EPR spectrum consisting of both three- and two-line EPR signals (due to (MGD)2-Fe(II)-14NO and (MGD)2-Fe(II)-15NO respectively) was observed, confirming that the trapped NO was generated through the NOS enzyme and not other chemical routes.

Animals↗
PubMed1998

Acute myelogenous leukemia with monosomy 7, inv(3) (q21q26), involving activated EVI 1 gene occurring after a complete remission of lymphoblastic lymphoma: a case report.

A 42-year-old female with a mediastinal tumor and massive pleural effusion ws admitted to our hospital in June 1993. Biopsy revealed lymphoblastic lymphoma. She had no evidence of distant metastasis except pleural effusion. Bone marrow examination revealed a normal karyotype (46, XY). The patient had been progression-free for more than 1 year after achieving complete remission by induction, consolidation and maintenance therapy according to the standard chemotherapy and involved-field radiation for lymphoblastic lymphoma. From May 1996 progressive leukopenia and thrombocytopenia developed. The diagnosis of refractory anemia with excess of blasts (RAEB) was made. Subsequently, in November 1996, she developed acute myelogenous leukemia (AML), M4 type by FAB classification. The karyotype of MDS and AML clones involved inversion (3) (q21q26) and monosomy 7. The EVI 1 gene was examined and was proved to be rearranged and activated. This may be the first case among the therapy-related cases of MDS/AML reported whose karyotypes were followed and in which the mRNA expression of EVI 1 gene involved was directly proved in the leukemogenesis process of chemotherapy-induced secondary MDS and AML.

Chromosome Inversion↗
PubMed1998

Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay.

We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.

Breast Diseases↗
PubMed1998

Successful treatment by radiation and hormone therapy of isolated local recurrence of breast cancer 24 years after mastectomy accompanied by immune thrombocytopenia: a case report.

We report a case of isolated local recurrence of breast cancer, which was accompanied by idiopathic thrombocytopenic purpura (ITP) and benign monoclonal gammopathy that presented 24 years after the patient underwent mastectomy. A 72-year-old female patient with a chest wall tumor was referred to our hospital in November 1994. Twenty-four years previously she had surgically treated breast cancer, of which the pathology was scirrhous carcinoma. Needle biopsy of the tumor revealed tubular carcinoma, which is compatible with local recurrence of breast cancer. She had no evidence of regional lymph node involvement or distant metastasis. Hematological and serological examination revealed a low platelet count accompanied by M-proteinemia (IgG, kappa-type) and a mild increase in platelet-associated IgG. She was initially treated with extensive-field chest wall radiation (60 Gy), followed by systemic administration of tamoxifen. Complete local control of isolated local recurrence (LR) was achieved after radiation therapy (RT) and the patient has been progression-free for more than 2 years. Platelet count recovered gradually to a normal level after achievement of complete remission induced by radiation and tamoxifen. This may be the first case suggestive of a paraneoplastic syndrome of immune thrombocytopenia accompanied by local recurrence of breast cancer.

Adenocarcinoma↗
PubMed1998

Successful treatment with nedaplatin in patients with ovarian cancer that recurred after platinum-containing chemotherapy: report of two cases.

We report the successful treatment with nedaplatin of two cases of ovarian cancer that recurred after platinum-containing chemotherapy. A 52-year-old woman presented in June 1994 with massive accumulation of ascitic fluid. Pathological diagnosis of the specimen obtained at surgery in July 1994 was serous papillary adenocarcinoma of the ovary. In September 1995, approximately seven months after the completion of six cycles of CAP chemotherapy (cyclophosphamide, adriamycin and cisplatinum), she was referred to our hospital because of massive accumulation of ascitic fluid. The carbohydrate antigen 125 (CA-125) value was 485 U/ml. Cytologic study of her ascitic fluid was positive for adenocarcinoma cells. She did not respond to intravenous irinotecan and two cycles of intraperitoneal cisplatin. Nedaplatin 100 mg/m2 was administered. Complete response was achieved in September 1996 and continued for four months with a total of seven cycles of nedaplatin. The second case was a 60-year-old woman who was admitted to our hospital in December 1994 because of ascitic fluid. Diagnosis of ovarian cancer was based on an elevated level of CA-125 (1380 U/ml). Treatment with CAP and CC (cyclophosphamide and carboplatin) maintained a partial response for seven months. In August 1996, her disease progressed, although she was receiving CC therapy. Nedaplatin 100 mg/m2 was administered. Partial response was achieved again in November 1996 and continued for four months, with a total of five cycles of nedaplatin. In the light of our experience, treatment with nedaplatin in a patient with recurrent ovarian cancer might be worthwhile as palliative chemotherapy.

Adenocarcinoma, Papillary↗