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Biomedical subjects

A Urabe

Publications and source records attributed to A Urabe.

At least 73 records · Page 4Linked to original sources

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

Adolescent↗

Tyrosine phosphorylation of vav protooncogene product in primary human myelogenous leukemic cells stimulated by granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor(G-CSF), but not granulocyte-macrophage CSF(GM-CSF), induced tyrosine phosphorylation of 95-kDa protein in 13 cases of primary human acute myelogenous leukemic cells. Electrophoretic mobility of 95-kDa phosphoprotein and the protooncogene product p95vav was identical. In addition, p95vav was tyrosine-phosphorylated only in G-CSF-stimulated cells. In contrast to primary leukemic cells, amount of p95vav was under detectable level and G-CSF did not induce tyrosine phosphorylation of 90-100-kDa proteins in human neutrophils. These results indicate specific involvement of vav product in signaling pathway of G-CSF in primary human leukemic cells.

Amino Acid Sequence↗

Granulocyte colony-stimulating factor in acute myeloid leukemia.

The clinical application of recombinant human G-CSF in patients with acute myeloid leukemia (AML) has been controversial because it stimulates the in vitro proliferation of leukemic cells. In order to explore the possibility of predicting in vivo leukemic proliferation after G-CSF administration to AML patients by using in vitro assays, we investigated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia following chemotherapy (G-CSF group) and 16 patients who did not (control group). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, while 11 of the 16 control patients developed leukemic resurgence. In the G-CSF group, the frequency of leukemic resurgence among patients whose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there were no significant differences between the G-CSF and control groups in [3H]thymidine incorporation by leukemic cells and leukemic colony formation after the addition of G-CSF to cultures. The G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 pM, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurgence occurred (200 in the G-CSF group and 260 in the control group) than when it did not (3400 and 3030, respectively). Immunophenotyping (for CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between blasts from the patients with and without leukemic resurgence in the G-CSF group. Thus, we conclude that the in vivo leukemic resurgence during G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine or with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptors with a high affinity irrespective of whether patients receive G-CSF.

Acute Disease↗

Hypereosinophilic syndrome in Hodgkin's disease with increased granulocyte-macrophage colony-stimulating factor.

We report a patient with eosinophilia accompanied by Hodgkin's disease who showed remarkable increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma but no increase in interleukin-5 (IL-5). The plasma GM-CSF level normalized as eosinophilia and lymphadenopathy disappeared after chemotherapy. Immunohistochemical study with immunoperoxidase staining technique showed a positive stain in lymph node cells by monoclonal anti-GM-CSF antibody. Eosinophilia is often accompanied by Hodgkin's disease, and several cases have been reported to show high levels of plasma IL-5. To our knowledge, this is the first report to show a high level of plasma GM-CSF in Hodgkin's disease with eosinophilia.

Aged↗

Differential cell- and immuno-biological properties of murine B16-F1 and F10 melanomas: oncogene c-fos expression, sensitivity to LAK cells and/or IL-2, and components of gangliosides.

Differential cell- and immuno-biological properties of two murine melanoma B16 variants, B16-F1 and F10, were investigated. Studies focused on the expression of proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of the expression of ganglioside components after treatment with IL-2. Proto-oncogene c-fos was found to be highly expressed in F10 lines by an in situ hybridization technique and also in F10 lung metastatic nests by immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2 treatment, but successive injections of a combination of LAK cells and IL-2 did cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major component of gangliosides of both F1 and F10 melanomas was GM3. Production of GM3 in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment was continued for 7 days, minor components of gangliosides, such as GM2, GM1, and GD1a, appeared only in F1 melanomas, while the increase of production of GM3 disappeared in both melanomas. These experimental results may provide clues for additional mechanisms which allow these two murine melanoma variants to show different implantation and metastasis rates.

Animals↗

[Efficacy of combination chemotherapy with miconazole and G-CSF in deep mycosis accompanying hematological diseases].

In order to examine the efficacy of the combination chemotherapy with miconazole and G-CSF, patients with deep mycosis and suspected deep mycosis were divided into 3 groups. Group I: miconazole and G-CSF were administered simultaneously. Group II: miconazole was administered later during G-CSF administration. Group III: only miconazole was administered. Of a total of 117 cases 105 cases were analyzed including group I 37 cases, group II 39 cases and group III 29 cases, excluding 12 dropout and inadequate cases. Of the 105 cases, deep mycosis were 31 and suspected deep mycosis were 74, and underlying diseases were hematological malignancies such as leukemias. Efficacy judged mainly by the change of fever was 62.2% (23/37) in group I, 43.6% (17/39) in group II, and 41.4% (12/29) in group III, respectively. Efficacy was better in the patients whose neutrophil counts increased from less than 500/microliters to more than 500/microliters (group I 75.0%, group II 72.7%) than in the patients whose neutrophil counts were less than 500/microliters throughout the time of miconazole administration (group I 33.3%, group II 33.3%). Adverse effects were minimal in 3 groups (group I 15.4%, group II 17.4%, group III 15.6%). It is concluded that the combination with miconazole and G-CSF is effective in the treatment of deep fungal infections.

Adult↗

Combination therapy with granulocyte colony-stimulating factor, all-trans retinoic acid, and low-dose cytotoxic drugs for acute myelogenous leukemia.

A 67-year-old man presented with acute myelogenous leukemia (M2). Peripheral blood examination revealed a leukocyte count of 1,700/mu l with 1% myeloblasts, and bone marrow aspiration showed 42.6% myeloblasts with Auer bodies. Culture of his marrow cells at diagnosis showed that granulocyte colony-stimulating factor (G-CSF) promoted cell proliferation, while all-trans retinoic acid (ATRA) inhibited the proliferative effect of G-CSF and induced differentiation. Combination therapy with G-CSF, ATRA, and low-dose cytotoxic drugs achieved complete remission without severe marrow suppression.

Aged↗

A simple method for measuring the amount of immunoglobulin A secreted onto the skin surface.

We developed a simple method for measuring the amount of the secretory form of immunoglobulin A (sIgA) present in sweat. A small disk (10 x 10 mm) made of cellulose membrane was attached to the skin surface for periods of 1 to 24 h. SIgA was absorbed to the membrane and accumulated during the period of application. Enzyme immunoassay using anti-sIgA and antisecretory component (SC) antibodies revealed distinct dots on the disk that corresponded to the eccrine excretory ducts. A densitograph was used to determine the number and density of the dots, thus obtaining the amount of sIgA excreted to the surface of the skin (per mm2). The amount of skin sIgA excreted differed inter-individually as well as intra-individually. That is, it varied according to the region of the skin, and its distribution roughly reflected that of the sweat ducts. SIgA excretion was maintained at a certain level, regardless of the increased sweating produced by either heat or exercise, which raised the output of sweat 3- to 15-fold. Immunohistochemical studies revealed that fewer glandular cells expressed SC in their cytoplasm as the amount of sIgA decreased. Such an independence of the excretion of sIgA from that of sweat may be necessary to the local immune defenses of the skin.

Absorption↗

[Clinical study of ciclosporin in patients with aplastic anemia and pure red-cell aplasia].

We administered cyclosporine to patients with aplastic anemia and pure red-cell aplasia as a multicenter clinical trial. The cyclosporine was given by a dose of 6 mg/kg orally daily for 16 weeks. The efficacy of cyclosporin for aplastic anemia was 13.8% after 8 weeks, and 28.0% after 16 weeks. The severity of the disease was improved, and the amount of blood transfusion was reduced. The efficacy of cyclosporine for patients with pure red-cell aplasia was 60.0% at 16 weeks treatment. Adverse effects of cyclosporine were observed in some patients and the hirsutism was seen most commonly. In laboratory data, an increase of serum creatinine was seen but was transient. Our results showed that cyclosporine is an effective drug for treatment of aplastic anemia and pure red-cell aplasia.

Adult↗

Malignant schwannoma in a case of type 1 neurofibromatosis with decreased immunoreactivity of smooth muscle alpha-actin in tumor vessels.

A malignant schwannoma in the left calf of a 37-year-old man with type 1 neurofibromatosis is herein reported. Since it is known that capillaries in benign neurofibromas are accompanied by hypertrophic pericytes expressing an abundant amount of smooth muscle alpha-actin (SMAA), we examined the immunohistochemical reactivity of SMAA within this malignant tumor and then compared it with that in surrounding benign areas. In the nests of malignant cells, decreased SMAA staining was found in the capillary walls. In the benign tissues around the malignant tumor, various extents of SMAA could be visualized in the vessels and myofibroblasts. Platelet-derived growth factor (PDGF) was also detected in the tumor, suggesting that cytokines secreted by malignant cells may have an influence on the expression of SMAA as well as on the alteration of the structure of blood vessels.

Actins↗

Expression of the fos oncogene in basal cell carcinoma.

Using immunohistochemical technique and Western blot analysis, we demonstrated the increased expression of the c-fos oncogene in the infiltrative type of solid basal cell carcinoma (BCC), but low or no expression in the circumscribed type of solid BCC. The infiltrative type is called aggressive BCC and had been shown to exhibit a higher rate of recurrence than the circumscribed type. Our results indicate that increased expression of the fos oncogene is closely related to the invasive ability of the tumor cells.

Blotting, Western↗

Effects of krestin (PSK) on tumorigenesis induced by two-stage and complete chemical carcinogenesis.

The effects of PSK on tumorigenesis in mouse skin were investigated either when mouse skins were initiated by benzo(a)pyrene and promoted by 12-O-tetradecanoyl-phorbol-13-acetate (Group I, two-stage carcinogenesis) or when both initiated and promoted by benzo(a)pyrene (Group II, complete carcinogenesis). Twelve mice in each group were fed chow with or without 0.4% PSK. This concentration of PSK was determined by calculation to give mice enough PSK to exert antitumorigenic activity without cytotoxicity. By the end of the experimental periods (26 weeks), two carcinoma-burdened mice in Group I without PSK were dead, but no carcinomas at all were identified in the mice fed with PSK, although considerable numbers of papillomas developed in both groups. In Group II, carcinomas started to evolve at the 15th week of the experiment regardless of PSK feeding. The number of carcinomas observed in the mice fed with PSK in Group II was statistically significantly lower than that in the mice fed without PSK. Histologically, mild inflammatory infiltrations were seen around the papillomas, and moderate to dense infiltrations, mainly composed of neutrophils, T lymphocytes, and macrophages, were observed in squamous cell carcinomas. There were apparently no significant differences in the number of the infiltrating cells around carcinomas in PSK (+) and PSK (-) groups in both early and fully developed lesions. However, considerable numbers of cells infiltrating into the nests were observed in the early lesions of elicited carcinomas in the mice fed with PSK, while such cells were rarely seen in carcinoma nests in the group without PSK at that stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Suppression of murine melanoma growth with a combination of microwave hyperthermia and local injection of interleukin 2.

Local microwave hyperthermia in combination with local injections of interleukin 2 (IL-2) was found to exert a remarkable suppressive effect on murine melanoma growth. Both of these therapeutic modalities caused marked tumour infiltration with natural killer cells. After microwave hyperthermia or IL-2 injection alone there was minimal T-cell infiltration, but T cells were more in evidence following combination therapy.

Animals↗

[Hypoplastic leukemia successfully treated by oral administration with cytarabine ocfosfate].

A 73-year-old man was admitted to our hospital with pancytopenia in December, 1992. The data of his peripheral blood were as follows: WBC 1,100/microliters (stab 9.0, seg 11.5, eosin 3.5, mono 1.0, lymph 75.0), RBC 176 x 10(4)/microliters, Hb 6.6 g/dl, platelet 4.6 x 10(4)/microliters. Bone Marrow was hypocellular (cell count 1.4 x 10(4)/microliters) and consisted of 30% blasts (peroxidase positive). He was diagnosed as having hypoplastic leukemia. Oral administration of cytarabine ocfosfate (50 mg/day) was begun from the 5th of January, 1993. The dose of cytarabine ocfosfate was increased to 100 mg/day since the 13th of January, 1993, and he was discharged from the hospital on the 23rd of January, 1993. Since then, he has been treated with cytarabine ocfosfate alone in the outpatient clinic. Pancytopenia began to improve in one month, and the data on the 7th of May, 1993 were as follows: WBC 3,500/microliters (stab 2.0, seg 37.5, eosin 1.5, baso 1.0, mono 16.5, lymph 41.5), RBC 249 x 10(4)/microliters, Hb 10.4 g/dl, platelet 15.4 x 10(4)/microliters. Bone marrow became normocellular (cell count 22.0 x 10(4)/microliters) and blasts decreased to 3.0%, and complete remission was confirmed. There were no adverse effects.

Administration, Oral↗

[Acute promyelocytic leukemia (APL) resulting in broad cerebral infarction during all-trans retinoic acid (ATRA) treatment].

A 27-year-old woman visited Kanto Teishin Hospital complaining of fever and petechiae in September, 1992. Her fetus had suddenly died in the uterus two weeks before (in the sixth month of pregnancy). Total white blood cell (WBC) count was 3.2 x 10(3)/microliters with 80% promyelocytes. Bone marrow was hypercellular with 90% promyelocytes. Disseminated intravascular coagulation (DIC) was recognized. She was diagnosed as having acute promyelocytic leukemia (APL), and treatment with daily oral administration of all-trans retinoic acid (ATRA) (70 mg/body/day) was begun. On day 4, hemiplegia and aphasia appeared. Broad cerebral infarction was suspected from computed tomography. On day 9, the WBC count increased rapidly, standard chemotherapy was added and she achieved complete remission. ATRA is known to have stimulatory effects on the differentiation of APL cells, but some reports have described thromboembolic events during the administration of ATRA. In this case, ATRA might have affected coagulability resulting in cerebral infarction.

Adult↗