Search PubMed⌕ Search

Biomedical subjects

F Takaku

Publications and source records attributed to F Takaku.

At least 235 records · Page 13Linked to original sources
PubMed1990

Expression of granulocyte and granulocyte-macrophage colony-stimulating factors by human non-hematopoietic tumor cells.

The expression of granulocyte colony-stimulating factor (G-CSF) mRNA was studied in human non-hematopoietic tumors, including 18 cases of lung cancers 10 cases of stomach cancers, three cases of glioblastomas, and one case each of breast phyllode sarcoma, thyroid cancer, and hepatocellular carcinoma. Northern blot analysis detected G-CSF mRNA in two of the lung cancer cases, in one of the glioblastoma cases, and in both the breast phyllode sarcoma and hepatocellular carcinoma cases. Since G-CSF receptors were not detected on the tumor cells by 125I-G-CSF binding assay, G-CSF autocrine loop are probably not involved in the growth of these G-CSF-producing tumors. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA was concomitantly expressed in most of these G-CSF-producing tumors. No major gene deletions or rearrangements of G-CSF and GM-CSF genes were demonstrated by Southern blot analysis in the tumors expressing G-CSF and GM-CSF mRNAs except for one of the glioblastomas (G3) in which one chromosome 17 allele was deleted. Although the mechanism of the concomitant expression of G-CSF and GM-CSF mRNA is unknown, relatively high frequency of this phenomenon suggests the presence of common transcriptional factors acting on regulatory regions of G-CSF and GM-CSF genomes.

Cell Line↗
PubMed1990

[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study].

The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days. Elevations of nadirs of absolute neutrophil counts (ANC) and significant shorting of neutropenic periods of ANC below 2,000/mm3 were observed with patients given KRN 8601. KRN 8601 is significantly superior over placebo (p less than 0.0001), while overall safety evaluation showed no significant difference between the two groups. All the above results indicate that KRN 8601 is extremely usefull for the neutropenia induced by chemotherapy.

Adult↗
PubMed1990

[Clinical effect of recombinant human granulocyte colony-stimulating factor in bone marrow transplantation. The Japan rhG-CSF Clinical Study Group].

To evaluate the safety and efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) derived from Chinese hamster ovary cells in bone marrow transplantation (BMT), we performed a multi-center phase II clinical study. Sixty-two bone marrow transplanted patients (46 with allograft, 16 with autograft) were enrolled in this study, and rhG-CSF was administered intravenously 30 min daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for 14 consecutive days from day 1 or day 5 after transplantation. Compared with historical control, blood neutrophil recovery in greater than or equal to 5 micrograms/kg/day group was clearly accelerated without delay in other blood cells. Consistent with the acceleration of neutrophil recovery, the number of days with body temperature (greater than or equal to 38 degrees C) decreased during from day 15 to day 28. No adverse effects were observed, and there was no evidence that rhG-CSF affected the incidence of graft-versus-host disease and relapse rates of myeloid leukemia. These results suggest that the posttransplant use of rhG-CSF may be an efficient strategy for reducing the risk of bacterial and/or fungal infection complications in BMT.

Adolescent↗
PubMed1990

Human granulocyte colony formation in serum-free cultures stimulated with purified recombinant granulocyte colony-stimulating factor.

Granulocyte colony formation by human bone marrow cells in serum-free cultures was studied using purified recombinant granulocyte colony-stimulating factor (rG-CSF). The cloning efficiency of the serum-free cultures was about 80% that of the serum-containing cultures. In addition to purified G-CSF, four ingredients were found to be essential to granulocyte colony formation: bovine serum albumin (BSA), iron-saturated human transferrin, cholesterol, and L-alpha-phosphatidylcholine. Their optimal concentrations were also investigated. Insulin was not indispensable for granulocyte colony formation, but its addition did increase the number of granulocyte colonies. Hydrocortisone was found to be inhibitory to granulocyte colony formation at high concentrations.

Blood↗
PubMed1990

Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils.

We investigated granulocyte colony-stimulating factor (G-CSF) receptors on neutrophils from three patients with chronic myelogenous leukemia (CML) in the chronic phase, in comparison with four normal volunteers. Because we experienced some difficulties in radioiodinating intact recombinant human G-CSF, we developed a new derivative of human G-CSF termed YPY-G-CSF. It was easy to iodinate this protein using the lactoperoxidase method because of two additional tyrosine residues, and its radioactivity was higher than that previously reported. The biological activity of YPY-G-CSF as G-CSF was fully retained. Scatchard analysis demonstrated that CML neutrophils had a single class of binding sites (1400 +/- 685/cell) with a dissociation constant (Kd) of 245 +/- 66 pM. The number of sites and Kd value of CML neutrophils were not significantly different from those of normal neutrophils (p greater than 0.9). Cross-linking studies revealed two specifically labeled bands of [125I]YPY-G-CSF-receptor complexes with apparent molecular masses of 160 and 110 kd on both normal and CML neutrophils. This is the first report describing two receptor proteins on neutrophils. According to the analyses of the proteolytic process of these cross-linked complexes and proteolytic mapping, we assume that alternative splicing or processing from a single gene may generate two distinct receptor proteins that bind specifically to G-CSF but have different fates in intracellular metabolism.

Adult↗
PubMed1990

[Clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome].

A clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome (MDS) was performed to investigate the hematopoietic effects and the increase of neutrophils. The rhG-CSF was administered daily by intravenous infusion over 30 min. to 21 patients with MDS (PARA = 11, RAEB = 4, RAEB in T = 6). The dose was escalated stepwise from 50 to 400 microgram/m2 every week. Within one week to 26 days after commencement of rhG-CSF administration, the increases of absolute neutrophil counts in peripheral blood were observed in all patients. Treatment with rhG-CSF enhanced normal marrow myeloid cell differentiation and maturation in 3 of 9 PARA patients and in 3 of 4 RAEB patients. None of patients changed to acute leukemia attributable to rhG-CSF, but one of RAEB patient and two of RAEB in T patients progressed to leukemic phase in 21 days or two months after treatment. Minor side effects or abnormal laboratory findings were observed in 3 patients (14.3%). These results suggested that treatment with rhG-CSF was well tolerated and effective for improving the neutropenia between 50 to 400 micrograms/m2 in patients with MDS.

Adult↗
PubMed1990

[Clinical effect of recombinant human granulocyte colony-stimulating factor on aplastic anemia].

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was studied in 30 patients with aplastic anemia (AA). RhG-CSF was administered intravenously daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for more than 7 days. In the patients whose absolute neutrophil counts (ANC) were more than 0.1 X 10(9)/l, the rhG-CSF injections at greater than or equal to 5 micrograms/kg/day caused rapid and selective elevation of ANC which maintained during the injection period. Most of the patients were well tolerated, and minor side effects were observed in only 3 patients. These findings suggest that daily injections of rhG-CSF at a dose of greater than or equal to 5 micrograms/kg/day may be an effective strategy for the treatment of bacterial and/or fungal infections in AA patients.

Adult↗
PubMed1990

[Clinical evaluation of recombinant human G-CSF in children with cancer].

Recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was administered in 69 chemotherapy-induced neutropenic pediatric patients (pts) with malignant tumors. Each pt received two cycles of the same chemotherapy and had neutropenia with absolute neutrophil counts (ANC) less than 500/microliter in the first cycle. Initiating 72 hours after termination of chemotherapy in the second cycle, rG-CSF (2 micrograms/kg/day) was given subcutaneously or intravenously to each pt for 10 days. rG-CSF significantly increased ANC at nadir; 72 +/- 14 vs. 206 +/- 40/microliter (data in the first cycle vs. data in the second cycle, respectively), and reduced the period of neutropenia with ANC less than 500/microliter; 9.7 +/- 0.6 vs. 5.1 +/- 0.6 days, and the period for restoration to ANC greater than or equal to 1,000/microliter after initiation of chemotherapy; 25.5 +/- 0.6 vs 17.5 +/- 0.9 days. rG-CSF did not affect other components of peripheral blood. The number of days with fever greater than or equal to 38 degrees C was significantly reduced by rG-CSF treatment. Neck pain and lumbago were observed in one pt, pollakisuria in one pt, and elevation of the serum levels of LDH and uric acid in one pt, however these were mild to moderate, transient, and resolved without any specific treatment. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for malignant tumors without any serious side effects.

Adolescent↗
PubMed1990

[Combination therapy with aztreonam and clindamycin on severe infections accompanying neutropenic patients with hematological disorders].

We studied effectiveness and safety of combination therapy of aztreonam (AZT) (2-6 g/day) and clindamycin (CLDM) (1,200-2,400 mg/day) on severe infections in neutropenic patients with hematological diseases. We administered AZT and CLDM to 250 consecutive patients and analyzed the results of a total of 212 cases for evaluation except 38 cases of exclusions and dropouts. Hematological malignancies constituted the dominating underlying diseases which represented 90.6% of all underlying diseases. The overall clinical efficacy of the combination therapy with AZT and CLDM was 65.6% and the following results were obtained for different categories: sepsis, 64.7%; suspected sepsis, 66.4%; and pneumonia 54.5%. Even severe patients with less than 100/microliters of neutrophil counts showed good responses with an efficacy rate at 57.4%. Side effects were observed in only 7 cases (2.8%). We concluded that the combination therapy with AZT and CLDM would be useful as empiric therapy against various infections in febrile neutropenic patients with hematological diseases.

Adult↗
PubMed1990

[Effectiveness of antilymphocyte and antithymocyte globulins for patients with severe aplastic anemia and pure red cell aplasia--analysis of immunologic parameters of peripheral lymphocytes concerning ALG and ATG therapy].

Four patients with severe aplastic anemia and one patient with pure red cell aplasia (PRCA) were treated with antilymphocyte and antithymocyte globulins. One patient in aplastic anemia who achieved good response by ALG administration had a possible diagnosis of myelodysplastic syndrome. ATG was administered to only one case of aplastic anemia and ALG was administered to the remainder. In the result, three out of 4 patients with aplastic anemia and one patient with PRCA achieved good response without severe side effects. Three patients with aplastic anemia had high CD4/CD8 ratio in their peripheral lymphocytes. This ratio normalized after ALG therapy in effective cases, but not in ineffective case. Natural killer activity elevated after ALG therapy in two effective cases of aplastic anemia and PRCA, but not in one ineffective case of aplastic anemia.

Adult↗
PubMed1990

[Reduction of myocardial infarct size by early intracoronary thrombolysis as assessed by serum cardiac myosin light chains and left ventricular function].

Cardiac myosin light chains are released from the infarcted myocardium soon after the onset of infarction, and the level of myosin light chains in the serum reflects infarct size, regardless of the presence of early coronary reperfusion. In this study, we used serum myosin light chains and assessed changes in left ventricular function to evaluate the effects of intracoronary thrombolysis on infarct size, with special reference to the interval between the onset of infarction and the time of reperfusion. Forty patients with acute myocardial infarction who underwent coronary angiography and intracoronary thrombolysis for the left anterior descending artery (LAD) early after the onset of infarction were categorized in four groups: in group A (n = 9) the LAD was already patent at the start of intracoronary thrombolysis, in group B (n = 12) antegrade flow in the LAD was achieved within three hours of the onset of symptoms, in group C (n = 10) antegrade flow was achieved later than three hours after the onset of symptoms, and in group D (n = 9) antegrade flow in the LAD was not achieved. The peak appearance time of creatine phosphokinase (CPK) in group D was significantly later than in the other groups. The total release of CPK in group C (3,119 +/- 414 IU/l) was greater than that in group A (1,332 +/- 346 IU/l) (p less than 0.01), but the total CPK release in group D (2,525 +/- 525 IU/l) was not statistically different from those of any other group. In all four groups myosin light chain I appeared in the serum from the first day on and reached their peak values between the third and fifth days. The peak values of myosin light chain I were 14.7 +/- 2.1 ng/ml for group A, 16.3 +/- 2.3 ng/ml for group B, 24.6 +/- 2.4 ng/ml for group C, and 25.1 +/- 1.8 ng/ml for group D. The peak myosin light chain levels in groups A and B were less than those in groups C and D. Twenty-nine of the 40 patients had no previous episodes of infarction, and these 29 patients were classified in two groups according to the Forrester's subset class on the first day: four of seven patients in group D were in subsets II, III or IV; whereas, the majority of patients in groups A, B and C were in subset I.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Vessels↗
PubMed1990

Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stimulating factor.

The receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surfaces of normal and leukemic myeloid cells were characterized using 125I-labeled bacterially synthesized GM-CSF. The binding was rapid, specific, time dependent, and saturable. Scatchard analysis of the 125I-GM-CSF binding to peripheral blood neutrophils indicated the presence of a single class of binding site (Kd = 99 +/- 21 pM; 2,304 +/- 953 sites/cell). However, for peripheral blood monocytes and two GM-CSF-responsive myeloid cell lines (U-937 and TF-1), the Scatchard plots were biphasic curvilinear, which were best fit by curves derived from two binding site model: one with high affinity (Kd1 = 10-40 pM) and the other with low affinity (Kd2 = 0.9-2.0 nM). For U-937 cells, the number of high-affinity receptors was 1,058 +/- 402 sites/cell and that of low-affinity receptors was estimated to be 10,834 +/- 2,396 sites/cell. Cross-linking studies yielded three major bands with molecular masses of 150 kDa, 115 kDa, and 95 kDa, which were displaced by an excess amount of unlabeled GM-CSF, suggesting 135-kDa, 100-kDa, and 80-kDa species for the individual components of the human GM-CSF receptor. These bands comigrated for different cell types including peripheral blood neutrophils, U-937 cells and TF-1 cells. In experiments using U-937 cells, only the latter two bands appeared to be labeled in a dose-dependent manner in a low-affinity state. These results suggest that the human GM-CSF receptor possibly forms a multichain complex.

Binding, Competitive↗
PubMed1990

[Two cases of advanced gastric cancer with diffuse carcinomatosis of the bone marrow showing a widespread osteoplastic bone metastasis].

Reported are 2 cases of an advanced gastric cancer with a "diffuse carcinomatosis of the bone marrow" (DCMB) showing a widespread osteoplastic bone metastasis. In a DCBM, a widespread invasion of cancer cells to the bone marrow occurs, causing leukoerythroblastosis, anemia, and disseminated intravascular coagulation. The local reaction in the bone, namely being osteoplastic or osteolytic, has not been discussed in previous papers. Our cases were characterized by an extremely high serum alkaline phosphatase, a "superscan" view of the bone scintigram, and a diffuse osteoplastic bone metastasis with an osteoid increase. Thus we think there are DCBM subtypes with a diffuse osteoplastic bone metastasis.

Adenocarcinoma, Mucinous↗
PubMed1990

[Clinical trial of KRN 8601 in patients with neutropenia induced by chemotherapy for lung cancer].

The clinical trial of KRN 8601 was conducted in patients with neutropenia induced by chemotherapy for lung cancer. Thirty-six patients were treated with KRN 8601 subcutaneously for 14 days once daily at the dose of 50 or 100 micrograms/m2, and the effects were compared with the control phase without KRN 8601 treatment. Both the elevation of neutrophil count and shortened period of neutropenia were observed by the administration of KRN 8601. The efficacy rate was 75% (18/24) at 50 micrograms/m2 and 100% (10/10) at 100 micrograms/m2. A side effect observed was fever in one patients, and in 2 patients, abnormal GOT, GPT and LDH elevation were observed in each. We concluded that KRN 8601 was clinically effective and safe at the dose of 50 micrograms/m2 or 100 micrograms/m2 for neutropenia induced by chemotherapy for lung cancer.

Adult↗
PubMed1990

Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease.

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.

Administration, Oral↗
PubMed1990

Glycosphingolipid composition of the gastric mucosa. A role of sulfatides in gastrointestinal mucosal defense?

The glycosphingolipid (GSL) compositions of the human, rabbit, and rat gastric mucosa were studied and compared. In neutral GSLs, although GalCer was the most abundant component in every tissue examined, species-specific differences were clearly observed in their composition. Acidic GSLs were composed of sulfatides and gangliosides. Every gastric mucosa contained sulfatides (GalCer-sulfate) in a high concentration. The concentrations of sulfatides per gram of dry weight were 416.0, 933.8, 394.0, 365.9, and 135.9 nmol for the human fundus, human antrum, rabbit fundus, rabbit antrum, and rat glandular stomach, respectively. On the other hand, gangliosides were less in these tissues. The molar ratios of sulfatides to GM3, a major ganglioside, were 4.3, 6.7, 11.1, 2.1, and 1.2 for each gastric mucosa described above, respectively. A high sulfatide concentration in animal gastric mucosa, with its structural similarity to sucralfate, implies that sulfatides may play an important role for gastrointestinal mucosal protection.

Animals↗
PubMed1990

[A multicenter clinical study of oral topical administration of G-512 on chemotherapy-associated intraoral mucosal lesions of patients with hematological malignancies. G-512 Therapeutic Study Group for Intraoral Mucosal Lesions].

We evaluated the usefulness of PGE2 on chemotherapy-associated oral mucosal lesions of the patients with hematological malignancies and compared the efficacy of the troche with that of the tablet. One hundred and fifty three patients were given 0.5 mg of these PGE2 topically three times daily. One hundred and fourty five cases were evaluable (Tablet; 85, Troche; 60). 1) Symptoms and signs were improved in 102/144 (70.8%) and 102/145 (70.3%), respectively. The overall response rate was 70.3%. 2) The improvement rates were 77.5% (55/71), 85.7% (6/7) and 62.7% (32/51) in leukocyte count-increased, -unchanged and -decreased patients, respectively. 3) No background factor of the patients except performance status affected the improvement rate. 4) Higher improvement rate was noted in the PGE2 early starting group (within 5 days after the appearance of oral lesions) than the late group (6 days and thereafter) (76.5% v.s. 55.8%: U-test p less than 0.1, chi2-test p less than 0.05). 5) There was no difference in the efficacy rate between the tablet and the troche. 6) Mild side effects were seen in 10 cases. These results suggest that topical administration of PGE2 is safe and useful for improving chemotherapy-associated oral mucosal lesions of patients with hematological malignancies.

Administration, Oral↗