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Biomedical subjects

M Okabe

Publications and source records attributed to M Okabe.

At least 217 records · Page 12Linked to original sources
PubMed1995

Analysis of the p53 gene mutations in acute myelogenous leukemia: the p53 gene mutations associated with a deletion of chromosome 17.

In order to determine the relevance of the p53 tumor suppressor gene mutations in acute myelogenous leukemia (AML), we analyzed the p53 gene in genomic DNA of 18 unselected cases of AML by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. We detected three cases (16.7%) with the p53 gene mutations showing only the mutant alleles; the high incidence in cases with loss of a whole chromosome 17 (two of three) contrasted with the low incidence in cases without abnormalities of chromosome 17 (one of 15). These cases containing the mutations of the p53 gene showed a poor prognosis. Although we analyzed a rather small series of patients, these findings suggest that the p53 gene mutations might be involved in the progression and prognosis of at least some cases of AML.

Base Sequence↗
PubMed1995

Megakaryocytic differentiation of a leukemic cell line, MC3, by phorbol ester: induction of glycoprotein IIb/IIIa and effects on expression of IL-6, IL-6 receptor, mpl and GATA genes.

We investigated megakaryocytic differentiation in a newly-established Ph1-positive leukemic cell line, MC3, which showed tri-lineage immunophenotypes (myeloid antigens2+, CD19(1+) and CD41a1+) and was positive for CD34 and CD38. TPA induced MC3 cells to differentiate to an early stage of megakaryocyte lineage exhibiting an increase in the expression of platelet glycoproteins (GP) IIb/IIIa (CD41a), and an increase in cell size and nuclear ploidy. TPA treatment also enhanced the expression of GPIIb mRNA, and induced the expression of interleukin-6 (IL-6) and its receptor mRNAs, while it did not induce transcripts of the genes IL-11 and mpl ligand, and further decreased the transcript of the mpl gene. Consistent with these findings, MC3 cells treated with TPA showed an increased expression of GATA-1, but not GATA-3 transcripts, whereas those without TPA treatment expressed only the GATA-2 transcript. These results provide an insight into the study for the regulatory mechanism of megakaryocytopoiesis and leukemic cell differentiation.

Antigens, CD↗
PubMed1995

Interferon-gamma-activated macrophages release interleukin-1 alpha to increase tube formation from endothelial cells of rat aorta.

Interferon (IFN)-gamma (160 and 460 pM)-treated peritoneal macrophages (M phi) increase tube formation from subcultured aortic endothelial cells (EC) of rat in type I collagen gel (Kobayashi et al., Immunopharmacology, 27: 23, 1994). The present study was carried out to identify factors released from these M phi. Interleukin (IL)-1 alpha, platelet-derived growth factor (PDGF)-BB and basic fibroblast growth factor (bFGF) increased tube formation, and their 50% effective concentrations were 0.46, 6.4 and 140 pM, respectively. A polyclonal anti-mouse IL-1 alpha antibody (0.33%) inhibited 57.7 +/- 6.5% of the activity of conditioned medium (CM) from IFN-gamma-treated M phi, but not from medium of basal M phi or EC. A monoclonal anti-human bFGF antibody (20 ng/ml) inhibited both the activities of CM from IFN-gamma-treated and basal M phi by 43.2 +/- 15.0% and 46.7 +/- 15.9%, respectively. However, a polyclonal anti-human PDGF-BB antibody (0.33%; 3.3 micrograms/ml) did not inhibit either activity of M phi. These results demonstrate that the effect of IFN-gamma-treated M phi on tube formation was caused by released IL-1 alpha. The release of IL-1 alpha was dependent on the action of IFN-gamma, a different mechanism from those of bFGF and PDGF-BB.

Angiogenesis Inducing Agents↗
PubMed1995

Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension.

PURPOSE: In this double-blind study, the authors compared the safety and efficacy of the investigational oral agent midodrine, a specific alpha 1-sympathomimetic agent, with ephedrine, a nonspecific alpha- and beta-adrenergic receptor agonist. Eight patients (4 men and 4 women) with refractory orthostatic hypotension resulting from autonomic failure were studied. This study was based on the notion that neurogenic orthostatic hypotension results from attenuation of adrenergic nerve traffic and not from alpha-adrenergic receptor dysfunction. Although arteriolar vasoconstrictors seem to be appropriate therapeutic agents, their success has been limited, and the search for an ideal drug is ongoing. METHODS: The authors employed a blocked, double-blind, randomized crossover design. The single-blind placebo run-in period was 2 days. The double-blind titration period with either midodrine or ephedrine was 3 to 5 days; the titration end point was to increase standing systolic blood pressure to > or = 80 mm Hg and to maintain a supine pressure below 180/100 mm Hg. The maintenance period was 3 to 5 days. A 4-day placebo washout period was interposed at the crossover point. RESULTS: The ability to stand improved in patients treated with midodrine but not with ephedrine. Midodrine significantly increased both systolic (P < 0.001) and diastolic (P < 0.001) standing blood pressure over placebo (P < 0.001) and ephedrine (P < 0.05). In contrast, ephedrine-induced changes in standing pressures did not significantly differ from placebo (P > 0.05). Midodrine treatment improved the frequency of the ability to stand as compared with ephedrine, and was associated with a significantly higher incidence of standing systolic pressures > 80 mm Hg than was placebo (P < 0.001). Both midodrine and ephedrine significantly increased supine systolic and diastolic blood pressures over placebo (P < 0.001, P < 0.01, P < 0.01, P < 0.01, respectively), but were not significantly different from each other. Ephedrine significantly increased (P < 0.05) the pulse rate as compared with placebo and midodrine, whereas midodrine produced a statistically significant (P < 0.05) but clinically minimal decrease in pulse rate compared with placebo. Neither drug affected clinical laboratory variables. CONCLUSIONS: Midodrine safely and effectively improved orthostatic hypotension caused by autonomic failure. Our data suggest that the ability to stand is improved better by midodrine than by ephedrine.

Adrenergic alpha-Agonists↗
PubMed1995

Characteristics of the antitumor activity of M-16 and M-18, major metabolites of a new mitomycin C derivative KW-2149, in mice.

The cell growth inhibitory activity, antitumor activity and toxicity of M-16 and M-18, the major metabolites of a new mitomycin C (MMC) derivative KW-2149, in mouse and human were compared with those of KW-2149 or MMC in vitro and in vivo. The growth inhibitory activity of M-18, a symmetrical disulfide dimer, against human uterine cervix carcinoma HeLa S3 cells was almost equivalent to that of KW-2149 and their IC50 values were about 10-fold smaller than that of MMC. The activity of M-16, a methyl sulfide form, was almost equivalent to that of MMC. The cell-killing activity of MMC and M-16 was augmented in the hypoxic condition, whereas that of KW-2149 and M-18 was reduced. M-16 also exhibited almost equivalent activities to MMC in vivo in terms of many biological profiles, i.e., antitumor activity against murine P388 leukemia, ascitic or solid B16 melanoma or human lung carcinoma xenograft L-27, and bone marrow toxicity in mice. These in vitro and in vivo results indicate that the antitumor activity and toxicity of KW-2149 might not be mediated by M-16 in mice. On the other hand, M-18 exhibited almost equivalent activities to KW-2149 in these regards, suggesting the involvement of M-18 in the biological activities of KW-2149. However, the small values of the area under the curve of M-18 in mice make this unlikely. Thus the biological activities of KW-2149 in mice are not explained by the M-16 or M-18 concentration in plasma and are postulated to be manifested by KW-2149 itself.

Animals↗
PubMed1995

Activation by alpha 1-adrenergic agonists of the progression phase in the proliferation of primary cultures of smooth muscle cells in mouse and rat aorta.

The effects of catecholamines on the competence and progression phases in the proliferation of vascular smooth muscle cells (SMCs) in mouse and rat were investigated in primary cultures: alpha,beta-Adrenergic agonists such as epinephrine and norepinephrine, and the alpha-adrenergic agonist, phenylephrine, stimulated proliferation of primary cultured SMCs, whereas the alpha 2-adrenergic agonist, clonidine, and beta-adrenergic agonist, isoproterenol, did not. The stimulating effect of epinephrine was maximal at 0.54 microM and was then decreased at higher concentrations. The alpha-adrenergic antagonist, phentolamine, and alpha 1-adrenergic antagonist, prazosin, inhibited epinephrine-induced SMC proliferation, while the alpha 2-adrenergic antagonist, yohimbine, and beta-adrenergic antagonist, propranolol, did not. In primary cultured and synchronized SMCs at the G0 phase, norepinephrine accelerated the rate of SMC proliferation, but did not change the starting time of DNA synthesis and proliferation. These results show that catecholamines activate the progression phase in primary cultured aortic SMCs alpha 1-adrenergic receptors.

Adrenergic alpha-Agonists↗
PubMed1995

Hinokitiol induces differentiation of teratocarcinoma F9 cells.

Hinokitiol, a constituent of the wood of Chamaecyparis taiwanensis, was found to induce differentiation of teratocarcinoma F9 cells. When examined by the agar-overlay method, in which expression of plasminogen activator as a differentiation marker protein was detected, this compound exhibited a dose- and time-dependent induction. Induction of differentiation by hinokitiol occurred irreversibly and required its addition for more than 12h. Among its structure-related compounds tested, tropolone and two colchicine-related compounds exerted potent activities comparable to that of hinokitiol. These findings indicate that free tropolone structure in the molecules plays an essential role in inducing differentiation of F9 cells. Hinokitiol showed a strong inhibitory effect of DNA synthesis in very early stages of culture, suggesting that this effect may be responsible for triggering differentiation of F9 cells.

Animals↗
PubMed1995

Anti-competence effects of synthetic phthalide derivatives on platelet-derived growth factor-induced DNA synthesis in primary cultures of rat aorta smooth muscle cells.

The inhibitory effect of 3-butylidene-4,5-dihydroxyphthalide (BP-42) on platelet derived growth factor (PDGF)-BB-induced DNA synthesis was investigated in synchronized smooth muscle cells (SMC) in primary culture of rat aorta. BP-42 (0.3-3 micrograms/ml) inhibited the PDGF-BB (30 ng/ml)-stimulated [3H]thymidine incorporation of the SMC in a concentration-dependent manner. BP-42 inhibited both the competence and progression phases of [3H]thymidine incorporation induced by PDGF-BB. Using the competence assay, BP-42 (0.3-10 micrograms/ml) delayed PDGF-BB (30 ng/ml)-accelerated starting time of [3H]thymidine incorporation in a concentration-dependent manner, confirming that BP-42 inhibited PDGF-BB-induced competence phase of DNA synthesis of SMC. BP-42 (1-10 micrograms/ml) also delayed basic fibroblast growth factor (bFGF: 30 ng/ml)-accelerated starting time of [3H]thymidine incorporation. The inhibitory potency of BP-42 for the competence action of PDGF-BB was similar to that for the action of bFGF. BP-421 (3-heptylidene-4,5-dihydroxyphthalide) and BP-422 (3-benzylidene-4,5-dihydroxyphthalide) had 3-fold greater inhibitory potencies than BP-42 for the PDGF-BB-induced competence activity. These results demonstrated that BP-42 inhibited PDGF-BB-induced competence activity of DNA synthesis in primary cultured SMC of rat aorta via a common signal transduction mechanism with bFGF. BP-421 and BP-422 were more potent inhibitors for the competence activity, suggesting that they may become a prototype of new anti-atherosclerotic drugs.

Animals↗
PubMed1995

Competence effect of PDGF on Ki-67 antigen and DNA contents, and its inhibition by trichostatin-A and a butylydene phthalide BP-421 in primary smooth muscle cells of rat aorta by flow cytometry.

We investigated with flow cytometry the platelet-derived growth factor (PDGF)-induced competence in primary cultured smooth muscle cells (SMC) of rat thoracic aorta. A cytogram was obtained by a double staining technique with fluorescein isothiocyanate-conjugated mouse monoclonal antibody against the proliferation-associated nucleus antigen Ki-67, and propidium iodide for total DNA content. (1) The nearly confluent SMC after 6 d-culture with 5% fetal bovine serum (FBS) were further cultured under serum starvation for 2d. (2) SMC was cultured with 5% FBS for 4 d, and then with 5% FBS+trichostatin-A (TS-A) (1 microgram/ml) for 2d. The cytogram showed the broadening of Ki-67 antigen signal for G0/G1 phase by TS-A compared with that of SMC under serum starvation, suggesting the existence of early and late phases of G1. (3) After serum starvation, the preculture with PDGF (100 ng/ml) for 3 h which was followed by a further 15 h-culture with 3% FBS caused significant more entry into S phase than control culture. The extent was greater than that with 15 h-culture with 10% FBS. (4) 15 h-culture with 1% FBS after PDGF (30 ng/ml) pretreatment stimulated entry into S phase cells, which was inhibited by TS-A (1 microgram/ml) and by a butylydene phthalide derivative BP-421 (3 micrograms/ml). Flow cytometric analysis demonstrate that PDGF pretreatment stimulates the entry into S phase by 20% of total SMC having early and late phases of G1, and that the PDGF-competence is inhibited by TS-A and BP-421.

Animals↗
PubMed1995

Improvement of fusing ability of human sperm to zona-free hamster eggs by conditioned media.

A conditioned medium (CM) was prepared by culturing human sperm at 3.0 x 10(6) sperm/ml for 12 h. The fusion index increased significantly when the sperm penetration assay (SPA) was performed with CM (0.6 without CM to 2.0 with CM). The conditioned medium was also effective on the sperm from 11 patients who showed a low or zero value in SPA and who's in vitro fertilization treatment failed. When CM from the sperm of healthy donors was added to these patients' sperm, the fusing ability to zona free hamster eggs was significantly restored.

Acrosome↗
PubMed1995

Effects of rhG-CSF on infection complications and impaired function of neutrophils secondary to chemotherapy for non-Hodgkin's lymphoma. Hokkaido Study Group of Malignant Lymphoma, and rhG-CSF, Japan.

It has been previously demonstrated that the administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF) ameliorates the decrease of the polymorphonuclear neutrophils (PMNs) count after the cytotoxic chemotherapies, thereby reducing the infection complications associated with neutropenia. In this multi-center study, we studied the prophylaxtic effect of rhG-CSF administration on infection complications in patients with non-Hodgkin malignant lymphoma, who received cytotoxic chemotherapies (CHOP or ProMACE/CytaBOM). rhG-CSF administration reduced the frequency of infection complications, and there was no obvious difference in it's frequency between the CHOP-treated and the ProMACE/CytaBOM-treated groups when administered with rhG-CSF, thereby indicating that third generation therapy for NHL may be safely completed in Japanese in combination with rhG-CSF administration. Furthermore, we investigated both the in vitro and the in vivo effects of rhG-CSF on the function of PMNs in patients with NHL and healthy donors, and revealed that the administration of rhG-CSF for NHL patients receiving cytotoxic chemotherapy brought on an improvement of the production of active oxygen but did not affect serum levels of IFNs, IL-1-beta, and IL-6, inspite of a slight elevation of TNF-alpha. Consistent with these results, in vitro treatment of PMNs with rhG-CSF induced no significant production of these inflammatory cytokines and their mRNA expressions. Furthermore, rhG-CSF administration showed no significant effects in vivo on the expression of CD11a, CD11b and LECAM-1 on PMNs and integrins on platelets.

Adult↗
PubMed1995

Establishment and characterization of a new Ph1-positive chronic myeloid leukemia cell line MC3 with trilineage phenotype and an altered p53 gene.

A new Ph1-positive leukemic cell line (MC3) expressing the P210bcr/abl oncoprotein was established from a patient with CML in blast crisis. The MC3 cells showed the trilineage phenotype of myeloid, lymphoid (CD19) and megakaryocytoid lineages, and had a proliferative response to rhIL-1 and rhIL-3 in the serum-free culture. These results and the expression of CD34 indicated that the MC3 cells have characteristics of hematopoietic progenitor cells. Recently, it has been documented that alterations of the p53 gene in leukemic cells are frequently detected during the blast crisis of CML. The MC3 cells contained the altered p53 gene. In addition, the original leukemic cells showed the point-mutational activation of the N-ras gene and an additional chromosomal abnormality inv(3q), but the MC3 cells contained no such abnormalities, indicating that not all of the original leukemic cells had these abnormalities. Thus, the MC3 cell line may provide several insights into investigations of the blast crisis in CML as well as hematopoietic progenitor cells.

3T3 Cells↗
PubMed1995

Administration of rhG-CSF increases complete remission rates after CHOP and ProMACE/CytaBOM for non-Hodgkin's lymphoma: a pilot study. Hokkaido Study Group of Malignant Lymphoma and rhG-CSF.

To evaluate the clinical effects of the administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy for patients with advanced-staged intermediate-grade or high-grade non-Hodgkin's malignant lymphoma (NHL), we conducted this multicenter study and compared the responses between both the regimens, CHOP as a first-generation chemotherapy and ProMACE/CytaBOM as a third-generation chemotherapy, when combined with the rhG-CSF administration. In this multicenter study, where forty patients were registered, patients in both the CHOP and ProMACE/CytaBOM groups were treated with the original regimen designs without the necessity of reducing drug dosages when combined with the administration of rhG-CSF. The administration of rhG-CSF post both of the cytotoxic therapies brought about much higher rates of complete remission in both the groups (CHOP, 75 percent; ProMACE/CytaBOM, 75 percent), as compared with those of the previous study without the rhG-CSF administration. Regarding response rates according to the International prognostic factor index, the CHOP group showed a lower rate of complete remission in patients with risk factors, compared with ProMACE/CytaBOM group. This result suggested that the administration of rhG-CSF may offer one important approach for improving the first-line therapy for aggressive NHL with high risk factors.

Adult↗
PubMed1995

[Oozing type left ventricular rupture: report of three cases].

Two cases of postinfarction oozing type left ventricular rupture and a case of oozing type left ventricular rupture due to catheter perforation for left ventriculography are reported. The technique used to repair the rupture is fibrin glue-oxycellulose fixation method. The post operative course of three cases were uneventful. But left ventricular aneurysm remained in two cases.

Aged↗
PubMed1995

[Enlargement of the aortic and mitral double valve rings with double valve replacement using coupling valve method].

A 46-year-old woman was hospitalized with congestive heart failure. She had undergone a mitral valve replacement (23 mm) 17 years earlier and complicated a left ventricular rupture. Upon admission, she was diagnosed with aortic and mitral stenoinsufficiency with narrowed annuli on both valves, tricuspid insufficiency, and a left ventricular pseudoaneurysm. The operative procedure consisted of enlarging the aortic and mitral valve rings and replacing them by the coupling valve method. The orifice of the pseudoaneurysm was repaired with a patch closure applied from the endocardial side. A tricuspid annuloplasty was performed using the DeVega's method. Her postoperative course was uneventful. This is the first report of a successful operation to correct double narrowed annuli along with a ruptured left ventricule. The coupling valve procedure employed here should prove useful for similar cases requiring enlargement and replacement of the aortic and mitral valves simultaneously.

Aneurysm, False↗
PubMed1995

Membrane cofactor protein (CD46) in seminal plasma is a prostasome-bound form with complement regulatory activity and measles virus neutralizing activity.

Human seminal plasma contains 0.55 microgram/ml of membrane cofactor protein (MCP; CD46) of 60,000 MW. By ultracentrifugation, gel filtration and immunoelectron microscope methods, we found that the MCP in seminal plasma was associated with prostasomes. The functional properties of the prostasome-bound MCP were assessed in comparison with a recombinant soluble form, gamma MCP1, which is composed of four short consensus repeats (SCR), type C of the serine/threonine-rich domain (STC), and unknown significance (UK). The MCP in seminal plasma, although demonstrably bound to prostasomes, behaved more like the soluble form of MCP. In the absence of detergent it, together with factor I, degraded the fluid-phase ligand, methylamine-treated C3 [C3(MA)], which is insensitive under no-detergent conditions to the membrane form of MCP and factor I. Moreover, C3dg fragment was generated as a final product instead of C3bi during the incubation, indicating that the prostasomal MCP and proteases may be responsible for the C3dg generation. The prostasomes neutralized measles virus (MV) infectivity, while gamma MCP1, for the most part, did not. These results, taken together with the CD59 concentration on the prostasomes, suggest that the prostasomes are potential immunomodulators for complement activation, providing the C3- and C9-step inhibitors. The present report also reinforces the idea that there are two different forms of MCP in semen. One is located in the inner acrosomal membrane of spermatozoa, which appears through acrosomal reaction and spermatoon-egg interaction. The other is a prostasome-bound form maintaining activities sufficient to regulate complement activation and, probably, MV infection.

Antigens, CD↗
PubMed1994

Cloning of a Drosophila melanogaster homologue of the mouse type-I bone morphogenetic proteins-2/-4 receptor: a potential decapentaplegic receptor.

The Drosophila melanogaster (Dm) decapentaplegic (dpp) gene product plays an essential role during several stages of Dm development. The DPP protein is a member of the transforming growth factor-beta (TGF-beta) superfamily and an orthologue of mammalian bone morphogenetic proteins (BMP-2 and -4). Recently, a cDNA clone encoding the mouse Ser/Thr kinase receptor specific for BMP-2/-4 (mTFR11) was isolated. Here, we describe the deduced primary structure, the cytogenetic position and expression pattern of the Dm homologue of mTFR11 (DTFR), a putative DPP receptor. The cytogenetic position of the Dm dtfr gene was mapped to 25D. DTFR has striking homology to mTFR11, especially in the cytoplasmic domain (approx. 63%), including a Ser + Gly-rich box that is characteristic of type-I receptors for the TGF-beta superfamily. Although the amino acid (aa) sequence of the extracellular domain is less conserved than that of the cytoplasmic domain, the extracellular domains of these two molecules were more homologous (approx. 27%) to each other than any other receptors for the TGF-beta superfamily. The spacing of Cys residues in the extracellular domain, which is considered crucial to ligand specificity, is highly conserved in these two receptors. During Dm embryonic development, its expression pattern changes in a dynamic fashion with high levels of expression in mesoderm and midgut, with some relation to dpp mutant phenotypes.

Amino Acid Sequence↗