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Biomedical subjects

K Ogata

Publications and source records attributed to K Ogata.

At least 253 records · Page 14Linked to original sources
PubMed1993

A novel megakaryocyte potentiator produced by MC-1 human lung cancer cell line.

The hematopoietic stimulating activity of a human lung cancer cell line, MC-1, was investigated. The protein fraction (MC-1 protein) was prepared from the serum-free culture supernatant of MC-1 cells using hydroxyapatite and concanavalin A-agarose columns. In serum-containing cultures, MC-1 protein stimulated colony formation by megakaryocyte colony-forming units (CFU), erythroid burst-forming units and granulocyte/macrophage (GM) CFU. The stimulating effect was strongest for megakaryocyte CFU. The factor having megakaryocyte colony-stimulating activity was shown to be a protein whose molecular weight was determined to be 23,000 daltons by gel filtration. By various analyses, this protein was shown to be molecularly different from the heretofore-identified cytokines that may affect megakaryocytopoiesis, i.e., interleukin-1 (IL-1), IL-2, IL-3, IL-6, IL-7, IL-11, granulocyte colony-stimulating factor (CSF), macrophage CSF, GM-CSF, leukemia inhibitory factor, stem cell factor and tumor necrosis factor. Under serum-free conditions, MC-1 protein augmented murine megakaryocyte colony formation in the presence of murine IL-3 and increased the acetylcholinesterase activity of purified murine megakaryocytes. It was also shown that MC-1 protein stimulated human megakaryocyte colony formation. It was concluded that MC-1 cells produce a megakaryocyte potentiator which is molecularly different from any heretofore-identified cytokines.

Animals↗
PubMed1993

Megakaryocyte, erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes.

Bone marrow progenitor cell assays of three cell lineages, i.e., colony-forming unit megakaryocytes (CFU-Meg), burst-forming unit erythrocytes (BFU-E) and colony-forming unit granulocyte-macrophages (CFU-GM), were performed for 21 patients with myelodysplastic syndromes (MDS). Markedly reduced or absent colony formation was found in 67% of the patients for CFU-Meg and all patients except 2 with refractory anemia (RA) for BFU-E. Abnormal CFU-GM colony formation was found in only 5 of 12 patients with RA and RA with ring sideroblasts, in contrast to all of the RA patients with excess of blasts and excess of blasts in transformation. Defective colony formation of all three cell lineages was seen in 63% of the MDS patients. The colony number of CFU-Meg correlated significantly with the numbers of both BFU-E and CFU-GM. These findings indicate that hematopoiesis in MDS patients is disturbed due to a qualitative or quantitative defect at the multipotent stem cell level.

Adolescent↗
PubMed1993

Inhibitory effects of S-(1,2-dicarboxyethyl)glutathione on collagen-induced platelet aggregation; enhancements of cyclic AMP level and adenylate cyclase activity in platelets by S-(1,2-dicarboxyethyl)glutathione.

S-(1,2-Dicarboxyethyl)glutathione (DCE-GS) in addition to being present in the liver, lens, and heart, also inhibited platelet aggregation. To clarify these inhibitory effects, the role of DCE-GS in the release of ATP and serotonin from platelets was studied, as was thromoboxane A2 formation, cyclic AMP level and adenylate cyclase activity in human platelets. The results are as follows: DCE-GS at a concentration of 1.3 mM inhibited ATP and serotonin release from platelets induced by collagen, by 77.4 +/- 4.3 and 78.7 +/- 6.3%, respectively. At 1.5 mM DCE-GS also inhibited the formation of thromboxane B2 by 79.6 +/- 4.1%. Incubation of human platelet rich plasma with 2 mM of DCE-GS for 10 min increased the cyclic AMP level and the activity of adenylate cyclase by 204 +/- 28 and 211 +/- 11.7%, respectively. These results suggest that the inhibitory effect of DCE-GS on the platelet aggregation induced by collagen is due to an increase in the cyclic AMP level in platelets, which in turn may be due to enhancement of the activity of adenylate cyclase.

Adenosine Triphosphate↗
PubMed1993

Successful treatment of life-threatening ventricular tachycardia with high-dose propranolol under extracorporeal life support and intraaortic balloon pumping.

The use of propranolol is generally contraindicated in patients with congestive heart failure. However, we successfully used a continuous high-dose infusion of propranolol, in combination with the use of extracorporeal life support (ECLS) and intra-aortic balloon pumping (IABP), to treat refractory life-threatening ventricular tachycardia in a patient with postoperative congestive heart failure. The early combined use of ECLS and IABP before irreversible myocardial damage contributed to the successful outcome.

Combined Modality Therapy↗
PubMed1993

[Effects of local anesthetics on rat macrophage phagocytosis].

We examined whether phagocytosis by macrophages (M phi s) is affected by local anesthetics (lidocaine HCl, prilocaine HCl, mepivacaine HCl, tetracaine HCl and procaine HCl). Opsonized zymosan, fetal bovine serum and one local anesthetic were added to each M phi sample. After a 30-min incubation, M phi s were washed to make Giemsa stained slides for counting. The phagocytosis rate was calculated by counting the phagocytosizing M phi s per 200 cells with an optical microscope, and rates for the samples containing local anesthetics were compared with those for the non-treated samples. Inhibition of phagocytosis was reversible, dose-dependent and pH dependent for all local anesthetics. Tetracaine HCl inhibited phagocytosis most and procaine HCl, least. These results suggest that local anesthetics at the level of clinical use inhibit leukocyte phagocytosis and therefore may interfere with the normal function of cells fundamental to host defense.

Anesthetics, Local↗
PubMed1993

Application of low-dose etoposide therapy for myelodysplastic syndromes.

The therapy for myelodysplastic syndromes (MDS) and acute leukemia (AL) transformed from MDS is not well established. Etoposide (VP 16-213) at low concentrations shows differentiation-inducing activity against leukemic cells in vitro. A prior study showed that oral low-dose etoposide therapy was effective in patients with chronic myelomonocytic leukemia. We used low-dose etoposide to treat six patients with refractory anemia with excess blasts in transformation (RAEB-t) and seven patients with AL transformed from MDS. The etoposide (50 mg, 2-7 times/week) was usually administered intravenously to ensure reliable bioavailability. Of 12 assessable patients, four RAEB-t patients achieved a partial response and one AL patient achieved complete remission. The responders became transfusion-independent, and this continued for 2-9 months while etoposide therapy was continued. Three of five responders had been resistant to prior repeated low-dose cytarabine therapy. The side effects were mild and well tolerated. Heterogeneous mechanisms were surmised to explain the clinical effects of low-dose etoposide. Several aspects, including the optimal schedule of low-dose etoposide therapy, the effect of this therapy on the patients' survival, the usefulness of combination therapy with other chemotherapeutic drug(s) and/or cytokine(s), should be investigated in the future.

Acute Disease↗
PubMed1993

Production of dihydrofolate reductase by an improved continuous flow cell-free translation system using wheat germ extract.

We have examined the characteristics of protein synthesis in an improved continuous flow cell-free translation system prepared from wheat germ extract with dihydrofolate reductase mRNA as the translated message. Continuous buffer flow and separation of the product from the reaction mixture were accomplished by the use of a modified Amicon ultrafiltration chamber as the reaction vessel. The system worked for 19 hours and produced 1.52 nmol (27.4 micrograms) of enzymatically active dihydrofolate reductase.

Base Sequence↗
PubMed1993

Fibronectin expression in salivary gland pleomorphic adenoma.

The distribution of fibronectin in the normal and pleomorphic adenoma of the salivary gland was investigated in forty cases of surgically resected tumor specimens. The immunoreactivity of fibronectin using polyclonal antibody (anti-fibronectin A2 45, Dakopatts, Denmark) was detected in the cytoplasm of intercalated duct cells and certain striated duct cells in normal salivary glands. Pleomorphic adenoma showed few fibronectin positive cells with a scattered or isolated distribution within the epithelial tumor elements of tubulo-ductal or solid foci of tumor cells. Modified myoepithelial cells and luminal cells of tubulo-ductal structures reacted strongly to fibronectin. In hyalinous, myxoid and chondroid areas, fibrillary myoepithelial cells expressed strongly positive reactivity but with diffuse staining in the myxoid and chondroid areas suggesting that fibronectin plays an important role in tumor cell-extracellular matrix interactions to produce the complex histopathological features of pleomorphic adenoma.

Adenoma, Pleomorphic↗
PubMed1993

Solution structures of Myb DNA-binding domain and its complex with DNA.

The DNA-binding domain of Myb consists of three imperfect tandem repeats, each of which contains three conserved tryptophans. The solution structure of the third repeat was established by NMR; it includes three helices maintained by a hydrophobic core formed by three tryptophans, together with two histidines, and the second and third helices form a helix-turn-helix-related motif. Here, we report the whole structure of the DNA-binding domain, as determined by NMR. Each of the first and second repeats resembles the third one in structure, retaining three helices. As a whole, the DNA-binding domain contains an entirely unique structure, a triple helix-turn-helix-related motif. To determine the role of each repeat in DNA-binding, a 16-mer DNA duplex that is specifically recognized by Myb was synthesized and then its complex with the DNA-binding domain has been investigated by 3D-NMR. The interaction mode between the whole DNA-binding domain and the duplex has shown that the third helix in each repeat likely locates in the majour groove of DNA. It is suggested that the Myb DNA-binding domain wraps around the DNA duplex by fitting the triply repeated helix-turn-helix-related motifs in the majour groove.

Base Sequence↗
PubMed1993

Antioxidant and pro-oxidant assay for a new drug GEPC: detected by ESR spectrometry and by protective effects on lipid peroxidation and biomolecule degradation.

L-Ascorbic acid 2-(20 beta-11-oxo-olean-12-en-29-oic acid ethylester-3-beta-yl hydrogen phosphate) sodium salt (GEPC) is a newly synthesized compound representing a phosphate diester linkage of glycyrrhetic acid ethylester and ascorbic acid. In the present study, we found that GEPC effectively inhibited Fe(III)-ADP/NADPH-induced peroxidation of liver microsomes. The inhibitory effect was much greater than that of glycyrrhetic acid (GA), and contrasted with the stimulatory effect of ascorbic acid. An ESR study showed that GEPC appeared to have a great loss of the DPPH and superoxide radical scavenging effects of ascorbic acid. However, GEPC, like ascorbic acid, inhibited hydroxyl radicals generation in both Fe(II)-H2 O2 and Cr(VI)-H2 O2 systems. GEPC, unlike ascorbic acid, showed no pro-oxidant effect and acted as an effective iron-chelating agent in the ESR study or in the iron-induced deoxyribose and DNA degradation assays. The hydroxyl radical scavenging effect of GEPC was further demonstrated by its protective effect on the hydroxyl radical- induced degradation of certain biomolecules, i.e., carbohydrates, amino acids, and DNA. These results demonstrate that beside its protective effect on ascorbic acid autoxidation and increasing water solubility of GA, GEPC is also an antioxidant though not so powerful as ascorbic acid but more powerful than GA.

Amino Acids↗
PubMed1993

[Interaction of cardiovascular effect of calcium channel blocking drugs and those of inhalation anesthetics in humans].

The hemodynamics in the patients undergoing craniotomy was studied to evaluate the interaction of cardiovascular effects of calcium blocking drugs (nicardipine NCR or diltiazem DL) and those of inhalation anesthetics (0.6% isoflurane Iso or 0.9% sevoflurane Sevo). (Group I = NCR alone, Group II = NCR+Iso, Group III = NCR+Sevo, Group IV = DL alone, Group V = DL+Iso, Group VI = DL+Sevo) Anesthesia was maintained with neuroleptanesthesia (N2O 60%). A 30% reduction in systolic blood pressure was achieved and this was maintained for 60 minutes in each groups. The following effects were observed during induced hypotension. 1) Heart rate increased in the group I and II, but decreased in the group IV, V and VI. 2) Cardiac output increased in the group I and II, but significantly decreased in the group VI. 3) Systemic vascular resistance and left ventricular stroke work decreased in all the groups. 4) Pulmonary vascular resistance decreased slightly in all the groups. 5) Cardiac arrhythmias were observed in 4 cases of the group IV and VI. These results suggest that the presence of Iso or Sevo at low concentrations does not have a marked effect on the pharmacologic action of NCR or DL in humans.

Adult↗
PubMed1993

[Activity of defensins from human neutrophils against Mycobacterium avium complex].

We examined the activity of defensins from human neutrophils against Mycobacterium avium complex (MAC). MAC were cultured in the presence of defensins at 37 degrees C for 4-48 hours. After incubation, colony counts were enumerated by colony-forming units (CFU). Human neutrophil peptide-1 (HNP-1) at 5 micrograms/ml had the ability to kill MAC. We tested 8 strains of MAC. HNP-1 was successful in killing every strain, although the degree of killing varied from strain to strain. We also found that HNP-2 and HNP-3 were as effective in killing MAC as HNP-1. We suggest that defensins play an important role in the host defenses against MAC.

Blood Bactericidal Activity↗
PubMed1993

[Post-operative intra-arterial chemotherapy for high grade malignant musculoskeletal sarcoma].

Twenty-nine patients with high grade malignant musculoskeletal sarcoma were treated with chemotherapy. Intra-arterial chemotherapy was performed post-operatively for patients with local recurrence, patients with poor response to pre-operative chemotherapy or patients with intra-lesional or marginal surgical margin. The local recurrence rate in patients with intra-arterial chemotherapy (8.8%) was lower than in those with intravenous chemotherapy (37.5%). Patients with post-operative intra-arterial chemotherapy showed no local recurrence. Of the 29 patients except stage 3 with intra-arterial chemotherapy, the metastatic rate in patients with intra-arterial chemotherapy (41.4%) was lower than in chemotherapy patients with intravenous chemotherapy (83.3%). The rate in the post-operative group (28.6%) was lower than in the pre-operative group (42.9%) or pre- and post-operative group (50.0%). The ten-year survival curve of patients given intra-arterial chemotherapy (51.0%) was higher than in patients on intravenous chemotherapy (17.9%). Among the 34 patients who underwent intra-arterial chemotherapy, the survival rate in the other pre- and post-operative groups and the post-operative group (55.6%) was higher than in the pre-operative group and pre- and post-operative group (49.8%).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Caesarean section in a patient with past history of fulminant malignant hyperthermia].

Caesarean section in a 26 year old patient (50 kg, normal weight 36 kg) with past history of fulminant malignant hyperthermia (f-MH) is reported. Hyperthermia over 42 degrees C and subsequent cardiac arrest occurred during general anesthesia with nitrous oxide-oxygen-halothane and succinylcholine when she had been planned to perform hip joint arthroplasty at the age of 7. Prophylactic oral dantrolene administration started 4 days before the operation and the dose went up to 75 mg. Further 25 mg was given as premedication on the day of the operation. Intravenous dantrolene was administered 1.2 mg.kg-1 during the operation and 0.6 mg.kg-1 on the day after surgery. The Caesarean section was performed under spinal anesthesia with hyperbaric tetracaine 20 mg. No clinical symptoms of MH occurred during perioperative period. The delivered baby was a healthy female and no side effects of dantrolene were observed.

Adult↗
PubMed1993

[Two cases of acute leukemia with t(6;9) (p23;q34)].

Two cases of acute leukemia with a t (6;9) (p23;34) chromosome abnormality are reported. The first case was a 34-year-old female who was hospitalized in October 1989. A diagnosis of FAB-M1 was made. Chromosomal analysis of the bone marrow cells showed a 46, XX, t (6;9) (p23;q34). Complete remission was achieved after two courses of BHAC-DMP therapy. In September 1991, at the time of relapse, chromosomal analysis revealed two abnormal clones consisting of a 46, XX, t (6;9) (p23;q34), -12, -17, +der (12) t (12;17) (p11.2;q11.2) with a residual normal clone. She died in February 1992. The second case was a 42-year-old male who was hospitalized in January 1990. He was diagnosed as having RAEB. Chromosomal analysis of the bone marrow cells showed 46, XY, t (6;9) (p23;q34). Three months later, the disease progressed to acute leukemia accompanied by leg ulceration with leukemic cell infiltration. Small-dose ara-C therapy was given, but with no effect. After two subsequent courses of therapy with low-dose etoposide, complete remission was achieved. Four months later, relapse occurred, and the patient died of sepsis in February 1991. In the literature, 31 cases of myeloproliferative disorders with t (6;9) have been reported.

Acute Disease↗
PubMed1992

Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.

The DNA-binding domain of the c-myb protooncogene product consists of three imperfect tandem repeats of 51 or 52 amino acids, each of which contains three conserved tryptophans, spaced 18 or 19 amino acids apart. The structure of the third repeat, which is essential for sequence-specific DNA binding, has been determined by NMR with distance geometry calculation. It includes three well-defined helices (residues 149-162, 166-172, and 178-187) maintained by a hydrophobic core that includes the three conserved tryptophans, together with two histidines. Helices 2 and 3 form a structure related to but distinct from a canonical helix-turn-helix motif. In particular, the turn between these helices is one amino acid longer than the corresponding turn in bacterial repressors and homeodomains and contains a proline residue. In addition, the architecture of the three helices is different from those of homeodomains and DNA-binding domains of bacterial repressors. Based on the present structure, the binding mode of Myb repeat 3 with a specific DNA is also discussed.

Amino Acid Sequence↗
PubMed1992

Spermine down-regulates superoxide generation induced by fMet-Leu-Phe in electropermeabilized human neutrophils.

Effect of spermine, a naturally occurring polyamine, was investigated on superoxide generation in intact and electropermeabilized human neutrophils. Spermine suppressed N-formyl-methionyl leucyl phenylalanine (fMLP)-induced superoxide generation in permeabilized cells by reducing the rate and shortening the duration time. The inhibition was specific for spermine comparing with its precursor amines, spermidine and putrescine. The inhibition was not observed when cells were preincubated with spermine without permeabilization. Concanavalin A-induced superoxide generation was also down-regulated by spermine in permeabilized cells, but the activation induced by non receptor-mediated agonist (dioctanoylglycerol, phorbol myristate acetate, and arachidonate) was not affected by spermine. On the other hand, GTP-gamma-S-induced activation of superoxide generation was substantially suppressed by spermine. These results indicate that spermine inhibition occurs at a step prior to protein kinase C in signal transduction or in a pathway which is independent of the kinase.

Cell Membrane Permeability↗