Search PubMed⌕ Search

Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 235 records · Page 13Linked to original sources
PubMed1999

Action of a new mammalian DNA polymerase inhibitor, sulfoquinovosyldiacylglycerol.

We found and previously reported a new mammalian DNA polymerase inhibitor from a sea alga, Gigartina tenella, (Ohta K., et al., Chem. Pharm. Bull., 46, 684-686, 1998). It was a new sulfolipid compound that belonged in the class of sulfoquinovosyldiacylglycerol. The biochemical properties have been investigated here. The compound, temporarily designated KM043, potently inhibited the activities of mammalian DNA polymerase alpha(pol. alpha) and DNA polymerase beta(pol. beta) and terminal deoxynucleotidyl transferase (TdT), and moderately, human immunodeficiency virus reverse transcriptase (HIV-RT). KM043 dose-dependently inhibited their activities, and each of their IC50 values was 0.25 microM for pol. alpha, 0.38 microM for TdT, 3.6 microM for pol. beta, or 11.2 microM for HIV-RT, and almost complete inhibition of each was achieved at 1.0 to 2.0 microM for pol. alpha and TdT, 7.5 microM for pol. beta and about 30 microM for HIV-RT. However, the compound did not influence the activities of prokaryotic DNA polymerases such as E. coli DNA polymerase I, and DNA metabolic enzymes like DNase 1. Inhibition of pol. alpha or beta by KM043 was non-competitive with both the DNA template and the substrate deoxythymidine 5'-triphosphate (dTTP). KM043 was weakly cytotoxic to cultured HeLa-S3 cells, and the IC50 value was 80 microM. KM043 could synergistically enhance the cytocidal effect of an anti-cancer chemotherapy agent, bleomycin. In the presence of 50 microM KM043, the effect ratio of (bleomycin plus KM043)/(bleomysin only) decreased from 0.76 to 0.22.

Animals↗
PubMed1999

Retinoid X receptor-antagonistic diazepinylbenzoic acids.

Several dibenzodiazepine derivatives were identified as novel retinoid X receptor (RXR) antagonists on the basis of inhibitory activity on retinoid-induced cell differentiation of human promyelocytic leukemia cells HL-60 and transactivation assay using retinoic acid receptors (RARs) and RXRs in COS-1 cells. 4-(5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-n- propyldibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX603, 6c) is an N-n-propyl derivative of an RXR pan-agonist HX600 (6a), and exhibited RXR-selective antagonistic activity. Similar RXR-antagonistic activities were observed with 4-(5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyl- 8-nitrodibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX531, 7a) and 4-(5H-10,11-dihydro-5,10-dimethyl-2,3-(2,5-dimethyl- 2,5-hexano)-dibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX711, 8b), which also inhibited transactivation of RARs induced by an RAR agonist, Am80. These compounds inhibited HL-60 cell differentiation induced by the combination of a low concentration of the retinoid agonist Am80 with an RXR agonist (a retinoid synergist, HX600). These results indicated that HX603 (6c), and the related RXR antagonists inhibit the activation of RAR-RXR heterodimers as well as RXR homodimers, which is a distinct characteristic different from that of the known RXR antagonist, LG100754 (9).

Animals↗
PubMed1999

Dicarba-closo-dodecaboranes as a pharmacophore. Novel potent retinoidal agonists.

The synthesis and biological evaluation of the dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Retinoidal activity was examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for the retinoid receptor RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. 4-[4-(1,2-Dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids and 4-[3-(1,2-dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids showed potent agonistic activity at concentrations of 10(-8)-10(-9) M. The results indicate that carboranes are applicable as the hydrophobic moiety of biologically active molecules.

Boron Compounds↗
PubMed1999

[Ligand recognition and activation mechanism of histamine H1 receptor].

Five amino acid residues of the human histamine H1 receptor that participate in histamine binding were identified using mutant H1 receptors by site-directed mutagenesis and 3D computer modeling of the receptor. The computer modeling provided two conformations of the receptor, non-active and active forms, and it was hypothesized that the binding of histamine to the receptor leads to the active state through the rewinding of the alpha-helix of TM-V. The binding sites of histamine were divided into two groups, one determined the ligand affinity and the other directly participated in the conformational change of the receptor, and the H1 antagonists bound only to the former. The mode of binding of histamine to the H1 receptor was different from those of catecholamine to the beta-receptor and of histamine to the H2 receptor.

Binding Sites↗
PubMed1999

Expression of osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells.

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) inhibits osteoclast differentiation, activity, and survival; therefore OPG/OCIF may regulate the resorption of dental hard tissues, such as alveolar bone, cementum, and dentin. To investigate this issue, reverse transcriptase-polymerase chain reaction using specific primers for OPG/OCIF was performed with total RNAs isolated from human gingival keratinocytes (HGKs), human gingival fibroblasts (HGFs), human periodontal ligament cells (HPDLs), and human pulp cells (HPCs) in culture. PCR products were found in HGFs, HPDLs, and HPCs, but not in HGKs, and the DNA sequence of these products was 100% identical to the reported sequence of the OPG gene. Northern blot analyses also showed that HGFs, HPDLs, and HPCs, but not HGKs, expressed OPG/OCIF transcripts of approximately 2.5 kb. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) increased OPG/OCIF mRNA levels in a dose-and time-dependent manner in HPDL. After 12 h of treatment, IL-1beta at 3 ng/ml and TNF-alpha at 3 ng/ml increased OPG/OCIF mRNA expression by 190% and 110%, respectively, with a maximal effect. The stimulatory effects of IL-1beta and TNF-alpha were also seen in HPC. However, IL-6 and transforming growth factor-beta had little effect on OPG/OCIF mRNA levels in HPDL. These findings suggest that OPG/OCIF synthesized by dental mesenchymal cells locally regulates the resorption of dental hard tissues through cytokines.

Cells, Cultured↗
PubMed1999

Isolation of two novel alternative splicing variants of allograft inflammatory factor-1.

Allograft inflammatory factor-1 (AIF-1) was initially cloned from rat cardiac allografts undergoing chronic rejection. AIF-1, possessing an EF-hand-like motif, is thought to be a Ca2+ binding protein. In this study, we identified two novel alternatively spliced variants of AIF-1 by reverse-transcription polymerase chain reaction. One variant encodes an AIF-1 protein that lacks 14 amino acids corresponding to one exon. The other variant encodes a truncated AIF-1 protein due to a frameshift introduced by an 85-bp insertion, and its C-terminal region differs from that of AIF-1. Interestingly, these variants have incomplete and no EF-handlike motifs, respectively. The expression level of the latter variant is high in peripheral blood leukocytes, and it is selectively expressed in macrophage-like cell lines.

Alternative Splicing↗
PubMed1999

Identification of protein kinase C phosphorylation sites involved in phorbol ester-induced desensitization of the histamine H1 receptor.

The histamine H1 receptor (H1R)-mediated signaling cascade is inhibited by phorbol ester-induced protein kinase C (PKC) activation. Cloning studies of the H1Rs have shown that several potential PKC phosphorylation sites are located in the third intracellular loop of H1R. To elucidate the molecular mechanism of PKC-mediated desensitization, we identified amino acid residues that are involved in the desensitization of the H1R. Two amino acid residues (Ser396, Ser398) were determined to be PKC phosphorylation sites by in vitro phosphorylation studies using a series of synthetic peptides. Treatment with phorbol ester decreased histamine-induced accumulation of inositol phosphates in Chinese hamster ovary cells expressing the H1R with a rightward shift in the EC50 value, which implies the uncoupling of the receptor from the G protein. Site-directed mutagenesis studies showed that substitution of alanine for Ser398 but not for Ser396 markedly attenuated the effect of phorbol ester, which suggests that the Ser398 residue was primarily involved in PKC-mediated desensitization.

Amino Acid Sequence↗
PubMed1999

[Human parvovirus B19-induced aplastic crisis in a patient treated with fibrin sealant].

A 42-year-old woman underwent a myomectomy on March 31, 1998. On the 10th postoperative day, leukopenia and reticulocytopenia were observed. Bone marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting a recent parvovirus infection. Both anti-parvovirus B19 IgM antibody and IgG antibody seroconversion was observed, and human parvovirus B19 DNA was detected by polymerase chain reaction (PCR) methods. The hematologic data on the patient rapidly improved thereafter. It was determined that acute-phase serum had inhibited CFU-E and BFU-E derived colony formation. Based on these findings, parvovirus B19-induced aplastic crisis was diagnosed. Fibrin sealant, which is a typical hemostatic agent produced from blood, had been during the operation. Human parvovirus B19 DNA was detected in the fibrin sealant by PCR. Our case report documents the transmission of human parvovirus B19 by fibrin sealant.

Acute Disease↗
PubMed1999

[Vasculo-Behcet's disease with fatal massive hemoptysis].

A 39-year-old man was admitted to our hospital because of hemoptysis. A chest X-ray film on admission showed a patchy shadow in the left lower lung field. Computed tomography revealed nodular opacities in the left pulmonary artery. The patient had history of oral ulcers, erythema nodosum, pustular lesions, and genital ulcers. Furthermore, the needle reaction was positive. Our diagnosis was an incomplete type of Behcet's disease. A radionuclide-venography and lung-perfusion study disclosed deep-vein thrombosis. Combined therapy with prednisolone, colchicine, and indomethacin farnesil was initiated, but the patient died of massive hemoptysis. Pathological examination revealed a ruptured aneurysm in the bronchus segmentalis apacalis and thrombotic angitis in the inferior vena cava. Behcet's disease is rarely a cause of hemoptysis. However, the prevalence of hemoptysis due to pulmonary vasculitis in patients with Behcet's disease has been reported to be 5 to 10% which is not so rare. Because of the poor prognosis, we want to emphasize Behcet's disease as a cause of hemoptysis.

Adult↗
PubMed1999

[Changes in intrapulmonary compression gas volume during measurement of the flow-volume curve].

Changes in intrapulmonary compression gas volume during flow-volume curve measurement were studied in 77 patients with bronchial asthma, 20 patients with emphysema, and 14 patients with pulmonary fibrosis. The peak point of intrapulmonary compression gas volume was observed at FEF 75 in the bronchial asthma and emphysema patients, and of FEF 25 in the pulmonary fibrosis patients. In the bronchial asthma patients, intrapulmonary compression gas volume increased significantly compared to the healthy control groups; that increase was especially obvious in cases where airway obstruction was severe, e.g. when FEV 1.0% was below 69% (p < 0.05). By contrast, the emphysema patients did not exhibit any significant increase in intrapulmonary compression gas volume compared to healthy control groups despite the existence of obstructive impairments. This study demonstrated that the intrapulmonary compression gas volume-curve is a useful index for the diagnosis of pulmonary diseases when combined with measurements of FVC and FEV 1.0%.

Adult↗
PubMed1999

[Benign clear cell tumor of the lung diagnosed by transbronchial biopsy].

A 26-year-old woman had an abnormal shadow on chest X-ray films during a general medical examination. A chest roentgenogram showed a nodular shadow 8 mm in diameter in the middle field of the right lung. Transbronchial biopsy specimens revealed that the coin lesion was a benign clear cell tumor. Benign clear cell tumors of the lung are rare; only 21 cases, including the present case, have been reported in Japan. Although the diagnosis in most of the cases reported required an open thoracotomy, for our patient the diagnosis was based solely on the findings of a transbronchial biopsy.

Adult↗
PubMed1999

Effects of experimental ocular inflammation on ocular immune privilege.

PURPOSE: To determine whether the inflammation of endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) alters key in vivo and in vitro parameters of ocular immune privilege. METHODS: For EIU induction, C3H/HeN mice received 200 microg lipopolysaccharide (LPS). For EAU induction, B10.A mice were immunized with 50 microg interphotoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell proliferation. Eyes with EAU were assessed for the capacity to support anterior chamber (AC)-associated immune deviation (ACAID) induction after injection of ovalbumin (OVA). RESULTS: Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH promptly lost its capacity to suppress T-cell proliferation and became mitogenic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 days and continued to remain elevated thereafter. Whereas 11-day EAU AqH failed to suppress T-cell proliferation, AqH at later time points reacquired immunosuppressive properties. Injection of OVA into the AC of eyes of mice with EAU failed to induce ACAID. CONCLUSIONS: The intraocular inflammation of EIU and EAU disrupted important parameters of immune privilege, ranging from breakdown of the blood- ocular barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate immune expression and inflammation can be a property even of inflamed eyes.

Animals↗
PubMed1999

[Allogeneic peripheral blood stem cell transplantation].

Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation (allo-BMT). Medication of granulocyte colony stimulating factor (G-CSF) and apheresis are well tolerated by donors and supply adequate numbers of stem cells for the engraftment. Patients engraft sooner using PBSCT compared to allo-BMT. Allo-PBSCT is a safe alternative to allo-BMT and has distinct advantages for donors and patients. Faster engraftment results in fewer transfusion, shorter hospitalization, and decreased cost. However future research to determine if long-term side effects from G-CSF will negatively affect donors is essential. Data regarding durability of hematopoiesis and incidence for graft versus host disease warrant further analysis.

Graft vs Host Disease↗
PubMed1999

[PBSCT and GVHD].

Allogeneic peripheral blood stem cell transplantation (PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation. Allo-PBSCT can provide rapid engraftment of neutrophils and platelets. Although the recipients of allogeneic PBSCT are infused 10-fold T cells compared with BMT, there is no evidence for a significant difference between PBSCT and BMT with regard to incidence and severity of acute graft-versus-host disease (GVHD). On the other hand, several reports have indicated a high risk for developing chronic GVHD after allogeneic PBSCT as opposed to BMT.

Acute Disease↗
PubMed1999

[Recurrent hemolytic uremic syndrome induced by pranoprofen].

A 25-year-old woman was admitted to our hospital because of dark red urine in 1993. A diagnosis of hemolytic uremic syndrome (HUS) because of findings of hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal dysfunction. The patient achieved remission with steroids and diuretics. In 1998 she caught a cold and happened to take the nonsteroidal anti-inflammatory drug, pranoprofen. Six hours later, she was rehospitalized because of dark red urine. Hemolytic anemia, fragmented erythrocytes, thrombocytopenia and renal dysfunction were observed again, also. A diagnosis of HUS was made. The patient was treated with steroid pulse therapy, infusion of fresh plasma, and plasma exchange transfusion. She recovered completely. In 1993 she had taker pranoprofen just prior to her first HUS episode. This was a recurrent case of HUS induced by pranoprofen.

Adult↗
PubMed1999

[Chronic bronchitis].

Chronic bronchitis (CB) is diagnosed from symptoms. It is important for the diagnosis to distinguish from other diseases accompanying similar symptoms. Recently, some diseases such as diffuse panbronchiolitis (DPB) have been recognized to have some characteristics different from CB, which used to include these diseases. The pathogenesis of CB is mostly smoking and to quit smoking is the basic and most important therapy. Target of medication in CB consists of hypersecretion, airway limitation and infection. A 14-membered ring macrolide such as erythromycin has been found to be effective in some patients with CB.

Anti-Bacterial Agents↗
PubMed1999

[Non-hemophilic patient with inhibitor against factor VIII produced after the second delivery].

A 33-year-old woman who had been healthy and had no history of abnormal bleeding developed widespread ecchymoses and intramuscular bleeding 4 months after her second delivery. On admission, laboratory examination data revealed that factor VIII activity was markedly reduced (4%) and APTT was prolonged (119.7s). Factor VIII inhibitor titer was high, at 19 Bethesda units. Her chemical and serological data were normal. No antinuclear antibodies were detected. We concluded that factor VIII inhibitor had been spontaneously produced after the second delivery and was responsible for her bleeding tendency. Prednisolone (60 mg/day) and factor VIII concentrates were administered to stop the bleeding, but factor VIII activity did not increase while factor VIII inhibitor titer increased to 29 Bethesda units. Therefore, treatment with factor VIII concentrate (was stopped while prednisolone was continued resulting in reduction of factor VIII inhibitor titer and improvement of her bleeding tendency. At 8 months after admission, factor VIII inhibitor titer was not detected by the Bethesda method and factor VIII activity and APTT were normal.

Adult↗