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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 325 records · Page 18Linked to original sources

Upregulation of low density lipoprotein receptor by gemfibrozil, a hypolipidemic agent, in human hepatoma cells through stabilization of mRNA transcripts.

Gemfibrozil reduces the plasmal levels of cholesterol and triglyceride in patients with hyperlipidemia by a mechanism that is not well understood. The present study evaluated the effect of gemfibrozil on the LDL receptor in human hepatoma cells compared with that of pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Exposure to gemfibrozil, 40 mumol/L, for 3 days increased the binding of 125I-LDL to the surface of three lines of human hepatoma cell, HepG2, HuH7, and HLE by 1.5- to 2.0-fold. Similar findings were observed with pravastatin. Scatchard analysis with 125I-LDL indicated an increased number of LDL receptors on the cell surface of HepG2 cells when treated with gemfibrozil and pravastatin. However, the gemfibrozil-treated cells exhibited no increase in the binding of 125I-epidermal growth factor (EGF). Gemfibrozil increased the levels of LDL receptor mRNA and protein in HepG2 cells. The increase in LDL receptor activity induced by pravastatin was abolished by concomitant administration of mevalonic acid, 770 mumol/L. This effect was not seen with gemfibrozil, suggesting the mechanism differs for the two lipid-lowering drugs. To determine whether this increase in mRNA was due to transcriptional activation, we prepared HepG2 cells transfected with an LDL receptor promoter-reporter construct that contained a sterol regulatory element. The expression of LDL receptor regulated by the sterol regulatory element was increased by pravastatin, but not by gemfibrozil. We evaluated the stability of the mRNA in the presence of actinomycin D to explain the increase in the LDL receptor mRNA. Gemfibrozil prolonged the half-life of the mRNA for LDL receptor but not that for the EGF receptor. Stabilization of the LDL receptor mRNA is suggested to be the novel mode of action of gemfibrozil.

Carcinoma, Hepatocellular↗

Resin glycosides. XXV. Multifidins I and II, new jalapins, from the seed of Quamoclit x multifida.

Alkaline hydrolysis of the ether-soluble resin glycoside fraction of seeds of Quamoclit (Q.) x multifida, a hybrid between Q. pinnata and Q. coccinea, gave new glycosidic acids, multifidinic acids A and B, along with two known glycosidic acids, quamoclinic acid A and operculinic acid A, and three organic acids, (2S)-2-methylbutyric acid, n-decanoic acid and n-dodecanoic acid. Further, as major ether-soluble resin glycosides, new jalapins named multifidins I and II, were isolated accompanied by quamoclins I-IV, which were previously obtained from seeds of Q. pinnata. The structures of multifidins I and II, and multifidinic acids A and B have been determined on the basis of chemical and spectral data.

Butyrates↗

Characterization of canine herpesvirus glycoprotein D (hemagglutinin).

Glycoprotein D (gD) of canine herpesvirus (CHV) YP2 strain was expressed in COS-7 and insect (Spodoptera frugiperda; Sf9) cells. The gDs expressed in COS-7 and Sf9 cells reacted with a panel of monoclonal antibodies (MAbs) against CHV gD (hemagglutinin) and an MAb 25C9 against feline herpesvirus type 1 (FHV-1) gD by indirect immunofluorescence assay, and possessed a molecular weight (MW) of approximately 51-55 and 41-46 kilodalton (kDa), respectively, when examined by immunoblot analysis. After treatment with tunicamycin, the MW of the gD expressed in Sf9 cells became approximately 37 kDa. By hemadsorption (HAD) tests using canine or feline red blood cells (RBC), COS-7 cells expressing CHV gD adsorbed only canine RBC, but not feline RBC, whereas control COS-7 cells expressing FHV-1 gD adsorbed feline RBC, but not canine RBC. By hemagglutination (HA) tests, lysates of Sf9 cells expressing CHV gD agglutinated canine RBC, but not feline RBC. These HA and HAD activities were inhibited by HA-inhibition MAbs against CHV gD. Control lysates of Sf9 cells expressing FHV-1 gD agglutinated only feline RBC. Serum from mice inoculated with lysates of Sf9 cells expressing CHV gD possessed a high titer of virus-neutralizing activities against CHV infection. These results indicated that CHV gD is structurally similar to FHV-1 gD, but is functionally different from FHV-1 gD.

Alphaherpesvirinae↗

Adhesion of insect cells expressing the feline herpesvirus type 1 hemagglutinin (gD) to feline cell lines.

Feline herpesvirus type 1 (FHV-1) gD-expressing Sf9 cells adhered to two feline cell lines, but not to the porcine, bovine, or canine cell lines tested. In addition, this adhesion activity was inhibited by a monoclonal antibody against FHV-1 gD. These results showed that the FHV-1 gD might bind to a specific-molecule(s) on the surface of feline cell lines. We discussed a possible importance of the FHV-1 gD in host cell restriction to FHV-1 infection.

Alphaherpesvirinae↗

Identification and DNA sequence analysis of the Marek's disease virus serotype 2 gene homologous to the herpes simplex virus type 1 glycoprotein H.

Marek's disease virus (MDV) serotype 2 (MDV2) gene homologous to the glycoprotein H (gH) gene of herpes simplex virus type 1 was identified and sequenced. The predicted region encoding for the MDV2 gH gene was 2436 nucleotide and the primary translation product was 812 amino acids with a molecular weight of 89.4 kDa. The protein encoded by MDV2 gH gene has a number of features characteristic of a membrane-associated glycoprotein. First, there are 9 potential N-linked glycosylation sites and 11 cysteine residues, and 6 of the sites and 8 of the residues were conserved among all of the three MDV serotypes. Second, this protein had N-terminal and C-terminal hydrophobic regions, which were a signal sequence and a transmembrane-anchor domain, respectively. From the northern blot analysis, it was suggested that a transcript encoding MDV2 gH and a poly-cistronic transcript encoding MDV2 thymidine kinase, gH, and possibly other genes of downstream on this strand existed. Alignment of the amino acid sequences of the gH homologues among the three MDV serotypes showed 57.5% (MDV1 and MDV2), 56.2% (MDV1 and HVT), and 50.1% (MDV2 and HVT) identities.

Amino Acid Sequence↗

Effect of attenuated Erysipelothrix rhusiopathiae vaccine in pigs infected with porcine reproductive respiratory syndrome virus.

Twenty 2nd specific pathogen-free pigs were divided into 4 groups: Group A were infected with porcine reproductive and respiratory syndrome (PRRS) virus at 6 weeks of age and treated with available swine erysipelas and swine fever combined vaccine (vaccinated) at 7 weeks of age; Group B were vaccinated at 7 weeks of age and infected with PRRS virus at 8 weeks of age; Group C were vaccinated at 7 weeks of age: Group D were neither vaccinated nor infected with PRRS virus. All pigs were challenged to Erysipelothrix rhusiopathiae C42 strain at 10 weeks of age. No clinical signs appeared after vaccination of group A and B pigs, thus confirming that the safety of the vaccine was not influenced by infection with PRRS virus. None of the pigs in Groups A and C developed erysipelas after challenge exposure to E. rhusiopathiae. In contrast, fever and/or urticaria appeared transiently in all pigs of Group B after challenge exposure. At the time of challenge exposure to E. rhusiopathiae, the PRRS virus titer was high in sera of Group B, but was low in those from Group A. However, vaccination of pigs with attenuated E. rhusiopathiae was effective in dual infection with PRRS virus and E. rhusiopathiae, because the clinical signs were milder and the E. rhusiopathiae strain was less recovered from these pigs compared to pigs of group D.

Animals↗

Role of interleukin-1beta in superovulation in rats.

In this study, the changes in interleukin-1beta (IL-1beta) mRNA expression and its localization in the ovary were studied in pregnant mares' serum gonadotropin (PMSG)-human CG (hCG) injected immature rats. Moreover, to study the in vivo role of IL-1 during ovulation, the IL-1 receptor antagonist (IL-1ra) was injected into the bilateral bursae (100 microg/15 microl/bursa) immediately or at the 3rd, 5th, 10th h after hCG injection. IL-1beta mRNA expression in the ovary had significantly (P<0.05) increased at the 6th h after hCG injection, and its level depended on the time interval between PMSG and hCG injections; the maximal IL-1beta mRNA expression was observed when hCG was injected 48 h after the PMSG injection. The signals of IL-1beta mRNA localized in the thecal layer, particularly in the large preovulatory follicles. Intrabursal IL-1ra injection at the 3rd h after hCG injection showed a trend toward lowering the number of ova shed, and the injection at the 5th h significantly (P<0.01) decreased the number of ova shed compared with the saline injected control group. At the 24th h after hCG injection, there were a few large preovulatory follicles with distinguishable theca and granulosa layers in the IL-1ra treated ovary, although these two layers were indistinguishable in the control ovary. These results indicated that IL-1beta mRNA expression was definitely induced by hCG stimulation, and, moreover, this expression was dependent on the stage of follicular maturation. IL-1 may be important for the ovulation in the superovulatory cycle by PMSG in rats.

Animals↗

Surgical repair for atrial septal defect in patients over 70 years of age.

Atrial septal defect (ASD) is the most common congenital heart anomaly encountered in adults. For patients over 60 years old, acceptable operative mortality and symptomatic improvement following surgery have been reported. We reviewed patients with ASD aged over 70 years and studied their preoperative hemodynamics, the surgical procedures used and the results. Between January 1994 and December 1996, 18 patients over the age of 40 years underwent surgical repair of ASD. Four patients were over 70 years of age (Group A). The other 14 patients were studied as a control group (Group B). We compared the preoperative clinical status, hemodynamic data, and surgical results between the two groups. The postoperative clinical status of Group A was studied during the follow-up period. The NYHA functional class of the elderly patients was greater than that of the middle-aged patients. None of the elderly patients had pulmonary hypertension. Moderate or severe tricuspid valve regurgitation (TR) due to annular dilatation was found, and tricuspid annuloplasty was performed in all four elderly patients. There were no operative or hospital deaths in either group. The NYHA functional class and TR improved in all the aged patients after surgery. In order to prevent progressive tricuspid annular dilatation due to an intraatrial left to right shunt, surgical closure of ASD should be performed for physically active adult patients.

Adult↗

Mitral valve repair with extensive resection of the anterior leaflet for regurgitation due to Barlow's disease. Report of a case.

We recently performed mitral valve repair for a case of mitral regurgitation due to Barlow's disease, which is relatively rare in Japan. Both the anterior and posterior leaflets were affected by advanced myxomatous change, and appeared markedly thickened and redundant. Although extensive resection of the anterior leaflet is not a generally accepted method, nearly one fourth of the anterior leaflet was resected in this case. Now, at 36 months after the operation, there is only trivial regurgitation and the patient is doing well and without symptoms. We believe that extensive resection of the anterior leaflet can be a useful treatment for repair of a redundant anterior leaflet with excess tissue.

Cardiac Surgical Procedures↗

[Intrathecal immunoglobulin synthesis evaluation in bone marrow transplantation].

The central nervous system involvement in chronic graft versus host disease (GVHD) has been suggested. Chronic GVHD resembles auto immune connective tissue disorders. In order to investigate the immunoglobulin intra blood brain barrier (BBB) synthesis during chronic GVHD, and contribute to understanding the pathophysiology of the disease, we studied 33 patients who underwent allogeneic bone marrow transplants (BMT) from HLA identical related donors. Immunoglobulin intra BBB synthesis was investigated quantitative and qualitatively. The samples were collected pre BMT, pos BMT and during chronic GVHD. There were no evidence of immunoglobulin intra BBB synthesis, and no oligoclonal bands were found. Only isolated cases suggested IgO and IgA intra BBB synthesis, and in one case IgM during GVHD.

Adult↗

[Blood-brain barrier evaluation in bone marrow transplantation].

The blood-brain barrier (BBB) contributes to the central nervous system (CNS) immunological isolation. BBB has never been studied in patients who developed chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplants (BMT), from HLA identical related donors. BBB disruption was investigated through the cerebrospinal fluid (CSF) proteins, quantitative and graphically, in order to detect the incidence and possible pathophysiology of the CNS involvement in chronic GVHD. Thirty three CSF and matched serum samples from chronic myeloid leukemia patients were collected pre BMT pos BMT and during chronic GVHD. There was no evidence of BBB disruption in any patient studied.

Adolescent↗

A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis.

Corticosteroids are effective in bringing about a clinical remission in patients with ulcerative colitis. However, in severely relapsed cases, corticosteroids are not always effective even when a high dosage is administered. In addition, the long-term use of corticosteroids often causes serious side effects. Therefore, an alternative treatment for active ulcerative colitis is necessary in order to avoid these clinical problems. In the present pilot study, the efficacy of leukocytapheresis using a centrifugal procedure was evaluated for corticosteroid-resistant, active ulcerative colitis. Fourteen patients with corticosteroid-resistant severely active ulcerative colitis were treated by leukocytapheresis. Thirteen patients (92.9%) achieved clinical remission within 4 weeks after the apheresis, and remained in remission for 8 months on average without any additional corticosteroid therapy. In the remaining patient, in whom remission was not induced, a total colectomy was performed immediately after the fourth course of leukocytapheresis. No significant side effects were noticed throughout the therapy. Both colonoscopic and histological examinations confirmed the beneficial effect of this procedure in terms of the reduction of severe inflammation of the affected colon. We found that the expression of two adhesion molecules, L-selectin and VLA4a, on the surface of peripheral leukocytes was decreased after this new therapy.

Adrenal Cortex Hormones↗

Aflastatin A, a novel inhibitor of aflatoxin production by aflatoxigenic fungi.

Aflastatin A, a novel inhibitor of the production of aflatoxin by aflatoxigenic fungi, has been isolated from the solvent extract of mycelial cake of Streptomyces sp. and its molecular formula was determined as C62H115NO24. Aflastatin A completely inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999 in liquid medium or on agar plate at a concentration of 0.5 microgram/ml. The mycelial growth of this fungus was not affected in the liquid medium at the same concentration, while the hyphal extension rate was reduced on the plate together with some morphological changes. The growth of the fungus was not completely inhibited even at a concentration of 100 micrograms/ml. Aflastatin A exhibits antimicrobial activity against some bacteria, yeasts and fungi as well as antitumor activity.

Aflatoxins↗

[Development of anti tumor agents targeting angiogenesis].

Aberrant angiogenesis is closely involved in invasion/metastasis as well as enlargement of tumor. One recent highlight is to develop anti angiogenic drugs by targeting tumor angiogenesis. Here we describe how tumor angiogenesis is regulated and also recent topics related to angiogenic drug in clinical trials.

Antineoplastic Agents↗

Stereo fluoroscopy-assisted percutaneous needle puncture of the vertebral body.

The purpose was to determine whether real-time three-dimensional imaging by stereo fluoroscope could alleviate the nuisance of moving the fluoroscope C-arm during needle biopsy of the spine. Fifteen lumbar vertebrae of four beagle dog cadavers were used in a simulation. We used a newly devised portable-type stereo fluoroscope, which alternatively exposes the X-ray from left and right X-ray tubes so that a surgeon can decode left and right images displayed alternately on a monitor by using polarizing glasses. A 2-mm-diameter Kirschner wire was inserted into the vertebral bodies by a posterolateral approach without moving the C-arm. An axial view of the roentgenogram of each vertebra found all 15 wires to be appropriately inserted. This would appear to be a time-saving feature.

Animals↗

[Axonal Guillain-Barré syndrome associated with antibodies to Ga1NAc-GD1a and unidentified acidic glycolipids].

A 19-year-old male student with Guillain-Barré syndrome (GBS) was described. Neurologic examination revealed severe and moderate degrees of weakness in the distal and proximal muscles, respectively, in both upper and lower limbs. He was unable to walk even with support. Both superficial and deep sensations were normal. Serial electrophysiologic studies indicated that the predominant pathologic process of the peripheral nerve was axonal degeneration of motor nerves. Enzyme-linked immunosorbent assay showed that serum from the patient had markedly high titer of IgG antibody to Ga1NAc-GD1a (1:204,800). Thin-layer chromatography with immunostaining revealed that his serum IgG strongly reacted with Ga1NAc-GD1a prepared from both bovine brain and cauda equina, and additionally with unidentified acidic glycolipids prepared only from bovine cauda equina. Serum containing antibody to Ga1 NAc-GD1a and the unidentified acidic glycolipids may be responsible for axonal degeneration of motor nerves in this patient.

Acetylgalactosamine↗