[Drug transporter: Molecular mechanism of polyspecific substrate recognition].
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Animals↗
Biomedical subjects
H Endo
Publications and source records attributed to H Endo.
A modified "elephant trunk" procedure for aortic arch replacement.
OBJECTIVES: We have devised a modified "elephant trunk" technique for primary aortic arch replacement that strengthens the distal anastomosis by preventing access of the blood stream to the distal suture line. The technique entails suturing an elephant trunk graft to the inner surface of the arch graft circumferentially just distal to the fourth of its 4 limbs. The inner graft is then inserted into the distal aortic lumen while the edge of the arch graft orifice is anastomosed to the aortic stump. This clinical trial was conducted to clarify its usefulness. METHODS: This technique was used in 5 cases of total arch replacement to reinforce distal anastomoses. RESULTS: All patients tolerated surgery well without complications such as paraplegia or thromboembolism. CONCLUSIONS: The advantages of this modified technique include simplicity and reproducibility.
Aged↗
[Antimicrobial activities of meropenem against clinically isolated strains in 1999].
We determined the antibacterial activity of meropenem (MEPM) and control drugs against clinical isolates of 310 strains of Gram-positive bacteria (14 species), 590 strains of Gram-positive bacteria (21 species), and 120 strains of anaerobic bacteria (10 species) in 1999. We compared the results thus obtained with those in 1993 and 1997. The results were as follows; 1. MEPM showed excellent antibacterial activities against most of the species tested, except for MRSA, E. faecium, E. avium, and methicillin-resistant S. epidermidis (MRSE). 2. MEPM had much higher activity than IPM and PAPM against Gram-negative bacteria including S. marcescens and P. aeruginosa, part of which have been reported to produce metallo-beta-lactamase. 3. There was little difference in the susceptibility of clinical isolates to MEPM between 1993 and 1999. Thus MEPM was shown to retain its potent and broad antibacterial activity now at the same level as before available for use in 1995.
Bacteria, Anaerobic↗
[A case of primary antiphospholipid syndrome complicated with pulmonary hypertension].
We describe the case of 55-year old male with antiphospholipid syndrome (APS) who developed pulmonary hypertension without any thromboembolic episode. Multiple pulmonary perfusion defects suggestive of in situ thrombosis were observed. Hematological findings revealed microangiopathic hemolytic anemia and thrombocytopenia. These findings were improved by anticoagulant therapy. We monitored mean pressure of pulmonary artery (mPAP) and total pulmonary vascular resistance (TPR) before and after using vasodilator agents by Swan-Ganz catheter. mPAP and TPR showed improvement on treatment with oxygen supplementation therapy and Isosorbide administration. Previously 11 cases with APS complicated with pulmonary hypertension were reported. Majority of these patients have had recurrent venous thrombosis, particularly deep vein thrombosis often accompanied by pulmonary thromboembolism (8/11 cases, 72%). However in this case pulmonary hypertension with APS may be induced by in situ thrombosis in pulmonary micro vessels.
Anemia, Hemolytic↗
[Antimicrobial activities of carbapenems and fourth generation cephems against clinically isolated strains].
We determined the antibacterial activities of 4 carbapenems (imipenem, panipenem, meropenem and biapenem) and 2 forth generation cephems (cefozopran and cefepime) against 850 bacterial strains (18 species) isolated during the period from January 1998 through September 2000. The 4 carbapenems showed excellent antibacterial activities against methicillin-susceptible S. aureus (MSSA), S. pneumoniae, E. faecalis, P. aeruginosa, M. (B). catarrhalis, B. fragilis and Peptostreptococcus spp. as compared with the cephems except the activity of panipenem against P. aeruginosa. Meropenem showed the highest antibacterial activity against 10 species of all Gram-negative strains determined. The antibacterial activities of 2 forth generation cephems against 6 species of Enterobacteriaceae were equal to or higher than those of carbapenems except meropenem. All drugs showed low antibacterial activities against methicillin-resistant S. aureus (MRSA).
Bacteria↗
[A case of metastatic breast cancer showing extraosseous accumulation of 99mTc-HMDP in axillary lymph nodes on bone scintigraphy].
We report a case of metastatic breast cancer that showed extraosseous accumulation of 99mTc-HMDP in left axillary lymph nodes on bone scintigraphy. Our patient had a giant left breast mass and multiple lymph node metastases with atypical calcifications. It is known that breast cancer sometimes is positively visualized as extraosseous accumulation on bone scintigraphy. Accumulation to metastatic lymph nodes of breast cancer has rarely been reported. It is suggested that bone scintigraphy is of benefit in detecting the metastatic lymph nodes of breast cancer as a screening or follow-up method.
Axilla↗
[Pediatric patients with common cold together with bacterial infection of upper respiratory tract--bacterial isolates from pharynx].
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Bronchitis↗
Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells.
Recent studies show that a mononuclear phagocyte lineage, including microglia, plays a possible role in the pathogenesis of Alzheimer's disease through nitric oxide (NO)-mediated neurotoxicity. Epidemiological studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) have a protective effect against Alzheimer's disease. Based on these observations, it has been hypothesized that an anti-Alzheimer's disease effect of NSAIDs could result from the inhibition of NO synthesis. We report here that indomethacin or ibuprofen dose-dependently reduce beta-amyloid protein and interferon-gamma-induced NO production, accompanied by an inhibition of inducible nitric oxide synthase mRNA expression in J774 cells, a murine macrophage cell line. Aspirin, however, does not produce such an effect, suggesting that the cyclooxygenases pathway is not involved in the inhibitory effects of NSAIDs on beta-amyloid protein and interferon-gamma-induced NO production in J774 cells.
Alzheimer Disease↗
Proteoliposomes colocalized with endogenous mitochondria in mouse fertilized egg.
Colocalization of mitochondria is the first step of intermitochondrial interaction or fusion in a cell. Here, we showed colocalization between exogenous mitochondria and endogenous ones or between exogenous proteoliposomes and endogenous mitochondria in mouse fertilized eggs by confocal laser microscopy. Isolated mitochondria from mouse liver and proteoliposomes containing mitochondrial membrane were directly labeled with red fluorescent aliphatic marker, PKH26, which is incorporated into lipid membrane, and then were microinjected into fertilized mouse eggs. Exogenous mitochondria appeared to be almost colocalized with endogenous mitochondria at the 4- and 8-cell stages, when mitochondria were stained with Rhodamine 123 (green fluorescent marker). On the contrary, when liposomes consisted of soy bean phospholipid were microinjected into the eggs as a control, their localization was different from that of endogenous mitochondria. Next, the submitochondrial particles and proteoliposomes were microinjected. Both the proteoliposomes and the submitochondrial particles appeared to colocalize with endogenous mitochondria at the 4-cell stage. These results suggest the existence of a factor that makes liposomes colocalize with mitochondria. Such a proteoliposome would be useful for the development of mitochondrial gene transfer techniques.
Animals↗
Telomerase activity and telomere length in benign and malignant human thyroid tissues.
Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P<0.006), respectively. Our findings suggest that change in telomerase activity and telomere length may be important for development of thyroid tumors.
Adenoma↗
Plasma cortisol levels in elderly female subjects with Alzheimer's disease: a cross-sectional and longitudinal study.
We investigated the plasma cortisol levels at a fasting state in elderly female Alzheimer's disease (AD), vascular dementia (VD), and non-demented subjects (n=66, 28 and 21, respectively). Twenty-eight AD subjects were followed for 40 months. The plasma cortisol levels in AD and VD subjects were significantly higher than those of non-demented subjects at baseline. In AD subjects in relatively early stages of the disease [Mini-Mental State Examination (MMSE)], at baseline, high plasma cortisol led to rapid declines in MMSE scores over a 40-month period.
Aged↗
Ganglioside GD3 and its mimetics induce cytochrome c release from mitochondria.
Ganglioside GD3 induced the release of cytochrome c from isolated rat liver mitochondria. This process was completely prevented by cyclosporin A and partially prevented by a cysteine protease inhibitor, n-acetyl-leu-leu-norleucinal. Cyclosporin A is a potent inhibitor of the permeability transition pore, whereas n-acetyl-leu-leu-norleucinal has no effect on this pore. These results indicate that the release of cytochrome c from mitochondria requires both the opening of the permeability transition pore and a cysteine protease inhibitor-sensitive mechanism. Gangliosides GD1a, GD1b, GT1b, and GQ1b along with the synthetic GD3 mimetics TMS-42 and CI-22, which are glycerophospholipids carrying a disialo residue, also induced cytochrome c release. In contrast, gangliosides GM1, GM2, and GM3 did not induce cytochrome c release. These results indicate that two sialo residues must play an important role in the induction of cytochrome c release by gangliosides.
Animals↗
Molecular cloning of the crustacean DD4 cDNA encoding a Ca(2+)-binding protein.
A cDNA, named DD4, was identified in the prawn Penaeus japonicus in a search for genes that were expressed during calcification of the crustacean exoskeleton. DD4 transcripts were detected in the epidermal cells underlying the exoskeleton specifically during the postmolt stage, when the calcification takes place. In the DD4 cDNA an open reading frame of 542 amino acids was found. The deduced protein was acidic and proline-rich, and exhibited similarity to the Drosophila Ca(2+)-binding protein calphotin in the amino acid sequence and composition. The DD4 cDNA was expressed in Escherichia coli to characterize Ca(2+)-binding of the encoded protein, and Ca(2+) was found to bind to a central segment of 186 amino acids. The DD4 protein is suggested to play a role in the calcification of the crustacean exoskeleton.
Amino Acid Sequence↗
Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and bioavailability of a poorly water-soluble drug from tablets prepared using macrogol and HPMC.
The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC.
Administration, Oral↗
Membrane decoration by amphiphilic block copolymers in bicontinuous microemulsions.
The effect of various amphiphilic block copolymers of different molar masses on the structure and phase behavior of ternary amphiphilic systems (water, oil, and nonionic surfactant) is investigated. Small amounts of PEP-PEO block copolymer lead to a dramatic increase in the volumes of oil and water, which can be solubilized in a bicontinuous microemulsion. High-precision neutron scattering experiments with a sophisticated contrast variation technique demonstrate that the polymers form uniformly distributed mushroom conformations on the surfactant membrane. Based on these observations, we propose a universal mechanism for the swelling behavior, which is due to the variation of the membrane curvature elasticity.
Cell Membrane↗
Differential regulation of exonic regulatory elements for muscle-specific alternative splicing during myogenesis and cardiogenesis.
Muscle-specific isoform of the mitochondrial ATP synthase gamma subunit (F(1)gamma) was generated by alternative splicing, and exon 9 of the gene was found to be lacking particularly in skeletal muscle and heart tissue. Recently, we reported that alternative splicing of exon 9 was induced by low serum or acidic media in mouse myoblasts, and that this splicing required de novo protein synthesis of a negative regulatory factor (Ichida, M., Endo, H., Ikeda, U., Matsuda, C., Ueno, E., Shimada, K., and Kagawa, Y. (1998) J. Biol. Chem. 273, 8492-8501; Hayakawa, M., Endo, H., Hamamoto, T., and Kagawa, Y. (1998) Biochem. Biophys. Res. Commun. 251, 603-608). In the present report, we identified a cis-acting element on the muscle-specific alternatively spliced exon of F(1)gamma gene by an in vivo splicing system using cultured cells and transgenic mice. We constructed a F(1)gamma wild-type minigene, containing the full-length gene from exon 8 to exon 10, and two mutants; one mutant involved a pyrimidine-rich substitution on exon 9, whereas the other was a purine-rich substitution, abbreviated as F(1)gamma Pu-del and F(1)gamma Pu-rich mutants, respectively. Based on an in vivo splicing assay using low serum- or acid-stimulated splicing induction system in mouse myoblasts, Pu-del mutation inhibited exon inclusion, indicating that a Pu-del mutation would disrupt an exonic splicing enhancer. On the other hand, the Pu-rich mutation blocked muscle-specific exon exclusion following both inductions. Next, we produced transgenic mice bearing both mutant minigenes and analyzed their splicing patterns in tissues. Based on an analysis of F(1)gamma Pu-del minigene transgenic mice, the purine nucleotide of this element was shown to be necessary for exon inclusion in non-muscle tissue. In contrast, analysis of F(1)gamma Pu-rich minigene mice revealed that the F(1)gamma Pu-rich mutant exon had been excluded from heart and skeletal muscle of these transgenic mice, despite the fact mutation of the exon inhibited muscle-specific exon exclusion in myotubes of early embryonic stage. These results suggested that the splicing regulatory mechanism underlying F(1)gamma pre-mRNA differed between myotubes and myofibers during myogenesis and cardiogenesis.
ATP Synthetase Complexes↗
Low plasma epinephrine in elderly female subjects of dementia of Alzheimer type.
One of the robust features of brain pathologies of dementia of Alzheimer type (DAT) is the impairment of the hippocampus, especially the cholinergic system. Several animal studies have suggested that the cholinergic system in the hippocampus is involved in the control of the plasma level of catecholamines and glucose. The stimulation of the hippocampal cholinergic system has resulted in the elevation of plasma catecholamines and glucose in rats. In the present study, we measured the plasma level of epinephrine, norepinephrine, dopamine, glucose, and insulin during a fasting state in the morning in hospitalized DAT (n=66), vascular dementia (VD) (n=28), or non-demented (ND) (n=21) females (mean age DAT=82. 49+/-4.98, VD=82.86+/-5.86, ND=82.95+/-7.77, respectively). Statistical analysis showed that the plasma level of epinephrine during a fasting state in DAT subjects was significantly lower than that of ND subjects; however, in VD subjects the level of epinephrine was not different from that of ND subjects. Other values did not differ significantly among the groups.
Aged↗
Multipotency of a bone marrow stromal cell line, TBR31-2, established from ts-SV40 T antigen gene transgenic mice.
Bone marrow is believed to contain multipotential stromal stem cells which can differentiate into osteoblasts, chondrocytes, adipocytes, and myoblasts (Prockop, D. J. Science 276, 71-74, 1997). Therefore, characterization and identification of the stem-like cell within the stromal cells are important to understand bone marrow function in relation to the hematopoietic microenvironment, and repair/regeneration of tissue defects. TBR31-2 cell, a bone marrow stromal cell line established from bone marrow of transgenic mice harboring temperature-sensitive (ts) simian virus (SV) 40T-antigen gene for immortality, is induced toward both adipocytic and osteogenic cells under conditions of the inactivation of T-antigen (Okuyama, R., Yanai, N., Obinata, M. Exp. Cell Res. 218, 424-429, 1995). In this work, using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, mRNA expressions of tissue-specific differentiation markers for adipocyte (lipoprotein lipase), osteoblast (type I collagen and osteocalcin), chondrocyte (type II and X collagen), and muscle cell (desmin) were examined during a long-term culture of the cell. In addition, histochemical studies showed the appearance of adipocytic, osteoblastic, chondrocytic, and muscle cells during this long-term culture. Thus, TBR31-2, which has characteristics of an undifferentiated cell, has the potential to express the multipotential cell lineages. These results indicated that a multipotential progenitor cell including potential to differentiate into a muscle cell and which is situated in the mesenchymal cell lineage was first obtained.
Animals↗