Three oligosaccharide esters, telephioses A-C, from Polygala telephioides.
Three new oligosaccharide esters named telephioses A-C, were isolated from Polygala telephioides WILLD. and their structures were characterized by spectroscopic data.
Esters↗
Biomedical subjects
M Ono
Publications and source records attributed to M Ono.
Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice.
We previously reported that brain-derived neurotrophic factor (BDNF) regulates both food intake and blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice. To elucidate the effect of BDNF on glucose metabolism, we designed a novel pellet pair-feeding apparatus to eliminate the effect of appetite alteration on glucose metabolism. The apparatus was used to synchronize food intake precisely between BDNF-treated and vehicle-treated db/db mice. It was shown using this pellet pair-feeding apparatus that BDNF administered daily (20 mg x kg(-1) x day(-1)) to db/db mice significantly lowered blood glucose compared with pellet pair-fed db/db mice. To evaluate the effect of BDNF on insulin action, we used streptozotocin-induced type 1 diabetic mice. In this case, BDNF did not lower blood glucose concentration but rather enhanced the hypoglycemic action of insulin. In hyperglycemic db/db mice, pancreatic insulin content was reduced and glucagon content was increased compared with normoglycemic db/m mice. BDNF administered to db/db mice significantly restored both pancreatic insulin and glucagon content. Histological observations of aldehyde-fuchsin staining and immunostaining with anti-insulin indicated that insulin-positive pancreatic beta-cells were extensively regranulated by BDNF administration. We also studied the effect of BDNF on KK mice, normoglycemic animals with impaired glucose tolerance. In these mice, BDNF administration improved insulin resistance in the oral glucose tolerance test. To elucidate how blood glucose was metabolized in BDNF-treated animals, we investigated the effect of BDNF on the energy metabolism of db/db mice. Body temperature and oxygen consumption of the pellet pair-fed vehicle-treated mice were remarkably lower than the ad libitum-fed vehicle-treated mice. Daily BDNF administration for 3 weeks completely ameliorated both of the reductions. Finally, to clarify its action mechanism, the effect of intracerebroventricular administration of BDNF on db/db mice was examined. Here, a small dose of BDNF was found to be effective in lowering blood glucose concentration. This indicates that BDNF regulates glucose metabolism by acting directly on the brain.
Animals↗
Overproduction of IL-8 results in suppression of bone metastasis by lung cancer cells in vivo.
HARA-B cells were established from the bone lesion in nude mice formed after an intracardiac inoculation of the human lung cancer-derived cells (HARA), and production of IL-8 in HARA-B cells was decreased as compared to that in the parental HARA cells. This suggests a possible relationship between IL-8 production and bone metastasis. Thus, we examined the effect of IL-8 on bone metastasis using HARA-B cells transfected with experimental (IL-8-cDNA) and/or control plasmid in the experimental bone metastasis model in nude mice. Growth rates of both cells in vitro were similar. Control cells developed radiologically detectable bone metastases in 50% of nude mice tested, whereas experimental cells did not develop bone metastases. Osteoclastic bone resorption is an important step in the process of bone metastasis, and IL-8 possesses an inhibitory effect on osteoclastic bone resorption. These results suggest that IL-8 suppresses bone metastasis, which might be attributed to the inhibitory effect of IL-8 on osteoclastic bone resorption.
Animals↗
Blasticidin A as an inhibitor of aflatoxin production by Aspergillus parasiticus.
Blasticidin A, an antibiotic, showed strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. Its structure was characterized by NMR and chemical degradation experiments as 1, which is a tetramic acid derivative with a highly oxygenated long alkyl chain similar to aflastatin A (2). Absolute configurations of the eight chiral centers at C-4, 6, 31, 32, 33, 34, 35 and 37 of 1 were chemically determined. Blasticidin A almost completely inhibited aflatoxin production at 0.5 microM.
Aflatoxins↗
Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus.
Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis.
Aflatoxins↗
[Cardiac tamponade due to ruptured intramural hematoma of the ascending aorta: a case report].
A 72-year-old man with a history of hypertension for 20 years was admitted with symptoms of acute aortic dissection. Computed tomography showed a crescentic thickening of the ascending aortic wall, suggesting an intramural hematoma. Sixteen hours after admission, he underwent urgent repair of the ascending aorta because of cardiac tamponade. We inspected the inside of the aorta from the aortic valve to the arch. Subadventitial hematoma due to hemorrhage from the outer media was confirmed. Rupture of the vasa vasorum was thought to be an initiating mechanism. The affected aortic wall was simply resutured and was not replaced with a graft because the intima was intact and the media was not dissected and the aortic wall was considered to be tolerable to normal blood pressure. The patient continues to do well 18 months following operation. An intramural hematoma of the ascending aorta should be regarded as a precursor of imminent rupture or classic dissection.
Aged↗
[A patient with severe left ventricular hypertrophy suffering sudden death].
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Amyloidosis↗
[Recent donation and clinical results of homograft tissue].
Between August 1995 and July 1999, we have experienced 14 donors for allografts (mean age: 39.8 +/- 15.8, M/F = 10/4, mean warm ischemic time: 359 minutes). Donated tissues were included 12 aortic valves and 12 pulmonary valves, respectively. Since February 1994, clinical diagnoses of 14 patients included 7 congenital heart disease, 5 infective heart disease, 1 artificial graft infection, and 1 thrombosed valve. There was no graft-transmitted disease. In congenital heart disease, 3 patients (HLHS: 1, Truncus: 1, TOF + PA: 1) died (early mortality, 42%) and 1 with TGA had residual conduit stenosis. However, in infective heart disease, all patients survived without recurrent infection and did not need reoperation (early mortality, 0%). Our clinical results of homograft implantation for infective heart disease were excellent, but more careful consideration will be needed for congenital heart disease in neonates and/or patients with poor preoperative condition.
Adolescent↗
[Results of molecular screening of anti-cancer agents. 8. Results of screening of possible anti-cancer agents in Japan].
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Antineoplastic Agents↗
Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes.
Hepatocyte growth factor (HGF) is thought to play a role in cell motility and invasion. Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. We have previously reported that the Ets-oncogene family transcription factor E1AF positively regulates transcription of MMP genes in transient expression assays and that overexpression of the E1AF gene confers an invasive phenotype on breast cancer cells. Here we examined the effect of HGF on E1AF and MMP gene expression in terms of the invasive potential of the oral squamous cell carcinoma cell line HSC3. HGF stimulated expression of the E1AF gene. The levels of MMP-1, -3 and -9 mRNAs increased in cells treated with HGF and correlated with E1AF upregulation. In contrast, no obvious upregulation of MMP-1 and -9 mRNA was observed in ASE1AFHSC3 cells transfected with the antisense E1AF expression vector into parental HSC3 cells. The wild-type MMP-9 gene promoter was activated by endogenous E1AF in HSC3 cells, and chloramphenicol acetyltransferase (CAT) activities increased when HGF was added to transfected cells. On the other hand, CAT activity was reduced to almost two-thirds of the wild-type activity when HSC3 cells were transfected with a CAT reporter plasmid driven by a mutant MMP-9 promoter lacking the Ets-binding site, and induction of CAT activity was not observed upon addition of HGF. Analysis of organotypic raft cultures revealed that HSC3 cells invaded and degraded collagen gel actively upon addition of HGF. These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion.
Adenovirus E1A Proteins↗
[The countermeasure to pollinosis by a web site of Internet].
For the countermeasure to pollinosis, we opened "the web site of pollinosis by allergic group of otorhinolaryngology, Jikei Medical School" and provided the information of pollinosis for patients in the web site of internet from the spring of 1997. In the web site we kept to be informed of the pollen forecast, daily dispersed pollens, and medical information being renewed frequently of prevention and therapy for pollinosis. For the principle of therapy, we adopted the guideline for allergic rhinitis which was produced by Japan Allergic Societies and recommended visitors to get standard therapy for pollinosis. Consequently, the web site was accessed up to 160,000 times by the summer of 1999 and we received 204 medical questions by e-mail and answered to these all mails. We then made a questionnaire study after 3 each pollen seasons and received over 200 answers which showed that our fresh information was useful to decrease symptoms of pollinosis. These results show that information by web site seems to be useful for the countermeasure to pollinosis and will be more important to support medical treatment in hospitals in future.
Adolescent↗
[Anesthetic management of a patient with Brugada syndrome].
Brugada syndrome is characterized by right bundle-branch block, ST elevation in leads V 1 through V 3 and normal QT interval. Ventricular fibrillation frequently occurs in patients with Brugada syndrome. There have been few reports of anesthetic management of Brugada patients. We managed a 47-year-old man with Brugada syndrome, who underwent hemilaminectomy under general anesthesia, without untoward cardiovascular events. Potential problems in anesthetic management of patients with Brugada syndrome are also discussed.
Anesthesia, General↗
[A new spacer, Babyhaler, for BDP inhalation therapy in severe infantile asthma].
Recently, it has been recognized that airway inflammation is the most important pathogenesis of bronchial asthma, and inhaled corticosteroids therapy is effective for childhood asthma. However, using metered dose inhalers (MDI) of beclomethasone dipropionate (BDP) is difficult for infants. In this study, we administered BDP inhalation therapy with a new spacer, Babyhaler, for five cases of early childhood with severe infantile asthma that we could not control even by combination of theophylline round the clock (RTC) therapy and disodium cromoglycate (DSCG) + beta 2 stimulant (beta 2) regular use. We compared symptom score of asthma attack between the pre-treatment period (prior 2 weeks) and post-treatment period (following 8 weeks) of BDP inhalation therapy with Babyhaler. As a result, symptom score decreased significantly within 4 weeks after treatment of BDP with Babyhaler as compared with the score before treatment of BDP. These findings suggest that Babyhaler is useful for BDP inhalation therapy in infantile asthma.
Administration, Inhalation↗
Analysis of relationship between Anopheles subpictus larval densities and environmental parameters using Remote Sensing (RS), a Global Positioning System (GPS) and a Geographic Information System (GIS).
Remote Sensing (RS), a Global Positioning System (GPS) and a Geographic Information System (GIS) were used to analyze relationship between Anopheles subpictus larval densities and environmental parameters in the Sekotong district on Lombok Island, Indonesia. Distance from the coast to larval habitats, season and surface water were considered as environmental parameters for determining An. subpictus larval densities. Japanese Earth Resources Satellite (JERS) Visible and Near Infrared Radiometer (VNIR) satellite imagery for the area acquired by National Space Development Agency of Japan (NASDA) were used to detect water, which could be used to characterize larval habitats. Data on larval sampling sites obtained from a GPS were entered into a GIS for mapping larval habitats to measure distance between the coast and the larval habitats. A GIS was used for overlaying of data coverages (i.e., water distribution from RS data and larval habitats coupled with data on larval densities) to identify factors that may explain the spatial distribution patterns of larval densities. An. subpictus larval densities were significantly associated with season and distance from the coast to larval habitats. The rainy season and the distance from the coast to larval habitats were critical environmental determinants for presence of An. subpictus larvae in the study. In this paper, we investigated relationship between An. subpictus larval densities and the environmental parameters using RS/GPS/GIS to determine if these tools could be used to predict larval densities.
Animals↗
Proportion of membrane proteins in proteomes of 15 single-cell organisms analyzed by the SOSUI prediction system.
A software system, SOSUI, was previously developed for discriminating between soluble and membrane proteins and predicting transmembrane regions (Hirokawa et al., Bioinformatics, 14 (1998) 378-379). The performance of the system was 99% for the discrimination between two types of proteins and 96% for the prediction of transmembrane helices. When all of the amino acid sequences from 15 single-cell organisms were analyzed by SOSUI, the proportion of predicted polytopic membrane proteins showed an almost constant value of 15-20%, irrespective of the total genome size. However, single-cell organisms appeared to be categorized in terms of the preference of the number of transmembrane segments: species with small genomes were characterized by a significant peak at a helix number of approximately six or seven; species with large genomes showed a peak at 10 or 11 helices; and species with intermediate genome sizes showed a monotonous decrease of the population of membrane proteins against the number of transmembrane helices.
Archaea↗
Stimulatory function of paired immunoglobulin-like receptor-A in mast cell line by associating with subunits common to Fc receptors.
Paired Ig-like receptors (PIR) are polymorphic type I transmembrane proteins belonging to an Ig superfamily encoded by multiple isotypic genes. They are expressed on immune cells such as mast cells, macrophages, and B lymphocytes. Two subtypes of PIR have been classified according to the difference in the primary structure of the PIR transmembrane and cytoplasmic regions. These subtypes are designated as PIR-A and PIR-B. In this study, the transmembrane and cytoplasmic regions of the PIR-A subtype were shown to mediate activation signal events such as cytoplasmic calcium mobilization, protein tyrosine phosphorylations, and degranulation in rat mast cell line RBL-2H3. The association of the Fc receptor gamma and beta subunits with PIR-A was shown to be responsible for PIR-A function but not required for membrane expression of PIR-A on COS-7 cells. We further revealed the role of two charged amino acid residues in the transmembrane region, namely arginine and glutamic acid, in PIR-A function and its association with the above subunits. In contrast to the inhibitory nature of the PIR-B subtype, present findings reveal that PIR-A potentially acts as a stimulatory receptor in mast cells, suggesting a mechanism for regulation of mast cell functions by the PIR family.
Amino Acid Sequence↗
The W(sh), W(57), and Ph Kit expression mutations define tissue-specific control elements located between -23 and -154 kb upstream of Kit.
The Kit and PDGFRa receptor tyrosine kinases are encoded in close proximity at the murine white spotting (W) and patch (Ph) loci. Whereas W mutations affect hematopoiesis, melanogenesis, and gametogenesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. The W(sh), W(57), and Ph mutations diminish Kit expression in certain cell types such as mast cells and enhance it in others. The W(sh), W(57), and Ph mutations arose from deletions and inversions affecting sequences in between the Kit and PDGFRa genes. We have determined the precise location of the breakpoint of the W(sh) inversion and the endpoints of the W(57) deletion upstream of the Kit transcription start site and examined the effect of these mutations on Kit expression in mast cells and hematopoietic stem cells and lineage progenitors. Our results indicate that positive elements controlling Kit expression in mast cells mapping in between -23 and -154 kb from the transcription start site can be dissociated from negative elements controlling Kit misexpression during embryonic development in the vicinity of the PDGFRa gene. In addition, we have identified two clusters of hypersensitive sites in mast cells at -23 -28 kb and -147 -154 kb from the Kit gene transcription start site. Analysis of these hypersensitive sites in mutant mast cells indicates a role for HS4-6 in Kit expression in mast cells. These findings provide a molecular basis for the phenotype of these Kit expression mutations and they provide insight into the complex mechanisms governing the regulation of Kit expression.
Animals↗
Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2).
We established stable human canalicular multispecific organic anion transporter (cMOAT/MRP2) cDNA transfectants, CHO/cMOAT from non-polarized Chinese hamster ovary (CHO)-K1 and LLC/cMOAT from polarized pig kidney epithelial LLC-PK1. Human cMOAT was mainly localized in the plasma membrane of CHO/cMOAT and in the apical membrane of LLC/cMOAT. The ATP-dependent uptake of leukotriene C4 (LTC4) into CHO/cMOAT membrane vesicles was enhanced compared with empty vector transfectants. Km values in CHO/cMOAT membrane vesicles were 0.24 microM for LTC4 and 175 microM for ATP. Drug sensitivity to vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not to etoposide. Cellular accumulation of vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not of etoposide. The uptake of LTC4 into CHO/cMOAT membrane vesicles was inhibited by exogenous administration of vincristine or cisplatin, but not that of etoposide. Moreover, this inhibition was more enhanced in the presence of glutathione. These consequences indicate that drug resistance to vincristine or cisplatin appears to be modulated by human cMOAT through transport of the agents, possibly in direct or indirect association with glutathione.
Adenosine Triphosphate↗