PubMed Health⌕ Search

Biomedical subjects

F Ikeda

Publications and source records attributed to F Ikeda.

At least 19 recordsLinked to original sources
PubMed2006

Amelioration of glucose tolerance by hepatic inhibition of nuclear factor kappaB in db/db mice.

AIMS/HYPOTHESIS: Recent studies have identified the involvement of inhibitor IkappaB kinase (IKK) in the pathogenesis of insulin resistance. To investigate the mechanism involved, we examined the role of nuclear factor kappaB (NF-kappaB), the distal target of IKK, in hepatic glucose metabolism. METHODS: To inhibit NF-kappaB activity, db/db mice were infected with adenovirus expressing the IkappaBalpha super-repressor. RESULTS: The IkappaBalpha super-repressor adenovirus infection caused a moderate reduction of NF-kappaB activity in liver. The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin-stimulated phosphorylation of Akt. On the other hand, quantification of mRNA in the liver revealed marked reduction of expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, concurrent with reduced expression of gene encoding peroxisome proliferator-activated receptor gamma coactivator-1alpha (PPARGC1A, also known as PGC-1alpha). Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection. CONCLUSIONS/INTERPRETATION: Our results indicate that moderate inhibition of NF-kappaB improved glucose tolerance through decreased gluconeogenesis associated with reduced PGC-1alpha gene expression in db/db mice, and suggest that inhibition of NF-kappaB activity in liver is a potentially suitable strategy for the normalisation of blood glucose concentration in type 2 diabetes.

AMP-Activated Protein Kinases↗
PubMed2006

Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility.

The micafungin and caspofungin susceptibilities of Candida albicans laboratory and clinical isolates and of Saccharomyces cerevisiae strains stably hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters involved in azole resistance were determined using three separate methods. Yeast strains hyperexpressing individual alleles of ABC transporters or an MFS transporter from C. albicans gave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2 showed slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyperexpressing CDR1 or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. A C. albicans clinical isolate overexpressing both Cdr1p and Cdr2p relative to its azole-sensitive isogenic progenitor acquired resistance to azole drugs and showed reduced susceptibility to caspofungin and slightly increased susceptibility to micafungin in agar plate drug resistance assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The antifungal activities of micafungin and caspofungin were similar in agarose diffusion assays, although the shape and size of the caspofungin inhibitory zones were affected by medium composition. The assessment of micafungin and caspofungin potency is therefore assay dependent; the differences seen with agar plate drug resistance assays occur over narrow ranges of echinocandin concentrations and are not of clinical significance.

ATP-Binding Cassette Transporters↗
PubMed2002

Core-binding factor alpha 1 (Cbfa1) induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5.

Core-binding factor alpha(1) (Cbfa1) is an essential transcription factor for osteoblastic differentiation and osteogenesis. Bone morphogenetic protein (BMP) is also a powerful inducer of differentiation of pluripotent mesenchymal cells to osteoblast lineage and bone formation. Recent studies suggest that Cbfa1 plays a critical role during BMP-induced osteoblastic differentiation through association with cytoplasmic BMP signaling molecules, Smads. However, other studies have suggested that Cbfa1 may exhibit its osteogenic function without interaction with Smads. Therefore, it remains unclear whether association with Smad is essential for Cbfa1 function. In this study we examine the effects of Cbfa1 on osteoblastic differentiation in the presence or absence of interactions with Smad1 or Smad5 using C2C12 undifferentiated mesenchymal cells. Cbfa1 expression was induced upon stimulation with BMP-2 in C2C12 cells. Introduction of Cbfa1 into C2C12 cells induced osteoblastic differentiation and promoted transactivation of osteocalcin gene promoter without forming the complex with Smad1 or Smad5. Furthermore, in C2C12 cells in which the association of Cbfa1 with Smad1/Smad5 was prevented by the overexpression of the natural antagonist, Smad6, Cbfa1 still induced osteoblastic differentiation and transactivated osteocalcin gene promoter, regardless of BMP-2 stimulation. These results suggest that the interactions with Smad1 or Smad5 are not essential for Cbfa1 to demonstrate its osteogenic actions. However, interactions with Smad1/Smad5 enhance these osteogenic actions of Cbfa1. Of note, BMP-2-induced or Smad-induced osteoblastic differentiation was inhibited by dominant-negative Cbfa1, suggesting that the function of Cbfa1 is critical for BMP-2-induced osteoblastic differentiation. Our results suggest that Cbfa1 is essential and also sufficient to induce osteoblastic differentiation in undifferentiated mesenchymal cells, and establishment of an association with Smad1/Smad5 enhances the osteogenic actions of Cbfa1. On the other hand, Cbfa1 expression requires the activation of Smad1/Smad5 by BMP-2.

Animals↗
PubMed2002

In vitro activity of FK463, a novel lipopeptide antifungal agent, against a variety of clinically important molds.

The in vitro antifungal activity of FK463 against a variety of clinically important opportunistic molds was compared with amphotericin B, itraconazole and fluconazole by using the broth microdilution method M27-A specified by the National Committee for Clinical Laboratory Standards. FK463 exhibited potent activity against Aspergillus species, which was superior to those of all other compounds tested. FK463 was also active against the dematiaceous fungi Cladosporium trichoides, Exophiala spinifera, Fonsecaea pedrosoi, and Exophiala dermatitidis except for certain clinical isolates. However, FK463 had no activity against Fusarium solani, Pseudallesheria boydii, and the zygomycetes Absidia corymbifera, Cunninghamella elegans, Rhizopus oryzae, and Rhizopus microsporus var. rhizopodiformis. These results suggest that FK463 has potential utility for the treatment for infections caused by Aspergillus species and dematiaceous fungi.

Aspergillus↗
PubMed2001

Synthesis and biological activity of novel macrocyclic antifungals. modification of the tyrosine moiety of the lipopeptidolactone FR901469.

A series of tyrosine-modified derivatives of the macrocyclic lipopeptidolactone FR901469 have been prepared and evaluated for in vitro and in vivo antifungal activity and for hemolytic activity towards red blood cells. Compound 14 displayed significantly reduced hemolytic potential at 1mg/mL and a comparable protective effect to FR901469 in a mouse candidiasis model.

Animals↗
PubMed2001

High prevalence of TT virus in human bile juice samples: importance of secretion through bile into feces.

TT virus (TTV) is much more prevalent than we once imagined. With the use of primers designed from the noncoding regions, a more than 90% rate of TTV infection in the general population by polymerase chain reaction (PCR) has been reported, showing that nonparenteral transmission must play an important role to its epidemiology. We considered that TTV may be secreted through bile juice into feces to establish nonparenteral infection. Paired bile juice and serum samples were obtained from 26 patients who were receiving bile drainage. Feces were also recovered after the drainage tube was removed. TTV DNA was detected from 22 patients in serum (84.6%), and they were all TTV DNA positive in bile juice. Most feces samples recovered from TTV-positive patients were also TTV DNA positive. Secretion of TTV into bile juice appears to be common, and this could play an important role to its transmission and its epidemiology.

Bile↗
PubMed2001

Laparoscopic findings in primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by segmental narrowing and dilatation of bile ducts. Few studies have been performed on the laparoscopic findings associated with this disease, and the present study was intended to assess the usefulness of laparoscopy for the diagnosis and staging of PSC. PATIENTS AND METHODS: Six patients were examined by laparoscopy with liver biopsy. Repeated laparoscopy was performed in three patients. RESULTS: Laparoscopy revealed coarse surface irregularity and discoloration. Surface irregularity was classified into four grades: smooth, shallowly depressed, undulated, and nodular. The affected area showed whitish yellow discoloration. The discolored area was demonstrated as a poorly stained area by intravenous injection of indocyanine green (ICG). Lobular markings became apparent because of the yellow color change in the portal tract, resulting in a leopardskin-like appearance. Lymph-vessel dilatation was seen in advanced stages. Repeated laparoscopy of a patient without treatment demonstrated a progression from a smooth surface to a shallow depression with leopardskin-like markings. On the other hand, the two patients treated with immunosuppressive agents showed improvement of liver swelling and disappearance of the leopardskin-like markings and lymph-vessel dilatation. CONCLUSIONS: Laparoscopy may provide useful information for the diagnosis and staging of PSC.

Adolescent↗
PubMed2001

Mechanism of therapeutic effectiveness of cefixime against typhoid fever.

beta-Lactams have been considered ineffective against organisms growing inside mammalian cells because of their poor penetration into cells. However, cefixime has been shown to be clinically effective against typhoid fever. The probable mechanism of therapeutic effectiveness of cefixime against typhoid fever was investigated using Salmonella enterica serovar Typhimurium instead of S. enterica serovar Typhi both in a cellular and in a mouse infection model. Cefixime was able to inhibit the growth of serovar Typhimurium inhabiting monocyte-derived THP-1 cells. Elongation of serovar Typhimurium in THP-1 cells was observed microscopically. Apparent morphological changes of serovar Typhimurium in THP-1 cells were also observed by electron microscopy. The concentration of cefixime inside THP-1 cells was almost half (46 to 48%) of the concentration outside the cells when serovar Typhimurium coexisted in the solution. The length of time after oral dosing (8 mg/kg) that cefixime was present-calculated from levels in serum-at a concentration above the MIC at which 90% of the serovar Typhi organisms inside human cells were inhibited was presumed to be more than 12 h. Cefixime also showed excellent activity in the mouse systemic and oral infection models based on infections caused by serovar Typhimurium. It is concluded that a fair amount of cefixime can enter mammalian cells and inhibit the growth of bacteria inside cells when the bacteria are sensitive enough to cefixime, as are serovars Typhimurium and Typhi.

Animals↗
PubMed2001

Cold activation of serum complement in patients with chronic hepatitis C: study on activating pathway and involvement of IgG.

It has been documented that the serum complement activities measured by hemolytic assay (CH50) are decreased after storage of sera at a low temperature in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factors involved in the cold activation of complement (CAC). To clarify what pathway is activated in CAC, we measured complement cleavage products after cold storage of sera. C4d increased significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not increase in any of the groups. In order to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them retained hemolytic activities to some extent after cold storage. Column chromatography through Superose 6HR of CAC-positive serum identified the fractions containing molecules that induced CAC in normal serum, which were depleted by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produced in hepatitis C virus infection may be an important factor in inducing CAC, a common extrahepatic manifestation of hepatitis C.

Adult↗
PubMed2000

Efficient enhancement of priming effect by intermittent treatment with interferon.

To improve the efficacy of interferon (IFN) therapy for chronic hepatitis C, we proposed a therapy with twice-a-day injection of IFNbeta as the induction. To assess its biological enhancement, we compared antiviral activities in vitro using intermittent treatment schedules simulating the clinical condition. FL cells were treated with IFNbeta twice in 12 h interval (Single treatment, 1000 and 0 IU/ml; Double treatment, 500 IU/ml each) and challenged with Sindbis virus. Antiviral activities were determined with 50% cytopathic effect. Activities and mRNA expressions of 2'5'oligoadenylate synthetase (2'5'AS) were also examined. Single treatment showed its peak activity at 9 h, while Double treatment was at 3 h after the second treatment. Double treatment had a significantly higher peak activity. The up-regulated activities of 2'5'AS lasted much longer with Double treatment. The present findings demonstrated Double treatment could induce efficient biological enhancement, which is thought based on the priming effect.

2',5'-Oligoadenylate Synthetase↗
PubMed2000

Early clearance of circulating hepatitis C virus enhanced by induction therapy with twice-a-day intravenous injection of IFN-beta.

To improve the long-term efficacy of interferon (IFN) for treatment of chronic hepatitis C virus (HCV) infection, we proposed induction therapy with twice-a-day IFN-beta injection. This study was intended to clarify the antiviral mechanism. Thirty patients were randomly assigned to two groups: group A (twice-a-day therapy) received 3 MU IFN-beta intravenously (i.v.) twice a day for 2 weeks; group B (once-a-day therapy) received 6 MU of IFN-beta daily. HCV RNA, IFN-beta, alanine aminotransferase (ALT), 2'5'-oligoadenylate synthetase (2'5'-AS) activity, and beta2-microglobulin in serum were compared between the two groups during the first 2 weeks of IFN therapy. The clearance rate of serum HCV RNA in group A (86.7%) was significantly higher than that in group B (13.3%) at day 3 (p = 0.0006). No accumulation of IFN-beta was shown in serum throughout the therapy. The ratio (day 3/day 1) of 2'5'-AS activity was significantly higher in group A. Multivariate analysis indicated twice-a-day IFN-beta injection therapy led to significantly early clearance of circulating HCV. Twice-a-day IFN-beta injection therapy could induce biologically enhanced antiviral activities and be an efficient induction therapy for eradication of HCV.

Adult↗
PubMed2000

Microlaparoscopy for an intact ectopic pregnancy and endometriosis with the use of a diode laser: case report.

Microlaparoscopy is a development of endoscopic surgery which further reduces invasiveness of surgical procedures. The use of a diode laser in microlaparoscopy for the treatment of a patient with an intact ectopic pregnancy and endometriosis is described for the first time. As the diode laser has easy management and widely recognized precision, its use could be highly advantageous in such situations. The success achieved in this case contributes to the wider use of micro-endoscopic procedures.

Adult↗
PubMed2000

In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi.

The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, <==0.0039 to 2 microg/ml) and Aspergillus species (MIC range, <==0.0039 to 0.0313 microg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 microg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.

Antifungal Agents↗
PubMed2000

Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of disseminated candidiasis and aspergillosis.

The efficacy of intravenous injection of FK463, a novel water-soluble lipopeptide, was evaluated in mouse models of disseminated candidiasis and aspergillosis and was compared with those of fluconazole (FLCZ) and amphotericin B (AMPH-B). In the candidiasis model, FK463 significantly prolonged the survival of intravenously infected mice at doses of 0.125 mg/kg of body weight or higher. In disseminated candidiasis caused by Candida species, including FLCZ-resistant Candida albicans, FK463 exhibited an efficacy 1.4 to 18 times inferior to that of AMPH-B, with 50% effective doses (ED(50)s) ranging from 0.21 to 1.00 mg/kg and 0.06 to 0.26 mg/kg, respectively, and was much more active than FLCZ. The protective effect of FK463 was not obviously influenced by the fungal inoculum size, the starting time of the treatment, or the immunosuppressed status of the host. The reduction in efficacy was less than that observed with FLCZ or AMPH-B. The efficacy of FK463 was also evaluated in the disseminated candidiasis target organ assay and was compared with those of FLCZ and AMPH-B. Efficacies were evaluated on the basis of a comparison between the mean log(10) CFU in kidneys in the groups treated with antifungal agents and that in control group. A single dose of FK463 at 0.5 mg/kg or higher significantly reduced the viable counts in kidneys compared with the numbers of yeast cells before treatment, and its efficacy was comparable to that of AMPH-B, while FLCZ at 4 mg/kg showed only a suppressive effect on the growth of C. albicans in the kidneys. In the disseminated aspergillosis model, FK463 given at doses of 0.5 mg/kg or higher significantly prolonged the survival of mice infected intravenously with Aspergillus fumigatus conidia. The efficacy of FK463 was about 2 times inferior to that of AMPH-B, with ED(50)s ranging from 0.25 to 0.50 mg/kg and 0.11 to 0.29 mg/kg, respectively. These results indicate that FK463 may be a potent parenterally administered therapeutic agent for disseminated candidiasis and aspergillosis.

Animals↗