PubMed Health⌕ Search

Biomedical subjects

I Yano

Publications and source records attributed to I Yano.

At least 19 recordsLinked to original sources
PubMed2006

Interferon-gamma independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis.

The mechanisms by which pulmonary granuloma formation is caused by administration of mycobacterial glycolipids such as trehalose dimycolate (TDM), lipoarabinomannan (LAM) and phosphatidylinositol mannosides (PIM) were investigated. When peritoneal and alveolar macrophages were stimulated with TDM, LAM and PIM in vitro, TDM exhibited the strongest tumour necrosis factor (TNF)-inducing activity. Responsiveness of macrophages from mice defected Toll-like receptor 4 (TLR4) was much higher than that of the wild-type mice. Although PIM and LAM also had a significant activity, LAM rather than PIM stimulated higher TNF-alpha production by alveolar macrophage. When mycobacterial glycolipids were injected as water-in-oil-in-water emulsion into mice via the tail vein, development of pulmonary granuloma in response to glycolipids were related closely to their TNF-inducing activity and TDM exhibited the strongest activity. Granuloma formation was observed not only in mice lacking interleukin (IL)-12 signalling but also interferon (IFN)-gamma knock-out mice. Granuloma formation caused by glycolipids correlated with TNF-alpha levels in lungs. Administration of anti-TNF-alpha monoclonal antibody into TDM-injected IFN-gamma knock-out mice decreased in granuloma formation, suggesting that development of pulmonary granuloma by mycobacterial glycolipids such as TDM is due to IFN-gamma-independent and TNF-alpha-dependent pathway.

Adjuvants, Immunologic↗
PubMed2001

Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2.

Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent. Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions. Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.

Adenosine Triphosphate↗
PubMed2001

Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306.

Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 6-monomycolate. The length of carbon chains and number of double bonds of mycolic acids were C(34), C(36)and C(38)saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C(78-88)monoenoic and dienoic). Among them, only TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity.

Actinomycetales Infections↗
PubMed2001

Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation.

OBJECTIVE: To characterize the pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation (LDLT). METHODS: Thirty-five patients were given tacrolimus as 18- to 60-h intravenous infusions after surgery, followed by a 4-week course of oral dose therapy (at 0900 hours and 2100 hours). Blood samples were collected daily in the morning (0800 hours) beginning the day after surgery. Whole blood concentration data were evaluated by nonlinear mixed-effect modeling using the program NONMEM and were characterized using a one-compartment model. RESULTS: The clearance (CL, l h(-1)) was related to the grafted hepatic weight, postoperative days (POD), and hepatic and renal dysfunction. Interindividual variabilities in CL, volume of distribution (V), and bioavailability (F) were 57.4%. 39.7%, and 63.0%, respectively, and the correlation between individual CL and F was 0.776. Residual intraindividual variability was 2.9 ng ml(-1). Based on the estimated final parameters, a typical recipient of LDLT with grafted hepatic weight of 600 g and normal hepatic and renal function would have a CL of 0.737 l h(-1) on POD 0 and 1.14 l h(-1) on POD 30, V of 1.52 l kg(-1) and F of 6.8%. CONCLUSIONS: Nonlinear mixed-effect modeling was useful for analysis of pharmacokinetic characteristics of tacrolimus in LDLT patients. Immediately after surgery, patients receiving LDLT showed a smaller CL value than other transplant patients, and CL value increased with POD within 30 days after surgery. The estimated population pharmacokinetic parameters can be applied for a priori dosage calculations in adult patients with LDLT.

Adolescent↗
PubMed2001

Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and upregulation of CD1d1 on murine macrophages.

Trehalose 6,6'-dimycolate (TDM, cord factor) has frequently been used as an adjuvant to stimulate antibody production. Although it also induces cellular immunity, detailed studies about the underlying events do not exist. To determine the kinetics of TDM-specific changes promoting a T helper 1 (Th1) response, we injected mice with TDM or 2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL, sulfolipid), another mycobacterial trehalose-containing glycolipid without mycolic acid. TDM, but not SL, caused a strong increase in serum interferon-gamma (IFN-gamma) levels 2 days later, accompanied by expansion of natural killer (NK) cells. Subsequent TDM effects included depletion of normal-density CD4(+) NK1.1(+) TCRalpha/beta(intermediate) cells from day 7 on, upregulation of MHC class II and CD1d1 on macrophages (peaking on day 21), and an increased proportion of Th1 cells evident after 3 weeks. TDM, but not a similar glycolipid without mycolic acid, can therefore initiate a cascade of events starting with strong release of IFN-gamma and NK cell expansion, resulting in the appearance of macrophages activated for antigen presentation. Our data therefore provide the basis for optimized immunization schedules with TDM as the adjuvant component of a Th1 vaccine.

Adjuvants, Immunologic↗
PubMed2001

Transport of levofloxacin in the OK kidney epithelial cell line: interaction with p-aminohippurate transport.

PURPOSE: To evaluate the mechanism of renal transport of quinolone antibacterial drugs, we examined the interaction of levofloxacin with p-aminohippurate (PAH) transport systems and the transport of levofloxacin in renal epithelial cells. METHODS: Transport of [14C]PAH or [14C]levofloxacin was measured using OK cell monolayers grown on microporous membrane filters. RESULTS: Transcellular transport from the basolateral to the apical side and cellular accumulation of [14C]PAH were inhibited by levofloxacin. Both the initial uptake of [14C]PAH from the basolateral side and the efflux to the apical side were inhibited by levofloxacin. The basolateral-to-apical transcellular transport of [14C]levofloxacin was greater than that in the opposite direction. [14C]Levofloxacin efflux to the apical side was greater than that to the basolateral side. Unlabeled levofloxacin and grepafloxacin inhibited the transcellular transport of [14C]levofloxacin, accompanied by an increase of cellular accumulation. However, neither PAH nor an anion transport inhibitor 4-4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) affected the basolateral-to-apical transport of [14C]levofloxacin nor its uptake from the basolateral side. CONCLUSIONS: These results indicated that levofloxacin inhibits PAH transport across both the basolateral and apical membranes of OK cells, but are not transported via the systems for PAH transport. The existence of a specific transport system for quinolones was indicated in OK cells.

Animals↗
PubMed2001

The need for mixed-effects modeling with population dichotomous data.

Over the past 25 years sophisticated data analytic techniques have been developed which can lead to improved analyses, but at additional computational cost. In particular, this applies to the approach where interindividual random effects are included in a data analytic model for population pharmacokinetic data, which can often lead to substantially improved estimates of fixed-effect parameters. However, there are also commonly occurring situations, notably with some types of pharmacodynamic data, where such improvement is not realized. This study simulates some simple population dichotomous data, and secondarily, some related continuous data. These data are analyzed using both mixed-effect (ME) models that include interindividual random effects and naive (NA) models that do not include interindividual random effects, and it is seen that use of an ME model does not inevitably lead to gains over use of an NA model. In fact, using maximum likelihood estimation with both types of models, the root mean square estimation errors for fixed effect parameters can actually be larger with an ME model than with the corresponding NA model. Using a form of restricted maximum likelihood estimation with the ME model, the two types of models yield root mean square errors which are comparable, but which still do not suggest that there is always marked advantage in using the ME model.

Humans↗
PubMed2001

Immunological properties of trehalose dimycolate (cord factor) and other mycolic acid-containing glycolipids--a review.

Mycolic acids are characteristic fatty acids of Mycobacteria and are responsible for the wax-like consistence of these microorganisms. Decades of research revealed that mycolic acid-containing glycolipids, in particular trehalose-6,6'-dimycolate (TDM, cord factor) as their best-studied representative, exert a number of immunomodifying effects. They are able to stimulate innate, early adaptive and both humoral and cellular adaptive immunity. Most functions can be associated with their ability to induce a wide range of chemokines (MCP-1, MIP-1alpha, IL-8) and cytokines (e.g., IL-12, IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10). This review tries to link well-known properties of mycolic acid-containing glycolipids, e.g., stimulation of cellular and humoral immunity, granuloma formation and anti-tumor activity, with recent findings in molecular immunology and to give an outlook on potential practical applications.

Adjuvants, Immunologic↗
PubMed2001

Trehalose 6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis induces foreign-body- and hypersensitivity-type granulomas in mice.

Granulomatous inflammation is characterized morphologically by a compact organized collection of macrophages and their derivatives. It is classified as either a hypersensitivity type or a foreign-body type. Lipid components of the Mycobacterium tuberculosis cell wall participate in the pathogenesis of infection. Strains of M. tuberculosis have cord factor (trehalose 6,6'-dimycolate [TDM]) on their surface. To clarify host responses to TDM, including immunogenicity and pathogenicity, we have analyzed the footpad reaction, histopathology, and cytokine profiles of experimental granulomatous lesions in immunized and unimmunized mice challenged with TDM. In the present study, we have demonstrated for the first time that TDM can induce both foreign-body-type (nonimmune) and hypersensitivity-type (immune) granulomas by acting as a nonspecific irritant and T-cell-dependent antigen. Immunized mice challenged with TDM developed more severe lesions than unimmunized mice. At the active lesion, we found monocyte chemotactic, proinflammatory, and immunoregulatory cytokines. The level was enhanced in immunized mice challenged with TDM. This result implies that both nonimmune and immune mechanisms participate in granulomatous inflammation induced by mycobacterial infection. Taken together with a previous report, this study shows that TDM is a pleiotropic molecule against the host and plays an important role in the pathogenesis of tuberculosis.

Animals↗
PubMed2001

Clinical evaluation of anti-tuberculous glycolipid immunoglobulin G antibody assay for rapid serodiagnosis of pulmonary tuberculosis.

Previously we reported the development of a highly sensitive enzyme-linked immunosorbent assay specific for anti-tuberculous glycolipid (anti-TBGL) for the rapid serodiagnosis of tuberculosis. In this study, the usefulness of an anti-TBGL antibody assay kit for rapid serodiagnosis was evaluated in a controlled multicenter study. Antibody titers in sera from 318 patients with active pulmonary tuberculosis (216 positive for Mycobacterium tuberculosis in smear and/or culture tests and 102 smear and culture negative and clinically diagnosed), 58 patients with old tuberculosis, 177 patients with other respiratory diseases, 156 patients with nonrespiratory diseases, and 454 healthy subjects were examined. Sera from 256 younger healthy subjects from among the 454 healthy subjects were examined as a control. When the cutoff point of anti-TBGL antibody titer was determined as 2.0 U/ml, the sensitivity for active tuberculosis patients was 81.1% and the specificity was 95.7%. Sensitivity in patients with smear-negative and culture-negative active pulmonary tuberculosis was 73.5%. Even in patients with noncavitary minimally advanced lesions, the positivity rate (60.0%) and the antibody titer (4.6 +/- 9.4 U/ml) were significantly higher than those in the healthy group. These results indicate that this assay using anti-TBGL antibody is useful for the rapid serodiagnosis of active pulmonary tuberculosis.

Antibodies, Bacterial↗
PubMed2001

New diagnostic approach for ocular tuberculosis by ELISA using the cord factor as antigen.

BACKGROUND/AIMS: Diagnosis of ocular tuberculosis is difficult, particularly the retinal vasculitis type, because most cases occur without concurrent active pulmonary tuberculosis. Recently, it has been reported that detection of antibodies against purified cord factor (trehalose-6,6'-dimycolate, TDM), the best studied, most antigenic, and most abundant cell wall component of tubercule bacilli, is very useful for rapid serodiagnosis of pulmonary tuberculosis. In this study, an attempt was made to evaluate whether the detection of anticord factor antibody is also useful for diagnosis of ocular tuberculosis and the necessity of antituberculous therapy for tuberculous retinochoroiditis was discussed. METHODS: Cases consisted of 15 patients with uveitis and retinal vasculitis, nine patients with presumed ocular tuberculosis, three patients with sarcoidosis, and three patients with Behçet's disease. IgG antibodies against purified cord factor prepared from Mycobacterium tuberculosis H37Rv were detected by enzyme linked immunosorbent assay. RESULTS: All cases of clinically presumed ocular tuberculosis were positive, whereas all of the cases of sarcoidosis or Behçet's disease were negative for anticord factor antibodies. When the anticord factor antibody titres were compared on the basis of the presence or absence of previous antituberculosis chemotherapy, the mean anticord factor antibody titre of the untreated group showed a tendency to be higher than in the treated group, but not significantly (p=0.07). CONCLUSIONS: The detection of anticord factor antibody may be useful to support the diagnosis of ocular tuberculosis. Additionally, a positive result for anticord factor antibody may indicate that tubercule bacilli are present in some organ(s) of the patient even in the absence of active systemic disease.

Adult↗
PubMed2001

Granulomatous tissue formation of shikon and shikonin by air pouch method.

"The extract of shikon" (SK) and shikonin play important roles in the development of granulomatous tissue formation. To reveal the augmenting effect of SK or shikonin on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granulomatous tissue induced by SK and shikonin, comparing them to pouches in which trehalose 6,6'-dimycolate (TDM) was injected. The development of granulomatous tissue formation was evaluated by the wet weight of pouch walls. At day 5 and 7 after SK and shikonin injection, prominent granulomatous tissue formation was detected. Histological observations on the development of granulomatous tissue showed that the pouch was formed in the submuscular connective tissue and necrotic tissue directly facing the cavity and granulomatous tissue developed in the connective tissue. At day 1, VEGF-positive neutrophils accumulated in the pouch wall. Granulomatous tissue formation and neovascularization by injection of SK or shikonin was not more prominent than TDM. However, the present results indicate that SK and shikonin induce neovascularization in granulomatous tissue.

Animals↗
PubMed2001

Induction of thymic apoptosis by Shiga toxin from Escherichia coli O157:H7 in vivo and in vitro.

It is not known how Shiga toxins (Stxs), which are major virulence factors of enterohemorrhagic Escherichia coli, can affect the host immune system. We investigated the effect of Stx2 on murine thymic cells in vivo and in vitro. After intraperitoneal administration of Stx2, the body weight of mice (BW) and the organ index of thymocytes (OIT) gradually decreased from day 1 to day 4. Apoptosis of thymocytes, assessed by TUNEL staining, and DNA fragmentation assay, was marked on day 3 and day 4. Decrease in BW and OIT due to Stx2 was antagonized by the simultaneous administration of murine anti-Stx2 IgG antibody with Stx2. In vitro administration of Stx2 also induced apoptosis of cultured thymocytes on day 3 and day 4 in a dose-dependent fashion. These results showed that Stx2 directly caused apoptosis of thymocytes in vivo and in vitro. Our findings imply that StA2 may be intimately related to pathogenesis of E. coli O157:H7 infection, by causing apoptosis of thymus.

Animals↗
PubMed2000

Mycolic acids from Rhodococcus, Gordonia, and Dietzia.

The mycolic acids from 11 species of Rhodococcus, seven species of Gordonia, and one species of Dietzia were analyzed using capillary gas chromatography and mass spectrometry (GLC/MS). All strains tested in this study were divided into three groups according to the degree of double bonds and the average carbon number (Av.Nc.) of their mycolic acids. The genus Gordonia belongs to the first group possessing an Av.Nc. in the upper 50s and 60s with 0 to 5 double bonds. Some Rhodococcus species possessed Av.Nc. in the 40s with a variety of distributions of polyunsaturated fatty acids from 0 to 4. The rest of the Rhodococcus species and the genus Dietzia possessed Av.Nc. in the 30s with saturated fatty acids. We previously reported on Nocardia strains whose Av.Nc. were in the 50s. Considering the identification of mycolic acid-containing Actinomycetales at the generic level, the Av.Nc. proved to be useful as a means of differentiating the genera Rhodococcus, Gordonia and Nocardia. The genus Dietzia was found to have its own characteristic constitution of mycolic acid molecular species. The mycolic acids from D. maris 58001T were characterized by an almost equal amount of constituents of even- and odd-numbered carbon chains, whereas the major components of mycolic acids in all other strains had even-numbered carbon chains. Another characteristic of Dietzia was some even-numbered mycolic acids which contained odd-numbered straight chains with odd-numbered alpha-branches. These characteristics indicated that Dietzia might possess a novel fatty acid biosynthesis system.

Actinomycetales↗
PubMed2000

Transepithelial transport of levofloxacin in the isolated perfused rat kidney.

PURPOSE: The transepithelial transport of levofloxacin was evaluated in the isolated perfused kidney to investigate its renal secretory mechanisms. METHODS: Levofloxacin was instantaneously administered into the renal artery together with inulin and Evans blue-labeled albumin, and the single-pass dilution curves of the renal venous and urinary outflow were determined in the absence or presence of various compounds. Kinetic parameters were computed based on non-compartment moment analysis. RESULTS: The ratio of fractional excretion to filtration fraction (FE/FF) for levofloxacin was 2.99 +/- 0.18, indicating the involvement of tubular secretion. In the presence of cimetidine and quinolones, the FE/FF of levofloxacin was significantly decreased and the transepithelial mean transit time (Tcell) of levofloxacin was prolonged. The Tcell showed a negative correlation with renal secretion of levofloxacin, while the volume of distribution of levofloxacin showed no correlation. CONCLUSIONS: Transport on the brush-border membrane plays a determining step in the renal secretion of levofloxacin, and cimetidine and quinolones interact with levofloxacin transport on the brush-border membrane.

Animals↗
PubMed2000

Highly selective antibacterial activity of novel alkyl quinolone alkaloids from a Chinese herbal medicine, Gosyuyu (Wu-Chu-Yu), against Helicobacter pylori in vitro.

To elucidate the antibacterial activity of Gosyuyu, the crude extract from the fruit of Evodia rutaecarpa, a Chinese herbal medicine, has been fractionated chromatographically, and each fraction was assayed for antibacterial activity against Helicobacterpylori (H. pylori) in vitro. As the result, a single spot having marked antibacterial activity against H. pylori was obtained and the chemical structure was analyzed. The isolated compound was revealed to be a novel alkyl quinolone alkaloid based on the solubility, IR spectra, NMR analysis and mass spectrometric data after purification by TLC of silica. We compared the antimicrobial activity of this compound with that of other antimicrobial agents and examined susceptibility of various intestinal pathogens. As the result, the new quinolone compounds obtained from Gosyuyu extracts were found to be a mixture of two quinolone alkaloids, 1-methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone and 1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone (MW: 339), reported previously. The minimum inhibitory concentration (MIC) of these compounds against reference strains and clinically isolated H. pylori strains were less than 0.05 microg/ml, which was similar to the MIC of amoxicillin and clarithromycin that are used worldwide for the eradication of H. pylori, clinically. Furthermore, it was noted that the antimicrobial activity of these compounds was highly selective against H. pylori and almost non-active against other intestinal pathogens. The above results showed that these alkyl methyl quinolone (AM quinolones) alkaloids were useful for the eradication of H. pylori without affecting other intestinal flora.

Alkaloids↗
PubMed2000

Trehalose 6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis induces corneal angiogenesis in rats.

Neovascularization or angiogenesis is required for the progression of chronic inflammation. The mechanism of inflammatory neovascularization in tuberculosis remains unknown. Trehalose 6, 6'-dimycolate (TDM) purified from Mycobacterium tuberculosis was injected into rat corneas. TDM challenge provoked a local granulomatous response in association with neovascularization. Neovascularization was seen within a few days after the challenge, with the extent of neovascularization being dose dependent, although granulomatous lesions developed 14 days after the challenge. Cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), IL-1beta, and vascular endothelial growth factor (VEGF), were found in lesions at the early stage (within a few days after the challenge) and were detectable until day 21. Neovascularization was inhibited substantially by neutralizing antibodies to VEGF and IL-8 but not IL-1beta. Treatment with anti-TNF-alpha antibodies resulted in partial inhibition. TDM possesses pleiotropic activities, and the cytokine network plays an important role in the process of neovascularization.

Animals↗