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  • 1
    ISSN: 1432-1041
    Keywords: Key words Pranidipine ; Grapefruit juice/orange ; juice interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially available, were used in this study. Methods: Sixteen healthy male Japanese subjects participated in this study and were divided into two groups for grapefruit juice and orange juice treatment. The study followed an open-labelled crossover design, comparing the effects of a single oral dose of 2 mg pranidipine taken together with 250 ml citrus juice or 250 ml water. Serum pharmacokinetics of pranidipine, adverse reactions, blood pressure, heart rate, 12-lead ECG, haematology, clinical chemistry and urinalysis were measured throughout the study. Results: For grapefruit juice, mean Cmax and AUC0–24 h were significantly higher than those of water (P = 0.0003 and 0.0005, respectively, ANOVA) with the ratios of log transformed values being 1.50 and 1.74, respectively. There were no differences in tmax and t½ between the juice and water treatments. A significant increase in heart rate (P = 0.0240, ANOVA with repeated measurements) was observed in the juice treatment whereas there were no significant differences in systolic and diastolic blood pressure between the two treatments. For orange juice, a small decrease in mean Cmax was observed compared with water (P = 0.0218, ANOVA) with the ratio being 0.86, but there was no significant difference in AUC0–24 h between the two treatments. No marked differences were observed in tmax and t½. Oral pranidipine administration with orange juice did not affect heart rate, systolic and diastolic blood pressures or other parameters for safety evaluation. Conclusions: Oral co-administration with grapefruit juice and pranidipine was associated with increased bioavailability and changed the pharmacodynamics of pranidipine, particularly with regard to heart rate. Orange juice intake with pranidipine did not markedly affect the pharmacokinetics and no clinically significant changes were observed in the pharmacodynamics and safety evaluation.
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  • 2
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cytomegalvirus (CMV) establishes a latent infection in its host; however, the organ sites of viral latency and its mechanism still remain to be fully clarified. To elucidate this issue, a latent infection with murine (M) CMV was attempted to induce in mice and the organ sites of the latent viral genome were examined for more than one year by a polymerase chain reaction (PCR). As a result, latent MCMV DNA was detectable in both the lung and the spleen as late as 59 weeks after infection. The heart was also observed to be a target organ of latent MCMV DNA, though the amount of viral DNA was much less than that seen in the lung and spleen. In germfree (GF) mice, on the other hand, no such latent viral DNA was observed in the spleens, while it was seen, but to a significantly smaller degree, in the lungs and the hearts than in the same organs of specific pathogen-free (SPF) mice. The amount of infectious virions generated in the host appeared to be almost equal between the GF and SPF mice. The above findings therefore suggest that the spleen, lung and heart are target organs for MCMV latency and the indigenous bacterial flora, which are not colonizing in GF mice, play an important role in the establishment of such viral latency in SPF mice.
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  • 3
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A long period of clinical latency before development of symptoms is characteristic of human immunodeficiency virus type 1 (HIV-1) infection. OM10.1, a promyelocyte cell line latently infected with HIV-1, has been developed as a model for studying the mechanism of viral latency and the activation of virus expression. We found that this latently infected cell line with heat shock at 42°C for 2 h resulted in a high level of HIV-1 production without addition of any cytokines. The mechanism of activation was analyzed by using anti-TNF-α antibody and various inhibitors. Although the TNF-α level in culture supernatants was below the sensitivity of an ELISA assay system, addition of anti-TNF-α antibody in culture medium could partially suppress the heat shock induced HIV-1 production. Staurosporine (PKC inhibitor), pentoxifylline (NF-ϰB inhibitor), and Ro5-3335 (HIV-1 Tat inhibitor) also inhibited significantly the heat shock induced virus activation. In particular, staurosporine achieved approximately 90% inhibition of the HIV-1 antigen expression in heat shock-treated OM10.1 at a non-toxic concentration. Although the mechanism of HIV-1 activation with heat shock has not been fully elucidated yet, it is presumed PKC plays an important role in HIV-1 activation. Thus, the present observations will provide a further insight into the pathogenesis of HIV-1 infections.
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  • 4
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The administration of bovine lactoferrin (LF) with 1 mg/g body weight before the murine cytomegalovirus (MCMV) infection completely protected the BALB/c mice from death due to the infection. In these LF-treated mice, a significant increase in the activity was found in the NK cells but not in the cytolytic T lymphocytes which recognized an MCMV-derived peptide. Moreover, the elimination of the NK cell activity by an injection with anti-asialo GM1 antibody abrogated such augmented resistance, thus supporting the hypothesis that the LF-mediated antiviral effect in vivo is performed through the augmentation of NK cell activity. No such LF-mediated antiviral effect in vivo with the increased NK cell activity was found in athymic nude mice, whereas it was restored completely by the transfer of splenic T cells from LF-treated donors. These findings therefore suggest that T lymphocytes induce both the augmentation of NK cell activity and the resultant antiviral effect in the LF-treated hosts.
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  • 5
    ISSN: 1432-0533
    Keywords: Adult T cell leukemia ; HTLV-I ; Immunohistochemistry ; In situ polymerase chain reaction ; p53 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the pathological changes in skeletal muscle from a patient with acute adult T cell leukemia (ATL). HTLV-I provirus was detected in infiltrating cells using in situ polymerase chain reaction in frozen sections. Furthermore, aberrant expression of the p53 protein was observed in the infiltrating cells. As p53 protein was not observed in mononuclear inflammatory cells in patients with polymyositis, expression of the p53 protein was considered to be one of the characteristic findings in ATL cells. This is the first direct detection of ATL cells in skeletal muscle.
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  • 6
    ISSN: 1432-0533
    Keywords: Key words In situ polymerase chain reaction ; Immunohistochemistry ; Human T cell lymphotropic ; virus type I ; Proviral DNA ; Polymyositis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have analyzed muscle biopsy specimens from polymyositis patients who are also positive for human T cell lymphotropic virus type I (HTLV-I) using both immunohistochemistry for surface antigens of lymphocytes and macrophages and in situ polymerase chain reaction for HTLV-I proviral DNA on the same sections. We found HTLV-I in CD4+ cells but not in macrophages. This finding suggests that most of the HTLV-I-containing CD4+ cells are not macrophages but lymphocytes.
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  • 7
    ISSN: 1432-0630
    Keywords: PACS: 68.35 ; 81.10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract.  C70 single crystals, free from solvent contamination, were grown via vapor phase transport technique. The (0001) face of the C70 crystal was imaged with Atomic Force Microscopy (AFM) under ambient atmosphere. Low-resolution images of a freshly prepared crystal revealed well-ordered faceted regions with multiple terraces extending over a region of several hundred square nanometers. The terraced structure in the images indicates that the crystals formed as a layer growth. In the high-resolution images, C70 molecules were resolved in a hexagonal close packed (hcp) structure with an average center-to-center distance of 10.5 ± 0.5 Å. After one month’s exposure to the ambient atmosphere, the molecules rearranged into a mixed structure consisting of hcp and face centered cubic (fcc) regions.
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  • 8
    ISSN: 1432-0630
    Keywords: PACS: 61.48.+c; 68.35.-p; 68.35.Bs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: 60 single crystals. The (111) and the (001) faces of C60 single crystals were illuminated with photons with energies below the band gap (generation of Frenkel-type excitons) or above the band gap. In the case of sub-band-gap illumination, reconstructed surfaces formed on the crystals. The reconstruction was represented by fringes running in the [11 ] and [0 0] directions on the (111) and (001) surfaces, respectively. As a result of supra-band-gap illumination, however, there appeared only cracks, without any fringes, which were oriented in directions characteristic of each face. The results suggest that the photo-induced surface reconstruction of C60 single crystals is induced via the recombination of Frenkel-type excitons.
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Adult T cell leukemia ; HTLV-I ; Immunohistochemistry ; In situ polymerase chain reaction ; p53 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the pathological changes in skeletal muscle from a patient with acute adult T cell leukemia (ATL). HTLV-I provirus was detected in infiltrating cells using in situ polymerase chain reaction in frozen sections. Furthermore, aberrant expression of the p53 protein was observed in the infiltrating cells. As p53 protein was not observed in mononuclear inflammatory cells in patients with polymyositis, expression of the p53 protein was considered to be one of the characteristic findings in ATL cells. This is the first direct detection of ATL cells in skeletal muscle.
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  • 10
    ISSN: 1432-0533
    Keywords: Key words Immunohistochemistry ; Polymerase chain ; reaction in situ hybridization ; HTLV-I-associated ; myelopathy/tropical spastic paraparesis ; Double ; staining ; Fresh frozen sections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HTLV-I-infected cells play an important role in pathogenesis HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Our previous studies of quantitative polymerase chain reaction (PCR) and in situ PCR suggested that T cells infiltrating in the spinal cord lesion were infected with HTLV-I. To elucidate the localization of HTLV-I proviral DNA directly, we performed double staining using immunohistochemistry and PCR in situ hybridization (PCR-ISH). Fresh frozen sections of the spinal cord from four HAM patients taken at autopsy were first immunostained with antibodies to pan T cells (UCHL-1), macrophages (KP-1) and helper/inducer T cells (OPD4). Then PCR-ISH was carried out with specific primers and probe for the HTLV-I pX region. UCHL-1-positive cells were noted around perivascular areas and, to some extent, in the parenchyma. Of the UCHL-1-positive cells, 9.4% (case 1), 9.6% (case 2), 1.1% (case 3) and 6.7% (case 4) became positive in HTLV-I PCR-ISH. UCHL-1-negative cells were HTLV-I PCR-ISH negative and almost all KP-1-positive cells were HTLV-I negative. HTLV-I was localized to OPD4-positive cells in examined lesions of cases 2 and 4. These data are a direct demonstration of HTLV-I proviral DNA localizing to infiltrated T cells in HAM/ TSP spinal cord lesions.
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