Biomedical subjects

Kazutoshi Shibuya

Publications and source records attributed to Kazutoshi Shibuya.

22 records · Page 2Linked to original sources

PubMed2002

Histopathology of deep-seated fungal infections and detailed examination of granulomatous response against cryptococci in patients with acquired immunodeficiency syndrome.

This understood without starting paper describes general histopathological features of deep-seated mycoses in patients with acquired immunodeficiency syndrome (AIDS) detailed histological examination on cryptococcal lesions with a consideration of morphological modification caused by treatment with highly active antiretroviral therapy (HAART). In a histopathological review of 164 patients with total human immunodeficiency virus (HIV) infection, the microscopical appearance of esophageal candidiasis which was common in those with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida pneumonia. Nineteen patients including one treated with HAART had generalized cryptococcosis, representing the most common generalized fungal disease. The essential histologic features of the disease were yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from those induced by both Candida and Aspergillus infections. Three histologic patterns were recognized in the pulmonary cryptococcal lesions, two of which could be graded with respect to the degree and type of inflammatory reaction. The first was a mild one consisting of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. The second pattern involved massive cryptococcal infection, which might have been simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in the eighteen patients who had not been treated with HAART. The absence of T cells and decreasing function of antigen-presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream dissemination by Cryptococci. The third pattern demonstrated in the patient treated with HAART was characterized by the presence of CD4+ cells, greater response of histiocytes and multinucleated giant cell formation, and lack of massive capillary involvement.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages.

Phenylpropanoids may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds. 4-cis, 8-cis-Bis (4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo-[3.3.0]octane-2,6-dione (bis-FA, compound 2), a dimer of ferulic acid, was synthesized from ferulic acid (1), and its effect on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells was compared with those of the parent ferulic acid (1) and of iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid) (3). LPS-induced gene expression of COX-2 was markedly inhibited by compound 2 at a concentration of 10 microM and by compound 3 at 100 microM, but was not inhibited by compound 1 at 100 microM. This observation suggests that compound 2 may possess potent anti-inflammatory activity. These ferulic acid-related compounds were able to scavenge the stable 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. The 50% inhibitory concentration for DPPH radicals declined in the order 3 (40.20 mM) > 2 (3.16 mM) > 1 (0.145 mM). Compound 1 possessed potent anti-radical activity, but no COX-2 inhibitory activity, which may be a result of enhancement of its conjugate properties by abstraction of an H atom from the phenolic OH group, causing loss of phenolic function. In contrast, inhibition of COX-2 expression by compounds 2 and 3 could be caused by their increased phenolic function, which is associated with decreased anti-radical activity. Compounds 2 and 3, particularly 2, may have potential as NSAID-like compounds.

Actins↗

PubMedDate not supplied

Induction of cytotoxicity and apoptosis and inhibition of cyclooxygenase-2 gene expression, by curcumin and its analog, alpha-diisoeugenol.

Cytotoxici and alpha-diisoeugenol were investigated. The cytotoxicity of curcumin and a-diisoeugenol against human promyelocytic leukemia cells (HL-60 cells) and human submandibular cancer cells (HSG cells) was similar (CC50 1-3 microM). However, curcumin induced much more apoptosis, particularly in HL-60 cells compared with HSG cells, as revealed by measurement of the sub-G1/G0 DNA fraction in flow cytometric histograms. Treatment with 15 microM curcumin increased the number of cells with a sub-G1/G0 DNA fraction from control levels of <5% to 55% in HL-60 cells and 30% in HSG cells. Flow cytometry, after staining with annexin V-FITC/PI (the exposure of phosphatidylserine (PS) on the surface of apoptotic cells), showed a dose-dependent induction of early apoptosis by curcumin, which reached about 65% in HL-60 cells and about 20% in HSG cells after treatment with 10 microM curcumin. In contrast, alpha-diisoeugenol failed to induce apoptosis in either cell type. For both cell types, the proportion of late apoptotic/necrotic cells increased rapidly at concentrations of curcumin and a-diisoeugenol greater than 10 microM. The generation of intracellular reactive oxygen species (ROS) in curcumin-treated HL-60 cells was greater than that in HSG cells, as judged by CDFH-DA staining. In both cell types, ROS generation by a-diisoeugenol was at control levels. ROS generation by curcumin was suppressed by antioxidants such as N-acetyl-L-cysteine (NAC) and glutathione (GSH) and by scavengers of hydroxy radicals such as mannitol, but, conversely, was promoted by prooxidants such as the transition metal ions Cu(II) and Zn(II). ROS generation may play a part in the exposure of PS. Curcumin, but not a-diisoeugenol, at 10 microM inhibited LPS (lipopolysaccharide)-induced COX-2 gene expression in RAW 264.7 cells. Semiempirical PM 3 calculations suggested that this activity of curcumin, in which it behaves as a non-steroidal anti-inflammatory drug (NSAID)-like compound, is dependent on its phenolic function, which is more pronounced than that of alpha-diisoeugenol. Taken together, our results suggest that the bioactivity of curcumin is a result of its ability to act as both a prooxidant and an antioxidant.

Animals↗

PubMedDate not supplied

Kinetic radical-scavenging activity of melatonin.

Carbon-centred free radicals can be involved in damage to biological systems under hypoxiclanoxic conditions as well as in ischaemia/reperfusion injury. The antioxidant activities of melatonin against carbon-centred radicals are poorly understood. The aim of this study was to investigate the antioxidant properties of melatonin against carbon-centred radicals in a biomimetic model system consisting of growing methyl methacrylate (MMA) radicals (poly-MMA radicals, PMMA*). The kinetics of the polymerization of MMA initiated by thermal decomposition of 2,2'-azobis(isobutyronitrile) (AIBN; R* radical) or benzoyl peroxide (BPO; PhCOO* radical) in the presence of melatonin were investigated by the induction period method under nearly anaerobic conditions. As melatonin concentrations increased, the length of the induction period (IP) increased, but for the BPO system the IP reached a plateau at a molar ratio of BPO to melatonin of 5:1, indicating that the oxidation of melatonin by PhCOO* was limited. At low concentrations of melatonin, the stoichiometric factor (n, the number of free radicals trapped by the antioxidant moiety) for melatonin was approximately 2, but as the melatonin concentration increased the n value decreased markedly to 0.1. These observations suggest that melatonin may possess catalytic activity contributing to radical avoidance. The initial rate of polymerization (Rp) in the BPO system was markedly suppressed by high concentrations of melatonin, suggesting a strong interaction between oxidative end-products formed from melatonin and PMMA*. Under conditions where n was about 2, the kinh values for melatonin in the BPO system and the AIBN system were 6.58 x 10(4) M(-1)S(-1) and 2.49 x 10(3) M(-1)s(-1), respectively. In the BPO system, the kinh of melatonin was of a similar magnitude to that of a-tocopherol, whereas in the AIBN system the kinh of melatonin was 100-fold greater than that of tocopherol. The present findings suggest that melatonin may be able to scavenge harmful carbon-centred radicals in vivo.

Antioxidants↗