[Refractory Behçet's disease requiring repeated intestinal resection].
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Adolescent↗
Biomedical subjects
Yasuo Suzuki
Publications and source records attributed to Yasuo Suzuki.
Butyrate reduces colonic paracellular permeability by enhancing PPARgamma activation.
Butyrate may have a role in preventing ulcerative colitis, but its precise mechanism is unknown. Also, PPARgamma (peroxisome proliferator-activated receptor gamma) is expressed at high levels both in the colonic epithelium and colon cancer cell lines, but no report was shown on the relationship between PPARgamma activation and the effect of butyrate. We investigated the effects of butyrate and PPARgamma agonist on paracellular permeability. To discover whether PPARgamma expressed in the cell lines treated with butyrate was functional or not, we transfected HT-29 cells with an acyl-CoA oxidase promoter-luciferase reporter plasmid containing a PPRE (peroxisome proliferator responsive element) and analyzed the luciferase activity. Butyrate and PPARgamma agonist significantly reduced paracellular permeability of the colon cell line (p<0.05) and this effect indicated that butyrate and PPARgamma agonist decreased HT-29 cell growth and increased differentiation (p<0.01). PPRE activation treated with butyrate was approximately four and a half times that in untreated cells (p<0.01). These findings suggest that the effect of butyrate on paracellular permeability has apparently taken place through PPARgamma activation and this effect attributes to preventing inflammation of the colon.
Butyrates↗
Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis.
The initial event in the process of leukocyte infiltration is characterized by leukocyte rolling on the surface of the endothelium, which is mediated by selectins. P- and L-selectin bind to the sulphated sugar chains of their natural ligands, including sulphated glycolipids such as sulphatide. Recently, it has been demonstrated that sulphated glycolipids and sulphated oligosaccharides interfere with selectin binding pathways. This study synthesized sulphated hyaluronic acid (SHA), which is a potential selectin-blocking agent, and examined its therapeutic effect on the experimental progressive mesangial proliferative glomerulonephritis induced by anti-Thy-1 monoclonal antibody (1-22-3 MAb) after unilateral nephrectomy. The selectin-inhibitory effect of SHA in vitro was confirmed. SHA inhibited the binding of P- and L-selectin to sulphatide, which is a glycolipid ligand for P- and L-selectin, at a concentration of 1.5 micro g/ml and 100 micro g/ml. Immunohistochemical examination showed that P-selectin was up-regulated in the glomeruli in the 1-22-3 MAb nephritis model, while the ligands for L-selectin were not detected in the glomerular tufts. A single administration of SHA ameliorated proteinuria and glomerular leukocyte infiltration in 24 h after the injection of anti-Thy-1 MAb. Anti-P-selectin MAb, but not anti-L-selectin MAb, inhibited proteinuria and glomerular leukocyte infiltration. To examine further the therapeutic effect of SHA on chronic glomerulonephritis, SHA was administered daily from day 3 to day 14 in this model. Proteinuria and glomerular leukocyte infiltration were significantly diminished in SHA-treated rats on day 14. These results suggest that SHA ameliorated rat progressive mesangial proliferative glomerulonephritis by inhibiting P-selectin-dependent leukocyte infiltration in glomeruli. Sulphated oligosaccharides may be beneficial for the therapy of mesangial proliferative glomerulonephritis.
Animals↗
Asialo-GM1 and asialo-GM2 are putative adhesion molecules for Moraxella catarrhalis.
Moraxella catarrhalis is an important pathogen of respiratory and middle ear infections. We previously reported that the attachment of M. catarrhalis to pharyngeal epithelial cells is mediated by ganglioside M2 (GM2). Several sets of adhesins or receptors are involved in such attachment process. In this study, we used the same strains and similar bacterial culture conditions as those in our previous study, and demonstrated by thin layer chromatography that M. catarrhalis can also bind to asialo-GM1 (Gg4Cer) and asialo-GM2 (Gg3Cer). GalNAcbeta1-->4Galbeta1 is a common sequence in both Gg4Cer and Gg3Cer, and in many respiratory bacteria, this sequence acts as a receptor for attachment to host cells. Treatment of human pharyngeal epithelial cells with anti-GM2 and anti-Gg4Cer antibodies significantly decreased attachment of M. catarrhalis to these cells; however, treatment with anti-Gg3Cer antibody did not decrease M. catarrhalis attachment. Immunofluorescence microscopy revealed that human pharyngeal epithelial cells are positive for GM2 and Gg4Cer, but not for Gg3Cer. Our results indicate that Gg4Cer on human pharyngeal epithelial cells, and Gg3Cer,possibly on other cells, could serve as molecules for attachment of M. catarrhalis.
Adhesins, Bacterial↗
Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A.
1. Medium-chain triglyceride (MCT) is often administered to patients with Crohn's disease (CD) or short-bowel syndrome. However, little is known about the effects of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8 secretion by differentiated Caco-2 cells. 2. We found for the first time that caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the transcriptional level when precultured together for 24 h. We also tried to clarify the mechanism of IL-8 gene inhibition by examining the activation of NF-kappaB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation. 3. The result of dual-luciferase assay using Caco-2 cells transfected with IL-8 promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the activation of IL-8 promoter. 4. Similar results were observed when cells were precultured with the well-known potent histone deacetylase inhibitor trichostatin A (TSA). 5. We examined the state of H4 acetylation in IL-8 promoter using the technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4 acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These results suggest that the inhibition of IL-8 gene transcription induced by caprylic acid and TSA does not necessarily require the marked suppression of transcription factors, and the mechanism of inhibition of IL-8 gene transcription may be different between caprylic acid and TSA.
Caco-2 Cells↗
Suppression of Helicobacter pylori-induced interleukin-8 production in gastric cancer cell lines by an anti-ulcer drug, geranylgeranylacetone.
BACKGROUND: Geranylgeranylacetone (GGA) is an antigastritis and anti-ulcer agent, with as yet an unknown mechanism of action. In this study, we investigated the effect of GGA on Helicobacter pylori-induced interleukin (IL)-8 production and IL-8 mRNA expression in KATOIII cells, an established gastric cell line. METHODS: Interleukin-8 production in H. pylori-infected KATOIII cells was measured by using enzyme-linked immunoassay. The cytotoxicity of H. pylori on KATOIII cells was measured by a 51Cr release assay. The effect of GGA on H. pylori-induced IL-8 mRNA expression was measured by using northern blotting. RESULTS: Interleukin-8 production increased with time and H. pylori dose; the most significant increase was seen within 6-24 h of coculture with H. pylori. A dose of 0.1 mmol GGA suppressed IL-8 production (P = 0.0077) and inhibited H. pylori-induced IL-8 mRNA expression (P = 0.0019). Furthermore, H. pylori-induced gastric mucosal cell injury associated with IL-8 and neutrophil activation was enhanced by NH3, and this enhancement was suppressed by GGA (P = 0.0043). CONCLUSIONS: Helicobacter pylori-infected gastric mucosal cells produce IL-8, which can promote neutrophil activation, thus contributing to mucosal tissue injury associated with H. pylori infection. Agents like GGA, which can suppress IL-8 production may have a protective role in the treatment of mucosal tissue damage seen in H. pylori infection.
Analysis of Variance↗
An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses.
The compound Neu5Ac3alphaF-DSPE (4), in which the C-3 position was modified with an axial fluorine atom, inhibited the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolates examined. With the positive results obtained for inhibition of hemagglutination and hemolysis induced by A/Aichi/2/68 virus, the inhibitory effect of Neu5Ac3alphaF-DSPE (4) against MDCK cells was examined, and it was found that 4 inhibits the viral infection with IC50 value of 5.6 microM based on the cytopathic effects. The experimental results indicate that compound 4 not only inhibits the attachment of virus to the cell surface receptor but also disturbs the release of the progeny viruses from infected cells by inhibiting both hemagglutinin and sialidase of the influenza viruses. The study suggested that the compound is a new class of bifunctional drug candidates for the future chemotherapy of influenza.
Binding Sites↗
Oligosaccharides as receptors for JC virus.
JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and in humans causes a demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy. Its hemagglutination activity and entry into host cells have been reported to depend on an N-linked glycoprotein containing sialic acid. In order to identify the receptors of JCV, we generated virus-like particles (VLP) consisting of major viral capsid protein VP1. We then developed an indirect VLP overlay assay to detect VLP binding to glycoproteins and a panel of glycolipids. We found that VLP bound to sialoglycoproteins, including alpha1-acid glycoprotein, fetuin, and transferrin receptor, and that this binding depended on alpha2-3-linked sialic acids and N-linked sugar chains. Neoglycoproteins were synthesized by using ovalbumin and conjugation with oligosaccharides containing the terminal alpha2-3- or alpha2-6-linked sialic acid or the branched alpha2-6-linked sialic acid. We show that the neoglycoprotein containing the terminal alpha2-6-linked sialic acid had the highest affinity for VLP, inhibited the hemagglutination activity of VLP and JCV, and inhibited the attachment of VLP to cells. We also demonstrate that VLP bound to specific glycolipids, such as lactosylceramide, and gangliosides, including GM3, GD2, GD3, GD1b, GT1b, and GQ1b, and that VLP bound weakly to GD1a but did not bind to GM1a, GM2, or galactocerebroside. Furthermore, the neoglycoprotein containing the terminal alpha2-6-linked sialic acid and the ganglioside GT1b inhibited JCV infection in the susceptible cell line IMR-32. These results suggest that the oligosaccharides of glycoproteins and glycolipids work as JCV receptors and may be feasible as anti-JCV agents.
Gangliosides↗
Transverse myelitis in systemic lupus erythematosus.
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Cyclophosphamide↗
Gross total removal of gliomas in the pulvinar and correlative microsurgical anatomy.
Tumors in the pulvinar tend to present as circumscribed lesions with exophytic growth into the lateral and third ventricles. These lesions may be best explored via a parietal-transcortical-transventricular approach. If the tumor extends posteriorly or inferiorly, a posterior-interhemispheric-transtentorial approach may provide a good angle of access. Gross total removal of the tumors in the pulvinar of two patients was achieved by surgical sectioning of the unilateral crus of the fornix or the splenium via a transventricular or interhemispheric approach with acceptable risk. These patients are now doing well as students about 6 years following the first operations. During tumor removal, a posterior-interhemispheric-transtentorial approach combined with above-mentioned approaches was useful for orientation of the critical structures in the posterior incisural space. Knowledge of the anatomical relationships of the pulvinar to the crus of the fornix and the choroid plexus, and to the critical structures located in the posterior incisural space is extremely important for neurosurgeons.
Adolescent↗
[Bone destruction and bone loss in rheumatoid arthritis--mechanism, prevention and treatment].
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Arthritis, Rheumatoid↗
[Von Willebrand factor-cleaving protease activity in patients of collagen disease with antiphospholipid antibodies].
Acquired thrombotic thrombocytopenic purpura (TTP), characterized by widespread thrombus formation in the microcirculation, is a ponderous complication of antiphospholipid syndrome. Recently, von Willebrand factor-cleaving protease (VWF-CPase) activity has been reported as a possible determinant for the occurrence of TTP. To clarify the role of VWF-CPase in the thrombus formation associated with antiphospholipid syndrome, we investigated plasma VWF-CPase activity in patients of collagen diseases with lupus anticoagulant (LA). Decreased plasma VWF-CPase activity less than 50% of the normal activity was observed in 25.7% (n = 18) in 70 patients with collagen diseases and 7 (10%) cases of them showed more lower VWF-CPase activity less than 25%. The IgG fractions obtained from 2 patients with the low VWF-CPase activity strongly inhibited the proteolytic reaction of normal VWF-CPase. There was no significant relationship between LA and plasma VWF-CPase activity. Thrombotic episodes, especially arterial thrombosis, were more frequently observed in LA-positive patients with low VWF-CPase activity. These results suggest that decreased activity of VWF-CPase, partly due to IgG type inhibitor to the enzyme activity may be an additional risk factor for arterial thrombosis in collagen disease patients with antiphospholipid antibodies.
ADAM Proteins↗
[Methotrexate for the treatment of rheumatoid arthritis in Japan--much more still remains to be resolved].
Methotrexate(MTX) is an antifolic agent and has been widely used for RA since early 1980s. Since 1999 when MTX was approved as an antirheumatic drug in Japan, patients taking MTX has been increasing and about sixty thousands patients are estimated to be taking MTX for the treatment of RA. The highest efficacy relative to toxicity of MTX is supported by the highest retention rate among current DMARDs. Therefore, most of rheumatologist places MTX as a golden standard of DMARD. Recent RCT data in European and North American countries showed that ACR 20 and 50 responses are ranging from 60 to 70% and from 40 to 50%, respectively. In these clinical trials, MTX was usually started at a dose of 7.5 mg weekly and then increased to 15-20 mg/week if the disease activity was still present since the clinical effect of MTX is related to the dose in the range 5 to 20 mg weekly. However, an upper limit of clinical dose of MTX (Rheumatrex) for RA is set to 8 mg weekly and this is a major problem because the majority of patients with active RA need higher doses for the suppression of arthritis. This matter needs an immediate solution. If MTX would be used aggressively for the early suppression of RA, informed consent regarding MTX dose and side effects including their earlier signs should be obtained, especially when patients are taking more than 8 mg weekly.
Antirheumatic Agents↗
Effects of an eyeglass-free 3-D display on the human visual system.
PURPOSE: To investigate the effect on the human visual system of viewing 3-dimensional (3-D) computer graphics (CG) images with an eyeglass-free rear-cross-lenticular-type 3-D display. METHODS: Positive accommodation velocity (GRAD) during the accommodative step response was measured in ten healthy young adults before and after they viewed CG images. Although the distance between the viewer and the 3-D display was 600 mm, the apparent distance between the viewer and the virtual object was varied (515, 600, and 722 mm) by changing the visual disparity. RESULTS: A significant slowdown of average GRAD was observed by 60 min after a 30-min 3-D viewing of 3-D CG images [P<0.05, analysis of variance (ANOVA)] but not after a 30-min viewing of the CG images on a 2-D display or after a 15-min 3-D viewing. When the virtual object was at 722 mm, a significant slowdown of average GRAD was observed only at 30 min after the 30-min 3-D viewing (P<0.05, ANOVA). When the virtual object was at 515 mm, a significant slowdown of average GRAD was observed at 30 and 60 min after the 3-D viewing (P<0.05, ANOVA). CONCLUSIONS: The effect on the human visual system of 3-D viewing of 3-D CG images depends on both the duration of the viewing and the apparent distance between the viewer and the virtual objects.
Accommodation, Ocular↗
Visual field defects associated with sick sinus syndrome.
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Bradycardia↗
A review of 244 orbital tumors in Japanese patients during a 21-year period: origins and locations.
PURPOSE: To review 244 cases of orbital tumors to determine the distribution of patient age, pathology, and tumor origin and location. METHODS: We reviewed cases of histopathologically or radiologically verified orbital tumors at our institution from 1981 through 2002, and studied the distribution of patient age, pathology, origin of tumors, and tumor location in the orbit in 244 consecutive patients (aged from 0 to 90 years, mean, 48.7 years; 114 men, 130 women). RESULTS: Among the 244 cases, 213 (89%) were primary orbital tumors, 23 (9%) were secondary tumors originating in contiguous spaces, and 8 (2%) were metastatic tumors. Regarding the location in the orbit, 122 tumors (50%) were extraconal, 36 (15%) were intraconal, and 86 (35%) were in the lacrimal gland area. The common tumors were reactive lymphoid hyperplasia (22%) and malignant lymphoma (20%) in the extraconal area; cavernous hemangioma (25%), optic nerve glioma (14%), and optic nerve sheath meningioma (14%) in the intraconal area; and malignant lymphoma (40%) and pleomorphic adenoma (24%) in the lacrimal gland area. The age distribution of the 244 patients exhibited two peaks, at 0 to 9 years and 60 to 69 years. In the 0- to 9-year-old patients, the most common tumors were dermoid cyst (26%), optic nerve glioma (11%), capillary hemangioma (11%), and hemorrhagic lymphangioma (11%). On the other hand, in patients over 40 years of age, the common tumors were malignant lymphoma (31%), orbital pseudotumor (24%), pleomorphic adenoma (10%), and cavernous hemangioma (9%). CONCLUSIONS: The pathologic profiles of orbital tumors were characterized according to patient age and the location of the tumor in the orbit. The age of onset, tumor location, and radiological findings provide us with important information for the diagnosis of a tumor prior to biopsy or tumor resection and for the determination of the treatment strategy.
Adolescent↗
Transition from upbeat to downbeat nystagmus observed in a patient with Wernicke's encephalopathy.
BACKGROUND: We report an unusual case of Wernicke's encephalopathy presenting with transient upbeat nystagmus that changed to a persistent downbeat nystagmus. CASE: A 27-year-old man presented with upbeat nystagmus. Three months earlier, he had been diagnosed with Wernicke's encephalopathy after fasting for a month. OBSERVATIONS: This diagnosis was supported by his symptoms (ataxia, a confused state). Clinical recovery followed thiamine therapy. His upbeat nystagmus had linear slow phases with average amplitude and frequency (+/-SD) during fixation straight ahead of 2.8 +/- 0.7 degrees and 4.6 +/- 2.2 Hz, respectively. Two months later, the primary position upbeat nystagmus had diminished and downbeat nystagmus (0.9 +/- 0.5 degrees and 3.2 +/- 0.7 Hz on average) for a 20 degrees downward gaze had developed. Then, 8 months later, he showed only downbeat nystagmus, which obeyed Alexander's law. His primary position downbeat nystagmus was completely suppressed by clonazepam, a gamma-aminobutyric acid (GABA) agonist. CONCLUSIONS: Owing to an underlying central vestibular imbalance, even after the recovery of acute neurological symptoms, Wernicke's encephalopathy can be complicated by persistent downbeat nystagmus, which can be treated by a GABA agonist.
Adult↗