The prevalence of Tropheryma whippelii DNA in saliva from healthy controls and patients with spondyloarthropathy.
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Carrier State↗
Biomedical subjects
Tae-Hwan Kim
Publications and source records attributed to Tae-Hwan Kim.
Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2.
Blau syndrome (BS) is a rare familial granulomatous disease manifested by uveitis, arthritis and skin rash. BS has recently been found to be associated with a distinctive mutation in NOD2, which encodes an intracellular toll-like receptor. We have compared host cell interaction with bacterial challenge in U937 cells expressing wild type human NOD2 (NOD2(wt)), mutant NOD2 (NOD2(Blau)), or a vector control (VC). The cells were incubated with Salmonella typhimurium. Intracellular uptake was assessed by harvesting the cells at different time points following invasion and quantitating the CFU, recovered after gentamicin treatment to kill extracellular organisms. Expression of TNF-alpha, TLR2 and TLR4 was determined by semi-quantitative RT-PCR under resting conditions and after stimulation by bacteria. Invasion of target cells with S. typhimurium was diminished in the presence of NOD2(Blau). Expression of TNF-alpha mRNA was enhanced following bacterial invasion in all cell lines but NOD2(Blau) was associated with a more rapid decline in TNF-alpha expression. Kinetics of intracellular clearance of bacteria indicated a relative defect in NOD2(Blau) compared to controls. This clearance defect may be related to the lack of sustained TNF-alpha seen in the early stages. These events were not related to differential TLR2 or TLR4 expression since there were no significant differences seen between the cell lines after bacterial stimulation. Our findings indicate that the NOD2 mutation associated with this syndrome alters host:microbial interaction, and this may have relevance to triggering factors in the ocular and joint inflammation seen in BS.
Arthritis↗
Successful treatment of acquired amegakaryocytic thrombocytopenia with cyclosporine in adult onset Still's disease.
Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disorder, characterized by severe thrombocytopenia and selective, marked decrease or absence of megakaryocytes in the bone marrow. We describe a 29-year-old female with adult onset Still's disease preceding a diagnosis of AAT and autoimmune hemolytic anemia, which was successfully treated with cyclosporine. This is the first case of AAT in a patient with adult onset Still's disease.
Adult↗
Cyclooxygenase-2 polymorphisms and risk of systemic lupus erythematosus in Koreans.
Cyclooxygenase-2 (COX-2) is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. Upregulation of COX-2 in human lupus T cells resists anergy and apotosis. We investigated the COX-2 gene for functional variants that may influence susceptibility, clinical outcomes and severity of systemic lupus erythematosus (SLE) in a Korean population. The study included 345 patients with SLE and 400 unrelated healthy controls. Genotyping for the -765G --> C polymorphism of COX-2 was performed by PCR-RFLP analysis. No difference in the distribution of the genotype frequencies between patients and controls was found. COX-2 genotypes were not associated with clinical features except hematologic abnormalities and anti-RNP antibody. We did not detect any association between COX-2 genotype and disease severity in SLE patients. These results suggest that the -765G --> C polymorphism of COX-2 does not play a significant role in the development of SLE in a Korean population. A possible protective effect of the low activity C allele against the production of anti-RNP antibodies merits further investigation.
Adult↗
Polymerized rodlike nanoparticles with controlled surface charge density.
Stable rodlike nanoparticles with highly controlled surface charge density have been developed by the free radical polymerization of the mixture of polymerizable cationic surfactant, cetyltrimethylammonium 4-vinylbenzoate (CTVB), and hydrotropic salt sodium 4-styrenesulfonate (NaSS) in aqueous solution. The surface charge of the polymerized CTVB/NaSS rodlike nanoparticles was controlled by varying the NaSS concentration during the polymerization process, and the charge variation was interpreted in terms of the overcharging effect in colloidal systems. The SANS measurements show that the diameter of the polymerized CTVB/NaSS rodlike nanoparticles is constant at 4 nm and the particle length ranges from 24 to 85 nm, depending on the NaSS concentration. The polymerized particles are longest when the NaSS concentration is 5 mol % which corresponds to the charge inversion or neutral point. The SANS and zeta potential measurements show that the Coulomb interactions between the particles are strongly dependent on the NaSS concentration and the zeta potential of the polymerized CTVB/NaSS nanoparticles changes from positive to negative (+12.8 approximately -44.2 mV) as the concentration of NaSS increases from 0 to 40 mol %. As the NaSS concentration is further increased, the zeta potential is saturated at approximately -50 mV.
Journal Article↗
Biomarkers in spondylarthritis: a peripheral vision.
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Biomarkers↗
Clinical image: Coexistence of diffuse idiopathic skeletal hyperostosis and ossification of the posterior longitudinal ligament of the cervical spine in a patient with ankylosing spondylitis.
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Cervical Vertebrae↗
Biomarkers in spondyloarthritis.
In spondyloarthritis, in particular ankylosing spondylitis (AS), a need exists for clinically meaningful biomarkers, both for diagnosis and prognosis. Earlier diagnosis has become an imperative since the advent of biologic therapy, which has proved effective in controlling axial inflammation. Presently, however, there are no biomarkers that reliably distinguish inflammatory back pain from the far more prevalent mechanical back pain. The target sites in AS--sacroiliac joints and the spine--are relatively inaccessible to the investigator and clinician, so defining markers associated with or predictive of axial inflammation remains an important goal. Cytokines, metalloproteinases, and cartilage catabolic products are all candidates for the important role of biomarker in spondyloarthritis.
Biomarkers↗
Temporal cDNA microarray analysis of gene expression in human hepatocellular carcinoma upon radiation exposure.
Radiotherapy is not commonly used for the treatment of human hepatocellular carcinoma, due to its poor response rate and poor tolerance of normal liver to ionizing radiation. Recently developed microarray technology makes it possible to verify genes responsive to anticancer therapy of human cancers by simultaneous analysis of gene expression profiles. In the present study, the expression profile of radiation-responsive genes in human hepatocellular carcinoma was evaluated through time-dependent cDNA microarray analysis of expressional variation, following exposure to ionizing radiation. Upon exposure to radiation, more than 13% of genes in both radiation-resistant and -sensitive cells responded to radiation. Time-dependent analysis of radiation-responsive genes revealed that, irrespective of radiation sensitivity, greatly different subsets of genes sequentially participated in cellular response to radiation at their specific activation or deactivation time points. The majority of radiation-responsive genes were differentially but not commonly expressed between radiation-resistant and -sensitive cells. When these differentially regulated genes were classified according to their physiological and functional characteristics and radiation sensitivity, it was prominently obvious that DNA repair-promoting genes were up-regulated in radio-resistant cells and down-regulated or unchanged in radiation-sensitive cells. The present findings indicate that different subsets of genes are sequentially working and DNA repair capacity may control the radiation sensitivity of human hepatocellular carcinoma cells more than any other physiological factor.
Carcinoma, Hepatocellular↗
Femoral bone mineral density is associated with vertebral fractures in patients with ankylosing spondylitis: a cross-sectional study.
OBJECTIVE: To determine the association between vertebral fractures and clinical, laboratory, and radiological variables in patients with ankylosing spondylitis (AS). METHODS: Sixty-eight men with AS and 91 sex- and age-matched controls were consecutively enrolled. Vertebral fractures were assessed according to a visual semiquantitative grading system using plain radiographs of the lumbar spine obtained from patients with AS. Disease activity variables including C-reactive protein, erythrocyte sedimentation rate, finger-to-ground distance score, Schober's Index score, Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score, and syndesmophyte score were identified. Assessments of bone mineral density (BMD) of the lumbar spine and the femur in patients and controls were performed using an anteroposterior dual energy x-ray absorptiometry technique. RESULTS: Eleven patients (16.2%) out of the total of 68 patients with AS had vertebral fractures; these were identified as wedge deformities (n = 5) or biconcave (n = 6) deformities. BMD levels of the lumbar spine and femur in patients were significantly reduced compared with those of age-matched controls. There were significant differences in the Schober's Index scores, finger-to-ground distance scores, BASRI scores of the lumbar spine, syndesmophyte scores, and intertrochanter values of BMD among AS patients both with and without vertebral fractures. Multiple logistic regression analyses revealed that intertrochanteric BMD values also were independently associated with vertebral fractures in AS (p = 0.041). CONCLUSION: We demonstrated evidence of a correlation between low femoral BMD levels and risk of vertebral fractures in patients with AS, especially at the intertrochanteric area. Longitudinal studies in a large population are required to determine the diagnostic implications of femur BMD for increased risk of vertebral fractures in AS.
Absorptiometry, Photon↗
Somatostatin down-regulates LFA-1 activation by modulating Rap1 expression in CD4+ and CD8+ T cells.
Leukocyte function-associated antigen-1 (LFA-1) is one of the integrins that are expressed on the leukocytes, and has been shown to play an important role in leukocyte trafficking. The adhesive activity of LFA-1 is governed partially by the Rap1. This study examined that the relationship between LFA-1 and Rap1 mRNA expressions by anti-CD3 and anti-CD3+SOM treatment in the CD4+ and CD8+ T cells. The LFA-1 mRNA expression levels following the anti-CD3 and anti-CD3+SOM treatment for 30 min was greater on the CD8+ T cells, and the LFA-1 expression of the CD8+ T cells with anti-CD+SOM treatment was affected more severely than that of the CD4+ T cells. The Rap1 mRNA expression patterns following anti-CD3 and anti-CD3+SOM stimulation in the CD4+ and CD8+ T cells were similar to the LFA-1 expression patterns, and the expression level following anti-CD3+SOM treatment was suppressed more significantly in the CD8+ T cells. These results suggest that the difference in the Rap1 expression level after stimulation might explain the differences in the LFA-1 expression level on the T cell subsets, and that the down-regulation of Rap1 expression following SOM treatment is closely related to the diminished LFA-1 expression.
Animals↗
Cartilage biomarkers in ankylosing spondylitis: relationship to clinical variables and treatment response.
OBJECTIVE: Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures. METHODS: Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Patients were stratified with respect to joint involvement and baseline levels of inflammatory markers, and responders were defined according to the Assessments in Ankylosing Spondylitis 20% criteria. Serial measurements of interferon-gamma, tumor necrosis factor alpha, transforming growth factor beta (TGFbeta), interleukin-10 (IL-10), and IL-1 were done at each time point. The following biomarkers were measured by enzyme-linked immunosorbent assay: the proteoglycan aggrecan 846 epitope, a marker of cartilage turnover; C-propeptide of type II collagen (CPII), a biosynthesis marker; and the Col2-3/4(long mono) (C2C) and Col2-3/4(short) (C1-2C) neoepitopes, reflecting collagen cleavage of type II collagen and type I/type II collagen, respectively. RESULTS: At baseline, patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII-to-C2C (CPII:C2C) ratio (but not C2C or C1-2C) compared with normal controls. Of the biomarkers examined, only CPII:C2C showed a correlation with the C-reactive protein (CRP) level. Among the biomarker-cytokine relationships, TGFbeta demonstrated a trend toward a positive correlation with the 846 epitope. CONCLUSION: In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII:C2C ratio might prove to be a useful marker of disease activity in AS.
Adult↗
Innate immunity and arthritis: neutrophil Rac and toll-like receptor 4 expression define outcomes in infection-triggered arthritis.
OBJECTIVE: The role of innate immunity in Chlamydia-induced arthritis has not been defined. The purpose of this study was to examine the role of neutrophils in experimental arthritis in mice with targeted elimination of the small GTPases Rac1 and Rac2, as well as the role of Toll-like receptors (TLRs) in this model. METHODS: Arthritis was induced by intraarticular inoculation of synoviocyte-packaged Chlamydia trachomatis. The degree of arthritis was assessed according to joint swelling and pathology scores. The persistence of Chlamydia in joints was assessed by immunoassay. The expression of TLR-2 and TLR-4 in neutrophils was detected by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: In the acute phase, wild-type mice developed more severe arthritis than did Rac-deficient mice, with abundant infiltration of neutrophils into the joint. In the chronic phase, the Rac-deficient mice developed more severe arthritis and demonstrated defective clearance of the pathogen from the joint. In vitro stimulation of neutrophils with Chlamydia up-regulated the expression of TLR-4, but not TLR-2, in wild-type mice. However, neutrophils from Rac-deficient mice did not show this up-regulation of TLR-4. Sustained TLR-4 expression in neutrophils was found to be dependent on the expression of Rac. Mice genetically deficient in TLR-4 demonstrated more severe arthritis than did the controls. Thus, Rac expression plays a profound role in infection-triggered arthritis and demonstrates a bimodal influence on the disease process, exacerbating acute joint inflammation but controlling chronic arthritis. Rac deficiency was associated with diminished TLR-4 expression, impaired host clearance of the pathogen, and more severe chronic arthritis. CONCLUSION: In infection-triggered arthritis, innate immunity plays a critical role. Effective host clearance of an arthritogenic pathogen depends on intact expression of Rac and appropriate expression of TLR-4 by neutrophils.
Animals↗
p53 and cell-cycle-regulated protein expression in small intestinal cells after fast-neutron irradiation in mice.
The involvement of the p53 gene in apoptosis of many cell types towards y-radiation is well established. However, little information is available on the relationship between p53 status and cells' ability to undergo apoptosis following exposure to fast neutrons. The aim of this study was to characterize the apoptotic pathway traveled by neutrons in mouse intestinal crypt cells. Each mouse received whole body doses of 0.25-8 Gy fast neutrons and were sacrificed 0, 4, 6, 12, 24, 48, and 72 h, respectively, after irradiation. Apoptosis of crypt cells and expression of p53, cyclin A, cyclin B, cyclin D, and cyclin E were measured. The apoptosis in crypt cells was maximal at 4 and 6 h after irradiation, showing a gradual decline at 24 h. The highest frequency of apoptosis was seen at a 1 Gy dose and then declined gradually beyond a 2 Gy dose with high levels of damage. In immunoblot analysis, apoptosis was confirmed to be dependent on p53 function after fast-neutron irradiation. In addition, cyclin B1, cyclin D, and cyclin E were overexpressed in intestinal cells after fast-neutron irradiation and their immunoreactivities were increased strongly in round and oval cells of laminar propria in villi core and crypts. The results of the current study suggest that apoptosis in crypt cells shows a time- and dose-dependent increase after fast-neutron irradiation. In addition, fast-neutron-induced apoptosis in mouse intestinal crypt cells appears to be related to the increase in functional p53 proteins to a level sufficient to initiate apoptosis and up-regulation of cell-cycle-regulated proteins, which may lead to resistance to DNA damage through cell cycle arrest, is involved deeply in protection of gastrointestinal cells after low doses of fast-neutron irradiation.
Animals↗
Pathogenesis of ankylosing spondylitis and reactive arthritis.
PURPOSE OF REVIEW: The hallmark of ankylosing spondylitis is acute and chronic spinal inflammation initiating in the sacroiliac joints, often coupled with enthesitis, presenting as chronic inflammation at the sites of ligamentous and tendinous insertions into bone. Peripheral joint synovitis can be a prominent feature as well. Reactive arthritis is a sterile synovitis arising after an extra-articular infection of enteric or urogenital tracts. HLA-B27 has been known for about the past 30 years to be associated with ankylosing spondylitis and reactive arthritis, but the pathogenesis of ankylosing spondylitis and reactive arthritis is still not well defined. Although the clinical manifestations of ankylosing spondylitis and reactive arthritis may differ, this update discusses the two diseases together and focuses on recent evidence in both. RECENT FINDINGS: With respect to HLA-B27 several recent studies address arthritogenic peptides, molecular mimicry, and aberrant forms of B27. Several candidate genes in addition to B27 have been implicated in recent genetic studies. With respect to bacterial infection, recent findings in bacterial antigenicity, host response through interactions of antigen-presenting cells, T cells, and cytokines are providing new understanding of host-pathogen interactions and the pathogenesis of arthritis. Endogenous host factors such as proteoglycans may play a role as autoantigens and contribute to chronic inflammation on that basis. SUMMARY: Recent advances provide additional new insights into distinct pathogenetic mechanisms in AS and ReA that arise from a complex interplay between genetic factors including HLA-B27 and environmental factors.
Arthritis, Reactive↗
Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats.
To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation, hepatic necrosis, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts, and mast cells) in an inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.
Alanine Transaminase↗
Protective effects of bio-active ceramic water on alcohol-induced hepatic injury in pigs.
Among many detrimental injuries, alcohol is implicated in hepatitis, fatty liver, hepatic fibrosis, and cirrhosis. The purpose of this study was to evaluate the protective effect of bio-active ceramic water on alcohol-induced hepatic injury in pigs. Twelve male Landrace pigs were divided into 3 groups. Groups 1, 2, and 3 were fed with bio-active ceramic water + normal liquid diet, bio-active ceramic water + liquid diet containing 15% ethanol, and tap water + liquid diet containing 15% ethanol for 12 weeks, respectively. For serological, histopathological, and immunohistochemical analysis, all pigs were sacrificed at week 12. In group 3, serum ALT and AST levels increased, and mild fatty change and moderate necrosis were detected in the liver. Collagen fibers, myofibroblasts, and CYP2E1 were also increased or activated in group 3. In group 2, there were mild hepatic injuries compared to group 3. However, injuries and activations were not observed in the liver in group 1. We suggest that the bio-active ceramic water used in the present study had protective capability against ethanol-induced hepatic injury and that having no toxic effect on the pig liver. The bio-active ceramic water might be useful as a therapeutic drinking water in patients suffering from alcoholic liver diseases.
Alanine Transaminase↗
Interleukin 1 and nuclear factor-kappaB polymorphisms in ankylosing spondylitis in Canada and Korea.
OBJECTIVE: The interleukin 1alpha and 1beta (IL-1alpha, IL-1beta) are potent mediators of inflammation and immunity. IL-1 receptor antagonist (IL-1Ra) is a protein that binds to IL-1 receptors and competitively inhibits the binding of IL-1alpha and IL-1beta. There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS), but the results have been inconsistent. NFKB1 encodes the genes for the p50 and p101 nuclear factor-kappaB (NF-kappaB) isoforms, which are recognized as critical to inflammatory disease. To date there have been no reports examining an association between NFKB1 and AS. We investigated polymorphisms of IL-1 complex and NF-kappaB1 with 2 genetically and geographically different populations. METHODS: Subjects with AS satisfied modified New York criteria for AS. Healthy controls were recruited at each respective site. Subjects with AS were genotyped for the following: IL-1alpha-889 single nucleotide polymorphism (SNP); IL-1beta +3953 SNP; IL-1Ra (86 base pair variable number tandem repeat within intron 2); and NFKB1 (-94 insertion/deletion polymorphism). RESULTS: In total, 205 subjects with AS and 200 controls from Seoul, Korea, and 68 subjects with AS and 164 controls from Toronto, Canada, were genotyped for the IL-1alpha and IL-1beta polymorphisms and 115 controls for the IL-1Ra and NF-kappaB polymorphisms. There were no differences of IL-1alpha, IL-1beta, IL-1Ra, and NF-kappaB polymorphisms between AS patients and controls in these populations. CONCLUSION: Our analysis of these SNP in the IL-1 complex and NF-kappaB genes does not support a major role for either in AS susceptibility in the Seoul and Toronto populations.
Adult↗