Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease: a nationwide population-based study in South Korea.

BACKGROUND: The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. AIM: To evaluate the risk of incident TB among IBD patients. METHODS: Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications. RESULTS: The IR, SIR and NNS for TB in IBD patients were 223.9/100 000 person-years, 2.64 (2.30-3.01) and 446.6 (392.8-517.6), respectively. The TB IR in Crohn's disease (CD) patients was significantly higher than that in ulcerative colitis (UC) patients (340.1/100 000 person-years vs. 165.5/100 000 person-years, respectively; P < 0.001). The SIR and NNS for TB among CD patients were 4.00 (3.59-4.45) and 604.2 (506.1-749.6), respectively; those among UC patients were 1.95 (1.66-2.27) and 294.0 (246.9-363.4). The TB IRs in IBD patients did not differ significantly by age or gender (Ptrend  = 0.505 and P = 0.861, respectively). The TB IRs among IBD patients prescribed 5-ASA, corticosteroids, immunomodulators and anti-TNF-α were 143.5, 208.5, 284.6 and 554.1 per 100 000 person-years, respectively. Among IBD patients treated using anti-TNF-α, the TB IR was significantly higher than that among all IBD patients (P < 0.001); the SIR and NNS for TB were 6.53 (5.99-7.09) and 180.5 (144.6-240.1) respectively. CONCLUSION: Clinicians should be aware of the increased risk of active tuberculosis in patients with IBD who are receiving anti-TNF-α therapy.

Percutaneous radiofrequency ablation for symptomatic uterine leiomyomas: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) in the treatment of uterine leiomyomas. MATERIALS AND METHODS: Medline, Embase, and Cochrane databases were searched through August 2014 for all relevant studies on RFA for uterine leiomyomas. The efficacy and safety of RFA were assessed using the outcome measures of tumor volume, symptom severity score, health-related quality of life (HRQL) score, procedure-related complications, and reintervention. The authors calculated pooled event rates with 95% confidence intervals using random-effects model to assess the effects of RFA. RESULTS: Eight observational studies were identified as eligible for inclusion in this meta-analysis and included 370 patients. All analyzed outcomes showed statistically significant improvements from baseline to final follow-up. Twenty-seven complications were identified and five of them qualified as major complications. Five patients required reintervention after RFA. CONCLUSIONS: Percutaneous RFA is an effective and safe treatment for patients with uterine leiomyomas.

Crustacean hyperglycemic hormones of two cold water crab species, Chionoecetes opilio and C. japonicus: isolation of cDNA sequences and localization of CHH neuropeptide in eyestalk ganglia.

Crustacean hyperglycemic hormone (CHH) is primarily known for its prototypical function in hyperglycemia which is induced by the release of CHH. The CHH release takes place as an adaptive response to the energy demands of the animals experiencing stressful environmental, physiological or behavioral conditions. Although >63 decapod CHH nucleotide sequences are known (GenBank), the majority of them is garnered from the species inhabiting shallow and warm water. In order to understand the adaptive role of CHH in Chionoecetes opilio and Chionoecetes japonicus inhabiting deep water environments, we first aimed for the isolation of the full-length cDNA sequence of CHH from the eyestalk ganglia of C. opilio (ChoCHH) and C. japonicus (ChjCHH) using degenerate PCR and 5' and 3' RACE. Cho- and ChjCHH cDNA sequences are identical in 5' UTR and ORF with 100% sequence identity of the putative 138aa of preproCHHs. The length of 3' UTR ChjCHH cDNA sequence is 39 nucleotides shorter than that of ChoCHH. This is the first report in decapod crustaceans that two different species have the identical sequence of CHH. ChoCHH expression increases during embryogenesis of C. opilio and is significantly higher in adult males and females. C. japonicus males have slightly higher ChjCHH expression than C. opilio males, but no statistical difference. In both species, the immunostaining intensity of CHH is stronger in the sinus gland than that of X-organ cells. Future studies will enable us to gain better understanding of the comparative metabolic physiology and endocrinology of cold, deep water species of Chionoecetes spp.

Overexpression of the Brassica rapa transcription factor WRKY12 results in reduced soft rot symptoms caused by Pectobacterium carotovorum in Arabidopsis and Chinese cabbage.

Chinese cabbage (Brassica rapa L. ssp. pekinensis), an important vegetable crop, can succumb to diseases such as bacterial soft rot, resulting in significant loss of crop productivity and quality. Pectobacterium carotovorum ssp. carotovorum (Pcc) causes soft rot disease in various plants, including Chinese cabbage. To overcome crop loss caused by bacterial soft rot, a gene from Chinese cabbage was isolated and characterised in this study. We isolated the BrWRKY12 gene from Chinese cabbage, which is a group II member of the WRKY transcription factor superfamily. The 645-bp coding sequence of BrWRKY12 translates to a protein with a molecular mass of approximately 24.4 kDa, and BrWRKY12 was exclusively localised in the nucleus. Transcripts of BrWRKY12 were induced by Pcc infection in Brassica. Heterologous expression of BrWRKY12 resulted in reduced susceptibility to Pcc but not to Pseudomonas syringae pv. tomato in Arabidopsis. Defence-associated genes, such as AtPDF1.2 and AtPGIP2, were constitutively expressed in transgenic lines overexpressing BrWRKY12. The expression of AtWKRY12, which is the closest orthologue of BrWRKY12, was down-regulated by Pcc in Arabidopsis. However, the Atwrky12-2 mutants did not show any difference in response to Pcc, pointing to a difference in function of WRKY12 in Brassica and Arabidopsis. Furthermore, BrWRKY12 in Chinese cabbage also exhibited enhanced resistance to bacterial soft rot and increased the expression of defence-associated genes. In summary, BrWRKY12 confers enhanced resistance to Pcc through transcriptional activation of defence-related genes.

Expression analysis of rice VQ genes in response to biotic and abiotic stresses.

WRKY transcription factors are encoded by a large gene superfamily with a broad range of roles in plants. Proteins containing a short VQ (FxxxVQxLTG) motif have been recently shown to interact with WRKY transcription factors, implying that AtVQ proteins are important in the plant defense responses in Arabidopsis, either as positive or negative cofactors of WRKY transcription factors. Thirty-nine Oryza sativa genes containing the VQ motif (OsVQs) were identified and the genome structures of OsVQ proteins were characterized through genome-wide analysis in rice. Also, phylogenetic tree analysis was performed with the VQ domain of Arabidopsis and rice. The expression patterns of these OsVQ genes in plants under several stress treatments were assessed, specifically, following infection with the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), treatment with abscisic acid (ABA), or exposure to drought. The cellular localization of a few OsVQ proteins was examined using rice protoplast system. Based on our results, we suggest that OsVQ proteins function as important co-regulators during the plant defense response to biotic and abiotic stresses.

Upregulation of stromal cell-derived factor by IL-17 and IL-18 via a phosphatidylinositol 3-kinase-dependent pathway.

Th17 cells that produce interleukin (IL)-17 play a key role in the pathogenesis of autoimmune inflammation. Among the various cytokines that are involved in the IL-17 pathway, members of the IL-1ß family, including IL-18, have recently gained attention. In this study, we stimulated synovial fibroblasts with a combination of IL-17 and IL-18 and quantified their stromal cell-derived factor-1 (SDF-1) production by enzyme-linked immunosorbent assay and their transcript levels by reverse transcription-polymerase chain reaction. Both IL-17 and IL-18 significantly increased the level of SDF-1, not only individually but also synergistically (P< 0.05). The synergism was effectively suppressed by anti-IL-17 and -IL-18 antibodies, and a PI3K inhibitor. To the best of our knowledge, this is the first report of PI3K-dependent synergism between IL-18 and IL-17, and this work adds a novel perspective of the role of IL-18 in immune regulation. The individual effects of these two cytokines, and their interactions, suggest an interrelationship between the IL-1 family and IL-17.

Estrogen replacement reverses olanzapine-induced weight gain and hepatic insulin resistance in ovariectomized diabetic rats.

OBJECTIVES: We investigated whether estrogen replacement modulated energy and glucose metabolic changes induced by olanzapine (OZP) and risperidone (RPD) in 90% pancreatectomized diabetic rats, some of whom had also been ovariectomized (OVX) and some of whom had not (sham). METHODS: OVX diabetic rats were subcutaneously injected with estrogen replacement (17beta-estradiol, 30 microg/kg/day) or a vehicle. Each group was divided into 3 subgroups, and each subgroup was orally either given a placebo, RPD (0.5 mg/kg body weight/day) or OZP (2 mg/kg body weight/day) for 8 weeks. Sham rats were also divided into 3 subgroups and given drugs in the same manner as the OVX rats were. All rats were fed high-fat diets. RESULTS: OZP increased body weight and epididymal fat pads more than the control (vehicle) in sham and OVX rats. Increased body weight in OZP-treated sham and OVX rats was due to the increment in food intake, which was associated with potentiating the phosphorylation of hypothalamic adenosine-monophosphate-activated protein kinase. At euglycemic hyperinsulinemic clamping, OZP decreased glucose infusion rates and increased hepatic glucose output in OVX diabetic rats. In sham rats, OZP increased hepatic glucose output but not as much as in OVX rats. Hepatic insulin signaling and glucose sensing were attenuated in OZP-treated OVX rats, and the attenuation increased hepatic phosphoenolpyruvate carboxykinase expression to induce gluconeogenesis. These negative and harmful effects noted among OZP-treated OVX rats were reversed by estrogen replacement treatment. However, RPD did not alter body weight and peripheral insulin sensitivity in sham and OVX rats. CONCLUSIONS: OZP treatment should be avoided when treating diabetic and schizophrenic women, especially those in their postmenopausal period.

'1-8 interferon inducible gene family': putative colon carcinoma-associated antigens.

D(b-/-)xbeta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA-A2.1/D(b)-beta2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.

Kinetic studies of attachment and detachment of microbial cells from soil.

A mathematical model was developed to describe the kinetics of cell attachment and detachment from soil. Soil-column experiments were performed to evaluate the model parameters. Pseudomonas putida G7 capable of degrading naphthalene was used as a model microorganism. A sediment sample taken from an uncontaminated area near a coal tar waste site in upstate New York, USA was used as a test soil. The kinetics of cell attachment and detachment from the model soil could be described by the developed first-order model. The equilibrium constant of attachment (11.4 ml g(-1)), the rate coefficient of cell attachment (0.299 ml g(-1) min(-1) and the rate coefficient of cell detachment (0.0263 min(-1)) were determined from the soil-column experiment. The equilibrium constant of attachment determined in this study (11.4 ml g(-1)) was within the range of those reported in the literature for bacterial attachment to soil (0.55 to 12.6 ml g(-1)). The kinetic model succesfully predicted the data of batch experiment for cell attachment and detachment soil.

Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment.

Patients who require long-term steroid use are at risk for the development of osteonecrosis. However, the risk period for developing osteonecrosis of the femoral head has not yet been defined. The authors attempted to determine the onset of osteonecrosis of the femoral head following steroid treatment. Medical record data of patients with steroid-related osteonecrosis of the femoral head from four university hospitals were reviewed. Information was collected regarding the duration and dose of steroid use for patients who were diagnosed at the early stage by magnetic resonance imaging (MRI) without positive findings on plain radiographs (Association Research Circulation Osseous stage I osteonecrosis). Twenty-two patients were diagnosed at Association Research Circulation Osseous stage I. There were eight male and 14 female patients ranging in age from 17 to 60 years (mean 33). The total dose of steroid, which was used until the time of detection of osteonecrosis by MRI, ranged from 1800 to 15 505 mg prednisolone or its equivalent (mean 5928 mg). The period from the start of steroid treatment to the diagnosis by MRI ranged from 1 month to 16 months (mean 5.3 months). Twenty-one of 22 patients were diagnosed within 12 months of the initiation of steroid treatment. The duration of steroid treatment within this period ranged from 1 month to 12 months (mean 4.5 months). There may be a risk period of 12 months for developing femoral head osteonecrosis in patients receiving long-term steroid treatment. Close observation and more aggressive screening are recommended within the first year of long-term steroid treatment to prevent advanced osteonecrosis of the femoral head.

Biodegradation of toluene by a lab-scale biofilter inoculated with Pseudomonas putida DK-1.

The biodegradation of toluene by biofiltration inoculated with Pseudomonas putida DK-1 was investigated with variation of the several environmental parameters, such as temperature, bed length, gas flow rate and optimal humidity zone. The optimal temperature range to treat toluene gas was found to be 32-35 degrees C. Increasing the gas flow rate showed an inverse effect on the elimination capacity and the removal efficiency. The optimal gas flow rate was obtained at 65 ml min(-1) from the relation between the removal efficiency and the elimination capacity. The biodegradation rate of the toluene with respect to the bed lengths (3, 6, 9, 12 and 15 cm) increased up to 80 h but was then independent of the bed lengths after 80 h except for the 3 cm bed length. The elimination capacity was improved by about 70% compared with that reported in other literature and was also in agreement with theoretical models.

Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues.

We investigated a correlation between the expression of human sodium iodide symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors. 99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The normalized mRNA expression of hNIS was higher in tumors with positive uptake on the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate uptake is correlated with the hNIS expression in the breast tumor.

Torsion angle based design of peptidomimetics: a dipeptidic template adopting beta-I turn (Ac-Aib-AzGly--NH(2)).

We have attempted to design a model dipeptide (acetyl dipeptide amide, Ac-CA1-CA2--NH(2)) that can adopt specifically typical torsion angles of the beta-I turn (phi(i+1), psi(i+1), phi(i+2), psi(i+2)=-60 degrees, -30 degrees, -90 degrees, 0 degrees ). The key of the design is the combination of constrained amino acids that prefer to adopt the desired torsion angles. We chose Aib (aminoisobutyric acid) as the first residue of which phi and psi angles must be -60 degrees and -30 degrees, respectively. Then, we selected an azaamino acid as the second residue since previous studies have indicated that they prefer to adopt +/-90 degrees of phi angle and 0 degrees or 180 degrees of psi angle. The conformational preference of the resulting Ac-Aib-AzGly--NH(2) is investigated using ab initio methods. The conformations implying beta-I and beta-I' turns are energetically most favorable, as we expected. Thus, we synthesized the designed molecule on the solid phase considering the future generation of combinatorial libraries using an automatic peptide synthesizer. Then, NMR spectroscopy was carried out to confirm their conformational preference in solution was carried out. The results indicated that the Ac-Aib-AzGly--NH(2) adopt beta-I or beta-I' turns in solution forming an intramolecular hydrogen bonding between Ac--C(O) and terminal NH(2). We believe that such a small peptidomimetic template is highly useful for the design of drug candidates and molecular devices.

Growth inhibition and chemosensitivity of poorly differentiated human thyroid cancer cell line (NPA) transfected with p53 gene.

BACKGROUND: We investigated whether retroviral p53 transfection could enhance growth inhibition and chemosensitivity in a p53 mutant papillary thyroid cancer cell line (NPA). METHODS: NPA cells were transfected with either LXSN/p53 or mock infection in the presence of Adriamycin. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with NPA cells after transfection with either LXSN/p53 or mock infection on opposite sides, and the tumor growth was compared. RESULTS: There was a dose-dependent inhibition of tumor growth with LXSN/p53 transfection. Tumor growth was inhibited more by p53 gene transfection relative to mock transfection in the presence of Adriamycin. CONCLUSION: These treatment modalities could be beneficial in the treatment of p53 mutant positive thyroid cancers.

Clonorchis sinensis: molecular cloning and characterization of 28-kDa glutathione S-transferase.

A 28-kDa glutathione S-transferase (Cs28GST) was purified from a Clonorchis sinensis cytosolic fraction through anion-exchange and glutathione-affinity column chromatographies. A monoclonal antibody raised against Cs28GST reacted specifically to the C. sinensis antigen among trematode proteins. A putative peptide of 212 amino residues deduced from a cDNA clone appeared homologous with 28-kDa GST of trematodes, and its secondary structural elements predicted a GSH-binding site. Recombinant Cs28GST showed GST enzyme activity with CDNB substrate and was sensitive to the model inhibitors. The recombinant Cs28GST was antigenically indistinguishable from the native form and was recognized specifically by C. sinensis-infected human sera. The Cs28GST was localized in the tegument and underlying mesenchymal tissues. It is suggested that Cs28GST may play significant physiological roles against bioreactive molecules and be a useful reagent for serodiagnosis of clonorchiasis.

A viral double-stranded RNA up regulates the fungal virulence of Nectria radicicola.

Double-stranded RNAs (dsRNAs) are widespread in plant pathogenic fungi, but their functions in fungal hosts remain mostly unclear, with a few exceptions. We analyzed dsRNAs from Nectria radicicola, the causal fungus of ginseng root rot. Four distinct sizes of dsRNAs, 6.0, 5.0, 2.5, and 1.5 kbp, were detected in 24 out of the 81 strains tested. Curing tests of individual dsRNAs suggested that the presence of 6.0-kbp dsRNA was associated with high levels of virulence, sporulation, laccase activity, and pigmentation in this fungus. The 6.0-kbp dsRNA-cured strains completely lost virulence-related phenotypes. This 6.0-kbp dsRNA was reintroduced by hyphal anastomosis to a dsRNA-cured strain marked with hygromycin resistance, which resulted in the restoration of virulence-related phenotypes. These results strongly suggest that 6.0-kbp dsRNA up regulates fungal virulence in N. radicicola. Sequencing of several cDNA clones derived from 6.0-kbp dsRNA revealed the presence of a RNA-dependent RNA polymerase (RDRP) gene. Phylogenetic analysis showed that this gene is closely related to those of plant cryptic viruses. Biochemical analyses suggested that the 6.0-kbp dsRNA may regulate fungal virulence through signal-transduction pathways involving cyclic AMP-dependent protein kinase and protein kinase C.

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Molecular cloning and characterization of an antigenic protein with a repeating region from Clonorchis sinensis.

In the course of immunoscreening of Clonorchis sinensis cDNA library, a cDNA CsRP12 containing a tandem repeat was isolated. The cDNA CsRP12 encodes two putative peptides of open reading frames (ORFs) 1 and 2 (CsRP12-1 and -2). The repetitive region is composed of 15 repeats of 10 amino acids. Of the two putative peptides, CsRP12-1 was proline-rich and found to have homologues in several organisms. Recombinant proteins of the putative peptides were bacterially produced and purified by an affinity chromatography. Recombinant CsRP12-1 protein was recognized by sera of clonorchiasis patients and experimental rabbits, but recombinant CsRP12-2 was not. One of the putative peptide, CsRP12-1, is designated CsPRA, proline-rich antigen of C. sinensis. Both the C-termini of CsRP12-1 and -2 were bacterially produced and analysed to show no antigenicity. Recombinant CsPRA protein showed high sensitivity and specificity. In experimental rabbits, IgG antibodies to CsPRA was produced between 4 and 8 weeks after the infection and decreased thereafter over one year. These results indicate that CsPRA is equivalent to a natural protein and a useful antigenic protein for serodiagnosis of human clonorchiasis.

Iliacus hematoma and femoral nerve palsy after revision hip arthroplasty: a case report.

Femoral nerve palsy occurred in a 65-year-old man after he had undergone a revision total hip arthroplasty using cementless components. The magnetic resonance imaging scan showed a mass in the iliacus muscle. The mass showed increased signal intensity on T1-weighted and T2-weighted spin-echo images and contained linear septa and a nodule. The gadolinium-enhanced T1-weighted image showed a rim of significant enhancement in the nodule. The findings of magnetic resonance images were suggestive of iliacus hematoma and of liposarcoma. The patient underwent surgery, and the mass was identified as an iliacus hematoma. The femoral nerve was stretched by the hematoma. After removal of the hematoma, the nerve palsy was improved completely. Iliacus hematoma may occur after total hip arthroplasty, even without anticoagulant therapy. The hematoma might appear to be a liposarcoma on magnetic resonance imaging scans.