Ankylosing spondylitis in a patient with myelodysplastic syndrome: an association with HLA-B27 or coincidence?
The authors report an unusual case of myelodysplastic syndrome (MDS) associated with ankylosing spondylitis (AS). A 40-year-old-man with MDS presented with chronic low back pain for 6 years. Four years ago, MDS was diagnosed during routine blood analysis for the work-up of his articular complaints. His initial articular complaints were attributed to extramedullary manifestations of MDS. Persistent low back pain with increasing intensity finally led the patient to seek medical attention. Radiograph of the pelvis showed bilateral asymmetric sacroiliitis. A diagnosis of AS was established on the basis of modified New York criteria. Although various autoimmune phenomena associated with MDS have been described, this is the first report of AS in the setting of MDS. Causal relationship between these two disorders is currently unknown. Increased risk of hematological diseases as well as AS in individuals with a positive HLA-B27 provides a feasible explanation for this rare observation.

title: Successful cyclophosphamide therapy with complete resolution of pulmonary artery aneurysm in Hughes–Stovin syndrome patient
abstract: Hughes–Stovin syndrome is an exceedingly rare disorder of unknown etiology, and it is characterized by multiple pulmonary artery aneurysms and peripheral venous thrombosis. We report a case of Hughes–Stovin syndrome with complete resolution of pulmonary artery aneurysm after treatment with cyclophosphamide. A 48-year-old man presented with massive hemoptysis, fever, and weight loss of 4-month duration. Computed tomography angiography revealed multiple pulmonary arterial aneurysms of variable sizes in both lung fields. Inferior vena caval thrombosis was also noted. Despite multiple surgical procedures including embolectomy and lobectomy combined with steroid therapy, new aneurysms continued to appear with persistent hemoptysis. Thorough history and physical examination did not suggest any evidence of Behcet’s disease. Hughes–Stovin syndrome was subsequently diagnosed. High-dose prednisolone combined with oral cyclophosphamide therapy was initiated. Chest radiography follow-up in 3 months revealed complete resolution of pulmonary aneurysm. No new aneurysm was detected at 15 months of follow-up.

title: MRI findings in Kirner deformity: normal insertion of the flexor digitorum profundus tendon without soft-tissue enhancement
abstract: Kirner deformity is characterized by volar and radial incurvature of the distal phalanx of the 5th finger. A proposed causative mechanism includes abnormal distal insertion of the flexor digitorum profundus tendon along the volar surface of the distal phalanx of the 5th finger. A chronic inflammatory process or altered vascularisation of the soft tissues has also been suggested as the underlying causative mechanism based on MRI findings. We present a teenage boy with Kirner deformity, along with supplementary imaging of his father who also has the deformity, to illustrate MRI findings that dispute the above hypotheses. MRI in both son and father show normal insertion of the deep flexor tendon and no signs of inflammation.

title: CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.

title: Underexpression of TIM-3 and Blunted Galectin-9-Induced Apoptosis of CD4+ T Cells in Rheumatoid Arthritis
abstract: The aim of this study is to compare the expression of TIM-3 from CD4+ T cells from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+ T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T cells was measured using real-time polymerase chain reaction. CD4+ T cells were activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin-V staining, respectively. TIM-3 mRNA expression was significantly lower in CD4+ T cells from RA patients compared with those in healthy controls (p = 0.028). CD4+ T cell survival as measured by MTT assay when incubated with Gal-9 (15 nM) was significantly higher in RA patients than in healthy controls (p = 0.002). Apoptotic activity of CD4+ T cells from healthy controls as measured by annexin staining increased with graded doses of Gal-9 (0 nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of CD4+ T cells from RA patients did not change despite the stimulation with Gal-9. Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with Gal-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target.

title: Extended dosing of etanercept 25 mg can be effective in patients with ankylosing spondylitis: a retrospective analysis
abstract: As a measure of healthcare cost containment, the total number of vials of entanercept (25 mg) that can be prescribed for patients with inflammatory arthritis is restricted in Korea. Consequently, attempts to extend the dosing interval while maintaining the efficacy have not been an uncommon clinical practice. The aim of this study was to determine if extended doing interval of etanercept can be effective in patients with ankylosing spondylitis (AS). We performed a retrospective analysis using medical records at a single tertiary hospital. One hundred and nine patients with AS and 79 patients with rheumatoid arthritis (RA) started on etanercept between November 2004 and November 2009 were indentified. Etanercept (25 mg) was started with twice-weekly dosing schedule. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein (CRP), and etanercept dosing interval for AS patients at 0, 3, 9, 15, 21 months were reviewed. Dosing interval for RA patients was analyzed for comparison. In AS, mean dosing interval was 4.7 ± 2.1 days at 3 months and was increased to 12.1 ± 7.0 days at 21 months. Despite the progressive increase in the dosing interval, the mean BASDAI declined rapidly at 3 months, and continued to decrease over 21 months. Mean CRP declined after 3 months of therapy and remained low thereafter. In RA, mean dosing interval was 4.0 ± 1.2 days at 3 months and 5.1 ± 1.8 days at 21 months. In conclusion, in AS, extended dosing of etanercept can be effective without compromising clinical and laboratory markers of disease activity as measured by BASDAI and CRP, respectively. Tapering of etanercept was less accommodating in RA when compared to AS.

title: Multidrug-resistant tuberculosis in a lung transplant recipient.
abstract: Tuberculosis infection has been a relatively rare complication after lung transplantation. However, as more countries in which Mycobacterium tuberculosis infection remains endemic embark on lung transplant programs, the occurrence of multidrug-resistant tuberculosis after transplantation is a genuine threat. We report the first case of multidrug-resistant tuberculosis in a double-lung transplant recipient who probably acquired the disease from the donor. We discuss the problems in clinical management of post-transplant tuberculosis infection and of drug-resistance.

title: Validation of Stereophotogrammetry of the Human Torso
abstract: The objective of this study was to determine if measurements of breast morphology computed from three-dimensional (3D) stereophotogrammetry are equivalent to traditional anthropometric measurements obtained directly on a subject using a tape measure. 3D torso images of 23 women ranged in age from 36 to 63 who underwent or were scheduled for breast reconstruction surgery were obtained using a 3dMD torso system (3Q Technologies Inc., Atlanta, GA). Two different types (contoured and line-of-sight distances) of a total of nine distances were computed from 3D images of each participant. Each participant was photographed twice, first without fiducial points marked (referred to as unmarked image) and second with fiducial points marked prior to imaging (referred to as marked image). Stereophotogrammetry was compared to traditional direct anthropometry, in which measurements were taken with a tape measure on participants. Three statistical analyses were used to evaluate the agreement between stereophotogrammetry and direct anthropometry. Seven out of nine distances showed excellent agreement between stereophotogrammetry and direct anthropometry (both marked and unmarked images). In addition, stereophotogrammetry from the unmarked image was equivalent to that of the marked image (both line-of-sight and contoured distances). A lower level of agreement was observed for some measures because of difficulty in localizing more vaguely defined fiducial points, such as lowest visible point of breast mound, and inability of the imaging system in capturing areas obscured by the breast, such as the inframammary fold. Stereophotogrammetry from 3D images obtained from the 3dMD torso system is effective for quantifying breast morphology. Tools for surgical planning and evaluation based on stereophotogrammetry have the potential to improve breast surgery outcomes.

title: Development of a conditional gene expression system using a zearalenone-inducible promoter for the ascomycete fungus Gibberella zeae.
abstract: The ascomycete fungus Gibberella zeae is an important plant pathogen that causes fusarium head blight on small grains. Molecular studies of this fungus have been performed extensively to uncover the biological mechanisms related to pathogenicity, toxin production, and sexual reproduction. Molecular methods, such as targeted gene deletion, gene overexpression, and gene fusion to green fluorescent protein (GFP), are relatively easy to perform with this fungus; however, conditional expression systems have not been developed. The purpose of this study was to identify a promoter that could be induced by zearalenone (ZEA) for the development of a conditional expression system in G. zeae. Through microarray analysis, we isolated one zearalenone response gene (ZEAR) whose expression was increased more than 50 times after ZEA treatment. Northern blot analysis showed that the ZEAR transcript dramatically increased after 1 h of ZEA treatment. To determine the utility of the ZEAR promoter, called Pzear, in a conditional expression system, we transformed a Pzear::GFP fusion construct into G. zeae. Our data showed a ZEA concentration-dependent increase in GFP expression. We also replaced the promoter of G. zeae metE (GzmetE), an essential gene for methionine biosynthesis, with the Pzear promoter. The growth of the Pzear-GzmetE mutant on minimal medium was dependent on the ZEA concentration supplemented in the medium and showed that GzMetE expression was induced by ZEA. This study is the first report of an inducible promoter in G. zeae. Our system will be useful for the characterization of essential gene functions in this fungus through differential and ZEA-dependent gene expression. In addition, the Pzear promoter may be applicable as a biosensor for the detection of ZEA contamination in agricultural products.

title: Development and validation of a scale for the end of life caregiving appraisal.
abstract: End-of-life caregiving experiences can be complex. Family members experience physical and mental suffering as they anticipate their impending loss. Healthcare providers should be able to provide good quality of end-of-life (EOL) care and support for primary EOL caregivers. Studies have highlighted the role of healthcare providers providing information in the EOL situation to caregivers of chronic disease patients. This has resulted in the development of the End-of-life Caregiving Experience Appraisal Scale (EOLCAS) presented in this paper. The purposes of this study were to develop a scale that can evaluate the experiences of EOL caregivers, and to test the reliability and validity of this scale.



The scale domains were derived from systematic review of 35 relevant studies. We then examined its content validity with nurse scholars and clinicians using content validity index. To examine construct validity, a total of 175 caregivers from tertiary hospital setting in Korea participated in this study from December 2007 to May 2008. For the construct validity, factor analysis was utilized.



The scale was composed of 32 items with four subscales: two negative appraisals (physical suffering and burden), one positive appraisal (maturation), and one neutral appraisal (social support pursuit). In this sample, the Cronbach's alpha for the entire scale was .84 indicating adequate reliability. However, Cronbach's alpha of subscales was varied.



Nurses and other healthcare professionals could use the EOLCAS to assess the experiences of EOL caregivers to understand their experience in the EOL and enhance their quality of life although psychometrics of EOLCAS shows limited findings.

title: High Levels of Sequence Diversity in the 5′ UTRs of Human-Specific L1 Elements
abstract: Approximately 80 long interspersed element (LINE-1 or L1) copies are able to retrotranspose actively in the human genome, and these are termed retrotransposition-competent L1s. The 5′ untranslated region (UTR) of the human-specific L1 contains an internal promoter and several transcription factor binding sites. To better understand the effect of the L1 5′ UTR on the evolution of human-specific L1s, we examined this population of elements, focusing on the sequence diversity and accumulated substitutions within their 5′ UTRs. Using network analysis, we estimated the age of each L1 component (the 5′ UTR, ORF1, ORF2, and 3′ UTR). Through the comparison of the L1 components based on their estimated ages, we found that the 5′ UTR of human-specific L1s accumulates mutations at a faster rate than the other components. To further investigate the L1 5′ UTR, we examined the substitution frequency per nucleotide position among them. The results showed that the L1 5′ UTRs shared relatively conserved transcription factor binding sites, despite their high sequence diversity. Thus, we suggest that the high level of sequence diversity in the 5′ UTRs could be one of the factors controlling the number of retrotransposition-competent L1s in the human genome during the evolutionary battle between L1s and their host genomes.