Risk factors for avascular bone necrosis in systemic lupus erythematosus

OBJECTIVE: To study the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). METHOD: The records of 38 SLE patients who developed clinically apparent AVN during the course of their disease were reviewed. Information on clinical presentation, corticosteroid usage and autoantibody profiles was obtained, and comparison was made between these patients and 143 consecutive control SLE patients who did not have AVN. RESULTS: The point prevalence of AVN in our SLE population was 12%. Patients with AVN, when compared with controls, had a significantly higher incidence of neurological disease (39% vs 14%; P < 0.001) and Cushingoid body habitus after steroid treatment (79% vs 53%; P = 0.004). The highest cumulative prednisolone dose in 1 and 4 months was significantly higher in the AVN group than the controls (1.8 vs 1.1 and 4.5 vs 2.8 g, respectively; P < 0.01 in both) and showed a linear trend with the incidence of AVN (chi2 test for trend, P < 0.01 in both). Lupus anticoagulant was associated with AVN (P = 0.02, odds ratio 2.88 [1.14- 7.28]). Logistic regression analysis revealed that the highest cumulative prednisolone dose administered in 4 months, the maximum and mean daily prednisolone dosage, and the lupus anticoagulant were independent risk factors for AVN. CONCLUSIONS: Corticosteroid remains the major predisposing factor for AVN in SLE. Patients who require an initial high-dose steroid for disease control are at risk of AVN, especially if they are positive for the lupus anticoagulant or develop Cushingoid habitus after steroid treatment. High-risk patients should be closely monitored so that early AVN can be diagnosed by sensitive techniques such as magnetic resonance imaging and radioisotope bone scanning.      

Isolation and partial purification of an enzyme catalyzing the formation of O-xylosylzeatin in Phaseolus vulgaris embryos

An enzyme catalyzing the formation of a cytokinin metabolite, an O-pentosyl derivative of zeatin [Lee, Y. H., Mok, M. C., Mok, D. W. S., Griffin, D. A. & Shaw, G. (1985) Plant Physiol. 77, 635-641], was isolated from Phaseolus vulgaris embryos. Of all the potential pentose donors tested, UDP-xylose was the only substrate recognized by the enzyme. This indicates that the O-pentosyl derivatives previously obtained are O-xylosylzeatin and its ribonucleoside. The enzyme (UDP-xylose:zeatin O-xylosyltransferase, EC 2.4.2.-) has high affinity for trans-zeatin (K_m 2 μM) and dihydrozeatin (K_m 10 μM) but does not recognize cis-zeatin or ribosylzeatin. The molecular weight of the enzyme is approximately 50,000 and the pH optimum of the reaction is 8-8.5. Under comparable isolation and reaction conditions, similar enzyme activity could not be detected in P. lunatus embryos, confirming the genetic differences observed in vivo.     

Disease activity assessment in ankylosing spondylitis in a Chinese cohort: BASDAI or ASDAS?

Recently, the Ankylosing Spondylitis Disease Activity Score (ASDAS), a new index, has been shown to be validated and highly discriminatory in assessing ankylosing spondylitis (AS) disease activity. This study is to evaluate the performance of ASDAS in a local Chinese cohort of AS in a cross-sectional setting and to compare it with the existing instrument, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Consecutive patients with AS were recruited from a local rheumatology clinic. Data, including BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Visual Analogue Scale (VAS) for spinal pain, and patient and physician global assessments were gathered during clinic visit. Inflammatory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and high-sensitivity (hs)-CRP were collected. ASDAS was calculated accordingly. The discriminatory capacity of BASDAI and ASDAS was compared by: (1) standardized mean difference statistics, (2) R ² in linear regressions, and (3) area under receiver operating characteristic curve (AUC) in logistic regression models. Both ASDAS and BASDAI showed satisfactory predictive value on disease activity with reference to patient and physician global assessment. R ² in linear regression models ranged from 0.6–0.7. Both indices also demonstrated good discriminatory capacity as evidenced by a relatively high AUC (> 0.8) under the logistic regression models using either patient or physician global assessment score ≥4 and <4 as cut off of high and low disease activity status, respectively. Although we could not demonstrate significant differences in the performance between them, subgroup analysis suggested better discriminatory ability of ASDAS in the high inflammatory marker subgroup. ASDAS and BASDAI showed similarly good performance in a cross-sectional setting in a local Chinese AS cohort. ASDAS performed better in subgroup with raised inflammatory markers.     

Functioning and health-related quality of life in Chinese patients with systemic sclerosis: a case–control study

The objective of the study was to study the functioning and health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) and its associated factors. Consecutive SSc patients and an equal number of age- and gender-matched healthy controls were recruited for the assessment of functioning and HRQoL by the Health assessment questionnaire disability index (HAQ-DI) and Medical Outcomes Study Short Form 36 (SF-36), respectively. The extent of skin involvement of SSc was assessed by the modified Rodnan skin score (mRSS), and disease severity was assessed by the Medsger severity index. Factors associated with functioning and HRQoL in SSc patients were studied by linear regression. Seventy-eight Chinese SSc patients were studied (87 % women; age 50.2?±?12.1 years; disease duration 7.8?±?6.5 years; 81 % limited cutaneous subtype). The median mRSS of the patients was 8 (IQR 0–10). Patients with SSc had significantly higher HAQ-DI (0.69?±?0.69 vs 0.04?±?0.18; p?<?0.001) but lower SF36 scores (p?<?0.05 in all domains) than matched controls. Linear regression revealed that the mRSS was inversely associated with the physical component (beta?=??0.39; p?=?0.001) and mental component scores (beta?=??0.27; p?=?0.031) of the SF36 but positively correlated with the HAQ-DI score (beta?=?0.51; p?<?0.001) adjusted for age, sex, and disease duration. The SF36 and HAQ-DI scores also correlated significantly with the Medsger SSc severity index in the general, peripheral vascular, skin, tendon/joint, and heart domains. SSc patients had impaired physical and social functioning and poorer HRQoL than healthy individuals. The extent of skin involvement, tendon/joint contracture, damage in the heart, and peripheral vascular system were associated with poorer functioning and HRQoL.     

Frontal and temporal contributions to understanding the iconic co‐speech gestures that accompany speech

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions—left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)—responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture‐speech integration, was not sensitive to the gesture‐speech relation. Together, these findings clarify the neurobiology of gesture‐speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech. Hum Brain Mapp 35:900–917, 2014. © 2012 Wiley Periodicals, Inc.     

A familial frontotemporal dementia associated with C9orf72 repeat expansion and dysplastic gangliocytoma

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 gene (C9orf72) was recently identified as the most common genetic cause of frontotemporal dementia/amyotrophic lateral sclerosis. Here we describe the clinical, pathologic, and genetic features of a Finnish C9orf72 expansion carrier, who developed a dysplastic gangliocytoma (Lhermitte-Duclos disease), a rare hamartoma/overgrowth syndrome of cerebellar granule cells associated with mutations in the phosphatase and tensin homolog gene. In addition to the dysplastic gangliocytoma, the patient showed typical transactive response DNA-binding protein with M_r 43 kD (TDP-43) pathology mainly in the cortex and the substantia nigra and numerous p62-positive/TDP-43-negative inclusions in the cerebellar granule cells. His sister carried the same gene defect and showed a similar type of TDP-43/p62 pathology in her brain. Our findings confirm that the clinical and pathologic picture of C9orf72 mutation carriers is more heterogeneous than originally thought and warrants further studies on the possible involvement of phosphatase and tensin homolog gene pathway in the specific cerebellar granule cell pathology associated with C9orf72 expansion.     

The CD6/ALCAM pathway promotes lupus nephritis via T cell–mediated responses

T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6⁺ and ALCAM⁺ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.