High prevalence of autoantibodies to RNA helicase A in Mexican patients with systemic lupus erythematosus

Introduction

Autoantibodies to RNA helicase A (RHA) were reported as a new serological marker of systemic lupus erythematosus (SLE) associated with early stage of the disease. Anti-RHA and other autoantibodies in Mexican SLE patients and their correlation with clinical and immunological features were examined.

Methods

Autoantibodies in sera from 62 Mexican SLE patients were tested by immunoprecipitation of ³⁵S-labeled K562 cell extract and enzyme-linked immunosorbent assay (anti-U1RNP/Sm, ribosomal P, β2GPI, and dsDNA). Anti-RHA was screened based on the immunoprecipitation of the 140-kDa protein, the identity of which was verified by Western blot using rabbit anti-RHA serum. Clinical and immunological characteristics of anti-RHA-positive patients were analyzed.

Results

Anti-RHA was detected in 23% (14/62) of patients, a prevalence higher than that of anti-Sm (13%, 8/62). Prevalence and levels of various autoantibodies were not clearly different between anti-RHA (+) vs. (-) cases, although there was a trend of higher levels of anti-RHA antibodies in patients without anti-U1RNP/Sm (P = 0.07). Both anti-RHA and -Sm were common in cases within one year of diagnosis; however, the prevalence and levels of anti-RHA in patients years after diagnosis did not reduce dramatically, unlike a previous report in American patients. This suggests that the high prevalence of anti-RHA in Mexican patients may be due to relatively stable production of anti-RHA.

Conclusions

Anti-RHA was detected at high prevalence in Mexican SLE patients. Detection of anti-RHA in races in which anti-Sm is not common should be clinically useful. Racial difference in the clinical significance of anti-RHA should be clarified in future studies.     

Perception of timbral analogies.

Recent studies have investigated the structure of perceptual relations among musical instrument timbres by multidimensional scaling (MDS) techniques. These studies have employed both acoustically produced tones and digitally synthesized imitations and hybrids of acoustic instrument tones. The analyses of dissimilarity ratings for all pairs of a set of tones are usually represented as geometrical structures in a two- or three-dimensional Euclidean space in which the shared 'perceptual' axes are shown to have a qualitative correspondence to acoustic properties such as spectral energy distribution, onset characteristics and degree of change in spectral distribution over the duration of the tone. The present study took as a point of departure a MDS analysis for complex, synthetic tones with the aim of testing whether musician and non-musician listeners used the relations defined by the perceptual space to perform an analogies task of the sort: timbre A is to timbre B as timbre C is to which of two possible timbres, D or D'? A parallelogram model was used to select the D timbres: if the relation between A and B is represented as a vector with both magnitude and direction components, then the appropriate D should form a vector with C having similar magnitude and direction in the timbre space. Aside from conceptual difficulties with the task for both non-musicians and composers, choices for both groups provide support for the parallelogram model indicating a capacity in listeners to perceive abstract relations among the timbres of complex sounds without specific training in such a task.     

Hyperpolarized 129Xe MR Imaging of Alveolar Gas Uptake in Humans

Background

One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange.

Methods and Principal Findings

Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) ¹²⁹Xe to probe the regional uptake of alveolar gases by directly imaging HP ¹²⁹Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP ¹²⁹Xe magnetization is rapidly replenished by diffusive exchange with alveolar ¹²⁹Xe. The dissolved HP ¹²⁹Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs.

Conclusions

The features observed in dissolved-phase ¹²⁹Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP ¹²⁹Xe imaging reports on pulmonary function at a fundamental level.     

Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4)

Background  

Differences in responses to bacterial surface lipopolysaccharides (LPSs) are apparent between and within mammalian species. It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene (Tlr4), the product of which is thought to bind LPS and mediate LPS signal transduction in immune system cells.     

The architecture and conservation pattern of whole-cell control circuitry

The control circuitry that directs and paces Caulobacter cell cycle progression involves the entire cell operating as an integrated system. This control circuitry monitors the environment and the internal state of the cell, including the cell topology, as it orchestrates orderly activation of cell cycle subsystems and Caulobacter's asymmetric cell division. The proteins of the Caulobacter cell cycle control system and its internal organization are co-conserved across many alphaproteobacteria species, but there are great differences in the regulatory apparatus' functionality and peripheral connectivity to other cellular subsystems from species to species. This pattern is similar to that observed for the “kernels” of the regulatory networks that regulate development of metazoan body plans. The Caulobacter cell cycle control system has been exquisitely optimized as a total system for robust operation in the face of internal stochastic noise and environmental uncertainty. When sufficient details accumulate, as for Caulobacter cell cycle regulation, the system design has been found to be eminently rational and indeed consistent with good design practices for human-designed asynchronous control systems.     

Role of environmental factors in autoantibody production - importance of a detailed analysis in a small cohort

In the previous issue of Arthritis Research & Therapy, Muro and colleagues reported a detailed epidemiologic analysis in central Japan on one of the new myositis-specific autoantibodies to MDA-5 (melanoma differentiation-associated gene 5), which is associated with clinically amyopathic dermatomyositis accompanying interstitial lung disease. The increasing prevalence of anti-MDA-5, higher prevalence in small rural towns, and geographical clustering in two areas along the Kiso River suggest a role of environmental factors associated with rural communities or the river/water system or both. A detailed analysis of a small cohort may offer clues, which is ignored in multi-center studies, to the pathogenesis of systemic rheumatic diseases and autoantibody production.     

Evolution of miniaturization and the phylogenetic position of <Emphasis Type="Italic">Paedocypris</Emphasis>, comprising the world's smallest vertebrate

Background  

Paedocypris, a highly developmentally truncated fish from peat swamp forests in Southeast Asia, comprises the world's smallest vertebrate. Although clearly a cyprinid fish, a hypothesis about its phylogenetic position among the subfamilies of this largest teleost family, with over 2400 species, does not exist. Here we present a phylogenetic analyses of 227 cypriniform taxa, including 213 cyprinids, based upon complete mitochondrial DNA cytochrome b nucleotide sequences in order to determine the phylogenetic position of Paedocypris and to study the evolution of miniaturization among cyprinids.     

Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.