A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.

BackgroundManagement of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.MethodsUrine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.ResultsForty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.ConclusionsA number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers

The alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers mediate cell attachment to distinct sites on laminin.

This study was undertaken to determine the roles of individual alpha/beta 1 integrin heterodimers in promoting cellular interactions with the different attachment-promoting domains of laminin (LN). To do this, antibodies to the integrin beta 1 subunit or to specific integrin alpha subunits were tested for effects on cell attachment to LN, to elastase fragments E1-4 and E1, derived from the short arms and core of LN's cruciform structure, and to fragment E8 derived from the long arm of this structure. The human JAR choriocarcinoma cells used in this study attached to LN and to fragments E1 and E8. Attachment to E1-4 required a much higher substrate coating concentration, suggesting that it is a poor substrate for JAR cell attachment. The ability of cells to attach to different LN domains suggested the presence of more than one LN receptor. These multiple LN receptors were shown to be beta 1 integrin heterodimers because antibodies to the integrin beta 1 subunit inhibited attachment of JAR cells to LN and its three fragments. To identify the individual integrin alpha/beta 1 heterodimers that mediate interactions with these LN domains, mAbs specific for individual beta 1 heterodimers in human cells were used to study JAR cell interactions with LN and its fragments. An anti-alpha 6/beta 1-specific mAb, GoH3, virtually eliminated cell attachment to E8 and partially inhibited attachment to E1 and intact LN. Thus the major alpha 6/beta 1 attachment domain is present in fragment E8. An alpha 1/beta 1-specific mAb (S2G3) strongly inhibited cell attachment to collagen IV and partially inhibited JAR attachment to LN fragment E1. Thus, the alpha 1/beta 1 heterodimer is a dual receptor for collagen IV and LN, interacting with LN at a site in fragment E1. In combination, the anti-alpha 1- and anti-alpha 6-specific antibodies completely inhibited JAR cell attachment to LN and fragment E1. Thus, the alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers each function as LN receptors and act together to mediate the interactions of human JAR choriocarcinoma cells with LN

Evaluation of some non-elementary integrals involving sine, cosine, exponential and logarithmic integrals: Part I

The non-elementary integrals $\text{Si}_{\beta,\alpha}=\int [\sin{(\lambda x^\beta)}/(\lambda x^\alpha)] dx,\beta\ge1,\alpha\le\beta+1$ and $\text{Ci}_{\beta,\alpha}=\int [\cos{(\lambda x^\beta)}/(\lambda x^\alpha)] dx, \beta\ge1, \alpha\le2\beta+1$, where $\{\beta,\alpha\}\in\mathbb{R}$, are evaluated in terms of the hypergeometric functions $_{1}F_2$ and $_{2}F_3$, and their asymptotic expressions for $|x|\gg1$ are also derived. The integrals of the form $\int [\sin^n{(\lambda x^\beta)}/(\lambda x^\alpha)] dx$ and $\int [\cos^n{(\lambda x^\beta)}/(\lambda x^\alpha)] dx$, where $n$ is a positive integer, are expressed in terms $\text{Si}_{\beta,\alpha}$ and $\text{Ci}_{\beta,\alpha}$, and then evaluated. $\text{Si}_{\beta,\alpha}$ and $\text{Ci}_{\beta,\alpha}$ are also evaluated in terms of the hypergeometric function $_{2}F_2$. And so, the hypergeometric functions, $_{1}F_2$ and $_{2}F_3$, are expressed in terms of $_{2}F_2$.The exponential integral $\text{Ei}_{\beta,\alpha}=\int (e^{\lambda x^\beta}/x^\alpha) dx$ where $\beta\ge1$ and $\alpha\le\beta+1$ and the logarithmic integral $\text{Li}=\int_{\mu}^{x} dt/\ln{t}, \mu>1$ are also expressed in terms of $_{2}F_2$, and their asymptotic expressions are investigated. It is found that for $x\gg\mu$, \text{Li}\sim {x}/{\ln{x}}+\ln{\left(\frac{\ln{x}}{\ln{\mu}}\right)}-2-\ln{\mu}\hspace{.075cm} _{2}F_{2}(1,1;2,2;\ln{\mu}), where the term \ln{\left(\frac{\ln{x}}{\ln{\mu}}\right)}-2-\ln{\mu}\hspace{.075cm} _{2}F_{2}(1,1;2,2;\ln{\mu}) is added to the known expression in mathematical literature $\text{Li}\sim {x}/{\ln{x}}$.Comment: 23 pages, 1 figure, Accepted for publication by the Ural Math.