Chryseobacterium meningosepticum in a parapneumonic effusion in a chronic kidney disease patient on hemodialysis.

Chryseobacterium meningosepticum is an uncommon human pathogen, which is an inhabitant of soil and water. It should be included in the list of suspected nosocomial infections, especially in patients with immunocompromised status. C.

Glutathione S-transferase Mu 2-transduced mesenchymal stem cells ameliorated anti-glomerular basement membrane antibody-induced glomerulonephritis by inhibiting oxidation and inflammation.

Introduction: Oxidative stress is implicated in tissue inflammation, and plays an important role in the pathogenesis of immune-mediated nephritis. Using the anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) mouse model, we found that increased expression of glutathione S-transferase Mu 2 (GSTM2) was related to reduced renal damage caused by anti-GBM antibodies. Furthermore, mesenchymal stem cell (MSC)-based therapy has shed light on the treatment of immune-mediated kidney diseases.

Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population.

Purpose: To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population.

Methods: Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy.

Molecular basis of 9G4 B cell autoreactivity in human systemic lupus erythematosus.

9G4(+) IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific fashion and react with different lupus Ags including B cell Ags and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. In this study, a large panel of recombinant 9G4(+) mAbs from single naive and memory cells was generated and tested against B cells, apoptotic cells, and other Ags.

Atypical femoral fractures: transverse morphology at lateral cortex is a critical feature.

In 2010, the American Society for Bone and Mineral Research (ASBMR) task force defined major and minor features to assist in the case finding and reporting of atypical femoral fractures (AFFs). One major feature that was proposed was a "transverse or short oblique configuration." Our primary aim was to compare the conventional overall fracture morphology (OFM) with its associated angle (OFMA) and our proposed lateral cortical fracture angle (LCFA) in the assessment of fracture configuration in suspected AFFs and non-AFFs.

Kallikrein transduced mesenchymal stem cells protect against anti-GBM disease and lupus nephritis by ameliorating inflammation and oxidative stress.

Previously we have shown that kallikreins (klks) play a renoprotective role in nephrotoxic serum induced nephritis. In this study, we have used mesenchymal stem cells (MSCs) as vehicles to deliver klks into the injured kidneys and have measured their therapeutic effect on experimental antibody induced nephritis and lupus nephritis. Human KLK-1 (hKLK1) gene was transduced into murine MSCs using a retroviral vector to generate a stable cell line, hKLK1-MSC, expressing high levels of hKLK1.

Overexpression of membrane-bound fas ligand (CD95L) exacerbates autoimmune disease and renal pathology in pristane-induced lupus.

Loss-of-function mutations in the Fas death receptor or its ligand result in a lymphoproliferative syndrome and exacerbate clinical disease in most lupus-prone strains of mice. One exception is mice injected with 2,6,10,14-tetramethylpentadecane (TMPD), a hydrocarbon oil commonly known as pristane, which induces systemic lupus erythematosus-like disease. Although Fas/Fas ligand (FasL) interactions have been strongly implicated in the activation-induced cell death of both lymphocytes and other APCs, FasL can also trigger the production of proinflammatory cytokines.

A genopedia of lupus genes - lessons from gene knockouts.

Systemic lupus erythematosus (SLE) is the quintessential complex, multifactorial systemic autoimmune disease. In particular, it is highly polygenic in origin in both humans and animal models. Mouse models of lupus help uncover the genetic and cellular etiologies of the disease, which often implicate homeostatic imbalances in specific cell types and pathways.

SLE peripheral blood B cell, T cell and myeloid cell transcriptomes display unique profiles and each subset contributes to the interferon signature.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients.

Serial non-invasive assessment of antibody induced nephritis in mice using positron emission tomography.

Mouse models of experimental anti-glomerular basement membrane (anti-GBM) nephritis provide an analytical tool for studying spontaneous lupus nephritis. The potential of Positron Emission Tomography (PET) was evaluated using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) as a probe to monitor the progression of anti-GBM induced nephritis in a mouse model. The imaging results were compared to conventional measures of renal function and pathological changes.

Urinary angiostatin--a novel putative marker of renal pathology chronicity in lupus nephritis.

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation.

Synthesis of imidazo[1,2-a]pyridines: "water-mediated" hydroamination and silver-catalyzed aminooxygenation.

Aqueous syntheses of methylimidazo[1,2-a]pyridines without any deliberate addition of catalyst are reported. Imidazo[1,2-a]pyrazine and imidazo[2,1-a]isoquinoline were also obtained in good yields under similar conditions. With acetonitrile as solvent, Ag-catalyzed intramolecular aminooxygenation produced imidazo[1,2-a]pyridine-3-carbaldehydes in moderate to good yields.

Protein kinase Cβ is required for lupus development in Sle mice.

Objective: To evaluate the requirement for protein kinase Cβ (PKCβ) in the development of lupus in mice, and to explore the potential of targeting PKCβ as a therapeutic strategy in lupus.

Methods: Congenic mice bearing the disease loci Sle1 or Sle1 and Sle3, which represent different stages of severity in the development of lupus, were crossed with PKCβ-deficient mice. The effect of PKCβ deficiency in lupus development was analyzed.

Inducible expression of kallikrein in renal tubular cells protects mice against spontaneous lupus nephritis.

Objective: To ascertain whether engineered expression of kallikreins within the kidneys, using an inducible Cre/loxP system, can ameliorate murine lupus nephritis.

Methods: In mice with a lupus-prone genetic background, we engineered the expression of tamoxifen-inducible Cre recombinase under the control of a kidney-specific promoter whose activation initiates murine kallikrein-1 expression within the kidneys. These transgenic mice were injected with either tamoxifen or vehicle at age 2 months and then were monitored for 8 months for kallikrein expression and disease.

DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN.

Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN.

Lupus nephritis - alarmins may sound the alarm?

A growing body of literature has documented the elevated levels of the alarmin HMGB1 in lupus skin and serum. Two recent reports highlight the increased expression of HMGB1 in lupus nephritis, within the diseased kidneys or in the urine. Taken together with previous reports, these findings suggest that the interaction of HMGB1 with a variety of receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptors, might play a role in the pathogenesis of lupus nephritis.

The lupus-prone NZM2410/NZW strain-derived Sle1b sublocus alters the germinal center checkpoint in female mice in a B cell-intrinsic manner.

C57BL/6 (B6) mice carrying the Sle1b sublocus (named B6.Sle1b), which harbors the lupus-associated NZM2410/NZW SLAM family genes, produce antinuclear Abs (ANAs). However, the role and mechanism(s) involved in the alteration of the germinal center (GC) tolerance checkpoint in the development of ANAs in these mice is not defined.

Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus.

Introduction: Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity.

Serial non-invasive monitoring of renal disease following immune-mediated injury using near-infrared optical imaging.

Background: Non-invasive monitoring of disease progression in kidney disease is still a major challenge in clinical practice. In vivo near-infrared (NIR) imaging provides a new tool for studying disease mechanisms and non-invasive monitoring of disease development, even in deep organs. The LI-COR IRDye® 800CW RGD optical probe (RGD probe) is a NIR fluorophore, that can target integrin alpha v beta 3 (α(v)β(3)) in tissues.

Foot drop after ethanol embolization of calf vascular malformation: a lesson on nerve injury.

Ethanol is often used in sclerotherapy to treat vascular malformations. Nerve injury is a known complication of this procedure. However, the management of this complication is not well described in literature.

Inflammation associated anemia and ferritin as disease markers in SLE.

Introduction: In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia.

Methods: A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls.

Radiographic features of multifocal endosteal thickening of the femur in patients on long-term bisphosphonate therapy.

Objectives: To describe the characteristics of multifocal endosteal thickening in patients on bisphosphonate therapy.

Method: A retrospective study of 68 patients with atypical femoral fractures (as defined by ASBMR) whilst on bisphosphonate therapy was performed. Femoral radiographs were assessed for: focal endosteal thickening, number of lesions, lesion location, femoral bowing, periosteal beak and black line.

Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis.

Introduction: Although renal pathology is highly predictive of the disease course in lupus nephritis, it cannot be performed serially because of its invasive nature and associated morbidity. The goal of this study is to investigate whether urinary levels of CXC ligand 16 (CXCL16), monocyte chemotactic protein-1 (MCP-1) or vascular cell adhesion molecule-1 (VCAM-1) in patients with lupus nephritis are predictive of particular features of renal pathology in renal biopsies obtained on the day of urine procurement.

Methods: CXCL16, MCP-1, and VCAM-1 levels were measured in urine samples from 74 lupus nephritis patients and 13 healthy volunteers.

IgG and IgM autoantibody differences in discoid and systemic lupus patients.

Systemic lupus erythematosus (SLE) patients with discoid lupus erythematosus (DLE) were reported to have milder disease. To test this observation, we used sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE-SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE-) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE-SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE- (N=23), and healthy subjects (N=22).

Metabolic disturbances associated with systemic lupus erythematosus.

The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays.