Granulicatella Causing Infective Endocarditis and Glomerulonephritis.

Granulicatella is a type of nutritionally variant Streptococcus (NVS) that requires special medium for growth. It has shown to cause infective endocarditis which is associated with higher mortality and complications. We present a case of Granulicatella causing endocarditis and glomerulonephritis. There has only been one such prior case report. An adult male with a remote history of gastric bypass presented with shortness of breath with exertion, lower extremity swelling of 1-month duration. Blood cultures 4/4 bottles grew Granulicatella albicans with infected tooth being the source. Transesophageal echocardiogram revealed a vegetation on the mitral valve. He received intravenous vancomycin. He was found to have acute kidney injury requiring hemodialysis. Kidney biopsy revealed immune complex deposits in the mesangium and along the capillary basement membrane suggestive of post infectious glomerulonephritis. It is crucial to recognize NVS as potential cause for endocarditis in cultures that are slow growing. NVS require a special medium. Though it is rare, NSV can also cause glomerulonephritis. Early recognition is important to help with determining treatment options which may include immunosuppressive therapy along with treatment of underlying infection.

Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction.

Sphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFß1 and αSMA when compared to wild type controls. We found a consistently significant increase in anti-inflammatory (M2) macrophages in obstructed Sphk2-/- kidneys by flow cytometry and a decrease in mRNA levels of the inflammatory cytokines, MCP1, TNFα, CXCL1 and ILß1, suggesting an anti-inflammatory bias in the absence of Sphk2. Indeed, metabolic profiling showed that the pro-inflammatory glycolytic pathway is largely inactive in Sphk2-/- bone marrow-derived macrophages. Furthermore, treatment with the M2-promoting cytokines IL-4 or IL-13 demonstrated that macrophages lacking Sphk2 polarized more efficiently to the M2 phenotype than wild type cells. Bone marrow transplant studies indicated that expression of Sphk2-/- on either the hematopoietic or parenchymal cells did not fully rescue the pro-healing phenotype, confirming that both infiltrating M2-macrophages and the kidney microenvironment contribute to the damaging Sphk2 effects. Importantly, obstructed kidneys from mice treated with an Sphk2 inhibitor recapitulated findings in the genetic model. These results demonstrate that reducing Sphk2 activity by genetic or pharmacological manipulation markedly decreases inflammatory and fibrotic responses to obstruction, resulting in diminished renal injury and supporting Sphk2 as a novel driver of the pro-inflammatory macrophage phenotype.

Treatment with the immunomodulator FTY720 (fingolimod) significantly reduces renal inflammation in murine unilateral ureteral obstruction.

PURPOSE: The S1P signaling pathway represents an important potential target for the modulation of tissue inflammation/injury. The immunomodulator FTY720, also known as fingolimod, is a potent agonist for multiple S1P receptors that was approved by the Food and Drug Administration to treat multiple sclerosis. We examined the therapeutic role of FTY720 for renal injury secondary to unilateral ureteral obstruction. MATERIALS AND METHODS: CB57BL/6 mice underwent a sham procedure or unilateral ureteral obstruction and were treated with FTY720 by gavage for 1, 3 and 5 days. Control groups received vehicle. Ligated and unligated renal tissue was examined for histopathological changes, inflammatory and fibrotic markers, TGF-ß1, α-SMA, and macrophage infiltration by Western blot and immunohistochemistry. Proinflammatory and profibrotic cytokines were profiled by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Pathological evaluation revealed that FTY720 treatment resulted in a significant reduction in inflammatory infiltration in obstructed kidneys compared to controls. Immunohistochemical and Western blot showed that TGF-ß1 and α-SMA protein levels were similarly decreased, as was macrophage infiltration into the renal interstitial space, compared to untreated mice. In agreement with these observations quantitative reverse transcriptase-polymerase chain reaction revealed that inflammatory and fibrotic cytokines (MCP-1, IL-1ß, CXCL1, TNF-α and TGF-ß1) were also significantly decreased in the FTY720 group. CONCLUSIONS: This study suggests that in a murine ureteral obstruction model FTY720 significantly inhibited the production of inflammatory cytokines and factors regulating interstitial fibrosis and extracellular matrix accumulation. These findings were associated with decreased evidence of renal injury on pathological examination, suggesting that FTY720 or related compounds may be valuable modulators of obstruction induced renal injury.

Prognostic implications of lymph node involvement in bladder cancer: are we understaging using current methods?

To review the current and newer, alternative methods for evaluating lymph nodes for tumor involvement in bladder cancer as relapse rates for organ-confined disease remain high despite improvements in surgical technique, suggesting the possibility of understaging. To propose a research agenda based on these findings. A PubMed literature search was performed to identify studies examining the prognostic implications of and outcomes associated with lymph node involvement in bladder cancer as well as those that utilized newer methodologies to identify the possibility for metastatic disease. Lymph node involvement remains one of the strongest predictors of clinical outcome in bladder cancer. Histologic and molecular techniques for identification of lymph node metastasis provide a sensitivity and specificity equal to if not higher than standard pathologic evaluation. Further research into this field would help to elucidate the potential utility of these techniques with regard to proper staging and potential relevance to clinical outcomes.

Membranoproliferative glomerulonephritis in a postpartum woman with sickle cell disease.

Renal insufficiency occurs in a considerable proportion of patients with sickle cell disease. Common advanced glomerular lesions include focal segmental glomerulosclerosis and nonimmune membranoproliferative glomerulonephritis. Due to the paucity of data supporting an immune-mediated pathophysiology, anti-inflammatory and immunosuppressive therapies have not been successfully evaluated in such patients. We present a case of membranoproliferative glomerulonephritis in a postpartum patient with sickle cell disease, where treatment with steroids was helpful.

Characterization of a WiT49 cell line derived orthotopic model of Wilms tumor.

Wilms tumor is the most common malignant renal tumor in children. However, to date no Wilms tumor mouse model is available due to the lack of Wilms tumor cell lines. Herein for the first time we report an orthotopic xenograft mouse model utilizing the recently described Wilms tumor cell line WiT49. It has a high tumor occurrence rate (85%) without metastasis. Hematoxylin and eosin staining showed it is subcapsular in location and mainly biphasic with stromal and epithelial components while blastemal component is unappreciable. This model provides the prerequisite for the screening and development of new anti-tumor agents for Wilms tumor.

Malignant peripheral nerve sheath tumor of the renal pelvis.

Malignant peripheral nerve sheath tumors (MPNST) of the urothelial collecting system are rare. These tumors contain both malignant epithelial and sarcomatous components. Metastatic spread of MPNST is common, however, metastases to the kidney and perirenal tissues are rare. There are only 4 cases reported of MPNST of the kidney. We report a rare case of MPNST arising from the submucosa of the renal pelvis.

S1P/S1P1 signaling stimulates cell migration and invasion in Wilms tumor.

Sphingosine-1-phosphate (S1P) is an important regulator of cellular functions via interaction with its receptors S1P(1-5). To date, nothing is known about the S1P receptor expression and the effects of S1P signaling in Wilms tumor. In this study, we found ubiquitous expression of S1P receptors in Wilms tumor specimens and cell lines. We demonstrated that S1P(1) acted as a promigratory modulator by employing S1P(1) antagonist VPC44116, S1P(1) siRNA and adenoviral transduction in Wilms tumor cells. Further, we clarified that S1P(1)-mediated migration occurred via Gi coupling and activation of PI3K and Rac1. In addition, S1P stimulated WiT49 cell invasion through S1P(1)/Gi signaling pathway. We consider that targeting S1P(1) may be a point of therapeutic intervention in Wilms tumor.

Henoch-Schönlein Purpura Presenting as a Rash and Proteinuria in a 59-Year-Old Woman.

Henoch-Schönlein purpura is a disease of unknown etiology. it is predominantly seen in children, although adults are also affected, and comprises a rash, arthritis, abdominal pain, and renal dysfunction. there is no effective treatment, although the syndrome is self-limiting and generally subsides without sequelae. The authors present a case of Henoch-Schönlein purpura in a 59-year-old woman who presented with a rash of six months' duration and a high level of urinary protein.

Palpable lesions resistant to corticosteroids.

A woman with a history of leukocytoclastic vasculitis is resistant to treatment with prednisone. The lesions are particularly prominent over the buttocks, waist, and sock line. The patient's symptoms are described in detail. Various possible solutions are described in detail. Various possible solutions are discussed.