Cordifolide A, a sulfur-containing clerodane diterpene glycoside from Tinospora cordifolia.

Cordifolide A (1), a novel unprecedented sulfur-containing clerodane diterpene glycoside, together with other two new diterpene glycosides, cordifolides B (2) and C (3), and four known analogues, was isolated from a methanol-soluble extract of the stems of Tinospora cordifolia. The structures of the new compounds were determined on the basis of spectroscopic data interpretation, with that of cordifolide A (1) confirmed by a single-crystal X-ray crystallographic analysis. All isolates were evaluated for their in vitro immunomodulatory activity using mouse bone marrow-derived dentritic cells (BMDCs).

5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy.

Background/aims: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN).

Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens.

Background: After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies.

The composition and signaling of the IL-35 receptor are unconventional.

Interleukin 35 (IL-35) belongs to the IL-12 family of heterodimeric cytokines but has a distinct functional profile. IL-35 suppresses T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells (iTr35 cells). Here we found that IL-35 signaled through a unique heterodimer of receptor chains IL-12Rβ2 and gp130 or homodimers of each chain.

Characterization of glomerular diseases using proteomic analysis of laser capture microdissected glomeruli.

The application of molecular techniques to characterize clinical kidney biopsies has the potential to provide insights into glomerular diseases that cannot be revealed by traditional renal pathology. The present work is a proof-of-concept approach to test whether proteomic analysis of glomeruli isolated from clinical biopsies by laser capture microdissection can provide unique information regarding differentially expressed proteins relevant to disease pathogenesis. The proteomes of glomeruli isolated by laser capture microdissection from biopsies of normal kidneys (living-related donor kidneys) were compared with those from patients with diabetic nephropathy, lupus nephritis, and fibronectin glomerulopathy.

Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis.

Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L.

Endothelial microparticles in transplant patients - great potential but a long way to go.

This overview provides information on the current state of endothelial microparticle research. Microparticles are small membrane vesicles shed by different cell types, which contain cell surface proteins and cytoplasmic components of the original cell. The microparticle production is a part of normal cell function, but it increases by apoptotic cells and cells under stress.

Pulmonary T cell activation in response to chronic particulate air pollution.

The purpose of this study was to investigate the effects of chronically inhaled particulate matter <2.5 μm (PM(2.5)) on inflammatory cell populations in the lung and systemic circulation.

Role of co-stimulation in Leishmaniasis.

Leishmania are obligate intracellular parasites that cause a wide spectrum of diseases ranging from cutaneous, mucocutaneous and the visceral kind. Persistence or resolution of leishmaniasis is governed by host immune response. Co-stimulation is an important secondary signal that governs the extent, strength and direction of the immune response that follows.

TLR2 mediates immunity to experimental cysticercosis.

Information concerning TLR-mediated antigen recognition and regulation of immune responses during helminth infections is scarce. TLR2 is a key molecule required for innate immunity and is involved in the recognition of a wide range of viruses, bacteria, fungi and parasites. Here, we evaluated the role of TLR2 in a Taenia crassiceps cysticercosis model.

Discrepancies in glomerular and tubulointerstitial/vascular immune complex IgG subclasses in lupus nephritis.

Background And Objectives: Lupus nephritis is characterized by glomerular and extraglomerular immune complex deposition in the kidney. It is unclear whether the same circulating immune complexes deposit in the glomeruli and in extraglomerular structures, or whether they are pathogenetically different. Differences in the IgG subclass composition may point towards different pathways in the formation of glomerular and extraglomerular immune complexes.

Strong transthyretin immunostaining: potential pitfall in cardiac amyloid typing.

Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ.

IL-10-IFN-γ double producers CD4+ T cells are induced by immunization with an amastigote stage specific derived recombinant protein of Trypanosoma cruzi.

During the acute phase of infection, T. cruzi replicates extensively and releases immunomodulatory molecules that delay parasite-specific responses mediated by effector T cells. This mechanism of evasion allows the parasite to spread in the host.

Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation.

An acute increase in international normalized ratio (INR) to >3.0 in patients with chronic kidney disease (CKD) can associate with an unexplained acute increase in serum creatinine and accelerated progression of CKD. A subset of these patients have renal tubular obstruction by casts of red blood cells, presumably the dominant mechanism of the acute kidney injury described as warfarin-related nephropathy.

Relapse or worsening of nephrotic syndrome in idiopathic membranous nephropathy can occur even though the glomerular immune deposits have been eradicated.

Background: Relapse or worsening of nephrotic syndrome (NS) in idiopathic membranous nephropathy (IMN) is generally assumed to be due to recurrent disease. Here we document that often that may not be the case.

Subjects And Methods: This is a prospective study of 7 consecutive IMN patients whose renal status improved, then worsened after completing a course of immunosuppressive therapy.

A patient presenting with diffuse cutaneous leishmaniasis (DCL) as a first indicator of HIV infection in India.

Opportunistic parasitic infections such as leishmaniasis are common in human immunodeficiency virus (HIV)-infected patients and are usually acquired several days after initial diagnosis of HIV infection. Here, we report on a patient who presented with diffuse cutaneous leishmaniasis (DCL) caused by Leishmania tropica as the first and only clinical manifestation of HIV infection. To the best of our knowledge, this is the first case that illustrates that DCL could be the first clinical indicator of HIV infection.

Proliferative glomerulonephritis with monoclonal IgG deposits recurs or may develop de novo in kidney allografts.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMIGD) is a recently recognized glomerular disease. Light microscopy usually resembles membranoproliferative glomerulonephritis. Glomerular deposits are mostly IgG3 κ; however, unlike in the usual forms of monoclonal immunoglobulin deposition disease, extraglomerular deposits are absent.

Histopathology and outcome of acute humoral rejection in renal allografts.

Our purpose was to see if histopathologic features of acute antibody-mediated rejection (AMR) in renal allografts have prognostic value; and to compare two-year graft survival with and without additional therapy with plasmapheresis and intravenous immunoglobulin (IVIG). We reviewed renal allograft biopsies taken within the first 6 months after transplant from patients with C4d positive AMR, performed between January 2000 to December 2005 (n=57). We formed two groups: Group 1: biopsied between 2003 and 2005 (n=26), when C4d staining was routinely performed and option for plasmapheresis and IVIG was available; Group 2: biopsied between 2000 and 2002 (n=31), retrospectively found to be C4d positive.

Macrophage migration inhibitory factor: a downregulator of early T cell-dependent IFN-gamma responses in Plasmodium chabaudi adami (556 KA)-infected mice.

Neutralization of macrophage migration inhibitory factor (MIF) increases anti-tumor cytotoxic T cell responses in vivo and IFN-γ responses in vitro, suggesting a plausible regulatory role for MIF in T cell activation. Considering that IFN-γ production by CD4(+) T cells is pivotal to resolve murine malaria and that secretion of MIF is induced by Plasmodium chabaudi adami parasites, we investigated the effect of MIF deficiency on the infection with this pathogen. Infections with P.

Mammalian antimicrobial peptide influences control of cutaneous Leishmania infection.

Cathelicidin-type antimicrobial peptides (CAMP) are important mediators of innate immunity against microbial pathogens acting through direct interaction with and disruption of microbial membranes and indirectly through modulation of host cell migration and activation. Using a mouse knock-out model in CAMP we studied the role of this host peptide in control of dissemination of cutaneous infection by the parasitic protozoan Leishmania. The presence of pronounced host inflammatory infiltration in lesions and lymph nodes of infected animals was CAMP-dependent.

Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate.

An acute increase in the international normalized ratio (INR; a comparison of prothrombin time to monitor the effects of warfarin) over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine (SC) and an accelerated progression of CKD. Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. We termed this warfarin-related nephropathy (WRN), and previously reported cases of WRN only in patients with CKD.

Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers.

Background: The development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans.