Mechanisms of Kidney Injury in Lupus Nephritis - the Role of Anti-dsDNA Antibodies

published_or_final_versio

Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis

published_or_final_versio

Mediators of Inflammation and Their Effect on Resident Renal Cells: Implications in Lupus Nephritis

published_or_final_versio

Conceptualising the spirituality of Chinese older adults: a Delphi study

Free Paper Session II : Mental Health / End-Of-Life CareINTRODUCTION: Service provision in geriatric health and social care is increasingly guided by holistic principles, in which many aspects, including physical, psychological, social, and spiritual aspects, are equally emphasized to enhance well-being and enrich life. However, little is known about the degree of consensus among multidisciplinary professionals in the Chinese context on the central components of spirituality that most promote spiritual well-being among Chinese older adults. This study is intended to identify the core components of ...published_or_final_versio

Fibrosis-related growth factors in peritoneal dialysate during peritonitis

Session - Basic Research on Biocompatibility, Immunology, Inflammation, and Fibrosispublished_or_final_versio

A family study of endophenotypes for psychosis within an early intervention programme in Hong Kong: Rationale and preliminary findings

The study of endophenotypes may be a viable strategy to tackle the genetic complexity and phenotypic heterogeneity of psychosis, but this research direction is relatively under-developed in China as compared to Western countries. We have recently initiated one of the first family studies of endophenotypes for psychosis in China. Patients entering an established early psychosis intervention service are recruited into this research project for phenotyping, endophenotyping and genotyping. At the endophenotypic level, four domains (neurological soft signs, neurocognition of prospective memory, social cognition of facial emotion recognition, and affective cognition of anticipatory and consummatory pleasure) are studied in the sample of patients with psychosis and their unaffected siblings. This article illustrates the benefit of a research-oriented clinical programme and its findings based on the data collected as of early 2011. © 2011 Science China Press and Springer-Verlag Berlin Heidelberg.link_to_subscribed_fulltex

Immunorestitution disease involving the innate and adaptive response

Immunorestitution disease (IRD) is defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection that is temporally related to the recovery of the immune system. We report the temporal sequence of events that led to IRD caused by Pneumocystis carinii and Aspergillus terreus in 2 human immunodeficiency virus (HIV)-negative patients soon after the recovery of adaptive and innate immunity, respectively, and we review episodes noted in the English-language literature that fit the definition of IRD (109 episodes in 107 patients). The median time from the recovery of neutrophil counts or termination of steroid therapy to the development of IRD was 8 days in cases of pulmonary aspergillosis (23 episodes) and hepatosplenic candidiasis (8) and 21 days for viral diseases such as hepatitis B (24) and viral pneumonitis (6). For IRD due to mycobacteriosis (27 episodes) and cryptococcosis (4) in HIV-positive patients, the median interval between the initiation of highly active antiretroviral therapy (HAART) and the onset of IRD was 11 days; for viral infections, including those due to cytomegalovirus (14), hepatitis B virus (1), and hepatitis C virus (2), the median interval was 42 days. As an emerging clinical entity, IRD merits further study to optimize treatment of immunosuppressed patients.published_or_final_versio

Mesangial cell-binding activity of serum immunoglobulin G in patients with lupus nephritis

In vitro data showed that immunoglobulin G (IgG) from patients with lupus nephritis (LN) could bind to cultured human mesangial cells (HMC). The clinical relevance of such binding was unknown. Binding of IgG and subclasses was measured in 189 serial serum samples from 23 patients with Class III/IV+/-V LN (48 during renal flares, 141 during low level disease activity (LLDA)). 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals were used as controls. HMC-binding was measured with cellular ELISA and expressed as OD index. HMC-binding index of total IgG was 0.12+/-0.09, 0.36+/-0.25, 0.59+/-0.37 and 0.74+/-0.42 in healthy subjects, NLGD, LN patients during LLDA, and LN flares respectively (P = 0.046, LN flare vs. LLDA; P<0.001, for healthy controls or NLGD vs. LN during flare or LLDA). Binding of serum IgG1 to HMC was 0.05+/-0.05, 0.15+/-0.11, 0.41+/-0.38 and 0.55+/-0.40 for the corresponding groups respectively (P = 0.007, LN flare vs. remission; P<0.001, for healthy controls or NLGD vs. LN during flare or remission). IgG2, IgG3 and IgG4 from patients and controls did not show significant binding to HMC. Total IgG and IgG1 HMC-binding index correlated with anti-dsDNA level (r = 0.26 and 0.39 respectively, P<0.001 for both), and inversely with C3 (r = -0.17 and -0.45, P<0.05 for both). Sensitivity/specificity of total IgG or IgG1 binding to HMC in predicting renal flares were 81.3%/39.7% (ROC AUC 0.61, P = 0.03) and 83.8%/41.8% (AUC 0.63, P = 0.009) respectively. HMC-binding by IgG1, but not total IgG, correlated with mesangial immune deposition in LN renal biopsies under electron microscopy. Our results showed that binding of serum total IgG and IgG1 in LN patients correlates with disease activity. The correlation between IgG1 HMC-binding and mesangial immune deposition suggests a potential pathogenic significance.published_or_final_versio

Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy

OBJECTIVE: Sulodexide is a mixture of glycosaminoglycans that may reduce proteinuria in diabetic nephropathy (DN), but its mechanism of action and effect on renal histology is not known. We investigated the effect of sulodexide on disease manifestations in a murine model of type I DN. METHODS: Male C57BL/6 mice were rendered diabetic with streptozotocin. After the onset of proteinuria, mice were randomized to receive sulodexide (1 mg/kg/day) or saline for up to 12 weeks and renal function, histology and fibrosis were examined. The effect of sulodexide on fibrogenesis in murine mesangial cells (MMC) was also investigated. RESULTS: Mice with DN showed progressive albuminuria and renal deterioration over time, accompanied by mesangial expansion, PKC and ERK activation, increased renal expression of TGF-β1, fibronectin and collagen type I, III and IV, but decreased glomerular perlecan expression. Sulodexide treatment significantly reduced albuminuria, improved renal function, increased glomerular perlecan expression and reduced collagen type I and IV expression and ERK activation. Intra-glomerular PKC-α activation was not affected by sulodexide treatment whereas glomerular expression of fibronectin and collagen type III was increased. MMC stimulated with 30 mM D-glucose showed increased PKC and ERK mediated fibronectin and collagen type III synthesis. Sulodexide alone significantly increased fibronectin and collagen type III synthesis in a dose-dependent manner in MMC and this increase was further enhanced in the presence of 30 mM D-glucose. Sulodexide showed a dose-dependent inhibition of 30 mM D-glucose-induced PKC-βII and ERK phosphorylation, but had no effect on PKC-α or PKC-βI phosphorylation. CONCLUSIONS: Our data demonstrated that while sulodexide treatment reduced proteinuria and improved renal function, it had differential effects on signaling pathways and matrix protein synthesis in the kidney of C57BL/6 mice with DN.published_or_final_versio

p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation

Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.published_or_final_versio