Phase I trial of a humanized, Fc receptor nonbinding anti-CD3 antibody, hu12F6mu in patients receiving renal allografts.

Hu12F6mu is an Fc-mutated, humanized anti-CD3 antibody developed in our lab. The aim of this study was to assess single dose escalation pharmacokinetics (PK) and safety profile of hu12F6mu and to measure the effects of the antibody on levels of circulating T cells over time. Twenty-seven patients receiving renal allografts were randomized to receive hu12F6mu intravenously at a single-dose of 2.

Control of dissected leaf morphology by a Cys(2)His(2) zinc finger transcription factor in the model legume Medicago truncatula.

Plant leaves are diverse in their morphology, reflecting to a large degree the plant diversity in the natural environment. How different leaf morphology is determined is not yet understood. The leguminous plant Medicago truncatula exhibits dissected leaves with three leaflets at the tip.

Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial.

Background: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine. A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN. However, the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive.

An improved image alignment procedure for high-resolution transmission electron microscopy.

Image alignment is essential for image processing methods such as through-focus exit-wavefunction reconstruction and image averaging in high-resolution transmission electron microscopy. Relative image displacements exist in any experimentally recorded image series due to the specimen drifts and image shifts, hence image alignment for correcting the image displacements has to be done prior to any further image processing. The image displacement between two successive images is determined by the correlation function of the two relatively shifted images.

Slope of changes in renal function in the first year post-transplantation and one-yr estimated glomerular filtration rate together predict long-term renal allograft survival.

Background:   Few studies have examined the predictive value of the slope of changes in renal function in the first year post-transplantation when combined with one-yr estimated glomerular filtration rate (eGFR).

Methods:   We reviewed 1062 recipients who underwent renal transplantations from deceased donors between January 1992 and June 2003. Recipients were stratified into four groups: (a) one-yr eGFR < 45 mL/min and slope <-2 mL/min/month, (b) one-yr eGFR < 45 mL/min and slope >-2 mL/min/month, (c) one-yr eGFR > 45 mL/min and slope <-2 mL/min/month, and (d) one-yr eGFR > 45 mL/min and slope > -2 mL/min/month.

The effect of pregnancy on paternal skin allograft survival.

Elucidation of maternal-fetal tolerance mechanisms clarifies the role of regulatory T cells (Treg) in transplant tolerance. This study aim to investigate the effect of pregnancy on paternal skin allograft survival. Flow cytometry techniques, mixed lymphocytes reaction (MLR), PCR, real-time PCR and skin transplantation were key methods.

Adjunctive continuous high-volume hemofiltration in acute severe pancreatitis patients: a retrospective study.

OBJECTIVE. To evaluate the efficacy of continuous high-volume hemofiltration for the treatment of severe acute pancreatitis patients and the impact of acute physiology and chronic health evaluation (APACHE) II score on the efficacy of high-volume hemofiltration. MATERIAL AND METHODS.

Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and a new case report.

Purpose: Fibrates are used to manage mixed dyslipidemia. However, these drugs have the potential risk of inducing rhabdomyolysis. This paper gives an overview of the literature on rhabdomyolysis associated with fibrate therapy.

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection.

Background: Endothelial cell antigens are important targets in acute rejection (AR). Our goal was to measure the serum concentrations of pre-transplant anti-endothelial cell antibody (AECA) in panel reactive antibody (PRA) negative recipients and its impact on AR within 6 months following renal transplantation.

Methods: We retrospectively examined pre-transplant sera from 392 patients using cellular enzyme linked immunosorbent assay (ELISA) with substrate from a permanent endothelial cell line EAhy926.

PI-3 kinase pathway can mediate the effect of TGF-beta1 in inducing the expression of SHARP-2 in LLC-PK1 cells.

We aim to investigate the effect of transforming growth factor (TGF)-beta1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-beta1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-beta1 treatment to probe the signaling pathway.

Efficacy and safety of induction therapy with alemtuzumab in kidney transplantation: a meta-analysis.

Background: Alemtuzumab, a humanized CD52 monoclonal antibody, with its profound lymphocyte depletion property, was expected to be a promising induction therapy agent for kidney transplantation (KTx). However, currently no consensus is available about its efficacy and safety. The aim of this meta-analysis was to make a profound review and an objective appraisal of this issue.

C4d deposition in allograft renal biopsies is an independent risk factor for graft failure.

Aim: Association between C4d deposition and renal allograft survival is still uncertain. We retrospectively evaluated the clinical outcome of C4d deposition in allograft renal biopsies.

Methods: One hundred and fifty biopsies from 150 patients with a histological diagnosis of acute rejection from December 1997 to March 2007 were included.

Construction of bioartificial renal tubule assist device in vitro and its function of transporting sodium and glucose.

To explore a new way of constructing bioartificial renal tubule assist device (RAD) in vitro and its function of transporting sodium (Na(+)) and glucose and to evaluate the application of atomic force microscope in the RAD construction, rat renal tubular epithelial cell line NRK-52E was cultured in vitro, seeded onto the outer surfaces of hollow fibers in a bioreactor, and then cultured for two weeks to construct RAD. Bioreactor hollow fibers without NRK-52E cells were used as control. The morphologies of attached cells were observed with scanning electron microscope, and the junctions of cells and polysulfone membrane were observed with atomic force microscope.

Efficacy and safety of glucocorticoids therapy for IgA nephropathy: a meta-analysis of randomized controlled trials.

Background: Published reports examining the efficacy and safety of glucocorticoids for preserving renal function in immunoglobulin A nephropathy (IgAN) have yielded conflicting results. To systematically evaluate the efficacy and safety of glucocorticoids agents for IgAN, we conducted a meta-analysis of the published randomized controlled trials (RCTs).

Methods: MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for RCTs that compared glucocorticoids with placebo and any other non-immunosuppressive agents for treating IgAN.

A comparison of a standard-dose prednisone regimen and mycophenolate mofetil combined with a lower prednisone dose in Chinese adults with idiopathic nephrotic syndrome who were carriers of hepatitis B surface antigen: a prospective cohort study.

Background: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV.

Objective: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV.

Methods: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV.

Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR.

Background: In a proportion of adults with steroid-resistant nephrotic syndrome (SRNS), intravenous cyclophosphamide therapy fails. Tacrolimus may be a promising alternative to cyclophosphamide for such patients.

Study Design: Prospective observational study.

Angiotensin (1-7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5/6 nephrectomy mice.

The renin-angiotensin system (RAS) plays a critical role in chronic renal failure associated with heart failure. In the past few years, angiotensin (Ang) (1-7) have been reported to counteract the effects of angiotensin II (Ang II) and were even considered as a new therapeutical target in RAS. The purposes of this study were to examine whether the Ang (1-7) improves the heart function and remodeling of the left ventricle (LV) in mice with 5/6 nephrectomy (NC).

The E3 ubiquitin ligase SCFTIR1/AFB and membrane sterols play key roles in auxin regulation of endocytosis, recycling, and plasma membrane accumulation of the auxin efflux transporter PIN2 in Arabidopsis thaliana.

The PIN family of auxin efflux transporters exhibit polar plasma membrane (PM) localization and play a key role in auxin gradient-mediated developmental processes. Auxin inhibits PIN2 endocytosis and promotes its PM localization. However, the underlying mechanisms remain elusive.

Successful prevention of cuffed hemodialysis catheter-related infection using an antibiotic lock technique by strictly catheter-restricted antibiotic lock solution method.

Background: Catheter-related infection (CRI) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions. But the safety of long-term use of antimicrobial lock still needs to be defined.

Methods: Patients with a new inserted permanent tunneled cuffed hemodialysis catheter were randomly assigned to an antibiotic lock solution of gentamicin (4 mg/ml) heparin (G group) or heparin alone (H group).

Urinary fractalkine is a marker of acute rejection.

Chemokines and their receptors play an important role in the development of allograft rejection through directing mononuclear cell invasion of the graft. To study whether chemokine assays in the urine could prove to be predictive of acute rejection, we measured the urinary excretion of several chemokines, including fractalkine, chemokine monokine induced by interferon-gamma, interferon-gamma-inducible protein 10, macrophage inflammatory protein-3 alpha, granzyme B, and perforin in 215 allograft recipients and in 80 healthy control subjects. The 67 patients with acute rejection had significantly higher levels of all urinary chemokines compared to the healthy controls or patients having chronic allograft nephropathy but with stable renal function.

A pilot study of GC/MS-based serum metabolic profiling of acute rejection in renal transplantation.

Aims: Acute allograft rejection is one of the important complications after renal transplantation, and it is a deleterious factor for long-term graft survival. Rejection is a complex pathophysiologic process, which has been explained by transcriptome and proteome in RNA transcripts and proteins level respectively. How are serum metabolite levels in response to acute rejection? Can metabolite levels in serum be used to diagnose and explain acute renal allograft rejection?

Methods: Gas chromatograph-mass spectrometry (GC-MS) was used to analyze serum metabolome in 22 recipients of acute rejection and 15 stable renal transplant recipients.

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population.

Purpose: To determine whether the main mitochondrial DNA (mtDNA) haplogroups of the Han people have an impact on long-term clinical outcome.

Methods: We prospectively studied 181 individuals who were sequentially admitted to the intensive care unit. Demographic and clinical data were recorded along with clinical outcome over 180 days.

Pretreatment with granulocyte colony-stimulating factor attenuated renal ischaemia and reperfusion injury via activation of PI3/Akt signal pathway.

Aim: Granulocyte colony-stimulating factor (G-CSF) has been shown to exert protective effects in various tissues and experimental models of ischaemia-induced injury. However, the mechanism of renoprotective action in ischaemia/reperfusion (I/R) renal injury of G-CSF was unknown.

Methods: Male C57BL/6J mice, subjected to renal ischaemia for 45 min, 48 h and 7 days reperfusion, were administered either saline, wortmannin, G-CSF, and G-CSF plus wortmannin 3 days prior to I/R.

The significance of BOLD MRI in differentiation between renal transplant rejection and acute tubular necrosis.

Background: Blood oxygen level-dependent MRI (BOLD MRI) can be used to assess intra-renal oxygen bioavailability by measuring the R2(*) level, which reflects tissue deoxyhaemoglobin levels. This study was designed to identify the significance of BOLD MRI in differentiation of acute rejection (AR) and acute tubular necrosis (ATN) in patients within 6 months after kidney transplantation.

Methods: Eighty-two patients with normal graft function and 28 patients with biopsy-proven AR (n = 21) or ATN (n = 7) were enrolled.

Control of compound leaf development by FLORICAULA/LEAFY ortholog SINGLE LEAFLET1 in Medicago truncatula.

Molecular genetic studies suggest that FLORICAULA (FLO)/LEAFY (LFY) orthologs function to control compound leaf development in some legume species. However, loss-of-function mutations in the FLO/LFY orthologs result in reduction of leaf complexity to different degrees in Pisum sativum and Lotus japonicus. To further understand the role of FLO/LFY orthologs in compound leaf development in legumes, we studied compound leaf developmental processes and characterized a leaf development mutant, single leaflet1 (sgl1), from the model legume Medicago truncatula.