Interaction of antibodies with human glomerular epithelial cells

We tested the hypothesis that the pathogenesis of human idiopathic membranous glomerulonephritis is similar to that of Heymann glomerulonephritis, a model of membranous glomerulonephritis induced in rats by immunization with renal brush border preparations; the characteristic subepithelial deposits result from interaction of antibodies with a brush border antigen (gp330) expressed on the plasma membrane of glomerular visceral epithelial cells (GEC), followed by redistribution and shedding of gp330 immune complexes. The experiments were performed in cultured glomerular visceral epithelial cells, in living monkeys and rats, and in isolated perfused human, monkey, and rat kidneys. Antigens from plasma membranes of human renal brush border vesicles (HBBV) and GEC vesicles (HGECV) and their corresponding polyclonal and monoclonal antibodies reactive with human and monkey GEC were prepared. First, polyclonal antibodies to HGECV bound diffusely to cultured GEC; monoclonal antibody 8G5, recognizing a 60-kDa protein, mainly bound to the coated pits and apical invaginations; both polyclonal HGECV and 8G5 monoclonal antibodies induced antigen redistribution (capping) at 37 degrees C. Second, monkeys were actively or passively immunized, and isolated human and monkey kidneys were perfused with the antibodies. Active immunization with HBBV induced tubular immune deposits, whereas active immunization with HGECV did not provoke renal lesions. After passive immunization HBBV and HGECV antibodies bound diffusely to glomerular cells, and subepithelial deposits were observed during the autologous phase; in contrast, 8G5 induced early (day 3) granular deposits. Third, fine granular deposits developed in glomeruli of human and monkey kidneys perfused for 4 hours at 37 degrees C with 8G5; these deposits were more difficult to detect by electron microscopy than those occurring in kidneys of Lewis rats perfused with sheep antiHBBV. The results show that some antibodies redistribute antigens at the surface of human and monkey GEC in vitro, in vivo, and ex vivo and induce formation of granular deposits in human glomerular capillary walls. Failure to induce more severe lesions in human and monkey kidneys may be ascribed to lack of GEC antigens comparable to rat gp330, insufficient cross linking by monoclonal antibody, lack or insufficient concentration of epitope-specific antibodies, insufficient time of kidney perfusion, or a combination of these factors.     

Laparoscopic assisted distal gastrectomy for early gastric cancer: Is it an alternative to the open approach?

ObjectiveThis study aims to compare short term outcomes and oncological value of laparoscopy assisted (LADG) and open distal gastrectomy (ODG) in the treatment of early gastric cancer.MethodsMeta-analysis of 12 studies, including three randomized controlled trials, published between 2000 and 2007, comparing laparoscopy assisted and open distal gastrectomy in 951 patients with early gastric cancer, was done. Outcomes of interest were operative data, lymph node clearance, postoperative recovery complications.ResultsOverall morbidity rate was significantly less with LADG (10.5% versus 20.1%, P = 0.003, OR 0.52, CI 0.34–0.8). A mean of 4.61 less number of lymph nodes dissected than ODG (CI ?5.96, ?3.26 P < 0.001) when all studies are included. There was no difference between the two groups in number of lymph nodes dissected when less than D2 lymphadenectomy was done (2.44 nodes less in LADG group, CI ?5.52, 0.63; P = 0.12). LADG patients had less operative blood loss (mean of 151 ml, P < 0.001), less time to walking, oral intake and flatus. LADG patients had less length of hospital stay (5.7 days, P < 0.001), postoperative fever and pain. ODG group showed significantly less operative time. There was no significant difference between the two groups in the incidence of anastomotic complications and wound infection.ConclusionLADG is a safe technical alternative to ODG for early gastric cancer with a lower overall complication rate and enhanced postoperative recovery. Endorsing LADG as a better alternative to ODG requires data on long term survival, quality of life and cost effectiveness.     

Central serous chorioretinopathy: a review of epidemiology and pathophysiology

Central serous chorioretinopathy (CSCR) is a common retinal cause of vision loss. This review surveys the epidemiology, risk factors, clinical presentation, natural history and pathophysiology of CSCR. Studies suggest an annual incidence rate of 10 per 100 000 in men, with CSCR occurring six times more commonly in men compared with women. Most acute CSCR cases resolve spontaneously within 2–3 months. Prognosis is highly dependent on presenting visual acuity; patients with initial visual acuities of 6/6 remain at that level, while patients with initial visual acuities of less than 6/9 recover on average two to three Snellen lines over the next few years. The main risk factors for CSCR are systemic corticosteroid use, type A personality, pregnancy and endogenous Cushing's syndrome. The pathophysiology of CSCR remains obscure, although disorders in both the choroidal circulation and retinal pigment epithelium are implicated.     

转移抑制与metastamiR调节的联系

BRMS1:乳腺癌转移抑制因子1;HDAC:组蛋白去乙酰化酶;EGFR:表皮生长因子受体;miRNA:小分子RNA;miR:小分子RNA;pri-miRNA:初始小分子RNA;pre-miRNA:小分子RNA前体     

Evaluation of a modified circular stapler for use as a viscerotomy formation and closure device in natural orifice surgery

Background  

The most challenging of the many hurdles surgeons must overcome to perform natural orifice translumenal endoscopic surgery (NOTES) safely is viscerotomy closure. The perfect device must be easy to deploy, suitable for use on any viscera, and able to create a rapid, reliable, and durable closure. The authors developed a novel device based on an existing circular stapler platform to create and then subsequently close a viscerotomy. The device was tested initially on an ex vivo porcine stomach model, then used on a survival canine model to confirm adequacy of gastric closure and rapidity of deployment.     

Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2-year follow-up

The objective was to evaluate the functional performance over a 2-year period following autologous chondrocyte implantation (ACI) in an open knee procedure compared to microfracture. Objective functional outcome was studied as secondary analysis in a subgroup of patients, in a randomized clinical trial, with concealed allocation and independent evaluators. Sixty-seven patients with local cartilage defect, with a mean size of 2.4 cm2 (SD 1.5) of the femoral condyle of the knee were included. Thirty-three patients underwent the microfracture and 34 the ACI procedure. An identical rehabilitation protocol was implemented for both groups. Active knee flexion and extension range, anterior laxity, knee extension strength (concentric at 60°/s) and single leg hop performance (single hop, crossover triple hop and 6 m timed hop test) were evaluated pre-surgery and at 6, 9,12 and 24 months post-surgery. We calculated the symmetry index for individual and four performance tests pooled. Mixed linear model analyses were used with confidence interval set at 95%. The change over 2 years for the pooled performance-based tests was comparable between the two treatment arms. At 2 years, 70% (38/54) of all patients returned to >85% symmetry in overall functional performance. A decrease in functional performance at 6 months following ACI resulted in slower recovery at 9 and 12 months compared to microfracture. Rehabilitation following both cartilage repair procedures is a lengthy process. At 2 years after surgery, ACI patients have similar overall functional outcome compared to microfracture patients.