Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

From IP to Start-up： Building a Robust Life Science Incubator

An incubator is an organization that supports new ventures to grow and survive during the early stages. Mainly dedicated to information technology, life science may appear to be the next hot spot for incubators. Are there stabilized good practices？ Are the business models in information technology and in life science comparable when it goes to start-ups＇ incubation？ Leveraging our experience as practitioner in this field and using an inductive methodology, this paper tends to propose simple principles to help build robust incubators in life science, and to contribute to disseminate an entrepreneurial approach through an industry still dominated by blue chips.     

Use of pentastarch solution in the treatment of patients with hemorrhagic hypovolemia: randomized phase II study in the emergency room

The weeping fig, Ficus benjamina (Fb), is a relatively common indoor allergen. Many cases of perennial allergic rhinoconjunctivitis and allergic asthma caused by Fb hypersensitivity are not detected. These patients typically have proven sensitization to housedust mites and do not improve after avoidance of exposure (encasing) and specific immunotherapy. The number of Fb sensitizations is increasing in Germany, which can partly be explained by the cross-reactivity between Hevea brasiliensis (Hb) latex and Fb and the rapidly increasing number of mostly occupational latex allergies. But Fb itself is a potential sensitizer which is widely spread as ornamental plant in homes and offices. As relevant indoor allergen Fb ranks third after housedust mites and pets but before molds among our allergy patients. For diagnosis, prick-tests with Fb-latex seem to be more sensitive than in vitro-methods (RAST, CAPRAST). Fb plants should not be kept in the homes of atopic individuals or persons with latex (Hb) allergy.     

Solving the advection–diffusion equation on unstructured meshes with discontinuous/mixed finite elements and a local time stepping procedure

Explicit schemes are known to provide less numerical diffusion in solving the advection–diffusion equation, especially for advection‐dominated problems. Traditional explicit schemes use fixed time steps restricted by the global CFL condition in order to guarantee stability. This is known to slow down the computation especially for heterogeneous domains and/or unstructured meshes. To avoid this problem, local time stepping procedures where the time step is allowed to vary spatially in order to satisfy a local CFL condition have been developed. In this paper, a local time stepping approach is used with a numerical model based on discontinuous Galerkin/mixed finite element methods to solve the advection–diffusion equation. The developments are detailed for general unstructured triangular meshes. Numerical experiments are performed to show the efficiency of the numerical model for the simulation of (i) the transport of a solute on highly unstructured meshes and (ii) density‐driven flow, where the velocity field changes at each time step. The model gives stable results with significant reduction of the computational cost especially for the non‐linear problem. Moreover, numerical diffusion is also reduced for highly advective problems. Copyright © 2009 John Wiley & Sons, Ltd.     

Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells

Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM ( 1 ), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC₅₀ values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen). 1 was previously found highly efficacious in MDA-MB-231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M-CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1 . We also demonstrate a p53 independent mechanism of action.     

An exponential SRGM with a bound on the number of failures

An exponential software reliability growth model (SRGM) incorporating a situation where more than one failure can be attributed to one fault/error has been proposed. Different model parameters have been estimated and an optimal release policy which minimizes the software cost, subject to achieving a given level of reliability, has been discussed. Finally, a numerical example illustrating the applicability of the model and a few practical situations where this model can be applied are also given.