No abstract

Primary intraocular lymphoma (PIOL) is a type of primary central nervous system lymphoma (PCNSL). It is the most common neoplastic masquerade syndrome involving the eye. Its protean ocular manifestations, plus in many cases the initial positive response to corticosteroid therapy for presumed uveitis, delay accurate diagnosis. A high index of suspicion is essential, followed by tissue biopsy with cytology and ancillary studies. Current treatment is based on chemotherapy featuring high-dose methotrexate and radiation therapy. Prognosis is poor due to CNS involvement, but newer therapies have had some success in prolonging survival.

Background-A panel of experts developed stroke rehabilitation guidelines for the Veterans Health Administration andDepartment of Defense Medical Systems. Methods-Starting from previously established guidelines, the panel evaluated published literature through 2002, using criteria developed by the US Preventive Services Task Force. Recommendations were based on evidence from randomized clinical trials, uncontrolled studies, or consensus expert opinion if definitive data were lacking. Results-Recommendations with Level I evidence include the delivery of poststroke care in a multidisciplinary rehabilitation setting or stroke unit, early patient assessment via the NIH Stroke Scale, early initiation of rehabilitation therapies, swallow screening testing for dysphagia, an active secondary stroke prevention program, and proactive prevention of venous thrombi. Standardized assessment tools should be used to develop a comprehensive treatment plan appropriate to each patient's deficits and needs. Medical therapy for depression or emotional lability is strongly recommended. A speech and language pathologist should evaluate communication and related cognitive disorders and provide treatment when indicated. The patient, caregiver, and family are essential members of the rehabilitation team and should be involved in all phases of the rehabilitation process. These recommendations are available in their entirety at http://stroke.ahajournals.org/cgi/content/full/36/9/e100. Evidence tables for each of the recommendations are also in the full document. Conclusions-These recommendations should be equally applicable to stroke patients receiving rehabilitation in all medical system settings and are not based on clinical problems or resources unique to the Federal Medical System.

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

No abstract

The results indicate that exogenous sCD44 adversely affects RGC-5 and TM cell survival in vitro by activating proapoptotic pathways.

No abstract

Adoptive cell transfer of ex vivo expanded regulatory T cells (Tregs) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such Treg therapies to the clinic has been slow. Because Treg homeostasis is known to require continuous T cell receptor (TCR) ligation and exogenous interleukin-2 (IL-2), some investigators have explored the use of low-dose IL-2 injections to increase endogenous Treg responses. Systemic IL-2 immunotherapy, however, can also lead to the activation of cytotoxic T lymphocytes and natural killer cells, causing adverse therapeutic outcomes. Here, we describe a drug delivery platform, which can be engineered to autostimulate Tregs with IL-2 in response to TCR-dependent activation, and thus activate these cells in sites of antigen encounter. To this end, protein nanogels (NGs) were synthesized with cleavable bis(N-hydroxysuccinimide) cross-linkers and IL-2/Fc fusion (IL-2) proteins to form particles that release IL-2 under reducing conditions, as found at the surface of T cells receiving stimulation through the TCR. Tregs surface-conjugated with IL-2 NGs were found to have preferential, allograft-protective effects relative to unmodified Tregs or Tregs stimulated with systemic IL-2. We demonstrate that murine and human NG–modified Tregs carrying an IL-2 cargo perform better than conventional Tregs in suppressing alloimmunity in murine and humanized mouse allotransplantation models. In all, the technology presented in this study has the potential to improve Treg transfer therapy by enabling the regulated spatiotemporal provision of IL-2 to antigen-primed Tregs.