A Randomized Trial and the Treatment of Pemphigus Vulgaris

Pemphigus vulgaris is a rare, life-threatening autoimmune disease. Mycophenolate mofetil is a potent immunosuppressant medication approved by the Food and Drug Administration to be used after solid organ transplantation and to treat pemphigus vulgaris. Mycophenolate mofetil has not become the “wonder drug” that had been anticipated based on initial clinical reports. Studies like that reported by Beissert et al. in this issue are essential to improve dermatologic care

A note on compactly generated co-t-structures

The idea of a co-t-structure is almost "dual" to that of a t-structure, but with some important differences. This note establishes co-t-structure analogues of Beligiannis and Reiten's corresponding results on compactly generated t-structures.Comment: 10 pages; details added to proofs, small correction in the main resul

Cellular Origin of Spontaneous Ganglion Cell Spike Activity in Animal Models of Retinitis Pigmentosa

Here we review evidence that loss of photoreceptors due to degenerative retinal disease causes an increase in the rate of spontaneous ganglion spike discharge. Information about persistent spike activity is important since it is expected to add noise to the communication between the eye and the brain and thus impact the design and effective use of retinal prosthetics for restoring visual function in patients blinded by disease. Patch-clamp recordings from identified types of ON and OFF retinal ganglion cells in the adult (36–210 d old) rd1 mouse show that the ongoing oscillatory spike activity in both cell types is driven by strong rhythmic synaptic input from presynaptic neurons that is blocked by CNQX. The recurrent synaptic activity may arise in a negative feedback loop between a bipolar cell and an amacrine cell that exhibits resonant behavior and oscillations in membrane potential when the normal balance between excitation and inhibition is disrupted by the absence of photoreceptor input

Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression

Latency reversal and viral clearance to cure HIV-1

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society

Countering HIV - Three's the charm?

Antibodies have grown in importance as medicines over the more than 40 years since Köhler and Milstein first produced monoclonal constructs. 1 However, the ability of human immunodeficiency virus (HIV) type 1 (HIV-1) to evade the humoral immune response has until recently thwarted the effective use of antibodies in this important disease. The extraordinary plasticity of the HIV envelope allows exceptional antigenic diversity, leading to the rapid escape of the virus from most antibody responses

Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease.

BACKGROUND: Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use. METHODS: A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders. RESULTS: CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36-0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09-0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39-0.56)]. CONCLUSIONS: Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals

Combined approaches for HIV cure

A serious effort has begun to develop therapies that may be capable of eradicating established HIV infection in man. Because of the biological complexity of HIV infection that persists despite potent antiretroviral therapy, it is widely believed that if such therapies can be developed they will involve complex, multimodality approaches. We highlight some of the recent studies in this effort

Psoriasis Is Common, Carries a Substantial Burden Even When Not Extensive, and Is Associated with Widespread Treatment Dissatisfaction

The impact of psoriasis on quality of life has been studied in select patient populations. Population-based data detailing the distribution of extent of disease, associated problems in everyday life, and treatment satisfaction for the US population have been lacking. Our population-based survey indicates that approximately 4.5 million adults have been diagnosed as having psoriasis. Most (59%) have little or no involvement, but 650,000 adults have at least three palms of body surface involved and more than 1,000,000 indicate substantial dissatisfaction with their treatment. Only 5% of patients (56,000) who report severe dissatisfaction with current therapy have extensive disease (10 palms). Many individuals with little psoriasis at the time of interview considered the disease to be a large problem in everyday life

Nuclear Receptor Signaling Atlas (): hyperlinking the nuclear receptor signaling community

The nuclear receptor signaling (NRS) field has generated a substantial body of information on nuclear receptors, their ligands and coregulators, with the ultimate goal of constructing coherent models of the biological and clinical significance of these molecules. As a component of the Nuclear Receptor Signaling Atlas (NURSA)—the development of a functional atlas of nuclear receptor biology—the NURSA Bioinformatics Resource is developing a strategy to organize and integrate legacy and future information on these molecules in a single web-based resource (). This entails parallel efforts of (i) developing an appropriate software framework for handling datasets from NURSA laboratories and (ii) designing strategies for the curation and presentation of public data relevant to NRS. To illustrate our approach, we have described here in detail the development of a web-based interface for the NURSA quantitative PCR nuclear receptor expression dataset, incorporating bioinformatics analysis which provides novel perspectives on functional relationships between these molecules. We anticipate that the free and open access of the community to a platform for data mining and hypothesis generation strategies will be a significant contribution to the progress of research in this field