Doxycycline alters metabolism and proliferation of human cell lines.

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism

Loss of Foveal Cone Structure Precedes Loss of Visual Acuity in Patients With Rod-Cone Degeneration.

PurposeTo assess the relationship between cone spacing and visual acuity in eyes with rod-cone degeneration (RCD) followed longitudinally.MethodsHigh-resolution images of the retina were obtained using adaptive optics scanning laser ophthalmoscopy from 13 eyes of nine RCD patients and 13 eyes of eight healthy subjects at two sessions separated by 10 or more months (mean 765 days, range 311-1935 days). Cone spacing Z-score measured as close as possible (average <0.25°) to the preferred retinal locus was compared with visual acuity (letters read on the Early Treatment of Diabetic Retinopathy Study [ETDRS] chart and logMAR) and foveal sensitivity.ResultsCone spacing was significantly correlated with ETDRS letters read (ρ = -0.47, 95%CI -0.67 to -0.24), logMAR (ρ = 0.46, 95%CI 0.24 to 0.66), and foveal sensitivity (ρ = -0.30, 95%CI -0.52 to -0.018). There was a small but significant increase in mean cone spacing Z-score during follow-up of +0.97 (95%CI 0.57 to 1.4) in RCD patients, but not in healthy eyes, and there was no significant change in any measure of visual acuity.ConclusionsCone spacing was correlated with visual acuity and foveal sensitivity. In RCD patients, cone spacing increased during follow-up, while visual acuity did not change significantly. Cone spacing Z-score may be a more sensitive measure of cone loss at the fovea than visual acuity in patients with RCD

Dysflective Cones in Healthy and Retinal Disease Eyes

Robust, sensitive measures of foveal health and cone loss, particularly ones that rely on structural measures rather than subjective and time consuming psychophysical measures, could facilitate measurement of disease progression. The research described in this document uses multimodal high-resolution imaging techniques to study the relationship between structure of cone photoreceptors and visual function in both healthy and diseased eyes. Visualizing cone structure in living eyes offers a way to detect and monitor retinal disease and assess the health of cone photoreceptors. It is generally the case that regions that lack normal reflections from the photoreceptors correspond to regions that lack functional cones. However, areas of hyporeflective cones (cones that reflect significantly less than normal) even over large areas have been reported to have function, and these are defined as dysflective cones. The research described in this document focuses on determining the presence of these dysflective cones in healthy subjects, the timeline of dysflective cone reflectivity changes, and the sensitivity differences between healthy appearing cones and dysflective cones. Healthy dysflective cones were found to have similar function to surrounding areas, while dysflective areas in participants with retinal disease were found to have worse function, elevated thresholds, compared to surrounding areas

The 2007 Selfhelp Home Interviews 2007

A collection of 30 video interviews (including transcripts) with residents of the Selfhelp Home of Chicago, filmed in 2007.Interview with Rina AvniInterview with Rachel BensingerInterview with Ellen BerlandInterview with Elsbeth DreyfusInterview with Hella GersonInterview with Hentry HartmannInterview with Ida HasselsonInterview with Klaus HellmannInterview with Fred HerzogInterview with Irmgard HeymannInterview with Abraham HorstInterview with Frank MayerInterview with Marion MayerInterview with Liselotte MelberInterview with Hannah MessingerInterview with Bernard NahmInterview with Helen NovikInterview with Dorothy PlautInterview with Irene PollInterview with Thea ReisInterview with Marietta RybaInterview with Edith SteinInterview with Hal StraussInterview with Paula TritschInterview with Anna UhlmannInterview with Marianne WallenbergInterview with Marianne WeinbergInterview with Max WeinblumInterview withFanny WolfInterview with Lilo WolfAn “archive of memories” established in order to preserve the testimony of 30 individuals who had been the victims of Nazi persecution and were spending their ‘golden years’ at the Selfhelp Home in Chicago.Each of these residents grew up in a European environment, which encouraged strong family ties and values, hard work, education, and in many cases participation in Jewish traditions. They reached adulthood by the mid 1930s and had to experience the horrors of concentration camps; ghettos; hiding; or survival as refugees.They clearly describe their experiences in Europe, their lives in third countries (e.g. China; Palestine/Israel) where they have found refuge, and their rehabilitation in the United States.digitize

Patches of Dysflective Cones in Eyes With No Known Disease

PurposeTo characterize the structure and function of patches of dysflective cones in the foveal region of subjects with normal vision and no known pathology. Dysflective cones are cones that have little or no reflective properties in optical coherence tomography (OCT) or adaptive optics scanning laser ophthalmoscope (AOSLO) images yet exhibit measurable function.MethodsAOSLO images were surveyed for the presence of hyporeflective cone patches, and subjects were brought back for imaging to determine the changes in the hyporeflective region. Adaptive optics microperimetry (AOMP) was used to assess the function of hyporeflective patches in four subjects to determine that they did, in fact, contain dysflective cones. AOMP utilized a stimulus size of less than 1 arcmin to measure thresholds inside and outside the hyporeflective region.ResultsNineteen out of 47 individuals retrospectively reviewed had one or more regions with hyporeflective cone patches in one or both eyes. Ten subjects with hyporeflective cone patches were brought back for imaging. Seven of the 10 had resolved at follow up, and in three subjects new hyporeflective patches appeared in a different location. All AOMP-measured subjects had measurable function in the dysflective cone region. Three out of four subjects showed no difference in light sensitivity in the dysflective region compared to adjacent areas, and one subject showed a 3× reduction in sensitivity in the area.ConclusionsPatches of dysflective cone have been identified in subjects with normal vision and no known pathology, and we have observed instances where dysflective cones in these subjects regain normal reflective properties

Methods to Assess Ocular Motor Dysfunction in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system causing the immune-mediated demyelination of the brain, optic nerve, and spinal cord and resulting in ultimate axonal loss and permanent neurological disability. Ocular motor dysfunction is commonly observed in MS but can be frequently overlooked or underappreciated by nonspecialists. Therefore, detailed and quantitative assessment of eye movement function has significant potential for optimization of patient care, especially for clinicians interested in treating visual symptoms or tracking disease progression. METHODS:: A brief history of eye tracking technology followed by a contextualized review of the methods that can be used to assess ocular motor dysfunction in MS-including a discussion of each method's strengths and limitations. We discuss the rationale for interest in this area and describe new tools capable of tracking eye movements as a possible means of monitoring disease. RESULTS/CONCLUSIONS:: This overview should inform clinicians working with patients with MS of how ocular motor deficits can best be assessed and monitored in this population. It also provides a rationale for interest in this field with insights regarding which techniques should be used for studying which classes of eye movements and related dysfunction in the disease

Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa.

Purpose:To study cone structure and function in patients with retinitis pigmentosa (RP) owing to mutations in rhodopsin (RHO), expressed in rod outer segments, and mutations in the RP-GTPase regulator (RPGR) gene, expressed in the connecting cilium of rods and cones. Methods:Four eyes of 4 patients with RHO mutations, 5 eyes of 5 patients with RPGR mutations, and 4 eyes of 4 normal subjects were studied. Cone structure was studied with confocal and split-detector adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography. Retinal function was measured using a 543-nm AOSLO-mediated adaptive optics microperimetry (AOMP) stimulus. The ratio of sensitivity to cone density was compared between groups using the Wilcoxon rank-sum test. Results:AOMP sensitivity/cone density in patients with RPGR mutations was significantly lower than normal (P < 0.001) and lower than patients with RHO mutations (P < 0.015), whereas patients with RHO mutations were similar to normal (P > 0.9). Conclusions:Retinal sensitivity/cone density was lower in patients with RPGR mutations than normal and lower than patients with RHO mutations, perhaps because cones express RPGR and degenerate primarily, whereas cones in eyes with RHO mutations die secondary to rod degeneration. High-resolution microperimetry can reveal differences in cone degeneration in patients with different forms of RP

Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa.

Purpose:To study cone structure and function in patients with retinitis pigmentosa (RP) owing to mutations in rhodopsin (RHO), expressed in rod outer segments, and mutations in the RP-GTPase regulator (RPGR) gene, expressed in the connecting cilium of rods and cones. Methods:Four eyes of 4 patients with RHO mutations, 5 eyes of 5 patients with RPGR mutations, and 4 eyes of 4 normal subjects were studied. Cone structure was studied with confocal and split-detector adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography. Retinal function was measured using a 543-nm AOSLO-mediated adaptive optics microperimetry (AOMP) stimulus. The ratio of sensitivity to cone density was compared between groups using the Wilcoxon rank-sum test. Results:AOMP sensitivity/cone density in patients with RPGR mutations was significantly lower than normal (P < 0.001) and lower than patients with RHO mutations (P < 0.015), whereas patients with RHO mutations were similar to normal (P > 0.9). Conclusions:Retinal sensitivity/cone density was lower in patients with RPGR mutations than normal and lower than patients with RHO mutations, perhaps because cones express RPGR and degenerate primarily, whereas cones in eyes with RHO mutations die secondary to rod degeneration. High-resolution microperimetry can reveal differences in cone degeneration in patients with different forms of RP