Retinitis pigmentosa (RP), a common group of human retinopathic diseases, is characterized by late-onset night blindness, loss of peripheral vision, and diminished or absent electroretinogram (ERG) responses. Mutations in the photoreceptor-specific gene RP1 account for 5-10% of cases of autosomal dominant RP. We generated a mouse model of the RP1 form of RP by targeted disruption of the mouse ortholog (Rp1) of human RP1. In Rp1 ؊͞؊ mice, the number of rod photoreceptors decreased progressively over a period of 1 year, whereas that of cone photoreceptors did not change for at least 10 months. Light and electron microscopic analysis revealed that outer segments of Rp1 ؊͞؊ rods and cones were morphologically abnormal and became progressively shorter in length. Before photoreceptor cell death, rhodopsin was mislocalized in inner segments and cell bodies of Rp1 ؊͞؊ rods. Rod ERG amplitudes of Rp1 ؊͞؊ mice were significantly smaller than those of Rp1 ؉͞؉ mice over a period of 12 months, whereas those of Rp1 ؉͞؊ mice were intermediate. The decreases in cone ERG amplitudes were slower and less severe than those in rods. These findings demonstrate that Rp1 is required for normal morphogenesis of photoreceptor outer segments and also may play a role in rhodopsin transport to the outer segments. The phenotype of Rp1 mutant mice resembles the human RP1 disease. Thus, these mice provide a useful model for studies of RP1 function, disease pathology, and therapeutic interventions. R etinitis pigmentosa (RP) is a common inherited retinopathy that affects Ϸ1 in 3,500 persons worldwide (1). Clinical findings in RP include progressive loss of night and peripheral vision that usually culminates in severe visual impairment or blindness. The disease is characterized by an abnormal or absent response on electroretinography (ERG) and is associated with retinal atrophy, deposition of pigment, and attenuation of retinal vessels. RP is heterogeneous clinically and genetically (2).We identified a gene, designated RP1, that is mutated in families with the RP1 form of autosomal dominant RP (3-8).The patients who are heterozygous for the RP1 mutations have very similar classic type 2 autosomal dominant RP phenotypes with relatively late onset of night blindness (usually by the third decade of life). However, within the same family, there is extensive variation in the age at which clinical disease is detected (7, 9). Moreover, in some families such as the UCLA-RP01, two members who are homozygous for an RP1 mutation have substantially more severe retinal degeneration than other family members who are heterozygous for the mutation (9). The human RP1 gene encodes a protein of 2,156 aa, the function of which is currently unknown. However, its N terminus shares significant homology with that of human doublecortin (DCX), a mutant form of which is involved in cerebral cortical abnormalities (10,11). This region of DCX is known to interact with microtubules (12, 13).To understand the function of the RP1 protein in the retina and the mechanism of reti...

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Indices of overall dietary patterns are used in epidemiologic research to examine the relationship between nutrition and health. The objective of this study was to develop and validate an interpretable summary measure of dietary intake of whole plant foods (WPF-whole grains, vegetables, whole fruit, legumes, nuts, seeds) due to their similar nutritional characteristics and health effects. Six candidate WPF measures were calculated using data from subjects (age≥6y) participating in the 1999–2000 and 2001–2002 National Health and Nutrition Examination Survey (NHANES). Measures differed by the inclusion or exclusion of potatoes and whether they were expressed as total intake or as a proportion of energy (1000 kcal) or mass (kg) consumed. Both standard and non-truncated (allowed to vary proportionally with intake) Health Eating Index-2005 (HEI-2005) scores were calculated. Regression analysis examined associations between WPF and HEI-2005 measures, and between all diet measures and serum carotenoid concentration, serum lipids, fasting glucose, insulin, c-peptide and c-reactive protein. Mean total WPF intake was 3.6 cup/oz equivalents, or 1.7 cup/oz equivalents per 1000 kcal and per kg. The largest R2 between WPF and HEI-2005 measures was found for energy-adjusted WPF including potatoes and non-truncated HEI-2005 (R2 =0.50). All diet measures were positively related to serum carotenoids (p<0.001) and were similarly related with health indicators (R2 range from 0.003–0.16, p<0.045 for regressions indicating significant associations between WPF measures and health indicators). WPF measures are interpretable indicators of dietary intake that are significantly related to nutrition and health biomarkers, and may be of public health utility.

We hypothesized an association between renal calculi and bone mineral density (BMD) deficits, shown in adults, exists in survivors of childhood acute lymphoblastic leukemia (ALL). Thus, we analyzed the associations between quantitative computed tomography (QCT)-determined renal calcifications and clinical parameters (gender, race, age at diagnosis and age at the time of QCT), BMD, treatment exposures and Tanner stage. We investigated the associations between stone formation and nutritional intake, serum and urinary calcium and creatinine levels, and urinary calcium/creatinine ratio. Exact v 2 -test was used to compare categorical patient characteristics, and the Wilcoxon-Mann-Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%) were males; 371 (87.5%) were nonblack. Most (n ¼ 270; 63.7%) were X3.5 years at ALL diagnosis. Mean (s.d.) and median (range) BMD Z-scores of the entire cohort were À0.4 (1.2) and À0.5 (À3.9 to 5.1), respectively. Nineteen participants (10 males; 10 Caucasians) had kidney stones (observed prevalence of 4.5%; 19/424) with a significant negative association between stone formation and body habitus (body mass index, P ¼ 0.003). Stone formation was associated with treatment protocol (P ¼ 0.009) and treatment group (0.007). Thus, kidney stones in childhood ALL survivors could herald the future deterioration of renal function and development of hypertension. Long-term follow-up imaging may be warranted in these patients to monitor for progressive morbidity.