134 research outputs found

    Resonance transition 795-nm rubidium laser using He buffer gas

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    Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach

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    Despite progress in the treatment of glioblastoma, more than 95% of patients suffering from this disease still die within 2 years. Recent findings support the belief that cancer stem-like cells are responsible for tumor formation and ongoing growth. Here a method combining lectin microarray and LC-MS/MS was used to discover the cell surface glycoprotein markers of a glioblastoma-derived stem-like cell line. Lectin microarray analysis of cell surface glycans showed that two galactose-specific lectins Trichosanthes kirilowii agglutinin (TKA) and Peanut agglutinin (PNA) could distinguish the stem-like glioblastoma neurosphere culture from a traditional adherent glioblastoma cell line. Agarose-bound TKA and PNA were used to capture the glycoproteins from the two cell cultures, which were analyzed by LC-MS/MS. The glycoproteins were quantified by spectral counting, resulting in the identification of 12 and 11 potential glycoprotein markers from the TKA and PNA captured fractions respectively. Almost all of these proteins were membrane proteins. Differential expression was verified by Western blotting analysis of 6 interesting proteins, including the up-regulated Receptor-type tyrosine-protein phosphatase zeta, Tenascin-C, Chondroitin sulfate proteoglycan NG2, Podocalyxin-like protein 1 and CD90, and the down-regulated CD44. An improved understanding of these proteins may be important for earlier diagnosis and better therapeutic targeting of glioblastoma

    Frequency of symptoms, determinants of severe symptoms, validity of and cut-off score for Menopause Rating Scale (MRS) as a screening tool: A cross-sectional survey among midlife Nepalese women

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    <p>Abstract</p> <p>Background</p> <p>Majority of Nepalese women live in remote rural areas, where health services are not easily accessible. We determined the validity of Menopause Rating Scale (MRS) as a screening tool for identification of women with severe menopausal symptoms and cut-off MRS score for referral.</p> <p>Methods</p> <p>A cross-sectional survey was carried out between February and August, 2008. Trained health workers administered MRS and a questionnaire to 729 women (40 to 65 years) attending health screening camps in Kaski district of Western Development Region of Nepal. Information about demographics, menopausal status, and use of hormone replacement therapy (HRT), chronic disease, self-perceived general health and reproductive history was also collected. Menopausal status was classified according to the Staging of Reproductive Ageing Workshop (STRAW). We calculated rates of menopausal symptoms, sensitivity, and specificity and likelihood ratios of MRS scores for referral to a gynaecologist. We also carried out multivariate analyses to identify the predictors for referral to a gynaecologist for severe symptoms.</p> <p>Results</p> <p>A total 729 women were interviewed. Mean age at menopause was 49.9 years (SD 5.6). Most frequently reported symptoms were, sleeping problems (574, 78.7%), physical and mental exhaustion (73.5%), hot flushes (508, 69.7%), joint and muscular discomfort (500, 68.6%) and dryness of vagina (449, 61.6%). Postmenopausal women (247, 33.9%) and perimenopausal (215, 29.5%) women together experienced significantly higher prevalence of all symptoms than the premenopausal (267, 36.6%) women. MRS score of β‰₯16 had highest ratio for (sensitivity + specificity)/2. Women who reported urogenital symptoms [OR 5.29, 95% CI 2.59, 10.78], and self perceived general health as poor [OR 1.29, 95% CI 1.11, 1.53] were more likely to be referred to a gynaecologist for severe menopausal symptoms. While women reporting somatic [OR 0.72, 95% CI 0.63, 0.82] and psychological [OR 0.86, 95% CI 0.74, 0.99] symptoms were less likely to be referred.</p> <p>Conclusion</p> <p>MRS may be used as a screening tool at a cut-off score of β‰₯16 with least misclassification rate. However, its utility may be limited by woman's general health status and occurrence of urogenital symptoms.</p

    Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

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    The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individualsβ€”but not allβ€”develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease
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