Novel mutations in the anoctamin 5 gene ( ANO5 ) associated with limb‐girdle muscular dystrophy 2L

Introduction: We present a Jordanian man with the typical LGMD 2L phenotype of early, asymmetric quadriceps weakness and subsequent biceps brachii weakness. Methods: Case report. Results: Muscle biopsies document a progressive dystrophic pattern unrelated to known sarcolemmal defects associated with muscular dystrophy. Genetic testing revealed novel, heterozygote Anoctamin 5 gene mutations. Conclusions: This case report expands the known mutations resulting in LGMD 2L and supports the assertion that Anoctamin 5 mutations are more prevalent than previously recognized. Muscle Nerve, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96310/1/23542_ftp.pd

Selective localization of γ-enolase in stromal cells of cerebellar hemangioblastomas

Three cases of cerebellar hemangioblastoma were studied using the immunoperoxidase technique to localize γ-enolase, also known as neuron-specific enolase. The stromal cells demonstrated positive staining for γ-enolase, while endothelial cells and pericytes showed no reactivity. Two vascular lesions, an angiosarcoma and a cutaneous angioma, were studied and found to be nonreactive for γ-enolase. All tumors were also tested for factor VIII/von Willebrand factor, glial fibrillary acidic protein, and the S-100 protein. The lack of expression of γ-enolase in endothelial cells of hemangioblastomas demonstrates a clear antigenic distinction from neighboring γ-enolase-positive stromal cells. The significance of this finding and its implications for stromal cell histogenesis are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47228/1/401_2004_Article_BF00691102.pd

Myelopathy following intrathecal chemotherapy in a patient with extensive burkitt's lymphoma and altered immune status

A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired Immune deficiency syndrome. Following chemotherapy that included Intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur In myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25727/1/0000284.pd

Raman spectroscopy of a single ion coupled to a high-finesse cavity

We describe an ion-based cavity-QED system in which the internal dynamics of an atom is coupled to the modes of an optical cavity by vacuum-stimulated Raman transitions. We observe Raman spectra for different excitation polarizations and find quantitative agreement with theoretical simulations. Residual motion of the ion introduces motional sidebands in the Raman spectrum and leads to ion delocalization. The system offers prospects for cavity-assisted resolved-sideband ground-state cooling and coherent manipulation of ions and photons.Comment: 8 pages, 6 figure

Products of cultured neuroglial cells: II. The production of fibronectin by C6 glioma cells

The possibility of fibronectin production by C6 glioma cells was examined with assays which require protein synthesis. Proteins produced by C6 cells using radiolabeled amino acid precursors were tested for affinity to collagen by binding to immobilized gelatin. The predominant collagen binding protein made by C6 coelectrophoresed with fibronectin synthesized by control fibroblasts and with the larger of the two proteins in unlabeled fibronectin when applied to polyacrylamide gels with sodium dodecyl sulfate (SDS). In addition, C6 produced a larger collagen binding protein of approximately 270,000 molecular weight. Solubilities in urea solutions of the collagen-binding proteins made by C6 cells and fibroblasts were similar. Immunofluorescence showed fibronectin associated with the C6 cell monolayer, but less abundant than the fibronectin associated with fibroblasts. Results provide evidence for the production of fibronectin by the C6 glioma cell line.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45400/1/11064_2004_Article_BF00964399.pd

Primary cerebellar glioblastoma multiforme

Glioblastoma multiforme in adults arising in the cerebellum is a rare tumor, well documented in only 13 cases in the literature. We report a fourteenth case, an 80-year-old female, and reassess the clinical and CT aspects of this tumor based on a review of the world's literature. The median age of patients is 53 years with a median survival of three months, which is less than adult cerebral hemisphere malignant gliomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45390/1/11060_2004_Article_BF00151226.pd

Need for recovery amongst emergency physicians in the UK and Ireland: A cross-sectional survey

OBJECTIVES: To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores. DESIGN: Cross-sectional electronic survey. SETTING: Emergency departments (EDs) (n=112) in the UK and Ireland. PARTICIPANTS: Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019. MAIN OUTCOME MEASURE: NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery. RESULTS: The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5-90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%-50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%-75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%-100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9). CONCLUSION: Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible

A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.

The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis

A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers

The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium