Avoiding Negative Dysphagia Outcomes Tanner, Dennis; Culbertson, William
Online journal of issues in nursing,
05/2014, Letnik:
19, Številka:
2
Journal Article
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Dysphagia in adults affects their quality of life and can lead to life-threatening conditions. The authors draw on both 30 years of experience as clinicians and also on expert testimony in adult, ...dysphagia-malpractice cases to make five recommendations with the aim of preventing dysphagia-related deaths. They discuss the importance of informed consent documents and suggest the following nursing actions to reduce these often unnecessary tragedies: consider the importance of diet status; understand and follow speech-language-pathologists’ recommendations; be familiar with the dysphagia assessment; be responsive to the need for an instrumental assessment; and ensure dysphagia communication is accurate and disseminated among healthcare professionals. They conclude that most negative dysphagia-management outcomes can be prevented and that nurses play a pivotal role in this prevention.
Upf3p, which is required for nonsense-mediated mRNA decay (NMD) in yeast, is primarily cytoplasmic but accumulates inside the nucleus when UPF3 is overexpressed or when upf3 mutations prevent nuclear ...export. Upf3p physically interacts with Srp1p (importin-alpha). Upf3p fails to be imported into the nucleus in a temperature-sensitive srp1-31 strain, indicating that nuclear import is mediated by the importin-alpha/beta heterodimer. Nuclear export of Upf3p is mediated by a leucine-rich nuclear export sequence (NES-A), but export is not dependent on the Crm1p exportin. Mutations identified in NES-A prevent nuclear export and confer an Nmd(-) phenotype. The addition of a functional NES element to an export-defective upf(-) allele restores export and partially restores an Nmd(+) phenotype. Our findings support a model in which the movement of Upf3p between the nucleus and the cytoplasm is required for a fully functional NMD pathway. We also found that overexpression of Upf2p suppresses the Nmd(-) phenotype in mutant strains carrying nes-A alleles but has no effect on the localization of Upf3p. To explain these results, we suggest that the mutations in NES-A that impair nuclear export cause additional defects in the function of Upf3p that are not rectified by restoration of export alone.
Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was ...undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio OR = 2.82; 95% confidence interval CI = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.
A single base change in the helicase superfamily 1 domain of the yeast Saccharomyces cerevisiae SEN1 gene results in a heat-sensitive mutation that alters the cellular abundance of many RNA species. ...We compared the relative amounts of RNAs between cells that are wild-type and mutant after temperature-shift. In the mutant several RNAs were found to either decrease or increase in abundance. The affected RNAs include tRNAs, rRNAs and small nuclear and nucleolar RNAs. Many of the affected RNAs have been positively identified and include end-matured precursor tRNAs and the small nuclear and nucleolar RNAs U5 and snR40 and snR45. Several small nucleolar RNAs co-immunoprecipitate with Sen1 but differentially associate with the wild-type and mutant protein. Its inactivation also impairs precursor rRNA maturation, resulting in increased accumulation of 35S and 6S precursor rRNAs and reduced levels of 20S, 23S and 27S rRNA processing intermediates. Thus, Sen1 is required for the biosynthesis of various functionally distinct classes of nuclear RNAs. We propose that Sen1 is an RNA helicase acting on a wide range of RNA classes. Its effects on the targeted RNAs in turn enable ribonuclease activity.
The prevalence data of splenic diseases from 3 sources were studied. Group 1 consisted of a general diagnostic survey of accessions submitted from private veterinary hospitals in California during a ...period of approximately 4 years and included 1,372 submissions of canine splenic tissue. Group 2 consisted of surgical splenectomy specimens from 92 dogs; the specimens were submitted to the laboratory for gross and histologic evaluation prior to fixation, and a questionnaire was subsequently sent to determine the outcome of the disease. Group 3 was made up of specimens of 105 splenic lesions derived from a large colony of Beagles with complete medical records and records of pathologic findings. In this study, splenic hematoma and hyperplastic nodule, not hemangiosarcoma, made up the bulk of splenic lesions. Hemangiosarcoma was the most frequent neoplasm of the canine spleen, but the combined prevalence of all other splenic neoplasms was similar to that of hemangiosarcoma alone. Splenic hematoma and hemangiosarcoma were grossly indistinguishable in most cases. Hyperplastic lymphoid nodules and hematomas of the spleen appeared to represent a continuum. If that finding was correlated with microscopic splenic blood flow, specific causal relationship could be suggested. Prognostically, the live/dead ratio and mean survival of dogs with various splenic lesions differed significantly.
Sense versus nonsense in DNA diagnostics Culbertson, Michael R
Nature biotechnology,
200105, 2001-May, 2001-5-00, 20010501, Letnik:
19, Številka:
5
Journal Article
In Saccharomyces cerevisiae the UPF1 protein is required for nonsense-mediated mRNA decay, the accelerated turnover of mRNAs containing a nonsense mutation. Several lines of evidence suggest that ...translation plays an important role in the mechanism of nonsense mRNA decay, including a previous report that nonsense mRNAs assemble in polyribosomes. In this study we show that UPF1 and ribosomal protein L1 co-localize in the cytoplasm and that UPF1 co-sediments with polyribosomes. To detect UPF1, three copies of the influenza hemagglutinin epitope were placed at the C-terminus. The tagged protein, UPF1-3EP, retains 86% (+/- 5%) of function. Using immunological detection, we found that UPF1-3EP is primarily cytoplasmic and was not detected either in the nucleus or in the mitochondrion. UPF1-3EP and L1 co-distributed with polyribosomes fractionated in a 7-47% sucrose gradient. The sucrose sedimentation profiles for UPF1-3EP and L1 exhibited similar changes using three different sets of conditions that altered the polyribosome profile. When polyribosomes were disaggregated, UPF1-3EP and L1 accumulated in fractions coincident with 80S ribosomal particles. These results suggest that UPF1-3EP associates with polyribosomes. L3 and S3 mRNAs, which code for ribosomal proteins of the 60S and 40S ribosomal subunits, respectively, were on average about 100-fold more abundant than UPF1 mRNA. Assuming that translation rates for L3, S3, and UPF1 mRNA are similar, this result suggests that there are far fewer UPF1 molecules than ribosomes per cell. Constraints imposed by the low UPF1 abundance on the functional relationships between UPF1, polyribosomes, and nonsense mRNA turnover are discussed.