ABSTRACT
Screening for inhibitors of bacterial protein synthesis Initiation Factor 2 (IF2) binding to N-formyl-Methionyl-transfer RNA (fMet-tRNA((fMet))) identified a series of aminoglycosides, that included amikacin and kanamycin A1, as inhibitors of this interaction. Subsequent testing revealed that aminoglycosides displayed a wide range of inhibitory activity. However, the failure of these compounds to completely inhibit binding of IF2 to fMet-tRNA((fMet)), the known ability of aminoglycosides to bind RNA, and the ability of the aminoglycosides to displace PicoGreen bound to fMet-tRNA((fMet)) suggest these compounds act by binding fMet-tRNA((fMet)). This hypothesis is further supported by isothermal denaturation experiments that failed to show any interaction between the IF2 protein and the aminoglycosides.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/metabolism , Prokaryotic Initiation Factor-2/metabolism , RNA, Transfer, Met/metabolism , Amikacin/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Carbohydrate Sequence , Escherichia coli/drug effects , Escherichia coli/metabolism , Kanamycin/pharmacology , Molecular Sequence Data , Prokaryotic Initiation Factor-2/drug effects , Protein Denaturation , RNA, Transfer, Met/drug effectsABSTRACT
Most early-onset familial Alzheimer disease is associated with missense mutations in S182, a membrane protein on chromosome 14. We investigated amyloid-beta protein (A beta) precursor (A beta PP) metabolism in skin fibroblasts from S182 (Glu246)-affected individuals and unaffected family members. Steady-state A beta PP levels were similar among all lines as was the degree of increase in soluble A beta PP released upon stimulation of cells with either phorbol ester or serum. Among all lines studied, A beta levels were consistently detectable only in the medium of a single line of S182 (Glu246) cells, consistent with the conclusion that some S182 mutant lines may accumulate A beta in their conditioned media. Studies of cells from additional individuals and under other conditions will be required to establish this association of elevated A beta levels with S182 mutations.
Subject(s)
Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/metabolism , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Point Mutation , Age of Onset , Alzheimer Disease/pathology , Blood Physiological Phenomena , Case-Control Studies , Cells, Cultured , Culture Media, Conditioned , Fibroblasts/metabolism , Humans , Phorbol 12,13-Dibutyrate/pharmacology , Presenilin-1 , Skin/cytology , Skin/metabolismABSTRACT
The role of the head nurse continues to expand within the contemporary health care system, and the impact of that role will seriously affect the financial viability of health care organizations. Therefore, it is apparent that these organizations must reevaluate this role in relationship to its goals and objectives. They must also adopt strategies to select the appropriate individual for the particular job and provide sufficient training for successful management behaviors. The organization that expects its novice managers to hit the ground running must prepare these managers to clear the high hurdles, endure the marathons, and sprint to the finish line.
Subject(s)
Nurse Administrators/psychology , Nursing, Supervisory/organization & administration , Attitude of Health Personnel , Data Collection , Humans , Leadership , Personnel Selection , Professional Competence , Statistics as Topic , Stress, Psychological/prevention & control , United StatesABSTRACT
Four postlinguistically deaf adults were evaluated presurgically with a one- or two-channel vibrotactile aid and postsurgically with a multichannel, multielectrode, intracochlear implant. Although the vibrotactile aid provided awareness of sound and enhanced flow of conversation, benefit to lipreading was small on videotaped tests and speech tracking. Scores on recorded, sound-only speech tests were not significantly above chance except in discrimination of noise from voice. With the cochlear implant, benefit to lipreading was significantly greater than with the vibrotactile aid, and scores on sound-only tests were significantly above chance. Communication was markedly better with the implant than with the vibrotactile aid. In counseling those who get no benefit from a hearing aid, the results of this study provide data on the amount of benefit one- or two-channel vibrotactile aids provide postlinguistically deaf adults who are subsequently implanted.
