Functional MR of the primary auditory cortex: an analysis of pure tone activation and tone discrimination.

PURPOSETo use functional MR imaging to measure the effect of frequency (pitch), intensity (loudness), and complexity of auditory stimuli on activation in the primary and secondary auditory cortexes.METHODSMultiplanar echo-planar images were acquired in healthy subjects with normal hearing to whom auditory stimuli were presented intermittently. Functional images were processed from the echo-planar images with conventional postprocessing methods. The stimuli included pure tones with a single frequency and intensity, pure tones with the frequency stepped between 1,000, 2,000, 3,000, or 4,000 Hz, and spoken text. The pixels activated by each task in the transverse temporal gyrus (TTG) and the auditory association areas were tabulated.RESULTSThe pure tone task activated the TTG. The 1,000-Hz tone activated significantly more pixels in the TTG than did the 4,000-Hz tone. The 4,000-Hz tone activated pixels primarily in the medial TTG, whereas the 1,000-Hz tone activated more pixels in the lateral TTG. Higher intensity tones activated significantly more pixels than did lower intensity tones at the same frequency. The stepped tones activated more pixels than the pure tones, but the difference was not significant. The text task produced significantly more activation than did the pure tones in the TTG and in the auditory association areas. The more complex tasks (stepped tones and listening to text) tended to activate more pixels in the left hemisphere than in the right, whereas the simpler tasks activated similar numbers of pixels in each hemisphere.CONCLUSIONAuditory stimuli activate the TTG and the association areas. Activation in the primary auditory cortex depends on frequency, intensity, and complexity of the auditory stimulus. Activation of the auditory association areas requires more complex auditory stimuli, such as the stepped tone task or text reading.     

Repeated survey on changes in musculoskeletal complaints relative to age and work demands.

OBJECTIVES: To examine changes in musculoskeletal complaints over four years in groups of employees relative to age and work demands. METHODS: Repeated questionnaire data of male employees in heavy physical work (exposed group, n = 7324) and mental work (control group, n = 4686), stratified for age (20-9, 30-9, 40-9, 50-9), were analysed. For each employee, data on the occurrence of musculoskeletal complaints from two surveys with a mean interval of around four years were available. Changes in prevalences over the follow up interval were analysed. Proportions of new, recovered, and chronic cases as well as those free of complaints at both surveys were studied. RESULTS: For most complaints, there were significantly greater increases in prevalences in the exposed group compared with the control group over the follow up interval particularly within the group aged 40-9 for back, neck, and several sites of the upper and lower limbs. The 20-9 year age group also had significantly greater changes for several musculoskeletal complaints. Within the oldest age group (50-9) exposure to heavy physical work demands only affected changes in prevalences of neck and upper arm complaints. After four years in the cohort free of complaints at the start of the follow up the group aged 40-9 had the highest prevalence of complaints of the back, neck, and the upper and lower limbs. CONCLUSIONS: Middle aged and younger employees develop musculoskeletal complaints as a result of exposure to heavy physical work. In the oldest age group health related selection seems to mask the occupational health risks under study. To prevent the expected increase in musculoskeletal disorders and related work disability in our aging workforce, preventive measures should be taken at all stages of a working life.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Evidence that the Receptor for Soluble CD14:LPS Complexes may not be the Putative Signal-Transducing Molecule Associated with Membrane-Bound CD14

Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.     

Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis.