Scleral fibroblasts. Human leukocyte antigen expression and complement production

The authors investigated the ability of recombinant human gamma-interferon (rhIFN-gamma) to influence production of complement and expression of human leukocyte antigens (HLA) by human scleral fibroblasts in culture. Cell cultures were established by explanting sclera from normal human donor eyes. To study complement production, fibroblasts were treated with 500 units/ml rhIFN-gamma in cell culture, and media were tested for complement components by hemolytic assay after 0, 1, 3, 6, 9, and 11 days. To induce Class II HLAs, fibroblasts were exposed to rhIFN-gamma at concentrations ranging from 10-500 units/ml and incubated for 1, 3, and 6 days. The HLAs were detected by immunofluorescence in conjunction with flow cytometry. Class I antigen was detected using a monoclonal antibody directed against beta 2-microglobulin. Class II histocompatibility antigens were identified using monoclonal antibodies specific for HLA-DR, -DP, and -DQ. Although complement component C1 was produced constitutively in cell culture, the addition of rhIFN-gamma resulted in an increase in production. Complement components C2 and C4 were detected only after treatment with rhIFN-gamma. Complement production was completely inhibited by cycloheximide, and C3, C5, C6, and C7 were not present in cell culture media with or without rhIFN-gamma. Class I antigen was present on all cells before induction, and an increase in expression was noted after exposure to rhIFN-gamma. Class II antigens were absent before induction with rhIFN-gamma. After treatment with rhIFN-gamma, scleral fibroblasts expressed HLA-DR, -DP, and -DQ in a dose-dependent, time-related fashion. These findings suggest that rhIFN-gamma has multiple effects on scleral fibroblasts: (1) increased production of C1, (2) production of C2 and C4, (3) up-regulation of Class I antigen expression, and (4) expression of Class II antigens. They also suggest that scleral fibroblasts have the potential to participate in immunologic diseases of the eye.     

Magnetization Transfer and T2 Relaxation Components in Tissue

T₂ relaxation makes an important contribution to tissue contrast in magnetic resonance (MR) imaging. Many tissues are known to exhibit multicomponent T₂ relaxation that suggests some compartmental segregation of mobile protons on a T₂ timescale. Magnetization transfer (MT) is another relaxation mechanism that can be used to produce tissue contrast in MR imaging. The MT process depends strongly on water-macromolecular interactions. To investigate the relationship between multicomponent T₂ relaxation and the MT process, multiecho T₂ measurements have been combined with MT measurements for freshly excised samples of cardiac muscle, striated muscle, and white matter. For muscle, short T₂ components show greater MT than long T₂ components, consistent with the belief that they represent distinct water environments. For white matter, quantitative MT measurements were identical for the two major T₂ components, apparently because of exchange between the T₂ compartments on a timescale characteristic of the MT experiment. Implications for accurate modeling of MT in tissue and the use of MT for MR image contrast are discussed.     

The effects of anesthesia on otoacoustic emissions

We have measured transient-evoked and distortion-product otoacoustic emissions (OAEs) in the chinchilla and compared them in the awake and anesthetized animal (using either ketamine or barbiturate agents). We report a significant increase in OAE amplitudes during anesthesia, particularly using ketamine. These effects are most evident for transient-evoked otoacoustic emissions (TEOAEs) as measured in the non-linear mode. Our data support the hypothesis that tonic activity levels in cochlear efferents may be reduced by anesthetic effects, either directly or indirectly (e.g., by general reductions in descending pathway activity), and that reduced cochlear efferent activity will result in the observed increase of OAE amplitudes.     

Automated neuropsychological assessment metrics (ANAM) measures of cognitive effects of Alzheimer's disease.

Eight individuals with Alzheimer's disease, and eight age-matched controls, were administered the MMSE, the Yesavage GDS, and a customized subset of the Automated Neuropsychological Assessment Metrics (ANAM) Battery. Accuracy (percent correct) and efficiency (number of correct responses per minute) of performance on six ANAM tasks were assessed. The patients' GDS scores indicated no depression. Although their MMSE scores (mean approximately 25) were significantly lower than those of the controls, they nonetheless indicated that the patients were still functioning at a fairly high level. Analysis of ANAM accuracy scores indicated that the patients were significantly impaired on three tasks measuring working memory. A discriminant function analysis revealed 93.8% correct classification. Analysis of ANAM efficiency scores revealed that except for simple reaction time, the patients were significantly impaired on all tasks. A discriminant function analysis correctly classified 100% of the participants. Given the small size of the groups in the present study, this finding especially underscores the sensitivity of ANAM to the cognitive effects of Alzheimer's disease, as indicated by the large effect sizes. The findings further indicate that ANAM might be capable of detecting more subtle effects of the disease at an earlier stage in its progress.