Spinal cord neuronal pathology in multiple sclerosis.

The objective of this study was to assess neuronal pathology in the spinal cord in multiple sclerosis (MS), both within myelinated and demyelinated tissue. Autopsy material was obtained from 38 MS cases and 21 controls. Transverse sections were taken from three spinal cord levels and stained using Luxol Fast Blue/Cresyl Violet and myelin protein immunohistochemistry. Measurements of neuronal number and size were made for all neurons within the anterior horns of the gray matter. Neurons were classified as motoneurons or interneurons according to size criteria. In comparison with controls, both motoneuron and interneuron number were reduced in MS cases at the upper cervical (interneuron P = 0.0549; motoneuron P = 0.0073) and upper thoracic (interneuron P = 0.0507; motoneuron P = 0.0144), but not the lumbar level. Interneuron cross-sectional area was reduced in MS cases at all levels (upper cervical, P = 0.0000; upper thoracic, P = 0.0002; lumbar, P = 0.0337). Neuronal loss appears to be predominantly related to local gray matter plaques, whereas interneuron atrophy occurs in both myelinated and demyelinated areas.

Spinal cord gray matter demyelination in multiple sclerosis-a novel pattern of residual plaque morphology.

The extent and pattern of gray matter (GM) demyelination in the spinal cord in multiple sclerosis (MS) has not been examined in detail. Human autopsy material was obtained from 36 MS cases and 12 controls. Transverse sections were taken from five levels of the spinal cord (upper cervical, lower cervical, upper thoracic, lower thoracic and lumbar levels) and the extent of GM and white matter (WM) demyelination evaluated using proteolipid protein immunohistochemistry (IHC). The proportion of the GM that was demyelinated (33%) was significantly greater than the proportion of demyelinated WM (20%) (P < 0.0001). Similarly, demyelination was more extensive in the GM than in the WM at each of the five cord levels. The extent of GM demyelination was not significantly different between the five cord levels while WM demyelination was greatest at the upper cervical level. Morphologically, the borders of a proportion of the GM plaques show a strict respect for the GM/WM boundary. We demonstrate that extensive demyelination occurs in the GM of the spinal cord in MS. Myelin protein IHC reveals a novel pattern of residual plaque morphology challenging previous work suggesting that MS plaques display a total disregard for anatomical boundaries.

Spinal cord atrophy in multiple sclerosis caused by white matter volume loss.

OBJECTIVE: To assess the relative contributions of white matter (WM) and gray matter (GM) volume loss to spinal cord atrophy in multiple sclerosis (MS). DESIGN: Postmortem study of transverse sections obtained from 5 levels of the spinal cord, with measurement of the cross-sectional GM and WM areas. SETTING: Department of Neuropathology, University of Nottingham, Nottingham, England. PATIENTS: Fifty-five MS cases and 33 controls. MAIN OUTCOME MEASURES: Size of the WM and GM areas. RESULTS: The WM area was significantly reduced in MS cases in the upper but not the lower cord levels. The GM area was not significantly different between MS and control cases. CONCLUSION: Spinal cord atrophy in MS is due to WM rather than GM volume loss.

Protein adsorption and human osteoblast-like cell attachment and growth on alkylthiol on gold self-assembled monolayers.

Protein adsorption and growth of primary human osteoblasts on self-assembled monolayers of alkylthiols on gold (SAMs) with carboxylic acid and hydroxyl and methyl termini were investigated. Single-component SAMs and SAMs patterned by photolithographic techniques were used. Cell growth on patterned SAMs demonstrated preferences for one pattern region in all combinations of alkylthiols, with the hierarchical preference COOH > OH > CH(3). Patterned SAMs and immunochemistry were used to investigate adsorption of fibronectin and albumin with respect to different alkylthiol termini. Fibronectin adsorption from both pure solution and serum containing cell culture medium (SDMEM) followed the sequence COOH > OH > CH(3). Albumin adsorption from pure solution followed the sequence OH > COOH > CH(3); from SDMEM the sequence was CH(3) > OH > COOH. Cell attachment to SAMs with the above termini, after preadsorption with fibronectin, albumin, or mixtures of fibronectin and albumin, was measured. Attachment was maximal on COOH-terminated SAMs precoated with fibronectin. Attachment to COOH was significantly reduced only when fibronectin was omitted from the protein preadsorption solution. On OH and CH(3) SAMs increasing the proportion of albumin in the solution was sufficient to significantly reduce cell attachment. The distribution vinculin and the integrins alpha(5)beta(1) and alpha(v)beta(3) indicated that focal contact formation by cells varied with alkylthiol termini in the following sequence: COOH > OH > CH(3).