The CD44 antigen is a proteoglycan recently implicated in several adhesion events including that of lymphocytes to endothelium. The CD44 antigen, reactive with monoclonal antibody (MAb) 44D10, has been shown previously to be expressed in normal human white matter homogenates and to be found at higher concentrations in brain homogenates of victims of multiple sclerosis (MS). The cellular localization of CD44 in human brain of normal individuals and in those afflicted with MS has now been determined. Monoclonal antibody 44D10 reacted with astrocyte-like cells in 40 microns thick paraformaldehyde-fixed sections but not in thin (6 microns) fixed sections. A double labeling experiment performed on a frozen brain section with MAb 44D10 and rabbit anti-glial fibrillary acidic protein (GFAP), a cytoplasmic marker of astrocytes, confirmed the co-localization of these two antigens. The reactivity with brain tissue sections of a rabbit antiserum produced against lymphocyte-CD44 could be absorbed by a preparation of the CD44 glycoprotein, purified 2,100-fold from a white matter homogenate. The antiserum was shown by Western blot analysis to be specific for p80 glycoprotein in brain extracts derived from a normal and MS patients. This antibody reacted with fibrous astrocytes predominantly in white matter; staining was also noted in subependymal and subpial regions. Inhibition studies using a cellular radioimmunoassay indicated that the highest concentrations of CD44 in three MS victims were found in plaques, followed by periplaques and non-involved areas of white matter which were higher than normal white matter. Reactive astrocytes, identified in active lesions, expressed high levels of CD44 on their surfaces. Thus, CD44 is associated with astrocytes in human brain and the increased expression observed in MS brain may reflect activation and/or proliferation of astrocytes implicated in the pathogenesis of this disease.

1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle that originates bilaterally on the humerus and inserts beneath the dermis of back and flank skin. A nociceptive stimulus applied to the skin elicits a localized reflex contraction in that region of the CTM underlying the site of sensory stimulation. While this "local sign" character of the CTM reflex corresponds to the segmental distribution of the afferent nerves (the dorsal cutaneous nerves, or DCNs) that enter the spinal cord in the lower thoracic and the lumbar levels, the motor output originates entirely from a circumscribed region of the cervical spinal cord. 2. Electrophysiological analysis of EMG activity in the muscle reflexly evoked by direct electrical stimulation of individual DCNs revealed a distinct topographic relationship, in that the shortest latency response of EMG activity in the muscle was consistently located approximately 1.0 cm rostral to the dermatome of the stimulated DCN. 3. Histochemical studies of the CTM show that individual muscle fibers run rostrocaudally, are focally innervated, and in adult rats, are approximately 3.0 cm in length. The major motor nerves exit from the brachial plexus, and functionally they divide the muscle into longitudinal (rostrocaudal) territories, which thus lie orthogonal to the dermatomal pattern of sensory innervation. The localized reflex responses to focal sensory stimuli indicate that the major longitudinal muscle fields contain many "reflex compartments." 4. The compartmentalized nature of the reflex response in the CTM suggests that nociceptive input from any one sensory dermatome has a preferred access to that fraction of the motoneuron pool that supplies the area of muscle underlying that specific region of skin, i.e., there is a sort of "matching" between groups of primary sensory neurons, interneurons, and motoneurons, which relates to the peripheral location of the stimulated nerve endings and of the muscle fibers that are reflexly activated. Although the partitioning of sensory input to motor nuclei has been shown most clearly for monosynaptic Ia connections, the CTM reflex suggests that sensory partitioning may also be demonstrated in a polysynaptic circuit.

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