The decerebrate human: associative learning

Phasic changes in cardiac reactivity to innocuous stimuli, presented in a sensory disparity paradigm, were used to evaluate habituation and learning processes in five decerebrate subjects. Three subjects showed systematic changes over trials in the pattern of cardiac response to simple auditory or visual stimuli, indicative of habituation. In addition, tests for associative learning were given after repeated presentations of two paired stimuli. The appearance of a marked cardiac orienting response, to the unpredictable omission of the second stimulus, documented the development of a conditioned association in these same three subjects. One additional subject failed to show a consistent pattern of response to the stimuli, and another demonstrated a consistent response which was not subject to habituation. Overall, these findings support the view that learning processes are not solely the product of the cerebral hemispheres, but reflect general integrative features of the human neuraxis.     

Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTalpha-, and LTbeta-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.     

A molecular basis for the different local anesthetic affinities of resting versus open and inactivated states of the sodium channel

Among patients with severe mental illness attending a large, urban, outpatient mental health clinic, fathers are described and compared with nonfathers and with mothers on demographic, clinical, and child-related characteristics, and on resources and service needs. While fathers and nonfathers with mental illness differed significantly on most variables, fathers and mothers with mental illness were remarkably similar except on child-related characteristics. Issues regarding fathers' experiences and service needs are discussed.     

Cell surface regulators of complement, 5I2 antigen, and CD59, in the rat eye and adnexal tissues

PURPOSE: Cell surface complement regulatory proteins have been identified in high levels in ocular tissues, but no experimental model is available for examining their physiological roles. To develop such a model, the distribution of 5I2 antigen, a protein possessing the functions of the human decay-accelerating factor (DAF [CD55]) and membrane cofactor protein (MCP [CD46]), and rat inhibitory protein (CD59), the homologue of the human membrane inhibitor of reactive lysis (MIRL[CD59]) were characterized in the rat eye and ocular adnexal structures. METHODS: After euthanasia of female Wistar rats, followed by orbital exenteration, eyelids and orbital tissue including the lacrimal gland were separated from the globes and immediately snap-frozen in liquid nitrogen at -70 degrees C. Tissues then were sectioned at -20 degrees C and examined immunohistochemically for 5I2 antigen and rat CD59. RESULTS: Both molecules were found to be present in high levels in multiple sites. Corneal and conjunctival epithelia showed moderate to intense labeling for both regulators. Fibroblasts in the corneal stroma, conjunctiva, and sclera labeled similarly. Corneal endothelial cells showed intense labeling for rat CD59 but not for 5I2 antigen. The iris and ciliary body showed intense labeling for both proteins. The retina showed labeling at multiple levels, with that of rat CD59 being more intense than that of 5I2 antigen. The lacrimal gland labeled for both regulators. Vessels, muscle, and nerves in the orbit labeled intensely for both antigens. In the eyelid, conjunctiva, sebaceous glands, and muscle and nerve tissues labeled moderately to intensely for both molecules, whereas skin epithelium labeled less intensely. CONCLUSIONS: 5I2 antigen and rat CD59 are expressed in high levels and distributed similarly in the rat eye and lacrimal gland to DAF, MCP, and MIRL in the human eye and lacrimal gland. These findings establish the rat ocular surface as a model for studying the role of cell surface complement regulators in this site. This first identification of copious expression of these proteins in eyelid structures, which also participate in protection of the ocular surface, further suggests an important role for surface complement regulatory proteins in this location.