Facilitation and suppression of single striate-cell activity by spatially discrete pattern stimuli presented beyond the receptive field.

Visual stimulation of a region outside the receptive field of single cells in visual cortex often results in the modulation of their responses. The modulatory effects are thought to be mediated through lateral connections within visual cortex. Research on lateral interactions commonly shows suppression. There has been no systematic study of the optimal conditions for facilitation. Here we have studied the nature of the modulation using a new type of compound stimulus: contrast reversal of pattern stimuli made of three discrete grating patches. The middle patch, optimally fitted to the receptive field in orientation, size, and spatial as well as temporal frequencies, was flanked by two similar patches presented well outside the receptive field. We found that (1) both facilitation and suppression occurred often in the same cells, when orientations of the target and flankers matched the receptive-field's optimal orientation; (2) facilitation with collinear flankers occurred most frequently at target contrasts just above the cell's firing threshold and suppression prevailed at high contrasts; (3) facilitative or suppressive modulation was obtained with target-flankers separation of up to 12 deg or more; (4) collinear facilitation was lost when flankers' orientation was rotated by 90 deg, while keeping all other parameters the same; and (5) neither the modulation mode nor the proportion of modulated cells was related to the cell types (simple vs. complex cells) and cells' laminar locations. Here we have provided physiological evidence for contrast-dependent, collinear facilitation probably underlying perceptual grouping in humans.

Hypothalamically induced emotional behavior and immunological changes in the cat.

Numerous animal studies on the correlation between stress and immunity have been performed but few such studies have been made concerning the relationship between various kinds of stress-related emotional behavior and immunological changes. Electrical stimulation of the hypothalamus in cats elicits various emotional behaviors such as restlessness, defensive attack, defensive retreat and quiet biting attack. We examined changes in the lymphocyte proliferative responses and plasma cortisol level which accompanied such emotional behavior. A significant increase in plasma cortisol was observed in the restlessness, defensive attack and defensive retreat groups, but not in the quiet biting attack or non-response (control) groups. A significant increase in the lymphocyte proliferative responses to phytohemagglutinin (PHA) was observed in the restlessness and defensive attack groups but not in the defensive retreat, quiet biting attack or non-response groups. These results suggest that various kinds of emotional behavior appear to be differentially correlated with the lymphocyte proliferative responses, while also being differentially correlated with the plasma cortisol concentration. Because the changes in lymphocyte responses and plasma cortisol did not always completely correlate with one another, the changes in the lymphocyte responses are not considered to be influenced by plasma cortisol alone.

Successful prevention of autoimmune disease by transplantation of adequate number of fully allogeneic hematopoietic stem cells.

BACKGROUND: We have previously shown successful engraftment of allogeneic hematopoietic stem cells (HSCs) when transplanted across the major histocompatibility antigen barriers if transplanted along with a preparation of facilitator cells (osteoblasts). We have investigated whether or not fully allogeneic HSCs from healthy mouse donors prevent the development of autoimmunities in the autoimmune-prone W/B F1 mice. METHODS: W/B F1 is a strain of mice that spontaneously develop autoimmunities, a coronary vascular disease, thrombocytopenia, and systemic lupus-like syndrome. The 6- to 8-week-old (before the onset of the disease) W/B F1 mice have been transplanted with either a preparation of HSCs alone, or along with facilitator cells from MHC-incompatible autoimmune-resistant BALB/c mice, then followed to determine longterm survival and whether or not they developed signs of the autoimmune disease. RESULTS: The number of the transplanted HSCs acts as the determining factor in achieving successful and durable engraftment. Survival of the W/B F1 mice significantly improved by transplantation of increasing numbers of HSCs, either alone or along with facilitator cells. When W/B F1 mice were transplanted with 2-5 million HSCs, more than 1-year survival was 100%, all the transplanted mice were fully engrafted with allogeneic HSCs, and were free of signs of the autoimmune disease. Histological sections of the hearts, lungs, and kidneys of the transplanted mice showed absence of the autoimmune-associated pathology. CONCLUSIONS: We thus report herein the successful prevention of autoimmune disease by transplantation of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.

Anthocyanin production of Glehnia littoralis callus cultures.

A stable callus line that produces anthocyanins was established from callus derived from a petiole of a Glehnia littoralis seedling and subcultured in the dark. The major anthocyanin which made up about 60% of the total anthocyanins was determined as cyanidin 3-O-(6-O-(6-O-(E)-feruloyl-beta-D-glucopyranosyl) -2-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) by chemical and spectroscopic analyses. Anthocyanin contents in the cells cultured on B5 basal medium containing NAA (1 mg l-1), kinetin (0.01 mg l-1) and 3% sucrose reached 14% (dry wt basis) and the productivity has been sustained for 5 years.

Collinear stimuli regulate visual responses depending on cell's contrast threshold.

Neurons in the primary visual cortex are selective for the size, orientation and direction of motion of patterns falling within a restricted region of visual space known as the receptive field. The response to stimuli presented within the receptive field can be facilitated or suppressed by other stimuli falling outside the receptive field which, when presented in isolation, fail to activate the cell. Whether this interaction is facilitative or suppressive depends on the relative orientation of pattern elements inside and outside the receptive field. Here we show that neuronal facilitation preferentially occurs when a near-threshold stimulus inside the receptive field is flanked by higher-contrast, collinear elements located in surrounding regions of visual space. Collinear flanks and orthogonally oriented flanks, however, both act to reduce the response to high-contrast stimuli presented within the receptive field. The observed pattern of facilitation and suppression may be the cellular basis for the observation in humans that the detectability of an oriented pattern is enhanced by collinear flanking elements. Modulation of neuronal responses by stimuli falling outside their receptive fields may thus represent an early neural mechanism for encoding objects and enhancing their perceptual saliency.

Restraint stress-induced immunosuppression by inhibiting leukocyte migration and Th1 cytokine expression during the intraperitoneal infection of Listeria monocytogenes.

In this study, a murine model of Listeria monocytogenes infection was used to investigate effects of restraint stress (RST) on host defense. We observed that the L. monocytogenes infection as well as RST induced an elevation of endogenous corticosterone (CORT) levels and RST synergistically enhanced endogenous CORT levels during the listerial infection. RST suppressed the migration of leukocytes including macrophages, neutrophils, NK cells and lymphocytes into the peritoneal cavities after the intraperitoneal inoculation of L. monocytogenes. RST also suppressed the increase of the surface MHC class II antigen expression in both peritoneal macrophages and B cells during the listerial infection. Interestingly, gene expression of iNOS, MCP-1 (JE) and Th1-type cytokines including IFN-gamma and IL-12 was down-regulated but Th2-type cytokine (IL-4 and IL-6) gene expression in the PEC was rather up-regulated on day 7 after infection, indicating that Th2-type immune response is more resistant to the elevated endogenous CORT levels than Th1-type response. Treatment of mice with RU486, a glucocorticoid receptor antagonist, restored the immune responses suppressed by RST to their normal levels in the infected mice, suggesting that the RST-induced elevation of endogenous corticosterone levels is mainly responsible for the induction of the immunosuppressive events during L. monocytogenes infection.

Restraint stress-induced elevation of endogenous glucocorticoid suppresses migration of granulocytes and macrophages to an inflammatory locus.

It has been reported that restraint stress gives rise to various immunosuppressive events. In the present study, we focused our interest on an early stage of the host-defense system in which granulocytes, macrophages and natural killer (NK) cells are involved. We observed that an elevation of endogenous glucocorticoid levels in mice induced by 24 h-restraint stress (acute stress) did not significantly reduce the NK activity of the spleen cells but profoundly suppressed the migration of macrophages and granulocytes into peritoneal cavities of the mice at 24 h after an intraperitoneal injection of proteose peptone. The reduced number of the migrated granulocytes and macrophages corresponded to a down-regulated gene expression of such chemotactic factors as MCP-1/JE in the peritoneal exudate cells of the stress-loaded mice. The stress-loaded mice recovered from such a suppressive state upon treatment with the glucocorticoid antagonist, RU-486, or upon adrenalectomy, suggesting that the elevated level of endogenous glucocorticoid is responsible for these suppressive effects of acute stress.

Neuronal responsiveness in areas 19 and 21a, and the posteromedial lateral suprasylvian cortex of the cat.

Responsiveness to slits and pattern stimuli was quantified in a total of 68 cells sampled in the posterior extreme of the lateral suprasylvian (PS) cortex as response indices. The cells were studied in relationship to their locations in several subareas of the PS cortex, including areas 19 (n = 15) and 21a (n = 32) and the posteromedial lateral suprasylvian cortex (PMLS; n = 21). These subareas were identified based on retrograde labelling from area 17 and also supplemented with photic responsiveness. This analysis revealed that each cortical area contains cells expressing different combinations of stimulus features. Area 19 contained two major groups of cells: (1) those with strong end-stop selectivity combined with moderate orientation or direction selectivity, and (2) those with weak end-stop selectivity combined with strong orientation selectivity. The groups of cells with strong or moderate orientation selectivity showed a strong preference for stripe over visual noise patterns and relatively large modulatory responses to motion of individual stripes. The PMLS contained one major group of cells with strong end-stop and direction selectivities and with poor orientation selectivity. They also showed stronger preference for visual noise than cells in the other cortical areas and rather weak modulatory responses. Area 21a contained only one group of cells with strong orientation selectivity and length summation property rather than end-stop selectivity, and they also lacked direction selectivity. These cells exhibited a strong preference for stripe patterns and moderate or weak modulatory responses. Altogether, these findings indicate that each cortical area is specialized in expressing different stimulus features. The two groups of cells in area 19 may encode the position and motion of discontinuous visual elements such as corners and line ends and continuous elements such as lines and edges. PMLS cells may encode the motion of single elements or associated motion of multiple discontinuous elements such as textures and backgrounds. Area 21a cells may specifically encode the orientation of long, continuous elements such as lines and edges. In support of this view, two types of statistical analyses demonstrated that the combinations of the response properties expressed in individual PS cells are highly correlated with their locations in cortical areas and that the anatomical locations of individual PS cells are reliably predicted from the sets of response indices expressed in these cells.

Application of psychoimmunotherapy in patients with alopecia universalis.

Mental stress and immunological abnormality have recently been listed as causes of alopecia universalis. This disease is difficult to treat with only ordinary pharmacotherapy. Thus, from the standpoint of psychoneuroimmunology, stress was relieved by relaxation and image therapy, and administration of small doses of a strong immunosuppressant was effective, leading to clinically favorable results. In addition, changes were recognized in the subpopulation of peripheral lymphocytes and in beta-endorphin before and after relaxation and image therapy. The treatment of alopecia universalis favorably changed the subpopulations of T cells. A patient suffering from alopecia is always under stress. Alleviating this stress facilitates recovery of immunological competence. Our method was effective in 5 of 6 cases with refractory alopecia universalis.

Specular microscopic studies of the corneal endothelia of Japanese diabetics.

We did a specular microscopic study with computer-assisted morphometric analysis of individual cells on the corneal endothelia of 69 Japanese diabetics and 53 age-matched nondiabetics. No statistically significant differences were seen in the mean cell areas of diabetics and nondiabetics. However, the coefficient of variation of cell area was significantly higher and the percentage of hexagonal cells was significantly lower in diabetics than in nondiabetics. Although racial differences of the corneal endothelia exist between Japanese and Americans, diabetic changes are quite similar in the two populations.

Neuronal responsiveness in area 21a of the cat.

Photic responsiveness was studied in cells of area 21a which was identified as a region containing few cells projecting to area 17, and was bounded to two other visual areas (posteromedial lateral suprasylvian area and area 19) providing abundant efferent projection to area 17. Area 21a cells were characterized by strong orientation, but demonstrated poor direction and end-stop selectivity, in contrast to strong direction or end-stop selectivity of cells in another two visual areas.