Identification of cells of origin of long fiber connections in the cat's spinal cord by means of the retrograde axonal horseradish peroxidase technique

The location of the cells of origin of the propriospinal and long ascending spinal fibers has been determined by injecting horseradish peroxidase (HRP) unilaterally into the white and gray matter of the cat's spinal cord at cervical, thoracic and lumbar levels. In all cases retrogradely labeled neurons were present in the intermediate zone throughout the spinal cord. Caudal to the injections labeled neurons were also present in the dorsal horn, the column of Clarke and the area of the spinal border cells.     

Dendritic cells of the oral mucosa and the induction of oral tolerance. A local affair.

The oral mucosa is an important site to induce immunological tolerance to protein antigens. Previously we have established that oral contacts to allergen can lead to systemic tolerance in both humans and experimental animals. Because of the importance of tolerance induction as a possible way to modulate allergic reactivity, we wished to study the mechanisms involved in efficient tolerance induction via the oral mucosa. Dendritic Langerhans' cells in both skin and oral epithelium are the first cells to encounter antigen. Therefore, possible functional differences between Langerhans' cells from skin and oral mucosa were studied by migration and transfer experiments. It was found that dendritic cells derived from the oral mucosa were not able to transfer tolerance, but that they acted as antigen-presenting cells in sensu stricto irrespective of the source and route of antigen administration.     

A surface molecule on guinea pig lymphocytes involved in adhesion and homing

A monoclonal antibody, CT 4, which recognizes an antigenic determinant on the majority of guinea pig lymphocytes, was tested for its ability to interfere with adherence and homing capacity of lymphocytes. Incubation with F(ab')2 fragments of the antibody blocks the in vitro binding to high endothelial venules (HEV) of both peripheral lymph nodes and Peyer's patches. When tested in vivo using a short-term homing assay with radiolabeled cells also a reduction of migration into the spleen was observed. Fluorescence-activated cell sorter analysis of lymph node cells showed a separation into duller and brightly positive cells whereas in the thymus the bright population is absent. Thymus cells adhere less effectively to HEV and this binding can only marginally be blocked by CT 4 incubation. The results suggest a role of CT 4 in adhesion processes.     

The role of CD45+CD4+CD3– cells in lymphoid organ development

Summary: In the last 10 years the continuing search for gene function has yielded many mutant mice that unexpectedly showed a complete lack of lymph nodes and/or Peyer's patches. With the realization that all these functionally highly diverse genes are involved at some point in the development of lymphoid organs, the challenge now is to assign a function to the molecules involved in lymphoid organ development. It will be important to determine the sequence of molecular events and assign this to the cellular events that lead to an accumulation of hematopoietic cells in one location, ultimately forming an organized lymphoid organ. Here we will focus on CD45⁺CD4⁺CD3^– cells that are the early colonizing cells in lymph nodes and Peyer's patches and develop a hypothetical model of their contribution to the creation of organized lymphoid structures.     

Radiotoxicity of 111indium

Bone marrow cells were labelled with various concentrations of 111Indium-oxine and their capacity to form colonies (CFU-s) in an adoptive transfer was investigated. Labelling with more than 0.1 muCi/ml/107 cells impaired colony formation. It is concluded that the 111Indium-oxine complex is detrimental to cell proliferation.     

Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages.

We have examined by limit dilution analysis the frequency of several types of DBA/2-specific precursor cells found in the draining lymph nodes of BALB/c mice following anterior chamber or subconjunctival inoculations of P815 tumour cells. Assays for precursors of cytotoxic T cells (pTc) and T-helper cells [interleukin-2 (IL-2)- and IL-4-producing cells] were conducted periodically during a 6-month interval after injection of tumour cells. The results indicate that nodes of both sets of recipients contained primed P815-specific CD8+ pTc that were detectable within 2 weeks of tumour implantation, and persisted throughout the 6-month observation period. Early after tumour inoculation, but not thereafter, these CD8+ cells also secreted Il-2. By contrast, only lymph nodes from mice that received P815 cells into the subconjunctival space contained CD4+ cells that secreted both IL-2 and IL-4; eventually, IL-4-secreting cells formed the vast majority of P815-specific CD4+ cells in these mice. Lymph nodes of mice that received P815 cells in the anterior chamber contained CD4+ T cells that were clonally expanded, and secreted IL-2, but not IL-4. These IL-2-secreting cells proved to be short-lived and were not present 6 months after inoculation. It is proposed that the IL-2- and IL-4-secreting T cells found in lymph nodes of subconjunctival tumour recipients are in vivo homologues of Th0 cells, that these cells can mediate delayed hypersensitivity responses, and that they are the forerunners of, or are themselves, memory T cells. These data indicate that the failure of mice that receive P815 tumour cells in the anterior chamber to display antigen-specific delayed hypersensitivity results from an inability to convert antigen-activated, IL-2-only-secreting CD4+ T cells (pTh) into Th0 cells. These findings also imply that mice with anterior chamber-associated immune deviation (ACAID) fail to develop memory CD4+ T cells.     

Pain, Anxiety, and Cooperativeness in Children with Cerebral Palsy After Rhizotomy: Changes Throughout Rehabilitation

Assessed pain, anxiety, physical functioning, and cooperativenessin 32 childrenn with spastic cerebral palsy. This is the firststudy to assess children throughout rehabilitation followingselective posterior rhizotomy. Results of the ObservationalScale of Behavioral Distress and observer Likert ratings confirmedthe hypothesis that children's pain and anxiety decrease overtime. Children's physical functioning and cooperativeness improveover time. No significant correlation was found between painand changes in physical functioning. Cognitive impairment, parentalinvolvement, and children's pain behaviors explained 77% and56% of the variance in two forms of cooperativeness. Researchand clinical implications are discussed, and special considerationsregarding pain assessment and management in this populationare addressed     

Effects of iodide on class II-MHC antigen expression in iodine deficient hyperplastic thyroid glands

The expression of major histocompatibility complex class II molecules (Ia antigen) has been analyzed by immunoperoxidase staining in thyroids of normal C3H mice, of iodine-deficient mice with a hyperplastic goiter and of mice during goiter involution induced by administration of either a high iodide dose (HID, 10 micrograms/day) for 0.5 to 8 days or a moderate iodide dose (MID, 1 microgram/day) or triiodothyronine (T3, 1 micrograms/day) for 2 days. In normal and in hyperplastic thyroids, few interstitial cells were Ia positive (monoclonal antibodies, mAb, M5/114, ER-TR3). Their number was unchanged when goiter involution was induced by MID or by T3, but was significantly increased (p less than 0.05) after HID. It was maximal at days 1 and 2 of involution, decreased thereafter but remained higher (p less than 0.05) than in controls after 8 days. The Ia positive cells were mainly macrophages and, to a lesser extent, dendritic cells. Macrophages were identified by their heterogeneous content and their numerous lysosomes. They were stained with anti-Mac-1 (M1/70) and anti-Mac-2 (M3/38) mAb. Dendritic cells were characterized by their slender cytoplasmic processes, indented nucleus and pale cytoplasm. They were positive for NLDC-145 and MIDC-8 mAb whose specificity for dendritic cells has been demonstrated in lymphoid organs. During the whole period of involution analyzed, Ia antigens were not expressed on follicular cells. Since macrophages and dendritic cells are known to be involved in the pathogenesis of immune disorders, the inflammation induced by administration of HID to iodine-deficient mice could be considered as the early step of an immunological reaction.     

The selective localization of B lymphocytes in the spleen and the role of complement receptors

The role of complement receptors on the localization of T and B cells in the spleen of mice was studied using short-term homing experiments in cobra venom factor (CoF)-treated animals. The localization ratio of B and T cells in the spleen of CoF-treated mice decreased significantly compared to control recipients. No changes could be found in the relative distribution of resident T and B cells in the spleen or other lymphoid organs of CoF-treated animals and when their spleen or lymph node cells were transferred, the localization pattern was normal. When cells were incubated in serum prior to transfer a disturbed localization ratio in the spleen of untreated recipients was observed. This was due to a blockade of complement receptors as determined by the inability of the incubated cells to form EAC rosettes. No blockade of EAC rosettes and no changes in localization ratios upon transfer could be observed when the cells were incubated in functionally C3-depleted serum. The results suggest a role for the complement-receptor on B cells in the initial localization in the spleen, whereas no influence upon the selective localization in high endothelial venules-bearing organs was found.     

Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.