Immunologic aspects of neurological and neuromuscular diseases.
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Central Nervous System Diseases↗
Biomedical subjects
A I Levinson
Publications and source records attributed to A I Levinson.
Calcium signalling by the high affinity macrophage Fc gamma receptor requires the cytosolic domain.
Hematopoietic cells express multiple receptors which bind the Fc domain of IgG. We utilized transfection of COS-1 cells, a cell line which lacks endogenous Fc receptors, to study the expression and function of Fc gamma RI, the high affinity Fc gamma receptor in the absence of other Fc gamma receptors. Fc gamma RI was efficiently expressed in transiently transfected COS-1 cells as measured by flow cytometry and the binding of IgG sensitized RBCs (EA). In addition, analysis at the single cell level demonstrated that individually transfected COS-1 cells release cytosolic free Ca2+ [(Ca2+)i] upon activation with anti-Fc gamma RI antibody. The calcium response required Fc gamma RI cross-linking. COS-1 cells transfected with mutant Fc gamma RI lacking the cytosolic domain expressed Fc gamma receptors and bound EA as well as wild type receptors, but failed to induce an increase in [Ca2+]i. These data indicate that Fc gamma RI in the absence of other Fc gamma receptors mediates a calcium signal and that the cytoplasmic domain of Fc gamma RI contains the elements required for calcium dependent signal transduction.
Amino Acid Sequence↗
Human Fc gamma RII: the structure of the Fc gamma RII cytosolic domain governs phagocytic function.
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Amino Acid Sequence↗
Suppressor cell function in atopic dermatitis associated with elevated immunoglobulin E.
Suppressor cell function was evaluated in 11 patients with atopic dermatitis (AD) and elevated IgE levels (mean, 4,554 IU/ml +/- 1,825 SEM) and compared to 11 matched nonatopic controls (135 IU/ml +/- 52 SEM). Two assays were employed to evaluate suppressor cell function. In the first assay, concanavalin A--activated suppressor cell activity of AD and control subjects were compared. In the second assay, peripheral blood mononuclear cells (PBM) from the same AD and control subjects were stimulated with varying doses of mitogen at day 0 and after 24 hr of preculture. In this system, increased proliferative response of precultured cells as compared to 0-hr cells has previously been shown in normals to represent loss of suppressor cell function in vitro. The lack of such an increase implies aberrant suppressor cell function. The data from both assays showed no significant difference in the degree of suppressor cell function of the patient population vs the control population. Thus, suppressor cell function as tested in these proliferative assays appears normal in AD patients with increased IgE.
Cells, Cultured↗
Evaluation of a patient with cold and cholinergic urticaria.
A-20-year-old male Army paratrooper presented with a history of inducible urticaria associated with exercise as well as cold exposure. Upon evaluation, he not only had a positive ice cube test, but also had a positive mecholyl skin test with numberous satellite lesions and generalized punctate urticaria following exercise challenge. Thus, he appeared to have combined cold and cholinergic urticaria. When mediator release was examined during cold and exercise challenge, histamine release was observed in each instance; a rapid rise and fall of plasma histamine was seen after cold challenge, while a lag phase followed by sustained elevation of plasma histamine was associated with exercise challenge. This represents the fourth reported case of combined cold and cholinergic urticaria and is the first in whom mediator release was assessed. The time-course of histamine release was characteristic of each disorder.
Adult↗
The late phase skin reaction: evidence for activation of the coagulation system in an IgE-dependent reaction in man.
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Allergens↗
Evaluation of the adverse effects of long-term hyposensitization.
This study was undertaken to determine if long-term hyposensitization causes late sequelae, particularly those reflecting aberrant immunologic responses. Atopic individuals receiving five or more years of hyposensitization with allergenic extracts showed no increased autoimmune, collagen vascular, or lymphoproliferative disease. In addition, chronic hyposensitization did not have adverse effects on immunologic reactivity as assessed by a number of immune parameters. Particularly noteworthy was the absence of immune complexes in the serum of patients undergoing long-term hyposensitization. This study represents the first systematic investigation of potential adverse effects of long-term hyposensitization.
Adolescent↗
Systemic vasculitis with coexistent large and small vessel involvement. A classification dilemma.
A patient with systemic vasculitis had the palpable purpuric lower extremity lesions of leukocytoclastic vasculitis and the renal aneurysms of polyarteritis nodosa, features thought to clearly separate these two syndromes. Questions are raised pertinent to the classification, diagnosis, treatment, and prognosis of systemic vasculitis.
Aneurysm↗
Severe persistent biphasic local (immediate and late) skin reactions to insulin.
A patient with adult-onset insulin-requirging diabetes mellitus had persistent severe local reactions to all available insulins of animal origin. Skin reactions were biphasic in nature with both immediate and late characteristics. An extensive immunologic investigation of this problem was undertaken, revealing evidence of reaginic antibody involvement in the reactions. Routine histologic studies suggested the possibility that Arthus-type mechanisms played a part, although this impression was not confirmed by immunofluorescent microscopy. A program of medical management provided some relief of symptoms.
Aspergillus fumigatus↗
Immunologic aspects of leprosy.
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Antibody Formation↗
Reactive and non-reactive lymphocytes in experimental allergic encephalomyelitis.
Myelin basic protein (BP),induces an increased in vitro proliferative response of peritoneal exudate cells (PEC), compared with that given by pheripheral blood lymphocytes (PBL), in guinea-pigs with experimental allergic encephaloMYELITIS (EAE). This response is determined by the nature of the lymphocytes in such exudates. We have also found that: (a) the majority of peritoneal lymphocytes from non-sensitized animals are E-rosetting (T cells) (59 percent) or null cells (greater than 40 percent) with EAC-rosetting (B cells) comprising 1 percent or less of cells; (b) both T cells and null cells respond equally to BP as determined by a technique combining rosette-formation and autoradiography; (c) the increased in vitro peritoneal lymphocyte response in animals with EAE cannot be explained solely by the number of null cells since peripheral blood and lymph nodes also contain appreciable numbers of null cells.
Animals↗
Reactive and nonreactive lymphocytes in experimental allergic encephalomyelitis. I. Possible role of macrophage-lymphocyte interactions.
Previous studies have shown that peritoneal inflammatory exudate cells from guinea pigs with experimental allergic encephalomyelitis proliferate prominently when cultured with the sensitizing myelin basic protein. Peripheral blood lymphocytes (PBL) obtained at the same time responded little, if at all. In the present studies, recombination experiments using appropriate mixtures of peritoneal exudate macrophages and PBL show that the presence of such macrophages will not enhance in vitro reactivity of the PBL to basic protein. The oil-induced peritoneal inflammatory response appears to deplete the PBL somewhat of antigen-reactive lymphocytes, but does not totally explain the difference in in vitro responsiveness between the lymphocytes in the peritoneal exudate and in the peripheral blood.
Animals↗
Immunologic characterization of cerebrospinal fluid lymphocytes: preliminary report.
Cellular immunocompetence of cerebrospinal fluid lymphocytes was investigated in several neurologic diseases. Microtechniques were developed to enable determination of E-rosetting capacity and phytohemagglutinin responsiveness of scant numbers of cells present in the cerebrospinal fluid specimens studied. Although most individuals had phytohemagglutinin-responsive cells in their CSF, reactivity was somewhat less than that found simultaneously in their blood. Three of eight patients had comparable percentages of E rosettes in their blood and CSF. Int the remainder, the values differed significantly. Although preliminary, these result illustrate a new approach to immunologic characterization of CSF lymphocytes in diseases.
Brain Abscess↗
Coexistent lymphoid interstitial pneumonia, pernicious anemia, and agammaglobulinemia.
Immunologic factors have been incriminated in the pathogenesis of lymphoid interstitial pneumonia. The discovery of a patient with coexistent lymphoid interestitial pneumonia, pernicious anemia, and common variable hypogammaglobulinemia focused attention on the possible autoimmune nature of this pulmonary disease. Extensive immunologic studies demonstrated a noticeably impaired bonemarrow-dependent (B cell) system and intact thymus-dependent (T cell) system. No evidence of humoral or cellular hypersensitivity to homologous lung determinants was found.
Agammaglobulinemia↗
T and B lymphocytes in multiple sclerosis.
The percentage and total number of E and EAC rosettes, as indicators of T and B lymphocytes respectively, were studied in the blood of subjects with multiple sclerosis (MS) and normals. MS patients in acute exacerbation were found to have a decrease in E rosettes and an increase in EAC rosettes. The relationship of these findings to the pathogenesis of MS is unclear; several possible pathogenetic implications are considered.
Adult↗
The use of IVIG in neurological disease.
The studies cited herein highlight the potential benefits of IVIG therapy in a group of neurological disorders that are associated with aberrant immune responses. Indeed, all of the disorders discussed, except epilepsy, are associated with autoreactivity. The trials are preliminary and short-term and, except for idiopathic CIDP, uncontrolled. Interpretation of the findings of these uncontrolled studies is complicated by the fact that the natural history of all of these disorders is to show fluctuations. IVIG appears to be a potentially useful and safe agent in the treatment of patients with MG, intractable epilepsy, MS, and CIDP. Its place in the therapeutic approach to these neurological diseases must await the completion of controlled trials. Since other therapeutic modalities have already proven to be useful in several of these disorders, it will be important to determine if IVIG is more efficacious, safer, and more cost-effective. It is also worth considering whether the combination of IVIG and any of these more traditional approaches would provide added therapeutic benefit.
Autoimmune Diseases↗