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Biomedical subjects

I Green

Publications and source records attributed to I Green.

At least 19 recordsLinked to original sources

Rhinovirus 39 infection in allergic and nonallergic subjects.

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Humans

Cloning, expression and characterization of ovine interleukins 1 alpha and beta.

Ovine interleukin 1 alpha (IL-1 alpha) c-DNA, obtained by polymerase chain reaction, has been cloned into pTZ18R and pTZ19R. The resulting DNA sequence shows close homology with the bovine sequence. The derived amino-acid sequence shows conserved motifs similar to those observed in all species studied so far. No signal peptide is seen. Northern blots of RNA from lipopolysaccharide (LPS)-stimulated ovine alveolar macrophages show IL-1 beta m-RNA to be produced earlier than and to be more transient than IL-1 alpha m-RNA. c-DNAs coding for the IL-1 alpha proprotein and IL-1 alpha and IL-1 beta mature proteins have been cloned and expressed in the yeast Ty-VLP system as fusion proteins. The resultant IL-1 protein preparations, cleaved from their fusion partners by the action of activated coagulation Factor Xa, are 80-95% pure and show biological activity in standard thymocyte co-mitogen and cartilage degradation assays for IL-1. Some species specificity is observed in that sheep thymocytes are more responsive to ovine rIL-1 than are mouse thymocytes. The presence of a Factor Xa cleavage site in the IL-1 alpha proprotein suggests that Factor Xa may be involved in the processing of ovine IL-1 alpha to its mature form.

Amino Acid Sequence

Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer.

Levamisole has been used in a wide array of clinical research and treatment settings over the past two decades, ranging from such diseases as helminthic infestations to various autoimmune diseases. Numerous preclinical evaluations and clinical trials with levamisole in the cancer arena have been sponsored by the National Cancer Institute and other agencies worldwide with the hopes of demonstrating anticancer activity. Trials in advanced breast cancer, lung cancer, colorectal cancer, melanoma, and lymphoproliferative diseases have generally been negative or inconclusive. However, there is some indication that levamisole may be useful by itself as an adjuvant therapy for resected melanoma; recently it has been shown to be effective in combination with fluorouracil (5-FU) as adjuvant therapy for tumor-node-metastasis (TNM) stage III (Dukes' C) colon carcinoma. In the aggregate, the past 20 years of clinical experience with levamisole has resulted in as many questions as answers. However, further testing of the anticancer activity of levamisole can be expected in clinical research trials over the next few years. Hopefully, these future trials will include studies of the mechanisms of action of this agent.

Animals

Studies of immune functions of patients with systemic lupus erythematosus.

In normal individuals T cells are stimulated to proliferate by autologous non-T cells; this is called the autologous mixed lymphocyte reaction (MLR). Previous studies demonstrated that such an autologous MLR was markedly impaired in patients with active systemic lupus erythematosus (SLE). To determine whether the defect resided in the responding cell or the stimulating cell, mixing experiments were performed using cells from identical twins. We identified two sets of identical twins discordant for SLE activity and correspondingly discordant in their degree of responsiveness in the autologous MLR. Reciprocal mixing experiments were performed in which T cells from one twin of each pair were mixed with non-T cells from the other twin of that pair. These studies indicated that patients with active SLE have a defect in the ability of non-T cells to stimulate as well as a defect in the ability of both Tgamma and Tnongamma cells to respond in the autologous MLR. Patients with inactive SLE have a defect only in responsiveness of Tgamma cells.

Adult

Concanvalin-A-binding proteins on the surface of human malignant and normal lymphocytes.

The concanavalin-A-binding cell surface glycoproteins from normal and certain leukaemic human lymphocytes were radiolabelled and then solubilized with detergent, isolated by affinity chromatography on Con A insolubilized on agarose beads, and subsequently analysed by SDS-polyacrylamide gel electrophoresis. Leukaemic T cells from patients with Sezary syndrome were found to express major concanavalin-A-binding glycoproteins on their outer surface similar to those of normal T lymphocytes. Leukaemic B cells from patients with chronic lymphocytic leukaemia expressed Con-A-binding proteins similar to those of B-cell lines. HLA antigens were predominant among the major Con-A-binding proteins on the surface of the normal and the malignant T cells studied. Human Ia-like antigens, HLA antigens, and the cell surface immunoglobulins IgD and IgM represented the major Con-A-binding proteins on the B cells studied. beta 2-microglobulin was found associated with HLA antigens on both leukaemic and non-leukaemic T and B cells. The presence of additional Con-A-binding proteins expressed on the surface of the different cell types studied is discussed along with some physical characteristics of the human Ia-like antigens isolated.

B-Lymphocytes

Studies of immune functions of patients with systemic lupus erythematosus. Complement-dependent immunoglobulin M anti-thymus-derived cell antibodies preferentially inactivate suppressor cells.

Patients with systemic lupus erythematosus (SLE) produce excessive amounts of autoantibodies. It has also been demonstrated in several systems that such patients have a relative loss of suppressor thymus-derived (T) cells that inhibit the immune response. This loss of suppressor cells has been suggested as one of the causes of the excessive production of antibodies in patients with SLE. In the present report we have tested the hypothesis that anti-T-cell antibodies found in the plasma of some patients with SLE preferentially kill suppressor cells. T cells from normal individuals can be activated by concanavalin A to develop suppressor cell activity. We therefore cultured normal T cells together with concanavalin A in the presence of plasma or plasma fractions from patients with SLE. We found that plasma from patients with active SLE, in which anti-T-cell antibodies were present, inhibited the development of suppressor activity in such cultures. In contrast, plasma from other active patients and patients with inactive SLE, in which no anti-T-cell antibodies could be detected, failed to block the development of such suppressor activity. Absorption of the plasma that contained anti-T-cell antibodies with T cell, but not non-T cells, could eliminate the suppressor-inhibiting activity of the SLE plasma that contained anti-T-cell antibodies. The immunoglobulin (Ig)M, but not the IgG, fraction of the plasma was shown to possess the inhibiting property and complement was found to be necessary for the effect of such anti-T-cell antibodies. We also demonstrated that exposure of normal T cells to such anti-T-cell antibodies and complement did not affect another population of T cells that could proliferate in response to mitogens.Thus, certain patients with SLE have in their plasma an antibody of the IgM class that can selectively eliminate a population of T cells capable of developing suppressor function. The loss of suppressor T cells in patients with SLE may be the result of the effects of such antibody activity in vivo.

Adult

Studies of immune functions of patients with systemic lupus erythematosus. T-cell subsets and antibodies to T-cell subsets.

Antibodies to T cells present in the plasma of patients with active systemic lupus erythematosus (SLE) plus complement are able to eliminate concanavalin A-induced suppressor function for the proliferative responses of T cells to allogeneic lymphocytes (MLR) and of B cells to pokeweed mitogen (PWM). Such antibodies were found to be effective in eliminating suppressor function only when T cells were treated before activation; there was no effect when treatment was performed after activation. These studies indicate that the antibodies preferentially interact with a T cell necessary for the generation of suppressor cells, rather than with mature, activated suppressor cells. Studies of individual SLE patients indicate that the same defects observed in SLE T cells were induced in normal T cells by plasma from that patient. Such observations suggest that many T-cell defects associated with active SLE may not be intrinsic T-cell abnormalities, but, rather, secondary effects of anti-T-cell antibodies. Studies of the T-cell subpopulations responsible for suppression of the MLR and PWM responses indicate that only T gamma cells (T cells bearing receptors for the Fc portion of immunoglobulin [Ig]G) acted as precursors of suppressor cells for the MLR, whereas both T gamma and T non-gamma cells (T cells not bearing receptors for the Fc portion of IgG) could be activated to suppress the PWM response. Consistent with this observation, SLE anti-T-cell antibodies that preferentially killed T gamma cells preferentially eliminated suppressor cells for the MLR.

Autoantibodies

Gamete vaccines and transmission-blocking immunity in malaria.

We have recently proposed an approach to malaria control based on immunization of the host against extracellular malarial gametes, the stage in the mosquito guts, in order to block transmission by the mosquito vector. Our studies with avian and primate models have demonstrated that immunization of the host with extracellular gametes totally suppresses infectivity to the mosquito of a subsequent blood meal. Gametocytes within the erythrocytes are unaffected by the immunity, since resuspending the gametocytes in serum from normal nonimmune animals restores their infectivity to mosquitos. Immunity is mediated by antibodies that are ingested with the blood meal. These antibodies interact with extracellular gametes and prevent fertilization (the fusion of male and female gametes). Thus the infection in the mosquito is blocked, and in this way transmission is interrupted.

Animals

Immune response to levan. II. T independence of suppression of cross-reactive idiotypes by anti-idiotype antibodies.

Pretreatment of BALB/c mice with antisera to a cross-reactive idiotype (E109IdX) expressed on many anti-bacterial levan (BL) and anti-inulin (Inu) antibodies leads to a prolonged suppression in production of IdX-bearing molecules in response to BL immunization. There is a comparable suppression in numbers of plaque-forming cells secreting IdX-bearing anti-BL and anti-Inu molecules. Furthermore, spleen cells from anti-E109IdX pretreated mice are unable to transfer to irradiated recipients the ability to produce IdX-bearing anti-BL and anti-Inu antibodies. These results indicate that the suppressive effect is at the precursor level and not simply a clearance of antibodies bearing the IdX. Suppression of IdX production can be achieved by pretreating nu/nu BALB/c mice with anti-E109IdX antibodies. Furthermore, spleen cells from pretreated mice do not inhibit the capacity of spleen cells from normal mice transferred to irradiated recipients to produce E109IdX in response to BL. This indicates that the suppression of IdX production in the anti-BL system is T independent and probably represents direct inhibition of precursors by anti-IdX.

Animals

Growth and development of congenitally dislocated hips reduced in early infancy.

We determined the acetabular angles, center-edge angles, comprehensive quotients, and Shenton's lines from sequential roentgenograms of thirty-seven children with congenitally dislocated hips treated by closed non-manipulative reduction in early infancy. The values were compared with those obtained from roentgenograms of 164 normal children who ranged in age from three months to five years and of forty-three adolescents and adults. The hip recovering from congenital dislocation developed similarly to the normal hip but differed in that it showed a greater rate of decrease of the acetabular angle and an increase in the center-edge angle. Significant development after the age of five years still was manifested in the reduced hips.

Acetabulum

Malaria immunization in Rhesus monkeys. A vaccine effective against both the sexual and asexual stages of Plasmodium knowlesi.

Rhesus monkeys were immunized with a preparation of Plasmodium knowlesi parasites containing principally microgametes with lesser numbers of macrogametes and asexual trophozoites. The antigen mixture was emulsified in Freund's complete adjuvant (FCA) and administered intramuscularly. After one or two inoculations of from 10(5) to 10(7) microgametes in FCA, monkeys showed high levels of circulating anti-gamete antibodies as demonstrated by various in vitro microgamete immobilization or transmission blocking tests. After challenge with P. knowlesi, immunized monkeys developed low level asexual parasitemias and were not infectious to feeding mosquitoes as measured by growth of the parasite on the mosquito gut. Control monkeys developed rapidly rising, usually fatal infections and were highly infectious to mosquitoes. Anti-gamete antibodies appear to neutralize the sexual parasites and prevent mosquito infection within the gut of the recently fed mosquito vector. Suppression of asexual parasitemia in immunized monkeys may be due to the presence of asexual trophozoites in the antigen mixture or to antigens common to both sexual and asexual stages of the parasite. A vaccine effective as a single injection capable of interrupting malaria transmission from man to man whereas reducing the severity of the disease in infected individuals offers a new approach to the control of one of the major diseases affecting man.

Animals

Failure of autologous mixed lymphocyte reactions between T and non-T cells in patients with systemic lupus erythematosus.

Normal human T cells proliferate vigorously when stimulated with autologous non-T cells. This autologous mixed lymphocyte reaction (MLR) between T and non-T cells was defective in patients with active systemic lupus erythematosus (SLE). In contrast, T cells and non-T cells from active SLE patients behaved normally as responding and stimulating cells, respectively, in the allogeneic MLR. The etiology of the impaired autologous MLR was further examined by studying the functional capacity of subsets of stimulating or responding cells. B cells, L cells, and monocytes from active SLE patients failed to stimulate autologous T cells but these cells effectively stimulated allogeneic T cells. Fc(IgG)+ T cells from active patients were unable to respond in both the autologous and allogeneic MLR; their Fc(IgG)-T cells responded well in the allogeneic but not in the autologous MLR. The Fc(IgG)+ T cells, but not the Fc(IgG)- T cells, from inactive SLE patients also failed to respond in the both autologous and allogeneic MLR. These studies indicate that patients with SLE have functionally defective Fc(IgG)+ T cells and a defective autologous MLR, both of which may contribute to impaired regulation of immune functions.

Adult