cyclic-gmp and Immunologic-Deficiency-Syndromes

The results of clinical-roentgenological and hormonal-immunological studies showed that immunohomeostasis peculiarities and adaptation in children with thymomegaly and pneumonia-complicated thymomegaly are determined by prolonged 'metabolic stress' effect associated with thymomegaly and coexistent intercurrent infection. Immune control of children with thymomegaly is appreciably determined by the hormonal function of hypothalamus-hypophysis-thymus-adrenal cortex system and by optimum balance of its constituents. Hypothalamic-hypophysial-adrenal system, cAMP and cGMP as universal intracellular mediators, and, essentially, thymus hormonal function are basic contributors to immunohomeostatis and adaptive reaction control in children with thymomegaly.

Topics: Adrenocorticotropic Hormone; B-Lymphocytes; Child, Preschool; Cyclic AMP; Cyclic GMP; Female; Humans; Hydrocortisone; Immunologic Deficiency Syndromes; Infant; Lymphatic Diseases; Male; Pneumonia; T-Lymphocytes; Thymus Gland

Guanine ribonucleosides, substituted at the C8 position with either a bromine or thiol group, are potent adjuvants when added to culture with antigen. Responses from both naive and antigen-experienced B cells are augmented by the presence of the nucleoside derivatives. Like the induction of B cell proliferation and polyclonal immunoglobulin secretion, enhancement of antibody responses is not attributable to structural analogy between 8BrGuo and the cyclic nucleotide 8Br-cGMP, because the latter compound is unable to augment the antibody response. The capacity of 8MGuo to augment both T-independent and T helper factor-supported antibody responses suggests that the nucleoside acts by directly interacting with B cells and/or antigen-presenting cells. 8MGuo retains its full adjuvant activity even when added 3 days after culture initiation, a time that is too late for freshly added T cells to support a response. Finally, supplementation of cultures of spleen cells from immunodeficient (CBA/N x CBA/CaJ)F1 male mice with the nucleoside effectively restored to normal their capacity to generate an antibody response.

Topics: Adjuvants, Immunologic; Animals; Antigens, T-Independent; Cyclic GMP; Guanosine; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Isoantibodies; Male; Mice; Mice, Inbred CBA; T-Lymphocytes; Thionucleosides

Thymosin fraction 5 contains a family of polypeptides with varying biological activities. Current efforts in the thymosin research program are involved in further chemical characterization of thymosin peptides and evaluation of clinical immunotherapeutic protocols. Recent clinical studies with thymosin fraction 5 have shown therapeutic potentials for treatment of patients with primary immunodeficiency diseases and cancer.

Topics: Cyclic GMP; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Neoplasms; Thymosin; Thymus Hormones

Our current research program centers around the biologic and chemical characterization of the family of polypeptides present in thymosin fraction 5. A system of nomenclature has been developed and the peptides are being systematically isolated and chemically characterized. Thymosin fraction 5 and its component parts influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, and expression of certain surface markers. Thymosin is being used in clinical trials to investigate its effects on immunodeficiency diseases, malignant diseases, and autoimmune diseases.

Topics: Animals; Autoimmune Diseases; Chemical Phenomena; Chemistry; Cyclic AMP; Cyclic GMP; Drug Evaluation; Guinea Pigs; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Lymphocytes; Neoplasms; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Animals; B-Lymphocytes; Calcium; Cyclic AMP; Cyclic GMP; Feedback; Humans; Immunologic Deficiency Syndromes; Lectins; Lymphocyte Activation; Lymphocytes; Models, Biological; T-Lymphocytes