thymosin and Myasthenia-Gravis

Topics: Adolescent; Adult; Aged; Antibodies; Atrophy; Autoimmune Diseases; Child; Child, Preschool; Epithelial Cells; Epithelium; Female; Hematopoietic Stem Cells; Humans; Inclusion Bodies; Infant; Lymphocytes; Lysosomes; Male; Middle Aged; Muscles; Myasthenia Gravis; Neuromuscular Blocking Agents; Neuromuscular Junction; Neurotransmitter Agents; Teratoma; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms; Vacuoles

The thymus is a critical organ for the elimination of autoreactive T cells by apoptosis. We studied the expression of apoptosis-associated genes, bcl-xL, bad, caspase-3, and c-myc family genes in myasthenia gravis (MG) thymuses. We observed that the mRNA levels of myc family genes, c-myc and max, were markedly reduced in MG thymuses. These results indicate that c-myc-mediated signaling is abnormal in MG thymuses. The levels of molecules whose expressions are associated with myc, such as STAM, prothymosin-alpha, and NFkappaB, were also analyzed.

Topics: Adaptor Proteins, Signal Transducing; Adult; Apoptosis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic-Leucine Zipper Transcription Factors; bcl-Associated Death Protein; bcl-X Protein; Carrier Proteins; Caspase 3; Caspases; DNA-Binding Proteins; Endosomal Sorting Complexes Required for Transport; Female; Humans; Male; Myasthenia Gravis; NF-kappa B; Phosphoproteins; Protein Precursors; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-rel; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; T-Lymphocytes; Thymosin; Thymus Gland; Transcription Factor RelA; Transcription Factors

To understand the thymic hormone production in thymic tumors and the myasthenic thymus, we have studied the concentrations of two thymic hormones (prothmosin alpha and thymosin beta 4) in these tissues. A total of forty four thymus or thymic tumor tissues were obtained from patients who underwent thoracic operation. These tissues consisted of a control group (n = 25) and three study groups including a thymoma group (N = 8), thymic carcinoma group (n = 3) and myasthenic thymus group (n = 8). The age-related curve of the control group, which provided histologically normal thymic tissues for the production of prothymosin alpha and thymosin beta 4, was established. It was found that in the control group the concentrations (microgram/g tissue) of prothymosin alpha and thymosin beta 4 decreased with age, and that the ranges were from 171 micrograms/g to trace and from 243 micrograms/g to trace, respectively. The amounts were highest at puberty and then gradually decreased, and only trace amounts of both polypeptides were present at age 60. Study cases which deviated from the standard curves were identified. Our results indicated that the contents of thymic hormones significantly increased in the tissues of invasive or non-invasive thymoma, decreased in thymic carcinoma, and were not significantly changed in myasthenic thymus as compared with those of the age-related normal thymus tissues. These findings confirm the notion that only thymomas produce significantly higher thymic hormones.

Topics: Adolescent; Adult; Aged; Aging; Amino Acids; Child; Female; Humans; Infant; Male; Middle Aged; Myasthenia Gravis; Protein Precursors; Reference Values; Thymectomy; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms

Forty five human thymomas were studied immunohistochemically using antibodies to thymosin x-1, thymosin beta-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin x-1 (80%) and thymosin beta-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were consider to be of cortical origin.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Infant, Newborn; Myasthenia Gravis; Phenotype; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms

Topics: Adolescent; Adult; Child; Cytoplasmic Granules; Humans; Microscopy, Electron; Myasthenia Gravis; Thymosin; Thymus Gland

Topics: Adolescent; Adult; Child; Drug Evaluation; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Thymosin

The localization of the three best-defined thymic hormones, namely, thymulin, thymopoietin and thymosin alpha 1 was studied by immunofluorescence using antibodies directed against these three molecules. With both human thymus frozen sections and cultured cells, thymic hormones were found exclusively in the epithelial component (recognized by its keratin content), in normal as well as pathological thymuses. The double-labeling experiments using the different anti-thymic hormone antibodies showed that the same epithelial cells contained the three hormones. These results suggest that the production of different hormones in the thymus is accomplished by the same epithelial cells.

Topics: Cells, Cultured; Fluorescent Antibody Technique; Freezing; Histological Techniques; Humans; Myasthenia Gravis; Thymalfasin; Thymic Factor, Circulating; Thymoma; Thymopoietins; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms

We studied the interaction of the thymic hormone thymosin alpha 1 with peripheral blood B and T lymphocytes in patients with myasthenia gravis (MG), using antibodies against thymosin alpha 1 in an immunofluorescence technique. Eleven of 16 patients with symptomatic MG had an increased number of T lymphocytes bearing surface thymosin alpha 1 (T alpha 1); 5 patients with asymptomatic disease had normal levels of T alpha 1. In six young adults with symptomatic MG who subsequently responded to thymectomy, the number of T alpha 1 cells returned to normal 1 month after thymectomy. Because levels of T alpha 1 correlated with symptoms and thymosin alpha 1 specifically recruits helper T cells, our findings suggest that T alpha 1 may play an immunoregulatory role in the pathogenesis of MG. Determination of T alpha 1 levels may prove to be helpful in assessing residual thymic activity after thymectomy.

Topics: Fluorescent Antibody Technique; Humans; Leukocyte Count; Myasthenia Gravis; T-Lymphocytes; Thymectomy; Thymosin; Thymus Hormones

Topics: Adult; Female; Humans; Lupus Erythematosus, Systemic; Myasthenia Gravis; Thymectomy; Thymosin

Topics: Culture Media; Humans; Immunologic Deficiency Syndromes; Myasthenia Gravis; Nucleotidases; T-Lymphocytes; Theophylline; Thymosin; Thymus Gland

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Cytotoxicity, Immunologic; Humans; Lupus Erythematosus, Systemic; Lymphocyte Culture Test, Mixed; Lymphocytes; Myasthenia Gravis; Thymalfasin; Thymosin; Thymus Gland; Thymus Hormones

Thymosin alpha 1 (alpha 1) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin alpha 1, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells: this was markedly evident in thymomas. "Involuted" MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-alpha 1 stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone alpha 1 to be the thymic epithelial cell; (b) raise the possibility that excess alpha 1 may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) suggest that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their positivity in tissue culture.

Topics: Adolescent; Adult; Child; Epithelium; Fluorescent Antibody Technique; Humans; Middle Aged; Myasthenia Gravis; Thymalfasin; Thymoma; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms

Thymosin-alpha 1 (alpha 1) is a potent thymic polypeptide hormone. Using anti-alpha 1 antibodies, we applied indirect immunofluorescence to human normal thymus of different ages and to hyperplastic, thymomatous, and "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassell's corpuscles, and proliferated in thymomas. Whereas normal thymuses and fewer and weakly stained cells, MG thymuses had many strongly positive epithelial cells; this was more evident in thymomas. Germinal centers were unstained. "Involuted" MG thymuses had small islands of brightly stained cells lying among the fatty tissue. In cultured thymuses from three MG patients, epithelial cells but not fibroblasts were brightly stained for alpha 1. Our findings (a) demonstrate the location, and presumably the origin, of alpha 1 to be the thymic epithelial cell; (b) suggest the possibility that excess alpha 1, because of its known effect on T-lymphocyte maturation and transformation of precursors to helper T-cells, may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) indicate that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their alpha 1 positivity in culture.

Topics: Adolescent; Adult; Cells, Cultured; Epithelium; Fluorescent Antibody Technique; Humans; Middle Aged; Myasthenia Gravis; T-Lymphocytes; Thymalfasin; Thymosin; Thymus Gland; Thymus Hormones

Topics: Female; Humans; Immunotherapy; Male; Myasthenia Gravis; Thymosin; Transfer Factor

Topics: Humans; Myasthenia Gravis; Thymosin; Thymus Hormones

Thymus-derived (T) lymphocytes in the peripheral blood and cellular immune function have been studied in ten patients with myasthenia gravis and in fifteen different myasthenic patients more than 10 years after thymectomy. The results were compared with those of a normal control population. The non-thymectomized myasthenic patients had normal T lymphocyte concentrations measured by rosetting with native sheep red cells. These patients also showed normal sensitization and recall of delayed hypersensitivity, phytohaemagglutinin (PHA) induced lymphocyte transformation and antibody-assisted (K cell) cytotoxicity; however, PHA-induced cytotoxicity was markedly reduced (P less than 0.001). The thymectomized group exhibited a lower mean percentage and absolute number of E-rosette-forming cells, which returned toward normal after in vitro treatment with thymosin. PHA-induced lymphocyte cytotoxicity, however, was normal in the patients who had undergone thymectomy, as were lymphocyte transformation, antibody-assisted cytotoxicity and sensitization to dinitrochlorobenzene (DNCB); there was a decrease in recall of established delayed hypersensitivity. Adult thymectomy in man, therefore, produces a partial and dissociated decrease in T cell responses and it is unlikely that the beneficial effect of this operation in myasthenia gravis is related to immunosuppression.

Topics: Adolescent; Adult; Aged; Antibody-Dependent Cell Cytotoxicity; Female; Humans; Hypersensitivity, Delayed; Lymphocyte Activation; Male; Middle Aged; Myasthenia Gravis; Rosette Formation; Skin Tests; T-Lymphocytes; Thymectomy; Thymosin