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PubMed1989

Therapy of secondary T-cell immunodeficiencies with biological substances and drugs.

Thymus-dependent (T) lymphocyte defects are common in cancer. Recent advances in the understanding of the regulation of T-cell development by biologicals and drugs now allow the formulation of better strategies of immune reconstitution to correct these defects. Thymic hormone preparations of several types offer one type of approach; however, they are somewhat limited in their reconstitutive ability. Interleukins (IL), particularly IL-1 and IL-2, appear to be complementary to the actions of thymic hormones in promoting T-cell development. Two classes of thymomimetic drugs have been identified and are represented by levamisole and isoprinosine. These drugs mimic by indirect and direct actions, respectively, the actions of thymic hormones. Newer analogs of these compounds have emerged which appear more effective. Also new factors, e.g. pituitary factors, are emerging which may be potent regulators of the immune system and useful in therapy. These agents may now be more effectively integrated with cytodestructive therapy in cancer treatment.

Biological Factors↗
PubMed1980

Thymic hormonal effect on human peripheral blood lymphocytes in vitro. III. Conditions for mixed lymphocyte-tumor culture assay.

Conditions for the reproducible measurement of thymic hormonal effect on the functional activity of human peripheral blood lymphocytes (PBL) were determined using a mixed lymphocyte-tumor culture assay. Three thymic hormonal preparations (thymopoietin, thymic humoral factor and TP-1) were tested by this assay and found to have a significant enhancing effect on the blastogenic response. Essential for the demonstration of the hormonal effect was the selection of suboptimal stimulation conditions, with the appropriate cell lines, including the number of stimulating cells and the time in culture. The most reproducible results were achieved when 1 x 10(5) PBL were co-cultured for 4 days with 1 x 10(4) mitomycin-C treated Raji lymphoma cells, after 1 h preincubation with one of the thymic preparations. However, strong enhancing effects of the thymic preparations could also be demonstrated with other tumor cel lines, especially IgR3 melanoma cells.

Adenocarcinoma↗
PubMed1977

Is there acetylcholine receptor in human thymus?

Recent studies have suggested that thymus tissue of the calf may bear nicotinic acetylcholine receptors. The presence of similar receptors in thymus tissue of man could thereby serve as a source of antigen for the production of antibody to the acetylcholine receptor in patients with myasthenia gravis. In the present experiments, human thymus tissue was examined for the presence of acetylcholine receptor. Both [125I] alpha-bungarotoxin binding and antiserum to the human acetylcholine receptor were used in tests for acetylcholine receptor in thymus glands from normal individuals and from patients with myasthenia gravis. Neither normal nor myasthenic thymus tissue were found to possess the [125I] alpha-bungarotoxin binding or the antigenic properties of the acetylcholine receptor.

Antibodies↗
PubMed1984

Demonstration of terminal deoxynucleotidyl transferase in single cells by indirect immunofluorescence. II. An examination of specificity.

Advantages in the use of indirect immunofluorescence for the identification of terminal transferase (TdT) in single cells may be offset by lack of specificity, as compared to the biochemical assay of the enzyme, especially in analyses of lymphocyte populations. False positive results were obtained in 15/15 tonsillectomy samples and in 9/27 specimens from children with acute lymphoblastic leukemia in remission, perhaps due to antihuman lymphocyte activity in the rabbit heteroantisera which are used in the indirect immunofluorescence technique. This phenomenon may be more pronounced in 'activated' normal lymphocytes. Such reactions are not due to antibodies directed against adenovirus, papovavirus or EB virus antigens, although these are common constitutents of human tonsillar cells. Additional problems with TdT heteroantisera may result from immunization with non-TdT determinants in calf thymus extracts, as was manifest in human non-lymphoid (KB) cells cultured in fetal bovine serum. These difficulties will be overcome only by production of a monoclonal antibody using human TdT as the antigen.

Adult↗
PubMed1986

The assay of the activity of protein kinase C with the synthetic oligopeptide substrate designed for histone kinase II.

The activity of histone kinase II was determined on the basis of its ability to phosphorylate the nonapeptide Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide designed previously as a specific substrate for this enzyme. Histone kinase II was purified from calf thymus extract by DEAE-cellulose chromatography followed by hydroxylapatite chromatography and high-performance liquid chromatography on a Protein Analysis column (I-125). The Mr value of histone kinase II estimated by the latter method was 50,000-55,000, but several observations indicated that histone kinase II was a product of a proteolytic process. Since the substrate specificity determinants for histone kinase II known from our previous investigations are very similar to those for protein kinase C, it was presumable that histone kinase II was the proteolytic fragment of protein kinase C. Therefore, the nonapeptide was tested as a substrate for protein kinase C prepared from rabbit brain extract by DEAE-cellulose chromatography. The activity of histone kinase II was also detected in brain extract. Histone kinase II was eluted from the DEAE-cellulose in the known position of the proteolytic fragment of protein kinase C. The nonapeptide Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide proved to be a better substrate than H1 histone for the detection of the activity of protein kinase C because it was not phosphorylated by the cAMP-dependent protein kinase and the Vmax of protein kinase C was about one order of magnitude higher with the peptide than with H1 histone. The apparent Km of protein kinase C for the peptide was identical with that of histone kinase II (0.2 mM).

Animals↗
PubMed2003

Failure of blood-thymus barrier as a mechanism of tumor and trophoblast escape.

A major process through which the immune system becomes tolerant to self-proteins involves the deletion of self-reactive clones in the thymus, but clonal deletion is not single mechanisms of thymic tolerance. There is now much evidence that intrathymic antigen expression results in anergy induction of T helper type-1 (Th1) clones in the periphery. Blood-thymus barrier is most important structure for prevention of unwanted penetration of antigens into the thymus. Impermeability of the barrier restrain induction of acquired thymic tolerance on unwanted antigens like microbes and tumor cells. Nevertheless, one of most important mechanism of tumor and trophoblast escape is in anergy of Th1 cells and in Th2 cells domination. Many mechanisms are included in disarrangement of Th1/Th2 balance in pregnancy and tumor bearers, but one of possibility is in failure of blood-thymus barrier. Possible consequences of blood-thymus barrier failure are trophoblast-specific or tumor-specific antigens penetrate into the thymus, deletion or anergy of antigen-specific clones and acquired thymic tolerance induction. Blood-thymus barrier is variable structure in anatomical and functional sense so that in certain condition foreign antigens probably can permeate across the barrier. Probability that some factors like hormones, cytokines, prostaglandine and neuromediators can affect blood-thymus barrier permeability and contribute in mechanisms of trophoblast and tumor escape is real but relatively unexplored.

Animals↗
PubMed1985

Thymic peptide hormones: basic properties and clinical applications in cancer.

The manuscript will provide an in-depth and critical review of the nomenclature, biochemistry, biological properties, and a summary of published and on-going clinical trials with all reported thymic preparations, including both partially purified thymic factors (e.g., thymosin fraction 5, thymostimulin) as well as purified and synthesized thymic peptides (e.g., thymosin alpha 1, thymulin). Particular emphasis will be placed on which thymic peptides should be categorized as true hormones. In addition, the comparative biochemistry and biological activity in animals will be summarized and contrasted for all the currently available thymic factors. The effects, in vitro of thymic factors, on peripheral blood lymphocytes isolated from normal donors and patients with primary immunodeficiency disorders, autoimmune disorders, and neoplastic disorders will also be reviewed. Finally, a detailed critical summary of the clinical trials performed with each of the thymic preparations will be presented with an emphasis on treatment of patients with cancer.

Amino Acid Sequence↗
PubMed2004

Isolation and identification of a new thymic peptide from calf thymus.

Various thymic peptides (including thymulin, thymic humoral factor, thymopoietin, etc.) play important roles in the process of T cell maturation and development. We isolated a new peptide from calf thymus and named it thymus activity factor II (TAF-II). A yield of 0.92 mg of TAF-II was purified from 500 g calf thymus. Analysis by LC/MSD-Trap showed the amino acid sequence of this hexapeptide to be Glu-Ala-Lys-Ser-Gln-Gly-OH with molecular weight 618.5 daltons. We have also begun to investigate the influence of TAF-II.

Adult↗