Isolation and partial chemical characterization of THF, a thymus hormone involved in immune maturation of lymphoid cells.
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Amino Acids↗
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Results for “Thymus Extracts”
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Effect of thymic humoral factor in vitro on human bone marrow and blood cells from B-, T- and null-cell acute lymphatic leukemia.
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Adolescent↗
Management of human papilloma virus vulvo-perineal infection with systemic beta-interferon and thymostimulin in HIV-positive patients.
OBJECTIVES: To evaluate the effect of a combined therapy based on beta-interferon and thymostimulin in HIV-seropositive women with florid vulvoperineal condylomatosis. METHODS: Nineteen HIV-seropositive women affected by HPV florid vulvo-perineal infection were studied. Their ages ranged from 19 to 32 years (mean = 26); all were smokers; 11 (57.89%) were intravenous drug users with a mean period of drug addiction of 5 years. No patient was on AZT therapy. All patients underwent a combined medical therapy based on beta-interferon administration with doses of 3,000,000 IU i.m. daily for 7 days and subsequently on alternate days for 2 weeks associated with the administration of 70 mg i.m. of thymostimulin per day on alternate days for 30 days. RESULTS: Seven (36.84%) patients showed complete recovery at the end of follow-up; 5 (26.31%) patients showed partial recovery and 7 (36.84%) did not respond to therapy. CONCLUSION: A pro-host immunotherapy seems to be indicated in patients affected by immunodeficiency syndrome.
AIDS-Related Opportunistic Infections↗
Analysis of the mammalian recombination protein complex RC-1.
Based on a novel cell-free assay for DNA recombination, we previously reported the purification and initial characterization of RC-1, a protein complex catalyzing the recombinational repair of deletions and gaps. RC-1 was isolated from calf thymus nuclear extracts and shown to copurify with several enzymatic activities, among them a DNA polymerase. Here, additional evidence is reported identifying the polymerase as DNA polymerase epsilon. Furthermore, a novel DNA structure-dependent endonuclease associated with RC-1 was observed, which recognizes and cleaves branched DNA substrates at specific sites. Implications of this endonuclease activity for the recombination reaction are discussed.
Base Sequence↗
Description of a serological reaction characteristic of polymyositis.
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Animals↗
Serum thymic factor in subacute sclerosing panencephalitis patients.
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Child↗
Functional properties in Sézary cells with an unusual phenotype.
The immunological and functional characteristics of Sézary cells with an unusual phenotype are reported. The clinical, histologic, and hematologic picture was typical for Sézary syndrome. Studies with monoclonal antibodies showed that 80% Sézary cells had an CD3+, CD4+, CD5+, CD7-, CD8-, Leu-7+, Leu-8-, Leu-11-, OKM1- phenotype. By two-color immunofluorescence assay 80% FACS-sorted Leu-7+ cells coexpressed CD4 antigen and did not express the myeloid antigen OKM1, CD8, and antigens characteristic of immature T cells. The cells had no NK activity but did display a high helper activity. Unseparated and FACS-sorted Leu-7+ and Leu-7- Sézary cells did not respond to mitogens but were able to grow in the presence of exogenous IL-2. FACS sorted Leu-7- cells, cultured for 7 days in the presence of 20% IL-2, acquired the receptors for Leu-7. IL-2 and IFN-gamma production was studied in unseparated Leu-7+ and Leu-7- FACS-sorted Sézary cells. IL-2 production was lower than in normal cells. The addition of PHA or PHA plus TPA led to an increase in IL-2 production. Also IFN-gamma production was marked lower than in normal controls but increased after 7-day culture in exogenous IL-2. In conclusion in this case the Sézary cells may represent a neoplastic expansion of the CD3+, CD4+, CD5+, Leu-7+, Leu-11- subpopulation which is equivalent to the 2-4% of the Leu-7+ population in normal lymphocytes.
Aged↗
Chemical synthesis of a peptide fragment of thymopoietin II that induces selective T cell differentiation.
Thymopoietin is a polypeptide hormone of the thymus that consists of a 49 amino acid polypeptide chain of 5562 daltons. A peptide corresponding to positions 29-41 of bovine thymopoietin II was synthesized by the Merrifield solid-phase technique. This peptide was shown to have a purity (correct sequence) of 96% by amino acid and C terminal analyses and by a complete determination of the amino acid sequence by manual Edman degradations. It displayed a selectivity of action similar to that of thymopoietin itself, inducing the differentiation of T lymphocytes but not of complement receptor (CR+) B lymphocytes. Although a number of substances induce the differentiation of both T cells and CR+B cells under the conditions of assay in vitro, only thymopoietin and the synthetic peptide described in this report have been shown to induce the differentiation of T cells selectively. Our data establish that the key residues involved in the active site of thymopoietin are present within a synthetic polypeptide which constitutes a minor portion of the amino acid sequence of thymopoietin. Since this peptide had 3% activity by comparison with thymopoietin, the tertiary structure of thymopoietin may be required for optimal configuration of the active site to produce full biological activity.
Amino Acid Sequence↗
Distribution of actin content in human B and T lymphocytes by DNAse 1 inhibition test.
The DNAse inhibition assay, which allows for the titration of two forms of soluble actin in cell extracts, has been applied to normal human lymphocytes from peripheral blood. Actin-like activities associated with the membrane-rich fraction of extracts from thymus dependent (T) lymphocytes are significantly higher than those from bone marrow derived (B) lymphocytes, on a per cell basis, provided care is paid to the elimination of monocytic and polymorphonuclear cells which produce significantly higher DNAse 1 inhibition. The apparent discrepancy with a recent report that normal T and B lymphocytes do not differ in their total actin content is discussed with respect to the functional uniqueness of membrane-associated DNAse 1 inhibitions and the importance of using purified lymphocyte populations.
Actins↗
Visualization of poly(ADP-ribose) synthetase associated with polynucleosomes by immunoelectron microscopy.
Antibodies showing a high specificity for poly(ADP ribose) synthetase have been purified. A fraction binding nonspecifically to histones present in antiserum and non-immune serum has been demonstrated by immunoblotting and separated by histone-Sepharose chromatography. The antibody without the nonspecific binding fraction was analyzed by Western blot with calf thymus protein extract and was found to react only with a band at 116 kDa. There was no reaction with purified topoisomerase I, this weak activity was copurified with poly(ADP-ribose) synthetase preparation. The specific IgG fraction has been used for the visualization of the interaction of poly(ADP-ribose) synthetase with chromatin by indirect gold-labelling. This immunomicroscopic study suggests that the synthetase is located in the inner part of polynucleosomes and would be associated preferentially with the core nucleosome.
Animals↗
Effect of thymostimulin in models of cell-mediated and humoral autoreactivity and on T-dependent suppression.
To explore the therapeutic potential of the thymic hormone preparation thymostimulin (TS) in animal models of cell-mediated and humoral autoimmunity, its effects were investigated on experimental allergic encephalomyelitis in guinea pigs and on anti-erythrocytic autoantibody production in C57B1/6 mice. In both autoimmunity models, TS produced significant therapeutic effects in terms of proportion of diseased animals, disease severity and/or disease duration; however, both the TS dose and the time of treatment start relative to the disease-inducing stimulus critically influenced results. TS effects on the generation and expression of suppressive activity induced in C57B1/6 mice by a supraoptimal immunization with 10(10) SRBC were also examined. TS given after 10(10) SRBC did not influence the level of suppression, and the activity of effectors of suppression was not modified by this agent. Conversely, using a treatment protocol analogous to that effective in reducing murine autoantibody production, TS administration prior to 10(10) SRBC was associated with a significant increase in the subsequent generation of T-dependent, antigen-specific suppressive activity. These findings suggest that effects of TS on the development of suppressor cells may be involved in the activity of this agent in animal models of autoaggression.
Animals↗
The combined administration of thymomodulin and interleukin 2 reverses T-cell unresponsiveness in mice infected with Mycobacterium bovis-BCG.
Mice infected intravenously with high doses of M. bovis, strain BCG, showed a marked impairment of delayed-type hypersensitivity to PPD evaluated in in vivo skin tests and in vitro as splenocyte blast transformation. However, this state of unresponsiveness could be partially reversed after 1 month of infection by the intraperitoneal injection of a calf thymus acid lysate (thymomodulin). Furthermore, BCG-infected mice treated in vivo simultaneously with both thymomodulin and interleukin 2 immediately developed positive skin reactions and blast transformation to PPD and did not become anergic in the course of infection.
Animals↗
The combined treatment of human peripheral blood mononuclear cells with thymolymphotropin and interleukin 2 increases PPD-driven T-cell proliferation and IL-2 induced cellular cytotoxicity against HIV-infected cells.
Two in vitro systems (the DNA synthetic response to mycobacterial antigens and cytotoxicity against lymphoid cells) were used to analyse the effect of thymolymphotropin (TLT) on peripheral blood mononuclear cells (PBMC). Purified protein derivative of mycobacteria (PPD)-driven T-cell proliferation in low-responder donors was increased by the combined treatment with TLT and suboptimal doses of recombinant interleukin 2 (IL-2). Similarly, the activities of natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been enhanced in PBMC cultures pretreated with TLT. Also, TLT showed an enhancing effect on the development of LAK cells capable of lysing Epstein-Barr virus (EBV)-transformed B-lymphocytes infected or uninfected with the human immunodeficiency virus (HIV).
Cytotoxicity, Immunologic↗
Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder.
We have investigated the effect of thymostimulin on the major histocompatibility (MHC) unrestricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) from patients with superficial transitional cell carcinoma (TCC) of the bladder. PBMNC from patients and healthy controls were incubated in the presence of thymostimulin for varying periods of time (2 or 18 h or 5 days), and were used as effectors against 51Cr-radiolabeled natural killer (NK)-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxic assays. In 6 out of 14 patients analyzed, thymostimulin enhanced the cytotoxic activity of PBMNC against NK-sensitive target cells in a dose-dependent manner. This cytotoxic inducer effect of thymostimulin was maximal after 18 h of culture. Thymostimulin failed to induce lytic activity in PBMNC from TCC patients against NK-resistant target cells. We also found that thymostimulin could synergize with interleukin-2 in inducing non-MHC restricted cytotoxic activity in PBMNC from TCC patients. In conclusion, we have demonstrated that thymostimulin can enhance the natural killer cytotoxic activity of PBMNC from patients with TCC of the bladder.
Adjuvants, Immunologic↗
CD4-8- T-cells increase in MRI/lpr mice treated with thymic factors.
The in vivo effect of thymic factors on immature lymphocytes was analysed in MRL/lpr mice. This strain carries a genetic defect that causes during their life cycle a block of T-cell differentiation and abnormal proliferation of CD4-8- (double-negative, DN) T-lymphocytes. In vivo administration of four preparations of thymic factors, thymopentin (TP-1), thymopoietin (TP-5), thymolymphotropin (TLT), and thymomodulin (TMD) into young (2-month-old) MRL/lpr mice induced a significant increase of DN T-cells both in the thymus and in the peripheral lymph nodes, with a concomitant decrease of double-positive (DP) T-cells in the thymus and of single-positive (SP) T-cells in the lymph nodes. The level of DNA fragmentation measured as propidium iodide fluorescence was increased in the thymus population of young mice and in the lymph node population of old mice treated with TLT. SCID mice transplanted with lymph node cells from MRL/lpr donors (MRL-->SCID) developed graft versus host (GvH) reaction due to the activation of MRL CD8+ alloreactive T-cells. This model was used to analyse the effect of TMD/TLT in vivo on MRL cell proliferation and expansion; in fact, spleen cells from MRL-->SCID mice after treatment with TMD/TLT showed an increased cell proliferation, and an expansion of DN T-cells with a concomitant decrease of SP cells (both CD4+ and CD8+ cells). Decreased SP cell numbers in this context could explain why TMD/TLT treatment of SCID mice engrafted with MRL cells increased their survival compared to untreated MRL-->SCID mice.
Animals↗
Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin.
In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti-TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the results from enzyme-linked immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Adjuvants, Immunologic↗
Clinical improvement and partial correction of the T cell defects of acquired immunodeficiency syndrome (AIDS) and lymphoadenopathy syndrome (LAS) by a calf thymus acid lysate.
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Acquired Immunodeficiency Syndrome↗
A calf thymus acid lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report.
Thymomodulin is a calf thymus acid lysate capable of inducing T lymphocyte maturation. Fifteen patients with HIV infection at different stages according to the Walter Reed classification were treated with 60 mg/day of thymomodulin syrup for more than 50 days. Two WR6B subjects had clinical and immunological parameters unchanged and died, while the patient suffering from Kaposi's sarcoma presented an evident clinical and laboratory improvement with remission of the neoplasia. The other 12 patients ranging from WR2 to WR5B showed an improvement of clinical symptoms after thymomodulin therapy accompanied by the normalization of CD4/CD8 ratio (P less than 0.001). This helpers/suppressors increase was due to a significant increase of CD4 cells (P less than 0.01) and also to a decrease of the CD8 lymphocytes (P less than 0.05). Thymomodulin administration did not cause an enhancement of the urinary levels of neopterin, a marker of T-cell activation.
Acquired Immunodeficiency Syndrome↗