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Autoimmune response to the Ro/SSA particle is directed to the human antigen.

Autoantibodies to defined cellular antigens in systemic lupus erythematosus (SLE) are usually directed to conserved epitopes on ubiquitous macromolecules including histone, Sm + nRNP (URNP particles), DNA, and La(SSB). We report here that the autoimmune response to the Ro(SSA) RNA protein particle is directed to epitopes on the human antigen which are not conserved in evolution. Ro(SSA) from bovine, rat, and mouse Ro(SSA) particles cross-react with human autoantibodies less effectively than does human Ro(SSA), and antigenically active Ro(SSA) is not detectable in chicken thymus extracts with the assays employed. These data suggest a special role for the Ro(SSA) antigen in the initiation and/or perpetuation of the anti-Ro(SSA) response in autoimmune disease.

Absorption↗

Influence of thymic preparations on the result of experimental infection with Taenia crassiceps (Zeder, 1800) in ICR mice.

Thymalin (Thymarin) and T-activin--thymic preparations of polypeptidic character--were used for influencing the parasitic infection in a model system mouse--Taenia crassiceps. A single subcutaneous application of 100 micrograms of Thymalin per mouse at the day of infection resulted in a decrease (by 54.9%) in the number of cysticerci in peritoneal cavity of experimental mice compared with the controls. Administration of Thymalin with T. crassiceps larval homogenate at various intervals before and after infection resulted in a statistically significant increase of the level of specific antibodies in the serum of infected mice, this increase, however, did not correlate with the corresponding protective effect. Immunosuppressant azathioprine, injected subcutaneously from 7th to 3rd day preceding infection at a dose of 100 micrograms resulted in a significant increase in the number of T. crassiceps larvae in the peritoneal cavity of experimental mice compared with the controls (by 48.7%). T-activin, injected subcutaneously to mice, immunosuppressed by azathioprine, led to a restoration of resistance of mice to T. crassiceps infection. Subcutaneous application of T-activin alone had a significant protective effect (decrease in cysticerci number by 53.7% in comparison with the controls). Correlation of the level of specific antibodies in the serum of infected mice, value of spleen index and number of T. crassiceps cysticerci in peritoneal cavity of mice was not detected.

Adjuvants, Immunologic↗

Prepubertal rat thymus secretes a factor that modulates gonadotropin secretion in cultured rat pituitary cells.

Thymus development and function are influenced by endocrine glands. On the other hand, the absence of thymus results in endocrine disturbances. The aim of the present paper is to investigate the direct influence of thymus products on the gonadotropin secretion of rat pituitary cells in culture. In this study, a chromatographic fraction obtained from the acetonic powder of thymus from 14-15 day-old rats (TF) increased the GnRH stimulated LH and FSH secretion from cultured pituitary cells, but had no effect on the basal secretion of these gonadotropins. The addition of incubation medium from thymus (TIM) to cultured pituitary cells further enhanced GnRH stimulated FSH and LH production, the effect was dose related. The GnRH potentiating effect of thymus incubation medium was also present in a chromatographic fraction of around 28 Kd obtained from this medium. These data suggest that the prepubertal thymus contains and secretes a factor that modulates pituitary cells secretion potentiating the Gn-RH effect.

Age Factors↗

Thymostimulin: an immunohistochemical and immunological evaluation.

The immunohistochemical and immunological properties of a rabbit serum raised against the calf thymic hormonal factor "Thymostimulin" were studied on mammalian and human thymuses, discussing the problem of species-specificity. The serum was also injected in chick embryos to study the possible interrelationship between avian thymus and Bursa of Fabricius.

Animals↗

[The relation of changes in the surface markers and the induction of thymocyte functional activity under the action of humoral thymic factors].

Mouse thymocytes were fractionated on PNA+- and PNA-cells. The PNA+-fraction was treated by tactivin--a preparation of thymic hormones. The treatment resulted in the loss of PNA-receptors from the surface of 10-12% of PNA+-cells. The treated suspension was again fractionated by the same method. PNA-thymocytes derived from both the first and the second procedure of fractionation expressed less Thy-1.2 antigen and SBA-receptors than PNA+-cells. Primary and induced PNA-thymocytes were able to produce IL-2 after mitogen stimulation. The data can be interpreted as an evidence of the ability of thymic hormones to induce not only a phenotypical but also a functional maturation of PNA+-thymocytes and of linkage of all the observed signs of maturation.

Adjuvants, Immunologic↗

Localization of thymostimulin in mammalian thymuses: comparative evaluation.

An anti-thymostimulin (TS) serum was tested on rabbit, guinea-pig, lamb and pig thymuses to study the localization of the hormonal factor. The immuno-peroxidase method, with some modifications, was applied to tissue fixed in Bouin's or in Bouin-PAF liquids and embedded in paraffin wax. Immuno-reactivity was shown in reticulo-epithelial cells in the cortex, in the medulla and in the external cells of the Hassall's corpuscles. The intensity of the immuno-reaction is stronger in pig thymus, whereas in lamb, rabbit and guinea-pig thymuses it is more uniform and pale, but to varying degrees. Comparison with the localization of TS in thymuses of other mammals and man and the problem of species-specificity were discussed.

Animals↗

[Comparative study of the effect of the thymus preparations thymoptin and thymalin on fibrin-monomer polymerization].

Thymoptin was shown to possess the ability of lysis of the nonstabilized fibrin in vitro and of increasing the nonenzymatic fibrinolytic activity of blood plasma after eight daily intramuscular injections to rats in doses of 1 and 100 micrograms/kg body weight and during incubation with purified fibrin monomer to produce its depolymerization. Thymalin possessed no nonenzymatic fibrinolytic activity in vitro and in contrast to thymoptin at a relatively high concentration (1000 and 100 micrograms/ml) enhanced fibrin-monomer polymerization.

Animals↗

[Analysis of immunoregulatory peptides of the thymus using high performance liquid chromatography].

High performance liquid chromatography (gel filtration and chromatography in the reverse phase) was applied to analyse a composition of the heterogenous immunoregulating peptide preparation T-activine isolated from calf thymus. Gel chromatography at high pressure on the column TSK G2000 SW enabled to separate T-activine into 3 subfractions at a preparative scale. Physico-chemical properties and biological activity of these fractions were studied in vitro. Subfraction B with molecular mass of 1.0-3.5 kD and pI below 5.9 proved to be the most active.

Animals↗

[Assessment of the action of taktivin on different stages of T-lymphocyte maturation].

Tactivin, the thymic hormone preparation, evokes some phenotype alterations in T-cell precursors (elimination of SC-1 antigen and expression of Thy-1-antigen) and cortical thymocytes (a decrease in the number of thymocytes carrying PNA-receptor) similar to those arising in T-cell differentiation. Tactivin induces PNA+ -thymocyte response to PHA action and increases PHA response to PNA- -thymocytes. It is weakly mitogenic for T-cell precursors and PNA- -thymocytes. The data suggest that Tactivin may be used for the treatment of immune deficiencies with T-cell differentiation and function defects.

Adjuvants, Immunologic↗

The effect of La(SSB) on PWM-induced immunoglobulin synthesis by anti-La(SSB) positive SLE patients and healthy controls.

The effect of affinity purified La(SSB) on immunoglobulin synthesis in vitro by mononuclear cells (MNC) from anti-La(SSB)-positive systemic lupus erythematosus (SLE) patients and healthy controls was studied. La(SSB) was prepared from calf thymus extract and characterized by SDS-polyacrylamide gel electrophoresis and immunoblotting. Silver staining of gels reveals nine major bands at 68 kD, 43-48 kD and 30-33 kD, of which six were recognized on immunoblots by sera from anti-La(SSB) positive SLE patients. Studies in vitro showed that La(SSB) alone did not stimulate total IgG or IgM synthesis in controls or SLE patients. Low concentrations of La(SSB) (optimal dose less than 0.02 ng/ml) suppressed pokeweed mitogen (PWM)-driven IgG synthesis by controls but not by anti-La(SSB) positive SLE patients. IgM responses were unaffected. Anti-La(SSB) and anti-DNA were detected in PWM-stimulated cultures from both study groups. In the presence of La(SSB) IgM anti-La(SSB) synthesis was enhanced in anti-La(SSB)-positive patients in a dose-dependent manner. In contrast, La(SSB) inhibited anti-La(SSB) production by controls (maximal at 2 ng/ml). La(SSB) had no effect on anti-DNA production in either group. Pre-incubation of control or anti-La(SSB)-positive SLE MNC with La(SSB) before addition to autologous PWM-driven cultures did not induce suppressor cells, although pre-incubation with Concanavalin A (ConA) did. Thus we suggest that La(SSB)-induced suppression of IgG synthesis in PWM-driven control cultures may not be due to induction of regulator cells, possibly missing from SLE cultures, but perhaps is a direct effect on B cells.

Adult↗

[The role of thymic microenvironment in T-cell maturation].

The role played by different components of thymic microenvironment in T-cell-maturation is examined: antibodies to a soluble thymic factor (STF) were thus shown to inhibit T-cell maturation in the chicken while incubation of bursal "null" cells with STF could induce the differentiation of some of them into T cells. In addition to STF, whose properties resemble those of other soluble thymic factors, an insoluble thymic factor (ITF) is described: it is localized mainly in membranes associated with medullary blood vessels, and its injection to mice provokes an influx of marrow stem cells into the thymus.

Animals↗

Thymus hormones.

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Humans↗

In vitro and in vivo induction of terminal deoxynucleotidyl transferase activity in bone marrow cells by thymic humoral factors derived from a tumor cell of thymic epithelial origin.

Thymic epithelial tumor cell supernatant fraction 5 isolated from the cell culture medium of a tumor cell of thymic epithelial origin was tested for its ability to induce TdT expression. TdT activity could be induced in fractionated and unfractionated bone marrow cells from athymic nude rnu/rnu rats by supernatant fraction 5. Incubation with supernatant fraction of 5 rnu/rnu bone marrow cells isolated from the interface between 23% and 26% BSA restored the level of TdT activity to levels normally found in the thymus-bearing rnu/+ littermates. A does-related response was observed in vitro and in vivo in the expression of TdT. TdT induction in vitro was maximal with 5 micrograms/ml supernatant fraction 5 and in vivo with 200 micrograms supernatant fraction 5/rat/day. The effect was specific in that neither saline nor culture medium fraction 5 treated cells were induced to express TdT. The data presented in this study demonstrate that thymic epithelial tumor cell supernatant fraction 5 exerts an influence on the early maturation and differentiation of bone marrow stem cells.

Animals↗

[Effect of a low-molecular humoral factor of the thymus gland on the lymphocyte sensitivity to phytohemagglutinin].

The preincubation of mouse spleen lymphocytes with a low molecular lymphocytosis-stimulating substance from the thymus (LSS), or the addition of the LSS to the cultures caused inhibition of the mitotic response of lymphocytes to phytohemagglutinin (PHA). LSS induced transformation of murine thymocytes to the blast cells capable of mitotic division. This transformation was depressed by PHA. The lymphocytes of the mice injected LSS in vivo responded weakly to PHA at first, but in 5 days a significant intensification on the response to PHA was observed. It is concluded that LSS may activate the T-cells responding to PHA.

Animals↗

The effect of thymic substances on T circulating cells of patients treated for Hodgkin's disease.

Forty-one patients with Hodgkin's disease staged as IA(4), IIA/B(4/6) IIIA/B(6/9) and IVA/B(3/9) who had had radiotherapy (subtotal nodal irradiation (STNI) or total nodal irradiation (TNI), or combined one (STNI/TNI plus chemotherapy MOPP or MOPP/ABVD) have been enrolled consequently and randomized to receive thymic hormone (17 patients) or pentapeptide treatment (14 patients) for 3-6 months at the end of the therapeutic regimens. In all patients severe immunodeficiency evaluated either as leukopenia (WBC less than 4000/mm3) or lymphocytopenia (lymphocytes less than 1500/mm3) or CD3 and CD2 cell reduction, or imbalance of helper/suppressor (H/S) ratio have been documented before starting thymic therapy. Different results by immunorestorative therapy have been registered according to the entity of immunodeficiency. In fact in the group of 15 patients with severe lymphopenia (lymphocytes less than 1000/mm3) either the thymic hormone or the synthetic drug produced a significant increase of all subsets examined: CD3-CD2-CD4-CD8 without or with minimal influence on H/S ratio, due to the increase of absolute lymphocytes count. In the remaining patients with mild or no lymphopenia the two drugs resulted ineffective on T cells. Comparing the overall group of patients who received thymic therapy with a control group of patients who did not, an advantage in terms of recruitment of T cell compartment has been observed in the former group when mean values are compared. According to the clinical impact of the immunotherapy with thymic substances on these patients, a significant decrease in incidence of herpes virus infection (HVI) has been observed in patients who had had thymic therapy compared with the incidence of HVI in the control group (18% versus 53.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

[Characteristics of the inhibition of thymus endocrine function and synthesis of substances with thymosin-like activity caused by thymostimulin and splenin during DMBA-induced mammary gland carcinogenesis in rats].

The contents of thymic hormones and endogenous substances with thymosin-like activity (TLA) was studied under conditions of administering thymostimulin and splenin during DMBA-induced carcinogenesis in rat mammary glands. It has been established that during latent carcinogenesis there is an inhibition of thymic endocrine function which persists in tumour-bearing animals. Injections of thymostimulin and splenin induce synthesis of substances with TLA, accompanied by an inhibition of blastoma development.

9,10-Dimethyl-1,2-benzanthracene↗