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PubMedDate not supplied

Study of thymic factors. II. Failure of thymosin to alter the natural history of NZB and NZB/NZW mice.

The effects of daily injections of thymosin, bovine fraction V, on the natural history of NZB and NZB/NZW F1 mice were investigated. With the use of several dose schedules, no significant differences were discovered in treated versus control groups when survival, autoantibodies, and mitogen responsiveness were compared. These results provide further evidence that thymosin may have little or no role in the treatment of the autoimmune disease of New Zealand mice. More encouraging research in thymic extracts and their measurement is necessary before clinical trials in SLE are considered.

Animals↗
PubMedDate not supplied

[The effect of complete thymic extract on motility and progressive motility of spermatozoa in asthenozoospermia].

The thymic gland is involved in immunologic and endocrinologic heomostasis of the body. Neonatal thymectomy of experimental animals leads to gonadal dysgenesis. Both eostrogen and androgen receptors have been identified in thymic epitelial cells, and sex steroids can be modulated by secretion of thymosin. High levels of thymosin alpha-1 in seminal plasma are correlated with sperm count, viability and motility in fertile males as compared to infertile ones. In this study we examined the effects of complete thymic extract on motility and progressive motility of spermatozoa obtained from asthenozoospermic men. In the first part of experiment, we studied the influence of complete thymic extract, as a bioactive medium component, on movement of spermatozoa samples with initial motility lower than 30%, in vitro. The study was carried out on two groups of sperm samples, 40 samples each, obtained by masturbation after a 72-hour-abstinence. After completed liquefaction at room temperature (30-40 min.), we determined the usual parameters of sperm quality. Total motility (M%) and progressive motility (PM%) of spermatozoa were analyzed in 10 microscopic view fields. Each group of sperm samples was prepared by swim-up and swim-down method. Then, we estimated the total motility and progressive motility of "washed" spermatozoa in every sample. In addition, every sample was divided in two equal parts. One part was immediately left in thermostat (control). To the second part we added 0.2 mg of complete thymic extract before incubation (experimental group). Total and progressive motilities were analyzed after 1, 4, 12 and 24 hours of incubation. The t-test was used for statistical analysis of results. The second part of the study was carried out on a group of 10 asthenozoospermic men (volunteers). We examined the influence of complete thymic extract, as intra-muscular injection, in a doze of 150 mg daily, during seven days, on motility and progressive motility of spermatozoa. Sperm samples were obtained by masturbation after four days of abstinence. We compared the parameters before and after the therapy. They were statistically processed by a method of difference. The results showed that the complete thymic extract increased the total and progressive motilities of spermatozoa separated by swim-down method (p < 0.001), in vitro (Table 1-4). The parenteral application of complete thymic extract, statistically significantly increased motility and progressive motility of spermatozoa in asthenozoospermic men (p < 0.05) (Table 5). These findings could be useful in assisted reproductive technology.

Adult↗
PubMed1996

Suppressive effects of Lactobacillus casei cells, a bacterial immunostimulant, on the incidence of spontaneous thymic lymphoma in AKR mice.

The mean survival age of female AKR/J mice was significantly prolonged, the enlargement of thymus was markedly suppressed, and the proliferation of ecotropic and recombinant murine leukemia viruses (MuLV) was markedly inhibited when 8-week-old female AKR/J mice were injected intraperitoneally (i.p.) with heat-killed Lactobacillus casei cells twice weekly for 8 weeks. In contrast, such actions of heat-killed L. casei cells were not seen in 20-week-old female AKR/J mice. The leukemogenic activity of the cell-free extract of thymus from adult female AKR/J mice in newborn female AKR/J mice was drastically reduced by i.p. treatment with heat-killed L. casei cells. The difference in adjuvant effectiveness of heat-killed L. casei cells on 8- and 20-week-old animals may be dependent on the difference in the enhancing activity of the cell-mediated immune systems between the groups induced by heat-killed L. casei cells, and, as a result, on the difference in the degree of proliferation of ecotropic and recombinant MuLV in thymus, which consequently causes thymic lymphoma.

Adjuvants, Immunologic↗
PubMed1985

Identification of a tumor cell-derived differentiation antigen on mouse colony-forming units in the spleen and progenitor cells.

Surface membrane antigen(s) expressed on a mouse mast cell line (FMP1) have also been shown to occur on hemopoietic spleen colony-forming units (CFU-S) and granulocyte/macrophage colony- and erythroid burst-forming cells, using a xeno-antiserum raised against FMP1 cells. This mast cell model has been used to obtain antiserum and large quantities of antigen for the biochemical identification of CFU-S and progenitor cell antigen(s). Immunoprecipitation of FMP1 membrane antigens with the antiserum and subsequent polyacrylamide gel electrophoresis revealed the presence of five membrane proteins with molecular weights of 28,000, 32,000, 36,000, 50,000, and 70,000. Mouse B-lymphoma cell line W279 which reacted with anti-FMP1 serum was found to possess three immunoprecipitable surface proteins with molecular weights of 32,000, 50,000, and 70,000. Attempts have been made to identify the antigen(s) expressed by CFU-S and progenitors which were revealed by immunoprecipitation from the tumor lines. The three lower-molecular-weight proteins (Mr 28,000-36,000) were chosen for initial study. Membrane extracts of FMP1 cells were fractionated on Sephacryl S-200, and selective pools of these antigens were made. Antisera to these pools exhibited complement-dependent cytotoxicity to FMP1 cells, bone marrow CFU-S, granulocyte/macrophage colony-forming cells, and erythroid burst-forming units. These antisera immunoprecipitated Mr 28,000, 32,000, and 36,000 proteins from FMP1 cell membrane extracts but not the Mr 50,000 and 70,000 antigens. The W279 line has only one antigen (Mr 32,000) in the lower-molecular-weight range and is able to absorb anti-CFU-S and anti-progenitor activity, which suggests that it is this antigen which is expressed on hemopoietic cells. In addition, thymocytes react with anti-FMP1 serum, and the Mr 32,000 antigen was immunoprecipitated from thymus cell extracts. Binding studies with concanavalin A, wheat germ agglutinin, and lentil lectin indicated that the Mr 28,000-36,000 proteins were glycoproteins. The apparent molecular weights of these proteins on polyacrylamide gels were not altered by reduction and alkylation and therefore do not contain disulfide-linked subunits.

Animals↗
PubMed1977

Xenogeneic neoplastic transplants in adult rats pretreated with thymic foetal extracts.

The paper deals with the effect of thymic extracts from young foetal pigs and calves on the development of tumour xenografts, i.e. mouse ascites Ehrlich carcinoma and hamster malignant melanoma, in rats. The results of experiments showed that Ehrlich carcinoma developed in 4 out of 72 animals, i.e., in those animals which had received thymic extracts from young foetal pigs, Ehrlich carcinoma led to their death. Ehrlich carcinoma assumed a solid form and the cells changed in their shape. It developed normally, when retransplanted to mice. Hamster melanoma, when transplanted to rats given thymic extracts from young foetal calves, developed and survived for long periods of time (in one animal up to 190 days, and in the remaining animals much longer than in the controls and the animals injected with liver extracts from young foetal calves). The melanoma xenograft was not morphologically changed. A normal development of the malignant process occurred when melanoma was retransplanted to hamsters. Animals injected with thymic extracts from young foetal calves exhibited lymphopoenia and a fall in gamma globulin levels before tumour transplantation.

Animals↗
PubMed2006

A comprehensive study of p53 transcriptional activity in thymus and spleen of gamma irradiated mouse: high sensitivity of genes involved in the two main apoptotic pathways.

PURPOSE: Gamma-irradiation leads to activation of p53 tumour suppressor gene and to p53-dependant stimulation of a large panel of cellular genes including proapoptotic genes involved in intrinsic and extrinsic pathways. Most in vivo published data referred to high (lethal) irradiation doses. The present study was performed to analyse the p53-dependent response to more relevant low irradiation doses. MATERIALS AND METHODS: Mice were whole body exposed to irradiation doses decreasing from 5 - 0.05 Gy. Gene expression was estimated by real time reverse transcriptase polymerase chain reaction measurements on RNA extracted from thymus and spleen. Apoptosis was evaluated by the percentage of either annexin V positive or sub-G1 cells. RESULTS: A 0.1 Gy irradiation dose already gives a significant stimulation of Puma (p53 up-regulated modulator of apoptosis), and 0.2 Gy of Bax (Bcl-2-associated X protein) and Killer/DR5 (Death Receptor 5). The expression of genes involved in the two apoptotic pathways was induced as soon as 1 h post-irradiation and reached a maximum at 3 h, the induction level depending on both the gene and the organ. A significant increase in the number of apoptotic cells is already detectable at 0.5 Gy with a maximum of induction at 6 h. CONCLUSIONS: Our results reveal the high in vivo sensitivity of p53-dependent transcriptional activation of genes involved in the two main apoptotic pathways, their stimulation preceding the induction of apoptosis.

Animals↗
PubMedDate not supplied

Hypothalamic modulation of immunoreactive oxytocin in the rat thymus.

Immunoreactive oxytocin was determined in a peptidic extract of rat thymus by means of a highly specific radioimmunoassay combined with high pressure liquid chromatography fractionation. Rat thymus was found to contain 80 +/- 7.5 pg/g wet tissue (congruent to 0.56 pg/mg protein) of oxytocin-like immunoreactivity, which behaved like synthetic oxytocin in the radioimmunoassay and in two different high pressure liquid chromatography columns. Oxytocin concentration was increased by bilateral electrolytic lesion of the paraventricular nucleus of the hypothalamus (PVN), and by high doses of corticosterone (10 mg/kg IM for 7 days) but was not modified by low doses of corticosterone (1 mg/kg IM for 7 days) or by hypophysectomy. The results suggest that rat thymus synthesizes oxytocin and that thymic oxytocin concentration is modulated by the hypothalamus.

Animals↗
PubMed1981

Purification and characterization of the Ca2+ plus Mg2+-dependent endodeoxyribonuclease from calf thymus chromatin.

Ca2+ plus Mg2+-dependent endodeoxyribonuclease was extracted from calf thymus chromatin and purified to a state free from contamination by other DNases. This DNase required both Ca2+ and Mg2+, or Mn2+ alone for its activity and the optimum pH for activity was at 6.5-7.5. No specificity for the 5'-base was observed. The molecular weight of the DNase was estimated to be about 25,000-30,000 by glycerol gradient centrifugation. Actin and antibody for pancreatic DNase (DNase I) did not inhibit the enzyme, whereas both strongly inhibited DNase I, suggesting that these two DNases are different enzymes.

Actins↗
PubMed1984

[Persistent generalized lymphadenopathy: pre-AIDS. First description of a case observed in Italy].

Persistent Generalized Lymphadenopathy (PGL) is considered a possible early stage of AIDS (pre-AIDS), caused by the same virus and characterized by the same immunologic abnormalities. So far, no case of PGL has been reported in Italy: therefore we describe a typical clinical history, immunologic studies and lymph-node histology of a young italian patient affected by PGL. We treated him with thymocyte protein extract (TP-1). We think PGL is not rare in Italy and probably a percentage of cases, especially in heroin addicts and homosexual males, is not recognized.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Induction of stress proteins in a panel of mouse tissues by fever-range whole body hyperthermia.

When exposed to environmental stress, cell survival is supported by the upregulation of stress proteins such as heat shock proteins (HSPs) or glucose regulated proteins (GRPs), which help prevent protein denaturation. To begin to characterize the ability of a physiologically relevant heat exposure to induce stress protein expression, the cerebellum, cerebrum, colon, heart, kidney, liver, lung, lymph nodes, muscle, serum and thymus were extracted from BALB/c mice at various times after fever-range whole body hyperthermia (FR-WBH, 39.5-40 degrees C for 6 h) treatment. The expression of three stress proteins, HSP70, HSP110 and GRP170, was determined in these tissues and serum and compared to constitutive levels in control tissues and serum using Western analysis. Constitutive expression of GRP170 was not affected by FR-WBH in any tissue. In contrast, FR-WBH did enhance HSP expression: HSP70 in heart, kidney, lung, lymph nodes and thymus; and HSP110 in lung, lymph nodes and thymus. The lymphoid tissues displayed the most consistent upregulation of both HSP70 and HSP110 upon FR-WBH treatment. The apparent sensitivity of immunologically relevant tissues to FR-WBH may relate to the enhanced immune responses that are observed during febrile temperatures.

Animals↗
PubMed1975

Non-histone chromosomal proteins easily extractible from chick erythrocytes.

Those non-histone chromosomal proteins which are easily extractible from chick erythrocytes differ substantially from proteins similarly extracted from other tissues of various species. Although a protein P1 was isolated along with histone H1 by extraction of calf thymus chromatin with HC1O4, the same procedure did not extract this protein from chick erythrocyte chromatin of either normal or regenerating blood. Likewise , non-histone proteins extracted with 0.35 M NaCl from calf thymus differed from those of normal chick erythrocytes, which were qualitatively identical but quantitatively inferior to those of regenerating blood. The major protein of about 25 000 molecular weight, totally extracted with 0.35 M NaCl from calf thymus, was not found in chick erythrocyte chromatin, but rather another major protein of about 35 000 molecular weight was partially extracted from erythrocytes.

Amino Acids↗
PubMed1982

Enhancement by TP-1, a thymic extract, of pokeweed mitogen-induced differentiation of B cells from normal subjects but not of those from patients with systemic lupus erythematosus.

We studied the ability of TP-1, a calf thymic extract, to influence in vitro pokeweed mitogen (PWM)-induced plasma cell generation and blastogenesis of peripheral blood lymphocytes from normal donors and from patients with systemic lupus erythematosus (SLE). In normal subjects, TP-1 significantly increased plasma cell generation, but did not affect the mitogenic response to PWM. On the contrary, differentiation of B cells from SLE patients was not enhanced by this extract. The action on the differentiation of normal B cells could either be due to a direct effect on B cells or be mediated by activation of helper T cells.

Animals↗
PubMed1983

Isolation of thymosin alpha 1 from thymosin fraction 5 of different species by high-performance liquid chromatography.

High-performance liquid chromatography (muBondapak C18 column with 0.05% trifluoroacetic acid in acetonitrile as solvent system) was used to isolate thymosin alpha 1 (alpha 1) from thymosin fraction 5 (f5) of various species (calf, pig, sheep and mouse). Each of the f5 preparations gave a protein peak similar in retention time to bovine thymosin alpha 1. This peak coincided with the immunoreactive peak determined by a radioimmunoassay for alpha 1. Chromatographic analysis of fresh thymus tissue extracts using a high-performance liquid chromatographic similar system did not reveal a detectable protein peak or immunoreactive peak at the alpha 1 position. Our results suggest that alpha 1 may be synthesized in a precursor form in animal tissues.

Animals↗
PubMed1976

Influenza: response of T-cell lymphopenia to thymosin.

Eighteen volunteers in tow study groups were inoculated with influenza A (H3N2) and their peripheral blood T, B and null cells enumerated at subsequent intervals. Infection with wild-type virus or with a live, attenuated virus vaccine markedly reduced the proportion and absolute number of T-cell rosettes 24 hours after inoculation. T-Cell depression preceded the onset of clinical illness in symptomatic subjects, continued during illness, and returned to normal with recovery. T-cell lymphopenia was most pronounced in volunteers infected with wild-type virus and was accompanied by an increase in null cells. Lymphocytes from six wild-virus recipients with T-cell leukopenia were incubated in vitro with a calfthymus extract (thymosin), significantly increasing the percentage of T rosettes in all six subjects (P less than 0.0001). These data indicate that influenza is accompanied by pronounced quantitative and functional changes in T cells.

Adult↗
PubMed1991

Effect of thymic extract on allogeneic MLR and mitogen-induced responses in patients with chronic active hepatitis B.

Cell-mediated immune reactions are involved in the development of chronic active hepatitis (CAH-B). The present studies confirm that lymphocyte from patients with CAH-B have a decreased allogeneic mixed lymphocyte reaction (allo-MLR) and mitogen-induced responses. These abnormalities probably play a role in the immunological dysfunctions underlying chronic liver diseases. Twenty one patients with biopsy-proven CAH-B and a significantly lowered CD4:CD8 cell number ratio were treated with thymic extract (Thymomodulin-TFX) for 6 months. The results of immunological, serological and biochemical findings indicate that this preparation has an immunoregulatory action and produces beneficial clinical effect in patients with CAH-B.

Adult↗
PubMed1984

Thymic hormonal effect on recovery from early and late CCNU induced immunosuppression.

The alkylating agent 1(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) caused a prolonged suppression of antibody response to sheep red blood cell challenge in mice. Two phases of suppression could be observed, an early (first three weeks after CCNU administration) and late phase (4-10 weeks). The late immunosuppression was more severe than the early one. Treatment by the thymic extract thymostimulin (TP-1R) caused a complete recovery of antibody response, with overshoot, during early phase, but only partial recovery during late phase. It is suggested that the known CCNU induced damage to stem cells, manifested at late phase, reduces the responding pool for the restorative effect of thymostimulin.

Animals↗
PubMed1978

Characterization of a soluble factor that specifically suppresses the in vitro generation of cells cytotoxic for syngeneic tumor cells in mice.

A tumor-specific soluble factor found in extracts of thymocytes from mice bearing small P815 tumors has been demonstrated. This factor is capable of significantly suppressing the in vitro generation of syngeneic cells cytotoxic for P815 targets if it is added to culture vessels within the first 30 hr of culture. The suppressive factor eluted from Sephadex G-100 after hemoglobin and was estimated to have a m.w. in the range of 40 to 60,000. Preparative isoelectric focusing of thymic extracts established that the suppressive material has an isoelectric point in the range of pH 4.6 to 4.9. The suppressive activity of extracts could be removed by passage of the material through immunoadsorbent columns prepared from membrane proteins of P815 cells but not by analogous columns prepared by using L1210 membrane proteins. The suppressive material was not removed by its passage through immunoadsorbent columns containing anti-mouse immunoglobulin.

Animals↗