An RNA 5'-triphosphatase activity hydrolyzing gamma-phosphate from pppN-RNA was found to be associated with mRNA guanylyltransferase partially purified from rat liver nuclei. The activity specifically removed 32P as inorganic phosphate from [gamma-32P]pppA(pA)n, but not from [beta-32P]pppA(pA)n or from [gamma-32P]ATP. Free SH group(s) were required for its activity, and the reaction was inhibited by N-ethylmaleimide. Divalent cations were not required, but were rather inhibitory for the reaction. The RNA 5'-triphosphatase activity could not be separated from the guanylyltransferase activity through successive chromatographies on Sephadex G-150, CM-Sephadex and blue dextran-Sepharose columns. Both activities remained physically associated during sedimentation in glycerol density gradients after high salt treatment. The heat stability of the RNA 5'-triphosphatase activity was almost identical with that of the guanylyltransferase activity. These results indicate that the 69000 mol. wt. protein purified from rat liver nuclei as guanylyltransferase possesses both mRNA capping and RNA 5'-triphosphatase activities.

Acid Anhydride Hydrolases↗

PubMed1983

Protective activity of thymosin alpha 1 against tumor progression in immunosuppressed mice.

The effect of thymosin alpha 1 was examined in mice immunosuppressed by cytostatics or X-ray irradiation. Inoculation of B16 melanoma or L1210 leukemic cells into these immunosuppressed mice caused a high incidence of pulmonary metastasis or rapid death, respectively. Thymosin alpha 1 given concomitantly with cytostatics or after X-ray prevented such deleterious effects of these agents. One of possible mechanisms causing the rapid death and increasing the metastasis is the damage to NK cells. Thymosin alpha 1 prevented the reduction of NK cell activity caused by these agents. The preventive activity could be transferred to immunosuppressed recipients by spleen cells and those deprived of T cells, but not by those deprived of NK cells. Another possible mechanism is the aberration of the barrier system for spread of tumor cells in blood circulation, which may allow the tumor cells to migrate to various sites in the host. In 5-FU-treated mice, distribution of 125I-L1210 cells upon inoculation was higher in blood and lung, but lower in liver and spleen as compared with that in normal mice. On the other hand, when thymosin alpha 1 was given with 5-FU, the pattern of the tissue distribution was almost the same as that in normal mice. Thus, thymosin alpha 1 protected mice which received immunosuppressive agents from undesirable effects of the agents on surveillance systems against tumor. Thymosin alpha 1 may be useful as an adjuvant in cancer therapies.

Animals↗

PubMed1983

Thymosin alpha 1 restores NK-cell activity and prevents tumor progression in mice immunosuppressed by cytostatics or X-rays.

The effect of thymosin against tumor progression was examined in mice immunosuppressed by cytostatics or X-ray irradiation. When pretreated with cytostatic agents, such as 5-fluorouracil (5-FU) or BCNU, or by X-ray, and then inoculated with P388 or L1210 leukemias, mice died rapidly within a few days. In these systems, thymosin alpha 1 given concomitantly with the cytostatic agents or after X-irradiation prevented rapid death and extended survival, although the mice eventually died with leukemia like normal mice inoculated with cells of the same tumor. Rapid death in the 5-FU-treated mice was also prevented by adoptive transfer of spleen cells from the donor mice if these had been treated with 5-FU plus thymosin alpha 1, but not if they had received 5-FU alone. However, the restorative activity of the donor spleen cells was abrogated by treatment with anti-asialo GM1, but not by treatment with anti-Thy 1 or anti-mouse Ig serum, suggesting that the effector cells in the spleen are NK cells. In fact, thymosin alpha 1, when given concomitantly with 5-FU or after X-irradiation, maintained the NK activity of spleen, which was damaged by treatment with 5-FU or X-irradiation alone. The present study indicates that thymosin alpha 1 exerts a preventive activity against progression of leukemias at least in part through an effect on NK cells or their progenitor cells.

Animals↗

PubMed1983

Immunomodulating activity of thymosin fraction 5 and thymosin alpha 1 in immunosuppressed mice.

We found that both thymosin from calf thymus and its constituent peptide alpha 1 prepared by chemical synthesis restore cell-mediated immunity following its suppression in mice by injection of 5-FU. Conditions suitable for assessing the thymosin activity by means of footpad reaction were established in such immunosuppressed mice. In this new animal model, thymosin alpha 1-peptide showed activity at a low dose of 5-50 micrograms/kg, which was 100-1,000 times less than that required for thymosin F-5 preparations. Further studies utilizing the adoptive transfer technique showed that alpha 1-peptide corrects the 5-FU-induced suppression of mature T cells, transferring the DTH response as well as that of macrophage function responsible for the expression of footpad reaction. Furthermore, regeneration of lymph node and bone marrow cells as well as CFU-c (progenitor cells of macrophages and granulocytes) was enhanced by thymosin alpha 1 in the 5-FU-treated mice. All these results indicate that thymosin alpha 1 accelerates the replenishment and maturation of haematopoietic cells, including not only T cells but also macrophages, when they have been severely damaged by the 5-FU treatment.

Animals↗

PubMed1983

Protective activity of thymosin against opportunistic infections in animal models.

Animal models for opportunistic infections were developed by using mice immunosuppressed by 5-FU. These mice were susceptible to various microorganisms, while normal mice had greater tolerance to such microbial infections. In these models, thymosin alpha 1 was found to protect mice against lethal infections with Candida albicans, Listeria monocytogenes, Pseudomonas aeruginosa, and Serratia marcescens when it was administered during 5-FU treatment prior to the infections. Thymosin alpha 1 was effective in some infections at 0.4-400 micrograms/kg/day IP, about 1/100 of the dose required for thymosin fraction 5. Activity was also demonstrated against L-monocytogenes and Ps. aeruginosa by counting the viable bacteria in the liver after infection. The protective activity against Candida, elimination of which macrophages were essential, was abrogated by anti-thymocyte serum and/or carrageenan, indicating that thymosin alpha 1 serves to maintain the functions of macrophages by reducing the damage to T cells by 5-FU. On the other hand, the activity against Pseudomonas infection was not affected by anti-thymocyte serum or carrageenan. It is probable that thymosin alpha 1 also exerts its effect on neutrophils without participation of T cells and macrophages.

Animals↗

PubMed1983

Modification of Streptococcus faecalis sex pheromones after acquisition of plasmid DNA.

Recipient strains of Streptococcus faecalis excrete multiple, peptide sex pheromones that induce mating responses in donors harboring certain conjugative plasmids. Acquisition of plasmid DNA leads to a "shutting off" of pheromone excretion, and such cells become responsive to exogenous pheromone. Data are presented showing that donors excrete low levels of a modified, inactive form of the pheromone. This substance, when mixed in excess with active pheromone, inhibits pheromone activity (probably by competition for a receptor site on the donor). Modified forms of both cPD1 and cAD1 were revealed, and each appeared to have a mass about 350-400 daltons larger than the active pheromone. In both cases, pheromone activity could be regenerated by treatment with phosphodiesterase II.

Animals↗

PubMed1983

Plasmid content of Streptococcus faecalis strain 39-5 and identification of a pheromone (cPD1)-induced surface antigen.

Streptococcus faecalis 39-5 is a haemolytic, bacteriocinogenic strain harbouring six plasmids. One of these plasmids, pPD1 (36.4 MDal) determines a bacteriocin and encodes a conjugative response to the sex pheromone cPD1 excreted by recipient (plasmid-free) strains. The pheromone response is characterized by the formation of mating aggregates of donors (responders) with recipients. Aggregation required the presence of phosphate and divalent cations and was inhibited by agents or conditions that destroy protein structure. Aggregation was postulated to be due to synthesis of a new proteinaceous molecule on the donor cell surface. Referred to as 'aggregation substance', such a material was identified and found to exhibit antigenic properties not associated with uninduced cells; it could be detected by immunoelectron microscopy. Aggregation substance could be extracted from induced cells but not uninduced cells as demonstrated by crossed immunoelectrophoresis. Antibody raised against the aggregation substance controlled by pPD1 cross-reacted with aggregation substance determined by other plasmid systems which respond to pheromones unrelated to cPD1.

Animals↗

PubMed1983

Identification and partial characterization of a pheromone-induced adhesive surface antigen of Streptococcus faecalis.

A surface protein antigen that is produced only during the induction of aggregation of Streptococcus faecalis was shown to contribute to and perhaps be primarily responsible for aggregation. The antigen is an immunodominant surface component of induced cells. F(ab) fragments of immunoglobulins specific for this antigen prevented aggregation, providing direct evidence that the antigen is an adhesin. Consistent with this proposed association was the coincident timing of appearance of the antigen and the timing of aggregation after induction.

Adhesiveness↗

PubMed1983

Population of K-lymphocytes in various kinds of thyroid disease.

We have measured the population of Killer (K) lymphocytes in the peripheral blood of 108 patients with various kinds of thyroid disease. In the patients with Hashimoto's thyroiditis and Graves' disease, the relative and absolute numbers of K-lymphocytes were significantly lower than those seen in healthy controls (p less than 0.001), and the longer the duration of medication, the lower the K-lymphocyte population. However, there was no apparent correlation between the serum titers of thyroid autoantibodies and the K-lymphocyte population. In the patients with malignant and benign thyroid tumors, the relative and absolute numbers of K-lymphocytes significantly decreased when compared with those of controls (p less than 0.001), the decrease was more prominent after surgical operation than before operation. A prominent decrease in the K-lymphocyte population was evoked to maximum 2 to 4 weeks after surgical operation. The patients with both malignant and benign tumors having abundant lymphocytic infiltration in their surgical specimens generally revealed a lower K-lymphocyte population than those having no lymphocytic infiltration.

Adult↗

PubMed1983

[Correlation between estrogen receptor(ER), progesterone receptor(PR) and human keratin protein (hKP) in endometrial carcinoma].

We extracted hKP by Sun and Green's method and injected it into a rabbit to raise antibody. hKP was demonstrated in 14/18 well differentiated EC by Sternberger's Pap method. In 2/4 hKP (+) cases, the carcinoma cells invaded. If hKP was present, undifferentiated EC (5/5) and clear cell carcinoma (2/2) all invaded. Among ER (+) PR (+) cases, hKP was demonstrated in 6/10; 4 of these invaded. Both ER (+) PR (-) (1/1) and ER (-) PR (-) (6/6) cases revealed invasion with hKP. In the foci of squamous arrangements and at the top of the invading carcinoma cells, hKP was strongly demonstrated. These results suggest that hKP endows the cells with "stiffness" and that this protein is closely associated with cancer invasive growth, no less than are ER, PR or/and microscopical architecture.

Adenocarcinoma↗

PubMed1983

Changes in leukocyte count, blood glucose and coagulation system in calves injected with Escherichia coli endotoxin.

Responses of leukocyte, blood glucose and coagulation system in calves were investigated to injection with Escherichia coli endotoxin. Severe leukopenia and hyperglycemia following transient hypoglycemia were noted within 24 hours after injection. In the coagulation system, a definite decrease in platelet count, prolongation of prothrombin time and activated partial thromboplastin time were observed. Fibrinogen, soluble fibrin monomer complex and clotting time, however, varied.

Animals↗

PubMed1983

A case of severe childhood aplastic anemia associated with lymphocyte mediated hemopoietic suppression: recovery following cyclophosphamide treatment.

Explore the source record for details and available documents.

Anemia, Aplastic↗

PubMed1982

Mapping of Streptococcus faecalis plasmids pAD1 and pAD2 and studies relating to transposition of Tn917.

Plasmids pAD1 (37.8 megadaltons) and pAD2 (17.1 megadaltons) of Streptococcus faecalis strain DS16 have been mapped with restriction enzymes. The location of a hemolysin-bacteriocin determinant on the conjugative pAD1 plasmid was derived from analyses of transposon insertions. Electron microscope and hybridization analyses located Tn917(Em) and the streptomycin (Sm) and kanamycin (Km) resistance determinants on the nonconjugative pAD2 plasmid. It was shown previously that the erythromycin (Em) resistance associated with Tn917 is inducible and that transposition from pAD2 to pAD1 is also stimulated by exposure of cells to low concentrations of Em. Here we show that inducing concentrations of Em also increase the conjugative transfer potential of pAD1; this is possibly related to a mild and short-lived inhibitory stress placed on the cells before full induction of resistance. Selection of Em-resistant transconjugants arising from matings between DS16 and a plasmid-free recipient gave rise to transconjugants which primarily harbor stable pAD1::pAD2 cointegrates. A 30-min exposure of donors to Em (0.5 microgram/ml) before mating resulted in a severalfold increase in the number of such transconjugants. However, a small fraction (e.g., 3 of 40) of these Emr Smr Kmr transconjugants harbored pAD1::Tn917 and pAD2 molecules. Since we believe pAD2 is incapable of being mobilized by pAD1 without being covalently linked, it is likely that transfer in these cases involved cointegrates representing structural intermediates in the transposition of Tn917 from pAD2 to pAD1. It follows that such intermediates probably had two copies of Tn917 and readily resolved after transfer. (These cointegrates are different from the stable cointegrates which were shown to have only a single copy of Tn917; the latter are assumed not to be related to transposition.) Two variants with altered Tn917 transposition properties were derived. One of them transposed at an elevated frequency, whereas the other showed no detectabel transposition. In neither case was transposition influenced by Em exposure; however, both remained inducible for Em resistance.

Anti-Bacterial Agents↗