Allergenic properties of the substance produced by the Streptococcus strain sp. Thom-1606

The newly isolated biologically active agent "STP" (the substance produced by Streptococcus strain sp. TOM-1606) has been found to possess no allergenic properties. This new preparation has shown hyposensitizing activity on the level with the allergen. The morphological data obtained in the study of the organs of experimental animals have revealed the immunostimulating action of preparation "STP" on the body, that is confirmed by the characteristic transformation of the internal organs of experimental animals.     

Metabolic changes in the peritoneal macrophages of mice differing in the H-2 locus of histocompatibility after intraperitoneal administration of salmozan

The activity of 5'-nucleotidase in mouse peritoneal macrophages differing by histocompatibility locus H-2 after intraperitoneal injection of salmozan, an immunostimulating agent, has been studied. The character of changes in the activity of 5'-nucleotidase in peritoneal exudate macrophages after the intraperitoneal injection of salmozan has proved to be unrelated to the genotype of mice. The injection of salmozan induces a deep and prolonged decrease in the activity of 5'-nucleotidase in these macrophages. In mice of different strains changes in the activity of 5'-nucleotidase after the intraperitoneal injection of salmozan are of a linear type and can be approximated by a linear regression model.     

DNA strand transfer protein beta from yeast mitotic cells differs from strand transfer protein alpha from meiotic cells

We have purified to homogeneity an activity from mitotic cell extracts of the yeast Saccharomyces cerevisiae, which promotes the transfer of a strand from a duplex linear DNA molecule to a complementary circular single strand. This activity does not require any nucleotide cofactor and is greatly stimulated by yeast single-stranded DNA-binding protein. It consists of a single polypeptide of an apparent molecular mass of 180 kDa as determined by SDS-polyacrylamide gel electrophoresis. This activity, which we call DNA strand transfer protein beta (STP beta), has reaction properties similar to those of DNA strand transfer protein alpha (STP alpha) purified from crude extracts of yeast meiotic cells (Sugino, A., Nitiss, J., and Resnick, M. A. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 3683-3687). However, STP beta differs from STP alpha in its molecular weight and column chromatographic behavior as well as by immunological comparison. Furthermore, the STP beta polypeptide remains in cells in which the STP alpha gene has been disrupted. Thus, we conclude the STP beta activity is encoded by a gene different from that for STP alpha. Although STP beta was isolated from mitotic cells, the amount of STP beta increases severalfold during meiosis. STP beta also appears to differ in molecular weight from similar activities described by other groups and may be an intact form of their activities.     

Shigella antigens in early pathogenetic therapy of experimental acute radiation sickness

In experiments on gamma-irradiated hamsters it is shown that antigens, obtained from Sh. flexneri and sonnei by the sparing method, have a radioprotective therapeutic action. The antigens exhibit the immunostimulating activity which is perhaps one of the aspects of the mechanism involved in the formation of resistance to infectious complications in irradiated animals and of the favourable radioprotective effect.     

Effect of "rasayanas", a herbal drug preparation on immune responses and its significance in cancer treatment.

Rasayanas are considered to be immunostimulating preparations used extensively in indigenous medical practice. However there are only very few reports to substantiate this claim, and this paper gives preliminary evidence for the potentiation of immunity by Rasayanas given to mice orally. Administration of Rasayanas were found to enhance the proliferation of spleen cells significantly especially in the presence of mitogen. Similar result was also seen with bone marrow cells; however mitogenic stimulation could not be observed. Esterase activity was found to be enhanced in bone marrow cells indicating increased maturation of cells of lymphoid linkage. Rasayanas also enhanced humoral immune response as seen from the increased number of antibody forming cells and circulating antibody titre. These results indicate the usefulness of Rasayana as immunostimulating agent.     

ISCOM-based vaccines: the second decade

The immunostimulating complex or 'iscom' was first described 20 years ago as an antigen delivery system with powerful immunostimulating activity. Iscoms are cage-like structures, typically 40 nm in diameter, that are comprised of antigen, cholesterol, phospholipid and saponin. ISCOM-based vaccines have been shown to promote both antibody and cellular immune responses in a variety of experimental animal models. This review focuses on the evaluation of ISCOM-based vaccines in animals over the past 10 years, as well as examining the progress that has been achieved in the development of human vaccines based on ISCOM adjuvant technology.     

The synergistic activity of BCG on the stimulation of lymphocytes with concanavalin A and lipopolysaccharide

Summary A synergistic activity of BCG on the mitogen stimulation of mouse and human lymphocytes could be demonstrated. In this test BCG vaccines produced in a homogeneously dispersed culture proved to be more potent than vaccines which were grown as a surface pellicle and homogenized in a ball mill. Both B- and T-cell activation were enhanced by the addition of BCG. The possible mechanism and the implications of these observations for the use of BCG as an immunostimulating agent in the treatment of cancer patients are discussed.     

Effect of immunomodulators on resistance to gas gangrene. The enhanced resistance of white mice to perfringens toxin type A as affected by prodigiozan

Experiments on 575 noninbred white mice have revealed that the nonspecific resistance of the animals to type A C. perfringens toxin can be enhanced by the administration of Prodigiosan, a commercial immunostimulating agent. Prodigiosan, introduced in 3-4 injections (the last one made 24 hours before intoxication) has been found to enhance the resistance of the animals to the subcutaneous injection of type A C. perfringens toxin by 40-60% and to its intraperitoneal injection by 60-97%.     

The collagen repeat sequence is a determinant of the degree of herpesvirus saimiri STP transforming activity

Herpesvirus saimiri (HVS) is divided into three subgroups, A, B, and C, based on sequence divergence at the left end of genomic DNA in which the saimiri transforming protein (STP) resides. Subgroup A and C strains transform primary common marmoset lymphocytes to interleukin-2-independent growth, whereas subgroup B strains do not. To investigate the nononcogenic phenotype of the subgroup B viruses, STP genes from seven subgroup B virus isolates were cloned and sequenced. Consistent with the lack of oncogenic activity of HVS subgroup B viruses, STP-B was deficient for transforming activity in rodent fibroblast cells. Sequence comparison reveals that STP-B lacks the signal-transducing modules found in STP proteins of the other subgroups, collagen repeats and an authentic SH2 binding motif. Substitution mutations demonstrated that the lack of collagen repeats but not an SH2 binding motif contributed to the nontransforming phenotype of STP-B. Introduction of the collagen repeat sequence induced oligomerization of STP-B, resulting in activation of NF-kappaB activity and deregulation of cell growth control. These results demonstrate that the collagen repeat sequence is a determinant of the degree of HVS STP transforming activity.     

Study of immunomodulatory effects of extracellular HSP70 in a mouse model of allergic airway inflammation

Immunostimulatory properties of extracellular heat shock proteins 70 kDa (HSP70) became interesting for investigators a long time ago. However, in recent years a series of works showing a significant relation of the immunostimulating effects of recombinant HSP70 to contamination of the protein samples with bacterial endotoxins (lipopolysaccharide, LPS) has been published. The authors showed that intensive elimination of LPS from the protein samples resulted in inversion of immunostimulating effects of HSP70 to immunosuppressive activity of the protein. Nevertheless, at present the conception of immunostimulating, proinflammatory action of extracellular HSP70 is the most common. In this work, we studied immunomodulatory effects of exogenous HSP70 in a mouse model of allergic inflammation of airways. We also analyzed the dynamics of the level of the extracellular pool of HSP70 in the site of inflammation. The results demonstrated a considerable content of extracellular HSP70 in bronchoalveolar lavages with dynamics reflecting the stages of development of the induced inflammation. Oropharyngeal injection of exogenous HSP70 in the acute phase of allergic inflammation of airways resulted in significant suppression of the inflammatory process, which conforms to published data demonstrating an immunosuppressive activity of the extracellular pool of HSP70.     

Effect of terrilitin on the proteolytic activity of the blood and formation of an immunostimulating factor by spleen cells

Terrilitin is studied for its effect on proteolytic activity of blood and formation of immunostimulating factors by spleen cells. The preparation is shown to induce isolation of the immunostimulating factor (molecular mass 10-15 kDalton) from the spleen cells. The preparation is destroyed by trypsin and RNAase and is stable to the action of lysozyme. Spleen cell factor of the animals with administered terrilitin increases general antiproteolytic activity of the blood serum and concentration of alpha 2-macroglobulins. At the same time, it decreases the general proteolytic activity and callicrein activity of blood serum for syngenic animals.     

Structure activity studies of a novel cytotoxic benzodiazepine

Analogues of Bz-423, a pro-apoptotic 1,4-benzodiazepine with potent activity in animal models of systemic lupus erythematosus and rheumatoid arthritis, have been designed, synthesized, and evaluated in cell-culture assays. The results of these experiments have defined the structural elements of this new cytotoxic agent required for activity.     

<Emphasis Type="Italic">Ulva lactuca</Emphasis>: A potential seaweed for tumor treatment and immune stimulation

This is the first report on the antitumor and immunostimulating activities ofUlva lactuca. Using the WSM (water-soluble fraction of a methanol extract fromUlva lactuca), a concentration of 140 g/mL was found to inhibit 50% of the human leukemia cell line U937 in growth, while splenocyte growth was stimulated up to a concentration of 100 μg/mL. In addition, NO production by a macrophage cell line (RAW 264.7) and alkaline phosphatase activity in mouse splenocytes were both stimulated with 10 μg/mL of WSM. Dose-dependent patterns were observed on all three cell-lines. Accordingly, the current results indicate thatUlva lactuca may be useful as a natural antitumor and immunostimulating agent.     

Relation of the immunogenicity of artificial antigens to the number of polyelectrolyte-bound protein molecules

Complexes and covalent conjugates of protein antigens with polyelectrolytes of different molecular mass have been synthesised. The structure and composition of the resulting water-soluble complex particles were determined. Artificial antigen immunogenicity was shown to depend on the amount of protein molecules complexed with polyelectrolytes. Direct correlation between immunostimulating activity of the polymer-carrier, immunogenicity of complex antigens and size-dependent capacity of the polymer molecule to aggregate protein globules has been established.     

Effects of multipotent hematopoietic stem cell inhibitory factor on formation of immune response to viral antigen]

An immunostimulating effect of PIF was studied. The augmentation of antibody production to Coxsackie A13 virus as well as protective effect during influenza infection have been found out in mice after PIF injections. An immunostimulating effect of PIF after SRBC immunization of mice has been also revealed. Possible mechanisms of immunostimulating effect of PIF are discussed.     

Design and synthesis of DNA-intercalating 9-fluoren-beta-O-glycosides as potential IFN-inducers, and antiviral and cytostatic agents

Novel 9-fluoren-beta-O-glycosides, designed as DNA-intercalating agents in structural correlation with antiviral tilorone and anticancer anthracyclines, have been prepared with yields in beta-anomers ranging between 25 and 63%. They have been screened for antiproliferative, immunostimulating and antiviral properties against HSV-1 and HSV-2 viruses. Compounds displaying significant antiviral activity against HSV-2 are acetylated 1 and deprotected 6 9-fluorenyl-O-d-arabinopyranoses, whereas 9-fluorenyl-O-d-glucopyranose 3 is the most effective on HSV-1 replication, followed by 1 and 6. The conformational properties of these compounds have been evaluated by molecular modelling techniques.     

Short Term Depression Unmasks the Ghost Frequency

Short Term Plasticity (STP) has been shown to exist extensively in synapses throughout the brain. Its function is more or less clear in the sense that it alters the probability of synaptic transmission at short time scales. However, it is still unclear what effect STP has on the dynamics of neural networks. We show, using a novel dynamic STP model, that Short Term Depression (STD) can affect the phase of frequency coded input such that small networks can perform temporal signal summation and determination with high accuracy. We show that this property of STD can readily solve the problem of the ghost frequency, the perceived pitch of a harmonic complex in absence of the base frequency. Additionally, we demonstrate that this property can explain dynamics in larger networks. By means of two models, one of chopper neurons in the Ventral Cochlear Nucleus and one of a cortical microcircuit with inhibitory Martinotti neurons, it is shown that the dynamics in these microcircuits can reliably be reproduced using STP. Our model of STP gives important insights into the potential roles of STP in self-regulation of cortical activity and long-range afferent input in neuronal microcircuits.