Experimental evaluation of immunotoxicity of olipifat

The paper presents our data on the influence of Olipifat on the mass and cell patterns of the immune system organs, phagocytic activity of macrophages, number of antibody-producing B-lymphocytes and immune rosette-forming T-lymphocytes. Olipifat showed no immunotoxic characteristics; it stimulated T-system immunity as evidenced by a significant increase in the number of immune rosette-forming T-lymphocytes in mice after injection of 100 or 50 mg/kg.     

Modification of Mechanical Properties in Directed Energy Deposition by a Static Magnetic Field: Experimental and Theoretical Analysis

The superimposed magnetic field affects the microstructure and mechanical properties of additively manufactured metal parts. In this work, the samples were fabricated from Inconel 718 superalloy by directed energy deposition under a 0.2 T static field. The magnetohydrodynamic 1D model is proposed for the estimation of a fluid flow inside a molten pool. According to the theoretical predictions, the fluid flow is slightly decreased by an applied field. The estimated thermoelectric magnetic convection in the mushy zone is shown to be negligible to change in subgrain size, but enough to reduce the hard-to-dissolve Nb-rich phase, thereby improving the average ultimate elongation from 23% to 27%. The obtained results confirm that an external static magnetic field can modify and enhance the mechanical properties of additively manufactured materials.     

Point mutations in the conserved box 1 region inactivate the human granulocyte colony-stimulating factor receptor for growth signal transduction and tyrosine phosphorylation of p75c-rel

The human granulocyte colony-stimulating factor receptor (hG-CSFR) belongs to the cytokine receptor superfamily. As with other members of this family, the cytoplasmic domain of hG-CSFR lacks intrinsic tyrosine kinase activity. To identify critical regions mediating growth signal transduction by hG-CSFR, deletions or site-directed amino acid substitutions were introduced into the cytoplasmic domain of hG-CSFR, and the mutant cDNAs were transfected into the murine interleukin-3 (IL- 3)-dependent Ba/F3 and FDCP cell lines. Truncation of the carboxy- terminal end of the receptor to the membrane-proximal 53 amino acids of the cytoplasmic domain, which retained the conserved Box 1 and Box 2 sequence motifs, decreased the ability of hG-CSFR to transduce G-CSF- mediated growth signals without an associated loss in receptor binding affinity. Substitution of proline by alanine at amino acid positions 639 and 641 within Box 1 completely abolished the G-CSF-mediated growth signal. Rapid induction of tyrosine phosphorylation of several cellular proteins, including a 75-kD protein (p75) identified as c-rel, was an early event associated with transduction of proliferative signals by hG- CSFR in Ba/F3 transfectants. Mutant receptors containing Pro-to-Ala substitutions that inactivated the receptor for mitogenic activity also inactivated the receptor for tyrosine-specific phosphorylation of p75. These results show that the conserved Box 1 sequence motif (amino acids 634 to 641) is critical for mitogenesis and activation of cellular tyrosine kinases by hG-CSFR.     

Growth-stimulating phase of macrophage response to activation: the phenomenon and its implications for tumour growth and immunotherapy

Summary The dynamics of growth-stimulating and cytotoxic activity of mouse peritoneal macrophages (PMo) in response to in vivo and in vitro bacillus Calmette-Guérin (BCG) or bestatin treatment was studied. It was shown that BCG and bestatin induce cytotoxicity in PMo, and that after the cytotoxic response strong growth-stimulating activity develops. PMo, rendered cytotoxic in vivo and afterwards cultivated in vitro, displayed the same switch from a cytotoxic to a growth-stimulating phase. These results suggest that the growth-stimulating phase is the obligatory PMo response to biological response modifiers (BRM) at least to BCG and bestatin. The growth rate of tumours, transplanted into mice during the cytotoxic phase of the response to BCG, was suppressed, whereas tumours transplanted during the growth-stimulating phase were stimulated. It appears that the development of a growth-stimulating phase after the cytotoxic phase of response to activation by BRM could be one of the reasons for the limited effectiveness of immunotherapy based on the application of macrophage activators.Abbreviations PMo peritoneal macrophages - Mo macrophages - LLC Lewis lung carcinoma - BCG bacillus Calmette-Guérin - BEM basal Eagle's medium - IL-1 interleukin-1 - TNF tumour necrosis factor - BRM biological response modifier     

C hyperfine interactions of CO2 in irradiated tooth enamel as studied by EPR

The EPR spectrum of tooth enamel caused by ¹³C hyperfine interactions of the CO₂⁻ radical were studied on γ-irradiated powdered samples annealed for 40 min at different temperatures up to 250°C. The lineshape and hyperfine splitting of the spectra were found to depend on the annealing temperature. Experimental spectra were compared with calculated ones assuming that EPR spectra are formed by two CO₂⁻ species—axial (rotating) and orthorhombic (braked) radicals. We assumed that the axial CO₂⁻ radicals are centers located in perfect areas of the hydroxyapatite crystals of tooth enamel whereas the orthorhombic CO₂⁻ radicals are rotating centers which are braked by defects. The thermal treatment of enamel samples leads to defective annealing and transformation of the orthorhombic centers into axial ones. This results in an increasing axial CO₂⁻ radical contribution to the EPR spectrum with increase of annealing temperature.     

The synthetic peptide related to the central part of human interleukin-2 molecule accelerates growth and vascularization of sarcoma 180 in mice.

The synthetic peptide C-1-6 related to the central part of human interleukin 2 molecule (sequence 59-72; N- and C-modified) had been shown previously to inhibit cytotoxic activity of macrophages converting them to synthesis of growth factors. In this paper the effect of C-1-6 on growth of sarcoma 180 in mice was studied. C-1-6 significantly accelerated tumor growth having been injected into mice in dose 5 or 50 microg per animal since the 4th day after tumor cells transplantation. Supernatants of Mphi in vitro activated by C-1-6 (10 microg/ml) and injected into mice also accelerated significantly sarcoma mass diurnal increasing as compared to mice treated with supernatants of non-activated Mphi or activated with bacterial lipopolysaccharide. A single injection of C-1-6 into mice either at the day or at the next day of tumor cells inoculation increased significantly the number of vessels growing up to transplant, thus the forming of the vascular bed had preceded tumor volume enlargement.     

Effect of epidermal chalones on induction and growth of tumors of the cervicovaginal epithelium in mice

During induction of tumors of the cervicovaginal epithelium by means of dimethylbenzanthracene in female BALB/c mice or after their appearance, a 1% solution of chalones contained in 55–81% ethanol extracts of rat skin or liver (control) was applied intravaginally. The use of skin extract during induction of tumors, but not the use of liver extract, was shown to retard growth of tumors of the vagina and cervix uteri a little and to reduce the frequency of their appearance; as a result of their action on neoplasms already formed in this situation the chalones prolonged the survival of the animals with tumors.Laboratories of Experimental Tumors, Endocrinology, and Pathomorphology, N. N. Petrov Research Institute of Oncology, Ministry of Health of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Serebrov.) Translated from Beulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 335–337, March, 1980.