The isolation of immunoglobulin G and albumin protein standards and the study of their oligomerization and antigenity during storage in saturated ammonium sulfate solution

The feasibility of the isolation and purification of immunoglobulin (Ig) G and albumin from human and animal blood serum by means of a uniform laboratory technique using non-chromatographic and chromatographic fractionating stages is demonstrated. The oligomerization of these proteins when stored in strong solutions of ammonium sulfate is revealed. It was ascertained that storage in sulfate suspension did not cause the fragmentation of IgG and albumin, and the degree of protein oligomerization up to 3% had no effect on the sensibility of the immunoferment assay.     

Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

Despite therapeutic advances, the long-term survival rates for acute myeloid leukemia (AML) are estimated to be 10% or less, pointing to the need for better treatment options. AML cells express the myeloid marker CD33, making it amenable to CD33-targeted therapy. Thus, the in vitro and in vivo anti-tumor activities of lintuzumab (SGN-33), a humanized monoclonal anti-CD33 antibody undergoing clinical evaluation, were investigated. In vitro assays were used to assess the ability of lintuzumab to mediate effector functions and to decrease the production of growth factors from AML cells. SCID mice models of disseminated AML with the multi-drug resistance (MDR)-negative HL60 and the MDR⁺, HEL9217 and TF1-α, cell lines were developed and applied to examine the in vivo antitumor activity. In vitro, lintuzumab significantly reduced the production of TNFα-induced pro-inflammatory cytokines and chemokines by AML cells. Lintuzumab promoted tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) activities against MDR⁻ and MDR⁺ AML cell lines and primary AML patient samples. At doses from 3 to 30 mg/kg, lintuzumab significantly enhanced survival and reduced tumor burden in vivo, regardless of MDR status. Survival of the mice was dependent upon the activity of resident macrophages and neutrophils. The results suggest that lintuzumab may exert its therapeutic effects by modulating the cytokine milieu in the tumor microenvironment and through effector mediated cell killing. Given that lintuzumab induced meaningful responses in a phase 1 clinical trial, the preclinical antitumor activities defined in this study may underlie its observed therapeutic efficacy in AML patients.     

Genes for the SMC Family Proteins in a Common Vole Microtus arvalis

Genes for four subfamilies of SMC (structural maintenance of chromosomes) proteins have been isolated from the genome of a common vole Microtus arvalis. The high degree of homology between representatives of each SMC protein subfamily of different classes of organisms has been demonstrated. The full-sized copy of a mammalian gene encoding SMC4 protein has been isolated and analyzed for the first time. The SMC proteins enter into the composition of complexes responsible for cohesion of sister chromatids, formation of mitotic chromosomes, recombination, DNA repair, and regulation of gene expression. We discuss the possible participation of the SMC proteins in inactivation of the X chromosome in mammalian females. Common voles of genus Microtusgroup arvalis serve a unique model for the study of the inactivation process.     

Modified water maze for studying spatial memory of rats

A method for evaluation of impairments of spatial memory in rats is put forward. Sensitivity of the advanced method based on the principles of Morris' water maze was compared with that of the classic prototype. Efficiency of the advanced method was assessed by dose- and time-dependent effects of agroclavine on the spatial memory of rats. Agroclavine (10 micrograms/kg) was shown to produce spatial memory impairment in rats. The obtained results also indicate that the modernized maze is more sensitive in revealing impairments of the spatial memory in rats than the classic water maze.