Biomedical subjects

Y Chernajovsky

Publications and source records attributed to Y Chernajovsky.

76 records · Page 5Linked to original sources

PubMed1979

An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA.

A phosphodiesterase characterized by a generally higher activity on 2'-5' than on 3'-5' phosphodiester bonds was isolated from mouse L cells treated with interferon. A similar enzyme was purified from mouse reticulocytes. The phosphodiesterase 2'-PDi splits the 2'-phosphate bond of pppA2'p5'A2'p5'A, the oligonucleotide activator of ribonuclease F. The level of phosphodiesterase 2'-PDi is increased by interferon treatment of L cells. The phosphodiesterase was also shown to degrade the C-C-A terminus of tRNA and to reduce the amino acid acceptance of tRNA in cell-free extracts, thereby causing a tRNA-reversible inhibition of mRNA translation.

Amino Acyl-tRNA Synthetases↗

PubMed1979

Kinetics of the induction of three translation-regulatory enzymes by interferon.

Three enzymes that cause inhibition of mRNA translation, eukaryotic initiation factor 2 protein kinase PK-i, oligoisoadenylate synthetase E, and phosphodiesterase 2'-PDi, have been recently isolated from interferon-treated cells. We show that the rise in these three enzyme activities may be used to study the response of uninfected cells to interferon. For each enzyme, a specific microassay that can be carried out on extracts from 2-5 x 10(4) monolayer cells from mouse, monkey, or man was developed. With these assays, the kinetics of induction of the three enzymes in mouse L cells are compared. The dose dependence for protein kinase PK-i induction is shown to be similar to that for the development of the antiviral state. Actinomycin D and anti-interferon serum block enzyme induction if added to the cells early after interferon treatment. The quantitative measurements of the intracellular level of these enzymes provide a new and convenient model to study the cell's response to interferon.

Adenine Nucleotides↗

PubMedDate not supplied

Different efficacy of in vivo herpes simplex virus thymidine kinase gene transduction and ganciclovir treatment on the inhibition of tumor growth of murine and human melanoma cells and rat glioblastoma cells.

Initial studies have demonstrated the therapeutic efficacy for cancer treatment of in vivo transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir (GCV) treatment. However, recent studies have questioned the validity of this approach. Using retroviral vector-producing cells (VPC) as a source for in vivo gene transfer, we evaluated the efficacy of in vivo transduction of malignant cells using three different tumor cell models: B16 murine and IIB-MEL-LES human melanomas and a C6 rat glioblastoma. In vitro studies showed a bystander effect only in C6 cells. In vivo studies showed an inhibition of tumor growth in the two melanoma models when tumor cells were coinjected with VPC-producing retroviral vectors carrying the herpes simplex virus thymidine kinase gene, followed by GCV treatment; however, 100% of mice developed tumors in both models. Under similar experimental conditions, 70% (7 of 10) of syngeneic rats completely rejected stereotactically transferred C6 tumor cells; most of them (5 of 10) showed a prolonged survival. Treating established C6 tumors with VPC-producing retroviral vectors carrying the herpes simplex virus thymidine kinase gene and GCV led to the cure of 33% (4 of 12) of the animals. Rats that rejected tumor growth developed an antitumor immune memory, leading to a rejection of a stereotactic contralateral challenge with parental cells. The immune infiltrate, which showed the presence of T lymphocytes, macrophages, and polymorphonuclear cells at the site of the first injection and mainly T lymphocytes and macrophages at the site of tumor challenge, strengthened the importance of the immune system in achieving complete tumor rejection.

Animals↗

PubMedDate not supplied

Systemic gene therapy for arthritis.

Based on the beneficial effects of antibodies to tumor necrosis factor (TNF)-alpha and inhibitory cytokines, gene delivery of cytokines and cytokine inhibitors has been tried and shown to be of therapeutic benefit in the collagen-induced arthritis model in DBA/1 mice. The clinical beneficial effects are accompanied by an effect at the level of immune functions. We have tested the cytokines transforming growth factor (TGF)-beta 1 and interferon (IFN)-beta, a small molecular weight dimeric p75 TNF receptor, as well as a p55 TNF receptor on an immunoglobulin (Ig) backbone. Inhibition of the complement system using a soluble form of complement receptor 1 also has been shown to block B- and T-cell functions. These molecules were expressed in vivo from syngeneic arthritogenic lymphocytes or immortalized fibroblasts. Because in human disease the antigen driving the autoimmune arthritic response is not defined, we have engaged in the targeting of T-cells to collagen type II, by engineering chimeric antibody-type recognition fused to cytoplasmic signaling domains of cellular receptors. From this spectrum of gene therapy approaches, effective in the mouse, it is hoped that some will be able to be transferred to humans.

Journal Article↗