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Biomedical subjects

G Merlin

Publications and source records attributed to G Merlin.

46 records · Page 3Linked to original sources
PubMed1982

Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells.

In human cells treated with interferons, there is an increase in the amount of HLA-A,B,C and beta 2-microglobulin exposed on the cell surface. We have used a cloned HLA-A,B,C cDNA probe to demonstrate by molecular hybridization that this effect of interferon is preceded by a large increase in the amount of HLA mRNA in the cell. This effect was found in five different human cell lines, with purified leukocyte and fibroblast interferons. The increase in HLA mRNA is comparable in its kinetics and dose-response to the induction of (2'-5') oligo(A) synthetase mRNA by interferons. Therefore, interferons seem to activate at least two cellular genes which have different biochemical functions.

Cells, Cultured↗
PubMed1982

Comparison of (2'-5') oligo-adenylate synthetase and interferon blood-levels in mice early after viral infection.

The level of the IFN-induced enzyme (2'-5') oligo A synthetase in the peripheral blood mononuclear cells (PBMC) was determined in mice at different times following virus infection. There was a significant increase (4-7-fold) of the enzyme level within less than 12 h after i.p. injection of either VSV (10(7) pfu) or Sindbis virus (2.10(4) pfu). The elevated level was maintained for about a week and then the activity returned to normal. There was, however, a marked difference in the pattern of serum level of IFN during infection by the two viruses; while in the mice infected by VSV, serum IFN was very high on the first day and declined to an undetectable level by the fourth day, in the mice infected with Sindbis virus, serum IFN was barely detectable at the first day and then increased towards the fourth day of infection. Antiviral antibodies could be detected in the serum only about a week after infection. We conclude that viral infection can result in a rapid elevation of (2'-5') oligo A synthetase in the PBMC, even when serum IFN remains low. Thus, quantitation of the enzyme level can be a useful diagnostic aid in viral infection particularly in the early stages and in cases in which antiviral antibodies and IFN can not be detected.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Variation of (2'-5') oligo A synthetase level in lymphocytes and granulocytes of patients with viral infections and leukemia.

Using a simplified technique for the determination of oligoisoadenylate synthetase activity, we have compared the cellular level of this interferon (IFN)-induced enzyme in multiple samples of peripheral blood leukocytes. In mononuclear cells (PBMC) of healthy donors the enzyme level was remarkably constant, but in the cells of about 85% of patients with viral infections enzyme activity was significantly elevated. In contrast, the incidence of elevated activity in bacterial infections was low. Synthetase activity could be also detected in granulocytes, although normally its level in these cells was considerably lower than in PBMC. A sharp increase in the enzyme level in granulocytes was found in cells exposed in vitro to IFN, as well as in cells from patients undergoing IFN therapy. Increased synthetase activity was also detected in the granulocytes of patients with viral infections. We have also determined the level of the enzyme in patients with various types of leukemias. In a large proportion of the patients with acute lymphoblastic leukemia (ALL) we found severely decreased enzyme levels (10-20% of control value). The decreased activity could usually be correlated to predominance of blast cells in the peripheral blood.

2',5'-Oligoadenylate Synthetase↗
PubMed1981

Assay of an interferon-induced enzyme in white blood cells as a diagnostic aid in viral diseases.

Interferon is part of the system of defence against viral infections and has important cell-regulatory and immunoregulatory functions. It is, however, not always possible to quantify circulating interferon in patients. An assay has been developed to measure an interferon-induced enzyme in white blood cells. The activity of this enzyme is constant in healthy subjects but increases by 2-10 times in 85% of patients with acute viral infections. It is also enhanced in autoimmune diseases and in virus-related malignancies and neurological disorders. The enzyme level was not raised in bacterial infections or non-infectious diseases studied. This simple and rapid biochemical assay of the interferon system could be used for diagnosis and evaluation of many diseases.

2',5'-Oligoadenylate Synthetase↗
PubMed1981

Monitoring of interferon therapy by assay of (2'--5') oligo-isoadenylate synthetase in human peripheral white blood cells.

With the increasing number of patients undergoing experimental interferon therapy, there is a need for a method for monitoring how the patients respond to the drug. Interferon induces in cells exposed to it the accumulation of several enzymes, among them the (2'-5') oligo-A synthetase. A simple method previously developed was used to measure this enzyme in extracts of a small number of peripheral white blood cells. In 60 healthy volunteers, the enzyme level in the mononuclear cell fraction was found to be relatively high and constant. Daily intramuscular injections of 1--2 x 10(6) units leukocyte type interferon (IFN-alpha) increased the enzyme level 7--8 fold in mononuclear cells and in granulocytes. The enzyme stayed high until IFN injections were stopped. Patients with defective response to IFN were identified. We propose that this method be used for continuous monitoring of the patient's response whenever interferon therapy is undertaken.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Qualitative differences in effects of recombinant alpha-, beta- and gamma-interferons on human peripheral blood leukocytes in vitro.

The in vitro effects of bacteria-produced human interferons alpha 2, beta and gamma on several properties of peripheral blood leukocytes from different healthy donors were compared. Treatment with HuIFN-alpha 2 or HuIFN-beta resulted in inhibition of the proliferative response to phytohaemagglutinin and in closely parallel induction of 2'-5'-oligoadenylate synthetase activity. In contrast, HuIFN-gamma had no significant effect on these two activities. However, all three HuIFN were able to enhance natural killer cell cytotoxicity and the expression of HLA-DR surface antigens, with only quantitative variations from donor to donor. Similar results were observed with glycosylated recombinant hamster-cell-derived HuIFN-gamma and with natural HuIFN-gamma. These data demonstrate qualitative differences in the effects of HuIFN-gamma compared to those of HuIFN-alpha 2 or -beta on cells of the immune system.

2',5'-Oligoadenylate Synthetase↗