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Biomedical subjects

A Lazar

Publications and source records attributed to A Lazar.

At least 73 records · Page 4Linked to original sources
PubMed1983

Human lymphoblastoid interferon for clinical trials: large scale purification and safety tests.

Human lymphoblastoid cell lines are one of the best sources for the production of large amounts of human interferon for clinical trials. The potential risk of using transformed cell lines for production of a substance for human use can be overcome by an extensive purification of the interferon to a high degree, and by carefully testing the final product for DNA content and toxic materials. In previous reports we described a method for large scale production of interferon by a human lymphoblastoid cell line (Namalva). In this report a system for large scale purification of Namalva interferon and safety tests is presented. The procedure consists of three main steps: 1. Concentration of crude interferon by ultrafiltration. II. Gel filtration on Sephadex G-75 or Ultrogel AcA 54 columns. III. Affinity chromatography on anti-interferon antibody column. All steps were adapted for the processing of batches of hundreds of litres and can be easily further scaled-up. The final highly purified product undergoes a series of quality control tests such as purity, sterility, toxicity, pyrogenicity and DNA content. After passing all tests the IFN is released for clinical trials.

Cell Line↗
PubMed1981

Interferon production and lymphocyte transformation in lymphocytes of leukemic patients.

The high incidence of viral infections in patients with lymphocytic leukemia is well documented, but the role played by interferon in the pathogenesis of such infections is not known. In this study, we investigated the possibility that gamma (gamma) interferon production, induced by phytohemagglutinin (PHA) might be impaired in leukocytes from patients with acute lymphocytic leukemia (ALL). We also compared this response with alpha (alpha) interferon production, and with PHA-stimulated lymphocyte transformation. We have shown that the gamma interferon response of leukocytes from patients, both in relapse and in remission, was markedly lower than in leukocytes from normal donors. However, the alpha interferon response in leukocytes from the patients was normal. In contrast the defective gamma interferon response to PHA stimulation of cells from patients in remission, lymphocyte transformation by PHA was normal. Lymphocytes from patients in relapse has a delayed response. Our findings suggest (1) that the defective gamma interferon response which occurs in cells from patients with ALL, both in relapse and remission, contributes to increased susceptibility to viral infections, (2) that alpha interferon may not be the optimal type of interferon for treatment of certain viral infections, and (3) that different triggering mechanisms, or different receptors, exist for PHA-induced gamma interferon production and for lymphocyte transformation in cells of patients with ALL.

Adolescent↗
PubMed1981

Isolation of two species of human lymphoblastoid (Namalva) cell-derived interferon that differ in rates of clearance, size, and cell specificity.

Chromatography of human lymphoblastoid (Namalva) interferon on blue dextran Sepharose has separated the interferon activity into two species which differ in affinity to the dye Cibacron Blue F3GA. The separated species differ also in rates of clearance from the circulation of mice, size, and specificity toward human and bovine cells. The species retained by the dye manifests a slower clearance rate, is about 20,000 mol. wt., and is equally active on both human fibroblasts FS-11A and bovine cell line MDBK. The unretained species disappears from the circulation at a faster rate, is 16,000 mol. wt., is active on bovine cells, but almost inactive on human cells. It is suggested that a comparative study of the two species may aid in the elucidation of the causes responsible for the rapid clearance or bioinactivation of interferon.

Animals↗
PubMed1981

Interferon production by a human lymphoblastoid cell line (DG-75) free of the Epstein-Barr genome.

A new lymphoblastoid cell line, DG-75, was investigated for its ability to produce interferon. DG-75 cells, previously shown to be free of Epstein-Barr virus genome and receptors, could be grown in submerged culture and could produce interferon in titers comparable to interferon produced by Namalva cells. The interferon produced was similar in size to the Namalva interferon as determined by gel filtration in Ultrogel AcA54. The DG-75 cells present a new source of large quantities of interferon which may be safer for human use than the Namalva interferon.

Cell Line↗
PubMed1981

Factors affecting the large scale production of human lymphoblastoid interferon.

Large scale production of human lymphoblastoid (Namalva) interferon (IFN) is carried out in pilot-plant-scale fermentors having up to 250 liter culture volume. Cells are grown in a semi-continuous culture. For IFN production, which is an IFN-alpha (Ly), harvested cells were induced by Sendai virus. Variations in IFN yields of up to ten-fold were observed during long-term cell cultivation. Several factors such as cell concentration, virus concentration, "age" of induced cells and serum substitutions, were investigated for their effect on the fluctuation in the IFN yields. Optimization of the above factors were found to be of great importance in controlling the IFN production and maintaining a stable and high IFN yield.

Cell Division↗
PubMed1981

Colorimetric determination of disulfiram in tablets: collaborative study.

The colorimetric reaction of cuprous iodide and disulfiram has been collaboratively studied in 8 laboratories to determine the drug in tablet form at 2 dosage levels. The disulfiram was extracted from the tablet matrix with methylene chloride. After a basic wash with 1 M NaOH, an aliquot of the methylene chloride solution was reacted with solid cuprous iodide, and the absorbance of the resulting color was measured. Single assays on 2 synthetic preparations of known disulfiram content were performed with average recoveries of 98.4 and 99.2% for 93.3 and 105.3 mg, respectively. Duplicate determinations on 2 commercial tablet preparations declared at 250 and 500 mg gave mean and standard deviation values of 246.6 +/- 6.40 and 493.6 +/- 12.0 mg, respectively. The results agreed closely with those obtained by the author using the NF iodometric titration procedure. The method has been adopted official first action.

Chromatography, Thin Layer↗
PubMed1980

Humoral and cellular immune responses of seronegative children vaccinated with a cold-adapted influenza A/HK/123/77 (H1N1) recombinant virus.

Humoral and cell-mediated immune responses of young, seronegative children were assessed after intranasal vaccination with a cold-adapted influenza. A/HK/77 (H1N1) CR 35 recombinant virus. Vaccines shedding influenza virus experienced a rise in hemagglutinin-inhibition antibody 15 to 30 days after vaccination. Vaccinees showed low but significant lymphocyte transformation to A/USSR (H1N1) by day 8 after vaccination, which decreased to prevaccination levels at 30 to 34 days. The lymphocyte transformation response occurred before serum antibody rises were detected by hemagglutinin-inhibition assay. No change in lymphocyte responsiveness was observed after vaccination as measured by phytohemagglutinin stimulation. Lymphocytes responded to in vitro incubation with inactivated influenza (H1N1) virus by producing interferon. The interferon produced was of type I and was observed in vaccinees and nonvaccinees both before and after vaccination.

Antibodies, Viral↗
PubMed1980

Cell-mediated immune response of human lymphocytes to influenza A/USSR (H1N1) virus infection.

Cell-mediated immunity to influenza A/USSR (H1N1) virus was assessed by measuring transformation response and interferon production by Ficoll-Hypaque-purified peripheral blood lymphocytes from children and adults. Lymphocyte transformation was found to be related to the individual's previous experience with H1N1 influenza virus. Lymphocyte cultures, obtained from adults who had their last contact with the H1N1 virus over 20 years ago, were able to transform when incubated with H1N1 influenza antigens. This response suggests that influenza virus can induced long-term cell-mediated immunity for periods of at least 20 years. Interferon produced by stimulated lymphocytes was found to be unrelated to previous contact with influenza H1N1 virus; seronegative as well as seropositive individuals were capable of producing interferon in response to viral antigens. The interferon produced was type I.

Adult↗
PubMed1976

[Efficiency of revascularization of the liver by intra-hepatic implantation of the splenic vascular pedicle].

Experiments carried out in 12 dogs with ligature of the hepatic lobar artery, show that intra-hepatic implantation of the splenic artery, or vascular pedicle, offers limited revascularisation. This produces a fall in blood flow in the implanted artery, reduction in glycogen and hepatic A.T.P., associated with a fall in the total protein content and hepatosine. At the same time, although there is a rich network of neoformed vessels, the hepatic transaminase and lactate activities undergo a pronounced rise.

Adenosine Triphosphate↗