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T Bino

Publications and source records attributed to T Bino.

28 records · Page 2Linked to original sources

Treatment of life-threatening viral infections with interferon alpha: pharmacokinetic studies in a clinical trial.

The effectiveness of human leukocyte interferon (IFN alpha) therapy was studied in 15 patients with acute life-threatening viral illnesses. All patients were critically ill, many close to death, when IFN therapy was begun. Included were six patients with acute fulminant hepatitis, four immunosuppressed patients with spreading herpes simplex, three severely ill patients with encephalitis, one case of severe fulminant juvenile laryngeal papillomatosis, and one of postmeasles dermatitis. Twelve of the 15 patients recovered, some dramatically, including 3 of the 6 fulminant hepatitis patients. Pharmacokinetic studies showed defective antiviral IFN responses in most of the patients--in particular, absence of in vivo IFN production. Because the patients were not producing IFN in response to the viral infection, the peripheral blood mononuclear cells were not primed into an antiviral state. Treatment with IFN alpha led to the rapid development of an antiviral state of the cells, which paralleled clinical recovery. In our opinion, IFN is the treatment of choice in acute viral infections, often lifesaving, provided it is given early in the infection before irreversible cell and tissue damage has taken place. Its use is most effective in those seriously ill patients with defective antiviral IFN responses.

Adolescent↗

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↗

A new cellulose-based microcarrier culturing system.

A search for new substrates to be used as microcarriers for culturing mammalian cells was carried out. Commercially available microgranular anion exchange DEAE-cellulose (DE-52 of Whatman) were investigated as microcarriers for anchorage-dependent-cells. Cells from CCL-1 mouse cell line were grown on the investigated microcarriers. Mouse interferon was successfully produced after induction with Sendai virus. Interferon yield per cell was similar to that obtained in monolayer culture.

Animals↗

Pilot plant scale production of human lymphoblastoid interferon.

Pilot plant scale production of human lymphoblastoid (Namalva) interferon (IF) is described. Namalva cells were grown in a semicontinuous cultivation method in pilot plant scale fermentors having up to 40-liter culture volume. The harvested Namalva cells were suspended in a serum-free medium at a concentration of 10(7) cells per ml and were induced to produce IF by infection with Sendai virus. The content of IF and protein in the culture supernatant ranged between 2.5 to 5.0 x 10(4) IF units and 150 to 250 microgram protein per ml, respectively. Concentration and partial purification of the IF was done by trichloroacetic acid precipitation, followed by gel filtration through an Ultrogel AcA 54 column. The specific activities of the IF preparations ranged between 2 to 4 x 10(6) IF units per mg protein. Scaling-up the IF production system to 300 liter fermentor scale is under research and development.

Cell Division↗

Variable efficacy of interferon-alpha treatment on growth of human hepatoma cell lines in vitro.

Three human hepatoma cell lines, PLC/PRF/5, Mahlavu and Sk-Hep 1, two of which contain integrated HBV DNA, were grown in culture and treated with human alpha-IFN for up to 14 days. IFN treatment caused a varying suppression of cell growth of the three hepatoma cell lines. While doubling time and cloning efficiency were significantly reduced for all three hepatoma cell lines tested, 3[H]thymidine incorporation was markedly suppressed, in a dose-dependent fashion, only in treated PLC/PRF/5 cells but not in Sk-Hep 1 and Mahlavu cells. The inhibiting effect of interferon treatment on growth of PLC/PRF/5 cells in vitro was neutralized by antibodies to human IFN. IFN treatment caused a significant suppression of HBsAg and alpha FP secretion by PLC/PRF/5 hepatoma cells. This effect, while constant throughout the observation period for HBsAg, was cumulative for alpha FP secretion. Following discontinuation of treatment, suppression of PLC/PRF/5 hepatoma cell growth was rapidly reversed, and HBsAg and alpha FP secretion returned to their pretreatment levels. These experiments suggest that human alpha-IFN suppresses the growth of some human hepatoma cells in culture but that this effect is dependent on the continuous presence of IFN in the growth medium. Finally, the inhibitory effects of IFN on cell growth differed for the various hepatoma cell lines tested.

Animals↗

Absence of interferon activity during acute attacks of familial Mediterranean fever.

The pharmacokinetics of interferon, the symptoms caused by its administration, the decreased prevalence of viral diseases in FMF patients and the fact that colchicine, the drug of choice in the prevention of FMF attacks is an interferon antagonist, raised the question whether interferon may have a role in the pathogenesis of FMF attacks. An interferon activity was not detected in sera obtained at the height of FMF attacks in 8 patients, six of them under colchicine treatment. It is possible that the interferon activity has to be searched at the very beginning of FMF attacks, since at their height it already disappeared from the serum, while the symptoms of the attack are further mediated by other interferon-induced lymphokines.

Acute Disease↗