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Biomedical subjects

S Baron

Publications and source records attributed to S Baron.

At least 181 records · Page 10Linked to original sources
PubMed1978

Interferon inhibits C-type virus at a posttranscriptional, prerelease step.

The mode of action of interferon in JLSV 5-cells, chronically infected with Rauscher murine leukemia virus (MLV), was studied by examining the fate of preexisting labelled viral RNA in interferon-treated cells and by determining the infectivity/physical particle ratio of cell-associated and extracellular virus. Interferon added together with 3H-uridine inhibited the production of labelled virus particles even when it was only allowed to act after all viral RNA synthesis had been stopped by actinomycin D. This indicated that the interferon-induced antiviral state primarily functions at a posttranscriptional step. When interferon was given after a 3H-uridine pulse label and arrest of label incorporation by glucosamine and unlabelled uridine, it prevented a portion of the preexisting radioactive RNA from occurring in extracellular particles. However, part of the labelled viral RNA had reached a stage beyond which interferon could not prevent it from occurring in extracellular virus particles. The notion that interferon primarily affects release of fully assembled and enveloped MLV particles may be eliminated: interferon-treatment did not affect the release of particle-bound reverse transcriptase in cells treated with cycloheximide after the antiviral state had been established. It was confirmed that interferon-treated JLSV 5-cells contained an increased number of virus particles associated with the cell membrane. However, these particles were found to have a reduced infectivity compared to those associated with control cells, thus confirming the view that virions produced by interferon-treated cells are defective; perhaps lacking in certain components.

Cell Line↗
PubMed1978

Various heterologous cells exhibit interferon induced transfer of viral resistance.

Previously it was shown that cocultivation of mouse L and human WISH or baby hamster kidney cells in the presence of mouse interferon resulted in decreased viral yield from both cell species. We now show that this phenomenon also occurs when rabbit kidney and human WISH cells, with their corresponding interferons, are cocultivated with human WISH and baby hamster kidney cells, respectively. This finding increases the number of donor cell types to three. The related finding that monkey VERO and chick embryo cells can be recipients of transferred resistance expands the number of heterologous recipient cell species capable of receiving transferred resistence to five. Not all cell types tested have been shown to function in this transfer system. The fact that VERO cells, which do not produce interferon, are capable of receiving transferred resistence is significant because it indicates that the mechanism of transfer does not involve production or interferon by the recipient cells.

Animals↗
PubMed1978

Rapid activation of the interferon system in vivo.

Experiments were carried out to study the kinetics of local interferon production in the subcutaneous tissues of rats stimulated with Newcastle disease virus. Specifically, the interferon produced and released in the extracellular fluids was collected at various intervals of time in micropore chambers implanted into the subcutaneous tissue of rats. Interferon was detected at moderate titers 1 h after induction, and it was present at high titer at 2 h. The interferon levels remained remarkably high in the samples collected after 3, 5, and 24 h, and in some rats it was still detectable after 48 and 72 h. Since control experiments showed that it requires 2 to 3 h for interferon to penetrate the chambers, it may be concluded that high concentrations of interferon are present in the extracellular fluid within 1 h of induction. The evaluation of the kinetics of production and of the concentrations attained in the extracellular fluid suggests that in a solid tissue a cell infected by a potent interferon inducer may produce interferon early enough and in sufficient quantity to protect neighboring cells before the production of progeny virions.

Animals↗
PubMed1978

The role of interferon in virus infections and antibody formation.

Virus-type interferon is capable of suppressing the antibody response both in vivo and in vitro. Interferon induced by antigen or mitogen (immune interferon), primarily in T-lymphocytes, also appears capable of suppressing the antibody response. Cyclic AMP has a regulatory effect on the induction of both virus-type and immune interferon. The immunosuppressive effects of virus-type and immune interferon may differ at the cellular or subcellular level.

Animals↗
PubMed1977

Effect of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid complex on yellow fever in rhesus monkeys (Macaca mulatta).

Rhesus monkeys (Macaca mulatta) treated with a newly developed nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid, poly-L-lysine, and carboxymethylcellulose [poly (ICLC)] did not die after challenge with virulent Asibi strain yellow fever (YF) virus. The strain of virus is sensitive to the effects of interferon in vitro and is lethal for rhesus monkeys four to six days after subcutaneous administration of 1,000 plaque-forming units of the virus. The mortality rate was reduced in monkeys initially treated 8 hr before or after inoculation of virus but was unchanged in monkeys initially treated 24 hr after challenge. Treated monkeys developed neutralizing antibody to YF virus. The successful treatment of yellow fever in a primate model with use of poly (ICLC) suggests a meaningful role for the interferon system in the host defense against this viral infection.

Animals↗
PubMed1977

Clinical studies of an interferon inducer, polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)], in children.

Fifteen children ranging in age from one and one-half to 14 years received intravenous polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)], an interferon inducer. The patients all had serious neurologic illness either directly or circumstatially related to viral infection. Peak titers of interferon in serum ranged from 8 to 500 units/ml in response to doses of poly (I)-poly (C) of 0.1-1.0 mg/kg. Serum interferon persisted for less than or equal to 24 hr after induction. Hyporesponsiveness to a second dose of poly (I)-poly (C) persisted for seven days after initial induction, after which time full response again occurred. The half-life of poly (I) poly (C) in plasma as measured in three patients was less than 30 min. poly (I-poly(C) appears to be safe when given intravenously, but the low titers of interferon induced may limit its clinical usefulness as an antiviral drug.

Adolescent↗
PubMed1977

Interferon induction in cynomolgus and rhesus monkey after repeated doses of a modified polyriboinosinic-polyribocytidylic acid complex.

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid . polyribocytidylic acid complex per kg, composed of polyriboinosinic acid . polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.

Animals↗
PubMed1977

Interferon induction by radioprotective mercaptoalkylamines and derived thiophosphates.

Radioprotective thiols (five mercaptoalkylamines and four derived thiophosphates) induced interferon and resistance to virus infection. Interferon production occurred in human and mouse nonlymphoid cell cultures. One of the thiols, S,2-aminoethylisothiourea, given intraperitoneally, protected mice against two unrelated viruses--Semliki forest virus and Herpesvirus hominis type 1. Two structurally different radioprotective thiols--the disulfide cystamine and L-cysteine--were unable to induce the firus resistance state or interferon.

Animals↗
PubMed1977

Effect of interferon, elevated temperature, and cell type on replication of acute hemorrhagic conjunctivitis viruses.

Five strains of enterovirus type 70 (E 70) and four of coxsackievirus type A 24 (CA 24) were studied for their sensitivity to interferon (IF), ability to induce IF, replication at various temperatures, and adaptability to human and mouse cell cultures. We found that isolates ranged from 0.01 to 16 times as sensitive to fibroblast IF as vesicular stomatitis virus, depending upon the cell type used and the multiplicity of infection. Most of the isolates induced no detectable IF; however, when induction occurred the titers were relatively low (5 to 300 U). Only E 70 virus isolates were adaptable to growth in L-cells. Replication of all viruses was inhibited approximately 90% at 37 to 39 degrees C depending upon the cell type. These results and the accessibility of the eye to application of IF and/or heat suggests the possibility of their use for treatment. The adaptation of certain E 70 viruses to mouse L-cells opens the possibility of development of a mouse model infection.

Cell Line↗
PubMed1977

Variables affecting viral plaque formation in microculture plaque assays using homologous antibody in a liquid overlay.

A liquid antibody microculture plaque assay and the variables that govern its effectiveness are described. The assay is based on the principle that low concentrations of homologous antibody can inhibit secondary plaque formation without inhibiting formation of primary plaques. Thus, clear plaques that followed a linear dose response were produced. The assay was found to be more rapid, less cumbersome, and less expensive than assays using agar overlays and larger tissue culture plates. It was reproducible, quantitative, and had about the same sensitivity as the agar overlay technique in measuring infectious coxsackievirus type B-3. It was more sensitive in assaying adenovirus type 3 and Western equine encephalomyelitis, vesicular stomatitis, Semliki forest, Sendai, Sindbis, and Newcastle disease viruses than were liquid, carboxymethylcellulose, and methylcellulose microculture plaque assays. The variables influencing sensitivity and accuracy, as determined by using coxsackievirus type B-3, were: (i) the inoculum volume of virus; (ii) the incubation period of virus; and (iii) the incubation temperature.

Adenoviruses, Human↗
PubMed1977

Benign ulceration of the cecum.

Three proved cases of benign ulceration of the cecum are presented, 2 with acute onset of abdominal pain, the third with acute hemorrhage. The clinical, pathological, and variable radiographic features are described.

Adult↗