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Biomedical subjects

S Baron

Publications and source records attributed to S Baron.

At least 163 records · Page 9Linked to original sources

Broadly active inhibitor of viruses spontaneously produced by many cell types in culture.

A broadly active inhibitor of viruses (vaccinia, polio 1, and vesicular stomatitis) was found in the culture fluid from many types of normal human and mouse cells in culture. Virus plaque-inhibiting activity appeared in culture fluids within a few hour after incubation of cultures with fresh medium. Peak inhibitory activity occurred within 24 h. Blockade of cellular ribonucleic acid or protein synthesis decreased appearance of the inhibitor, thereby substantiating that it is a cell-produced viral inhibitor. Inhibition of virus required the simultaneous presence of inhibitor, virus, and cells (due to the reversible nature of the inhibition of virus attachment and penetration, as shown in the accompanying paper [T. K. Hughes et al., Infect Immun. 32:454-457, 1981]). The degree of inhibitory activity depended on the animal species of origin of the inhibitor, the cell type used for assay, and the virus type used for challenge. No cell species barrier against inhibitor action was found. Strong inhibition of multicycle yields of vesicular stomatitis virus and Sindbis virus was caused by low doses of inhibitor. These specific characteristics of the present inhibitor separate it from commonly recognized inhibitors. Possible biological significance of the inhibitor is discussed.

Animals↗

Cell-produced viral inhibitor: possible mechanism of action and chemical composition.

A newly recognized cell-produced viral inhibitor appeared to be spontaneously released from most cells in tissue culture. It strongly inhibited the replication of a variety of viruses but did not exhibit species specificity as does interferon. These studies on the inhibitor's mechanism of action indicated that it inhibited attachment and penetration of virus by a readily reversible reaction requiring the presence of both virus and cells. Studies of inactivation by specific enzymes or chemicals indicated that for activity the inhibitor required intact protein but not lipid, carbohydrate, deoxyribonucleic acid, or ribonucleic acid.

Animals↗

Mechanism of recovery from systemic herpes simplex virus infection. I. Comparative effectiveness of antibody and reconstitution of immune spleen cells on immunosuppressed mice.

The role of cellular immunity, humoral antibody, and interferon in recovery from primary systemic infection in mice due to herpes simplex virus type 1 (HSV-1) was studied. Immunosuppression by three methods--each of which was sufficient to suppress humoral and cellular immunity--markedly potentiated primary systemic HSV-1 infection. Immunosuppressed mice did not form neutralizing antibody to HSV-1, but passive transfer of physiologic amounts of neutralizing antibody as late as day 6 after infection exerted a protective effect. Passive transfer of 10(8) immune spleen cells on day 3 after infection was only partially protective and did not thereafter reverse the effect of X-irradiation on HSV-1 infection. Furthermore, mice that received immune cells appeared to make sufficient antibody to explain the protective effect of the transferred cells. These results suggest that antibody to HSV-1 has a critical role in promoting recovery from primary infection in this model. The findings neither favor nor exclude a defensive role for immune cells in this experimental primary HSV-1 infection.

Animals↗

Human fibroblast interferon in tears of patients with picornavirus epidemic conjunctivitis.

We report the levels of coxsackievirus type A24 (CA24) and the levels and type of interferon produced early during naturally acquired picornavirus epidemic conjunctivitis. Virus levels ranging from 10(1.8) to 10(5.8) 50% tissue culture infective doses per ml were detected in 29 of 37 acute (collected 1 to 4 days after onset of conjunctivitis) tear samples. Interferon (10(1.5) to 10(3.3) U/ml) was detected in 12 of 29 tear samples collected on day 1, in 2 of 6 tear samples collected on day 2, and in 1 tear sample collected on day 3 after onset of conjunctivitis. The interferon activity in pooled tear samples was completely neutralized by antiserum against human fibroblast interferon, stable at pH 2.0, and active against different viruses. In addition, the interferon activity in tears, like human fibroblast and leukocyte interferons produced in vitro, protected human and rabbit, but not mouse, cells. This is the first report of production and identification of the antigenic type of interferon induced by an enterovirus during natural infection. The early appearance of fibroblast interferon suggests that it may be an important host defense at the local site of implantation against this and possibly other enterovirus infections.

Animals↗

Potentiation of antitumor effect of virus-induced interferon by mouse immune interferon preparations.

In inbred DBA/2 mice, the antitumor activities of separate and combined preparations of mouse immune interferon and mouse virus-induced interferon on the development of P388 tumors were studied. Immune interferon alone (25 U/day) did not affect tumor development. Virus-induced interferon alone (25,000 U/day) delayed tumor development and increased survival time. The mouse immune interferon preparations significantly enhanced or potentiated the antitumor effects of mouse virus-induced interferon when the interferons were used in combined therapy.

Animals↗

Early-appearing antiviral activity in human tears during a case of picornavirus epidemic conjunctivitis.

The clinical, virological, and immunological courses of a laboratory-acquired hemorrhagic conjunctivitis were followed. Coxsackievirus type A24 (CA24) was isolated from tears for only two days but from sputum and fecal samples for 20 days. Maximal levels of virus were detected in the right eye (10(5.1) 50% tissue culture infective doses/ml) 5-7 hr before conjunctivitis in the right eye, and in feces (10(2.8) 50% tissue culture infective doses/g) and sputum (10(2.5) 50% tissue culture infective doses/ml) five and eight days after onset of conjunctivitis, respectively. Specific neutralizing activity against CA24 was detected in tear samples 48-56 hr after exposure, and elimination of virus was associated with the rise in the neutralizing activity in tears. This activity was detected earlier than previously reported antibody responses of the eye. The absence of interferon and the association of this early neutralizing activity in tears with early elimination of virus from the eye suggest that neutralizing activity may play a major role in the clinical and pathological manifestations of this infection.

Antibodies, Viral↗

Effect of specific antibodies on chronic echovirus type 5 encephalitis in a patient with hypogammaglobulinemia.

The effects of specific antibodies in chronic echovirus type 5 (echo 5) encephalitis were investigated in a patient with x-linked hypogammaglobulinemia. Virus was detected in cerebrospinal fluid (CSF) and blood despite treatment with commercial human gammaglobulin that contained low titers of antibodies to echo 5 (0.6 x 10(4) units per injection). Virus disappeared from blood and CSF when plasma containing high concentrations of antibodies (total dose, 1--4 x 10(4) units/kg) was administered intravenously. Maximal inhibition of virus was achieved in culture and in the patient's CSF when the titer of antibody to echo 5 in CSF was greater than or equal to 16 units/ml. Although the patient died, hyperimmune plasma improved the neurologic status and eliminated detectable virus from the blood and CSF.

Agammaglobulinemia↗

Mechanisms of interferon induced transfer of viral resistance between animal cells.

The sequence of events initiated by interferon and leading to the antiviral state were studied as possible sites for the cell-to-cell transfer of interferon induced viral resistance. The possible role of interferon produced by recipient cells was negated by the demonstration of transfer of resistance in the presence of anti-human interferon antibody and under conditions of a single cycle of VSV growth. Transfer of sensitivity of WISH cells to mouse interferon, possibly through transfer of a membrane receptor, seems unlikely since resistance was transferred in the absence of mouse interferon. From kinetic data and the fact that actinomycin D blocked resistance in human cells for 3 h longer than in mouse cells, it seems unlikely that the mouse antiviral protein itself or its mRNA alone is a likely candidate for the transfer of resistance. Thus, by a process of elimination, we suggest that secondary messenger molecules which transmit the interferon signal from the membrane to the nucleus are the effector substance(s) for the transfer process.

Animals↗