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Dive into the research topics where William E. Stewart is active.

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Featured researches published by William E. Stewart.


Virology | 1975

Molecular heterogeneity of human leukocyte interferon: two populations differing in molecular weights, requirements for renaturation, and cross-species antiviral activity.

William E. Stewart; Jan Desmyter

Abstract The finding that human leukocyte interferon preparations could be completely renatured after boiling in sodium dodecyl sulfate (SDS) but could be only partially reactivated after boiling in SDS under reducing conditions suggested that human leukocyte interferons contain two types of interferons. Here we report that human leukocyte interferon preparations do, indeed, contain two molecular populations that can be distinguished physically, chemically, and biologically. Leukocyte interferon boiled in SDS was electrophoresed in SDS-polyacrylamide gels, and two peaks of activity were obtained, a major peak at approximately 15,000 daltons and a minor peak at approximately 21,000 daltons. Leukocyte interferon boiled in SDS under reducing conditions was electrophoresed in SDS-polyacrylamide gels and only the minor peak, at 21,000 daltons, was obtained: the amount of activity recovered at 21,000 daltons was identical whether the samples were reduced or not, but the activity at 15,000 daltons was completely eliminated by reduction. The two populations of leukocyte interferons also exhibited disparity in cross-reactivity on rabbit cells: the population with a molecular weight of 21,000 daltons was active to the same extent on human diploid cells and on secondary rabbit kidney cells, whereas the population with a molecular weight of 15,000 daltons expressed only about 5% of its homologous titer on rabbit cells.


Virology | 1974

Distinct molecular species of interferons

William E. Stewart

Abstract Interferons induced in mouse L 929 cells could be renatured from the protein-dissociating system of sodium dodecyl sulfate (SDS), mercaptoethanol, and urea after boiling at 100°. Therefore, SDS-polyacrylamide gel electrophoresis under reducing conditions was used to analyze mouse L cell interferons. Preparations, crude or partially purified, contained two well-separated molecular species of interferon: a major component (about 90% of the total activity) at 38,000 daltons and a minor component (about 10% of the total activity) at 22,000 daltons. That the smaller component was not a subunit of the larger component was evident from the finding that, while the amount of activity of the smaller species recoverable was essentially unchanged whether the preparations were reduced or not, the amount of activity of the larger species recoverable was greatly increased (about 10-fold), rather than decreased, under reducing conditions. Also, when the interferon eluted from unreduced gels at 38,000 daltons was boiled in SDS, mercaptoethanol, and urea, latent activity was “unmasked” giving an increase of about 10-fold in activity. The data indicate that mouse L cell interferon preparations contain two molecular species of interferon: a smaller species renaturable with or without reduction and a larger and predominant species requiring disruption of disulfide bonds for efficient renaturation.


Virology | 1976

Molecular modification of interferon: attainment of human interferon in a conformation active on cat cells but inactive on human cells.

Jan Desmyter; William E. Stewart

Abstract Human leukocyte interferon (HLIF) was found to be more active on cat cells than on human cells; fibroblast interferon was less cross-reactive. Treatment of HLIF with SDS under reducing conditions did not affect its activity on cat cells, but destroyed most of its homologous activity. After SDS-polyacrylamide gel electrophoresis of unreduced HLIF, its activity on cat cells was found to reside in the two molecular populations which were active on human cells (MW of about 15,000 and 21,000). After treatment with SDS under reducing conditions, the interferon activity of the 15,000 MW population was entirely reactivated for cat cells, but was completely abolished for human cells. The data suggest that certain interferons can be modified to attain a conformation which, though inactive in homologous cells, is fully able to induce antiviral activity in heterologous cells. Also, certain interferon molecules with high activity on cat cells, but little or no activity on human cells, appear to be present in unreduced HLIF.


Journal of General Virology | 1975

Distinct Molecular Species of Human Interferons: requirements for Stabilization and Reactivation of Human Leukocyte and Fibroblast Interferons

William E. Stewart; P. De Somer; Victor G. Edy; Kurt Paucker; Kurt Berg; Clifton A. Ogburn

Human fibroblast interferon preparations were completely stabilized to 100 degrees C by sodium dodecyl sulphate (SDS) in the presence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS without mercaptoethanol. On the contarary, human leukocyte interferon preparations were completely stabilized to 100 degrees C by SDS in the absence of mercaptoethanol, but only a minor fraction of their activities were stabilized by SDS in the presence of mercaptoethanol. Furthermore, human fibroblast interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS under reducing conditions, but only a minor part of their activities were restored by SDS in the absence of reduction. On the contrary, human leukocyte interferon preparations whose activities had been destroyed by boiling at 100 degrees C were completely reactivated by SDS in the absence of reduction, but only a minor part of their activities were restored by SDS under reducing conditions. These data suggest that there are distinct molecular species of human interferons.


Journal of General Virology | 1973

Specificity of interferon-induced enhancement of toxicity for double-stranded ribonucleic acids.

William E. Stewart; E. De Clercq; P. De Somer

Summary Interferon-treated cells exhibited an increased susceptibility to the toxicity of several natural and synthetic double-stranded RNA molecules and to vaccinia virus, provided the latter was able to undergo replicative events. However, interferon-treated cells exhibited no enhanced susceptibility to several other toxic materials or to vaccinia virus that was unable to replicate. These findings suggest that interferon-treated cells exhibit a specific enhanced susceptibility to the toxicity of double-stranded RNA molecules. Since neither RNA nor protein synthesis was required for toxicity to occur in interferon-treated cells exposed to polyriboinosinic-polyribocytidylic acid, it appears that the double-stranded RNA configuration is directly lytic for interferon-treated cells.


Virology | 1973

Poly(rI) more important than poly(rC) in the interferon induction process by poly(rI)·poly(rC)

Erik De Clercq; William E. Stewart; Pierre De Somer

Abstract A significantly greater interferon production has been obtained in primary rabbit kidney cell cultures exposed to poly(rI) followed by poly(rC) than in cell cultures exposed to poly(rC) followed by poly(rI). The interferon response in cell cultures exposed to poly(rI) followed by poly(rC) was markedly more resistant to poly- l -lysine and pancreatic ribonuclease treatment than was the interferon response in cell cultures exposed to poly(rC) followed by poly(rI). In addition, poly- l -lysine treatment removed a substantially greater proportion of cell-associated radioactivity from cells exposed to [ 3 H]poly(rC) followed by poly(rI) than from cells exposed to poly(rI) followed by [ 3 H]poly(rC). These findings suggest that the poly(rI) · poly(rC) complex is more tightly and efficiently bound to the cell (surface) when the homopolymers are added in the order poly(rI), poly(rC) than when they are added in the order poly(rC), poly(rI) and that it is more effectively attached to the cell receptor site by its poly(rI) strand rather than by its poly(rC) strand.


Journal of General Virology | 1974

Relationship of cytotoxicity and interferon-inducing activity of polyriboinosinic acid. Polyribocytidylic acid to the molecular weights of the homopolymers.

William E. Stewart; E. De Clercq

Summary The molecular size of poly I.poly C required for lysis of interferon-treated L cells was the same as the size required for induction of interferon in these cells. The size requirement for both interferon induction and toxicity for interferon-treated L cells resided in the poly I strand, while variations of the poly C strand size were without effect on interferon induction or cell lysis. The size of poly I.poly C required to induce interferon in primed L cells or primed primary rabbit kidney cells was the same as the size required to induce interferon in normal L cells or normal rabbit kidney cells. Again, these requirements proved more stringent for the poly I strand than for the poly C strand. These data suggest that both primed and normal cells recognize the same molecular ‘trigger’ for interferon induction.


Science | 1974

Interferon induction: tool for establishing interactions among homopolyribonucleotides

E. De Clercq; Paul F. Torrence; Bernhard Witkop; William E. Stewart; P. De Somer

Hitherto unrecognized interactions between homopolyribonucleotides and complexes thereof are suggested by interferon induction data obtained in a highly sensitive assay system of primary rabbit kidney cell cultures superinduced by metabolic inhibitors.


Journal of General Virology | 1974

Integrity of Cell-bound Poly(I).Poly(C)

E. De Clercq; William E. Stewart

Summary The acid-insoluble radioactivity associated with the cells following incubation of the cells with [3H]-labelled poly(I).poly(C) [poly(I).poly(C) * for 1 h has been analysed by sucrose gradient velocity ultracentrifuging. Intact (poly(I).poly(C) * was recovered from primary rabbit kidney (PRK) cells, partially degraded poly(I). poly(C) * was recovered from mouse L 929 cells and completely degraded material was recovered from HeLa and VERO cells. Priming of the cells with homologous interferon did not alter the sedimentation profile of cell-associated poly(I).poly(C) * in PRK, L 929 or HeLa cells.


Journal of General Virology | 1974

Renaturation of Inactivated Interferons: requirement for Reduction of a Major Component; lack of Requirement for Reduction of a Minor Component

William E. Stewart; P. De Somer; E. De Clercq

Summary Mouse L cell interferon that had been either partially or completely inactivated by heating at 56 °C, boiling at 100 °C, shaking, repeated freezing and thawing, or treatment with mercaptoethanol and urea could be partly reactivated by addition of the anionic detergents, decyl-, dodecyl-, or tetradecyl sulphate. For complete reactivation it was necessary to disrupt disulphide bonds of interferon in solutions containing detergents.

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E. De Clercq

Rega Institute for Medical Research

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P. De Somer

Katholieke Universiteit Leuven

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Erik De Clercq

Rega Institute for Medical Research

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Pierre De Somer

Rega Institute for Medical Research

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Jan Desmyter

Rega Institute for Medical Research

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Alfons Billiau

Katholieke Universiteit Leuven

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Hubertine Heremans

Katholieke Universiteit Leuven

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Victor G. Edy

Rega Institute for Medical Research

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Bernhard Witkop

National Institutes of Health

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