scholarly journals AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM

1953 ◽  
Vol 97 (5) ◽  
pp. 627-638 ◽  
Author(s):  
Richard E. Shope

Helenine exerts a therapeutic effect against Semliki Forest virus infections of mice. Cures, that is to say the survival of treated animals, were more frequently observed in Semliki Forest virus infections than they were in SK virus infections. It is believed that this difference in end-result probably represented only a quantitative difference in the therapeutic effect of helenine against these two viruses and not a qualitative difference in its mechanism of therapeutic action. The findings reported in this paper with regard to the treatment of Semliki Forest virus infections with helenine parallel very closely those described in an accompanying paper which deals with the action of helenine on SK. virus infections.

1966 ◽  
Vol 123 (2) ◽  
pp. 213-227 ◽  
Author(s):  
Richard E. Shope

1. Helenine injected intraperitoneally 24 hr prior to a regularly fatal dose of Semliki Forest virus saves most of the mice to which it is administered. 2. Mice saved by helenine develop no viral immunity and regularly succumb when rechallenged 2 wk later with the same dose of virus from which they were originally saved. 3. The time during which helenine is optimally effective in protecting mice from death by Semliki Forest virus covers a period of approximately 36 hr beginning after about 12 hr and extending to 48 hr before virus infection. When periods of less than 12 hr, or more than 48 hr, elapse between the time of helenine administration and virus inoculation, its protective effectiveness diminishes progressively. 4. Repeated injections of helenine at 2- or 3-day intervals, if continued long enough, exhaust the capacity of a host to respond favorably to helenine administered 24 hr before virus inoculation. 5. Helenine injections at intervals of 4, 3, and 2 wk before its administration 24 hr prior to infection do not decrease the effectiveness of this final dose in protecting mice from fatal infection by the virus. The experimental results here reported indicate that, as suggested by the findings of earlier work, helenine does not act directly as an antiviral substance, but instead exerts its effect through some substance that it induces the host to elaborate. The nature of this induced antiviral substance is as yet unknown though, to judge from the failure of spared mice to acquire viral immunity, it appears to act at a stage in viral replication prior to that at which antigenic viral protein is produced. The findings with helenine and those thus far reported for interferon afford no factual basis for judging the relationship of the two, if any.


1953 ◽  
Vol 97 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Richard E. Shope

A culture of P. funiculosum isolated on Guam proved capable of elaborating a substance which exerted a favorable therapeutic effect against swine influenza virus infections in white mice. The culture was extremely variable and irregular in its production of the antiviral substance, and during maintenance in the laboratory for several years gradually lost this property. Efforts to restore it were unsuccessful. Subsequently it was found that the mold elaborated a substance, now designated helenine, which is therapeutically effective against Columbia SK encephalomyelitis virus infections in mice. Helenine appears to differ from the substance earlier procured from the mold, which was active against swine influenza virus infections in mice. It is frequently present in greater or lesser amount in the fluid portions of stationary cultures of P. funiculosum but is more regularly obtained and in larger amount, from the cellular components of the pellicles. When liberated from these latter by mechanical bruising and fracturing, it goes into solution in the culture fluids. It is precipitable from aqueous solution by 50 per cent acetone. Infected mice injected with helenine in amounts less than the amount which produces a maximal therapeutic effect exhibit a dosage response. Increasing the dose above the optimum fails to increase the therapeutic effect. Helenine exerts its maximum effect when given within the first 10 hours after viral infection but its influence is apparent even when treatment is delayed for up to 24 hours. It is not effective against massive amounts of virus and gives the best therapeutic results when used in the treatment of animals infected with from 10 to 1000 fatal doses of virus. Treatment of infected mice with helenine delays the entrance of virus into their brains for from 24 to 48 hours. The mechanism by which helenine exerts its therapeutic effect against SK virus is not known but the findings presented suggest either that it causes an inhibition or interruption of multiplication of the virus, slowing down the whole process of infection and spread to the central nervous system, or that in some way it interferes temporarily with the neuroinvasiveness of the virus.


1966 ◽  
Vol 124 (1) ◽  
pp. 15-31
Author(s):  
Richard E. Shope

1. Helenine prevents the establishment in mice of passive viral immunity by anti-Semliki serum of swine, rabbit, or guinea pig origin. 2. A period of 12 days must elapse, between the antiviral serum administration and challenge with virus, for prevention of the establishment of passive immunity to become apparent. This period is believed to correspond to that in which injected antibody persists in circulation in the injected host. 3. Helenine is effective in preventing the establishment of passive viral immunity by heterologous antiviral sera when it is administered any time during a period of 6 days, extending from 4 days before to 2 days after injection of the antiviral serum. 4. Helenine does not prevent the establishment of passive viral immunity by antiviral sera of mouse origin (homologous). 5. Evidence is presented to indicate that the phenomenon of the prevention of the establishment of passive viral immunity by heterologous antiviral sera is not effected directly, but rather is mediated through some substance that helenine induces the injected host to elaborate. 6. The capacity to prevent the establishment of passive viral immunity could not be exhausted by repeated preceding injections of helenine at 2- or 3-day intervals. 7. Evidence is presented to indicate that the helenine-induced material does not act upon antiviral antibody per se but rather on heterologous foreign protein that happens to be labeled as Semliki Forest virus antibody. This helenine-induced material, whatever its nature, appears to enhance the capacity of the injected host to recognize and dispose of foreign protein. 8. Statolon, a material that like helenine is a known inducer of interferon, is, like helenine, also capable of preventing the establishment of passive viral immunity by heterologous antiviral sera. 9. Experiments designed to determine whether the induced material responsible for the antipassive immunity effect of helenine is interferon have yielded inconclusive answers thus far.


1966 ◽  
Vol 124 (5) ◽  
pp. 915-919 ◽  
Author(s):  
Richard E. Shope

Helenine, NDV, and statolon, all known inducers of interferon in mice, all exerted a marked antiviral effect against Semliki Forest virus. This AV effect was, so far as can be demonstrated, mediated through, the induced interferon. The same three materials also exerted a marked antipassive immunity effect. All the evidence that can be brought to bear indicates that this API effect like the AV effect is mediated through interferon known to be induced by the three materials. If the API effect does indeed have interferon as its basis, this represents a new and totally unsuspected action of interferon.


1969 ◽  
Vol 51 (1) ◽  
pp. 71-76
Author(s):  
H. Irizarry ◽  
J. Howard Ellison ◽  
Portia Orton

Two mature, dark-green asparagus plants (one female and one male) termed "persistent-green" were selected in a New Jersey asparagus field on November 11, 1959, when the other plants were yellow or brown. The two persistent-green plants were crossed; each of them was crossed also with normal plants for the genetic study of this character. A secondary part of this study was to determine the effect of the color gene or genes on the plant-pigment system by means of spectrophotometric analyses. An attempt also was made to identify the persistent-green mutants in the seedling stage. The study of the phenotypes of 17 F1, F2, and reciprocal BC1 progenies indicated that persistent-green color in asparagus is inherited as a single recessive gene. There was a large quantitative difference in chlorophyll and carotene between the persistent-green and normal plant complexes in October, but not in July. Apparently the persistent-green mutants retain chlorophyll and carotene much later in the season than do the normal plants. No qualitative difference in pigment was found in either July or October. Asparagus seedlings were easily classified as to persistent-green (green foliage) or normal (yellow foliage) in the greenhouse when the plants were 6 weeks old.


1953 ◽  
Vol 97 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Richard E. Shope

Helenine is moderately stable in solution at refrigerator temperature and can be kept for long periods of time without evident loss of activity if stored frozen at the temperature of solid CO2. It is filterable through a Seitz pad but not dialyzable. Crude SPS preparations of helenine do not lose activity when dried from the frozen state. Some conditions are described, however, which influence the preservation or inactivation of acetone-precipitated helenine when freeze-dried. Helenine is partially inactivated by exposure for 3 minutes to the temperature of a boiling water bath and is completely inactivated by autoclaving at 15 pounds' pressure for 15 minutes. The data presented suggest that helenine acts, either directly or by triggering some mechanism of the host itself, to destroy virus by a process which renders the latter non-antigenic. This effect may be exerted by action upon the virus itself or by interference with some stage in the developmental cycle of the virus. While the chemical nature of helenine is not known, the presence of a large proportion of polysaccharide in crude active preparations might suggest the possible importance of this class of substance in helenine activity. It is believed that helenine differs from the polysaccharide reported by Horsfall and McCarty and the penicillin impurity reported by Groupé and Rake to be active against certain viruses. It may be related, however, to the antiviral substance recently reported by Powell and his co-workers.


1975 ◽  
Vol 141 (6) ◽  
pp. 1278-1290 ◽  
Author(s):  
C Bianco ◽  
F M Griffin ◽  
S C Silverstein

We have examined the roles of Fc receptors and complement receptors in mediating the interaction of sensitized sheep erythrocytes (E) with activated and with nonactivated mouse peritoneal macrophages. Both activated and nonactivated macrophages ingest IgG-coated erythrocytes [E(IgG)]; activated cells intest 1.5-2 times as man E(IgG) as do nonactivated macrophages. Thus, there is a quantitative difference in Fc receptor-mediated ingestion between activated and nonactivated macrophages. There is, however, a qualitative difference in function of complement receptors of activated and nonactivated macrophages. Nonactivated macrophages avidly bind complement-coated E [E(IgM)Ia1, but do not ingest them to a significant degree. Activated macrophages, on the other hand, bind and ingest E(IgM)C. The possibility of Fc receptor participation in mediating ingestion of E(IgM)C by activated macrophages was eliminated by blocking Fc receptors with an antimacrophage IgG fraction. Activated macrophages treated with antimacrophage IgG did not ingest E(igG) but did ingest both E(IgM)C AND E(IgM)C. Nonactivated macrophages treated with antimacrophage IgG did not interact at all with E(IgG). These cells bound, but did not ingest, E(IgM)C and E(IgM)C. Complement receptor-mediated ingestion is a marker for macrophage activation and may be physiologically important in the elimination of complement-coated particles.


1990 ◽  
Vol 13 (2) ◽  
pp. 91-102 ◽  
Author(s):  
Donald F. Smee ◽  
Hassan A. Alaghamandan ◽  
Ai Jin ◽  
Brahma S. Sharma ◽  
Weldon B. Jolley

Author(s):  
Ashwitha M. ◽  
Sumithra T. Gowda

The use of herbo mineral preparations is vast in Ayurveda medicine. Even its benefit is extensive. It also impacts on health of sense organs. The Netra Chikitsa has also included Rasa Dravyas in different folds. The minerals are necessary for the normal functions of the body. It plays as a catalyst, co factor for an enzyme and many more. The references of preparation and the therapeutic effect of herbomineral complexes are available in plenty. The complexes help in exerting faster action of the drug.


Author(s):  
Jasmijn Esther Bosch ◽  
Sharon Unsworth

Abstract The present study investigated cross-linguistic influence (CLI) in the word order of Dutch-English bilingual children, using elicited production and acceptability judgment tasks. The goal was to examine whether monolingual and bilingual children produced and/or accepted V2 word orders in English, as in * Yesterday painted she an apple. We investigated whether the likelihood of CLI was related to language dominance, age at testing, and the degree of surface overlap (i.e., V2 word orders with auxiliaries versus main verbs). Even though none of the participants produced V2 word orders in English, in the acceptability judgment task bilingual children were more likely to accept V2 word orders than monolingual peers. Whilst monolinguals sometimes accepted V2 word orders with auxiliaries, bilinguals did so significantly more often (constituting a quantitative difference) and with main verbs, too (implying a qualitative difference). Therefore, we conclude that CLI can occur independently of surface overlap and that it can lead to both quantitative and qualitative differences between bilinguals and monolinguals. The likelihood of CLI was predicted by language dominance, but not by age. Some bilinguals still accepted V2 word orders at age ten, suggesting that in some cases CLI may be more persistent than previously thought.


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