Selection and in vitro properties of inhibitor-nonsensitive influenza A (H3N2) strains

1974 ◽  
Vol 20 (4) ◽  
pp. 491-498
Author(s):  
J. Lecomte ◽  
A. Boudreault ◽  
V. Pavilanis

Selection of stable variants, nonsensitive to horse serum inhibitors, was achieved by growing influenza A (H3N2) strains, originally sensitive, in the allantois-on-shell system with incorporated normal horse serum. Most of these variants, when compared to their respective parental line, showed a greater eluting activity not related to a greater enzymatic activity. Investigation of the ability to agglutinate erythrocytes from different animal species and the thermostability of the hemagglutinin and the neuraminidase did not reveal a complete correlation between these markers and resistance to horse serum inhibitors. When applied to known attenuated strains, also nonsensitive, these same markers could not be linked directly to the attenuation of these viruses for man.


1984 ◽  
Vol 160 (2) ◽  
pp. 552-563 ◽  
Author(s):  
A R Townsend ◽  
J J Skehel

Using genetically typed recombinant influenza A viruses that differ only in their genes for nucleoprotein, we have demonstrated that repeated stimulation in vitro of C57BL/6 spleen cells primed in vivo with E61-13-H17 (H3N2) virus results in the selection of a population of cytotoxic T lymphocytes (CTL) whose recognition of infected target cells maps to the gene for nucleoprotein of the 1968 virus. Influenza A viruses isolated between 1934 and 1979 fall into two groups defined by their ability to sensitize target cells for lysis by these CTL: 1934-1943 form one group (A/PR/8/34 related) and 1946-1979 form the second group (A/HK/8/68 related). These findings complement and extend our previous results with an isolated CTL clone with specificity for the 1934 nucleoprotein (27, 28). It is also shown that the same spleen cells derived from mice primed with E61-13-H17 virus in vivo, but maintained in identical conditions by stimulation with X31 virus (which differs from the former only in the origin of its gene for NP) in vitro, results in the selection of CTL that cross-react on target cells infected with A/PR/8/1934 (H1N1) or A/Aichi/1968 (H3N2). These results show that the influenza A virus gene for NP can play a role in selecting CTL with different specificities and implicate the NP molecule as a candidate for a target structure recognized by both subtype-directed and cross-reactive influenza A-specific cytotoxic T cells.



2003 ◽  
Vol 31 (3) ◽  
pp. 257-265 ◽  
Author(s):  
María José Gómez-Lechón ◽  
Teresa Donato ◽  
Xavier Ponsoda ◽  
José V. Castell

Drug metabolism is the major determinant of drug clearance, and the factor most frequently responsible for inter-individual differences in drug pharmacokinetics. The expression of drug metabolising enzymes shows significant interspecies differences, and variability among human individuals (polymorphic or inducible enzymes) makes the accurate prediction of the metabolism of a new compound in humans difficult. Several key issues need to be addressed at the early stages of drug development to improve drug candidate selection: a) how fast the compound will be metabolised; b) what metabolites will be formed (metabolic profile); c) which enzymes are involved and to what extent; and d) whether drug metabolism will be affected directly (drug-drug interactions) or indirectly (enzyme induction) by the administered compound. Drug metabolism studies are routinely performed in laboratory animals, but they are not sufficiently accurate to predict the metabolic profiles of drugs in humans. Many of these issues can now be addressed by the use of relevant human in vitro models, which speed up the selection of new candidate drugs. Human hepatocytes are the closest in vitro model to the human liver, and they are the only model which can produce a metabolic profile of a drug which is very similar to that found in vivo. However, the use of human hepatocytes is restricted, because limited access to suitable tissue samples prevents their use in high throughput screening systems. The pharmaceutical industry has made great efforts to develop fast and reliable in vitro models to overcome these drawbacks. Comparative studies on liver microsomes and cells from animal species, including humans, are very useful for demonstrating species differences in the metabolic profile of given drug candidates, and are of great value in the judicious and justifiable selection of animal species for later pharmacokinetic and toxicological studies. Cytochrome P450 (CYP)-engineered cells (or microsomes from CYP-engineered cells, for example, Supersomes™) have made the identification of the CYPs involved in the metabolism of a drug candidate more straightforward and much easier. However, the screening of compounds acting as potential CYP inducers can only be conducted in cellular systems fully capable of transcribing and translating CYP genes.





1920 ◽  
Vol 32 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Ida W. Pritchett

1. No demonstrable antiopsonins are formed in rabbits following the intravenous injection of monovalent pneumococcus horse sera, Types I, II, and III. 2. The serum of rabbits injected with immune pneumococcus horse serum, Type I, II, or III, or with normal horse serum, when mixed in the proportion of 1:4 with Type I or Type II pneumococcus horse serum, can greatly augment, in vitro, the opsonization and agglutination of Type I and Type II pneumococci by the homologous immune horse sera. No similar effect is obtained with Type III serum and pneumococci. 3. The increase in opsonization and agglutination is dependent upon (a) specific sensitization of the pneumococci by the homologous immune serum and (b) the presence of the precipitating serum. In the absence of sensitization, as when a heterologous or normal horse serum is employed, opsonization and agglutination do not occur, even though a precipitating mixture is provided. The substitution of normal rabbit serum for the precipitating rabbit serum gives opsonization and agglutination in dilutions slightly higher than are effected with salt solution only, due possibly to the more favorable medium created for the leucocytes by the addition of 25 per cent of whole rabbit serum. 4. Different methods of combining the immune horse serum, precipitating rabbit serum, and pneumococci yield very similar results, preliminary sensitization of the bacteria before precipitation, or precipitation in the rabbit-horse serum mixture before the addition of the pneumococci for sensitization causing little if any difference in result from that obtained when immune horse serum, precipitating rabbit serum, and pneumococci are all mixed and incubated together. 5. This increased opsonization in the test-tube does not seem to be paralleled by increased protective power, or at any rate such protection is not readily demonstrated.



Parasitology ◽  
1960 ◽  
Vol 50 (3-4) ◽  
pp. 431-448 ◽  
Author(s):  
Ann Bishop ◽  
Elspeth W. McConnachie

1. Gametocytes of Plasmodium gallinaceum emerged from the erythrocytes and the male gametocytes exflagellated normally in vitro, in normal or inactivated horse serum, or in rabbit plasma.2. Gametocytes, washed and suspended in normal horse serum, completed their sexual development and produced oocysts in mosquitoes.3. Hyperimmune chick plasma, as compared with normal chick plasma, did not significantly affect the time of onset or the frequency of exflagellation.4. In a solution, isotonic to bird blood and adjusted to approximately pH 8, containing NaCl, KC1, CaCl2, Na2HPO4, MgSO4, NaHCO3 and Tris buffer, the in vitro development of the gametocytes was normal, and the numbers developing were comparable to those in horse serum, or in plasma or serum from the normal host. The development of the gametocytes was inhibited by the omission of Na or HCO3 ions, but the omission of Mg, K, Ca, SO4 or HPO4 ions had no effect.5. Further experiments showed that the gametocytes emerged from the corpuscles and the males exflagellated normally in a solution containing only Na, C1 and HCO3 ions. Other combinations of ions were tested, but although gametocytes emerged from the corpuscles in some of these solutions, exflagellation either did not take place or did so infrequently, and the gametes produced were feeble in their movements. Within the range of inorganic salts tested, Na, HCO3 and C1 ions constituted the minimal requirement for the normal in vitro development of the male gametocytes.



1949 ◽  
Vol 28 (5 Pt 1) ◽  
pp. 861-863 ◽  
Author(s):  
Robert J. Reedy ◽  
Stanley W. Wolfson


2021 ◽  
Vol 22 (8) ◽  
pp. 960-960
Author(s):  
V. A.

Studying the effect of normal horse serum in vivo and in vitro on staphylococci, Benedek (Zeit. F. 1mm. U. Exper. Ther., B. 47, H. 2) found that it has antitoxic, bactericidal and tissue immunizing effects.



Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
R Bertóti ◽  
Á Alberti ◽  
A Böszörményi ◽  
R Könye ◽  
T Horváth ◽  
...  


1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.



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