Interferons and Their ApplicationsP.E. Came, W.A. Carter Today, the basic mood of researchers and clinical investigators, both at the center and on the periphery of interferon studies, is optimistic regarding the future of interferons as therapeutic substances. Many also feel these polypeptides will prove invaluable probes in unraveling certain fundamental biochemical processes which control the life cycle and developmental pattern of many human cells. In contrast, only a year or two ago, this optimism had given way to an attitude almost of disenchantment as public and scientific expectations were raised steeply, then rapidly waned, as it turns out, prematurely. Both the mUltiple actions of interferons (a virtual cascade of biochemical reactions may be induced, as documented herein) and the high visibility of interferon research provided by the millions of dollars invested both by national health agencies and by multinational pharmaceutical companies, contributed to an upsweep in public attention to drug development probably unprecedented in this century. Virtually every oncologist, it would seem, was plagued by requests for the experimental agent, although they already had therapies of more proven value. As recently as 1980, even though interferon had achieved success against certain cancers and certain viral diseases, the variability in clinical results was seemingly ever present and little evidence emerged to suggest interferons could cure advanced diseases. Why then the resurgence of an optimistic mood? There are almost always many elements which contribute to happiness, and this is certainly true of the broad frontier of interferon and its place in biochemical research and treatment. |
Contents
| 1 | |
| 8 | |
H Conclusion | 14 |
CHAPTER 2 | 23 |
Data Analysis Unitage and Standardization | 30 |
E Radioimmunoassays | 37 |
CHAPTER 3 | 44 |
Structural Evolution of the 3 Noncoding Region | 54 |
CHAPTER 15 | 305 |
Purification of IFNy | 312 |
83 | 320 |
F The Prospect of Using IFN for Treatment of Viral and Neoplastic | 331 |
85 | 334 |
CHAPTER 16 | 338 |
Recombinant DNADerived Interferons | 346 |
87 | 351 |
F Concluding Remarks | 61 |
E Comparative Structure of Some IFNα and ẞ₁ Chromosomal Genes | 73 |
Human Interferony | 83 |
Protein Structure and Interferon Activity | 89 |
References | 97 |
CHAPTER 6 | 101 |
B Regulatory Control of IFN Action | 110 |
Other Factors Influencing IFN Action | 117 |
Clinical Considerations | 124 |
of Human Interferon Genes | 137 |
Cloning IFNy | 143 |
References | 149 |
The Molecular Mediators of Interferon Action | 152 |
F Conclusions | 164 |
B Cell Growth Inhibition by IFN | 170 |
Other Cellular Effects of IFN | 184 |
H Conclusions and Epilogue | 194 |
79 | 202 |
CHAPTER 10 | 205 |
80 | 210 |
E One Molecule of dsRNA as the Interferon Inducer Moiety of Different | 214 |
References | 228 |
82 | 231 |
B Nucleic Acid Strandedness and Its Consequences for Interferon Induction | 234 |
The Effectiveness of a Nucleic Acid Complex as an Interferon Inducer | 242 |
F The Spectrum of Biologic Activity of Exogenous Nucleic Acids | 250 |
CHAPTER 12 | 259 |
Characterization | 266 |
Interferon Formed by Lymphoblastoid Cells After Induction | 274 |
References | 283 |
888 | 286 |
CHAPTER 17 | 357 |
Summary | 369 |
Comparative Interferon Antiviral and Antitumor Activity | 376 |
References | 382 |
E Hormones | 390 |
F Growth Factors | 391 |
Conclusion | 398 |
Effects of Interferon on Cell Surface Antigen Expression on Lymphoid | 405 |
E Effects of Interferon on DelayedType Hypersensitivity Responses | 411 |
89 | 416 |
H Summary and Concluding Comments | 423 |
CHAPTER 21 | 433 |
90 | 441 |
Miscellaneous Virus Infections | 447 |
91 | 448 |
CHAPTER 22 | 454 |
Other Virus Infections | 461 |
93 | 467 |
CHAPTER 23 | 471 |
Conclusions | 488 |
CHAPTER 24 | 498 |
F Conclusion | 509 |
B Thiolated Derivatives | 517 |
H Antiviral Studies in Monkeys | 523 |
Comparison of Interferon Inducers with Exogenous Interferon | 531 |
CHAPTER 26 | 534 |
Modulating the Spectrum of Activities Triggered by dsRNA | 545 |
CHAPTER 27 | 557 |
94 | 565 |
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Common terms and phrases
Acad Sci USA amino acid antibody anticellular antigen antitumor antiviral antiviral activity assay Baglioni Biochem biologic Cancer Cantell cDNA cell growth cell lines cellular chromosome 21 CLERCQ clinical cloned cytotoxic defective interfering particles disease doses double-stranded dsRNA effect of interferon effects of IFN enhanced Epstein feron fibroblast Gen Virol genome GOEDDEL GRESSER GROSSBERG herpes HuIFN-y human fibroblast interferon human interferon human leukocyte interferon hybrids IFN-a IFN-ẞ IFN-y immune Immunol induce interferon infection inhibition inhibitor inter interferon gene interferon inducers interferon preparations interferon production L-cells leukemia lymphoblastoid lymphocytes macrophages MARCUS Merigan TC mice molecular molecule mRNA murine mutant Natl Acad Sci NK cell nucleic acid nucleotide particles patients poly(I polymerase polynucleotide Proc Natl Acad prostaglandin protein synthesis purified receptor response Sendai virus serum specific STEWART structure studies terferon tion titer TORRENCE treatment tumor cells U/ml vesicular stomatitis virus viral Virology viruses vitro vivo