Renato Dulbecco

Bio: Renato Dulbecco is an academic researcher from Salk Institute for Biological Studies. The author has contributed to research in topics: Virus & DNA. The author has an hindex of 57, co-authored 154 publications receiving 13980 citations. Previous affiliations of Renato Dulbecco include California Institute of Technology & National Research Council.

Plaque formation and isolation of pure lines with poliomyelitis viruses.

Abstract: Plaques have been produced with the three types of poliomyelitis viruses on monolayer tissue cultures of monkey kidney and monkey testis. The number of plaques was proportional to the concentration of the virus. Each plaque originates, therefore, from a single virus particle, defined as the virus unit that is unseparable by dilution. The plaques are due to the specific action of the virus since they are suppressed by type-specific antiserum. Pure virus lines were established by isolating the virus population produced in single plaques. These derived virus lines had the same morphological, serological, and pathogenic properties as the parent strain. High titer virus stocks, with titers up to 7 x 10(8) plaque-forming particles per ml., were obtained.

Production of Plaques in Monolayer Tissue Cultures by Single Particles of an Animal Virus

Abstract: Research on the growth characteristics and genetic properties of animal viruses has stood greatly in need of improved quantitative techniques, such as those used in the related field of bacteriophage studies.

Topoinhibition and serum requirement of transformed and untransformed cells.

Abstract: The multiplication of tissue culture cells is controlled by several different physiological characteristics, the quantities of which can be measured. Transformed cells are characterized by the values of some of these physiological parameters.

The Integrated State of Viral DNA in SV40-Transformed Cells

Abstract: It has been shown by a modified DNA-RNA hybridization technique that the nuclei of cells transformed by either polyoma virus or SV40 contain viral DNA.1 This method employs RNA synthesized in vitro with form I viral DNA2–4 and E. coli RNA polymerase. The number of viral DNA equivalents per cell varies from 5 to 60, depending on the cell line. In this communication, we will report on the physical state of the viral DNA in SV3T3 cells, an SV40-transformed cell line that contains 20 SV40 DNA equivalents per cell.

The serial cultivation of human diploid cell strains.

Abstract: The isolation and characterization of 25 strains of human diploid fibroblasts derived from fetuses are described. Routine tissue culture techniques were employed. Other than maintenance of the diploid karyotype, ten other criteria serve to distinguish these strains from heteroploid cell lines. These include retention of sex chromatin, histotypical differentiation, inadaptability to suspended culture, non-malignant characteristics in vivo , finite limit of cultivation, similar virus spectrum to primary tissue, similar cell morphology to primary tissue, increased acid production compared to cell lines, retention of Coxsackie A9 receptor substance, and ease with which strains can be developed. Survival of cell strains at − 70 °C with retention of all characteristics insures an almost unlimited supply of any strain regardless of the fact that they degenerate after about 50 subcultivations and one year in culture. A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level. With these characteristics and their extremely broad virus spectrum, the use of diploid human cell strains for human virus vaccine production is suggested. In view of these observations a number of terms used by cell culturists are redefined.

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

Abstract: The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

Dengue and Dengue Hemorrhagic Fever

Abstract: Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.

A rapid method for the isolation of functional thymus‐derived murine lymphocytes

Abstract: A rapid method is described for effectively removing immunoglobulin-bearing cells from either primed or unprimed mouse spleen and lymph node cell suspensions. Incubation of cell suspensions in nylon wool columns for 45 min at 37 °C resulted in a 9 to 100-fold depletion of immunoglobulin-bearing cells and a complementary 1.5 to 2-fold enrichment of T cells in the column effluent populations. The effluent population, derived from passage of spleen cells through these columns, was virtually devoid of B precursor and memory cell activity, but contained all of the helper cell and cytotoxic effector cell precursor activity when compared to unfractionated spleen cells.