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Biomedical subjects

D Gillespie

Publications and source records attributed to D Gillespie.

97 records · Page 6Linked to original sources

Metabolic events occurring during recovery from prolonged glucose starvation in Escherichia coli.

The effects of starving Escherichia coli for glucose and required amino acids were determined. The disappearance of the majority of the ribosomal population, particularly of the ribonucleic acid (RNA) moiety, was noted. The events during recovery are detailed, with emphasis placed on the timing, requirements, and control of deoxyribonucleic acid, RNA, and protein synthesis and on ribosome reassembly. Finally, the applicability of the system to the study of temperature-sensitive mutants is documented and discussed.

Bacterial Proteins↗

Screening of Escherichia coli temperature-sensitive mutants by pretreatment with glucose starvation.

A system for screening Escherichia coli temperature-sensitive mutants is described. The system involves glucose starvation and minimizes ambiguities introduced by the interdependencies of macromolecular synthesis during balanced growth. The system permits the quick recognition of protein synthesis mutants and their classification into two general catagories. Complete protein synthesis mutants are unable to make any polypeptide material, whereas partial protein synthesis mutants are able to produce inactive proteins. The phenotypes of several mutants are described.

Bacterial Proteins↗

Synergistic inhibition of AZT-resistant HIV by AZT combined with poly(I):poly(C12U), without synergistic toxicity to bone marrow progenitor cell elements.

Mutation of human immunodeficiency virus (HIV) to drug resistance is an obstacle to HIV containment, and may account for the transitory nature of the improvement in CD4 cell counts of patients receiving azidothymidine (AZT). The emergence of AZT-resistant (AZTR) virus might be suppressed if a second therapeutic could be added; however, such a regimen would have to confer not only additional control over HIV replication but also no additional toxicity, especially to bone marrow progenitor cells. In the present study, HIV was isolated from patients receiving AZT alone and was studied for sensitivity to the mismatched double-stranded RNA, poly(I):poly(C12U) (ampligen). In addition, the combination of poly(I):poly(C12U) plus AZT was studied in vitro for toxicity to bone marrow CFU-GM and in patients receiving combined therapy for bone marrow toxicity. HIV isolated from patients receiving AZT alone showed higher resistance to AZT than wildtype virus, but remained sensitive to poly(I):poly(C12U). Poly(I):poly(C12U) and AZT were synergistic in inhibiting all isolates of HIV tested, regardless of their AZTR phenotype. Furthermore, the combination of poly(I):poly(C12U) and AZT showed no toxicity in vitro to bone marrow CFU-GM compared to AZT alone. In 11 HIV infected individuals receiving the combinational regimen, bone marrow function gradually improved. These results indicate that poly(I):poly(C12U) was active against AZTR HIV, synergistic with AZT and did not convey added toxicity.

Antiviral Agents↗