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R L O'Brien

Publications and source records attributed to R L O'Brien.

85 records · Page 5Linked to original sources
PubMed1966

Chloroquine: physiological basis of drug resistance in Plasmodium berghei.

Mouse erythrocytes, parasitized by chloroquine-sensitive plasmodia, concentrate this drug in vivo to levels over twice as high as erythrocytes parasitized by chloroquine-resistant plasmodia; nonparasitized red cells accumulate little chloroquine. Selective toxicity of this drug may depend upon a special drug-concentrating mechanism of plasmodic impairment of such mechanism.

Animals↗
PubMed1965

DNA: reaction with chloroquine.

Diflerence spectrophotometry shows that double-stranded DNA produces mnarked changes in the absorption spectrum of chloroquine; only minor changes occur with single-stranded DNA. A DNA-chloroquine complex was demonstrated to sediment in the analytical ultracentrifuge. Chloroquine strongly elevated the thermal dissociation temperature, T(m), of DNA. It is concluded that the drug forms a complex with DNA by ionic interaction and stabilizes the helix.

Chemical Phenomena↗
PubMedDate not supplied

Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice.

Transgenic mice were produced by microinjection of a rearranged, functional immunoglobulin kappa gene into fertilized mouse eggs and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were mated and the DNA, RNA and serum kappa chains of their offspring were analysed. The data from offspring of three different transgenic mice indicate that the microinjected gene is expressed in the spleen, but not the liver of mice which inherited the injected gene.

Animals↗
PubMedDate not supplied

High expression of cloned immunoglobulin kappa gene in transgenic mice is restricted to B lymphocytes.

Immunoglobulin genes are normally expressed only in cells of the B lymphocyte lineage after a variable (V) and constant (C) gene rearrangement has occurred. To study the control of immunoglobulin gene expression in a defined situation, we have produced transgenic mice by microinjecting a rearranged mouse immunoglobulin kappa gene (designated pB1-14) into fertilized mouse eggs. We present here the analysis of six different kappa-transgenic mouse lines. All the transgenic mice express the microinjected kappa gene in a completely tissue-specific fashion. Transcripts from pB1-14 are found at a high level in the spleen, but are undetectable in nonlymphoid tissues of testis, liver, kidney, heart, muscle, brain and thyroid gland. In lymphoid cell subpopulations, the level of pB1-14 transcripts is correlated with the relative number of B cells; there is no correlation with the proportion of T lymphocytes. We concluded, therefore, that the microinjected kappa gene contains target sequences for B lymphocyte-specific gene activation signals that override the influence of the integration site.

Animals↗
PubMedDate not supplied

Somatic hypermutation of an immunoglobulin transgene in kappa transgenic mice.

Initial studies of somatically acquired mutations in immunoglobulin V regions from hybridomas and myelomas that are not derived from joining aberrations, suggested a controlled and specific hypermutation process, because spontaneous mutation rates observed for other genes are extremely low. Some evidence for the idea that mutations are introduced during V-gene rearrangement came from the clustering of mutations at the joining sites, from the absence of mutations in unrearranged V genes and from the low level of mutations in only partially (D-J) rearranged nonproductive heavy-chain alleles. Another model in which mutations accumulate with each cell division, rather than being introduced all at once, was supported by the finding that immunoglobulin genes of hybridomas derived from a single mouse frequently had several mutations in common, and so might be derived from the same precursor cell whose daughters then accumulated additional mutations. But the common mutations in some cases could be due to as yet unidentified related germline genes, or could represent the effect of antigen selection for certain amino acids. To try to detect hypermutation in the absence of V-gene rearrangement, we isolated B lymphocytes with endogenous heavy-chain gene mutations from transgenic mice carrying pre-rearranged kappa-transgenes. We found that these kappa-transgenes were also somatically mutated. This and other observations indicated that: ongoing rearrangement is not required for mutation; there are signals for hypermutation in the transgenes; the mutations are found only in the variable region, so the constant region may not be a target; different transgene insertion sites are compatible with hypermutations and more than one transgene is expressed in the same cell.

Animals↗