PubMed Health⌕ Search

Biomedical subjects

R C Welch

Publications and source records attributed to R C Welch.

7 recordsLinked to original sources
PubMed1988

The late spliced 19S and 16S RNAs of simian virus 40 can be synthesized from a common pool of transcripts.

The late transcripts from the simian virus 40 (SV40) are alternatively spliced into two classes of spliced RNAs, 19S and 16S in size. We are interested in understanding the precursor-product relationships that result in the excision of different intervening sequences (introns) from the late transcripts. SV40 mutants containing precise deletions of the introns for each of the spliced 19S and 16S RNA species, including a previously undetected doubly spliced 19S RNA species, were isolated. Analysis by S1 mapping and a modified primer extension technique of the viral RNAs made in monkey cells transfected with each of these mutants led to the following conclusions. (i) Spliced late 19S RNA is not an intermediate in the synthesis of the late 16S RNAs. (ii) The 3' splice site used in the synthesis of the late 16S RNAs can join, albeit inefficiently, with alternative 5' splice sites in the absence of the 5' splice site normally used to synthesize 16S RNA. (iii) There is no obligatory order of excision of introns in the formation of the doubly spliced SV40 late 19S and 16S RNA species. A mutant was constructed by site-directed mutagenesis in which the 5'-proximal 3' splice site used in the synthesis of the doubly spliced RNAs is inactive. Cells transfected with this mutant processed transcripts into 19S RNA which, in wild-type-transfected cells, would have become doubly spliced 16S RNA. Therefore, we conclude that some of the spliced late 19S and 16S RNA can be synthesized from a common pool of transcripts.

Animals↗
PubMed1988

Both VP2 and VP3 are synthesized from each of the alternative spliced late 19S RNA species of simian virus 40.

The late 19S RNAs of simian virus 40 consist of a family of alternatively spliced RNAs, each of which contains open reading frames corresponding to all three of the virion proteins. Two approaches were used to test the hypothesis that each alternatively spliced 19S RNA species is translated to synthesize preferentially only one of the virion proteins. First, we analyzed the synthesis of virion proteins in simian virus 40 mutant-infected monkey cells that accumulate predominantly either only one spliced 19S RNA species or only the 19S RNAs. Second, we determined the virion proteins synthesized in a rabbit reticulocyte lysate programmed with specific, in vitro-transcribed 19S RNA species. These results indicated that VP2 and VP3, but not VP1, are synthesized from all 19S RNA species. Quantitative analysis of these data indicated that individual 19S RNA species containing a translation initiation signal upstream of the VP2 AUG codon were translated in a cell extract three- to fivefold less efficiently than were 19S RNA species lacking this signal and that the precise rate of synthesis of VP2 relative to VP3 varied somewhat with the sequence of the leader region. These data are consistent with the synthesis of VP2 and VP3 occurring by a leaky scanning mechanism in which initiation of translation at a specific AUG codon is affected by both (i) the intrinsic efficiency of ribosomes recognizing the sequences surrounding the AUG codon as an initiation signal and (ii) partial interference from 5'-proximal initiation signals and their corresponding open reading frames.

Animals↗
PubMed1987

Missense mutations in the VP1 gene of simian virus 40 that compensate for defects caused by deletions in the viral agnogene.

Simian virus 40 mutants lacking sequences in the late leader region are viable but produce smaller plaques than does wild-type virus. Within three passages at low multiplicities of infection, virus stocks of several such mutants accumulated variants that synthesized an altered form of the major virion protein, VP1, having a slightly faster mobility in sodium dodecyl sulfate-polyacrylamide gels than did the wild-type protein. Because these variants overgrew the original virus stocks, we consider them to be second-site revertants. By construction and characterization of a series of recombinants, the second-site mutations were shown to map to at least two different regions of the VP1 gene. Nucleotide sequence analysis indicated that single-amino-acid changes were responsible for the rapid mobility of VP1. When combined in cis with either a wild-type or mutant leader region, these VP1 mutations sped up by 10 to 20 h the time course of accumulation of infectious progeny but not of viral DNA or VP1. LP1, the protein encoded by the agnogene, was shown previously to be necessary for the efficient transport of the virion proteins to the nucleus or for their efficient assembly with viral minichromosomes. The VP1 missense mutations reported here compensate for the lack of LP1 by facilitating this process. On the basis of these findings and findings reported previously by us and others, we hypothesize that LP1 facilitates the formation of infectious particles by inhibiting the polymerization of VP1 molecules until the time they interact with viral minichromosomes; the VP1 mutations reported here compensate for the loss of LP1 by lessening the potential of VP1 for self-polymerization.

Animals↗
PubMed1982

Intraocular lens quality control.

A mislabeled lens was found to have a diopter power of 19.66 on the optical bench, although it was labeled as a 13.00 diopter lens. Both the surgeon and patient were unnecessarily frustrated. In addition, three consecutive posterior chamber lenses examined from one manufacturer showed poor loop quality. It is obvious from these examples that implant surgeons must continue their vigil over lens manufacturers to ensure implant lens quality and accuracy.

Equipment Failure↗
PubMed1977

Femur-bending properties as influenced by gravity: I. Ultimate load and moment for 3-G rats.

Fresh experimental bones can withstand greater bending forces and moments after 1.0 to 2.5 weeks of 3-G exposure. This appears more attributable to a 50% greater strength of bone material than to effects upon size or shape, and is most measurable for animals of 5 to 8 weeks of age. Experimental bone material seems to grow to its mature level at a younger age rather than there being so marked an effect upon the mature level itself. We simulated 3.1 G by chronic centrifugation of 66 albino rats and compared them to 63 1-G controls. Extrapolation of the simplest mathematical description of the present results to weaker, zero-G bones could be tested by a total of 60 space-based control and experimental animals. A flight of only 15 animals would be necessary for comparison to ground-based control animals. This is consistent with reports of bone demineralization during space-flight. In light of the differences in bone histology, however, extrapolation of these results to humans would be premature and, if at all applicable, are most likely to be so for children rather than adults.

Age Factors↗
PubMed1977

Femur-bending properties as influenced by gravity: II. Ultimate load, moment, and stress for 3-G mice.

Material strength as approximated from bending studies of fresh femurs grew during 1 to 8 weeks of hypergravity at rates which were not measurably affected, even though the animal's body growth was measurably slower. As a result, femurs could support greater ultimate loads, moments, and stresses when compared to control bones of comparable rotational moments of their cross-sectional areas. Chronic centrifugation simulated 3.1 G for 45 male. Swiss Webster mice compared to 37 control animals. Effects were most noticeable after the first week of exposure and for younger animals. Effect were only about 50% that noted in comparable treatment of rats. This suggests that four times more mice than rats may be necessary for space-experiments designed to test the effects of weightlessness.

Animals↗