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C L Simpson

Publications and source records attributed to C L Simpson.

At least 19 recordsLinked to original sources
PubMed2006

Using high-throughput SNP technologies to study cancer.

Identifying genes involved in the development of cancer is crucial to fully understanding cancer biology, for developing novel therapeutics for cancer treatment and for providing methods for cancer prevention and early diagnosis. The use of polymorphic markers, in particular single nucleotide polymorphisms (SNPs), promises to provide a comprehensive tool for analysing the human genome and identifying those genes and genomic regions contributing to the cancer phenotype. This review summarizes the various analytical methodologies in which SNPs are used and presents examples of how each of these methodologies have been used to locate genes and genomic regions of interest for various cancer types. Additionally many of the current SNP-analysing technologies will be reviewed with particular attention paid to the advantages and disadvantages of each and how each technology can be applied to the analysis of the genome for identifying cancer-related genes.

Genetic Linkage↗
PubMed2000

Risk of injury in African American hospital workers.

Very few data exist that describe the risk of injury in African American health care workers, who are highly represented in health care occupations. The present study examined the risk for work-related injury in African American hospital workers. Hospital Occupational Health Service medical records and a hospital human resource database were used to compare risk of injury between African American and white workers after adjusting for gender, age, physical demand of the job, and total hours worked. Risk of work-related injury was 2.3 times higher in African Americans. This difference was not explained by the other independent variables. Differences in injury reporting, intra-job workload, psychosocial factors, and organizational factors are all potential explanations for racial disparity in occupational injury. More research is needed to clarify these findings.

Accidents, Occupational↗
PubMed1998

Identification of a homolog of CcpA catabolite repressor protein in Streptococcus mutans.

A locus containing a gene with homology to ccpA of other bacteria has been cloned from Streptococcus mutans LT11, sequenced, and named regM. Upstream of the regM gene, on the opposite strand, is a gene encoding an X-Pro dipeptidase, pepQ. A 14-bp palindromic sequence with homology to the consensus catabolite-responsive element sequence lay in the promoter region between the two genes. To study the function of regM, the gene was inactivated by insertion of an antibiotic resistance marker. Diauxic growth of S. mutans on a number of sugars in the presence of glucose was not affected by disruption of regM. The loss of RegM increased glucose repression of alpha-galactosidase, mannitol-1-P dehydrogenase, and P-beta-galactosidase activities. These results suggest that while RegM can affect catabolite repression in S. mutans, it does not conform to the model proposed for CcpA in Bacillus subtilis.

Amino Acid Sequence↗
PubMed1998

Intracellular alpha-amylase of Streptococcus mutans.

Sequencing upstream of the Streptococcus mutans gene for a CcpA gene homolog, regM, revealed an open reading frame, named amy, with homology to genes encoding alpha-amylases. The deduced amino acid sequence showed a strong similarity (60% amino acid identity) to the intracellular alpha-amylase of Streptococcus bovis and, in common with this enzyme, lacked a signal sequence. Amylase activity was found only in S. mutans cell extracts, with no activity detected in culture supernatants. Inactivation of amy by insertion of an antibiotic resistance marker confirmed that S. mutans has a single alpha-amylase activity. The amylase activity was induced by maltose but not by starch, and no acid was produced from starch. S. mutans can, however, transport limit dextrins and maltooligosaccharides generated by salivary amylase, but inactivation of amy did not affect growth on these substrates or acid production. The amylase digested the glycogen-like intracellular polysaccharide (IPS) purified from S. mutans, but the amy mutant was able to digest and produce acid from IPS; thus, amylase does not appear to be essential for IPS breakdown. However, when grown on excess maltose, the amy mutant produced nearly threefold the amount of IPS produced by the parent strain. The role of Amy has not been established, but Amy appears to be important in the accumulation of IPS in S. mutans grown on maltose.

Amino Acid Sequence↗
PubMed1997

A dominant mutation in the Chlamydomonas reinhardtii nuclear gene SIM30 suppresses translational defects caused by initiation codon mutations in chloroplast genes.

A suppressor of a translation initiation defect caused by an AUG to AUU mutation in the Chlamydomonas reinhardtii chloroplast petD gene was isolated, defining a nuclear locus that we have named SIM30. A dominant mutant allele at this locus, sim30-1d, was found to increase the translation initiation rate of the mutant petD mRNA. sim30-1d was also able to suppress the translational defect caused by an AUG to AUC mutation in the petD gene, and an AUG to AUU mutation in the chloroplast petA gene. We therefore suggest that the SIM30 gene may encode a general chloroplast translation factor. The ability of sim30-1d to suppress the petD AUG to AUU mutation is diminished in the presence of one or more antibiotic resistance markers located within the 16S and 23S rRNAs, suggesting that the activity of the sim30-1d gene product in translation initiation may involve interaction with ribosomal subunits.

Animals↗
PubMed1996

A chloroplast transcript lacking the 3' inverted repeat is degraded by 3'-->5' exoribonuclease activity.

Chlamydomonas reinhardtii strains harboring deletions of the chloroplast atpB 3' inverted repeat (IR) are weakly phototrophic due to reduced accumulation of discrete atpB transcripts and the chloroplast ATPase beta-subunit protein. A sequence of 18 guanosine residues, which can impede a 3'-->5' exoribonuclease in vitro, is able to substitute for the atpB IR in vivo. Strains containing the poly-guanosine tract in place of the atpB 3' IR are phototrophic and accumulate near wild-type levels of discrete atpB transcripts and the ATPase beta-subunit protein. Because these atpB transcripts contain the 18 guanosine residues, and the poly-guanosine tract is not a terminator of transcription, the accumulation of discrete atpB transcripts is likely the result of impediment of 3'-->5' exoribonuclease activity. These findings support a model in which atpB transcripts lacking the 3' IR are degraded by 3'-->5' exoribonuclease activity, and demonstrate that the poly-guanosine tract can be used to study chloroplast RNA metabolism in vivo.

Adenosine Triphosphatases↗
PubMed1995

Streptococcus salivarius ATCC 25975 possesses at least two genes coding for primer-independent glucosyltransferases.

Fractionation of the culture medium showed that Streptococcus salivarius ATCC 25975 secreted a glucosyltransferase (Gtf) that was primer independent. On the basis of this observation, a gene library of S. salivarius chromosomal DNA cloned into lambda L47.1 was screened for a gene(s) coding for such an activity. As a result of this screening process, two new gtf genes, gtfL and gtfM, both of which coded for primer-independent Gtf activities, were isolated. GtfL produced an insoluble glucan that was refractory to digestion by the endo-(1-->6)-alpha-D-glucanase. of Chaetonium gracile, while GtfM produced a soluble glucan that was readily degraded by the glucanase. Comparison of the deduced amino acid sequences of gtfL and gtfM with 10 other available Gtf sequences allowed the relatedness of the conserved catalytic regions to be assessed. This analysis showed that the 12 enzymes did not form clusters based on their primer dependencies or on their product solubilities. Further analysis of the YG repeats in the C-terminal glucan-binding domains of GtfJ, GtfK, GtfL, and GtfM from S. salivarius showed that there was strong homology between a block of contiguous triplet YG repeats present in the four alleles. These blocks of YG repeats were coded for by a region of each gene that appeared to have arisen as a result of a recent duplication event(s).

Amino Acid Sequence↗
PubMed1993

A method for the isolation of RNA from Streptococcus salivarius and its application to the transcriptional analysis of the gtfJK locus.

The glucosyltransferases from oral streptococci cleave sucrose and polymerize the glucose moieties. In Streptococcus salivarius ATCC 25975, two glucosyltransferase-encoding genes, gtfJ and gtfK, are closely linked and transcribed in the same direction. A procedure for the isolation of intact RNA from this organism was devised. The procedure incorporated a high-temperature mutanolysin treatment and selective precipitation by LiCl. The RNA was subject to Northern hybridization and RNase protection assays and it was concluded that the two genes are transcribed separately. A potential factor-independent transcription terminator was located in the intergenic region.

Base Sequence↗
PubMed1993

Sequence of the gtfK gene of Streptococcus salivarius ATCC 25975 and evolution of the gtf genes of oral streptococci.

Many strains of oral streptococci secrete glucosyltransferases (GTFs) that polymerize sucrose into glucans that form an integral part of the plaque matrix on the tooth surface. Recently, we reported the cloning of two closely linked GTF-encoding genes (gtfJ and gtfK) from Streptococcus salivarius ATCC 25975 as well as the sequence of gtfJ, which encodes a primer-dependent GTF that synthesizes an insoluble product (a GTF-I). In this communication we report the sequence of gtfK, which encodes a primer-dependent GTF that synthesizes a soluble product (a GTF-S), as well as the sequence of a small downstream open reading frame of unknown function. The deduced sequence of GtfK was compared with those of seven other streptococcal Gtfs and an unrooted phylogenetic tree constructed. This analysis suggested that Gtfs with similar product specificities do not form phylogenetic clusters and was consistent with currently accepted phylogenetic schemes. The tree was tested by constructing a series of 'sub-trees' from different blocks of the alignment. Evidence was obtained for recombination events involving gtfB and gtfC from S. mutans GS-5, gtfJ and gtfK from S. salivarius, as well as the gtfI genes from S. downei and S. sobrinus. The recombination events between gtfB and gtfC, and between the two gtfI genes, were confirmed by examining divergences at silent sites.

Algorithms↗
PubMed1991

Molecular characterization of a cluster of at least two glucosyltransferase genes in Streptococcus salivarius ATCC 25975.

The oral micro-organism Streptococcus salivarius ATCC 25975 synthesizes extracellular glucosyltransferases (GTFs) which polymerize the glucose moiety of sucrose into glucan polymers. Two separate genes encoding the activities of a GTF-I (a GTF that synthesizes an insoluble product) and a GTF-S (a GTF that synthesizes soluble product) were cloned into bacteriophage lambda L47.1. The inserts in the lambda-clones were characterized by restriction mapping and Southern hybridization and were found to overlap, implying that the two genes lay very close to one another on the S. salivarius chromosome. Both genes were subcloned into phagemid vector pIBI30 where they were expressed at a high level. The GTF-I-encoding gene was named gtfJ and the GTF-S-encoding gene, gtfK. Nucleotide sequencing showed that gtfJ and most probably gtfK were closely related to the gtf genes of the mutans streptococci. Sequence alignment also indicated that gtfK lay very close to and downstream from gtfJ, and that both were transcribed in the same direction.

Amino Acid Sequence↗
PubMed1980

The prevention of cyclophosphamide-induced bladder swelling in the rat by I.V. administration of sodium-2-mercaptoethane sulfonate.

In a preliminary experiment the wet weight of the rat urinary bladder appeared to correlate with cyclophosphamide toxicity. The effect of a proposed antidote (SMES), given on various time schedules, was studied using the wet weight as a measure of toxicity. At a cose of 20 mg/kg/SMES it was found to neutralize the toxicity of 100 mg cytoxan only when given simultaneously. It is suggested that this model might be used in further studies.

Animals↗