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Biomedical subjects

M Robertson

Publications and source records attributed to M Robertson.

At least 109 records · Page 6Linked to original sources
PubMed1994

A survey of nucleic acid services in core laboratories.

Core facility services related to DNA synthesis and sequencing were surveyed by the Association of Biomolecular Resource Facilities. Responses from 85 facilities offering DNA synthesis and 37 facilities offering DNA sequencing were obtained. Data on instrumentation, volume, number of users, cost, methodology and a number of other criteria were obtained. The volume of work performed by these centralized core facilities was quite substantial (combined synthesis output of 4 million bases per year and a combined sequencing output of 35 million bases per year). The large number of users supported by these facilities and the high sample throughput make these core resource facilities good indicators of technological trends.

Costs and Cost Analysis↗
PubMed1994

A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9.

Club foot is one of the most common human congenital malformations. Distal arthrogryposis type I (DA-1) is a frequent cause of dominantly inherited club foot. Performing a genomewide search using short tandem repeat (STR) polymorphisms, we have mapped a DA-1 gene to the pericentromeric region of chromosome 9 in a large kindred. Linkage analysis has generated a positive lod score of 5.90 at theta = 0, with the marker GS-4. Multiple recombinants bracketing the region have been identified. Analysis of an additional family demonstrated no linkage to the same locus, indicating likely locus heterogeneity. Of the autosomal congenital contracture disorders causing positional foot deformities, this is the first to be mapped.

Arthrogryposis↗
PubMed1994

Genetic mapping of the BRCA1 region on chromosome 17q21.

Chromosome 17q21 harbors a gene (BRCA1) associated with a hereditary form of breast cancer. As a step toward identification of this gene itself we developed a number of simple-sequence-repeat (SSR) markers for chromosome 17 and constructed a high-resolution genetic map of a 40-cM region around 17q21. As part of this effort we captured genotypes from five of the markers by using an ABI sequencing instrument and stored them in a locally developed database, as a step toward automated genotyping. In addition, YACs that physically link some of the SSR markers were identified. The results provided by this study should facilitate physical mapping of the BRCA1 region and isolation of the BRCA1 gene.

Base Sequence↗
PubMed1993

Alleles of the APC gene: an attenuated form of familial polyposis.

An attenuated form of familial adenomatous polyposis coli, AAPC, causes relatively few colonic polyps, but still carries a significant risk of colon cancer. The mutant alleles responsible for this attenuated phenotype have been mapped in several families to the adenomatous polyposis coli (APC) locus on human chromosome 5q. Four distinct mutations in the APC gene have now been identified in seven AAPC families. These mutations that predict truncation products, either by single base pair changes or frameshifts, are similar to mutations identified in families with classical APC. However, they differ in that the four mutated sites are located very close to one another and nearer the 5' end of the APC gene than any base substitutions or small deletions yet discovered in patients with classical APC.

Adenomatous Polyposis Coli↗
PubMed1993

A rapid screening method to detect nonsense and frameshift mutations: identification of disease-causing APC alleles.

A functional screen for nonsense and frameshift mutations has been devised that allows genes of interest to be scanned in segments. This assay is based on the cloning of these segments in-frame with a colorimetric marker gene (lacZ) followed by screening for the level of functional activity from the marker polypeptide (beta-galactosidase). Individuals at risk for any one of a number of genetic diseases, in particular familial adenomatous polyposis coli (APC), can be quickly screened for chain-terminating mutations introduced by stops and frameshifts. At present, scanning of the APC gene for mutation requires significant effort because it is a large gene and most APC mutations are unique. Therefore, this assay offers a powerful option for the diagnosis of this and other genetic diseases, as well as great potential for the development of a similar rapid screen to detect APC mutations in colorectal adenomas and carcinomas.

Alleles↗
PubMed1993

Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.

Clinical and electrophysiological data have outlined a spectrum of similar yet distinct periodic paralyses, including potassium-sensitive (hyperkalemic periodic paralysis [HYPP]) and temperature-sensitive (paramyotonia congenita [PC]) forms. Recent work has revealed that these disorders result from allelic defects in the alpha-subunit of the adult, human skeletal muscle sodium channel. We report an additional mutation, a leucine-->arginine substitution in the S3 segment of domain 4 (L1433R), that results in the PC phenotype. Five other HYPP and PC families have been ascertained, and previously reported sodium channel mutations have been identified in each. Characterization of these mutations and phenotypic variations in such families will contribute to the understanding of sodium channel structure and function relationships, as well as channel malfunction in the periodic paralyses.

Adult↗
PubMed1993

Expression of alternative forms of differentiation inhibiting activity (DIA/LIF) during murine embryogenesis and in neonatal and adult tissues.

Differentiation inhibiting activity/leukaemia inhibitory factor (DIA/LIF) is a pleiotropic cytokine which has been implicated in a variety of developmental and physiological processes in mammals due to its broad range of biological activities in vitro. A role in very early development is suggested by the requirement for DIA/LIF to support the self-renewal of cultured embryonic stem (ES) cells. Other data point to potential roles in the establishment and maintenance of primordial germ cells, in osteogenesis and in haematopoiesis, and possibly in neuronal specification. DIA/LIF may also act as a mediator of the hepatic acute phase response. In the present study the expression of DIA/LIF transcripts during murine development and in adult mice has been determined using a highly sensitive ribonuclease protection analysis. In contrast to previous reports, it is apparent that DIA/LIF transcripts are present at low levels in many adult mouse tissues. Higher levels of expression are observed in skin, lung, intestine, and uterus. Elevated amounts of mRNA are also found in certain foetal tissue during late gestation and neonatally. In earlier embryogenesis, however, DIA/LIF mRNA is produced primarily in extraembryonic tissues. The alternative transcripts which produce either soluble or matrix-associated DIA/LIF exhibit overlapping but non-identical patterns of expression, consistent with the proposition that the two isoforms may have distinct biological functions. These findings are suggestive of widespread roles for DIA/LIF in vivo and are discussed in the light of available data on the phenotype of homozygous DIA/LIF-deficient mice.

Aging↗
PubMed1993

Polymorphic SSR (simple-sequence-repeat) markers for chromosome 20.

Chromosome 20-specific simple-sequence-repeat (SSR) markers were developed from a flow-sorted phage library (LL20NS01), subcloned in Bluescript, and screened with a tetranucleotide repeat, (AAAG)6, to identify potentially polymorphic loci. Of 100 clones sequenced, 39 were selected to construct primers. Of these 39, 22 were polymorphic. Reference to the CEPH linkage database (version 5) permitted genetic mapping of 16 of the new markers to specific regions of chromosome 20. Ten of the SSRs showed heterozygosity indices (above 70%) that would qualify them as potential index markers.

Base Sequence↗
PubMed1993

Regulation of glucose transporter (GLUT 3) and aldose reductase mRNA inbovine retinal endothelial cells and retinal pericytes in high glucose and high galactose culture.

The regulation of GLUT-3 and aldose reductase mRNA in retinal endothelial cells and retinal pericytes was studied in response to variations in the extracellular concentration of hexoses. In physiological concentrations of glucose (5 mmol/l), an increase in the level of GLUT-3 mRNA was observed in cultured cells compared to the level of mRNA found in the absence of glucose. In contrast, there was little change in the level of GLUT-3 mRNA when the cells were cultured in the presence of 5 mmol/l galactose. In high concentrations of glucose, there was a decline in GLUT-3 mRNA indicating that the GLUT-3 mRNA is regulated by the extracellular concentration of glucose. In contrast, at both 5 mmol/l and 25 mmol/l glucose, the level of aldose reductase mRNA was increased. Furthermore, there were differences in the magnitude of the increase of aldose reductase mRNA between bovine retinal pericytes and bovine retinal endothelial cells with a greater increase being observed in the pericytes. We propose that this demonstration of a facilitative glucose transporter system within retinal cells, and in particular the specific response to different hexoses and the known distinct kinetic parameters of the transporter system in specific cell types, highlights the heterogeneity of hexose transport mechanisms in retinal cells. Thus, hypergalactosaemia as a model system for the study of diabetic retinopathy should be used with caution.

Aldehyde Reductase↗
PubMed1993

Seizures due to lidocaine toxicity in a child during cardiac catheterization.

A 17-month-old boy developed grand mal seizures secondary to lidocaine toxicity during balloon dilatation of a congenital pulmonary valve stenosis. Lidocaine at 38 mg/kg (nine times the recommended maximum dose of 4.5 mg/kg) was administered during a 90-min period in order to optimize local anesthesia. This resulted in toxic serum lidocaine levels (8.7 mg/L; therapeutic range, 1.5-5 mg/L) at the time of seizures. Caution should be exercised with local anesthetics during invasive cardiac catheterizations. Hypercarbia (which lowers the seizure threshold to local anesthetics) should be avoided and the temptation to exceed the maximum recommended dose resisted.

Anesthesia, Local↗