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Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 325 records · Page 18Linked to original sources
PubMed1993

Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK).

A cDNA encoding the human homologue of mouse RYK (related to receptor tyrosine kinases) has been cloned from an interleukin 1 (IL-1)-stimulated human hepatoma cDNA library by cross-species hybridization using the mouse RYK cDNA as a probe. The sequence of the 3067-bp cDNA clone encoding human RYK predicts a transmembrane protein with a cytoplasmic domain that contains the consensus sequences (subdomains I-XI) of the protein tyrosine kinase (PTK) family. The highly conserved motif -D-F-G- (subdomain VII) of the catalytic domain of other receptor-type tyrosine kinases is altered to -D-N-A- in human RYK. In addition, a number of other changes were found in the ATP binding site (subdomains I and II) and the motif [-I-H-R-D-L-A-A-R-N-] found in subdomain VI. Comparison of the human and mouse RYK sequences shows a 92% conservation at the nucleotide level and 97% at the amino acid level. There was no significant homology between the extracellular domain of RYK and the other families of receptor tyrosine kinases described to date. RYK therefore appears to define a new subclass of receptor-type tyrosine kinases whose structure has remained highly conserved across species.

Amino Acid Sequence↗
PubMed1993

The morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3.

The gene for N-acetylgalactosamine-6-sulfatase, the deficiency of which results in Morquio A syndrome (mucopolysaccharidosis type IVA), was assigned to chromosome 16 at band q24.3 by fluorescence in situ hybridization. Localization of this band was confirmed by PCR analysis of a somatic cell hybrid panel used for fine mapping of chromosome 16.

Animals↗
PubMed1993

Incidence and origin of "null" alleles in the (AC)n microsatellite markers.

Twenty-three (AC)n repeat markers from chromosome 16 were typed in the parents of the 40 CEPH (Centre d'Etude du Polymorphisme Humain) families. Where parents were informative, the entire families were then typed. There were seven markers in which null alleles were demonstrated, as recognized by the apparent noninheritance, by a sib, of a parental allele. Four of these markers showed a null allele in a single sibship, while in the other three at least 30% of the CEPH sibships were shown to have a null allele segregating. One null allele was sequenced and shown to be the result of an 8-bp deletion occurring within the priming sequence for PCR amplification of the (AC)n repeats. In gene mapping or in application to diagnosis, the presence of a segregating null allele will not corrupt the linkage data but could result in loss of information. In isolated instances a segregating null allele may be interpreted as nonpaternity. The presence of a null allele may generate misleading data when individuals are haplotyped to determine the presence of linkage disequilibrium with a disease gene.

Alleles↗
PubMed1992

Construction of a map of chromosome 16 by using radiation hybrids.

A human-hamster cell hybrid carrying a single copy of chromosome 16 as the only human genetic material was irradiated with a single dose of gamma-rays (7000 rads; 1 rad = 0.01 Gy) and then fused with a thymidine kinase-deficient hamster cell line (RJKM) to generate radiation hybrids retaining unselected fragments of this human chromosome. In two experiments, 223 hybrids were isolated in hypoxanthine/aminopterine/thymidine (HAT) medium and screened with 38 DNA probes, corresponding to anonymous DNA or gene sequences localized on chromosome 16. The most likely order and location of the 38 DNA sequences were established by multiple pairwise analysis and scaled to estimate physical distance in megabases. The order and the distances thus obtained are mostly consistent with available data on genetic and physical mapping of these markers, illustrating the usefulness of radiation hybrids for mapping.

Chromosome Mapping↗
PubMed1992

The interleukin-7 receptor gene is at 5p13.

A DNA probe for the interleukin-7 receptor gene was used for in situ hybridisation and Southern blot analysis of a series of rodent-human hybrid cell lines. The IL-7 receptor gene maps to 5p13.

Animals↗
PubMed1992

Colour Doppler velocity imaging of the myocardium.

A technique has been developed for producing images of the velocity of tissue motion within the myocardium. It has been demonstrated that Colour Flow Doppler imagers can be operated to depict the velocities within the myocardium rather than moving blood in the cardiac chambers. The technique exhibits the normal advantages of diagnostic ultrasound, i.e., real-time imaging with relatively inexpensive equipment and no hazard to the patient. Further work requires to be done to determine the optimum signal processing algorithms for moving tissue echoes and to ascertain whether the technique is of value in clinical applications.

Echocardiography↗
PubMed1992

Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16.

A cosmid library of human chromosome 16 has been subcloned, and (AC)n microsatellite positive clones have been identified and sequenced. Oligonucleotide primers flanking the repeat were designed and synthesized for (AC)n microsatellites with n greater than 16. These microsatellite loci were then mapped by PCR using a somatic cell hybrid panel of human chromosome 16, and their heterozygosities and allele frequencies determined. Fourteen (AC)n microsatellites were mapped to discrete physical intervals of human chromosome 16 defined by a mouse/human hybrid panel. Nine of these have expected heterozygosities ranging between 0.60 and 0.79, four have expected heterozygosities between 0.02 and 0.49, and one detected three loci where the alleles could not be resolved.

Alleles↗
PubMed1992

Fragile X syndrome without CCG amplification has an FMR1 deletion.

We describe a patient with typical clinical features of the fragile X syndrome, but without cytogenetic expression of the fragile X or an amplified CCG trinucleotide repeat fragment. The patient has a previously uncharacterized submicroscopic deletion encompassing the CCG repeat, the entire FMR1 gene and about 2.5 megabases of flanking sequences. This finding confirms that the fragile X phenotype can exist, without amplification of the CCG repeat or cytogenetic expression of the fragile X, and that fragile X syndrome is a genetically homogeneous disorder involving FMR1. We also found random X-inactivation in the mother of the patient who was shown to be a carrier of this deletion.

Adult↗
PubMed1992

Flow measurement using duplex Doppler ultrasound: haemodynamic changes in patients with colorectal liver metastases.

Duplex Doppler ultrasound has been used to make measurements of liver blood flow. The relationship between time average velocity as measured using pulsed Doppler and the true mean velocity was determined using a flow phantom. Correction factors were applied to measured time average velocities of blood in the hepatic artery and portal vein. Blood flow was calculated from the product of corrected velocities and the cross-sectional area of the vessels. There was no significant difference in total liver blood flow for patients with colorectal liver metastases when compared with controls. However, the ratio of the hepatic arterial flow to the sum of the portal and hepatic arterial flows (Doppler perfusion index, DPI) was markedly elevated (P < 0.0001) in the patients with metastases when compared with the controls. The DPI values for a third group of subjects who had undergone resection for colonic cancer but who had no proven liver metastases overlapped the values for the other two groups. When attention is paid to technique, the procedure can detect and quantify the changes in liver blood flow which occur in the presence of metastases.

Blood Flow Velocity↗
PubMed1992

Characterisation of a new rare fragile site easily confused with the fragile X.

A new fragile site (FRAXE) in Xq28 is described. It appears to be a typical folate sensitive fragile site. The fragile site is not associated with mental retardation, it does not give abnormal results when subjected to Southern analysis with probe pfxa3 which detects the unstable DNA sequence characteristic of fragile X syndrome. In situ hybridization mapping locates the fragile site between 150 kb and 600 kb distal to FRAXA. The distinction between the two fragile sites is important clinically since cytogenetic detection of FRAXE, without molecular analysis, could result in misdiagnosis of fragile X syndrome.

Cells, Cultured↗
PubMed1992

Transoesophageal echocardiographic evaluation of atrial morphology in children with congenital heart disease.

In a prospective study, atrial morphology was evaluated by both transoesophageal and precordial echocardiography in 86 unoperated children with congenital heart disease (age range = 0.2 to 14.8 years, mean = 3.8 years) to determine what advantages, if any, might be inherent in the transoesophageal approach. The information derived from both ultrasound approaches was correlated and compared to information obtained during subsequent cardiac catheterization (78 patients) and, or, surgical inspection (53 patients). Atrial appendage morphology and hence atrial situs was determined by transoesophageal echocardiography in every case (82 solitus, two right atrial isomerism, two left atrial isomerism). In addition, the transoesophageal approach indicated left juxtaposition in four patients, compared to only one by precordial examination. Probe patency of the foramen ovale was correctly predicted in 21 patients by transoesophageal imaging, but in only 10 by precordial imaging. In two children significant secundum defects, undetected by the precordial route, were identified. Multiple atrial septal defects were correctly defined in four patients by transoesophageal study but in only one by precordial study. Sinus venosus defects were documented in four by the transoesophageal approach, but in only one by the precordial. Primum defects were equally well documented (nine patients) by either technique, but the associated valve leaflet morphology was better documented by transoesophageal study in 5/9. A subtotal cor triatriatum was diagnosed in one child only by transoesophageal investigation. Transoesophageal echocardiography allows a much more detailed evaluation of atrial morphology than precordial imaging even in infants. It provides direct diagnosis of atrial situs, detection of juxtaposed atrial appendages and improved demonstration or definitive exclusion of atrial septal defects.

Adolescent↗
PubMed1992

Mannitol does not affect energy metabolism in forebrain ischemia.

Mannitol has a beneficial effect on ischemic injury following a short-duration forebrain ischemic insult in rats. Using the same animal model, we attempted to show that this effect of mannitol could be traced (via an improvement in cerebral blood flow) to a tempering of the collapse in the high-energy phosphates that occurs during the insult. A 10 min ischemic insult was induced by bilateral carotid artery occlusion followed by a reduction of the blood pressure to 50 mmHg through removal of blood via a tail catheter. 31P NMR spectroscopy was used to monitor the energy state and the pH prior to, during, and after the insult. The studies show that mannitol administered in doses of 0.25 g kg-1 or 1.0 g kg-1 prior to the insult has no significant effect on the high-energy phosphate levels or on the cerebral pH during ischemia, or on their post-ischemia recovery.

Animals↗