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Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 271 records · Page 15Linked to original sources

Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa.

The microsatellite marker DXS426 maps to the interval Xp21.1-Xp11.21, the chromosomal region which contains two loci for X-linked retinitis pigmentosa (XLRP; RP2 and RP3). We have refined the localization of DXS426 both physically, by mapping it to a deletion which spans the interval Xp21.3-Xp11.23, and genetically, by studying multiply informative crossovers which indicate that DXS426 lies between DXS7 and DXS255 (i.e., Xp11.4-Xp11.22). As this is the region which contains the RP2 gene, RP2 families could be identified on the basis of linkage of XLRP to DXS426. Multiply informative crossovers in two RP2 families indicate that the most likely location of the RP2 gene is between DXS426 and DXS7. DXS426 is therefore an important highly informative marker for the purposes of carrier detection and early diagnosis of RP2 and for the localization of the disease gene.

Base Sequence↗

Protein phosphorylation regulates transcription of the beta-glucoside utilization operon in E. coli.

We have investigated the interaction between BglF and BglG, two proteins that regulate expression of the E. coli bgl operon. BglF is both a negative regulator of operon expression and a phosphotransferase involved in uptake of beta-glucosides. BglG is a positive regulator that functions as a transcriptional antiterminator. We show here that BglF is phosphorylated by the soluble components of the phosphotransferase system: Enzyme I, HPr, and the phosphate donor phosphoenolpyruvate. Phosphorylated BglF can then transfer phosphate either to beta-glucosides or to wild-type BglG. Mutant BglG derivatives, which give constitutive expression of the bgl operon, show little or no phosphorylation by BglF. Hence BglF exerts its negative effect on operon expression by phosphorylating BglG, blocking its action as an antiterminator. BglG is dephosphorylated only in the presence of both BglF and beta-glucosides. Based on these results, we propose the following mechanism: In the absence of beta-glucosides, BglG is phosphorylated by BglF and is inactive in antitermination. Addition of inducer stimulates BglF to dephosphorylate BglG, allowing BglG to function as a positive regulator of operon expression. Beta-Glucosides are then phosphorylated and transported into the cell by BglF.

Bacterial Proteins↗

Predictive testing for Huntington's disease with linked DNA markers.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

Adult↗

No linkage of chromosome 5q11-q13 markers to schizophrenia in Scottish families.

Recent work suggests that an autosomal dominant gene for schizophrenia may be located on the 5q11-q13 region of chromosome 5 (refs 1 and 2): a report of schizophrenia associated with trisomy 5q11-q13 in two members of a family of Chinese origin prompted the discovery of linkage with markers p105-599Ha and p105-153Ra in five Icelandic and two English schizophrenic families. The strongest linkage was observed when the phenotype was broadly defined to include minor psychiatric diagnoses not traditionally considered part of the schizophrenia spectrum. By contrast, no evidence was found of linkage in a single multiplex Swedish schizophrenic pedigree. To determine whether these conflicting results arise from genetic and/or uncertainties in defining the schizophrenic phenotype, we examined fifteen Scottish schizophrenic families with restriction fragment length polymorphisms that span this region. We found no evidence for linkage, regardless of how broadly or narrowly the schizophrenic phenotype is defined, and conclude that a susceptibility locus, whose presence awaits confirmation, on the proximal portion of the long arm of chromosome 5 can be responsible for only a minority of cases of familial schizophrenia.

Chromosomes, Human, Pair 5↗

Cytotoxic T lymphocytes specific for self tumor immunoglobulin express T cell receptor delta chain.

CTL are thought to play a role in the elimination of transformed cells in vivo. The effectiveness of such CTL is in part dependent on recognition of tumor specific antigens. Among the best characterized tumor-specific antigens are the unique or idiotypic determinants on the Ig of B cell lymphomas. Here we describe the generation and properties of human CTL specific for the idiotype on autologous B cell tumors. These cells are CD3+,CD4-,CD8- and express the delta chain of the TCR. Such cells may prove useful in tumor-specific adoptive therapy.

Adolescent↗

The recording of brain evoked potentials resulting from intra-articular focused ultrasonic stimulation: a new experimental model for investigating joint pain in humans.

Pain was induced in the proximal interphalangeal joint of the index finger in human volunteers using a high powered focused ultrasonic generator. Eighty, 100 ms pulses were applied during each test. This test was repeated at hourly intervals for a period of 5 h. A brain evoked potential with a characteristic wave form was recorded, resulting from the application of these stimuli. A computerised visual analogue scale system was used to measure subject's perception of the painfulness of each stimulus. A significant correlation was found between evoked potential amplitude and mean visual analogue scale score. There was some variation in evoked potential amplitude and mean visual analogue scale score as a result of repeated application of the test but this was not significant over the 5 h time period.

Adult↗

Morphology of left anterior descending coronary territory lesions as a predictor of anterior myocardial infarction: a CASS Registry Study.

Despite a growing awareness of the correlation of coronary artery stenoses morphology with clinical syndromes, no comprehensive, prospective analysis of the implications of stenosis morphology on risk of myocardial infarction has been reported. Angiograms from 118 patients, representative of the 4.9% of medically treated Coronary Artery Surgery Study (CASS) patients who during subsequent 3 year follow-up study had an anterior myocardial infarction, were matched on the basis of arteriographic anatomy and disease with 141 patients who did not have an anterior infarction. Angiograms from these 259 patients with 557 left anterior descending artery stenoses were reviewed without knowledge of clinical outcome. Conditional regression analyses were performed to determine the importance of stenosis morphology, relative to computer-determined stenosis severity and other clinical variables, in the prediction of risk of infarction. Univariate analysis revealed luminal roughness (odds ratio 4.5; p = 0.001) and lesion length (odds ratio 1.7 per unit length; p = 0.007) to be highly correlated with future risk of infarction. Multivariate analysis revealed left anterior descending artery percent stenosis greater than or equal to 50%, lesion roughness, left circumflex artery stenosis and smoking, in that order, to be predictive of anterior myocardial infarction, whereas 22 other morphologic variables were not independently predictive of outcome. The importance of stenosis roughness may relate to its propensity for thrombogenesis and should be considered in clinical decision making.

Angiography↗

Outcome studies of low birth weight infants published in the last decade: a metaanalysis.

We conducted a metaanalysis and methods review of 80 studies, published in the last decade, that explored the outcome of low birth weight infants; 27% involved infants whose birth weights were less than or equal to 2500 gm (low birth weight), 44% less than or equal to 1500 gm (very low birth weight), and 29% less than or equal to 1000 gm (extremely low birth weight). Problems found in these studies were grouped into three categories: subject and methods issues, environmental factors, and outcome measurement. The combined average intelligence quotient/developmental quotient (IQ/DQ) of all low birth weight groups was 97.77 (SD 6.19); for control subjects the mean IQ/DQ was 103.78 (SD 8.16). This difference was statistically significant but perhaps not clinically significant. No differences in mean IQ/DQ scores were found among the low birth weight, very low birth weight, and extremely low birth weight subgroups. Statistically significant differences among all groups and control subjects were found when categoric data were analyzed, as were differences among the three subgroups; however, the variety of outcome criteria makes interpretation of the categoric analyses difficult.

Environment↗

Long-segment coronary ulcerations in survivors of sudden cardiac death.

Angiographically irregular coronary stenoses usually represent plaque rupture with or without superimposed thrombi. Long-segment coronary stenoses with diffuse irregularities (type IIB morphology) have been shown to be more prevalent than focal irregular lesions (type IIA morphology) in survivors of cardiac arrest without acute myocardial infarction. To further understand the pathogenetic importance of type IIB morphology, the clinical and angiographic characteristics in 59 such patients were analyzed. Type IIB lesions accounted for 63% of all type II lesions. Type IIB patients were older than type IIA patients (p less than 0.05). There was a tendency for type IIB morphology to be associated with more extensive disease than other types of lesion morphology (p less than 0.10). Type IIB morphology probably reflects more advanced atherosclerosis. Platelet microemboli may precipitate spasm and/or acute ischemic ventricular tachyarrhythmias. It is possible that long-segment coronary ulcerations are associated with a higher risk for local coronary thromboembolism, and hence with sudden death, than focal lesions.

Aged↗

An evaluation of topical anaesthesia for myringotomy.

The relative efficiency of 2 topical anaesthetic agents in controlling the pain arising from myringotomy and grommet insertion has been assessed by a prospective, single blind controlled trial. The 2 anaesthetics were 5% cocaine and a new lignocaine and prilocaine mixture named Emla. Following a standardized anaesthetic procedure the pain arising from myringotomy, aspiration of the middle ear and subsequent insertion of a grommet was recorded by the patient on a linear analogue scale. A multivariate analysis was performed to assess the factors which significantly affected the pain levels. Only the type of anaesthetic used played a major role, with Emla giving significantly better anaesthesia than cocaine.

Adolescent↗

Goode T-tubes: do the benefits of their use outweigh their complications?

In this retrospective study of 130 ears over a 5-year period, the effect of intubation with the Goode T-tube was evaluated. The tubes improved the hearing in 86% of ears with a conductive loss secondary to a middle ear effusion to an average 5 dB airbone gap. They improved the early stage retracted tympanic membrane but had no effect on the established postero-superior retraction pocket. They were successful in treating barotrauma. The main complication with their use was otorrhoea which occurred in 28% of ears, and persistent perforation occurring in 6% of the ears. Seventy-seven per cent of tubes were in place after 36 months. Extrusion was significantly related to infection in the ear, and also to the presence of glue on insertion but there was no correlation between the number of previous grommets or the age of the patient. The Goode T-tube is advocated for use in middle ear effusion refractory to conventional grommet insertion or that due to cleft palate.

Adolescent↗

Cloning of the gene encoding streptococcal immunoglobulin A protease and its expression in Escherichia coli.

We have identified and cloned a 6-kilobase-pair segment of chromosomal DNA from Streptococcus sanguis ATCC 10556 that encodes immunoglobulin A (IgA) protease activity when cloned into Escherichia coli. The enzyme specified by the iga gene in plasmid pJG1 accumulates in the periplasm of E. coli MM294 cells and has a substrate specificity for human IgA1 identical to that of native S. sanguis protease. Hybridization experiments with probes from within the encoding DNA showed no detectable homology at the nucleotide sequence level with chromosomal DNA of gram-negative bacteria that excrete IgA protease. Moreover, the S. sanguis iga gene probes showed no detectable hybridization with chromosomal DNA of S. pneumoniae, although the IgA proteases of these two streptococcal species cleaved the identical peptide bond in the human IgA1 heavy-chain hinge region.

Amino Acid Sequence↗

Lumbar spine: motion compensation for cerebrospinal fluid on MR imaging.

To determine whether the motion of cerebrospinal fluid (CSF) in the lumbar spine degrades T2-weighted magnetic resonance (MR) images, a spine phantom, three healthy volunteers, and a prospective series of 20 patients suspected of having lumbar spine disease underwent MR imaging with and without motion-compensation techniques. In the phantom, pulsation amplitudes as low as 3 mm (within the physiologic range of human lumbar CSF motion) reduced image quality on conventional images but not on motion-compensated images. Similar findings were observed in two volunteers and 11 patients. The magnitude of the artifacts was variable; they could impair visualization of the conus, decrease contrast or reduce the sharpness of the CSF-thecal sac interface, and cause focal regions of reduced CSF signal intensity adjacent to bulging disks. Image quality was most improved when peripheral gating was combined with even-echo rephasing. In the patient group, the use of motion-compensation techniques increased the CSF signal-to-noise ratio by an average of 29% (P less than .01); this resulted in improved contrast between the conus and extradural structures. The data suggest that CSF motion compensation is clinically useful during T2-weighted MR imaging of the lumbar spine.

Adult↗

Analysis of structural changes in the stria vascularis following chronic gentamicin treatment.

Changes in the stria vascularis following chronic gentamicin treatment have been examined using quantitative methods. Albino guinea pigs were given gentamicin at 100 mg.kg-1.day-1 subcutaneously for 10 days. Comparisons were made of strial tissue from the treated animals sacrificed either 1 h or 4 weeks following the last injection with that from saline-injected controls. Strial width (spiral prominence to Reissner's membrane) and marginal cell (MC) number across the stria were determined from scanning electron micrographs. Strial thickness (endolymphatic surface to spiral ligament) and the volume fractions of the strial components (MCs, intermediate cells (ICs), basal cells (BCs) and capillaries) were derived from thin sections. Qualitative changes to both MCs and ICs were apparent 1 h after the last injection. At four weeks post-treatment, there was a small, but statistically significant, decrease in the number of marginal cells and a highly significant decrease in strial thickness. This was almost entirely due to a highly significant decrease in the volume fraction of MCs (i.e. shrinkage). The volume fraction of ICs was increased but this could be accounted for by MC shrinkage; after allowing for the reduction in strial thickness, the volume occupied by ICs was unchanged. Thus, following chronic gentamicin treatment, the stria is affected but significant progressive and permanent structural effects are confined to the marginal cells.

Animals↗

Absence of cell surface LFA-1 as a mechanism of escape from immunosurveillance.

During studies of T-cell recognition of autologous tumour cells, a number of tumour cell lines derived from patients with lymphoma proved to be poor stimulators of both autologous and allogeneic T-cell responses. Analysis of the tumour cell surface molecules indicated that expression of the lymphocyte-function-associated antigen, LFA-1, was lacking, whereas normal leucocytes from these patients expressed normal levels of LFA-1. Examination of other lymphoid tumours revealed that most high grade lymphomas, but not most low or intermediate grade lymphomas, do not express the LFA-1 molecule. Furthermore, in an initial survey, the tumours from 5 of 7 patients with non-relapsing large cell lymphomas expressed LFA-1 whereas only 3 of 18 patients with relapsing lymphomas had tumours that did so. These findings suggest that tumour cells lacking surface LFA-1 cannot initiate an effective immune response in vivo. This lack of immunogenicity might contribute to escape from immunosurveillance.

Antigens, Surface↗