Search PubMed⌕ Search

Biomedical subjects

S Hughes

Publications and source records attributed to S Hughes.

At least 109 records · Page 6Linked to original sources

Evidence for two populations of N-methyl-D-aspartate receptors in neonatal rat spinal cord. The effect of peripheral nerve axotomy.

Quantitative autoradiography was used to characterise the binding of the N-methyl-D-aspartate (NMDA) receptor antagonist [3H]dizocilpine maleate (MK801) in the white matter and dorsal, intermediate and ventral subregions of the grey matter in the lumbar spinal cord of neonatal rats. The effect on the binding of unilateral sciatic nerve section on the day of birth was examined. In unoperated animals the Bmax and Kd of the binding had decreased in all subregions by two weeks, when the values were similar to those in the adult. After axotomy the Bmax values declined during the first 14 days in all subregions although the density appeared higher in the grey matter in the ventral horn compared to sham operated control. In the axotomised animals, the Kd values for the white matter and ventral horn grey matter had declined by two weeks but in the dorsal and intermediate subregions of the grey matter the values remained elevated. The results are consistent with the presence of two populations of NMDA receptor at birth. In the normal animals the lower affinity receptor disappears in all subregions, but after axotomy it is retained in the dorsal and intermediate subregions for at least 2 weeks.

Animals↗

Targeting of marker loci to chicken chromosome 16 by representational difference analysis.

Representational difference analysis (RDA) was initially used to identify differences between two inbred lines of chickens, line N and line 15I, on which the Compton mapping reference population is based. RDA was subsequently used to identify marker loci targeted specifically to chicken chromosome 16. Chromosome 16 contains the major histocompatibility complex (MHC), nucleolar organiser region (NOR) and Rfp-Y complex. To generate markers specific for this chromosome a bird was selected from the Compton mapping reference population which had inherited N line alleles for the MHC, NOR and Rfp-Y regions on this chromosome. DNA from this bird was compared with pooled DNA from 16 of its siblings, all of which had inherited line 15I alleles for the MHC, NOR and Rfp-Y regions. Initially amplicons were derived from BamHI digested samples, RDA products were cloned after the first round of hybridisation and 113 clones were investigated: 45 of these identified BamHI polymorphisms in this population. Of the 45 polymorphic clones, 17 have been mapped in the reference population so far, and these have identified seven new loci on chromosome 16. Interestingly a group of 16 other loci were linked on chromosome 4. The same birds were also compared by RDA following digestion with TaqI. Again large numbers of clones were generated of which 65 were investigated. Of these 17 clones were polymorphic and of five clones mapped so far three lie on chromosome 16. Two of the loci mapped to chromosome 16 have been used to identify yeast artificial chromosome (YAC) clones.

Animals↗

Localization of mouse hepatitis virus open reading frame 1A derived proteins.

We have investigated the intracellular localization of proteolytic cleavage products encoded in the 5' portion of mouse hepatitis virus (MHV) gene 1. Immunofluorescent labeling of cells with an antiserum which recognizes p28, the ORF1a N-terminal cleavage product, resulted in widespread somewhat granular cytoplasmic staining, indicating that this protein is widely distributed in the cytoplasm of MHV-infected, but not control uninfected cells. Immunofluorescent staining of infected cells with antisera which recognize the downstream polypeptides, p65, p240 and p290 labeled discrete vesicular perinuclear structures. Double immunofluorescent labeling of BHK cells expressing the MHV receptor (BHK(MHVR1)) and infected with MHV-A59 with a Golgi-specific anti-mannosidase II monoclonal antibody and with antiserum recognizing each of these anti-MHV ORF1a polypeptides, showed that the p240 and p290 polypeptides were localized in discrete vesicular structures that overlapped the Golgi complex. Labeling with antibodies specific for p65 colocalized with the Golgi region, and showed staining of the perinuclear cytoplasm as well. Plasmids containing sequences contained in the first 6.75 kb of ORF1a have been expressed using the coupled vaccinia virus-T7 polymerase system. Immunofluorescent labeling of transfectants with the anti-ORF1a antisera showed patterns of antigen distribution similar to those observed in cells infected with MHV-A59. A deletion analysis with constructs containing only portions of the ORF1a sequence indicated that 303 amino acids containing the first papain-like protease domain (PLP-1) was sufficient to associate this protein with the Golgi.

Animals↗

Telephone follow-up: an extension of the surgical outpatient department.

A total of 112 surgical patients took part in telephone follow-up, conducted by non-medical staff, after discharge home. Successful telephone follow-up was achieved in 93% of patients at 6 weeks, 91% at 3 months and 79% at 12 months. Telephone follow-up by non-medical staff is a practical method of assessing patient outcome after surgery. Wider use of this technique would free up time in the surgical clinics, without compromising audits of outcome and purchaser demands for evidence of efficacy.

Ambulatory Surgical Procedures↗

N-methyl-D-aspartate receptors in motoneurones after unilateral axotomy in the neonatal rat.

Quantitative autoradiography was used to characterise the binding of the N-methyl-D-aspartate receptor antagonist [3H]dizocilpine maleate in the ventral horns of the lumbar spinal cord of normal, sham-operated, and axotomized neonatal rats. Specific binding sites were revealed on the cell membranes of the motoneurones. In the normal neonate both the Bmax and the Kd values for the binding declined over the first 14 days of life. At 14 days the Kd value was similar to that in adult rats. Unilateral sciatic nerve section was performed in neonates on the day of birth. Axotomy caused the death of approximately 53% of motoneurones. The Bmax and Kd values for [3H]dizocilpine maleate binding declined in the first 2 weeks on operated and contralateral sides in both axotomized and sham-operated animals. However, the specific binding per motoneurone was significantly higher on the sectioned side in axotomized animals at all times examined after the day of birth. The results are consistent with two populations of NMDA receptors with different binding affinities being present in motoneurones at birth, and the lower affinity receptor gradually disappearing over the first few days. The lower affinity receptor may be responsible for the plasticity of motoneurones during embryonic and neonatal life, and for determining which motoneurones die after axotomy.

Animals↗

G-protein(S), G alpha q/G alpha 11, in the olfactory neuroepithelium of the channel catfish (Ictalurus punctatus) is altered by the herbicide, dichlobenil.

The immunohistochemical localization of G alpha q/G alpha 11 was studied in the olfactory neuroepithelium of the channel catfish. Antigenicity in the rosette was found at the apical surfaces of cells, within the apical neck regions of some cells, and within the area of the basal nerve tracts. Specific labeling was eliminated by preincubation of the G alpha q/G alpha 11 antibodies with the cognate peptide. Catfish, exposed to a 20 ppm dose of the herbicide, dichlobenil, displayed a reduction in G alpha q/G alpha 11 antigenicity. Proteins were extracted from olfactory tissues and solubilized. Using SDS-PAGE and Western blotting, bands corresponding in apparent molecular weight to a 38 kD protein were found. These data demonstrate that the herbicide may be a potent nasal olfactory toxicant in aquatic situations.

Animals↗

The major compositional transitions in the vertebrate genome.

The vertebrate genome underwent two major compositional transitions, between therapsids and mammals and between dinosaurs and birds. These transitions concerned a sizable part (roughly one-third) of the genome, the gene-richest part of it, and consisted in an increase in GC levels (GC is the molar fraction of guanine + cytosine in DNA) which affected both coding sequences (especially third codon positions) and noncoding sequences. These major transitions were studied here by comparing GC3 levels (GC3 is the GC of third codon positions) of orthologous genes from Xenopus, chicken, calf, and man.

Animals↗

The effect of dominant vestigial alleles upon vestigial-mediated wing patterning during development of Drosophila melanogaster.

The vestigial gene product is required for the completion of wing development in Drosophila melanogaster. In the absence of vestigial gene expression, cells within the larval wing and haltere imaginal discs fail to proliferate normally thus producing adults with severely reduced wings. Of a large number of vestigial mutations that have been characterized, only two are currently known to exist, vestigial(U) and vestigial(W), which manifest a significant dominant phenotype. Both are associated with chromosomal inversions that fuse the majority of the vestigial coding regions to other genes; mastermind in vestigial(U) and invected in vestigial(W) Examination of vestigial expression in the presence of these dominant alleles shows alterations in the disc-specific expression of vestigial during later stages of larval development. These patterning disruptions are specific to cells of the wing imaginal disc, as significant suppression of total levels of vestigial expression within entire larvae could not be detected. This dominant interference of vestigial patterning appears to be mediated in part by the vestigial coding sequences that are within the gene fusions. Further evidence that the dominant phenotype is the result of disrupted vestigial patterning comes from observations that the dominant alleles can be partially suppressed by mutations within the Drosophila-epidermal growth factor receptor gene. Mutagenesis of vestigial(U) and vestigial(W) produced a series of alleles with partially dominant phenotypes that restored various amounts of the adult wing. These phenotypes can be correlated with alterations in specific portions of the vestigial sequences associated with the dominant alleles. In the presence of these partially dominant alleles, wing imaginal discs have significantly more cells which express vestigial compared with the number associated with the original dominant phenotype. Additionally, eliminating some of the dominant effect causes alterations in the patterns of early stage apoptotic cell death associated with dominant vestigial alleles. Utilizing these new vestigial alleles, it is possible to correlate the consequence of altered vestigial expression to subsequent changes in patterning of the wing disc.

Animals↗

Sweet's syndrome: an unusual cutaneous feature of Crohn's disease or ulcerative colitis. The South West Gastroenterology Group.

Sweet's syndrome is characterized by tender, red inflammatory nodules or papules, usually affecting the upper limbs, face or neck. It is part of the group of acute neutrophilic dermatoses that includes pyoderma gangrenosum, but can be distinguished by its appearance, distribution and histological features. Four patients with Sweet's syndrome and Crohn's disease are reported. A total of 30 cases from the literature suggest that Sweet's syndrome is an unusual extraintestinal manifestation of either Crohn's disease or ulcerative colitis. There is a strong predilection for women (87%), patients with colonic disease (100%) and those with other extraintestinal features (77%). The rash is associated with active disease in 67-80%, but may precede the onset of intestinal symptoms in 21% and has been reported 3 months after proctocolectomy for ulcerative colitis.

Adult↗

Predictors of decline in manual performance in older adults.

OBJECTIVE: To determine factors that predict decline in manual performance using a multivariate model of determinants of functional limitation. DESIGN: Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics, residences of homebound individuals, and a continuing care retirement community. PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included continuing care retirement community (CCRC) residents (n = 215), chronically homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age at baseline was 78 years. MEASUREMENT: Independent variables included demographics, physician measures of upper-extremity joint impairment, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variable was 2-year decline in timed manual performance below a threshold associated with need for long-term care services. RESULTS: The proportion of subjects who exceed a Timed Manual Performance Test threshold of 350 seconds increased slowly from baseline through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the oldest group (> 85 years at baseline). Using a discrete survival model, we found that age, education, grip strength, and psychological status predicted crossing the manual performance threshold within a 2-year period. CONCLUSIONS: The findings, coupled with earlier findings that upper extremity joint impairment predicted both grip strength and manual performance, suggest that joint impairment may be an important risk factor for future functional limitation. Since diminished hand function has been shown to predict dependency, development and testing of interventions to maintain or restore upper extremity joint function and reduce pain would appear to be a high research priority.

Age Factors↗

Avian leukemias and lymphomas: interplay between retroviruses and herpesviruses.

Avian leukemias and lymphomas are caused primarily by retroviruses and herpesviruses. The protooncogenes activated by avian retroviral insertions in B & T-cell lymphomas will be summarized, with discussion on a new common insertion site, bravo, associated with RAV-O LTR insertion. Two novel interactions between avian retroviruses and Marek's disease herpesvirus (MDV) will be described: one involves direct interactions between putative viral oncoproteins and the other integrative recombination between these two viruses.

Alpharetrovirus↗