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Biomedical subjects

T Gibson

Publications and source records attributed to T Gibson.

At least 37 records · Page 2Linked to original sources

A new method for isolating tyrosine kinase substrates used to identify fish, an SH3 and PX domain-containing protein, and Src substrate.

We describe a method for identifying tyrosine kinase substrates using anti-phosphotyrosine antibodies to screen tyrosine-phosphorylated cDNA expression libraries. Several potential Src substrates were identified including Fish, which has five SH3 domains and a recently discovered phox homology (PX) domain. Fish is tyrosine-phosphorylated in Src-transformed fibroblasts (suggesting that it is a target of Src in vivo) and in normal cells following treatment with several growth factors. Treatment of cells with cytochalasin D also resulted in rapid tyrosine phosphorylation of Fish, concomitant with activation of Src. These data suggest that Fish is involved in signalling by tyrosine kinases, and imply a specialized role in the actin cytoskeleton.

3T3 Cells↗

The tyrosine-17 residue of Nef in SIVsmmPBj14 is required for acute pathogenesis and contributes to replication in macrophages.

The variant simian immunodeficiency virus termed SIVsmmPBj14 induces a rapidly fatal disease in pig-tailed macaques. The acute pathogenic effects of this virus appear to be associated with at least two in vitro characteristics: the ability to induce lymphocyte proliferation; and the ability to replicate in unstimulated PBMC. Two of the amino acids in Nef of PBj14 (the No. 17 residue, tyrosine, and the No. 18 residue, glutamic acid) appear to be linked to the virus' ability to induce lymphocyte activation. To further study the effects of these amino acids on PBj14-induced pathogenesis, we generated two mutant viruses from our molecular clone, PBj6.6, containing either changes in both the No. 17 and No. 18 residues (termed PBj6.6YE-RQ), or a single change in the No. 17 residue (termed PBj6.6Y-R). In vitro analyses of these viruses showed that while their replicative abilities in stimulated peripheral blood mononuclear cells (PBMC) were altered, they still maintained the ability to replicate in unstimulated PBMC. Replication of these viruses in macrophage populations was impaired relative to the wild-type virus. Both mutant viruses were unable to induce proliferation of macaque PBMC in vitro. Virus derived from PBj6.6Y-R was unable to induce acute disease in macaques, but did maintain the ability to induce lymphopenia and intestinal lymphoid hyperplasia. These results show that the tyrosine-17 residue of Nef is linked to lymphocyte proliferation and disease development, but also suggest that the pathogenic characteristics of SIVsmmPBj14 are dependent upon multiple genetic determinants.

Alleles↗

Prevalence of the major rheumatic disorders in the adult population of north Pakistan.

The prevalence of rheumatic diseases in developing countries is largely unknown. Studies which allow comparison of data within the contrasting communities of the Third World and the developed world have the potential to provide insights into disease aetiologies. The current study compared the frequency of rheumatic symptoms (point prevalence) amongst 1997 adults distributed evenly between poor rural and poor urban communities and relatively affluent urban people. Comparisons were also made with similarly but previously derived prevalence rates of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and Pakistanis in England. A significantly higher prevalence of joint pain was seen in the north compared with the south. RA was more common in the north and similar to the frequency amongst Pakistanis resident in England. Ethnic and genetic susceptibility might have accounted for this. There was significantly more soft-tissue rheumatism and back pain in the northern rural population compared with those in the city. Fibromyalgia was almost completely absent from the urban affluent, but osteoarthritis of the knee was significantly more common in this community, perhaps due to relative obesity. RA was least in the urban poor, a phenomenon that might be attributable to earlier death of females or other undetermined factors.

Adolescent↗

Day and night pain measurement in rheumatoid arthritis.

OBJECTIVE: An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogue scales (VAS) to distinguish and grade the severity of pain at night, during rest, and on joint movement and to determine if discriminate measurement of these three pain components enhances the value of VAS estimation. METHODS: Two hundred and fifty two consecutive RA patients were evaluated by a single observer using 10 cm VAS for pain at night, at rest during the day, and on movement. Values were correlated against age, disease duration, joint tenderness, swollen joint count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Larsen x ray scores. RESULTS: Night pain was recorded by 71 (28%) and this component of pain was lower than VAS scores for daytime rest and movement. However, those with nocturnal pain had significantly more joint tenderness (p < 0.0001), swollen joints (p < 0.0001), and higher ESR and CRP. Age, disease duration, and radiographic scores were similar in those with and without night pain. Correlations of joint tenderness were apparent for all three pain scores but only nocturnal pain correlated with swollen joints (p < 0.001) and CRP (p < 0.005). Age, disease duration, and radiographic severity correlated with daytime rest or movement scores but not nocturnal pain. CONCLUSION: Patients were able to distinguish and estimate the severity of pain at rest, on movement, and at night. The occurrence of night pain characterised those with more active disease and night pain VAS measurement correlated best with measures of joint inflammation whereas daytime pain scores, both at rest and on movement, seemed influenced by the degree of permanent joint damage. Thus, discrete measurement of rest, movement, and nocturnal pain may provide useful information about RA disease status.

Adult↗

Policy matters: critical policy analysis and nursing.

Policy is an integral part of nursing. At the organisational level, policies are constantly developed in a seemingly endless quest to provide more effective and efficient nursing services and outcomes. Such an increasing generation of policy appears to rest on the taken-for-granted assumption by nurses that policy is essential for good nursing practice. However, is it necessarily the case that the generation of policy documents advances the practice of nursing? Rather, does the apparent uncritical adoption of the role of policy by nurses actually serve to further regulate, control, and even limit the practice of nursing? This paper uses a critical perspective to explore nursing policy. In so doing it exposes the effect of policy on the construction and maintenance of everyday understandings of nursing practice.

Humans↗

Neuronal cell loss in the CA3 subfield of the hippocampus following cortical contusion utilizing the optical disector method for cell counting.

Unilateral cortical contusion in the rat results in cell loss in both the cortex and hippocampus. Pharmacological intervention with growth factors or excitatory neurotransmitter antagonists may reduce cell loss and improve neurological outcome. The window of opportunity for such intervention remains unclear because a detailed temporal analysis of neuronal loss has not been performed in the rodent cortical contusion model. To elucidate the time course of hippocampal CA3 neuronal death ensuing cortical contusion, we employed the optical disector method for assessing the total number of CA3 neurons at 1 and 6 hours, 1, 2, 10, and 30 days following injury. This stereological technique allows reporting of total cell numbers within a given region and is unaffected by change in the volume of the structure or cell size. A rapid and significant reduction in neurons/mm3 in the ipsilateral CA3 field was observed by 1 h following trauma. However, a significant increase in neurons/mm3 was seen at 30 days postinjury. This surprising finding is a result of CA3 volume shrinkage and redistribution of CA3 neurons. Utilization of the optical disector reveals that regardless of an increase in neurons/mm3 at 30 days following injury, CA3 cell loss reaches 41% of control animals by 1 day posttrauma and remains near that level at all subsequent time points examined. It is estimated that there are about 156,000 neurons in the CA3 region in control animals. By 1 h following cortical contusion the cell population decreases to 93,000 neurons indicating a very rapid cell loss. This suggests a window of less than 24 h for pharmacological intervention in order to save CA3 neurons following cortical contusion.

Animals↗

The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakistan.

The association of particular HLA-DR alleles and the shared epitope with rheumatoid arthritis (RA) is now well established. The strength of these links varies between races. Furthermore, the proposition that the presence of the shared epitope is indicative of severe disease has been more difficult to sustain in non-Europeans. This study examines the frequency of HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype frequencies were ascertained in 86 RA hospital out-patients and 79 healthy controls matched for age, gender and ethnicity. HLA-DR1 and HLA-DR4 frequency was similar in patients and controls. HLA-DR10 occurred in 26 instances (15%) in RA and in eight (5%) controls (Pcorr = 0.048). HLA-DR2 was also increased in patients (P = 0.053) and its major subtype DR15 was significantly increased (Pcorr = 0.03). HLA-DR5 frequency was 5% in patients and 19% in controls (Pcorr = 0.002). The HLA-DR4 alleles possessing the shared epitope were more common in RA (Pcorr = 0.03) and this difference was enhanced by inclusion of other alleles possessing the shared epitope (Pcorr = 0.002). Shared epitope alleles were observed in 43 (50%) patients and 17 (22%) controls (Pcorr = 0.003). The shared epitope did not distinguish patients with more severe disease, as reflected by pain, joint deformities, disability, rheumatoid factor or X-ray damage. The distribution of HLA-DR alleles in Pakistanis with RA supports the shared epitope hypothesis. In common with other non-European racial groups, HLA-DR4 was not associated with RA. Unlike other groups, there was a weak link of RA with HLA-DR2. A protective effect of HLA-DR5 was apparent. In accord with some other studies, the shared epitope in this hospital out-patient population was not a marker for more severe disease.

Adolescent↗

A comparison of the prevalence of rheumatoid arthritis and other rheumatic diseases amongst Pakistanis living in England and Pakistan.

The impact of environmental factors on the causation of rheumatoid arthritis (RA) is thought to be considerable. We explored this by comparing the prevalence of RA amongst Pakistanis living in England, where it is relatively high amongst ethnic English, and in Pakistan. The frequency of other rheumatic diseases was also compared. Information on 2056 adult Pakistanis in England and 4232 in Pakistan was obtained by house-to-house surveys using identical protocols. Positive respondents were examined by the same two clinicians in both countries. Rheumatic complaints increased with age and were more common in females in both communities. The standardized morbidity ratio (SMR) (95% CI) of RA in England was 2.1 (1.1-3.1) compared with Pakistan, a difference that was entirely attributable to females. The SMR (95% CI) for women was 3.0 (0.4-5.6) and for men 0.86 (-0.84 to 2.56). In Pakistan, there was a trend to more reporting of some but not all rheumatic complaints amongst the affluent segment of the population. This was increasingly apparent amongst those resident in England and the possibility of an impact of easier ascertainment amongst the more educated cannot be discounted. Low back pain was significantly more common in England. Furthermore, the colder climate was frequently invoked as a cause of more symptoms in England. Thus, several factors may have influenced the observation that RA is more common amongst Pakistanis in England compared with Pakistan. An environmental factor cannot be excluded. However, the frequency of non-specific musculoskeletal pain was similar. The regions of Pakistan from which the two populations were derived were also different and immunogenetic heterogeneity might also have contributed to the difference in RA prevalence.

Adolescent↗

Spinal bone SPECT in chronic symptomatic ankylosing spondylitis.

Bone SPECT has acquired a useful role in the evaluation of acute and chronic back pain. Spinal pain is also a characteristic of chronic ankylosing spondylitis. The authors investigated the bone SPECT appearances of the lower thoracic and lumbar spine in 28 symptomatic patients with established ankylosing spondylitis, half of whom had complete ankylosis of the sacroiliac and one third complete ankylosis of the intervertebral joints. SPECT abnormalities were identified in 89%. Facetal joint uptake was found in 16 (57%) patients, of whom 7 (25%) had three or more, and 2 (7%) had seven or more active sites. The only other common site of uptake was in the vertebral body, in which 15 patients (54%) showed increased uptake with three or more sites found in 3 (11%) patients. The authors conclude that SPECT abnormalities in the lower thoracic and lumbar spine are frequently found in patients with ankylosing spondylitis, with the most common sites of abnormality in the facetal joints or vertebral body. Multiple sites of uptake in the facetal joints maybe striking in such patients and has not been previously described.

Adult↗

The politics of collaboration as viewed through the lens of a collaborative nursing research project.

Collaborative research has much to offer nursing. However, the collaborative research process is fraught with issues arising from the 'politics of collaboration'. Such politics operate at the individual and institutional levels and can have debilitating effects on the research enterprise if they are not dealt with. This paper explores what is meant by collaboration and the politics of collaboration. Drawing on a critical perspective, it uses Brookfield's themes of impostorship, cultural suicide and roadrunning as the theoretical framework for the analysis. The paper uses an actual collaborative research project to ground the discussion provided.

Cooperative Behavior↗

A comparison of the clinical features of hospital out-patients with rheumatoid disease and osteoarthritis in Pakistan and England.

Several studies have demonstrated differences between ethnic groups in the severity and pattern of rheumatoid arthritis (RA) and osteoarthritis (OA). The current investigation compared RA and OA in Pakistani and British White Caucasian out-patients in two teaching hospitals. There were 88 RA patients in each setting, matched for age, gender and disease duration. The pattern of OA was sought by recording the details of 44 consecutive new referrals to each clinic. Amongst the RA patients, joint deformity and tenderness were similar, but disability was more severe, ESR higher, anaemia more pronounced and RA latex more often positive amongst the Pakistani patients. X-ray damage was more pronounced amongst the British patients, especially in the feet. The British were also more likely to have rheumatoid nodules and to have undergone disease-modifying treatment or joint surgery. The paradox of more severe indices of disease activity and disability with less X-ray erosion in hands and feet might be explained by the impact of treatment on joint inflammation and the beneficial influence of surgery on disability in the British. The worse X-ray scores in the White Caucasians might indicate a genetic predisposition to radiologically more severe disease. The age of the British OA patients was significantly higher, but this is unlikely to have influenced the striking disparity in the frequency of isolated knee OA, which was significantly greater in the Pakistani patients. Comparison with age- and sex-matched healthy Pakistani subjects suggested that susceptibility to knee OA was strongly associated with body weight, but not with knee bending at prayer or with joint laxity. Amongst the Pakistanis, Heberden nodes, hip involvement and evidence of generalized OA were significantly less, but these observations may have been due to their younger age. The study confirmed differences in the clinical presentation of both RA and OA amongst patients in Pakistan compared with White Caucasians in Britain. Several confounding factors, such as patient recruitment, culture, treatment and age, may have influenced the results, but it remains likely that genetic factors are important.

Adult↗

The value of SPECT scans in identifying back pain likely to benefit from facet joint injection.

Lumbar facet disease is sometimes implicated in low back pain. Identification is difficult and this may account for a variable response. Single photon emission computerized tomography (SPECT) is a scanning technique which enables localization of facet joint pathology. We determined whether recognition of facet disease by this method improved the response to corticosteroid injection treatment. Fifty-eight patients with low back pain and displaying accepted clinical criteria for facet joint disease were evaluated by SPECT. Twenty-two had facetal uptake of isotope. These and the tender facet joints of 36 scan-negative patients were injected with 40 mg methylprednisolone and 1 ml 1% lignocaine under X-ray control. Pain was assessed by a blind observer using the McGill questionnaire (MGQ), Present Pain Intensity score (PPI) and a Visual Analogue Scale (VAS). VAS, PPI and MGQ were reduced in the scan-positive patients at 1 month (P = 0.05, P = 0.0005, P = 0.005) and MGQ at 3 months (P = 0.01), whilst scan-negative patients were unchanged. The percentage of scan-positive patients who reported improvement was 95% at 1 month and 79% at 3 months, significantly greater than the control group (P = 0.0005, P = 0.01). Within 6 months, pain improvement in the SPECT-positive group was no longer statistically significant. Tenderness did not correlate with increased uptake on SPECT scan. Osteoarthritis of the facets was more common in the SPECT-positive patients (P < 0.001), but did not correspond with sites of increased uptake on SPECT scan. These results suggest that SPECT can enhance the identification of back pain sufferers likely to obtain short-term benefit from facet joint injection.

Adolescent↗

Knee pain amongst the poor and affluent in Pakistan.

The frequency of joint symptoms was determined amongst 2022 affluent and 2210 poor adults in Karachi, Pakistan. Joint pain was significantly (P = 0.025) more common amongst the affluent (6.6%) compared with the poor (5%) and this was due to a significantly greater frequency of knee pain in the richer community (3% vs 1.8%; P = 0.008). The prevalence increased with age and was more common in females. Almost half were associated with varus deformity, suggesting the presence of associated OA in a high proportion. The overall frequency of knee pain seemed no greater than in series reported from the West. Compared with age- and sex-matched controls, body weight was significantly greater amongst those with knee pain, both amongst the affluent (P = 0.005) and the poor (P = 0.02). Control subjects were heavier in the affluent population, suggesting that the greater frequency of knee symptoms in this community was due to their relative obesity. Knee bending at prayer was most common amongst the affluent controls and may indicate that religious observance also contributed to the problem in the richer population. Squatting was a characteristic of the poor who had less knee pain than the affluent. Knee flexing could not therefore be confidently implicated. No relationship could be demonstrated between knee pain and joint laxity.

Adolescent↗

The discursive construction of the role of the nurse in medication administration: an exploration of the literature.

This paper draws on postmodern thought to interrogate the literature relating to nurses and medications. An examination of the representation of a specific nursing activity in the literature-the administration of medications-reveals much about the way in which the role of the nurse is discursively constructed. This is particularly evident from an analysis of the procedures shaping that role. These procedures, which nurses themselves develop and institute as rules to guide nursing practice, can have the effect of reducing nursing work to a series of rituals which contribute to the discursive construction of the nurse's role in medication administration.

Ceremonial Behavior↗

High-affinity RNA ligands to Escherichia coli ribosomes and ribosomal protein S1: comparison of natural and unnatural binding sites.

High-affinity RNA ligands were generated against intact 30S ribosomes, S1-depleted 30S ribosomes, and purified ribosomal protein S1. Sequence analysis indicated two classes of ligand: unstructured RNAs containing a Shine-Dalgarno sequence and structured RNAs containing a pseudoknot. The Shine-Dalgarno-containing ligands were generated against S1-depleted 30S ribosomes but, surprisingly, not against intact 30S ribosomes or ribosomal protein S1. In contrast, pseudoknot-containing ligands were generated against intact ribosomes as well as purified S1 protein. The two classes of ligand exhibited specificity for their respective targets, as well as conserved sequence and secondary structure reminiscent of naturally occurring, cis-acting mRNA elements.

Base Sequence↗