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Biomedical subjects

I Campbell

Publications and source records attributed to I Campbell.

At least 19 recordsLinked to original sources
PubMed1997

Factors controlling T-cell migration across rat cerebral endothelium in vitro.

The migration of lymphocytes through primary cultures of rat brain microvascular endothelial cell monolayers was examined in vitro by time-lapse videomicroscopy. Antigen-specific T cell line migration was dependent on the duration of culture (post-antigen stimulation) with exogenous interleukin-2 (IL-2). Peak migration (approximately 50% of T-cells during the 4 h migration assay) occurred after 4 days of culture with IL-2 but did not coincide with maximal expression of LFA-1, VLA-4 or the IL-2 receptor. On unstimulated endothelia antibody blockade of LFA-1 or ICAM-1 inhibited T-cell line migration to 8.0% and 6.8% of control values, respectively, whereas blocking VLA-4 and VCAM-1 had no effect. On IL-beta activated endothelium blocking LFA-1 and ICAM-1 was less effective (24.9% and 27.3% of control values, respectively) and blockade of VLA-4 and VCAM-1 brought about a reduction to 63.0% and 68.3% of controls respectively. Inhibition of IL-2-dependent proliferation with an IL-2 receptor blocking antibody also significantly inhibited T-cell migration to 22.2% of controls. Peripheral lymph node (PLN) lymphocytes could also be induced to migrate through untreated cerebral endothelial cell monolayers by cross-linking CD3 which was also time and IL-2-dependent with maximal migration (22.7%) occurring after three days in the presence of exogenous IL-2. Blocking LFA-or ICAM-1 resulted in a significant reduction in migration across IL-1 beta-activated endothelial cells to 17.4% and 20.9% of control values respectively although blocking the VLA-4/VCAM-1 interaction had no significant effect. Activation of PLN lymphocytes with concanavalin A for up to 5 days did not induce migration but when left in contact with the endothelial monolayer for 24 h migration reached 31.0%. These studies indicate that T-cells require a combination of signals to trigger the migratory phenotype which is necessary to enable them to penetrate the blood-brain barrier.

Animals↗
PubMed1997

The role of Engrailed in establishing the dorsoventral axis of the chick limb.

Expression and mutation analyses in mice suggest that the homeobox-containing gene Engrailed (En) plays a role in dorsoventral patterning of the limb. During the initial stages of limb bud outgrowth, En-1 mRNA and protein are uniformly distributed throughout the ventral limb bud ectoderm. Limbs of En-1(-/-) mice display a double dorsal phenotype suggesting that normal expression of En-1 in the ventral ectoderm is required to establish and/or maintain ventral limb characteristics. Loss of En-1 function also results in ventral expansion of the apical ectodermal ridge (AER), suggesting that En-1 is also required for proper formation of the AER. To further investigate the role En plays in dorsoventral patterning and AER formation, we have used the replication competent retroviral vector, RCAS, to mis-express mouse En-1 in the early chick limb bud. We show that ectopic En-1 expression in dorsal ectoderm is sufficient to repress the endogenous expression of the dorsal ectodermal marker Wnt7a, with a resultant decrease in Lmx1 expression in underlying dorsal mesenchyme. Furthermore, the AER is disrupted morphologically and the expression patterns of the AER signalling molecules Fgf-8 and Fgf-4 are altered. Consistent with recent evidence that there is a reciprocal interaction between signalling molecules in the dorsal ectoderm, AER, and zone of polarising activity (ZPA), loss of Wnt7a, Fgf-8 and Fgf-4 expression leads to a decrease in expression of the signalling molecule Shh in the ZPA. These results strongly support the idea that, in its normal domain of expression, En-1 represses Wnt7a-mediated dorsal differentiation by limiting the expression of Wnt7a to the dorsal ectoderm. Furthermore, our results provide additional evidence that En-1 is involved in AER formation and suggest that En-1 may act to define ventral ectodermal identity.

Alpharetrovirus↗
PubMed1996

A pilot study of the introduction of audit into nursing homes.

In 1993, all 37 private nursing homes in Mid-Staffordshire were invited to take part in this study, and 16 agreed. Over 1 year, a nurse audit facilitator visited these homes to teach staff, and stimulate and assist with audit projects. At the beginning and end of the 12-month period, the residents were assessed by administered questionnaires and by the short Geriatric Depression Scale. Thirteen of the 16 homes undertook at least one audit project during the study (ten of these had never previously carried out audit). Ten homes made at least one major procedural change during the study. Of the 570 residents of the 16 homes, 138 answered both questionnaires. The main reasons for non-inclusion were poor mental and physical conditions. Satisfaction levels improved significantly in six out of the 11 aspects of care studied. The mean Geriatric Depression Score in these 138 residents fell from 4.73 at the start, to 4.25 at the end of the study (p = 0.02). The fall in the mean score was significantly greater in the ten homes that had made at least one major change (from 4.40 to 3.81) than in the six homes that had made no major change (from 5.33 to 5.17). The introduction of audit into co-operative private nursing homes is associated with improvements in the standards of care, but it is uncertain whether this is a direct consequence of the audit carried out, or is due to the non-specific effects of an outside assessor visiting the homes. There is a need for methods of assessment that can be applied to higher proportions of nursing home residents.

Activities of Daily Living↗
PubMed1996

Mdm-2 is not induced by p53 in human keratinocytes in vivo.

Normal p53 protein protects the genome after DNA damage by delaying replication and allowing DNA repair. mdm-2 is a recently discovered protein that controls p53 activity by binding to and inactivating p53 protein. A negative feedback loop has been suggested in which p53 induces mdm-2 expression. We have shown that doses of ultraviolet B radiation that cause mild sunburn clinically, produce thymine dimers in keratinocytes detectable by immunocytochemistry. This causes an elevation of p53 protein without a concomitant p53-mediated induction of mdm-2.

DNA Damage↗
PubMed1996

Anxiety and depression in general practitioners: associations with type of parctice, fundholding, gender and other personal characteristics

Background. There is evidence both that a doctor's own well-being is closely associated with efficiency and positive attitude to patients, and that levels of stress, anxiety and depression in doctors are rising. Objective. This postal survey aimed to measure anxiety and depression levels in general practitioners in 1994 and identify any associations with personal and practice characteristics. Method. All general practitioners with patients in Staffordshire were invited to complete the Hospital Anxiety and Depression (HAD) scale. Results. Six hundred and twenty of 896 general practitioners replied (response rate 69%). No gender differences were found in rates of anxiety and depression; overall, 19% of respondents were 'cases' of depression and 16% others had borderline depression scores. Anxiety 'caseness' was associated with living alone, amount of on-call duties undertaken, and being fourth/fifth wave fundholders. Depression 'caseness' was associated with having little free time from practice work, amount of on-call, being single handed, and working in a non-training practice. Conclusions. The authors concluded that the level of mental ill-health in general practitioners is a matter of concern and is associated with workload. Keywords. Anxiety, depression, general practitioners, personal characteristics, practice characteristics.

Journal Article↗
PubMed1996

Anxiety and depression in general practitioners: associations with type of practice, fundholding, gender and other personal characteristics.

BACKGROUND: There is evidence both that a doctor's own well-being is closely associated with efficiency and positive attitude to patients, and that levels of stress, anxiety and depression in doctors are rising. OBJECTIVES: This postal survey aimed to measure anxiety and depression levels in general practitioners in 1994 and identify any associations with personal and practice characteristics. METHODS: All general practitioners with patients in Staffordshire were invited to complete the Hospital Anxiety and Depression (HAD) scale. RESULTS: Six hundred and twenty of 896 general practitioners replied (response rate 69%). No gender differences were found in rates of anxiety and depression; overall, 19% of respondents were 'cases' of anxiety and 22% others had borderline anxiety scores; 10% were 'cases' of depression and 16% others had borderline depression scores. Anxiety 'caseness' was associated with living alone, amount of on-call duties undertaken, and being fourth/fifth wave fundholders. Depression 'caseness' was associated with having little free time from practice work, amount of on-call, being single handed, and working in a non-training practice. CONCLUSIONS: The authors concluded that the level of mental ill-health in general practitioners is a matter of concern and is associated with workload.

Adult↗
PubMed1996

Gender differences in general practitioners at work.

BACKGROUND: The proportion of female general practitioners is steadily increasing. AIM: To compare male and female general practitioners with respect to their job satisfaction and professional commitments within and outside their practices. METHOD: A questionnaire was sent to all 896 general practitioner principals with patients in Staffordshire in 1994. The main elements were: job satisfaction (on a five-point scale) from eight possible sources; whether personal responsibility was taken for 12 different practice tasks; and professional commitments outside the practice. RESULTS: A total of 620 (69%) general practitioners responded. Female doctors derived more satisfaction than male doctors from relationships with patients (P = 0.002). Female doctors were more likely to be working in training practices, and were likely to be on-call less and to work fewer sessions. Male general practitioners were more likely to take lead responsibility for practice computers, minor surgery, meeting external visitors and finance, whereas female practitioners were more likely to be responsible for looking after women patients' health. CONCLUSION: Considerable differences were found between male and female general practitioners. These differences are likely to have an increasing impact as the percentage of female general practitioners continues to rise.

Attitude of Health Personnel↗
PubMed1996

Stresses, coping mechanisms and job satisfaction in general practitioner registrars.

BACKGROUND: There is concern about the morale of general practitioner registrars. There may be stress-provoking factors that could be avoided or minimized. AIMS: The aims of the study were to assess the sources of stress and job satisfaction of general practitioner registrars, to compare registrars' job satisfaction with that of established principals using a recently published survey and to identify registrars' usual responses to stress. METHOD: A postal questionnaire survey was sent to all 143 general practitioner registrars in the West Midlands Region. The main measures were: self-rating scales of stresses associated with work and training; the Warr, Cook and Wall job satisfaction scale; and self-reported responses to stress. RESULTS: A total of 118 (83%) general practitioner registrars responded. The most potent sources of stress were family-job conflict, working for the Membership of the Royal College of General Practitioners, patients' unrealistic expectations and disruption of social life. Registrars practised good coping responses to stress. Registrars in this study had significantly greater job satisfaction than general practitioner principals in a 1993 survey for three out of 10 items measured (responsibility given, hours of work and the job as a whole) and significantly worse scores for three items (recognition for good work, rate of pay and variety of work). CONCLUSIONS: Registrars have additional stresses to those of established principals because they need to study for examinations, learn new tasks in general practice and carry out their service commitments at a stage in life when many are newly married or have a young family. Training in stress management for general practitioner registrars is recommended.

Adaptation, Psychological↗
PubMed1995

Two newly established cell lines derived from the same colonic adenocarcinoma exhibit differences in EGF-receptor ligand and adhesion molecule expression.

Two morphologically distinct cell lines, GP2d and GP5d, derived from the same adenocarcinoma of the colon, have been established and characterised. Both clones have the same genetic changes, consistent with the usual pattern of tumour progression in colon cancer. The cells also have an inverted duplication of bands 10q11 to 10q21, but Southern blot analysis failed to identify any translocations involving the ret protooncogene, which maps to this region. GP2d grew by spreading from the edges of microcolonies to form a confluent layer of cells. GP5d grew in discrete islands of cells forming multi-layered colonies. These differing patterns of growth correlated with variation in expression or cellular distribution of alpha 2-integrin, desmoplakin and e-cadherin. Only GP2d responded to exogenously added epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) or insulin with an increase in cell numbers, even though both cell lines possessed similar numbers of EGF receptors. Analysis of EGF receptor ligand expression showed that GP5d cells expressed relatively more TGF alpha mRNA than did GP2d; in contrast, amphiregulin mRNA, which was abundant in GP2d, was virtually undetectable in GP5d. Even though GP5d failed to exhibit a growth response to EGF, it underwent a marked epithelial-mesenchymal transition when treated with EGF, indicating separation of growth and morphological responses to EGF.

Adenocarcinoma↗
PubMed1995

Endemic pemphigus foliaceus (fogo selvagem) in native Americans from Brazil.

BACKGROUND: Fogo selvagem (FS) is an autoimmune disease that is endemic in certain regions of Brazil and appears to be precipitated by an environmental factor. OBJECTIVE: Our purpose was to confirm the occurrence and prevalence of FS in a population of Xavante Indians living in an endemic region of central Brazil. METHODS: Clinical, anthropologic, and immunologic studies were carried out in patients and in normal inhabitants of the Pimentel Barbosa Indian Reservation, Mato Grosso, Brazil. RESULTS: FS was identified and confirmed in 10 patients from a patient pool of 295 with various skin diseases. The Xavante settlement has a total population of 746. Anti-desmoglein 1 autoantibodies were detected in all patients with FS and were absent from more than 300 serum samples collected from randomly selected unaffected persons. CONCLUSION: FS is strongly linked to outdoor activities and is largely restricted to immunogenetically predisposed persons. FS appears to have been endemic in certain regions of South America for several centuries.

Adolescent↗