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Biomedical subjects

S Ford

Publications and source records attributed to S Ford.

At least 37 records · Page 2Linked to original sources

An integrated physical and genetic map spanning chromosome band 10q24.

Chromosome band 10q24 is rich in genes involved in development, tumorigenesis, neurological disorders, hormone metabolism, and environmentally induced disease susceptibility. We have constructed an STS-based integrated physical and genetic map of 10q24 derived from the CEPH-Généthon mega-YAC contig data for this region. This map consists of 42 fluorescence in situ hybridization-mapped overlapping CEPH mega-YACs spanning approximately 15 Mb to which 49 STS markers have been assigned, including 24 Généthon CA repeat genetic markers, 10 known gene loci from the 10q24 region (IFI56, IDE, PDE6C, RBP4, CYP2C, CD39, DNTT, GOT1, WNT8B, and PAX2) and 11 additional expressed sequences of unknown function.

Chromosome Banding↗

The cytokine interleukin-5 (IL-5) effects cotransport of its receptor subunits to the nucleus in vitro.

Interleukin (IL)-5 is central in regulating eosinophilia in allergic disease and parasitic infections. We have recently shown that human (h) IL-5 both possesses a functional nuclear localization signal capable of targeting a heterologous protein to the nucleus and localises to the nucleus of intact receptor-expressing cells. In this study, the extracellular domains of the hIL-5 alpha- and beta-receptor subunits were expressed in baculovirus, fluorescently labelled and assayed for nuclear targeting in vitro in the absence and presence of IL-5. The beta-subunit, which lacks IL-5 binding activity, only accumulated in the nucleus in the presence of both the hIL-5 binding alpha-subunit and hIL-5. The IL-5-binding alpha-subunit showed similar results. IL-5 thus effected nuclear transport of its alpha- and beta-receptor subunits apparently through a 'piggy back' mechanism, raising the possibility that IL-5's nuclear signalling role may be to cotarget its receptor subunits to the nucleus. This is the first demonstration of nuclear protein piggy back transport in vitro.

Animals↗

Accreditation of prior experimental learning.

Accreditation of prior experimental learning (AP(E)L) has gained momentum as a way of achieving academic credit. This article outlines the steps to be taken when making an AP(E)L claim.

Certification↗

A functional bipartite nuclear localisation signal in the cytokine interleukin-5.

Interleukin (IL)-5 is central in regulating eosinophilia in allergic disease and parasitic infections. We have identified a bipartite nuclear localisation signal (NLS) within amino acids 95-111 of human IL-5 (hIL-5), also present in mouse IL-5 (mIL-5). hIL-5 and mIL-5 were labelled fluorescently, and nuclear uptake subsequent to membrane binding and internalisation by intact receptor expressing cells visualised and quantified using confocal laser scanning microscopy. hIL-5 and mIL-5 were shown to be transported to the nucleus in in vivo and in vitro nuclear protein import assays. The hIL-5 NLS was able to target a heterologous protein to the nucleus both in vivo and in vitro. Mutations within the proximal arm of the NLS abrogated nuclear targeting activity, confirming its bipartite nature. The results imply a nuclear signalling role for IL-5 additional to pathways linked to the membrane receptor system.

Amino Acid Sequence↗

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Health Care Reform↗

Doctor-patient interactions in oncology.

Studies which apply content analysis techniques to the cancer consultation are few. This descriptive study examines the structure and content of the bad news cancer consultations of 117 outpatients newly referred to the Medical Oncology Department of a large London teaching hospital. From previous communication research three main hypotheses are formed: (i) the cancer consultation is clinician-dominated rather than patient-centred; (ii) the level of psychosocial discussion between clinicians and patients is low and (iii) patient characteristics such as sex, age and prognostic category influence clinician behaviours. Each patient had two consultations with one of 5 oncologists. Both these were audiotaped with the patients' consent. The tapes were content coded using the Roter Interaction Analysis System. Results showed that clinicians tended to use closed rather than open questions. Patients asked few questions and were seldom given space to initiate discussion. Thus, the level of patient-centredness was low. Despite the fact that consultations concerned life threatening disease and often contained information regarding toxic treatment which is known to provoke psychological dysfunction, the number of questions relating to patients' psychological health were few. The amount of discussion concerning medical topics from both parties was 2.5 times greater than the amount of psychosocial discussion. Although there was a suggestion in the data that 3 clinicians showed variations in behaviour according to patient age and prognostic group, the number of patients for each doctor was small. Patients were well informed about their diagnosis, prognosis and treatment options, but their emotional well-being was rarely probed.

Adult↗

Myocardial ischaemia associated with Ehlers-Danlos syndrome.

A 38-yr-old man with an unusual type of Ehlers-Danlos syndrome presented for elective abdominal aortic aneurysm repair. During surgery he developed acute myocardial ischaemia, resulting in abandonment of the procedure. He was shown subsequently to have severe triple vessel coronary artery disease. Silent ischaemia associated with severe coronary artery disease, although rare, may be associated with the syndrome and is difficult to recognize as other cardiac abnormalities are frequently present.

Acute Disease↗

Unilateral nasal allergen challenge leads to bilateral release of prostaglandin D2.

BACKGROUND: Multiple mediators including prostaglandin D2 and leukotriene B4 have been shown to increase in nasal secretions during the early response to nasal challenge with antigen. OBJECTIVE: Our objective was to investigate the time course of prostanoid and leukotriene B4 release into nasal secretions on both the ipsilateral and contralateral side after a unilateral nasal allergen challenge. METHODS: We performed a controlled, randomized trial. Six volunteers were challenged unilaterally with antigen or diluent in a randomized order and discs were used to collect nasal secretions from both nostrils at 2 min intervals for 20 min after the challenge. Prostanoids and leukotriene B4 (LTB4) in recovered nasal secretions were measured by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS). RESULTS: Nasal allergen challenge resulted in a significant and immediate increase in symptoms and sneezing. PGD2 was significantly elevated above diluent values (0.6 +/- 0.6 pg) 30 s after removal of the allergen disc (P < 0.05), reached its peak (423.2 +/- 182.4 pg) at 2 min and then slowly decreased. PGD2 also increased on the contralateral side after unilateral allergen challenge, reaching peak values about six times lower than on the ipsilateral side (70.8 +/- 21.7 pg at 6 min). Levels of 9a, 11b-PGF2 after antigen provocation became significantly higher than after diluent (0 +/- 0 pg) on the ipsilateral side at 2 min (17.2 +/- 5.9 pg), and reached peak levels at 4 min (25.1 +/- 8.0 pg). LTB4 also increased significantly on the side of challenge. For the other prostanoids measured (PGF2, PGF2 alpha, TxB2, 6kPGF1 alpha), no significant changes in either ipsilateral or contralateral secretions were observed after allergen challenge. CONCLUSIONS: Our study described the kinetics of PGD2 and LTB4 release as well as the contralateral release of PGD2.

Adult↗

Voluntary anonymous linked study of the prevalence of HIV infection and hepatitis C among inmates in a Canadian federal penitentiary for women.

OBJECTIVE: To determine the seroprevalence of HIV infection and hepatitis C among inmates of a federal penitentiary for women. DESIGN: Voluntary, anonymous, linked, point-prevalence study involving testing of blood samples for antibodies to HIV and hepatitis C virus. PARTICIPANTS: All inmates of the multilevel security federal Prison for Women, Kingston, Ont., who volunteered to participate in the study. Inmates at this long-stay facility are from across Canada. OUTCOME MEASURE: Seroprevalence rate among participants of antibodies to HIV and hepatitis C virus. RESULTS: Of the 130 inmates available for study 113 (86.9%) agreed to donate a blood sample. One woman (0.9%) was HIV positive; 45 (39.8%) were positive for hepatitis C antibody. CONCLUSIONS: It is possible to obtain a high participation rate in a voluntary, anonymous, linked point-prevalence study in a long-stay penitentiary. The HIV seroprevalence rate of 0.9% is lower than that found in studies in provincial (short-stay) prisons. However, the high rate of antibodies to hepatitis C suggests a significant level of risk behaviour, most likely injection drug use, and suggests the potential for a rapid increase in the rate of HIV infection should the number of newly admitted HIV-positive inmates who use injection drugs rise.

Adolescent↗

A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24.

The CYP2C gene cluster on chromosome 10q24 encodes the P450IIC enzymes, members of the cytochrome P450 monooxygenase superfamily. The P450-IIC enzymes are required for the metabolism of a number of foreign compounds, including the drugs mephenytoin and tolbutamide, and are also thought to be involved in the metabolism of endogenous steroid hormones. Several different CYP2C cDNA clones have been isolated; however, the exact number of genes and the genomic arrangement of the CYP2C cluster have remained unknown. Using a combination of STS and restriction mapping to characterize YAC clones, we have constructed a 2.4-Mb physical map that incorporates the CYP2C gene cluster. The cluster spans approximately 500 kb on proximal 10q24 and comprises four genes arranged in the order CYP2C8-CYP2C9-CYP2C19-CYP2C18. The map also includes an adjacent gene, the serum retinol binding protein gene (RBP4). The incorporation of Généthon CA repeat genetic markers suggests the orientation of the loci to be Cen-RBP4-CYP2C18-CYP2C19-CYP2C9-CYP2C8-Tel .

Aryl Hydrocarbon Hydroxylases↗

Psychological morbidity in newly referred patients with cancer.

Over the last 10 yr, research has shown that although the majority of patients are able to cope with the stresses of cancer, a substantial number have difficulties which require some form of psychological help. This study reports on the levels of psychological distress in a heterogeneous group of 117 newly referred out-patients with cancer over a 6-month period. Each patient reported their levels of distress by completing two self-administered questionnaires (the GHQ-30 and HADS) on three separate occasions. A descriptive examination of the socio-demographic characteristics of the sample was also carried out. At the first assessment 30% of the sample scored above the threshold for probable psychiatric disorder on the GHQ-30 and 26% on the HADS anxiety scale. At 6 months follow-up levels had fallen to 21% for the GHQ-30 and 10% for HADS anxiety. The numbers of probable cases of HADS depression was 7% at the first assessment and 5% at follow-up. Differences in levels of psychological morbidity according to age, sex, partner status and socioeconomic group were demonstrated. However, we were unable to make any firm conclusions as to whether these effects were independent of each other as a controlled multivariate analysis of the data set was not possible.

Adaptation, Psychological↗