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Biomedical subjects

J Fordham

Publications and source records attributed to J Fordham.

8 recordsLinked to original sources
PubMed2001

Analysis of cellular adhesion by microarray expression profiling.

Microarrays of oligonucleotides or cDNAs can be used to establish the expression profiles of numerous genes in a single experiment. We have established a microarray platform to identify genes in a number of different pathological conditions, particularly those with an inflammation component. This platform utilised the output of an eosinophil sequencing project in which 1069 sequences were identified that were not represented in the public domain. An eosinophil model cell line, AML14.3D10, was used to investigate cell adhesion. The transcription profile of adhered and non-adhered AML 14.3D10 cells was shown to be both technically and biologically reproducible. A number of genes were found differentially expressed in the adhered vs. non-adhered populations. In the adhered population, the expression of these genes was restricted compared to brain, lung, kidney and especially bone marrow. However, the differentially regulated genes were not among those genes most restricted to eosinophils. We discuss the implications of transcription profiling on gene annotation and its potential utility for the identification of targets for drug intervention.

Base Sequence↗
PubMed2001

Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes.

The increase in eosinophils at the site of antigen challenge has been used as evidence to suggest that this cell type plays a role in the pathophysiology of asthma. Aberrant production of several different cytokines, particularly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 influences the development and maturation of eosinophils in a number of different ways. Of note is the ability of IL-5 to act as a survival factor for eosinophils specifically inhibiting apoptosis. The precise mechanism by which IL-5 exerts its effect remains obscure. We used microarray technologies to investigate the changes in the messenger RNA expression profile of eosinophils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total of 80 genes were observed to be regulated by 2-fold or greater. Many of the genes previously identified as regulated by IL-5 were regulated in our microarray experiments. Of the 73 genes found to be upregulated, many were shown to play a role in adhesion, migration, activation, or survival of eosinophils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survivability of eosinophils, we used an alternative cellular model, TF1.8 cells, whose survival was also dependent on IL-5. Comparison of these models identified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regulation was similarly coordinated in both systems. Identification of Pim-1 and SLP-76 as regulated by IL-5 led us to suggest a direct role for these proteins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restricted to the eosinophil compared with their expression in brain, bone marrow, kidney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiquitous in their expression by microarray.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Bone densitometry at a district general hospital: evaluation of service by doctors and patients.

OBJECTIVE: To assess doctors' and patients' views about a district general hospital bone densitometry service and to examine existing practice to influence future provision. DESIGN: Three postal surveys: (a) of doctors potentially using the service, (b) of patients undergoing a bone densitometry test during a six month period, and (c) of the referring doctors of the patients undergoing the test. SETTING: Bone densitometry service at South Cleveland Hospital, Middlesbrough and two district health authorities: South Tees and Northallerton. SUBJECTS: All general practitioners (n=201) and hospital consultants in general medicine, rheumatology, obstetrics and gynaecology, orthopaedics, radio therapy and oncology, haematology, and radiology (n=61); all patients undergoing an initial bone densitometry test (n=309) during a six month period; and their referring doctors. MAIN MEASURES: Service awareness and use, knowledge of clinical indications, test results, influence of test results on patient management, satisfaction with the service and its future provision. RESULTS: The overall response rates for the three surveys were 87%, 70%, and 61%. There was a high awareness of the service among doctors and patients; 219(84%) doctors were aware and 155 of them (71%) had used it, and patients often (40%) suggested the test to their doctor. The test was used for a range of reasons including screening although the general use was consistent with current guidelines. Two hundred (65%) bone densitometry measurements were normal, 71(23%) were low normal, and 38(12%) were low. Although doctors reported that management of patients had been influenced by the test results, the algorithm for decision making was unclear. Patients and doctors were satisfied with the service and most (n=146, 68%) doctors wanted referral guidelines for the service. CONCLUSIONS: There was a high awareness of, use of, and satisfaction with the service. Patients were being referred for a range of reasons and a few of these could not be justified, many tests were normal, and clinical decision making was not always influenced by the test result. It is concluded that bone densitometry services should be provided but only for patients whose management will be influenced by test results and subject to guidelines to ensure appropriate use of the technology.

Absorptiometry, Photon↗
PubMed1990

Assessment of broadband ultrasound attenuation in the os calcis in vitro.

1. We have examined the relationship between the attenuation of broadband ultrasound in the os calcis in vitro and its bone mineral density measured by quantitative computed tomography and by physical density. 2. Broadband ultrasound attenuation was found to correlate closely with physical density (r = 0.85, P less than 0.0001), but the correlation was less than that observed between quantitative computed tomography and physical density (r = 0.92, P less than 0.0001). Measurements of broadband ultrasound attenuation and quantitative computed tomography were significantly correlated (r = 0.80, P less than 0.0001). 3. Partial correlation analysis showed a significant relationship between broadband ultrasound attenuation and bone density, but when the effect of physical density was taken into account no significant correlation was found between broadband ultrasound attenuation and quantitative computed tomography (r = 0.08, not significant). 4. Broadband ultrasound attenuation in three prospective amputees showed a high degree of concordance between measurements in vivo and in vitro, with no interference by surrounding soft tissues. 5. The correlation between physical density and broadband ultrasound attenuation was independent of quantitative computed tomography, suggesting that the technique measures aspects of density which differ from its mineral density. Broadband ultrasound attenuation holds promise as a reproducible, rapid, radiation-free assessment of skeletal status.

Aged↗
PubMed1989

In vitro comparison of quantitative computed tomography and broadband ultrasonic attenuation of trabecular bone.

In vitro measurements of os calces and trabecular bone samples have been carried out using broadband ultrasonic attenuation (BUA) and quantitative computed tomography (QCT). The correlation between the measurements was 0.92 and 0.86 for the heelbones and the trabecular samples respectively, and the QCT and BUA correlated equally well with the physical density of the samples, indicating that the new ultrasonic technique is potentially useful for the evaluation of trabecular bone for the diagnosis of osteoporosis.

Adult↗
PubMed1986

Management skills.

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Administrative Personnel↗