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Biomedical subjects

D L Gordon

Publications and source records attributed to D L Gordon.

At least 19 recordsLinked to original sources
PubMed2003

Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-gamma and dexamethasone, whilst the pro-inflammatory cytokine TNF-alpha had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.

Arthritis, Rheumatoid↗
PubMed2003

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis.

Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans. Thirty-five patients with pulmonary nocardiosis were identified in two tertiary referral hospitals. A retrospective review of the patient characteristics, clinical and laboratory features including antimicrobial susceptibility at diagnosis was carried out. Radiological features derived from chest radiographs and CT scans were also documented. In our population, the predominant risk factors were immuno-compromised state, corticosteroid therapy, and underlying pulmonary pathology. The presenting features were similar to those previously described but disseminated infection was not common. The radiological changes were diverse and non-specific. Nocardia asteroides was the commonest species. Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and cotrimoxazole. Co-existing microbial agents are common and reflect the underlying complex disorders.

Adult↗
PubMed2001

Multiple ligand binding sites on domain seven of human complement factor H.

Foreign particles and damaged host cells can activate the complement system leading to their destruction by the host defense system. Factor H (fH) plays a vital role in restricting complement activation on host cells through interactions with polyanions such as heparin, while allowing activation to proceed on foreign surfaces. Complement activation by damaged host cells is also down regulated by fH, which is localized to injured areas through interactions with C-reactive protein (CRP). A number of pathogens have developed mechanisms by which they can also bind fH and thus exploit its protective properties. One such organism is Group A Streptococcus (GAS) which mediates fH binding via its surface expressed M-protein. fH consists of 20 conserved short consensus repeat (SCR) units and mutagenesis studies indicate that the seventh repeat is responsible for interactions with heparin, CRP and M-protein. We recently performed molecular modelling of fH SCR 7 and identified a cluster of positively charged residues on one face of the domain. By alanine replacement mutagenesis, we demonstrated that these residues are involved in heparin, CRP and M protein binding, which indicates that there is a common site within fH SCR 7 responsible for multiple ligand recognition.

Amino Acid Sequence↗
PubMed2001

Complement C3b interactions studied with surface plasmon resonance technique.

The surface plasmon resonance (SPR) phenomenon is utilized in a number of new real time biosensors. In this study, we have used this technique to study interactions between the central complement component C3b and its multiple ligands by using the Biacore equipment. The SPR technique is particularly suitable for analysis of the alternative complement pathway (AP) because the inherent nature of the latter is to amplify deposition of C3b on various surfaces. C3b was coupled onto the sensor surface and the coupling efficiency was compared under various conditions on both polystyrene and carboxymethylated dextran surfaces. After enzymatic C3b coupling or standard amine C3b coupling, we analyzed and compared the binding of four C3b ligands to the surface: factor B, factor H, C5 and the soluble complement receptor 1 (sCR1, CD35). Binding of each ligand to C3b was detected when C3b had been coupled either enzymatically or using the amine coupling, but the half-lives of the interactions were found to vary depending on the coupling procedure. Factor H binds to C3b via three interaction sites. The target sites are exposed on the C3b, C3c and C3d fragments of C3, respectively. Therefore, we also tested by using the Biacore whether factor B, C5 and sCR1 bind to C3c and/or C3d. It was found that factor B bound to C3d, but not to C3c. On the other hand, both C5 and sCR1 bound to C3c, but not to C3d. In conclusion, this study shows that SPR is a powerful tool in analyzing and mapping the interactions of C3b with its multiple ligands.

Binding Sites↗
PubMed2001

Amoebic liver abscess in pregnancy.

We describe the case of an amoebic liver abscess (ALA) presenting in the third trimester of pregnancy which raised both diagnostic and treatment dilemmas as well as being associated with preterm labour. Amoebic liver abscess is caused by the protozoan organism Entamoeba histolytica which is endemic in many parts of the developing world. Invasion of the colonic mucosa results in the clinical syndrome of amoebic dysentery and in some cases dissemination to the liver or other organs occurs resulting in abscess formation. Amoebic liver abscess is a rare complication of pregnancy and there are few reports in the world literature, these being mostly from endemic areas. We present here the case of a caucasian female who presented with an amoebic liver abscess in the third trimester of pregnancy, thirteen months after returning to Australia from a short holiday in Bali.

Adult↗
PubMed2001

Teamwork. University of Miami uses competition to sharpen EMS team performance.

Many argue that experience is the best teacher. However, it's often dangerous for the patient and impractical for an EMS system to assess prehospital providers in their actual working environment. Simulated scenario competition fosters clearer thinking and translates into more effective action and enhanced patient outcomes during true emergencies.

Clinical Competence↗
PubMed2000

Fine-needle aspiration of the thyroid: rate and causes of cytohistopathologic discordance.

Fine-needle aspiration (FNA) of the thyroid gland is a widely utilized, sensitive, specific, and cost-effective method for the evaluation of thyroid nodules. The purpose of this study was to evaluate the accuracy of thyroid FNA and causes of cytohistological discordance in our institution. Six hundred twenty-five thyroid FNAs obtained from 503 females (mean age, 54) and 122 males (mean age, 51) in whom histopathologic follow-up material was available for review, were analyzed. FNAs were classified as: nondiagnostic, negative, intermediate, and positive for malignancy, and the histopathologic material was categorized as benign or malignant. The review revealed 93% sensitivity and 96% specificity for the FNA diagnoses. The FNA results were diagnostic in 87%, indeterminate in 6%, and nondiagnostic in 7% of the cases. Cytohistologic correlation was achieved in 88% of the cases. The false-negative rate was 4% and the false-positive rate was 8%. The most common pitfalls for false-negative diagnoses consisted of suboptimal material and underdiagnosis of papillary carcinoma due to cystic degeneration. The most common pitfall for false-positive cases was overdiagnosis of follicular neoplasms. Our study confirmed that FNA of thyroid nodules can be performed with high sensitivity and specificity by experienced clinicians or pathologists. The application of strict specimen adequacy rules for FNA interpretation is likely to decrease the rate of false-negative and false-positive diagnoses.

Adult↗
PubMed2000

Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study.

Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system. The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20. Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al., Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues. The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.

Amino Acid Sequence↗
PubMed1999

Simulation technology for health care professional skills training and assessment.

Changes in medical practice that limit instruction time and patient availability, the expanding options for diagnosis and management, and advances in technology are contributing to greater use of simulation technology in medical education. Four areas of high-technology simulations currently being used are laparoscopic techniques, which provide surgeons with an opportunity to enhance their motor skills without risk to patients; a cardiovascular disease simulator, which can be used to simulate cardiac conditions; multimedia computer systems, which includes patient-centered, case-based programs that constitute a generalist curriculum in cardiology; and anesthesia simulators, which have controlled responses that vary according to numerous possible scenarios. Some benefits of simulation technology include improvements in certain surgical technical skills, in cardiovascular examination skills, and in acquisition and retention of knowledge compared with traditional lectures. These systems help to address the problem of poor skills training and proficiency and may provide a method for physicians to become self-directed lifelong learners.

Anesthesiology↗
PubMed1999

Epoxy resin allergy from microscopy immersion oil.

A bacteriology technical officer presented with episodes of burning pruritus and urticarial-like lesions on the face and forearms. Patch testing was strongly positive for epoxy resin. The exposure was occupational to the re-formulation of microscopy immersion oil.

Adult↗
PubMed1999

Changes in thyroid nodule volume caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size.

The effectiveness of TSH suppression therapy for thyroid nodules remains controversial. Prior studies have assumed that the fine-needle aspiration biopsy (FNAB), used to confirm a benign condition before the establishment of control and treatment groups, has no effect on nodule volume. Seventeen untreated euthyroid patients with clinical solitary thyroid nodules that were solid (on high-resolution ultrasound) and a colloid goiter (on cytologic examination) had ultrasound measurements of nodule volume before a FNAB, immediately thereafter, and 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. No significant difference in mean thyroid nodule volume was present at any point after the FNAB; however, the changes in nodule volume were quite marked and bidirectional among patients masking the cumulative effect. The variability of the change in individual nodule volume was statistically significant when comparisons were made across time (P = 0.0032). FNAB of thyroid nodules results in significant individual changes in volume after the procedure. Studies, such as the effect of TSH suppression on thyroid nodule volume, that incorporate the FNAB in both control and treatment arms of the experimental design, need to take these changes into account, less erroneous conclusions result.

Biopsy, Needle↗
PubMed1999

Diabetes and obesity in the Louisiana Coushatta Indians.

OBJECTIVE: In order to assist their community in planning intervention and prevention programs, prevalence rates for diabetes and obesity were examined among the Louisiana Coushatta. RESEARCH DESIGN AND METHODS: Coushatta individuals participated in a health survey (questionnaires and physical examinations). Those without known diabetes underwent oral glucose tolerance testing and were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). Those with known DM had the diagnosis confirmed by history and/or elevated hemoglobin A1c. Waist-to-hip ratio (WHR), body mass index (BMI), and percent body fat (%BF) were determined as measures of central adiposity and obesity. Prevalence rates of diabetes and obesity among those examined were calculated. The prevalence of those with more than one anthropometric index positive for obesity was also determined. RESULTS: The prevalence of DM was 30% and IGT was 17% among the first 151 Coushatta participants. For males, the prevalence of obesity was 62%, 57%, and 52%, and for females, 59%, 54%, 45%, as determined by the BMI, %BF, and WHR, respectively. Obesity was more prevalent among those with glucose intolerance (IGT + DM) than those with NGT, and those who were obese had the highest prevalence of glucose intolerance. A greater percentage of those with glucose intolerance had more than one positive obesity measure as compared to those with NGT, and those with more than one index consistent with obesity had a greater prevalence of IGT + DM. CONCLUSIONS: Prevalence rates of DM and obesity are high among the Louisiana Coushatta, and obesity is associated with glucose intolerance. Clustering of the three obesity measures occurs in a high percentage of individuals. Data from the current survey are providing information that is being used by the Coushatta community for health planning and development of intervention and prevention programs.

Adolescent↗