D L Gordon

Publications (38)137.38 Total impact

• Source

  Available from: oxfordjournals.org

  Article: A febrile illness with generalized papular rash involving the palms and soles.

  M A Boyd, P Menon, S Graves, D L Gordon
  Clinical Infectious Diseases 04/2007; 44(5):704, 755-6. · 9.15 Impact Factor
• Article: Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis.

  C H Hui, V W K Au, K Rowland, J P Slavotinek, D L Gordon
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  ABSTRACT: 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.
  Respiratory Medicine 07/2003; 97(6):709-17. · 2.47 Impact Factor
• Article: Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.

  M A Friese, T Manuelian, S Junnikkala, J Hellwage, S Meri, H H Peter, D L Gordon, H Eibel, P F Zipfel
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  ABSTRACT: 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.
  Clinical & Experimental Immunology 07/2003; 132(3):485-95. · 3.36 Impact Factor
• Article: Multiple ligand binding sites on domain seven of human complement factor H.

  E Giannakis, D A Male, R J Ormsby, C Mold, T S Jokiranta, S Ranganathan, D L Gordon
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  ABSTRACT: 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.
  International Immunopharmacology 04/2001; 1(3):433-43. · 2.38 Impact Factor
• Article: Complement C3b interactions studied with surface plasmon resonance technique.

  T S Jokiranta, J Westin, U R Nilsson, B Nilsson, J Hellwage, S Löfås, D L Gordon, K N Ekdahl, S Meri
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  ABSTRACT: 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.
  International Immunopharmacology 04/2001; 1(3):495-506. · 2.38 Impact Factor
• Article: Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study.

  S Ranganathan, D A Male, R J Ormsby, E Giannakis, D L Gordon
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  ABSTRACT: 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.
  Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 02/2000;
• Article: Epoxy resin allergy from microscopy immersion oil.

  Y C Lee, D L Gordon, L A Gordon
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  ABSTRACT: 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.
  Australasian Journal of Dermatology 12/1999; 40(4):228-9. · 1.00 Impact Factor
• Article: Concurrent infection due to Shewanella putrefaciens and Mycobacterium marinum acquired at the beach.

  K Papanaoum, G Marshmann, L A Gordon, R Lumb, D L Gordon
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  ABSTRACT: Infection with marine bacteria is uncommon. A patient with systemic lupus erythematosus who developed concurrent infection with Shewanella putrefaciens and Mycobacterium marinum (M. marinum) is described. After bathing leg ulcers in sea water, severe cellulitis of the left leg with necrotic areas and extensive bullae developed. Infection due to S. putrefaciens was confirmed and a long course of hospitalization, oral ciprofloxacin and skin grafting was required. During hospitalization subcutaneous nodules developed on the other leg. Biopsy revealed acid-fast bacilli and culture grew M. marinum. These lesions responded to rifampicin and cotrimoxazole. Patients with leg ulcers, peripheral vascular disease, diabetes, or receiving immunosuppressive drugs may acquire unusual infections after salt water exposure.
  Australasian Journal of Dermatology 06/1998; 39(2):92-5. · 1.00 Impact Factor
• Source

  Available from: Vincent A Fischetti

  Article: M protein of the group A Streptococcus binds to the seventh short consensus repeat of human complement factor H.

  T K Blackmore, V A Fischetti, T A Sadlon, H M Ward, D L Gordon
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  ABSTRACT: Streptococcus pyogenes evades complement by binding the complement-regulatory protein factor H (fH) via the central conserved C-repeat region of M protein. However, the corresponding binding region within fH has not previously been precisely localized. fH is composed of 20 conserved modules called short consensus repeats (SCRs), each of which contains approximately 60 amino acids. A series of fH truncated and deletion mutants were prepared, and their interaction with M6 protein was examined. The M protein binding site was initially localized to SCRs 6 to 15 as demonstrated by ligand dot blotting, chemical cross-linking, and enzyme-linked immunosorbent assay. SCR 7 was then shown to contain the M protein binding site, as a construct consisting of the first seven SCRs bound M protein but a construct containing the first six SCRs did not bind. In addition, deletion of SCR 7 from full-length fH abolished binding to M protein. SCR 7 is known to contain a heparin binding domain, and binding of fH to M6 protein was almost totally inhibited in the presence of 400 U of heparin per ml. These results localize the M6 protein binding site of fH to SCR 7 and indicate that it is in close proximity to the heparin binding site.
  Infection and Immunity 04/1998; 66(4):1427-31. · 4.16 Impact Factor
• Article: Identification of the second heparin-binding domain in human complement factor H.

  T K Blackmore, J Hellwage, T A Sadlon, N Higgs, P F Zipfel, H M Ward, D L Gordon
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  ABSTRACT: Complement factor H (fH) regulates activation of the alternative pathway of C, reducing the amount of C3b deposited on sialic acid-rich surfaces. Heparin binding has been used as a model for examining the sialic acid-binding characteristics of fH. We have previously shown that of the 20 short consensus repeat (SCR) modules of fH, SCR 7 contains an important heparin binding site, but other SCRs also play a role in heparin binding. To localize the other sites, we prepared recombinant truncated and SCR deletion mutants of fH and tested them by heparin-agarose affinity chromatography. The 5 C-terminal SCRs were found to contain a heparin binding site as an SCR 7 deletion mutant of the N terminal 15 SCRs did not bind heparin, but a construct consisting of SCRs 16-20 was shown to bind heparin. Double deletion of SCRs 7 and 20 from fH abrogated binding to heparin, indicating that SCR 20 contains a heparin binding site. This finding was confirmed with the observation that attachment of SCR 20 to a group of nonbinding SCRs produced a heparin-binding protein. A protein consisting of SCRs 19 and 20 did not bind heparin, whereas SCRs 18-20 did, indicating that, although SCR 20 contains a heparin binding site, at least two nonspecific adjacent SCRs are required. fH-related protein-3 (FHR-3) possesses an SCR homologous to SCR 7 of fH and bound heparin, whereas FHR-4, which lacks such an SCR, did not. Thus, fH contains two separate heparin binding sites, which are located in SCRs 7 and 20.
  The Journal of Immunology 04/1998; 160(7):3342-8. · 5.79 Impact Factor
• Source

  Available from: Steve Wesselingh

  Article: Phaeoacremonium parasiticum infective endocarditis following liver transplantation.

  C H Heath, J L Lendrum, B L Wetherall, S L Wesselingh, D L Gordon
  Clinical Infectious Diseases 12/1997; 25(5):1251-2. · 9.15 Impact Factor
• Article: Identification of a heparin binding domain in the seventh short consensus repeat of complement factor H.

  T K Blackmore, T A Sadlon, H M Ward, D M Lublin, D L Gordon
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  ABSTRACT: Surface polyanions such as sialic acid and heparin are thought to enhance the binding of complement factor H (fH) to C3b deposited on particles and cell surfaces, thereby reducing complement activation. fH contains 20 short consensus repeat (SCR) domains, and it has been proposed that SCR 13 contains a heparin binding site. We used recombinant proteins to determine the heparin binding site on fH. Full-length fH (H20) and truncated and SCR deletion mutant proteins were cloned and expressed in Chinese hamster ovary cells. Supernatants were applied to heparin-agarose affinity columns to determine their binding and elution profiles. Deletion of SCR 13 from H20 did not prevent heparin binding nor alter its salt elution profile, indicating that SCR 13 does not contain an essential heparin binding site. We found that SCR 7 contains a heparin binding site, as SCRs 1 through 7 were the smallest truncated proteins to bind heparin (89 +/- 3%). Furthermore, deletion of SCR 7 from a protein containing SCRs 1 through 9 reduced heparin binding, whereas deletion of SCR 6 did not (17 +/- 13 vs 81 +/- 13%; p = 0.02). It is likely that other heparin binding sites exist within SCRs 10 through 20; an SCR 7 deletion mutant of H20 eluted earlier than H20, but still showed >99% binding to immobilized heparin. SCR 13 does not contain such a site because a double deletion of SCRs 7 and 13 from H20 showed >97% heparin binding and had an elution profile smilar to that of a single deletion of SCR 7.
  The Journal of Immunology 12/1996; 157(12):5422-7. · 5.79 Impact Factor
• Article: Emerging resistance in Enterococcus spp.

  C H Heath, T K Blackmore, D L Gordon
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  ABSTRACT: Enterococcus spp. are becoming increasingly important nosocomial pathogens. They are intrinsically resistant to most antibiotics, and effective therapy depends primarily on the penicillins, vancomycin and the aminoglycosides. Under antibiotic selection pressure they have developed high level resistance to these agents, and the first vancomycin-resistant enterococcal infection in Australia was described recently. The vancomycin-resistance genes are of particular concern because of their potential to transfer to other gram-positive organisms. The prevention and control of resistant enterococci is a major challenge that is best met by a combination of active infection control measures and restriction of broad-spectrum antibiotic use.
  The Medical journal of Australia 02/1996; 164(2):116-20. · 2.81 Impact Factor
• Article: Flucloxacillin hepatitis: an Australian epidemic--comment.

  T K Blackmore, S L Wesselingh, D L Gordon
  Australian and New Zealand journal of medicine 11/1995; 25(5):537.
• Article: Identification of complement regulatory domains in human factor H.

  D L Gordon, R M Kaufman, T K Blackmore, J Kwong, D M Lublin
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  ABSTRACT: Factor H, a regulator of complement activation, contains 20 short consensus repeat (SCR) domains common among the family of C3b/C4b-binding proteins. Chinese hamster ovary cells transfected with cDNA corresponding to the N-terminal tryptic fragment of factor H (containing SCR 1-5 and part of SCR 6) secreted protein with cofactor activity for factor I-dependent cleavage of C3b. A series of deletion mutants, each lacking one of the first five SCR, were constructed, and the supernatants of transfected Chinese hamster ovary cells were tested for cofactor activity. Supernatants of Chinese hamster ovary cells transfected with SCR 1, SCR 4, and SCR 5 deletion mutants retained cofactor function, although the SCR 1 deletion had reduced cofactor activity. Deletion of SCR 2 or 3 totally abolished cofactor activity. Expression and functional analysis of SCR units 1-3, 2-3, and 2-4 demonstrated that the SCR 1-3 unit is sufficient for cofactor activity, but SCR 1-4 is required for full activity. For assays involving cell protection, a construct linking SCR 1-5 to the glycosyl-phosphatidylinositol anchor of decay-accelerating factor was prepared, and stable transfectants were obtained. These cells were protected against complement-mediated cytotoxicity, similarly to decay-accelerating factor- and membrane cofactor protein-transfected cells. These studies define the complement regulatory domains in factor H and suggest that the general complement functional unit for C3 convertase regulation involves three or four consecutive SCR units.
  The Journal of Immunology 08/1995; 155(1):348-56. · 5.79 Impact Factor
• Source

  Available from: espol.edu.ec

  Article: Comparison of antigen detection, polymerase chain reaction and culture for detection of Chlamydia trachomatis in genital infection.

  P G Hallsworth, C Hefford, R G Waddell, D L Gordon
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  ABSTRACT: An in-house polymerase chain reaction (PCR) test using ribosomal RNA gene primers was compared with chlamydia antigen detection (DIF) and culture for the detection of Chlamydia trachomatis. Five hundred and forty-eight fresh (unstored) genital swabs and 174 urines (collected at the same time) from patients attending a sexually-transmitted diseases clinic were examined. PCR, DIF and culture detected chlamydia in 43, 35 and 42 swabs respectively from the 43 resolved positive cases. The specificity on the resolved negative specimens was 100% for each of the tests. From the urines, PCR and DIF detected the organism in 16 and 15 cases respectively of the 23 resolved positive males tested but in only 2 and 3 cases respectively of the 9 resolved positive females tested. Specificities were 100% in all cases. Both of the non-culture tests manifested problems with urine due to inhibitory activity (in PCR test) or excessive debris (in DIF test) in about 5% of the specimens. Culture of the urines yielded sensitivities of 40% in the males and 22% in the females. Overall PCR was more sensitive than either culture or DIF on both urethral and cervical swabs and urines. The urines yielded less than three-quarters the number of positives that was obtained from the swabs and were considered to be an unsatisfactory specimen for chlamydial diagnosis. It is concluded that PCR is a satisfactory alternative to culture on genital swabs and may be preferable in situations where the viability of the organisms is in question. DIF remains useful because of its speed and simplicity but is insufficiently sensitive to be relied upon by itself.
  Pathology 05/1995; 27(2):168-71. · 2.38 Impact Factor
• Article: Clinical utility of the polymerase chain reaction to diagnose Mycoplasma pneumoniae infection.

  T K Blackmore, M Reznikov, D L Gordon
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  ABSTRACT: The diagnosis of Mycoplasma pneumoniae infection currently relies on serological methods which may be slow to produce diagnostic results and may be inconvenient for both the clinician and the patient. This study was designed to assess whether or not the polymerase chain reaction (PCR) is a useful additional diagnostic method. Comparison was therefore made with serology as it is routinely practiced. PCR was used to examine for the presence of M. pneumoniae DNA in throat swab specimens obtained from 99 hospitalized patients investigated for a range of respiratory pathogens including M. pneumoniae. PCR detected M. pneumoniae DNA in 24 adults and 25 children, which is significantly more than the 32 patients found to be antibody positive by the particle agglutination test (p = 0.001). M. pneumoniae DNA was not detected in any of the throat swabs from 32 apparently healthy volunteers. PCR inhibitors were not detected in any of the samples tested. Significantly more children (88%) than adults (38%) were found to be anti-mycoplasma antibody-positive (p < 0.0001). Routine clinical practice was reflected in the fact that 56 patients (57%) had indeterminate serological results because only single sera were obtained. The sensitivity and specificity of PCR were assessed to be 92% and 98% respectively, using a combination of serological and clinical data as the benchmark. PCR appears to have advantages over serological testing, both with respect to accuracy and convenience of single specimen testing. The poor performance of serological tests in adults makes PCR especially useful in this age group.
  Pathology 05/1995; 27(2):177-81. · 2.38 Impact Factor
• Article: Comparison of nasopharyngeal aspirates and throat swab specimens in a polymerase chain reaction-based test for Mycoplasma pneumoniae.

  M Reznikov, T K Blackmore, J J Finlay-Jones, D L Gordon
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  ABSTRACT: Nasopharyngeal aspirates and throat swab specimens were compared in a polymerase chain reaction (PCR)-based test for Mycoplasma pneumoniae. The pathogen was detected in 50% and 45% of throat swab specimens and aspirates, respectively. However, in specimens negative for Mycoplasma pneumoniae by PCR, amplification inhibitors were detected in 0% and 36% of throat specimens and aspirates, respectively. Further investigations confirmed that no throat specimens, but one-quarter of aspirates, are likely to be rejected for containing inadequate respiratory material or excess amplification inhibitors. Because rejection of most of the unsuitable specimens is possible only after PCR, the use of aspirates is less cost-effective. This, and the reluctance to subject patients to aspiration, make the aspirate an inferior specimen for detection of Mycoplasma pneumoniae by PCR.
  European Journal of Clinical Microbiology 02/1995; 14(1):58-61. · 2.86 Impact Factor
• Article: Enhancement of NK cell-mediated antibody-dependent lysis of recombinant gp120-coated CD4 cells by complement.

  S J Parker, T A Sadlon, D L Gordon
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  ABSTRACT: The contribution of complement to NK cell lysis of CD4 cells expressing recombinant gp120 (rgp120) was investigated. Peripheral blood mononuclear cells were used as effector cells in a Cr release assay against purified CD4 target cells that had been coated with rgp120. Assays included human immunodeficiency virus (HIV) antibodies and a complement source alone and in combination to determine their importance in mediating cytotoxicity. NK cells were confirmed to be the effector cells in the lysis of rgp120-coated CD4 targets. Anti-HIV was crucial for lysis and cytotoxicity was enhanced by C3 deposition on targets. However, a prozone effect was observed, with reduced IgG binding, C3 deposition, and NK cell lysis at serum concentrations > 10 micrograms IgG/mL. The susceptibility of these CD4-gp120-antibody-C3 complexes to NK cell lysis may contribute to progressive depletion of CD4 cells in HIV infection.
  The Journal of Infectious Diseases 01/1995; 171(1):186-9. · 6.41 Impact Factor
• Article: Regulation of C3 deposition on gp120 coated CD4 positive cells by decay accelerating factor and factor H.

  T A Sadlon, S J Parker, D L Gordon
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  ABSTRACT: We investigated complement activation by recombinant gp120 (rgp120) treated CD4 cells and the role host complement regulatory proteins play in controlling C3 deposition. Complement activation was determined by detection of C3 on rgp120 coated cells in the presence and absence of HIV seropositive sera using flow cytometry. Treatment of rgp120 coated cells with complement resulted in C3 deposition only if HIV positive sera was included. Examination of C3 fragments on these cells demonstrated rapid cleavage of C3b to iC3b. The role of the regulatory proteins was examined by pretreating cells with mAb to block decay accelerating factor (DAF) or membrane cofactor protein (MCP) or by using factor H depleted sera as a complement source. Inhibition of DAF or use of factor H depleted sera significantly increased C3 deposition on rgp120 coated cells. In contrast, C3 deposition on rgp120 coated cells was not increased after blocking MCP. The sensitivity of rgp120 coated cells to complement lysis was unchanged after inhibition of the regulatory proteins, despite the increase in C3 deposited. These results indicate that in a model of virus infected cells, C3 deposition is regulated by DAF and factor H but MCP appears to have no role.
  Immunology and Cell Biology 01/1995; 72(6):461-70. · 3.66 Impact Factor