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Biomedical subjects

B Currie

Publications and source records attributed to B Currie.

At least 37 records · Page 2Linked to original sources
PubMed1997

Human antibodies to the conserved region of the M protein: opsonization of heterologous strains of group A streptococci.

A 20-mer peptide (p145) in the carboxyl-terminal region of the M protein of group A streptococci (GAS) has previously been defined as the target of bactericidal antibodies. Sequence analysis of seven field isolates from indigenous Australians living in an area highly endemic for GAS and five laboratory reference strains (encompassing nine unique serotypes plus three nontypeables) demonstrates that this region is highly conserved (sequence identity ranging from 65 to 95%) with six of the 12 sequences being identical to p145. Most of the sequence dissimilarity is contained within the last seven amino acids of p145. Competitive ELISA demonstrates that human antibodies specific for p145 cannot discriminate between p145 and synthetic peptides representing four from four of the variant sequences tested. Ig purified from endemic sera was able to opsonize each of the GAS isolates and free p145 as well as a peptide expressing a minimal conformational epitope within p145 (requiring amino acids between positions 2 and 13 of p145), but not an irrelevant peptide, were able to partially or completely inhibit opsonization of all isolates and reference strains. Thus adult endemic sera contain antibodies which are bactericidal for multiple GAS serotypes and which are specific for a sequence of 12 amino acids contained within the p145 region of the M protein.

Amino Acid Sequence↗
PubMed1997

Toxin production by Burkholderia pseudomallei strains and correlation with severity of melioidosis.

An exotoxin lethal to cells in culture (cytolethal toxin, CLT) was identified in culture filtrates of Burkholderia pseudomallei, the causative organism of melioidosis. CLT could pass through a 10-kDa cut-off ultrafilter and its properties suggest that it is a peptide. Isolates from soil, animals and man showed differential cytolethality in vitro. The isolates were divided into low, medium and high CLT producers with soil isolates being low producers and isolates from patients with melioidosis encephalitis being high producers. CLT levels are subject to regulation, as a strain isolated from an infected goat was one of the highest producers whereas the same strain isolated from soil was a low producer. In addition to CLT, all isolates produced a protein with cell-elongating activity which was also present in culture filtrates.

Animals↗
PubMed1997

Melioidotic osteomyelitis in northern Australia.

BACKGROUND: Osteomyelitis is a well-recognized manifestation of melioidosis, a significant disease that is endemic in South-East Asia and northern Australia. Diagnosis requires a high degree of clinical suspicion and is dependent on microbiological confirmation; important clues are travel to or residence in an endemic area. Infection often but not always occurs in well-recognized risk groups, especially diabetics and alcoholics. Subacute presentations often mimic other disease processes and patients may not always be clinically septic. Treatment requires surgical drainage in combination with multiple antibiotic therapy, including at least 2 weeks of intravenous ceftazidime and oral therapy continuing for 3-6 months. Non-compliance usually results in relapse. Due to the potential long latency of the disease and the possibility of reactivation, follow-up should probably be life-long. METHODS: A prospective study of 115 patients presenting with melioidosis between 1989 and 1995 was undertaken. RESULTS: Four patients were found to have osteomyelitis. CONCLUSION: It is important to be aware of this condition so that early treatment can be initiated.

Adolescent↗
PubMed1997

Isolation and identification of Burkholderia pseudomallei from soil using selective culture techniques and the polymerase chain reaction.

An environmental soil survey to detect Burkholderia pseudomallei was performed during the dry and wet seasons in Darwin, Northern Territory, Australia. Soil was sampled at regular intervals during a 15-month period at different depths from areas which were representative of the local, soil environment. Selective culture techniques using Ashdown's and Galimand and Dodin's methods and the polymerase chain reaction (PCR) using specific 16S rRNA primers were used to detect and identify the organism and determine its distribution within the soil stratum over the change in seasons. Results showed that Ashdown's method gave higher isolation rates in the dry season, and Galimand and Dodin's method gave higher isolation rates during the wet season. PCR of the soil enrichment proved to be a more sensitive method than culture and was also a useful confirmatory test in determining the identification of isolates where biochemical tests gave inconsistent results. The PCR primers were specific and able to detect 10(1) cfu g-1 soil and 10(4) cfu g-1 of soil using Ashdown's enrichment broth and Galimand and Dodin's broth, respectively. Overall the isolation of B. pseudomallei was greatest during the dry season and at the higher and lower soil depths, which is contradictory to epidemiological evidence that melioidosis occurs primarily during the wet season among patients exposed to contaminated surface soil and water.

Burkholderia pseudomallei↗
PubMed1996

Cognitive deficits in Machado-Joseph disease.

Cognitive function was examined in 6 patients with genetically confirmed Machado-Joseph disease (MJD) and 15 age- and ethnically matched controls using a series of subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), a touch screen-based testing system previously validated in a number of movement and neurodegenerative disorders. The MJD patients had deficits in visual attentional function that were characterized by a slowing of the processing of visual information when task demands were high and an inability to shift attention to previously irrelevant stimulus dimensions to discriminate between complex stimuli. Tests of learning and visual memory were normal. These results demonstrate that specific cognitive deficits occur in patients with MJD, independent of motor dysfunction, and these deficits may reflect disruption to frontosubcortical pathways.

Adult↗
PubMed1996

Opsonic human antibodies from an endemic population specific for a conserved epitope on the M protein of group A streptococci.

This study demonstrates the presence of epitope-specific opsonic human antibodies in a population living in an area endemic for group A streptococci (GAS) infection. Antibodies recognizing a conserved C-terminal region epitope (p145, sequence in single letter amino acids: LRRDLDASREAKKQVEKALE) of the M protein of GAS were isolated from human patients by affinity chromatography and were shown to be of the immunoglobulin G1 (IgG1) and IgG3 subclasses. These antibodies could reduce the number of colonies of serotype 5 GAS in an in vitro opsonization assay by 71-92%, compared with an equal amount of IgG from control adult donors living in non-endemic areas and without antibodies to p145. Addition of the peptide, p145, completely inhibited this opsonization. Indirect immunofluorescence showed that p145-specific antibodies were capable of binding to the surface of M5 GAS whereas control IgG did not. Using chimeric peptides, which contain overlapping segments of p145, each 12 amino acids in length, inserted into a known helical peptide derived from the DNA binding protein of yeast, GCN4, we have been able to further define two minimal regions within p145, referred to as pJ2 and pJ7. These peptides, pJ2 and pJ7, were able to inhibit opsonization by p145 specific antibodies. Finally, we have observed an association between the age-related development of immunity to GAS and the acquisition of antibodies to the conserved epitope, p145, raising the possibility of using this epitope as a target in a prophylactic vaccine administered during early childhood.

Adolescent↗
PubMed1996

Positional cloning of a sequence from the breakpoint of chromosome 9 commonly associated with the loss of cytoadherence.

Isolates of Plasmodium falciparum commonly undergo a large, subtelomeric deletion of the right end of chromosome 9 during in-vitro cultivation. This deletion is usually accompanied by loss of ability to cytoadhere to melanoma cells, loss of a var-gene product from the red-cell surface and a reduction in gametocyte production. However, cytoadherence is stable in the isolate ItG2, remaining after many generations in culture. Deletions in all the non-cytoadherent clones examined have breakpoints within or delete a novel open-reading frame, called the breakpoint open-reading frame (BPORF), that is a unique sequence in the genome. In ItG2, surprisingly, BPORF has been removed by a 15-kb deletion, internal in chromosome 9. These results indicate mechanisms to explain why the deletion of chromosome 9 occurs so frequently and why cytoadherence is stable in ItG2.

Animals↗
PubMed1996

Chromoblastomycosis: a retrospective study of six cases at the Royal Darwin Hospital from 1989 to 1994.

Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused by pigmented fungi, is most common in the world's tropical and subtropical zones. The condition rarely occurs in Australia. We present 6 cases of chromoblastomycosis seen at the Royal Darwin Hospital, Northern Territory, from 1989 to 1994 and affecting predominantly male Caucasians ranging from 38 to 71 yrs of age. Clinically the lesions were verrucous or nodular. They mimicked basal or squamous cell carcinoma, nevi or solar keratoses. Histopathologic findings were nonspecific. The only pathognomonic finding was the presence of brown spores or sclerotic bodies within granulomata or within microabscesses in the skin.

Adult↗
PubMed1996

Fundoplication in children: experience with 106 cases.

BACKGROUND: Gastro-oesophageal reflux (GOR) is a physiological problem in infancy that can become pathological and life-threatening in certain cases. Fundoplication has been shown previously to be effective in the control of this problem when medical therapy fails. METHODS: A retrospective review of the hospital records and the Department of Paediatric Surgery database was carried out, in order to demonstrate the Prince of Wales Children Hospital's (POWCH) experience with 106 fundoplications between February 1989 and March 1993. RESULTS: There was a failure rate of 7.5% and a long-term mortality rate of 7.8%. The children most at risk of mortality and morbidity are shown to be the neurologically impaired. The special problems associated with these children as compared with neurologically normal children with pathological GOR are discussed and the literature reviewed. CONCLUSION: Fundoplication is shown to be a safe operation that can be life-saving in certain circumstances.

Cerebral Palsy↗
PubMed1996

Anti-streptokinase antibodies and streptokinase resistance in an Aboriginal population in northern Australia.

BACKGROUND: Thrombolytic treatment with streptokinase in acute myocardial infarction has proven to be safe and effective in Caucasian populations with relatively low levels of anti-streptokinase IgG and streptokinase resistance. Higher levels of antibodies, as seen in previous recipients of streptokinase therapy, cause more adverse reactions and may result in lower efficacy. AIMS: To examine the levels of anti-streptokinase IgG and streptokinase resistance in a population subjected to endemic streptococcal infections. METHODS AND RESULTS: Thirty Aboriginal adults from a remote community in Northern Australia with endemic streptococcal infections and 15 non-Aboriginal adults from an urban community without endemic infections participated in this study. Aboriginal adults exhibited levels of anti-streptokinase IgG and streptokinase resistance that, respectively, were almost 20 and 15 times greater than the values of non-Aboriginal adults. At least 23% of Aboriginal adults had sufficiently high levels of streptokinase resistance to neutralise a standard 1.5 million unit dose of streptokinase. CONCLUSIONS: Aboriginal adults from a remote community had dramatically elevated levels of anti-streptokinase IgG and in vitro streptokinase resistance. Prospective studies are needed to assess the clinical relevance of streptokinase resistance in populations from areas with endemic streptococcal infection.

Adult↗
PubMed1996

Machado-Joseph disease in east Arnhem Land, Australia: chromosome 14q32.1 expanded repeat confirmed in four families.

Four kindreds of east Arnhem Land Australian aboriginal people from Groote Eylandt and adjacent communities display symptoms of a similar spinocerebellar degeneration (multiple-system degenerative disease). The familial pattern indicates an autosomal dominant inheritance, though with varying penetrance in different families. This condition is clinically and pathologically consistent with Machado-Joseph disease (MJD), and there is the possibility of Portuguese ancestry. These families exhibit anticipation, particularly in the case of paternal inheritance, with those with earlier age of onset presenting a clinical pattern consistent with MJD type I. There was no expansion of the CAG repeat region of the SCA1 gene in these families. The demonstration of expansion of the CAG repeat on chromosome 14q32.1 in all four families confirms the diagnosis of MJD.

Australia↗
PubMed1995

Isolation, culture, and characterization of equine oviduct epithelial cells in vitro.

Oviduct epithelial cells (OEC) increasingly are used to support embryonic development and to study gamete interactions with the female reproductive tract in vitro. This series of experiments was designed to characterize monolayers derived from oviduct epithelium. Epithelial cells harvested from the isthmus and ampulla of the oviducts of five estrous mares were cultured with or without the basal lamina extract, Matrigel. Within each group OEC were cultured in the presence of either estradiol-17 beta or a carrier control. All groups were subcultured three times. Epithelial cell morphology and function were examined by microscopy, analysis of secreted proteins, and immunocytochemistry. Epithelial cells attached more rapidly and reached confluence sooner when cultured on Matrigel than in uncoated wells. Cells showed variable evidence of ciliary activity up to 12 days in primary culture. Cells grown on Matrigel had a more polarized appearance in primary culture than those in uncoated wells, although no morphologic difference between anatomic site of origin or between steroid treated groups was noted. Anatomic site of origin had no effect, and steroid treatment had minimal effects, on patterns of secreted proteins. However, some differences were noted in protein secretion between cells grown with or without Matrigel. These data suggest that culture substrate may affect structure and function of OEC monolayers.

Animals↗
PubMed1995

Nosocomial and community-acquired Xanthomonas maltophilia infection in tropical Australia.

Xanthomonas maltophilia infection is recognized as a serious problem in association with immunosuppressive and invasive therapies, and with the use of broad-spectrum antibiotics. In Darwin Hospital in Australia's Northern Territory preliminary evidence of nosocomial transmission of X. maltophilia prompted this retrospective examination of all X. maltophilia isolates over a 30 month period. X. maltophilia was most frequently isolated in the 'wet season' corresponding to times of increased antibiotic treatment of the serious community-acquired pneumonias encountered in this tropical region. A relatively high proportion of community-acquired isolates (4/18; 22%) was documented. This study demonstrates that X. maltophilia infection is an emerging cause of morbidity in tropical regions where endemic infections require the use of broad-spectrum beta-lactams.

Adolescent↗
PubMed1995

RAPD analysis of isolates of Burkholderia pseudomallei from patients with recurrent melioidosis.

Twenty-seven isolates of Burholderia pseudomallei (formerly Pseudomonas pseudomallei) from ten patients with recurrent melioidosis were analysed by RAPD. In two cases RAPD patterns in recurrent isolates differed from the original isolates; one was considered a likely reinfection while the other may represent relapse from one of two strains initially infecting the patient. In two cases where a change in antibiotic resistance had occurred between original and relapse isolates, slight changes in RAPD patterns were found with one of the four primers used. In the other six cases the relapse was clearly due to the original strain re-emerging unchanged, with identical RAPD patterns with all four primers.

Adult↗
PubMed1995

Expression and immune recognition of stress proteins in sarcoidosis and other chronic interstitial lung diseases.

Stress proteins (SP) are major immunogens in a number of microbial infections and have been implicated in some autoimmune diseases. The aetiology of sarcoidosis, a non-caseating granulomatous disease, remains unknown, but mycobacteria as well as autoimmunity have been considered. In the present study, patients diagnosed with sarcoidosis and other interstitial lung diseases (ILD), as well as healthy volunteers were studied to determine: (i) the level of expression of SP in alveolar macrophages and blood monocytes; (ii) the serum levels of antibodies specific for mycobacterial SP65 and SP70; and (iii) the reactivity of peripheral blood and alveolar lymphocytes to mycobacterial SP65. Our results suggest that SP are expressed constitutively at high levels in alveolar macrophages, retrieved by bronchoalveolar lavage, from all individuals regardless of health status. In contrast, freshly isolated blood monocytes express low levels of SP, which are, however, readily upregulated following exposure to IFN-gamma and TNF-alpha. Lymphocyte reactivity and presence of antibodies against mycobacterial SP may reflect the current state of in vivo inflammation rather than the cause of inflammation.

Antibodies, Monoclonal↗
PubMed1995

Disseminated Penicillium marneffei: presenting illness of advanced HIV infection; a clinicopathological review, illustrated by a case report.

BACKGROUND: Until recently Penicillium marneffei rarely caused human disease. It is now a frequently encountered opportunistic mycosis in HIV positive residents of, and travellers to, south-east Asia. AIMS: To review aspects of clinical presentation, pathology, treatment, epidemiology and ecology of P. marneffei. To report a case of disseminated P. marneffei occurring in the Northern Territory which illustrates many typical clinical and pathological features of this infection. CASE PRESENTATION: A Burmese immigrant presented to Royal Darwin Hospital, Australia with a non-specific, subacute, febrile illness and a diffuse papular rash. The etiological agent was Penicillium marneffei, disseminated in association with advanced HIV infection. The typical travel history and umbilicated papular rash were recognized on admission. Fungal stains of skin biopsies and touch smears facilitated rapid diagnosis, and early antifungal therapy resulted in clinical cure. CONCLUSIONS: Early distinction of penicilliosis from other opportunistic mycoses, tuberculosis, Leishmaniasis, and molluscum contagiosum is critical for effective management. The characteristic histological and mycological properties of P. marneffei are easily recognizable if the diagnosis is considered. In view of geographic proximity, travel and immigration from endemic areas, Australia should expect further imported penicilliosis as illustrated by this case report.

AIDS-Related Opportunistic Infections↗
PubMed1995

Antigens released at schizont burst stimulate Plasmodium falciparum-specific CD4+ T cells from non-exposed donors: potential for cross-reactive memory T cells to cause disease.

In an individual experiencing the first attack of malaria, symptoms of disease can occur at very low parasitemia. T cells and cytokines have been implicated in the etiology of disease symptoms, and others and ourselves have shown that T cells from non-exposed individuals can be stimulated by malaria parasites. Here, we show that nine from 11 blood samples, naturally infected with malaria parasites, could stimulate proliferation of a malaria-specific T cell clone derived from a non-exposed donor. T cells were able to respond to infected blood at a parasitaemia as low as 0.000003% (comparable to the level at which individuals can first experience symptoms of malaria) and secrete cytokines implicated in pathology. Antigens capable of stimulating T cells are expressed throughout the blood stage, but are specifically released at the time of schizont rupture. While most TCR V beta genes are expressed during the T cell response of naive donors to malaria parasites, processing of parasite antigens is blocked by chloroquine and monensin, and activation of 36 of 41 malaria-specific clones tested was restricted by defined MHC class II allelic antigens, strongly suggesting that parasites do not act as mitogens nor as superantigens. The clones react to various commonly encountered pathogenic and non-pathogenic microbes. These data support the concept that activation of cross-reactive memory T cells by malaria parasites contributes to disease symptoms in individuals experiencing their first attack of malaria.

Adolescent↗