Infectious Diseases - Research Publications

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    ETHICAL ISSUES AND ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
    JUDD, FK ; BIGGS, BA ; BURROWS, GD (AUSTRALIAN NZ J PSYCHIATRY, 1989-12)
    Acquired Immunodeficiency Syndrome (AIDS) has received much publicity and medical attention. Interest has focused on education, epidemiology, treatment and prevention of the syndrome. This paper raises other issues for consideration, including problems associated with HIV testing, confidentiality, informed consent and the dilemmas facing those involved in the treatment of patients suffering from HIV infection.
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    Plasmodium falciparum: Cytoadherence of a knobless clone
    BIGGS, BA ; CULVENOR, JG ; NG, JS ; KEMP, DJ ; BROWN, GV (Elsevier, 1989-07)
    Sequestration of Plasmodium falciparum-infected erythrocytes is crucial to parasite survival as it prevents destruction in the liver and spleen. Knobs have been considered necessary but not sufficient for cytoadherence to vascular endothelial cells in vivo and to melanoma or umbilical vein endothelial cells in vitro. We describe here a knobless clone that cytoadheres strongly to C32 melanoma cells. This clone cannot express the knob-associated histidine-rich protein (KAHRP) due to the deletion of the KAHRP gene. Our results raise the possibility of an alternative mechanism for in vitro cytoadherence and suggest that the use of long term cultured isolates and melanoma cells as a model for cytoadherence in vivo may be misleading.
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    Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro
    BIGGS, BA ; KEMP, DJ ; BROWN, GV (National Academy of Sciences, 1989-04-01)
    Subtelomeric deletions are responsible for the loss of expression of several Plasmodium falciparum antigens, including the knob-associated histidine-rich protein (KAHRP). Such deletions are detectable by two-dimensional pulsed-field gradient electrophoresis (PFGE) in which the chromosomes separated in dimension 1 are cleaved with Apa I, and the sizes of telomeric fragments are determined in dimension 2. This sensitive technique has enabled us to examine the role of subtelomeric deletions in two aspects of the biology of Plasmodium falciparum. First, we show that similar subtelomeric deletions to those that occur in vitro also occur in field isolates. Second, we demonstrate a correlation between subtelomeric deletions and loss of the phenotype of "cytoadherence" in cultured isolates. Subclones were generated from the cytoadherent cloned isolate ItG2F6, and their phenotypes were examined with respect to cytoadherence, the expression of "knobs," and agglutination of infected erythrocytes with rabbit antiserum. The only chromosomal change detectable by two-dimensional PFGE among subclones that differ from wild type in each of these three characteristics is a deletion of approximately 100 kilobases at one end of chromosome 2. This deletion includes the gene coding for KAHRP and the subtelomeric repeat designated rep20.
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    AMINO-ACID CHANGES LINKED TO PYRIMETHAMINE RESISTANCE IN THE DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE GENE OF PLASMODIUM-FALCIPARUM
    COWMAN, AF ; MORRY, MJ ; BIGGS, BA ; CROSS, GAM ; FOOTE, SJ (NATL ACAD PRESS, 1988-12)
    We describe the isolation and the sequence of the gene for the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS; EC 1.5.1.3 and EC 2.1.1.45, respectively) from two pyrimethamine-resistant clones of Plasmodium falciparum, HB3 and 7G8. We have also derived the sequence of the DHFR portion of the gene, by amplification using polymerase chain reaction, for the pyrimethamine-sensitive clone 3D7 and the pyrimethamine-resistant strains V-1, K-1, Csl-2, and Palo-alto. The deduced protein sequence of the resistant DHFR portion of the enzyme from HB3 contained a single amino acid difference from the pyrimethamine-sensitive clone 3D7. It is highly likely that this difference is involved in the mechanism of drug resistance in HB3. The sequence of the DHFR gene from other pyrimethamine-resistant strains contains the same amino acid difference from the sensitive clone 3D7. However, they all differ at one other site that may influence pyrimethamine resistance. The DHFR-TS gene is present as a single copy on chromosome 4 in all pyrimethamine-sensitive and pyrimethamine-resistant isolates tested. Therefore, the molecular basis of pyrimethamine resistance in the parasites tested is not amplification of the DHFR-TS gene.
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    Comparison of a multiple puncture tuberculin test, ‘imotest’, and the mantoux test in an Australian population
    BIGGS, B ; CONNOR, H ; DWYER, BW ; SPEED, BR (Churchill Livingstone, 1987-12-01)
    The new multiple puncture tuberculin testing device, 'Imotest', was compared to the Mantoux test (10 I.U.) in an Australian population. The tests were applied simultaneously to opposite forearms of 105 volunteers. Sixty-eight per cent of the Mantoux tests were positive compared to 39% of the 'Imotests', resulting in a false negative rate of 44% and the difference was highly significant. A further 30 volunteers were tested with a different batch of 'Imotest' and similar results were obtained. When multiple 'Imotests' were applied simultaneously to each of two subjects in a separate study, there was a wide variation of response within each subject, and positive and negative reactions occurred side by side. These results indicate that the 'Imotest' is significantly less sensitive than the Mantoux test and is unsuitable for use as a diagnostic or screening test.
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    AIDS RELATED KAPOSIS-SARCOMA PRESENTING AS ULCERATIVE-COLITIS AND COMPLICATED BY TOXIC MEGACOLON
    BIGGS, BA ; CROWE, SM ; LUCAS, CR ; RALSTON, M ; THOMPSON, IL ; HARDY, KJ (BRITISH MED JOURNAL PUBL GROUP, 1987-10)
    Gastrointestinal Kaposi's sarcoma is a well described and usually asymptomatic manifestation of the acquired immune deficiency syndrome. We report a patient who had extensive colonic Kaposi's sarcoma and presented with an ulcerative colitis like illness. Total colectomy was subsequently required as an emergency procedure for toxic megacolon. The patient remains well on maintenance interferon therapy 21 months after surgery.
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    HUMAN INFECTION WITH CRYPTOSPORIDIUM SPP - RESULTS OF A 24-MONTH SURVEY
    BIGGS, BA ; MEGNA, R ; WICKREMESINGHE, S ; DWYER, B (AUSTRALASIAN MED PUBL CO LTD, 1987-08-17)
    We report the findings of a two-year survey of faecal specimens for the protozoal pathogen, Cryptosporidium. Of the 2248 patients who were tested, 55 (2.5%) patients were found to have cryptosporidial infection. Transmission of the parasite appeared mainly to occur from person to person. In immunocompetent patients it caused an acute and sometimes severe gastroenteritis. Immunoincompetent patients experienced a variable illness that ranged from asymptomatic carriage to severe diarrhoea, causing malabsorption and ultimately death. Cryptosporidium is an important cause of gastroenteritis and may be the presenting feature of the acquired immunodeficiency syndrome. Therefore, it is pertinent to screen for this pathogen in all patients with acute diarrhoea.
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    Does regular treatment with ketotifen inhibit bronchoconstriction induced by isocapnic hyperventilation?
    Rafferty, P ; Tweeddale, PM ; Ferguson, RJ ; Biggs, BA ; Grant, IWB (Wiley, 1987-07-01)
    Eight asthmatic patients completed a 12-week, double-blind, placebo controlled study to assess the efficacy of ketotifen, 1 mg twice daily, in the inhibition of bronchoconstriction induced by isocapnic hyperventilation (IH). There was no significant difference in the degree of bronchoconstriction produced by IH after treatment with ketotifen or placebo.
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    Penicillins and related drugs
    Biggs, BA ; Kucers, A (Australasian Medical Publishing Company, 1986-12-01)
    Penicillin was discovered by Fleming in 1929 and introduced into clinical medicine by Florey, Chain and associates. Later, with the discovery of the penicillin nucleus, 6-aminopenicillanic acid, it became possible to synthesize new penicillins by the introduction ofa thiazolidine ring, a beta-lactam ring and a side-chain. More recently, related drugs, such as penems and carbapenems, have been found in nature, and some of these are useful. Clinically. All penicillins and related drugs are beta-lactam antibiotic agents. This review includes all these compounds that are available currently in Australia plus one (imipenem/cilastatin) which may be introduced shortly. Cephalosporins and related drugs, which are also beta-lactams, have been reviewed previously.
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    Acute HTLV-III infection: A case followed from onset to seroconversion
    BIGGS, B ; NEWTONJOHN, HF (Australasian Medical Publishing Company, 1986-05-01)
    An acute febrile illness with mouth ulcers and a skin rash was observed in a 37-year-old homosexual man. Acute human T-lymphotropic virus type III (HTLV-III) infection was suspected. The clinical features were documented prospectively, and striking changes in circulating T lymphocytes were demonstrated shortly after the onset of the illness. Seroconversion for HTLV-III antibody occurred between 46 and 78 days after the onset of the illness.