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R Doherty

Publications and source records attributed to R Doherty.

At least 19 recordsLinked to original sources
PubMed2006

The global atmospheric environment for the next generation.

Air quality, ecosystem exposure to nitrogen deposition, and climate change are intimately coupled problems: we assess changes in the global atmospheric environment between 2000 and 2030 using 26 state-of-the-art global atmospheric chemistry models and three different emissions scenarios. The first (CLE) scenario reflects implementation of current air quality legislation around the world, while the second (MFR) represents a more optimistic case in which all currently feasible technologies are applied to achieve maximum emission reductions. We contrast these scenarios with the more pessimistic IPCC SRES A2 scenario. Ensemble simulations for the year 2000 are consistent among models and show a reasonable agreement with surface ozone, wet deposition, and NO2 satellite observations. Large parts of the world are currently exposed to high ozone concentrations and high deposition of nitrogen to ecosystems. By 2030, global surface ozone is calculated to increase globally by 1.5 +/- 1.2 ppb (CLE) and 4.3 +/- 2.2 ppb (A2), using the ensemble mean model results and associated +/-1 sigma standard deviations. Only the progressive MFR scenario will reduce ozone, by -2.3 +/- 1.1 ppb. Climate change is expected to modify surface ozone by -0.8 +/- 0.6 ppb, with larger decreases over sea than over land. Radiative forcing by ozone increases by 63 +/- 15 and 155 +/- 37 mW m(-2) for CLE and A2, respectively, and decreases by -45 +/- 15 mW m(-2) for MFR. We compute that at present 10.1% of the global natural terrestrial ecosystems are exposed to nitrogen deposition above a critical load of 1 g N m(-2) yr(-1). These percentages increase by 2030 to 15.8% (CLE), 10.5% (MFR), and 25% (A2). This study shows the importance of enforcing current worldwide air quality legislation and the major benefits of going further. Nonattainment of these air quality policy objectives, such as expressed by the SRES-A2 scenario, would further degrade the global atmospheric environment.

Air Pollutants↗
PubMed1996

Health care and its costs for children with perinatally acquired HIV infection.

OBJECTIVE: To describe survival patterns, use of health services and related costs for Australian children with perinatally acquired human immunodeficiency virus (HIV) infection. METHODOLOGY: A retrospective cross-sectional survey was made of 20 children with HIV infection (91% of those diagnosed) and 13 children with maternal antibodies who subsequently seroreverted, treated at 10 medical centres. Details of disease progression and use of health services were obtained from hospital medical records. Monthly costs for three phases of infection were estimated by linking service usage rates with estimates of the unit cost of each service. The average lifetime cost was estimated by combining monthly costs and phase duration estimates from the literature. RESULTS: Patterns of disease progression were similar to those reported internationally, with a median survival of 8 years. Use of health services increased with severity of illness. Mean monthly costs were $120 per month (1992 Australian dollars) for children with maternal antibodies who subsequently seroreverted, $320 per month for children with HIV infection but no acquired immunodeficiency syndrome (AIDS)-defining illness, and $1830 per month for children with AIDS. The present value of total lifetime cost for a child with HIV infection was $48174, 46% of which was for treatment of AIDS. DISCUSSION: The mean lifetime cost for a perinatally infected child was just over half that for a man with HIV in Australia. Health service usage and costs were lower for Australian than American children with HIV.

Australia↗
PubMed1995

Reverse transcriptase mutations in sequential HIV-1 isolates in a patient with AIDS.

Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained over a 29-month period from a person before, during, and after AZT therapy. DNA sequence analysis of polymerase chain-amplified reverse-transcriptase gene showed a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70, and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from the patient was again sensitive to AZT, these mutations had all returned to the pretherapy sequence.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Australia's contribution to tropical health: past and present.

Australian research workers have made important contributions to tropical medicine and tropical public health. Recognised high points of international significance (for example, Joseph Bancroft and filariasis, 1876; Thomas Bancroft and dengue fever, 1906; Burnet and Australian X disease, 1934; Derrick and Q fever, 1937; and Fairley and malaria, 1947) must be seen in the context of much detailed work of national relevance by institutions and individuals. The directions of Australian research can be related to several major themes: the large extent of Australia that is tropical or subtropical; interactions with neighbouring countries, especially Papua New Guinea; and concern for the health of Australian Aborigines.

Australia↗
PubMed1993

Hepatitis viruses and protection against infection in children.

Molecular biology techniques are now a vital part of hepatitis virology, with a central role in studies of diagnosis, epidemiology, virology, pathogenesis, and natural history of infection. Cloning of the genome of hepatitis E virus has allowed its tentative classification as a calici- or related virus, and is the first step toward the development of a vaccine. Long-term implications of hepatitis C for groups such as children with hemophilia, thalassemia, and even leukemia can be better understood by comparison of virus load measured by molecular amplification of the plasma viral RNA with the serologic and clinical status of the respective cohorts of children. A new vaccine for hepatitis A has been licensed in several European countries, and recent experience with severe hepatitis in infants after unexpected transmission of hepatitis B from anti-hepatitis B e positive mothers reemphasizes the value of universal hepatitis B immunization programs. Mother-to-infant transmission of hepatitis C virus has now been well documented, but there are still insufficient data on the dynamics of this, particularly in the absence of passive immunoprophylaxis or a vaccine, to permit recommendations regarding the management of individual pregnancies or deliveries. There is especially too little information to suggest whether breast feeding may be an important mechanism for transmission.

Base Sequence↗
PubMed1992

Clinical effects and in vitro studies of trifluorothymidine combined with interferon-alpha for treatment of drug-resistant and -sensitive herpes simplex virus infections.

Three AIDS patients with severe cutaneous herpes simplex virus (HSV) infection refractory to therapy with acyclovir and foscarnet (2 patients) were treated with a topical preparation of trifluorothymidine (TFT) and interferon-alpha. Complete healing of lesions occurred in 1 patient; a second had significant regression of the infected area. In the third, the lesion was stabilized twice after application of the preparation and reduced in size after a subsequent treatment. In vitro studies confirmed that isolates from these patients were acyclovir- or acyclovir/foscarnet-resistant. In addition, they revealed strong synergy between TFT and interferon-alpha for these isolates and for strains with wild-type drug sensitivity profiles. Topical TFT/interferon-alpha may be of benefit in the therapy of mucocutaneous HSV infections, especially when they are resistant to treatment with systemic antiviral agents.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex.

OBJECTIVE: To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS). DESIGN: Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING: Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS: One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES: Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS: Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION: Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.

AIDS-Related Complex↗
PubMed1990

Simplified colorimetric analysis of polymerase chain reactions: detection of HIV sequences in AIDS patients.

We have previously described a colorimetric test, designated an amplified DNA assay (ADA), for specific segments of DNA amplified by polymerase chain reactions (PCRs), suited to diagnostic applications. This relied on binding the amplified DNA via a sequence in one oligodeoxyribonucleotide (oligo) to the DNA-binding protein GCN4 coated on the wells of a microtiter dish. Avidin-peroxidase was then bound to biotin at the 5' end of the other oligo and detected colorimetrically. Two successive PCRs with nested oligos were utilized. We describe here several modifications that greatly simplify the ADA. First, we bind the DNA to a glutathione S-transferase-GCN4 fused polypeptide (GST-GCN4) and avidin-peroxidase simultaneously, rather than successively. Second, we carry out the two successive PCRs in the one reaction mixture, using the thermal stabilities of oligos of differing lengths to separate the two reactions. Third, PCRs can be performed in the wells of a microtiter dish and the amplified DNA captured and detected via GST-GCN4 immobilized on beads attached to the lid of the microtiter dish. Hence it is only necessary to pipette the DNA sample once, and up to 96 samples can then be handled simultaneously.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Kinetics of HIV-1 replication and intracellular accumulation of particles in HTLV-I-transformed cells.

The replication kinetics of HIV were examined in HTLV-I-transformed MT-2 cells. The duration of the initial replication cycle was 20 hours, determined by the first detection of infectious progeny virus, development of syncytia, and production of viral RNA and protein. A phase of exponential virus production followed until 62 h postinfection. Cell death occurred in the final phase of infection during which infectious virus production remained constant even though viral RNA and protein production increased at an exponential rate. Accumulations of HIV particles were observed within cytoplasmic vacuoles of infected MT-2 cells. Although cell lysates contained high titers of infectious virus, our data show that an increasing proportion of particles produced late in infection were not infectious.

Cell Line, Transformed↗
PubMed1990

Decreased in vitro susceptibility to zidovudine of HIV isolates obtained from patients with AIDS.

This study tested isolates of human immunodeficiency virus, obtained before and after zidovudine therapy from 10 patients, for susceptibility to the drug in vitro. The isolates collected after therapy were less susceptible to zidovudine as assessed by replication in MT-2 cells and production of reverse transcriptase activity by infected mononuclear leucocytes in the presence of the drug. Furthermore, pretherapy isolates were sensitive to a range of zidovudine concentrations when 100% inhibition was used as the end point. The loss of zidovudine susceptibility did not correlate with any clinical or virologic consequences in this small group of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effects of transport inhibitors on the generation and transport of a soluble viral glycoprotein.

The generation and transport of the soluble glycoprotein (Gs) of wild-type vesicular stomatitis virus (VSV) were studied using cell fractionation and transport inhibitors. Gs was found in the rough endoplasmic reticulum (RER) and the Golgi-enriched membrane fractions of infected Chinese hamster ovary cells. The identity of intracellular Gs was confirmed by its precipitation with a monoclonal antibody to the ectodomain but not with a anti-peptide antibody directed against the first 15 amino acids at the carboxy terminus of the VSV transmembrane glycoprotein G. Their extracellular appearance was affected in a concentration-dependent manner by monensin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) and was completely inhibited by incubation at 20 degrees. Inhibitors failed to dissociate the transport of Gs from G. These experiments indicate that in fibroblast cells Gs can be generated intracellularly, probably in the RER, and that Gs, like G, is transported from there to the Golgi complex and then presumably to the extracellular environment.

Animals↗
PubMed1987

Molecular genetic approaches to cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal genetic disease of white populations. The underlying biochemical defect remains unknown, but recently polymorphic DNA markers linked to the cystic fibrosis gene have been discovered. These markers provide useful tools both for antenatal diagnosis and carrier detection, and for isolating the cystic fibrosis gene. In this paper we present data summarizing the results of retrospective and prospective antenatal series as well as a report on molecular approaches to isolation of the cystic fibrosis gene.

Cystic Fibrosis↗