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Biomedical subjects

G J Jones

Publications and source records attributed to G J Jones.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of biomarker and pathological responses in flounder (Platichthys flesus L.) induced by ingested polycyclic aromatic hydrocarbon (PAH) contamination.

This study investigated the response of biomarker measurements and histopathological indicators of polycyclic aromatic hydrocarbon (PAH) exposure in the flounder (Platichthys flesus L.). Flounder were fed food spiked with a mixture of four PAHs at an environmentally relevant range of concentrations for either one or six months. Ethoxyresorufin-O-deethylase (EROD) activity was elevated following 1 month exposure to PAH concentrations up to 50 mgkg(-1) in food. Bile metabolite concentrations were found to increase with PAH concentration, up to 500 mgkg(-1) PAH. By comparison, no DNA adducts were detected and there were no significant histopathological changes observed. After 6 months exposure, EROD levels were not elevated but bile metabolites showed a similar dose dependent relationship as in the 1 month experiment, while DNA adducts were only detected in the highest PAH exposure groups. No significant histopathological changes were observed. The results are discussed with respect to the implications for the use of these methods in environmental monitoring studies.

Animals↗
PubMed2001

Comparative loss and maturation of peripheral blood dendritic cell subpopulations in African and non-African HIV-1-infected patients.

OBJECTIVES: To quantify the percentage of the two major subpopulations of blood dendritic cells (DC) in HIV-1-seropositive Ugandan individuals infected with non-clade B viruses and compare this with that seen in clade B HIV-1 infected non-African individuals. DC maturation/activation status was also investigated via the expression of CD86. METHODS: The percentage of blood DC was quantified by using flow cytometry. DC were identified as the lineage (CD3, CD14, CD16, CD19, CD20, CD56)-negative, HLA-DR-positive population and the two major subpopulations were differentiated by CD11c expression. RESULTS: The percentage of blood DC was reduced significantly in HIV-1-seropositive African individuals when compared with controls (0.21 and 0.39% respectively). A similar reduction was also seen in non-African patients residing in the UK (0.19% compared with 0.36% for controls). However, there was no selective loss in either CD11c-positive or CD11c-negative subpopulations. The percentage of blood DC expressing CD86 was significantly greater in HIV-1-seropositive individuals when compared with controls and the increased expression was largely confined to CD11c-negative DC. CONCLUSIONS: Africans infected with non-clade B HIV-1 showed similar reductions in the percentage of blood DC to non-Africans infected with clade B viruses. There was no selective loss of either DC subpopulation, suggesting that the ability of DC to acquire and present antigens or to produce interferon-alpha may both be impaired in HIV-1 infection.

Adult↗
PubMed2001

Ingestion of toxic Microcystis aeruginosa by dairy cattle and the implications for microcystin contamination of milk.

Microcystin (MCYST) toxins can be produced by the bloom-forming cyanobacterium Microcystis aeruginosa. They are chemically stable compounds and have both acute and chronic effects on the health of mammals, including cattle and humans. Cattle will drink water containing lethal cell concentrations of M. aeruginosa. When cattle consume sub-lethal doses of microcystins, the fate of those toxins is unknown. We provided drinking water containing 1 x 10(5) cells ml(-1) M. aeruginosa (strain MASH01-A19) to four lactating Holstein-Friesian dairy cattle for 21 days to determine if MCYST-LR produced by the cyanobacteria, could be detected in milk produced by the cattle. Cattle consumed up to 15 mg MCYST-LR at an ingestion rate of 1.21 microg kg (live weight) d(-1). Analysis by HPLC and ELISA indicated that no detectable amounts of microcystin from the cyanobacteria were present in the milk obtained from the treated animals. Based on the level of quantitation of the ELISA analyses, the maximum possible concentration in the milk was less than 2 ng l(-1). This is more than three orders of magnitude less that the concentration that could be considered problematic for milk of 0.86 microg l(-1) which we calculated using the World Health Organization derived tolerable daily intake for MCYST-LR and the per capita daily consumption of milk in Australia.

Animals↗
PubMed2001

Cellular microcystin content in N-limited Microcystis aeruginosa can be predicted from growth rate.

Cell quotas of microcystin (Q(MCYST); femtomoles of MCYST per cell), protein, and chlorophyll a (Chl a), cell dry weight, and cell volume were measured over a range of growth rates in N-limited chemostat cultures of the toxic cyanobacterium Microcystis aeruginosa MASH 01-A19. There was a positive linear relationship between Q(MCYST) and specific growth rate (mu), from which we propose a generalized model that enables Q(MCYST) at any nutrient-limited growth rate to be predicted based on a single batch culture experiment. The model predicts Q(MCYST) from mu, mu(max) (maximum specific growth rate), Q(MCYSTmax) (maximum cell quota), and Q(MCYSTmin) (minimum cell quota). Under the conditions examined in this study, we predict a Q(MCYSTmax) of 0.129 fmol cell(-1) at mu(max) and a Q(MCYSTmin) of 0.050 fmol cell(-1) at mu = 0. Net MCYST production rate (R(MCYST)) asymptotes to zero at mu = 0 and reaches a maximum of 0.155 fmol cell(-1) day(-1) at mu(max). MCYST/dry weight ratio (milligrams per gram [dry weight]) increased linearly with mu, whereas the MCYST/protein ratio reached a maximum at intermediate mu. In contrast, the MCYST/Chl a ratio remained constant. Cell volume correlated negatively with mu, leading to an increase in intracellular MCYST concentration at high mu. Taken together, our results show that fast-growing cells of N-limited M. aeruginosa are smaller, are of lower mass, and have a higher intracellular MCYST quota and concentration than slow-growing cells. The data also highlight the importance of determining cell MCYST quotas, as potentially confusing interpretations can arise from determining MCYST content as a ratio to other cell components.

Bacterial Proteins↗
PubMed2001

Characterisation of a gene cluster involved in bacterial degradation of the cyanobacterial toxin microcystin LR.

A novel pathway for degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR was identified in a newly isolated Sphingomonas sp. (Bourne et al. 1996 Appl. Environ. Microbiol. 62: 4086-4094). We now report the cloning and molecular characterisation of four genes from this Sphingomonas sp. that exist on a 5.8-kb genomic fragment and encode the three hydrolytic enzymes involved in this pathway together with a putative oligopeptide transporter. The heterologously expressed degradation pathway proteins are enzymatically active. Microcystinase (MlrA), the first enzyme in the degradative pathway, is a 336-residue endopeptidase, which displays only low sequence identity with a hypothetical protein from Methanobacterium thermoautotrophicum. Inhibition of microcystinase by EDTA and 1,10-phenanthroline suggests that it is a metalloenzyme. The most likely residues that could potentially chelate an active-site transition metal ion are in the sequence HXXHXE, which would be unique for a metalloproteinase. Situated immediately downstream of mlrA with the same direction of transcription is a gene mlrD, whose conceptual translation (MlrD, 442 residues) shows significant sequence identity and similar potential transmembrane spanning regions to the PTR2 family of oligopeptide transporters. A gene mlrB is situated downstream of the mlrA and mlrD genes, but transcribed in the opposite direction. The gene encodes the enzyme MlrB (402 residues) which cleaves linear microcystin LR to a tetrapeptide degradation product. This enzyme belongs to the "penicillin-binding enzyme" family of active site serine hydrolases. The final gene in the cluster mlrC, is located upstream of the mlrA gene and is transcribed in the opposite direction. It codes for MlrC (507 residues) which mediates further peptidolytic degradation of the tetrapeptide. This protein shows significant sequence identity to a hypothetical protein from Streptomyces coelicolor. It is suspected to be a metallopeptidase based on inhibition by metal chelators. It is postulated on the basis of comparison with other microorganisms that the genes in this cluster may all be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR.

Amino Acid Sequence↗
PubMed2000

Anti-CD4-binding domain antibodies complexed with HIV type 1 glycoprotein 120 inhibit CD4+ T cell-proliferative responses to glycoprotein 120.

HIV-specific CD4+ helper T cell responses, particularly to the envelope glycoproteins, are usually weak or absent in the majority of HIV-seropositive individuals. Since antibodies, by their capacity to alter antigen uptake and processing, are known to have modulatory effects on CD4+ T cell responses, we investigated the effect of antibodies produced by HIV-infected individuals on the CD4+ T cell response to HIV-1 gp120. Proliferative responses of gp120-specific CD4+ T cells were inhibited in the presence of either serum immunoglobulin from HIV-infected individuals or human monoclonal antibodies specific for the CD4-binding domain (CD4bd) of gp120. Human monoclonal antibodies to other gp120 epitopes did not have the same effect. The anti-CD4bd antibodies complexed with gp120 suppressed T cell lines specific for varying gp120 epitopes but did not affect T cell proliferation to non-HIV antigens. Moreover, inhibition by the anti-CD4bd/gp120 complexes was observed regardless of the types of antigen-presenting cells used to stimulate the T cells. These results indicate that the presence of anti-CD4bd antibodies complexed with gp120 can strongly suppress CD4+ helper T responses to gp120.

Amino Acid Sequence↗
PubMed1999

Immunization with human immunodeficiency virus type 1 rgp120W61D in QS21/MPL adjuvant primes T cell proliferation and C-C chemokine production to multiple epitopes within variable and conserved domains of gp120W61D.

Human immunodeficiency virus type 1 (HIV-1) gp120W61D-specific T cell lines (TCL) were generated from an HIV-1-seronegative volunteer who received rgp120W61D in QS21/MPL adjuvant with emulsion. TCL were challenged with pools of consecutive, overlapping peptides spanning the gp120W61D sequence and then with the individual peptides of the immunostimulatory pool. T cell epitopes were found within both variable and conserved domains, and there was no evidence of a single immunodominant epitope. The two most frequently recognized peptides were located in the C1 domain and in the C-terminal region of the V3 loop. Several TCL were shown to recognize multiple peptides from nonoverlapping regions. Peptides from both conserved and variable domains were capable of inducing MIP-1alpha, MIP-1beta, and RANTES production. When tested against the equivalent peptide from the HIV-1IIIB sequence, however, TCL were able to tolerate only minor conserved changes in the amino acid sequence.

AIDS Vaccines↗
PubMed1998

Membrane current noise in dark-adapted and light-adapted isolated retinal rods of the larval tiger salamander.

1. Low-frequency light-sensitive membrane current noise in isolated rod photoreceptors of the larval tiger salamander was recorded using suction electrodes, in the dark, and during light adaptation by backgrounds or by bleaching visual pigment. 2. In background light, noise variance increases and then decreases. For rods desensitized to similar levels by bleaching visual pigment, the noise variance either does not change (weak adaptation) or decreases (with stronger adaptation). 3. The power spectral density of the current noise in dark-adapted rods shows a component with half-power cut-off frequency at about 0.1 Hz, attributed to spontaneous single events and continuous noise from dark phosphodiesterase activity. A second component, with half-power cut-off frequency at about 1 Hz, may be due to slow components in the light-sensitive channel gating. 4. The power spectral density of the noise in background light is dominated by noise generated by the background. Background light adapts at least the first component of the noise seen in dark-adapted cells. For cells desensitized by bleaching, light adaptation of both components of the dark-adapted noise is observed. 5. The results confirm that the low-frequency noise in dark-adapted cells arises from the transduction mechanism of the rod, in that both components can be light adapted, and show that, for rods permanently desensitized by bleaching, the desensitization is not due to the presence of active visual pigment molecules similar to those produced by background light.

Adaptation, Ocular↗
PubMed1998

Effect of high irradiance and iron on volatile odour compounds in the cyanobacterium Microcystis aeruginosa.

The cyanobacterium, Microcystis aeruginosa was exposed to direct sunlight for 3, 6 or 9 h in media containing either low or high concentrations of iron, in order to determine any effects on the composition of volatile odour compounds (VOCs) released under photooxidative conditions. The most abundant VOCs detected included aliphatic hydrocarbons (C15-C21), naphthalene and the terpenoid compounds, beta-cyclocitral, and beta-ionone. Exposure to sunlight and low iron concentrations resulted in a decrease in beta-cyclocitral, beta-ionone, heptadecane and the total VOCs concentration after 9 h with respect to the control cultures. Six VOCs detected in the low iron cells were not detected in any of the high iron cells. However, those VOCs present in the high iron cells, in general, occurred at higher concentrations than the equivalent low iron cells after exposure to the sunlight conditions. Consequently, it was concluded that exposure to both high irradiance and high iron concentrations influenced the VOCs composition in cyanobacteria and this was interpreted to represent a cellular change during the photooxidation-promoting conditions.

Hydrocarbons↗
PubMed1997

Isolation and toxicity of Cylindrospermopsis raciborskii from an ornamental lake.

In Australia, the tropical/subtropical cyanobacterium Cylindrospermopsis raciborskii forms substantial blooms in some drinking water supply reservoirs, rivers and recreational water bodies during the warmer months of the year. This paper describes the isolation, culture and toxicity characterisation of Cylindrospermopsis from a water bloom in a small lake in NSW, Australia. The cyanobacterium grew as straight trichomes terminating with a characteristic heterocyst. The toxic alkaloid cylindrospermopsin was separated and identified by high-performance liquid chromatography at a concentration of 5.5 mg/g dry cells, 0.026 pg/cell. Intraperitoneal injection of sonicated cells caused liver, kidney, intestinal and lung damage, with an LD50 of 52 mg cells/kg mouse body weight at 24 hr, and 32 mg/kg at 7 days. The 24 hr mouse toxicity is not consistent with previous studies using pure cylindrospermopsin, and is suggestive of other toxic compounds in this isolate.

Alkaloids↗
PubMed1996

Equivalence of background and bleaching desensitization in isolated rod photoreceptors of the larval tiger salamander.

Psychophysical experiments have shown an equivalence between sensitivity reduction by background light and by bleaches for the human scotopic system. We have compared the effects of backgrounds and bleaches on the light-sensitive membrane-current responses of isolated rod photoreceptors from the salamander Ambystoma tigrinum. The quantum catch loss was factored out from the desensitization due to bleaching to give the fraction of "extra" desensitization due to adaptation. For backgrounds, desensitization is well described by the Weber/Fechner equation. The extra desensitization after bleaches can also be described by the Weber/Fechner equation, if an "equivalent" background produced by bleaching is made linearly proportional to the fraction of pigment bleached. A background which produces an extra desensitization of a factor of two is equivalent to a fractional bleach of approximately 6%. Equivalent background and bleaching desensitizations were associated with similar reductions in circulating current. There is a linear relation between log flash sensitivity and decrease in circulating current. Equivalent background and bleaching desensitizations were associated with similar increases in cGMP phosphodiesterase and guanylate cyclase activity. These were inferred from membrane current changes after steps into lithium or IBMX solutions. There were also similar reductions in the integration times of dim flash responses for equivalent desensitizations produced by backgrounds and bleaches. These results suggest that the equivalence between background and bleaching found psychophysically may arise at the very earliest stages of visual processing and that these two processes of desensitization have similar underlying mechanisms.

Adaptation, Physiological↗
PubMed1996

Enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin microcystin LR.

An isolated bacterium, identified as a new Sphingomonas species, was demonstrated to contain a novel enzymatic pathway which acted on microcystin LR, the most common cyanobacterial cyclic peptide toxin. Degradation of microcystin LR was mediated by at least three intracellular hydrolytic enzymes. The use of classic protease inhibitors allowed (i) the classification of these enzymes into general protease families and (ii) the in vitro accumulation of otherwise transient microcystin LR degradation products. The initial site of hydrolytic cleavage of the parent cyclic peptide by an enzyme that we designate microcystinase is at the 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda)-Arg peptide bond. Two intermediates of microcystin LR enzymatic degradation have been identified; one is linearized (acyclo-) microcystin LR, NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-Leu-beta-methylas partate-Arg-OH, and the other is the tetrapeptide NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-OH. The intermediate degradation products were less active than the parent cyclic peptide; the observed 50% inhibitory concentrations for crude chicken brain protein phosphatase were 0.6 nM for microcystin LR, 95 nM for linear LR, and 12 nM for the tetrapeptide. These linear peptides were nontoxic to mice at doses up to 250 micrograms/kg. Ring opening of the potent hepatotoxin microcystin LR by bacterial microcystinase effectively renders the compound nontoxic by dramatically reducing the interaction with the target protein phosphatase.

Amino Acid Sequence↗
PubMed1995

Light adaptation and the rising phase of the flash photocurrent of salamander retinal rods.

1. Both theory and analysis of photocurrents in retinal rods show that phosphodiesterase activity after a flash rises initially as a delayed ramp. 2. The effect of light adaptation on the flash-induced rise in phosphodiesterase activity deduced from photocurrent responses was investigated. 3. Background adaptation reduces the deduced rate of rise of phosphodiesterase activity. The effect is most prominent for bright backgrounds and moderate flashes. There is little reduction for bright flashes, even in bright backgrounds. There is no effect for weak backgrounds. 4. Light adaptation after bleaching visual pigment produces a reduction in the deduced rise of phosphodiesterase activity for all flashes. For bright flashes, the reduction is explained by the reduction in quantum catch. For moderate flashes, there is an extra reduction, similar to the reduction produced by the equivalent background. 5. The results provide support for the idea that a reduction in the amplification step of phototransduction functions as part of the mechanism of light adaptation in rods. The dependence on flash intensity of the background-induced reduction in phosphodiesterase activation could imply a feedback mechanism on the activation steps of phototransduction.

Adaptation, Ocular↗
PubMed1995

Bioaccumulation of paralytic shellfish poisoning (PSP) toxins from the cyanobacterium Anabaena circinalis by the freshwater mussel Alathyria condola.

The Australian freshwater mussel Alathyria condola accumulated high levels of paralytic shellfish poisoning (PSP) toxins when fed the neurotoxic cyanobacterium Anabaena circinalis, shown recently to contain high concentrations of C-toxins and gonyautoxins. Significant accumulation (>80 mu g/100 g of mussel flesh) was detected following 2-3 exposure to water containing 2 x 105 cells/ml A. circinalis. Only trace accumulation of PSP toxins was demonstrated over long-term (5 week) exposure at low concentration (c. 104 cells/ml). The relative abundance of C-toxins, gonyautoxins and saxitoxins in mussels generally matched the toxin profiles of the dietary A. circinalis, although there were differences in the GTX2/3 and C1/2 ratios with time, and an increase in abundance of decarbamoylgonyautoxins. Analysis of mussel tissues after 7 days, exposure to A. circinalis revealed that 96% of the toxins were accumulated in the viscera. As in marine waters, the bioaccumulation of PSP toxins in freshwater mussels may pose a health risk to humans and animals, especially in areas where seasonally decreasing water levels expose mussel beds to surface scums of toxic cyanobacteria.

Anabaena↗
PubMed1995

Sheep mortality associated with paralytic shellfish poisons from the cyanobacterium Anabaena circinalis.

This is the first report of sheep mortalities associated with paralytic shellfish poisons (PSPs) from the cyanobacterium Anabaena circinalis Rabenhorst. Fourteen sheep died within 150 m of a farm dam containing a dense bloom of A. circinalis. Extracts from both the cyanobacterium and small intestine from a dead ewe were analysed by high-performance liquid chromtography (HPLC) and found to contain PSPs. The toxin profiles of the cyanobacterium contained a high proportion of C-toxins (70%), whereas toxins in the small intestine content were dominated by gonyautoxin 5 (87%). This observation could be explained by desulfation of the C-toxins in the gut of the sheep. The LD100 of bloom material calculated from HPLC data was consistent with mouse bioassay data (12-25 mg/kg). The symptoms of affected sheep, mouse bioassay data, coupled with HPLC analysis of toxins from the bloom samples and the intestine contents, and the absence of other cyanobacterial alkaloid toxins, indicate that PSPs were responsible for the deaths of the sheep.

Animals↗
PubMed1995

Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome.

The hypoxaemia of hepatopulmonary syndrome, seen in severe chronic liver dysfunction, occurs as a result of precapillary pulmonary arterial dilatation and arteriovenous communications. These abnormalities contribute to the mismatch between ventilation and perfusion, and the right to left blood flow shunting. Nitric oxide (NO) is a powerful vasodilator concerned with the regulation of pulmonary vascular tone in man. Using a chemiluminescence analyser, we have measured endogenously produced NO in the exhaled air of three patients with the hepatopulmonary syndrome, six normoxaemic cirrhotic patients and six healthy volunteers. The subjects breathed NO-free air throughout the measurements. The molar rate of production of exhaled NO was raised almost threefold in the patients with hepatopulmonary syndrome compared with normal volunteers and with normoxaemic cirrhotic patients. Hypoxia per se, achieved in the normal volunteers by breathing a hypoxic gas mixture, reduced rather than increased the exhaled NO. One hepatopulmonary syndrome patient received an orthotopic liver transplant and achieved normoxaemia after 3 months. The exhaled NO also returned to normal. Increased pulmonary production of NO could contribute to the development of the hepatopulmonary syndrome.

Blood Gas Analysis↗
PubMed1994

Degradation of the cyanobacterial hepatotoxin microcystin by aquatic bacteria.

Bacterial degradation of the cyanobacterial cyclic peptide hepatotoxin microcystin was confirmed in natural waters and by isolated laboratory strains. Degradation of 1 mg L-1 microcystin LR typically began 2-8 days after addition to surface water samples. At concentrations greater than 1 mg L-1 there was an initial slow removal of microcystin LR, rather than a distinct lag (or conditioning) phase, before rapid degradation commenced. The lag phase was absent upon re-addition of microcystin LR to the water. Both single strains and mixed bacterial cultures capable of degrading microcystin LR were isolated from surface water samples. One single strain isolated was a gram-negative rod and appeared to be a Pseudomonas sp., although standard taxonomic tests have given inconclusive results. Degradative activity was mostly intracellular and equally active against microcystin LR and RR, but not against nodularin.

Biodegradation, Environmental↗