PubMed Health⌕ Search

Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 19 recordsLinked to original sources
PubMed1995

Kinetic disposition of xylene-based or aqueous formulations of deltamethrin applied to the dorsal mid-line of sheep and their effect on lice.

A xylene-based topical formulation of the synthetic pyrethroid insecticide deltamethrin was applied to the dorsal mid-line of 2 groups of 5 Merino sheep within 24 h after shearing. One group was free of ectoparasites and the second was infested with sheep body lice, Bovicola (Damalinia) ovis. A water-based deltamethrin formulation was applied to the dorsal mid-line of a third group of 5 Merinos which were infested with lice. Insecticide concentrations on the wool of the back, upper and lower body and in the skin and bloodstream were measured at regular intervals between 1 and 98 days after treatment. Movement of the deltamethrin from the back to the lower body occurred within 24 h on all 3 groups, but maximum concentrations took 4-5 days to develop on the fleece in sheep treated with the xylene-based formulation and 11 days in sheep treated with the water-based formulation. There was a significant difference in concentration of deltamethrin close to the dorsal mid-line between the groups treated with the different formulations. Overall, concentrations of deltamethrin were lower at all sites examined on the sheep treated with the water-based formulation. Levels of deltamethrin in the tip of the fleece were significantly greater than those in the base and there was little movement of deltamethrin down the staple. The concentration of deltamethrin in the skin was significantly lower than the concentration in the wool and fell below the amount required to kill lice fully susceptible to deltamethrin after 12 days. Deltamethrin levels in the blood were near the limits of detection in all groups at all observations, indicating that there was little absorption or re-distribution of deltamethrin via the bloodstream. Most lice were killed after 20 h of exposure in vitro, to wool samples collected between 1 and 14 days after treatment. However, many lice survived in samples containing the same concentration of deltamethrin, but collected between 16 and 98 days after treatment. Numbers of lice surviving increased with the sampling time after treatment, suggesting that the bio-availability of the deltamethrin changed as the insecticide aged in the fleece.

Animals↗
PubMed1995

Rhodococcus equi--an increasingly recognized opportunistic pathogen. Report of 12 cases and review of 65 cases in the literature.

Rhodococcus equi, a gram-positive, weakly acid-fast coccobacillus, initially isolated from horses, is becoming increasingly recognized as an important pathogen for immunosuppressed human hosts since the first human case was reported in 1967. A review of the English medical literature yielded 53 cases. During the last 11 years, the microbiology laboratories of the authors isolated the organism from 12 patients. Of the total 65 cases, 60 occurred in immunosuppressed patients with HIV infection, malignant neoplasms, or chronic immunosuppressive therapy. The lung is the most common primary site of infection. Typically, the lesion is densely infiltrated by histiocytes with multiple microabscesses. Intracellular gram-positive coccobacilli are easily demonstrated. R equi grows well on routine non-selective media at 35 degrees C. Previously, many cases may have been missed because the organism resembles oropharyngeal commensal diphtheroids. Clinical information with gram and Kinyoun strains on fresh isolates is helpful in recognizing the possibility of R equi infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL.

The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch.

Acid Anhydride Hydrolases↗
PubMed1994

H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response.

Microbial elicitors or attempted infection with an avirulent pathogen strain causes the rapid production of reactive oxygen intermediates. We report here that H2O2 from this oxidative burst not only drives the cross-linking of cell wall structural proteins, but also functions as a local trigger of programmed death in challenged cells and as a diffusible signal for the induction in adjacent cells of genes encoding cellular protectants such as glutathione S-transferase and glutathione peroxidase. Thus, H2O2 from the oxidative burst plays a key role in the orchestration of a localized hypersensitive response during the expression of plant disease resistance.

Blotting, Northern↗
PubMed1994

Oxygen sensitivity and metal ion-dependent transcriptional activation by NIFA protein from Rhizobium leguminosarum biovar trifolii.

The NIFA protein from Rhizobium leguminosarum biovar trifolii (R. trifolii) strain ANU843 lacks an N-terminal domain present in homologous NIFA proteins from other diazotrophs. The R. trifolii nifA gene product is unstable when expressed in Escherichia coli under both aerobic and microaerobic conditions. Stability is increased by fusion of additional amino acids to the N-terminus of the protein or by expression of nifA in sno mutant (presumed protease deficient) strains of E. coli. Transcriptional activation in vivo by R. trifolii NIFA decreases under aerobic growth conditions, or when cultures are depleted of metal ions. In sno mutant strains this decrease in activity reflects a loss of specific activity rather than proteolytic degradation, implying that R. trifolii NIFA requires metal ions for activity and is oxygen sensitive. The addition of 30 amino acids to the amino-terminus of R. trifoli NIFA results in an oxygen-tolerant protein, with metal ion-dependent activity. Metal ions are therefore not only required for oxygen sensing by R. trifolii NIFA but may play an additional role in determining NIFA structure or activity.

Amino Acid Sequence↗
PubMed1994

Spectrophotometric determination of acadesine (AICA-riboside) in plasma using a diazotization coupling technique with N-(1-naphthyl)ethylenediamine.

A simple spectrophotometric assay has been developed for determining concentrations of the new cardioprotective agent, acadesine (AICA-riboside), in human plasma. The method is adapted from the Bratton-Marshall (BMA) procedure for detection of primary aromatic amines. The assay was developed to measure concentrations of the drug in plasma during i.v. infusion to patients undergoing coronary artery bypass graft (CABG) surgery. The limit of quantitation of the assay is 0.25 microgram/ml using a 0.25 ml sample of plasma. Use of 96-well titer plates and reader can rapidly process many samples at one time. The colorimetric assay correlates well (r = 0.98) with a previously described high performance liquid chromatographic (HPLC) procedure in terms of range of quantitation, limit of quantitation, and precision.

Aminoimidazole Carboxamide↗
PubMed1993

The use of ampligen alone and in combination with ganciclovir and coumermycin A1 for the treatment of ducks congenitally-infected with duck hepatitis B virus.

Ampligen, a known immunomodulator and interferon inducer, was used alone and in combination with other antiviral agents to treat ducks congenitally-infected with duck hepatitis B virus. These antiviral agents included the conventional nucleoside analogue ganciclovir and the prokaryotic DNA gyrase B inhibitor coumermycin A1. When used alone, ampligen decreased the amount of serum and liver viral DNA, but had no effect on circulating duck hepatitis B surface antigen (DHBsAg). In combination with ganciclovir, the antiviral effect appeared at least additive with a greater inhibition of viral DNA replication within the liver. The combination of ampligen with coumermycin A1 also resulted in inhibition of viral replication but to a lesser extent than ampligen alone. When all three agents were used together, viral DNA replication was again inhibited, but as with previous treatment regimes, serum DHBsAg levels remained unchanged. At the end of the treatment period for all regimes, analysis of viral DNA forms in the liver showed that the viral relaxed circular and supercoiled DNA forms had persisted. Within 1 week of cessation of therapy, viral replication had often returned to pre-treatment levels. Interferon-like activity was detected in the sera of the majority of the treated ducks during the ampligen therapy, but no clear relationship between the presence of interferon and antiviral effect could be established. These observations in the duck hepatitis B model may provide a rational basis for the use of combinations of antiviral and immunomodulatory regimes for the management of chronic hepatitis B infection in man.

Aminocoumarins↗
PubMed1993

The function of the upstream region of the sigma 54-dependent Klebsiella pneumoniae nifL promoter is sensitive to DNA supercoiling.

The positive control protein NTRC activates transcription from the sigma 54-dependent nifL and glnAp2 promoters of Klebsiella pneumoniae by binding to upstream enhancer-like sequences and contacting downstream bound sigma 54-RNA polymerase via looping of the intervening DNA. In contrast to the glnAp2 promoter, the activity of the nifL promoter is very sensitive to changes in DNA supercoiling both in vivo and in vitro. We have shown previously that the downstream elements of the nifL promoter are involved in the supercoiling response. In this study we find that the upstream region of nifL influences the supercoiling response of a hybrid nifL-glnAp2 promoter both in vivo and in vitro, demonstrating that the nifL upstream region also confers supercoiling sensitivity. DNA supercoiling did not appear to influence binding of NTRC to its sites in the nifL upstream region, suggesting that another function of this region, most probably DNA loop formation, is sensitive to changes in DNA topology.

Bacterial Proteins↗
PubMed1992

DNA supercoiling response of the sigma 54-dependent Klebsiella pneumoniae nifL promoter in vitro.

Transcription from the sigma 54-dependent Klebsiella pneumoniae nifL and glnAp2 promoters is activated by the general nitrogen regulatory protein NTRC. Unlike the glnAp2 promoter, which is relatively insensitive to changes in DNA supercoiling, transcription from nifL in vitro in a chloride-based buffer is supercoiling-dependent at physiological salt concentrations. The replacement of chloride with an acetate-based buffer decreases the stringency of the nifL supercoiling response, but open complexes formed on linear nifL promoter DNA under these conditions are unstable and less extensive than those found on supercoiled (form I) DNA. We have introduced mutations in particular elements of the nifL promoter that increase its homology to glnAp2. At the wild-type nifL promoter, sigma 54-RNA polymerase makes only limited contacts with the promoter in the absence of NTRC. However, a G to T change at -26 (nifL74) allows the formation of a stable closed complex with sigma 54-holoenzyme on both linear and form I templates in the absence of the activator. The combination of C to T mutations at -3 and -1 (nifL18) increases the A+T rich nature of the melted region and stabilizes open complexes formed on linear DNA. Open complex formation as a function of superhelical density was assessed at each promoter. Formation of open complexes at glnAp2 peaks at -0.024 and declines at higher superhelical densities, whereas at the wild-type nifL promoter, open complex formation peaks at -0.067 and is not detectable at superhelical densities less than -0.032. Both the nifL74 and nifL18 mutations altered the supercoiling response, increasing the ability to form open complexes at low superhelical densities. The presence of the nifL74 and nifL18 mutations in combination further altered the response of the promoter to DNA supercoiling. These observations suggest that the promoter as a whole, and not any one promoter element, mediates the transcriptional response to DNA supercoiling.

Base Sequence↗
PubMed1992

The prokaryotic enhancer binding protein NTRC has an ATPase activity which is phosphorylation and DNA dependent.

The prokaryotic activator protein NTRC binds to enhancer-like elements and activates transcription in response to nitrogen limitation by catalysing open complex formation by sigma 54 RNA polymerase holoenzyme. Formation of open complexes requires the phosphorylated form of NTRC and the reaction is ATP dependent. We find that NTRC has an ATPase activity which is activated by phosphorylation and is strongly stimulated by the presence of DNA containing specific NTRC binding sites.

Adenosine Triphosphatases↗
PubMed1992

Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo.

The effects of extracts of five Australian Phyllanthus species (P. hirtellus, P. gunnii, P. gasstroemii, P. similis and P. tenellus), other plant extracts and the antiviral drug foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp) activity were compared. All 5 Phyllanthus species caused 50% inhibition at concentrations of dry weight between 350-800 micrograms/ml, which is comparable with the effect described for P. amarus on the DNAp of human and woodchuck hepatitis B viruses. Incubation of P. hirtellus with 100 ID50 DHBV neutralized infection. However, neither P. gasstroemi extract, given by intraperitoneal injection (i.p.) at a dose of 20 mg/kg 3 times per week to ducklings early in the incubation period, or P. hirtellus extract, given to established DHBV carrier ducklings, prevented or eliminated infection.

Animals↗
PubMed1992

Voluntary immunomodulation: a preliminary study.

This study explored the effects of relaxation and imagery procedures on the voluntary self-regulation of immune responses. Immune studies of 19 adults were made before and after a 45 minute intervention consisting of relaxation with imagery aimed at enhancing immune activity. A self-report measure of psychological distress was completed before each blood sample. Results indicate that the seven blood measures of immune functioning were measured with adequate reliability and consisted of two sets of immune parameters. A statistically significant increase in one of the mitogen measures and a marginally significant increase in one of the blood count measures was found following the relaxation/imagery procedure. Age, hypnotizability, and their interaction significantly predicted change on the set of blood count measures but not on the set of mitogen measures. As expected, level of subjective psychological distress generally decreased following the intervention. The methodological limitations of this study included limited sample size and absence of a control group.

Adult↗
PubMed1992

Streptomyces ATP nucleotide 3'-pyrophosphokinase and its gene.

Streptomyces ATP nucleotide 3'-pyrophosphokinase is an extracellular, ribosome-independent, and stringent factor-mimic ppGpp synthetase with an unusually broad acceptor spectrum. The gene-containing DNA fragments cloned from chromosomal DNA of a producer S. morookaensis into pIJ699 and pUC plasmids were found to express the active enzyme in the transformed S. lividans TK24 and enteric E. coli JM109 and nitrogen-fixing Klebsiella pneumoniae M5a1 and 5022, respectively. Base sequence of the structural gene and the deduced amino acid sequence exhibited little homology to those of E. coli stringent factor and related proteins. Growth retardation was seen in some transformants.

Base Sequence↗
PubMed1991

Influence of a mutation in the putative nucleotide binding site of the nitrogen regulatory protein NTRC on its positive control function.

A mutation, serine 170 to alanine, in the proposed ATP binding site of the activator protein NTRC prevents transcriptional activation at sigma 54-dependent promoters both in vivo and in vitro. The rate of phosphorylation of the mutant protein by NTRB and the stability of mutant NTRC-phosphate were similar to those of wild-type NTRC. The phosphorylated mutant protein shows only a slight decrease in affinity (around 2-fold) for tandem NTRC binding sites in the Klebsiella pneumoniae nifL promoter suggesting that the mutation primarily influences the positive control function of NTRC. Moreover the mutant protein is trans dominant to the wild-type protein with respect to transcriptional activation at both the glnAp2 and nifL promoters. In vitro footprinting experiments reveal that the mutant protein is unable to catalyse isomerisation of closed promoter complexes between sigma 54-RNA polymerase and the nifL promoter to open promoter complexes. However, the mutant protein retains the ability to increase the occupancy of the -24, -12 region by sigma 54-RNA polymerase, forming closed complexes at the nifL promoter, which are not detectable in the absence of NTRC. These data support a model in which the activator influences the formation of closed complexes at the nifL promoter in addition to its role in catalysing open complex formation.

Adenosine Triphosphate↗
PubMed1991

AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent.

AICA-riboside (5-amino-4-imidazole carboxamide ribonucleoside) is a novel adenosine-regulating agent that is currently being investigated for the treatment of ischemic heart disease. In a placebo-controlled, double-blind study in healthy men, we evaluated the safety and kinetics of the drug after oral and IV administration of 10, 25, 50, and 100 mg/kg doses. At each dose level, four subjects received active drug and two subjects received placebo with a 1-week wash-out period between the IV and oral doses. The drug was well tolerated at all dose levels with only mild and transient side effects reported in some instances by the subjects who received placebo and those patients who received the drug. The post-infusion plasma concentrations of AICA-riboside declined rapidly in a biphasic fashion, and the terminal elimination phase had a harmonic mean t1/2 beta of 1.4 hours. Total plasma clearance (CL), mean residence time (MRTIV), and volume of distribution at steady-state (VSS) were 2.5 L/hr/kg, 0.7 hr, and 1.6 L/kg, respectively. The drug was not protein bound, and there was rapid uptake and phosphorylation in RBCs to its 5'-monophosphate nucleotide. Renal clearance (CLR) was 0.2 L/hr/kg with only 8% of the IV dose excreted in the urine as intact AICA-riboside. Although there was a trend towards a decrease in CL with increasing dose, there were no significant differences (P greater than .05) in the mean estimates of t1/2 beta, CL, CLR, MRTIV and VSS associated with dose. The drug was poorly bioavailable (less than 5%) when administered orally in solution.

Administration, Oral↗
PubMed1991

Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections.

From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency.

Adolescent↗