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Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 91 records · Page 5Linked to original sources
PubMed1996

Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study.

OBJECTIVES: To determine whether patients with primary Sjögren's syndrome (SS), diagnosed according to San Diego criteria, had improvement in their laboratory or clinical features during treatment with hydroxychloroquine (6-7 mg/kg/day) for at least two years. METHODS: The study population included 50 consecutive patients with primary SS who were diagnosed according to San Diego criteria, and in whom hydroxychloroquine was suggested as treatment. This group included 10 patients who were early dropouts (side effects or desire not to take antimalarial drugs) and 40 patients who received drugs for at least two years (range 24-48 months). In a subset of SS patients, values for ESR (westergren) and quantitative immunoglobulins were available for comparison. Improvement with therapy was defined as: (a) > or = 20% improvement in variables of tear flow (Schirmer's test I) or corneal integrity (rose Bengal): (b) > or = 20% salivary function (flow rate); and (c) improvement in at least two of the following measures: physicians assessment of global disease activity by > or = 20%, patient assessment of improvement in pain or fatigue by > or = 20%, and ESR improved by > or = 20 mm/hr. RESULTS: In a retrospective study of SS patients who completed the trial, a significant improvement was noted in ocular symptoms (pain and dryness) in patients (55 and 57%) and improved corneal integrity (rose Bengal straining) in 53% of patients. The Schirmer's test was improved by > or = 2 mm/5 minutes in 50% in patients. Improvement was noted in oral symptoms (pain and dryness) in patients (57 and 60%) and salivary flow rate was increased in 82% of patients. In a subset of SS patients evaluated, the ESR improved by > or = 20 mm/hr in 17/32 patients (53%) and quantitative IgG level by > or = 20% in 8/13 patients (61%). Physician global assessment of overall patient status and patient assessment of overall status indicated improvement in over 62% of patients. CONCLUSION: In a retrospective study of patients fulfilling San Diego Criteria for SS, we found: (a) sustained improvement of local symptoms (painful eyes, painful mouth) and improvement of systemic manifestations (arthralgias and myalgias) after treatment with hydroxychloroquine 6-7 mg/kg/day over mean three-year follow-up; (b) laboratory analysis showed a significant improvement in their ESR and their quantitative IgG levels; (c) no significant late toxicity was observed in this study cohort. A prospective study of hydroxychloroquine in patients fulfilling San Diego criteria for SS is indicated.

Adolescent↗
PubMed1995

Signal-transduction pathways controlling light-regulated development in Arabidopsis.

All metazoan cells are able to make decisions about cell division or cellular differentiation based, in part, on environmental cues. Accordingly, cells express receptor systems that allow them to detect the presence of hormones, growth factors and other signals that manipulate the regulatory processes of the cell. In plants, an unusual signal-light-is required for the induction and regulation of many developmental processes. Past physiological and molecular studies have revealed the variety and complexity of plant responses to light but until recently very little was known about the mechanisms of those responses. Two major breakthroughs have allowed the identification of some photoreceptor signalling intermediates: the identification of photoreceptor and signal transduction mutants in Arabidopsis, and the development of single-cell microinjection assays in which outcomes of photoreceptor signalling can be visualized. Here, we review recent genetic advances which support the notion that light responses are not simply endpoints of linear signal transduction pathways, but are the result of the integration of a variety of input signals through a complex network of interacting signalling components.

Arabidopsis↗
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

Kinetic disposition of an emulsifiable concentrate formulation of deltamethrin applied to sheep in a plunge-dip and its effect on lice.

An emulsifiable concentrate formulation of the synthetic pyrethroid insecticide deltamethrin was applied in a plunge dip, 3 weeks after shearing, to a group of 5 Merino sheep infested with sheep body lice, Bovicola ovis. Deltamethrin concentrations on the wool were measured at regular intervals between 1 and 98 days after treatment and were not significantly different (P > 0.05) between sites on the dorsal mid-line, upper or lower flank. Levels in the tip of the fleece were significantly greater than those in the base, indicating that there was little movement of deltamethrin down the staple as the wool grew. Most lice were killed after 20 h of exposure in vitro to wool samples collected between 1 and 28 days after treatment. However, many lice survived in samples containing a similar concentration of deltamethrin, but collected between 35 and 98 days after treatment. Numbers of lice surviving increased with the sampling time after treatment, suggesting that the bioavailability of the deltamethrin changed as the insecticide aged in the fleece. Some transfer of deltamethrin occurred from treated to untreated sheep. The levels of deltamethrin were higher in sheep placed in contact with the treated group at 14 days after treatment than in those which were in contact from 43 days after treatment.

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

Blood product costing: relationship to price and clinical efficacy.

Detailed information is provided about primary product costing and price issues as they affect transfusion manufacturing practice and clinical transfusion practice. Product price is shown to have a crucial influence upon clinical practice and associated research. By focusing particularly upon cost-benefit analysis of blood product transfusion therapy a substantive conclusion is drawn that price should equal the associated manufacturing cost. Clinical outcome studies relate clinical efficacy to the manufacturing specification of the product, which should therefore determine the product cost. Thus, the true manufacturing cost is the sum of all the process activity costs that create the final product specification, e.g. red cell number+volume reduction+leucocyte reduction+microbiological safety, for processed red cells. Sometimes different product specifications may compete for a single activity cost, e.g. one-spin processing achieves volume reduction and leucocyte reduction for processed red cells but also plasma removal for protein fractionation. A method for understanding the relative clinical importance of different products is described, which guides the cost allocation process. Furthermore, for some products there is uncertainty about the clinical benefits of some components of the specification, e.g. leucocyte load and immunomodulation, and a method is described for ranking this quality-uncertainty level objectively. The optimal costing model must ensure that the product with the highest uncertainty ranking is assured a high degree of cost stability. These concepts prepare the way for a Quality Associated Costing model for blood products that correlates with clinical efficacy.

Blood Transfusion↗
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↗
PubMed1994

Purification and in vitro activities of the native nitrogen fixation control proteins NifA and NifL.

The prokaryotic enhancer-binding protein NifA stimulates transcription at a distance by binding to sequences upstream of nitrogen fixation (nif) promoters and catalyzing the formation of open promoter complexes by RNA polymerase containing the alternative sigma factor, sigma 54. The activity of NifA in vivo is modulated by the negative regulatory protein NifL in response to environmental oxygen and fixed nitrogen. To date, a detailed biochemical analysis of these proteins from the model diazotroph Klebsiella pneumoniae has been hindered by their insolubility. We have now purified NifA and NifL from Azotobacter vinelandii in their native form. NifA is competent in specific DNA binding, transcriptional activation, and response to negative regulation by NifL in vitro. In contrast to the conserved mechanism of phosphotransfer demonstrated by other two-component regulatory systems, our results support a model in which NifL regulates the activity of NifA via a protein-protein steric block interaction rather than a catalytic modification of NifA.

Azotobacter vinelandii↗
PubMed1993

Acadesine (AICA-riboside): disposition and metabolism of an adenosine-regulating agent.

Acadesine (AICA-riboside) is a purine nucleoside analog with anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. The safety, tolerance, and pharmacokinetics of the drug have previously been reported in this journal (J Clin Pharmacol 1991; 31:342-347). Recently, the authors studied the disposition and metabolism of acadesine in healthy males (n = 4) after a 15-minute intravenous infusion of 25 mg/kg of 2-14C-acadesine. The postinfusion total 14C concentrations in plasma declined in a multiexponential manner, and the terminal phase had an apparent t1/2 of about 1 week. Intact acadesine was only measurable for 2 hours after infusion. Total plasma clearance was 2.2 +/- 0.2 L/hour/kg, the acadesine blood/plasma ratio was unity, and plasma protein binding was negligible (approximately 1%). Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion. In whole blood, acadesine 5'-monophosphate was present in the red blood cells, and the nucleotide represented 30% of the total blood 14C at the end of the infusion. The nucleotide was confined to the RBCs and was not present in plasma. Urine and fecal recoveries over 2 weeks accounted for 48% of the total 14C dose, with 44% excreted in urine and 4% in feces. Only 5% of the dose was excreted in urine as intact acadesine. Uric acid was the major metabolite in urine together with small amounts of hypoxanthine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1993

How Tennessee finances Medicaid.

Tennessee is fortunate to have a comprehensive Medicaid program involving some 22 optional services, all financed through a combination of state revenues. These range from general state revenues to provider-donated funds, provider-specific taxes, and recently, a privilege tax. The state pays approximately $920 million to participate in Medicaid; the state's share generates $1.9 billion in federal dollars. The current system for financing the state's Medicaid program is unsustainable. Because Tennessee is relatively poor, legislators cannot afford to continue to increase its share of Medicaid expenditures at a rate 10 times greater than the general revenue increase from the entire state. To continue a comprehensive Medicaid program, Tennessee must move forward with alternative strategies to control Medicaid expenditures and manage resources.

Cost Control↗