Search PubMed⌕ Search

Biomedical subjects

K Alexander

Publications and source records attributed to K Alexander.

At least 19 recordsLinked to original sources
PubMed2003

Influencing medication adherence among women with AIDS.

This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N = 174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44 = 3.1, p < 0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44 = 2.0, p > 0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88 = 5.97, p < 0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Synthesis and biological evaluation of clitocine analogues as adenosine kinase inhibitors.

Adenosine kinase (AK) is the primary enzyme responsible for adenosine metabolism. Inhibition of AK effectively increases extracellular adenosine concentrations and represents an alternative approach to enhance the beneficial actions of adenosine as compared to direct-acting receptor agonists. Clitocine (3), isolated from the mushroom Clitocybe inversa, has been found to be a weak inhibitor of AK. We have prepared a number of analogues of clitocine in order to improve its potency and demonstrated that 5'-deoxy-5'-amino-clitocine (7) improved AK inhibitory potency by 50-fold.

Adenosine Kinase↗
PubMed2001

Mechanism of termination of DNA replication of Escherichia coli involves helicase-contrahelicase interaction.

Using yeast forward and reverse two-hybrid analyses, we have discovered that the replication terminator protein Tus of Escherichia coli physically interacts with DnaB helicase in vivo. We have confirmed this protein-protein interaction in vitro. We show further that replication termination involves protein-protein interaction between Tus and DnaB at a critical region of Tus protein, called the L1 loop. Several mutations located in the L1 loop region not only reduced the protein-protein interaction but also eliminated or reduced the ability of the mutant forms of Tus to arrest DnaB at a Ter site. At least one mutation, E49K, significantly reduced Tus-DnaB interaction and almost completely eliminated the contrahelicase activity of Tus protein in vitro without significantly reducing the affinity of the mutant form of Tus for Ter DNA, in comparison with the wild-type protein. The results, considered along with the crystal structure of Tus-Ter complex, not only elucidate further the mechanism of helicase arrest but also explain the molecular basis of polarity of replication fork arrest at Ter sites.

Bacterial Proteins↗
PubMed2001

A single domain of the replication termination protein of Bacillus subtilis is involved in arresting both DnaB helicase and RNA polymerase.

The current models that have been proposed to explain the mechanism of replication termination are (i) passive arrest of a replication fork by the terminus (Ter) DNA-terminator protein complex that impedes the replication fork and the replicative helicase in a polar fashion and (ii) an active barrier model in which the Ter-terminator protein complex arrests a fork not only by DNA-protein interaction but also by mechanistically significant terminator protein-helicase interaction. Despite the existence of some evidence supporting in vitro interaction between the replication terminator protein (RTP) and DnaB helicase, there has been continuing debate in the literature questioning the validity of the protein-protein interaction model. The objective of the present work was two-fold: (i) to reexamine the question of RTP-DnaB interaction by additional techniques and different mutant forms of RTP, and (ii) to investigate if a common domain of RTP is involved in the arrest of both helicase and RNA polymerase. The results validate and confirm the RTP-DnaB interaction in vitro and suggest a critical role for this interaction in replication fork arrest. The results also show that the Tyr(33) residue of RTP plays a critical role both in the arrest of helicase and RNA polymerase.

Azides↗
PubMed2001

A new application for the Antoine equation in formulation development.

Characterization of formulation components in pre-formulation and formulation studies will be made easier if a rapid method to evaluate the evaporation characteristics of an ingredient in the formulation is developed. This study aims at providing a simple and rapid thermogravimetric method for estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero-order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 degrees C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in the literature, and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization (k macro) was determined to be 124,525+/-0.8, with units being reported in the S.I. system. The corresponding vapor-pressure plots were obtained for the remaining compounds and their Antoine constants calculated.

Algorithms↗
PubMed2001

Requirement for p27(KIP1) in retinoblastoma protein-mediated senescence.

In vivo and in vitro evidence indicate that cells do not divide indefinitely but instead stop growing and undergo a process termed cellular proliferative senescence. Very little is known about how senescence occurs, but there are several indications that the retinoblastoma protein (pRb) is involved, the most striking being that reintroduction of RB into RB(-/-) tumor cell lines induces senescence. In investigating the mechanism by which pRb induces senescence, we have found that pRb causes a posttranscriptional accumulation of the cyclin-dependent kinase inhibitor p27(KIP1) that is accompanied by an increase in p27(KIP1) specifically bound to cyclin E and a concomitant decrease in cyclin E-associated kinase activity. In contrast, pRb-related proteins p107 and p130, which also decrease cyclin E-kinase activity, do not cause an accumulation of p27(KIP1) and induce senescence poorly. In addition, the use of pRb proteins mutated in the pocket domain demonstrates that pRb upregulation of p27(KIP1) and senescence induction do not require the interaction of pRb with E2F. Furthermore, ectopic expression of p21(CIP1) or p27(KIP1) induces senescence but not the morphology change associated with pRb-mediated senescence, uncoupling senescence from the morphological transformation. Finally, the ability of pRb to maintain cell cycle arrest and induce senescence is reversibly abrogated by ablation of p27(KIP1) expression. These findings suggest that prolonged cell cycle arrest through the persistent and specific inhibition of cdk2 activity by p27(KIP1) is critical for pRb-induced senescence.

Carrier Proteins↗
PubMed2000

Rehabilitation of a person with severe traumatic brain injury.

A case study report of a long and intensive rehabilitation programme for a young woman after she sustained a severe diffuse axonal injury in a motor vehicle accident is described in detail. The purpose of this paper is to encourage specialist brain injury rehabilitation services to offer extended rehabilitation programmes to patients, even with very severe injuries. Significant functional improvements and enhanced quality of life frequently reward the high cost and hard work involved.

Accidents, Traffic↗
PubMed2000

The use of conjoint analysis to elicit community preferences in public health research: a case study of hospital services in South Australia.

AIMS: To demonstrate the use of conjoint analysis (CA) in public health research through a survey of the South Australian community about aspects of their public hospital services. METHODS: A series of focus groups determined the most important attributes in choice of hospital services. These were built into a CA survey, using the discrete choice approach. The survey was posted to a representative sample of 700 South Australians. Theoretical validity, internal consistency and non-response bias were all investigated. RESULTS: Some 231 individuals returned the questionnaire. The attribute, 'improvement in complication rates' was positively associated with choice of hospital. Three attributes were found to be negatively associated with such choice: 'waiting times for casualty', 'waiting times for elective surgery' and, anomalously, 'parking and transport facilities'. 'Travel time' and the cost attribute, 'Medicare levy' were not statistically significant. Trade-offs between the significant attributes were estimated, as were satisfaction or utility scores for different ways of providing hospital services. Results concerning internal consistency and internal validity were encouraging, but some potential for non-response bias was detected. CONCLUSION: A high premium is placed on the quality of hospital care and members of the community are prepared to choose between hospitals largely on the basis of outcomes and length of waiting times for elective surgery and in casualty. IMPLICATIONS: CA can yield potentially policy-relevant information about community preferences for health services.

Adult↗
PubMed2000

ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2, 3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties: I. In vitro characterization and acute antinociceptive effects in the mouse.

Adenosine (ADO) is an inhibitory neuromodulator that can increase nociceptive thresholds in response to noxious stimulation. Inhibition of the ADO-metabolizing enzyme adenosine kinase (AK) increases extracellular ADO concentrations at sites of tissue trauma and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. ABT-702 is a novel and potent (IC(50) = 1. 7 nM) non-nucleoside AK inhibitor that has several orders of magnitude selectivity over other sites of ADO interaction (A(1), A(2A), A(3) receptors, ADO transporter, and ADO deaminase). ABT-702 was 1300- to 7700-fold selective for AK compared with a number of other neurotransmitter and peptide receptors, ion channel proteins, neurotransmitter/nucleoside reuptake sites, and enzymes, including cycloxygenases-1 and -2. ABT-702 was equipotent (IC(50) = 1.5 +/- 0. 3 nM) in inhibiting native human AK (placenta), two human recombinant isoforms (AK(long) and AK(short)), and AK from monkey, dog, rat, and mouse brain. Kinetic studies revealed that AK inhibition by ABT-702 was competitive with respect to ADO and noncompetitive with respect to MgATP(2-). AK inhibition by ABT-702 was demonstrated to be reversible after 4 h of dialysis. ABT-702 is orally active and fully efficacious in reducing acute somatic nociception (ED(50) = 8 micromol/kg i.p.; 65 micromol/kg p.o.) in the mouse hot-plate assay. ABT-702 also dose dependently reduced nociception in the phenyl-p-quinone-induced abdominal constriction assay. The antinociceptive effects of ABT-702 in the hot-plate assay were blocked by the nonselective ADO receptor antagonist theophylline, and by the A(1)-selective antagonist cyclopentyltheophylline (10 mg/kg i.p.), but not by a peripherally selective ADO receptor antagonist 8-(p-sulfophenyl)-theophylline (50 mg/kg i.p.), by the A(2A)-selective antagonist 3, 7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) or the opioid antagonist naloxone (5 mg/kg i.p.). Thus, ABT-702 is a novel and potent non-nucleoside AK inhibitor that effectively reduces acute thermal nociception in the mouse by a nonopioid, non-nonsteroidal anti-inflammatory drug, ADO A(1) receptor-mediated mechanism.

Adenosine Kinase↗
PubMed2000

Part time GPs.

Explore the source record for details and available documents.

Australia↗
PubMed1999

Workday communication and ambulatory blood pressure: implications for the reactivity hypothesis.

Ambulatory blood pressure monitoring was used to investigate the cardiovascular correlates of naturally occurring interpersonal interactions. Participants were New York City traffic agents, who routinely engage in conflict-prone communication with the public under relatively fixed conditions. Talking with the public, supervisors, or coworkers was associated with levels of systolic and diastolic blood pressure and heart rate that exceeded a resting baseline. Blood pressure was higher when agents were talking to the public than when they were talking to coworkers or engaged in a noncommunicative work task. Systolic blood pressure response during communication was associated with the agent's mood. Blood pressure effects associated with communication appear to persist after the communication has ceased. Implications of these data for the reactivity hypothesis of the pathogenesis of cardiovascular disease are discussed.

Adult↗
PubMed1999

Primary prevention of childhood lead exposure: A randomized trial of dust control.

BACKGROUND: Dust control is recommended as one of the primary strategies to prevent or control children's exposure to residential lead hazards, but the effect of dust control on children's blood lead levels is poorly understood. OBJECTIVE: To determine the effectiveness of dust control in preventing children's exposure to lead, as measured by blood lead levels, during their peak age of susceptibility. DESIGN: A randomized, controlled trial. SETTING: Rochester, NY. PARTICIPANTS: A total of 275 urban children were randomized at 6 months of age, of whom 246 (90%) were available for the 24-month-old follow-up visit. INTERVENTIONS: Children and their families were randomly assigned to an intervention group (n = 140), which received cleaning equipment and up to eight visits by a dust control advisor, or a control group (n = 135). OUTCOME MEASURES: Geometric mean blood lead levels and prevalence of elevated blood lead levels (ie, >10 microg/dL, 15 microg/dL, and 20 microg/dL). RESULTS: At baseline, children's geometric mean blood lead levels were 2.9 microg/dL (95% confidence interval [CI] = 2.7, 3.1); there were no significant differences in characteristics or lead exposure by group assignment, with the exception of water lead levels. For children in the intervention group, the mean number of visits by a dust control advisor during the 18-month study period was 6.2; 51 (36%) had 4 to 7 visits, and 69 (49%) had 8 visits. At 24 months of age, the geometric mean blood lead was 7.3 microg/dL (95% CI = 6.6, 8.2) for the intervention group and 7.8 microg/dL (95% CI = 6.9, 8. 7) for the control group. The percentage of children with a 24-month blood lead >/=10 microg/dL, >/=15 microg/dL, and >/=20 microg/dL was 31% versus 36%, 12% versus 14%, and 5% versus 7% in the intervention and control groups, respectively. CONCLUSIONS: We conclude that dust control, as performed by families and in the absence of lead hazard controls to reduce ongoing contamination from lead-based paint, is not effective in the primary prevention of childhood lead exposure.

Dust↗
PubMed1999

Allosteric modulation and accelerated resensitization of human P2X(3) receptors by cibacron blue.

The activity of ATP as a fast neurotransmitter is mediated by the P2X family of ligand-gated ion channels. P2X receptor subtypes are subject to functional modulation by a diverse set of factors, including pH, divalent cations, and temperature. The human P2X(3) (hP2X(3)) receptor subunit is expressed primarily in sensory ganglia where it exists as either a homomultimeric receptor or, in combination with P2X(2), as a heteromultimeric receptor. This article describes the allosteric modulatory effect of the putative P2X receptor antagonist cibacron blue on the activity of recombinant hP2X(3) receptors. In 1321N1 cells expressing the hP2X(3) receptor, cibacron blue mediated a 3- to 7-fold increase in both the magnitude and the potency of ATP-activated Ca(2+) influx and transmembrane currents. The half-maximal concentration of cibacron blue required to mediate maximal potentiation (EC(50) = 1.4 microM) was independent of the agonist used to activate the hP2X(3) receptor. The nonselective P2 receptor antagonist PPADS (pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid) caused a rightward shift of the cibacron blue concentration-effect curve, whereas increasing concentrations of cibacron blue attenuated PPADS antagonism. In addition to potentiating the effects of ATP at the hP2X(3) receptor, cibacron blue also produced a 6-fold increase in the rate of hP2X(3) receptor recovery from desensitization (from T(1/2) = 15.9 to 2.6 min), as evidenced by its ability to restore ATP responsiveness to acutely desensitized receptors. Consistent with the properties of other ligand-gated ion channels, these results suggest that hP2X(3) receptor activity can be allosterically modulated by a ligand distinct from the endogenous agonist.

Adenosine Triphosphate↗
PubMed1999

Observations on medical device design, Part I: Current practice.

Medical devices must be designed and proven to be fit for the purpose that they were intended. Good design practice ensures this fitness for purpose and is reflected in the commercial success of products. This two-part article focuses on current industry design practice and proposes that there are significant benefits to be obtained by defining good design practice: better products and reduced development costs.

Equipment Design↗
PubMed1999

Observations on medical device design, Part II: Good practice.

Current guidance on design is inadequate. This second article in a two-part series presents a framework for good design practice that attempts to improve designers' awareness of manufacturing and validation issues. Seven design tactics, derived from observations of current industry practice and design literature, seek to encourage good practice and achieve safer, more profitable devices.

Equipment Design↗
PubMed1998

Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.

BACKGROUND: Administration of L-arginine improves nitric oxide (NO) formation and endothelium-dependent vasodilation in atherosclerotic patients. OBJECTIVES: We investigated in this double-blind, controlled study whether prolonged intermittent infusion therapy with L-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium-independent vasodilator prostaglandin E1, and control patients. METHODS: Thirty-nine patients with intermittent claudication were randomly assigned to receive 2 x 8 g L-arginine/day, or 2 x 40 microg prostaglandin E1 (PGE1)/day or no hemodynamically active treatment, for 3 weeks. The pain-free and absolute walking distances were assessed on a walking treadmill at 3 km/h, 12% slope, and NO-mediated, flow-induced vasodilation of the femoral artery was assessed by ultrasonography at baseline, at 1, 2 and 3 weeks of therapy and 6 weeks after the end of treatment. Urinary nitrate and cyclic guanosine-3', 5'-monophosphate (GMP) were assessed as indices of endogenous NO production. RESULTS: L-Arginine improved the pain-free walking distance by 230+/-63% and the absolute walking distance by 155+/-48% (each p < 0.05). Prostaglandin E1 improved both parameters by 209+/-63% and 144+/-28%, respectively (each p < 0.05), whereas control patients experienced no significant change. L-Arginine therapy also improved endothelium-dependent vasodilation in the femoral artery, whereas PGE1 had no such effect. There was a significant linear correlation between the L-arginine/asymmetric dimethylarginine (ADMA) ratio and the pain-free walking distance at baseline (r=0.359, p < 0.03). L-Arginine treatment elevated the plasma L-arginine/ADMA ratio and increased urinary nitrate and cyclic GMP excretion rates, indicating normalized endogenous NO formation. Prostaglandin E1 therapy had no significant effect on any of these parameters. Symptom scores assessed on a visual analog scale increased from 3.51+/-0.18 to 83+/-0.4 (L-arginine) and 7.0+/-0.5 (PGE1; each p < 0.05), but did not significantly change in the control group (4.3+/-0.4). CONCLUSIONS: Restoring NO formation and endothelium-dependent vasodilation by L-arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.

Aged↗