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Biomedical subjects

Michael Johnson

Publications and source records attributed to Michael Johnson.

At least 19 recordsLinked to original sources
PubMed2026

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8 μg/m3 (5.9), and exposures ranged from 1.3 to 46.8 μg/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7 μg/m3, 0.1 μg/m3, and 0.7 μg/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9 μg/m3) performed poorly (R2 = 0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot↗
PubMed2006

Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by a convergent approach based on ring-closing metathesis.

A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce >400 kg of cyclized product.

Antiviral Agents↗
PubMed2006

The impact of improved wood-burning stoves on fine particulate matter concentrations in rural Mexican homes.

To evaluate the impact of improved wood burning stoves on indoor air pollution, 53 homes in a rural town in Michoacán, Mexico, were selected from a health intervention study and monitored before and after receiving improved wood-burning stoves. Fine particulate matter--particles with aerodynamic diameter less than 2.5 microm (PM(2.5))--concentrations were measured in the central plaza of the community and in three microenvironments in the home (next to the stove, in the kitchen away from the stove, and outdoor patio). Forty-eight hour mean PM(2.5) concentrations in homes that burned wood in open fires were 693 microg/m(3) (95% CI: 246-1338) near the stove, 658 microg/m(3) (95% CI: 67-1448) in the kitchen away from the stove, and 94 microg/m(3) (95% CI: 36-236) on the patio. Mean ambient 24-h concentrations in the main plaza of the community were 59 microg/m(3) (95% CI: 29-92). Paired measurements before and after the installation of the Patsari improved wood-burning stove indicate a median 71% reduction in PM(2.5) concentrations near the stove and 58% reductions in kitchen concentrations, whereas patio and main plaza concentrations remain unaffected. Only 44% of participants reported to use their Patsari stoves exclusively during the transition period. Even with the predominant mixed use of the Patsari stove with open fires, estimated daily average personal exposures to PM(2.5) were reduced by 50%.

Air Pollutants↗
PubMed2006

G-protein-coupled receptor microarrays for multiplexed compound screening.

Conventional assay methods for discovering and profiling drug-target interactions are typically developed on a target-by-target basis and hence can be cumbersome to enable and orchestrate. Herein the authors report a solid-state ligand-binding assay that operates in a multiplexed mode to report compound activity against a micorarray-configured panel of G-protein-coupled receptor (GPCR) targets. The pharmacological fidelity of the system is high, and its miniaturized "plug-and-play" format provides improved efficiency both in terms of execution time and reagent consumption. Taken together, these features make the system ideally suited to explore the structure-activity relationship of compounds across a broad region of target class space.

Drug Evaluation, Preclinical↗
PubMed2005

Functional GPCR microarrays.

This paper describes G-protein-coupled receptor (GPCR) microarrays on porous glass substrates and functional assays based on the binding of a europium-labeled GTP analogue. The porous glass slides were made by casting a glass frit on impermeable glass slides and then coating with gamma-aminopropyl silane (GAPS). The emitted fluorescence was captured on an imager with a time-gated intensified CCD detector. Microarrays of the neurotensin receptor 1, the cholinergic receptor muscarinic 2, the opioid receptor mu, and the cannabinoid receptor 1 were fabricated by pin printing. The selective agonism of each of the receptors was observed. The screening of potential antagonists was demonstrated using a cocktail of agonists. The amount of activation observed was sufficient to permit determinations of EC50 and IC50. Such microarrays could potentially streamline drug discovery by helping integrate primary screening with selectivity and safety screening without compromising the essential functional information obtainable from cellular assays.

Drug Evaluation, Preclinical↗
PubMed2005

Whole-genome allelotyping identified distinct loss-of-heterozygosity patterns in mucinous ovarian and appendiceal carcinomas.

PURPOSE: Mucinous adenocarcinoma of the ovary is one of the common histologic types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the differential diagnosis of metastatic mucinous carcinomas to the ovaries, particularly those originating from the appendix, remains challenging. The purpose of this study is to identify molecular biomarkers for mucinous ovarian adenocarcinoma and compare them with those of appendiceal origin. EXPERIMENTAL DESIGN: Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA isolated from 28 microdissected primary mucinous ovarian carcinomas and five appendiceal adenocarcinomas. Markers from high-loss regions were selected for further analysis on a total of 32 ovarian and 14 appendiceal cancers. RESULTS: High levels of LOH rates (>40%) were detected on chromosome arms 9p, 17p, and 21q in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar between high-grade and low-grade mucinous ovarian carcinoma cases but was significantly higher in ovarian versus appendiceal cases. In addition, LOH rates on five chromosomal loci were statistically different between ovarian and appendiceal carcinomas. CONCLUSION: A high frequency of LOH can be found in mucinous ovarian adenocarcinomas independent of grade. Despite histologic similarities between mucinous ovarian carcinomas and metastatic appendiceal carcinomas, they have distinct LOH profiles, which may be used for distinguishing the two diseases.

Adenocarcinoma, Mucinous↗
PubMed2005

Cytoplasmic phospholipase A2 levels correlate with apoptosis in human colon tumorigenesis.

Colon cancers often display perturbations in arachidonic acid metabolism, with elevated levels of cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) production frequently observed. Whereas COX-2 and PGE(2) are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death. To further explore how cancer cells exploit the progrowth actions of prostaglandins while suppressing the proapoptotic actions of intracellular arachidonic acid, we determined the cytoplasmic phospholipase A(2) (cPLA(2)) and COX-2 expression levels in a panel of human colon tumors by immunohistochemistry. Although high levels of cPLA(2) and COX-2 expression are predicted to facilitate maximal prostaglandin production, tumors frequently displayed a high-COX-2/low-cPLA(2) phenotype. The least represented phenotype was the high expression of cPLA(2), a characteristic predicted to generate the highest levels of intracellular arachidonic acid. The potential proapoptotic role of cPLA(2) was supported by a higher frequency of terminal deoxynucleotidyl transferase-mediated nick end labeling staining in cPLA(2)-positive tumors. Moreover, analysis of preneoplastic aberrant crypt foci from high-risk patients suggests that acquisition of the high-COX-2/low-cPLA(2) phenotype may arise at an early stage of colon carcinogenesis. We additionally inhibited cPLA(2) in HT-29 cells using antisense oligonucleotides. Our results indicate that cPLA(2) plays an important role in tumor necrosis factor alpha-induced apoptosis in human colon cancer cells. Our data further support the model in which colon cancer growth is favored when intracellular arachidonic acid levels are suppressed by inhibition of cPLA(2) or by a high-COX-2/low-cPLA(2) phenotype.

Apoptosis↗
PubMed2005

Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services.

The most effective means of preventing human immunodeficiency virus (HIV) infection is preventing exposure. The provision of antiretroviral drugs to prevent HIV infection after unanticipated sexual or injection-drug--use exposure might be beneficial. The U.S. Department of Health and Human Services (DHHS) Working Group on Nonoccupational Postexposure Prophylaxis (nPEP) made the following recommendations for the United States. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be HIV infected, when that exposure represents a substantial risk for transmission, a 28-day course of highly active antiretroviral therapy (HAART) is recommended. Antiretroviral medications should be initiated as soon as possible after exposure. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person of unknown HIV status, when such exposure would represent a substantial risk for transmission if the source were HIV infected, no recommendations are made for the use of nPEP. Clinicians should evaluate risks and benefits of nPEP on a case-by-case basis. For persons with exposure histories that represent no substantial risk for HIV transmission or who seek care >72 hours after exposure, DHHS does not recommend the use of nPEP. Clinicians might consider prescribing nPEP for exposures conferring a serious risk for transmission, even if the person seeks care >72 hours after exposure if, in their judgment, the diminished potential benefit of nPEP outweighs the risks for transmission and adverse events. For all exposures, other health risks resulting from the exposure should be considered and prophylaxis administered when indicated. Risk-reduction counseling and indicated intervention services should be provided to reduce the risk for recurrent exposures.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Teams in organizations: from input-process-output models to IMOI models.

This review examines research and theory relevant to work groups and teams typically embedded in organizations and existing over time, although many studies reviewed were conducted in other settings, including the laboratory. Research was organized around a two-dimensional system based on time and the nature of explanatory mechanisms that mediated between team inputs and outcomes. These mechanisms were affective, behavioral, cognitive, or some combination of the three. Recent theoretical and methodological work is discussed that has advanced our understanding of teams as complex, multilevel systems that function over time, tasks, and contexts. The state of both the empirical and theoretical work is compared as to its impact on present knowledge and future directions.

Adaptation, Psychological↗
PubMed2005

Pigeons' choices between fixed-interval and random-interval schedules: utility of variability?

Pigeons' choosing between fixed-interval and random-interval schedules of reinforcement was investigated in three experiments using a discrete-trial procedure. In all three experiments, the random-interval schedule was generated by sampling a probability distribution at an interval (and in multiples of the interval) equal to that of the fixed-interval schedule. Thus the programmed delays to reinforcement on the random alternative were never shorter and were often longer than the fixed interval. Despite this feature, the fixed schedule was not strongly preferred. Increases in the probability used to generate the random interval resulted in decreased preferences for the fixed schedule. In addition, the number of consecutive choices on the preferred alternative varied directly with preference, whereas the consecutive number of choices on the nonpreferred alternative was fairly constant. The probability of choosing the random alternative was unaffected by the immediately prior interval encountered on that schedule, even when it was very long relative to the average value. The results loosely support conceptions of a "preference for variability" from foraging theory and the "utility of behavioral variability" from human decision-making literatures.

Animals↗
PubMed2004

Molecular properties of adsorbates that affect the growth kinetics of archerite (KDP).

We explore the molecular properties of adsorbates that dramatically affect growth kinetics and morphology of the [100] face of archerite, also known as potassium dihydrogen phosphate (KH(2)PO(4) or KDP). Aqueous complexes of Al(III), Fe(III), and Cr(III) are known to affect KDP growth, albeit the actual step-pinning complex(es) is unknown. Using in situ atomic force microscopy (AFM), we measured changes in the growth rates of the [100] face of KDP with supersaturation in the presence of trace amounts of [Co(NH(3))(6)](3+), [Fe(CN)(6)](3-), eta(1)-[Co(NH(3))(5)HPO(4)](+), eta(2)-[Co(NH(3))(4)HPO(4)](+), eta(2)-[Co(NH(3))(4)P(2)O(7)H(2)](+), and [Rh(H(2)PO(4))(2)(H(2)O)(4)](+). Unlike in experiments using trivalent-metals, these complexes do not change stoichiometry or structure on the timescale of step motion, so that the actual molecular interactions that affect growth can be studied. Step velocity and morphology on the [100] face are unaffected by outer-sphere coordination complexes of either charge. Surprisingly, inner-sphere phosphatoammine complexes do not affect growth rates regardless of how the phosphate group is coordinated to the metal. However, doping the growth solution with [Rh(H(2)PO(4))(2)(H(2)O)(4)](+) results in profound step pinning, matching the behavior of KDP surfaces grown in the presence of Rh(III) after an equilibration period. Not only is an inner-sphere phosphate group needed to dock a trivalent metal to the step edge, but compatible hydrogen bonding of the remainder of the inner-sphere ligands with the bulk lattice is also essential.

Journal Article↗
PubMed2004

POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer.

DNA arrays are valuable tools in molecular biology laboratories. Their rapid acceptance was aided by the release of plans for a pin-spotting microarrayer by researchers at Stanford. Inkjet microarraying is a flexible, complementary technique that allows the synthesis of arrays of any oligonucleotide sequences de novo. We describe here an open-source inkjet arrayer capable of rapidly producing sets of unique 9,800-feature arrays.

DNA, Fungal↗
PubMed2004

Selection of functional mutations in the U5-IR stem and loop regions of the Rous sarcoma virus genome.

BACKGROUND: The 5' end of the Rous sarcoma virus (RSV) RNA around the primer-binding site forms a series of RNA secondary stem/loop structures (U5-IR stem, TpsiC interaction region, U5-leader stem) that are required for efficient initiation of reverse transcription. The U5-IR stem and loop also encode the U5 integrase (IN) recognition sequence at the level of DNA such that this region has overlapping biological functions in reverse transcription and integration. RESULTS: We have investigated the ability of RSV to tolerate mutations in and around the U5 IR stem and loop. Through the use of viral libraries with blocks of random sequence, we have screened for functional mutants in vivo, growing the virus libraries in turkey embryo fibroblasts. The library representing the U5-IR stem rapidly selects for clones that maintain the structure of the stem, and is subsequently overtaken by wild type sequence. In contrast, in the library representing the U5-IR loop, wild type sequence is found after five rounds of infection but it does not dominate the virus pool, indicating that the mutant sequences identified are able to replicate at or near wild type levels. CONCLUSION: These results indicate that the region of the RNA genome in U5 adjacent to the PBS tolerates much sequence variation even though it is required for multiple biological functions in replication. The in vivo selection method utilized in this study was capable of detecting complex patterns of selection as well as identifying biologically relevant viral mutants.

Avian Sarcoma Viruses↗
PubMed2004

AANA journal course. Update for nurse anesthetists. 2. Anticoagulation and spinal and epidural anesthesia.

An increasing number of surgical patients preoperatively are taking anticoagulant medications. These patients are at an increased risk for development of epidural hematoma with spinal or epidural anesthesia. It is the responsibility of the anesthesia provider to understand and anticipate this risk and to alter the anesthetic plan accordingly. The purpose of this AANA Journal course is to update anesthesia providers regarding the common anticoagulants used for surgical patients, the risks associated with epidural and spinal anesthesia in conjunction with anticoagulation, and recommendations for the use of epidural and spinal anesthesia in anticoagulated patients. Antiplatelet drugs, oral anticoagulants, heparin, low-molecular-weight heparin, other new anticoagulants, and herbal medications are reviewed. When spinal or epidural anesthesia is considered for a patient who has been taking anticoagulant medications, the risk of epidural hematoma vs the benefits of regional anesthesia must be weighed carefully. Appropriate management of the patient extends well into the postoperative period and should include anesthesia providers, attending physicians, and nurses.

Anesthesia, Epidural↗
PubMed2003

Cardiac enkephalins attenuate vagal bradycardia: interactions with NOS-1-cGMP systems in canine sinoatrial node.

Endogenous opioids and nitric oxide (NO) are recognized modulators of cardiac function. Enkephalins and inhibitors of NO synthase (NOS) both produce similar interruptions in the vagal control of heart rate. This study was conducted to test the hypothesis that NO systems within the canine sinoatrial (SA) node facilitate local vagal transmission and that the endogenous enkephalin methionine-enkephalin-arginine-phenylalanine (MEAP) attenuates vagal bradycardia by interrupting the NOS-cGMP pathway. Microdialysis probes were inserted into the SA node, and they were perfused with nonselective (Nomega-nitro-l-arginine methyl ester) and neuronal (7-nitroindazole) NOS inhibitors. The right vagus nerve was stimulated and both inhibitors gradually attenuated the resulting vagal bradycardia. The specificity of these inhibitions was verified by an equally gradual reversal of the inhibition with an excess of the NOS substrate l-arginine. Introduction of MEAP into the nodal interstitium produced a quickly developing but quantitatively similar interruption of vagal bradycardia that was also slowly reversed by the addition of l-arginine and not by d-arginine. Additional support for convergence of opioid and NO pathways was provided when the vagolytic effects of MEAP were also reversed by the addition of the NO donor S-nitroso-N-acetyl-penicillamine, the protein kinase G activator 8-bromo-cGMP, or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. MEAP and 7-nitroindazole were individually combined with the direct acting muscarinic agonist methacholine to evaluate potential interactions with muscarinic receptors within the SA node. MEAP and 7-nitroindazole were unable to overcome the bradycardia produced by methacholine. These data suggest that NO and enkephalins moderate the vagal control of heart rate via interaction with converging systems that involve the regulation of cAMP within nodal parasympathetic nerve terminals.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Rapid oxidation of sulfide mine tailings by reaction with potassium ferrate.

The chemistry of sulfide mine tailings treated with potassium ferrate (K2FeO4) in aqueous slurry has been investigated. The reaction system is believed to parallel a geochemical oxidation in which ferrate ion replaces oxygen. This chemical system utilized in a pipeline (as a plug flow reactor) may have application eliminating the potential for tailings to leach acid while recovering the metal from the tailings. Elemental analyses were performed using an ICP spectrometer for the aqueous phase extract of the treated tailings; and an SEM-EDX for the tailing solids. Solids were analyzed before and after treatments were applied. ICP shows that as the mass ratio of ferrate ion to tailings increases, the concentration of metals in the extract solution increases; while EDX indicates a corresponding decrease in sulfur content of the tailing solids. The extraction of metal and reduction in sulfide content is significant. The kinetic timeframe is on the order of minutes.

Chemical Precipitation↗
PubMed2003

The relationship between nucleoside triphosphate hydrolase (NTPase) isoform and Toxoplasma strain virulence in rat and human toxoplasmosis.

Avirulent strains of Toxoplasma gondii possess only the nucleoside triphosphate hydrolase II (NTPaseII) isoform, whilst virulent strains possess both NTPaseI and NTPaseII. To determine if it is possible to identify the infective strain type (virulent or avirulent) in T. gondii infections by serological methods, we developed isoform-specific peptide ELISAs from the NTPaseI and NTPaseII antigens of T. gondii. When rats were immunized with either recombinant NTPaseI or NTPaseII, the ELISA could differentially identify antibody reactivity to each NTPase isoform. This ELISA was then used to test six groups of rats that were infected with either one of three virulent (RH, P or Ent) or three avirulent (Me49, C or TPR) strains of T. gondii. No differential antibody reactivity was detected by either whole recNTPase ELISA or peptide ELISA in the sera of rats, whether infected by virulent or avirulent strains of T. gondii. We also studied a panel of human sera from patients infected with known laboratory strains of T. gondii or naturally infected patients where the parasite was isolated and its virulence determined in mice. Differential reactivity to whole recNTPase isoforms was detected in some human sera, but this reactivity was not detected by the isoform-specific peptide ELISAs. Although the NTPase peptides do exhibit differential antibody reactivity, this is not correlated with the virulence status of the infecting strain.

Acid Anhydride Hydrolases↗