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At least 19 recordsLinked to original sources
PubMed2001

Cardioselective beta-blocker use in patients with reversible airway disease.

BACKGROUND: Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease. OBJECTIVES: To assess the effect of cardioselective beta-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component. SEARCH STRATEGY: A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to February, 2000. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language. SELECTION CRITERIA: Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta-agonist administration, or the presence of asthma as defined by the American Thoracic Society. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta-agonist given after the study drug. MAIN RESULTS: Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta-agonist response compared to placebo, a response not seen with beta-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]). REVIEWER'S CONCLUSIONS: Cardioselective beta-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be withheld from patients with mild-moderate reversible airway disease.

Acebutolol↗
PubMed1997

The structures and relative stabilities of d(G x G) reverse Hoogsteen, d(G x T) reverse wobble, and d(G x C) reverse Watson-Crick base-pairs in DNA crystals.

We have solved the structures of the homoduplex d(Gm5CGCGCG)2, and the heteroduplexes d(GCGCGCG)/d(TCGCGCG) and d(GCGCGCG)/d(CCGCGCG). The structures form six base-pairs of identical Z-DNA duplexes with single nucleotides overhanging at the 5'-ends. The overhanging nucleotide from one strand remains stacked and sandwiched between the blunt-ends of two adjacent Z-DNA duplexes, while the overhanging base of the opposing strand is extra-helical. The stacked and the extra-helical bases from adjacent duplexes pair to form a distorted d(G x G) reverse Hoogsteen base-pair in the d(Gm5CGCGCG)2 homoduplex, and d(G x T) reverse wobble and d(G x C) reverse Watson-Crick base-pairs in the d(GCGCGCG)/d(TCGCGCG) and d(GCGCGCG)/d(CCGCGCG) heteroduplexes, respectively. Interestingly, only the d(G,T) and d(G x C) base-pairs were observed in the heteroduplexes, suggesting that both the d(G x T) reverse wobble and d(G x C) reverse Watson-Crick base-pairs are more stable in this crystal environment than the d(G x G) reverse Hoogsteen base-pair. To estimate the relative stability of the three types of reverse base-pairs, crystals were grown using various mixtures of sequences and their strand compositions analyzed by mass spectrometry. The d(G x C) reverse Watson-Crick base-pair was estimated to be more stable by approximately 1.5 kcal/mol and the d(G x T) reverse wobble base-pair more stable by approximately 0.5 kcal/mol than the d(G x G) reverse Hoogsteen base-pair. The step during crystallization responsible for discriminating between the strands in the crystal is highly cooperative, suggesting that it occurs during the initial nucleating event of crystal growth.

Computer Simulation↗
PubMed1994

Biocatalysis in reverse self-assembling structures: reverse micelles and reverse vesicles.

The use of two reverse self-assembling systems, such as reverse micelles and reverse vesicles, to model the enzymatic function of biological membranes is discussed. They permit direct measurement of enzyme kinetics since these ternary systems form optically transparent solutions. The physicochemical characteristics of both systems are differentiated since they clearly affect enzyme behavior. The four enzymatic profiles that have been described in reverse micelles as a function of micelle size (omega 0) and the kinetic models developed to explain them are discussed. Reverse vesicles, first described in 1991, are also presented as a new system that shares properties with reverse micelles and liposomes, and in which enzymes show unexpected behavior. Finally, the potential use of these systems in protein extraction, hydrophobic protein stabilization, and biotechnology are noted, although a better physicochemical characterization is needed in order to explore their full potential.

Catalysis↗
PubMed1991

Reversal of rapid axonal transport at a lesion: leupeptin inhibits reversed protein transport, but does not inhibit reversed organelle transport.

The hypothesis that the reversal of rapid axonal transport requires a proteolytic conversion of anterograde transport vesicles was examined using sciatic nerve preparations from Xenopus laevis and leupeptin as an inhibitor of proteolysis. The transport of newly synthesized 35S-labeled proteins was studied with a position-sensitive detector of radiation. Organelle transport in isolated myelinated axons was studied by video microscopy. Leupeptin (0.1-0.4 mM) reduced the anterograde-to-retrograde reversal of protein transport adjacent to an axonal lesion. In experiments in which organelle transport was observed close to lesions in axons maintained in a medium compatible with intracellular function, 1.0 mM leupeptin inhibited neither the anterograde-to-retrograde nor the retrograde-to-anterograde reversal of organelle transport. In addition, in experiments in which conditions approximated those used to study protein transport, organelle transport away from the lesion was not inhibited by 1.0 mM leupeptin. A comparison of the morphology of rapidly transported organelles that underwent anterograde transport to the morphology of those that returned from a lesion (with or without the presence of leupeptin) provided no evidence that a morphological conversion was a necessary step in transport reversal.

Animals↗
PubMed1988

Mutated forms of phosphoglycerate mutase in yeast affect reversal of metabolic flux. Effect of reversible and irreversible function of an enzyme on pathway reversal.

Phosphoglycerate mutase (GPM) functions reversibly in the glycolytic pathway. Mutations altering the reversibility of GPM have been obtained in the yeast, Saccharomyces cerevisiae. While wild-type cells grow on glycolytic (glucose) or gluconeogenic (ethanol) substrates, cells with altered GPMs fall into three categories based on their phenotypes 1) glucose- ethanol-, 2) glucose+ ethanol-, and 3) glucose- ethanol+. Cells with the first two phenotypes possessed GPMs that functioned irreversibly in the glycolytic direction. Cells that were glucose- ethanol+ possessed an enzyme that functioned reversibly. All of the altered GPMs had maximal velocities that were less than 3% of the wild-type level. The properties of the altered GPMs studied here provide a rationale for the occurrence in the glycolytic pathway of several glycolytic enzymes such as GPM, which function at high velocities in relation to the much smaller metabolic flux that they support. The altered GPMs were purified and estimates of their kinetic constants obtained. Free energy profiles were drawn for catalysis by the wild type and a mutant GPM that functioned irreversibly. The mutant enzyme was very inefficient. It was shown that an enzyme that functions irreversibly at a reaction with a Keq value close to 1 would necessarily be inefficient while it could evolve to be efficient when catalyzing a reaction that has a Keq value much greater than 1. In the glycolytic path this could be the reason for the characteristic presence of enzymes that function irreversibly at reactions with large Keq values.

Algorithms↗
PubMedDate not supplied

To reverse or not to reverse: an evaluation of reversal of mivacurium chloride in women undergoing outpatient gynecological procedures.

BACKGROUND: A double-blind, randomized study compared differences between patients administered edrophonium and those administered placebo after mivacurium infusion. Neuromuscular blockade was quantified using the ParaGraph 1800 nerve stimulator-monitor (Vital Signs, Totowa, NJ), which can deliver a train-of-four stimulus to the ulnar nerve and quantify the ratio of the fourth twitch to the first twitch. METHODS: With Investigational Review Board approval and informed consent, 30 healthy outpatient gynecological surgery patients ASA I or II, aged 21 to 37 years, were randomly assigned to treatment or placebo. In a double-blind manner, one group received edrophonium (1 mg/kg) and atropine (0.01 mg/kg) reversal (E/A) and the other group received placebo (P) to recover spontaneously from a mivacurium infusion. Anesthesia was induced and a rapid infusion of mivacurium chloride (0.2 mg/kg) was administered. An infusion of mivacurium chloride was then initiated at a rate of 6-7 microg/kg/min to maintain neuromuscular blockade. Group differences in recovery time (time between administration of the edrophonium or placebo and a 5-second head lift followed by tracheal extubation) were compared, as was time from tracheal extubation to discharge from the postanesthesia care unit (PACU). Nausea and vomiting were documented until the patient was discharged from the hospital; a 24-hour follow-up evaluation was completed by telephone. RESULTS: Each group contained 15 patients, and their demographics were similar. The mean recovery time for E/A was statistically shorter than for P (P, 9.7 +/- 4.8 minutes; E/A, 6.1 +/- 3.9 minutes; p = 0. 017). There were no statistically significant differences found in the incidence of nausea and vomiting (P, 4; E/A, 6) or in time to discharge from the PACU. CONCLUSION: Recovery from a mivacurium chloride infusion is shorter by 3.6 minutes (margin of error +/- 3.3 minutes) when reversal with edrophonium/atropine is used. There is no difference in time to discharge from PACU and no evidence of differences in nausea and vomiting.

Adult↗
PubMed1999

Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype.

OBJECTIVES: To study the effect of the interruption of reverse transriptase inhibitor (RTI) therapy or a switch from RTI to protease inhibitors, on the genotypic drug-resistance pattern of plasma HIV-1. METHODS: Nine patients who completely stopped all medication, and five patients who switched from a treatment with RTI to a regimen containing protease inhibitors only, were studied. Direct sequencing of the plasma HIV-1 RT and protease gene was performed on follow-up samples taken before and after the interruption of treatment. RESULTS: Comparison of the amino acid sequence of the RT and protease genes in successive samples showed the rapid reappearance of wild-type viral variants in 12 of the 14 patients studied. Wild-type virus replaced the mutant strains 14 days to 2 months after the interruption of therapy, even in patients with a long treatment history. CONCLUSION: The results of this study indicate the sustained lower fitness of mutant strains in vivo. As a result, wild-type virus remains capable of outcompeting the RT or protease mutant strains very fast after removal of the drug. These findings highlight the importance of 'treatment history' in addition to genotypic and phenotypic markers determined at one time-point, when making therapeutic decisions for patients.

Amino Acid Substitution↗
PubMed1998

Group II intron mobility in yeast mitochondria: target DNA-primed reverse transcription activity of aI1 and reverse splicing into DNA transposition sites in vitro.

The retrohoming of the yeast mtDNA intron aI1 occurs by a target DNA-primed reverse transcription (TPRT) mechanism in which the intron RNA reverse splices directly into the recipient DNA and is then copied by the intron-encoded reverse transcriptase. Here, we carried out biochemical characterization of the intron-encoded reverse transcriptase and site-specific DNA endonuclease activities required for this process. We show that the aI1 reverse transcriptase has high TPRT activity in the presence of appropriate DNA target sites, but differs from the closely related reverse transcriptase encoded by the yeast aI2 intron in being unable to use artificial substrates efficiently. Characterization of TPRT products shows that the fully reverse spliced intron RNA is an efficient template for cDNA synthesis, while reverse transcription of partially reverse spliced intron RNA is impeded by the branch point. Novel features of the aI1 reaction include a prominent open-circular product in which cDNAs are incorporated at a nick at the antisense-strand cleavage site. The aI1 endonuclease activity, which catalyzes the DNA cleavage and reverse splicing reactions, is associated with ribonucleoprotein particles containing the intron-encoded protein and the excised intron RNA. As shown for the aI2 endonuclease, both the RNA and protein components are used for DNA target site recognition, but the aI1 protein has less stringent nucleotide sequence requirements for the reverse splicing reaction. Finally, perhaps reflecting this relaxed target specificity, in vitro experiments show that aI1 can reverse splice directly into ectopic mtDNA transposition sites, consistent with the previously suggested possibility that this mechanism is used for ectopic transposition of group II introns in vivo.

DNA, Fungal↗
PubMed1999

Differences in top-down influences on the reversal rate of different categories of reversible figures.

Understanding the mechanisms underlying the multistability of reversible figures may provide valuable insights into the normal functioning of our visual system. The proposed factors that control the perceptual alternations of reversible figures can be classified into bottom-up and top-down processes. In the present study, we report differences in top-down effects on the reversal rate depending on whether a structural perspective (Necker cube, Schröder staircase) or a meaningful content (duck/rabbit figure, chef/dog figure) is subject to the reversal phenomenon. In order to activate top-down mechanisms explicitly the subjects had the instruction to bring the reversal rate under voluntary control. The results indicated that both slowing down and speeding up the rate of alternations was more effective for the content-reversal figures (duck/rabbit, chef/dog) than for the rather abstract perspective-reversal figures (Necker cube, Schröder staircase). In order to investigate the effect of meaningfulness in figure/ground reversals, the effect of the same instructional variable was also determined for Rubin's vase/faces and the Maltese cross. The results showed a similar tendency as in the case of the comparison between perspective reversals and content reversals. Possible cognitive processes that may play a role in top-down influences on figure reversal and theoretical implications of these findings for the interaction of bottom-up and top-down processes are discussed.

Analysis of Variance↗
PubMed2003

Sterilization failure, sterilization reversal, and pregnancy after sterilization reversal in Quebec.

OBJECTIVE: 1). To determine the likelihood of sterilization reversal and of subsequent sterilization after sterilization reversal among men and women and 2). to examine the likelihood of pregnancy after sterilization (contraceptive failure) and of pregnancy after sterilization reversal. METHODS: Payment data from the Quebec provincial health insurance system were obtained for each person undergoing vasectomy or female sterilization from January 1, 1980 to December 31, 1999 and linked through a unique identifying number for each person. Using standard techniques of survival analysis, we computed the cumulative probability of experiencing each of six events. RESULTS: Among women, 0.9% (of 311960) experienced a pregnancy after sterilization, 1.8% (of 321929) obtained a reversal after sterilization, 61% (of 4369) achieved a pregnancy after sterilization reversal and 48% achieved a delivery; 23% (of 4677) obtained a subsequent sterilization after reversal. Among men, 2.4% (of 310827) obtained a reversal after vasectomy and 18% (of 6694) obtained a subsequent vasectomy after reversal. All of these risks were much higher among those in the youngest age groups. CONCLUSION: Sterilization reversal and pregnancy after sterilization are not rare. Relatively high rates of reversal among the youngest age groups suggest a need for better counseling about alternative contraceptive strategies.

Adolescent↗
PubMed1986

The nature of reversible and not readily reversible bovine corpus luteum plasma membranes bound human chorionic gonadotropin.

125I-human chorionic gonadotropin (125I-hCG) bound to plasma membranes of bovine corpora lutea consisted of reversible and not readily reversible fractions. The not readily reversible fraction progressively increased as the length and the temperature of preincubation were increased. The not readily reversible fraction was, however, completely eluted after any time or temperature of preincubation. Although the not readily reversible and reversible bound 125I-hCG were precipitated equally well with 10% trichloroacetic acid, the not readily reversible bound 125I-hCG was able to rebind much higher to fresh plasma membranes compared to reversible bound 125I-hCG. These findings suggest that while not readily reversible bound 125I-hCG was intact, the reversible bound 125I-hCG was somewhat altered during the binding reaction.

Animals↗
PubMedDate not supplied

Morphologic changes in human immunodeficiency virus type 1 virions secondary to intravirion reverse transcription: evidence indicating that reverse transcription may not take place within the intact viral core.

INTRODUCTION: In the past, retroviral endogenous reverse transcription (ERT) was considered an artificial process, secondary to permeabilization of the viral envelope by detergents or amphipathic peptides. However, recently we have demonstrated that ERT may occur in a variety of lentiviruses without detergent treatment and may lead to increased infectivity of lentivirions in initially quiescent T lymphocytes and nonproliferating cells, such as macrophages. As full-length reverse transcripts could be synthesized within lentiviral particles, it is worth evaluating the potential alterations in lentiviral morphology due to the stimulation of intravirion reverse transcription. METHODS: Using quantitative DNA-polymerase chain reaction (PCR) and transmission electron microscopy (TEM), we characterized critical alterations in human immunodeficiency virus type 1 (HIV-1) virions after stimulation of intravirion reverse transcription. RESULTS: Intravirion reverse transcription in HIV-1 virions was stimulated using deoxyribonucleoside triphosphates (dNTPs) and physiologic polyamines. Our studies indicated that HIV-1 virions, in which intravirion reverse transcription was stimulated, showed dissolution of the p24-shelled viral core and absence of the core-envelope linkage (CEL) region by TEM. These changes in the structure of the core correlate with the in vitro alterations in virion infectivity on primary cells. CONCLUSIONS: Stimulation of intravirion HIV-1 reverse transcription leads to morphologic changes in the viral particles that suggest changes in the compact viral core, which is consistent with active reverse transcription before infection of target cells. Further, via this unique approach, we suggest that intravirion or intracellular reverse transcription of HIV-1 is unlikely to take place within intact viral cores made up of p24-containing outer shells. As such, these results suggest a new approach to further dissect the intravirion or intracellular reverse transcription machinery of lentiviruses.

DNA, Viral↗
PubMed1996

Kinetic analysis of intravirion reverse transcription in the blood plasma of human immunodeficiency virus type 1-infected individuals: direct assessment of resistance to reverse transcriptase inhibitors in vivo.

Intravirion reverse transcripts have been identified in the blood plasma of human immunodeficiency virus type 1 (HIV-1)-infected individuals. In the present studies, the kinetic processes of intravirion HIV-1 reverse transcription, in the blood plasma of HIV-1-infected persons treated with nevirapine, were investigated. Nevirapine is a nonnucleoside inhibitor of reverse transcriptase (RT) which decreases the level of HIV-1 viral particles in the blood plasma of infected individuals. By analyzing HIV-1 virions at different time points prior to and after initiation of nevirapine therapy in vivo, the levels of intravirion reverse transcripts have been demonstrated to be dramatically susceptible to this anti-RT agent, out of proportion to effects on plasma virion load. The intravirion reverse transcripts were also documented to rebound to the pretreatment levels, concomitant with the development of resistant viral mutants. In addition, the infectivity of HIV-1 virions dramatically decreased after nevirapine treatment, further indicating that the effects of this anti-RT agent begin within the cell-free virions. Since the levels of intravirion reverse transcripts were altered according to the susceptibility or resistance of the HIV-1 RT enzyme to this inhibitor, these data demonstrate that the formation of intravirion reverse transcripts is a dynamic process in vivo. Moreover, because the alteration in ratios between intravirion HIV-1 reverse transcripts and viral genomic RNA directly reflects the efficiency of reverse transcription, we propose that the determination of these ratios in the blood plasma of HIV-1-positive patients may be a useful and, most importantly, a direct assay to monitor the efficacy of anti-RT agents in vivo.

Base Sequence↗
PubMed1981

Reversibility of the transformed and neoplastic phenotype. I. Progressive reversion of the phenotype of X-ray-transformed C3H/10T1/2 cells under prolonged treatment with interferon.

X-ray transformed mouse C3H/10T1/2 cells were cultivated and passaged in the continuous presence of partially purified mouse interferon. This prolonged interferon treatment resulted in a stepwise progressive reversion of the transformed phenotype to the non-transformed phenotype. Thus interferon-treated cells displayed an epithelioid morphology, grew to a lower cell density, and were no longer tumorigenic. Reversion to the non-transformed phenotype was, however, stable only as long as interferon was continuously present in the culture medium. When interferon was removed, the cells "back reverted" to the transformed phenotype. Our results suggest that interferon induced a reversion of the transformed phenotype in the entire cell population rather than a selection of an interferon resistant cell population. C-type viral particles and significant levels of reverse transcriptase were present in transformed cells, but neither present in the parental 10T1/2 cells nor in interferon-treated cells. When interferon was removed form the culture medium, viral particles and reverse transcriptase activity were again detected. It is possible, therefore, that interferon induces reversion through its antiviral activity, or that it induces reversion by its effects on cell function and structure, independently of any antiviral effect. Inhibition of cell multiplication per se does no appear to be sufficient to induce reversion, since cycloheximide inhibited cell multiplication; however, even after ten passages, it did not affect tumorigenicity. Our results suggest the possibility that interferon may act in vivo not only by inhibiting tumor cell multiplication but also by inducing a reversion. Patients with some tumors may therefore benefit from long-term interferon treatment.

Animals↗
PubMed1999

Group II intron reverse transcriptase in yeast mitochondria. Stabilization and regulation of reverse transcriptase activity by the intron RNA.

Group II introns encode reverse transcriptases that function in both intron mobility and RNA splicing. The proteins bind specifically to unspliced precursor RNA to promote splicing, and then remain associated with the excised intron to form a DNA endonuclease that mediates intron mobility by target DNA-primed reverse transcription. Here, immunoblotting and UV cross-linking experiments show that the reverse transcriptase activity encoded by the yeast mtDNA group II intron aI2 is associated with an intron-encoded protein of 62 kDa (p62). p62 is bound tightly to endogenous RNAs in mitochondrial ribonucleoprotein particles, and the reverse transcriptase activity is rapidly and irreversibly lost when the protein is released from the endogenous RNAs by RNase digestion. Non-denaturing gel electrophoresis and activity assays show that the aI2 reverse transcriptase is associated predominantly with the excised intron RNA, while a smaller amount is associated with unspliced precursor RNA, as expected from the role of the protein in RNA splicing. Although the reverse transcriptase in wild-type yeast strains is bound tightly to endogenous RNAs, it is regulated so that it does not copy these RNAs unless a suitable DNA oligonucleotide primer or DNA target site is provided. Certain mutations in the intron-encoded protein or RNA circumvent this regulation and activate reverse transcription of endogenous RNAs in the absence of added primer. Although p62 is bound to unspliced precursor RNA in position to initiate cDNA synthesis in the 3' exon, the major template for target DNA-primed reverse transcription in vitro is the reverse-spliced intron RNA, as found previously for aI1. Together, our results show that binding to intron-containing RNAs stabilizes and regulates the activity of p62.

Amino Acid Sequence↗
PubMed1990

Reverse tolerance to amphetamine evokes reverse tolerance to 5-hydroxytryptophan.

Repeated intermittent administration of amphetamine in mice caused reverse tolerance to 5-hydroxy-L-tryptophan (5-HTP)-induced head twitch, as well as to amphetamine-induced stereotypy. The repeated administration of 5-HTP alone also resulted in reverse tolerance in the head-twitch test. Daily pretreatment with haloperidol prior to amphetamine administration blocked the development of both reverse tolerance to amphetamine and to 5-HTP, whereas daily pretreatment with cyproheptadine prior to amphetamine blocked only the reverse tolerance to 5-HTP. On the other hand, 5-HTP-induced reverse tolerance was blocked by daily pretreatment with cyproheptadine, but not with haloperidol. There appears to be no difference in the persistence of the reverse tolerance to 5-HTP, whether induced by amphetamine or by 5-HTP; in both instances, the persistence does not correlate with the persistence of reverse tolerance to amphetamine. The data suggest that the reverse tolerance to amphetamine and the associated reverse tolerance to 5-HTP are independent events, both of which are mediated by dopaminergic mechanisms.

5-Hydroxytryptophan↗