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PubMed1993

[Assessment of reverse redistribution on exercise 201Tl myocardial SPECT in patients with hypertrophic cardiomyopathy].

Reverse redistribution is revealed on exercise 201Tl myocardial SPECT in some cases with hypertrophic cardiomyopathy. Ten patients with hypertrophic cardiomyopathy without coronary artery disease who showed reverse redistribution visually were studied. Reverse redistribution was evaluated by the early and delayed images of exercise 201Tl myocardial SPECT. Relation between reverse redistribution and distribution of left ventricular hypertrophy estimated by echocardiography and magnetic resonance imaging was investigated, and the mechanism of reverse redistribution was analyzed by referring to Bull's eye display of washout rate. Reverse redistribution was displayed in non-hypertrophic region and washout rate was normal in that region and low in hypertrophic region. In conclusion, in order to interpret reverse redistribution it is necessary to recognize hypertrophic region and to refer to washout rate.

Adult↗
PubMed1995

Reverse 5' caps in RNAs made in vitro by phage RNA polymerases.

We show that about one-third of the RNAs produced in vitro by viral RNA polymerases in the presence of m7GpppG dinucleotides have unusual 5' caps. In these RNAs, the initiating dinucleotide is incorporated in an orientation opposite to that expected so that the 7-methyl guanine (m7G) nucleotide is adjacent to the body of the RNA, making a "reverse" cap. The doubly methylated dinucleotide, m7GpppGm, containing a 2' O-methylated guanine (Gm) is incorporated only in the reverse orientation. Precursors of U1 snRNAs containing reverse caps are recognized by antibodies specific for the m7G cap structure. When injected into Xenopus laevis oocyte nuclei, reverse-capped pre-U1 RNAs are exported considerably more slowly than normal. Furthermore, U1 RNAs with reverse caps exhibit a striking defect in nuclear import that can be attributed to the failure of reverse caps to be hypermethylated to m2,2,7G caps. Thus, the presence of reverse-capped RNAs in RNA preparations may affect conclusions about the efficiency and extent of certain m7G cap-dependent processes.

Animals↗
PubMed1996

Factors regulating the reversibility of long-term potentiation.

Theta burst stimulation (TBS) produces an extremely stable form of long-term potentiation (LTP). In contrast, a brief episode of single-pulse stimulation at theta frequency [theta pulse stimulation (TPS)] has been demonstrated to reverse LTP in area CA1 of slices and freely moving animals without causing depression when administered to nonpotentiated pathways. The present in vitro studies confirm these results and establish that the susceptibility of LTP to reversal and the degree of depotentiation are time-dependent. Specifically, a 1 min train of TPS delivered 30 sec after LTP induction produced an almost complete and lasting depotentiation but had increasingly less impact at longer delays and virtually no effect at 30 min. Increasing the duration of TPS did not cause more depotentiation. However, pharmacological facilitation of AMPA receptor-mediated currents significantly enhanced the strength of the reversal process and allowed TPS to produce robust depotentiation up to 30 min after LTP induction. The reversal effect was selective to potentiated synapses receiving TPS, was reversible, and was not blocked by NMDA receptor antagonism. Additional experiments indicated that AMPA receptor facilitation promotes depotentiation by enhancing an active process triggered by TPS that reverses expression without extending the time course of consolidation. These results suggest that the mechanisms responsible for LTP reversal are linked to the amplitude and/or duration of fast excitatory currents mediated by synaptic AMPA receptors and are effective up to the completion of LTP stabilization.

Animals↗
PubMed1996

Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging.

Homosynaptic long-term depression (LTD) and reversal of long-term potentiation (LTP) were examined extracellularly at CA3-CA1 synapses in stratum radiatum of slices from adult (6-9 months) and aged (20-24 months) Fischer 344 rats. Prolonged low-frequency stimulation (LFS) (900 pulses/1 Hz) of the Schaffer collaterals depressed the initial slope of the excitatory postsynaptic potential (EPSP) in aged but not adult rats. LTD at aged synapses was pathway-specific, persistent, and sensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Adult slices exhibited AP5-sensitive LTD in high [Ca2+] medium, whereas LTD in aged slices was blocked by high [Mg2+], suggesting that differences in Ca2+ regulation may underlie susceptibility to LTD. Despite age-related differences in LTD induction, no age difference in LTP magnitude was revealed. Additionally, LFS delivered 60 min after LTP induction resulted in similar LTP reversal for both age groups. Susceptibility differences to LTP reversal were indicated after multiple short-duration LFS bursts (30 pulses/1 Hz), with each burst separated by 10 min. Aged synapses exhibited significant reversal after a single burst and complete reversal after three LFS episodes. In adult slices, LTP reversal appeared after the fourth burst, and at no time was LTP depressed to initial baseline levels. This study provides the first characterization of homosynaptic LTD/LTP reversal in the aged animal and demonstrates that one form of plasticity, depression attributable to LFS, is increased during aging.

2-Amino-5-phosphonovalerate↗
PubMed1997

Reversal of multidrug resistance-associated protein-mediated drug resistance by the pyridine analog PAK-104P.

Three agents, verapamil, cepharanthine, and 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1, 3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-3-py ridinecarboxylate P-oxide (PAK-104P), that reverse drug resistance in P-glycoprotein (P-Gp)-mediated multidrug-resistant cells were examined for their activity to reverse drug resistance in multidrug resistance-associated protein (MRP)-mediated multidrug-resistant C-A120 cells. Agents other than PAK-104P could not reverse the resistance to doxorubicin in C-A120 cells. PAK-104P moderately reversed the doxorubicin resistance. In contrast, PAK-104P almost completely reversed the resistance to vincristine (VCR) in C-A120 cells as well as in KB-8-5 cells, and other agents moderately reversed the VCR resistance in C-A120 cells. PAK-104P at 10 microM enhanced the accumulation of VCR in C-A120 cells to the level of that in KB-3-1 cells without the agent. PAK-104P competitively inhibited the ATP-dependent [3H]leukotriene C4 uptake in membrane vesicles isolated from C-A120 cells. These findings demonstrate that PAK-104P can completely reverse the resistance to VCR in both P-Gp- and MRP-mediated multidrug-resistant cells and that PAK-104P directly interacts with MRP and inhibits the transporting activity of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Effects of halothane and sevoflurane on reversal of neuromuscular blockade induced by vecuronium in man].

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.

Adult↗
PubMed1999

Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system.

Fibrosis impairs cardiac function. This project has determined the expression and deposition of collagens and fibronectin and cardiac function in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat after inhibition of the renin-angiotensin system. DOCA-salt hypertension was induced in 8-wk-old male Wistar rats by uninephrectomy and administration of DOCA (25 mg every fourth day, subcutaneously) and 1% NaCl in the drinking water for 4 wk. Starting 2 wk after surgery, rats were given either oral captopril (100 mg/kg), oral candesartan cilexetil (2 mg/kg), or subcutaneous spironolactone (50 mg/kg) daily for 2 wk (reversal protocol). DOCA-salt rats failed to gain weight with markedly increased water intake and decreased food intake; drug treatment did not alter these parameters. Systolic BP increased from 116+/-5 mmHg in uninephrectomized rats to 179+/-7 mmHg in DOCA-salt rats and was not decreased by treatment (captopril 172+/-1 mmHg; candesartan 187+/-2 mmHg; spironolactone 178+/-3 mmHg). Captopril, candesartan, and spironolactone reversed the increased collagen I mRNA in DOCA-salt rats; only candesartan reversed the increased collagen III mRNA. Collagen IV mRNA was unchanged in DOCA-salt rats and following treatment. Total fibronectin mRNA increased without changing the proportion of fibronectin mRNA as the fetal isoforms EIIIA and EIIIB. Captopril, candesartan, and spironolactone reversed the increased deposition of perivascular and interstitial collagen in DOCA-salt rats; the increased cardiac fibronectin deposition was reversed by candesartan and spironolactone. Captopril, candesartan, and spironolactone also attenuated or reversed the increased diastolic stiffness and the increased dP/dt but not the increased rate-pressure products in DOCA-salt rat hearts. Thus, inhibition of the renin-angiotensin system reverses cardiac fibrosis in DOCA-salt rats and returns some indices of myocardial function to normal.

Angiotensin Receptor Antagonists↗
PubMed1980

The potential impact of reversibility on selection of tubal sterilization.

Despite continuing interest in development of reversible sterilization, baseline data regarding how much more acceptable reversible procedures would be than currently available methods have not been available. This study provides such data from 1074 randomly selected obstetric/gynecology patients or reproductive age in metropolitan San Antonio. Basic socio-demographic data and attitudinal information with respect to both permanent and hypothetically reversible tubal ligation were elicited via a self-administered questionnaire. Responses toward permanent and reversible sterilization were compared and analyzed for statistically significant differences. Results indicate that approval of, serious consideration of, intent to eventually undergo, and immediate demand for tubal sterilization would be increased 25%, 95%, 178%, and 163%, respectively, if reversible procedures were available. All increases are statistically significant at P < .0001. These data, confirming pilot study results reported a year ago, indicate that the option of reversibility is exceedingly important to potential candidates for sterilization and its availability would significantly increase the acceptability of female surgical sterilization as an alternative method of contraception.

Adolescent↗
PubMed2000

Inhibition of HIV-1 reverse transcriptase-catalyzed DNA strand transfer reactions by 4-chlorophenylhydrazone of mesoxalic acid.

DNA strand transfer reactions occur twice during retroviral reverse transcription catalyzed by HIV-1 reverse transcriptase. The 4-chlorophenylhydrazone of mesoxalic acid (CPHM) was found to be an inhibitor of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Using a model strand transfer assay system described previously [Davis, W. R., et al. (1998) Biochemistry 37, 14213-14221], the mechanism of CPHM inhibition of DNA strand transfer has been characterized. CPHM was found to target the RNase H activity of HIV-1 reverse transcriptase. DNA polymerase activity was not significantly affected by CPHM; however, it did inhibit the polymerase-independent RNase H activity with an IC(50) of 2.2 microM. In the absence of DNA synthesis, CPHM appears to interfere with the translocation, or repositioning, of RT on the RNA.DNA template duplex, a step required for efficient RNA hydrolysis by RNase H. Enzyme inhibition by CPHM was found to be highly specific for HIV-1 reverse transcriptase; little or no inhibition of DNA strand transfer or DNA polymerase activity was observed with MLV or AMV reverse transcriptase, T7 DNA polymerase, or DNA polymerase I. Examination of additional 4-chlorophenylhydrazones showed that the dicarboxylic acid moiety of CPHM is essential for activity, suggesting its important role for enzyme binding. Consistent with the role of the dicarboxylic acid in inhibitor function, Mg(2+) was found to chelate directly to CPHM with a K(d) of 2.4 mM. Together, these studies suggest that the inhibitor may function by binding to enzyme-bound divalent metal cofactors.

Animals↗
PubMed1996

Inhibitory RNA ligand to reverse transcriptase from feline immunodeficiency virus.

High-affinity, high-specificity RNA ligands for reverse transcriptase from feline immunodeficiency virus (FIV) were isolated from an RNA library by the SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure. The selected RNA ligands bound to FIV reverse transcriptase with dissociation constants in the nanomolar range. One of the ligands was a potent inhibitor of the RNA-dependent DNA polymerase activity of both the recombinant and the virion-derived FIV reverse transcriptase. It also inhibited the reverse transcriptase from an FIV mutant that is resistant to 3'-azido-3'-deoxythymidine (AZT). The inhibition of FIV reverse transcriptase was competitive with respect to template-primer and noncompetitive with respect to deoxyribonucleoside 5'-triphosphates. This ligand was specific for the FIV enzyme and did not inhibit other reverse transcriptases tested (avian myeloblastosis virus, Moloney murine leukemia virus, and human immunodeficiency virus type 1).

Animals↗
PubMed1996

Synthesis and biological evaluation of certain alkenyldiarylmethanes as anti-HIV-1 agents which act as non-nucleoside reverse transcriptase inhibitors.

Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized. The most potent of these proved to be 3',3"-dibromo-4',4"-dimethoxy-5'5"-bis(methoxycarbonyl)-1,1-diphenyl-1-+ ++heptene (8) ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture with an EC50 value of 7.1 microM and was active against an array of laboratory strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of HIV-2. In common with the other known non-nucleoside reverse transcriptase inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase (IC50 1 microM) with poly(rC).oligo(dG), but not with poly(rA).oligo(dT), as the template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases containing non-nucleoside reverse transcriptase inhibitor resistance mutations at residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT-resistant virus having four mutations in reverse transcriptase was more sensitive to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a structurally related analog may therefore be useful as an antiviral agent in combination with AZT or with other NNRTIs that are made ineffective by mutations at residues which do not confer resistance to ADAM 8.

Amino Acid Sequence↗
PubMed1986

Female sterilization: can the woman who will seek reversal be identified prospectively?

Demographic socio-economic and decision-making aspects of sterilization and reversal of sterilization were compared in a group of 103 women requesting reversal (RR) and 117 women about to undergo sterilization (S), to determine the practicality of identifying in advance the woman likely to request reversal. The willingness of patients to pay for these procedures and the ethical implications of these decisions were also examined. RR were younger at the first relationship, birth of first child and birth of last child. There were no differences (RR vs S) between the number of full-term pregnancies, living children and therapeutic abortions. The timing of sterilization (puerperal versus interval) did not influence the decision to be reversed. The level of education, partner's level of education and mean family income were lower in the group requesting reversal. Multiple regression analysis revealed three characteristics which were most discriminatory: youth at first birth; lack of spousal support; and failure to choose 'family complete' as a reason for sterilization. The predictability was not strong enough to provide an accurate assessment of the individual woman. RR were of significantly lower socio-economic standing but were more likely to be prepared to pay a large sum of money for the reversal. The ethical implications of this finding are discussed.

Adult↗
PubMed1997

Effects of radiofrequency versus neurotoxic cingulate lesions on spatial reversal learning in mice.

Mice with radiofrequency (RF) lesions of the posterior (PC) or anterior (AC) cingulate cortex were trained on spatial discrimination reversal learning in a T-maze. The results were compared with those obtained in an earlier study after ibotenic acid (IBO) cingulate lesions. PC-RF lesions facilitated the initial discrimination and first reversal, whereas they retarded subsequent reversals; in contrast, PC-IBO lesions yielded a deficit on the initial discrimination and first reversal, but had no effect on subsequent reversals. AC-IBO, but not AC-RF lesions, precluded the formation of a learning set across reversals. These data suggest that cingulum transection, which accompanies RF but not IBO lesions, can mask or even antagonize the specific effects of cingulate damage. Consequently, inferences made from the effects of conventional lesions to assess and distinguish the functions of the two cingulate areas appear subject to caution.

Animals↗
PubMed1999

HIV-1 reverse transcription: a brief overview focused on structure-function relationships among molecules involved in initiation of the reaction.

An early step in the life cycle of the human immunodeficiency virus type 1 (HIV-1) is reverse transcription of viral RNA into proviral DNA, which can then be integrated into the host cell genome. Reverse transcription is a discontinuous process carried out by the viral encoded reverse transcriptase that displays DNA polymerase activities on RNA and DNA templates as well as an RNase H activity that degrades transcribed RNA. DNA synthesis is initiated by cellular tRNALys3 that binds at its 3'-terminus to the complementary primer binding site of the genomic RNA. The initiation of reverse transcription is itself a complex reaction that requires tRNA placement onto viral RNA and the formation of a specific primer/template complex that is recognized by reverse transcriptase. After initiation takes place, the enzyme translocates from the initially bound RNA/RNA duplex into chimeric replication intermediates and finally accommodates newly synthesized DNA/RNA hybrids. This review focuses on structure-function relationships among these various molecules that are involved in the initiation of HIV-1 reverse transcription.

DNA, Viral↗
PubMed1989

Chronic neuroleptic effects on spatial reversal learning in monkeys.

Cebus apella monkeys were chronically administered the antipsychotic drug fluphenazine decanoate for periods ranging from 3.5 to 5.5 years. In the present study, four of these monkeys and two controls were tested for cognitive abilities on a spatial learning task, which consisted of an original discrimination and four reversals of that discrimination. No effect of fluphenazine administration was seen in the rate of learning the original discrimination, but the carryover of learning across discrimination reversals was significantly reduced by fluphenazine. After overtraining on the original discrimination, the controls showed the normal difficulty in learning the first reversal. The fluphenazine-treated monkeys showed no such disruption. On subsequent reversals, the controls showed continually improving performance, so that on the third and fourth reversals they had near-perfect scores. On the other hand, the fluphenazine-treated monkeys showed no change over the four reversals. Unlike normal monkeys, their learning did not improve with practice. Although simple forms of learning seem to be relatively unaffected by chronic fluphenazine administration, more complex learning is disrupted.

Animals↗
PubMed1995

Follow-up of women seeking sterilization reversal: a Brazilian experience.

OBJECTIVE: To analyze the follow-up of a cohort of women who requested reversal of surgical sterilization. METHODS: This retrospective study was carried out at the State University of Campinas, Brazil. A cohort of 394 women who requested sterilization reversal was followed up for one year after reversal surgery. The analysis includes the percentage of women who completed the steps between the initial consultation up to one year after reversal surgery. RESULTS: After an initial consultation, 55.1% of the patients decided not to continue with the procedures. Of the patients who did undergo laparoscopy (n = 177), 48.6% had no possibility of a successful surgical reversal because the Fallopian tubes were in very poor condition. Only 17.5% of the initial patients requesting reversal ultimately underwent surgery and 3.3% became pregnant. CONCLUSIONS: The analysis of regret about surgical sterilization should include not only women who undergo surgery but also women requesting surgery. Better patient selection and counseling prior to sterilization are necessary in order to prevent increasing rates of sterilization regret in Brazil.

Adult↗
PubMed1989

Guidance of visual reaching with the aid of a TV monitor: the effects of monitor position and of left/right and up/down reversals of the image in relation to age.

Children, aged 2-9 years, were seated alongside a wall containing an opening through which they could reach with their preferred hand. Targets ("ink blots"), which could not be felt, were attached to the other (rear) side of the wall, around the opening. The child could see directly neither the target nor its hand beyond the front side of the wall; but both were visible on a TV monitor. The image on the screen of the monitor originated from a camera viewing the rear (target) side of the wall at the level of the central opening. The monitor screen was either (a) parallel to the wall, but rotated 180 degrees with respect to the axis of the camera, i.e. facing the camera; or (b) at 90 degrees to the wall; or (c) in a position similar to (a) but visible in a mirror attached to the front side of the wall and therefore in effect "aligned" with the axis of the camera. The image the child saw was either (1) electronically unswitched, i.e. when the target was towards the east on the wall it was to the west on the monitor in monitor position (a), or to the north in position (b), or to the "east" in position (c); or (2) left/right reversed relative to (1); or (3) up/down reversed relative to (1); or (4) both left/right and up/down reversed. The dependent variable was the time taken for the child to place the palm of the hand over the target (time was measured to 0.1 sec on video-recorder with a superimposed time display). Position of the monitor, comparing conditions (a)-(c), gave only minor, perhaps age-related, effects. Left/right reversals were easier than up/down reversals under monitor positions (a) and (b), but not under (c); but both reversals could be achieved by age 3 or older; hardest was condition (4). However, with monitor positions (a) and (b) children, at all ages we tested, found condition (1) ("east gives west/north") easier than (2) ("east gives east/south"), whereas for adults these conditions were equally easy, or they found (2) easier than (1); but with monitor position (c) condition (1), now "east gives east", was easiest. Moreover, the claim that chimpanzees but not monkeys can achieve accurate reaching under the conditions varied in this study seems premature: the chimpanzees may have made use of strategies based on uncontrolled cues.

Attention↗
PubMed1993

Enhanced acquisition of reversal training in a spatial learning task in rats treated with chronic nimodipine.

Nimodipine levels were measured in blood and brain of rats implanted SC with sustained-release pellets of nimodipine (0, 10, 20, or 40 mg). Dose-dependent levels of nimodipine were detected in both plasma and brain. These results indicated the possible usefulness of these pellets in behavioral studies where long-term treatment is required. Therefore, the effects of chronic nimodipine, using 40-mg pellets, were examined on the performance of young, middle-aged, and aged rats in the Morris water maze. Following implantation of either nimodipine or placebo pellets, rats were trained for 6 days (three sessions/day) followed by 6 days of reversal training. During both initial and reversal training, every sixth trial was a probe trial. During initial training, there were clear age-related acquisition deficits in place training, with no effects of chronic nimodipine. Nimodipine did, however, enhance performance of rats during the first and second probe trials of reversal training. Time spent in the training quadrant by nimodipine-treated rats was approximately 30% longer on the first reversal probe and 35% longer on the second reversal probe than time spent in this quadrant by placebo-treated animals. These results indicate that chronic nimodipine enhances the performance of normal animals in reversal training on a spatial learning task.

Aging↗