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At least 145 records · Page 8Linked to original sources
PubMed1990

Reversible elimination of myofibrillar Ca2+ sensitivity by diamide and other sulfhydryl reagents: comparison with reversible contracture produced in intact cells.

Cardiac contractile activity is usually controlled by intracellular Ca2+, but it can also be modified by oxidizing agents. Incubation of guinea pig heart myofibrils with diamide (3 mM, 1 h) increased basal (no Ca2+) ATPase activity by 580% and abolished Ca2+ dependence. The effect was proportional to diamide concentration (0.01-1 mM) and duration of preincubation (up to 2 h). Dithiothreitol (5 mM, 1 h) reversed most of the basal ATPase activation and restored Ca2+ sensitivity. Other sulfhydryl reagents produced a similar effect but also produced inhibition of total ATPase. In intact cell preparations, diamide produced a slow tonic contraction, consistent with myofibril activation. In the perfused rat heart, 1 mM diamide slowly increased diastolic ventricular pressure; this increase was partially reversed by dithioerythritol. In isolated rat heart myocytes, 1 mM diamide produced a slow tonic contraction, increased contractility in response to stimulation. Cardiocytes superfused for 1 h with buffer containing EGTA to deplete Ca2+ did not contract in response to stimulation but showed a slow tonic contraction with diamide. This contraction could be slowly and only partially reversed by dithioerythritol. Response to stimulation was restored by addition of Ca2+. The results show that diamide can produce contraction in viable cells. This contraction does not require extracellular Ca2+ and is unlikely to involve intracellular Ca2+. The direct activation of myofibrillar ATPase may contribute to the increased myocardial stiffness seen in ischemia and to ischemic contracture.

Adenosine Triphosphatases↗
PubMed2006

Dynamic deformation and recovery response of red blood cells to a cyclically reversing shear flow: Effects of frequency of cyclically reversing shear flow and shear stress level.

Dynamic deformation and recovery responses of red blood cells (RBCs) to a cyclically reversing shear flow generated in a 30-microm clearance, with the peak shear stress of 53, 108, 161, and 274 Pa at the frequency of 1, 2, 3, and 5 Hz, respectively, were studied. The RBCs' time-varying velocity varied after the glass plate velocity without any time lag, whereas the L/W change, where L and W were the major and minor axes of RBCs' ellipsoidal shape, exhibited a rapid increase and gradual decay during the deformation and recovery phase. The time of minimum L/W occurrence lagged behind the zero-velocity time of the glass plate (zero stress), and the delay time normalized to the one-cycle duration remained constant at 8.0%. The elongation of RBCs at zero stress time became larger with the reversing frequency. A simple mechanical model consisting of an elastic linear element during a rapid elongation period and a parallel combination of elements such as a spring and dashpot during the nonlinear recovery phase was suggested. The dynamic response behavior of RBCs under a cyclically reversing shear flow was different from the conventional shape change where a steplike force was applied to and completely released from the RBCs.

Blood Flow Velocity↗
PubMed1987

Vertical reversal and lateral reversal as components of inversion in recognition memory for upside-down faces.

Subjects viewed upright photographs of faces, then attempted to recognize them unchanged, vertically reversed or inverted. In two of four conditions, hit scores were lower for inverted than vertically reversed faces, suggesting that lateral reversal is a meaningful component of inversion. The effect was not sufficiently strong, however, to overcome a generally high false-alarm rate for upside-down faces.

Attention↗
PubMed1998

Reversibility of reversible Chinese words.

Reversible Chinese words are words which can be read either from left to right or vice versa. The reversibility of reversible two-character Chinese words for 101 women and 73 men, native speakers of Chinese, was estimated.

Adolescent↗
PubMed1993

A model of reversible uremia employing isogenic kidney transplantation in the rat. Reversibility of secondary hyperparathyroidism.

Kidney transplanted patients with normalized kidney function may still exhibit a variety of problems such as bone problems, vascularly problems, and hormonal dysfunctions. A part of the symptoms may be persisting uremic symptoms, secondary to the pretransplanted period of chronic uremia. An experimental rat model, designed to the study of the reversibility of the chronic uremic implications is therefore described. A stable, severe chronic uremia was induced by 5/6 nephrectomy to inbred Lewis rats. Ten weeks later uremia was reverted by a successful isogenic rat kidney transplantation. During the period of chronic uremia the p-urea was elevated to an average of 21.8 +/- 0.9 mmol/l and p-creatinine to 105.7 +/- 5.7 microM/l. The isogenic kidney transplantation resulted in reestablishment of normal kidney function with an average level of p-urea of 7.6 +/- 0.2 mmol/l and p-creatinine 42.5 +/- 1.9 microM/l perfectly corresponding to the sham-operated rats, i.e. one-kidney rats. Reversibility of the secondary hyperparathyroidism due to chronic uremia was investigated in the model. In rats with chronic renal failure PTH increased from 52 +/- 4.9 pg/ml to 152 +/- 12.2 pg/ml and was normalized after transplantation. It is therefore concluded that the present described technique of introducing long term uremia followed up by a successful kidney transplantation in the rat may be a useful model to study the reversibility of different uremic manifestations.

Animals↗
PubMed1990

Reversal of the limited proteolysis of MP26 during the reversal and prevention of the galactose cataract in rat lenses.

The reversal and prevention of the galactose-induced cataract in rats were employed to study their effects on the acceleration of the limited proteolysis of MP26 into MP23-24 previously observed in cataractous lenses of galactose-fed animals. Lenses of rats on a cataract reversal-diet demonstrated the reversal of MP23-24 and MP26 levels to control levels in the clearing cortical areas but not in remaining cataractous nuclear areas. Acceleration of the limited proteolysis of MP26 was observed in the nucleus but not the cortex in the clear lenses of animals on a cataract prevention-diet. The results demonstrated that the limited proteolysis of MP26 may form part of a gradual aging process that although not directly (causally) related to cataractogenesis may at least be accelerated by cataractogenic agents or conditions.

Aging↗
PubMed1993

[Schizophrenia and reverse-Stroop interference in the group version of the Stroop and reverse-Stroop test].

Previous studies showed that attentional task performance of schizophrenics was significantly inferior to that of normals. The classical Stroop Color-Word Interference Test is an example of such attentional tasks and performance on the "reverse" Stroop task is reported to discriminate schizophrenics from normals better than the regular Stroop task. These results suggest that schizophrenics are more susceptible to "reverse" Stroop interference in reading incongruent word-color combinations than normals. The group version of the Stroop and reverse-Stroop Color-Word Test, where the response is to choose a matching alternative, was used to test the hypothesis. The results virtually supported the hypothesis. In addition, interference was closely related to the patient's control of impulsiveness. It was suggested that schizophrenics have generation (or translation) deficits between different codes.

Adolescent↗
PubMed1999

Reversible biventricular dysfunction secondary to ischemia in a patient with acute airway obstruction: a case report and review of the literature on reversible causes of acute ventricular dysfunction.

Reversible causes of acute myocardial dysfunction are important for clinicians to recognize. Reversible biventricular dysfunction secondary to myocardial ischemia is presented in a patient with acute upper airway obstruction. The differential diagnosis of reversible acute myocardial dysfunction is reviewed.

Acute Disease↗
PubMed2002

[Reversing malignant phenotypes of liver cancer cell lines with antisense gene to human telomerase reverse transcriptase].

OBJECTIVE: To explore the effect of antisense gene to human telomerase reverse transcriptase (hTRT) on reversing malignant phenotypes of liver cancer cell lines. METHODS: Sense and antisense eukaryotic expressing vector of hTRT gene was transfected into human liver cancer line HepG(2) with the DOTAP liposomal transfection method. Changes of cellular malignant phenotypes through proliferation capacity, telomerase activity, cloning formation in soft agar, invasive capacity in Borden's chamber model and tumorigenicity in nude mice were examined. RESULTS: Sense and antisense eukaryotic expressing vector was successfully transfected into HepG(2). The obtained transfectants termed HepG(2)-sense (HepG(2)-S) and HepG(2)-antisense (HepG(2)-AS) stably produced sense and antisense hTRT, respectively. HepG(2)-AS showed an obvious decrease in growth and telomerase activity. HepG(2)-AS penetrated cells through Matrigel were decreased significantly compared with HepG(2) and HepG(2)-S. Cloning efficiency in soft agar and tumorigenicity in nude mice was also markedly inhibited in HepG(2)-AS. CONCLUSIONS: Antisense gene to hTRT can significantly suppress cancer cell growth, partially reverse malignant phenotypes of HepG(2), which indicates that hTRT may be a new target gene for antisense gene therapy of liver cancer.

Animals↗
PubMed2002

Evidence of reverse mismatch with positron emission tomography imaging in a patient with reversible myocardial dysfunction.

We describe the case of a patient who came to our attention because of a reversible depression of myocardial contractility, probably due to myocarditis. A positron emission tomography study showed, in correspondence to the malfunctioning segments, a decreased F18-2-fluoro-2-deoxyglucose (F18-FDG) uptake in the presence of a normal perfusion as assessed by means of N13-labeled ammonia uptake. This phenomenon, called "reverse mismatch", shows that viability is not always dependent on FDG uptake and that it could be associated with the recovery of myocardial contractility. Some interpretations of the association between a reversible dysfunction and a reduced myocardial glucose metabolism are presented. The central role of nitric oxide and of cyclic guanosine monophosphate is hypothesized to explain both the mechanical and metabolic abnormalities.

Female↗
PubMed2003

[Synthesis and drug resistant reversal activities of taxane-like multi-drug resistant reversal agents].

AIM: To design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine. METHODS: Using Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-oxo group was introduced by PCC oxidation; 5-O-acetyl group was selectively removed by potassium tert-butoxide and finally the side chain was introduced by acylating with the corresponding acid. For type II compounds, 5-O-sidechain was introduced to the 5-deacetyl Sinenxan A which was obtained by selective hydrolysis with tBuOK. For type III compounds, 9-acetoxy group was introduced, then 5-OH was left free by thorough hydrolysis and reacetylation. Acylation at 5-position, the final product was obtained. Structure of the compounds have been confirmed by FABMS and 2DNMR. The activity of the compounds in vitro was tested on KB/V200 resistant cell line using MTT method. RESULTS: Nine compounds showed resistant reversal activity and enhancing the cytotoxicity of vicristine against KB/V200 cells. Compounds I2, I3, I4 restored the sensitivity of KB/V200 towards vicristine to a level of IC50 at 1 x 10(-8) mol.L-1 which is better than the positive control Verapamil. CONCLUSION: The drug resistant reversal activity of taxane derivatives can be affected by substitution at different positions and the length of side chains of Sinenxan A. It is worthy to be further studied.

Antineoplastic Agents↗
PubMed1978

Effect of RNA tumor virus-specific protein p30 on reverse transcriptase. Intraspecies and interspecies interaction between reverse transcriptase and p30.

Reverse transcriptase and p30 were purified from various retroviruses and the intra- and interspecific interaction between the two proteins were studied. The intraspecific complex stimulates [3H]TMP incorporation into (dT)12.(rA)n severalfold above that of the enzyme itself whereas DNA synthesis in the presence of the interspecific complex can stimulate DNA synthesis about 1.5-fold. The sedimentation rate value of the intraspecies complex varies between 12 and 16 S with an estimated molecular weight of 400,000. The molar ratio of p30:reverse transcriptase within the complex is 8:1. Both complexes can be dissociated into their original protein components by exposure to salt (kcl) solution, except that 0.3 M KCl will dissociate the interspecies complex whereas 0.8 M KCl is required for dissociation of the intraspecies complex. Competition studies in which an interspecies complex was exposed to p30 autologous to reverse transcriptase within the complex resulted in the displacement of the heterologous (p30) protein and the formation of a new intraspecific complex.

Molecular Weight↗
PubMed1997

In vitro selection for different mutational patterns in the HIV-1 reverse transcriptase using high and low selective pressure of the nonnucleoside reverse transcriptase inhibitor HBY 097.

In vitro resistance of HIV-1 against high levels of HBY 097 ((S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydro-quinoxaline-2(1H)-thione) and other quinoxaline nonnucleoside reverse transcriptase inhibitors (NNRTIs) is characterized by a specific amino acid substitution in the reverse transcriptase (RT), Gly 190Glu. This change results in decreased RT polymerase activity and in reduced growth properties of the corresponding viral variant. Here we show that the appearance of the crippling mutation at codon 190 can be prevented by lowering the selective pressure exerted by HBY 097. Under low selective pressure an accumulation of other NNRTI-specific mutations is observed. Up to five NNRTI-specific substitutions were detected in some of these virus lineages. In addition, we report novel RT amino acid changes which were not observed previously, including Val106lle, Val106Leu, and Gly190Thr. HBY 097 selects for different mutational patterns under high and low selective pressure conditions, respectively. Thus, the type of mutations which appear in HIV-infected patients undergoing therapy may be determined by the levels of the selecting drug.

Antiviral Agents↗
PubMed2006

Vif-deficient HIV reverse transcription complexes (RTCs) are subject to structural changes and mutation of RTC-associated reverse transcription products.

Reverse transcription (RTn) in HIV-infected cells occurs in a nucleoprotein complex termed the reverse transcription complex (RTC). RTCs containing RT activity and integrase (IN) were shown to be heterogeneous in size and density on sucrose velocity and equilibrium gradients. WT and Vif-deficient (Deltavif) RTCs produced by infection with virus from permissive cells displayed similar sedimentation characteristics, while RTCs from Deltavif virus produced in non-permissive cells demonstrated a reduction in the major RTC form and more of the RTn products in rapidly sedimenting structures. APOBEC3G derived from virions did not co-sediment with RTCs, but RTCs from Deltavif infections showed elevated levels of mutations in RTn products, consistent with APOBEC3G and other mutational mechanisms. The most mutated transcripts were present within rapidly sedimenting RTCs. Thus, virus without functional vif, produced from non-permissive cells, forms abnormal RTCs that contain increased mutation of RTC-associated RTn products in newly infected target cells.

APOBEC-3G Deaminase↗
PubMed2001

The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages.

We investigated the effects of the nonnucleoside reverse transcriptase inhibitor-resistant mutant Y181C on RNA 5'-end-directed RNase H cleavage by HIV-1 reverse transcriptase, using an RNA.DNA hybrid in which a radiolabeled RNA 5' end was recessed. Y181C produced a higher ratio of secondary (9 nucleotide long) to primary (18 nucleotide long) products than wild type. When the RNA was 3'-end-labeled, Y181C generated a long product, which results when secondary cleavage precedes the primary. When using an RNA.DNA hybrid in which the labeled RNA 5' end and DNA 3' end were flush, formation of secondary product by both enzymes was inhibited. Under these conditions, Y181C cleaved closer to the RNA 5' end than wild type. Studies with this substrate labeled at the RNA 3' end showed that Y181C is no more likely than wild type to cleave toward the RNA 3' end. Thus, Y181C RT has a strong preference to cleave in the direction of the RNA 5' end even when secondary cleavage is prevented, resulting in a disruption of the normal sequence of primary followed by secondary cleavages.

3' Untranslated Regions↗
PubMed2004

Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors.

We have determined the crystal structure of the HIV type 1 reverse transcriptase complexed with CP-94,707, a new nonnucleoside reverse transcriptase inhibitor (NNRTI), to 2.8-A resolution. In addition to inhibiting the wild-type enzyme, this compound inhibits mutant enzymes that are resistant to inhibition by nevirapine, efavirenz, and delaviridine. In contrast to other NNRTI complexes where tyrosines 181 and 188 are pointing toward the enzyme active site, the binding pocket in this complex has the tyrosines pointing the opposite direction, as in the unliganded protein structure, to accommodate CP-94,707. This conformation of the pocket has not been observed previously in NNRTI complexes and substantially alters the shape and surface features that are available for interactions with the inhibitor. One ring of CP-94,707 makes extensive stacking interactions with tryptophan 229, one of the few residues in the NNRTI-binding pocket that cannot readily mutate to give rise to drug resistance. In this conformation of the pocket, mutations of tyrosines 181 and 188 are less likely to disrupt inhibitor binding. Modeling the asparagine mutation of lysine 103 shows that a hydrogen bond between it and tyrosine 188 could form as readily in the CP-94,707 complex as it does in the apoenzyme structure, providing an explanation for the activity of this inhibitor against this clinically important mutant.

Benzothiazoles↗
PubMed2001

Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type 1 reverse transcriptase.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of the HIV type 1 (HIV-1) reverse transcriptase (RT). Yeast grown in the presence of many of these drugs exhibited dramatically increased association of the p66 and p51 subunits of the HIV-1 RT as reported by a yeast two-hybrid assay. The enhancement required drug binding by RT; introduction of a drug-resistance mutation into the p66 construct negated the enhancement effect. The drugs could also induce heterodimerization of dimerization defective mutants. Coimmunoprecipitation of RT subunits from yeast lysates confirmed the induction of heterodimer formation by the drugs. In vitro-binding studies indicate that NNRTIs can bind tightly to p66 but not p51 and then mediate subsequent heterodimerization. This study demonstrates an unexpected effect of NNRTIs on the assembly of RT subunits.

Amino Acid Substitution↗
PubMed1998

Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase.

The highly conserved Tyr-318 is part of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific lipophilic pocket of human immunodeficiency virus type I reverse transcriptase (RT) and makes contact within 4 A with the NNRTIs in all reported RT/NNRTI complexes. Using site-directed mutagenesis, six mutant RTs were constructed bearing the mutations Y318H, Y318K, Y318L, Y318C, Y318W, and Y318F. We found that only the Y318W and Y318F mutant RTs retained substantial RT activity, whereas the catalytic activities of the Y318K, Y318C, Y318H, and Y318L RT mutants were less than 5% of the wild-type activity. The Y318F mutant RT retained substantial sensitivity to the majority of NNRTIs tested, whereas the Y318W mutant RT showed varying degrees of resistance to NNRTIs. Subunit-specific site-directed mutagenesis revealed that there was no difference in the catalytic activity or resistance/sensitivity spectrum toward NNRTIs regardless of whether the Tyr-318 mutation was introduced in both subunits or only in the p66 subunit of RT. Recombinant viruses harboring the Y318F or Y318W mutation in the RT showed a similar resistance/sensitivity pattern to NNRTIs as their corresponding 318 mutant recombinant RTs. Our findings stress a functional or structural role for Tyr-318 in wild-type RT and argue for the design of novel NNRTIs that interact more closely with this amino acid in the NNRTI-specific pocket of human immunodeficiency virus type I RT.

Amino Acid Substitution↗