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PubMed1977

A procedure for dissociating Ayre scrape samples.

The dissociation of cervical cell suspensions after various chemical and enzymatic treatments was monitored by using the Centrifugal Cytology rotor to produce glutaraldehyde-fixed dispersions on conventional microscope slides and subsequent Pap staining. A special program was written in RPG II to record and analyze the results of the dissociation experiments in terms of white blood cells and the true cervical cells ("other cells"), and the degree of dissociation and recovery of both classes of cells. Since accurate differential counts on the untreated Ayre scrapes were difficult, the samples were syringed gently to break up the large or adventitious clumps. Cumulated results from control preparations indicate that the white blood cells and "other cells" are composed respectively of 92 and 63% single cells. The cells were further dissociated by: dissolving the cervical mucin sequentially with dithiothreitol and iodoacetic acid; depolymerizing the nucleohistone gel with ribonuclease; solubilizing the desmosomes with EDTA; removing the remaining cellular agglutinins with Varidase; and finally mechanical dispersion by hypertonic shock. The optimum procedure for dissociation involves the use of ribonuclease, dithiothreitol, iodoacetic acid EDTA, Varidase and sucrose shock. The white blood cells are now monodisperse and 81% of the "other cells" are found as single cells. If nuclear separation by two diameters is considered sufficient 98% of the "other cells" are single. The slide preparations are now sufficiently good that a scanning system is feasible.

Autoanalysis↗
PubMed1985

Intracellular kinetics of free catalytic units dissociated from adenosine 3',5'-monophosphate-dependent protein kinase in adrenocortical tumor cells (Y-1).

To define the role of cAMP in the actions of ACTH, the dissociation of cAMP-dependent protein kinase and the subsequent intracellular location of its free catalytic units were monitored after exposure of Y-1 cells to ACTH, FSH, or cyclic nucleotide analog. To accomplish this, a fluorescinated cytochemical probe was used that complexes specifically with free catalytic units from cAMP-dependent protein kinase. Also, the effects of hormone or nucleotide on secretion of fluorogenic steroids and DNA synthesis were examined. Y-1 cells dissociated protein kinase in a dose-dependent fashion when exposed to ACTH or cAMP analog, but did not respond to FSH, which was one of the control agents used. After 30 min of treatment with 1.5 X 10(-10) M ACTH, free catalytic units were observed only in the cytoplasm of Y-1 cells, whereas a similar time of exposure to 3 X 10(-10) M ACTH led to the appearance of catalytic units in nucleolus as well as in cytoplasm. ACTH (6 X 10(-10) M) caused a rise in cytoplasmic and nucleolar protein kinase dissociation proportionally greater than that seen in cultures exposed to 3 X 10(-10) M ACTH. Upon treatment with 6 X 10(-10) M ACTH, the amount of free catalytic units in cytoplasm and nucleolus was detectably greater than that in controls within 1 min of stimulation and continued to rise with increasing time of exposure to hormone. The nuclear, mostly nucleolar, content of free catalytic unit appeared to peak after 15 min of stimulation, while cytoplasmic enzyme levels continued to rise up to 60 min. Exposure of Y-1 cells to nucleotide analog caused cAMP-dependent protein kinase dissociation with temporal kinetics and a subcellular distribution similar to that seen after ACTH stimulation. We conclude that actions of ACTH are mediated by cAMP-dependent protein kinases. Further, there appear to be two intracellular pools of protein kinase, one nucleolar, the other cytoplasmic, and these may be independently regulated, with the nucleolar enzyme requiring higher concentrations of ACTH for dissociation than those needed for cytoplasm protein kinase. These observations may be relevant to the fact that more ACTH is required to inhibit DNA synthesis than is necessary to enhance steroid production.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo.

Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids. However, major side effects severely limit their therapeutic use. The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects. One possibility toward this goal is to try to dissociate two main activities of glucocorticoids, i.e. transactivation and transrepression. Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids, which exert strong AP-1 inhibition but little or no transactivation. Importantly, despite high ligand binding affinity, the prototypic dissociated compound, RU24858, acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells. Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene (TAT), which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis. To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids, several in vitro and in vivo models were used. Indeed, secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells. Moreover, in two in vivo models, these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone. These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery.

Animals↗
PubMed2003

Charge exchange in tandem mass spectrometry: dissociative single electron capture by doubly-charged toluene cations.

Single electron capture by doubly-charged toluene cations upon collision with various target gases has been investigated by sector tandem mass spectrometry. Both non-dissociative and dissociative charge transfer reactions leading to C(7)H(7)(+) + H and to C(5)H(5)(+) + [C(2),H(3)] are detected. Seven atomic or molecular target gases have been used with ionisation energies ranging from 8.8 eV to 14 eV. The branching ratios between the different non-dissociative and dissociative exit channels have been determined as well as the translational energy release on the dissociation products. The experimental data are compared to the predictions of a two-state semi-classical theoretical model that takes into account the non-adiabatic transition responsible for the charge transfer reaction. A wide reaction window shows up but the internal energies of the C(7)H(8)(+) cations produced by single electron capture are observed to be larger than expected. We assign this effect partly to the influence of the large density of vibrational states and to the multichannel nature of the process. Excited states of the dication are also most probably involved in the charge exchange reaction.

Journal Article↗
PubMed2001

Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27.

We previously showed that the aggregated form of Hsp27 in cultured cells becomes dissociated as a result of phosphorylation with various types of stress. In order to clarify the signal transduction cascade involved, the effects of various inhibitors of protein kinases and dithiothreitol on the dissociation of Hsp27 were here examined by means of an immunoassay after fractionation of cell extracts by sucrose density gradient centrifugation. The dissociation of Hsp27 induced by exposure of U251 MG human glioma cells to metals (NaAsO2 and CdCl2), hypertonic stress (sorbitol and NaCI), or anisomycin, an activator of p38 mitogen-activated protein (MAP) kinase, was completely suppressed by the presence of SB 203580 or PD 169316, inhibitors of p38 MAP kinase, but not by PD 98059 and Uo 126, inhibitors of MAP kinase kinase (MEK), nor by staurosporine, Go 6983, and bisindolylmaleimide I, inhibitors of protein kinase C. Phorbol ester (PMA)-induced dissociation of Hsp27 was completely suppressed by staurosporine, Go 6983, or bisindolylmaleimide I and partially suppressed by SB 203580, or PD 169316 but not by PD 98059 or Uo 126, indicating mediation by 2 cascades. The presence of 1 mM dithiothreitol in the culture medium during exposure to chemicals suppressed the dissociation of Hsp27 induced by arsenite and CdCl2 but not by other chemicals. These results suggest that the phosphorylation of Hsp27 is catalyzed by 2 protein kinases, p38 MAP kinase-activated protein (MAPKAP) kinase-2/3 and protein kinase C. In addition, metal-induced signals are sensitive to reducing power.

Anisomycin↗
PubMedDate not supplied

[Dissociation and reassociation of poliovirus. I. Effect of urea on the virion].

Poliovirus is dissociated by urea in the presence of mercaptoethanol or dithiothreitol into RNA and protein(s). Differences exist in the sensitivity of poliovirus type I, II or III toward these agents. The decrease in infectivity titer of the virion is in the range of 10(9). After appropriate dissociation no infectious virions are found in urea-treated poliovirus concentrates. The released viral RNA is infectious. Its infectivity (1 times 10(6) PFU/mug RNA) is comparable to that of phenol extracted RNA. Therefore, urea dissociation is a fast and reliable method for the preparation of infectious poliovirus RNA even at the microliter scale. The dissociation of poliovirus is dependent upon the concentration, temperature and pH. The decrease in virion infectivity is time dependent. It is preceded by a lag phase of different lengths for poliovirus type I, II or III. During the lag phase the virion undergoes configurational changes without losing infectivity. From the observed hyperchromic effect is it obvious that the secondary structure of the RNA inside the virion breaks down, giving rise to expanded forms of poliovirus particles. After the lag phase the RNA is released and the empty capsid dissociated into the appropriate polypeptides.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Dissociation and reassociation of poliovirus. II. Protein components obtained by urea treatment of the virus particle.

Dissociation of poliovirus by 9 M urea in 0.015 M NaCl at 25 degrees C resulted in the liberation of 35S RNA and of polypeptides sedimenting at 2S in sucrose gradients containing 9 M urea. However, a ribonucleopolypeptide (RNPP) complex sedimenting at 45S and oligomers of the viral polypeptides sedimenting at 7--8S were found in addition to the monomers sedimenting at 2S when the urea concentration was lowered to 5 M after the dissociation procedure. Ribonuclease treatment prevents the appearance of the RNPP-complex. The amount of the RNPP-complex decreased, when the dissociation was performed at higher ionic strength. Under these conditions small amounts of empty capsids were detected. Polyacrylamide gel electrophoresis showed that the RNPP-complex contained the polypeptide VP1. The oligomers (7--8S) contained the polypeptide VP3 and small amounts of VP2. The bulk of VP2 and some VP3 were found in the 2S position together with VP4. The molecular weight of the dissociation products in urea and phosphate buffer was determined by gel filtration to be about 30,000 for the monomeric polypeptides containing predominantly VP2 and about 70,000 for the oligomeric polypeptides containing predominantly VP3. Our results demonstrate that the oligomers and the RNPP-complex are not primary products obtained by dissociation of the virus particle by urea but are due to a reassociation of the polypeptides or of VP1 and RNA.

Centrifugation, Density Gradient↗
PubMedDate not supplied

Reversible pH-induced dissociation of glucose dehydrogenase from Bacillus megaterium. II. Kinetics and mechanism.

Glucose dehydrogenase from Bacillus megaterium exists as a stable, active tetramer at pH 6.5. By shifting the pH to 9, the enzyme is, completely and reversibly, dissociated into four inactive protomers. Kinetics and mechanism of this pH-induced dissociation have been studied, at various enzyme concentrations, by ultraviolet absorption, circular dichroism, normal and stopped-flow fluorescence as well as by light scattering and activity measurements. Dissociation of the fully active tetramer proceeds via three distinct kinetic steps: (1) fast conformational rearrangement of the tetramer, without any loss of activity (t1/2 0.0075 sec); (2) slow isomerization to a tetramer with lower specific activity (t1/2 27 sec); (3) subsequent dissociation of this rearranged tetramer into inactive monomers (t1/2 114 sec) with still intact native secondary structure. All three processes follow first-order kinetics. Both rate and extent of the dissociation are reduced, with a concomitant shift to higher reaction orders, by increasing the NaCl concentration in the buffer. This suggests the establishment of a dissociation/association equilibrium, due to the concentration-dependent stabilization of the tetrameric enzyme state by NaCl.

Bacillus megaterium↗
PubMed2004

Single-molecule investigations of RNA dissociation.

Given the essential cellular roles for ribonucleic acids (RNAs) it is important to understand the stability of three-dimensional structures formed by these molecules. This study aims to investigate the dissociation energy landscape for simple RNA structures via atomic-force-microscopy-based single-molecule force-spectroscopy measurements. This approach provides details on the locations and relative heights of the energy barriers to dissociation, and thus information upon the relative kinetic stabilities of the formed complexes. Our results indicate that a simple dodecamer RNA helix undergoes a forced dissociation process similar to that previously observed for DNA oligonucleotides. Incorporating a UCU bulge motif is found to introduce an additional energy barrier closer to the bound state, and also to destabilize the duplex. In the absence of magnesium ions a duplex containing this UCU bulge is destabilized and a single, shorter duplex is formed. These results reveal that a bulge motif impacts upon the forced dissociation of RNA and produces an energy landscape sensitive to the presence of magnesium ions. Interestingly, the obtained data compare well with previously reported ensemble measurements, illustrating the potential of this approach to improve our understanding of RNA stability and dissociation kinetics.

Magnesium↗
PubMedDate not supplied

Chloroform infrared multiphoton dissociation in the presence of O2 and NO2.

The infrared multiphoton dissociation (IRMPD) of CDCl3 in the presence of O2 and NO2 as acceptor gases has been studied. We have worked with both pure CDCl3 and mixtures with CHCl3. The reaction mechanism following IRMPD of CDCl3 is discussed in detail. CCl2O, CCl4 and DCl were found to be the main products. With added O2, the observed CDCl3 dissociation was larger than with nonoxygenated acceptor gases. The reaction mechanism probably involves a catalytic cycle initiated by the oxidation of CCl3. With the aim of discriminating the different CDCl3 dissociation mechanisms, the IRMPD of CDCl3 in the presence of NO2 was first studied. In order to make evident the CDCl3 dissociation produced by the catalytic cycle, we then studied the IRMPD of CDCl3 in mixtures with CHCl3 with O2 as the acceptor gas. In this case, the dissociation mechanism subsequent to IRMPD is evidenced in the competence between the two isotopic species.

Chloroform↗
PubMed1998

Late dissociation of the polyethylene liner from a modular acetabular metal shell after primary total hip arthroplasty--a report of five cases.

Modular designs of hip prostheses have become popular recently. Along with complications inherent in all hip arthroplasty systems, modular systems have the additional potential for dissociation of components. Five male patients underwent total hip arthroplasties, in which all of the acetabular components were Harris-Galante II porous acetabular cups. Many years after the operation, the polyethylene liners were dissociated without any previous trauma or dislocation of the femoral heads, these dissociations and dislodgements were managed with open reduction. This complication can be predicted from clinical symptoms and signs. Roentgenograms must be taken and carefully compared to previous roentgenograms. We postulated two causes for the dissociation. First, the polyethylene liner was not fixed securely within the acetabular metal shell at the time of operation. Second, the locking mechanism of the acetabular metal shell was not strong enough to firmly hold the polyethylene liner within the acetabular metal shell. It does warrant that certain precautions must be taken when implanting modular components. The locking mechanism of the harris-Galante II porous acetabular component is mechanically weak and fails easily, therefore its design must be improved in an attempt to prevent postoperative dissociation of the polyethylene liner.

Acetabulum↗
PubMed2006

Criteria for unconscious cognition: three types of dissociation.

To demonstrate unconscious cognition, researchers commonly compare a direct measure (D) of awareness for a critical stimulus with an indirect measure (I) showing that the stimulus was cognitively processed at all. We discuss and empirically demonstrate three types of dissociation with distinct appearances in D-I plots, in which direct and indirect effects are plotted against each other in a shared effect size metric. Simple dissociations between D and I occur when I has some nonzero value and D is at chance level; the traditional requirement of zero awareness is necessary for this criterion only. Sensitivity dissociations only require that I be larger than D; double dissociations occur whensome experimental manipulation has opposite effects on I and D. We show that double dissociations require much weaker measurement assumptions than do other criteria. Several alternative approaches can be considered special cases of our framework.

Cognition↗
PubMed1997

Uptake of 99mTc(5+)-complexes in ischemic myocardial slices and their dissociable ability.

AIM: To find how some technetium-complexes to deliver the active species, TcO4(3-), to the target tissue from a dissociable polynuclear Tc5+ species in preserved states in vivo. METHODS: Effect of dissociation ability of the polynuclear Tc5+ complexes on their accumulation in ischemic myocardium was tested. Ability of dissociation as having an appropriate conformation to become biologically functional after entering the blood circulation was tested using a simple dilution method by thin layer chromatography (TLC) analysis. Various degree of ischemic myocardium slices of rat were incubated with 1/100 diluted 99mTc(5+)-succimer, 99mTc(5+)-GH and 99mTc(5+)-PPi. RESULTS: The TLC patterns of 99mTc(5+)-GH and 99mTc(5+)-PPi showed the presence of a fast increasing of free Tc-species as dilution degree increased. The relative radioactivity of peak of free pertechnetate (Rf = 0.85-1.0) with 1:500 dilution was: 99mTc(5+)-succimer 0%, 99mTc(5+)-GH 28.1% +/- 1.3%, and 99mTc(5+)-PPi 46.0% +/- 2.9% respectively. The uptake of the myocardium after ischemia for 3 h was 99mTc(5+)-succimer 420% +/- 110% dose/g tissue, 99mTc(5+)-GH 710% +/- 180% dose/g tissue, and 99mTc(5+)-PPi 1295% +/- 390% dose/g tissue respectively. CONCLUSION: The dissociation and myocardial uptake showed: 99mTc(5+)-succimer < 99mTc(5+)-GH < 99mTc(5+)-PPi, the uptake by the ischemic myocardium is positively correlated to their dissociation.

Animals↗
PubMed2000

Mechanism of band 3 dimer dissociation during incubation of erythrocyte membranes at 37 degrees C.

The mechanism of dissociation of the stable dimer of band 3 was investigated during the incubation of isolated erythrocyte membranes or resealed ghosts at 37 degrees C. The kinetics of changes in the structural and functional integrity of the membrane domain of band 3 (MDB3) were measured and correlated with the change in the Stokes radius of band 3. MDB3 integrity was determined as follows: (1) by measuring the fluorescence emission spectrum of 4, 4'-di-isothiocyanostilbene-2,2'-disulphonate (DIDS) bound covalently to MDB3; (2) by measuring the number of DIDS covalent binding sites present after incubation of unlabelled resealed ghosts; and (3) by measuring the anion transport V(max) by using the same resealed ghosts. Incubation of membranes at 37 degrees C caused the dissociation of band 3 dimers to monomers but only after a lag period lasting approx. 50 h. The observation of such a lag implies that dissociation involves a sequence of molecular events beginning with some type of initial process. We have discovered that this initial process involves a conformation change in MDB3. There was a shift in the fluorescence spectrum for DIDS-labelled band 3 and a decrease in the DIDS binding capacity and transport activity of the unlabelled protein. Incubation of membranes at 4 degrees C inhibited the conformational change in MDB3 and the dissociation of dimers. Furthermore, no conformational change in MDB3 was observed when erythrocytes were incubated at 37 degrees C. We suggest that MDB3 unfolding is the molecular event responsible for the subsequent dissociation of stable dimers of band 3 to monomers during the incubation of erythrocyte membranes at 37 degrees C. The monomers so generated are either not functional in anion exchange or they have an attenuated functionality. The absence of a conformational change for band 3 in erythrocytes might imply that haemolysis perturbs the membrane structure and somehow predisposes band 3 to the conformational change that occurs during incubation at 37 degrees C.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Role of heat shock protein 90 dissociation in mediating agonist-induced activation of the aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AhR) is a cytosolic basic helix-loop-helix protein that associates with a chaperone complex that includes two molecules of heat shock protein 90 (HSP90). It has been hypothesized that after ligand binding, the AhR dissociates from its chaperone complex and translocates into the nucleus, where it heterodimerizes with its DNA binding partner, the AhR nuclear translocator (ARNT), and activates specific genes. However, it remains unclear whether nuclear translocation of the AhR occurs before or after dissociation of the HSP90/chaperone complex. Because sodium molybdate stabilizes the AhR-HSP90 interaction and inhibits the gene activation of a number of steroid receptors, we reasoned that molybdate would be a useful tool in delineating the role of HSP90 dissociation in AhR nuclear translocation. In this study, we demonstrate that molybdate inhibits AhR gene activation in both HepG2 and Hepa-1 cells in a concentration-dependent manner and protects the AhR against agonist-induced proteolysis. In addition, we demonstrate that AhR/ARNT dimerization, but not nuclear translocation of the AhR, is inhibited by molybdate. This indicates that 1) HSP90 dissociation is not required for nuclear translocation of the AhR, 2) HSP90 dissociation is essential for formation of the AhR/ARNT heterodimer, and 3) an additional undefined regulatory step is required for AhR/ARNT dimerization in the nucleus.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMedDate not supplied

[Study of population dissociation of collection strains of Erwinia carotovora].

Unusual dissociants of Erwinia carotovora subsp. atroseptica (EAT) population that emerge with high frequency (18-94%) during long-term storage of cultures were found. The dissociants (Poe-phenotype) differ from parental forms by slow growth and long development of the colour of colonies on EMB agar though they are not Lac-mutants. More than 60% of Poe-mutants of strain EAT 39A are characterized by 8- and 150-fold decrease of stability to erythromycin and oleandomicin, correspondingly. They are also sensitive to colicin-like carotovoricin, which is induced by mytomicin C, to carotovoricin of initial strain EAT 39A and to autocin, which they produce themselves during induction. A multiple phenotype of these dissociants (dissociants of the second type) is labeled: PoeOmSErSBnSAu. Its appearance as well as the appearance of pure Poe-variants is not associated with usual mutations and a loss of residential plasmids by cells. Population dissociants of the both types--Poe and PoeApSOmS--were also obtained from E. carotovora subsp. carotovora (J2) during growth at supraoptimal temperature. Poe-variants are more often observed in representatives of subspecies atroseptica than carotovora and can be useful when studying pathogeneity of these practically important erwinias.

Pectobacterium carotovorum↗
PubMed1975

[Cellular lysis and dissociative phase of the genus Bacillus].

The sensitivity of the dissociative variants "R", "RS" and "S" of the spore-forming bacilli to some lytic agents (lysozyme, sodium lauryl sulphate, lipase, trypsin and some of their associations) has been studied. The research has been carried out on 32 strains: 14 "R", 14 "RS" and 4 "S" of different species of the genus Bacillus. The results have shown that the sensitivity to the studied lytic agents is strictly correlated, not to the species, but to the dissociative phases: these results are in accordance with those obtained in previous researches, carried out by the same Authors, on other characters, both morphological and biological, of the same variants. Thus, also through this way, it is possible to reach the conclusion that within this genus, there is more similarity among the different species of the same dissociative phase than among different dissociative variants of the same species. The results obtained in the present study allow to advance hypothesis, based also on the data of the literature, about the composition of the cell walls of the three above mentioned dissociative variants of the strains belonging to the genus Bacillus.

Bacillus↗
PubMed1992

Dissociation of inhibitory effects of low-dose ASA on thromboxane production and platelet aggregation in ischemic stroke patients.

Acetylsalicylic acid (ASA) inhibits thromboxane production and hence platelet aggregation. However, individual variations in platelet aggregability and serum thromboxane B2 (TxB2) concentration after a low dose of ASA (40 mg/day) have been reported. To clarify this issue, we studied plasma thromboxane levels and platelet aggregation in 43 ischemic stroke patients. Of the 22 patients who received 100 mg of ASA daily, dissociation between inhibitory effects of ASA on the plasma TxB2 level and threshold concentrations of adenosine diphosphate was found in three cases after one month of drug administration, and in three cases after six, 12 and 18 months of ASA therapy. This dissociation also developed in two patients after one month and six months, respectively, of treatment in the 21 patients who received 300 mg of ASA daily. The dissociation between the inhibitory effects on plasma TxB2 and the circulating platelet aggregate ratio was found in two cases after taking medication for one month, and in four cases after six, 12, 18 and 24 months of therapy in the 100 mg ASA group. In the 300 mg ASA group, dissociation was noted in two cases after one month of medication, and in two cases after six and 12 months of medication. In these patients, although their TxB2 levels were inhibited to almost unmeasurable levels, platelet aggregation was still not inhibited. This ASA inhibitory dissociation phenomenon on platelet function may be due to the low dose of ASA, individual differences in platelet function in response to ASA therapy, or factors other than those involved in the cyclooxygenase system.

Aged↗