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At least 649 records · Page 36Linked to original sources
PubMed2003

Imatinib in combination with cytarabine for the treatment of Philadelphia-positive chronic myelogenous leukemia chronic-phase patients: rationale and design of phase I/II trials.

Imatinib (Gleevec) (formerly STI571) has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic BCR-ABL fusion protein of chronic myelogenous leukemia (CML) cells. In recent phase I and II studies testing this new compound in patients who had failed to respond to interferon (IFN), hematological and cytogenetic responses were reported in most of those with chronic-phase CML. However, in some patients resistance has been associated with a single amino acid substitution in a threonine residue of the Abl kinase domain. In vitro studies examining the effects of imatinib plus cytarabine (Ara-C) using CML cell lines and colony-forming assays of CML patient samples have shown synergistic antiproliferative effects of this combination. Thus several groups decided to investigate this new combination with the hypothesis that cell resistance would be less frequent. The CML French Group performed a phase II trial to determine the safety and tolerability of a combination of imatinib and Ara-C for previously untreated patients with chronic-phase CML. Treatment was administered on 28-day cycles for 12 months. Patients were treated continuously with imatinib orally at a dose of 400 mg daily. Ara-C was given on days 14 to 28 of each cycle at an initial dose of 20 mg/m(2)/d via subcutaneous injection, hydroxyurea (HU) being stopped at least 7 days before imatinib. Recently, the Dutch group decided to explore a combination of high-dose Ara-C with imatinib in patients in chronic-phase CML. Preliminary results are encouraging. However, a long follow-up is required before concluding that these strategies will overcome cell resistance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Relaxation processes in mixtures of liquid crystals and polymers near phase boundaries and during phase separation.

We present experimental studies of the relaxation of concentration fluctuations in a semidilute solution of polystyrene (PS) (30% by weight) in 4-cyano-4'-n-octyl-biphenyl (8CB) (70% by weight) using the photon correlation spectroscopy (PCS). In the homogeneous phase there are two modes of relaxation. The slow one (typical time scale is taus = 0.001 s) is due to the diffusion of polymer chains (of molecular mass 65,000) in the LC matrix (of molecular mass 290), while the fast one has the time scale of the order of tauf approximately 0.00001 s. The amplitude of the fast mode is much weaker than the one for the slow mode. Moreover it does not depend on the scattering wave vector, q. The value of the diffusion coefficient, Dc = 1/(tausq2) for the slow mode decreases with temperature according to the Arhenius law until we reach the coexistence curve. Its value close to the coexistence is Dc = 4 x 10(5) nm2/s and the activation energy in the homogeneous mixture is Ec=127 kJ/mol. If we gradually undercool the mixture below the coexistence into the metastable two-phase region without inducing the phase separation we find unexpectedly that Dc does not change with temperature even 4 degrees below the coexistence curve. The characteristic time of the fast mode does not depend on the scattering wave vector indicating that it is related to the transient gel structure. We have shown that it is possible to measure the short time relaxation of concentration fluctuations during the phase separation in the mixture. At low temperature close to the isotropic-nematic phase transition we have observed that the relaxation is well separated in time from the typical time of the domain growth. This relaxation mode is characterized by the large diffusion coefficient D = 2 x 10(8) nm2/s. The mode probably comes from the coupling between the orientational dynamics of liquid crystals and the transient gel structure of polymers.

Journal Article↗
PubMed2004

Combinatorial entropy and phase diagram of partially ordered ice phases.

A close analytical estimate for the combinatorial entropy of partially ordered ice phases is presented. The expression obtained is very general, as it can be used for any ice phase obeying the Bernal-Fowler rules. The only input required is a number of crystallographic parameters, and the experimentally observed proton site occupancies. For fully disordered phases such as hexagonal ice, it recovers the result deduced by Pauling, while for fully ordered ice it is found to vanish. Although the space groups determined for ice I, VI, and VII require random proton site occupancies, it is found that such random allocation of protons does not necessarily imply random orientational disorder. The theoretical estimate for the combinatorial entropy is employed together with free energy calculations in order to obtain the phase diagram of ice from 0 to 10 GPa. Overall qualitative agreement with experiment is found for the TIP4P model of water. An accurate estimate of the combinatorial entropy is found to play an important role in determining the stability of partially ordered ice phases, such as ice III and ice V.

Journal Article↗
PubMed1991

Influence of the mobile phase on salmon calcitonin analysis by reversed-phase liquid chromatography.

The retention properties of calcitonins on a reversed-phase column are examined using salmon calcitonin as the model compound. The effect of the concentration of organic modifier, buffer strength, pH of the mobile phase, and ion-pair reagent are studied. In the absence of an ionic modifier in the eluent the calcitonin peak shapes are not symmetrical. The addition of 0.1% trifluoroacetic acid (TFA), however, results in good peak characteristics without the need to add nonvolatile salts. The retention of the calcitonins was found to be very sensitive to the concentration of the organic modifier (acetonitrile) present in the mobile phase. A change of pH between 2 and 5 has only a slight effect of the k' of salmon calcitonin, but the k' increases significantly at higher pH values. The addition of a phosphate buffer to the mobile phase and an increase in the buffer concentration (0-0.2 M) causes a decrease in the retention of salmon calcitonin. Evidence shows that reproducible, quantitatively measurable data can be obtained using reversed-phase chromatography if the ion-pairing reagent and organic modifier concentrations are carefully controlled. The system also shows a good selectivity for the calcitonin series. Therefore, both highly selective methods (qualitative) as well as quantitative methods for analytical, pharmaceutical, and manufacturing use can be developed by adjusting the high-performance liquid chromatography (HPLC) conditions as discussed.

Amino Acid Sequence↗
PubMed1992

Promoter selectivity of the stationary-phase forms of Escherichia coli RNA polymerase and conversion in vitro of the S1 form enzyme into a log-phase enzyme-like form.

Upon growth transition of Escherichia coli cells from exponential to stationary phase, RNA polymerase is converted into at least three different forms (S1, S2 and S3), which could be separately isolated by phosphocellulose column chromatography (Ozaki et al., 1991 (2)). Here, the promoter selectivity of these three stationary-phase enzymes was examined using an in vitro mixed transcription system and an E. coli promoter collection. These altered forms of RNA polymerase showed different recognition properties of promoters from that by the log-phase holoenzyme (L1). One of the stationary-phase RNA polymerases, S1, was found to be converted in vitro into an enzyme like the log-phase form following incubation with nucleotides or pyrophosphate. The conversion was indicated by not only the shift of elution position from a phosphocellulose column but also the change in the promoter selectivity. These results may suggest that RNA polymerase is interconvertible between different forms with different promoter selectivity by interaction with a phosphorylated compound(s).

Adenosine Triphosphate↗
PubMed1992

N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery.

Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.

Animals↗
PubMed1998

Regulation of the spvR gene of the Salmonella typhimurium virulence plasmid during exponential-phase growth in intracellular salts medium and at stationary phase in L broth.

The authors previously showed that the SpvR-regulated spvABCD operon of the Salmonella typhimurium virulence plasmid is highly induced during exponential-phase growth by salmonellae intracellularly in mammalian cells and in a medium designed to mimic the intracellular environment of mammalian cells, intracellular salts medium (ISM), as well as at stationary phase in L broth (LB). The most relevant signal(s) for spv gene expression in vivo is not known. To elucidate the means by which salmonellae regulate the spv genes in response to the environment during the disease process, expression of the spvR gene, encoding the positive regulatory protein SpvR, was examined under these same growth conditions by using RNAse-protection analysis. spvR was expressed at a low, basal level during exponential growth in LB but was induced during exponential growth in ISM and during stationary phase in LB, the same conditions that increased expression of the spvABCD operon. Basal expression of spvR during exponential growth in LB was independent of both SpvR and the alternative sigma factor RpoS, whereas maximal induction of spvR was dependent on both SpvR and RpoS. In an RpoS- background, spvR message was decreased in stationary phase, whereas spvR exhibited residual RpoS-independent induction during exponential growth in ISM. Deletion of spvA from the virulence plasmid of S. typhimurium increased expression of spvR during stationary phase in LB, but not during exponential growth in ISM. These results suggest that expression of spvR is controlled by different regulatory factors, depending on the growth conditions encountered by the salmonellae.

Cloning, Molecular↗
PubMed2002

Coupling-reentrant phase transition, complex hysteretic behavior, and efficiency optimization in coupled phase oscillators submitted to colored flashing potentials.

A recent mean-field analysis of a model consisting of N nonlinear phase oscillators-under the joint influence of global periodic coupling with strength K0 and of local multiplicative and additive noises-has shown a nonequilibrium phase transition towards a broken-symmetry phase exhibiting noise-induced transport, or "ratchet" behavior. In a previous paper we focused on the relationship between the character of the (mean velocity vs load force F) hysteresis loop, the number of "homogeneous" mean-field solutions, and the shape of the stationary mean-field probability distribution function (PDF). Here we assume that the multiplicative noises of the model are Ornstein-Uhlenbeck with common strength Q and self-correlation time tau. By resorting to an effective Markovian approximation, we study the tau dependence of the phase boundary, and that of the line signaling the transition from the "interaction-driven regime" to the "noise-driven regime." We also study-for selected representative points of the K0 vs Q phase diagram-the tau dependence of the transport properties induced by coupling and colored multiplicative noise (including the efficiency epsilon of the mechanical rectification process) and that of the above-mentioned PDF.

Journal Article↗
PubMed2003

Detection of mutual phase synchronization in multivariate signals and application to phase ensembles and chaotic data.

This work presents a method for the detection of mutual phase synchronization in nonstationary time series. We show how the application of a cluster algorithm that considers spatiotemporal structures of data follows from the general condition of phase-synchronized data. In view of the topology of phasic data, we reformulate the K-means cluster algorithm on a flat torus and apply a segmentation index derived in an earlier work [A. Hutt and H. Riedel, Physica D 177, 203 (2003)]. This index is extended by means of averaging in order to reflect phase synchronization in ensembles of multivariate time series. The method is illustrated using simulated multivariate phase dynamics and arrays of chaotic systems, in which temporal segments of phase-synchronized states are registered. A comparison with results from an existing bivariate synchronization index reveals major advantages of our method.

Journal Article↗
PubMed2005

Induced and spontaneous deracemization in bent-core liquid crystal phases and in other phases doped with bent-core molecules.

Recently discovered chiral properties of several bent-core smectic liquid crystal phases are summarized and discussed in detail under the assumption that typical bent-core molecules may exist in chiral conformational states and are achiral only on average. Results of atomistic computer simulations are presented which indicate the existence of strongly chiral conformational states for typical bent-core mesogens. A theory is developed which describes a possible shift of equilibrium between left- and right-handed conformations in a macroscopically chiral phase. The theory describes a chirality induction in the B2 bent-core phase and a reduction of the helical pitch in cholesteric and chiral SmC* phases doped with bent-core molecules. Finally, the possibility of spontaneous deracemization in bent-core smectic phases is discussed in detail.

Journal Article↗
PubMed2005

Phase velocity and phase diffusion in periodically driven discrete-state systems.

We develop a theory to calculate the effective phase diffusion coefficient and the mean phase velocity in periodically driven stochastic models with two discrete states. This theory is applied to a dichotomically driven Markovian two-state system. Explicit expressions for the mean phase velocity, the effective phase diffusion coefficient, and the Pe clet number are analytically calculated. The latter indicates as a measure of phase-coherence forced synchronization of the stochastic system with respect to the periodic driving and exhibits a "bona fide" resonance. In a second step, the theory is applied to a non-Markovian two-state system modeling excitable systems. The results prove again stochastic synchronization to the periodic driving and are in good agreement with simulations of a stochastic FitzHugh-Nagumo system.

Journal Article↗
PubMed2001

Phase coexistence during surface phase transitions.

In contrast to standard thermodynamic models, we observe phase coexistence over an extended temperature range at a first-order surface phase transition. We have measured the domain evolution of the Si(111)-( 7x7) to ( 1x1) phase transition with temperature, using low-energy electron microscopy. Comparison with detailed, quantitative theoretical predictions shows that coexistence is due to long-range elastic and electrostatic domain interactions. Phase coexistence is predicted to be a universal feature of surface phase transitions.

Journal Article↗
PubMed2003

A study on phase-noise reduction method in phase-locked loop systems.

Experimental studies are carried out on phase noise and the correlation coefficient between the phase and average current noises of voltage-controlled oscillator in phased-locked loop (PLL) systems. The precise phase stabilization technique is discussed, and new methods to reduce the phase noise are described in PLL systems, using the correlation.

Letter↗
PubMed1992

Comparison of definitions of the lag phase and the exponential phase in bacterial growth.

Different definitions for the lag time and of the duration of the exponential phase can be used to calculate these quantities from growth models. The conventional definitions were compared with newly proposed definitions. It appeared to be possible to derive values for the lag time and the duration of the exponential phase from the growth models and differences between the various definitions could be quantified. All the different values can be calculated from the growth parameters microm, lambda and alpha. Therefore, it appeared to be unnecessary to use complicated mathematical equations; simple equations were adequate. For the Gompertz model the conventional definition of the lag time did not differ appreciably from the newly proposed definition. The end-point of the exponential phase and thus the duration of the exponential phase differed considerably for the two definitions. For the logistic model the two definitions lead to considerable differences for all quantities. It is recommended that the conventional definition is used for calculating the lag time. For the duration of the exponential phase it is recommended that the new definition is used. The value can be calculated, however, directly from the conventional growth parameters.

Bacteria↗
PubMed1990

Erythrocyte antibody screening in solid-phase: a comparison of two solid-phase microplate assays with the indirect antiglobulin test in polyethylene glycol for the detection of irregular erythrocyte antibodies.

The screening of a serum for irregular erythrocyte antibodies in the indirect antiglobulin test is a well-established technique. We compared the test results of two different solid-phase microplate indirect antiglobulin tests with a liquid-phase indirect antiglobulin test in tubes. Antibody screening with both solid-phase microplate techniques proved to be more sensitive than the liquid-phase indirect antiglobulin test. In addition, a difference in sensitivity between the two solid-phase techniques was observed: prior immobilization of test erythrocytes on the microplate followed by incubation with a serum and detection of sensitization with antihuman IgG-coated detector cells gave better test results than secondary immobilization on the microplate of test erythrocytes sensitized with antibodies and an antihuman globulin serum.

Antibodies↗
PubMed1982

Different sugar compositions of lipopolysaccharides isolated from phase I and pure phase II cells of Coxiella burnetii.

The compositions of lipopolysaccharides I and II, isolated from Coxiella burnetii phase I and pure phase II cells, respectively, showed drastic and clear-cut differences. Lipopolysaccharide II exhibited a comparatively simple composition. It contained, in addition to glucosamine (from lipid A) and a 2-keto-3-deoxyoctulosonic acid-related, thiobarbituric acid-positive substance, only two aldoses in high amounts, namely D-mannose and D-glycero-D-mannoheptose. Lipopolysaccharide I contained the same components, but it also contained at least eight other constituents including neutral sugars, e.g., an unusual branched sugar (3-C-methyl-6-deoxy-hexose) and unusual aminohexoses. Some components were characterized by a very high retention time in gas-liquid chromatography. The similarity of the phase variation in C. burnetii to the well-known smooth-to-rough mutation found in Enterobacteriaceae is discussed. Cells of phase I correspond to enterobacterial smooth forms, whereas cells of phase II might be compared to the rough forms.

Amino Sugars↗
PubMed2002

Exertion of the suppressive effects of IFN-gamma on experimental immune mediated blepharoconjunctivitis in Brown Norway rats during the induction phase but not the effector phase.

BACKGROUND/AIMS: Interferon gamma (IFN-gamma) knockout mice exhibit severe allergic conjunctivitis (AC), indicating that IFN-gamma regulates the development of AC. The authors examined whether this inhibitory effect of IFN-gamma is exerted during the induction or effector phase of experimental AC. METHODS: Experimental immune mediated blepharoconjunctivitis (EC) was induced in Brown Norway (BN) rats, using ovalbumin (OVA) as the antigen. To investigate the role of IFN-gamma in the induction phase, EC was induced by active immunisation and IFN-gamma (10 micro g/time, total 70 micro g), or phosphate buffered saline (PBS) as a control, was injected intraperitoneally every other day from the day of immunisation. The rats were challenged with OVA eye drops 13 days after immunisation, and 24 hours later, the eyes were harvested for histology. To examine the effects of IFN-gamma in the effector phase, OVA specific T cells were transferred into syngeneic rats and IFN-gamma (10 micro g/time, total 50 micro g) or PBS was injected each day after the transfer until induction of EC 4 days later with an OVA challenge. To investigate the role of endogenous IFN-gamma during the effector phase, an anti-IFN-gamma monoclonal antibody (3 mg/time) was injected on days 3 and 4. RESULTS: Injection of IFN-gamma into actively immunised rats suppressed eosinophilic infiltration but not infiltration of mononuclear cells. In contrast, neither IFN-gamma nor anti-IFN-gamma affected EC in passively immunised rats. CONCLUSION: IFN-gamma is a suppressive cytokine for the development of EC and exerts this suppressive effect during the induction phase.

Adoptive Transfer↗
PubMed1991

Quantitation of G0 and G1 phase cells in primary carcinomas. Antibody to M1 subunit of ribonucleotide reductase shows G1 phase restriction point block.

Human cancers have an apparent low growth fraction, the bulk of cells presumed to being out of cycle in a G0 quiescent state due to the inability in the past to distinguish G0 from G1 cells. The allosteric M1 subunit of ribonucleotide reductase (M1-RR) is constitutively expressed by cycling cells (i.e., G1, S, G2-M). It is acquired during transition from G0 to G1, lost during exit to G0 and thus distinguishes G0 from G1 cells. To estimate the proportion of G0 and G1 cells in primary human breast (n = 5) and colorectal (n = 12) adenocarcinomas, we used both analytical DNA flow cytometry (ADFC) and immunoperoxidase staining of sections with the monoclonal antibody to M1-RR (MAb M1-RR). ADFC of fresh tumors revealed a low percentage of cells in the S phase (4.0 +/- 3.4%) but immunoperoxidase staining for M1-RR revealed an unexpectedly high proportion of positive cells (52.4 +/- 12.7%) in the G1, S, G2-M phases indicating a high G1 content of primary human tumors. Thus, human cancers are blocked in transition in G1 and are not predominantly in a G0 or quiescent differentiated state. This block was interpreted to mean that human cancers are responding to putative regulatory events at a restriction point in the G1 phase, such as relative growth factor deficiency, density inhibition, antiproliferative cytokines, or gene products. Using flow cytometry for both DNA and M1-RR content we found that human colon cancer cell lines arrest in the G1 but not G0 phase upon serum deprivation or density inhibition. Similarly, human breast cancer cell lines are arrested in G1 but not G0 phase by medroxyprogesterone acetate (MPA) or tamoxifen exposure. These findings match our in situ observations, and support the concept of a restriction point block in primary human tumors.

Adenocarcinoma↗