We have recently isolated a rat homologue of theCaenorrhabditis elegans lin-10product. Although rat lin-10 is expressed in the cytosol and membrane fractions of various tissues, it is distributed ...only in the membrane fraction in brain where it is enriched in the synaptic plasma membrane and postsynaptic density fractions. We have isolated here a rat lin-10-interacting protein from rat brain and identified it to be neurabin-II/spinophilin, which has recently been isolated as a protein interacting with protein phosphatase I and F-actin. Neurabin-II/spinophilin is ubiquitously expressed but enriched in brain, especially in the synaptic plasma membrane and postsynaptic density fractions. We discuss the physiological significance of the interaction of rat lin-10 with neurabin-II/spinophilin.
The physiologically active metabolite of vitamin D3, 1,25-dihydroxycholecalciferol (D3), plays an important role in embryonic development and cell differentiation. Previously, we have demonstrated ...that D3 significantly induces differentiation and inhibits growth of LA-N-5 human neuroblastoma cells at concentrations of 24 nm and higher. In this study, we compared two D3 analogs, 20-epi-22oxa-25a,26a,27a-tri-homo-1,25-D3 (KH 1060) and 1,25-dihydroxy-22,24-diene, 24,26,27-trihomo (EB 1089), with D3 with respect to their effects on differentiation and growth inhibition. We report an inhibition of growth by 45-55% in cells treated with 0.24 nm EB 1089 and 0.24 nM KH 1060, similar to that seen in cells treated with 24 nM D3. At these concentrations, both EB 1089 and KH 1060 stimulate the differentiation of LA-N-5 neuroblastoma cells as shown by increased neurite outgrowth, decreased N-myc expression and decreased invasiveness in vitro. An increase in acetylcholinesterase activity, a functional measure of differentiation, was also exhibited. Previous reports have shown that treatment doses needed to achieve 24 nM serum concentrations of D3 in patients would result in hypercalcemia. EB 1089 and KH 1060 can cause the same in vitro effects on LA-N-5 human neuroblastoma cells at 1/100 of the concentration required of D3. These data suggest a potential clinical efficacy of EB 1089 and KH 1060 as biological response modifiers.
Pulsed ArF excimer laser (193 nm)-CW infrared (IR) tunable diode laser Herriott type absorption spectroscopic technique has been made for the detection of product hydrochloric acid HCl. Absorption ...spectroscopic technique is used in the reaction chlorine atoms with methyl iodide (Cl+CH3I) to the study of kinetics on reaction Cl+CH3I and the yield of (HCl). The reaction of Cl+CH3I has been studied with the support of the reaction Cl+C4H10 (100% HCl) at temperature 298 K. In the reaction Cl+CH3I, the total pressure of He between 20 and 125 Torr at the constant concentration of CH3I 7.0×10(14) molecule cm(-3). In the present work, we estimated adduct formation is very important in the reaction Cl+CH3I and reversible processes as well and CH3I molecule photo-dissociated in the methyl CH3 radical. The secondary chemistry has been studied as CH3+CH3ICl = product, and CH3I+CH3ICl = product2. The system has been modeled theoretically for secondary chemistry in the present work. The calculated and experimentally HCl yield nearly 65% at the concentration 1.00×10(14) molecule cm(-3) of CH3I and 24% at the concentration 4.0×10(15) molecule cm(-3) of CH3I, at constant concentration 4.85×10(12) molecule cm(-3) of CH3, and at 7.3×10(12) molecule cm(-3) of Cl. The pressure dependent also studied product of HCl at the constant CH3, Cl and CH3I. The experimental results are also very good matching with the modelling work at the reaction CH3+CH3ICl = product (k = (2.75±0.35)×10(-10) s(-1)) and CH3I+CH3ICl = product2 (k = 1.90±0.15)×10(-12) s(-1). The rate coefficients of the reaction CH3+CH3ICl and CH3I+CH3ICl has been made in the present work. The experimental results has been studied by two method (1) phase locked and (2) burst mode.
Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype.
To develop a population pharmacokinetic model for ...olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertensive patients, and to evaluate effects of covariates on the apparent oral clearance (CL/F), with particular emphasis on the effect of race.
Retrospective analysis of data from 12 phase I-III trials in the US, Europe and Japan.
Eighty-nine healthy volunteers and 383 hypertensive patients.
Nonlinear mixed-effects modelling was used to evaluate 7911 olmesartan plasma sample concentrations. The covariates included age, bodyweight, sex, race (Westerners including Caucasians and Hispanics versus Japanese), patient status (hypertensive patients versus healthy volunteers), serum creatinine level as an index of renal function and serum chemistry data as indices of hepatic function.
The pharmacokinetic data of olmesartan were well described by a two-compartment linear model with first-order absorption and an absorption lag-time, parameterised in terms of CL/F (6.66 L/h for a typical male Western hypertensive patient), absorption rate constant (1.46h-1), elimination rate constant (0.193h-1), rate constant from the central to peripheral compartment (0.061h-1), rate constant from the peripheral to central compartment (0.079h-1) and absorption lag-time (0.427h). Analysis of covariates showed that age, bodyweight, sex, patient status and renal function were factors influencing the clearance of olmesartan.
The population pharmacokinetic analysis of olmesartan showed that: (i) severe renal impairment (serum creatinine >265 micromol/L approximately 3 mg/dL) could cause a clearance decrease of > or =30%; (ii) older age, lower bodyweight and being female were determinants of lower clearance but their effects on olmesartan clearance were within 20%; (iii) no statistically significant difference in clearance was found between Westerners and Japanese.
Transverse momentum spectra and rapidity densities, dN/dy, of protons, antiprotons, and net protons (p-p) from central (0%-5%) Au+Au collisions at square root of S(NN)=200 GeV were measured with the ...BRAHMS experiment within the rapidity range 0</=y</=3. The proton and antiproton dN/dy decrease from midrapidity to y=3. The net-proton yield is roughly constant for y<1 at dN/dy approximately 7, and increases to dN/dy approximately 12 at y approximately 3. The data show that collisions at this energy exhibit a high degree of transparency and that the linear scaling of rapidity loss with rapidity observed at lower energies is broken. The energy loss per participant nucleon is estimated to be 73+/-6 GeV.
The following five antimony(V) tetraphenylporphyrins with σ-bonded antimony−carbon bonds were synthesized: (TPP)Sb(CH3)2+PF6 -, (TPP)Sb(OCH3)(OH)+PF6 -, (TPP)Sb(CH3)(OH)+ClO4 -, ...(TPP)Sb(CH3)(OCH3)+ClO4 -, and (TPP)Sb(CH3)(F)+PF6 -. Each compound is stable toward air and moisture and has a high melting point (>250 °C). The electrochemistry and spectroelectrochemistry of these σ-bonded porphyrins were examined in benzonitrile or dichloromethane containing 0.1 M tetrabutylammonium perchlorate as supporting electrolyte and the data compared to those for three previously synthesized OEP derivatives containing similar σ-bonded and/or anionic axial ligands. Each porphyrin shows two reversible reductions and up to a maximun of one oxidation within the potential window of the solvent. Spectroelectrochemical data indicate formation of a porphyrin π anion radical upon the first reduction as do ESR spectra of the singly reduced species. However, a small amount of the Sb(III) porphyrin products may be generated via a chemical reaction following electron tranfer. An X-ray crystallographic analysis of (TPP)Sb(CH3)(F)+PF6 - is also presented: monoclinic, space group C2/c, Z = 8, a = 24.068(5) Å, b = 19.456(4) Å, c = 18.745(3) Å, β = 94.69(2)°, R = 0.056.
Retinoic acid (RA) nuclear receptors (RARs) are thought to mediate the cellular and molecular effects of RA on a wide variety of tissues. In most cell types, RAR alpha expression remains relatively ...constant following exposure to RA, while that of RAR beta is rapidly induced. In this study, we show that in human neuroblastoma, a cell type exceptionally sensitive to RA-induced differentiation, RAR alpha as well as RAR beta is markedly up-regulated by RA treatment. This effect was consistent in all 5 neuroblastoma cell lines tested and was reflected in a 2- to 5-fold increase in receptor mRNA levels as assessed by Northern-blot analysis. Using LA-N-5 human neuroblastoma cells, we found that receptor up-regulation occurred in a time- and dose-dependent fashion with increases in both RAR alpha and beta mRNA detectable 1-2 hr after the addition of RA. These inductions were not abrogated by cycloheximide, indicating that protein synthesis was not required for the RA responses. Nuclear run-off experiments combined with Northern-blot analysis of RAR alpha stability directly demonstrated that the up-regulation of RAR alpha mRNA levels reflected an increased rate of transcription without changes in message half-life. These findings, showing direct activation by RA of RAR alpha gene transcription in human neuroblastoma cells, suggest differences in the overall regulation of this receptor from that found in most other RA-inducible tissue.
A statistical multifragmentation model (SMM) is applied to the experimentally observed multifragmentation events in an intermediate heavy ion reaction.Using the temperature and symmetry energy ...extracted from the isobaric yield ratio (IYR) method based on the Modified Fisher Model (MFM), SMM is applied to the reaction \(^{64}\)Zn + \(^{112}\)Sn at 40 MeV/nucleon. The experimental isotope distribution and mass distribution of the primary reconstructed fragments are compared without afterburner and they are well reproduced. The extracted temperature \(T\) and symmetry energy coefficient \(a_{sym}\) from SMM simulated events, using the IYR method, are also consistent with those from the experiment. These results strongly suggest that in the multifragmentation process there is a freezeout volume, in which the thermal and chemical equilibrium is established before or at the time of the intermediate-mass fragments emission.
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