Biomedical subjects

B Rosenstein

Publications and source records attributed to B Rosenstein.

At least 19 recordsLinked to original sources

PubMed2005

Equilibrium first-order melting and second-order glass transitions of the vortex matter in Bi2Sr2CaCu2O8.

The thermodynamic phase diagram of Bi2Sr2CaCu2O8 was mapped by measuring local equilibrium magnetization M(H,T) in the presence of vortex shaking. Two equally sharp first-order magnetization steps are revealed in a single temperature sweep, manifesting a liquid-solid-liquid sequence. In addition, a second-order glass transition line is revealed by a sharp break in the equilibrium M(T) slope. The first- and second-order lines intersect at intermediate temperatures, suggesting the existence of four phases: Bragg glass and vortex crystal at low fields, glass and liquid at higher fields.

Journal Article↗

PubMed2001

Precision calculation of magnetization and specific heat of vortex liquids and solids in type-II superconductors.

A new systematic calculation of magnetization and specific heat contributions of vortex liquids and solids is presented. We develop an optimized perturbation theory for the Ginzburg-Landau description of thermal fluctuations effects in the vortex liquids. The expansion is convergent in contrast to the conventional high temperature expansion which is asymptotic. In the solid phase we calculate the first two orders which are already quite accurate. The results are in good agreement with existing Monte Carlo simulations and experiments. Limitations of various nonperturbative and phenomenological approaches are noted. In particular, we show that there is no exact intersection point of the magnetization curves.

Journal Article↗

PubMed2001

TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage.

Activating transcription factor 2 (ATF2/CRE-BP1) is implicated in transcriptional control of stress-responsive genes. A yeast two-hybrid screen identified TBP-interacting protein 49b (TIP49b), a component of the INO80 chromatin-remodeling complex, as a novel ATF2-interacting protein. TIP49b's association with ATF2 is phosphorylation dependent and requires amino acids 150 to 248 of ATF2 (ATF2(150-248)), which are implicated in intramolecular inhibition of ATF2 transcriptional activities. Forced expression of TIP49b efficiently attenuated ATF2 transcriptional activities under normal growth conditions as well as after UV treatment, ionizing irradiation, or activation of p38 kinase, all of which induced ATF2 phosphorylation and increased TIP49b-ATF2 association. Constitutive expression of ATF2(150-248) peptide outcompeted TIP49b interaction with ATF2 and alleviated the suppression of ATF2 transcriptional activities. Expression of ATF2(150-248) in fibroblasts or melanoma but not in ATF2-null cells caused a profound G(2)M arrest and increased degree of apoptosis following irradiation. The interaction between ATF2 and TIP49b constitutes a novel mechanism that serves to limit ATF2 transcriptional activities and highlights the central role of ATF2 in the control of the cell cycle and apoptosis in response to stress and DNA damage.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2000

K(ATP) channel blocker HMR 1883 reduces monophasic action potential shortening during coronary ischemia in anesthetised pigs.

ATP-sensitive potassium channels (KATP) open during myocardial ischemia. The ensuing repolarising potassium efflux shortens the action potential. Accumulation of extracellular potassium is able to partially depolarise the membrane, reducing the upstroke velocity of the action potential and thereby impairing impulse conduction. Both mechanisms are believed to be involved in the development of reentrant arrhythmias during cardiac ischemia. The sulfonylthiourea HMR 1883 (1-[[5-[2-(5-chloro-O-anisamido)ethyl]-methoxyphenyl]sulfonyl]-3-m ethylthiourea) was designed as a cardioselective KATP channel blocker for the prevention of arrhythmic sudden death in patients with ischemic heart disease. The aim of this study was to show that this compound, which has already shown antifibrillatory efficacy in dogs and rats, is able to inhibit ischemic changes of the action potential induced by coronary artery occlusion in anesthetised pigs. Action potentials were taken in situ with the technique of monophasic action potential (MAP) recording. In a control group (n=7), three consecutive occlusions of a small branch of the left circumflex coronary artery resulted in reproducible reductions in MAP duration and a decrease in upstroke velocity. In a separate group (n=7), HMR 1883 (3 mg/kg i.v.) significantly (P<0.05) reduced the ischemia-induced shortening of the MAP: during the first and second control occlusion of the coronary artery in the HMR 1883-group, MAP50 duration shortened from 218.5 +/- 3.0 ms to 166.7 +/- 3.3 ms and from 219.7 +/- 4.5 ms to 164.9 +/- 1.8 ms, respectively. After HMR 1883, during the third occlusion, MAP duration decreased from 226.9 +/- 3.6 ms to 205.3 +/- 4.3 ms only corresponding to 59% inhibition. HMR 1883 also improved the upstroke velocity of the MAP, which was depressed by ischemia: in the two preceding control occlusions ischemia prolonged the time to peak of the MAP, an index for upstroke velocity, from 10.83 +/- 0.43 ms to 39.42 +/- 1.60 ms and from 12.97 +/- 0.40 ms to 37.17 +/- 2.98 ms, respectively. With HMR 1883, time to peak during ischemia rose from 12.42 +/- 0.51 ms to 25.53+/-2.51 ms only, corresponding to an average inhibitory effect of 53.4%. The irregular repolarisation contour of the ischemic MAP was also improved. In conclusion, the present results indicate that HMR 1883 effectively blocks myocardial KATP channels during coronary ischemia in anesthetised pigs, preventing an excessive shortening of the action potential and improving excitation propagation.

Action Potentials↗

PubMed1999

ATP-sensitive potassium channel blocker HMR 1883 reduces mortality and ischemia-associated electrocardiographic changes in pigs with coronary occlusion.

ATP-sensitive potassium (K(ATP)) channels are activated during myocardial ischemia. The ensuing potassium efflux leads to a shortening of the action potential duration and depolarization of the membrane by accumulation of extracellular potassium favoring the development of reentrant arrhythmias, including ventricular fibrillation. The sulfonylthiourea HMR 1883 was designed as a cardioselective blocker of myocardial K(ATP) channels for the prevention of arrhythmic sudden death in patients with ischemic heart disease. We investigated the effect of HMR 1883 on sudden cardiac arrhythmic death and electrocardiography (ECG) changes induced by 20 min of left anterior descending coronary artery occlusion in pentobarbital-anesthetized pigs. HMR 1883 (3 mg/kg i.v.) protected pigs from arrhythmic death (91% survival rate versus 33% in control animals; n = 12; p<.05). Ischemic areas were of a similar size. The compound had no effect on hemodynamics and ECG, including Q-T interval, under baseline conditions and no effect on hemodynamics during occlusion. In control animals, left anterior descending coronary artery occlusion lead to a prompt and significant depression of the S-T segment (-0.35 mV) and a prolongation of the Q-J time (+46 ms), the former reflecting heterogeneity in the plateau phase of the action potentials and the latter reflecting irregular impulse propagation and delayed ventricular activation. Both ischemic ECG changes were significantly attenuated by HMR 1883 (S-T segment, -0.14 mV; Q-J time, +15 ms), indicating the importance of K(ATP) channels in the genesis of these changes. In conclusion, the K(ATP) channel blocker HMR 1883, which had no effect on hemodynamics and ECG under baseline conditions, reduced the extent of ischemic ECG changes and sudden death due to ventricular fibrillation during coronary occlusion.

Anesthesia↗

PubMed1998

Benzo[a]pyrene enhances the formation of 8-hydroxy-2'-deoxyguanosine by ultraviolet A radiation in calf thymus DNA and human epidermoid carcinoma cells.

The objective of this study is to investigate if benzo[a]pyrene (BaP) and ultraviolet (UV) radiation synergistically induce oxidative DNA damage. Calf thymus DNA was incubated with BaP and irradiated with UVB (280-320 nm) and UVA (335-400 nm). BaP substantially enhanced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) by UVA, but only moderately increased the level of 8-OHdG by UVB. Formation of 8-OHdG proportionally correlated with both UV dose and BaP concentration. Human epidermoid carcinoma cells were incubated with 10 microg of BaP/mL for 24 h and then exposed to 10 kJ/m2 UVB and 25 kJ/m2 UVA. UVB plus BaP did not affect the level of 8-OHdG in cultured cells, whereas UVA plus BaP substantially increased 8-OHdG by over 4-fold compared to BaP and UVA controls. To confirm what reactive oxygen species (ROS) are involved in BaP plus UVA-induced oxidative DNA damage, less or more specific ROS quenchers were added to DNA solution. The results showed that only superoxide dismutase and genistein significantly quenched BaP plus UVA-induced 8-OHdG, whereas catalase, sodium azide, and mannitol exhibited no effect. Our studies suggest that BaP enhances the formation of 8-OHdG in purified DNA and cultured cells by UVA, but not by UVB, and that superoxide anion plays an important role in the synergistic induction of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Differential regulation of P53 and Bcl-2 expression by ultraviolet A and B.

The induction of apoptosis by ultraviolet (UV) radiation and other DNA damaging agents plays a critical role in monitoring the accumulation of genetic damage and the suppression of tumor development. We hypothesize that UVA and UVB induce apoptosis by modulating balances between p53 and/or bcl-2 genes. Using MCF-7 cells that express both wild-type P53 and Bcl-2 proteins, we demonstrated that UVA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. UVA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by approximately 40% at 4 h post-150 kJ UVA irradiation per m2 with a maximum downregulation (over 70%) at 24 h. The dose-response studies revealed that significant reduction of bcl-2 expression was observed at UVA doses ranging from 50 to 200 kJ per m2; however, p53 levels were not affected by UVA. In contrast, UVB exhibited a entirely different action than UVA in that UVB substantially induced p53 expression, but had no effect on bcl-2 expression. The induction of P53 by UVB was dose and time dependent with the maximum expression at 24 h post-2 and post-4 kJ UVB irradiation per m2. Down-regulation of bcl-2 and fragmentation of DNA induced by UVA occurred earlier (approximately at 4 h) than upregulation of p53 and DNA fragmentation by UVB (12-24 h). These results suggest that UVA and UVB cause cell damage through different mechanisms and that the balances between the expression of p53 and bcl-2 may play an important role in regulating the apoptosis induced by UV irradiation.

Apoptosis↗

PubMed1996