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Search Results: 1 - 10 of 123549 matches for " Edward T Olejniczak ? "
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A Surface Groove Essential for Viral Bcl-2 Function During Chronic Infection In Vivo
Joy Loh equal contributor,Qiulong Huang equal contributor,Andrew M Petros,David Nettesheim,Linda F. van Dyk,Lucia Labrada,Samuel H Speck,Beth Levine,Edward T Olejniczak,Herbert W Virgin IV ?
PLOS Pathogens , 2005, DOI: 10.1371/journal.ppat.0010010
Abstract: Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the γ-herpesvirus 68 (γHV68) Bcl-2 family protein (γHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the γHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type γHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of γHV68 from latency and efficient persistent γHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.
A high-field 3He Metastability Exchange Optical Pumping polarizer operating in a 1.5 T medical scanner for lung MRI
G. Collier,T. Pa?asz,A. Wojna,B. G?owacz,M. Suchanek,Z. Olejniczak,T. Dohnalik
Physics , 2013, DOI: 10.1063/1.4807836
Abstract: After being hyperpolarized using the technique of Metastability Exchange Optical Pumping (MEOP), 3He can be used as a contrast agent for lung magnetic resonance imaging (MRI). MEOP is usually performed at low magnetic field (~ 1 mT) and low pressure (~ 1 mbar), which results in a low magnetization production rate. A delicate polarization-preserving step of compression is also required. It was demonstrated in sealed cells that high nuclear polarization values can be obtained at higher pressures with MEOP, if performed at high magnetic field (non-standard conditions). In this work the feasibility of building a high-field polarizer that operates within a commercial 1.5 T scanner was evaluated. Preliminary measurements of nuclear polarization with sealed cells filled at different 3He gas pressures (1.33 to 267 mbar) were performed. The use of an annular shape for the laser beam increased by 25 % the achievable nuclear polarization equilibrium value (Meq) at 32 and 67 mbar as compared to a Gaussian beam shape. Meq values of 66.4 and 31 % were obtained at 32 and 267 mbar respectively and the magnetization production rate was increased by a factor of 10 compared to the best results obtained under standard conditions. To study the reproducibility of the method in a polarizing system, the same experiments were performed with small cells connected to a gas handling system. The polarization build-up times were approximately 3 times longer in the 20-30 mbar range of pressure than those obtained for the 32 mbar sealed cell. However, reasonable Meq values of 40-60 % were achieved in a 90 mL open cell. Based on these findings, a novel compact polarizing system was designed and built. Its typical output is a 3He gas flow rate of 15 sccm with a polarization of 33 %. In-vivo lung MRI ventilation images were acquired to demonstrate the polarizer s application.
Botulinum Toxin Injections for Simple Partial Motor Seizures Associated with Pain
Edward C. Mader Jr.,Bruce J. Fisch,Nicole R. Villemarette-Pittman,Piotr W. Olejniczak,Michael E. Carey
Case Reports in Medicine , 2012, DOI: 10.1155/2012/295251
Abstract: Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX) injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.
Typical Spike-and-Wave Activity in Hypoxic-Ischemic Brain Injury and its Implications for Classifying Nonconvulsive Status Epilepticus
Edward C. Mader Jr, Nicole R. Villemarette-Pittman, Sergei V. Kashirny, Lenay Santana-Gould and Piotr W. Olejniczak
Clinical Medicine Insights: Case Reports , 2012, DOI: 10.4137/CCRep.S9861
Abstract: Introduction: Typical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE “de novo” in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury. Case presentation: A 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour). Conclusion: This is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, ‘post-hypoxic’ TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.
Mono-, bi- and tri- graphene layers deposited on conductive Au/Cr/SiO2/Si substrate studied by scanning tunnelling spectroscopy
Z. Klusek,P. Dabrowski,P. Kowalczyk,W. Kozlowski,P. Blake,M. Szybowicz,T. Runka,W. Olejniczak
Physics , 2008,
Abstract: Graphene devices require electric contacts with metals, particularly with gold. Scanning tunneling spectroscopy studies of electron local density of states performed on mono-, bi- and tri- graphene layer deposited on metallic conductive Au/Cr/SiO2/Si substrate shows that gold substrate causes the Fermi level shift downwards which means that holes are donated by metal substrate to graphene which becomes p-type doped. These experimental results are in good accordance with recently published density function theory calculations. The estimated positions of the Dirac point show that the higher number of graphene layers the lower Fermi level shift is observed.
Multinuclear MAS NMR study of structural changes in LaF3 doped borosilicate glasses for optoelectronics
Marcin Sroda,Zbigniew Olejniczak
Optica Applicata , 2008,
Abstract: A new type of oxyfluoride glass-ceramics based on the silicate glassy matrix and the nano-phase of LaF3 was developed for generating the up-conversion luminescence processes. In such material, the low-phonon energy crystals of LaF3 are desirable host for the rare-earth elements. The effect of admixture of 3 mol% of La2F6 on the structural changes of glasses in the Na2O–B2O3–SiO2 system was investigated. The effect of LaF3 additive was studied using 29Si, 11B, and 23Na MAS NMR to learn more about the structural role of modifiers as well as fluorine in the glassy matrix. Glasses with compositions corresponding to different B2O3/Na2O and B2O3/(Na2O + 3La2F6) ratios in the 0.6–1.2 range were obtained by melt quenching. The 29Si MAS NMR spectra indicated that the [SiO4] units are more polymerized when the ratios and the fluorine admixture increase. The 11B NMR spectra revealed the presence of both [BO4] (Q4) and [BO3] (Q3) units. The fraction of Q3 increased with the decreasing sodium content. Glasses with the LaF3 additive showed higher BO3/BO4 ratios. The effect of thermal treatment for glasses with the tendency towards LaF3 crystallization was discussed in terms of structural changes.
The fungus Epichlo typhina in populations of a halophyte Puccinellia distans: salinity as a possible inhibitor of infection
Marlena Lembicz,Pawe? Olejniczak
Acta Societatis Botanicorum Poloniae , 2009, DOI: 10.5586/asbp.2009.011
Abstract: Puccinellia distans is a non-agricultural halophytic grass that has become another host plant for Epichloe typhina, hitherto not reported from Poland. In 1992 we noticed the first symptoms of choke disease in a single population of P. distans in central Poland. Since then we have observed choke disease in 5 populations of P. distans only in man-made habitats. These habitats are strongly anthropogenically salinated but they exhibit the pattern of species composition characteristic of natural salines. In this paper we test the hypothesis that the level of salinity affects the infection of P. distans by the fungus E. typhina. Seven plots were established in the field and each plot was divided into 25 subplots. Within each plot the level of infection in a spring generation of shoots was negatively correlated with salinity (common regression within the plots, beta = -0.674, df = 117, p < 0.001). Negative correlation was also found in an autumn generation within the plots (beta = -0.682, df = 94, p < 0.001) after excluding plot P in which the frequency of infected individuals was the lowest and equal only to 0.05. The proportion of individuals infected by the endophytic stage of the fungus in the populations was assessed using diagnostic polymerase chain reaction. The greatest percentage (98.3%) of infected individuals was found in the population growing in the habitat of the lowest salinity. The high salinity reduces the chance of P. distans to become infected, but may promote the stroma formation of E. typhina twice in the season. Disease expression in autumn clearly represents a misadaptation which could be explained by the fact that the species interactions described here appeared relatively recently as a result of human activity. This hypothesis requires further experimental verification.
The Cholera Pandemic, Still with Us after Half a Century: Time to Rethink
Edward T. Ryan
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001003
Gold compounds in medicine: Potential anti-tumour agents
Edward R. T. Tiekink
Gold Bulletin , 2003, DOI: 10.1007/BF03215502
Abstract: An overview of the use of gold drugs in the alleviation of the symptoms associated with the debilitating disease rheumatoid arthritis (RA) is presented. Other potential therapies based on gold compounds, such as against parasitic diseases, HIV and asthma are summarised. The development of gold compounds as novel anti-tumour agents is also described. Compounds containing gold(I), as utilised in the treatment of RA, and gold(III), show exciting potential in this regard, there being some very potent compounds targeting biological targets, such as DNA, and displaying selectivity in their cytotoxic profiles. In conclusion, very real potential exists for the development of anti-tumour agents based on gold.
Robotic excision of aortic valve papillary fibroelastoma and concomitant Maze procedure
Edward T Murphy
Global Cardiology Science & Practice , 2012, DOI: 10.5339/gcsp.2012.27
Abstract: Cardiothoracic surgeons have utilized the surgical robot to provide a minimally invasive approach to a number of intracardiac operations, including tumor resection, valve repair, and ablation of atrial arrhythmia. We report the case of a 58 year-old woman who was found to have a mobile mass on her aortic valve during evaluation of atrial fibrillation. Both of these conditions were addressed when she underwent a combined robotic biatrial Maze procedure and excision of the mass, which proved to be a papillary fibroelastoma of the aortic valve.
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