Enhancement of spectral editing efficacy of multiple quantum filters in in vivo proton magnetic resonance spectroscopy

Kim, Hyeonjin,Thompson, Richard B.,Allen, Peter S. Elsevier 2012 Journal of magnetic resonance Vol.223 No.-

<P>The performance of multiple quantum filters (MQFs) can be disappointing when the background signal also arises from coupled spins. Moreover, at 3.0 T and even higher fields the majority of the spin systems of key brain metabolites fall into the strong-coupling regime. In this manuscript we address comprehensively, the importance of the phase of the multiple quantum coherence-generating pulse (MQ-pulse) in the design of MQFs, using both product operator and numerical analysis, in both zero and double quantum filter designs. The theoretical analyses were experimentally validated with the examples of myo-inositol editing and the separation of glutamate from glutamine. The results demonstrate that the phase of the MQ-pulse per se provides an additional spectral discrimination mechanism based on the degree of coupling beyond the conventional level-of-coherence approach of MQFs. To obtain the best spectral discrimination of strongly-coupled spin systems, therefore, the phase of the MQ-pulse must be included in the portfolio of the sequence parameters to be optimized.</P>

Patient-reported Outcomes of Acupuncture for Symptom Control in Cancer

Lora M.A. Thompson,Sarah Rausch Osian,Paul B. Jacobsen,Peter A S Johnstone 사단법인약침학회 2015 Journal of Acupuncture & Meridian Studies Vol.8 No.3

Acupuncture is increasingly offered as a treatment option for managing cancer-related symptoms. In addition to randomized controlled trials, patient-reported outcomes may be needed to establish treatment effectiveness. This study retrospectively examined the symptoms and the satisfaction ratings of 90 patients receiving acupuncture at an integrative oncology clinic. At least two acupuncture sessions were completed by 72% of the sample. The prevalence rates of fatigue, pain, anxiety, physical distress, emotional distress, and poor quality of life before acupuncture were > 62%. Paired t tests revealed a significant reduction in symptoms from baseline until after the first acupuncture session and after the last session (p < 0.05). Fewer (21%) patients reported nausea, which was significantly reduced after the first session, but not the last session. Reductions represented clinically meaningful differences in 33–41% of patients after the first session and in 41–53% of patients after the last session for all symptoms, except nausea. A small subset of patients (0–8%) reported worsening symptoms after acupuncture. The majority were satisfied with the service. The results of this study suggest that acupuncture may be useful as an adjunct treatment for cancer symptom management. While high-quality trials are still needed to establish the treatment's efficacy, patients may benefit from these primarily safe, low-cost services.

Multiple Residues in the P-Region and M2 of Murine Kir 2.1 Regulate Blockage by External Ba2+

이영미,Gareth A. Thompson,Ian Ashmole,Mark Leyland,Insuk So,Peter R. Stanfield 대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on Ba2+ blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary (CHO) cells and used the whole cell patch-clamp technique to record K+ currents in the absence and presence of externally applied Ba2+. Wild type Kir2.1 was blocked by externally applied Ba2+ in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of Ba2+ blockage. The estimated Kd(0) was 108μM for Kir2.1 wild type, 124μM for a concatameric WT-Y145V dimer, 109μM for a WT-Y145L dimer, and 267μM for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for Ba2+, also showing two components with very different time courses. Mutants D172K and D172R (lining the central, aqueous cavity of the channel) showed both a decreased affinity to Ba2+ and a decrease in the on transition rate constant (kon). These results imply that residues stabilising the cytoplasmic end of the selectivity filter (T141, S165) and in the central cavity (D172) are major determinants of high affinity Ba2+ blockage in Kir 2.1.

Multiple Residues in the P-Region and M2 of Murine Kir 2.1 Regulate Blockage by External $Ba^{2+}$

Lee, Young-Mee,Thompson, Gareth A.,Ashmole, Ian,Leyland, Mark,So, In-Suk,Stanfield, Peter R. The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on $Ba^{2+}$ blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary(CHO) cells and used the whole cell patch-clamp technique to record $K^+$ currents in the absence and presence of externally applied $Ba^{2+}$. Wild type Kir2.1 was blocked by externally applied $Ba^{2+}$ in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of $Ba^{2+}$ blockage. The estimated $K_d(0)$ was 108 ${\mu}M$ for Kir2.1 wild type, 124 ${\mu}M$ for a concatameric WT-Y145V dimer, 109 ${\mu}M$ for a WT-Y145L dimer, and 267 ${\mu}M$ for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for $Ba^{2+}$, also showing two components with very different time courses. Mutants D172K and D172R(lining the central, aqueous cavity of the channel) showed both a decreased affinity to $Ba^{2+}$ and a decrease in the on transition rate constant(${\kappa}_{on}$). These results imply that residues stabilising the cytoplasmic end of the selectivity filter(T141, S165) and in the central cavity(D172) are major determinants of high affinity $Ba^{2+}$ blockage in Kir 2.1.

The Efficacy of Medial Patellofemoral Ligament Reconstruction Combined with Tibial Tuberosity Transfer in the Treatment of Patellofemoral Instability

( Tarek Boutefnouchet ),( Christopher Downham ),( James Bassett ),( Peter Thompson ),( Andrew Sprowson ) 대한슬관절학회 2016 대한슬관절학회지 Vol.28 No.2

A systematic review of the literature was undertaken to evaluate the efficacy of medial patellofemoral ligament (MPFL) reconstruction combined with tibial tuberosity transfer (TTT) in the treatment of patellofemoral instability. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search was carried out to identify and review the published literature pertinent to MFPL reconstruction combined with TTT. Relevant studies were critically appraised with narrative data synthesis. Studies that met the eligibility criteria were suitable for appraisal and consisted of case series and therapeutic series (levels IV & III). All studies had inherent variations in outcomes reporting and limited follow-up. Combined treatment offers restoration of normal anatomy, thus adding clinical value to the currently recommended anatomic approach to MPFL reconstruction. Nevertheless, the current body of evidence does not determine the threshold at which patellofemoral axis requires the need for adjunctive distal realignment as opposed to MPFL reconstruction alone. This review highlighted numerous recurring limitations in the conduct and presentation of the studies, which inadvertently mitigated the interpretation of their results. Future priority should be awarded to larger randomised controlled trials utilising validated patient reported outcome measures.

Multiple Residues in the P-Region and M2 of Murine Kir 2.1 Regulate Blockage by External Ba<SUP>2+</SUP>

Young Mee Lee,Gareth A. Thompson,Ian Ashmole,Mark Leyland,Insuk So,Peter R. Stanfield 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on Ba²⁺ blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary (CHO) cells and used the whole cell patch-clamp technique to record K⁺ currents in the absence and presence of externally applied Ba²⁺. Wild type Kir2.1 was blocked by externally applied Ba²⁺ in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of Ba²⁺ blockage. The estimated K_d(0) was 108ՌM for Kir2.1 wild type, 124ՌM for a concatameric WT-Y145V dimer, 109ՌM for a WT-Y145L dimer, and 267ՌM for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for Ba²⁺, also showing two components with very different time courses. Mutants D172K and D172R (lining the central, aqueous cavity of the channel) showed both a decreased affinity to Ba²⁺ and a decrease in the on transition rate constant (k_on). These results imply that residues stabilising the cytoplasmic end of the selectivity filter (T141, S165) and in the central cavity (D172) are major determinants of high affinity Ba²⁺ blockage in Kir 2.1.

Synthetic GPI array to study antitoxic malaria response

Kamena, Faustin,Tamborrini, Marco,Liu, Xinyu,Kwon, Yong-Uk,Thompson, Fiona,Pluschke, Gerd,Seeberger, Peter H NATURE PUBLISHING GROUP 2008 NATURE CHEMICAL BIOLOGY Vol. No.

Parasite glycosylphosphatidylinositol (GPI) is an important toxin in malaria disease, and people living in malaria-endemic regions often produce high levels of anti-GPI antibodies. The natural anti-GPI antibody response needs to be understood to aid the design of an efficient carbohydrate-based antitoxin vaccine. We present a versatile approach based on a synthetic GPI glycan array to correlate anti-GPI antibody levels and protection from severe malaria.