bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of low glucose on carotid body chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells
Authors: Gallego-Martin Teresa , Fernandez-Martinez Silvia , Rigual Ricardo , Obeso Ana , Gonzalez Constancio
Published: December 2011

The participation of the carotid body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB chemoreceptor cells are glucoreceptors. However, data generated in intact, freshly excised organs deny CB chemoreceptor cells' glucosensing properties. The physiological significance of the contention has prompted the present study, performed in a newly developed preparation of the intact CB organ in culture that maintains chemoreceptor cells' microenvironment. Chemoreceptor cells of intact CBs in culture retained their capacity to store, synthesize, and secrete catecholamine in response to hypoxia for at least 6 days. Aglycemia did not elicit neurosecretion in dissociated chemoreceptor cells or in intact CB in culture, but potentiated hypoxia-elicited neurosecretion, exclusively, in 1-day-old intact CB cultures and dissociated chemoreceptor cells cultured for 24 h. In fura 2-loaded cells, aglycemia (but not 1 mM) caused a slow Ca2+-dependent and nifedipine-insensitive increase in fluorescence at 340- to 380-nm wavelength emission ratio and augmented the fluorescent signal elicited by hypoxia. Association of nifedipine and KBR7943 (a Na+/Ca2+ exchanger inhibitor) completely abolished the aglycemic Ca2+ response. We conclude that chemoreceptor cells are not sensitive to hypoglycemia. We hypothesize that cultured chemoreceptor cells become transiently more dependent on glycolysis. Consequently, aglycemia would partially inhibit the Na+/K+ pump, causing an increase in intracellular Na+ concentration, and a reversal of Na+/Ca2+ exchanger. This would slowly increase intracellular Ca2+ concentration and cause the potentiation of the hypoxic responses. We discuss the nature of the signals detected by chemoreceptor cells for the CB to achieve its glycemic homeostatic role.
Hydroxyproline metabolism in mouse models of primary hyperoxaluria
Authors: Knight John , Holmes Ross P. , Cramer Scott D. , Takayama Tatsuya , Salido Eduardo
Published: December 2011

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source of glyoxylate and could account for a significant portion of the oxalate produced in PH. To determine the sensitivity of mouse models of PH1 and PH2 to Hyp-derived oxalate, animals were fed diets containing 1% Hyp. Urinary excretions of glycolate and oxalate were used to monitor Hyp catabolism and the kidneys were examined to assess pathological changes. Both strains of knockout (KO) mice excreted more oxalate than wild-type (WT) animals with Hyp feeding. After 4 wk of Hyp feeding, all mice deficient in glyoxylate reductase/hydroxypyruvate reductase (GRHPR KO) developed severe nephrocalcinosis in contrast to animals deficient in alanine-glyoxylate aminotransferase (AGXT KO) where nephrocalcinosis was milder and with a lower frequency. Plasma cystatin C measurements over 4-wk Hyp feeding indicated no significant loss of renal function in WT and AGXT KO animals, and significant and severe loss of renal function in GRHPR KO animals after 2 and 4 wk, respectively. These data suggest that GRHPR activity may be vital in the kidney for limiting the conversion of Hyp-derived glyoxylate to oxalate. As Hyp catabolism may make a major contribution to the oxalate produced in PH patients, Hyp feeding in these mouse models should be useful in understanding the mechanisms associated with calcium oxalate deposition in the kidney.
Interaction between uric acid and HMGB1 translocation and release from endothelial cells
Authors: Rabadi May M. , Kuo Mei-Chuan , Ghaly Tammer , Rabadi Seham M. , Weber Mia , Goligorsky Michael S. , Ratliff Brian B.
Published: December 2011

We aimed to investigate the potential relationship between alarmins [acting via Toll-like receptor-4 (TLR4)], uric acid (UA), and high-mobility group box-1 protein (HMGB1) during acute kidney injury. UA, which is significantly increased in the circulation following renal ischemia-reperfusion injury (IRI), was used both in vitro and in vivo as an early response-signaling molecule to determine its ability to induce the secretion of HMGB1 from endothelial cells. Treatment of human umbilical vein endothelial cells (HUVEC) with UA resulted in increased HMGB1 mRNA expression, acetylation of nuclear HMGB1, and its subsequent nuclear-cytoplasmic translocation and release into the circulation, as determined by Western blotting and immunofluorescence. Treatment of HUVEC with UA and a calcium mobilization inhibitor (TMB-8) or a MEK/Erk pathway inhibitor (U0126) prevented translocation of HMGB1 from the nucleus, resulting in reduced cytoplasmic and circulating levels of HMGB1. Once released, HMGB1 in autocrine fashion promoted further HMGB1 release while also stimulating NF-κB activity and increased angiopoietin-2 expression and protein release. Transfection of HUVEC with TLR4 small interfering (si) RNA reduced HMGB1 levels during UA and HMGB1 treatment. In summary, UA after IRI mediates the acetylation and release of HMGB1 from endothelial cells by mechanisms that involve calcium mobilization, the MEK/Erk pathway, and activation of TLR4. Once released, HMGB1 promotes its own further cellular release while acting as an autocrine and paracrine to activate both proinflammatory and proreparative mediators.
Frequency tuning of medial-olivocochlear-efferent acoustic reflexes in humans as functions of probe frequency
Authors: Lilaonitkul Watjana , Guinan John J.
Published: December 2011

The medial-olivocochlear (MOC) acoustic reflex is thought to provide frequency-specific feedback that adjusts the gain of cochlear amplification, but little is known about how frequency specific the reflex actually is. We measured human MOC tuning through changes in stimulus frequency otoacoustic emissions (SFOAEs) from 40-dB-SPL tones at probe frequencies ( fps) near 0.5, 1.0, and 4.0 kHz. MOC activity was elicited by 60-dB-SPL ipsilateral, contralateral, or bilateral tones or half-octave noise bands, with elicitor frequency ( fe) varied in half-octave steps. Tone and noise elicitors produced similar results. At all probe frequencies, SFOAE changes were produced by a wide range of elicitor frequencies with elicitor frequencies near 0.7–2.0 kHz being particularly effective. MOC-induced changes in SFOAE magnitude and SFOAE phase were surprisingly different functions of fe: magnitude inhibition largest for fe close to fp, phase change largest for fe remote from fp. The metric ΔSFOAE, which combines both magnitude and phase changes, provided the best match to reported (cat) MOC neural inhibition. Ipsilateral and contralateral MOC reflexes often showed dramatic differences in plots of MOC effect vs. elicitor frequency, indicating that the contralateral reflex does not give an accurate picture of ipsilateral-reflex properties. These differences in MOC effects appear to imply that ipsilateral and contralateral reflexes have different actions in the cochlea. The implication of these results for MOC function, cochlear mechanics, and the production of SFOAEs are discussed.
In vivo voltammetry monitoring of electrically evoked extracellular norepinephrine in subregions of the bed nucleus of the stria terminalis
Authors: Herr Natalie R. , Park Jinwoo , McElligott Zoé A. , Belle Anna M. , Carelli Regina M. , Wightman R. Mark
Published: December 2011

Norepinephrine (NE) is an easily oxidized neurotransmitter that is found throughout the brain. Considerable evidence suggests that it plays an important role in neurocircuitry related to fear and anxiety responses. In certain subregions of the bed nucleus of the stria terminalis (BNST), NE is found in large amounts. In this work we probed differences in electrically evoked release of NE and its regulation by the norepinephrine transporter (NET) and the α2-adrenergic autoreceptor (α2-AR) in two regions of the BNST of anesthetized rats. NE was monitored in the dorsomedial BNST (dmBNST) and ventral BNST (vBNST) by fast-scan cyclic voltammetry at carbon fiber microelectrodes. Pharmacological agents were introduced either by systemic application (intraperitoneal injection) or by local application (iontophoresis). The iontophoresis barrels were attached to a carbon fiber microelectrode to allow simultaneous detection of evoked NE release and quantitation of iontophoretic delivery. Desipramine (DMI), an inhibitor of NET, increased evoked release and slowed clearance of released NE in both regions independent of the mode of delivery. However, the effects of DMI were more robust in the vBNST than in the dmBNST. Similarly, the α2-AR autoreceptor inhibitor idazoxan (IDA) enhanced NE release in both regions but to a greater extent in the vBNST by both modes of delivery. Since both local application by iontophoresis and systemic application of IDA had similar effects on NE release, our results indicate that terminal autoreceptors play a predominant role in the inhibition of subsequent release.
Nonhomogeneous transfer reveals specificity in speech motor learning
Authors: Rochet-Capellan Amélie , Richer Lara , Ostry David J.
Published: December 2011

Does motor learning generalize to new situations that are not experienced during training, or is motor learning essentially specific to the training situation? In the present experiments, we use speech production as a model to investigate generalization in motor learning. We tested for generalization from training to transfer utterances by varying the acoustical similarity between these two sets of utterances. During the training phase of the experiment, subjects received auditory feedback that was altered in real time as they repeated a single consonant-vowel-consonant utterance. Different groups of subjects were trained with different consonant-vowel-consonant utterances, which differed from a subsequent transfer utterance in terms of the initial consonant or vowel. During the adaptation phase of the experiment, we observed that subjects in all groups progressively changed their speech output to compensate for the perturbation (altered auditory feedback). After learning, we tested for generalization by having all subjects produce the same single transfer utterance while receiving unaltered auditory feedback. We observed limited transfer of learning, which depended on the acoustical similarity between the training and the transfer utterances. The gradients of generalization observed here are comparable to those observed in limb movement. The present findings are consistent with the conclusion that speech learning remains specific to individual instances of learning.
Animal-to-animal variability of connection strength in the leech heartbeat central pattern generator
Authors: Roffman Rebecca C. , Norris Brian J. , Calabrese Ronald L.
Published: December 2011

The heartbeat central pattern generator (CPG) in medicinal leeches controls blood flow within a closed circulatory by programming the constrictions of two parallel heart tubes. This circuit reliably produces a stereotyped fictive pattern of activity and has been extensively characterized. Here we determined, as quantitatively as possible, the strength of each inhibitory synapse and electrical junction within the core circuit of the heartbeat CPG. We also examined the animal-to-animal variability in strengths of these connections and, for some, determined the correlations between connections to the same postsynaptic target. The core CPG is composed of seven bilateral pairs of heart interneurons connected via both inhibitory chemical synapses and electrical junctions. Fifteen different connections within the core CPG were measured for strength using extracellular presynaptic recordings and postsynaptic voltage-clamp recordings across a minimum of seven individuals each, and the animal-to-animal variability was characterized. Connection strengths within the core network varied three to more than sevenfold among individuals (depending on the specific connection). The balance between two inputs onto various postsynaptic targets was explored by within-individual comparisons and correlation across individuals. Of the seven comparisons made within the core CPG, three showed a clear correlation of connection strengths, while the other four did not. We conclude that the leech heartbeat CPG can withstand wide variability in connection strengths and still produce stereotyped output. The network appears to preserve the relative strengths of some pairs of inputs, despite the animal-to-animal variability.
Recording from the same neurons chronically in motor cortex
Authors: Fraser George W. , Schwartz Andrew B.
Published: December 2011

Two rhesus monkeys were implanted with silicon arrays of 96 microelectrodes. Neural activity was recorded periodically over a period of weeks to months. We have developed a method to determine whether single units in two separate recording sessions represent the same neuron. Pairwise cross-correlograms, the autocorrelogram, waveform shape, and mean firing rate were used together as identifying features of a neuron. When two units recorded on separate days were compared using these features, their similarity scores tended to be either high, indicating two recordings from the same neuron, or low, indicating different neurons. Although these metrics are individually weak, together they produce a strong classifier. Some neurons were recorded for >100 days. These monkeys performed a center-out reaching task, and we found that the firing properties of chronically recorded neurons were stable over time.
Development of Bio-Machine Based on the Plant Response to External Stimuli
Authors: Aditya K. , Udupa Ganesha , Lee Yongkwun
Published: December 2011

In the area of biorobotics, intense research work is being done based on plant intelligence. Any living cell continuously receives information from the environment. In this paper, research is conducted on the plant nameddescoingsiixhaworthioides(Pepe) obtaining the action potential signals and its responses to stimulations of different light modes. The plant electrical signal is the reaction of plant’s stimulation owing to various environmental conditions. Action potentials are responsible for signaling between plant cells and communication from the plants can be achieved through modulation of various parameters of the electrical signal in the plant tissue. The modulated signals are used for providing information to the microcontroller’s algorithm for working of the bio-machine. The changes of frequency of action potentials in plant are studied. Electromyography (EMG) electrodes and needle-type conductive electrodes along with electronic modules are used to collect and transform the information from the plant. Inverse fast Fourier transform (IFFT) is used to convert signal in frequency domain into voltage signal for real-time analysis. The changes in frequency of the plant action potentials to different light modes are used for the control of the bio-machine. This work has paved the way for an extensive research towards plant intelligence.
Dynamic Mechanical Response of Biomedical 316L Stainless Steel as Function of Strain Rate and Temperature
Authors: Lee Woei-Shyan , Chen Tao-Hsing , Lin Chi-Feng , Luo Wen-Zhen
Published: December 2011

A split Hopkinson pressure bar is used to investigate the dynamic mechanical properties of biomedical 316L stainless steel under strain rates ranging from 1 × 103 s-1to 5 × 103 s-1and temperatures between25∘Cand800∘C. The results indicate that the flow stress, work-hardening rate, strain rate sensitivity, and thermal activation energy are all significantly dependent on the strain, strain rate, and temperature. For a constant temperature, the flow stress, work-hardening rate, and strain rate sensitivity increase with increasing strain rate, while the thermal activation energy decreases. Catastrophic failure occurs only for the specimens deformed at a strain rate of 5 × 103 s-1and temperatures of25∘Cor200∘C. Scanning electron microscopy observations show that the specimens fracture in a ductile shear mode. Optical microscopy analyses reveal that the number of slip bands within the grains increases with an increasing strain rate. Moreover, a dynamic recrystallisation of the deformed microstructure is observed in the specimens tested at the highest temperature of800∘C.
How to Group Genes according to Expression Profiles?
Authors: Di Rienzo Julio A. , Valdano Silvia G. , Fernández Paula
Published: December 2011

The most commonly applied strategies for identifying genes with a common response profile are based on clustering algorithms. These methods have no explicit rules to define the appropriate number of groups of genes. Usually the number of clusters is decided on heuristic criteria or through the application of different methods proposed to assess the number of clusters in a data set. The purpose of this paper is to compare the performance of seven of these techniques, including traditional ones, and some recently proposed. All of them produce underestimations of the true number of clusters. However, within this limitation, the gDGC algorithm appears to be the best. It is the only one that explicitly states a rule for cutting a dendrogram on the basis of a testing hypothesis framework, allowing the user to calibrate the sensitivity, adjusting the significance level.
Gender-Specific Cytokine Pathways, Targets, and Biomarkers for the Switch from Health to Adenoma and Colorectal Cancer
Authors: Pellegrini Patrizia , Contasta Ida , Del Beato Tiziana , Ciccone Fabiana , Berghella Anna Maria
Published: December 2011

Studies focusing on gender have shown that differences exist in how the immune system responds to disease and therapy. Understanding how gender influences immunological mechanisms in health and disease and identifying gender-specific biomarkers could lead to specifically tailored treatment and ultimately improve therapeutic success rates. T helper1 (Th1) and Th2 cytokines (Th1/Th2) have pivotal roles in the homeostasis of Th1 and Th2 cell network functions in the immune response but sex steroids affect Th1/Th2 production in different ways and a natural sexual dimorphism in the immune response has been shown. In order to investigate these differences further, we developed Th-cytokine data-driven models of the immune response and evaluated healthy subject peripheral blood samples. Independent cohorts of colorectal cancer and adenoma patients were also studied for comparison purposes. Our results show that the interferon (IFN)γproduction pathway for immune response homeostasis is specific to men whilst the interleukin- (IL-) 6 production pathway for immune response homeostasis is specific to women. The IL-10 pathway for restoring immune system resting homeostasis was common to both but was controlled by the respective gender-specific pathways. These gender pathways could well be used as targets and biomarkers in translational research into developing new clinical strategies.
Hosting Infection: Experimental Models to AssayCandidaVirulence
Authors: MacCallum Donna M.
Published: December 2011

Although normally commensals in humans,Candida albicans,Candida tropicalis,Candida parapsilosis,Candida glabrata,andCandida kruseiare capable of causing opportunistic infections in individuals with altered physiological and/or immunological responses. These fungal species are linked with a variety of infections, including oral, vaginal, gastrointestinal, and systemic infections, withC. albicansthe major cause of infection. To assess the ability of differentCandidaspecies and strains to cause infection and disease requires the use of experimental infection models. This paper discusses the mucosal and systemic models of infection available to assayCandidavirulence and gives examples of some of the knowledge that has been gained to date from these models.
Zingiber officinaleImproves Cognitive Function of the Middle-Aged Healthy Women
Authors: Saenghong Naritsara , Wattanathorn Jintanaporn , Muchimapura Supaporn , Tongun Terdthai , Piyavhatkul Nawanant , Banchonglikitkul Chuleratana , Kajsongkram Tanwarat
Published: December 2011

The development of cognitive enhancers from plants possessing antioxidants has gained much attention due to the role of oxidative stress-induced cognitive impairment. Thus, this study aimed to determine the effect of ginger extract, orZingiber officinale, on the cognitive function of middle-aged, healthy women. Sixty participants were randomly assigned to receive a placebo or standardized plant extract at doses of 400 and 800 mg once daily for 2 months. They were evaluated for working memory and cognitive function using computerized battery tests and the auditory oddball paradigm of event-related potentials at three different time periods: before receiving the intervention, one month, and two months. We found that the ginger-treated groups had significantly decreased P300 latencies, increased N100 and P300 amplitudes, and exhibited enhanced working memory. Therefore, ginger is a potential cognitive enhancer for middle-aged women.
Glutaminase Immunoreactivity and Enzyme Activity Is Increased in the Rat Dorsal Root Ganglion Following Peripheral Inflammation
Authors: Miller Kenneth E. , Balbás John C. , Benton Richard L. , Lam Travis S. , Edwards Kristin M. , Kriebel Richard M. , Schechter Ruben
Published: December 2011

Following inflammation, primary sensory neurons in the dorsal root ganglion (DRG) alter the production of several proteins. Most DRG neurons are glutamatergic, using glutaminase as the enzyme for glutamate production, but little is known about glutaminase following inflammation. In the present study, adjuvant-induced arthritis (AIA) was produced in rats with complete Freund's adjuvant into the hindpaw. At 7 days of AIA, DRG were examined with glutaminase immunohistochemistry, Western blot immunoreactivity, and enzyme activity. Image analysis revealed that glutaminase was elevated most in small-sized neurons (21%) (P< 0.05). Western blot analysis revealed a 19% increase (P< 0.05) in total glutaminase and 21% in mitochondrial glutaminase (P< 0.05). Glutaminase enzyme activity was elevated 29% (P< 0.001) from 2.20 to 2.83 moles/kg/hr. Elevated glutaminase in primary sensory neurons could lead to increased glutamate production in spinal primary afferent terminals contributing to central sensitization or in the peripheral process contributing to peripheral sensitization.
Mercury Toxicity and Treatment: A Review of the Literature
Authors: Bernhoft Robin A.
Published: December 2011

Mercury is a toxic heavy metal which is widely dispersed in nature. Most human exposure results from fish consumption or dental amalgam. Mercury occurs in several chemical forms, with complex pharmacokinetics. Mercury is capable of inducing a wide range of clinical presentations. Diagnosis of mercury toxicity can be challenging but can be obtained with reasonable reliability. Effective therapies for clinical toxicity have been described.
Adaptive Binary Arithmetic Coder‐Based Image Feature and Segmentation in the Compressed Domain
Authors: Hsin Hsi-Chin , Sung Tze-Yun , Shieh Yaw-Shih , Cattani Carlo
Published: December 2011

Image compression is necessary in various applications, especially for efficient transmission over a band‐limited channel. It is thus desirable to be able to segment an image in the compressed domain directly such that the burden of decompressing computation can be avoided. Motivated by the adaptive binary arithmetic coder (MQ coder) of JPEG2000, we propose an efficient scheme to segment the feature vectors that are extracted from the code stream of an image. We modify the Compression‐based Texture Merging (CTM) algorithm to alleviate the influence of overmerging problem by making use of the rate distortion information. Experimental results show that the MQ coder‐based image segmentation is preferable in terms of the boundary displacement error (BDE) measure. It has the advantage of saving computational cost as the segmentation results even at low rates of bits per pixel (bpp) are satisfactory.
Ovarian Cancer: Opportunity for Targeted Therapy
Authors: Tagawa Tomoko , Morgan Robert , Yen Yun , Mortimer Joanne
Published: December 2011

Ovarian cancer is a common cause of cancer mortality in women with limited treatment effectiveness in advanced stages. The limitation to treatment is largely the result of high rates of cancer recurrence despite chemotherapy and eventual resistance to existing chemotherapeutic agents. The objective of this paper is to review current concepts of ovarian carcinogenesis. We will review existing hypotheses of tumor origin from ovarian epithelial cells, Fallopian tube, and endometrium. We will also review the molecular pathogenesis of ovarian cancer which results in two specific pathways of carcinogenesis: (1) type I low-grade tumor and (2) type II high-grade tumor. Improved understanding of the molecular basis of ovarian carcinogenesis has opened new opportunities for targeted therapy. This paper will also review these potential therapeutic targets and will explore new agents that are currently being investigated.
Highly Active Rare-Earth-Metal La-Doped Photocatalysts: Fabrication, Characterization, and Their Photocatalytic Activity
Authors: Anandan S. , Ikuma Y. , Murugesan V.
Published: December 2011

Efficient La-doped TiO2photocatalysts were prepared by sol-gel method and extensively characterized by various sophisticated techniques. The photocatalytic activity of La-doped TiO2was evaluated for the degradation of monocrotophos (MCPs) in aqueous solution. It showed higher rate of degradation than pure TiO2for the light of wavelength of 254 nm and 365 nm. The rate constant of TiO2increases with increasing La loading and exhibits maximum rate for 1% La loading. The photocatalytic activities of La-doped TiO2are compared with La-doped ZnO; the reaction rate of the former is ~1.8 and 1.1 orders higher than the latter for the lights of wavelength 254 nm and 365 nm, respectively. The relative photonic efficiency of La-doped TiO2is relatively higher than La-doped ZnO and commercial photocatalysts. Overall, La-doped TiO2is the most active photocatalyst and shows high relative photonic efficiencies and high photocatalytic activity for the degradation of MCP. The enhanced photocatalytic activity of La-doped TiO2is mainly due to the electron trapping by lanthanum metal ions, small particle size, large surface area, and high surface roughness of the photocatalysts.
Immune Modulation in PrimaryVaccinia virusZoonotic Human Infections
Authors: Gomes Juliana Assis Silva , de Araújo Fernanda Fortes , Trindade Giliane de Souza , Quinan Bárbara Resende , Drumond Betânia Paiva , Ferreira Jaqueline Maria Siqueira , Mota Bruno Eduardo Fernandes , Nogueira Maurício Lacerda , Kroon Erna Geessien , Abrahão Jônatas Santos , Côrrea-Oliveira Rodrigo , da Fonseca Flávio Guimarães
Published: December 2011

In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, includingMonkeypox,Cowpox,andVaccinia virus(VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.
Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation
Authors: Lian Jiqin , Ni Zhenhong , Dai Xufang , Su Chang , Smith Amber Rae , Xu Liang , He Fengtian
Published: December 2011

The natural BH3-mimetic (−)-gossypol shows promising efficacy in ongoing phase II/III clinical trials for human prostate cancer. Here, we show for the first time, that treatment with (−)-gossypol and multikinase inhibitor sorafenib synergistically suppresses the growth of androgen-independent prostate cancer cells (AI-PC) in vitro and in vivo. Our data suggest that sorafenib attenuates (−)-gossypol-induced Mcl-1 upregulation in AI-PCs. In this way, it serves as a potent chemosensitizer to affect cell death. Interestingly, (−)-gossypol and sorafenib induce cell death via two distinct pathways among different AI-PCs; DU145 cells via apoptosis and PC-3 via autophagy. The appointed death pathway may depend on the level of proapoptotic protein Bak, although the level of antiapoptotic protein Bcl-2 plays some role in it. DU145 cells with high Bak level prefer apoptosis induction, whereas PC-3 cells with low Bak prefer the induction of autophagy. Furthermore, inhibiting nondominant death pathways, that is, autophagy in DU145 and apoptosis in PC-3, enhances cell killing by (−)-gossypol/sorafenib combination therapy. Ultimately, our data expose a new action for sorafenib as an enhancer of (−)-gossypol-induced cell growth suppression and reveal a novel cell death mode by Bak activation manners in AI-PCs. These new insights may facilitate the rational design of clinical trials by selecting patients most likely to benefit from the Bcl-2–targeted molecular therapy. Mol Cancer Ther; 11(2); 416–26. ©2011 AACR.
Impact of Ventralis Caudalis Deep Brain Stimulation Combined with Stereotactic Bilateral Cingulotomy for Treatment of Post-Stroke Pain
Authors: Kim Joo Pyung , Chang Won Seok , Park Young Seok , Chang Jin Woo
Published: December 2011

Stroke is the third leading cause of death worldwide. As the elderly population grows, interest in the quality of life, management and treatment of patients with post-stroke pain has grown. Pharmacological treatment is usually the first line of management in these patients. However, if medications fail to achieve appropriate pain relief, neuroablative or neuromodulating procedures are used as alternative methods to interrupt the transmission of pain. We performed unilateral ventralis caudalis deep brain stimulation combined with stereotactic bilateral cingulotomy to maximize the effects of treatment for 3 patients with intractable post-stroke pain.
Some Capabilities for Model-Based and Model-Free Linkage Analysis using the Program Package S.A.G.E. (Statistical Analysis for Genetic Epidemiology)
Authors: Schnell A.H. , Sun X. , Igo, Jr. R.P. , Elston R.C.
Published: December 2011

For both model-free and model-based linkage analysis the S.A.G.E. (Statistical Analysis for Genetic Epidemiology) program package has some unique capabilities in analyzing both continuous traits and binary traits with variable age of onset. Here we highlight model-based linkage analysis of a quantitative trait (plasma dopamine β hydroxylase) that is known to be largely determined by monogenic inheritance, using a prior segregation analysis to produce the best fitting model for the trait. For a binary trait with variable age of onset (schizophrenia), we illustrate how using age of onset information to obtain a quantitative susceptibility trait leads to more statistically significant linkage signals, suggesting better power.
The Effect of Intraventricular Trajectory on Brain Shift in Deep Brain Stimulation
Authors: Kramer Daniel R. , Halpern Casey H. , Danish Shabbar F. , Jaggi Jurg L. , Baltuch Gordon H.
Published: December 2011

Background: Brain shift during deep brain stimulation (DBS) surgery may compromise target localization. Loss of cerebrospinal fluid is believed to be the underlying mechanism, thus an intraventricular trajectory during DBS surgery may be associated with increased shift, in addition to other complications, such as intraventricular hemorrhage. Objective: We set out to assess the effect of traversing the lateral ventricle on brain shift during DBS surgery. Methods: We performed a retrospective review of 65 pre- and postoperative MR images of patients who underwent bilateral subthalamic nucleus deep brain stimulator placement to treat advanced Parkinson’s disease. Patients were separated into two groups: Group A (intraventricular trajectory, n = 46) and Group B (no intraventricular trajectory, n = 19). In these patients, we compared pre- and postoperative frame coordinates of the red nucleus (RN). Results: Group B demonstrated significantly more posterior shift of the center of the RN (1.40 ± 1.32 mm) than Group A (0.64 ± 1.76 mm; p < 0.02). We found no increase in incidence of intraventricular hemorrhage or the number of microelectrode trajectory attempts. Conclusions: Intraventricular trajectories during DBS surgery do not appear to compromise safety or targeting accuracy.
Which Cortical Area Is Related to the Development of Dysphagia after Stroke? A Single Photon Emission Computed Tomography Study Using Novel Analytic Methods
Authors: Momosaki Ryo , Abo Masahiro , Kakuda Wataru , Uruma Go
Published: December 2011

Purpose: The purpose of this study is to clarify cortical areas related to the development of dysphagia in poststroke patients using novel analytic methods for single photon emission computed tomography (SPECT) imaging. Subjects and Methods: Twenty poststroke patients (age: 66.1 ± 5.1 years) with a left hemispheric lesion were studied. According to clinical evaluation, patients were divided into a dysphagia group (n = 10) and a control group (n = 10). In each patient, measurement of regional cerebral blood flow (rCBF) was performed by SPECT imaging with a 99mTc-ethylcysteinate dimer. For the analysis, an easy Z-score imaging system and voxel-based stereotactic extraction estimation were applied, with placing regions of interest segmented into the Brodmann area level. We compared rCBF in each area between the two groups, and receiver operating characteristic analysis to calculate the area under the curve was also performed. Results: The rCBF in Brodmann areas 4 and 24 was significantly lower in the dysphagia group. The highest area under the curve was found in Brodmann area 4. In this area, 80% sensitivity and 60% specificity for discriminating dysphagia were achieved with an optimal cutoff value. Conclusions: When analyzed with novel methods, SPECT imaging can be useful for predicting the risk of dysphagia and subsequent aspiration in poststroke patients.
Role of Endoscopic Ultrasonography in Patients Suspected of Pancreatic Cancer with Negative Helical MDCT Scan
Authors: Deerenberg Eva B. , Poley Jan-Werner , Hermans John J. , Ganesh Sjam , van der Harst Erwin , van Eijck Casper H.J.
Published: December 2011

Background: In some patients suspected of pancreatic cancer, no mass can be detected by multidetector computed tomography (MDCT) scan as the cause of biliary obstruction. Methods: All patients suspected of pancreatic cancer between January 2007 and 2009 with a negative MDCT were identified from a database. Results: MDCT was performed for suspected pancreatic cancer in 290 patients, and in 258 a pancreatic mass was found. MDCT failed to establish a diagnosis in 32 patients (11%). In 23 patients (74%) with complete endoscopic ultrasonography (EUS), the cause of the obstruction was correctly diagnosed. A mass in the pancreatic head was found in 15 patients; 13 patients had a malignant tumor, and 2 patients a benign cause of obstruction. Further, EUS diagnosed 3 patients with a superficial adenoma of the papilla and 8 patients with a benign cause of the obstruction. In 5 patients EUS could not detect the cause of obstruction but finally a pancreatic malignancy was diagnosed. The positive predictive value of EUS was 86% and the negative predictive value 63%. Accuracy of MDCT and EUS decreased in the presence of pancreatitis or a biliary endoprosthesis. Conclusion: In patients suspected of pancreatic cancer in whom MDCT fails to demonstrate the cause of obstructive jaundice, EUS identifies 74% of the underlying diseases correctly.
Visual Improvement following Continuous Positive Airway Pressure Therapy in Diabetic Subjects with Clinically Significant Macular Oedema and Obstructive Sleep Apnoea: Proof of Principle Study
Authors: Mason Rebecca H. , Kiire Christine A. , Groves Dawn C. , Lipinski Helen J. , Jaycock Alyson , Winter Barbara C. , Smith Lewis , Bolton Anne , Rahman Najib M. , Swaminathan R. , Chong Victor N. , Stradling John R.
Published: December 2011

Background: Diabetic retinopathy and diabetic macular oedema are more prevalent in patients with coexistent obstructive sleep apnoea (OSA). Objectives: We assessed if treatment of OSA with continuous positive airway pressure (CPAP) might improve visual acuity (VA). Methods: A total of 35 patients with clinically significant macular oedema (CSMO) and OSA [oxygen desaturation index (ODI) ≥10 or apnoea-hypopnoea index (AHI) ≥15] were identified and agreed to be studied. VA (expressed as the logarithm of the minimum angle of resolution, logMAR), macular thickness, fundal photographs, glycosylated haemoglobin (HbA1c) and rhodopsin mRNA were measured twice at baseline and at 3 and 6 months post-CPAP. Fluorescein angiography and the Epworth Sleepiness Scale (ESS) were obtained once at baseline and at 6 months. Results: Three patients withdrew before the first trial visit. Thus, a total of 32 patients (17 males) entered the study, and 4 subsequently withdrew; thus 28 completed 6 months of follow-up. Baseline characteristics of the subjects were as follows [mean (SD or inter-quartile range)]: age 66.2 (7.1) years, body mass index 31.7 (6.3), HbA1c 7.4% (1.44) [57.1 (15.7) mmol/mol], AHI 16.5 (11–25), ODI 16.0 (12–25), ESS 6.5 (4.0–12.0) and duration of diabetes 9.5 years (5.0–16.5). Participants were divided into 13 high and 15 low CPAP compliers (≥ and <2.5 h/night over the 6 months, respectively). At 6 months, the adjusted treatment effect on VA of high compliance versus low compliance was 0.11 (95% confidence interval 0.21 to –0.002; p = 0.047), equivalent to a one-line improvement on the logMAR chart. There was no significant improvement in macular oedema or fundal photographs. Conclusions: This hypothesis-generating, uncontrolled study suggests that ≥2.5 h/night CPAP usage over 6 months in individuals with CSMO and OSA may be associated with improvement in VA. This provides justification for a randomised controlled trial of CPAP therapy in such patients.
Sampling Aqueous Humor: Anterior Segment Anatomy, Anesthetic and Surgical Technique, and Rates of Yield
Authors: Bertelmann Thomas , Kičová Nadia , Kohlberger Laura , Spychalska Marta , Strodthoff Stefan , Irle Sebastian , Mennel Stefan
Published: December 2011

Purpose: To evaluate anterior segment anatomy and anesthetic and surgical techniques with respect to the amount of aqueous humor (AH) that can be sampled out of the anterior chamber (AC) at the beginning of standard cataract removal procedures (phacoemulsification). Methods: In a prospective survey, volumes of sampled AH from 123 eyes (110 patients) were analyzed in regard to AC anatomy (anterior chamber depth, ACD) and different anesthetic techniques (local and general anesthesia). Results: 107 eyes (87%) were included into our analysis, and 16 eyes (13%) had to be excluded due to failure of AH collection. We found a significant positive association between ACD and obtained AH volume (p = 0.007). In general anesthesia, a strong trend to acquire more AH in comparison to local anesthesia was apparent, but statistical significance failed (p = 0.167). Different anesthetic techniques seem to have no significant influence on ACD (p = 0.169). No training curve for the individual surgeon was obtained. No complications were observed. Conclusion: When AH sampling is performed in eyes with a deep AC and when the procedure is performed under general anesthesia, more AH can be aspirated.
Intracranial Radiosurgery: An Effective and Disruptive Innovation in Neurosurgery
Authors: Niranjan Ajay , Madhavan Ravindranath , Gerszten Peter C. , Lunsford L. Dade
Published: December 2011

Physicians are guided by the teachings of their chosen field, standards of accepted practice, peer pressure, prior training, and other sources of bias. When potential bias begins to impact recommendations for care in the field of tumor management, physicians may fail to realize the importance of emerging medical innovations. Some of these ultimately turn out to be ‘disruptive innovations.’ These innovations are more often than not both low risk and cost effective. But the leaders in the field often initially ignore these newer technologies in favor of more mature existing technologies. However, over time these technologies gradually improve and become mainstream management practices. Intracranial radiosurgery is one such innovation which was not embraced by the neurosurgical community in the beginning. Nowadays, a wide variety of brain and body disorders are treated with radiosurgery. Acoustic neuromas and brain metastases are examples of rapidly growing indications of radiosurgery. In this report, the authors describe the emergence of stereotactic radiosurgery as a disruptive innovation in the field of medicine.
Molecular Cytogenetic Aberrations in Tunisian Patients with Multiple Myeloma Identified by cIg-FISH in Fixed Bone Marrow Cells
Authors: Gmidène A. , Avet-Loiseau H. , Sennana H. , Ben Abdallah I. , Khlif A. , Meddeb B. , Elloumi M. , Saad A.
Published: December 2011

Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or ĸ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease.
Computing and Partitioning Cloud Feedbacks Using Cloud Property Histograms. Part II: Attribution to Changes in Cloud Amount, Altitude, and Optical Depth
Authors: Zelinka Mark D. , Klein Stephen A. , Hartmann Dennis L.
Published: December 2011

Cloud radiative kernels and histograms of cloud fraction, both as functions of cloud-top pressure and optical depth, are used to quantify cloud amount, altitude, and optical depth feedbacks. The analysis is applied to doubled-CO2 simulations from 11 global climate models in the Cloud Feedback Model Intercomparison Project.

Global, annual, and ensemble mean longwave (LW) and shortwave (SW) cloud feedbacks are positive, with the latter nearly twice as large as the former. The robust increase in cloud-top altitude in both the tropics and extratropics is the dominant contributor to the positive LW cloud feedback. The negative impact of reductions in cloud amount offsets more than half of the positive impact of rising clouds on LW cloud feedback, but the magnitude of compensation varies considerably across the models. In contrast, robust reductions in cloud amount make a large and virtually unopposed positive contribution to SW cloud feedback, though the intermodel spread is greater than for any other individual feedback component. Overall reductions in cloud amount have twice as large an impact on SW fluxes as on LW fluxes, such that the net cloud amount feedback is moderately positive, with no models exhibiting a negative value. As a consequence of large but partially offsetting effects of cloud amount reductions on LW and SW feedbacks, both the mean and intermodel spread in net cloud amount feedback are smaller than those of the net cloud altitude feedback. Finally, the study finds that the large negative cloud feedback at high latitudes results from robust increases in cloud optical depth, not from increases in total cloud amount as is commonly assumed.
‘To stop train pull chain’
Authors: Mitchell Lisa
Published: December 2011

Many political practices in India are today regarded as disruptive, extralegal, violent or otherwise detrimental to India’s democratic record, yet at the same time they have functioned in the past and continue to function as widespread forms of political communication. This article argues that such practices—often associated with those in positions of structural marginalisation—are as deserving of analysis and understanding as forms and sites of communication more conventionally associated with the history of democracy, such as the coffee houses and forms of print media associated with the bourgeois public sphere in Europe or practices associated with elections. Using the very common practice of alarm chain pulling to stop a train for political purposes as a specific example, the article also argues that it is important to place contemporary forms of political practice into their longer historical genealogies in order to fully understand their significance within the history and practice of democracy in India today.
Latino Parent Involvement
Authors: Jasis Pablo M. , Ordoñez-Jasis Rosario
Published: December 2011

This study examines the process of parent engagement at three community and school-based parent participation projects involving Latino immigrant families in California. Through the participants’ testimonios, the study investigates the motivations and interactions contextualizing their leadership development, participation, and organizing activities as well as the significance of their emerging school activism on other aspects of their lives. Specifically, the study explores the notions of tequío and women-led activism, seen as critical to understanding the participants’ engagement process and to increase the level and quality of Latino parent participation in schools, maximizing its positive impact on their children’s education and life prospects.
A Grounded Theory of Collaborative Synchronizing in Relation to Challenging Students
Authors: Thornberg Robert
Published: December 2011

The aim of this study was to investigate multiprofessional collaboration as well as collaboration between professionals and challenging students and their parents in which the focus for these collaborations was on handling the challenging students’ academic and social behavior. A grounded theory study of collaboration between a prereferral resource team and teachers, principals, challenging students, and their parents was conducted. Qualitative interview and focus group methods were used. The findings presented a grounded theory of collaborative synchronizing in relation to challenging students around two ideal types, human resource synchronizing and human resource desynchronizing.