UCI Authors in PubMed
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Potkin SG Department of Psychiatry, Robert R. Sprague Chair in Brain Imaging, Director, UCI Brain Imaging Center, University of California, Irvine, 5251 California Ave, Ste 240, Irvine, CA, USA. sgpotkin@uci.edu. |
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Asenapine: a clinical overview. J Clin Psychiatry. 2011;72 Suppl 1:14-8 Asenapine is a new, second-generation (atypical) antipsychotic medication with demonstrated efficacy for the acute and maintenance treatment of schizophrenia. It is administered as sublingual tablets in doses of 5 or 10 mg bid. It is well tolerated, with a dropout rate for adverse events similar to that of placebo. Asenapine is associated with a mean weight gain of less than 1 kg over a year and a relatively neutral effect on lipid and glucose levels. It can cause sedation and mild extrapyramidal side effects. Asenapine has a broad receptor affinity profile for most serotonergic, dopaminergic, and adrenergic receptors, with no appreciable affinity for muscarinic receptors. Asenapine may be a helpful treatment option for patients with schizophrenia when weight gain, dyslipidemia, and endocrine abnormalities are a concern. PMID: 22217438 |
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Simpson J,Nien CJ,Flynn K,Jester B,Cherqui S,Jester J Department of Biochemistry, Jawaharlal Nehru Medical College, Maharashtra, India. jens@uci.edu |
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Quantitative in vivo and ex vivo confocal microscopy analysis of corneal cystine crystals in the Ctns knockout mouse. Mol Vis. 2011;17:2212-20 The purpose of this study was to assess the ability of quantitative in vivo confocal microscopy to characterize the natural history and detect changes in crystal volume in corneas from a novel animal model of cystinosis, the cystinosin (Ctns(-/-)) mouse. PMID: 21897743 |
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Deeny SP,Winchester J,Nichol K,Roth SM,Wu JC,Dick M,Cotman CW Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA; Technology Management Division, Schafer Corporation, Arlington, VA, USA. |
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Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ɛ4 carriers. Alzheimers Dement. 2012 Jan 6;: BACKGROUND: The possibility that ɛ4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG-PET study aimed to better understand the relationship among ɛ4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory. METHODS: Participants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG-PET, which were collected at rest and during completion of the Sternberg working memory task. RESULTS: Resting FDG-PET did not differ between carriers and noncarriers. Significant effects of fitness on FDG-PET during working memory were noted in the ɛ4 carriers only. High fit ɛ4 carriers had greater glucose uptake in the temporal lobe than the low fit ɛ4 carriers, but low fit ɛ4 carriers had greater glucose uptake in the frontal and parietal lobes. CONCLUSIONS: We demonstrate that fitness differentially affects cerebral metabolism in ɛ4 carriers only, consistent with previous findings that the effects of fitness may be more pronounced in populations genetically at risk for cognitive decline. PMID: 22226798 |
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Gupta S,Madkaikar M,Singh S,Sehgal S Division of Basic and Clinical Immunology, University of California, Irvine, California. Institute of Immunohematology, Mumbai, India. Postgraduate Institute for Medical Education and Research, Chandigarh, India. |
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Primary immunodeficiencies in India: a perspective. Ann N Y Acad Sci. 2012 Jan 6;: Although primary immunodeficiency diseases (PIDs) were first reported in India in the 1970s, those diagnoses were based predominantly on clinical presentations-very limited immunological analyses were performed. Therefore, the validity of many early reports of PIDs may be questionable. However, in the last 10-15 years, diagnoses of PIDs have been based on flow cytometric analysis and, in a few cases, by mutational analysis. In India, PIDs in adults are markedly underreported. We present data from two major centers where diagnosis of PID has been focused primarily in children. We highlight some of the limitations and challenges in the diagnosis and therapy of PID, and more recent efforts to establish PID Centers of Excellence and a national PID registry in India. PMID: 22224794 |
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Fox JC,Richardson AG,Lopez S,Solley M,Lotfipour S University of California, Irvine, Department of Emergency Medicine, Orange, California. |
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Implications and approach to incidental findings in live ultrasound models. West J Emerg Med. 2011 Nov;12(4):472-4 Incidental findings during ultrasound examinations occur frequently with live models in training sessions. Because of the broad scope of training sessions available, the ethics and guidelines of dealing with incidental findings in live models need to be discussed. PMID: 22224140 |
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Chakravarthy B,Ter Haar E,Bhat SS,McCoy CE,Denmark TK,Lotfipour S University of California, Irvine, Department of Emergency Medicine, Orange, California. |
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Simulation in medical school education: review for emergency medicine. West J Emerg Med. 2011 Nov;12(4):461-6 Medical education is rapidly evolving. With the paradigm shift to small-group didactic sessions and focus on clinically oriented case-based scenarios, simulation training has provided educators a novel way to deliver medical education in the 21st century. The field continues to expand in scope and practice and is being incorporated into medical school clerkship education, and specifically in emergency medicine (EM). The use of medical simulation in graduate medical education is well documented. Our aim in this article is to perform a retrospective review of the current literature, studying simulation use in EM medical student clerkships. Studies have demonstrated the effectiveness of simulation in teaching basic science, clinical knowledge, procedural skills, teamwork, and communication skills. As simulation becomes increasingly prevalent in medical school curricula, more studies are needed to assess whether simulation training improves patient-related outcomes. PMID: 22224138 |
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Franklin SS Heart Disease Prevention Program, UCI School of Medicine, University of California, Irvine, Irvine, California. ssfranklinmd@earthlink.net. |
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What Can We Learn From the American Heart Association and American College of Cardiology Expert Consensus Document on Geriatric Hypertension? Clin Cardiol. 2012 Jan 4;: PMID: 22222942 |
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Grando SA Departments of Dermatology and Biological Chemistry, University of California, 134 Sprague Hall, Irvine, CA, 92697, USA, sgrando@uci.edu. |
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Muscarinic receptor agonists and antagonists: effects on keratinocyte functions. Handb Exp Pharmacol. 2012;208:429-50 The stratified epithelium enveloping the skin and lining the surfaces of oral and vaginal mucosa is comprised by keratinocytes that synthesize, secrete, degrade, and respond to acetylcholine via muscarinic and nicotinic receptors. The two pathways may compete or synergize with one another, so that net biologic effect represents the biologic sum of the effects of distinct acetylcholine receptors expressed by a keratinocyte at a particular stage of its development. Keratinocytes express a unique combination of muscarinic receptor subtypes at each stage of their development. Experimental results indicate that muscarinic receptors expressed in human keratinocytes regulate their viability, proliferation, migration, adhesion, and terminal differentiation, hair follicle cycling, and secretion of humectants, cytokines, and growth factors. Learning the muscarinic pharmacology of keratinocyte development and functions has salient clinical implications for patients with nonhealing wounds, mucocutaneous cancers, and various autoimmune and inflammatory diseases. Successful therapy of pemphigus lesions with topical pilocarpine and disappearance of psoriatic lesions due to systemic atropine therapy illustrate that such therapeutic approach is feasible. PMID: 22222709 |
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Ehlert FJ,Pak KJ,Griffin MT Department of Pharmacology, School of Medicine, University of California, Irvine, CA, 92697-4625, USA, fjehlert@uci.edu. |
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Muscarinic agonists and antagonists: effects on gastrointestinal function. Handb Exp Pharmacol. 2012;208:343-74 Muscarinic agonists and antagonists are used to treat a handful of gastrointestinal (GI) conditions associated with impaired salivary secretion or altered motility of GI smooth muscle. With regard to exocrine secretion, the major muscarinic receptor expressed in salivary, gastric, and pancreatic glands is the M(3) with a small contribution of the M(1) receptor. In GI smooth muscle, the major muscarinic receptors expressed are the M(2) and M(3) with the M(2) outnumbering the M(3) by a ratio of at least four to one. The antagonism of both smooth muscle contraction and exocrine secretion is usually consistent with an M(3) receptor mechanism despite the major presence of the M(2) receptor in smooth muscle. These results are consistent with the conditional role of the M(2) receptor in smooth muscle. That is, the contractile role of the M(2) receptor depends on that of the M(3) so that antagonism of the M(3) receptor eliminates the response of the M(2). The physiological roles of muscarinic receptors in the GI tract are consistent with their known signaling mechanisms. Some so-called tissue-selective M(3) antagonists may owe their selectivity to a highly potent interaction with a nonmuscarinic receptor target. PMID: 22222706 |
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Cramer SC,Procaccio V, Departments of Neurology and Anatomy & Neurobiology, University of California, Irvine, CA Department of Pediatrics and The Center For Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, CA, USA A complete listing of the GAIN Americas [1] and GAIN International [2] Study Investigators can be found elsewhere. |
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Correlation between genetic polymorphisms and stroke recovery: Analysis of the GAIN Americas and GAIN International Studies. Eur J Neurol. 2012 Jan 4;: Background and purpose: Recovery after stroke occurs on the basis of specific molecular events. Genetic polymorphisms associated with impaired neural repair or plasticity might reduce recovery from stroke and might also account for some of the intersubject variability in stroke recovery. This study hypothesized that the ApoE ε4 polymorphism and the val(66) met polymorphism for brain-derived neurotrophic factor (BDNF) are each associated with poorer outcome after stroke. Associations with mitochondrial genotype were also explored. Methods: Genotypes were determined in 255 stroke patients who also received behavioral evaluations in the Glycine Antagonist In Neuroprotection (GAIN) clinical trials. The primary outcome measure was recovery during the first month post-stroke, as this is the time when neural repair is at a maximum and so when genetic influences might have their largest impact. Two secondary outcome measures at 3 months post-stroke were also examined. Results: Genotype groups were similar acutely post-stroke. Presence of the ApoE ε4 polymorphism was associated with significantly poorer recovery over the first month post-stroke (P = 0.023) and with a lower proportion of subjects with minimal or no disability (modified Rankin score 0-1, P = 0.01) at 3 months post-stroke. Indeed, those with this polymorphism were approximately half as likely to achieve minimal or no disability (18.2%) versus those with polymorphism absent (35.5%). Findings were confirmed in multivariate models. Results suggested possible effects from the val(66) met BDNF polymorphism and from the R0 mitochondrial DNA haplotype. Conclusions: Genetic factors, particularly the ApoE ε4 polymorphism, might contribute to variability in outcomes after stroke. PMID: 22221491 |
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Clark AJ,Summers AP Department of Ecology and Evolutionary Biology, University of California - Irvine, 321 Steinhaus Hall, Irvine, CA 92697, U.S.A. |
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Ontogenetic scaling of the morphology and biomechanics of the feeding apparatus in the Pacific hagfish Eptatretus stoutii. J Fish Biol. 2012 Jan;80(1):86-99 The form and function of the support skeleton, musculature and teeth were examined in an ontogenetic series of Pacific hagfish Eptatretus stoutii spanning about a six-fold range in total length (L(T) ). Tooth area, feeding apparatus length, basal plate size, theoretical dental plate retractile force, penetration force and applied tooth stress were measured relative to body size. Morphological variables (e.g. tooth area and basal plate size) scaled with positive allometry and functional variables (e.g. retractile force and applied tooth stress) scaled isometrically with L(T) . These results suggest that juveniles do not undergo ontogenetic dietary changes and consume functionally equivalent prey to adults, although adults can grasp proportionally larger portions of food. Low tooth stress in juveniles and adults imposes mechanical constraints to puncturing and tearing, which are circumvented by a preference for softer prey tissue or the inclusion of knotting behaviours for reducing tougher prey. PMID: 22220891 |
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Mueller LD,Cabral LG Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697-2525 E-mail: ldmuelle@uci.edu. |
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Does phenotypic plasticity for adult size versus food level in drosophila melanogaster evolve in response to adaptation to different rearing densities? Evolution. 2012 Jan;66(1):263-71 Recent studies with Drosophila have suggested that there is extensive genetic variability for phenotypic plasticity of body size versus food level. If true, we expect that the outcome of evolution at very different food levels should yield genotypes whose adult size show different patterns of phenotypic plasticity. We have tested this prediction with six independent populations of Drosophila melanogaster kept at extreme densities for 125 generations. We found that the phenotypic plasticity of body size versus food level is not affected by selection or the presence of competitors of a different genotype. However, we document increasing among population variation in phenotypic plasticity due to random genetic drift. Several reasons are explored to explain these results including the possibility that the use of highly inbred lines to make inferences about the evolution of genetically variable populations may be misleading. PMID: 22220880 |
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Mahboubi H,Dwabe S,Fradkin M,Kimonis V,Djalilian HR Department of Otolaryngology Head and Neck Surgery, University of California, Irvine, 101 The City Drive South, Bldg 56, Suite 500, Rt 81, Orange, CA, 92868, USA. |
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Genetics of hearing loss: where are we standing now? Eur Arch Otorhinolaryngol. 2012 Jan 5;: Hearing loss (HL) is the most common sensory impairment and is caused by a broad range of inherited to environmental causes. Inherited HL consists 50-60% of all HL cases. The inherited form of HL is further classified to different categories. More than 300 syndromes and 40 genes have been identified to result in different levels of HL. Although several diagnostic or screening tests have been developed, yet there are controversies around their use. PMID: 22218850 |
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Hickok G Department of Cognitive Sciences, University of California, Irvine, California 92697, USA. gshickok@uci.edu. |
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Computational neuroanatomy of speech production. Nat Rev Neurosci. 2012 Jan 5;: Speech production has been studied predominantly from within two traditions, psycholinguistics and motor control. These traditions have rarely interacted, and the resulting chasm between these approaches seems to reflect a level of analysis difference: whereas motor control is concerned with lower-level articulatory control, psycholinguistics focuses on higher-level linguistic processing. However, closer examination of both approaches reveals a substantial convergence of ideas. The goal of this article is to integrate psycholinguistic and motor control approaches to speech production. The result of this synthesis is a neuroanatomically grounded, hierarchical state feedback control model of speech production. PMID: 22218206 |
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Lei X,Chen C,He Q,Moyzis R,Xue G,Chen C,Cao Z,Li J,Li H,Zhu B,Zhang M,Li J,Dong Q 1] State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China [2] Department of Psychology and Social Behavior, University of California, Irvine, CA, USA. |
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Haplotype Polymorphism in the Alpha-2B-Adrenergic Receptor Gene Influences Response Inhibition in a Large Chinese Sample. Neuropsychopharmacology. 2012 Jan 4;: Response inhibition refers to the suppression of inappropriate or irrelevant responses. It has a central role in executive functions, and has been linked to a wide spectrum of prevalent neuropsychiatric disorders. Increasing evidence from neuropharmacological studies has suggested that gene variants in the norepinephrine neurotransmission system make specific contributions to response inhibition. This study genotyped five tag single-nucleotide polymorphisms covering the whole alpha-2B-adrenergic receptor (ADRA2B) gene and investigated their associations with response inhibition in a relatively large healthy Chinese sample (N=421). The results revealed significant genetic effects of the ADRA2B conserved haplotype polymorphisms on response inhibition as measured by stop-signal reaction time (SSRT) (F(2, 418)=5.938, p=0.003). Individuals with the AAGG/AAGG genotype (n=89; mean SSRT=170.2 ms) had significantly shorter SSRTs than did those with either the CCAC/AAGG genotype (n=216; mean SSRT=182.4 ms; uncorrected p=0.03; corrected p=0.09) or the CCAC/CCAC genotype (n=116; mean SSRT=195.8 ms; corrected p<0.002, Cohen's d=0.51). This finding provides the first evidence from association research in support of a critical role of the norepinephrine neurotransmission system in response inhibition. A better understanding of the genetic basis of response inhibition would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped response inhibition as well as its related prevalent neuropsychiatric disorders.Neuropsychopharmacology advance online publication, 4 January 2012; doi:10.1038/npp.2011.266. PMID: 22218095 |
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Park SY,Lee SY,Chen Y Department of Informatics, Donald Bren School of Information and Computer Sciences, 5072 Donald Bren Hall, University of California, Irvine, USA. |
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The effects of EMR deployment on doctors' work practices: A qualitative study in the emergency department of a teaching hospital. Int J Med Inform. 2012 Jan 2;: OBJECTIVE: The goal of this study was to examine the effects of medical notes (MD) in an electronic medical records (EMR) system on doctors' work practices at an Emergency Department (ED). METHODS: We conducted a six-month qualitative study, including in situ field observations and semi-structured interviews, in an ED affiliated with a large teaching hospital during the time periods of before, after, and during the paper-to-electronic transition of the rollout of an EMR system. Data were analyzed using open coding method and various visual representations of workflow diagrams. RESULTS: The use of the EMR in the ED resulted in both direct and indirect effects on ED doctors' work practices. It directly influenced the ED doctors' documentation process: (i) increasing documentation time four to five fold, which in turn significantly increased the number of incomplete charts, (ii) obscuring the distinction between residents' charting inputs and those of attendings, shifting more documentation responsibilities to the residents, and (iii) leading to the use of paper notes as documentation aids to transfer information from the patient bedside to the charting room. EMR use also had indirect consequences: it increased the cognitive burden of doctors, since they had to remember multiple patients' data; it aggravated doctors' multi-tasking due to flexibility in the system use allowing more interruptions; and it caused ED doctors' work to become largely stationary in the charting room, which further contributed to reducing doctors' time with patients and their interaction with nurses. DISCUSSION: We suggest three guidelines for designing future EMR systems to be used in teaching hospitals. First, the design of documentation tools in EMR needs to take into account what we called "note-intensive tasks" to support the collaborative nature of medical work. Second, it should clearly define roles and responsibilities. Lastly, the system should provide a balance between flexibility and interruption to better manage the complex nature of medical work and to facilitate necessary interactions among ED staff and patients in the work environment. PMID: 22217802 |
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Chen AL,Wilson AC,Tan M Department of Microbiology & Molecular Genetics, University of California, Irvine, CA 92697-4025, USA. |
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A Chlamydia-specific C-terminal region of the stress response regulator HrcA modulates its repressor activity. J Bacteriol. 2011 Dec;193(23):6733-41 Chlamydial heat shock proteins have important roles in Chlamydia infection and immunopathogenesis. Transcription of chlamydial heat shock genes is controlled by the stress response regulator HrcA, which binds to its cognate operator CIRCE, causing repression by steric hindrance of RNA polymerase. All Chlamydia spp. encode an HrcA protein that is larger than other bacterial orthologs because of an additional, well-conserved C-terminal region. We found that this unique C-terminal tail decreased HrcA binding to CIRCE in vitro as well as HrcA-mediated transcriptional repression in vitro and in vivo. When we isolated HrcA from chlamydiae, we only detected the full-length protein, but we found that endogenous HrcA had a higher binding affinity for CIRCE than recombinant HrcA. To examine this difference further, we tested the effect of the heat shock protein GroEL on the function of HrcA since endogenous chlamydial HrcA has been previously shown to associate with GroEL as a complex. GroEL enhanced the ability of HrcA to bind CIRCE and to repress transcription in vitro, but this stimulatory effect was greater on full-length HrcA than HrcA lacking the C-terminal tail. These findings demonstrate that the novel C-terminal tail of chlamydial HrcA is an inhibitory region and provide evidence that its negative effect on repressor function can be counteracted by GroEL. These results support a model in which GroEL functions as a corepressor that interacts with HrcA to regulate chlamydial heat shock genes. PMID: 21965565 |
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Sanchez SA,Gratton E,Zanocco AL,Lemp E,Gunther G Laboratory for Fluorescence Dynamics, University of California Irvine, Irvine, California, United States of America. |
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Sucrose Monoester Micelles Size Determined by Fluorescence Correlation Spectroscopy (FCS). PLoS One. 2011;6(12):e29278 One of the several uses of sucrose detergents, as well as other micelle forming detergents, is the solubilization of different membrane proteins. Accurate knowledge of the micelle properties, including size and shape, are needed to optimize the surfactant conditions for protein purification and membrane characterization. We synthesized sucrose esters having different numbers of methylene subunits on the substituent to correlate the number of methylene groups with the size of the corresponding micelles. We used Fluorescence Correlation Spectroscopy (FCS) and two photon excitation to determine the translational D of the micelles and calculate their corresponding hydrodynamic radius, R(h). As a fluorescent probe we used LAURDAN (6-dodecanoyl-2-dimethylaminonaphthalene), a dye highly fluorescent when integrated in the micelle and non-fluorescent in aqueous media. We found a linear correlation between the size of the tail and the hydrodynamic radius of the micelle for the series of detergents measured. PMID: 22216230 |
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Levin ER Author's Affiliations: Division of Endocrinology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, Irvine; Department of Veterans Affairs Medical Center, Long Beach, Long Beach, California. |
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Elusive extranuclear estrogen receptors in breast cancer. Clin Cancer Res. 2012 Jan 1;18(1):6-8 Estrogen receptors at the plasma membrane and cytoplasm have been difficult to detect in breast cancer specimens. New imaging approaches are needed to determine the percentage of cancers expressing extranuclear estrogen receptors and their impact on cancer biology and treatment. Clin Cancer Res; 18(1); 6-8. ©2012 AACR. PMID: 22215901 |
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Bergethon K,Shaw AT,Ignatius Ou SH,Katayama R,Lovly CM,McDonald NT,Massion PP,Siwak-Tapp C,Gonzalez A,Fang R,Mark EJ,Batten JM,Chen H,Wilner KD,Kwak EL,Clark JW,Carbone DP,Ji H,Engelman JA,Mino-Kenudson M,Pao W,Iafrate AJ Kristin Bergethon, Alice T. Shaw, Ryohei Katayama, Eugene J. Mark, Julie M. Batten, Eunice L. Kwak, Jeffrey W. Clark, Jeffrey A. Engelman, Mari Mino Kenudson, and A. John Iafrate, Massachusetts General Hospital, Boston, MA; Sai-Hong Ignatius Ou and Christina Siwak-Tapp, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange; Keith D. Wilner, Pfizer, La Jolla, CA: Christine M. Lovly, Nerina T. McDonald, Pierre P. Massion, Adriana Gonzalez, David P. Carbone, and William Pao, Vanderbilt University Medical Center; Pierre P. Massion, Nashville Veterans Affairs Medical Center, Nashville, TN; Rong Fang and Hongbin Ji, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Haiquan Chen, Fudan University Shanghai Cancer Center; and Haiquan Chen, Shanghai Medical College, Fudan University, Shanghai, China. |
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ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers. J Clin Oncol. 2012 Jan 3;: PURPOSEChromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. PATIENTS AND METHODSUsing a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort.ResultsOf 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. CONCLUSIONROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC. PMID: 22215748 |
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Lott IT,Doran E,Nguyen VQ,Tournay A,Movsesyan N,Gillen DL Department of Pediatrics, School of Medicine, University of California, Irvine (UCI), Orange, CA, USA Department of Neurology, School of Medicine, University of California, Irvine (UCI), Irvine, CA, USA. |
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Down Syndrome and Dementia: Seizures and Cognitive Decline. J Alzheimers Dis. 2012 Jan 3;: The objective of this study was to determine the association of seizures and cognitive decline in adults with Down syndrome (DS) and Alzheimer's-type dementia. A retrospective data analysis was carried out following a controlled study of antioxidant supplementation for dementia in DS. Observations were made at baseline and every 6 months for 2 years. Seizure history was obtained from study records. The primary outcome measures comprised the performance-based Severe Impairment Battery (SIB) and Brief Praxis Test (BPT). Secondary outcome measures comprised the informant-based Dementia Questionnaire for Mentally Retarded Persons and Vineland Adaptive Behavior Scales. Because a large proportion of patients with seizures had such severe cognitive decline as to become untestable on the performance measures, time to "first inability to test" was measured. Adjustments were made for the potentially confounding co-variates of age, gender, APOE4 status, baseline cognitive impairment, years since dementia onset at baseline, and treatment assignment. The estimated odds ratio for the time to "first inability to test" on SIB comparing those with seizures to those without is 11.02 (95% CI: 1.59, 76.27), a ratio that is significantly different from 1 (p = 0.015). Similarly, we estimated an odds ratio of 9.02 (95% CI: 1.90, 42.85) on BPT, a ratio also significantly different than 1 (p = 0.006). Results from a secondary analysis of the informant measures showed significant decline related to seizures. We conclude that there is a strong association of seizures with cognitive decline in demented individuals with DS. Prospective studies exploring this relationship in DS are indicated. PMID: 22214782 |
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Mirbolooki MR,Constantinescu CC,Pan ML,Mukherjee J Preclinical Imaging Center, Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, 92697, USA. j.mukherjee@uci.edu. |
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Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation. EJNMMI Res. 2011;1(1):30 ABSTRACT: PMID: 22214183 |
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Bieszczad KM,Kant R,Constantinescu CC,Pandey SK,Kawai HD,Metherate R,Weinberger NM,Mukherjee J Department of Neurobiology & Behavior, University of California, Irvine, CA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA. |
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Nicotinic acetylcholine receptors in rat forebrain that bind (18) F-nifene: Relating PET imaging, autoradiography and behavior. Synapse. 2011 Dec 28;: Nicotinic acetylcholine receptors (nAChRs) in the brain are important for cognitive function; however, their specific role in relevant brain regions remains unclear. In this study we used the novel compound (18) F-nifene to examine the distribution of nAChRs in the rat forebrain, and for individual animals related the results to behavioral performance on an auditory-cognitive task. We first show negligible binding of (18) F-nifene in mice lacking the β2 nAChR subunit, consistent with previous findings that (18) F-nifene binds to α4β2* nAChRs. We then examined the distribution of (18) F-nifene in rat using three methods: in vivo PET, ex vivo PET and autoradiography. Generally, (18) F-nifene labeled forebrain regions known to contain nAChRs, and the three methods produced similar relative binding among regions. Importantly, (18) F-nifene also labeled some white matter (myelinated axon) tracts, most prominently in the temporal subcortical region that contains the auditory thalamocortical pathway. Finally, we related (18) F-nifene binding in several forebrain regions to each animal's performance on an auditory-cued, active avoidance task. The strongest correlations with performance after 14 days training were found for (18) F-nifene binding in the temporal subcortical white matter, subiculum and medial frontal cortex (correlation coefficients, r > 0.8); there was no correlation with binding in the auditory thalamus or auditory cortex. These findings suggest that individual performance is linked to nicotinic functions in specific brain regions, and further support a role for nAChRs in sensory-cognitive function. Synapse, 2011. © 2011 Wiley-Liss, Inc. PMID: 22213342 |
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Sakai T,Eskander RN,Guo Y,Kim KJ,Mefford J,Hopkins J,Bhatia NN,Zi X,Hoang BH Department of Orthopaedic Surgery, University of California Irvine, 101 The City Drive South, Orange, California 92868. |
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Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. J Orthop Res. 2011 Dec 29;: Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis. Treatment with FKB increased caspase 8, 9, and 3/7 activity compared to vehicle-treated controls, indicating that both extrinsic and intrinsic apoptotic pathways were activated. Furthermore, FKB treatment of both cell lines resulted in increased mRNA and protein expression of death receptor-5 and the mitochondrial pro-apoptotic proteins Bim and Puma, while down-regulating the expression of an inhibitor of apoptosis, survivin in a dose-dependent manner. Our results suggest the natural compound FKB has a pro-apoptotic effect on SS cell lines. FKB may be a new chemotherapeutic strategy for patients with SS and deserves further investigation as a potential agent in the treatment of this malignancy. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 22213202 |
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Kamanna VS,Ganji SH,Shelkovnikov S,Norris K,Vaziri ND Division of Nephrology and Hypertension, University of California, Irvine, Calif., USA. |
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Iron Sucrose Promotes Endothelial Injury and Dysfunction and Monocyte Adhesion/Infiltration. Am J Nephrol. 2011 Dec 29;35(2):114-119 Background/Aims: Intravenous (IV) iron preparations are widely used in the management of anemia in ESRD populations. Recent changes in reimbursement policy have dramatically increased the use of IV iron to lower the use of costly erythropoiesis-stimulating agents. These preparations are frequently administered with insufficient attention to the total body iron stores or presence of inflammation which is aggravated by excess iron. Endothelial injury and dysfunction are critical steps in atherosclerosis, thrombosis and cardiovascular disease. IV iron preparations raise plasma non-transferrin-bound iron which can promote oxidative stress, endothelial damage and dysfunction. We explored the effect of an IV iron preparation on endothelial cells, monocytes and isolated arteries. Methods: Primary cultures of human aortic endothelial cells (HAEC) were treated with pharmacologically relevant concentrations of iron sucrose (10-100 μg/ml) for 4-24 h. Endothelial cell morphology, viability, and monocyte adhesion were tested. Endothelial function was assessed by measuring the vasorelaxation response to acetylcholine in normal rat thoracic aorta rings preincubated with iron sucrose (200 μg/ml). Results: In contrast to the control HAEC which showed normal cobblestone appearance, cells treated with iron sucrose (50-100 μg/ml) for 4 h showed loss of normal morphological characteristics, cellular fragmentation, shrinkage, detachment, monolayer disruption and nuclear condensation/fragmentation features signifying apoptosis. HAEC exposure to iron sucrose (10-100 μg/ml) increased monocyte adhesion 5- to 25-fold. Incubation in media containing 200 μg/ml iron sucrose for 3 h caused marked reduction in the acetylcholine-mediated relaxation in phenylephrine-precontracted rat aorta. Conclusion: Pharmacologically relevant concentration of iron sucrose results in endothelial injury and dysfunction and marked increase in monocyte adhesion. PMID: 22212390 |
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