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La Jolla, CA, United States

Wetherill R.,University of California at San Diego | Wetherill R.,University of Pennsylvania | Tapert S.F.,VA San Diego Healthcare System
Psychology of Addictive Behaviors | Year: 2013

Adolescence is a unique developmental period characterized by major physiological, psychological, social, and brain changes, as well as an increased incidence of maladaptive, addictive behaviors. With the use of MRI techniques, researchers have been able to provide a better understanding of adolescent brain maturation and how neurodevelopment affects cognition and behavior. This review discusses adolescent brain development and its potential influence on psychotherapeutic change. We focus on cognitive-behavioral and mindfulness-based approaches for treating substance use and highlight potential brain mechanisms underlying response to psychotherapy. Finally, we discuss integrative neuroimaging and treatment studies and potential opportunities for advancing the treatment of adolescent addictive behaviors. © 2012 American Psychological Association. Source


McCarthy M.J.,University of California at San Diego | Leckband S.G.,VA San Diego Healthcare System | Kelsoe J.R.,University of California at San Diego
Pharmacogenomics | Year: 2010

Bipolar disorder (BD) is a serious mental illness with well-established, but poorly characterized genetic risk. Lithium is among the best proven mood stabilizer therapies for BD, but treatment responses vary considerably. Based upon these and other findings, it has been suggested that lithium-responsive BD may be a genetically distinct phenotype within the mood disorder spectrum. This assertion has practical implications both for the treatment of BD and for understanding the neurobiological basis of the illness: genetic variation within lithium-sensitive signaling pathways may confer preferential treatment response, and the involved genes may underlie BD in some individuals. Presently, the mechanism of lithium is reviewed with an emphasis on gene-expression changes in response to lithium. Within this context, findings from genetic-association studies designed to identify lithium response genes in BD patients are evaluated. Finally, a framework is proposed by which future pharmacogenetic studies can incorporate advances in genetics, molecular biology and bioinformatics in a pathway-based approach to predicting lithium treatment response. © 2010 Future Medicine Ltd. Source


Quinlan T.,San Diego State University | Roesch S.,San Diego State University | Granholm E.,VA San Diego Healthcare System | Granholm E.,University of California
Schizophrenia Research | Year: 2014

Neurocognitive impairment is associated with negative symptoms and poor real world functioning in schizophrenia. Dysfunctional attitudes (e.g., "If I fail partly, it is as bad as being a complete failure") have been found to mediate these relationships between neurocognition and negative symptoms and functioning. In this study, these relationships were examined in 179 participants with schizophrenia or schizoaffective disorder using structural equation modeling. Defeatist attitudes were found to mediate the relationship between neurocognition and negative symptoms but not the relationships between neurocognition and performance-based or self-reported functioning. A full model with the best fit showed mediation between neurocognition and self-reported functioning through two different pathways: One from neurocognition to functional skill capacity to real-world functioning, and a second from neurocognition to defeatist attitudes to negative symptoms to real-world functioning. These results may implicate skill deficits and defeatist attitudes as a separate treatment targets for negative symptoms and functioning in schizophrenia. © 2014. Source


PTHrP (parathyroid hormone-related protein) is abnormally expressed in a substantial majority of lung cancers, especially non-small cell lung cancers, and plays a key role in tumor progression. Thus, this oncoprotein could be a target for treating patients with lung cancer. This study screened combinatorial libraries of heterocyclic amines for inhibitory effects on PTHrP expression and cell proliferation. Two libraries of over 780,000 bis-cyclic thiourea and guanidine compounds each were tested in BEN lung carcinoma cells. The number of PTHrP inhibitors and the magnitude of the reduction in PTHrP were greater for thioureas. Selected lead thiourea compounds decreased cell PTHrP protein content in dose-dependent fashion, reduced relative abundance of PTHrP mRNA, decreased transcripts derived from the PTHrP P3 promoter and reduced activity of a full length PTHrP promoter luciferase construct. Similar effects on PTHrP mRNA were observed in A549 and H441 lung adenocarcinoma cells and in H727 lung carcinoid cells. However, the compounds only inhibited PTHrP protein levels in BEN cells and H727 cells. The compounds reduced the rate of cell proliferation in BEN cells and H727 cells, but not in lines that showed no inhibition of PTHrP protein. These results suggest that cyclic thiourea compounds inhibit PTHrP expression mediated by the P3 promoter, which is widely used in the majority of PTHrP-expressing cells, and that they may inhibit growth of lung cancer cells through the same mechanism. Further work will be necessary to investigate their mechanism for effects on growth of PTHrP-positive tumors in vivo. Source


Xu X.,VA San Diego Healthcare System | Xu X.,University of Washington
International Journal of Clinical and Experimental Pathology | Year: 2014

Anaplastic large cell lymphoma (ALCL) is a mature T cell lymphoma with characteristic morphologic, immunophenotypic and cytogenetic features. Current WHO classification includes anaplastic lymphoma kinase (ALK)-positive and ALK-negative variants. ALCL rarely presents with obstructive symptoms of the main airway. In addition to reporting a HIV-associated bronchial ALK-negative ALCL in a 44 year-old female, our literature review identified eight cases of bronchial ALCL with several interesting clinicopathological features, including: 1) a female predominance (67%); 2) two thirds of patients younger than 18 years old; 3) uniformly presented with respiratory symptoms and progressed to respiratory failure; 4) the tumor involving the main airways; 5) often with localized disease at the initial presentation. This unusual presentation of ALCL may pose as a diagnostic pitfall and delay the treatment. Source

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