Medical Specialties Commons^™

Assembly And Development Of The Pseudomonas Aeruginosa Biofilm Matrix., Luyan Ma, Matthew Conover, Haiping Lu, Matthew R. Parsek, Kenneth W. Bayles, Daniel J. Wozniak

Journal Articles: Pathology and Microbiology

Virtually all cells living in multicellular structures such as tissues and organs are encased in an extracellular matrix. One of the most important features of a biofilm is the extracellular polymeric substance that functions as a matrix, holding bacterial cells together. Yet very little is known about how the matrix forms or how matrix components encase bacteria during biofilm development. Pseudomonas aeruginosa forms environmentally and clinically relevant biofilms and is a paradigm organism for the study of biofilms. The extracellular polymeric substance of P. aeruginosa biofilms is an ill-defined mix of polysaccharides, nucleic acids, and proteins. Here, we directly visualize …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March

Journal Articles: Psychiatry

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).

METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined …

Apd2: The Updated Antimicrobial Peptide Database And Its Application In Peptide Design., Guangshun Wang, Xia Li, Zhe Wang

Journal Articles: Pathology and Microbiology

The antimicrobial peptide database (APD, http://aps.unmc.edu/AP/main.php) has been updated and expanded. It now hosts 1228 entries with 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal and 944 antibacterial peptides. The second version of our database (APD2) allows users to search peptide families (e.g. bacteriocins, cyclotides, or defensins), peptide sources (e.g. fish, frogs or chicken), post-translationally modified peptides (e.g. amidation, oxidation, lipidation, glycosylation or d-amino acids), and peptide binding targets (e.g. membranes, proteins, DNA/RNA, LPS or sugars). Statistical analyses reveal that the frequently used amino acid residues (>10%) are Ala and Gly in bacterial peptides, Cys and Gly in plant …

Epithelial Cell Gene Expression Induced By Intracellular Staphylococcus Aureus., Xianglu Li, William G. Fusco, Keun S. Seo, Kenneth W. Bayles, Erin E. Mosley, Mark A. Mcguire, Gregory A. Bohach

Journal Articles: Pathology and Microbiology

HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several …

A Genome-Wide Association Study In Chronic Obstructive Pulmonary Disease (Copd): Identification Of Two Major Susceptibility Loci, Sreekumar G. Pillai, Dongliang Ge, Guohua Zhu, Xiangyang Kong, Kevin V. Shianna, Anna C. Need, Sheng Feng, Craig P. Hersh, Per Bakke, Amund Gulsvik, Andreas Ruppert, Karin C. Lødrup Carlsen, Allen Roses, Wayne Anderson, Stephen I. Rennard, David A. Lomas, Edwin K. Silverman, David B. Goldstein, Icgn Investigators

Journal Articles: Pulmonary & Critical Care Med

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of alpha(1)-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial …

Stromal Gene Signatures In Large-B-Cell Lymphomas., G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted …

Acute Atomoxetine Treatment Of Younger And Older Children With Adhd: A Meta-Analysis Of Tolerability And Efficacy., Christopher J. Kratochvil, Denái R. Milton, Brigette S. Vaughan, Laurence L. Greenhill

Journal Articles: Psychiatry

BACKGROUND: Atomoxetine is FDA-approved as a treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years to adult. Among pediatric clinical trials of atomoxetine to date, six with a randomized, double-blind, placebo-controlled design were used in this meta-analysis. The purpose of this article is to describe and compare the treatment response and tolerability of atomoxetine between younger children (6-7 years) and older children (8-12 years) with ADHD, as reported in these six acute treatment trials.

METHODS: Data from six clinical trials of 6-9 weeks duration were pooled, yielding 280 subjects, ages 6-7 years, and 860 subjects, ages 8-12 years with …

Off-Label Psychopharmacologic Prescribing For Children: History Supports Close Clinical Monitoring., Julie M. Zito, Albert T. Derivan, Christopher J. Kratochvil, Daniel J. Safer, Joerg M. Fegert, Laurence L. Greenhill

Journal Articles: Psychiatry

The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring.

Feedback From Horizontal Cells To Rod Photoreceptors In Vertebrate Retina., Wallace B. Thoreson, Norbert Babai, Theodore M M. Bartoletti

Journal Articles: Ophthalmology

Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I(Ca)) that do not always generate detectable depolarizing responses. We therefore recorded I(Ca) directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in …

Antidepressant Prescribing Practices For The Treatment Of Children And Adolescents., Supriya K. Bhatia, Amy J. Rezac-Elgohary, Benedetto Vitiello, Michael A. Sitorius, Bruce A. Buehler, Christopher J. Kratochvil

Journal Articles: Psychiatry

OBJECTIVE: This study evaluates pediatric antidepressant prescribing practices of Nebraska clinicians.

METHODS: Surveys were sent in July, 2005, to 1,521 prescribing clinicians throughout Nebraska to assess pediatric antidepressant use along with any practice changes following the U.S. Food and Drug Administration (FDA) "black box" warning issued in October, 2004.

RESULTS: Over half (n = 866) of the clinicians responded to the survey, of which 96.8% reported awareness of the FDA "black box" warning. Of the respondents, 76.9% (n = 666) were prescribing antidepressants to children and/or adolescents. Clinicians reported decreased prescribing frequency for both children (15.5%) and adolescents (36.6%), with …

Nitrated Alpha-Synuclein Immunity Accelerates Degeneration Of Nigral Dopaminergic Neurons., Eric J. Benner, Rebecca Banerjee, Ashley D. Reynolds, Simon Sherman, Vladimir M. Pisarev, Vladislav Tsiperson, Craig Nemachek, Pawel Ciborowski, Serge Przedborski, R. Lee Mosley, Howard Gendelman

Journal Articles: Eppley Institute

BACKGROUND: The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.

METHODS AND FINDINGS: Nitrotyrosine (NT)-modified alpha-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN …

Microglia And Astrocyte Activation By Toll-Like Receptor Ligands: Modulation By Ppar-Gamma Agonists., Catherine Gurley, Jessica Nichols, Shuliang Liu, Nirmal K. Phulwani, Nilufer Esen, Tammy Kielian

Journal Articles: Pathology and Microbiology

Microglia and astrocytes express numerous members of the Toll-like receptor (TLR) family that are pivotal for recognizing conserved microbial motifs expressed by a wide array of pathogens. Despite the critical role for TLRs in pathogen recognition, when dysregulated these pathways can also exacerbate CNS tissue destruction. Therefore, a critical balance must be achieved to elicit sufficient immunity to combat CNS infectious insults and downregulate these responses to avoid pathological tissue damage. We performed a comprehensive survey on the efficacy of various PPAR-gamma agonists to modulate proinflammatory mediator release from primary microglia and astrocytes in response to numerous TLR ligands relevant …

One-Year Treatment With Mometasone Furoate In Chronic Obstructive Pulmonary Disease, Peter M.A. Calverley, Stephen I. Rennard, Harold S. Nelson, Jill P. Karpel, Eduardo H. Abbate, Paul Stryszak, Heribert Staudinger

Journal Articles: Pulmonary & Critical Care Med

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse …

Effects Of Atomoxetine On Growth In Children With Attention-Deficit/Hyperactivity Disorder Following Up To Five Years Of Treatment., Thomas J. Spencer, Christopher J. Kratochvil, R. Bart Sangal, Keith E. Saylor, Charles E. Bailey, David W. Dunn, Daniel A. Geller, Charles D. Casat, Robert S. Lipetz, Rakesh Jain, Jeffrey H. Newcorn, Dustin D. Ruff, Peter D. Feldman, Amanda J. Furr, Albert J. Allen

Journal Articles: Psychiatry

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine.

METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years.

RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected …

Clinical Implication Of Genome-Wide Profiling In Diffuse Large B-Cell Lymphoma And Other Subtypes Of B-Cell Lymphoma., Javeed Iqbal, Shantaram Joshi, Kavita N. Patel, Sofi I. Javed, Can Kucuk, Afeera Aabida, Francesco D'Amore, Kai Fu

Journal Articles: Pathology and Microbiology

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely …

A Pilot Study Of Atomoxetine In Young Children With Attention-Deficit/Hyperactivity Disorder., Christopher J. Kratochvil, Brigette S. Vaughan, Michelle L. Mayfield-Jorgensen, John S. March, Scott H. Kollins, Desiree W. Murray, Hima Ravi, Laurence L. Greenhill, Lisa A. Kotler, Natalya Paykina, Patricia Biggins, Julie Stoner

Journal Articles: Psychiatry

OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds.

METHOD: Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit.

RESULTS: Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p < 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p < 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p < 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children's Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p < 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p < 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy.

CONCLUSION: Atomoxetine was generally effective for reducing core ADHD …

Effects Of Low Dose Gm-Csf On Microglial Inflammatory Profiles To Diverse Pathogen-Associated Molecular Patterns (Pamps)., Nilufer Esen, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: It is well appreciated that obtaining sufficient numbers of primary microglia for in vitro experiments has always been a challenge for scientists studying the biological properties of these cells. Supplementing culture medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) partially alleviates this problem by increasing microglial yield. However, GM-CSF has also been reported to transition microglia into a dendritic cell (DC)-like phenotype and consequently, affect their immune properties.

METHODS: Although the concentration of GM-CSF used in our protocol for mouse microglial expansion (0.5 ng/ml) is at least 10-fold less compared to doses reported to affect microglial maturation and function (>/= …

Colon Carcinoma Cells Harboring Pik3ca Mutations Display Resistance To Growth Factor Deprivation Induced Apoptosis., J. Wang, Karen Kuropatwinski, Jennie Hauser, Michael R. Rossi, Yunfei Zhou, Alexis Conway, Julie L.C. Kan, Neil W. Gibson, James K.V. Willson, John K. Cowell, Michael G. Brattain

Journal Articles: Eppley Institute

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation …

Emotional Expression During Attention-Deficit/Hyperactivity Disorders Treatment: Initial Assessment Of Treatment Effects., Christopher J. Kratochvil, D. Faries, Brigette S. Vaughan, A. Perwien, J. Busner, K. Saylor, S. Kaplan, C. Buermeyer, R. Swindle

Journal Articles: Psychiatry

OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child's current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint.

RESULTS: In the validation study, no statistically significant differences in EESC scores were …

Long-Distance Three-Color Neuronal Tracing In Fixed Tissue Using Neurovue Dyes, Heather Jensen Smith, Brian Gray, Katharine Muirhead, Betsy Ohlsson-Wilhelm, Bernd Fritzsch

Journal Articles: Eppley Institute

Dissecting development of neuronal connections is critical for understanding neuronal function in both normal and diseased states. Charting the development of the multitude of connections is a monumental task, since a given neuron typically receives hundreds of convergent inputs from other neurons and provides divergent outputs for hundreds of other neurons. Although progress is being made utilizing various mutants and/or genetic constructs expressing fluorescent proteins like GFP, substantial work remains before a database documenting the development and final location of the neuronal pathways in an adult animal is completed. The vast majority of developing neurons cannot be specifically labeled with …

Lateral Wall Protein Content Mediates Alterations In Cochlear Outer Hair Cell Mechanics Before And After Hearing Onset, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

Specialized outer hair cells (OHCs) housed within the mammalian cochlea exhibit active, nonlinear, mechanical responses to auditory stimulation termed electromotility. The extraordinary frequency resolution capacity of the cochlea requires an exquisitely equilibrated mechanical system of sensory and supporting cells. OHC electromotile length change, stiffness, and force generation are responsible for a 100-fold increase in hearing sensitivity by augmenting vibrational input to non-motile sensory inner hair cells. Characterization of OHC mechanics is crucial for understanding and ultimately preventing permanent functional deficits due to overstimulation or as a consequence of various cochlear pathologies. The OHCs' major structural assembly is a highly-specialized lateral …

Atomoxetine Treatment In Children And Adolescents With Attention-Deficit Hyperactivity Disorder: What Are The Long-Term Health-Related Quality-Of-Life Outcomes?, Amy R. Perwien, Christopher J. Kratochvil, Douglas E. Faries, Brigette S. Vaughan, Thomas Spencer, Ronald T. Brown

Journal Articles: Psychiatry

OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in children. However, relatively few studies have addressed the impact of treatment on long-term subjective, psychosocial outcomes, such as health-related quality of life (HRQL). This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD.

METHODS: Participants included 6- to 17-year-old children and adolescents (n = 912) with ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine. Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely used measure of HRQL (The Child Health …

Treatment For Adolescents With Depression Study (Tads): Safety Results., Graham Emslie, Christopher J. Kratochvil, Benedetto Vitiello, Susan Silva, Taryn Mayes, Steven Mcnulty, Elizabeth Weller, Bruce Waslick, Charles Casat, John Walkup, Sanjeev Pathak, Paul Rohde, Kelly Posner, John March, The Columbia Suicidality Classification Group, Tads Team

Journal Articles: Psychiatry

OBJECTIVE: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO).

METHOD: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort.

RESULTS: Depressed adolescents reported high rates of …

Molecular Diagnosis Of Burkitt's Lymphoma., Sandeep S. Dave, Kai Fu, George W. Wright, Lloyd T. Lam, Philip Kluin, Evert-Jan Boerma, Timothy Greiner, Dennis D. Weisenburger, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Thomas M. Grogan, Elias Campo, Elaine S. Jaffe, Bhavana J. Dave, Warren Sanger, M Bast, Julie M. Vose, James O. Armitage, Joseph M. Connors, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Richard I. Fisher, Thomas P. Miller, Emilio Montserrat, Wyndham H. Wilson, Manisha Bahl, Hong Zhao, Liming Yang, John Powell, Richard Simon, Wing C. Chan, Louis M. Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.

RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target …

Selective Serotonin Reuptake Inhibitors In Pediatric Depression: Is The Balance Between Benefits And Risks Favorable?, Christopher J. Kratochvil, Benedetto Vitiello, John Walkup, Graham Emslie, Bruce D. Waslick, Elizabeth B. Weller, William J. Burke, John S. March

Journal Articles: Psychiatry

Recent controversies surrounding the use of selective serotonin reuptake inhibitors (SSRIs) have highlighted the need to reassess potential benefits, as well as potential risks of this class of medications in the treatment of pediatric depression. The recent availability of data from meta-analyses of published and unpublished antidepressant trials, epidemiological studies, and the Treatment for Adolescents with Depression Study (TADS) has facilitated a reanalysis of this risk/benefit relationship. Despite reviewing similar data, various regulatory agencies have arrived at rather disparate conclusions regarding the data, resulting in continued controversy. Although all groups appear to agree that careful assessment, education regarding risks, and …

Paired-Pulse Depression At Photoreceptor Synapses., Katalin Rabl, Lucia Cadetti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to …

Kinetics Of Exocytosis Is Faster In Cones Than In Rods., Katalin Rabl, Lucia Cadetti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures …

Quantitative 1h Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy In An Animal Model Of Parkinson's Disease., Michael D. Boska, Travis B. Lewis, Christopher J. Destache, Eric J. Benner, Jay A. Nelson, Mariano Uberti, R. Lee Mosley, Howard Gendelman

Journal Articles: Radiology

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for …

Tgf-Beta1 And Serum Both Stimulate Contraction But Differentially Affect Apoptosis In 3d Collagen Gels, Tetsu Kobayashi, Xiangde Liu, Hui Jung Kim, Tadashi Kohyama, Fu-Qiang Wen, Shinji Abe, Qiuhong Fang, Yun Kui Zhu, John R. Spurzem, Peter Bitterman, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-beta1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-beta1 and serum significantly augmented collagen gel contraction. TGF-beta1 also increased apoptosis assessed …