tbuckley/cabot-search huggingface dataset:
Abstract 5309: beta-Arrestin 1 (bArr1) and Ankyrin 2 (ANK2) Regulate Cav1.2 Trafficking through Complex G Protein Mediated Signaling
Authors: Maria A Diverse-Pierluissi, Rachele Lipsky, Akil A Puckerin, Joanne Stocks, Vivek Patel, Fadi G Akar
Journal: Circulation (2008)

Mechanisms governing the trafficking of cardiac voltage dependent calcium channels (Ca v 1.2) remain largely unknown. We have previously shown that neuronal calcium channels are internalized into clathrin coated vesicles upon G protein coupled receptor (GPCR) activation. Here, we hypothesize that GPCR mediated signaling regulate Ca v 1.2 trafficking and surface expression through interaction with cytoskeletal and signaling molecules. Methods : Sequential immunoprecipitation in adult rat cardiomyocytes was used to investigate the interaction between Ca v 1.2, cytoskeletal and signaling molecules. Live cell imaging and immunofluorescence microscopy were used to measure changes in the cellular localization of Ca v 1.2 and these proteins upon activation of GPCR signaling. Results : Cav1.2 interacts with ANK2, βArr1 and spectrin. Sustained β adrenergic receptor (βAR) activation increases Cav1.2/spectrin and decreases Ca v 1.2/ANK2 and Ca v 1.2/βArr1 interactions. Sustained βAR activation induces rapid (&lt;5 min) Cav1.2 internalization and dissociation from ANK2 as Ca v 1.2/ANK2 co-localization is markedly reduced (−58% p&lt;0.01) in isoproterenol treated myocytes. A cell permeant peptide (1.4 μg/ml) that disrupts Ca v 1.2/ANK2 interaction decreases (−40±12%, p&lt;0.01) Cav1.2 cell surface expression. Pretreatment with pertussis toxin prevents Ca v 1.2 internalization suggesting that G i/o mediates this response. Similarly, Src kinase inhibition reduces (by 90%) Ca v 1.2 internalization. Differential labeling of pre-existing Ca v 1.2 at the cell membrane and newly inserted Ca v 1.2 using fluorophore conjugated dihydropyridines reveal that activation of G i/o proteins underlies Ca v 1.2 internalization and insertion. In contrast, activation of the muscarinic M2 receptor (10μM carbachol) causes only insertion of new channels (n=14) and fails to alter the association of Ca v 1.2 with ANK2 and spectrin. Finally PI3 kinase inhibition (10nM wortmannin) prevents Ca v 1.2 membrane insertion. Conclusions : Our findings reveal novel signaling mechanisms that regulate Ca v 1.2 trafficking, internalization and membrane insertion in a receptor subtype dependent manner. These mechanisms may be central to pathologies associated with a hyperadrenergic state. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Detection of bloodstream pathogens in a bacille Calmette-GuéArin (BCG)-vaccinated pediatric population in Malawi: a pilot study
Authors: L.K. Archibald, O. Nwanyanwu, P.N. Kazembe, C. Mwansambo, M. Bell, H. Dobbie, L.B. Reller, W.R. Jarvis
Journal: Clinical Microbiology and Infection (2003)
Christian Psychiatry: the impact of evangelical belief on clinical practice
Authors: M Galanter, D Larson, E Rubenstone
Journal: American Journal of Psychiatry (1991)

The authors surveyed psychiatrists in the Christian Psychiatry movement to assess the role of religious belief in their practices.The psychiatrists were members of the Christian Medical and Dental Society; questionnaires were sent to 260, and usable responses were received from 193. The subjects were asked about demographic and practice variables, "born again" religious experiences, group cohesion, and beliefs about using the Bible and prayer in treatment.The respondents were somewhat more religious than Americans overall, who are themselves more religious than most psychiatrists. Nearly all reported having been "born again," after which they generally experienced a decrease in emotional distress. There was a significant difference in the respondents' affiliative feelings toward psychiatrists in the Christian Psychiatry movement and other psychiatrists. For acute schizophrenic or manic episodes, the respondents considered psychotropic medication the most effective treatment, but they rated the Bible and prayer more highly for suicidal intent, grief reaction, sociopathy, and alcoholism. Whether or not a patient was "committed to Christian beliefs" made a significant difference in whether the respondents would recommend prayer to the patient as treatment. About one-half said they would discourage strongly religious patients from an abortion, homosexual acts, or premarital sex, and about one-third said they would discourage other patients from these activities.Many studies have suggested a need for more sensitivity to religious issues by psychiatrists, and this study provides systematic findings on one approach. It remains important to evaluate ways in which a religious perspective can be related to clinical practice and what benefits and problems may derive from such a relationship.
Marsh JC, Bacigalupo A, Schrezenmeier H, et al. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood. 2012;119(23):5391-5396.
Authors: Judith C. Marsh, Andrea Bacigalupo, Hubert Schrezenmeier, Andre Tichelli, Antonio M. Risitano, Jakob R. Passweg, Sally B. Killick, Alan J. Warren, Theodora Foukaneli, Mahmoud Aljurf, H. A. Al-Zahrani, Britta Höchsmann, Philip Schafhausen, Alexander Roth, Anke Franzke, Tim H. Brummendorf, Carlo Dufour, Rosi Oneto, Philip Sedgwick, Alain Barrois, Shahram Kordasti, Modupe O. Elebute, Ghulam J. Mufti, Gerard Socie
Journal: Blood (2013)
Prevalence of Radiographic and Symptomatic Hip Osteoarthritis in an Urban United States Community: The Framingham Osteoarthritis Study
Authors: Chan Kim, Katherine D. Linsenmeyer, Steven C. Vlad, Ali Guermazi, Mary M. Clancy, Jingbo Niu, David T. Felson
Journal: Arthritis & Rheumatology (2014)

The last prevalence survey encompassing urban populations was part of the First National Health and Nutrition Examination Survey, conducted in the 1970s. The aim of the present study was to perform a prevalence survey of hip osteoarthritis (OA) among individuals in the Framingham Study Community cohort.
6q Deletions in Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphomas
Authors: Mats Merup, Teresa Calero Moreno, Mats Heyman, Kristina Rönnberg, Dan Grandér, Rut Detlofsson, Omid Rasool, Yie Liu, Stefan Söderhäll, Gunnar Juliusson, Gösta Gahrton, Stefan Einhorn
Journal: Blood (1998)
Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention-Deficit/Hyperactivity Disorder Symptoms in Children
Authors: Thiago Modesto, Henning Tiemeier, Robin P. Peeters, Vincent W. V. Jaddoe, Albert Hofman, Frank C. Verhulst, Akhgar Ghassabian
Journal: JAMA Pediatrics (2015)

Maternal thyroid hormone insufficiency during pregnancy can affect children's cognitive development. Nevertheless, the behavioral outcomes of children exposed prenatally to mild thyroid hormone insufficiency are understudied.To examine whether exposure to maternal mild thyroid hormone insufficiency in early pregnancy was related to symptoms of attention-deficit/hyperactivity disorder (ADHD) in children at 8 years of age.The study was embedded within the Generation R, a population-based birth cohort in the Netherlands. Children in the Generation R Study are followed up from birth (April 1, 2002, through January 31, 2006) until young adulthood. Of the 4997 eligible mother-child pairs with data on maternal thyroid levels (excluding twins), 3873 pairs of children and caregivers (77.5%) visited the Generation R research center for in-depth assessments and were included in the main analyses. Data collection in Generation R started December 1, 2001 (enrollment of pregnant women), and is ongoing. For this study, we used the data that were collected until January 1, 2014. Data analyses started on January 31 and finished June 30, 2014.Maternal hypothyroxinemia, characterized by low levels of free thyroxine coexisting with reference thyrotropin levels, and children's symptoms of ADHD. Maternal thyroid hormone levels (thyrotropin, free thyroxine, thyroid peroxidase antibodies) were measured at a mean (SD) of 13.6 (1.9) weeks of gestation. Children's ADHD symptoms were assessed at 8 years of age using the Conners' Parent Rating Scale-Revised Short Form; higher scores indicate more ADHD symptoms (possible range, 0-36).Maternal hypothyroxinemia (n = 127) in early pregnancy was associated with higher scores for ADHD symptoms in children at 8 years of age after adjustments for child and maternal factors (ie, sex, ethnicity, maternal age, maternal educational level, and income) (increase in ADHD scores, 7% [95% CI, 0.3%-15%]). The results remained essentially unchanged when women with elevated levels of thyroid peroxidase antibodies were excluded from the analyses (increase in ADHD scores, 8% [95% CI, 1%-16%]). Additional adjustment for children's IQ or comorbid autistic symptoms attenuated the association (increase in ADHD scores adjusted for autistic symptoms, 7% [95% CI, 1%-15%]; increase in ADHD scores adjusted for IQ, 6% [95% CI, 1%-14%]).Children exposed to maternal hypothyroxinemia in early pregnancy had more ADHD symptoms, independent of confounders. This finding suggests that intrauterine exposure to insufficient thyroid hormone levels influences neurodevelopment in offspring.
Incidence of rhinitis and asthma related to welding in Northern Europe
Authors: Torgeir Storaas, Jan-Paul Zock, Ana Espinosa Morano, Mathias Holm, Eythor Bjørnsson, Bertil Forsberg, Thorarinn Gislason, Christer Janson, Dan Norback, Ernst Omenaas, Vivi Schlünssen, Kjell Torén, Cecilie Svanes
Journal: European Respiratory Journal (2015)

Welding-related asthma is well recognised but less is known about rhinitis in relation to welding. The aim here, was to study associations between welding, rhinitis and asthma in a general population sample, and factors influencing selection into and out of a welding occupation.Adult-onset asthma and non-infectious rhinitis were investigated in the international multicentre population-based Respiratory Health in Northern Europe (RHINE) study, including 16,191 responders aged 26-54 years. Ever welding (n=2181), welding >25% of working time (n=747), and welding in stainless steel >6 months (n=173) were assessed by questionnaire. Subjects with rhinitis or asthma onset when aged <18 years were excluded. Incidence rates for asthma and rhinitis were calculated from year of disease onset, and start and end of welding job. Cox's proportional hazard models adjusting for age, sex, parental education and study centre, and Kaplan-Meier curves were used.Rhinitis incidence was higher among welders (hazard ratio (HR) 1.4, 95% CI 1.3-1.6), consistent in men and women, and across centres (pheterogeneity=0.4). In men, asthma incidence was higher among welders (HR 1.4, 95% CI 1.04-1.97). Quitting welding was indicated higher after adult-onset rhinitis (HR 1.1, 95% CI 1.0-1.3). Adult-onset rhinitis and asthma was higher among welders, consistent across population samples from Northern Europe. No pre-employment selection was found, whereas selection out of welding jobs was suggested.
Comorbidity of substance abuse and other psychiatric disorders in adolescents
Authors: O G Bukstein, D A Brent, Y Kaminer
Journal: American Journal of Psychiatry (1989)

Psychopathology coexisting with substance abuse in adolescents is often encountered in a variety of clinical settings. Research findings suggest a major role for substance use in the etiology and prognosis of psychiatric disorders such as affective disorders, conduct disorder and antisocial personality disorder, attention-deficit hyperactivity disorder, and anxiety disorders. Psychiatric disorders also appear to have an important role in the etiology of and vulnerability to substance use problems in adolescents. Although the comorbidity of substance abuse and other psychiatric disorders in adolescents is recognized as an important factor in the treatment of adolescents, further research is needed to establish its prevalence, genetics, and clinical implications.
Biomedical Applications of Trastuzumab: As a Therapeutic Agent and a Targeting Ligand
Authors: Hitesh Kulhari, Deep Pooja, Sri V. K. Rompicharla, Ramakrishna Sistla, David J. Adams
Journal: Medicinal Research Reviews (2015)

Trastuzumab (TZ) is a humanized monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor. TZ is approved by the Food and Drug Administration (FDA) for the treatment of HER2-overexpressing early stage and metastatic breast cancer and HER2-overexpressing metastatic gastric cancer. For breast cancer, it is recommended as both a single agent and in combination with standard chemotherapy. In the last few years, TZ has also been used as a targeting ligand. Overexpression of HER2 in breast cancer and the presence of free surface functional groups on TZ provide an opportunity to use it as a targeting ligand. TZ can be conjugated to various nanoparticulate systems such as dendrimers, polymeric, and protein nanoparticles to target drug delivery. TZ-conjugated inorganic nanoparticles have been reported for imaging and diagnostic purposes. This review summarizes the applications of TZ both as a therapeutic agent and as a targeting ligand.
The effect of depression treatment on elderly patients' preferences for life-sustaining medical therapy
Authors: L Ganzini, M A Lee, R T Heintz, J D Bloom, D S Fenn
Journal: American Journal of Psychiatry (1994)

This study was undertaken 1) to test the hypothesis that remission of depression results in an increase in desire for life-sustaining medical therapy and 2) to characterize patients whose desire for life-sustaining treatment increases substantially following depression therapy.Elderly patients, suffering from major depression, were interviewed on admission to a psychiatric inpatient unit and at discharge about their desire for specific medical therapies in their current state of health and in two hypothetical scenarios of medical illness. A psychiatrist rated the impact of depressive thinking on the subject's response to these questions. Forty-three subjects completed the study, and 24 were in remission from depression at the time of discharge.In the majority of patients, remission of depression did not result in an increase in desire for life-sustaining medical therapy. However, a clinically evident increase in desire for life-sustaining medical therapies followed treatment of depression in subjects (N = 11 [26%]) who had been initially rated as more severely depressed, more hopeless, and more likely to overestimate the risks and to underestimate the benefits of treatment.In major depression of mild to moderate severity, a patient's desire to forgo life-sustaining medical treatment is unlikely to be altered by depression treatment. On the other hand, severely depressed patients, particularly those who are hopeless, overestimate the risks of treatment, or underestimate the benefits of treatment, should be encouraged to defer advance treatment directives. In these patients decisions about life-sustaining therapy should be discouraged until after treatment of the depression.
Cell Of Origin Does Not Affect Outcomes In Early Stage Non-Bulky Diffuse Large B-Cell Lymphoma Treated With Short-Course Combined Modality Therapy
Authors: Matthew A. Lunning, Jocelyn C. Maragulia, Anita Kumar, Martin Bast, Philip Bierman, R. Gregory Bociek, Julie M Vose, James O. Armitage, Steven M. Horwitz, Andrew D Zelenetz
Journal: Blood (2013)
Doctors and homosexuality
Authors: V. J Holt
Journal: BMJ (1994)

health promotion package for primary care cannot be justified in its present form.We do not believe that these results leave practice nurses without a role-and the government's press statement that our programme was the responsibility of the nurses alone rather than the practice team was incorrect.Rather, we believe that it may be more appropriate to focus limited nursing and medical resources on high risk patients, including those with established coronary heart disease.
White matter hyperintensity signals in psychiatric and nonpsychiatric subjects
Authors: F W Brown, R J Lewine, P A Hudgins, S C Risch
Journal: American Journal of Psychiatry (1992)

As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals.Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated.Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects.These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.
Abstract 18240: Wnt Signaling Negatively Regulates the Proliferation of Adult Cardiac Progenitor Cells
Authors: Angelos Oikonomopoulos, Konstantina-Ioanna Sereti, Frank Conyers, Michael Bauer, Annette Liao, Jian Guan, Jung-Kyu Han, Hanhua Dong, Ahmad Bayomy, Gabriel C. Fine, Karen Westerman, Travis L. Biechele, Randall T. Moon, Thomas Force, Ronglih Liao
Journal: Circulation (2011)

Recent studies have demonstrated the existence of endogenous cardiac stem/progenitor cells capable of regenerating damaged myocardium following myocardial infarction (MI). Cardiac side population (CSP) cells are cardiac precursors found in the adult myocardium, which are able to differentiate into functional cardiomyocytes both in vitro and in vivo, following MI. In response to local tissue injury, CSP cells are maintained through a process of self-renewal. The molecular signals that control the self-renewal of adult progenitor cells in the heart remain unclear. Canonical Wnt signaling pathway has been implicated in the regulation of tumor progression, development and regeneration in various tissues. The goal of this study was to determine the effects of Wnt signaling pathway on the homeostasis of adult CSP cells under normal and disease conditions. Results: In contrast to previous work in embryonic or early post-natal cardiac stem cells, we reveal that Wnt signaling negatively regulates adult CSP progenitor cell proliferation, both in vitro and in vivo through suppression of cell cycle progression. Furthermore, we demonstrate that Wnt signaling exerts its anti-proliferative effect through the activation of insulin-like growth factor binding protein 3 (IGFBP3). Administration of recombinant Wnt3a protein in the infarct/border zone of mouse hearts, following MI decreases the amount of cardiac CSP cells and impairs the endogenous cardiac regenerative capacity, as evidenced by the decreased number of BrdU positive cardiomyocytes. Reduction of cardiac regenerative capacity mediates adverse effects on post-MI remodeling and performance. Conclusion: Our data demonstrate that Wnt signaling represents an effective negative regulator of adult cardiac progenitor cell proliferation, under physiologic conditions and post-MI. Inhibition of Wnt signaling may be considered as an approach to promote cardiac regeneration following ischemic injury.
Personal views: Everyman's view of doctors
Authors: Demetrios Matheou
Journal: BMJ (2001)

My first love was a medical student. I must recommend it. I always attributed her verve to an unabashed quest for anatomical knowledge, her lack of inhibition to the fact that she had pretty much seen it all. Along the way, minor ailments were treated and hypochondria dispelled, with adept matter of factness.

Not surprisingly, this was the best doctor-patient relationship I've ever had; long after we split up, the poor woman would still receive frantic calls from me: so what is male pattern baldness? Should I really have started shrinking at the age of 30? Can you prescribe me Viagra on the sly? Without her (she went ex-directory), my urge to consult doctors has declined, in keeping with that all too prevalent condition—medical uninterest. The symptoms of this are laziness, forgetfulness, fear of sharing one's problems with strangers, and a dislike of sitting in bland and uncompromisingly boring waiting rooms.

I imagine that in the field of self preservation, or maintenance, I am Everyman. I never think of looking after myself, or indeed visiting my general practitioner, unless I feel I really have to, unless there is pain, or blood, or both.

My experience, when I do decide to visit the GP, is strangely satisfying. I have always liked my doctors. They are polite, patient (ironically, once I'm there I really do bark on), and thorough. I've been surprised sometimes how one apparently innocuous symptom has produced a checklist of tests. The resulting weeks of x-rays, blood samples, and assorted probes leaves one feeling the happy recipient of a bloody good MOT.

The MOT is a decent analogy, since in hospitals one's prevailing sense of doctors is that they are technicians, engineers whose impersonal professionalism leads them to forget that little matter of pain. The most painful experience of my life—bar none—was as a result of a checklist probe, a cystoscopy. Having an umbrella stuck up one's plonker is a man's worst nightmare. Excruciating doesn't cover it. Shame doesn't begin to represent the experience of lying on an operating table surrounded by nurses, your nethers exposed, and tears in your eyes. Perhaps knowing all this, the consultant urging me to undergo the procedure informed me matter of factly (matter of fact is taught in the second year, is it not?) that “it's not at all painful.” When I checked this with the nurse, she laughed.

There is an interesting inversion here. In a GP's surgery, the receptionist and/or nurse tends to make you feel the least comfortable; representing delay, supervising the bleak anteroom to one's feared examination. In hospitals, the good cop-bad cop relationship is reversed—nurses give time, comfort, and honesty, while the docs whip in and out with all the aplomb of factory line inspectors.