tbuckley/cabot-search huggingface dataset:
Mapping of monilethrix to the type II keratin gene cluster at chromosome 12q13 in three new families, including one with variable expressivity
Authors: M.A. BIRCH-MACHIN, E. HEALY, R. TURNER, F. HALDANE, C.E. BELGAID, S. DARLINGTON, A.M. STEPHENSON, C. MUNRO, A.G. MESSENGER, J.L. REES
Journal: British Journal of Dermatology (1997)

Monilethrix is an autosomal dominant disorder chiefly affecting hair. The degree of hair dystrophy is highly variable, as is the presence of additional features, such as follicular keratoses. In three British families of monilethrix, linkage has recently been reported to the type II keratin gene cluster at chromosome 12q13, and it has been suggested that the disease is due to a defect in the hard keratins of hair and nail. If monilethrix is a keratin disorder, we would predict that some pedigrees might map to the type I keratin gene cluster on 17q where hard keratin genes are also found. We have now studied clinically and by linkage analysis three new and unrelated pedigrees from England, Scotland and Spain, the first of which showed a variant phenotype. In this family the disease was expressed in four of 12 cases only as a follicular keratosis of the neck, elbows and knees, and without clinical or historical evidence of hair anomalies: non‐penetrance in an obligate carrier was also observed. In all three families, we have established linkage to a series of microsatellite markers at the type II locus at 12q13 (Zmax=6.34 at 0=0.00 for D12S368) and have excluded linkage from the type I keratin gene cluster on 17q. It remains probable that monilethrix is a disorder of hard keratins, but at present there is no evidence that it is due to defects in type I keratins.
American Indians, African Americans: Their Common Histories
Authors: Deborah Chase
Journal: JAMA (1992)

To the Editor.  —The article by Blum et al 1 prompted me to consider the many similarities in the health risks of African Americans and American Indians. Both groups exhibit a high risk of death among young men, a pervasive sense of low self-esteem and hopelessness, and the absence of a complete nuclear family. 2 Perhaps these attributes, which appear to be less common in many other ethnic communities, are related to historical parallels in the experiences of African Americans and American Indians. Neither group entered white America out of choice. Both groups were forced into white society by white settlers, either as slaves or as conquered nations. Further study of the unique position of American Indians and African Americans and how this relates to and affects the similarity of their health risks could be important, particularly as policymakers and health care providers try to identify the health care and
Clinical response of patients with sickle cell anemia to cromolyn sodium nasal spray
Authors: Mehran Karimi, Omid R. Zekavat, Sedigeh Sharifzadeh, Kazem Mosavizadeh
Journal: American Journal of Hematology (2006)

Sickle cell anemia is the most common heritable hematological disease affecting humans. Although hydroxyurea is the most commonly used antisickling agent, several previous studies suggest that cromolyn sodium also prevents sickling when administered acutely. However, no previous studies have evaluated the safety or efficacy of prolonged administration of cromolyn to patients with sickle cell anemia. The purpose of this study, therefore, was to test the hypothesis that prolonged administration of cromolyn alone or in combination with hydroxyurea would decrease the incidence of pain crises and/or alter the chronic pain seen in patients with this disease. In this crossover, single-blind, in vivo and in vitro study, 17 patients with sickle cell disease were studied. Each patient had to fill out a standard pain chart. Every 3 months the patients' medications changed in the following manner: The first 3 months the patients used cromolyn sodium nasal spray; the second 3 months they received placebo nasal spray; the third 3 months they received cromolyn sodium nasal spray and hydroxyurea capsule; and the last 3 months they received hydroxyurea capsule and placebo nasal spray. The least pain was felt with the mixture of hydroxyurea capsule and cromolyn sodium nasal inhaler. Furthermore, with the other combinations of medications, there were no significant statistical changes in the number of sickled red blood cells. Every combination used in this survey had positive effects on decreasing the pain. cromolyn sodium nasal spray is significantly efficient in decreasing sickle cell crisis as well as pain intensity in patients with sickle cell anemia. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.
The fine art of the surgeon
Authors: T. Dalrymple
Journal: BMJ (2010)

Perhaps because they treat the body as a machine and see more than most of the grim side of human life, doctors, it used to be thought, were particularly liable to atheism. Whether or not this is so epidemiologically speaking, four of the eight authors of the Bridgewater Treatises defending the notion of a divine designer were doctors.

The Bridgewater Treatises were written in accordance with the terms of the will of the Right Honourable and Reverend Francis Henry, Earl of Bridgewater, who died in 1829, each treatise to be by a recognised scholar to illustrate “the Power, Wisdom and Goodness of God, as manifested in the Creation . . . as for instance the variety and …
Preclinical Optimization of MDM2 Antagonist Scheduling for Cancer Treatment by Using a Model-Based Approach
Authors: Brian Higgins, Kelli Glenn, Antje Walz, Christian Tovar, Zoran Filipovic, Sazzad Hussain, Edmund Lee, Kenneth Kolinsky, Shahid Tannu, Violeta Adames, Rosario Garrido, Michael Linn, Christophe Meille, David Heimbrook, Lyubomir Vassilev, Kathryn Packman
Journal: Clinical Cancer Research (2014)

Antitumor clinical activity has been demonstrated for the MDM2 antagonist RG7112, but patient tolerability for the necessary daily dosing was poor. Here, utilizing RG7388, a second-generation nutlin with superior selectivity and potency, we determine the feasibility of intermittent dosing to guide the selection of initial phase I scheduling regimens.A pharmacokinetic-pharmacodynamic (PKPD) model was developed on the basis of preclinical data to determine alternative dosing schedule requirements for optimal RG7388-induced antitumor activity. This PKPD model was used to investigate the pharmacokinetics of RG7388 linked to the time-course of the antitumor effect in an osteosarcoma xenograft model in mice. These data were used to prospectively predict intermittent and continuous dosing regimens, resulting in tumor stasis in the same model system.RG7388-induced apoptosis was delayed relative to drug exposure with continuous treatment not required. In initial efficacy testing, daily dosing at 30 mg/kg and twice a week dosing at 50 mg/kg of RG7388 were statistically equivalent in our tumor model. In addition, weekly dosing of 50 mg/kg was equivalent to 10 mg/kg given daily. The implementation of modeling and simulation on these data suggested several possible intermittent clinical dosing schedules. Further preclinical analyses confirmed these schedules as viable options.Besides chronic administration, antitumor activity can be achieved with intermittent schedules of RG7388, as predicted through modeling and simulation. These alternative regimens may potentially ameliorate tolerability issues seen with chronic administration of RG7112, while providing clinical benefit. Thus, both weekly (qw) and daily for five days (5 d on/23 off, qd) schedules were selected for RG7388 clinical testing.
Reversible encephalopathy after cryopreserved peripheral blood stem cell infusion
Authors: Madhav Dhodapkar, Stuart L. Goldberg, Ayalew Tefferi, Morse A. Gertz
Journal: American Journal of Hematology (1994)

Abstract We report two patients who experienced severe reversible encephalopathy following infusion of peripheral blood stem cells cryopreserved in 10% dimethylsulfoxide (DMSO). In one patient, reduction of DMSO level with plasmapheresis resulted in marked improvement in encephalopathy. Infusion of large volumes of cryopreserved stem cells may result in a signiflcant toxlc reaction. Plasmapheresis may be a treatment option for patients with significant toxicity related to DMSO. © 1994 Wiley‐Liss, Inc.
The Special Theory of Psycho therapeutic Interaction
Authors: Richard D. Chessick
Journal: Psychotherapy and Psychosomatics (1974)

Research Articles| February 12 2010 The Special Theory of Psychotherapeutic Interaction Subject Area: Psychiatry and Psychology Richard D. Chessick Richard D. Chessick Northwestern University Medical School, Chicago, Ill. Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (1974) 24 (4-6): 433–438. https://doi.org/10.1159/000286780 Article history Published Online: February 12 2010 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Richard D. Chessick; The Special Theory of Psychotherapeutic Interaction. Psychother Psychosom 31 December 1974; 24 (4-6): 433–438. https://doi.org/10.1159/000286780 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPsychotherapy and Psychosomatics Search Advanced Search Article PDF first page preview Close Modal 1974Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Free and complexed interleukin-8 in blood and bronchial mucosa in asthma.
Authors: J K Shute, B Vrugt, I J Lindley, S T Holgate, A Bron, R Aalbers, R Djukanović
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We have tested the hypothesis that the expression of interleukin-8 (IL-8) is increased in bronchial tissue and circulating leukocytes of atopic asthmatics, indicating a role for this chemokine in asthma. The concentration of IL-8 in its free form and complexed with IgG or IgA was measured by ELISA in bronchial tissue, serum, and lysates of freshly isolated peripheral blood mononuclear cells and granulocytes from subjects with mild or severe asthma and nonatopic nonasthmatic subjects. Serum ECP was measured by fluorescent enzyme immunoassay. Free IL-8 was detected in the sera (n = 44) and bronchial tissue (n = 9) of all subjects with severe atopic asthma, but it was undetectable in normal subjects and subjects with mild atopic asthma, suggesting that free IL-8 is a marker of severe asthma. A positive correlation between free IL-8 and serum ECP levels found in severe disease suggests that IL-8 is associated with eosinophil activation. Complexes of IL-8 with IgA and IgG were detected in all serum and tissue samples. However, the levels of the IL-8-IgA complex were increased in the bronchial mucosa in asthma, and in blood were related to disease activity. Together, these results point to upregulation of IL-8 production in asthma and the induction of IL-8 binding immunoglobulins of the IgA class in the inflamed mucosa. We suggest a proinflammatory role for these complexes in lung tissue.
Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy
Authors: Davide Gianni, Airong Li, Giuseppina Tesco, Kenneth M. McKay, John Moore, Kunal Raygor, Marcello Rota, Judith K. Gwathmey, G. William Dec, Thomas Aretz, Annarosa Leri, Marc J. Semigran, Piero Anversa, Thomas E. Macgillivray, Rudolph E. Tanzi, Federica del Monte
Journal: Circulation (2010)

Background— Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of β-amyloid impair cell function and lead to cell death. Methods and Results— We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca 2+ homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 ( PSEN1 ) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a. Conclusions— On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca 2+ handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function.
Angiotensin II Impairs Neurovascular Coupling in Neocortex Through NADPH Oxidase–Derived Radicals
Authors: Ken Kazama, Josef Anrather, Ping Zhou, Helene Girouard, Kelly Frys, Teresa A. Milner, Costantino Iadecola
Journal: Circulation Research (2004)

Angiotensin II (Ang II) exerts detrimental effects on cerebral circulation, the mechanisms of which have not been elucidated. In particular, Ang II impairs the increase in cerebral blood flow (CBF) produced by neural activity, a critical mechanism that matches substrate delivery with energy demands in brain. We investigated whether Ang II exerts its deleterious actions by activating Ang II type 1 (AT 1 ) receptors on cerebral blood vessels and producing reactive oxygen species (ROS) through NADPH oxidase. Somatosensory cortex CBF was monitored in anesthetized mice by laser-Doppler flowmetry. Ang II (0.25 μg/kg per minute IV) attenuated the CBF increase produced by mechanical stimulation of the vibrissae. The effect was blocked by the AT 1 antagonist losartan and by ROS scavenger superoxide dismutase or tiron and was not observed in mice lacking the gp91 phox subunit of NADPH oxidase or in wild-type mice treated with the NADPH oxidase peptide inhibitor gp91ds-tat. Ang II increased ROS production in cerebral microvessels, an effect blocked by the ROS scavenger Mn(III)tetrakis (4-benzoic acid) porphyrin and by the NADPH oxidase assembly inhibitor apocynin. Ang II did not increase ROS production in gp91-null mice. Double-label immunoelectron microscopy demonstrated that AT 1 and gp91 phox immunoreactivities were present in endothelium and adventitia of neocortical arterioles. Collectively, these findings suggest that Ang II impairs functional hyperemia by activating AT 1 receptors and inducing ROS production via a gp91 phox containing NADPH oxidase. The data provide the mechanistic basis for the cerebrovascular dysregulation induced by Ang II and suggest novel therapeutic strategies to counteract the effects of hypertension on the brain.
Cyclopropane in Non-explosive Mixture for Out-patient Anaesthesia
Authors: W. W. Mushin, P. W. Thompson
Journal: BMJ (1958)

The commonest anaesthetic for minor operations in this country is nitrous oxide.Inexpert administration often results in hypoxia, the dangers of which are well recognized.In 1939 Courville described the serious neurological sequelae of hypoxia which sometimes follow nitrous oxide anaesthesia.His observations have been amply confirmed; in many papers, of which only a selection are listed (Murphy, 1940;Chase, 1941;Batten, 1942;
Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis
Authors: Bodi Zhang, Konstantinos-Dionysios Alysandratos, Asimenia Angelidou, Shahrzad Asadi, Nikolaos Sismanopoulos, Danae-Anastasia Delivanis, Zuyi Weng, Alexandra Miniati, Magdalini Vasiadi, Alexandra Katsarou-Katsari, Benchun Miao, Susan E. Leeman, Dimitrios Kalogeromitros, Theoharis C. Theoharides
Journal: Journal of Allergy and Clinical Immunology (2011)
METHODS OF WATER PURIFICATION FOR LARGE CITIES
Authors: RUDOLPH HERING
Journal: JAMA (1913)

Ward and Henderson14 in this country, Vervoort" in Amsterdam, Seligmann1)!and Krank17 in Germany and ¡nany others have shown the reality of school infection m definite instances.Frank, for example, in studying an epidemic of diphtheria in 1910-1911 among tbe pupils °f a girls' school in Charlottenburg found that convey¬ ance of infection must have taken place in the school s¡iiee the children were recruited from all parts of the cjty, some of them coming from districts where at the time no diphtheria cases were known lo exist.In 1909 the number of children in Ibis school developing diph¬ theria amounted to only 0.7 per cent., which was about the average for the other schools of the city, while in 1910-1911 the number of diphtheria cases increased to 'I per cent.Detailed investigation of the school by classes
T2 hyperintensity along the cortico-spinal tract in cirrhosis relates to functional abnormalities
Authors: Juan Córdoba, Nuria Raguer, Montserrat Flavià, Víctor Vargas, Carlos Jacas, Juli Alonso, Alex Rovira
Journal: Hepatology (2003)

Magnetic resonance has shown T2 hyperintensity along the cortico–spinal tract in the brain of cirrhotic patients. This abnormality, which is reversible after liver transplantation, appears to correspond to mild edema. Because astrocytic edema present in hepatic encephalopathy may be responsible for neuronal dysfunction, we studied whether T2 hyperintensity along the cortico–spinal tract may relate to functional abnormalities. Twenty patients with cirrhosis underwent neuropsychologic tests, neurophysiologic study of the cortico–spinal tract with transcranial magnetic stimulation, and 1 H–magnetic resonance. The study was repeated 6 months after liver transplantation ( n = 15) and was compared with a control group of healthy subjects ( n = 11). Cirrhotic patients exhibited increased T2 signal and several functional abnormalities along the cortico–spinal tract (increased central motor conduction time, increased motor cortical threshold, and decreased motor–evoked potential amplitude). Functional abnormalities reversed after liver transplantation and were associated with normalization of T2 cortico–spinal hyperintensity and with improvement of minimal hepatic encephalopathy. In conclusion, T2 hyperintensity along the cortico–spinal tract in cirrhosis relates to functional abnormalities that are reversible after liver transplantation. These findings suggest that mild cerebral edema along the cortico–spinal pathway may cause neuronal dysfunction. These results support the participation of astrocytic edema in the pathogenesis of hepatic encephalopathy. (Hepatology 2003;38:1026-1033).
The Blood Pressure of Hypertensive Smokers-Reply
Authors: Samuel J. Mann
Journal: JAMA (1991)

<h3>In Reply.</h3> —We do not believe that the difference in waist-to-hip ratio between smokers and nonsmokers, raised by Dr Vasan, is related to the observed elevations of ambulatory systolic BP in smokers for several reasons. No major epidemiologic study has shown a higher office BP among smokers than among nonsmokers, even after controlling for body mass index.<sup>1-8</sup>Even if smokers have a higher hip-to-waist ratio than nonsmokers, and even if that is associated with hyperinsulinemia, and even if the hyperinsulinemia were sufficient to have a clinically noticeable effect on the BP, it would still have to be reflected in the office BP. In addition, it would not explain why this BP difference was seen in patients over the age of 50 years but not under the age of 50. Dr Appel's concern about the older age of the nonsmokers (51 years vs 45 years) was addressed in the article.
Machina Carnis: The Biochemistry of Muscular Contraction in Its Historical Development
Authors: Paul F. Cranefield
Journal: JAMA (1972)

Dorothy Needham's study of the historical development of the biochemistry of muscular contraction has resulted in a book that is long, very important, elegantly illustrated, magnificently produced, intelligently indexed, and very expensive. In form and style the book is an interpretative review of the relatively recent literature to a greater extent than it is a historical study. The superb bibliography contains more than 3,000 citations; more than a third of them refer to articles published in the 1960's; fewer than 10% refer to work published prior to 1920.  Such a review necessarily encompasses a great deal of abstruse material. Many details and even many major themes will elude the reader who is not a biochemist. Yet Mrs. Needham always attempts to explain and interpret the meaning and significance of the findings that she describes; in this task she is aided by her chronological and historical approach. The general reader willing
Thinking laterally about neurodegenerative proteinopathies
Authors: Todd E. Golde, David R. Borchelt, Benoit I. Giasson, Jada Lewis
Journal: Journal of Clinical Investigation (2013)

Many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and frontotemporal dementia, are proteinopathies that are associated with the aggregation and accumulation of misfolded proteins. While remarkable progress has been made in understanding the triggers of these conditions, several challenges have hampered the translation of preclinical therapies targeting pathways downstream of the initiating proteinopathies. Clinical trials in symptomatic patients using therapies directed toward initiating trigger events have met with little success, prompting concerns that such therapeutics may be of limited efficacy when used in advanced stages of the disease rather than as prophylactics. Herein, we discuss gaps in our understanding of the pathological processes downstream of the trigger and potential strategies to identify common features of the downstream degenerative cascade in multiple CNS proteinopathies, which could potentially lead to the development of common therapeutic targets for multiple disorders.