tbuckley/cabot-search huggingface dataset:
Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression
Authors: Shuji Terai, Hiroshi Aoki, Kozo Ashida, Snorri S. Thorgeirsson
Journal: Hepatology (2000)

The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key regulators in numerous developmental processes. The class I HLH proteins, such as E12 are ubiquitously expressed. Class II HLH proteins, such as MyoD, are expressed in a tissue-specific manner. Class I and II heterodimers can bind to E-boxes (CANNTG) and regulate lineage commitments of embryonic cells. In an attempt to identify partners for the E12 protein that may exert control during liver development, we performed the yeast 2-hybrid screen using an expression complementary DNA library from human fetal liver. A novel dominant inhibitory HLH factor, designated HHM (human homologue of maid), was isolated and characterized. HHM is structurally related to the Id family and was highly expressed in brain, pituitary gland, lung, heart, placenta, fetal liver, and bone marrow. HHM physically interacted with E12 in vitro and in mammalian cells. Comparison of the dominant inhibitory effects of HHM and Id2 on the binding of E12/MyoD dimer to an E-box element revealed a weaker inhibition by HHM. However, HHM but not Id2 specifically inhibited the luciferase gene activation induced by hepatic nuclear factor 4 (HNF4) promoter. The HHM was transiently expressed during stem-cell-driven regeneration of the liver at the stage in which the early basophilic foci of hepatocytes started to appear. These results suggest that HHM is a novel type of dominant inhibitory HLH protein that might modulate liver-specific gene expression.
Computed Tomography Correlates with Pulmonary Exacerbations in Children with Cystic Fibrosis
Authors: Alan S. Brody, Heidi Sucharew, Jonathan D. Campbell, Steven P. Millard, Paul L. Molina, Jeffrey S. Klein, Joanne Quan
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

High-resolution computed tomography (HRCT) has been suggested as a potential outcome surrogate for cystic fibrosis (CF) lung disease. An important attribute of a valid outcome surrogate is that the surrogate reflects true clinical outcomes.We performed this study to validate HRCT, a proposed surrogate outcome measure for CF lung disease, against a true clinical outcome, the number of respiratory tract exacerbations occurring in 2 yr, and to assess the correlation of CT scores and pulmonary function tests (PFTs) with this clinical outcome.CTs and PFTs were performed on 6- to 10-yr-old children at the beginning and end of a 2-yr study during which the number of exacerbations were recorded. Spearman correlations and Poisson models were used to assess the correlation of the number of exacerbations with baseline values and changes in PFTs and CT scores.Nine of 61 subjects had a total of 22 respiratory tract exacerbations. At baseline, PFTs and four CT scores showed significant correlation with number of exacerbations, but no variable by itself predicted exacerbations with high accuracy. For change over the 2-yr period, three CT scores showed significant correlation with exacerbations, whereas no PFTs showed significant correlation.This is the first study showing correlation between CT and a true clinical outcome. Change in CT scores correlates moderately well with the number of exacerbation. Poor correlation between change in FEV1 and exacerbations suggests that HRCT may be a more appropriate outcome surrogate for longitudinal studies of young children.
An Address on RINGWORM AND ITS TREATMENT
Authors: J. M. H. MacLeod
Journal: BMJ (1928)

Ix selecting inigwor-m as the subject for this lecture, which youri DiviS;on has so greatly hoInour-ed me by asking nie to deliver, I hiave been guided in iiiy chioice by expe- rienice that the recognition of ringwornm is liable to p0ove a sttumiiblinig block to the practitioInei, aind that the diffi- culties of its succeSsful treatment are apt to be so great as to render it almost a subject of reproach by the laity.Rinigwor0m is a common affection of the skii, dIUe to a group Of mou fUngi, which may attack tile glabrous skin, hiairs, nails, and in rare iistances, by extenision, the iiucous iiienibraiies, the clinical appearances of which differ accor ding to *the variety of fun1gus esponsible, the site of the lesioins, an1d the inidividual peculiarities of the skini affected.RINGWORM FUNGI.
Promotion of Gerontology
Authors: THEODORE R. REIFF
Journal: Annals of Internal Medicine (1973)

Letters, Comments, and Corrections1 February 1973Promotion of GerontologyTHEODORE R. REIFF, M.D.THEODORE R. REIFF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-2-314_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Since my last communication (Ann Intern Med 77:816, 1972) and after discussions with knowledgeable sources in Washington, it appears that a bill to establish a National Institute Of Aging within the National Institutes of Health will be introduced into the next Congress when it convenes in January 1973. It is considered virtually certain that this bill will again be passed by Congress and that, if the President exercises his veto, it will be overridden.The bill proposed by Senator Moss (S.2931) may or may not be brought onto the floor during the next Congress. Regardless of whether or... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1973Volume 78, Issue 2Page: 314-315KeywordsAgingExerciseGeriatricsHealth promotion Issue Published: 1 February 1973 PDF DownloadLoading ...
Studies of Cell Subpopulations Mediating Mitogen Hyporesponsiveness in Patients with Hodgkin's Disease
Authors: W. L. Sibbitt, A. D. Bankhurst, R. C. Williams
Journal: Journal of Clinical Investigation (1978)

Hodgkin's disease (HD) is associated with a deficit in T-cell immunity characterized by skin test anergy and decreased lymphocyte responses to phytohemagglutinin (PHA). To investigate this mitogen hyporesponsiveness in HD, we separated peripheral blood mononuclear cells on Ficoll-Hypaque gradients and determined their response to various suboptimal concentrations of PHA. As was expected, patients with HD demonstrated marked mitogen hyporesponsiveness relative to normal controls; however, if the cell suspensions were first passed through glass wool columns to remove adherent cells, the PHA responsiveness of the hyporesponsive HD cells was markedly increased. In contrast, the responsiveness of normal controls was decreased so that the responses of nonadherent normal and HD cells were statistically indistinguishable. Evidently, a glass wool-adherent suppressor cell had been removed from patients with HD, while a glass wool-adherent cell which enhanced mitogenic responses had been removed from normal controls during column passage. Previous to column depletion, patients with HD had decreased proportions of E-rosettes and increased proportions of cells with surface alpha-fetoprotein; however, the proportion of these cells was not changed after column passage. Significant changes with column depletion of glass wool-adherent cells in HD were recorded in the proportions of monocytes (13.2 vs 5.8%) and lymphocytes with C-3 receptors (12.6 vs. 7.8%). The only significant change in normal controls was a decrease in the proportion of monocytes (10 vs. 1.7%). To determine if glass-adherent cells would have a suppressor effect, HD-adherent cells were added in progressively increasing numbers to mononuclear cell suspensions depleted of glass wool-adherent cells. PHA responsiveness returned toward predepletion levels. In summary, patients with HD possess a glass wool-adherent suppressor cell which is responsible at least in part for in vitro mitogen hyporesponsiveness.
Conference on Experimental Clinical Cancer Chemotherapy, Washington, D. C., November 11 and 12, 1959
Authors: Warren H. Cole
Journal: JAMA (1961)

This volume includes the papers and panel discussions presented during a meeting held in Washington, D. C., Nov. 11, 1959, under the auspices of the Cancer Chemotherapy National Service Center. Persons representing the various groups cooperating to study the effect of therapy in the numerous types of malignant diseases were present. The program consisted of 5 or 6 formal presentations followed by 11 panels. The panels included such subjects as lung cancer, adjuvant chemotherapy, alkylating agents, acute and chronic leukemia, lymphomas, endocrine tumors, breast cancer, and newer techniques. The biologic screening systems were discussed by Dr. Chester Stock. Medical measurements for prediction of the course of the disease were presented by Dr. Edmund Gehan. In the panel discussing new types and structures for chemotherapeutic agents presented by Drs. Skipper, Baker, and Jones, Dr. Skipper emphasized the importance of the resistance developed by the tumor to the agent. He reported that
Chronic Pulmonary Histoplasmosis: Improved Lymphocyte Response with Transfer Factor
Authors: Craig R. Smith, Diane E. Griffin, J. Richard Graybill
Journal: Annals of Internal Medicine (1976)

Letters1 June 1976Chronic Pulmonary Histoplasmosis: Improved Lymphocyte Response with Transfer FactorCRAIG R. SMITH, M.D., DIANE E. GRIFFIN, M.D., PH.D., J. RICHARD GRAYBILL, M.D.CRAIG R. SMITH, M.D.Search for more papers by this author, DIANE E. GRIFFIN, M.D., PH.D.Search for more papers by this author, J. RICHARD GRAYBILL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-6-708 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptInfection with Histoplasma capsulatum may cause chronic cavitary pulmonary disease in humans. Approximately 12% to 17% of patients with chronic pulmonary histoplasmosis have an impaired cell-mediated immune response to histoplasmin (1). Alford and Goodwin (2) have suggested that this impairment may be reversed by transfer factor. We gave 3 U of transfer factor to a patient with anergic chronic pulmonary histoplasmosis and observed transient conversion of his skin test and lymphocyte transformation index (LTI).A 48-year-old man was well until 8 years before admission when he developed cavitary pulmonary tuberculosis. He was treated with isoniazid (INH), para-aminosalicylic acid (PAS), streptomycin,...References1. ALFORDGOODWIN RR: Patterns of immune response in chronic pulmonary histoplasmosis. J Infect Dis 125:269-275, 1970 CrossrefGoogle Scholar2. ALFORDGOODWIN RR: Variation in lymphocyte reactivity to histoplasmosis. Am Rev Resp Dis 108:85-92, 1973 MedlineGoogle Scholar3. GRAYBILLELLENBOGENDROSSMAN JCD: Transfer factor therapy of disseminated histoplasmosis, in press Google Scholar4. GRIFFINJOHNSON DR: Cellular immune response to viral infection: in vitro studies of lymphocytes from mice infected with sindbis virus. Cell Immunol 9:426-434, 1973 CrossrefMedlineGoogle Scholar5. CHAPARASSHEAGRENDEMEO SJA: Correlation of human skin reactivity with lymphocyte transformation induced by mycobacterial antigens and histoplasmin. Am Rev Resp Dis 101:67-73, 1970 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine The Johns Hopkins Medical Institutions 601 North Broadway Baltimore, MD 21205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHistoplasmosisChanges in immunoregulatory lymphocyte populations in patients with histoplasmosisImmune Responses to Fungal Infections 1 June 1976Volume 84, Issue 6Page: 708-709KeywordsHistoplasma capsulatumHistoplasmosisImmune responseInfectious diseasesIsoniazidLymphocytesPeriodic acid SchiffPulmonary diseasesSkin testsStreptomycin Issue Published: 1 June 1976 PDF downloadLoading ...
Giardia: both a harmless commensal and a devastating pathogen
Authors: Herbert L. DuPont
Journal: Journal of Clinical Investigation (2013)

The highly prevalent protozoan Giardia lamblia is an enteropathogen that can be asymptomatic in some individuals, while leading to persistent diarrhea and substantial morbidity in others. In this issue of the JCI, Bartelt et al. describe a mouse model of the disease and investigate the contribution of coincident malnutrition with the development of symptomatic infection. This work in part explains how Giardia infection can lead to growth retardation, and may offer insights that guide future therapeutic strategies.
Manipulating the Immune System with Immune Globulin
Authors: John A. Oates, Alastair J.J. Wood, John M. Dwyer
Journal: New England Journal of Medicine (1992)

ALMOST as soon as a therapeutically useful concentrated immune globulin product became available for intramuscular use, it was obvious that a preparation that could be administered intravenously would be advantageous.1 , 2 However, many years of immunochemical research were required before a concentrated, biologically active, and safe preparation of immune globulin suitable for intravenous use became available. In the past decade, chemists have learned how to prevent protein aggregation while concentrating immune globulin. Purification can be achieved by chromatography, and stabilization of the intact immune globulin is then promoted by acidification with pepsin or the addition of sugars, amino acids, or both. . . .
Email contact between doctor and patient
Authors: B. Pal
Journal: BMJ (1999)

The medical profession has been ahead of business and industry in its use of the telephone, but this is not the case with regard to its modern counterpart—email. However, with the rapid increase in the use of the internet the importance of email and its impact on health care cannot be ignored.

Face to face consultations are currently supplemented by mailed or faxed letters and telephone messages, but much more rapid communication is now available to patients and healthcare professionals via email. Email has many advantages that the others lack. For example, it is a direct means of contact between patients and doctors and is reassuring for the patients to know that the messages will be received. Doctors …
Pargyline, Cheese, and Acute Hypertension
Authors: Frederic S. Glazener, William A. Morgan, John M. Simpson, Paul K. Johnson
Journal: JAMA (1964)

SEVERE hypertensive episodes, sometimes fatal, may occur after the eating of ripened cheeses by patients receiving potent monoamine oxidase (MAO) inhibitors. Most reported cases have been associated with the mood-elevator tranylcypromine sulfate. This is a report of a severe, paradoxical hypertensive crisis occurring in a patient taking the antihypertensive MAO inhibitor, pargyline hydrochloride, apparently precipitated by the ingestion of aged cheddar cheese. <h3>Report of a Case</h3> A 59-year-old white widow, a laboratory technician at night, sought medical assistance at 11 PM on Dec 30, 1963, because of generalized pounding headache, profuse sweating, weakness, tremulousness, and anxiety. She had a long history of hypertension which was first noted in 1947 during routine blood pressure evaluation for a blood donation. From 1947 to 1959 she had no symptoms related to the hypertension and she received no antihypertensive medication. While she was working for a physician in 1959 her blood pressure was found
Generalized Urticaria From Sensitivity to Nifuroxime
Authors: Charles M. Aaronson
Journal: JAMA (1969)

<h3>To the Editor:—</h3> I am reporting what I consider to be a rather unusual case of generalized urticaria caused by sensitivity to nifuroxime, an antifungal agent, which is present in vaginal suppositories containing a nifuroxime and furazolidone mixture (Tricofuron). The patient, a 32-year-old white woman, first complained of a vaginal discharge in February 1968. She had been to her family physician several times without improvement when he prescribed the suppositories. The patient stated that initially she had no complaints from the use of the suppository; but about two weeks after commencing its use, severe itching developed around the vagina. Within another two weeks, generalized urticaria developed which resulted in hospitalization due to the threat of laryngeal edema. After a long, stormy treatment course involving systemic corticosteroids and a variety of antihistamines and tranquilizers, the patient has finally become able to work normally although she occasionally has urticaria. Skin tests with
Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice
Authors: Nader Ghebranious, Stewart Sell
Journal: Hepatology (1998)

The major risk factors for human liver cancer: hepatitis B virus (HBV) related liver injury, male gender, aflatoxin exposure, and p53 expression, are evaluated and compared in experimental transgenic mouse models. Transgenic mice that express hepatitis B surface antigen (HBsAg) in their liver and develop liver tumors at 18 months of age (HBV+ mice) were bred to p53 null mice (p53−/−) to produce mice p53+/−, HBV+ mice. These mice and control litter-mates ([p53+/+, HBV+], [p53+/−, HBV−], and [p53+/+, HBV−]) were divided into groups that did or did not receive an injection of aflatoxin at 1 week of age. At sacrifice at 13 months of age, 100% (7/7) of male mice with each of the three risk factors (p53+/−, HBV+, AFB 1 +) developed high-grade hepatocellular carcinomas (HCC). If any one of the risk factors was absent, the incidence drops: if both p53 alleles are present, 62% (10/16); if HBsAg is not expressed, 14% (1/7); if AFB 1 is not given, 25% (2/8). If only one of the risk factors is present no tumors above grade I are found. Similar results were observed in female mice except that HCC incidence in each group is less than in male mice. Some of the tumors in mice with more than one risk factor are of unusual histological types, such as hepatocholangiocarcinomas, adenocarcinomas and undifferentiated carcinomas that are not usually seen in HBV transgenic C57BL/6 mice. No loss or mutation of the p53 gene is detected in any of the tumors. Possibilities of how the four major risk factors for HCC interact to produce malignant liver tumors in these transgenic mouse models of hepatocarcinogenesis are discussed.
Sympathetic nervous system and pain: A clinical reappraisal
Authors: Helmut Blumberg, Ulrike Hoffmann, Mohsen Mohadjer, Rudolf Scheremet
Journal: Behavioral and Brain Sciences (1997)

The target article discusses various aspects of the relationship between the sympathetic system and pain. To this end, the patients under study are divided into three groups. In the first group, called “reflex sympathetic dystrophy” (RSD), the syndrome can be characterized by a triad of autonomic, motor, and sensory symptoms, which occur in a distally generalized distribution. The pain is typically felt deeply and diffusely, has an orthostatic component, and is suppressed by the ischemia test. Under those circumstances, the pain is likely to respond to sympatholytic interventions. In a second group, called “sympathetically maintained pain” (SMP) syndrome, the principal symptoms are spontaneous pain, which is felt superficially and has no orthostatic component, and allodynia. These symptoms, typically confined to the zone of a lesioned nerve, may also be relieved by sympathetic blocks. Since the characteristics of the pain differ between RSD and SMP, the underlying kind of sympathetic–sensory coupling may also vary between these cases. A very small third group of patients exhibits symptoms of both RSD and SMP. The dependence or independence of pain on sympathetic function reported in most published studies seems to be questionable because the degree of technical success of the block remains uncertain. Therefore, pain should not be reported as sympathetic function independent until the criteria for a complete sympathetic block have been established and satisfied.
All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells
Authors: Ruo-Jing Li, Xue Ying, Yan Zhang, Rui-Jun Ju, Xiao-Xing Wang, Hong-Juan Yao, Ying Men, Wei Tian, Yang Yu, Liang Zhang, Ren-Jie Huang, Wan-Liang Lu
Journal: Journal of Controlled Release (2010)
Combination Analysis of Activator Protein-1 Family Members, Sp1 and an Activator Protein-2α-Related Factor Binding to Different Regions of the Urokinase Receptor Gene in Resected Colorectal Cancers
Authors: Denis Martin Schewe, Tobias Biller, Gabriele Maurer, Irfan A. Asangani, Joerg H. Leupold, Ernst R. Lengyel, Stefan Post, Heike Allgayer
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Studies on the transactivation of genes via promoter elements have mostly been done on cell lines rather than resected tissues. This, however, is essential to address an in vivo or clinical relevance. We have previously shown tumor-specific binding of Sp1 and an activator protein (AP)-2–related factor to promoter region −152/−135 of the metastasis-related u-PAR gene in 60% of in vivo–resected cancer tissues. Cell lines have implicated an additional role, and potential synergism, of an AP-1 region (−190/−171) in u-PAR regulation. This study was done to (a) analyze AP-1 binding to this region in resected tumor and normal tissues, and define subgroups in which it is tumor-specific, and (b) to analyze transcription factor–binding patterns to both promoter motifs in resected tissues, supporting synergism, and draw first prognostic conclusions. Experimental Design: In 103 patients with colorectal cancer, electrophoretic mobility shift assay/supershift analysis for u-PAR promoter region −190/−171 was done in tumors and normal tissues. In 71 patients, region −152/−135 was also analyzed. U-PAR protein was measured by ELISA. Results: Tumor-specific AP-1 binding to region −190/−171 of the u-PAR promoter was found in 40% of patients. Subgroup analysis showed tumor-specific binding for c-Fos in 58%, for c-Jun in 50%, for JunD in 39%, and for Fra-1 in 4% of cases. AP-1 binding correlated significantly with u-PAR protein amounts in both normal and tumor tissues (P &amp;lt; 0.001), in contrast to a tumor-specific correlation with u-PAR of the AP-2/Sp1 region. In analyses for both promoter regions, 62% of cancers showed simultaneous binding for AP-1, AP-2, and Sp1, 11% for AP-1 and AP-2, 16% for AP-2 and Sp1, 4% for AP-2 only, 3% for AP-1 only, and 0% for Sp1 only. The binding of AP-1, AP-2, and Sp1 correlated significantly with each other (P &amp;lt; 0.001), the combination of AP-1 and AP-2 showing the highest correlation with u-PAR (P = 0.008). Preliminary survival analysis indicated a trend for poorer prognosis for binding of all three transcription factors. Conclusion: This is the first study differentiating transcription factor–binding to two important u-PAR promoter regions in a large series of resected tumors and normal tissues. The AP-1 site seems to be a less tumor-specific regulator than the Sp1/AP-2 motif. Nevertheless, data corroborate the hypothesis of synergism between both elements in resected tumors.