tbuckley/cabot-search huggingface dataset:
Human immunoglobulin (IgG) induced deletion of IgM rheumatoid factor B cells in transgenic mice.
Authors: H Tighe, P Heaphy, S Baird, W O Weigle, D A Carson
Journal: The Journal of Experimental Medicine (1995)

The singular ability of immunoglobulin genes to hypermutate their variable regions, while permitting the generation of high-affinity antibodies against foreign antigens, poses a problem in terms of maintenance of immunological self-tolerance. Immunoglobulin gene hypermutation driven by a foreign antigen has the potential to generate antibodies that cross-react with self-components. Consequently, there must exist a mechanism in the periphery for inactivation of mature autoreactive B cell clones. The classical experimental system used to address this problem is the induction of tolerance to soluble, deaggregated human IgG. We have analyzed the mechanism of induction of tolerance to human IgG using transgenic mice that express a human IgM rheumatoid factor (IgM RF) on a large proportion of their B cells. Injection of deaggregated human IgG caused a specific deletion of those B cells that express an intact IgM RF on their cell surface. The degree of RF B cell deletion was proportional to the reduction in the proliferative response of splenocytes to antigen (aggregated human IgG), or to F(ab')2 fragments of anti-human IgM antibodies. Control experiments showed that IgG administration had little effect on the numbers of mouse Ig-bearing cells or their ability to proliferate to a nonspecific mitogen. Thus, the effects of IgG on the human IgM RF B cell are antigen specific and are not due to nonspecific toxic effects of the human IgG preparation. These experiments demonstrate that peripheral exposure to IgG induces deletion of reactive B cells, without any evidence for anergy, and differ from data obtained by other investigators studying tolerance to soluble protein antigens. The results imply that human Igs have distinct properties as soluble antigens, and that peripheral nonresponsiveness to IgG may be due to lymphocyte deletion.
Azaribine for Psoriasis
Authors: H. RAŠKOVÁ
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 August 1971Azaribine for PsoriasisH. RAŠKOVÁ, J. ELISH. RAŠKOVÁSearch for more papers by this author, J. ELISSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-2-322 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with great interest the paper of W. R. Vogler and S. Olansky, "A Double-blind Study of Azaribine in the Treatment of Psoriasis," Ann Intern Med, 73:951-956, 1970. The results agree with our older double-blind study. Because European authors are less known in the United States we would like to comment briefly on some earlier publications relevant to the paper but not cited.1. After the publication of Turner and Calabresi a double-blind study was performed that confirmed the therapeutic effects of azaribine in psoriasis (1, 2).2. Vogler and Olansky reported in their study one...References1. RAŠKOVÁELISGUTOVÁ HJM: A new indication for 6-azauridine triacetate—psoriasis. Cas Lek Cesk 106:870-873, 1967 MedlineGoogle Scholar2. SLAVÍKELISRAŠKOVÁ MJH: Therapeutic effects of 6-azauridine triacetate in psoriasis. Pharmacologia Clinica 2:120-125, 1970 CrossrefGoogle Scholar3. ELISSLAVÍKRAŠKOVÁ JMH: Side effects of 6-azauridine triacetate in rheumatoid arthritis. Clin Pharmacol Ther 11:404-407, 1970 CrossrefMedlineGoogle Scholar4. ELISRAŠKOVÁ JH: Controlled clinical trial with new cytostatic preparations produced in Czechoslovakia. Rev Czech Med 12:9-19, 1966 MedlineGoogle Scholar5. RAŠKOVÁELIS HJ: Ein kontrollierter klinischer Versuch mit 6-azauracil riboside, einem neuen Cytostaticum. Proceedings IInd Conferentia therapeutica Hungarica, Hungarian Academic Press, 1963, p. 319-323 Google Scholar6. RAŠKOVÁELIS HJ: Kontrollierte therapeutische Versuche ein Mittel zur Bekämpfung von unrationeller Therapie. Proceedings IVth International Congress of the International Federation for Hygiene and Preventive Medicine, Vienna, 1965, pp. 301-308 Google Scholar7. ZÁRUBAKŮTAELIS FAJ: Treatment of mycosis fungoides with 6-azauracil riboside. Lancet 1:275, 1963 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Institute of Pharmacology Czechoslovak Academy of Sciences Prague Czechoslovakia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHodgkin Lymphoma of the Hepatobiliary TractHodgkin Lymphoma of the Hepatobiliary TractHepatic Hodgkin's disease without involvement of the spleen 1 August 1971Volume 75, Issue 2Page: 322-323KeywordsPsoriasis Issue Published: 1 August 1971 PDF DownloadLoading ...
Expansion of highly differentiated CD8+ T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation
Authors: A Kreutzman, K Ladell, C Koechel, E Gostick, M Ekblom, L Stenke, T Melo, H Einsele, K Porkka, D A Price, S Mustjoki, R Seggewiss
Journal: Leukemia (2011)
Spontaneous Remission in Pernicious Anemia
Authors: Kouichi R. Tanaka, George O. Clifford
Journal: New England Journal of Medicine (1958)

ONCE Addison's pernicious anemia has developed it is usually considered that therapy is necessary for the remainder of the patient's life. Since the absorption of vitamin B12 is apparently dependent upon adequate amounts of intrinsic factor, current concepts imply that intrinsic-factor activity must be reduced below a critical level for a considerable period, usually three to five years, before body stores of vitamin B12 are exhausted and Addison's pernicious anemia develops. This deficiency in intrinsic-factor activity, once it has occurred, is generally considered to persist throughout life. Although this is undoubtedly true of most of the patients in . . .
Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects
Authors: L Bankir
Journal: Cardiovascular Research (2001)

(1) Vasopressin (VP), or antidiuretic hormone, is secreted in response to either increases in plasma osmolality (very sensitive stimulus) or to decreases in plasma volume (less sensitive stimulus). Its normal plasma level is very low (about 1 pg/ml, i.e. 10−12 M), close to the detection limit of present immunoassays, and distinct antidiuretic effects are observed after infusion of small undetectable amounts of VP. (2) This antidiuretic action results from three main effects of VP on principal cells of the collecting duct (CD) mediated by occupancy of peritubular V2 receptors. (i) Increase in water permeability along the entire CD (via AQP2). (ii) Increase in urea permeability in only the terminal inner medullary CD (via UT-A1). (iii) Stimulation of sodium reabsorption, mainly in the cortical and outer medullary CD (via ENaC). VP also acts on medullary vasculature (V1a receptors) to reduce blood flow to inner medulla without affecting blood flow to outer medulla. Besides these actions, all concurring to increase urine osmolality in different and additive ways, other VP effects, probably exerted through V1a receptors located on luminal membrane, tend to limit the antidiuretic effects of the hormone. They induce the formation of prostaglandins which reduce V2-dependent cAMP accumulation in these cells and thus partially inhibit all three V2 effects. (3) Because urine is first diluted along the nephron before being concentrated in the medulla, VP is required, not only for urine concentration, but first for re-equilibration of tubular fluid osmolality with plasma osmolality, a step taking place in the renal cortex, and achieved through the reabsorption of large quantities of water (more than what is subsequently reabsorbed in the medulla to concentrate urine). Accordingly, VP effects on urine flow-rate are not linear. Small changes in plasma VP in the low range of urine osmolality will induce wide changes in urinary flow-rate, whereas in the upper range of urine osmolality larger changes in plasma VP induce much more limited further reduction in urine flow-rate. (4) Most likely, the different effects of VP require different levels of VP concentration to occur and are thus recruited successively with progressive rise in VP secretion.
Mycotic Aneurysm of Brachial Artery A Complication of Retrograde Catheterization
Authors: Behrooz Eshaghy
Journal: JAMA (1974)

CARDIAC catheterization has been associated with numerous and diverse complications.<sup>1</sup>We have recently seen a patient who developed a mycotic aneurysm, a rare entity in itself, at the site of brachial arteriotomy for catheterization of the left side of the heart. <h3>Report of a Case</h3> A 29-year-old white woman had a right antecubital artery cutdown for cardiac catheterization, which confirmed the presence of mild to moderate aortic stenosis and insufficiency. The arteriotomy was repaired, and at the time of hospital discharge, the radial pulse rate was normal and there was no swelling or bleeding at the cutdown site. Nine days after catheterization, pain, swelling, and bloody drainage from the cutdown site occurred. The swelling was thought to be a hematoma, for which the patient was given an analgesic and sent home. She returned the following day with the same complaint. The wound was explored and found to be clean
How to apply for charitable status.
Authors: M. Slevin, P. Ryan
Journal: BMJ (1989)

Child with hepatosplenomegaly, delayed development, and deafness due to intrauterine cytomegalovirus infection.Herpes simplex infection in the newborn infant is generally acquired at the time of birth, but infection early in pregnancy is probably associated with an increased risk of abortion, late fetal death, prematurity, and structural abnormalities of the central nervous system.Maternal varicella infection may also affect the fetus, causing abnormalities of the central nervous system and cutaneous scars.The risk of a fetus being affected by varicella infection is not known but is probably less than 10%, with a critical period during the third and fourth months of pregnancy.Affected infants seem to have a high perinatal mortality rate.
Ultrastructural features of alveolitis in sarcoidosis.
Authors: T Takemura, Y Hiraga, M Oomichi, M Oritsu, O Akiyama, Y Matsui, Y Eishi, R Mikami
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Seventy-nine specimens of lung parenchyma from 61 patients with sarcoidosis were examined ultrastructurally with a focus on alveolitis, and they were compared with specimens of hypersensitivity pneumonitis (HP) and the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF). Lymphocytes and monocytes were frequently observed in the capillary lumina, and these cells and macrophages were found in the interstitium of the alveolar walls in the specimens with alveolitis of sarcoidosis and HP. Increases in the percentage of lymphocytes in BALF correlated with the degree of alveolitis. Swelling and bleb formation of the endothelium of alveolar capillaries and changes in the capillary basement membrane were commonly found and were significantly increased in the specimens with alveolitis. The frequency of bleb formation was significantly higher in alveolitis of sarcoidosis than in that of HP. However, the changes in alveolar epithelium were not significant in sarcoidosis. Microvascular changes in alveolitis are not specific for sarcoidosis, but they are observed in other interstitial lung diseases. These alterations may play an important role in the development of pulmonary sarcoidosis.
Glucose and fructose absorption in idiopathic steatorrhoea.
Authors: C D Holdsworth, A M Dawson
Journal: Gut (1965)

<h3></h3> We present a fatal case of fulminant type 1 diabetes mellitus that was initially diagnosed as upper respiratory tract infection based on pharyngeal redness at a clinic. However, the patient then went into cardiopulmonary arrest, and was transferred to our hospital for treatment. Testing revealed very high levels of blood glucose (86.9 mmol/l), urinary glucose (2+) and ketones (4+). His glycosylated haemoglobin level was almost normal (6.2%; normal &lt;6.2%). Autopsy revealed marked depletion and atrophy of the islets of Langerhans.
Post‐transplant outcomes of induction therapy for myeloma: Thalidomide and dexamethasone versus doxorubicin, vincristine, and dexamethasone prior to high‐dose melphalan with autologous stem cell support
Authors: Dan T. Vogl, Stephen V. Liu, Elise A. Chong, Selina M. Luger, David L. Porter, Stephen J. Schuster, Donald E. Tsai, Alexander Perl, Alison W. Loren, Steven C. Goldstein, Sunita D. Nasta, Charalambos Andreadis, Patricia A. Mangan, Kimberly Hummel, Don L. Siegel, Eli Glatstein, Edward A. Stadtmauer
Journal: American Journal of Hematology (2007)

High-dose melphalan with autologous stem cell support improves survival as part of initial therapy for myeloma. Previous studies of pre-transplant induction regimens have compared paraprotein response rates but not long-term outcomes after transplant. We reviewed the records of all patients with multiple myeloma who received an autologous stem cell transplant at the University of Pennsylvania Medical Center. We compared outcomes for 69 patients who received high-dose melphalan conditioning after January 1, 2003 as part of initial therapy for myeloma, including 41 patients who received anthracycline-based induction (VAD or DVD) and 28 patients who received thalidomide and dexamethasone induction. Baseline characteristics in these two groups were not different, though potentially clinically important differences were apparent in assignment to post-transplant consolidation and maintenance therapy. Despite similar response rates during induction therapy, thalidomide and dexamethasone induction was associated with better progression-free survival (hazard ratio 0.18, P = 0.011) after transplant. This effect persisted in multivariable regression models including baseline characteristics and post-transplant treatment. Overall survival was not different between the two groups. These results suggest that the use of thalidomide during induction therapy may lead to improved long-term outcomes after transplant. Future trials comparing induction therapies should examine progression-free and overall survival after transplant to confirm this benefit.
Abstract B35: Activation of Putative Compensatory Pathways upon Deletion of <i>Erbb3</i> in Mutant <i>EGFR</i>-driven Lung Cancer
Authors: Xiaoling Song, Pang-Dian Fan, Udayan Guha, David Threadgill, Harold Varmus, Katerina Politi
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer-related death in the USA and worldwide. Mutant epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer represents 15% of lung adenocarcinomas. Tumors bearing EGFR mutations are sensitive to treatment with specific tyrosine kinase inhibitors (TKIs) and show radiographic responses in about 70% of cases. However, it is not known why the remaining 30% of the tumors do not respond to these drugs, and patients who initially respond to TKI treatment eventually develop drug resistance on average within a year. These facts underscore the need for a better understanding of the molecular mechanisms that underlie transformation of the lung epithelium by mutant EGFR. Mutant EGFR-induced signaling is initiated by the formation of EGFR homodimers or heterodimers with other members of the EGFR family (ERBB2, ERBB3 or ERBB4). To investigate the role of EGFR family members in the tumorigenic process driven by mutant EGFR, we used a tetracycline-inducible transgenic model to test the requirement for Erbb3 in mutant EGFR-induced lung tumorigenesis. In this model, deletion of Erbb3 had no effect on tumorigenesis induced by mutant EGFR, suggesting that it is not required to initiate tumorigenesis. Tumors that develop in the absence of Erbb3 remain sensitive to TKIs. Analysis of the biochemical consequences of Erbb3 deletion revealed increased levels of phosphorylation of EGFR and Erbb2 in tumors arising in the absence of Erbb3. Moreover, these tumors show increased activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Together these data suggest that recruitment of compensatory pathways may overcome the need for Erbb3 in tumorigenesis driven by mutant EGFR. Further experiments to test this are ongoing. Knowledge of the role EGFR heterodimerization partners play in mutant EGFR-driven lung cancer can help guide the selection of which EGFR family members to target in the treatment of this disease.
Consultants challenge Clarke
Authors: H. Keen
Journal: BMJ (1989)

Finally, we believe that the patient's interests are best served by having operations performed by surgeons who are suitably experienced in the particular disorder and operation concerned: their official specialty is secondary and the surgeon best satisfying these criteria currently varies from region to region.It is noteworthy that, although in the United Kingdom no specialist qualification in head and neck surgery exists, the FRCS (Otolaryngology) emphasises the subject more than its general counterpart.
Replacing the Enzyme α- <scp>l</scp> -Iduronidase at Birth Ameliorates Symptoms in the Brain and Periphery of Dogs with Mucopolysaccharidosis Type I
Authors: Ashley D. Dierenfeld, Michael F. McEntee, Carole A. Vogler, Charles H. Vite, Agnes H. Chen, Merry Passage, Steven Le, Sahil Shah, Jackie K. Jens, Elizabeth M. Snella, Karen L. Kline, Jennifer D. Parkes, Wendy A. Ware, Lori E. Moran, Amanda J. Fales-Williams, Jane A. Wengert, R. David Whitley, Daniel M. Betts, Amy M. Boal, Elizabeth A. Riedesel, William Gross, N. Matthew Ellinwood, Patricia I. Dickson
Journal: Science Translational Medicine (2010)

Replacing the enzyme α- l -iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I.
Normal growth and development of the trachea.
Authors: M P Wailoo, J L Emery
Journal: Thorax (1982)

A quantitative study of the trachea has been made in 452 children with apparently normal tracheas ranging from 28 weeks9 gestation to 14 years. In the neonatal period the trachea is funnel shaped with the upper end wider than the lower end. It becomes cylindrical with increasing age. The ratio of cartilage to muscle remains constant throughout childhood. The trachea appears to grow at a greater rate, in relation to crown-rump length, during the age of 1 month to 4 years than in utero or around puberty. Normal measurements for formalin-fixed tracheas related to crown-rump length are presented.
Transgenic approaches for modifying the mammary gland to produce therapeutic proteins.
Authors: D Romagnolo, R P DiAugustine
Journal: Environmental Health Perspectives (1994)

Bioengineering of the mammary gland to produce proteins of therapeutic and industrial value is the result of extensive investigation of the physiology of the mammary gland and the ability to generate transgenic animals. Targeting the expression of heterologous proteins to mammary tissue requires a thorough understanding of the biochemical events that coordinate growth and differentiation of the mammary gland and of the hormonal and developmental regulation of expression of milk protein genes. The characterization of mammary-specific promoter regions in milk protein genes and knowledge of the mechanisms that confer integration site-independent expression of transgenes have significantly contributed to modifying the mammary gland to produce heterologous proteins of therapeutic interest. The generation of large transgenic farm animals provides the opportunity for large-scale production of proteins in milk that have a therapeutic value but are naturally present at low concentrations in biological fluids. Transgenic mammary epithelial cells offer a versatile research model in biomedical, environmental health, and neonatal toxicology research.
Toward a triarchic theory of human intelligence
Authors: Robert J. Sternberg
Journal: Behavioral and Brain Sciences (1984)

Abstract This article is a synopsis of a triarchic theory of human intelligence. The theory comprises three subtheories: a contextual subtheory, which relates intelligence to the external world of the individual; a componential subtheory, which relates intelligence to the individual's internal world; and a two-facet subtheory, which relates intelligence to both the external and internal worlds. The contextual subtheory defines intelligent behavior in terms of purposive adaptation to, shaping of, and selection of real-world environments relevant to one's life. The normal course of intelligent functioning in the everyday world entails adaptation to the environment; when the environment does not fit one's values, aptitudes, or interests, one may attempt to shape the environment so as to achieve a better person-environment fit; when shaping fails, an attempt may be made to select a new environment that provides a better fit. The two-facet subtheory further constrains this definition by regarding as most relevant to the demonstration of intelligence contextually intelligent behavior that involves either adaptation to novelty, automatization of information processing, or both. Efficacious automatization of processing allows allocation of additional resources to the processing of novelty in the environment; conversely, efficacious adaptation to novelty allows automatization to occur earlier in one's experience with new tasks and situations. The componential subtheory specifies the mental mechanisms responsible for the learning, planning, execution, and evaluation of intelligent behavior. Metacomponents of intelligence control one's information processing and enable one to monitor and later evaluate it; performance components execute the plans constructed by the metacomponents; knowledge-acquisition components selectively encode and combine new information and selectively compare new information to old so as to allow new information to be learned.
Short-term Certification
Authors: M. A. Gilbert
Journal: BMJ (1966)

<h3>Abstract</h3> Graph-based reference genomes have become popular as they allow read mapping and follow-up analyses in settings where the exact haplotypes underlying a high-throughput sequencing experiment are not precisely known. Two recent papers show that mapping to graph-based reference genomes can improve accuracy as compared to methods using linear references. Both of these methods index the sequences for most paths up to a certain length in the graph in order to enable direct mapping of reads containing common variants. However, the combinatorial explosion of possible paths through nearby variants also leads to a huge search space and an increased chance of false positive alignments to highly variable regions. We here assess two prominent graph-based read mappers against a novel hybrid baseline approach that combines an initial path determination with a tuned linear read mapping method. We show, using a previously proposed benchmark, that this simple approach is able to improve accuracy of read-mapping to graph-based reference genomes. Our method is implemented in a tool, Two-step Graph Mapper, which is available at https://github.com/uio-bmi/two_step_graph_mapper along with data and scripts for reproducing the experiments.
Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin
Authors: Etgar Levy-Nissenbaum, Regina C Betz, Moshe Frydman, Michel Simon, Hadas Lahat, Tengiz Bakhan, Boleslaw Goldman, Anette Bygum, Monika Pierick, Axel M Hillmer, Nathalie Jonca, Jaime Toribio, Roland Kruse, Georg Dewald, Sven Cichon, Christian Kubisch, Marina Guerrin, Guy Serre, Markus M Nöthen, Elon Pras
Journal: Nature Genetics (2003)
The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses
Authors: Mir Munir A. Rahim, Peter Chen, Amelia N. Mottashed, Ahmad Bakur Mahmoud, Midhun J. Thomas, Qinzhang Zhu, Colin G. Brooks, Vicky Kartsogiannis, Matthew T. Gillespie, James R. Carlyle, Andrew P. Makrigiannis
Journal: Blood (2015)