tbuckley/cabot-search huggingface dataset:
Abstract BL-1: Brinker Award Lecture: How Does HER2 Contribute to Breast Cancer Progression?
Authors: Y Yarden
Journal: Cancer Research (2012)

Abstract HER2 (also called NEU and ERBB2), a receptor tyrosine kinase frequently overexpressed in breast cancer, is one of the most oncogenic kinases of the human kinome. Multiple mechanisms contribute to the transforming potential of HER2. Although HER2 is structurally similar to the receptors for EGF (EGFR) and neuregulins (ERBB3 and ERBB4), the cytoplasm-facing kinase domain of HER2 is characterized by relatively high basal activity, and unlike the ectodomains of EGFR and ERBB3/ERBB4, HER2?s extracellular part cannot bind any known growth factor with high affinity. Nevertheless, HER2 acts as the preferred partner of the other three receptors, and the heterodimers it forms display not only high kinase activity but also increased binding affinity toward a broad spectrum of growth factors. In addition, HER2-containing heterodimers typically interact with a relatively wide set of cytoplasmic effector proteins, such as the phosphoinositol 3-kinase and SHC, which recruits the mitogen-activated protein kinase pathway. The collective outcome of these functional features translates to prolonged and enhanced signaling capacity. One way to comprehend HER2 is offered by the evolutionary history of the family of receptor tyrosine kinases. Accordingly, HER2 and EGFR share a common precursor, but genome duplications denied a growth factor from HER2, and in parallel inactivated the catalytic function of ERBB3, to achieve a layered signaling network, whose autonomy and steady state are maintained by a dense web of feedback regulatory loops. In line with this scenario, HER2 cannot signal in isolation, but requires an activating growth factor receptor. Once recruited, HER2 enables evasion of negative feedback regulation, such as receptor ubiquitination and intracellular degradation: Unlike homodimers of EGFRs, which are targeted to lysosomes for degradation, HER2-containing heterodimers are targeted to a recycling pathway that replenishes the surface pool of HER2 molecules and further prolongs signaling. In-depth understanding of HER2?s oncogenic functions holds promise for therapy of a fraction of breast cancer patients. For example, the relatively high basal activation of the kinase domain means that HER2 relies on a chaperone called HSP90, hence blocking HSP90 might retard HER2-overexpressing tumors. Likewise, it is predictable that agents able to block either recycling of HER2 or its ability to form heterodimers, would curtail tumor growth. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr BL-1.
Selective Therapeutic Targeting of the Anaplastic Lymphoma Kinase With Liposomal siRNA Induces Apoptosis and Inhibits Angiogenesis in Neuroblastoma
Authors: Daniela Di Paolo, Chiara Ambrogio, Fabio Pastorino, Chiara Brignole, Cinzia Martinengo, Roberta Carosio, Monica Loi, Gabriella Pagnan, Laura Emionite, Michele Cilli, Domenico Ribatti, Theresa M Allen, Roberto Chiarle, Mirco Ponzoni, Patrizia Perri
Journal: Molecular Therapy (2011)

The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is involved in the pathogenesis of different types of human cancers, including neuroblastoma (NB). In NB, ALK overexpression, or point mutations, are associated with poor prognosis and advanced stage disease. Inhibition of ALK kinase activity by small-molecule inhibitors in lung cancers carrying ALK translocations has shown therapeutic potential. However, secondary mutations may occur that, generate tumor resistance to ALK inhibitors. To overcome resistance to ALK inhibitors in NB, we adopted an alternative RNA interference (RNAi)-based therapeutic strategy that is able to knockdown ALK, regardless of its genetic status [mutated, amplified, wild-type (WT)]. NB cell lines, transduced by lentiviral short hairpin RNA (shRNA), showed reduced proliferation and increased apoptosis when ALK was knocked down. In mice, a nanodelivery system for ALK-specific small interfering RNA (siRNA), based on the conjugation of antibodies directed against the NB-selective marker GD(2) to liposomes, showed strong ALK knockdown in vivo in NB cells, which resulted in cell growth arrest, apoptosis, and prolonged survival. ALK knockdown was associated with marked reductions in vascular endothelial growth factor (VEGF) secretion, blood vessel density, and matrix metalloproteinases (MMPs) expression in vivo, suggesting a role for ALK in NB-induced neoangiogenesis and tumor invasion, confirming this gene as a fundamental oncogene in NB.
Spontaneous loss and alteration of antigen receptor expression in mature CD4+ T cells.
Authors: S Kyoizumi, M Akiyama, Y Hirai, Y Kusunoki, K Tanabe, S Umeki
Journal: The Journal of Experimental Medicine (1990)

The TCR/CD3 complex plays a central role in antigen recognition and activation of mature T cells, and, therefore, abnormalities in the expression of the complex should induce unresponsiveness of T cells to antigen stimulus. Using flow cytometry, we detected and enumerated variant cells with loss or alteration of the surface TCR/CD3 expression among human mature CD4+ T cells. The presence of variant CD4+ T cells was demonstrated by isolating and cloning them from peripheral blood, and their abnormalities can be accounted for by alterations in TCR expression such as defects of protein expression and partial protein deletion. The variant frequency in peripheral blood increased with aging in normal donors and was highly elevated in patients with ataxia telangiectasia, an autosomal recessive inherited disease with defective DNA repair and variable T cell immunodeficiency. These findings suggest that such alterations in TCR expression are induced by somatic mutagenesis of TCR genes and can be important factors related to age-dependent and genetic disease-associated T cell dysfunction.
DEPRESSION IN THE PSYCHOSES OF MEMBERS OF RELIGIOUS COMMUNITIES OF WOMEN
Authors: M. WILLIAM KELLEY
Journal: American Journal of Psychiatry (1961)

This report is not intended to suggest that psychotic religious, or religious in general, are more depressed than other occupational or social classes, but to outline some possible reasons, specific to their life, why those who are depressed become so. Great stress is laid in religious life on hard work, high productivity, and "success" in the strictly religious and spiritual aspects of conventual life as well as in the "active" or professional works which they undertake. (The traits of the "American character" are quite faithfully mirrored in American religious communities.) In addition to these cultural influences, certain immature or poorly instructed religious are plagued by the suspicion that every failure is a sin, and for this reason their mental disturbances themselves become a circularly reinforcing cause of depression. The early onset and lengthy course of their disabling disorders, and the high rate of recurrence, further intensify their depression. Considering the carefully structured character of religious life, it would seem that more careful selection among those who apply for permission to undertake the life, joined with precise and accurate moral and psychological instruction of those admitted could do much to reduce appreciably the abnormally depressed states among religious.
NC-07 * CORRELATION OF MR SPECTROSCOPY IMAGE OF HIPPOCAMPUS REGION AND IMPAIRMENT OF NEUROCOGNITIVE FUNCTIONS IN PATIENTS AFTER WHOLE BRAIN RADIOTHERAPY - PRELIMINARY DATA
Authors: R. Jancalek, P. Pospisil, M. Bulik, M. Dobiaskova, T. Kazda, P. Slampa
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain metastases are considered one of the most serious complications of oncological illness. Although their optimal treatment remains still controversial, palliative whole brain radiotherapy (WBRT) is indicated in many patients because of numerous brain metastases, poor performance status or unmanageable extracranial illness. However, radiation of the hippocampus is supposed to development of late undesirable effects resulting in neurocognitive function (NCF) impairment with negative impact on quality of life in long-surviving patients. The aim of the project is to assess a correlation between neuronal depletion in the hippocampus measured by MR spectroscopy and relevant NCF alterations in patients after WBRT. METHODS: Patients with estimated longer survival based on standard prognostic indexes who were indicated for WBRT underwent MRI, MR spectroscopy focused on concentration of N-acetylaspartate (a neuronal marker), and quantitative psychological tests of the relevant mnestic functions. All the exams were then repeated 4 months after the WBRT and compared with the pre-radiotherapy results. Patients with brain metastases located in the hippocampal region and affecting the NCF by themselves were excluded form the study. RESULTS: Our preliminary data show alteration of the NCF after 4 months from radiotherapy accompanied by N-acetylaspartate concentration decline in the hippocampus reflecting a depletion of the neuronal pool. CONCLUSIONS: Our results support introduction of hippocampus-sparing radiotherapeutic methods in pursuit of minimalizing the side effects and improvement the quality of life. The project is supported by grants IGA MZCR NT/14120 and NT/14600 and the European Regional Development Fund Project FNUSA-IC RC (No. CZ.1.05/1.1.00/02.0123).
Clinical Endocrinology: Theory and Practice
Authors: Frederick G. Berlinger
Journal: JAMA (1977)

This new English translation of the second (1971) German edition of<i>Clinical Endocrinology</i>is a well-written, lengthy textbook that in nearly 1,100 pages attempts to cover the entire field of clinical endocrinology. Probably thestrongest point of this book, as Dr George W. Thorn points out in his introduction, is the emphasis on basic science at the beginning of each chapter. Most chapters start with a brief historical outline concerning the organ system involved, followed by concise but complete outlines of the embryology, gross anatomy, histology, chemistry, biochemistry, and physiology of the various endocrine organs and their secretions. These introductory sections are then followed by classical descriptions of the pathophysiological states that can be encountered. The emphasis on basic science makes this a most useful textbook of the practicing clinician as well as the advanced medical student and the resident physician. <i>Clinical Endocrinology</i>is written primarily for the practicing "generalist." The
SOME FACTORS INFLUENCING RESPONSE OF CANCER TO RADIATION
Authors: CONSTANCE A. P. WOOD
Journal: JAMA (1949)

During the past two decades great advances have been made in the treatment of cancer by radiation. These advances are largely the result of physical researches.  In Great Britain, the greatest importance has been attached to the close collaboration of radiotherapist and physicist. In all radiotherapy centers this partnership has for many years been regarded as essential to the efficient carrying out of the patient's treatment. Much time has been devoted to the establishment of methods of accurate dosage measurement for all types of radiation therapy, whether it be external irradiation from a roentgen or radium beam or local irradiation by radium needling or applicators. Whichever of these types of treatment is used, the dose delivered to the tumor is recorded in roentgens in the tissues at the site of the disease. These methods of accurate dosage measurement have done much toward placing the radiation treatment of cancer on a
How electronic communication is changing health care: Barriers to online learning networks need to be overcome
Authors: John E Sandars, Michele Langlois
Journal: BMJ (2004)

How electronic communication is changing health care Usability is main barrier to effective electronic information systemsEditor-Jadad and Delamothe celebrate "the return of the human" to health informatics in their editorial asking what's next for electronic communication and health care. 1 The question is not whether we need to merge human centred and technology centred approaches: the question is how to do it.If electronic resources are to improve health they have to be accessible, reliable, and usable.More than 80% of websites are currently not accessible by all, including most primary care trust and healthcare charity sites. 2 And according to our unpublished in-house survey, few electronic resources are subject to the rigour we would expect of reliable, evidence based publications, and many of the high quality resources that exist are prohibitively difficult to use in everyday practice.Usability concerns whether an information system is structured so that users can get an answer to fit their purpose.The solution to this problem is user centred design. 3So why isn't it happening in health care?In spite of considerable evidence that user centred design results in cost savings downstream, and a clear need to assess the usability of information systems, 4 the perception remains that it is too expensive.A good first step is the creation of effective, free tools that help us assess the usability of electronic resources quickly, such as our LIDA tool (www.minervation.com/downloads.html).These are needed to show where the problems are in resources that already exist.Once the usability problem has been identified and defined and both users and commissioners have been educated to expect better from information technology systems, momentum will be gathered towards genuinely high quality electronic information systems.
Penicillin Allergy: Clinical and Immunologic Aspects
Authors: Joseph E. Johnson
Journal: JAMA (1970)

Penicillin remains in many ways the ideal antibiotic. The drug is bacteriocidal, and toxicity is quite low at therapeutically effective levels. However, allergic reactions have presented serious problems which were not altogether circumvented by the development of a series of new penicillins and related agents such as the cephalosporins.  Mechanisms of drug allergy remained for the most part poorly understood until the last ten years beginning with the investigations of Eisen, Parker, Levine, de Weck, and others. In this brief decade penicillin allergy has become one of the best understood forms of allergy.   Penicillin Allergy: Clinical and Immunologic Aspects is an excellent summary of the state of knowledge about this important and intriguing subject. Drawing on 13 additional contributors, all of whom have been actively involved in investigations in the area, the editors have dealt effectively with clinical complications, experimental techniques, and the immunochemical basis for the various features of
Cosmetic and reconstructive surgery of the breast.
Authors: C M Ward
Journal: BMJ (1985)

Breasts come in different shapes, sizes, and degrees of symmetry and lost common breast deformities continue to change in the wake ofpregnancy, fluctuations in body which surgery is sought weight, aging, and breast disease.Women react in different ways to natural or pathological variations in breast form, and, though some may Breast hypertrophy accept the deformity and scarring that follow radical mastectomy and B radiotherapy for carcinoma of the breast, others will be unable to tolerate Breast hypoptosia M minor loss of breast shape and bulk after pregnancy and seek restoration. Breast asymmetryGiven that restorative and reconstructive surgery of the breast is objectivelyBreast ptosis not essential it can sometimes be difficult for a medical practitioner to l Ptscmdsympathise with the motivation ofa woman requesting surgery.ExperiencePostmostectomy deformity 0 and sound psychological evaluation have, however, shown that plastic and
Epidemiology of Skin Diseases in Africa.
Authors: James Marshall
Journal: British Journal of Dermatology (1962)

Journal Article Epidemiology of Skin Diseases in Africa. Get access James Marshall James Marshall The Department of Dermatology, University of Stellenbosch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 4, 1 April 1962, Page 158, https://doi.org/10.1111/j.1365-2133.1962.tb13481.x Published: 01 April 1962
Nutrition, Immunity, and Infection: Mechanisms of Interactions
Authors: Harry F. Dowling
Journal: JAMA (1978)

For many years evidence has been accumulating to indicate that under certain circumstances, the nutritional state of the host can considerably affect the outcome of an infection. Similarly, the nutritional state can affect the immune response. The current interest in nutrition and immunity makes this a good time to take a fresh look at the interrelationships of these subjects. The authors have "attempted to summarize and analyze critically the reported information, to bring out the controversies, and to point out the lacunae where further data are required." They have accomplished three of these purposes well, but they have done little critical summarizing, probably because so many "lacunae" often render evaluation impossible. Fortunately, the authors have not tried to force a conclusion where no valid deduction can be made. If anything, they lean in the other direction, leaving most of the problems to be settled by further research, and in this
Multiple Nodules of the Small Bowel
Authors: Bruce J. Haskin
Journal: JAMA (1967)

Dr. Bruce J. Haskin: This is the third Massachusetts General Hospital admission of a 45-year-old white man who was admitted because of gastrointestinal bleeding. For one month he had noted progressive fatigue, weakness, pallor, and light-headedness. The hematocrit reading was 27 and the guaiac test on the stool was strongly positive. <h3>Discussion</h3> Dr. Stanley M. Wyman: What is your opinion of this case, Dr. Bohrer? Dr. Stanley P. Bohrer: There is an obvious rounded defect in the fourth portion of the duodenum (Fig 1). The mucosal pattern adjacent to it looks fairly normal and is probably intact. I see nothing which suggests stretching or erosion of the mucosa. I am trying to decide whether it is an extramucosal defect or an intraluminal mass. I think I would favor the latter. There are some areas farther down in the bowel (Fig 2) which have a somewhat similar appearance, but I would
hTERT-Immortalized Prostate Epithelial and Stromal-Derived Cells: an Authentic <i>In vitro</i> Model for Differentiation and Carcinogenesis
Authors: Ira Kogan, Naomi Goldfinger, Michael Milyavsky, Merav Cohen, Igor Shats, Gabriele Dobler, Helmut Klocker, Bohdan Wasylyk, Maureen Voller, Tilly Aalders, Jack A. Schalken, Moshe Oren, Varda Rotter
Journal: Cancer Research (2006)

Abstract Prostate cancer is the most commonly diagnosed type of cancer in men, and there is no available cure for patients with advanced disease. In vitro model systems are urgently required to permit the study of human prostate cell differentiation and malignant transformation. Unfortunately, human prostate cells are particularly difficult to convert into continuously growing cultures. We report here the successful immortalization without viral oncogenes of prostate epithelial cells and, for the first time, prostate stromal cells. These cells exhibit a significant pattern of authentic prostate-specific features. In particular, the epithelial cell culture is able to differentiate into glandular buds that closely resemble the structures formed by primary prostate epithelial cells. The stromal cells have typical characteristics of prostate smooth muscle cells. These immortalized cultures may serve as a unique experimental platform to permit several research directions, including the study of cell-cell interactions in an authentic prostate microenvironment, prostate cell differentiation, and most significantly, the complex multistep process leading to prostate cell transformation. (Cancer Res 2006; 66(7): 3531-40)
Significance of Plasma Lead Levels in Normal and Lead-Intoxicated Children
Authors: John F. Rosen, Emma E. Trinidad
Journal: Environmental Health Perspectives (1974)

Plasma lead (Pb) levels have been measured in normal and lead-intoxicated children, newborns, and children with sickle cell disease. The results in all groups were contant over a wide range of red cell Pb concentration. These results support the thesis that the red cell represents a large repository for Pb, maintaining plasma Pb concentration within closely defined limits, and that methods other than measurements of plasma Pb will be necessary to uncover a presumably dynamic transport system between red cell and plasma. Indeed, we have demonstrated in vitro that ionized calcium (Ca(2+)) lowers red cell Pb content according to a linear dose-response curve. Ca(2+) may thereby control Pb transport from red cell to plasma, and fluctuations in the concentration of Ca(2+) in serum and extracellular fluid may influence the toxic activities of Pb. In bone organ culture, changes in the concentration of Ca(2+) and phosphate in the medium alter the release of previously incorporated (210)Pb from fetal rat bones in response to parathyroid hormone (PTH). Therefore, both PTH and the ionic milieu of the medium apparently regulate bone Pb metabolism.We would expect that understanding further the dynamics of Pb transport in plasma and bone may lead to a more exact definition of the real hazards of low level Pb toxicity in children.
Polycythemia vera in identical twins
Authors: Michael L. Friedland, Edward G. Wittels, Rita J. Robinson
Journal: American Journal of Hematology (1981)

Abstract The occurrence of polycythemia vera in family members has been a rare event, with little or no documentation in the literature to suggest a common genetic defect. We report here on the first case of polycythemia vera documented in identical twins. No chromosomal abnormalities have yet been detected in these patients. The criteria for the diagnosis of polycythemia vera are reviewed, and the possible implications of our findings are discussed.
A STUDY OF THE MECHANICAL OBSTRUCTION TO THE CIRCULATION OF THE KIDNEY PRODUCED BY EXPERIMENTAL ACUTE TOXIC NEPHROPATHY
Authors: Albert A. Ghoreyeb
Journal: The Journal of Experimental Medicine (1913)

1. Rabbits may have spontaneous nephropathy and show no casts or albumen in the urine. 2. If we leave out of consideration rabbits 17, 18, 19, and 20, which were perfused with Adler's solution, and rabbits 8, 9, 17, 18, and 28, which were injected subcutaneously with potassium chromate, rabbits 49 and 73 show that spontaneous nephropathy offers some impediment to the perfusing serum.
The Nuremberg Code, informed consent, and involuntary treatment
Authors: E. G. Howe
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In their Editorial, Dr Grodin and Mr Annas<sup>1</sup>state that the use of investigational drugs on US soldiers in the Gulf War without their consent, like the US military and cold war radiation experiments, directly violates the Nuremberg Code. They also emphasize that the important distinction between "treatment and research" not be blurred. Yet, by implicitly equating the use of investigational drugs with the radiation experiments and by stating that this use of investigational drugs violates the Nuremburg Code, they commit the very error they wish to prevent. The DOD, the FDA, and others involved in deciding whether investigational vaccines, drugs, or both should be used in Gulf War military personnel were clear from the time this question first was raised that these substances would be used as treatments only.<sup>2,3</sup>The paramount consideration throughout this discussion was how to prevent the possible loss of the lives of innumerable