tbuckley/cabot-search huggingface dataset:
Peripheral prion pursuit
Authors: Adriano Aguzzi
Journal: Journal of Clinical Investigation (2001)

Prion diseases are transmissible, fatal neurodegenerative diseases affecting animals and humans (1). The prototypical human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD), is thought to originate in the CNS, and no significant accumulation of the infectious agent (the prion) is found in extracerebral compartments. This may be one of the reasons why human-to-human transmission of sCJD has been essentially confined to neurosurgery, tissue transplants, or, before the advent of recombinant DNA technology, injection of cadaveric pituitary hormones.

The bovine spongiform encephalopathy (BSE) epizootic, however, has spurred many additional concerns (2). BSE is clearly transmissible to humans, and 109 Europeans have — at the time of writing — already succumbed to the human counterpart to BSE, which is called variant Creutzfeldt-Jakob disease (vCJD) (3). Unlike sCJD, BSE prions need to find their way to the CNS, which is the only organ system in which they can produce damage. The process by which prions migrate from the site of inoculation (e.g., the gastrointestinal [GI]tract) to the CNS is called neuroinvasion and represents a crucial step in the pathogenesis of most naturally occurring prion diseases.

A detailed understanding of the cells and the molecules responsible for neuroinvasion is of utmost importance for public health, since an arguably large fraction of the European population may have been exposed to BSE prions in the last 15 years. Moreover, presumptive rate-limiting steps, if they exist, are likely to represent gratifying targets for postexposure prophylaxis, i.e., for interventions aimed at preventing the clinical outbreak of the disease in persons who have been exposed to BSE prions.
National Initiatives for Care of the Medically Needy
Authors: James E. Davis
Journal: JAMA (1988)

The problem of access to health care by the disadvantaged has been exacerbated during the 1980s by a tight economy, a competitive health care environment, and an escalating national debt. After discussing the history and current status of the U.S. system for providing care to the underprivileged, Davis describes the initiatives taken by the American Medical Association and by individual physicians to alleviate the problem. The AMA has promoted legislative changes at the state and federal levels to broaden health insurance coverage and provide financial support through risk pools for those who are underinsured or uninsurable. Many physicians in fee-for-service practices are helping by providing free or reduced-fee care to the needy.
Spectrum of Mutations in Long-QT Syndrome Genes
Authors: Igor Splawski, Jiaxiang Shen, Katherine W. Timothy, Michael H. Lehmann, Silvia Priori, Jennifer L. Robinson, Arthur J. Moss, Peter J. Schwartz, Jeffrey A. Towbin, G. Michael Vincent, Mark T. Keating
Journal: Circulation (2000)

Long-QT Syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on ECG and presence of syncope, seizures, and sudden death. Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Mutations in KVLQT1 and KCNE1 also cause the Jervell and Lange-Nielsen syndrome, a form of LQTS associated with deafness, a phenotypic abnormality inherited in an autosomal recessive fashion.We used mutational analyses to screen a pool of 262 unrelated individuals with LQTS for mutations in the 5 defined genes. We identified 134 mutations in addition to the 43 that we previously reported. Eighty of the mutations were novel. The total number of mutations in this population is now 177 (68% of individuals).KVLQT1 (42%) and HERG (45%) accounted for 87% of identified mutations, and SCN5A (8%), KCNE1 (3%), and KCNE2 (2%) accounted for the other 13%. Missense mutations were most common (72%), followed by frameshift mutations (10%), in-frame deletions, and nonsense and splice-site mutations (5% to 7% each). Most mutations resided in intracellular (52%) and transmembrane (30%) domains; 12% were found in pore and 6% in extracellular segments. In most cases (78%), a mutation was found in a single family or an individual.
Academic Medicine in the 21st Century
Authors: Mark R. Laret
Journal: JAMA Internal Medicine (2013)

The achievements of academic medical centers in improving clinical care, advancing scientific discovery, and training the next generation of scientists and clinicians have been remarkable. But today, academic medicine is in great danger from shrinking support for each of its core missions—clinical care, research, and education. This unprecedented crisis also brings a unique opportunity for radical change in the culture, organization, and operation of academic medical centers.
Vanishing pancreas. Lipomatous infiltration of the pancreas
Authors: Stuart H. Danovitch, Robert Paley, Oscar Mann, Robert Choisser, Theodore Bayless
Journal: JAMA (1985)

THE "vanishing pancreas" is a sobriquet for lipomatous replacement of the gland and is occasionally a clinically evident phenomenon causing symptoms and malabsorption.<sup>1,2</sup>In children it is rare; it occurs with skeletal abnormalities and cytopenias and differs from cystic fibrosis in that sweat test results are normal.<sup>3,4</sup>In adults, the entity is recognized infrequently. Two cases were reported in 1959 from the Mayo Clinic, and their review revealed six other published cases in the literature.<sup>2</sup>Subsequently, scattered reports have appeared and the availability of computed tomography has increasingly led to the recognition of this entity prior to surgery or autopsy.<sup>4,5</sup>In the last six months we have seen two adults with long-standing digestive complaints, diabetes, and steatorrhea whose pancreata had vanished. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 70-year-old woman has had chronic problems of obesity, mild hypertension, episodic diarrhea, and flatulence for ten to 15 years.
Angiostatin-mediated Suppression of Cancer Metastases by Primary Neoplasms Engineered to Produce Granulocyte/Macrophage Colony–stimulating Factor
Authors: Zhongyun Dong, Junya Yoneda, Rakesh Kumar, Isaiah J. Fidler
Journal: The Journal of Experimental Medicine (1998)

We determined whether tumor cells consistently generating granulocyte/macrophage colony- stimulating factor (GM-CSF) can recruit and activate macrophages to generate angiostatin and, hence, inhibit the growth of distant metastasis. Two murine melanoma lines, B16-F10 (syngeneic to C57BL/6 mice) and K-1735 (syngeneic to C3H/HeN mice), were engineered to produce GM-CSF. High GM-CSF (>1 ng/10(6) cells)- and low GM-CSF (<10 pg/10(6) cells)-producing clones were identified. Parental, low, and high GM-CSF-producing cells were injected subcutaneously into syngeneic and into nude mice. Parental and low-producing cells produced rapidly growing tumors, whereas the high-producing cells produced slow-growing tumors. Macrophage density inversely correlated with tumorigenicity and directly correlated with steady state levels of macrophage metalloelastase (MME) mRNA. B16 and K-1735 subcutaneous (s.c.) tumors producing high levels of GM-CSF significantly suppressed lung metastasis of 3LL, UV-2237 fibrosarcoma, K-1735 M2, and B16-F10 cells, but parental or low-producing tumors did not. The level of angiostatin in the serum directly correlated with the production of GM-CSF by the s.c. tumors. Macrophages incubated with medium conditioned by GM-CSF- producing B16 or K-1735 cells had higher MME activity and generated fourfold more angiostatin than control counterparts. These data provide direct evidence that GM-CSF released from a primary tumor can upregulate angiostatin production and suppress growth of metastases.
The Changing Face of Medicine: Women Doctors and the Evolution of Health Care in America
Authors: Joslyn W. Fisher
Journal: Annals of Internal Medicine (2009)

Medical Writings: Book Notes15 September 2009The Changing Face of Medicine: Women Doctors and the Evolution of Health Care in AmericaJoslyn W. Fisher, MD, MPHJoslyn W. Fisher, MD, MPHFrom Baylor College of Medicine, Houston, Texas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-6-200909150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Boulis AK, Jacobs JA. 280 pages. Ithaca, NY: Cornell Univ Pr; 2008. $35.00. ISBN 9780801444463. Order at www.cornellpress.cornell.edu.Field of medicine: Medical sociology.Format: Hardcover book.Audience: Health professionals, social scientists, students interested in the health profession, and health policymakers.Purpose: To provide an explanatory model for the “feminization of medicine in the U.S.,” to address gender differences in career experiences for physicians and institutional and societal changes affecting work–family balance, and to describe the impact that women physicians have had on the practice and profession of medicine.Content: The authors explore how historical attitudes and social structures have influenced ... Author, Article, and Disclosure InformationAffiliations: From Baylor College of Medicine, Houston, Texas. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 2009Volume 151, Issue 6Page: 436KeywordsHealth careHealth information technologyInternetLibrariesMedical sociologyScientistsSexual identity ePublished: 15 September 2009 Issue Published: 15 September 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pulmonary Tumor Associated with Diffuse Bilateral Lung Uptake of Bone Imaging Agent
Authors: MOHAMED A. ANTAR, JOAN M. MACK, RICHARD P. SPENCER, JAMES M. CROTTY
Journal: Clinical Nuclear Medicine (1990)

Radiogallium accumulated in a large cell carcinoma of the left lung. A bone scan in the patient showed bilateral intense uptake of Tc-99m MDP in the lung fields, as well as in the tibias, by an undefined mechanism.
P3-07-26: How Generalizable Is the Patient Population Enrolled in ACOSOG Z11?
Authors: DR Lannin, BK Killelea, BJ Grube, N Horowitz, AB Chagpar
Journal: Cancer Research (2011)

Abstract Background: The recently published Z11 trial of observation vs. axillary dissection for patients with a positive sentinel lymph node showed amazingly low axillary recurrence rates in both groups, and has the potential to dramatically alter practice. However questions remain about whether the Z11 population is representative of the larger population of breast cancer patients. Methods: An institutional database was queried to identify all patients who underwent sentinel node biopsy at our breast center from 2004 to 2010. These cases were retrospectively reviewed to determine the percentage of patients who would have met the Z11 eligibility requirements, and the demographics and outcomes for this subset were compared to those for Z11. Results: Out of 1215 patients undergoing sentinel node biopsy, 282 (23%) had at least one positive sentinel node. However when patients were eliminated who had T3 or T4 tumors, more than 2 positive sentinel nodes, neo-adjuvant chemotherapy, or who underwent mastectomy, only 88 remained who would have been eligible for Z11 (31% of those with a positive sentinel node). These patients are compared to the Z11 patients in the following table. Our lumpectomy patients were generally quite similar to those of Z11 except ours had a lower percentage of micrometastases and a higher percentage of 4 or more positive nodes. As with most other published prediction models, the chance of having 4 or more positive nodes in our patients was directly proportional to tumor size and number of positive sentinel nodes, and inversely proportional to number of negative sentinel nodes. Conclusions: A relatively small percentage of node positive patients at our institution actually met the eligibility requirements for Z11, but this subset was similar in most respects to the Z11 population. We have developed an algorithm that can be prospectively tested that will allow the majority of these patients to forego axillary dissection but that will exclude patients most likely to have 4 or more positive nodes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-26.
Thrombocytosis in rheumatoid arthritis.
Authors: S M Rajah
Journal: Annals of the Rheumatic Diseases (1978)

faeces were collected at home and returned direct to our laboratory by post.Klebsiella pneumoniae was cultured from the faeces of 8 (33-3%) of the patients and 8 (30 8%) of the controls.This difference is not significant.When the results were analysed with regard to our classification of activity of their spondylitis, we found that 2 (33-3%), 5 (33 3%), and 1 (33 -3 %) of patients with definitely active, probably active, and inactive spondylitis respectively carried Klebsiella in their gastrointestinal tract.There are no differences between these three groups. 2(25-0%) and 6 (37 5%) of the spondylitic patients with and without gastrointestinal Klebsiella respectively had inflammatory disease of a peripheral joint at the time of study.No patient had active anterior uveitis.
Abstract 1187: The Champions TumorGraft Bank: A demographically-rich repository of preclinical TumorGraft models
Authors: Tin Khor, David Vasquez, Amanda Katz, Gilson Baia, Daniel Ciznadija, David Sidransky, Keren Paz
Journal: Cancer Research (2014)

Abstract Many oncology pharmaceuticals fail during phased clinical trials, having been advanced based on research using flawed preclinical models that do not accurately replicate human tumor biology. For example, numerous models are based on genetically-engineered mice, which are often generated from limited numbers of genetic aberrations. As such, they may not accurately represent either the chaotic heterogeneity that exists within intact human tumors or throughout the clinical population. TumorGrafts, in which patient-derived tumor tissue is directly engrafted into immunodeficient mice, offer a step forward in this unresolved issue. These models maintain the complex intra-tumoral heterogeneity and biology of an intact malignancy, as well its 3-dimensional interplay with stromal components and other cells fluxing into the immediate environment. The intrinsic cross-talk between the different compartments of the tumor is also retained. We wanted to generate a repository of these tumor models and make them available to the research community for use in pharmaceutical development and basic research processes. Here we describe our extensive bank of live TumorGrafts comprising a range of different tumor types, from more common cancers, including lung, colon, and breast, to a number of rare subtypes such as adenoid cystic carcinoma. These models were originally developed for personalizing cancer treatments and are derived from patient populations across all ages and ethnicities, encompassing both treatment-naïve and heavily-treated individuals. Furthermore, because of our distinct patient-focus, we maintain detailed clinical histories, as well as molecular data where available. Hence, the bank is a reasonable surrogate of the population from which treatment groups are typically drawn for clinical trials and could potentially be of value for predetermining target populations for therapeutic intervention. The Champions TumorGraft Bank provides superior pre-clinical models that faithfully capture all the biological and molecular features of cancer and can serve basic and clinical research groups as an increasingly valuable source for drug development and biomarker discovery. Citation Format: Tin Khor, David Vasquez, Amanda Katz, Gilson Baia, Daniel Ciznadija, David Sidransky, Keren Paz. The Champions TumorGraft Bank: A demographically-rich repository of preclinical TumorGraft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1187. doi:10.1158/1538-7445.AM2014-1187
Exercise as Protection against Heart Attack
Authors: Ralph S. Paffenbarger, Robert T. Hyde
Journal: New England Journal of Medicine (1980)

Williams and his associates report in this issue that a physical-conditioning program decreased fibrinolytic activity at rest and augmented the rise in fibrinolysis induced by experimental venous occlusion. They suggest that this effect of exercise may be an important mechanism by which habitual exertion protects against cardiovascular disease. Their study is one of a number of investigations that bolster with physiologic evidence the so-called "circumstantial" case for exercise as an essential protective element in human health. As they point out, if intravascular thrombus formation is implicated in the pathophysiology of myocardial infarction, stroke, and pulmonary embolism, exercise protects against these . . .
Egg white proteins as inhalant allergens associated with baker's asthma
Authors: C. Escudero, S. Quirce, M. Fernández‐Nieto, J. de Miguel, J. Cuesta, J. Sastre
Journal: Allergy (2003)

Bakery workers may develop IgE-mediated allergy to liquid and aerosolized hen's egg proteins that are commonly used in the baking and confectionery industries.We studied four bakery workers who had work-related allergic respiratory symptoms upon exposure to egg aerosols. The causative role of egg proteins in their respiratory symptoms was investigated by immunologic and specific inhalation challenge (SIC) tests.Skin prick tests to egg white extract and to lysozyme gave positives responses in all the subjects, to ovalbumin in two, to ovomucoid in one and to egg yolk in two subjects. They were also sensitized to wheat, rye and barley flours. Specific IgE determinations to egg white were positive in all patients, to lysozyme in two, to ovalbumin in three, to ovomucoid in two and to egg yolk in two of them. Methacholine inhalation tests revealed bronchial hyperresponsiveness in all workers (PC20 < 16 mg/ml). SICs were performed with aqueous extracts of lysozyme (n = 4), ovalbumin (n = 2) and ovomucoid (n = 1), which elicited isolated early asthmatic reactions in all subjects. Double-blind, placebo-controlled, oral challenge tests with raw egg white were positive in three subjects.These bakery workers had developed IgE-mediated occupational asthma to hen's egg white proteins.
Hepatocellular carcinoma p53 G &gt; T transversions at codon 249: the fingerprint of aflatoxin exposure?
Authors: T Lasky, L Magder
Journal: Environmental Health Perspectives (1997)

The molecular epidemiology of p53 mutations allows the possibility of correlating particular mutations with specific environmental carcinogens and establishing one step in the causal pathway between exposure to carcinogens and the development of cancer. A striking example is the G > T transversion at the third base pair of codon 249 observed in liver cancer patients possibly exposed to high levels of aflatoxins in their agricultural products. In this paper, we describe a systematic review of the literature and access the quality of the available data. We found methodologic limitations in the studies. In particular, the key independent variable, aflatoxin exposure, was not assessed in these studies, with the exception of one study that measured a marker of exposure. Instead, nationality, geographic residence, or geographic site of hospital were used as surrogate markers for exposure. Patients from areas with high aflatoxin levels were more likely to have p53 mutations than were patients from areas with low aflatoxin levels. In the group with p53 mutations, patients from areas with high aflatoxin levels had higher proportions of mutations with codon 249 G > T transversions. The differences in proportions with p53 mutations were significant, as were the differences in proportions of codon 249 G > T transversions among patients with p53 mutations. Aflatoxin may increase the proportion of p53 mutations by causing a single mutation, the codon 249 G > T transversion, thus explaining some of the excess liver cancer associated with aflatoxin exposure. However, it is premature to conclude that p53 mutations are established markers for environmental carcinogens.
Herpesvirus entry mediator regulates hypoxia-inducible factor–1α and erythropoiesis in mice
Authors: Yukimi Sakoda, Sudarshan Anand, Yuming Zhao, Jang-June Park, Yingjia Liu, Atsuo Kuramasu, Nico van Rooijen, Ling Chen, Scott E. Strome, Wayne W. Hancock, Lieping Chen, Koji Tamada
Journal: Journal of Clinical Investigation (2011)

Erythropoiesis, the production of red blood cells, must be tightly controlled to ensure adequate oxygen delivery to tissues without causing thrombosis or stroke. Control of physiologic and pathologic erythropoiesis is dependent predominantly on erythropoietin (EPO), the expression of which is regulated by hypoxia-inducible factor (HIF) activity in response to low oxygen tension. Accumulating evidence indicates that oxygen-independent mediators, including inflammatory stimuli, cytokines, and growth factors, also upregulate HIF activity, but it is unclear whether these signals also result in EPO production and erythropoiesis in vivo. Here, we found that signaling through herpesvirus entry mediator (HVEM), a molecule of the TNF receptor superfamily, promoted HIF-1α activity in the kidney and subsequently facilitated renal Epo production and erythropoiesis in vivo under normoxic conditions. This Epo upregulation was mediated by increased production of NO by renal macrophages. Hvem-deficient mice displayed impaired Epo expression and aggravated anemia in response to erythropoietic stress. These data reveal that HVEM signaling functions to promote HIF-1α activity and Epo production, and thus to regulate erythropoiesis. Furthermore, our findings suggest that this molecular mechanism could represent a therapeutic target for Epo-responsive diseases, including anemia.
Stereoselective interaction of sulfinpyrazone with racemic warfarin and its separated enantiomorphs in man.
Authors: R A O'Reilly
Journal: Circulation (1982)

Although serious hemorrhage during therapeutic coadministration of sulfinpyrazone and racemic warfarin occurs, no prospective studies have been done. In this study, single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects with and without oral sulfinpyrazone, 400 mg daily. Both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.05) were significantly augmented. To determine if this interaction was stereoselective, the experiments were repeated in the same subjects with R-and S-warfarin enantiomorphs. S-warfarin with sulfinpyrazone caused a highly significant augmentation of both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.001). R-warfarin with sulfinpyrazone did not significantly change the hypoprothrombinemia but significantly (p less than 0.05) reduced warfarin concentrations. Thus, sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin stereoselectively by reduced metabolic clearance of S-warfarin. Sulfinpyrazone and racemic warfarin are most dangerous when either drug is added to a stabilized regimen of the other drug.
HFEA and HTA will remain as separate bodies but will pool some support services
Authors: M. Limb
Journal: BMJ (2013)

The Human Fertilisation and Embryology Authority (HFEA) and the Human Tissue Authority (HTA), the UK’s fertility and human tissue regulators, will be retained as two separate bodies with “distinct identities” but will combine their support services to save money, the government has announced .1

Ministers had originally sought to abolish both bodies and transfer their functions elsewhere, but many health groups objected in a …