tbuckley/cabot-search huggingface dataset:
OBSERVATIONS IN ONE HUNDRED CASES OF SMALLPOX
Authors: T. W. Rhodes
Journal: JAMA (1930)

Over a period of four months, from Oct. 22, 1929, to Feb. 23, 1930, 100 patients with smallpox were quarantined. The ages of the patients ranged from 4 weeks to 87 years. The average age in this series of cases was 30 years. Twenty-nine of those under quarantine were school children, the average age being 10 years. Of the 100 patients, only six had been previously vaccinated. One of these was a woman, aged 60, who had two vaccination scars, the last one dating back forty-seven years. This patient had a relatively mild type of the disease, less than a dozen pustules developing, and scarcely any prodromal symptoms preceding the eruption. On the other hand, a man, aged 44, a laborer, had a well defined eruption with many pustules, although he had been successfully vaccinated about eight years previously. A modified type of eruption was noted in a man, aged
Abstract 4508: Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases
Authors: Hui Li
Journal: Cancer Research (2014)

Abstract Interrogating specific cellular activities often entails the dissection of posttranslational modifications or functional redundancy conferred by protein families, which demands more sophisticated research tools than simply eliminating a specific gene product by gene targeting or RNA interference. We have developed a novel methodology that involves engineering a single SCFbTrCP-based ubiquitin ligase that is capable of not only simultaneously targeting the entire family of ErbB receptor tyrosine kinases for ubiquitination and degradation, but also selectively recruiting only activated ErbBs. The engineered SCFbTrCP ubiquitin ligase effectively blocked ErbB signaling and attenuated oncogenicity in breast cancer cells, yet had little effect on the survival and growth of non-cancerous breast epithelial cells. Therefore, engineering ubiquitin ligases offers a simple research tool to dissect the specific traits of tumorigenic protein families, and provides a rapid and feasible means to expand the dimensionality of drug discovery by assessing protein families or posttranslational modifications as potential drug targets. Note: This abstract was not presented at the meeting. Citation Format: Hui Li. Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases. [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 4508. doi:10.1158/1538-7445.AM2014-4508
The Overdiagnosis of Lyme Disease
Authors: Joseph J. Burrascano
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The article by Steere et al<sup>1</sup>on the overdiagnosis of Lyme disease has caused a great deal of concern and anger among physicians and patients alike. Lyme disease is a clinical diagnosis,<sup>2</sup>for it is the patients' histories and symptoms that are the criteria on which the diagnosis is made. This fact is discounted by the authors, as are the results of serologic tests done elsewhere. However, the authors obviously lend great weight to their own test, despite the well-documented awareness of the unreliability and variability of serologic test results.<sup>3</sup>Indeed, there is no proof that their laboratory is any more accurate than the many others tested. Their own T-cell proliferative assay, used on some of their patients here, misses 55% of confirmed cases.<sup>4</sup> My experience in a practice that serves as a referral center for thousands of patients with chronic Lyme disease
Experimental Production of Congenital Anomalies
Authors: Theodore H. Ingalls, Francis J. Curley, Richard A. Prindle
Journal: New England Journal of Medicine (1952)

THE purpose of this communication is to sketch the status of acquired congenital anomalies of the mouse against a background of experimental embryology; to report progress in the induction of such anomalies by oxygen lack of different degrees maintained for a five-hour period during pregnancy; and to analyze the part played by fetal age (stage of development) as well as anoxic stress.With such excellent monographs as those of Needham,1 Brachet2 and Weiss3 available, no attempt is made to review the massive body of embryologic knowledge; the literature on the biology4 and genetics5 of the mouse alone is voluminous. To . . .
Direct Mailing as a Means of Disseminating NIH Consensus Statements
Authors: Itzhak Jacoby
Journal: JAMA (1986)

The Office of Medical Applications of Research of the National Institutes of Health conducted a survey to evaluate the effectiveness of mass mailing of consensus statements as compared with traditional dissemination methods. The consensus statement on osteoporosis, published earlier in JAMA, was selected for study. Physicians (N = 695) within each of five relevant specialties in two comparable metropolitan areas were surveyed. Findings suggest that while a small but significant increase of awareness resulted from direct mailing, this increase should be weighed against costs and effectiveness of other methods.
Ward Design in Relation to Postoperative Wound Infection: Part I
Authors: H. G. Smylie, A. I. G. Davidson, A. Macdonald, G. Smith
Journal: BMJ (1971)

The incidence of postoperative wound infection in a general surgical unit is reported both before and after transfer from a "Nightingale" type multibed ward to a new "race-track" type of surgical ward with controlled ventilation and with 40% of its beds in single rooms. Following transfer postoperative wound infection was reduced by about 55%. With the use of certain types of staphylococcal infection as an index of cross-infection it was shown that transfer was followed by a 72% reduction in cross-infection of wounds. A case is made for control of hospital cross-infection in surgical wards. The principal change in ward architecture resulting from the transfer was the extensive division of ward space into separate compartments (40% of single-bed rooms), which make controlled ventilation easier.
Toll-Like Receptor 6 Drives Differentiation of Tolerogenic Dendritic Cells and Contributes to LcrV-Mediated Plague Pathogenesis
Authors: R. William DePaolo, Fangming Tang, InYoung Kim, Mei Han, Nadine Levin, Nancy Ciletti, Anning Lin, Debra Anderson, Olaf Schneewind, Bana Jabri
Journal: Cell Host & Microbe (2008)
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus
Authors: Limin Zhu, Roger Vranckx, Philippe Khau Van Kien, Alain Lalande, Nicolas Boisset, Flavie Mathieu, Mark Wegman, Luke Glancy, Jean-Marie Gasc, François Brunotte, Patrick Bruneval, Jean-Eric Wolf, Jean-Baptiste Michel, Xavier Jeunemaitre
Journal: Nature Genetics (2006)
S4-1: Overdiagnosis in Breast Cancer Screening: Methodological Considerations of Current Estimates.
Authors: RA Smith, SW Duffy
Journal: Cancer Research (2011)

Abstract Background A harm that has received considerable attention in breast cancer screening is overdiagnosis, i.e., the detection through screening of breast cancer that is non-progressive. Since there is no way to distinguish a truly non-progressive tumor from one that is progressive, overdiagnosis is a statistical phenomenon that is estimated as the difference between observed and expected incidence rates. However, there is no agreement on the true rate of overdiagnosis in breast cancer screening. Estimates vary widely, with the highest estimates reported in the scientific literature having received significant media attention under the premise that a signifiant fraction of newly diagnosed breast cancers are non-progressive and thus overtreated. We examined the range of overdiagnosis estimates in the context of factors that influence observed and expected breast cancer incidence rates over time. Methods Only studies that compared incidence rates of invasive breast cancer, or invasive breast cancer and ductal carcinoma in situ (DCIS), in a group invited or exposed to mammography compared with a group not invited or not exposed to mammography were included in our analysis. Studies were evaluated based on whether or not they adjusted for contemporaneous trends in the underlying incidence of disease, which may differ in different age groups, and age-specific effect on incidence rates due to lead time. Results We identified 17 studies (Table 1) that attempted to estimate overdiagnosis of breast cancer resulting from mammography screening. The main determinant of high estimated rates of overdiagnosis was a failure to adjust for lead time. The highest rate of overdiagnosis (33%) occurred in the one study that did not correct for either lead time or confounders. Studies that only partially corrected for lead time and confounding also had high estimates of overdiagnosis (mean = 30%), whereas studies that corrected for both lead time and confounders had the lowest estimate of overdiagnosis (mean =5%). Conclusion The possibility that some breast cancers detected by mammography are indolent and not life threatening within the patient's natural life is real. However, it is clear from our analysis that the wide range of estimates of overdiagnosis are due to whether or not studies have adjusted for factors in and outside of screening programs known to influence incidence rates over time. Our findings suggest that the true rate of overdiagnosis associated with breast cancer screening, to the extent that it exits at all, is small. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-1.
Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections
Authors: Nobuhiro Nakano, Chiharu Nishiyama, Shunsuke Kanada, Yusuke Niwa, Naomi Shimokawa, Hiroko Ushio, Makoto Nishiyama, Ko Okumura, Hideoki Ogawa
Journal: Blood (2007)
Estradiol prevents homocysteine-induced endothelial injury in male rats
Authors: K Dimitrova
Journal: Cardiovascular Research (2002)

Objective: We investigated whether estradiol may prevent accelerated atherosclerosis due to hyperhomocysteinemia by enhancing the antioxidant system. Methods: Male Wistar rats were treated with placebo (P) or 1 mg (1E2) and 2 mg (2E2) 17β estradiol. Half of the animals (n=6) from each group received homocysteine (Hcy, 100 mg/kg/day) administered in the drinking water for 60 days (P/Hcy, 1E2/Hcy and 2E2/Hcy). Glutathione (GSH) content and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in myocardial tissues, as well as the serum Hcy concentrations and blood levels of hydrogen peroxide (H2O2). The relaxation response of aortic ring segments to acetylcholine (ACh) was used for the assessment of endothelial function, and hematoxylin-eosin stained thin sections of rat aorta were used for detection of the histological changes (namely endothelial damage and wall thickening). Results: Depression of relaxation to ACh occurred in P/Hcy compared to P (15.7±4% vs. 96.3±7%, P<0.0001), but estrogen significantly restored endothelium dependent relaxation in hyperhomocysteinemic rats (86.8±9.3%, P<0.001). Histological examination revealed aortic endothelial denudation in P/Hcy while the endothelial structures of the aorta from the 1E2/Hcy and 2E2/Hcy appeared normal. Significant reductions in GSH and G6PDH levels were detected in P/Hcy (1.5±0.01 μmol/g and 3.21±1.2 U/mg, respectively) compared to 1E2/Hcy (2.5±0.3 μmol/g and 12.81±1.5 U/mg, P<0.001) and 2E2/Hcy (3.11±1.1 μmol/g and 15.66±4 U/mg, P<0.001). In addition, blood H2O2 level in 1E2/Hcy and 2E2/Hcy remained low while it was raised significantly in P/Hcy compared to P (P<0.001). Conclusions: These data suggest that the observed reduction of GSH levels and suppression of G6PDH activity induced by Hcy coupled, with endothelial ultrastructural changes and impaired function, all reversed by estradiol, may have relevance to the mechanisms of atherogenesis and the beneficial effects of estrogen replacement therapy.
A CASE OF INTESTINAL OBSTRUCTION
Authors: J. M. W. Morison, L. White
Journal: BMJ (1918)

INTESTINAL OBSTRUCTION.5 Snm S13The patient gradually became more and miiore toxaemic, aild finally died eight weeks after admission.Post-mortem Examiination.The heart was not enlarged, nor was there any degree of myocardial degeneration.A large cauliflower-like vegetation was found on oue cusp of the aortic valve, almost completelv closing the orifice of the valve.There was a similar vegetation oIu the adjoining cusp; the third cusp was free.The summnit of the large vegetation was soft and friable, but the base was cartilaginous.The mitral valve had two or three similar but smaller vegetations on it.The right side of the heart was normal.The spleen was darl, about twice its usual size, and showed tw%o recent infarcts.There were also small infarcts in each kidlne, but the rest of the examination showed nothing abnormal.In a smear made from the aorti6 vegetation were seen enormous numbers of organisms resembling streptococci, rather large in size, aid,growing-in chains of three to five.Drawing of interior of left side of heart.The remarkable features about this case were the insidious and slow progress, the absence of any definite cardiac symptoms, and the fact that the heart never became enlarged, in spite of the severity of the aortic lesion and the long duration of the case.This may be attributed to the fact that the large vegetation prevented any real leaking of this valve.The patient was never really "cardiac"; there was no dyspnoea or oedeima, and the pulse maintained a steady, regular, slow beat till the end.He was in a " typhoid" state throughout the disease, and died eventually of a slow toxaemia.
PPARα Activators Inhibit Vascular Endothelial Growth Factor Receptor-2 Expression by Repressing Sp1-Dependent DNA Binding and Transactivation
Authors: Markus Meissner, Monika Stein, Carmen Urbich, Kerstin Reisinger, Guntram Suske, Bart Staels, Roland Kaufmann, Jens Gille
Journal: Circulation Research (2003)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, originally implicated in the regulation of lipid and glucose homeostasis. In addition, natural and synthetic PPAR activators may control inflammatory processes by inhibition of distinct proinflammatory genes. As signaling via the vascular endothelial growth factor receptor-2 (VEGFR2) pathway is critical for angiogenic responses during chronic inflammation, we explored whether known antiinflammatory effects of PPAR ligands are mediated in part through diminished VEGFR2 expression. In this study, PPARalpha agonists are found to inhibit endothelial VEGFR2 expression, whereas predominant PPARgamma ligands remained without discernible effects. Time- and concentration-dependent inhibition is demonstrated both at the level of protein and mRNA VEGFR2 expression. Inhibitory effects of PPARalpha agonists on transcriptional activity of the VEGFR2 promoter are conveyed by an element located between base pairs -60 and -37 that contains two adjacent consensus Sp1 transcription factor binding sites. Constitutive Sp1-containing complex formation to this sequence is decreased by PPARalpha treatment, indicating that VEGFR2 gene expression is inhibited by repressing Sp1 site-dependent DNA binding and transactivation. Our coimmunoprecipitation experiments revealed enhanced protein interactions between PPARalpha and Sp1 on PPARalpha activation, thus constituting a probable mechanism by which PPARalpha activators decrease Sp-dependent binding activity to the VEGFR2 promoter. Hence, molecular mechanisms by which PPARs modulate the rate of gene transcription may include direct interactions between specific transcription factors and PPARs that ultimately result in reduced DNA binding to their respective response elements.
Gonococcal Arthritis
Authors: Charles L. Cooke
Journal: JAMA (1971)

A survey of 54 cases of gonococcal arthritis shows it to be primarily a disease of young adults, with women outnumbering men. Misdiagnosis and resulting delay in treatment occurred in 25% of cases. Inspection of a gram-stained smear of either cervical or urethral discharge proved to be the most useful diagnostic tool. The wrist, knee, and ankle were the joints most frequently affected. If the possibility of gonococcal arthritis exists, the patient should be treated immediately with antibiotics without waiting for a definite diagnosis.
Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids. TNF-alpha priming increases glucocorticoid inhibition of TNF-alpha-induced cytotoxicity/apoptosis.
Authors: M Costas, T Trapp, M P Pereda, J Sauer, R Rupprecht, V E Nahmod, J M Reul, F Holsboer, E Arzt
Journal: Journal of Clinical Investigation (1996)

Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-alpha increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via the glucocorticoid response elements (GRE) in L-929 mouse fibroblasts transfected with a glucocorticoid-inducible reporter plasmid. In addition, TNF-alpha also enhanced GR number. The TNF-alpha effect on transcriptional activity was absent in other cell lines that express TNF-alpha receptors but not GRs, and became manifest when a GR expression vector was cotransfected, indicating that TNF-alpha, independent of any effect it may have on GR number, has a stimulatory effect on the glucocorticoid-induced transcriptional activity of the GR. Moreover, TNF-alpha increased GR binding to GRE. As a functional biological correlate of this mechanism, priming of L-929 cells with a low (noncytotoxic) dose of TNF-alpha significantly increased the sensitivity to glucocorticoid inhibition of TNF-alpha-induced cytotoxicity/apoptosis. TNF-alpha and IL-1 beta had the same stimulatory action on glucocorticoid-induced transcriptional activity of the GR via the GRE, in different types of cytokine/glucocorticoid target cells (glioma, pituitary, epithelioid). The phenomenon may therefore reflect a general molecular mechanism whereby cytokines modulate the transcriptional activity of the GR, thus potentiating the counterregulation by glucocorticoids at the level of their target cells.
Chromoblastomycosis
Authors: Michael Brown, Geoffrey Pasvol
Journal: New England Journal of Medicine (2005)

67-year-old man was admitted to the hospital with a 12-year history of swelling of his left leg.He had emigrated to the United Kingdom from Jamaica at the age of 31 years.When the patient was 41 years old, a golfball-sized nodule was excised from the dorsum of his left foot, and he was told he had a fungal infection.At that time, he did not receive any further treatment.At the age of 55 years, the patient noticed that a nodule had developed on his left shin.He did not seek medical attention until the lesion had spread and become so extensive that he was unable to walk (Panels A and B).A skin biopsy revealed a suppurative and granulomatous infiltrate with clusters of brown fungal organisms (muriform cells), a finding diagnostic of chromoblastomycosis (inset).A rhinocladiella species was cultured from skin scrapings.The patient was treated for 24 months with itraconazole and terbinafine, which resulted in improved mobility and substantial drying of the lesions, but warty changes, hyperpigmentation, and lymphedema persisted.
1097 CARDIOTROPHIN-1 DEFENDS AGAINST VIRAL-INDUCED LETHAL ACUTE LIVER FAILURE (ALF) OF RABBITS BY ATTENUATING LIVER INFLAMMATION AND INDUCING CYTOPROTECTIVE GROWTH FACTORS
Authors: M.J. Tuñón, B. San-Miguel, I. Crespo, E. Larrea, J.I. Riezu, F. Jorquera, M. Iñiguez, J. Ruiz, M. Alvarez, J. González-Gallego, J. Prieto
Journal: Journal of Hepatology (2011)
Long Intergenic Noncoding RNAs: New Links in Cancer Progression
Authors: Miao-Chih Tsai, Robert C. Spitale, Howard Y. Chang
Journal: Cancer Research (2011)

The process of cancer metastasis involves a series of sequential and complex steps. Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs. Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets.
Effect of Choline and Inositol on Plasma and Tissue Lipids and Atherosclerosis in the Cholesterol-Fed Chick
Authors: J. STAMLER, C. BOLENE, R. HARRIS, L. N. KATZ
Journal: Circulation (1950)

The lipotropic factors choline and inositol fail to exert a prophylactic effect against hypercholesterolemia, organ lipidosis and atherogenesis in the cholesterol-fed chick.
Dynamic Electrocardiographic Recording
Authors: Alfred Pick
Journal: JAMA (1979)

The purpose of this monograph is, according to the author's preface, "to present to the medical reader in a practical and usable format" the role of ambulatory electrocardiography in the framework of clinical cardiologic diagnostic. After a review of the extensive literature on the topic, various known methodologies and technical aspects are discussed, their advantages and pitfalls are pointed out, and indications for application of the method under various clinical conditions are enumerated and tabulated. In this survey the author has succeeded. However, if the illustrations are samples of his own experience with 1688 records, he has failed to demonstrate the usefulness of the technique and its place in registration of the cardiac irregularities, which do or do not require specific attention and management. Apart from the poor quality of most of these records, most stunning is the misinterpretation of many of them. For instance, in chapter 2, Fig 11
Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins.
Authors: A Kappas, G S Drummond
Journal: Environmental Health Perspectives (1984)

The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and bound to organic moieties, potently induce heme oxygenase, the rate limiting enzyme of heme degradation. The resulting increase in the rate of heme breakdown is reflected in a marked depression of cellular cytochrome P-450 content and impairment of the oxidative metabolism of natural and foreign chemicals dependent on this hemeprotein. Organometal complexes do not mimic in all their aspects the actions of the inorganic elements which they contain. For example, organotins, in contrast to inorganic tin, produce a prolonged induction response of heme oxygenase in the liver but not in the kidney. Co-protoporphyrin is a much more potent inducer of heme oxygenase in liver than is inorganic cobalt; and Sn-protoporphyrin inhibits heme oxygenase activity nearly completely, whereas inorganic tin is a powerful inducer of the renal enzyme. Contrasting effects on heme metabolism exist as well within the metalloporphyrin species as demonstrated by the effects in vivo of Co-protoporphyrin and Sn-protoporphyrin on heme oxygenase activity; the former induces the enzyme whereas the latter potently inhibits it. In vitro, however, both compounds competitively inhibit heme oxidation activity. These differences, among others which characterize metal actions in vivo and in vitro attest to the importance of pharmacokinetic, adaptive and other host factors in defining the responses of the heme-cytochrome P-450 systems to the impact of metals in the whole animal.
Study on the efficacy of biodegradable polyf(l-lactide) mesh for supporting transplanted particulate cancellous bone and marrow: experiment involving subcutaneous implantation in dogs
Authors: Yukihiko Kinoshita, Mitsuhiro Kirigakubo, Maseru Kobayashi, Takatoshi Tabata, Kaizo Shimura, Yoshito Ikada
Journal: Biomaterials (1993)