tbuckley/cabot-search huggingface dataset:
THE ÆTIOLOGY OF TYPHOID FEVER.
Authors: J. F. TODD
Journal: JAMA (1884)

In the selection of the subject of this paper, I was not unmindful of the fact that the ground had been traversed by the ripest men in our profession, and that I could add nothing new to the thoughts and opinions that have found a fitting place in medical literature. The topic was chosen because of its inherent interest and importance with the hope that the society might be stimulated to a discussion of the subject. The general prevalence of typhoid fever in this country and Europe during the past few years, and the revival of the theory of "a contagium vivum" constituting its essential cause, has served to develop general distrust in prevailing methods of treatment, and widely divergent opinions respecting its ætiology. The researches of Graves, Brettonneau, Louis, Murchison, Budd and Liebermeister, the contributions of scores of learned authorities, and the recorded observations of thousands of intelligent practitioners
Bowel motility and colonic cancer.
Authors: A. R. Walker, B. F. Walker
Journal: BMJ (1969)

BRITIShilarity and movement (presumably includ- ing eye movement) during the compression phase due to the combined effects of warmth and nitrogen narcosis, thus assisting the flow of nitrogen-laden tears between the lens and cornea, while during decompression the chamber was, as is usual, rather cold and foggy, with the subjects relatively immobile, thus minimizing any flow of tears which might have helped to wash out the nitrogen.As the other eye was only slightly affected, it must be presumed that there was a difference in the fit, and hence in the flow of tears under the two lenses, causing either less absorption or better elimination of gas from the other eye.-Iam, etc.,
Detection of Abdominal Hemangiomatosis During Technetium-99m DTP A Renal Imaging
Authors: RENE P. du CRET, D GORDON DRAKE, BECKY L. MURRAY, ROBERT J. BOUDREAU, MERLE K. LOKEN
Journal: Clinical Nuclear Medicine (1988)

Tc-99m DTPA renography is of unquestionable value in the pediatric patient with ascites. Flow phase imaging may provide additional benefit in the detection of hemangiomatosis as a cause of transudative ascites.
New insights into the pathogenesis of asthma
Authors: Jack A. Elias, Chun Geun Lee, Tao Zheng, Bing Ma, Robert J. Homer, Zhou Zhu
Journal: Journal of Clinical Investigation (2003)

Historical perspectiveAsthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity.Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary disorder characterized by the generalized reversible obstruction of airflow and to define reversibility as a greater than 12% increase in the patient's forced expiratory volume in 1 second (FEV 1 ) that occurs either spontaneously or with therapy.Airway hyperresponsiveness, an exaggerated bronchospastic response to nonspecific agents such as methacholine and histamine or specific antigens, is the physiologic cornerstone of this disorder.A diagnosis of asthma is established based on a history of recurrent wheeze, cough, or shortness of breath, reversible airway obstruction demonstrated by pulmonary-function testing, and, in cases where questions exist, a methacholine challenge demonstrating airway hyperresponsiveness.It has long been assumed that patients with asthma experience intermittent attacks and have relatively normal lung function during intervening periods.More recent studies have demonstrated that asthma can cause progressive lung impairment and, in some patients, eventuate in partially reversible or irreversible airway obstruction.Any discussion of asthma must take into account the recent increase in its prevalence.Since approximately 1980, the frequency of this disorder has almost doubled.As a result of this "epidemic," asthma now affects approximately 8-10% of the population in the US, is the leading cause of hospitalization among children less than 15 years of age, and costs society billions of dollars annually.This increase in prevalence is not simply due to diagnostic transference or increased diagnostic awareness, since asthma mortality rates have also increased during this interval.
Mathematical Models of Cancer Stem Cells
Authors: Franziska Michor
Journal: Journal of Clinical Oncology (2008)

Human cancers are thought to be sustained in their growth by a pathologic counterpart of normal adult stem cells: cancer stem cells. This concept was first developed in human myeloid leukemias and is today being extended to solid tumors such as breast and brain cancers. A quantitative understanding of cancer stem cells requires a mathematical framework to describe the dynamics of cancer initiation and progression, the response to treatment, and the evolution of resistance. In this review, I use chronic myeloid leukemia as an example to discuss how mathematical and computational techniques have been used to gain insights into the biology of cancer stem cells.
Abstract 4440: Identification and characterization of small molecule inhibitors that radiosensitize K-RAS mutant rectal cancers.
Authors: Laura B. Kleiman, Angela Krebs, Stephen Kim, Theodore S. Hong, Kevin M. Haigis
Journal: Cancer Research (2013)

Abstract Around 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with resistance to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) (“radiosensitizers”) that could be incorporated into current treatment strategies for K-RAS mutant locally advanced rectal cancer (LARC) patients. We first optimized a high-throughput assay for measuring individual and combined effects of SMIs and IR that produces similar results to the gold standard colony formation assay. Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5-fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and enhanced radiosensitization by AZD7762 but not by BEZ235. This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC. Citation Format: Laura B. Kleiman, Angela Krebs, Stephen Kim, Theodore S. Hong, Kevin M. Haigis. Identification and characterization of small molecule inhibitors that radiosensitize K-RAS mutant rectal cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4440. doi:10.1158/1538-7445.AM2013-4440
Localization of epidermal growth factor receptor in hepatocyte nuclei
Authors: Ulrich Marti, Susan Jo Burwen, Alan Wells, Mary E. Barker, Sandra Huling, Anna M. Feren, Albert L. Jones
Journal: Hepatology (1991)

Experiments undertaken to investigate the binding of epidermal growth factor by hepatocyte nuclei showed that: (a) isolated nuclei from both normal and regenerating rat liver are capable of binding 125I-epidermal growth factor, (b) the nuclear epidermal growth factor-binding protein is similar in molecular weight to the plasma membrane epidermal growth factor receptor, (c) monoclonal antibodies produced against the plasma membrane epidermal growth factor receptor recognize the nuclear epidermal growth factor receptor and (d) the nuclear receptor has an affinity for epidermal growth factor comparable to that of the plasma membrane receptor, but fewer (approximately 10%) nuclear receptors are available per protein unit compared with the plasma membrane.
From the authors:
Authors: P-O. Bridevaux, M. Gerbase, T. Rochat
Journal: European Respiratory Journal (2009)

We thank J.P. de Torres and co-workers for their interest in our recently published paper regarding the effect of body weight gain on systemic inflammation in subjects with chronic obstructive pulmonary disease (COPD) 1. Their comments highlight important issues concerning the sex discrepancies reported in the literature on the effect of systemic inflammation and COPD outcomes. First, we believe that this is still a subject of controversy; the potential prognostic advantage of females with COPD reported in some clinical studies has not been confirmed by other reports 2. There are multiple reasons for these conflicting findings. In clinical settings, under diagnosis of …
Abstract 2464: Angiomotin plays a tumor suppressor role by sequestering oncogenic YAP/TAZ proteins and decreasing amphiregulin secretion in lung cancer
Authors: Po-Lin Kuo, Jen-Yu Hung, Ya-Ling Hsu
Journal: Cancer Research (2014)

Abstract Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying the majority of lung cancer-related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic YAP/TAZ proteins, suggesting its potential role in tumor suppression. However, the functional role of AMOT in lung cancer remains unknown. We observed that the expression of AMOT was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreasing cytoplasmic sequestration and increasing nuclear translocation of oncogenic co-activators YAP/TAZ, resulting in an increased expression of the growth factor amphiregulin. The tumor promotion by AMOT knockdown was reversed when YAP/TAZ were absent or anti-amphiregulin antibodies were present. Further, AMOT knockdown increased the spread of Lewis lung carcinoma in vivo. Our findings suggest that AMOT is a crucial suppressor of lung cancer metastasis. These observations highlight the critical role of AMOT as a tumor suppressor, and the potential of AMOT as a prognostic biomarker and potential therapy target for lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Po-Lin Kuo, Jen-Yu Hung, Ya-Ling Hsu. Angiomotin plays a tumor suppressor role by sequestering oncogenic YAP/TAZ proteins and decreasing amphiregulin secretion in lung cancer. [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 2464. doi:10.1158/1538-7445.AM2014-2464
Does physical fitness of today's children foretell the shape of tomorrow's adult America?
Authors: J. W. Zylke
Journal: JAMA (1988)

ARE AMERICAN adults fitness fanatics or couch potatoes? Similarly, are children naturally active and fit or too sedentary? A recent study attempts to resolve these contrary perceptions by assessing activity patterns and fitness levels of young children and by investigating the factors affecting fitness. The National Children and Youth Fitness Study II, while not answering the question of whether the nation's younger children are more or less fit than in the recent past, suggests that their preparation for lifetime physical activity may be inadequate and provides a basis for future comparisons. Physical fitness in adults, of course, has been associated with a decreased risk of coronary heart disease, diabetes, obesity, and osteoporosis. Although no studies have directly examined the relationship between exercise patterns in childhood and fitness or health in adults, it seems "logical to expect that the experiences of kids would bear on their activity habits later in life,"
L-Asparaginase II Produced by Salmonella Typhimurium Inhibits T Cell Responses and Mediates Virulence
Authors: Amy L. Kullas, Michael McClelland, Hee-Jeong Yang, Jason W. Tam, AnnMarie Torres, Steffen Porwollik, Patricio Mena, Joseph B. McPhee, Lydia Bogomolnaya, Helene Andrews-Polymenis, Adrianus W.M. van der Velden
Journal: Cell Host & Microbe (2012)
Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset
Authors: Christelle Harly, Yves Guillaume, Steven Nedellec, Cassie-Marie Peigné, Hannu Mönkkönen, Jukka Mönkkönen, Jianqiang Li, Jürgen Kuball, Erin J. Adams, Sonia Netzer, Julie Déchanet-Merville, Alexandra Léger, Thomas Herrmann, Richard Breathnach, Daniel Olive, Marc Bonneville, Emmanuel Scotet
Journal: Blood (2012)
Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1
Authors: V. Kumari, M. Babina, T. Hazzan, M. Worm
Journal: British Journal of Dermatology (2014)

Thymic stromal lymphopoietin (TSLP) is an extensively studied cytokine linked to the pathogenesis of allergic diseases, but the inherent activities behind TSLP expression are not well defined.To explore the conditions favourable to TSLP induction outside of a typically allergic set-up and determine the associated mechanisms, and to assess whether TSLP is similarly controlled in murine and human skin.A combination of primary keratinocytes, skin explants/epidermal sheets and in vivo strategies was employed. The skin of wild-type and tumour necrosis factor knockout (TNF-/-) mice was subjected to acute irritation. Cells and specimens were stimulated with a range of TSLP inducers in the presence or absence of neutralizing antibodies. TSLP was quantitated by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry.In addition to cytokines, skin irritation brought about by various causes (e.g. shaving, scratching and chemical perturbation) elicited uniformly high-level production of TSLP, which entered the circulatory system. Despite the potency of TNF-α as an in vitro TSLP inducer, the use of TNF-/- mice revealed that this mechanism was completely independent of endogenous TNF-α. Conversely, irritation-elicited TSLP depended on interleukin (IL)-1, which had a more pronounced influence in human skin than in murine skin. Murine and human skin differed considerably regarding TSLP regulation.Thymic stromal lymphopoietin is a general responder to disrupted skin homeostasis and may have a role in triggering the alarm system of the skin. TSLP induction is rapid, transient and driven by a mechanism that does not involve TNF-α, but partially relies on the evolutionarily ancient IL-1 system. The irritated skin secretes TSLP into the circulatory system. TSLP regulation varies between species.
P121Impaired autophagic flux in Mybpc3-targeted mice with cardiac hypertrophy
Authors: S Schlossarek, S Singh, B Geertz, L Carrier
Journal: Cardiovascular Research (2014)

Background: The autophagy-lysosome pathway (ALP) is one of the major systems responsible for the degradation of cellular proteins and organelles. In cardiovascular diseases, activation or inhibition of this pathway has been described. However, there is not much known about alterations of the ALP in hypertrophic cardiomyopathy (HCM). Mutations in the MYBPC3 gene encoding cardiac myosin binding protein C (cMyBP-C) frequently cause HCM. In our previous study, elevated protein levels of autophagic markers, such as LC3 or p62, were obtained in Mybpc3-targeted knock-in (KI) and knock-out (KO) mice with HCM. However, these data did not allow distinguishing between impaired or activated ALP. We therefore investigated the autophagic flux in isolated neonatal cardiac myocytes and in vivo in KI, KO and wild-type (WT) mice. Methods: KI mice carry a Mybpc3 point mutation and express low levels of mutant cMyBP-C, whereas KO mice do not express any cMyBP-C. KI, KO and WT mice of different postnatal ages (10, 30, and 57-week-old) were treated with 40 mg/kg ALP inhibitor leupeptin for 1 hour. Neonatal cardiac myocytes were treated with 10 μM ALP inhibitor chloroquine for 24 h. Autophagic flux was analyzed by Western blot detecting the turnover of cytosolic LC3-I to autophagosome membrane-bound LC3-II. Lysosomal function was assayed by cathepsin D protein level and activity. Autophagosome-lysosome fusion was indirectly measured by Rab7 protein level. Results: Leupeptin treatment induced LC3-II accumulation in WT hearts, resulting in an increased LC3-II/LC3-I ratio. The increase in LC3-II/LC3-I ratio was less in KI than WT mice upon leupeptin treatment, suggesting ALP impairment in KI. The extent of impairment increased with age of the mice, being absent in neonatal cardiac myocytes, low in 10-, moderate in 30-, and severe in 57-week-old KI mice. Similar results were obtained in 57-week-old KO mice, excluding mutant cMyBP-C as a trigger. Protein level and activity of cathepsin D did not differ between groups, indicating intact lysosomal function. In contrast, Rab7 protein level was lower in KI and KO mice than in WT, suggesting a block in the fusion of autophagosomes and lysosomes. Conclusion: These data provide evidence for an impaired autophagic flux that becomes more severe with age in HCM mice lacking functional cMyBP-C. This impairment results probably from a block in autophagosome-lysosome fusion rather than a lysosomal dysfunction.
Treatment of platelet‐alloimmunization with cyclosporin a in a patient with aplastic anemia
Authors: Masahiro Yamamoto, Hiroshi Ideguchi, Junji Nishimura, Hajime Nawata, Shoichi Inaba, Kazuo Tokunaga, Hiroyuki Kiyokawa, Yoshiaki Maeda
Journal: American Journal of Hematology (1990)

Abstract The development of alloantibodies to platelets is a major problem in the supportive management of thrombocytopenia in patients with severe aplastic anemia. We report here a case of aplastic anemia refractory to platelet transfusion. An immunosuppressant, cyclosporin A, which was used for the therapy of aplastic anemia, modulated alloimmunization to platelets in this patient, followed by repeated platelet transfusion. The treatment reduced platelet alloantibodies detected by anti‐human immunoglobulin lymphocytotoxicity test, with change of the CD4/CD8 ratio in T lymphocytes in peripheral blood. These results suggest the usefulness of cyclosporin A for the prevention of platelet alloimmunization.
Distribution of radiocolloids after injection into knee
Authors: J. M. Gumpel
Journal: Annals of the Rheumatic Diseases (1977)

Distribution of radiocolloids after injection into knee Sir, Williams et al. (1976) have provided useful confirmation of the effectiveness of bed rest in ensuring maximum retention of isotope in a joint, particularly of gold 198.One sentence in their article is perhaps misleading.It should be clearly understood that in only one of the publications that they quote were some patients not strictly rested in bed (Gumpel et al., 1973).In our single centre comparison of four yttrium 90 colloids (Gumpel et al., 1975) we compared the retention of citrate, ferric hydroxide, resin, and silicate, in randomly selected patients in identical conditions.Although our figures for retention of ferric hydroxide were not grossly different from those given by Williams et al., the variability of retention in the knee in individual patients was much greater with ferric hydroxide than with silicate.This is clearly shown in one figure in this paper and the results that they have quoted from a paper on chromosomal damage (Gumpel and Stevenson, 1975) are only a brief synopsis of that study.For this reason we chose to use yttrium 90 silicate rather than ferric hydroxide.
MIGRATION INHIBITORY EFFECT OF CELL‐FREE SUPERNATANTS FROM PHA‐ACTIVATED CULTURES OF HUMAN MONONUCLEAR LEUKOCYTES
Authors: JENS ERIK CLAUSEN
Journal: Allergy (1976)

A two-step test for the demonstration of phytohaemagglutinin (PHA)-induced production of migration inhibitory factor (MIF) was investigated. In the first step, human purified mononuclear leukocytes were activated by incubation with PHA for 1 h. Then the cells were washed thoroughly and cultured for 1 to 4 days in TC medium without PHA. In the second step, the MIF-activity of the cell-free culture supernatants was tested on non-separated human leukocytes. The migration inhibition reaction was demonstrated by the agarose migration technique. The supernatants might have been contaminated by PHA, but it was shown that such contamination would be unable to cause any appreciable migration inhibition of the indicator leukocytes.
DIAGNOSTIC SIGNIFICANCE OF BLOOD SUGAR FINDINGS
Authors: Christopher J. McLoughlin
Journal: JAMA (1953)

During the past few years the American Diabetes Association has sponsored a Diabetes Detection Week throughout the entire country. Many screening tests have been devised for finding the unknown diabetic, and a tremendous amount of work has been done on diabetes detection. The late Dr. James Edgar Paullin, in 1949, challenged the Georgia Department of Public Health to incorporate a test for abnormal carbohydrate metabolism in their Voluntary Multiphasic Health Test program, which included a chest roentgenogram, a test for anemia, and a serologic test for syphilis. The Anthrone method of blood sugar analysis was developed, 1 and, in 1950, the rapid screening of large numbers of patients was begun. 2   Since April, 1950, about 600,000 persons in the state of Georgia have voluntarily submitted to this screening procedure for abnormal carbohydrate metabolism. A report on almost 250,000 of those screened during the past 18 months was made at a
Pressure Ulcer Treatment Strategies
Authors: M.E. Beth Smith, Annette Totten, David H. Hickam, Rongwei Fu, Ngoc Wasson, Basmah Rahman, Makalapua Motu’apuaka, Somnath Saha
Journal: Annals of Internal Medicine (2013)

Pressure ulcers affect as many as 3 million Americans and are major sources of morbidity, mortality, and health care costs.To summarize evidence comparing the effectiveness and safety of treatment strategies for adults with pressure ulcers.MEDLINE, EMBASE, CINAHL, Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database for English- or foreign-language studies; reference lists; gray literature; and individual product packets from manufacturers (January 1985 to October 2012).Randomized trials and comparative observational studies of treatments for pressure ulcers in adults and noncomparative intervention series (n > 50) for surgical interventions and evaluation of harms.Data were extracted and evaluated for accuracy of the extraction, quality of included studies, and strength of evidence.174 studies met inclusion criteria and 92 evaluated complete wound healing. In comparison with standard care, placebo, or sham interventions, moderate-strength evidence showed that air-fluidized beds (5 studies [n = 908]; high consistency), protein-containing nutritional supplements (12 studies [n = 562]; high consistency), radiant heat dressings (4 studies [n = 160]; moderate consistency), and electrical stimulation (9 studies [n = 397]; moderate consistency) improved healing of pressure ulcers. Low-strength evidence showed that alternating-pressure surfaces, hydrocolloid dressings, platelet-derived growth factor, and light therapy improved healing of pressure ulcers. The evidence about harms was limited.Applicability of results is limited by study quality, heterogeneity in methods and outcomes, and inadequate duration to assess complete wound healing.Moderate-strength evidence shows that healing of pressure ulcers in adults is improved with the use of air-fluidized beds, protein supplementation, radiant heat dressings, and electrical stimulation.