tbuckley/cabot-search huggingface dataset:
Abstract 3342: The p110β isoform of PI3K modulates response to growth factor receptor signaling in breast cancer cells irrespective of PTEN status
Authors: Stephanie J. Bouley, Lloye M. Dillon, Todd W. Miller
Journal: Cancer Research (2014)

Abstract The class 1a phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, survival, and metabolism. These PI3Ks are heterodimeric lipid kinases composed of a p85 regulatory subunit and a p110 catalytic subunit (p110α, p110β, or p110δ). p110α and p110β play distinct roles in PI3K signaling in carcinoma cells. p110α is activated by growth factor receptor kinase signaling. In contrast, p110β was shown to play a role in insulin metabolic action, G protein-coupled receptor (GPCR) signaling, and oncogenic transformation. Cancer cells deficient in PTEN, the tumor suppressor phosphatase that antagonizes PI3K signaling, have been shown to be sensitized to pharmacological inhibitors of p110β. As a result, early clinical studies with p110β inhibitors are restricted to patients with PTEN-deficient cancers. However, analysis of data from the Genomics of Drug Sensitivity in Cancer database revealed that genetic lesions in PTEN or PIK3CA (encodes p110α) were significantly and independently associated with increased sensitivity to the p110β inhibitor AZD6284. Among 668 cancer cell lines, 96, 57, and 5 lines harbored alterations in PTEN, PIK3CA, or both, respectively. Among 61 cell lines with IC50 values ≤2 μM, only 25 harbored an alteration in PTEN and/or PIK3CA. Thus, a significant fraction of cancer cell lines (and tumors) without PTEN alterations are likely to be sensitive to p110β inhibition. To explore the role of p110β in PI3K signaling in ER+ breast cancer, we treated cells with the p110β inhibitor GSK2636771 and monitored effects on growth factor-induced activation of AKT and MEK/ERK. We found that p110β inhibition reduced basal pAKT and pERK levels in PTEN-deficient cells. Furthermore, p110β inhibition reduced insulin-like growth factor 1 (IGF-1)-induced pAKT levels and delayed the onset of AKT phosphorylation in both PTEN-deficient and PTEN-wild-type cells. In contrast, p110β inhibition sensitized both PTEN-wildtype and PTEN-deficient cells to heregulin stimulation. These results indicate that p110β desensitizes cells to IGF-1 stimulation and hyper-sensitizes them to heregulin stimulation and suggests that p110β regulates downstream AKT and MEK/ERK activation in response to growth factor receptor activation. Our findings advocate for the testing of p110β inhibitors in cell lines (and tumors) selected based on growth factor dependence and PTEN status. Citation Format: Stephanie J. Bouley, Lloye M. Dillon, Todd W. Miller. The p110β isoform of PI3K modulates response to growth factor receptor signaling in breast cancer cells irrespective of PTEN status. [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 3342. doi:10.1158/1538-7445.AM2014-3342
Expression of Concern: Schiffl H, et al. Daily Hemodialysis and the Outcome of Acute Renal Failure. N Engl J Med 2002;346:305-10.
Authors: Jeffrey M. Drazen, Julie R. Ingelfinger, Gregory D. Curfman
Journal: New England Journal of Medicine (2003)

In the issue of January 31, 2002, we published a study by Helmut Schiffl, M.D., Susanne M. Lang, M.D., and Rainald Fischer, M.D.1 It has come to our attention, through communication with Klaus Peter, Dean of the Medical Faculty at Ludwig Maximilians University in Munich, Germany, that there is an ongoing investigation into potential scientific misconduct in the performance of this study. We will inform our readers of the outcome of this investigation when it is complete.
MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma
Authors: Aldo M. Roccaro, Antonio Sacco, Brian Thompson, Xavier Leleu, Abdel Kareem Azab, Feda Azab, Judith Runnels, Xiaoying Jia, Hai T. Ngo, Molly R. Melhem, Charles P. Lin, Domenico Ribatti, Barrett J. Rollins, Thomas E. Witzig, Kenneth C. Anderson, Irene M. Ghobrial
Journal: Blood (2009)
What Kind of Basic Science for Clinical Medicine?
Authors: Alvan R. Feinstein
Journal: New England Journal of Medicine (1970)

Abstract Clinical medicine involves explanatory decisions for the names, mechanisms and causes of disease, and managerial decisions for therapeutic interventions to prevent or alter disease. Although both types of decision depend on the intellectual constructions used in experiments, the scientific procedures required for managerial decisions about sick people differ from the methods used for explanatory science in the simpler materials of laboratory work. Because the scientific thrust of medicine has been directed mainly toward explanatory mechanisms, a suitable "basic science" has not yet been developed for making and evaluating managerial decisions. The challenges of the new "basic science" in clinical management include reducing observer variability, developing new systems of taxonomy, establishing criteria for diverse clinical judgments, and improving quantification for "normality," prognosis and therapy. Although language, logic, behavioral science and statistics will offer methodologic assistance, the fundamental strategies must be derived from direct clinical experience with patients.
Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation
Authors: Pieter J. Bakker, Loes M. Butter, Lotte Kors, Gwendoline J.D. Teske, Jan Aten, Fayyaz S. Sutterwala, Sandrine Florquin, Jaklien C. Leemans
Journal: Kidney International (2013)
Unidentified Gram-Negative Rod Infection
Authors: THOMAS BUTLER
Journal: Annals of Internal Medicine (1977)

A Gram-negative bacillus that defies identification was isolated from blood cultures of 17 patients with fever. Fifteen patients were male adults, and 14 patients had underlying diseases, including previous splenectomy in five, which impair host defenses against infection. Illnesses occurred in the summer and autumn in 14 cases and had been recently preceded by dog bites in 10 cases. Clincal syndromes included cellulitis in seven cases, primary bacteremia without localization in four, purulent meningitis in four, and endocarditis in three. Three patients died. The organism grows slowly on blood or chocolate agar in 10% CO, is oxidase- and catalase-positive, and is negative for nitrate reduction, indole production, and urease. It produces acid from glucose, lactose, and maltose. These features distinguish it from all previously described and classified bacteria. Furthermore, the epidemiologic features of the patients suggest that this organism is an opportunistic invader and may have an animal reservoir in nature.
Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis
Authors: Vitalyi Senyuk, Kislay K. Sinha, Donglan Li, Ciro R. Rinaldi, Sastry Yanamandra, Giuseppina Nucifora
Journal: Cancer Research (2007)

Abstract Recurring chromosomal translocations observed in human leukemia often result in the expression of fusion proteins that are DNA-binding transcription factors. These altered proteins acquire new dimerization properties that result in the assembly of inappropriate multimeric transcription complexes that deregulate hematopoietic programs and induce leukemogenesis. Recently, we reported that the fusion protein AML1/MDS1/EVI1 (AME), a product of a t(3;21)(q26;q22) associated with chronic myelogenous leukemia and acute myelogenous leukemia, displays a complex pattern of self-interaction. Here, we show that the 8th zinc finger motif of MDS1/EVI1 is an oligomerization domain involved not only in interaction of AME with itself but also in interactions with the parental proteins, RUNX1 and MDS1/EVI1, from which AME is generated. Because the 8th zinc finger motif is also present in the oncoprotein EVI1, we have evaluated the effects of the interaction between RUNX1 and EVI1 in vitro and in vivo. We found that in vitro, this interaction alters the ability of RUNX1 to bind to DNA and to regulate a reporter gene, whereas in vivo, the expression of the isolated 8th zinc finger motif of EVI1 is sufficient to block the granulocyte colony-stimulating factor–induced differentiation of 32Dcl3 cells, leading to cell death. As EVI1 is not detected in normal bone marrow cells, these data suggest that its inappropriate expression could contribute to hematopoietic transformation in part by a new mechanism that involves EVI1 association with key hematopoietic regulators, leading to their functional impairment. [Cancer Res 2007;67(12):5658–66]
802-1 Relationship between contractile reserve and diastolic function in hibernating myocardium
Authors: Erberto Carluccio, Paolo Biagioli, Mariagrazia Sardone, Federico Marroni, Gianfranco Alunni, Adriano Murrone, Gabriella Vincenti, Ketty Savino, Maurizio Bentivoglio, Temistocle Ragni, Claudio Giombolini, Giuseppe Ambrosio
Journal: Journal of the American College of Cardiology (2004)
Epithelial-mesenchymal transition of cultured rat neonatal hepatocytes is differentially regulated in response to epidermal growth factor and dimethyl sulfoxide
Authors: R Pagan, I Martin, M Llobera, S Vilaro
Journal: Hepatology (1997)

Neonatal rat hepatocytes cultured in the absence of added growth factors dedifferentiate by epithelial–mesenchymal transition (EMT). This involves the loss of their typical differentiation markers, the acquisition of a migrating morphology, and a change in the expression of the intermediate filament (IF) proteins. We attempted to determine whether the EMT of cultured neonatal rat hepatocytes could be modulated by factors that maintain and promote the differentiation state of adult and fetal hepatocytes such as epidermal growth factor (EGF) and dimethyl sulfoxide (DMSO). By (3H)–thymidine incorporation, Western blotting analysis, flow cytometry, and double–immunofluorescence studies, we found that both factors have marked but opposite effects on the EMT and on proliferation of neonatal liver cells. In DMSO treatment, albumin levels were higher than in the nontreated cells at all days studied. Moreover, DMSO reduced cytokeratin levels and inhibited cell proliferation, acquisition of the fibroblast–like morphology, and vimentin expression typical of the EMT. The increase in vimentin–positive cells in serum–free medium was not observed in DMSO cultures. EGF also increased albumin levels at all days studied. In contrast, EGF treatment induced hepatocyte proliferation and enhanced vimentin and cytokeratin expression. However, the increase in vimentin levels did not correlate with a significant increase in the number of vimentin–positive cells. Moreover, vimentin–positive cells in EGF treatment were also cytokeratin–positive and albumin–positive, and they maintained epithelioid morphology in spite of the vimentin network. These results indicate that EMT of cultured rat neonatal hepatocytes is differentially regulated in response to EGF and DMSO.
Treatment of Hay Fever by Dunbar's Remedies (Pollantin).
Authors: E. Gard Edwards
Journal: JAMA (1906)

<h3>La Junta, Colo., Aug. 22, 1906.</h3><h3>To the Editor:</h3> —I have read with interest the reports made throughThe Journalon the use of pollantin in hay fever. My experience has been very limited; I have never used it until within the last two months. Four cases treated resulted as follows: 1. A very aggravated case, in an aged person, who every year suffers intensely. The relief from the eye symptoms was immediate. For the nasal symptoms, which were but slightly relieved, a weak solution of adrenalin was ordered (this previously had given to this patient relief for a few moments only) to be followed by the pollantin. Relief was very marked and three weeks later patient reported herself as being more comfortable than she had ever dared hope to be. 2. First attack, in a person who has resided here several years. Eye symptoms predominated. Relief was very rapid.
Use of Resuscitation-Promoting Factor Proteins Improves the Sensitivity of Culture-based Tuberculosis Testing in Special Samples
Authors: Wei Huang, Yingjie Qi, Yujie Diao, Fei Yang, Xiaodan Zha, Cuiping Ren, Dake Huang, Kees L. M. C. Franken, Tom H. M. Ottenhoff, Qingsi Wu, Jijia Shen
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Restrictive Cardiomyopathy, Atrioventricular Block and Mild to Subclinical Myopathy in Patients With Desmin-Immunoreactive Material Deposits
Authors: Eloisa Arbustini, Patrizia Morbini, Maurizia Grasso, Roberta Fasani, Laura Verga, Ornella Bellini, Barbara Dal Bello, Carlo Campana, Giovanni Piccolo, Oreste Febo, Cristina Opasich, Antonello Gavazzi, Victor J Ferrans
Journal: Journal of the American College of Cardiology (1998)
Amoebic Abscess of Spleen
Authors: J. R. Frank
Journal: BMJ (1944)

MEDICAL JOUHNAL bowels were normal except for the distension of the latter with gas.The liver was of normal size, but notably pale.Gall-bladder was normal, and filled with very pale bile.The spleen was twice the normal size, and was red and soft.The suprarenals and pancreas appeared normal.Kidneys normal except for some dilatation of the right pelvis and ureter.Bladder normal.Uterus recently delivered; placenta had been attached at fundus posteriorly; well contracted, normal, no tears of cervix.Bruising of vagina.Tubes and ovaries normal.Skull, meninges, and brain all normal; no cerebral oedema, etc.Section Reports.-Thethyroid shows patchy epithelial hyperplasia and increase in stroma, but no appreciable lymphocytic infiltration.The thymus (see Fig. ) has typical Hassall's corpuscles.There is .......
Adjuvant irradiation for breast cancer
Authors: I. Kunkler
Journal: BMJ (2000)

The use of postoperative adjuvant irradiation in breast conservation and after mastectomy is increasing. However, concerns exist about the risks of cardiac morbidity and mortality induced by radiation. These risks are worrying because three randomised trials have suggested that locoregional irradiation after mastectomy, when combined with appropriate systemic therapy, improves local control and survival compared with systemic therapy alone in both premenopausal and postmenopausal women at high risk of local relapse.1–3 In 1995 the Early Breast Cancer Trialists' Collaborative Group contributed a valuable overview of 36 randomised trials of surgery and radiotherapy (including 28 405 women for whom data on mortality were available).4 There was no difference in overall survival between the irradiated and non-irradiated groups after mastectomy or breast conserving surgery. Although radiotherapy did reduce deaths from breast cancer, it was associated with an increased risk of death from other causes.

These other deaths were mainly cardiovascular. Patients aged 60 or older at the time of randomisation were particularly at risk of death from causes other than breast cancer. Data were not included on the laterality of the primary …
What functional imaging of the human brain can tell about handedness and language
Authors: Goulven Josse, Nathalie Tzourio-Mazoyer
Journal: Behavioral and Brain Sciences (2003)

Anatomo-functional studies in humans point out that handedness and language-related functional laterality are not correlated – except during language production; and that the convergence of language and hand control is located in the precentral gyrus, whereas executive functions required by movement imitation and phonological and semantic processing converge onto Broca's area. Multiple domains are likely to be actors in language evolution.
Mucosal expression and luminal release of epidermal and transforming growth factors in patients with duodenal ulcer before and after eradication of Helicobacter pylori.
Authors: P C Konturek, H Ernst, S J Konturek, A J Bobrzynski, G Faller, C Klingler, E G Hahn
Journal: Gut (1997)

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and protection but their involvement in Helicobacter pylori associated duodenal ulcer has been little examined.To assess gastric acid secretion, plasma gastrin concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of these peptides and their receptor (EGFr) as well as salivary and gastric luminal release of EGF under basal conditions and after pentagastrin stimulation in 10 healthy subjects and in 25 H pylori positive patients with duodenal ulcer before and after two weeks of triple anti-H pylori therapy and four weeks after the termination of this therapy.Pentagastrin stimulation caused a significant increase in salivary and gastric release of EGF both in healthy controls and patients with duodenal ulcers but in the patients, the eradication of H pylori resulted in several fold higher gastric luminal (but not salivary) EGF release than before the anti-H pylori therapy. Mucosal contents of immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and EGFr in H pylori positive patients with duodenal ulcer were significantly higher than those in healthy H pylori negative controls and this increase persisted after eradication of H pylori. Basal plasma gastrin was significantly reduced after two weeks of triple therapy and four weeks after the H pylori eradication all ulcers were completely healed.(1) H pylori infection in patients with duodenal ulcer was accompanied by enhanced plasma gastrin and increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and enhancement of gastric (but not salivary) luminal release of EGF, particularly after pentagastrin stimulation; and (3) enhanced mucosal content and expression of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute to ulcer healing after eradication of H pylori.
Mannitol and Amphotericin B
Authors: Seymour Jotkowitz
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In the brief clinical report by Dr Rosch and colleagues entitled "Reduction of Amphotericin B Nephrotoxicity With Mannitol" (235:1995, 1976), there may be an important omission. Nowhere is either the concentration or the volume of the infused mannitol mentioned. Since this report may have important therapeutic implication, it would seem important that the authors list their technique as precisely and unambiguously as possible. Until there are data showing that concentration is irrelevant, it is the obligation of the authors, referees, and editors that all necessary information be contained in the communication. Perhaps much of the conflicting data in the scientific literature today can be traced to ambiguous descriptions of techniques by the original authors and, thus, slight (but significant) variations in the experimental conditions by subsequent investigators. Perhaps with more awareness of the problem, corrective action can be taken.
More laboratories should test for Dientamoeba fragilis infection
Authors: J J Windsor, E H Johnson
Journal: BMJ (1999)

EDITOR— Dientamoeba fragilis was first described by Jepps and Dobell in 19181 and has subsequently been shown to be an important enteric pathogen. It is therefore surprising that only a few laboratories look for this pathogen. D fragilis infections are effectively treated with di-iodohydroxyquinoline or tetracyline.2 In contrast, no treatment is available for Cryptosporidium …
C3b inactivator in the rheumatic diseases. Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase.
Authors: K Whaley, P H Schur, S Ruddy
Journal: Journal of Clinical Investigation (1976)

C3b inactivator (C3bINA) has been measured in biologic fluids by radial immunodiffusion using a monospecific antiserum prepared in rabbits, and by a hemolytic assay which measures the reduction in the capacity of EAC43 cells bearing limited C3b sites to form C3B, the alternative pathway C3 convertase. The radial immunodiffusion and hemolytic assays show a good correlation (r = 0.86 P less than 0.001). Measurement of C3bINA concentrations in the sera of patients with systemic lupus erythematosus showed that during exacerbations of disease activity C3bINA concentrations tended to be lower, usually in association with reductions in C4, C3, factor B, and properdin, and sometimes with reductions of the alternative pathway proteins, factor B, and properdin alone. Supranormal values for C3bINA were found in the sera of 14 of 20 patients with seropositive rheumatoid arthritis and 3 of 9 seronegative patients, but none of 7 patients with degenerative joint disease. Synovial fluid concentrations of C3bINA, after correction for total synovial fluid protein and serum concentration of the enzyme, were significantly reduced in patients with rheumatoid arthritis compared to patients with degenerative joint disease (P less than 0.05). In both serum and synovial fluid from patients with rheumatoid arthritis, there was a good correlation between the concentrations of C3bINA and those of C3, factor B, and properdin, but not that of C4, suggesting that levels of C3bINA may serve to modulate recruitment of the properdin amplification loop in this disease.
Points from Letters: Merrison Report
Authors: S. Holliday
Journal: BMJ (1975)

Public health interventions and health technologies are commonly described as ‘complex’, as they involve multiple interacting components and outcomes, and their effects are largely influenced by contextual interactions and system-level processes. Systematic reviewers and guideline developers evaluating the effects of these complex interventions and technologies report difficulties in using existing methods and frameworks, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE). As part of a special series of papers on implications of complexity in the WHO guideline development, this paper serves as a primer on how to consider sources of complexity when using the GRADE approach to rate certainty of evidence. Relevant sources of complexity in systematic reviews, health technology assessments and guidelines of public health are outlined and mapped onto the reported difficulties in rating the estimates of the effect of these interventions. Recommendations on how to address these difficulties are further outlined, and the need for an integrated use of GRADE from the beginning of the review or guideline development is emphasised. The content of this paper is informed by the existing GRADE guidance, an ongoing research project on considering sources of complexity when applying the GRADE approach to rate certainty of evidence in systematic reviews and the review authors’ own experiences with using GRADE.