tbuckley/cabot-search huggingface dataset:
Autophagy: a druggable process that is deregulated in aging and human disease
Authors: Guido Kroemer
Journal: Journal of Clinical Investigation (2015)

Autophagy ("self-eating") constitutes one of the most spectacular yet subtly regulated phenomena in cell biology. Similarly to cell division, differentiation, and death, autophagy is perturbed in multiple diseases, in that excessive or deficient autophagy may contribute to pathogenesis. Numerous attempts have been launched to identify specific inducers or inhibitors of autophagy and to use them for the therapeutic correction of its deregulation. At present, several major disease categories (including but not limited to age-related, cardiovascular, infectious, neoplastic, neurodegenerative, and metabolic pathologies) are being investigated for pathogenic aberrations in autophagy and their pharmacologic rectification. Driven by promising preclinical results, several clinical trials are exploring autophagy as a therapeutic target.
528 IMPROVEMENT OF SURVIVAL IN 24 MONTHS OF PATIENTS IN LIVER TRANSPLANT LIST AFTER THE INTRODUCTION OF MELD IN BRAZIL
Authors: R.S. Castro, T. Sevá-Pereira, D.B. Dei Santi, H. Machado, J.R.S. Almeida, I.F.S.F. Boin, E.C. Soares
Journal: Journal of Hepatology (2011)
RECLASSIFICATION OF THE ANEMIAS
Authors: REUBEN OTTENBERG
Journal: JAMA (1933)

In the last ten years a revolution has occurred in the views of anemia. To indicate what the advance has been I propose (1) to review briefly the work of a series of experimenters and clinicians, (2) to present a new classification of the anemias based on their work, and (3) to discuss the methods of therapy.  REVIEW OF RECENT RESEARCH  The ball was set rolling, so to speak, by an extraordinary series of researches planned on a large scale, begun before 1920 and continued with great industry to the present day by Whipple and Robscheit-Robbins 1 at the University of Rochester, N. Y. These workers studied the treatment of long sustained secondary anemia in the dog by various diets and other forms of therapy. They cleared up many inconsistencies in the work of their predecessors by the manner in which they brought about the anemias in the dog. It
Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion
Authors: Hua Lin, Zhao-Hui Tong, Qian-Qian Xu, Xiu-Zhi Wu, Xiao-Juan Wang, Xiao-Guang Jin, Wan-Li Ma, Xiang Cheng, Qiong Zhou, Huan-Zhong Shi
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: IFN-γ–producing CD4+ T (Th1) cells and IL-17–producing CD4+ T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Th1 and Th17 cells in malignant pleural effusion (MPE) remains to be elucidated.Objectives: To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models.Methods: The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-γ−/−, IL-17−/−, and wild-type mice. The effects of Th1 and Th17 cells on the development of MPE and the survival of mice bearing MPE were also investigated.Measurements and Main Results: We have demonstrated that increased Th1 and Th17 cells could be found in MPE as compared with blood and spleen. Compared with wild-type mice, Th17 cells were markedly augmented in MPE from IFN-γ−/− mice, and improved survival could be seen in IFN-γ−/− mice. Th1 cell numbers were elevated in MPE from IL-17−/− mice, and decreased survival could be seen in IL-17−/− mice. The in vitro experiments showed that IFN-γ deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway.Conclusions: In mouse models of MPE, IFN-γ inhibited Th17-cell differentiation, whereas IL-17 inhibited Th1-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-γ promoted MPE formation and mouse death.
Superficial Femoral Vein Thrombosis: A Potentially Confusing Term
Authors: Richard Schreiber
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Dr Bundens and colleagues<sup>1</sup>are correct that confusion about nomenclature can have disastrous results. In their study, they emphasize the potential for missed diagnosis and, therefore, faulty treatment. As the following case reveals, the potential is real. A 74-year-old woman was admitted to the hospital because of congestive heart failure. Asymmetric swelling of the legs suggested a concomitant diagnosis of deep venous thrombosis. A Doppler study was performed, but the written report was unavailable. In this hospital, the medical staff can listen to the dictated report via telephone. The medical student, resident, and attending physician each listened to the report independently, and each thought the patient had only superficial thrombophlebitis. When the official report became available, it became clear that the superficial femoral vein was involved. Treatment with heparin was begun, and the patient recovered. All three listeners to the report had missed the key words
Ikaros inhibits megakaryopoiesis through functional interaction with GATA-1 and NOTCH signaling
Authors: Sébastien Malinge, Clarisse Thiollier, Timothy M. Chlon, Louis C. Doré, Lauren Diebold, Olivier Bluteau, Vinciane Mabialah, William Vainchenker, Philippe Dessen, Susan Winandy, Thomas Mercher, John D. Crispino
Journal: Blood (2013)
Itraconazole Therapy for Chronic Coccidioidal Meningitis
Authors: Richard M. Tucker, David W. Denning, Bertrand Dupont, David A. Stevens
Journal: Annals of Internal Medicine (1990)

Study Objective: To assess the efficacy of orally administered itraconazole in the treatment of coccidioidal meningitis. Design: Prospective, nonrandomized open trial. Setting: Multicenter trial at an urban county hospital, a university referral center, and referring institutions. Patients: Ten patients with culture or serologic evidence of coccidioidal meningitis refractory to standard therapy. Patients receiving other systemic antifungal therapy were excluded. Intervention: Itraconazole was administered orally at dosesof 300 to 400 mg/d for a median duration of 10 months. Disease activity and drug efficacy were evaluated at initiation of therapy and at the most recent follow-up using a standardized scoring system. Measurements and Main Results: Eight of ten patients are evaluable. Of five patients receiving itraconazole as sole therapy, four have responded. All three patients receiving intraamphotericin B have had that therapy discontinued and have no evidence of active disease in the absence of intrathecal therapy. Toxicity has been minimal; one patient had mild nausea. Conclusions: Itraconazole shows impressive activity in this series of patients with refractory coccidioidal meningitis. Itraconazole in this and other fungal meningitides should be evaluated further.
Overutilization of Cultures of CSF for Mycobacteria
Authors: Terry W. Crowson
Journal: JAMA (1984)

Over a five-year period, 1,883 specimens were cultured for mycobacterium tuberculosis (TB) at our hospital. All cultures were negative, and no cases of tuberculous meningitis were diagnosed. Culture rates (percent of CSF specimens cultured for TB) varied from 74% on the Medicine and Neurology services to 6% on the Pediatric service. These culture rates have been stable for five years. These data suggest that on the Medicine and Neurology services, TB cultures of CSF are persistently overutilized. A simple rule of not culturing CSF for TB if results of the CSF analysis are normal (ie, WBC count less than or equal to 4/cu mm, protein level less than or equal to 45 mg/dL, and glucose level greater than or equal to 45 mg/dL) could reduce utilization by at least 50% without adversely affecting quality of care.
Characterization of T cell repertoire changes in acute Kawasaki disease.
Authors: J Abe, B L Kotzin, C Meissner, M E Melish, M Takahashi, D Fulton, F Romagne, B Malissen, D Y Leung
Journal: The Journal of Experimental Medicine (1993)

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease.
Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis
Authors: P M Gustafsson, P A De Jong, H A W M Tiddens, A Lindblad
Journal: Thorax (2007)

<h3>Background:</h3> A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF. <h3>Methods:</h3> A retrospective study was performed in 44 consecutive patients with CF aged 5–19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV<sub>1</sub>) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF<sub>75</sub>)) were recorded. Abnormal structure was defined as a composite HRCT score of &gt;5%, the presence of bronchiectasis or air trapping &gt;30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV<sub>1</sub> or FEF<sub>75 </sub>below the predicted mean −1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done. <h3>Results:</h3> The sensitivity to detect abnormal lung structure was 85–94% for LCI, 19–26% for FEV<sub>1</sub> and 62–75% for FEF<sub>75</sub>. Specificity was 43–65% for LCI, 89–100% for FEV<sub>1</sub> and 75–88% for FEF<sub>75</sub>. LCI correlated better with HRCT scores (Rs +0.85) than FEV<sub>1</sub> (−0.62) or FEF<sub>75 </sub>(−0.66). <h3>Conclusions:</h3> LCI is a more sensitive indicator than FEV<sub>1</sub> or FEF<sub>75 </sub>for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.
Bioethics and Secular Humanism: The Search for a Common Morality
Authors: Kenneth V. Iserson
Journal: JAMA (1992)

In their book<i>The Abuse of Casuistry</i>, Jonsen and Toulmin describe how the members of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research were able to agree on moral actions, although they were not able to agree on the ethical reasoning behind their decisions. These representatives of society's moral spectrum exemplified the premise of Tristram Engelhardt's new book, that secular humanism is the route through which individuals with differing values, "moral strangers" in his terms, can peaceably come together to agree on a common path for a pluralistic, postmodern society. What makes our society postmodern is that it is governed by "neither the institutions of religious totality that marked the Middle Ages nor the convictions of rational totality that marked the modern age." Engelhardt, an "unreconstructed Texan," set for himself a daunting task, to find or develop a rational basis for ordering
Hypoplastic and fibrotic sinus node associated with intractable tachycardia in a neonate.
Authors: K M Fox, R H Anderson, K A Hallidie-Smith
Journal: Circulation (1980)

A case of fetal and neonatal persistent atrial tachycardia is described in a child with complete transposition of the great arteries. At autopsy, serial sections of the conducting tissue showed that the sinus node was hypoplastic and markedly fibrotic. The sinus node consisted of a small area of cells clustered around the nodal artery. Although the underlying mechanism of neonatal persistent tachycardia is unclear, it is possible that the hypoplasia and fibrosis of the sinus node was the substrate in the present case. This mechanism should be considered in any newborn infant in whom sinus rhythm cannot be established.
Abstract 1117: Characterization of BAT1 (UAP56) interaction with BARD1
Authors: Renato S. Carvalho, Thales C. Nepomuceno, Michael Sweet, Alvaro N. Monteiro, Marcelo A. Carvalho
Journal: Cancer Research (2010)

Abstract BARD1 (BRCA1-associated ring domain 1) was originally identified in a yeast-two-hybrid screen as a binding partner of BRCA1. The functional heterodimer BRCA1-BARD1 is required for several of the cellular and tumour-suppressor functions of BRCA1. Both proteins interact through the N-terminal RING domain to form a heterodimeric E3 ubiquitin ligase that constitutes the major catalytic activity of the BRCA1-BARD1 complex. BARD1 is also associated to p53-mediated apoptosis, in a BRCA1-independent manner. The carboxy terminus of BRCA1 is highly acidic and contains two tandem BRCA1 C-terminal (BRCT) domains, which are characteristic of members of a large superfamily of proteins involved in DNA repair and cell cycle checkpoint control. These domains are protein-protein interacting regions that mediate the association with a number of other proteins with a role in DNA replication, DNA damage repair (DDR) pathway, transcription, cell cycle control, and ubiquitination. BARD1 also contains two tandem BRCT repeats at its C-terminus, a region shown to bind serine-phosphorylated peptides in vitro. In order to identify putative interaction-proteins with BARD1 C-terminal region we performed a yeast two hybrid (Y2H) screening using BARD1 BRCT tandem domain (aa 554-777) to screen a human testis cDNA library. We identified, among other hits, a cDNA coding for residues 308-418 of BAT1 (UAP56, C-terminal region [OMIM 142560]). UAP56 is a member of DEAD box family of ATP-dependent RNA helicases. Several studies indicate that UAP56 protein is not only essential in pre-mRNA splicing but is also important in mRNA nuclear export and cytoplasmic mRNA localization. We confirmed BAT1-BARD1 interaction by conducting co-IP analysis of ectopic expressed BARD1 and BAT1 in HEK293T cells. We are using a Y2H system approach to determine the minimal region of interaction between BARD1 and BAT1; in parallel, we are also checking for the presence of a multicomponent complex, investigating the presence of BRCA1. In order to assess the biological significance of the interaction between BARD1 and BAT1 we will determine whether this interaction is important for the activation of, or recovery from, the G2/M cell cycle checkpoint after IR and also investigate its putative involvement in p53-dependent apoptosis pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1117.
Abstract 1094: MicroRNA-30a inhibits vimentin expression and as a prognostic marker in breast cancer
Authors: Chia-Wei Chang, Chun-Wen Cheng, Hsiao-Wei Wang, Cheng-You Chen, Hou-Wei Chu, Shian-ling Ding, Hui-Chun Wang, Jyh-Cherng Yu, Chen-Yang Shen
Journal: Cancer Research (2012)

Abstract Recent studies have suggested a significant role of microRNAs (miRNAs) in the regulation of cancer development. This study examined whether they play a role in breast cancer progression.A miRNA microarray analysis was performed on laser-capture microdissected breast tumors of different lymph-node metastasis status showing different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify specific miRNAs that exhibit significant differences in expression. Functional interaction between the candidate miRNA (i.e. miR-30a) and the gene (i.e. Vim gene, coding for vimentin, a protein involved in epithelial-mesenchymal transition) possibly regulated by miR-30a was verified. We further examined whether decreased expression of miR-30a was associated with breast cancer progression.miR-30a negatively regulated vimentin expression, by binding to the 3′-untranslated region of Vim. Ectopic expression of miR-30a was found to suppress the migration and invasiveness phenotypes of breast cancer cell lines. More importantly, breast cancer patients with decreased miR-30a level in primary cancerous sites were found to be associated with poor clinical features (late tumor stage and lymph node metastasis) and worse progression, demonstrating an increased hazard ratio (HR) for recurrence or recurrence plus mortality during the follow-up period (P&amp;lt;0.05). These findings provide a support of clinical importance of miR-30a in mediating breast tumor progression. Identification of miR-30a-mediated regulation of vimentin might provide a promising therapeutic target in treating breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1094. doi:1538-7445.AM2012-1094
Abdominal Aortic Aneurysm With Bony Erosion Mimicking Recurrent Non–Hodgkin Lymphoma on FDG PET/CT
Authors: Dae-Weung Kim, Woo Hyoung Kim, Chang Guhn Kim
Journal: Clinical Nuclear Medicine (2012)

An 80-year-old man with a history of non-Hodgkin lymphoma in complete remission after chemotherapy in 2009 presented with lumbar pain. MRI demonstrated anterior L4 bony erosions. FDG PET/CT revealed the large retroperitoneal mass with central photopenia and a mildly hypermetabolic rim. Ultrasound revealed a dilated aorta with atherosclerotic plaque and eccentric mural thrombus. A newly developed mass-like lesion in a patient with history of lymphoma could be mistaken for lymphoma recurrence on FDG PET/CT.
Fracture of the Femoral Neck in a Child
Authors: James E. Butler
Journal: JAMA (1971)

Dr. Butler: The patient is a 10-year-old girl who fell out of a tree. She experienced immediate pain in the right hip, but there were no other complaints. She was taken to the emergency room where a complete examination failed to disclose injury other than the fracture of the right femoral neck shown in Fig 1. The nervous and circulatory systems in the involved extremity were normal. We are privileged today to have the assistant director of the Newington (Conn) Children's Hospital to discuss this difficult problem. <h3>Discussion</h3> Dr. Cary: The injury demonstrated is a displaced fracture of the base of the neck of the femur in a 10-year-old girl. In view of the reported high incidence of complications of fracture healing, growth disturbance and vascular impairment of the proximal fragment, this must be considered a difficult fracture problem, with guarded prognosis. The key to understanding these difficulties, as well
Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways
Authors: Prerna Bhargava, Changlin Li, Kristopher J Stanya, David Jacobi, Lingling Dai, Sihao Liu, Matthew R Gangl, Donald A Harn, Chih-Hao Lee
Journal: Nature Medicine (2012)
Heme Oxygenase-1, a Potential Biomarker of Chronic Silicosis, Attenuates Silica-induced Lung Injury
Authors: Takashi Sato, Mitsuhiro Takeno, Koichi Honma, Hideyuki Yamauchi, Yoshiaki Saito, Takao Sasaki, Hiroshi Morikubo, Yoji Nagashima, Shigeto Takagi, Kouichi Yamanaka, Takeshi Kaneko, Yoshiaki Ishigatsubo
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis.Objectives: To investigate whether HO-1 can reduce silicosis in mice and humans.Methods and measurements: Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting.Main results: Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1.Conclusions: Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression.
Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia.
Authors: J E Williams, S A Moser, S H Turner, P G Standard
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis conida produces chronic pulmonary and disseminated blastomycosis characterized by pyogranulomatous inflammation. To study the evolution of the pulmonary infection, mice were killed at varying intervals after inoculation, their lungs cultured and examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas, which developed first as central microabscesses associated with a peripheral zone of M phi and giant cells containing internalized yeast, were a prominent feature of the infection. Lymphocytic and plasmacytic infiltrates, accumulating next to granulomas, formed the major peripheral component of the granuloma by Day 35. Formation of pyogranulomas was coincident with the host's failure to contain fungal growth measured by the sharp rise in colony-forming units recovered from lungs. Antibody against B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion. During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data contribute to our knowledge of this model and help form the basis for investigations into the roles of fungal pathogenic and host defense mechanisms in blastomycosis.