tbuckley/cabot-search huggingface dataset:
Splenic Metabolic Activity Predicts Risk of Future Cardiovascular Events
Authors: Hamed Emami, Parmanand Singh, Megan MacNabb, Esad Vucic, Zachary Lavender, James H.F. Rudd, Zahi A. Fayad, Joshua Lehrer-Graiwer, Magnus Korsgren, Amparo L. Figueroa, Jill Fredrickson, Barry Rubin, Udo Hoffmann, Quynh A. Truong, James K. Min, Amos Baruch, Khurram Nasir, Matthias Nahrendorf, Ahmed Tawakol
Journal: JACC. Cardiovascular imaging (2015)
Cannabis Use and Age at Onset of Schizophrenia
Authors: Natalie D. Veen, Jean-Paul Selten, Ingeborg van der Tweel, Wilma G. Feller, Hans W. Hoek, René S. Kahn
Journal: American Journal of Psychiatry (2004)

The purpose of the study was to assess the independent influences of gender and cannabis use on milestones of early course in schizophrenia.In this population-based, first-contact incidence study conducted in The Hague, the Netherlands, patients (N=133) were interviewed with the Comprehensive Assessment of Symptoms and History, and key informants were interviewed with the Instrument for the Retrospective Assessment of the Onset of Schizophrenia. Milestones of early course were 1) first social and/or occupational dysfunction, 2) first psychotic episode, and 3) first negative symptoms.Male patients were significantly younger than female patients at first social and/or occupational dysfunction, first psychotic episode, and first negative symptoms. Cannabis-using patients were significantly younger at these milestones than were patients who did not use cannabis. Multivariate analyses showed that cannabis use, but not gender, made an independent contribution to the prediction of age at first psychotic episode: male cannabis users were a mean of 6.9 years younger at illness onset than male nonusers. In contrast, age at first social and/or occupational dysfunction and the risk of developing negative symptoms before the first contact with a physician for treatment of possible psychotic disorder were predicted by gender, but not by cannabis use.The results indicate a strong association between use of cannabis and earlier age at first psychotic episode in male schizophrenia patients. Additional studies examining this possibly causal relationship are needed.
Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems
Authors: Joanna E. Adrian, Klaas Poelstra, Gerrit L. Scherphof, Grietje Molema, Dirk K.F. Meijer, Catharina Reker-Smit, Henriëtte W.M. Morselt, Jan A.A.M. Kamps
Journal: Journal of Hepatology (2005)
Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles
Authors: Stefan Fröhling, Claudia Scholl, Ross L. Levine, Marc Loriaux, Titus J. Boggon, Olivier A. Bernard, Roland Berger, Hartmut Döhner, Konstanze Döhner, Benjamin L. Ebert, Sewit Teckie, Todd R. Golub, Jingrui Jiang, Marcus M. Schittenhelm, Benjamin H. Lee, James D. Griffin, Richard M. Stone, Michael C. Heinrich, Michael W. Deininger, Brian J. Druker, D. Gary Gilliland
Journal: Cancer Cell (2007)
Ear, ear, what's going on in Norfolk?
Authors: E. CLARK, K. GAFFNEY, P. MERRY;, D. O'GRADAIGH, D. SCOTT
Journal: Annals of the Rheumatic Diseases (1999)

Cladribine in the treatment of systemic lupus erythematosus nephritisSystemic lupus erythematosus (SLE) nephritis often requires treatment with cyclophosphamide, which carries the risk of major side eVects including infection, ovarian failure and bladder malignancy.Therapeutic strategies that would specifically target lymphocytes are appealing.Following the first report of the use of the purine nucleoside analogue cladribine (2-chloro-2'deoxyadenosine), a selective lymphocyte depleting agent, in the treatment of lupus nephritis, 1 we report our experience in two patients with severe renal involvement.
Particulate Matter (PM) Research Centers (1999–2005) and the Role of Interdisciplinary Center-Based Research
Authors: Elinor W. Fanning, John R. Froines, Mark J. Utell, Morton Lippmann, Gunter Oberdörster, Mark Frampton, John Godleski, Tim V. Larson
Journal: Environmental Health Perspectives (2008)

ObjectiveThe U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the “Research Priorities for Airborne Particulate Matter” of the National Research Council (NRC). The centers were structured to promote interdisciplinary approaches to address research priorities of the NRC. In this report, we present selected accomplishments from the first 6 years of the PM Centers, with a focus on the advantages afforded by the interdisciplinary, center-based research approach. The review highlights advances in the area of ultrafine particles and traffic-related health effects as well as cardiovascular and respiratory effects, mechanisms, susceptibility, and PM exposure and characterization issues.Data sources and synthesisThe collective publications of the centers served as the data source. To provide a concise synthesis of overall findings, authors representing each of the five centers identified a limited number of topic areas that serve to illustrate the key accomplishments of the PM Centers program, and a consensus statement was developed.ConclusionsThe PM Centers program has effectively applied interdisciplinary research approaches to advance PM science.
Rescue of defective pancreatic secretion in cystic-fibrosis cells by suppression of a novel isoform of phospholipase C
Authors: Hu Zhu, Jin Xia Zhu, Pui Shan Lo, Jianmin Li, Ka Man Leung, Dewi Kenneth Rowlands, Lai Ling Tsang, Mei Kuen Yu, Jian Li Jiang, Sun Yee Lam, Yiu Wa Chung, Zuomin Zhou, Jiahao Sha, Hsiao Chang Chan
Journal: The Lancet (2003)
Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis
Authors: Stephen P. Messier, Shannon L. Mihalko, Claudine Legault, Gary D. Miller, Barbara J. Nicklas, Paul DeVita, Daniel P. Beavers, David J. Hunter, Mary F. Lyles, Felix Eckstein, Jeff D. Williamson, J. Jeffery Carr, Ali Guermazi, Richard F. Loeser
Journal: JAMA (2013)

Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity.
Interactions between RSV Infection, Asthma, and Atopy
Authors: P.G. Holt, P. D. Sly
Journal: The Journal of Experimental Medicine (2002)

In this issue, Culley et al. ([1][1]) present findings from an infant mouse model of respiratory syncitial virus (RSV) infection, which provides a new perspective on the pathogenesis of RSV-mediated lung disease in early life. RSV is one of the most common respiratory pathogens encountered in
STUDIES ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITRO
Authors: Lawrence N. Chessin, Jan Börjeson, Patricia D. Welsh, Steven D. Douglas, Herbert L. Cooper
Journal: The Journal of Experimental Medicine (1966)

A study of the kinetics of RNA and DNA synthesis in PWM-stimulated lymphocytes revealed that RNA synthesis preceded the onset of DNA synthesis by approximately 24 hr and that DNA synthesis and transformation was maximal between 66 to 78 hr. Histochemical and radioautographic studies on PWM stimulated cultures indicated that at 72 hr 50 to 60% of the cell population had been transformed by PWM, and that a distinct cell type bearing cytologic resemblance to the early plasma cell had emerged. The RNA sedimentation profile for newly synthesized RNA in PWM-stimulated cells showed that a large peak of 45 to 50 S material was formed after 24 and 40 hr. PWM thus produces a distinctive transformation of human peripheral blood lymphocytes.
Randomized Phase II Evaluation of 6 g/m<sup>2</sup> of Ifosfamide Plus Doxorubicin and Granulocyte Colony-Stimulating Factor (G-CSF) Compared With 12 g/m<sup>2</sup> of Ifosfamide Plus Doxorubicin and G-CSF in the Treatment of Poor-Prognosis Soft Tissue Sarcoma
Authors: Francis P. Worden, Jeremy M.G. Taylor, Janet S. Biermann, Vernon K. Sondak, Kirstin M. Leu, Rashmi Chugh, Cornelius J. McGinn, Mark M. Zalupski, Laurence H. Baker
Journal: Journal of Clinical Oncology (2004)

The relative value of increasing ifosfamide dose in combination chemotherapy for patients with soft tissue sarcoma (STS) is unclear. The purpose of this study was to compare the efficacy and toxicity of doxorubicin with high-dose (HD) ifosfamide or standard-dose (SD) ifosfamide in patients with STS.Chemotherapy-naive patients with STS were randomly assigned to receive doxorubicin 60 mg/m(2) and either SD ifosfamide (1.5 g/m(2)/d, days 1 through 4) or HD ifosfamide (3.0 g/m(2), days 1 through 4) every 21 days. Patients were stratified by the presence or absence of metastatic disease. End points were overall survival (OS), 1-year disease-free survival (DFS), and toxicity.The study group consisted of 79 patients (52 patients with localized disease and 27 patients with metastases). Both groups were well-balanced with respect to known prognostic factors. There was no significant difference in 1-year DFS comparing SD ifosfamide with HD ifosfamide (55% v 52%; P = .81). For SD ifosfamide, 2- and 3-year OS were 73% and 52% versus 57% and 49% for HD ifosfamide (P = .34). The incidence of grade 3/4 neutropenia, anemia, and thrombocytopenia were 49%, 23%, and 10%, respectively, on the SD ifosfamide arm, compared with 88%, 58%, and 63%, respectively, on the HD ifosfamide arm. There were five early deaths, all on the HD ifosfamide arm.When combined with doxorubicin, HD ifosfamide did not improve 1-year DFS and OS. Toxicity was clearly greater with the HD ifosfamide arm, and lack of outcome differences might be explained by toxicities with HD ifosfamide. These results suggest that HD ifosfamide combination regimens should not be used as first-line therapy for patients with STS.
Complement complicates pregnancies
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

Complement activation causes embryo loss (asterisks) in mouse uteri. During pregnancy, growth of new blood vessels into the placenta is required to nourish the developing fetus. On page 

[2165][2], Girardi et al. show that activation of the complement cascade blunts
Response to Letter Regarding Article, “Reactive Oxygen Species–Induced Stimulation of 5′AMP-Activated Protein Kinase Mediates Sevoflurane-Induced Cardioprotection”
Authors: Regis R. Lamberts, Geert Onderwater, M. Jumoke A. Vreden, Jeroen Steenhuisen, Stephan A. Loer, R. Arthur Bouwman, Nazha Hamdani, Etto C. Eringa, Ger J.M. Stienen
Journal: Circulation (2010)
PRAS40 Deregulates Apoptosis in Malignant Melanoma
Authors: SubbaRao V. Madhunapantula, Arati Sharma, Gavin P. Robertson
Journal: Cancer Research (2007)

Abstract Malignant melanoma is the most invasive and deadly form of skin cancer with no effective therapy to treat advanced disease, leading to poor survival rates. Akt3 signaling plays an important role in deregulating apoptosis in ∼70% of melanomas. Thus, targeting Akt3 signaling in melanoma patients has significant therapeutic potential for inhibiting melanomas, but no Akt3-specific chemotherapeutic agent exists. Unfortunately, nonspecific Akt inhibitors can cause systemic toxicity or increase metastasis. Identifying and targeting the Akt3 substrate that deregulates apoptosis might circumvent these complications but would require demonstration of its functional importance in disrupting normal apoptosis. In this study, PRAS40 was identified as an Akt3 substrate that deregulated apoptosis to promote melanoma tumorigenesis. Levels of phosphorylated PRAS40 (pPRAS40) increased during melanoma tumor progression paralleling increasing Akt3 activity. Majority of melanomas from patients with elevated Akt activity also had correspondingly higher levels of pPRAS40. Targeting PRAS40 or upstream Akt3 similarly reduced anchorage-independent growth in culture and inhibited tumor development in mice. Mechanistically, decreased pPRAS40 increased tumor cell apoptosis as well as sensitivity of melanoma cells to apoptosis-inducing agents, thereby decreasing chemoresistance. Collectively, these studies provide a solid mechanistic basis for targeting PRAS40 to inhibit the Akt3 signaling cascade and thereby retard melanoma development. [Cancer Res 2007;67(8):3626–36]
Phenotype, Localization, and Mechanism of Suppression of CD4<b>+</b>CD25<b>+</b> Human Thymocytes
Authors: Francesco Annunziato, Lorenzo Cosmi, Francesco Liotta, Elena Lazzeri, Roberto Manetti, Vittorio Vanini, Paola Romagnani, Enrico Maggi, Sergio Romagnani
Journal: The Journal of Experimental Medicine (2002)

Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4(+)CD25(+) T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4(+)CD25(-) thymocytes. Virtually all CD4(+)CD25(+) thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4(+)CD25(+) thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon gamma, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-beta1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) alpha-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti-CTLA-4 or anti-TGF-beta1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R alpha-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4(+)CD25(+) human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R alpha-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-beta1.
Reduced Infiltration of Class A Scavenger Receptor Positive Antigen-Presenting Cells Is Associated with Prostate Cancer Progression
Authors: Guang Yang, Josephine Addai, Wei-hua Tian, Anna Frolov, Thomas M. Wheeler, Timothy C. Thompson
Journal: Cancer Research (2004)

Abstract The class A macrophage scavenger receptor (SR-A) is expressed in antigen presenting cells and is involved in host immune responses. Germ-line mutation of this gene has been associated with increased risk of human prostate cancer. However, there is little known about its expression in normal or neoplastic human prostate tissues. Double immunofluorescent labeling with monoclonal antibodies to SR-A and specific macrophage and dendritic cell markers was used to identify cells expressing SR-A in human prostate tissues. SR-A immunohistochemical staining was performed on paraffin sections of normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancers from radical prostatectomy specimens. SR-A was expressed in a subset of macrophages and dendritic cells that infiltrated prostatic tissues. The majority of SR-A-positive cells coexpressed CD68, and a relatively low percentage expressed S100 protein. The number of SR-A-positive cells was significantly increased in PIN as compared with normal prostatic tissue (P = 0.0176). In contrast, the number of SR-A-positive cells decreased with tumor progression. A lower SR-A-positive cell density was associated with higher clinical stage (ρ = −0.26; P = 0.0234). Inverse associations were also found between SR-A density and positive lymph nodes (ρ = −0.23; P = 0.0437), tumor size (ρ = −0.31; P = 0.0100) and preoperative PSA levels (ρ = −0.32; P = 0.0057). SR-A density is a significant predictor of disease-free survival after surgery univariately (P = 0.0003), as well as multivariately, adjusted for known clinical and pathological markers including preoperative prostate-specific antigen, clinical stage, Gleason score, surgical margin, extraprostatic extension, and seminal vesicle invasion, as well as lymph node metastasis (P = 0.0021). The preferential accumulation of SR-A-positive cells in PIN suggests a role for SR-A in the APC response to early malignancy. A reduction in the number of SR-A-positive cells demarcates tumor progression as indicated by clinical and pathological correlations. Our results additionally indicate that systematic measurement of SR-A density is a strong prognostic marker for clinical outcome after surgery.
An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces
Authors: Marc D. Basson
Journal: Cancer Research (2008)

Abstract Increasing evidence suggests that tumor cells can regulate their own adhesion via intracellular signals that modulate integrin binding affinity. Although the full pathway has not yet been elucidated, the effects of pressure seem likely to require cytoskeletal mechanosensing, Src, phosphatidylinositol 3-kinase, focal adhesion kinase, and Akt-1 activation. Ultimately, activated focal adhesion kinase accumulates at the membrane in association with β1-integrin heterodimers and may modulate integrin binding affinity. This pathway may be a promising target for manipulation to inhibit metastatic cancer cell adhesion. [Cancer Res 2008;68(1):2–4]
Plasmapheresis in the management of heparin‐associated thrombocytopenia with thrombosis
Authors: Sucha Nand, John A. Robinson
Journal: American Journal of Hematology (1988)

Abstract Heparin‐associated thrombocytopenia with thrombosis (HATT) is fatal in 29% and leads to limb amputation in another 21% of patients. Patients with arterial thrombosis do worse than do those with venous thrombosis alone. Heparin‐associated thrombocytopenia is mediated through IgG or IgM immunoglobulin fractions and is believed to be an immune phenomenon, with heparin acting as a hapten. In addition, endothelial injury may be responsible for the development of thrombosis. Heparin‐induced platelet aggregation persists for weeks to months after its withdrawal in these patients. Acute management of HATT includes surgical thrombectomy, thrombolytic therapy, dextran, ancrod, lowmolecular‐weight heparin, and antiplatelet agents, but overall results remain unsatisfactory. We report the use of plasmapheresis, along with aspirin and dextran, in a patient with HATT. The patient experienced pain relief in 1 day; the heparin‐associated platelet aggregation test became negative in 5 days, and there was functional salvage of the affected limb. We suggest that plasmapheresis may be an effective therapy in the management of HATT.
Electrocardiographic Changes in Leptospirosis
Authors: M. Parsons
Journal: BMJ (1965)

The finding of electrocardiographic (E.C.G.) abnormalities in patients with leptospirosis who show clinical evidence of cardiac involvement is well recognized. In a review of the subject Sodeman and Killough (1951) reported the unexpected dis covery of abnormalities in three patients without such clinical signs, and expressed the opinion that  an active interest in the [cardiovascular] system is necessary to establish involvement. The fact that an apparently normal E.C.G. taken in the first week of the illness might give such evidence if compared with a later record supported their thesis. Moreover, Mackay-Dick and Robinson (1957) subsequently demonstrated transient minor changes in the QRST complex in two out of six consecutive patients with uncomplicated leptospirosis.
Antibiotics Versus Conservative Surgery for Treating Diabetic Foot Osteomyelitis: A Randomized Comparative Trial
Authors: José Luis Lázaro-Martínez, Javier Aragón-Sánchez, Esther García-Morales
Journal: Diabetes Care (2013)

No prospective trials have been carried out comparing antibiotic treatment alone with primarily surgical treatment in patients with diabetes and foot osteomyelitis. The aim of the current study was to compare the outcomes of the treatment of diabetic foot osteomyelitis in patients treated exclusively with antibiotics versus patients who underwent conservative surgery, following up the patients for a period of 12 weeks after healing.Between 1 January 2010 and 31 December 2012, a prospective randomized comparative trial (clinical trial reg. no. NCT01137903, clinicaltrials.gov) of patients with diabetes who had received a diagnosis of neuropathic foot ulcers complicated by osteomyelitis was carried out at the Diabetic Foot Unit at the Complutense University of Madrid. Patients were randomized into the following two groups: the antibiotics group (AG) and the surgical group (SG). Antibiotics were given for a period of 90 days in the AG. Patients in the SG received conservative surgery with postoperative antibiotic treatment for 10 days.Eighteen patients (75%) achieved primary healing in the AG, and 19 (86.3%) in the SG (P = 0.33). The median time to healing was 7 weeks (quartile [Q] 1 to Q5, Q3-Q8) in the AG and 6 weeks (Q1-Q3, Q3-Q9) in the SG (P = 0.72). The conditions of four patients from the AG worsened (16.6%), and they underwent surgery. Three patients from the SG required reoperation. No difference was found between the two groups regarding minor amputations (P = 0.336).Antibiotic therapy and surgical treatment had similar outcomes in terms of healing rates, time to healing, and short-term complications in patients with neuropathic forefoot ulcers complicated by osteomyelitis without ischemia or necrotizing soft tissue infections.
Regulation of Akt(ser473) phosphorylation by Choline kinase in breast carcinoma cells
Authors: Boon Tin Chua, David Gallego-Ortega, Ana Ramirez de Molina, Axel Ullrich, Juan Carlos Lacal, Julian Downward
Journal: Molecular Cancer (2009)

The serine/threonine kinase PKB/Akt plays essential role in various cellular processes including cell growth and proliferation, metabolism and cell survival. The importance of the Akt pathway is highlighted by the mutation of various components of the pathway such as the PTEN and PI3-kinase (P110α) in human cancers. In this paper, we employed an RNA interference library targeting all human kinases to screen for kinases involved in the regulation of Akt activation, in particular serine 473 phosphorylation. Here, we transfected the MDA-MB 468 breast cell line with the human kinome siRNA library and measured Akt activation using an antibody specific for phosphoserine 473 of Akt. The screen revealed that phosphorylation of Akt(ser473) can be regulated by more than 90 kinases. Interestingly, phosphorylation of Akt(ser473), but not thr308, can be severely reduced by inhibition of Choline kinase activity via siRNA or small molecule inhibitors. We show here that the regulation of Akt phosphorylation by Choline kinase is PI3K-independent. In addition, xenograft tumors treated with Choline kinase inhibitors demonstrated a statistically significant decrease in Akt(ser473) phosphorylation. Importantly, the reduction in phosphorylation correlates with regression of these xenograft tumors in the mouse model. High Choline kinase expression and activity has previously been implicated in tumor development and metastasis. The mechanism by which Choline kinase is involved in tumor formation is still not fully resolved. From our data, we proposed that Choline kinase plays a key role in regulating Akt(ser473) phosphorylation, thereby promoting cell survival and proliferation.