tbuckley/cabot-search huggingface dataset:
Non-genomic progesterone actions in female reproduction
Authors: B. Gellersen, M.S. Fernandes, J.J. Brosens
Journal: Human Reproduction Update (2008)

The steroid hormone progesterone is indispensable for mammalian procreation by controlling key female reproductive events that range from ovulation to implantation, maintenance of pregnancy and breast development. In addition to activating the progesterone receptors (PRs)-B and -A, members of the superfamily of ligand-dependent transcription factors, progesterone also elicits a variety of rapid signalling events independently of transcriptional or genomic regulation. This review covers our current knowledge on the mechanisms and relevance of non-genomic progesterone signalling in female reproduction. PubMed was searched up to August 2008 for papers on progesterone actions in ovary/breast/endometrium/myometrium/brain, focusing primarily on non-genomic signalling mechanisms. Convergence and intertwining of rapid non-genomic events and the slower transcriptional actions critically determine the functional response to progesterone in the female reproductive system in a cell-type- and environment-specific manner. Several putative progesterone-binding moieties have been implicated in rapid signalling events, including the 'classical' PR and its variants, progesterone receptor membrane component 1, and the novel family of membrane progestin receptors. Progesterone and its metabolites have also been implicated in the allosteric regulation of several unrelated receptors, such as gamma-aminobutyric acid type A, oxytocin and sigma(1) receptors. Identification of the mechanisms and receptors that relay rapid progesterone signalling is an area of research fraught with difficulties and controversy. More in-depth characterization of the putative receptors is required before the non-genomic progesterone pathway in normal and pathological reproductive function can be targeted for pharmacological intervention.
Survival of 1476 patients initially resuscitated from out of hospital cardiac arrest
Authors: S. M Cobbe, K. Dalziel, I. Ford, A. K Marsden
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To determine the short and long term outcome of patients admitted to hospital after initially successful resuscitation from cardiac arrest out of hospital. <b>Design</b>: Review of ambulance and hospital records. Follow up of mortality by "flagging" with the registrar general. Cox proportional hazards analysis of predictors of mortality in patients discharged alive from hospital. <b>Setting</b>: Scottish Ambulance Service and acute hospitals throughout Scotland. <b>Subjects</b>: 1476 patients admitted to a hospital ward, of whom 680 (46%) were discharged alive. <b>Main outcome measures</b>: Survival to hospital discharge, neurological status at discharge, time to death, and cause of death after discharge. <b>Results</b>: The median duration of hospital stay was 10 days (interquartile range 8-15) in patients discharged alive and 1 (1-4) day in those dying in hospital. Neurological status at discharge in survivors was normal or mildly impaired in 605 (89%), moderately impaired in 58 (8.5%), and severely impaired in 13 (2%); one patient was comatose. Direct discharge to home occurred in 622 (91%) cases. The 680 discharged survivors were followed up for a median of 25 (range 0-68) months. There were 176 deaths, of which 81 were sudden cardiac deaths, 55 were non-sudden cardiac deaths, and 40 were due to other causes. The product limit estimate of 4 year survival after discharge was 68%. The independent predictors of mortality on follow up were increased age, treatment for heart failure, and cardiac arrest not due to definite myocardial infarction. <b>Conclusion</b>: About 40% of initial survivors of resuscitation out of hospital are discharged home without major neurological disability. Patients at high risk of subsequent cardiac death can be identified and may benefit from further cardiological evaluation. <h3>Key messages</h3> Nearly 70% of patients discharged after cardiac arrest are alive four years after the event Patients whose cardiac arrest is not due to definite myocardial infarction require further cardiological assessment
Immunoproteomic Analysis of German Cockroach (Blattella germanica) Reveals Antigens Differentially Recognized As a Function of Disease Severity
Authors: Myles B. Dillon, Véronique M. Schulten, Denise Hinz, Carla Oseroff, Laura Dullanty, Victoria Tripple, John Pham, Sinu Paul, April Frazier, John Sidney, Bjoern Peters, Alessandro Sette
Journal: Journal of Allergy and Clinical Immunology (2015)
Hyper Immunoglobulin M Immunodeficiency (Dysgammaglobulinemia)
Authors: Raif S. Geha, Newton Hyslop, Samih Alami, Fuad Farah, Eveline E. Schneeberger, Fred S. Rosen
Journal: Journal of Clinical Investigation (1979)

The peripheral blood lymphocytes of nine patients with hyper immunoglobulin (Ig)M immunodeficiency were studied in an attempt to define the cellular basis of this disorder. B cells were normal in number but qualitatively abnormal in all patients. Approximately one-half of the B cell consisted of small lymphocytes (7-9 mum in diameter) bearing surface IgM and IgD, as well as C3 receptors. These cells were driven to secrete IgM but not IgG after in vitro stimulation by pokeweed mitogen. In the blood there were also large lymphocytes (10-14 mum in diameter) that possessed surface as well as intracytoplasmic IgM but lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. Such a subpopulation of lymphoid cells was not detected in normal peripheral blood and was unique for all patients with hyper IgM immunodeficiency studied.T cells from all patients were normal in number and in function both in vivo and in vitro and were able to generate adequate T-cell help to support IgG synthesis by normal B cells. No evidence was obtained for T cells capable of suppressing normal IgG synthesis in any of the patients after coculture with normal peripheral blood lymphocytes. The defect in hyper IgM immunodeficiency is intrinsic to B cells, which fail to switch from IgM to IgG synthesis.
Large granular lymphocyte leukemia presenting with both amegakaryocytic thrombocytopenic purpura and pure red cell aplasia: Clinical course and response to immunosuppressive therapy
Authors: Peter A. Kouides, Jacob M. Rowe
Journal: American Journal of Hematology (1995)

Large granular lymphocyte (LGL) leukemia is typically associated with neutropenia and occasionally pure red cell aplasia. We now report a new association of LGL leukemia with amegakaryocytic aplasia that was also accompanied by pure red cell aplasia. An 82-year-old female presented with a platelet count of 16,000/microliters at the time of a gastrointestinal bleed. The white blood cell count was within normal limits but there was a relative lymphocytosis of large granulated cells that by flow cytometric and gene rearrangement studies was consistent with a monoclonal process. Platelet and red cell transfusion dependence persisted over 17 months with numerous immunosuppressive treatments given including prednisone, cyclophosphamide, vincristine, cyclosporine, gammaglobulin, and azathioprine. Presently, 36 months since the time of presentation, she is in a clinical remission with follow-up flow cytometric and gene rearrangement studies of the peripheral blood without definite evidence of the LGL clone. This case report illustrates the various therapeutic approaches to be considered in LGL leukemia and is a reminder that severe and life-threatening thrombocytopenia can be a feature of LGL leukemia unlike the usual course of LGL leukemia with neutropenia as the major clinical feature.
Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.
Authors: M M Simon, A Reikerstorfer, A Schwarz, C Krone, T A Luger, M Jäättelä, T Schwarz
Journal: Journal of Clinical Investigation (1995)

To elucidate cellular concepts for protection against ultraviolet (UV) light we investigated the effect of heat shock protein 70 (hsp70) overexpression on cell viability and on the secretion of UV-inducible immunological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpression of hsp70 was sufficient to markedly increase cell viability upon treatment with UVB (290-320 nm). Since long wave UV (UVA, 320-400 nm) as well as UVB turned out to stimulate the release of O2- radicals we studied the cell viability upon oxidative stress. Hsp70 overexpression increased viability upon treatment with hydrogen peroxide or menadione, but had no influence on UV-induced O2- release. UV-light is known to upregulate immunologic and proinflammatory cytokines such as IL-1 and IL-6. Oxidative stress appeared to exert a similar effect. Hsp70 overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated suppression is confined to events caused by UV-light we determined IL-1-mediated effects. IL-1-induced IL-6 release was reduced by hsp70 overexpression, whereas the IL-1 mediated activation of nuclear factor kappa B was not affected. Our data suggests that hsp70 plays a central role not only in cell protection against UV-light, but also in the regulation of proinflammatory cytokine release induced by UV-exposure.
Fat Cells Gain New Identities
Authors: Emmani B. M. Nascimento, Mariëtte R. Boon, Wouter D. van Marken Lichtenbelt
Journal: Science Translational Medicine (2014)

ASC-1, PAT2, and P2RX5 are newly identified cell-surface proteins that may distinguish brown/beige from white adipocytes in mouse and human adipose tissue (Ussar et al ., this issue).
Distinct microRNA Expression Profiles in Prostate Cancer Stem/Progenitor Cells and Tumor-Suppressive Functions of let-7
Authors: Can Liu, Kevin Kelnar, Alexander V. Vlassov, David Brown, Junchen Wang, Dean G. Tang
Journal: Cancer Research (2012)

Abstract MiRNAs regulate cancer cells, but their potential effects on cancer stem/progenitor cells are still being explored. In this study, we used quantitative real-time-PCR to define miRNA expression patterns in various stem/progenitor cell populations in prostate cancer, including CD44+, CD133+, integrin α2β1+, and side population cells. We identified distinct and common patterns in these different tumorigenic cell subsets. Multiple tumor-suppressive miRNAs were downregulated coordinately in several prostate cancer stem/progenitor cell populations, namely, miR-34a, let-7b, miR-106a, and miR-141, whereas miR-301 and miR-452 were commonly overexpressed. The let-7 overexpression inhibited prostate cancer cell proliferation and clonal expansion in vitro and tumor regeneration in vivo. In addition, let-7 and miR-34a exerted differential inhibitory effects in prostate cancer cells, with miR-34a inducing G1 phase cell-cycle arrest accompanied by cell senescence and let-7 inducing G2–M phase cell-cycle arrest without senescence. Taken together, our findings define distinct miRNA expression patterns that coordinately regulate the tumorigenicity of prostate cancer cells. Cancer Res; 72(13); 3393–404. ©2012 AACR.
Hepatocellular carcinoma and sorafenib: too many resistance mechanisms?
Authors: Carmen Berasain
Journal: Gut (2013)

Hepatocellular carcinoma (HCC), the most common tumour of the liver, develops in more than 80% of cases on patients with chronically damaged livers owing to excessive alcohol consumption, hepatitis B or C virus (HBV or HCV) infection or obesity. Despite positive results of HBV vaccination programmes and the promising data from the new anti-HCV treatments,1 the incidence of HCC is increasing significantly in Western countries because of the progression of old HCV infections and the almost epidemic prevalence of obesity and metabolic syndrome-associated non-alcoholic fatty liver disease.2

The prognosis of patients with HCC is generally very poor. HCC tumours are resistant to chemotherapy and are usually diagnosed at a late stage when the curative strategies of surgical resection and orthotopic liver transplantation are not applicable. Targeted treatments against specific oncogenes have been shown to be effective in the treatment of leukaemias and solid tumours such as breast, colon and lung carcinomas.3 In 2008, the SHARP (Sorafenib HCC Assessment Randomised Protocol) trials showed an improved overall survival in Child–Pugh class A patients with advanced HCC upon treatment with the antiangiogenic and antiproliferative agent sorafenib.4 This multikinase inhibitor was established as the standard of care for patients with advanced HCC. However, the promising systemic treatment has demonstrated limited survival benefits with very low rates of tumour response, suggesting the existence of primary and acquired drug resistance mechanisms.5

In this situation HCC appears to be a moving target, and a rapid intervention in at …
Effects of Transforming Growth Factor-beta on Human Pulmonary Adenocarcinoma Cell Adhesion, Motility, and Invasion In Vitro
Authors: D. L. Mooradian, J. B. McCarthy, K. V. Komanduri, L. T. Furcht
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Transforming growth factor-βpl (TGF-β1), a potent growth modulator produced by a variety of tumor cells, as well as by platelets, has pleiotropic effects on cell-extracellular matrix interactions and may influence tumor cell invasion and metastasis. Purpose : Our purpose was to characterize the effects of TGF-β1 on the adhesion, motility, and invasiveness of a metastatic human pulmonary carcinoma (A549 cell line) in vitro. Methods : A549 cells were seeded onto type I collagen gels, and invasion over a 9-day period was measured in the presence or absence of TGF-β1 (0.1–10 ng/mL). In addition, cell adhesion to substrata coated with type I collagen (1–100 n M ) as well as haptotactic migration through filters coated with type I collagen (100 μg/mL) were measured following a 24-hour treatment with TGF-β1 (1–10 ng/mL). Results : TGF-β1 stimulated the invasion of A549 cells into type I collagen gels in a dose-dependent manner. Both the number of cells entering the gel and the depth of invasion into the gel were increased. In addition, the effects,of TGF-β1 were blocked in a dose-dependent manner by a purified polyclonal IgG against TGF-β1 but not by normal rabbit IgG. A549 cell invasion was accompanied by dramatic changes in A549 cell morphology that included the appearance of numerous long pseudo-podia, consistent with a change in the motile behavior of these cells. TGF-β1 stimulated by approximately fourfold the haptotactic migration of A549 cells on haptotactic migration of A549 cells on polycarbonate filters coated with type I collagen. The TGF-β1-mediated increase in invasion and motility was accompanied by a fourfold increase in A549 cell adhesion to type I collagen. Conclusions : The results suggest that TGF-β1 can influence cellular recognition of extracellular matrix components and can modulate cellular adhesion and migration on these components, leading to increased invasive potential. Implications : Given the widespread tissue distribution of TGF-β1 and its secretion by a variety of tumor cells as well as by platelets, TGF-β1 may be an important autocrineparacrine regulator of the invasive phenotype in vivo. (J Natl Cancer Inst 84: 523–527, 1992)
Alpha1-antitrypsin phenotypes in patients with cryptogenic fibrosing alveolitis: a case-control study
Authors: R Hubbard, Y Baoku, N Kalsheker, J Britton, I Johnston
Journal: European Respiratory Journal (1997)

Cryptogenic fibrosing alveolitis (CFA) is an interstitial lung disease, which by definition is of unknown aetiology. Recent evidence has suggested that smoking and occupational exposure to dusts may be environmental risk factors for the disease, but there has been little research into potential host risk factors. One previous study has suggested that the prevalence of abnormal alpha1-antitrypsin phenotypes may be increased in patients with CFA. Since alpha1-antitrypsin is important in regulating inflammation within the lung in response to environmental exposures, such abnormalities may be of aetiological importance in this disease. We have compared the alpha1-antitrypsin phenotypes of 189 patients with CFA with 189 age-, sex-, and community-matched controls. This sample size was sufficient to provide more than 95% power to detect an odds ratio (OR) of 2.5. Alpha1-antitrypsin phenotype was established by isoelectric focusing, and the prevalence of abnormal phenotypes in cases and controls was compared by conditional logistic regression. Personal smoking histories were obtained by postal questionnaire. The prevalence of abnormal alpha1-antitrypsin phenotypes was similar in cases and controls (12.7 versus 15.3%; OR 0.88; 95% confidence interval 0.49-1.57; p=0.66). No interaction was found between the presence of abnormal alpha1-antitrypsin phenotypes and a history of smoking. We conclude that cryptogenic fibrosing alveolitis is not associated with abnormal alpha1-antitrypsin phenotypes.
Mitochondrial protection restores renal function in swine atherosclerotic renovascular disease
Authors: Alfonso Eirin, Behzad Ebrahimi, Xin Zhang, Xiang-Yang Zhu, John R. Woollard, Quan He, Stephen C. Textor, Amir Lerman, Lilach O. Lerman
Journal: Cardiovascular Research (2014)

The mechanisms responsible for renal injury in atherosclerotic renovascular disease (ARVD) are incompletely understood, and few therapeutic options are available to reverse it. We hypothesized that chronic renal damage involves mitochondrial injury, and that mitochondrial protection would reduce renal fibrosis and dysfunction in ARVD pigs. Domestic pigs were studied after 10 weeks of ARVD or sham, treated for the last 4 weeks with daily subcutaneous injections (5 days/week) of vehicle or Bendavia (0.1 mg/kg), a tetrapeptide that preserves cardiolipin content in the mitochondrial inner membrane. Single-kidney haemodynamics and function were studied using fast-computer tomography, oxygenation using blood oxygen level-dependent magnetic resonance imaging, microvascular architecture, oxidative stress, and fibrosis ex vivo. Cardiolipin content was assessed using mass spectrometry and staining. Renal endothelial function was studied in vivo and ex vivo. In addition, swine renal artery endothelial cells incubated with tert-butyl hydroperoxide were also treated with Bendavia. Stenotic-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) decreased in ARVD + Vehicle compared with normal (318.8 ± 61.0 vs. 553.8 ± 82.8 mL/min and 48.0 ± 4.0 vs. 84.0 ± 3.8 mL/min, respectively) associated with loss of cardiolipin, intra-renal microvascular rarefaction, and hypoxia. Bendavia restored cardiolipin content in ARVD and improved vascular density, oxygenation, RBF (535.1 ± 24.9 mL/min), and GFR (86.6 ± 11.2 mL/min). Oxidative stress and fibrosis were ameliorated, and renovascular endothelial function normalized both in vivo and in vitro. Preservation of mitochondrial cardiolipin attenuated swine stenotic-kidney microvascular loss and injury, and improved renal oxygenation, haemodynamics, and function. These observations implicate mitochondrial damage in renal deterioration in chronic experimental ARVD, and position the mitochondria as a central therapeutic target.
Chloroquine in Cancer Therapy: A Double-Edged Sword of Autophagy
Authors: Tomonori Kimura, Yoshitsugu Takabatake, Atsushi Takahashi, Yoshitaka Isaka
Journal: Cancer Research (2013)

Abstract Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the other hand, however, the kidneys are highly vulnerable to chemotherapeutic agents. Recent studies have shown that autophagy plays a protective role against acute kidney injury, including cisplatin-induced kidney injury, and thus, we suspect that the use of chloroquine in combination with anticancer drugs may exacerbate kidney damage. Moreover, organs in which autophagy also plays a homeostatic role, such as the neurons, liver, hematopoietic stem cells, and heart, may be sensitive to the combined use of chloroquine and anticancer drugs. Here, we summarize the functions of autophagy in cancer and kidney injury, especially focusing on the use of chloroquine to treat cancer, and address the possible side effects in the combined use of chloroquine and anticancer drugs. Cancer Res; 73(1); 3–7. ©2012 AACR.
Malignant Melanoma Masquerading as an Angiofibroma in a Patient With MEN-1
Authors: G. Thomas Brown, Edward W. Cowen, Chyi-chia Richard Lee
Journal: JAMA Dermatology (2014)

Malignant Melanoma Masquerading as an Angiofibroma in a Patient With MEN-1Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant syndrome consisting of endocrine tumors of the parathyroid gland, pituitary gland, and pancreas.MEN-1 is caused by loss of function mutations in the MEN1 gene, which encodes the tumor suppressor protein menin.Cutaneous collagenomas and facial angiofibromas also have been associated with MEN-1 and may serve as diagnostic clues to the diagnosis.We present a case of amelanotic melanoma resembling a large angiofibroma in a young man with MEN-1.
EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases
Authors: N Duru, M C van der Goes, J W G Jacobs, T Andrews, M Boers, F Buttgereit, N Caeyers, M Cutolo, S Halliday, J A P Da Silva, J R Kirwan, D Ray, J Rovensky, G Severijns, R Westhovens, J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2013)

To develop recommendations for the management of medium to high-dose (ie, &gt;7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.