tbuckley/cabot-search huggingface dataset:
Management of adult patients with ascites caused by cirrhosis
Authors: Bruce A. Runyon
Journal: Hepatology (1998)

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in ≈90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting.
The Effect of Posture and of Congestion of the Head on Sodium Excretion in Normal Subjects
Authors: J. M. LEWIS, R. M. BUIE, S. M. SEVIER, T. R. HARRISON
Journal: Circulation (1950)

In healthy young subjects the sodium excretion is decidedly less in the sitting than in the recumbent posture. The difference can be partially overcome by compression of the neck in the sitting position. Some possible implications of these observations will be considered in the subsequent communications.
Tumor Necrosis Factor-α and Interleukin-1 Antagonists Alleviate Inflammatory Skin Changes Associated with Epidermal Growth Factor Receptor Antibody Therapy in Mice
Authors: David Surguladze, Dhanvanthri Deevi, Nidia Claros, Erik Corcoran, Su Wang, Mary Jane Plym, Yan Wu, Jacqueline Doody, David J. Mauro, Larry Witte, Klaus J. Busam, Bronek Pytowski, Ulrich Rodeck, James R. Tonra
Journal: Cancer Research (2009)

Cancer patients receiving epidermal growth factor receptor (EGFR) antibody therapy often experience an acneiform rash of uncertain etiology in skin regions rich in pilosebaceous units. Currently, this condition is treated symptomatically with very limited, often anecdotal success. Here, we show that a monoclonal antibody targeting murine EGFR, ME1, caused a neutrophil-rich hair follicle inflammation in mice, similar to that reported in patients. This effect was preceded by the appearance of lipid-filled hair follicle distensions adjacent to enlarged sebaceous glands. The cytokine tumor necrosis factor-alpha (TNFalpha), localized immunohistochemically to this affected region of the pilosebaceous unit, was specifically up-regulated by ME1 in skin but not in other tissues examined. Moreover, skin inflammation was reduced by cotreatment with the TNFalpha signaling inhibitor, etanercept, indicating the involvement of TNFalpha in this inflammatory process. Interleukin-1, a cytokine that frequently acts in concert with TNFalpha, is also involved in this process given the efficacy of the interleukin-1 antagonist Kineret. Our results provide a mechanistic framework to develop evidence-based trials for EGFR antibody-induced skin rash in patients with cancer.
Molecular Pathways: YAP and TAZ Take Center Stage in Organ Growth and Tumorigenesis
Authors: Stefano Piccolo, Michelangelo Cordenonsi, Sirio Dupont
Journal: Clinical Cancer Research (2013)

Abstract The evolution of a solid tumor is fueled by genetic aberrations. Yet, the tumor environment often dominates over the effects of genetics: normal tissues have powerful tumor-suppressive properties that constantly tame or eliminate cells carrying transforming mutations. Critical elements of such a suppressive microenvironment are structural characteristics of normal cells and tissues, such as cell polarity, attachment to the extracellular matrix (ECM), and epithelial organization. Once these tissue-level checkpoints have been overcome, tumor growth is enhanced by recruitment of stromal cells and remodeling of the ECM. Genetic inactivation in mouse models indicates the Hippo pathway as a fundamental inhibitor of organ growth during development and as a critical tumor suppressor in epithelial tissues, such as the liver, skin, and ovaries, and soft tissues. At the centerpiece of this pathway lie two related transcriptional coactivators, YAP and TAZ, that promote tissue proliferation and the self-renewal of normal and cancer stem cells, and incite metastasis. Strikingly, YAP and TAZ are controlled by the same architectural features that first inhibit and then foster cancer growth, such as ECM elasticity, cell shape, and epithelial-to-mesenchymal transition. These findings open unexpected opportunities for the development of new cancer therapeutics targeting key YAP/TAZ regulatory inputs such as Wnt signaling, cytoskeletal contractility, G-protein–coupled receptors, or YAP/TAZ-regulated transcription. Clin Cancer Res; 19(18); 4925–30. ©2013 AACR.
Effect of Vitamin A, C, and E Supplementation on Rectal Cell Proliferation in Patients With Colorectal Adenomas
Authors: Gian Maria Paganelli, Guido Biasco, Giovanni Brandi, Renato Santucci, Giuseppe Gizzi, Valeria Villani, Massimo Cianci, Mario Miglioli, Luigi Barbara
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Effect of Vitamin A, C, and E Supplementation on Rectal Cell Proliferation in Patients With Colorectal Adenomas Get access Gian Maria Paganelli, Gian Maria Paganelli Search for other works by this author on: Oxford Academic PubMed Google Scholar Guido Biasco, Guido Biasco Search for other works by this author on: Oxford Academic PubMed Google Scholar Giovanni Brandi, Giovanni Brandi Search for other works by this author on: Oxford Academic PubMed Google Scholar Renato Santucci, Renato Santucci Search for other works by this author on: Oxford Academic PubMed Google Scholar Giuseppe Gizzi, Giuseppe Gizzi Search for other works by this author on: Oxford Academic PubMed Google Scholar Valeria Villani, Valeria Villani Search for other works by this author on: Oxford Academic PubMed Google Scholar Massimo Cianci, Massimo Cianci Search for other works by this author on: Oxford Academic PubMed Google Scholar Mario Miglioli, Mario Miglioli Search for other works by this author on: Oxford Academic PubMed Google Scholar Luigi Barbara Luigi Barbara Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 47–52, https://doi.org/10.1093/jnci/84.1.47 Published: 01 January 1992 Article history Received: 01 July 1991 Revision received: 10 October 1991 Accepted: 11 October 1991 Published: 01 January 1992
Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation.
Authors: M J Truong, V Gruart, J P Kusnierz, J P Papin, S Loiseau, A Capron, M Capron
Journal: The Journal of Experimental Medicine (1993)

It has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains unclear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express Fc epsilon RII/CD23, but rather Mac-2/epsilon binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.
c-Kit–Positive Cardiac Stem Cells Nested in Hypoxic Niches Are Activated by Stem Cell Factor Reversing the Aging Myopathy
Authors: Fumihiro Sanada, Junghyun Kim, Anna Czarna, Noel Yan-Ki Chan, Sergio Signore, Barbara Ogórek, Kazuya Isobe, Ewa Wybieralska, Giulia Borghetti, Ada Pesapane, Andrea Sorrentino, Emily Mangano, Donato Cappetta, Chiara Mangiaracina, Mario Ricciardi, Maria Cimini, Emeka Ifedigbo, Mark A. Perrella, Polina Goichberg, Augustine M. Choi, Jan Kajstura, Toru Hosoda, Marcello Rota, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2013)

Rationale: Hypoxia favors stem cell quiescence, whereas normoxia is required for stem cell activation, but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. Objective: A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Methods and Results: Here, we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot re-enter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Conclusions: Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggest that a pool of functionally competent CSCs persists in the senescent heart and that this stem cell compartment can promote myocyte regeneration effectively, partly correcting the aging myopathy.
A unilateral whiteout: when not to insert a chest drain
Authors: Nigel E Drury, Cassiano Moro, Neil Cartwright, Ayyaz Ali, Samer AM Nashef
Journal: Journal of the Royal Society of Medicine (2010)

An elderly man presented to the AE it was easily removed and the puncture site repaired under direct vision with a pledgeted 3/0 polypropylene suture. The patient made an uneventful recovery and was transferred back to his local hospital for further management. Discussion
Reply to B.A. Kamen et al
Authors: Torben S. Mikkelsen, William E. Evans
Journal: Journal of Clinical Oncology (2011)

hour 42 was more effective than a 100 mg/m 2 intravenous push that was escalated as tolerated every 10 days (with asparaginase). 13 The difference in time, specifically above a minimum threshold concentration, may explain the benefit as compared with the high concentrations that resulted from the higher dose regimen.Still another solution, given that antifolate metabolism to a polyglutamate is a critical parameter, would be to find an antifolate that was better metabolized and orally bioavailable because it is also clear that compounds like aminopterin and pralatrexate that form polyglutamates in tumor cells may be even more effective than MTX. 14,15 We have made huge strides since Farber et al 16 introduced antifolates in the late 1940s.The cure of children with ALL is still founded on the same drugs, 50 years old or older, which are now used more optimally on the basis of findings of both basic and clinical trials, as shown here.How to personalize the scheduling and dosing of MTX and other drugs is becoming more of a reality and can be performed in real time.
Threshold-free high-power methods for the ontological analysis of genome-wide gene-expression studies
Authors: Björn Nilsson, Petra Håkansson, Mikael Johansson, Sven Nelander, Thoas Fioretos
Journal: Genome biology (2007)

Abstract Ontological analysis facilitates the interpretation of microarray data. Here we describe new ontological analysis methods which, unlike existing approaches, are threshold-free and statistically powerful. We perform extensive evaluations and introduce a new concept, detection spectra, to characterize methods. We show that different ontological analysis methods exhibit distinct detection spectra, and that it is critical to account for this diversity. Our results argue strongly against the continued use of existing methods, and provide directions towards an enhanced approach.
Azathioprine lacks efficacy in hidradenitis suppurativa: a retrospective study of nine patients
Authors: M. Nazary, E.P. Prens, J. Boer
Journal: British Journal of Dermatology (2015)

DEAR EDITOR,  
Hidradenitis suppurativa (HS) is a chronic inflammatory and debilitating skin disease characterized by painful nodules, abscesses and fistulas. It usually arises after puberty and can have a severe negative impact on quality of life. It has an estimated prevalence of 1–4%. Obesity, smoking, genetics, mechanical friction, hormonal influences and an aberrant local immune response are considered important risk factors for the development of HS. Careful histological examinations have revealed that perifollicular inflammation in combination with follicular hyperkeratosis and follicular dilation characterize the early stages.  
The main treatment options include long-term systemic anti-inflammatory antibiotics; hormonal, immunomodulatory and immunosuppressive treatments such as antitumour necrosis factor (anti-TNF)-a biologics; and surgical interventions. The choice of treatment depends mostly on the severity of the disease. [...]
Mobilisation kinetics of primitive haemopoietic cells following G-CSF with or without chemotherapy for advanced breast cancer
Authors: I. Baumann, R. Swindell, M.E.H.M. Van Hoeff, T.M. Dexter, E. de Wynter, C. Lange, T. Luft, A. Howell, N.G. Testa
Journal: Annals of Oncology (1996)

The objective of this study was to determine the optimal conditions for blood progenitor cell harvest for transplantation, with main emphasis on the mobilisation kinetics of primitive, marrow repopulating cells.Sixteen patients with advanced breast cancer were treated with 4 cycles of dose escalating FAC chemotherapy (5-fluorouracil, adriamycin, cyclophosphamide) each followed by 10 micrograms/kg/d G-CSF for 13 days. We assessed the number of colony-forming cells (CFC), and estimated the long-term culture initiating cells (LTC-IC) and CD34+ cells during the recovery phase of cycle 1 and 4 of chemotherapy, and during additional periods of G-CSF administration either preceding or following the full course of chemotherapy.The highest peak numbers of CFC per ml of blood (median 10489, range 860-39282) were mobilised after the first cycle of chemotherapy. The lowest peak numbers of CFC were obtained during the recovery phase from cycle 4 (median 4739, range 40-26789). In contrast, the numbers of CD34+ cells per ml of blood were significantly higher in cycle 4 (median 650, range 30-2600 x 10(2)) compared to those of cycle 1 (median 240, range 20-770 x 10(2)). The peak numbers of CFC mobilised by G-CSF before commencement and after the cessation of chemotherapy were equivalent, with a median of 5470 (range 1056-25669) and 5948 (range 2710-38975) per ml of blood, respectively. However, while mononuclear cells (MNC) collected at the days of maximal CFC mobilization following G-CSF administration before or after cycle 1 were similar to normal bone marrow MNCs in their ability to generate haemopoiesis when seeded onto performed irradiated stroma, those collected after cycle 4 or during G-CSF administration after the cessation of chemotherapy were markedly compromised in this respect.Our results indicate that repeated cycles of FAC chemotherapy followed by G-CSF result in a far lower number of LTC-IC than of CFC mobilised into the circulation. Furthermore although the combination of chemotherapy and G-CSF mobilised the highest numbers if CFC, G-CSF alone pre-chemotherapy was more effective at mobilising LTC-IC. These data indicate that neither the numbers of CFC mobilised nor the numbers of CD34+ cells are necessarily a reliable indicator for the putative marrow repopulating capability of the blood cells mobilised with chemotherapy plus G-CSF.
527 SOLID ORGAN CANCER INCIDENCE AFTER LIVER TRANSPLANTATION (LT) IS 4-FOLD HIGHER THAN IN GENERAL POPULATION
Authors: C. Carenco, Y. Duny, E. Assenat, S. Faure, A. Herrero, M. Bismuth, F. Navarro, S. Jaber, D. Larrey, G.P. Pageaux
Journal: Journal of Hepatology (2011)
Oestrogen metabolism and excretion in liver disease
Authors: J. B. Brown, G. P. Crean, J. Ginsburg
Journal: Gut (1964)

EDITORIAL SYNOPSIS Raised urinary oestrogen excretion was noted in 16 men and women with liver disease.The study suggests that the increased output of urinary oestrogens was usually due to increased secretion rates of the primary oestrogenic hormones rather than to impaired oestrogen metabolism by the liver.
CCR6 Recruits Regulatory T Cells and Th17 Cells to the Kidney in Glomerulonephritis
Authors: Jan-Eric Turner, Hans-Joachim Paust, Oliver M. Steinmetz, Anett Peters, Jan-Hendrik Riedel, Annette Erhardt, Claudia Wegscheid, Joachim Velden, Susanne Fehr, Hans-Willi Mittrücker, Gisa Tiegs, Rolf A.K. Stahl, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2010)

T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis.
Role of Endogenous Adrenomedullin in the Regulation of Vascular Tone and Ischemic Renal Injury
Authors: Hiroaki Nishimatsu, Yasunobu Hirata, Takayuki Shindo, Hiroki Kurihara, Masao Kakoki, Daisuke Nagata, Hiroshi Hayakawa, Hiroshi Satonaka, Masataka Sata, Akihiro Tojo, Etsu Suzuki, Kenji Kangawa, Hisayuki Matsuo, Tadaichi Kitamura, Ryozo Nagai
Journal: Circulation Research (2002)

Adrenomedullin (AM) is a potent depressor peptide whose vascular action is suggested to involve nitric oxide (NO) release. To explore the role of endogenous AM in vascular and renal function, we examined the effects of acetylcholine (ACh), AM, and AM receptor antagonists AM(22-52) and CGRP(8-37) on the renal perfusion pressure (RPP) of kidneys isolated from AM transgenic (TG)/heterozygote knockout (KO) mice and wild-type littermates (WT). Furthermore, we evaluated the renal function and histology 24 hours after bilateral renal artery clamp for 45 minutes in TG, KO, and WT mice. Baseline RPP was significantly lower in TG than in KO and WT mice (KO 93.4±4.6, WT 85.8±4.2, TG 72.4±2.4 mm Hg [mean±SE], P &lt;0.01). ACh and AM caused a dose-related reduction in RPP, but the degree of vasodilatation was smaller in TG than that in KO and WT (%ΔRPP 10 −7 mol/L ACh: KO −48.1±3.9%, WT −57.5±5.6%, TG −22.8±4.8%, P &lt;0.01), whereas N G -nitro- l -arginine methyl ester (L-NAME) caused greater vasoconstriction in TG (%ΔRPP 10 −4 mol/L: KO 33.1±3.3%, WT 55.5±7.2%, TG 152.6±21.2%, P &lt;0.01). Both AM antagonists increased RPP in TG to a greater extent compared with KO and WT mice (%ΔRPP 10 −6 mol/L CGRP(8-37): KO 12.8±2.6%, WT 19.4±3.6%, TG 41.8±8.7%, P &lt;0.01). In mice with ischemic kidneys, serum levels of urea nitrogen and renal damage scores showed smaller values in TG and greater values in KO mice (urea nitrogen: KO 104±5&gt;WT 98±15&gt;TG 38±7 mg/dL, P &lt;0.05 each). Renal NO synthase activity was also greater in TG mice. However, the differences in serum urea nitrogen and renal damage scores among the 3 groups of mice were not observed in mice pretreated with L-NAME. In conclusion, AM antagonists increased renal vascular tone in WT as well as in TG, suggesting that endogenous AM plays a role in the physiological regulation of the vascular tone. AM is likely to protect renal tissues from ischemia/reperfusion injury through its NO releasing activity.
Cytogenetic and scanning study of patients receiving intra-articular injections of gold-198 and yttrium-90.
Authors: A C Stevenson, J Bedford, G W Dolphin, R J Purrott, D C Lloyd, A G Hill, H F Hill, J M Gumpel, D Williams, J T Scott, N W Ramsey, F E Bruckner, C B Fearn
Journal: Annals of the Rheumatic Diseases (1973)

An account of the chromosome damage found in the lymphocytes of thirteen patients who had received injections of gold-198 into knee joints was reported in a preliminary communication (Stevenson, Bedford, Hill, and Hill, 1971a).There were great differences in the amount of damage which followed injections of the same amount of activity in these patients.How- ever, the mean level of damage appeared too high to be explained by the assumption either that it oc- curred as a result of irradiation of lymphocytes in the injected joint, or that the radionuclide was distribu- ted throughout the whole body, for the average radiation dose to the body would only be about 0 5 rad from the gamma radiation per mCi of gold-198.It was suggested that the high level of chromosome damage in lymphocytes relative to the amount of activity injected was most probably due to the movement of gold from the knee along the lymphatics to the inguinal lymph nodes, where enormous numbers of lymphocytes in transit through the nodes would come within the range of the beta emission of the radionuclide.Many patients have been treated with benefit by gold-198 or yttrium-90 intra-articular injections (Ansell, Crook, Mallard, and Bywaters, 1963; Delbarre, Cayla, Menkes, Roucayrol, Ingrand, and Aignan, 1969; Bridgnan, Bruckner, and Bleehen, 1971), and it seemed important to try to assess more accurately the amount of chromosome damage in lymphocytes in order to attempt to elucidate the prognostic significance, if any, to patients from these procedures.For this reason, and because there is very little available information on the cytogenetic effects of parenterally-administered radioactive isotopes in man, it was decided to investigate further cases.Including those reported in the preliminary paper, 48 patients who have had gold-198 injections, and 22 who have had yttrium-90 injections have now been investigated.None of these patients received any external radiotherapy.As the appendices show, blood samples from some patients were not taken until several months or years after the injections.Some were taken both before and at intervals after treatment, and some patients were scanned after injection in order to determine the distribution of the isotopes.The colloidal gold-198 (half life 65 hrs) and yttrium-90 (half life 64 hrs) were obtained from the Radiochemical Centre, Amersham, catalogue numbers GCS1P and YAS3P respectively.The gold preparation is a colloidal suspension of metallic gold stabilized with gelatin and with particle sizes of up to 20 pm.Most of the activity is in the 10-13 pm particles.The yttrium preparation is ionic yttrium bound to a colloidal ion exchange resin with a particle size range from 20 to 50 pum.