tbuckley/cabot-search huggingface dataset:
The major neutral proteinase of Entamoeba histolytica.
Authors: W E Keene, M G Petitt, S Allen, J H McKerrow
Journal: The Journal of Experimental Medicine (1986)

FPLC anion-exchange and chromatofocusing chromatography were used to purify the major neutral proteinase from secretions of axenically cultured Entamoeba histolytica trophozoites. HM-1 strain trophozoites, which were more proteolytically active than the less virulent HK-9 strain, were used for purification of the enzyme. It is a thiol proteinase with a subunit Mr of approximately 56,000, a neutral pH optimum, and a pI of 6. The importance of this enzyme in extraintestinal amoebiasis is suggested by its ability to degrade a model of connective tissue extracellular matrix as well as purified fibronectin, laminin, and type I collagen. The enzyme caused a loss of adhesion of mammalian cells in culture, probably because of its ability to degrade anchoring proteins. Experiments with a peptide substrate and inhibitors indicated that the proteinase preferentially binds peptides with arginine at P-1. It is also a plasminogen activator, and could thus potentiate host proteinase systems.
Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment.
Authors: S A Rubin, H V Brown, H J Swan
Journal: Circulation (1982)

Arterial oxygen transport (cardiac output x arterial oxygen content) may be decreased in heart failure. We studied the determinants of arterial oxygen transport in 15 patients with chronic, severe myocardial failure at rest and during cycle ergometry. During control therapy at rest, arterial oxygen tension was normal (81 +/- 8 mm Hg, mean +/- SD) and increased slightly during exercise (90 +/- 14 mm Hg). During hydralazine therapy at rest, arterial oxygen tension was slightly higher (87 +/- 9 mm Hg) and also increased during exercise (92 +/- 15 mm Hg). Hydralazine did not increase arterial oxygen tension (0.10 greater than p greater than 0.05), but exercise did (p less than 0.02). Arterial oxygen saturation and content were normal and did not change under any condition or treatment. During control therapy at rest, arterial oxygen transport was low (313 +/- 74 ml/min . m2) and remained abnormally low during exercise (434 +/- 124 ml/min . m2). During hydralazine therapy, arterial oxygen transport was higher at rest (457 +/- 100 ml/min . m2) and during exercise (577 +/- 131 ml/min . m2). Hydralazine increased arterial oxygen transport (p less than 0.01) because it increased stroke volume at rest and during exercise, but it did not change arterial oxygenation. Arterial oxygenation is normal in chronic heart failure patients at rest and during exercise. Hydralazine increases cardiac output and arterial oxygen transport without changing arterial oxygenation.
Xenografts of Human Hepatocellular Carcinoma: A Useful Model for Testing Drugs
Authors: Hung Huynh, Khee Chee Soo, Pierce K.H. Chow, Lawrence Panasci, Evelyn Tran
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Our aims were to establish and characterize primary human hepatocellular carcinoma xenografts. They were used to screen new drugs and improve our current treatment regimens used in hepatocellular carcinoma. Experimental Design: Primary hepatocellular carcinomas were used to create the xenografts. Western blotting was used to determine the changes in proteins in these xenografts before and after therapies. Apoptotic and cell proliferation were analyzed by immunohistochemistry. Results: Seven lines of xenografts were established from primary human hepatocellular carcinomas. Lines 4-1318, 2-1318, 2006, and 26-1004 grew rapidly in severe combined immunodeficient (SCID) mice and doubled its volume every 48 to 72 hours. Series 5-1318 (5-1318, 30-1004, and 29-1104) grew relatively slowly in SCID mice and required ∼6 to 10 days to double its tumor volume. Western blot analysis revealed that the growth rate of these xenografts was associated with abnormal expression of proteins associated with the cell cycle, signaling pathways, and tumor suppressor genes. Although hepatocellular carcinoma xenografts expressed the receptors for androgens, estrogens, and progesterone, their growth rate was not affected by either castration or sex steroid hormone supplementation. Cisplatin, oxaliplatin, vitamin D analogue EB1089, and Iressa had no effects on the growth rate in SCID mice. Although 5-fluorouracil exerted mild growth inhibition of these xenografts, i.p. delivery of 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) or doxorubicin resulted in a significant growth inhibition. Doxorubicin-induced growth suppression was associated with elevation of p53 and p21Cip1/Waf1. In addition to up-regulation of p53 and p21Cip1/Waf1, SarCNU also increased the levels of phosphorylated cdc-2 at Tyr15. Conclusion: Hepatocellular carcinoma xenografts are powerful tools for screening drugs and SarCNU may be useful in the treatment of this fatal disease.
Molecular Basis of Electrophilic and Oxidative Defense: Promises and Perils of Nrf2
Authors: Qiang Ma, Xiaoqing He
Journal: Pharmacological Reviews (2012)

Induction of drug-metabolizing enzymes through the antioxidant response element (ARE)-dependent transcription was initially implicated in chemoprevention against cancer by antioxidants. Recent progress in understanding the biology and mechanism of induction revealed a critical role of induction in cellular defense against electrophilic and oxidative stress. Induction is mediated through a novel signaling pathway via two regulatory proteins, the nuclear factor erythroid 2-related factor 2 (Nrf2) and the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Nrf2 binds to Keap1 at a two site-binding interface and is ubiquitinated by the Keap1/cullin 3/ring box protein-1-ubiquitin ligase, resulting in a rapid turnover of Nrf2 protein. Electrophiles and oxidants modify critical cysteine thiols of Keap1 and Nrf2 to inhibit Nrf2 ubiquitination, leading to Nrf2 activation and induction. Induction increases stress resistance critical for cell survival, because knockout of Nrf2 in mice increased susceptibility to a variety of toxicity and disease processes. Collateral to diverse functions of Nrf2, genome-wide search has led to the identification of a plethora of ARE-dependent genes regulated by Nrf2 in an inducer-, tissue-, and disease-dependent manner to control drug metabolism, antioxidant defense, stress response, proteasomal degradation, and cell proliferation. The protective nature of Nrf2 could also be hijacked in a number of pathological conditions by means of somatic mutation, epigenetic alteration, and accumulation of disruptor proteins, promoting drug resistance in cancer and pathologic liver features in autophagy deficiency. The repertoire of ARE inducers has expanded enormously; the therapeutic potential of the inducers has been examined beyond cancer prevention. Developing potent and specific ARE inducers and Nrf2 inhibitors holds certain new promise for the prevention and therapy against cancer, chronic disease, and toxicity.
Repeatable Battery for the Assessment of Neuropsychological Status as a Screening Test in Schizophrenia, I: Sensitivity, Reliability, and Validity
Authors: James M. Gold, Caleb Queern, Virginia N. Iannone, Robert W. Buchanan
Journal: American Journal of Psychiatry (1999)

Cognitive impairment is an important feature of schizophrenia and is correlated with functional outcome. However, psychiatry lacks a screening instrument that can reliably assess the types of cognitive impairment often seen in schizophrenia. The authors assessed the sensitivity, convergent validity, and reliability of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as well as the relationship of the RBANS to symptoms and employment status. This newly published test takes 25 minutes to administer and was standardized on a U.S.-Census-matched adult population. The test provides a total score and five index scores, each with a mean value of 100 (SD = 15).RBANS data were obtained from 129 patients with schizophrenia in the outpatient and inpatient programs of the Maryland Psychiatric Research Center. RBANS data were correlated with WAIS-III and Wechsler Memory Scale, 3rd ed. performance in 38 patients. Reliability data for alternate forms of the RBANS were obtained from 53 patients; symptom ratings were obtained from 48 patients; and employment status was examined in 77 patients.The patients with schizophrenia demonstrated marked impairment on the RBANS (their mean total score was 71.4). The patients' index scores suggested that they had relatively less impairment of language and visual functions than of memory and attention. The RBANS demonstrated high correlations with full-scale IQ and memory measures. The total score demonstrated good reliability. RBANS performance minimally correlated with Brief Psychiatric Rating Scale ratings but was strongly related to employment outcome.The RBANS appears to be a useful cognitive screening instrument in schizophrenia. The instrument may be a useful prognostic indicator and offers a means of assessing cognitive status.
GnRH agonist for triggering final oocyte maturation: time for a critical evaluation of data
Authors: E.M. Kolibianakis, G. Griesinger, C.A. Venetis
Journal: Human Reproduction Update (2012)

GnRH agonist for triggering final oocyte maturation: time for a critical evaluation of data Sir, We read with great interest the manuscript by Humaidan et al. (2011).In this review, the authors summarize the published evidence regarding the use of GnRH agonist for triggering final oocyte maturation in patients undergoing IVF.By combining the results of six recently published randomized controlled trials (RCTs), the authors suggest that when a modified luteal phase support (LPS) is employed, following GnRH agonist triggering, pregnancy rates are comparable with those achieved after hCG triggering and standard LPS.Moreover, they suggest that GnRH agonist triggering combined with a modified LPS results in elimination of ovarian hyperstimulation syndrome (OHSS).These findings are very interesting, since they support the notion that GnRH agonist triggering when combined with a modified LPS is both an effective and safe treatment.We would like to elaborate on the data presented by the authors and extend the implications of the available evidence on the efficacy and safety of GnRH agonist triggering.
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Authors: William B. Ershler, Evan T. Keller
Journal: Annual Review of Medicine (2000)

Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer’s disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.
Galectin-3 Modulates Ureteric Bud Branching in Organ Culture of the Developing Mouse Kidney
Authors: SIMON L. BULLOCK, TANYA M. JOHNSON, QI BAO, R. COLIN HUGHES, PAUL J. D. WINYARD, ADRIAN S. WOOLF
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Galectin-3 is a mammalian β-galactoside—specific lectin with functions in cell growth, adhesion, and neoplastic transformation. On the basis of expression patterns in humans, it is proposed that galectin-3 modulates fetal collecting duct growth. This article provides evidence that galectin-3 can modulate branching morphogenesis of the mouse ureteric bud/collecting duct lineage. With the use of immunohistochemistry, galectin-3 was not detected in early metanephrogenesis but was upregulated later in fetal kidney maturation when the protein was prominent in basal domains of medullary collecting ducts. Addition of galectin-3 to embryonic days 11 and 12 whole metanephric cultures inhibited ureteric bud branching, whereas galectin-1 did not perturb morphogenesis, nor did a galectin-3 mutant lacking wild-type high-affinity binding to extended oligosaccharides. Exogenous galectin-3 retarded conversion of renal mesenchyme to nephrons in whole metanephric explants but did not affect nephron induction by spinal cord in isolated renal mesenchymes. Finally, addition of a blocking antiserum to galectin-3 caused dilation and distortion of developing epithelia in embryonic day 12 metanephroi cultured for 1 wk. The upregulation of galectin-3 protein during kidney maturation, predominantly at sites where it could mediate cell/matrix interactions, seems to modulate growth of the ureteric tree.
Metastatic Cells Can Escape the Proapoptotic Effects of TNF-α through Increased Autocrine IL-6/STAT3 Signaling
Authors: Shun Li, Ni Wang, Pnina Brodt
Journal: Cancer Research (2011)

The liver is a common site for cancer metastases in which the entrance of tumor cells has been shown to trigger a rapid inflammatory response. In considering how an inflammatory response may affect metastatic colonization in this setting, we hypothesized that tumor cells may acquire resistance to the proapoptotic and tumoricidal effects of TNF-α, a cytokine that is elevated in a proinflammatory tissue microenvironment. In this study, we investigated molecular mechanisms by which such resistance may emerge using tumor cells in which the overexpression of the type I insulin-like growth factor receptor (IGF-IR) enhanced the inflammatory and metastatic capacities of poorly metastatic cells in the liver. Mechanistic investigations in vitro revealed that IGF-IR overexpression increased cell survival in the presence of high levels of TNF-α, in a manner associated with increased autocrine production of interleukin-6 (IL)-6. In turn, tumor cell-derived IL-6 induced gp130 and IL-6R-dependent activation of STAT3, leading to reduced caspase-3 activation and apoptosis. We found that IL-6 production and cell death resistance were dose dependent with increasing TNF-α levels. In addition, RNA interference-mediated knockdown of either IL-6 or gp130 that established a blockade to autocrine STAT3 induction was sufficient to abolish the prosurvival effect of TNF-α and to inhibit liver metastasis. Taken together, our findings define an IGF-IR-mediated mechanism of cancer cell survival that is critical for metastatic colonization of the liver.
Histidine-rich glycoprotein inhibits the antiproliferative effect of heparin on smooth muscle cells.
Authors: D P Hajjar, D B Boyd, P C Harpel, R L Nachman
Journal: The Journal of Experimental Medicine (1987)

Histidine-rich glycoprotein (HRGP), an alpha-glycoprotein in human plasma that is also present in platelets and macrophages, binds heparin with high affinity and neutralizes its anticoagulant activity. We now report that HRGP specifically inhibits the antiproliferative effect of heparin on arterial smooth muscle cells while other heparinoid-binding proteins do not influence mitogenesis. The multicellular inflammatory response to endothelial injury characterized, in part, by the influx of platelets and macrophages, may be associated with HRGP release into the arterial microenvironment. This release of HRGP may allow smooth muscle cell proliferation and atherogenesis by inhibiting the action of endothelial cell-derived heparinoid substances.
Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals
Authors: Susan Moir, Jason Ho, Angela Malaspina, Wei Wang, Angela C. DiPoto, Marie A. O'Shea, Gregg Roby, Shyam Kottilil, James Arthos, Michael A. Proschan, Tae-Wook Chun, Anthony S. Fauci
Journal: The Journal of Experimental Medicine (2008)

Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20hi/CD27lo/CD21lo) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20hi/CD27−/CD21lo) when compared with B cells with a classical memory (CD27+) or naive (CD27−/CD21hi) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.
Response to Egede
Authors: Steven A. Grover, Louis Coupal, Hanna Zowall
Journal: Diabetes Care (2001)

We thank Dr. Egede (1) for his letter in this issue of Diabetes Care and for taking the time to read our study (2) and provide us with his thoughtful comments. He raises several important points.

The first point concerns the choice of years of life saved rather than quality-adjusted life years in the cost-effectiveness analysis. Dr. Egede’s point that both diabetes and cardiovascular disease may have a significant impact on quality of life is well taken. We agree with him that it would be desirable to include quality-of-life issues in …
Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
Authors: Lili Jing, Owen J. Tamplin, Michael J. Chen, Qing Deng, Shenia Patterson, Peter G. Kim, Ellen M. Durand, Ashley McNeil, Julie M. Green, Shinobu Matsuura, Julien Ablain, Margot K. Brandt, Thorsten M. Schlaeger, Anna Huttenlocher, George Q. Daley, Katya Ravid, Leonard I. Zon
Journal: The Journal of Experimental Medicine (2015)

Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1+/cmyb+ HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl+ hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP–protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.
Personalized Medicine and Cancer Supportive Care: Appropriate Use of Colony-Stimulating Factor Support of Chemotherapy
Authors: N. M. Kuderer, G. H. Lyman
Journal: JNCI Journal of the National Cancer Institute (2011)

Myelosuppression and neutropenic complications remain major dose-limiting toxicities of cancer chemotherapy resulting in increased morbidity, mortality, and costs (1,2). The major factors that are associated with the risk of mortality from febrile neutropenia (FN) include older age, cancer type and stage, documented infection, bacteremia, sepsis, venous thromboembolism, and the number of serious comorbid conditions (2–6). The risk for neutropenic complications, including FN, is greatest during the first cycle of chemotherapy when most patients are still receiving the full dose and schedule (7,8). When subsequent full-dose chemotherapy is continued on schedule without colony-stimulating factor (CSF) prophylaxis despite a previous neutropenic event, the risk of FN remains high throughout the period of chemotherapy treatment (9). Initiation of the CSFs early in the first cycle of chemotherapy and continuation through all cycles of a chemotherapy regimen (primary prophylaxis) has been shown to substantially reduce the risk of FN as well as infection-related and early all-cause mortality, while decreasing the need for chemotherapy dose reductions and delays (10,11). Furthermore, most of the pivotal trials of primary prophylaxis with CSFs permitted secondary prophylaxis after a neutropenic event in the control arms, providing reasonable evidence that primary prophylaxis is superior to secondary prophylaxis (10). There are also increasing data from randomized controlled trials (RCTs) of patients with solid tumors and lymphoma on the potential value of CSF support of chemotherapy to improve overall survival (12).
Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma
Authors: Kouki Nio, Taro Yamashita, Hikari Okada, Mitsumasa Kondo, Takehiro Hayashi, Yasumasa Hara, Yoshimoto Nomura, Sha Sha Zeng, Mariko Yoshida, Tomoyuki Hayashi, Hajime Sunagozaka, Naoki Oishi, Masao Honda, Shuichi Kaneko
Journal: Journal of Hepatology (2015)
Potential impact of public access defibrillators on survival after out of hospital cardiopulmonary arrest: retrospective cohort study
Authors: J. P Pell
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To estimate the potential impact of public access defibrillators on overall survival after out of hospital cardiac arrest. <b>Design:</b> Retrospective cohort study using data from an electronic register. A statistical model was used to estimate the effect on survival of placing public access defibrillators at suitable or possibly suitable sites. <b>Setting:</b> Scottish Ambulance Service. <b>Subjects:</b> Records of all out of hospital cardiac arrests due to heart disease in Scotland in 1991-8. <b>Main outcome measures:</b> Observed and predicted survival to discharge from hospital. <b>Results:</b> Of 15 189 arrests, 12 004 (79.0%) occurred in sites not suitable for the location of public access defibrillators, 453 (3.0%) in sites where they may be suitable, and 2732 (18.0%) in suitable sites. Defibrillation was given in 67.9% of arrests that occurred in possibly suitable sites for locating defibrillators and in 72.9% of arrests that occurred in suitable sites. Compared with an actual overall survival of 744 (5.0%), the predicted survival with public access defibrillators ranged from 942 (6.3%) to 959 (6.5%), depending on the assumptions made regarding defibrillator coverage. <b>Conclusions:</b> The predicted increase in survival from targeted provision of public access defibrillators is less than the increase achievable through expansion of first responder defibrillation to non-ambulance personnel, such as police or firefighters, or of bystander cardiopulmonary resuscitation. Additional resources for wide scale coverage of public access defibrillators are probably not justified by the marginal improvement in survival.