tbuckley/cabot-search huggingface dataset:
Blood Collection, Processing Methods and Maternal Char-acteristics and the Potential Impact on Study Results in a Longitudinal Birth Cohort Study
Authors: K.A. Roberg, K.T. Sullivan-Dillie, K.S. Anklam, L.A. Rosenthal, D.F. DaSilva, C.J. Tisler, T.E. Pappas, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2006)
Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway
Authors: Tatsuya Yoshihara, Fumi Takahashi-Yanaga, Fumie Shiraishi, Sachio Morimoto, Yutaka Watanabe, Masato Hirata, Sumio Hoka, Toshiyuki Sasaguri
Journal: Molecular Cancer (2010)

Abstract Background Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces cell differentiation in Dictyostelium discoideum . DIF-1 inhibits proliferation of various mammalian tumor cells by suppressing the canonical Wnt/β-catenin signaling pathway. To assess the potential of a novel cancer chemotherapy based on the pharmacological effect of DIF-1, we investigated whether DIF-1 exhibits anti-angiogenic effects in vitro and in vivo . Results DIF-1 not only inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) by restricting cell cycle in the G 0 /G 1 phase and degrading cyclin D1, but also inhibited the ability of HUVECs to form capillaries and migrate. Moreover, DIF-1 suppressed VEGF- and cancer cell-induced neovascularization in Matrigel plugs injected subcutaneously to murine flank. Subsequently, we attempted to identify the mechanism behind the anti-angiogenic effects of DIF-1. We showed that DIF-1 strongly decreased vascular endothelial growth factor receptor-2 (VEGFR-2) expression in HUVECs by inhibiting the promoter activity of human VEGFR-2 gene, though it was not caused by inhibition of the Wnt/β-catenin signaling pathway. Conclusion These results suggested that DIF-1 inhibits angiogenesis both in vitro and in vivo , and reduction of VEGFR-2 expression is involved in the mechanism. A novel anti-cancer drug that inhibits neovascularization and tumor growth may be developed by successful elucidation of the target molecules for DIF-1 in the future.
Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212).
Authors: V A Tron, M D Coughlin, D E Jang, J Stanisz, D N Sauder
Journal: Journal of Clinical Investigation (1990)

Nerve growth factor (NGF) is a polypeptide that is required for normal development and maintenance of the sympathetic and sensory nervous systems. Skin has been shown to contain relatively high amounts of NGF, which is in keeping with the finding that the quantity of NGF in a tissue is proportional to the extent of sympathetic innervation of that organ. Since the keratinocyte, a major cellular constituent of the skin, is known to produce other growth factors and cytokines, our experiments were designed to determine whether keratinocytes are a source of NGF. Keratinocyte-conditioned media from the keratinocyte cell line PAM 212 contained NGF-like activity, approximately 2-3 ng/ml, as detected by the neurite outgrowth assay. Freshly isolated BALB/c keratinocytes contained approximately 0.1 ng/ml. Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes. Since ultraviolet radiation (UV) is a potentially important modulating factor for cytokines in skin, we examined the effect of UV on NGF mRNA expression. Although UV initially inhibited the expression of keratinocyte NGF mRNA (4 h), by 24 h an induction of NGF mRNA was seen. The NGF signal could also be induced by phorbol esters. Thus, keratinocytes synthesize and express NGF, and its expression is modulated by UVB and phorbol esters.
1026-61 Quantitative evaluation of coronary reperfusion by transthoracic doppler echocardiography in patients with anterior acute myocardial infarction
Authors: Souki Lee, Yutaka Otuji, Shinichi Minagoe, Shuichi Hamasaki, Koichi Toyonaga, Hachirou Obata, Takurou Takumi, Hitoshi Toda, Chuwa Tei
Journal: Journal of the American College of Cardiology (2004)
Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner
Authors: Michael Sebbagh, Jocelyne Hamelin, Jacques Bertoglio, Eric Solary, Jacqueline Bréard
Journal: The Journal of Experimental Medicine (2005)

Caspase activation in target cells is a major function of granzyme B (grB) during cytotoxic lymphocyte granule-induced apoptosis. grB-mediated cell death can occur in the absence of active caspases, and the molecular targets responsible for this additional pathway remain poorly defined. Apoptotic plasma membrane blebbing is caspase independent during granule exocytosis–mediated cell death, whereas in other instances, this event is a consequence of the cleavage by caspases of the Rho effector, Rho-associated coiled coil–containing protein kinase (ROCK) I. We show here that grB directly cleaves ROCK II, a ROCK family member encoded by a separate gene and closely related to ROCK I, and this causes constitutive kinase activity and bleb formation. For the first time, two proteins of the same family are found to be specifically cleaved by either a caspase or grB, thus defining two independent pathways with similar phenotypic consequences in the cells. During granule-induced cell death, ROCK II cleavage by grB would overcome, for this apoptotic feature, the consequences of deficient caspase activation that may occur in virus-infected or malignant target cells.
Prospective clinical trials of intracranial low-grade glioma in adults and children
Authors: Edward G. Shaw, Jeffrey H. Wisoff
Journal: Neuro-Oncology (2003)

Over the last decade, the results of 5 prospective clinical trials of intracranial low-grade glioma (LGG) have been published, 4 in adults with supratentorial LGG and 1 in children with infra- and supratentorial LGG. The data from the more than 1600 patients treated on these studies are summarized herein. European Organization for Research and Treatment of Cancer study 22845 randomized 311 adults to postoperative observation or radiation therapy (RT). There was no difference in the 5-year overall survival (OS) rate between the 2 arms. Irradiated patients had a significantly improved 5-year progression-free survival (PFS) rate. European Organization for Research and Treatment of Cancer study 22844 randomized 379 adults to low-dose (45 Gy) versus high-dose (59.4 Gy) RT. Similarly, an intergroup study conducted by the North Central Cancer Treatment Group, Radiation Therapy Oncology Group, and Eastern Cooperative Group randomized 203 adults to low-dose (50.4 Gy) versus high-dose (64.8 Gy) RT. There was no difference in the 5-year OS or PFS rates between the 2 dose groups in either study. A Southwest Oncology Group study randomized 54 adults with incompletely resected LGG to RT alone or RT plus CCNU (lomustine) chemotherapy. There was no difference in outcome between the 2 treatment arms. Important prognostic factors for OS in these 4 adult trials included extent of surgical resection, histology, tumor size, and age. An intergroup study of the Children's Cancer Group and Pediatric Oncology Group enrolled 660 pediatric patients with management based on the extent of surgical resection: Children who underwent gross total tumor resection were observed postoperatively, whereas those who had subtotal resection or biopsy were either observed or administered RT at the discretion of their physician. Survival was most impacted by several prognostic factors, primarily extent of resection. Besides extent of resection, other prognostic factors that were consistent in predicting survival in these 5 clinical trials included patient age and tumor location, size, and histology. The data from these 5 studies indicate that for intracranial LGG in adults, postoperative RT is associated with improved 5-year PFS but not OS rates compared to postoperative observation. Radiation doses of 45 to 54 Gy result in 5-year OS and PFS rates that are similar to those for higher doses. The strategies of chemotherapy alone and RT plus chemotherapy are under investigation. For pediatric LGG, extent of surgical resection is the most important prognostic factor associated with favorable 5-year OS and PFS. Radiation therapy and chemotherapy are generally used in the settings of incomplete resection and recurrent disease, and these strategies are being investigated in prospective clinical trials. The schemata from recently completed and ongoing studies in both adult and pediatric intracranial LGG are reviewed.
Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
Authors: Sophie Brouard, Leo E. Otterbein, Josef Anrather, Edda Tobiasch, Fritz H. Bach, Augustine M.K. Choi, Miguel P. Soares
Journal: The Journal of Experimental Medicine (2000)

Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-α. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO.
One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group
Authors: T. Tandstad, O. Ståhl, U. Håkansson, O. Dahl, H.S. Haugnes, O.H. Klepp, C.W. Langberg, A. Laurell, J. Oldenburg, A. Solberg, K. Söderström, E. Cavallin-Ståhl, U. Stierner, R. Wahlquist, N. Wall, G. Cohn-Cedermark
Journal: Annals of Oncology (2014)
Spontaneous Gastroesophageal Reflux and Airway Patency during the Night in Adult Asthmatics
Authors: GIUSEPPINA CUTTITTA, FABIO CIBELLA, ALFREDO VISCONTI, NICOLA SCICHILONE, VINCENZO BELLIA, GIOVANNI BONSIGNORE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Controversies still exist on the role of nighttime gastroesophageal reflux (GER) in precipitating nocturnal asthma. We tested the relationship between GER and nocturnal bronchoconstriction by continuously and simultaneously monitoring both respiratory resistances and esophageal pH in seven asthmatics with moderate to severe GER disease. Twenty-nine GER episodes were found during the study night lasting more than 5 min (lGER) and 72 not longer than 5 min (sGER). Both long (lGER) and short (sGER) gastroesophageal refluxes were able to maintain significantly higher lower respiratory resistances (Rlr) at the resolution of each GER episode (Rlr e) with respect to baseline values. Rlr, expressed as the area under the Rlr curve along each GER episode (AUCr LR) and as Rlr e, showed significant correlations with GER duration. Moreover, a significant correlation was found between Rlr measured 10 min after GER resolution and GER duration during each episode. We conclude that GER itself is able to elicit nocturnal bronchoconstriction in asthmatics with moderate to severe GER disease and that bronchoconstriction severity and duration are related to GER duration. Cuttitta G, Cibella F, Visconti A, Scichilone N, Bellia V, Bonsignore G. Spontaneous gastroesophageal reflux and airway patency during the night in adult asthmatics.
Balloon or bougie for dilatation of benign oesophageal stricture? An interim report of a randomised controlled trial.
Authors: J G Cox, R K Winter, S C Maslin, R Jones, G K Buckton, R C Hoare, D R Sutton, J R Bennett
Journal: Gut (1988)

Seventy one patients with benign oesophageal strictures were randomised to receive balloon or bougie dilatation. Sixty five patients were eligible for analysis. At the end of five months the balloon group had significantly more dysphagia and the calibre of the strictures in the balloon group had narrowed by a greater degree. The methods were equally safe and acceptable to patients. While the choice of the method of dilatation depends on the individual patient9s needs and operator experience, bougie dilatation is more effective in reducing dysphagia and maintaining stricture patency.
More adverse renal prognosis of autosomal dominant polycystic kidney disease in families with primary hypertension.
Authors: S Geberth, E Stier, M Zeier, G Mayer, M Rambausek, E Ritz
Journal: Journal of the American Society of Nephrology (1995)

Marked variability of age at renal death is noted in autosomal dominant polycystic kidney disease (ADPKD). The hypothesis that the coexistence of primary hypertension and ADPKD within families is associated with earlier renal death was tested. Of a total of 162 ADPKD patients treated in one Austrian and three German centers, 57 propositi were identified whose families provided (1) information concerning blood pressure; (2) documented presence of ADPKD (by sonography or autopsy) in one parent; and (3) age at renal death in the propositus. Hypertension of the unaffected parent was defined as blood pressure above 140/90 mm Hg or antihypertensive treatment before age 60 yr. Age at renal death in the propositus was defined as the start of renal replacement therapy. Median age at renal death of 23 offspring (11 male, 12 female) from families with a history of primary hypertension of the nonaffected parent was lower than that of 34 offspring (16 male, 18 female) from families without a known history of primary hypertension of the nonaffected parent, i.e., 49 yr (26 to 64) versus 54 yr (28 to 82) (P < 0.03). The data are consistent with the notion that genetic predisposition to primary hypertension is associated with an earlier onset of terminal renal failure in families with ADPKD.
Widespread Promiscuous Genetic Information Transfer From DNA to RNA
Authors: Aravinda Chakravarti
Journal: Circulation Research (2011)

N ew genomic studies show that the transfer of genetic information from DNA to RNA within humans is not very faithful.If true, frequent, or purposeful, then the implications for human health and disease are significant, but the burden of proof required is significant.Commentary: Molecular biology and genetics has a "central dogma."First postulated by Francis Crick 1,2 in 1958, shortly after the discovery of the double helix, it states that the molecular transfer or flow of genetic information occurs only as DNA3 RNA3 protein.This argument is intrinsic to our understanding of genotypes, phenotypes, and human disease.The central "dogma," a word whose precise meaning Crick acknowledged he did not precisely know 3 and that could have been given the less glamorous moniker "hypothesis," is frequently misunderstood as also implying high accuracy or even inflexibility. 2We now know that genetic information flow can be sometimes corrupted and can also occur in other directions in particular biological systems.A recent study by Li and colleagues, 4 from the laboratory of Vivian Cheung at the University of Pennsylvania, now demonstrates apparent widespread DNA3 RNA sequence differences in humans.The experiments they conducted involved sequencing reverse-transcribed RNA from cultured B cells isolated from 27 different humans and comparing them with their host genome sequences.Surprisingly, after appropriate quality controls, they discovered numerous base positions at which the RNA sequence was different from the DNA sequence in multiple molecules, a phenomenon they refer to as RDD (RNA-DNA difference).Specifically, they identified 28766 RDDs in the 27 individuals at 10210 exonic sites within 4741 genes.Each individual had high-quality RNA-based sequence data at 9.8 million sites: so, RDD was
Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma
Authors: Melanie B. Thomas, Jeffrey S. Morris, Romil Chadha, Michiko Iwasaki, Harmeet Kaur, Elinor Lin, Ahmed Kaseb, Katrina Glover, Marta Davila, James Abbruzzese
Journal: Journal of Clinical Oncology (2009)

The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity.Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated.The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each).The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.
Alteration of autonomic influence on left ventricular contractility by epicardial superfusion with hexamethonium and procaine
Authors: R. J Applegate, W. C Little
Journal: Cardiovascular Research (1994)

Journal Article Alteration of autonomic influence on left ventricular contractility by epicardial superfusion with hexamethonium and procaine Get access Robert J Applegate, Robert J Applegate Department of Internal Medicine (Section of Cardiology), The Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA: R J Applegate, W C Little. Correspondence to Dr Applegate. Search for other works by this author on: Oxford Academic PubMed Google Scholar William C Little William C Little Department of Internal Medicine (Section of Cardiology), The Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA: R J Applegate, W C Little. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 1042–1048, https://doi.org/10.1093/cvr/28.7.1042 Published: 01 July 1994 Article history Received: 29 September 1993 Accepted: 17 January 1994 Published: 01 July 1994
'Myocardial hibernation'—questions and controversies
Authors: G Heusch
Journal: Cardiovascular Research (1997)

Time for primary review 44 days.

The term ‘hibernation’ has been borrowed from zoology and implies an adaptive reduction of energy expenditure through reduced activity in a situation of reduced energy supply. In the context of coronary artery disease, myocardial hibernation was originally seen as a chronic , adaptive reduction of myocardial contractile function in response to a reduction of myocardial blood flow. It was also viewed as a condition where there would be a complete recovery of contractile function upon restoration of flow. Thus, in the concept of myocardial hibernation, the observed chronic reduction of myocardial contractile function was not regarded as the result of a persistent energetic deficit, but instead as a regulatory event which acted to avoid an ongoing energy deficit and thereby maintain myocardial integrity and viability.

The concept of myocardial hibernation did not originate in the laboratory, instead it was entirely founded on clinical grounds when, in the early eighties, Rahimtoola reviewed the results of coronary bypass surgery trials and identified a subset of patients with coronary artery disease and chronic left ventricular dysfunction that improved upon revascularization [1, 2]. Rahimtoola then popularized the term ‘hibernation’ previously coined by Diamond et al. [3]. Whereas originally the idea of an adaptive reduction of contractile function in response to a reduction in blood flow was straightforward and simple, the situation of chronic, yet reversible contractile dysfunction in the setting of coronary artery disease is now recognized to be enormously complex and controversial. The aim of this article is not to give definite answers to any questions, but rather to identify the most pressing questions and controversies in the field of hibernation.

The introduction of the concept of hibernation has challenged the traditional view that the extent of chronic contractile dysfunction reflects the amount of infarcted … 

* Corresponding author. Abteilung fur Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Hufelandstrase 55, 45122 Essen, Germany. Tel.: +49 (201) 7234480; fax: +49 (201) 7234481.
Effect of Blood and Saline Infusion on Cardiac Performance in Normal Dogs and Dogs with Arteriovenous Fistulas
Authors: THOMAS B. FERGUSON, DONALD E. GREGG, OSCAR W. SHADLE
Journal: Circulation Research (1954)

Maximum left ventricular work response (and other hemodynamic changes) to infusion of saline and whole blood was compared in normal dogs and in dogs with aorta-caval and multiple peripheral fistulas. In the dogs with fistulas the augmented preinfusion levels of cardiac work and left ventricular end-diastolic pressure approximated those in normal dogs after maximum response to infusion. Following infusion in the dogs with fistulas, end-diastolic pressure characteristically increased but cardiac work did not. Thus maximum cardiac work was of the same order of magnitude in the normal dogs and in the dogs with fistulas. In all groups maximum left ventricular work was effected mainly through an increased cardiac output.
Effect of dietary cereals on intestinal permeability in experimental enteropathy in rats.
Authors: J S Sandhu, D R Fraser
Journal: Gut (1983)

A sensitivity to dietary cereal has been reported previously in niacin-deficient rats by measuring a change in the intestinal absorption of radioactively-labelled cellobiotol and mannitol. The possibility that other stimuli could produce this sensitivity, the range of cereals that could induce the permeability change and the nature of the toxic component in cereal have now all been investigated. Treatment with triparanol induces sensitivity in rats to wheat, rye, barley, oats, and maize but not to rice or soybean. These cereals caused a similar response in niacin-deficient rats. Mucosal damage produced by methotrexate or cetrimide, however, did not sensitise the intestinal mucosa to dietary cereals. Gluten, zein, and pepsin/trypsin digests of gluten all induced the permeability defect in triparanol-treated rats. It is concluded that although gross disruption of the mucosal structure may not sensitise rats to cereals, various causes of mucosal cell damage can produce a susceptibility to gluten toxicity that resembles gluten-sensitivity in man.