tbuckley/cabot-search huggingface dataset:
Low-Dose 12-<i>O</i>-Tetradecanoylphorbol-13-Acetate Enhances Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis in Prostate Cancer Cells
Authors: Xiaoping Zhang, Wenhua Li, Aria F. Olumi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Previously, we have shown that c-Fos/activator protein-1 (AP-1) promotes tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL)–induced apoptosis by repressing the antiapoptotic molecule c-FLIP(L). In this study, we investigated whether synthetic induction of c-Fos/AP-1 by 12-O-tetradecanoylphorbol-13-acetate (TPA) converts the phenotype of TRAIL-resistant prostate cancer cells to a TRAIL-sensitive phenotype in vitro and in vivo. Experimental Design: Low-dose TPA was used to determine whether LNCaP prostate cancer cells could be converted to a TRAIL-sensitive phenotype in in vitro and in vivo studies. We also assessed whether TPA enhancement of TRAIL-induced apoptosis varies between androgen-sensitive and androgen-insensitive prostate cancer cells and evaluated the role of TRAIL receptors, DR4 and DR5, in TPA-enhanced TRAIL-induced apoptosis. Results: We show that the combination of TRAIL with low-dose TPA has no effect on nonmalignant prostate epithelial cells; however, TPA up-regulates most AP-1 proteins and AP-1 activity, reduces c-FLIP(L), and potentiates TRAIL-induced apoptosis. We show that the combination of TPA + TRAIL is effective in promoting apoptosis in both hormone-sensitive LNCaP and hormone-insensitive LNCaP-C4-2 prostate cancer cells. Although TPA enhances the TRAIL-receptor 1 (DR4) level, sensitization of prostate cancer cells seems to be more dependent on TRAIL-receptor 2 (DR5) than TRAIL-receptor 1 levels. In vivo xenograft experiments suggest that TPA elevates the expression of c-Fos and reduces c-FLIP(L). Combination of TPA with TRAIL-receptor 2 agonist antibody, lexatumumab, effectively increases apoptosis and reduces LNCaP xenograft tumor burden. Conclusions: TPA, when combined with the proapoptotic agent TRAIL, is effective in changing the phenotype of some TRAIL-resistant prostate cancer cells to a TRAIL-sensitive phenotype.
Comparison of Methods for Determining Renal Function Decline in Early Autosomal Dominant Polycystic Kidney Disease
Authors: Andrew D. Rule, Vicente E. Torres, Arlene B. Chapman, Jared J. Grantham, Lisa M. Guay-Woodford, Kyongtae T. Bae, Saulo Klahr, William M. Bennett, Catherine M. Meyers, Paul A. Thompson, J. Philip Miller
Journal: Journal of the American Society of Nephrology (2006)

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (<i>e.g.</i>, iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance &gt;70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (<i>e.g.</i>, creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.
Macrophage type 3 complement receptors mediate serum-independent binding of Leishmania donovani. Detection of macrophage-derived complement on the parasite surface by immunoelectron microscopy.
Authors: A O Wozencraft, G Sayers, J M Blackwell
Journal: The Journal of Experimental Medicine (1986)

In this study, direct visual evidence for local opsonization of L. donovani by macrophage (M phi)-derived complement components was obtained using immunoelectron microscopy. C3 deposition was detected on the surface of both promastigotes and amastigotes after 20 min serum-free incubation with murine resident peritoneal M phi (RPM), followed by fixation and incubation first with specific antibody directed against C3 and then with gold-labelled protein A. Gold deposition was not observed around either form of the parasite if the anti-C3 antibody was omitted. For promastigotes, the degree of C3 deposition under serum-free conditions was comparable with that observed in the presence of an exogenous (serum) source of C3, but did not result in the same severe damage to the parasite as did the latter. Addition of sodium salicyl hydroxamate, which prevents covalent binding of C3 to activator surfaces, abrogated promastigote binding. Hence, although the anti-C3 antibody did not distinguish between native C3 and its breakdown product iC3b, these data support our earlier conclusion that promastigote binding to the CR3 of murine RPM is complement dependent. For amastigotes, gold deposition and binding to murine RPM were not eliminated by sodium salicyl hydroxamate. The presence of normal mouse serum resulted in increased gold deposition, but did not mediate either enhanced binding to M phi or damage to the amastigote. These data suggest that a proportion of C3 binding to the amastigote surface may be via noncovalent linkages, and that the C3 bound may not be in the correct form to mediate binding to CR3.
Soup to Tree: The Phylogeny of Beetles Inferred by Mitochondrial Metagenomics of a Bornean Rainforest Sample
Authors: Alex Crampton-Platt, Martijn J.T.N. Timmermans, Matthew L. Gimmel, Sujatha Narayanan Kutty, Timothy D. Cockerill, Chey Vun Khen, Alfried P. Vogler
Journal: Molecular Biology and Evolution (2015)

In spite of the growth of molecular ecology, systematics and next-generation sequencing, the discovery and analysis of diversity is not currently integrated with building the tree-of-life. Tropical arthropod ecologists are well placed to accelerate this process if all specimens obtained through mass-trapping, many of which will be new species, could be incorporated routinely into phylogeny reconstruction. Here we test a shotgun sequencing approach, whereby mitochondrial genomes are assembled from complex ecological mixtures through mitochondrial metagenomics, and demonstrate how the approach overcomes many of the taxonomic impediments to the study of biodiversity. DNA from approximately 500 beetle specimens, originating from a single rainforest canopy fogging sample from Borneo, was pooled and shotgun sequenced, followed by de novo assembly of complete and partial mitogenomes for 175 species. The phylogenetic tree obtained from this local sample was highly similar to that from existing mitogenomes selected for global coverage of major lineages of Coleoptera. When all sequences were combined only minor topological changes were induced against this reference set, indicating an increasingly stable estimate of coleopteran phylogeny, while the ecological sample expanded the tip-level representation of several lineages. Robust trees generated from ecological samples now enable an evolutionary framework for ecology. Meanwhile, the inclusion of uncharacterized samples in the tree-of-life rapidly expands taxon and biogeographic representation of lineages without morphological identification. Mitogenomes from shotgun sequencing of unsorted environmental samples and their associated metadata, placed robustly into the phylogenetic tree, constitute novel DNA "superbarcodes" for testing hypotheses regarding global patterns of diversity.
Diabetes Comorbidity and Age Influence Rehabilitation Outcomes After Hip Fracture
Authors: Timothy A. Reistetter, James E. Graham, Anne Deutsch, Samuel J. Markello, Carl V. Granger, Kenneth J. Ottenbacher
Journal: Diabetes Care (2011)

To examine the influence of diabetes on length of stay (LOS), functional status, and discharge setting in individuals with hip fracture.This work included secondary analyses of 79,526 individuals from 915 rehabilitation facilities in the U.S. Patients were classified into three groups using the Centers for Medicare and Medicaid Services comorbidity structure: individuals without diabetes (77.0%), individuals with non-tier diabetes (18.3%), and individuals with tier diabetes (4.7%).Mean age was 79.4 years (SD 9.6), and mean LOS was 13.3 days (SD 5.3). Tier diabetes was associated with longer LOS, lower functional status ratings, and reduced odds of discharge home when compared with individuals with no diabetes and non-tier diabetes. Statistically significant interactions (P < 0.05) were found between age and diabetes classification for LOS, functional status, and discharge setting.The impact of diabetes on recovery after hip fracture is moderated by age.
Synergistic effects of acute hypoxemia and hypercapnic acidosis in conscious dogs. Renal dysfunction and activation of the renin-angiotensin system.
Authors: C E Rose, D P Kimmel, R L Godine, D L Kaiser, R M Carey
Journal: Circulation Research (1983)

The effects of acute hypoxemia and hypercapnic acidosis were examined in five unanesthetized dogs in which sodium intake was controlled at 80 mEq/24 hours for 4 days prior to study. Each animal was studied during combined acute hypoxemia and hypercapnic acidosis (Pao2 = 36 +/- 1 mm Hg, Paco2 = 52 +/- 1 mm Hg, pH = 7.18 +/- 0.02), acute hypoxemia alone (Pao2 = 32 +/- 1 mm Hg, Paco2 = 32 +/- 1mm Hg, pH = 7.34 +/- 0.01), and acute hypercapnic acidosis alone (Pao2 = 82 +/- 2 mm Hg, Paco2 = 51 +/- 1 mm Hg, pH = 7.18 +/- 0.02). Although mean arterial pressure, cardiac output, and heart rate increased during combined hypoxemia and hypercapnic acidosis, effective renal plasma flow and glomerular filtration rate decreased. In addition, filtered sodium load and urinary sodium excretion decreased during combined hypoxemia and hypercapnic acidosis. Either acute hypoxemia or hypercapnic acidosis alone resulted in increased mean arterial pressure, cardiac output, and heart rate. However, in contrast to their combined effects, renal hemodynamic function was unchanged and natriuresis was observed. Measurement of plasma renin activity and angiotensin II concentrations indicated that hypoxemia or hypercapnic acidosis alone resulted in moderate activation of the renin-angiotensin system. Moreover, combined hypoxemia and hypercapnic acidosis acted synergistically resulting in major renin-angiotensin activation. Systemic angiotensin II blockade using 1-sarcosine, 8-alanine, angiotensin II (2 micrograms/kg per min) during combined acute hypoxemia and hypercapnic acidosis resulted in decreased renal hemodynamic function. We conclude that acute hypoxemia and hypercapnic acidosis act synergistically to increase mean arterial pressure, diminish renal hemodynamic function and activate the renin-angiotensin system. Systemic angiotensin inhibition studies suggest activation of the renin-angiotensin system maintains renal hemodynamic function during combined hypoxemia and hypercapnic acidosis, instead of mediating the renal vasoconstriction.
ACUTE PULMONARY EMBOLISM TREATED WITH TISSUE PLASMINOGEN ACTIVATOR
Authors: SamuelZ. Goldhaber, JohnE. Markis, MichaelF. Meyerovitz, DuckSoo Kim, DouglasL. Dawley, Arthur Sasahara, DouglasE. Vaughan, AndrewP. Selwyn, Joseph Loscalzo, CraigM. Kessler, G.V.R.K. Sharma, ElliottB. Grossbard, Eugene Braunwald
Journal: The Lancet (1986)
Aquaporin-1 Facilitates Epithelial Cell Migration in Kidney Proximal Tubule
Authors: Mariko Hara-Chikuma, A.S. Verkman
Journal: Journal of the American Society of Nephrology (2005)

Aquaporin-1 (AQP1) is the principal water-transporting protein in cell plasma membranes in kidney proximal tubule, where it facilitates transepithelial water transport. Here, a novel role for AQP1 in kidney involving the migration of proximal tubule cells is reported. Migration was compared in primary cultures of proximal tubule cells from wild-type and AQP1 null mice. Cell cultures from AQP1 null mice were indistinguishable from those of wild-type mice in their appearance, growth/proliferation, and adhesiveness, although, as expected, they had reduced plasma membrane water permeability. Migration of AQP1-deficient cells was reduced by >50% compared with wild-type cells, as measured in a Boyden chamber in the presence of a chemotactic stimulus. Comparable slowing of migration of AQP1-deficient cells was also found in an in vitro scratch assay of wound healing, with reduced appearance of lamella-like membrane protrusions at the cell leading edge. Adenoviral-mediated expression of AQP1 in the AQP1-deficient cells, which increased their water permeability to that of wild-type cells, corrected their migration defect. The potential relevance of these in vitro findings to the intact kidney was tested in an in vivo model of acute tubular injury caused by 30 min of renal artery occlusion. At 3 to 5 d after ischemia-reperfusion, kidneys in AQP1 null mice showed remarkably greater tubular injury and cellular actin disorganization than kidneys in wild-type mice. These results provide evidence for the involvement of AQP1 in migration of proximal tubule cells and possibly in the response of the proximal tubule to injury.
Estrogen-related receptor γ controls hepatic CB<sub>1</sub>receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol
Authors: Don-Kyu Kim, Yong-Hoon Kim, Hyun-Hee Jang, Jinyoung Park, Jung Ran Kim, Minseob Koh, Won-Il Jeong, Seung-Hoi Koo, Tae-Sik Park, Chul-Ho Yun, Seung Bum Park, John Y L Chiang, Chul-Ho Lee, Hueng-Sik Choi
Journal: Gut (2012)

The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor γ (ERRγ) is a constitutively active transcriptional activator regulating gene expression.To investigate the role of ERRγ in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRγ inverse agonist.For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1(-/-) mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice.Hepatic ERRγ gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRγ gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRγ inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRγ and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice.ERRγ, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure.
Survey shows haphazard provision of UK stroke services
Authors: M. Pownall
Journal: BMJ (1999)

A survey published this week by the Stroke Association, a UK charity, has found that 2000 to 3000 stroke patients may die every year because of “haphazard” provision of specialised stroke services.

The study was carried out by Dr Shah Ebrahim from the University of Bristol and Dr Judith Redfern from the Royal Free and University College Medical School, London, who surveyed doctors responsible for stroke care throughout the United Kingdom. Over 1700 completed questionnaires were returned by consultants …
DIETARY FIBER: How Did We Get Where We Are?
Authors: Martin Eastwood, David Kritchevsky
Journal: Annual Review of Nutrition (2005)

Dietary fiber has been a topic of considerable interest among nutritionists and clinicians for the past 50 years. Many studies on fiber have concentrated on fiber isolates, resulting in findings that have ignored fiber as a component of fruits, vegetables, nuts, cereals, and legumes in the general diet. The principle actions of fiber are to alter the nature of the contents of the gastrointestinal tract and to modify the absorption of other nutrients and chemicals. Fiber is but one component of plant food, and to neglect the other components--be they proteins, lipids, vitamins, minerals, antioxidants, or the secondary metabolites--is to seriously limit our understanding. Much of the effort expended in defining fiber and studying the fiber isolate would have been better focused using this whole-plant-food approach. Greater progress in our understanding of the relevance of fiber in the etiology of disease would have been achieved if a more holistic approach had been followed.
Coagulation and inhibitory and fibrinolytic proteins in essential hypertension.
Authors: N D Vaziri, D H Smith, R L Winer, M A Weber, E C Gonzales, J M Neutel
Journal: Journal of the American Society of Nephrology (1993)

Arterial hypertension (HTN) increases the risk of cerebral coronary, and other vascular complications that frequently involve platelet activation and blood coagulation. Several key proteins in the blood coagulation, fibrinolytic and inhibitory systems were studied in 29 men with HTN (aged 45 +/- 3 yr) and 15 normal men of the same age. Plasma levels of high-molecular-weight kininogen and factors XII, IX, VII, X, II, and XIII, as well as von Willebrand factor (vWF), fibrinogen, fibronectin, alpha 2-antiplasmin, tissue-plasminogen activator, D-dimer, platelet factor-4, and protein C were measured by the use of appropriate functional and immunologic assays before and after a cardiopulmonary exercise stress test. The concentrations of vWF, alpha 2-antiplasmin, and D-dimer were significantly (P < 0.02) higher in the HTN group as compared with the control group. The exercise stress test resulted in significant rises in the plasma vWF, alpha 2-antiplasmin, and tissue-plasminogen activator levels in the two groups. The concentrations of vWF and D-dimer were related to diastolic blood pressure (r = 0.44 and 0.40, respectively; P < 0.02). Levels of vWF also were related to left ventricular mass index and left ventricular posterior wall and septal thickness (r = 0.34, 0.43, and 0.34, respectively; P < 0.05). The constellation of these findings suggests a low-grade fibrin formation and degradation, the magnitude of which is related to the diastolic blood pressure. The observed abnormalities can potentially contribute to the cardiovascular complications of untreated HTN.
Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses.
Authors: W E Biddison, P C Doherty, R G Webster
Journal: The Journal of Experimental Medicine (1977)

Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.
Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
Authors: Katie M. Applebaum, Margaret R. Karagas, David J. Hunter, Paul J. Catalano, Steven H. Byler, Steve Morris, Heather H. Nelson
Journal: Environmental Health Perspectives (2007)

Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC).We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC.Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls.There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom).Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.
Long-term efficacy of twice-daily aclidinium bromide in COPD patients: A one-year study
Authors: Donald Tashkin, Arthur Gelb, Barry Make, Xiaoyun Zhong, Esther Garcia Gil, Cynthia Caracta
Journal: European Respiratory Journal (2012)

INTRODUCTION:

Aclidinium bromide is a long-acting muscarinic antagonist currently under investigation for the long-term maintenance treatment of COPD. In this study, the long-term efficacy and safety of twice-daily (BID) aclidinium 200 µg and 400 µg in moderate-to-severe COPD patients were assessed. The efficacy results are reported here.

METHODS:

Patients were randomized (1:1) to receive aclidinium 200 µg or 400 µg BID in a double-blind manner. The primary endpoint was change from baseline to Week 52 in trough FEV1. Other efficacy parameters included change from baseline to Week 52 in peak FEV1, trough and peak FEV1 by study visit, normalized FEV1AUC0-3, and change from baseline to Week 52 in SGRQ and EuroQol scores.

RESULTS:

A total of 605 patients were randomized to this study. Both aclidinium 200 µg and 400 µg BID resulted in improvements from baseline to Week 52 in trough and peak FEV1 (Table), with numerically larger increases seen with the 400 µg dose. At study end, change from baseline in normalized AUC0-3 FEV1 was also improved for both groups, with greater improvements seen with the higher aclidinium dose (Table). Both treatment groups showed clinically significant improvements in SGRQ Total score and improvements in EuroQoL parameters from baseline to Week 52 (Table).

![Figure][1] 



CONCLUSIONS:

Treatment with aclidinium 200 µg or 400 µg BID results in benefits in lung function and health status in COPD patients over 1 year.

 [1]: pending:yes