tbuckley/cabot-search huggingface dataset:
Impaired myogenic responsiveness of the afferent arteriole in streptozotocin-induced diabetic rats
Authors: K Hayashi, M Epstein, R Loutzenhiser, H Forster
Journal: Journal of the American Society of Nephrology (1992)

Evidence suggests that diabetes is associated with an impairment of renal autoregulation. It has previously been demonstrated that pressure-induced (myogenic) afferent arteriolar vasoconstriction is well preserved in the isolated perfused hydronephrotic kidney. In this study, pressure-induced afferent arteriolar vasoconstriction was examined in kidneys from streptozotocin-induced diabetic rats. Vessel diameters were measured by videomicroscopy as renal arterial pressure was elevated from 80 to 180 mm Hg. In normal kidneys, the afferent arteriole vasoconstricted progressively as renal arterial pressure was increased (-24 +/- 2% decrement in diameter at 180 mm Hg; N = 35; P less than 0.001). In contrast, afferent arterioles of diabetic kidneys exhibited a greatly attenuated response to pressure (i.e., -3 +/- 2% change at 180 mm Hg; N = 60). In vitro treatment with 100 microM ibuprofen completely restored myogenic vasoconstriction (-21 +/- 2% change at 180 mm Hg), but did not alter myogenic responses of control (i.e., nondiabetic) kidneys. The control of hyperglycemia by insulin treatment resulted in a partial preservation of myogenic vasoconstriction (i.e., -11 +/- 3% change at 180 mm Hg), which was further restored by the administration of a low dose (10 microM) of ibuprofen (-21 +/- 1% change at 180 mm Hg). These observations indicate that diabetes is associated with an impaired responsiveness of the afferent arteriole to pressure that is mediated by an alteration in eicosanoid metabolism. This deranged renal microcirculatory response to pressure may represent a functional impairment of the diabetic kidney that may contribute to the progression of diabetic nephropathy.
High-resolution analysis of condition-specific regulatory modules in Saccharomyces cerevisiae
Authors: Hun-Goo Lee, Hyo-Soo Lee, Sang-Hoon Jeon, Tae-Hoon Chung, Young-Sung Lim, Won-Ki Huh
Journal: Genome biology (2008)

We present an approach for identifying condition-specific regulatory modules by using separate units of gene expression profiles along with ChIP-chip and motif data from Saccharomyces cerevisiae. By investigating the unique and common features of the obtained condition-specific modules, we detected several important properties of transcriptional network reorganization. Our approach reveals the functionally distinct coregulated submodules embedded in a coexpressed gene module and provides an effective method for identifying various condition-specific regulatory events at high resolution.
A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer
Authors: H.L. Kindler, D.A. Richards, L.E. Garbo, E.B. Garon, J.J. Stephenson, C.M. Rocha-Lima, H. Safran, D. Chan, D.M. Kocs, F. Galimi, J. McGreivy, S.L. Bray, Y. Hei, E.G. Feigal, E. Loh, C.S. Fuchs
Journal: Annals of Oncology (2012)
Concurrent Chemoradiotherapy vs Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: Phase III Randomized Trial
Authors: Qiu-Yan Chen, Yue-Feng Wen, Ling Guo, Huai Liu, Pei-Yu Huang, Hao-Yuan Mo, Ning-Wei Li, Yan-Qun Xiang, Dong-Hua Luo, Fang Qiu, Rui Sun, Man-Quan Deng, Ming-Yuan Chen, Yi-Jun Hua, Xiang Guo, Ka-Jia Cao, Ming-Huang Hong, Chao-Nan Qian, Hai-Qiang Mai
Journal: JNCI Journal of the National Cancer Institute (2011)

Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown.Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m(2) on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the χ(2) test. All statistical tests were two-sided.With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly.Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC.
Insulin transport across capillaries is rate limiting for insulin action in dogs.
Authors: Y J Yang, I D Hope, M Ader, R N Bergman
Journal: Journal of Clinical Investigation (1989)

This study examined the relationship between transcapillary insulin transport and insulin action in vivo. During euglycemic clamps (n = 7) in normal conscious dogs we simultaneously measured plasma and thoracic duct lymph insulin and glucose utilization (Rd). Clamps consisted of an activation phase with constant insulin infusion (0.6 mU/kg per min) and a deactivation phase. [14C]Inulin was infused as a passively transported control substance. While [14C]inulin reached an equilibrium between plasma and lymph, steady-state (ss) plasma insulin was higher than lymph (P less than 0.05) and the ratio of 3:2 was maintained during basal, activation, and deactivation phases: 18 +/- 2 vs. 12 +/- 1, 51 +/- 2 vs. 32 +/- 1, and 18 +/- 3 vs. 13 +/- 1 microU/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 +/- 2 vs. 31 +/- 5 and 8 +/- 2 vs. 32 +/- 6 min (P less than 0.02). Rd increased from 2.6 +/- 0.1 to a ss of 6.6 +/- 0.4 mg/kg per min within 50 +/- 8 min. There was a remarkable similarity in the dynamics of insulin in lymph and Rd: the time to reach ss for Rd was not different from lymph insulin (P greater than 0.1), and the relative increases of the two measurements were similar, 164 +/- 45% and 189 +/- 29% (P greater than 0.05). While there was only a modest correlation (r = 0.78, P less than 0.01) between Rd and plasma insulin, the dynamic changes of lymph insulin and Rd showed a strong correlation (r = 0.95, P less than 0.01). The intimate relationship between lymph insulin and Rd suggests that the transcapillary insulin transport is primarily responsible for the delay in Rd. Thus, transcapillary transport may be rate limiting for insulin action, and if altered, it could be an important component of insulin resistance in obesity and diabetes mellitus.
Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial
Authors: Peter Hoskin, Oliver Sartor, Joe M O'Sullivan, Dag Clement Johannessen, Svein I Helle, John Logue, David Bottomley, Sten Nilsson, Nicholas J Vogelzang, Fang Fang, Mona Wahba, Anne-Kirsti Aksnes, Christopher Parker
Journal: The Lancet Oncology (2014)
HYBRID FORMATION BETWEEN BACTERIAL ENDOTOXINS
Authors: Jon A. Rudbach, Kelsey C. Milner, Edgar Ribi
Journal: The Journal of Experimental Medicine (1967)

When endotoxins extracted from enteric bacteria were mixed in the presence of sodium deoxycholate, and the bile salt was subsequently removed by dialysis or by extraction with ethanol, a new type of endotoxin was formed. The latter material was as biologically active as the original endotoxins and possessed a combination of antigenic determinants that were previously unique to each of the individual endotoxins in the mixture. This hybrid formation between endotoxins was detected by immunodiffusion and radioautography and by quantitative precipitation procedures.
Distant entry pneumothorax in a competitive fencer.
Authors: P A Harmer, J Moriarity, M Walsh, M Bean, J Cramer
Journal: British Journal of Sports Medicine (1996)

An elite level fencer sustained a penetrating wound to the upper arm after his opponent's blade broke. Standard care for a deep puncture wound was given but it was some time before the athlete presented symptoms of a pneumothorax, which was confirmed by radiograph. Although resolution of this case was unremarkable, the possibility of penetrating thoracic injury, even when the point of entry is well outside the thorax and the athlete is not immediately symptomatic, should be born in mind by medical personnel working with fencers.
Human Dermal CD14 + Cells Are a Transient Population of Monocyte-Derived Macrophages
Authors: Naomi McGovern, Andreas Schlitzer, Merry Gunawan, Laura Jardine, Amanda Shin, Elizabeth Poyner, Kile Green, Rachel Dickinson, Xiao-nong Wang, Donovan Low, Katie Best, Samuel Covins, Paul Milne, Sarah Pagan, Khadija Aljefri, Martin Windebank, Diego Miranda-Saavedra, Anis Larbi, Pavandip Singh Wasan, Kaibo Duan, Michael Poidinger, Venetia Bigley, Florent Ginhoux, Matthew Collin, Muzlifah Haniffa
Journal: Immunity (2014)

Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141hiXCR1+CLEC9A+ DCs and CD1c+ DCs are murine CD103+ DCs and CD64−CD11b+ DCs. In addition, human tissues also contain CD14+ cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14+ cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14+ monocytes and dermal CD14+ cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14+ cells are CD11b+CD64+ monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.
Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies
Authors: Bryce Chackerian, Douglas R. Lowy, John T. Schiller
Journal: Journal of Clinical Investigation (2001)

High avidity and long-lasting autoantibodies to a self-polypeptide (TNF-alpha) were generated after parenteral vaccination of mice with low doses of virus-like particle-based (VLP-based) vaccines that were constructed by linking mouse TNF-alpha peptides to the surface of papillomavirus VLPs. High-titer autoantibodies were induced with or without coadministration of potent conventional adjuvants, but were enhanced by coadministration of CFA. Compared with immunization with the fusion protein alone, attachment to VLPs increased autoantibody titers 1,000-fold. A comparison of Ab responses against the self (TNF-alpha) and foreign components of the fusion protein showed that VLP conjugation abrogated the ability of the humoral immune system to distinguish between self and foreign. Similar levels of IgM were detected to self and foreign epitopes regardless of the assembly state of the antigen, suggesting that conjugation of self-peptides to VLPs promotes survival or expansion of mature autoreactive B cells. In a mouse model, vaccination with conjugated particles inhibited development of type II collagen-induced arthritis. Together, these results suggest a potentially flexible method to efficiently generate autoantibodies against specific self-proteins that mediate arthritis and other diseases.
Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes
Authors: Wayne B. Batchelor, Thaddeus R. Tolleson, Yao Huang, Rhonda L. Larsen, R. Michael Mantell, Patricia Dillard, Marie Davidian, Daowen Zhang, Warren J. Cantor, Michael H. Sketch, E. Magnus Ohman, James P. Zidar, Daniel Gretler, Peter M. DiBattiste, James E. Tcheng, Robert M. Califf, Robert A. Harrington
Journal: Circulation (2002)

The relative anti-aggregatory effects of currently prescribed platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous coronary intervention for acute coronary syndromes have not been established.We randomized 70 acute coronary syndrome patients undergoing percutaneous coronary intervention to receive abciximab, eptifibatide, or tirofiban at doses used in the Evaluation of Platelet IIb/IIIa Inhibitor for STENTing (EPISTENT), Platelet glycoprotein IIb/IIIa in Unstable angina Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet Receptor Inhibition in ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS)/Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trials, respectively. Platelet aggregation (PA) in response to 20 micro mol/L of adenosine diphosphate was measured with turbidimetric aggregometry in both D-phenylalanyl-L-prolyl-L-arginine chloromethylketone and citrate-anticoagulated blood early (15 and 30 minutes) and late (4, 12, and 18 to 24 hours) after drug initiation. At 15 and 30 minutes, PA was significantly less inhibited by the tirofiban-RESTORE regimen compared with abciximab (P=0.028) and eptifibatide regimens (P=0.0001). The abciximab regimen, however, showed increasingly varied anti-aggregatory effects during continued infusion for > or =4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated, the eptifibatide regimen inhibited PA most consistently throughout both the early and late periods.Currently recommended drug regimens to inhibit the platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles that might affect their relative efficacy in acute coronary syndromes and percutaneous coronary intervention.
Birth order of twins and risk of perinatal death related to delivery in England, Northern Ireland, and Wales, 1994-2003: retrospective cohort study
Authors: Gordon C S Smith, Kate M Fleming, Ian R White
Journal: BMJ (2007)

<b>Objective</b> To determine the effect of birth order on the risk of perinatal death in twin pregnancies. <b>Design</b> Retrospective cohort study. <b>Setting</b> England, Northern Ireland, and Wales, 1994-2003. <b>Participants</b> 1377 twin pregnancies with one intrapartum stillbirth or neonatal death from causes other than congenital abnormality and one surviving infant. <b>Main outcome measures</b> The risk of perinatal death in the first and second twin estimated with conditional logistic regression. <b>Results</b> There was no association between birth order and the risk of death overall (odds ratio 1.0, 95% confidence interval 0.9 to 1.1). However, there was a highly significant interaction with gestational age (P&lt;0.001). There was no association between birth order and the risk of death among infants born before 36 weeks9 gestation but there was an increased risk of death among second twins born at term (2.3, 1.7 to 3.2, P&lt;0.001), which was stronger for deaths caused by intrapartum anoxia or trauma (3.4, 2.2 to 5.3). Among term births, there was a trend (P=0.1) towards a greater risk of the second twin dying from anoxia among those delivered vaginally (4.1, 1.8 to 9.5) compared with those delivered by caesarean section (1.8, 0.9 to 3.6). <b>Conclusions</b> In this cohort, compared with first twins, second twins born at term were at increased risk of perinatal death related to delivery. Vaginally delivered second twins had a fourfold risk of death caused by intrapartum anoxia.
Absorption of ampicillin from the human lung.
Authors: J L Maddocks
Journal: Thorax (1975)

The absorption of ampicillin from the lungs after intratracheal administration was studied in a healthy human. Doses of 50 mg, 250 mg, and 1,250 mg were given by intratracheal injection, and absorption of ampicillin from the lungs was assessed by measuring plasma levels, the area under the plasma level-time curve, and urinary excretion. All these indices of absorption increased with the dose of ampicillin. An intratracheal dose of 100 mg of probenecid together with 250 mg of ampicillin failed to reduce the absorption of ampicillin from the lungs. The uptake of ampicillin by human foetal bronchial slices in vitro was also studied; although viable, they did not accumulate ampicillin. These preliminary results suggest that ampicillin is absorbed from the lungs by passive diffusion.
Sympathetic Neural Burst Amplitude Distribution
Authors: Yrsa Bergmann Sverrisdóttir, Bengt Rundqvist, Gudmundur Johannsson, Mikael Elam
Journal: Circulation (2000)

Background —Human muscle sympathetic nerve activity (MSNA) is usually measured as the number of pulse-synchronous bursts in multiunit mean voltage recordings. We recently suggested burst amplitude distribution as a more sensitive indicator of altered MSNA in congestive heart failure (CHF). Here, we test whether this distribution can discriminate between different conditions with increased MSNA burst frequency and whether it reflects single vasoconstrictor fiber firing intensity. Methods and Results —We analyzed resting multiunit MSNA in 36 CHF patients (24 with mild to moderate CHF, 12 with severe CHF investigated before and after heart transplantation), 14 patients with pituitary deficiency, 25 matched healthy control subjects, and an additional 56 healthy men with a wider age range (21 to 71 years). Pituitary deficiency was associated with increased MSNA burst frequency (60 versus 37 bursts/min in control subjects), equivalent to that in mild to moderate CHF (61 bursts/min). However, burst amplitude distribution in hypopituitary patients (median burst amplitude, 37%) did not deviate from matched control subjects (36%), whereas amplitudes increased with disease severity in CHF (43% in mild to moderate, 52% in severe) and normalized after transplantation (36%). In the larger healthy group, MSNA burst frequency increased with age, and burst amplitude distribution remained unaffected. In 8 CHF patients, single-unit firing frequency showed a close positive relationship to multiunit burst amplitude distribution ( r =0.82, P &lt;0.01) but none to burst frequency ( r =0.39, P =0.3). Conclusions —Muscle vasoconstrictor fiber activity is better reflected by multiunit MSNA burst amplitude distribution than by burst frequency, at least in CHF. This distribution can discriminate between conditions with increased burst frequency.
Alterations in Chandelier Neuron Axon Terminals in the Prefrontal Cortex of Schizophrenic Subjects
Authors: Joseph N. Pierri, Adil S. Chaudry, Tsung-Ung W. Woo, David A. Lewis
Journal: American Journal of Psychiatry (1999)

Abnormalities in prefrontal cortical gamma-aminobutyric acid (GABA) neurotransmission may contribute to cognitive dysfunction in schizophrenia. The density of chandelier neuron axon terminals (cartridges) immunoreactive for the GABA membrane transporter (GAT-1) has been reported to be reduced in the dorsolateral prefrontal cortex of schizophrenic subjects. Because cartridges regulate the output of pyramidal cells, this study analyzed the laminar distribution of GAT-1-immunoreactive cartridges to determine whether certain subpopulations of pyramidal cells are preferentially affected.Measurements were made of the density of GAT-1 -immunoreactive cartridges in layers 2-3a, 3b-4, and 6 of dorsolateral prefrontal cortex area 46 in 30 subjects with schizophrenia, each of whom was matched to one normal and one psychiatric comparison subject. GAT-1-immunoreactive cartridge density was also examined in monkeys chronically treated with haloperidol.Relative to both comparison groups, the schizophrenic subjects had significantly lower GAT-1-immunoreactive cartridge density in layers 2-3a and 3b-4. The decrease was most common and most marked in layers 3b-4, where 80% of the schizophrenic subjects exhibited an average 50.1% decrease in cartridge density in comparison with the matched normal subjects. In contrast, GAT-1-immunoreactive cartridge density was unchanged in the haloperidol-treated monkeys.These findings demonstrate that the density of GAT-1-immunoreactive cartridges is reduced in the majority of schizophrenic subjects and that this alteration may most prominently affect the function of pyramidal cells located in the middle cortical layers. This abnormality may reflect a number of underlying deficits, including a primary defect in dorsolateral prefrontal cortex circuitry or a secondary response to altered thalamic input to this region.
Matrix Metalloproteinase-19 Promotes Metastatic Behavior<i>In Vitro</i>and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer
Authors: Guoying Yu, Jose D. Herazo-Maya, Tomoko Nukui, Marjorie Romkes, Anil Parwani, Brenda M. Juan-Guardela, Jennifer Robertson, Jack Gauldie, Jill M. Siegfried, Naftali Kaminski, Daniel J. Kass
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Matrix metalloproteinases (MMPs) have been implicated in the development and progression of lung cancer, but their role in the molecular pathogenesis of lung cancer remains unclear. We have found that MMP19, a relatively novel member of the MMP family, is overexpressed in lung tumors when compared with control subjects.To test the hypothesis that MMP19 plays a significant role in the development and progression of non-small cell lung cancer (NSCLC).We have analyzed lung cancer gene expression data, immunostained lung tumors for MMP19, and performed in vitro assays to test the effects of MMP19 in NSCLC cells.We found that MMP19 gene and protein expression is increased in lung cancer tumors compared with adjacent and histologically normal lung tissues. In three independent datasets, increased MMP19 gene expression conferred a poorer prognosis in NSCLC. In vitro, we found that overexpression of MMP19 promotes epithelial-mesenchymal transition, migration, and invasiveness in multiple NSCLC cell lines. Overexpression of MMP19 with a mutation at the catalytic site did not impair epithelial-mesenchymal transition or expression of prometastasis genes. We also found that miR-30 isoforms, a microRNA family predicted to target MMP19, is markedly down-regulated in human lung cancer and regulates MMP19 expression.Taken together, these findings suggest that MMP19 is associated with the development and progression of NSCLC and may be a potential biomarker of disease severity and outcome.