tbuckley/cabot-search huggingface dataset:
Neurogenic vasodilation of cat cerebral arteries.
Authors: T J Lee, W R Hume, C Su, J A Bevan
Journal: Circulation Research (1978)

Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.
Erythromycin attenuates an experimental model of chronic bronchiolitis<i>via</i>augmenting monocyte chemoattractant protein‐1
Authors: T. Takahashi, M. Suga, A. Matsukawa, K. Sato, T. Okamoto, H. Ichiyasu, S. Ohkawara, M. Yoshinaga, M. Ando
Journal: European Respiratory Journal (2001)

The mechanisms underlying the therapeutic efficacy of erythromycin (EM) in diffuse panbronchiolitis (DPB) was investigated. For this purpose, an experimental rabbit model of DPB induced by Pseudomonas aeruginosa inoculation was employed. Daily administration of EM (3 mg·kg·day −1 ) led to an increase in the number of macrophages in bronchoalveolar lavage fluid (BALF) at an early phase, while reducing the size of granulomatous lesions at the late phase without affecting the number of viable bacteria recovered from the infected lung. Reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemical studies showed that monocyte chemoattractant protein (MCP)‐1 was produced in both BALF and infected lung. EM treatment resulted in a significant increase in the level of MCP‐1 in BALF, while reducing that of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐8. EM also increased MCP‐1 messenger ribonucleic acid (mRNA) and protein expression in the infected lung. MCP‐1 blockade abolished the protective effect of EM, as neutralization of MCP‐1 with anti-MCP‐1 antibodies reduced the EM-induced increase in the number of macrophages in BALF, and augmented size of the granulomatous lesions, as compared to control. The results of the present study suggest that erythromycin attenuates the pulmonary granuloma formation, at least in part, by increasing the production of monocyte chemoattractant protein‐1.
A new VO<sub>2max</sub>protocol allowing self-pacing in maximal incremental exercise
Authors: Alexis R Mauger, Nick Sculthorpe
Journal: British Journal of Sports Medicine (2011)

Introduction The traditional maximal oxygen uptake (VO 2max ) protocol has received criticism for being an unnatural form of exercise, lacking ecological validity and producing different VO 2max responses depending on protocol duration and work rate increments. Purpose The purpose of this investigation was to design and test a new VO 2max protocol allowing subjects to self-pace their work rate while maintaining an incremental test structure. Methods 16 untrained subjects completed a self-paced VO 2max protocol (SPV) and a traditional VO 2max test in a counter-balanced, crossover design. The SPV used incremental ‘clamps’ of ratings of perceived exertion (RPE) over 5 × 2-min stages (10-min duration) while allowing subjects to vary their power output (PO) according to the required RPE. Results Subjects achieved significantly higher (p &lt; 0.05) VO 2max values (40 ± 10 ml/kg/min vs 37 ± 8 ml/kg/min) and peak POs (273 ± 58 W vs 238 ± 55 W) in the SPV. Higher VO 2max values were observed in the SPV even when a plateau (VO 2 –time slope &lt;0.05 l/min) occurred in the traditional test. No differences were found between any other measured physiological variable (minute ventilation, heart rate and respiratory exchange ratio). Conclusions As SPV is a closed-loop test (10-min duration) that allows subjects to self-pace their work rate, it disregards the need for experimenters to estimate starting work rates, stage lengths and increments in order to bring about volitional exhaustion in 8–10 min. The observation that the SPV may also elicit higher VO 2max values than a traditional test warrants further research in this area and its consideration as standard measure to elicit VO 2max .
Cutaneous malignant melanoma in women and the role of oral contraceptives
Authors: None Gefeller, None Hassan, None Wille
Journal: British Journal of Dermatology (1998)

The role of oral contraceptives (OC) in the aetiology of cutaneous malignant melanoma (CMM) has been controversially discussed over the last two decades. In an extensive literature search we identified 18 case-control studies, published between 1977 and 1996, offering information on this relationship. Using a meta-analytical approach we combined the study-specific risk estimates and derived a summary odds ratio of 0.95 (95% confidence interval: 0.87–1.04). Based on the data of 3796 cases and 9442 controls, we thus found no evidence for an aetiological role of OC use in the development of CMM.
Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure
Authors: Christopher Rose, Lars M. Ytrebφ, Nathan A. Davies, Sambit Sen, Geir I. Nedredal, Mireille Belanger, Arthur Revhaug, Rajiv Jalan
Journal: Hepatology (2007)

We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF+MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF+MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP ( r 2 = 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups. Conclusion : The observation that brain oxygen consumption and mitochondrial complex enzyme activity changed in parallel in both ALF- and MARS-treated animals indicates that the attenuation of increased extracellular brain ammonia (and extracellular brain glutamate) in the MARS-treated animals reduces energy demand and increases supply, resulting in attenuation of increased extracellular brain lactate. The mechanism of how MARS reduces extracellular brain ammonia requires further investigation. (Hepatology 2007.)
Detection and Quantification of Left Atrial Structural Remodeling With Delayed-Enhancement Magnetic Resonance Imaging in Patients With Atrial Fibrillation
Authors: Robert S. Oakes, Troy J. Badger, Eugene G. Kholmovski, Nazem Akoum, Nathan S. Burgon, Eric N. Fish, Joshua J.E. Blauer, Swati N. Rao, Edward V.R. DiBella, Nathan M. Segerson, Marcos Daccarett, Jessiciah Windfelder, Christopher J. McGann, Dennis Parker, Rob S. MacLeod, Nassir F. Marrouche
Journal: Circulation (2009)

Atrial fibrillation (AF) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage. These changes are indicators of AF severity and appear to be predictors of treatment outcome. In this study, we report the utility of delayed-enhancement magnetic resonance imaging (DE-MRI) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome.Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation. Six healthy volunteers also were scanned. DE-MRI images were manually segmented to isolate the left atrium, and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure. Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation, with an average follow-up of 9.6+/-3.7 months (range, 6 to 19 months). On the basis of the extent of preablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement, 8.0+/-4.2%), 30 as having moderate enhancement (21.3+/-5.8%), and 8 as having extensive enhancement (50.1+/-15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate enhancement, and 6 (75%) with extensive enhancement (P<0.001).DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression.
High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults
Authors: P. Pedrazzoli, J.A. Ledermann, J.-P. Lotz, S. Leyvraz, M. Aglietta, G. Rosti, K.M. Champion, S. Secondino, F. Selle, N. Ketterer, G. Grignani, S. Siena, T. Demirer
Journal: Annals of Oncology (2006)
Pooled Analysis of Phase II Window Studies in Children With Contemporary High-Risk Metastatic Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Joanne J. Lager, Elizabeth R. Lyden, James R. Anderson, Alberto S. Pappo, William H. Meyer, Philip P. Breitfeld
Journal: Journal of Clinical Oncology (2006)

Purpose The Soft Tissue Sarcoma Committee of the Children's Oncology Group has conducted five upfront window trials in patients with newly diagnosed metastatic rhabdomyosarcoma to identify promising new treatment agents. Patients and Methods This pooled analysis identified a total of 420 patients (115 from Intergroup Rhabdomyosarcoma Study III [IRS-III] and 305 from the five window trials). We assessed window therapy response rate, failure-free survival (FFS), and overall survival (OS). Results Response rates (complete + partial response) assessed at week 6 of window therapy ranged from 41% to 55% and did not predict FFS (P = .073) or OS (P = .31). FFS was influenced by trial (P = .048); patients enrolled onto IRS-III and the ifosfamide/etoposide and ifosfamide/doxorubicin trials fared best. When grouped and compared with topoisomerase I poison trials, ifosfamide/topoisomerase II inhibitor trials had superior FFS (P = .013). However, there was no difference in survival. Conclusion Upfront phase II window trials can efficiently provide robust estimates of activity for new agents and combinations in newly diagnosed patients with high-risk rhabdomyosarcoma. Our data indicate that, for some phase II window trials, the risk of treatment failure may be increased but that the trend towards lower survival for some of the window trials compared with IRS-III is not statistically significant. Window nonresponders did not suffer worse FFS or OS than patients who responded to window therapy. Finally, these results provide a rationale for incorporating ifosfamide, etoposide, doxorubicin, and topoisomerase I poisons in future trials of high-risk metastatic rhabdomyosarcoma.
Association of <i>PIK3CA</i> Mutation Status before and after Neoadjuvant Chemotherapy with Response to Chemotherapy in Women with Breast Cancer
Authors: Hua Yuan, Jiuan Chen, Yiqiang Liu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie
Journal: Clinical Cancer Research (2015)

The association between PIK3CA mutations and response to neoadjuvant chemotherapy in women with primary breast cancer is not fully elucidated.PIK3CA mutations in breast cancer tissues that were taken prior to the initiation of neoadjuvant chemotherapy were identified in 729 operable primary breast cancer patients who received neoadjuvant chemotherapy. Among these, the PIK3CA mutations were also reassessed in tumor tissues procured following operation in 102 patients after completion of neoadjuvant chemotherapy.A total of 206 out of 729 (28.3%) patients had PIK3CA mutations, and 19.5% of patients (142/729) in this cohort achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy. Patients with PIK3CA mutations exhibited a lower pCR rate than did those with wild-type (14.6% vs. 21.4%, P = 0.035). No significant differences in disease-free survival (DFS) or distant disease-free survival (DDFS) were observed between PIK3CA mutant and wild-type in the entire study population. Among the 102 patients with PIK3CA mutation statuses available before and after neoadjuvant chemotherapy, 24 patients (23.5%) had PIK3CA mutations before neoadjuvant chemotherapy. Of these 24 patients, 15 patients retained their initial PIK3CA mutations and 9 patients lost their initial mutations after neoadjuvant chemotherapy. Patients who retained the initial mutations after neoadjuvant chemotherapy (n = 15) had a worse DDFS than the remaining patients (n = 87) in this subgroup [unadjusted HR, 2.34; 95% confidence interval (CI), 0.98-5.62; P = 0.050].Patients with PIK3CA mutations are less likely to respond to neoadjuvant chemotherapy. Patients who retain their initial PIK3CA mutations after neoadjuvant chemotherapy have an unfavorable survival.
Response letter to: the Hispanic paradox further unraveled?
Authors: Rhea Powell, R Graham Barr
Journal: Thorax (2013)

Response letter to: the Hispanic paradox further unraveled?Dr Young and Ms Hopkins 1 suggest that the lack of a confirmation of the 'Hispanic paradox' for lung phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study could be due to differences in the distribution of Hispanic subgroups and lower smoking exposure in MESA compared to the study by Bruse et al. 2 As suggested, we repeated our analyses stratifying the Hispanic group into those of Mexican and non-Mexican origin and found similar results to initial findings.In a sensitivity analysis including only those Hispanic-Americans who identified Mexico as their country of origin, we again found that among both women and men, genetic ancestry did not modify the effect of pack-years of cigarette smoking on either the forced expiratory volume at 1 s (FEV 1 ) or the ratio of the FEV 1 to the forced vital capacity (all p values >0.20).Furthermore, in analyses restricted to smokers with greater than 10 pack-years, findings were again unchanged ( p>0.4).While the results of these sensitivity analyses were underpowered and should not be taken as definite statements on this topic, they support our general conclusion that smoking is similarly harmful across these race/ethnic groups.Although the prevalence of COPD varies by race/ethnic groups in the USA, there is relatively little evidence to suggest that the risk of developing COPD varies substantially by race/ethnicity after accounting for established risk factors.For example, the prevalence of COPD among non-Hispanic blacks is higher than that of Mexican-Americans, and the prevalence of smoking is higher as well. 3Indeed, our results for both self-reported and genetically estimated ancestry do not show evidence of greater susceptibility to cigarette smoke among those of African ancestry. 4hat said, we agree with Dr Young and Ms. Hopkins that non-genetic and genetic factors may play an important role in the risk of developing COPD, including dietary explanations, as suggested, and some of these factors may vary substantially across continents and cultures.
Plant proteinase from bauhinia bauhinioides kallikrein inhibitor (BbKI) attenuates inflammation and remodelling induced by elastase in mice
Authors: Edna A. Leick, Bruno Tadeu Martins Oliveira, Rafael Almeida-Reis, Leandro Vilela Oliva, Osmar A. Theodoro, Carla Máximo Prado, Mílton A. Martins, Maria Luiza Vilela Oliva, Iolanda F.L.C. Tibério
Journal: European Respiratory Journal (2013)

Proteinases plays a key role on emphysema development. This study evaluated the capacity of the plant proteinase inhibitor BbKI in the inactivation of elastase and its response modulator. Methods: C57Bl6 mice received elastase intratracheal or saline (Ve group). Afterwards, mice were treated with BbKI (2mg/kg) on days 1, 14, 21 after elastase instillation (I-E group) or saline instilation. On day 30 mice were anesthetized and mechanically ventilated and we analyzed respiratory system resistance (Rrs), elastance (Ers), tissue elastance (Htis), tissue damping (Gtis), airway resistance (Raw) and exhaled nitric oxide (ENO). Afterwards, bronchoalveolar lavage fluid (BALF) was performed and lungs were removed. By morphometry, we quantified the mean linear intercept (Lm), and the amount of collagen and elastic fibers in distal lung parenchyma. Results: In elastase group there was a significant increase in the Ers, Rrs, Raw, Htis, Lm, ENO, total and, macrophages, neutrophils and lymphocytes in BALF, and elastic and collagen fibres compared to controls (p
Rapid Cytotoxic T Lymphocyte Activation Occurs in the Draining Lymph Nodes After Cutaneous Herpes Simplex Virus Infection as a Result of Early Antigen Presentation and Not the Presence of Virus
Authors: Scott N. Mueller, Claerwen M. Jones, Chris M. Smith, William R. Heath, Francis R. Carbone
Journal: The Journal of Experimental Medicine (2002)

Localized cutaneous herpes simplex virus type 1 (HSV-1) infection leads to arming and initial expansion of cytotoxic T lymphocytes (CTLs) in the draining popliteal lymph nodes (PLNs) followed by migration and further proliferation in the spleen. To accurately characterize the sequence of events involved in the activation and generation of anti-HSV CTLs, we used T cell receptor (TCR) transgenic mice specific for the immunodominant epitope from HSV glycoprotein B (gB(498-505)). We describe the detection of the initiation of antigen presentation in the draining lymph nodes by 4-6 h after infection with HSV-1. Analysis of CD69 up-regulation revealed activation of gB-specific CD8(+) T cells by 6-8 h after infection. Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs. These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation. Consequently, we have defined the initiation of the CD8(+) T cell-mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.
Mechanical Stress–Induced Heat Shock Protein 70 Expression in Vascular Smooth Muscle Cells Is Regulated by Rac and Ras Small G Proteins but Not Mitogen-Activated Protein Kinases
Authors: Qingbo Xu, Georg Schett, Chaohong Li, Yanhua Hu, Georg Wick
Journal: Circulation Research (2000)

Abstract —Previous studies have documented that acute elevation in blood pressure results in heat shock protein (hsp) 70–mRNA expression followed by hsp70-protein production in rat aortas. In this article, we provide evidence that mechanical forces evoke rapid activation of heat shock transcription factor (HSF) and hsp70 accumulation. In our study, Western blot analysis demonstrated that hsp70-protein induction peaked between 6 and 12 hours after treatment with cyclic stain stress (60 cycles/minute, up to 30% elongation). Elevated protein levels were preceded by hsp70-mRNA transcription, which was associated with HSF1 phosphorylation and activation stimulated by mechanical forces, suggesting that the response was regulated at the transcriptional level. Conditioned medium from cyclic strain–stressed vascular smooth muscle cells (VSMCs) did not result in HSF-DNA–binding activation. Furthermore, mitogen-activated protein kinases (MAPKs), including extracellular signal–regulated kinases, c-Jun NH 2 -terminal protein kinases or stress-activated protein kinases, and p38 MAPKs, were also highly activated in response to cyclic strain stress. Inhibition of extracellular signal–regulated kinase and p38-MAPK activation by their specific inhibitors (PD 98059 and SB 202190) did not influence HSF1 activation. Interestingly, VSMC lines stably expressing dominant-negative rac (rac N17) abolished hsp-protein production and HSF1 activation induced by cyclic strain stress, whereas a significant reduction of hsp70 expression was seen in ras N17–transfected VSMC lines. Thus, our findings demonstrate that cyclic strain stress–induced hsp70 expression is mediated by HSF1 activation and regulated by rac and ras GTP–binding proteins. Induction of hsp70 could be important in maintaining VSMC homeostasis during vascular remodeling in response to hemodynamic stimulation.