tbuckley/cabot-search huggingface dataset:
Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary artery endothelium.
Authors: S S Jun, Z Chen, M C Pace, P W Shaul
Journal: Journal of Clinical Investigation (1998)

Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation in the perinatal period and its synthesis in the pulmonary vasculature increases markedly during late gestation due to enhanced expression of the rate-limiting enzyme cyclooxygenase-1 (COX-1). The hormone estrogen may play a role in COX-1 upregulation since fetal estrogen levels rise dramatically during late gestation and estrogen enhances PGI2 synthesis in nonpulmonary vascular cells. We therefore studied the direct effects of estrogen on COX-1 expression in ovine fetal pulmonary artery endothelial cells (PAEC). Exposure to estradiol-17beta (E2beta, 10(-)10 to 10(-)6 M) caused a dose-related increase in COX-1 mRNA expression that was evident after 48 h and maximal at 10(-)8 M (fourfold increase). COX-1 mRNA stability was unchanged, suggesting that the upregulation is mediated at the level of transcription. E2beta treatment (10(-)8 M for 48 h) also caused a threefold increase in COX-1 protein expression and a threefold increase in PGI2 synthesis stimulated by bradykinin, the calcium ionophore A23187, or arachidonic acid. The estrogen receptor (ER) antagonist ICI 182,780 fully reversed the effects of the hormone on COX-1 protein expression and on arachidonic acid-stimulated PGI2 synthesis, and ER expression was evident in the PAEC by immunoblot analysis. These findings indicate that physiologic levels of estrogen cause upregulation of COX-1 expression and PGI2 synthesis in fetal PAEC via activation of PAEC ER. This process may play a critical role in optimizing the capacity for PGI2-mediated pulmonary vasodilation at birth, and it may also be involved in estrogen responsiveness in other vascular beds.
The Inducible Nitric Oxide Synthase Inhibitor BBS-2 Prevents Acute Lung Injury in Sheep after Burn and Smoke Inhalation Injury
Authors: Perenlei Enkhbaatar, Kazunori Murakami, Katsumi Shimoda, Akio Mizutani, Lillian Traber, Gary B. Phillips, John F. Parkinson, Robert Cox, Hal Hawkins, David Herndon, Daniel Traber
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In this study we examined the role of inducible nitric oxide synthase (iNOS) in acute respiratory distress syndrome (ARDS) in sheep with severe combined burn and smoke inhalation injury. BBS-2, a potent and highly selective iNOS dimerization inhibitor, was used to exclude effects on the endothelial and neuronal NOS isoforms. Seven days after surgical recovery, sheep were given a burn (40% of total body surface, 3rd degree) and insufflated with cotton smoke (48 breaths, < 40 degrees C) under anesthesia. BBS-2 was provided by constant infusion at 100 microg/kg/hour, beginning 1 hour after injury. During 48 hours, control sheep developed multiple signs of ARDS. These included decreased pulmonary gas exchange, increased pulmonary edema, abnormal lung compliance, and extensive airway obstruction. These pathologies were associated with a large increase in tracheal blood flow and elevated plasma NO2-/NO3- (NOx) levels. These variables were all stable in sham animals. Treatment of injured sheep with BBS-2 attenuated the increases in tracheal blood flow and plasma NOx levels, and significantly attenuated all the pulmonary pathologies that were noted. The results provide definitive evidence that iNOS is a key mediator of pulmonary pathology in sheep with ARDS resulting from combined burn and smoke inhalation injury.
Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension
Authors: Z-C. Jing, X. Jiang, Z-Y. Han, X-Q. Xu, Y. Wang, Y. Wu, H. Lv, C-R. Ma, Y-J. Yang, J-L. Pu
Journal: European Respiratory Journal (2009)

The aim of this study was to confirm the utility of aerosolised iloprost for identifying long-term responders to calcium channel blockers (CCBs) in patients with idiopathic pulmonary arterial hypertension (IPAH). While undergoing right heart catheterisation, 74 patients with IPAH sequentially received incremental infusions of adenosine and aerosolised iloprost. The effects of the two vasodilators on haemodynamic parameters were recorded. All acute responders identified by aerosolised iloprost were subsequently treated with high doses of a CCB and were re-evaluated after 12 months. Both adenosine and iloprost produced significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance, and significant increases in cardiac index. Adverse effects were experienced by 35 out of the 74 patients with adenosine, but by only two with iloprost. Aerosolised iloprost identified more acute responders than infused adenosine (10 versus eight, respectively) according to the criteria recommended in recent consensus guidelines. Nine responders identified by iloprost were followed-up after 12 months of high-dose CCB therapy. Five had normal or near-normal haemodynamics and a World Health Organization functional classification of I or II after 12 months. Aerosolised iloprost is an appropriate new agent to identify long-term responders to CCBs in patients with IPAH. It is as effective in this regard as infused adenosine but is better tolerated.
Incidence and sources of native and prosthetic joint infection: a community based prospective survey
Authors: C. J E Kaandorp, H. J Dinant, M. A F J van de Laar, H. J B. Moens, A P. A Prins, B. A C Dijkmans
Journal: Annals of the Rheumatic Diseases (1997)

OBJECTIVES To determine the incidence and sources of bacterial arthritis in the Amsterdam health district and the maximum percentage of cases that theoretically would be preventable. METHODS Patients with bacterial arthritis diagnosed between 1 October 1990 and 1 October 1993 were prospectively reported to the study centre by all 12 hospitals serving the district. Data were gathered on previous health status, source of infection, and microorganisms involved. RESULTS 188 episodes of bacterial arthritis were found in 186 patients. Most of the 38 children were previously healthy. Fifty per cent of the adults were 65 years or older. Of the adults 84% had an underlying disease, in 59% a joint disorder. Joint surgery constituted the largest part of direct infections (33%) and skin defects were the most important source of haematogenous infections (67%). Infection of joints containing prosthetic or osteosynthetic material by a known haematogenous source occurred 15 times (8%). Staphylococcus aureus was the causative organism in 44% of all positive cultures. CONCLUSION The incidence of bacterial arthritis was 5.7 per 100 000 inhabitants per year. Preventive measures directed to patients with prosthetic joints or osteosynthetic material, and a known haematogenous source would have prevented at most 8% of all cases.
Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease
Authors: Coen A. C. Ottenheijm, Leo M. A. Heunks, Gary C. Sieck, Wen-Zhi Zhan, Suzanne M. Jansen, Hans Degens, Theo de Boo, P. N. Richard Dekhuijzen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause of death in chronic obstructive pulmonary disease (COPD). However, the pathophysiology of failure of the diaphragm to generate force in COPD is in part unclear. Objectives: The present study investigated contractile function and myosin heavy chain content of diaphragm muscle single fibers from patients with COPD. Methods: Skinned muscle fibers were isolated from muscle biopsies from the diaphragm of eight patients with mild to moderate COPD and five patients without COPD (mean FEV1 % predicted, 70 and 100%, respectively). Contractile function of single fibers was assessed, and afterwards, myosin heavy chain content was determined in these fibers. In diaphragm muscle homogenates, the level of ubiquitin-protein conjugation was determined. Results: Diaphragm muscle fibers from patients with COPD showed reduced force generation per cross-sectional area, and reduced myosin heavy chain content per half sarcomere. In addition, these fibers had decreased Ca2+ sensitivity of force generation, and slower cross-bridge cycling kinetics. Our observations were present in fibers expressing slow and 2A isoforms of myosin heavy chain. Ubiquitin-protein conjugation was increased in diaphragm muscle homogenates of patients with mild to moderate COPD. Conclusions: Early in the development of COPD, diaphragm fiber contractile function is impaired. Our data suggest that enhanced diaphragm protein degradation through the ubiquitin-proteasome pathway plays a role in loss of contractile protein and, consequently, failure of the diaphragm to generate force.
Sports psychology in India
Authors: Chaitanya Sridhar
Journal: British Journal of Sports Medicine (2010)

Consider the following scenario – a highly talented player on whom rests a million hopes is well prepared physically and dreaming of gold. But then just at the start of the match, he realises he hasn't learnt to deal with his nerves (and thoughts), which are essential to focus and perform. Now is it solely the players fault that he didn't know how to manage the psychological aspects of the game? It is a well established fact that mental skills training is an integral component to achieve peak performance. Why then is sports psychology still in its infancy in India? Countries like Australia and USA have a sport psychologist attached to every team. Why it is still not accepted in our country? One of the main reasons could be the negative connotation associated with psychology. Till date many a players and coaches think going to a psychologist means there is a ‘problem’. Some of the other reasons are the lack of resource personnel, lack of awareness, following traditional methods of coaching with little emphasis on sport psychology and sports science. Also, ‘image management’ is a key issue in India, especially in sports. Players want to maintain ‘I'm cool and have no problem attitude’. Mental skills training ought to be treated as a component of peak performance akin to physical training. Only, then can we think of achievement. What then is the solution? An integrative approach involving coaching with psychology and sports science is the ‘need of the hour’.
Reproducibility of [11C]Choline-Positron Emission Tomography and Effect of Trastuzumab
Authors: Laura M. Kenny, Kaiyumars B. Contractor, Rainer Hinz, Justin Stebbing, Carlo Palmieri, Jie Jiang, Sami Shousha, Adil Al-Nahhas, R. Charles Coombes, Eric O. Aboagye
Journal: Clinical Cancer Research (2010)

Abstract Purpose: This study sought to evaluate the reproducibility of [11C]choline-positron emission tomography and the effect of trastuzumab in breast cancer. Experimental Design: Twenty-one patients with newly diagnosed and recurrent breast cancer stage II-IV had a baseline dynamic [11C]choline-PET scan, 10 patients had a second [11C]choline-PET scan to examine reproducibility, and 6 patients had a second scan within a month after trastuzumab. Analysis of [11C]choline uptake was measured as the semiquantitative standardized uptake value at 30 and 60 minutes (SUV30 and SUV60), and quantitatively as the net irreversible retention of the radiotracer at steady-state (Ki) and plasma to tissue exchange at 60 minutes (IRF60min). Results: Breast tumor lesions in all patients were visualized by [11C]choline PET. The difference in tumor versus normal tissue uptake was significant for SUV30, SUV60, Ki, and IRF60 minutes (Wilcoxon P &amp;lt; 0.0001). At 60 minutes postinjection, 15.1 ± 2.16% of plasma radioactivity was due to unmetabolized [11C]choline radioactivity. [11C]Choline uptake was reproducible in breast tumor lesions (r2 = 0.9 for SUV, 0.9 for Ki, and 0.8 for IRF60). Early responses to trastuzumab measured by [11C]choline-PET were significant in three lesions occurring in two patients who responded clinically. Conclusions: [11C]Choline-PET uptake variables can be reproducibly assessed. Initial studies show that trastuzumab decreases [11C]choline uptake. Clin Cancer Res; 16(16); 4236–45. ©2010 AACR.
When Did Decapods Invade Hydrothermal Vents? Clues from the Western Pacific and Indian Oceans
Authors: Jin-Shu Yang, Bo Lu, Dian-Fu Chen, Yan-Qin Yu, Fan Yang, Hiromichi Nagasawa, Shinji Tsuchida, Yoshihiro Fujiwara, Wei-Jun Yang
Journal: Molecular Biology and Evolution (2012)

Abstract Hydrothermal vents are typically located in midocean ridges and back-arc basins and are usually generated by the movement of tectonic plates. Life thrives in these environments despite the extreme conditions. In addition to chemoautotrophic bacteria, decapod crustaceans are dominant in many of the hydrothermal vents discovered to date. Contrary to the hypothesis that these species are remnants of relic fauna, increasing evidence supports the notion that hydrothermal vent decapods have diversified in more recent times with previous research attributing the origin of alvinocarid shrimps to the Miocene. This study investigated seven representative decapod species from four hydrothermal vents throughout the Western Pacific and Indian Oceans. A partitioned mix-model phylogenomic analysis of mitochondrial DNA produced a consistent phylogenetic topology of these vent-endemic species. Additionally, molecular dating analysis calibrated using multiple fossils suggested that both bythograeid crabs and alvinocarid shrimps originated in the late Mesozoic and early Cenozoic. Although of limited sampling, our estimates support the extinction/repopulation hypothesis, which postulates recent diversification times for most hydrothermal vent species due to their mass extinction by global deep-water anoxic/dysoxic events during the Late Cretaceous and Early Tertiary. The continental-derived property of the West Pacific province is compatible with the possibility that vent decapods diversified from ancestors from shallow-water regions such as cold seeps. Our results move us a step closer toward understanding the evolutionary origin of hydrothermal vent species and their distribution in the Western Pacific–Indian Ocean Region.
The effect of Y-27632, a Rho/ Rho kinase inhibitor, on leukotriene D4- and histamine-induced airway microvascular leage in guinea pigs
Authors: K. Tokuyama, H. Nishimura, K. Iizuka, M. Kato, H. Arakawa, H. Mochizuki, A. Morikawa
Journal: Journal of Allergy and Clinical Immunology (2005)
Granuloma formation in the different phenotypes of Crohn's disease
Authors: F Hofstaedter
Journal: Gut (2005)

Granulomas may be more than diagnostic tools and could be significant in the biology and clinical course of Crohn’s disease

Our immunological and molecular knowledge base1 in idiopathic chronic inflammatory bowel disease (IBD) has seen a tremendous increase over the past few years. Laboratory application of sophisticated new methodologies has revealed a plethora of agonistic and antagonistic factors involved in the pathogenesis of both ulcerative colitis and Crohn’s disease. Proinflammatory and Th2 derived anti-inflammatory cytokines are secreted by and act on various different cell types by forming a complex network of interdigitating molecular pathways with profound effects on epithelial cells, lymphocytes, endothelial cells, and monocytes. This multilayered interplay of humoral factors and various cells at different stages of differentiation appears similar to a symphony where the end result is perfect yet the role of various single instruments remains obscure to the casual listener.

Some of the …
Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study
Authors: Pascale Mariani, Joëlle Blumberg, Alain Landau, Daniela Lebrun-Jezekova, Estelle Botton, Olivier Beatrix, Didier Mayeur, Robert Herve, Pascal Maisonobe, Laure Chauvenet
Journal: Journal of Clinical Oncology (2012)

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. Results More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P &lt; .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P &lt; .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. Conclusion These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.
Studies of the Mechanism of the Antidiarrheal Effect of Codeine
Authors: Lawrence R. Schiller, Glenn R. Davis, Carol A. Santa Ana, Stephen G. Morawski, John S. Fordtran
Journal: Journal of Clinical Investigation (1982)

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.
The miR-17/92 Polycistron Is Up-regulated in Sonic Hedgehog–Driven Medulloblastomas and Induced by N-myc in Sonic Hedgehog–Treated Cerebellar Neural Precursors
Authors: Paul A. Northcott, Africa Fernandez-L, John P. Hagan, David W. Ellison, Wesia Grajkowska, Yancey Gillespie, Richard Grundy, Timothy Van Meter, James T. Rutka, Carlo M. Croce, Anna Marie Kenney, Michael D. Taylor
Journal: Cancer Research (2009)

Abstract Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. Profiling the expression of 427 mature microRNAs (miRNA) in a series of 90 primary human medulloblastomas revealed that components of the miR-17/92 polycistron are the most highly up-regulated miRNAs in medulloblastoma. Expression of miR-17/92 was highest in the subgroup of medulloblastomas associated with activation of the sonic hedgehog (Shh) signaling pathway compared with other subgroups of medulloblastoma. Medulloblastomas in which miR-17/92 was up-regulated also had elevated levels of MYC/MYCN expression. Consistent with its regulation by Shh, we observed that Shh treatment of primary cerebellar granule neuron precursors (CGNP), proposed cells of origin for the Shh-associated medulloblastomas, resulted in increased miR-17/92 expression. In CGNPs, the Shh effector N-myc, but not Gli1, induced miR-17/92 expression. Ectopic miR-17/92 expression in CGNPs synergized with exogenous Shh to increase proliferation and also enabled them to proliferate in the absence of Shh. We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas. [Cancer Res 2009;69(8):3249–55]
Late neurodegeneration in the Tau transgenic mouse model rTg4510
Authors: Lone Helboe, Christiane Volbracht
Journal: Molecular Neurodegeneration (2013)

Materials and methods The rTg4510 mice express the TauP301L mutation under control of a tetracycline-responsive operon promoter. rTg4510, single transgenic tTA and non-transgenic littermates (129S6/FVB/N F1 hybrid) were bred at Taconic, Denmark. Paraffin sections were stained for p-Tau, astroand microglial markers, ubiquitin, doublecortin and tangles. Western blot was performed on soluble (S1) and sarkosyl-insoluble (P3) brain fractions. Hippocampal CA1 neuron numbers and cortical neuronal densities were assessed by un-biased stereology at Gubra, Denmark.
Immune Reconstitution in Patients with HIV Infection
Authors: Gregory D. Sempowski, Barton F. Haynes
Journal: Annual Review of Medicine (2002)

▪ Abstract The peripheral T cell pool is damaged by HIV-1 infection and can be regenerated by production of new T lymphocytes either from the thymus or from proliferation of post-thymic T cells. A critical question for AIDS patients is whether treatment with antiretroviral drugs can restore the capability to produce new T lymphocytes. The development of a new assay of thymus function in adults (the measurement of T cell receptor excision circles, TRECs), and studies of thymus biopsies in untreated and treated HIV-1-infected patients, have suggested that in select patients the thymus can regenerate on antiretroviral therapy. New strategies to overcome the thymic atrophy of aging are needed to improve thymic function in the majority of AIDS patients.