tbuckley/cabot-search huggingface dataset:
Exercise Behavior, Functional Capacity, and Survival in Adults With Malignant Recurrent Glioma
Authors: Emily Ruden, David A. Reardon, April D. Coan, James E. Herndon, Whitney E. Hornsby, Miranda West, Diane R. Fels, Annick Desjardins, James J. Vredenburgh, Emily Waner, Allan H. Friedman, Henry S. Friedman, Katherine B. Peters, Lee W. Jones
Journal: Journal of Clinical Oncology (2011)

Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the prognostic significance of exercise behavior and functional capacity in this population.Using a prospective design, 243 patients with WHO grades 3 to 4 recurrent malignant glioma and Karnofsky performance status (KPS) ≥ 70 completed a self-administered questionnaire that assessed exercise behavior and performed a 6-minute walk test (6MWT) to assess functional capacity. Cox proportional models were used to estimate the risk of all-cause mortality according to 6MWT distance (6MWD; < 390 meters, 390-489 meters, > 489 meters) and exercise behavior (metabolic equivalent [MET] -h/wk) adjusted for KPS and other important clinical factors.Median follow-up was 27.43 months. During this period, 149 deaths were recorded (61% of the total sample). Exercise behavior was an independent predictor of survival (P = .0081). Median survival was 13.03 months for patients reporting < 9 MET-h/wk relative to 21.84 months for those reporting ≥ 9 MET-h/wk. Exercise behavior added incremental prognostic value beyond that provided by KPS, age, sex, grade, and number of prior progressions (P < .001). Compared with patients reporting < 9 MET-h/wk, the adjusted hazard ratio for mortality was 0.64 (95% CI, 0.46 to 0.91) for patients reporting ≥ 9 MET-h/wk. Functional capacity was not an independent predictor of prognosis.Exercise behavior is a strong independent predictor of survival that provides incremental prognostic value to KPS as well as traditional markers of prognosis in malignant recurrent glioma.
ROLE OF <i>H-2</i> LYMPHOCYTE-DEFINED AND SEROLOGICALLY-DEFINED COMPONENTS IN THE GENERATION OF CYTOTOXIC LYMPHOCYTES
Authors: Barbara J. Alter, Fritz H. Bach
Journal: The Journal of Experimental Medicine (1974)

The cell-mediated lympholytic capability of mouse spleen cells stimulated in mixed lymphocyte culture is determined by lymphocyte-defined (LD) and serologically-defined (SD) antigenic differences present during sensitization. Cells which are activated by LD differences alone are markedly less effective in causing lysis of target cells. This lack of cytotoxicity is shown to be, at least in part, due to the inability of LD differences to allow the efficient generation of cytotoxic lymphocytes. SD antigens not only serve as good targets for CML but are also shown to be important for the generation of cytotoxic lymphocytes during the mixed lymphocyte culture.
Hypothalamic Y2 receptors regulate bone formation
Authors: Paul A. Baldock, Amanda Sainsbury, Michelle Couzens, Ronaldo F. Enriquez, Gethin P. Thomas, Edith M. Gardiner, Herbert Herzog
Journal: Journal of Clinical Investigation (2002)

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor–deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation.
Serine-Arginine Protein Kinase 1 Overexpression Is Associated with Tumorigenic Imbalance in Mitogen-Activated Protein Kinase Pathways in Breast, Colonic, and Pancreatic Carcinomas
Authors: Gregory M. Hayes, Patricia E. Carrigan, Laurence J. Miller
Journal: Cancer Research (2007)

Abstract Aberrant patterns of pre-mRNA processing are typical of human malignancies, yet the mechanisms responsible for these changes remain undefined. We have recently shown overexpression of a core splice regulatory protein, serine-arginine protein kinase 1 (SRPK1), in dysplastic and neoplastic pancreatic ductular cells. In the present study, we have established that SRPK1 levels are similarly up-regulated in breast and colonic tumors where its expression increases coordinately with tumor grade. Targeting SRPK1 for inhibition using small interfering RNA in breast and colonic tumor cell lines in vitro resulted in both increased apoptotic potential and enhanced cell killing after treatment with gemcitabine and cisplatin. Recent reports have described multifaceted interactions between the mitogen-activated protein kinase (MAPK) and AKT signaling networks and the splice regulatory machinery. Consequently, we have shown that targeted inhibition of SRPK1 in tumor cells results in reduced phosphorylation of MAPK3, MAPK1, and AKT. Alterations in the splice pattern and resulting expression of MAPK kinase are implicated in mediating the antitumoral effects resulting from SRPK1 down-regulation. The up-regulation of SRPK1 in multiple cancers and its ability to regulate multiple relevant signaling pathways provide support for developing agents to inhibit this kinase for possible broad application to treat epithelial cancers. [Cancer Res 2007;67(5):2072–80]
Shoulder pathoanatomy in marathon kayakers
Authors: G Hagemann, A M Rijke, M Mars
Journal: British Journal of Sports Medicine (2004)

To determine the prevalence of soft and hard tissue abnormalities and their interrelations in the shoulders of marathon kayakers and to examine the pathoanatomical factors that predispose these athletes to injury.Fifty two long distance kayakers completed a questionnaire. Their shoulders were examined for range of motion, pain, and stability using a standard set of 10 clinical tests. The shoulder was subsequently scanned by magnetic resonance imaging (MRI) in three planes and evaluated for evidence of injury or other abnormality. The relation of clinical symptoms and MRI findings was investigated with respect to kayaker's age, number of years kayaking, and number of marathon races completed.Thirty subjects were asymptomatic at the time of scanning, and twenty two showed symptoms of pain and/or instability. MRI showed acromioclavicular hypertrophy, acromial or clavicular spur, supraspinatus tendinitis, and partial tear of the supraspinatus as the most common abnormalities. Kayaker's age, number of years kayaking, and number of races completed did not relate significantly to symptoms or to the presence of an abnormality on MRI scan. Of all the pathoanatomical findings that are reported to predispose to rotator cuff injury, only acromial and clavicular spurs were found to correlate highly with supraspinatus muscle pathology.Rotator cuff injuries make up a large portion of the injuries seen in marathon kayakers, about twice the number reported for sprint kayakers. These injuries are the result of secondary impingement factors associated with overuse, possibly specific to kayakers, and not the result of bony restrictions around the shoulder joint. Acromioclavicular hypertrophy is a common finding in marathon kayakers, but is possibly the result of portaging or a previous injury.
Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up
Authors: P. Colombat, N. Brousse, G. Salles, F. Morschhauser, P. Brice, P. Soubeyran, V. Delwail, E. Deconinck, C. Haioun, C. Foussard, C. Sebban, H. Tilly, C. Thieblemont, L. Bergougnoux, F. Lazreg, P. Solal-Celigny
Journal: Annals of Oncology (2012)
Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms
Authors: Timothy S.C. Hinks, Xiaoying Zhou, Karl J. Staples, Borislav D. Dimitrov, Alexander Manta, Tanya Petrossian, Pek Y. Lum, Caroline G. Smith, Jon A. Ward, Peter H. Howarth, Andrew F. Walls, Stephan D. Gadola, Ratko Djukanović
Journal: Journal of Allergy and Clinical Immunology (2015)

Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13-secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine-high) and nonatopic forms.The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.
Cross sectional, community based study of care of newborn infants in Nepal
Authors: D. Osrin
Journal: BMJ (2002)

To determine home based newborn care practices in rural Nepal in order to inform strategies to improve neonatal outcome.Cross sectional, retrospective study using structured interviews.Makwanpur district, Nepal.5411 married women aged 15 to 49 years who had given birth to a live baby in the past year.Attendance at delivery, hygiene, thermal care, and early feeding practices.4893 (90%) women gave birth at home. Attendance at delivery by skilled government health workers was low (334, 6%), as was attendance by traditional birth attendants (267, 5%). Only 461 (8%) women had used a clean home delivery kit, and about half of attendants had washed their hands. Only 3482 (64%) newborn infants had been wrapped within half an hour of birth, and 4992 (92%) had been bathed within the first hour. 99% (5362) of babies were breast fed, 91% (4939) within six hours of birth. Practices with respect to colostrum and prelacteals were not a cause for anxiety.Health promotion interventions most likely to improve newborn health in this setting include increasing attendance at delivery by skilled service providers, improving information for families about basic perinatal care, promotion of clean delivery practices, early cord cutting and wrapping of the baby, and avoidance of early bathing.
Early-life pulmonary arterial hypertension with subsequent development of diffuse pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia type 1
Authors: C J Mache, A Gamillscheg, H H Popper, S G Haworth
Journal: Thorax (2007)

The case history is presented of a male infant who was thought to have idiopathic pulmonary arterial hypertension (PAH) at 3 months of age. Subsequently the PAH decreased unexpectedly and diffuse pulmonary arteriovenous malformations (PAVMs) were seen at 6.9 years of age for the first time. Hereditary haemorrhagic telangiectasia type 1 (HHT1) related to an endoglin mutation was diagnosed. At 10.3 years of age a lung biopsy showed diffuse PAVMs as well as pulmonary arteriopathy with medial hypertrophy. This is the first case of HHT1 presenting with PAH at such a young age. The subsequent decrease in pulmonary arterial pressure (PAP) was probably caused by the development of PAVMs. In the presence of PAVMs, measurement of the PAP may underestimate the extent of PAH-related vasculopathy.
Chronic Stridor Caused by Laryngomalacia in Children
Authors: BRIGITTE FAUROUX, JÉRÔME PIGEOT, MICHAEL I. POLKEY, GILLES ROGER, MICHÈLE BOULÉ, ANNICK CLÉMENT, FRÉDÉRIC LOFASO
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Breathing pattern, gas exchange, and respiratory effort were assessed in five awake children with chronic stridor caused by laryngomalacia during spontaneous breathing (SB) and noninvasive mechanical ventilation (NIMV). During SB, the youngest children were able to maintain normal gas exchange at the expense of an increased work of breathing as assessed by calculated diaphragmatic pressure-time product (PTPdi), whereas the opposite was observed in the older children. NIMV increased tidal volume, from 8.77 ± 2.04 ml/kg during SB to 11.67 ± 2.52 ml/kg during NIMV, p = 0.04, and decreased respiratory rate, from 24.4 ± 5.6 breaths/ min during SB to 16.6 ± 0.9 breaths/min during NIMV, p = 0.04. NIMV unloaded the respiratory muscles as reflected by the significant reduction in PTPdi, from a mean value of 541.0 ± 196.6 cm H2O · s · min− 1 during SB to 214.8 ± 116.0 cm H2O · s · min− 1 during NIMV, p = 0.04. Therefore, NIMV successfully relieves the additional load imposed on the respiratory muscles. Long-term home NIMV was provided to a total of 12 children with laryngomalacia (including these five) and was associated with clinical improvement in sleep and growth.
Putrescine as a comitogen of epidermal growth factor in rat liver growth
Authors: Sumiko Nagoshi, Kenji Fujiwara
Journal: Hepatology (1994)

Putrescine can stimulate regeneration of the remnant liver after partial hepatectomy in rats when exogenously administered, but its mitogenic action has not been shown in cultured hepatocytes. To find its action site(s) in the regulation of hepatocyte proliferation, we examined its effect on hepatocyte DNA synthesis in relation to mitogenic action of epidermal growth factor in vitro and in vivo. When putrescine was added to the medium of adult rat hepatocytes in primary culture 36 hr after plating, DNA synthesis at 50 hr induced by addition of epidermal growth factor at 24 hr was significantly enhanced. This enhancement disappeared by removal of epidermal growth factor at the time of putrescine addition. Putrescine added to the medium was taken up in a dose-related manner by hepatocytes, irrespective of the presence of epidermal growth factor, whereas 125I-epidermal growth factor binding to hepatocytes was not affected by addition of putrescine. When rats received epidermal growth factor at 2-hr intervals until 10 hr, 5-bromo-2'-deoxyuridine labeled and mitotic hepatocytes were increased in number at 48 hr with increased hepatic DNA content. These increases were not affected by concomitant administration of putrescine until 10 hr, but significantly enhanced by additional administration of putrescine and epidermal growth factor from 20 to 30 hr. We conclude that putrescine may stimulate proliferation of hepatocytes that have entered the G1-phase of the cell cycle as a comitogen of epidermal growth factor, probably through action at the molecular levels to enhance its mitogenic activity.
A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells
Authors: Alexander J. Stokes, Lori M.N. Shimoda, Murielle Koblan-Huberson, Chaker N. Adra, Helen Turner
Journal: The Journal of Experimental Medicine (2004)

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)-dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.
A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer
Authors: J.A. Treat, R. Gonin, M.A. Socinski, M.J. Edelman, R.B. Catalano, D.M. Marinucci, R. Ansari, H.H. Gillenwater, K.M. Rowland, R.L. Comis, C.K. Obasaju, C.P. Belani
Journal: Annals of Oncology (2009)
In vitro effects of IL-12 and IL-2 on NK cells, cytokine release and clonogenic activity in myelodysplastic syndromes (MDS)
Authors: B Sarina, A Cortelezzi, C Cattaneo, M Pomati, I Silvestris, M Di Stefano, D Lambertenghi-Deliliers, C Hu, M Monza, AT Maiolo
Journal: Leukemia (1997)
<i>Phosphatidylinositol 3′-Kinase Catalytic Subunit α</i> Gene Amplification Contributes to the Pathogenesis of Mantle Cell Lymphoma
Authors: Amanda Psyrri, Sotirios Papageorgiou, Elisavet Liakata, Andreas Scorilas, Dimitra Rontogianni, Christos K. Kontos, Pinelopi Argyriou, Dimitrios Pectasides, Nikolaos Harhalakis, Vassiliki Pappa, Aggeliki Kolialexi, Christina Economopoulou, Frida Kontsioti, Eirini Maratou, George Dimitriadis, Panagiota Economopoulou, Theofanis Economopoulos
Journal: Clinical Cancer Research (2009)

Activation of phosphatidylinositol 3'-kinase pathway is implicated in the pathogenesis of mantle cell lymphoma (MCL). The genetic change in phosphatidylinositol 3'-kinase catalytic subunit alpha (PIK3CA) in MCL has not been identified.Thirty-five primary MCL cases and 2 MCL cell lines (GRANTA-519 and Rec-1) were used to investigate somatic mutation and gene copy number of PIK3CA. Gene copy number was determined using quantitative real-time PCR and fluorescence in situ hybridization. We used quantitative real-time reverse transcription-PCR to measure PIK3CA transcription levels. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and phoshorylated AKT protein levels were analyzed using Western blotting and immunohistochemistry. Flow cytometry was used to assess apoptosis after treatment of MCL cell lines and one control cell line with LY294002, a specific inhibitor of PI3KCA.Fifteen of 22 (68%) MCL cases and the MCL cell lines harbored a gain (> or =3) of PIK3CA gene copy number. In addition, cases with increased PIK3CA gene copy number had elevated PIK3CA mRNA levels. Furthermore, amplification of PIK3CA correlated with the status of AKT phosphorylation in 7 of 12 (58%) primary MCL cases. Inhibition of PIK3CA induced increased apoptosis in the MCL cell lines. PTEN protein expression was present in all 14 primary MCL cases and cell lines by Western blotting, whereas 5 of 33 (15%) cases tested by immunohistochemistry had loss of PTEN expression.We conclude that a gain of gene copy number of PIK3CA is frequent genetic alteration that contributes to MCL progression. PIK3CA is a promising therapeutic target in MCL.
Peak Flow as Predictor of Overall Mortality in Asthma and Chronic Obstructive Pulmonary Disease
Authors: EJVIND FRAUSING HANSEN, JØRGEN VESTBO, KLAUS PHANARETH, AXEL KOK-JENSEN, ASGER DIRKSEN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Lung function is a strong predictor of overall mortality in asthma and chronic obstructive pulmonary disease (COPD). FEV1 is considered to be the "gold standard," whereas peak expiratory flow (PEF) is mostly used in absence of FEV1 measurements. We compared the predictive power of PEF and FEV1, measured after maximal bronchodilation, which included a short course of oral corticosteroids. The study population comprised 491 asthmatics and 1,095 subjects with COPD. Pulmonary function tests were performed between 1983 and 1988, and survival data were obtained by September 1997, when 127 asthmatics and 723 subjects with COPD had died. Predictors of survival were examined by Cox proportional hazards analyses. After controlling for age, smoking, sex, and body mass index, we found best PEF to be at least equal to best FEV1 as predictor of overall mortality in subjects with COPD. The predictive power of best PEF was in part maintained after controlling for best FEV1. In asthma, best FEV1 seemed to be a better predictor of mortality than best PEF. Despite close correlation to FEV1, PEF apparently provides independent prognostic information in patients with COPD. This may be due to PEF and FEV1 reflecting different components of COPD, i.e., chronic bronchitis, small airways disease, and emphysema. Furthermore, extrapulmonary components such as muscle mass and general "vigour" probably affect PEF to a greater extent than they affect FEV1.