tbuckley/cabot-search huggingface dataset:
Do worsening scleroderma capillaroscopic patterns predict future severe organ involvement? a pilot study
Authors: Vanessa Smith, Saskia Decuman, Alberto Sulli, Carolien Bonroy, Yves Piettte, Ellen Deschepper, Filip de Keyser, Maurizio Cutolo
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma patterns ('early', 'active' and 'late') with future severe clinical involvement in a systemic sclerosis (SSc) population. <h3>Methods</h3> Sixty-six consecutive patients with SSc according to the LeRoy and Medsger criteria underwent NVC assessment at baseline. Videocapillaroscopic images were classified into 'normal', 'early', 'active' or 'late' NVC pattern. Clinical evaluation was performed for nine organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart and kidney) according to the disease severity scale of Medsger (DSS) at 18–24 months of follow-up. Severe clinical involvement was defined as category 2–4 per organ of the DSS. <h3>Results</h3> NVC patterns were significantly associated with future severe, peripheral vascular/lung involvement at 18–24 months. The OR rose steadily throughout the patterns. The OR for future severe peripheral disease based on simple/multiple (correcting for disease duration, subset and medication) logistic regression was 2.49/2.52 (95% CI 1.33 to 5.43, p=0.003/1.11 to 7.07, p=0.026) for early, 6.18/6.37 for active and 15.35/16.07 for late NVC scleroderma patterns versus the normal NVC pattern. The OR for future severe lung involvement based on simple/multiple regression was 2.54/2.33 (95% CI 1.40 to 5.22, p=0.001/1.13 to 5.52, p=0.021) for early, 6.43/5.44 for active and 16.30/12.68 for late NVC patterns. <h3>Conclusions</h3> This pilot study is the first demonstrating an association between baseline NVC patterns and future severe, peripheral vascular and lung involvement with stronger odds according to worsening scleroderma patterns. This may indicate a putative role of capillaroscopy as a biomarker.
Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption
Authors: Shumpei Niida, Masato Kaku, Hitoshi Amano, Hisahiro Yoshida, Hiroshi Kataoka, Satomi Nishikawa, Kazuo Tanne, Norihiko Maeda, Shin-Ichi Nishikawa, Hiroaki Kodama
Journal: The Journal of Experimental Medicine (1999)

We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF-induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.
Cardiorespiratory Fitness as a Feature of Metabolic Syndrome in Older Men and Women
Authors: Maija Hassinen, Timo A. Lakka, Kai Savonen, Hannu Litmanen, Leena Kiviaho, David E. Laaksonen, Pirjo Komulainen, Rainer Rauramaa
Journal: Diabetes Care (2008)

We studied the associations of cardiorespiratory fitness with metabolic syndrome in older men and women, because such data are limited in representative population samples.We studied a population sample of 671 men and 676 women aged 57-79 years at baseline of a randomized controlled intervention study. We assessed maximal oxygen uptake (Vo(2max)) by respiratory gas analysis during a maximal bicycle exercise test.Vo(2max) had a strong, inverse, and graded association with the risk of having metabolic syndrome as defined by the National Cholesterol Education Program criteria. Men and women in the lowest third of Vo(2max) had 10.2- and 10.8-fold higher risks and those in the middle third had 2.9- and 4.7-fold higher risks (P < 0.001 all) of metabolic syndrome than those with the highest Vo(2max) after multivariable adjustments. Factor analysis generated a principal factor that was strongly loaded by the main components of metabolic syndrome and Vo(2max) (-0.68 in men and -0.70 in women).Low cardiorespiratory fitness is associated with metabolic syndrome in older men and women. Our findings suggest that low cardiorespiratory fitness could be considered a feature of metabolic syndrome.
Pathophysiological role of leptin in obesity-related hypertension
Authors: Megumi Aizawa-Abe, Yoshihiro Ogawa, Hiroaki Masuzaki, Ken Ebihara, Noriko Satoh, Hidenori Iwai, Naoki Matsuoka, Tatsuya Hayashi, Kiminori Hosoda, Gen Inoue, Yasunao Yoshimasa, Kazuwa Nakao
Journal: Journal of Clinical Investigation (2000)

To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKAy mice with hyperleptinemia, in which hypothalamic melanocortin system is antagonized by ectopic expression of the agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion are elevated in transgenic skinny mice relative to nontransgenic littermates. The BP elevation in transgenic skinny mice is abolished by α1-adrenergic, β-adrenergic, or ganglionic blockers at doses that do not affect BP in nontransgenic littermates. Central administration of an α-melanocyte–stimulating hormone antagonist causes a marked increase in cumulative food intake but no significant changes in BP. The obese KKAy mice develop BP elevation with increased urinary catecholamine excretion relative to control KK mice. After a 2-week caloric restriction, BP elevation is reversed in nontransgenic littermates with the Ay allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the Ay allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKAy mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.
Aspirin-induced urticaria and angioedema, but not bronchoconstriction, associated with cysteinyl leukotriene overproduction in 2 patients with asthma
Authors: Noritaka Higashi, Masami Taniguchi, Haruhisa Mita, Ai Higashi, Kazuo Akiyama
Journal: Journal of Allergy and Clinical Immunology (2002)
Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network)
Authors: Laura Perez, Christophe Declercq, Carmen Iñiguez, Inmaculada Aguilera, Chiara Badaloni, Ferran Ballester, Catherine Bouland, Olivier Chanel, Francisco B. Cirarda, Francesco Forastiere, Bertil Forsberg, Daniela Haluza, Britta Hedlund, Koldo Cambra, Marina Lacasaña, Hanns Moshammer, Peter Otorepec, Miguel Rodríguez-Barranco, Sylvia Medina, Nino Künzli
Journal: European Respiratory Journal (2013)

Recent epidemiological research suggests that near road traffic-related pollution may cause chronic disease, as well as exacerbation of related pathologies, implying that the entire “chronic disease progression” should be attributed to air pollution, no matter what the proximate cause was. We estimated the burden of childhood asthma attributable to air pollution in 10 European cities by calculating the number of cases of 1) asthma caused by near road traffic-related pollution, and 2) acute asthma events related to urban air pollution levels. We then expanded our approach to include coronary heart diseases in adults. Derivation of attributable cases required combining concentration–response function between exposures and the respective health outcome of interest (obtained from published literature), an estimate of the distribution of selected exposures in the target population, and information about the frequency of the assessed morbidities. Exposure to roads with high vehicle traffic, a proxy for near road traffic-related pollution, accounted for 14% of all asthma cases. When a causal relationship between near road traffic-related pollution and asthma is assumed, 15% of all episodes of asthma symptoms were attributable to air pollution. Without this assumption, only 2% of asthma symptoms were attributable to air pollution. Similar patterns were found for coronary heart diseases in older adults. Pollutants along busy roads are responsible for a large and preventable share of chronic disease and related acute exacerbations in European urban areas.
The COL1A1 gene and acute soft tissue ruptures
Authors: Malcolm Collins, Michael Posthumus, Martin P Schwellnus
Journal: British Journal of Sports Medicine (2009)

Three studies have suggested that the rare TT genotype of the functional Sp1 binding site polymorphism within intron 1 of COL1A1 is associated with cruciate ligament ruptures (CL), shoulder dislocations (SD) and/or Achilles tendon ruptures. Similar genotype distributions were reported for the control and the injury groups in all three studies. In this report, the data from these studies were combined and analyzed. The TT genotype, when compared to the control group (4.1%, n=24 of 581), was significantly under-represented in the (1) CL (0.3%, n=1 of 350, OR=15.0, P=0.0002), (2) CL and SD (0.4% TT genotype, n=2 of 476, OR=10.2, P<0.0001), and (3) CL, SD and Achilles tendon ruptures (0.4% TT genotype, n=2 of 517, OR=11.1, P<0.0001) groups. This combined analysis indicates that the TT genotype appears to be protective against acute soft tissue ruptures and should be incorporated into multifactorial models determining risk of acute soft tissue ruptures.
A Compendium of Potential Biomarkers of Pancreatic Cancer
Authors: H. C. Harsha, Kumaran Kandasamy, Prathibha Ranganathan, Sandhya Rani, Subhashri Ramabadran, Sashikanth Gollapudi, Lavanya Balakrishnan, Sutopa B. Dwivedi, Deepthi Telikicherla, Lakshmi Dhevi N. Selvan, Renu Goel, Suresh Mathivanan, Arivusudar Marimuthu, Manoj Kashyap, Robert F. Vizza, Robert J. Mayer, James A. DeCaprio, Sudhir Srivastava, Samir M. Hanash, Ralph H. Hruban, Akhilesh Pandey
Journal: PLoS Medicine (2009)

The Health in Action section is a forum for individuals or
Management of hypertension in angiogenesis inhibitor-treated patients
Authors: H. Izzedine, S. Ederhy, F. Goldwasser, J.C. Soria, G. Milano, A. Cohen, D. Khayat, J.P. Spano
Journal: Annals of Oncology (2009)

Hypertension (HTN) is one of the most frequent side-effects of systemic inhibition of vascular endothelial growth factor (VEGF) signaling. Its incidence and severity are dependent on the type of drugs, dose, and schedule used. The recognition of this side-effect is an important issue because poorly controlled HTN could lead to serious cardiovascular events. On another hand, HTN induced by anti-VEGF agents maybe a predictive factor of oncologic response. Knowledge of this clinical toxicity and/or therapeutic target or novel biomarker of drug activity can aid clinicians choosing the optimal and least toxic regimen suitable for an individual patient.A Medline search was carried out using the following criteria: (i) all Medline listings as of 1 January 2000 with abstracts, (ii) English language, and (iii) Humans. The following phrases were used to query the database: ('hypertension', OR 'blood pressure') AND ('anti-VEGF' OR 'VEGF inhibition' OR 'bevacizumab' OR 'sunitinib' OR 'sorafenib' OR 'VEGF Trap'). The references of each article identified were carefully reviewed for additional reference.Lifestyle modification should be encouraged. However, these nonpharmacologic strategies are not always suitable to patients with altered performance status related to metastatic cancer necessitating early drug intervention. Only one randomized study showed a beneficial effect of a calcium channel blocker use to prevent or minimize HTN secondary to antiangiogenic therapy. Nitrates looks as effective in controlling such side-effect.No clear recommendation for an antihypertensive agent can be made in this context because there is a lack of controlled studies addressing the subject. Blood pressure-lowering drugs should be individualized to the patient's clinical circumstances and angiogenic inhibitors should be withheld only from patients who experienced hypertensive crisis.
Ca <sup>2+</sup> Influx–Induced Sarcoplasmic Reticulum Ca <sup>2+</sup> Overload Causes Mitochondrial-Dependent Apoptosis in Ventricular Myocytes
Authors: Xiongwen Chen, Xiaoying Zhang, Hajime Kubo, David M. Harris, Geoffrey D. Mills, Jed Moyer, Remus Berretta, Sabine Telemaque Potts, James D. Marsh, Steven R. Houser
Journal: Circulation Research (2005)

Increases in Ca 2+ influx through the L-type Ca 2+ channel (LTCC, Cav1.2) augment sarcoplasmic reticulum (SR) Ca 2+ loading and the amplitude of the cytosolic Ca 2+ transient to enhance cardiac myocyte contractility. Our hypothesis is that persistent increases in Ca 2+ influx through the LTCC cause apoptosis if the excessive influx results in SR Ca 2+ overload. Feline ventricular myocytes (VMs) in primary culture were infected with either an adenovirus (Ad) containing a rat Cav1.2 β 2a subunit-green fluorescent protein (GFP) fusion gene (Adβ 2a ) to increase Ca 2+ influx or with AdGFP as a control. Significantly fewer β 2a -VMs (21.4±5.6%) than GFP-VMs (99.6±1.7%) were viable at 96 hours. A fraction of β 2a -VMs (20.8±1.8%) contracted spontaneously (SC-β 2a -VMs), and viability was significantly correlated with the percentage of SC-β 2a -VMs. Higher percentages of apoptotic nuclei, DNA laddering, and cytochrome C release were detected in β 2a -VMs. This apoptosis was prevented with pancaspase or caspase-3 or caspase-9 inhibitors. L-type calcium current (I Ca-L ) density was greater in β 2a -VMs (23.4±2.8 pA/pF) than in GFP-VMs (7.6±1.6 pA/pF). SC-β 2a -VMs had higher diastolic intracellular Ca 2+ (Indo-1 ratio: 1.1±0.1 versus 0.7±0.03, P &lt;0.05) and systolic Ca 2+ transients (1.89±0.27 versus 0.80±0.08) than GFP-VMs. Inhibitors of Ca 2+ influx, SR Ca 2+ uptake and release, mitochondrial Ca 2+ uptake, mitochondrial permeation transition pore, calpain, and Bcl-2-associated X protein protected β 2a -VMs from apoptosis. These results show that persistent increases in Ca 2+ influx through the I Ca-L enhance contractility but lead to apoptosis through a mitochondrial death pathway if SR Ca 2+ overload is induced.
Inhibitory effect of ceramide on insulin-induced protein kinase Cζ translocation in rat adipocytes
Authors: Atsushi Miura, Kazuo Kajita, Masayoshi Ishizawa, Yoshinori Kanoh, Yasunori Kawai, Yoshiyuki Natsume, Hiroya Sakuma, Yoritsuna Yamamoto, Keigo Yasuda, Tatsuo Ishizuka
Journal: Metabolism (2003)
Rheumatoid arthritis in women: still associated with an increased mortality
Authors: N Goodson
Journal: Annals of the Rheumatic Diseases (2002)

In recent onset RA excess mortality is not related to disease severity

The mortality associated with rheumatoid arthritis (RA) has been extensively studied over the past 50 years. Many studies have shown that patients with RA have higher mortality rates than those of the general population.1–4 Hospital based cohorts of patients with RA tend to have higher standardised mortality rates than RA cohorts derived from the community.3 This suggests that the excess mortality in RA is related to disease severity.

Most studies of mortality in RA have been carried out in cohorts of patients with established RA. However, more recently, there have been a number of studies of the mortality of inception cohorts of patients with RA. Two studies of RA inception cohorts with disease onset in the 1980s, recruited from hospital settings, failed to find any increase in mortality during the early years of follow up.5,6 By contrast, three other studies of inception cohorts, identified from the community or primary care during an equivalent period of time, showed continuing greater mortality in women with RA even in the early years of the disease.7–9

In this issue of the Annals of the Rheumatic Diseases investigators of the Iowa Women’s Health Study report that mortality is increased in women with older onset RA during the early …
Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice
Authors: Clinton S. Robbins, Carla M. T. Bauer, Neda Vujicic, Gordon J. Gaschler, Brian D. Lichty, Earl G. Brown, Martin R. Stämpfli
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents.Objective: The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden after respiratory infection with influenza A.Methods: C57BL/6 mice were sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 × 103 pfu (low dose) or 2.5 × 105 pfu (high dose) influenza virus.Measurements and Main Results: Although smoke exposure attenuated the airway's inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed compared with sham-exposed mice after infection with high-dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necrosis factor-α, interleukin-6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral rechallenge.Conclusion: Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact.
The MIF Receptor CD74 in Diabetic Podocyte Injury
Authors: Maria Dolores Sanchez-Nin[Combining Tilde]o, Ana Belen Sanz, Pekka Ihalmo, Markus Lassila, Harry Holthofer, Sergio Mezzano, Claudio Aros, Per-Henrik Groop, Moin A. Saleem, Peter W. Mathieson, Robert Langham, Matthias Kretzler, Viji Nair, Kevin V. Lemley, Robert G. Nelson, Eero Mervaala, Deborah Mattinzoli, Maria Pia Rastaldi, Marta Ruiz-Ortega, Jose Luis Martin-Ventura, Jesus Egido, Alberto Ortiz
Journal: Journal of the American Society of Nephrology (2008)

Although metabolic derangement plays a central role in diabetic nephropathy, a better understanding of secondary mediators of injury may lead to new therapeutic strategies. Expression of macrophage migration inhibitory factor (MIF) is increased in experimental diabetic nephropathy, and increased tubulointerstitial mRNA expression of its receptor, CD74, has been observed in human diabetic nephropathy. Whether CD74 transduces MIF signals in podocytes, however, is unknown. Here, we found glomerular and tubulointerstitial CD74 mRNA expression to be increased in Pima Indians with type 2 diabetes and diabetic nephropathy. Immunohistochemistry confirmed the increased glomerular and tubular expression of CD74 in clinical and experimental diabetic nephropathy and localized glomerular CD74 to podocytes. In cultured human podocytes, CD74 was expressed at the cell surface, was upregulated by high concentrations of glucose and TNF-alpha, and was activated by MIF, leading to phosphorylation of extracellular signal-regulated kinase 1/2 and p38. High glucose also induced CD74 expression in a human proximal tubule cell line (HK2). In addition, MIF induced the expression of the inflammatory mediators TRAIL and monocyte chemoattractant protein 1 in podocytes and HK2 cells in a p38-dependent manner. These data suggest that CD74 acts as a receptor for MIF in podocytes and may play a role in the pathogenesis of diabetic nephropathy.
BCL-2 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease predicts a poorer prognosis in patients treated with ABVD or equivalent regimens
Authors: George Z. Rassidakis, L. Jeffrey Medeiros, Theodoros P. Vassilakopoulos, Simonetta Viviani, Valeria Bonfante, Gianpaolo Nadali, Marco Herling, Maria K. Angelopoulou, Roberto Giardini, Marco Chilosi, Christos Kittas, Timothy J. McDonnell, Gianni Bonadonna, Alessandro M. Gianni, Giovanni Pizzolo, Gerassimos A. Pangalis, Fernando Cabanillas, Andreas H. Sarris
Journal: Blood (2002)
Phase II Trial of Infusional Fluorouracil, Irinotecan, and Bevacizumab for Metastatic Colorectal Cancer: Efficacy and Circulating Angiogenic Biomarkers Associated With Therapeutic Resistance
Authors: Scott Kopetz, Paulo M. Hoff, Jeffrey S. Morris, Robert A. Wolff, Cathy Eng, Katrina Y. Glover, Rosie Adinin, Michael J. Overman, Vincete Valero, Sijin Wen, Christopher Lieu, Shaoyu Yan, Hai T. Tran, Lee M. Ellis, James L. Abbruzzese, John V. Heymach
Journal: Journal of Clinical Oncology (2009)

Purpose We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m 2 ), bolus FU (400 mg/m 2 ), and leucovorin (400 mg/m 2 ) followed by a 46-hour infusion of FU (2,400 mg/m 2 ). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P &lt; .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P &lt; .001). Conclusion Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.