tbuckley/cabot-search huggingface dataset:
Differential expression of melanoma-associated growth factors in keratinocytes and fibroblasts by ultraviolet A and ultraviolet B radiation
Authors: M. Brenner, K. Degitz, R. Besch, C. Berking
Journal: British Journal of Dermatology (2005)

Besides the direct DNA-damaging effects of ultraviolet (UV) radiation on cells, indirect effects on the microenvironment of the skin may facilitate melanoma development. A stimulation of growth factor production by cells in the immediate environment of melanocytes may lead to a paracrine activation and proliferation of melanocytes that in turn become more susceptible to transformation.We investigated whether the expression of growth factors for melanocytes can be modulated in keratinocytes and fibroblasts by UVA or UVB.After irradiation with different doses of UVA or UVB, protein expression of basic fibroblast growth factor (bFGF), endothelin (ET)-1, transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AA, stem cell factor (SCF) and hepatocyte growth factor (HGF) was analysed by quantitative enzyme-linked immunosorbent assay. The mRNA expression of bFGF and ET-1 was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction.In keratinocytes, UVB and UVA increased bFGF protein levels up to 2.6-fold. This increase was paralleled by elevated mRNA levels. UVB also induced ET-1 protein up to 1.8-fold, while UVA led to an 80% decrease. Secreted TGF-beta1 and PDGF-AA were downregulated by UVA by less than 50%, while there was no significant alteration by UVB. Secreted SCF was not changed significantly by UVA or UVB. In fibroblasts, bFGF protein levels were increased 11-64-fold by UVA and 34-61-fold by UVB. This was paralleled by elevated mRNA levels for bFGF up to 2.7-fold. HGF protein was stimulated by UVA up to 2.8-fold and by UVB up to 6.7-fold, while TGF-beta1 protein was increased up to 2.7-fold by UVB and 1.7-fold by UVA.UVA and UVB can stimulate and inhibit the production of growth factors for melanocytes in keratinocytes and fibroblasts dependent on the cell type and wavelength. We show for the first time that UVA and UVB can activate bFGF, HGF and TGF-beta1 in fibroblasts, while bFGF was the most inducible factor both in fibroblasts and in keratinocytes. The induction of bFGF and HGF in fibroblasts by UVA suggests that stroma cells in the dermis may be involved in the UV activation of melanocytes via paracrine ways and thus promote melanoma development.
THE EFFECTS OF ALTI-VIT ON EXERCISE PERFORMANCE AT ALTITUDE
Authors: E Youngman, C Howe, HJ Moir
Journal: British Journal of Sports Medicine (2013)

This study examined the effects of ALTI-VIT supplementation on exercise performance and Acute Mountain Sickness (AMS) at altitude. Seven healthy males with no experience of exercise at altitude completed two 16 km cycle time-trials at a simulated altitude of 2400 m in an altitude chamber. Using a single-blind, randomised, crossover design, participants consumed 2 capsules (270 mg) of ALTI-VIT (A) or a placebo (Pl) 24-hours prior to testing and 2 capsules on the morning of testing. Time-trial completion was faster in the A condition (30.04±4.39 min) than the Pl condition (31.02±5.22 min) ( P =0.05). RER was lower in the A condition (A: 1.03±0.11 vs . Pl: 1.13±0.12; P =0.044) and the incidence of AMS (A: 0.4±0.5 vs. Pl: 3±1; P =0.002) and severity of symptoms were reduced ( P &lt;0.05). No differences were found between conditions for HR, RPE, VO 2 , VE, VO 2 max , speed, power output and RPM ( P &gt;0.05). These results demonstrated that 24-hour supplementation of ALTI-VIT enhanced exercise performance at altitude and reduced the incidence and severity of AMS.
TCT-489 Association of Dual Antiplatelet Therapy Cessation with Ischemic and Bleeding Events Following Cobalt-Chromium Everolimus-Eluting Stent Implantation in Chinese Population: First Two-Year Reports of the Prospective Multicenter SEEDS Study
Authors: Yelin Zhao, Bo Xu, Yaling Han, Bao Li, Qiang Liu, Junyu Cui, Lang Li, Shuzheng Lu, Yuejin Yang
Journal: Journal of the American College of Cardiology (2014)
Does this patient have appendicitis?
Authors: T. M. Schneider
Journal: JAMA (1997)

To the Editor.  —Dr Wagner and colleagues1have made an interesting and valuable contribution by correlating a number of the large-scale studies regarding acute appendicitis over the last 20 years. As a practicing general surgeon, I can attest to the protean manifestations of acute appendicitis and the difficulties that sometimes occur in making the diagnosis. The enumeration by the authors of a number of the more important aspects of the history and examination is, for the most part, accurate. However, I must take exception to the conclusion astute clinicians will recognize that the absence of anorexia, nausea, or vomiting has little impact on the likelihood of appendicitis. To the contrary, anorexia is an extremely common finding in acute appendicitis, and it is rare to find a patient with appendicitis who is hungry. The absence of anorexia should cause the physician to question the diagnosis of appendicitis in a patient
Time domain echo pattern evaluations from normal and atherosclerotic arterial walls: a study in vitro.
Authors: E Picano, L Landini, F Lattanzi, M Salvadori, A Benassi, A L'Abbate
Journal: Circulation (1988)

The aim of this study in vitro of human fresh specimens was to quantitatively evaluate the contribution of the aqueous phase-intima interface (the first 400 msec of the reflected signal) in normal and atherosclerotic arterial walls. Seventy-five samples were studied, 15 normal, 15 fatty, 15 fibrofatty, 15 fibrous, and 15 calcific. A broadband transducer (4 to 14 MHz) was used. The aqueous phase-intima reflection (expressed in dB, mean +/- SD) was lowest in the fatty plaques (-35.3 +/- 2.5), differing in a highly significant way from that in all other groups: normal (-13.2 +/- 8.8), fibrofatty (-20.4 +/- 8.3), fibrous (-13.0 +/- 9.7), calcific (-5.9 +/- 3.4). The echo coming from the intima-media transition was of relatively low amplitude in normal and in fatty samples; typically, strong reflections from the intima-media transitions were present in the other pathologic subsets. In conclusion, the time domain echo pattern of the arterial wall may provide a useful clue to the structure of the plaque.
Positional hyperventilation-induced hypoxaemia in pectus excavatum
Authors: B. Wallaert, B. Cavestri, C. Fournier, R. Nevière, B. Aguilaniu
Journal: European Respiratory Journal (2006)

The presented case is of a young male (aged 19 yrs) with a pectus excavatum who showed significant exercise intolerance, despite normal pulmonary function at rest, including carbon monoxide diffusing capacity. Clinical exercise testing led to a strong suspicion of a right-to-left shunt due to an abnormally wide alveolo–arterial oxygen gradient (26.4 kPa) at peak oxygen uptake, with severe arterial hypoxaemia (arterial oxygen tension 12.54 kPa). A right-to-left shunt was confirmed by transoesophageal echocardiography demonstrating a permeable foramen ovale, despite normal right heart pressures. The right-to-left venous flow was mainly dependent on the upright body position and the deep inspiration. Indeed, i.v. dobutamine infusion to selectively affect cardiac output and hyperventilation induced by tidal volume expansion at constant breathing rate in the supine position did not result in arterial oxygen desaturation or shunting. Closure of the foramen ovale through atrial umbrella placement dramatically improved clinical and physiological abnormalities. This observation demonstrates that a hyperventilatory manoeuvre in the upright position is able to detect a permeable foramen ovale favouring flow in the inferior vena cava in the direction of the abnormal pre-existing atrial channel in a patient with a pectus excavatum.
The Phosphoinositide 3‐Kinase Isoform PI3Kβ Regulates Osteoclast‐Mediated Bone Resorption in Humans and Mice
Authors: Dávid Győri, Dániel Csete, Szilvia Benkő, Suhasini Kulkarni, Péter Mandl, Csaba Dobó‐Nagy, Bart Vanhaesebroeck, Len Stephens, Phillip T. Hawkins, Attila Mócsai
Journal: Arthritis & Rheumatology (2014)

While phosphoinositide 3-kinases (PI3Ks) are involved in various intracellular signal transduction processes, the specific functions of the different PI3K isoforms are poorly understood. We have previously shown that the PI3Kβ isoform is required for arthritis development in the K/BxN serum-transfer model. Since osteoclasts play a critical role in pathologic bone loss during inflammatory arthritis and other diseases, we undertook this study to test the role of PI3Kβ in osteoclast development and function using a combined genetic and pharmacologic approach.The role of PI3Kβ in primary human and murine osteoclast cultures was tested with the PI3Kβ-selective inhibitor TGX221 and by using PI3Kβ(-/-) mice. The trabecular bone architecture of PI3Kβ(-/-) mice was evaluated using micro-computed tomography and histomorphometric analyses.The expression of PI3Kβ was strongly and specifically up-regulated during in vitro osteoclast differentiation. In vitro development of large multinucleated osteoclasts from human or murine progenitors and their resorption capacity were strongly reduced by the PI3Kβ inhibitor TGX221 or by the genetic deficiency of PI3Kβ. This was likely due to defective cytoskeletal reorganization and vesicular trafficking, since PI3Kβ(-/-) mouse multinucleated cells failed to form actin rings and retained intracellular acidic vesicles and cathepsin K. In contrast, osteoclast-specific gene expression and the survival and apoptosis of osteoclasts were not affected. PI3Kβ(-/-) mice had significantly increased trabecular bone volume and showed abnormal osteoclast morphology with defective resorption pit formation.PI3Kβ plays an important role in osteoclast development and function and is required for in vivo bone homeostasis.
Soluble CD40 Ligand Plasma Levels in Lung Cancer
Authors: Mario Roselli, Tommaso C. Mineo, Stefania Basili, Francesca Martini, Sabrina Mariotti, Simona Aloe, Girolamo Del Monte, Vincenzo Ambrogi, Antonella Spila, Raffaele Palmirotta, Roberta D’Alessandro, Giovanni Davì, Fiorella Guadagni, Patrizia Ferroni
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. Experimental Design: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. Results: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P &amp;lt; 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P &amp;lt; 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P &amp;lt; 0.05). sCD40L levels significantly correlated with sP-selectin (P &amp;lt; 0.001), prothrombin fragment 1 + 2 (P &amp;lt; 0.001), or thrombin-antithrombin III complex (P &amp;lt; 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. Conclusions: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.
A Cascade of Modules of a Network Defines Cancer Progression
Authors: Sam Thiagalingam
Journal: Cancer Research (2006)

Abstract Similar histologic subtypes of cancers often exhibit different spectrum of genetic and epigenetic alterations. The heterogeneity observed due to lack of consistent and defined alterations affecting a unique set of gene(s) or gene products in cancers derived from a specific tissue, or an organ, pose a challenge in unraveling the molecular basis of the disease. This dilemma also complicates diagnosis, prognosis, effective management, and treatment modalities. To streamline the available and emerging data into a coherent scheme of events, a multimodular molecular network (MMMN) cancer progression model is presented as a roadmap to dissect the complexity inherent to this disease. The fact that disruption/dysregulation of more than one alternate target gene could affect the functionality of each specific module of a cascade provides a molecular basis for genetic and epigenetic heterogeneity in any given cancer. Polymorphisms/mutations as well as the extracellular matrix and or the epigenetically/genetically conditioned surrounding stromal cells could also influence the rate of tumorigenesis and the properties of the tumor cells. The formulation of MMMN cancer progression models for specific cancers is likely to provide the blueprints for the markers and targets to aid diagnosis, prevention, and therapy of this deadly disease. (Cancer Res 2006; 66(15): 7379-85)
Prognosis of Men Returning to Work after First Myocardial Infarction
Authors: GEORGE E. DIMOND
Journal: Circulation (1961)

The 5-year prognosis of 202 railway operating employees returning to full-time work after their initial myocardial infarction and the 10-year survival rates of 97 of these men have been described. The 5-year survival rate was 83 per cent and the 10-year survival rate was 57 per cent. Twenty-five per cent of these men died or were totally disabled at the end of 5 years and 50 per cent at the end of 10 years. The cause of death or disability following the initial infarction was largely due to recurrent myocardial infarction. The prognosis for men returning to fulltime activity after the first myocardial infarction is better than that reported for those surviving without consideration for their functional recovery. This better prognosis is not due to freedom from second infarctions but to a decreased incidence of myocardial failure and the ability better to survive and tolerate a second infarction.
Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-Measures Study
Authors: Irina Mordukhovich, Elissa Wilker, Helen Suh, Robert Wright, David Sparrow, Pantel S. Vokonas, Joel Schwartz
Journal: Environmental Health Perspectives (2009)

Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects.We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter < or = 2.5 microm (PM(2.5))], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense.We performed a repeated-measures analysis in elderly men to analyze associations between PM(2.5) and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1.A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1-2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2-1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM(2.5) and BP.We observed positive associations between BP and BC, but not between BP and PM(2.5), and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.
Leydig cell–derived heme oxygenase-1 regulates apoptosis of premeiotic germ cells in response to stress
Authors: Nobuaki Ozawa, Nobuhito Goda, Nobuya Makino, Tokio Yamaguchi, Yasunori Yoshimura, Makoto Suematsu
Journal: Journal of Clinical Investigation (2002)

Stress-induced downregulation of spermatogenesis remains poorly understood. This study examined the induction of heme oxygenase-1 (HO-1), a carbon monoxide–generating inducible enzyme, in modulation of spermatogenesis. Rats were exposed to cadmium chloride (CdCl2), a stressor causing oligozoospermia, and HO-1–induction was monitored by following HO isozyme expression. CdCl2-treated testes increased HO-1 activity and suppressed microsomal cytochromes P450, which are required for steroidogenesis. CdCl2-elicited HO-1 occurred mostly in Leydig cells and coincided with CO generation, as judged by bilirubin-IXα immunoreactivity. Under these circumstances, germ cells in peripheral regions of seminiferous tubules exhibited apoptosis; laser flow cytometry revealed that these apoptotic cells involve diploid and tetraploid germ cells, suggesting involvement of spermatogonia and primary spermatocytes in CdCl2-elicited apoptosis. Pretreatment with zinc protoporphyrin-IX, an HO inhibitor, but not copper protoporphyrin-IX, which does not block the enzyme, attenuated the CdCl2-induced apoptosis. Such antiapoptotic effects of zinc protoporphyrin-IX were repressed by supplementation of dichloromethane, a CO donor. Upon CdCl2-treatment, both Sertoli cells and the germ cells upregulated Fas ligand; this event was also suppressed by zinc protoporphyrin-IX and restored by dichloromethane. Thus, Leydig cells appear to use HO-1–derived CO to trigger apoptosis of premeiotic germ cells and thereby modulate spermatogenesis under conditions of stress.
Coronary Stent Restenosis in Patients Treated With Cilostazol
Authors: John S. Douglas, David R. Holmes, Dean J. Kereiakes, Cindy L. Grines, Elizabeth Block, Ziyad M.B. Ghazzal, Douglas C. Morris, Henry Liberman, Karen Parker, Claudine Jurkovitz, Nancy Murrah, Jovonne Foster, Pamela Hyde, G.B. John Mancini, William S. Weintraub
Journal: Circulation (2005)

Background— Restenosis after implantation of coronary artery stents remains a significant clinical problem. We undertook a randomized, double-blind, placebo-controlled trial to determine whether cilostazol, a drug that suppresses intimal proliferation, would reduce renarrowing in patients after stent implantation in native coronary arteries. Methods and Results— We assigned 705 patients who had successful coronary stent implantation to receive, in addition to aspirin, cilostazol 100 mg BID or placebo for 6 months; clopidogrel 75 mg daily was administered to all patients for 30 days. Restenosis was determined by quantitative coronary angiography at 6 months. The minimal luminal diameter at 6 months for cilostazol-treated patients was 1.77 mm for the analysis segment (stent plus 5-mm borders) compared with 1.62 mm in the placebo group ( P =0.01). Restenosis, defined as ≥50% narrowing, occurred in 22.0% of patients in the cilostazol group and in 34.5% of the placebo group ( P =0.002), a 36% relative risk reduction. Restenosis was significantly lower in cilostazol-treated diabetics (17.7% versus 37.7%, P =0.01) and in those with small vessels (23.6% versus 35.2%, P =0.02), long lesions (29.9% versus 46.6%, P =0.04), and left anterior descending coronary artery site (19.3% versus 39.8%, P =0.001). There was no difference in bleeding, rehospitalization, target-vessel revascularization, myocardial infarction, or death. Conclusions— Treatment with the drug cilostazol resulted in a significantly larger minimal luminal diameter and a significantly lower binary restenosis rate compared with placebo-treated patients. These favorable effects were apparent in patients at high risk for restenosis.
Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis
Authors: William R Ferrell, Elizabeth B Kelso, John C Lockhart, Robin Plevin, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2010)

Objective Osteoarthritis is a global clinical challenge for which no effective disease-modifying agents currently exist. This study identified protease-activated receptor 2 (PAR-2) as a novel pathogenic mechanism and potential therapeutic target in osteoarthritis. Methods Experimental osteoarthritis was induced in wild-type and PAR-2-deficient mice by sectioning the medial meniscotibial ligament (MMTL), leading to the development of a mild arthropathy. Cartilage degradation and increased subchondral bone formation were assessed as indicators of osteoarthritis pathology. Results Four weeks following MMTL section, cartilage erosion and increased subchondral bone formation was evident in wild-type mice but was substantially reduced in PAR-2-deficient mice. Crucially, the therapeutic inhibition of PAR-2 in wild-type mice, using either a PAR-2 antagonist or a monoclonal antibody targeting the protease cleavage site of PAR-2, was also equally effective at reducing osteoarthritis progression in vivo. PAR-2 was upregulated in chondrocytes of wild-type but not sham-operated mice. Wild-type mice showed further joint degradation 8 weeks after the induction of osteoarthritis, but PAR-2-deficient mice were still protected. Conclusions The substantial protection from pathology afforded by PAR-2 deficiency following the induction of osteoarthritis provides proof of concept that PAR-2 plays a key role in osteoarthritis and suggests this receptor as a potential therapeutic target.
Neoadjuvant Short-term Intensive Intravesical Mitomycin C Regimen Compared with Weekly Schedule for Low-grade Recurrent Non–muscle-invasive Bladder Cancer: Preliminary Results of a Randomised Phase 2 Study
Authors: Renzo Colombo, Lorenzo Rocchini, Nazareno Suardi, Fabio Benigni, Giorgia Colciago, Arianna Bettiga, Federico Pellucchi, Carmen Maccagnano, Alberto Briganti, Andrea Salonia, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2012)
What health services could do about climate change
Authors: Anna Coote
Journal: BMJ (2006)

What health services could do about climate changeThey must embrace sustainable development and reduce their ecological footprints A dvocates for action on climate change face two main challenges.The first is to make everyone aware of the enormity of the problem.The second is to persuade anyone that anything can be done about it.Ignorance is bad enough, but inertia-induced by despair, denial, or the hope of a miraculous technical fix-is even more dangerous.Climate change, as Robin Stott argues in this week's BMJ, 1 poses grave risks to health. 2 It threatens the essentials of life.It brings drought, floods, storms, and extremes of heat and cold that can lead to famine, homelessness, dislocation, destruction of communities, the spread of disease, and even mass migrations and armed conflict as people vie with each other for land, water, food, and energy.And let's not forget the effects on mental health of anxiety, insecurity, and a sense of powerlessness as we watch the grass wither and the icecaps melt.If medicine is about saving lives, not just by last ditch interventions but by trying to avert illness, then working to alter patterns of behaviour that contribute to climate change could arguably become a priority for clinicians-as an urgent preventive measure.Debating the health implications of climate change may also be the best way to get the general public to take the problem seriously.Concepts such as "sustain-