Tamás Dolinay

Publications (6)22.68 Total impact

• Article: Heme Oxygenase-1/CO as protective mediators in cigarette smoke- induced lung cell injury and chronic obstructive pulmonary disease.

  Tamás Dolinay, Augustine M K Choi, Stefan W Ryter
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  ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a disease involving airways restriction, alveolar destruction, and loss of lung function, primarily due to cigarette smoke (CS) exposure. The inducible stress protein heme oxygenase-1 (HO-1) has been implicated in cytoprotection against the toxic action of many xenobiotics, including CS. HO-1 also protects against elastase-induced emphysema. Differential expression of HO-1 in epithelial cells and macrophages may contribute to COPD susceptibility. Genetic polymorphisms in the HO-1 gene, which may account for variations in HO-1 expression among subpopulations, may be associated with COPD pathogenesis. Carbon monoxide (CO), a primary reaction product of HO-1 has been implicated in cytoprotection in many acute lung injury models, though it's precise role in chronic CS-induced lung injury remains unclear. CO is a potential biomarker of CS exposure and of inflammatory lung conditions. To date, a single clinical trial has addressed the possible therapeutic potential of CO in COPD patients. The implications of the cytoprotective potential of HO-1/CO system in CS-induced lung injury and COPD are discussed.
  Current pharmaceutical biotechnology 09/2012; 13(6):769-76. · 3.40 Impact Factor
• Source

  Available from: Stefan W Ryter

  Article: Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury.

  Tamás Dolinay, Wei Wu, Naftali Kaminski, Emeka Ifedigbo, A Murat Kaynar, Mária Szilasi, Simon C Watkins, Stefan W Ryter, Alexander Hoetzel, Augustine M K Choi
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  ABSTRACT: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(2)-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3(-/-)) or c-Jun-NH(2)-terminal kinase-1 (jnk1(-/-)) were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3(-/-) or jnk1(-/-) mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1(-/-) mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1(-/-) mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8) and GADD45alpha. Functional characterization of MMP8 revealed that mmp8(-/-) mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH(2)-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage.
  PLoS ONE 02/2008; 3(2):e1601. · 4.09 Impact Factor
• Article: Gene expression profiling of target genes in ventilator-induced lung injury.

  Tamás Dolinay, Naftali Kaminski, Martina Felgendreher, Hong P Kim, Paul Reynolds, Simon C Watkins, Dörte Karp, Stefan Uhlig, Augustine M K Choi
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  ABSTRACT: In the lungs, high-pressure mechanical ventilation induces an inflammatory response similar to that observed in acute respiratory distress syndrome. To further characterize these responses and to compare them with classical inflammatory pathways, we performed gene expression profiling analysis of 20,000 mouse genes in isolated blood-free (to exclude genes from sequestered leukocytes) perfused mouse lungs exposed to low-pressure ventilation (10 cmH2O), high-pressure ventilation (25 cmH2O, overventilation), and LPS treatment. A large number of inflammatory and apoptotic genes were increased by both overventilation and LPS. However, certain growth factor-related genes, as well as genes related to development, cellular communication, and the cytoskeleton, were only regulated by overventilation. We validated and confirmed increased mRNA expression pattern of five genes (amphiregulin, gravin, Nur77, Cyr61, interleukin-11) by real-time PCR; furthermore, we confirmed increased protein expression of amphiregulin by immunohistochemistry and immunoblotting assays. These genes represent novel candidate genes in ventilator-induced lung injury.
  Physiological Genomics 07/2006; 26(1):68-75. · 2.73 Impact Factor
• Article: [Results in 42 non-resectable NSCLC IIA-B patients with initial concurrent Taxotere-Cisplatin chemoradiotherapy].

  Mária Szilasi, Akos Horváth, Tamás Dolinay, János Szántó, László Brugós, László Lengyel, Sándor Sz Kiss, Magdolna Kiss, Zsolt Adamecz
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  ABSTRACT: A prospective multicenter study to treat non-small cell lung cancer (NSCLC) with inductive chemoradiotherapy for improving chances of operability. If used as first-line therapy, combined treatment improves survival and it is well tolerated with a low rate of side effects. 42 patients with stage IIIA-B NSCLC from which 36 could be followed. A full dose Taxotere-Cisplatin chemotherapy was given to patients with concurrent radiotherapy in 2 Gy fractions up to 60 Gy via conformal irradiation. Local response was very high and 40.47% of patients became operable while in inoperable cases consolidation chemotherapy showed similar results as other protocols. We also found a low rate of side effects. The high rate of brain metastasis suggests that prophylactic cranial irradiation (PCI) should be considered.
  Magyar Onkológia 02/2006; 50(3):233-6.
• Source

  Available from: webio.hu

  Article: Pathology of chronic obstructive pulmonary disease.

  Mária Szilasi, Tamás Dolinay, Zoltán Nemes, János Strausz
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  ABSTRACT: Chronic obstructive pulmonary disease is one of the leading causes of death and morbidity worldwide. Despite intensive investigation, its pathology and pathophysiology are not well understood. The hallmarks of the disease are irreversible airflow limitation and chronic inflammation. Small airway obstruction due to progressive inflammation and fibrosis, and the loss of elastic recoil mediated by elastolysis and apoptosis equally contribute to pathologic changes. However, it is debated to what extent the obstruction of large airways leads to altered lung function. Three morphologic entities are described in the literature under one disease; chronic bronchitis, obstructive bronchiolitis and emphysema may appear in the same patient at the same time. The authors review pathologic changes observed in chronic obstructive pulmonary disease, including acute exacerbations and secondary pulmonary hypertension as severe but common complications of the disease. Furthermore, we detail recent scientific evidences for major cellular and molecular inflammatory pathway activation. These mechanisms result in accelerated apoptosis, remodeling and increased proinflammatory cytokine release. Targeting intracellular pathological changes may lead to the discovery of a new generation of drugs that could reduce chronic obstruction before airway irreversibility is established.
  Pathology & Oncology Research 02/2006; 12(1):52-60. · 1.37 Impact Factor
• Source

  Available from: atsjournals.org

  Article: Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury.

  Tamás Dolinay, Mária Szilasi, Mingyao Liu, Augustine M K Choi
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  ABSTRACT: Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major by-product of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-alpha levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-kappaB pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI.
  American Journal of Respiratory and Critical Care Medicine 10/2004; 170(6):613-20. · 11.08 Impact Factor