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Kharitonov, S. A., A. U. Wells, bronchiectasis." al. (1995). "Elevated levels of exhaled nitric oxide in 151(6): 1889-93. Kharitonov, S. A., D. yates, et al. (1995). "Increased nitric oxide in exhaled air of normal human subjects with upper respiraiory tract infections." European Resoiratory Journal 8(2):295-7. Kharitonov, S. A., D. yates, et al. (1994). "Increased nitric oxide in exhaled air of asthmatic patients." Lancet. Jan 15;343(8890): 133-5' Kharito;ov, s. A., D. yuto, .t ui. (tqqs). 'iExhaled nitric oxide is increased in asthma." chest 107 (3 SupPl): l565-157S. Kharitonov, S. A., D. H. yates, et al. (1996). "Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients." American Journal of Respiratory & Critical Care Medicine. Jan: 153(1): 454-7. Khatri, S. B., J. Hammel, et al. (2003). "Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge." Journal of Applied Physiology 95(1): 436-4O; discussion 435. Kim, c. t
Kleinert, H., T. Wallerath, et al. (1998). "Cytokine induction of NO synthase II in human DLD-I cells: roles of the JAK-STAT, AP-l and NF-kappaB-signaling pathways." British Journal of Pharmacology 125(1): 193-201. Knowles, M. 8., D. J. McWeeny, et al. (1974). "Interaction of nitrite with proteins at gastric pH. " Nature ?47 (439): 288-9. Knowles, R. G. and S. Moncada (1992). "Nitric oxide as a signal in blood vessels." Trends in Biochemical Sciences 17(10): 399-402. Knowles,R.G.andS.Moncada(|994).''Nitricoxidesynthasesinmammals.''@ Journal 298(Pt 2): 249-58. Kobzik, L., D. S. Bredt, et al. (1993). "Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization." American Journal of Respiratory Cell & Molecular Biology. 9(4):371-7. Koh, J. Y., S. Peters, et al. (1986). "Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity." &i@ 234(4772):73-6. Koh, Y. Y., J. H. Jeong, et al. (1999). "Development of wheezing in patients with cough variant asthma during an increase in airway responsiveness." European Respiratory Journal l4(2):302-8. Kolbe, J., G. Richards, et al. (1996). "Relationship of non-specific airway hypenesponsiveness (AIIR) to measures of peak expiratory flow @EF) variability." Australian & New Zealand Journal of Medicine 26(I):59-65. Kondo, R., M. Haniuda, et al. (2003). "Effects of expiratory pressure on nitric oxide in exhaled breath. Is exhaled nitric oxide really unaffected by pressure?" Respiratory Physiology & Neurobiology 139(l): 33-40. Kooiker, R. H., L. M. Schuman, et al. (1963). "Nitrogen Dioxide Poisoning." Archives of Environmental Health 7: 13-32. Kooy, N. W. and J. A. Royall (1994). "Agonist-induced peroxynitrite production from endothelial cells." Archives of Biochemistry & Biophysics 310(2): 352-9. Koprowski, H., Y. M. Zheng, et al. (1993). "In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases." Proceedings of the National Academy of Sciences of the United States of America 90(7): 3024-7. Koshino, T., S. Teshima, et al. (1993). "Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma." Clinical & Experimental Allergy 23(11):9r9-2s. Kristjansson, S., T. Shimizu, et al. (1994). "Eosinophil cationic protein, myeloperoxidase and tryptase in children with asthma and atopic dermatitis." Pediatric Allergy & Immunology 5(4): 223-9. Kristjanssotr, S., I. L. Strannegard, et al. (1996). "Urinary eosinophil protein X in children with atopic asthma: a useful marker of antiinflarnmatory treatment." Journal of Allergy & Clinical Immunology 97(6): ll79-87. Kristjanssotr, S., I. L. Strannegard, et al. (1996). "Inflammatory markers in childhood asthma." Annals of Medicine 28(5): 395-9. Kroesbergeil, A., Q. Jobsis, et al. (1999). "Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis." European Respiratory Joumal t4(0:871-5. Kroncke, K. D., K. Fehsel, et al. (1994). "Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9." Biochemical & Biophysical Research Communications 200(2): I 105-10. Krug, N., V. J. Erpenbeck, et al. (2001). "Cytokine profile of bronchoalveolar lavage-derived CD4(+), CD8(+), and gammadelta T cells in people with asthma after segmental allergen challenge." American Journal of Respiratory Cell & Molecular Biology 25(1): r25-3r. 312
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UNIVERSITV OF AUCKI'AND Abstract -
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There was no significant difference
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This is Dedicated: Dedication To th
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New Zealand The Paediatric Departme
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Contents Abstract ........tr Dedica
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6.5.4 The subjects............... .
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XIV
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List of Figures Figure l.l: Top l0
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List of Abbreviations ABPA allergic
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LADA N*N* dimethyl L-arginine LFA1
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t}ryem(eNoS)Typeltrendothelialnifti
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area, some of it has been expanded
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In addition, both of these groups a
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studies conducted throughout the Un
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Video clips of infants with a varie
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the Paediatric Society of New 7*ala
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inhaled anti-cholinergic agents and
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ecommended to monitor asthma at hom
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improvement to 70Vo PEF would have
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Furthermore, investigators have als
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poorer predictor of a diagnosis of
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Bronsky et al. 1998), and a long-te
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SIGN guideline (SIGN 2005) stated "
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In brief, the human airway can be d
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The ability to biopsy has led to st
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small proportion of cells recovered
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methodology of sputum induction and
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et al. 1999; Giannini, Di Franco et
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over a six month treatment prograrn
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There are other studies suggesting
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So is induced sputum in adults and
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asymptomatic patients independent o
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onchial hyper-responsiveness (Reich
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led to research which looked for le
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analyser machines. This thesis pres
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The pollution of the 'great smog of
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adults greater than 65 years (Ostro
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levels compared to those children l
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More recently 'Air Quality Indexes'
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acetylcholine. These were known to
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cyclase does not produce significan
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Garthwaite l99l), and the non adren
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significant complication, this trea
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locus for the enzyme is a susceptib
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NO synthesis and in so doing blocke
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3.1 Chapter 3: The synthesis, react
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BHa = tetrahyrobiopterin, FAD = fla
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(Knowles, McWeeny et al. 1974) and
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more potent at low oxygen tensions
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toxic products such as isoprostanes
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Figure 3.3: The nitric oxide syntha
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providing NO as a neurotransmitter
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The enzyme of this second pathway -
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inappropriate production from comme
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Nicotinamide adenosine dinucleotide
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enzyme and are competitively revers
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4.1 Introduction Chapter 4: Methods
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4.4 Nitrite and nitrate The measure
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insensitive (Braker and Mossman 197
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A group of instruments have been de
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The original group demonstrated tha
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equired it. For example, there was
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helium for 30 minutes to remove Oz.
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(Postlethwait and Bidani 1990; Post
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is set at 5ppm (AIHA 1966) based on
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5.1 Chapter 5: Methodological asses
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wanted to compare the patterns of e
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in different colours that became th
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an advisor for this work and main s
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Delay time: the time between turnin
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led to an increased water content t
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Chapter 6: Methodological studies o
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pulmonary circulation appeared to c
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al found levels of 10.3ppb compared
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Authors and Pap€r Sublect numbers
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only those measured by mouth or low
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6. Check that the pens work. Fill w
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keys but it is currently in the mid
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Calibration pressures: the test por
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T-piece: tO The first figure shows
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the rotameter. Tracings of each par
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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subjects with respiratory disease,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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had last used her p2 agonist inhale
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higher level of exhaled NO at 4.9pp
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9.1 Introduction Chapter 9: Exhaled
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For the oral measurements options i
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Table 9.1: The recommended standard
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taken from the available literature
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compartment correlated with the ser
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measurement with variable expirator
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to settle. We may have been measuri
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9.5 Off-line measurement NO determi
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(Hyde, Geigel et al. 1997; Tsoukias
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9.6 Nasal nitric oxide measurement
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measured over two 24 hour periods,
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women who coincidently experienced
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While these cross-sectional and the
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symptoms. Steroid response was sign
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'difficult asthma' also had higher
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season and then reduced down to bas
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of cross sectional studies with a t
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Ciabattoni et al. 2004; Petersen, A
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FEV9.5, symptom score and airways r
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Indomethacin - This medication alte
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89Vo for PCD, and above that exclud
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This low NO occurs despite higher t
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patients were followed through one
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differences noted based on filter,
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9.L6 Nitric oxide levels in exercis
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another study of 111 school childre
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Almost all studies used sedation, w
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peak exhaled NO production in the f
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flow and to minimize nasal contamin
Page 283 and 284: ecruit blood vessels in the lung. S
Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291 and 292: o Cass Byrnes & Nicky Holt. "Drugs
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: Appendix 2: Questionnaire for enrol
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: Archer, S. L., P. J. Shultz, et al.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319 and 320: Frey, U., J. Stocks, et al. (2000).
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333: Kercsmar, C. M. (2006). Wheezing in
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
Page 341 and 342: Lymar, S. V. and J. K. Hurst (1996)
Page 343 and 344: Massaro, A. F., S. Mehta, et al. (1
Page 345 and 346: Miyabara, Y., R. Yanagisawa, et al.
Page 347 and 348: contribute to impaired endothelium-
Page 349 and 350: ODell, T. J., R. D. Hawkins, et al.
Page 351 and 352: Panza, J. A., C. E. Garcia, et al.
Page 353 and 354: Peters, S. P. (2006). "Safety of in
Page 355 and 356: Prieto, L., L. Bruno, et al. (2003)
Page 357 and 358: Ribbons, K. A., X. J. Zhang, et al.
Page 359 and 360: Sacco, O., R. Sale, et al. (2003).
Page 361 and 362: Sessa, W. C., K. Pritchard, et al.
Page 363 and 364: Silvestri, M., F. Sabatini, et al.
Page 365 and 366: Stamler, J. S. (1994). "Redox signa
Page 367 and 368: Stuehr, D. J., N. S. Kwon, et al. (
Page 369 and 370: Tierney, W. M., J. F. Roesner, et a
Page 371 and 372: Upchurch, G. R., G. N. Welch, et al
Page 373 and 374: Wadsworth, R., E. Stankevicius, et
Page 375 and 376: Williams, O., R. Y. Bhat, et al. (2
Page 377 and 378: Yates, D. H., S. A. Kharitonov, et
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