Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-63 |
Sentence |
denotes |
Protective Role of Eosinophils and TNFa after Ozone Inhalation. |
T2 |
64-77 |
Sentence |
denotes |
Introduction: |
T3 |
78-125 |
Sentence |
denotes |
Exposure to ozone induces deleterious responses |
T4 |
126-174 |
Sentence |
denotes |
in the airways that include shortness of breath, |
T5 |
175-213 |
Sentence |
denotes |
inflammation, and bronchoconstriction. |
T6 |
214-220 |
Sentence |
denotes |
People |
T7 |
221-269 |
Sentence |
denotes |
with asthma have increased airway sensitivity to |
T8 |
270-296 |
Sentence |
denotes |
ozone and other irritants. |
T9 |
297-318 |
Sentence |
denotes |
Dr. Allison Fryer and |
T10 |
319-369 |
Sentence |
denotes |
colleagues addressed how exposure to ozone affects |
T11 |
370-411 |
Sentence |
denotes |
the immune and physiological responses in |
T12 |
412-424 |
Sentence |
denotes |
guinea pigs. |
T13 |
425-460 |
Sentence |
denotes |
Guinea pigs are considered a useful |
T14 |
461-518 |
Sentence |
denotes |
animal model for studies of respiratory and physiological |
T15 |
519-557 |
Sentence |
denotes |
responses in humans; their response to |
T16 |
558-609 |
Sentence |
denotes |
airborne allergens is similar to that in humans and |
T17 |
610-650 |
Sentence |
denotes |
shares some features of allergic asthma. |
T18 |
651-695 |
Sentence |
denotes |
Fryer and colleagues had previously observed |
T19 |
696-744 |
Sentence |
denotes |
that within 24 hours of exposure, ozone not only |
T20 |
745-792 |
Sentence |
denotes |
induced bronchoconstriction but also stimulated |
T21 |
793-840 |
Sentence |
denotes |
the production of new cells in the bone marrow, |
T22 |
841-877 |
Sentence |
denotes |
where all white blood cells develop. |
T23 |
878-889 |
Sentence |
denotes |
As a result |
T24 |
890-935 |
Sentence |
denotes |
of ozone exposure, increased numbers of newly |
T25 |
936-992 |
Sentence |
denotes |
synthesized white blood cells, particularly eosinophils, |
T26 |
993-1024 |
Sentence |
denotes |
moved into the blood and lungs. |
T27 |
1025-1072 |
Sentence |
denotes |
The central hypothesis of the current study was |
T28 |
1073-1120 |
Sentence |
denotes |
that newly synthesized eosinophils recruited to |
T29 |
1121-1174 |
Sentence |
denotes |
the lungs 3 days after ozone exposure were beneficial |
T30 |
1175-1223 |
Sentence |
denotes |
to the animals because they reduced ozoneinduced |
T31 |
1224-1244 |
Sentence |
denotes |
bronchoconstriction. |
T32 |
1245-1262 |
Sentence |
denotes |
The investigators |
T33 |
1263-1312 |
Sentence |
denotes |
also hypothesized that the beneficial effect seen |
T34 |
1313-1366 |
Sentence |
denotes |
in normal (nonsensitized) animals was lost in animals |
T35 |
1367-1417 |
Sentence |
denotes |
that had been injected with an allergen, ovalbumin |
T36 |
1418-1431 |
Sentence |
denotes |
(sensitized). |
T37 |
1432-1460 |
Sentence |
denotes |
They also planned to explore |
T38 |
1461-1522 |
Sentence |
denotes |
the effects of inhibitors of certain cytokines (cellsignaling |
T39 |
1523-1534 |
Sentence |
denotes |
molecules). |
T40 |
1535-1577 |
Sentence |
denotes |
Immune responses in sensitized animals are |
T41 |
1578-1628 |
Sentence |
denotes |
dominated by a Th2 pattern, which is characterized |
T42 |
1629-1671 |
Sentence |
denotes |
by the synthesis of cytokines (interleukin |
T43 |
1672-1723 |
Sentence |
denotes |
[IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+ |
T44 |
1724-1780 |
Sentence |
denotes |
T lymphocytes and the cells they activate (predominantly |
T45 |
1781-1816 |
Sentence |
denotes |
eosinophils, and B lymphocytes that |
T46 |
1817-1858 |
Sentence |
denotes |
switch to making immunoglobulin E [IgE]). |
T47 |
1859-1864 |
Sentence |
denotes |
Thus, |
T48 |
1865-1916 |
Sentence |
denotes |
sensitized animals were used as a model of allergic |
T49 |
1917-1958 |
Sentence |
denotes |
humans, whose immune responses tend to be |
T50 |
1959-1976 |
Sentence |
denotes |
dominated by IgE. |
T51 |
1977-1986 |
Sentence |
denotes |
Approach: |
T52 |
1987-2037 |
Sentence |
denotes |
Fryer and colleagues exposed normal and sensitized |
T53 |
2038-2087 |
Sentence |
denotes |
(allergic) guinea pigs to 2 ppm ozone or filtered |
T54 |
2088-2132 |
Sentence |
denotes |
air for 4 hours and measured changes in cell |
T55 |
2133-2180 |
Sentence |
denotes |
numbers and airway responses 1 or 3 days later. |
T56 |
2181-2230 |
Sentence |
denotes |
They counted the numbers of eosinophils and other |
T57 |
2231-2279 |
Sentence |
denotes |
white blood cells (macrophages, neutrophils, and |
T58 |
2280-2335 |
Sentence |
denotes |
lymphocytes) in bone marrow, blood, and bronchoalveolar |
T59 |
2336-2354 |
Sentence |
denotes |
lung lavage fluid. |
T60 |
2355-2372 |
Sentence |
denotes |
The investigators |
T61 |
2373-2421 |
Sentence |
denotes |
also measured important physiological responses, |
T62 |
2422-2452 |
Sentence |
denotes |
including bronchoconstriction. |
T63 |
2453-2470 |
Sentence |
denotes |
Some animals were |
T64 |
2471-2523 |
Sentence |
denotes |
pretreated with etanercept and monoclonal anti-IL-5, |
T65 |
2524-2576 |
Sentence |
denotes |
which block tumor necrosis factor-a (TNFa) and IL-5, |
T66 |
2577-2590 |
Sentence |
denotes |
respectively. |
T67 |
2591-2628 |
Sentence |
denotes |
TNFa and IL-5 blockers have been used |
T68 |
2629-2659 |
Sentence |
denotes |
to treat patients with asthma. |
T69 |
2660-2717 |
Sentence |
denotes |
A key feature of the study was a technique to distinguish |
T70 |
2718-2764 |
Sentence |
denotes |
which white blood cells were synthesized after |
T71 |
2765-2819 |
Sentence |
denotes |
exposure from those that already existed, by injecting |
T72 |
2820-2858 |
Sentence |
denotes |
animals with bromodeoxyuridine (BrdU). |
T73 |
2859-2863 |
Sentence |
denotes |
BrdU |
T74 |
2864-2917 |
Sentence |
denotes |
is a thymidine analogue that is incorporated into the |
T75 |
2918-2969 |
Sentence |
denotes |
DNA of dividing cells, serving as a marker of newly |
T76 |
2970-2985 |
Sentence |
denotes |
produced cells. |
T77 |
2986-3023 |
Sentence |
denotes |
Therefore, a snapshot can be obtained |
T78 |
3024-3078 |
Sentence |
denotes |
of the proportion of newly synthesized (BrdU-positive) |
T79 |
3079-3126 |
Sentence |
denotes |
versus pre-existing (BrdU-negative) cell types. |
T80 |
3127-3139 |
Sentence |
denotes |
Key results: |
T81 |
3140-3142 |
Sentence |
denotes |
1. |
T82 |
3143-3191 |
Sentence |
denotes |
Allergic and normal animals differed in the time |
T83 |
3192-3241 |
Sentence |
denotes |
course of bronchoconstriction and changes in cell |
T84 |
3242-3269 |
Sentence |
denotes |
types after ozone exposure. |
T85 |
3270-3288 |
Sentence |
denotes |
In normal animals, |
T86 |
3289-3335 |
Sentence |
denotes |
bronchoconstriction increased substantially at |
T87 |
3336-3386 |
Sentence |
denotes |
day 1 but decreased by day 3 after ozone exposure. |
T88 |
3387-3439 |
Sentence |
denotes |
In contrast, in allergic animals bronchoconstriction |
T89 |
3440-3463 |
Sentence |
denotes |
remained high at day 3. |
T90 |
3464-3484 |
Sentence |
denotes |
Ozone also increased |
T91 |
3485-3522 |
Sentence |
denotes |
the percentage of newly formed, BrdU2 |
T92 |
3523-3566 |
Sentence |
denotes |
positive eosinophils in the bone marrow and |
T93 |
3567-3608 |
Sentence |
denotes |
lungs of normal but not allergic animals. |
T94 |
3609-3611 |
Sentence |
denotes |
2. |
T95 |
3612-3657 |
Sentence |
denotes |
Pretreatment with the TNFa blocker etanercept |
T96 |
3658-3701 |
Sentence |
denotes |
had complex effects, which differed between |
T97 |
3702-3730 |
Sentence |
denotes |
normal and allergic animals. |
T98 |
3731-3749 |
Sentence |
denotes |
In normal animals, |
T99 |
3750-3798 |
Sentence |
denotes |
etanercept decreased ozone-induced new synthesis |
T100 |
3799-3836 |
Sentence |
denotes |
of eosinophils in the bone marrow and |
T101 |
3837-3886 |
Sentence |
denotes |
blocked eosinophil migration to the lung; it also |
T102 |
3887-3935 |
Sentence |
denotes |
increased bronchoconstriction at day 3 (relative |
T103 |
3936-3965 |
Sentence |
denotes |
to day 1 without etanercept). |
T104 |
3966-3986 |
Sentence |
denotes |
In allergic animals, |
T105 |
3987-4035 |
Sentence |
denotes |
etanercept had no effect on any cell type in the |
T106 |
4036-4083 |
Sentence |
denotes |
bone marrow or lung after exposure to ozone and |
T107 |
4084-4127 |
Sentence |
denotes |
did not change bronchoconstriction compared |
T108 |
4128-4178 |
Sentence |
denotes |
with allergic animals not treated with etanercept. |
T109 |
4179-4223 |
Sentence |
denotes |
Etanercept tended to increase the numbers of |
T110 |
4224-4267 |
Sentence |
denotes |
blood monocytes and lymphocytes in air- and |
T111 |
4268-4312 |
Sentence |
denotes |
ozone-exposed normal and allergic animals at |
T112 |
4313-4361 |
Sentence |
denotes |
day 3, but had no effect on eosinophils in blood |
T113 |
4362-4381 |
Sentence |
denotes |
at this time point. |
T114 |
4382-4419 |
Sentence |
denotes |
This was one of the few statistically |
T115 |
4420-4464 |
Sentence |
denotes |
significant findings in the blood of exposed |
T116 |
4465-4486 |
Sentence |
denotes |
animals in the study. |
T117 |
4487-4489 |
Sentence |
denotes |
3. |
T118 |
4490-4542 |
Sentence |
denotes |
Anti-IL-5 reduced bronchoconstriction at day 3 after |
T119 |
4543-4581 |
Sentence |
denotes |
exposure of allergic animals to ozone. |
T120 |
4582-4594 |
Sentence |
denotes |
In contrast, |
T121 |
4595-4636 |
Sentence |
denotes |
bronchoconstriction was greatly increased |
T122 |
4637-4678 |
Sentence |
denotes |
in normal animals treated with anti-IL-5. |
T123 |
4679-4691 |
Sentence |
denotes |
Conclusions: |
T124 |
4692-4745 |
Sentence |
denotes |
Fryer and colleagues explored the airway and cellular |
T125 |
4746-4788 |
Sentence |
denotes |
responses in guinea pigs exposed to ozone. |
T126 |
4789-4792 |
Sentence |
denotes |
The |
T127 |
4793-4845 |
Sentence |
denotes |
HEI Review Committee, which conducted an independent |
T128 |
4846-4891 |
Sentence |
denotes |
review of the study, agreed that the findings |
T129 |
4892-4943 |
Sentence |
denotes |
supported the authors’ hypothesis (1) that exposure |
T130 |
4944-4997 |
Sentence |
denotes |
to ozone stimulates production of eosinophils in bone |
T131 |
4998-5053 |
Sentence |
denotes |
marrow, (2) that these newly formed eosinophils migrate |
T132 |
5054-5103 |
Sentence |
denotes |
to the lungs, and (3) that those eosinophils play |
T133 |
5104-5157 |
Sentence |
denotes |
a delayed but potentially beneficial role in reducing |
T134 |
5158-5210 |
Sentence |
denotes |
ozone-induced inflammation in the airways of healthy |
T135 |
5211-5266 |
Sentence |
denotes |
normal animals, but not in allergen-sensitized animals. |
T136 |
5267-5309 |
Sentence |
denotes |
The Committee also agreed that guinea pigs |
T137 |
5310-5366 |
Sentence |
denotes |
were a good model for studying responses to an allergen, |
T138 |
5367-5410 |
Sentence |
denotes |
because a major subtype of asthma (the high |
T139 |
5411-5466 |
Sentence |
denotes |
Th2 or allergic type) is associated with high levels of |
T140 |
5467-5492 |
Sentence |
denotes |
eosinophils in the blood. |
T141 |
5493-5545 |
Sentence |
denotes |
A novel finding was that the TNFa blocker etanercept |
T142 |
5546-5594 |
Sentence |
denotes |
decreased ozone-induced formation of eosinophils |
T143 |
5595-5636 |
Sentence |
denotes |
in the bone marrow and blocked eosinophil |
T144 |
5637-5677 |
Sentence |
denotes |
migration to the lung in normal animals. |
T145 |
5678-5686 |
Sentence |
denotes |
However, |
T146 |
5687-5748 |
Sentence |
denotes |
because injecting etanercept had little effect on eosinophils |
T147 |
5749-5792 |
Sentence |
denotes |
and did not decrease bronchoconstriction in |
T148 |
5793-5850 |
Sentence |
denotes |
allergic guinea pigs, the potential for treating patients |
T149 |
5851-5904 |
Sentence |
denotes |
with allergic asthma with TNFa blockers is uncertain. |
T150 |
5905-5957 |
Sentence |
denotes |
This is consistent with the poor performance of TNFa |
T151 |
5958-6007 |
Sentence |
denotes |
blockers in clinical studies of asthma treatment. |
T152 |
6008-6061 |
Sentence |
denotes |
Blocking the cytokine IL-5 with an anti-IL-5 antibody |
T153 |
6062-6108 |
Sentence |
denotes |
substantially decreased bronchoconstriction in |
T154 |
6109-6128 |
Sentence |
denotes |
sensitized animals. |
T155 |
6129-6167 |
Sentence |
denotes |
This suggests that therapies targeting |
T156 |
6168-6213 |
Sentence |
denotes |
IL-5 and eosinophils would be promising in at |
T157 |
6214-6241 |
Sentence |
denotes |
least some types of asthma. |
T158 |
6242-6265 |
Sentence |
denotes |
The Committee expressed |
T159 |
6266-6316 |
Sentence |
denotes |
caution toward experiments with cytokine blockers, |
T160 |
6317-6363 |
Sentence |
denotes |
both in animal models and humans, because such |
T161 |
6364-6421 |
Sentence |
denotes |
blockers are often not specific to a particular cell type |
T162 |
6422-6468 |
Sentence |
denotes |
and may differ at different sites in the body. |
T163 |
6469-6476 |
Sentence |
denotes |
Without |
T164 |
6477-6528 |
Sentence |
denotes |
further detailed confirmation of the effects of the |
T165 |
6529-6589 |
Sentence |
denotes |
blockers, interpreting these experiments can be challenging. |
T166 |
6590-6637 |
Sentence |
denotes |
The Committee concluded that the study by Fryer |
T167 |
6638-6693 |
Sentence |
denotes |
and colleagues raises several intriguing directions for |
T168 |
6694-6744 |
Sentence |
denotes |
future research, including exploring ways in which |
T169 |
6745-6794 |
Sentence |
denotes |
newly formed eosinophils differ from pre-existing |
T170 |
6795-6843 |
Sentence |
denotes |
ones, and how such findings apply to humans with |
T171 |
6844-6862 |
Sentence |
denotes |
allergy or asthma. |
T1 |
0-63 |
Sentence |
denotes |
Protective Role of Eosinophils and TNFa after Ozone Inhalation. |
T2 |
64-77 |
Sentence |
denotes |
Introduction: |
T3 |
78-125 |
Sentence |
denotes |
Exposure to ozone induces deleterious responses |
T4 |
126-174 |
Sentence |
denotes |
in the airways that include shortness of breath, |
T5 |
175-213 |
Sentence |
denotes |
inflammation, and bronchoconstriction. |
T6 |
214-220 |
Sentence |
denotes |
People |
T7 |
221-269 |
Sentence |
denotes |
with asthma have increased airway sensitivity to |
T8 |
270-296 |
Sentence |
denotes |
ozone and other irritants. |
T9 |
297-318 |
Sentence |
denotes |
Dr. Allison Fryer and |
T10 |
319-369 |
Sentence |
denotes |
colleagues addressed how exposure to ozone affects |
T11 |
370-411 |
Sentence |
denotes |
the immune and physiological responses in |
T12 |
412-424 |
Sentence |
denotes |
guinea pigs. |
T13 |
425-460 |
Sentence |
denotes |
Guinea pigs are considered a useful |
T14 |
461-518 |
Sentence |
denotes |
animal model for studies of respiratory and physiological |
T15 |
519-557 |
Sentence |
denotes |
responses in humans; their response to |
T16 |
558-609 |
Sentence |
denotes |
airborne allergens is similar to that in humans and |
T17 |
610-650 |
Sentence |
denotes |
shares some features of allergic asthma. |
T18 |
651-695 |
Sentence |
denotes |
Fryer and colleagues had previously observed |
T19 |
696-744 |
Sentence |
denotes |
that within 24 hours of exposure, ozone not only |
T20 |
745-792 |
Sentence |
denotes |
induced bronchoconstriction but also stimulated |
T21 |
793-840 |
Sentence |
denotes |
the production of new cells in the bone marrow, |
T22 |
841-877 |
Sentence |
denotes |
where all white blood cells develop. |
T23 |
878-889 |
Sentence |
denotes |
As a result |
T24 |
890-935 |
Sentence |
denotes |
of ozone exposure, increased numbers of newly |
T25 |
936-992 |
Sentence |
denotes |
synthesized white blood cells, particularly eosinophils, |
T26 |
993-1024 |
Sentence |
denotes |
moved into the blood and lungs. |
T27 |
1025-1072 |
Sentence |
denotes |
The central hypothesis of the current study was |
T28 |
1073-1120 |
Sentence |
denotes |
that newly synthesized eosinophils recruited to |
T29 |
1121-1174 |
Sentence |
denotes |
the lungs 3 days after ozone exposure were beneficial |
T30 |
1175-1223 |
Sentence |
denotes |
to the animals because they reduced ozoneinduced |
T31 |
1224-1244 |
Sentence |
denotes |
bronchoconstriction. |
T32 |
1245-1262 |
Sentence |
denotes |
The investigators |
T33 |
1263-1312 |
Sentence |
denotes |
also hypothesized that the beneficial effect seen |
T34 |
1313-1366 |
Sentence |
denotes |
in normal (nonsensitized) animals was lost in animals |
T35 |
1367-1417 |
Sentence |
denotes |
that had been injected with an allergen, ovalbumin |
T36 |
1418-1431 |
Sentence |
denotes |
(sensitized). |
T37 |
1432-1460 |
Sentence |
denotes |
They also planned to explore |
T38 |
1461-1522 |
Sentence |
denotes |
the effects of inhibitors of certain cytokines (cellsignaling |
T39 |
1523-1534 |
Sentence |
denotes |
molecules). |
T40 |
1535-1577 |
Sentence |
denotes |
Immune responses in sensitized animals are |
T41 |
1578-1628 |
Sentence |
denotes |
dominated by a Th2 pattern, which is characterized |
T42 |
1629-1671 |
Sentence |
denotes |
by the synthesis of cytokines (interleukin |
T43 |
1672-1723 |
Sentence |
denotes |
[IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+ |
T44 |
1724-1780 |
Sentence |
denotes |
T lymphocytes and the cells they activate (predominantly |
T45 |
1781-1816 |
Sentence |
denotes |
eosinophils, and B lymphocytes that |
T46 |
1817-1858 |
Sentence |
denotes |
switch to making immunoglobulin E [IgE]). |
T47 |
1859-1864 |
Sentence |
denotes |
Thus, |
T48 |
1865-1916 |
Sentence |
denotes |
sensitized animals were used as a model of allergic |
T49 |
1917-1958 |
Sentence |
denotes |
humans, whose immune responses tend to be |
T50 |
1959-1976 |
Sentence |
denotes |
dominated by IgE. |
T51 |
1977-1986 |
Sentence |
denotes |
Approach: |
T52 |
1987-2037 |
Sentence |
denotes |
Fryer and colleagues exposed normal and sensitized |
T53 |
2038-2087 |
Sentence |
denotes |
(allergic) guinea pigs to 2 ppm ozone or filtered |
T54 |
2088-2132 |
Sentence |
denotes |
air for 4 hours and measured changes in cell |
T55 |
2133-2180 |
Sentence |
denotes |
numbers and airway responses 1 or 3 days later. |
T56 |
2181-2230 |
Sentence |
denotes |
They counted the numbers of eosinophils and other |
T57 |
2231-2279 |
Sentence |
denotes |
white blood cells (macrophages, neutrophils, and |
T58 |
2280-2335 |
Sentence |
denotes |
lymphocytes) in bone marrow, blood, and bronchoalveolar |
T59 |
2336-2354 |
Sentence |
denotes |
lung lavage fluid. |
T60 |
2355-2372 |
Sentence |
denotes |
The investigators |
T61 |
2373-2421 |
Sentence |
denotes |
also measured important physiological responses, |
T62 |
2422-2452 |
Sentence |
denotes |
including bronchoconstriction. |
T63 |
2453-2470 |
Sentence |
denotes |
Some animals were |
T64 |
2471-2523 |
Sentence |
denotes |
pretreated with etanercept and monoclonal anti-IL-5, |
T65 |
2524-2576 |
Sentence |
denotes |
which block tumor necrosis factor-a (TNFa) and IL-5, |
T66 |
2577-2590 |
Sentence |
denotes |
respectively. |
T67 |
2591-2628 |
Sentence |
denotes |
TNFa and IL-5 blockers have been used |
T68 |
2629-2659 |
Sentence |
denotes |
to treat patients with asthma. |
T69 |
2660-2717 |
Sentence |
denotes |
A key feature of the study was a technique to distinguish |
T70 |
2718-2764 |
Sentence |
denotes |
which white blood cells were synthesized after |
T71 |
2765-2819 |
Sentence |
denotes |
exposure from those that already existed, by injecting |
T72 |
2820-2858 |
Sentence |
denotes |
animals with bromodeoxyuridine (BrdU). |
T73 |
2859-2863 |
Sentence |
denotes |
BrdU |
T74 |
2864-2917 |
Sentence |
denotes |
is a thymidine analogue that is incorporated into the |
T75 |
2918-2969 |
Sentence |
denotes |
DNA of dividing cells, serving as a marker of newly |
T76 |
2970-2985 |
Sentence |
denotes |
produced cells. |
T77 |
2986-3023 |
Sentence |
denotes |
Therefore, a snapshot can be obtained |
T78 |
3024-3078 |
Sentence |
denotes |
of the proportion of newly synthesized (BrdU-positive) |
T79 |
3079-3126 |
Sentence |
denotes |
versus pre-existing (BrdU-negative) cell types. |
T80 |
3127-3139 |
Sentence |
denotes |
Key results: |
T81 |
3140-3142 |
Sentence |
denotes |
1. |
T82 |
3143-3191 |
Sentence |
denotes |
Allergic and normal animals differed in the time |
T83 |
3192-3241 |
Sentence |
denotes |
course of bronchoconstriction and changes in cell |
T84 |
3242-3269 |
Sentence |
denotes |
types after ozone exposure. |
T85 |
3270-3288 |
Sentence |
denotes |
In normal animals, |
T86 |
3289-3335 |
Sentence |
denotes |
bronchoconstriction increased substantially at |
T87 |
3336-3386 |
Sentence |
denotes |
day 1 but decreased by day 3 after ozone exposure. |
T88 |
3387-3439 |
Sentence |
denotes |
In contrast, in allergic animals bronchoconstriction |
T89 |
3440-3463 |
Sentence |
denotes |
remained high at day 3. |
T90 |
3464-3484 |
Sentence |
denotes |
Ozone also increased |
T91 |
3485-3522 |
Sentence |
denotes |
the percentage of newly formed, BrdU2 |
T92 |
3523-3566 |
Sentence |
denotes |
positive eosinophils in the bone marrow and |
T93 |
3567-3608 |
Sentence |
denotes |
lungs of normal but not allergic animals. |
T94 |
3609-3611 |
Sentence |
denotes |
2. |
T95 |
3612-3657 |
Sentence |
denotes |
Pretreatment with the TNFa blocker etanercept |
T96 |
3658-3701 |
Sentence |
denotes |
had complex effects, which differed between |
T97 |
3702-3730 |
Sentence |
denotes |
normal and allergic animals. |
T98 |
3731-3749 |
Sentence |
denotes |
In normal animals, |
T99 |
3750-3798 |
Sentence |
denotes |
etanercept decreased ozone-induced new synthesis |
T100 |
3799-3836 |
Sentence |
denotes |
of eosinophils in the bone marrow and |
T101 |
3837-3886 |
Sentence |
denotes |
blocked eosinophil migration to the lung; it also |
T102 |
3887-3935 |
Sentence |
denotes |
increased bronchoconstriction at day 3 (relative |
T103 |
3936-3965 |
Sentence |
denotes |
to day 1 without etanercept). |
T104 |
3966-3986 |
Sentence |
denotes |
In allergic animals, |
T105 |
3987-4035 |
Sentence |
denotes |
etanercept had no effect on any cell type in the |
T106 |
4036-4083 |
Sentence |
denotes |
bone marrow or lung after exposure to ozone and |
T107 |
4084-4127 |
Sentence |
denotes |
did not change bronchoconstriction compared |
T108 |
4128-4178 |
Sentence |
denotes |
with allergic animals not treated with etanercept. |
T109 |
4179-4223 |
Sentence |
denotes |
Etanercept tended to increase the numbers of |
T110 |
4224-4267 |
Sentence |
denotes |
blood monocytes and lymphocytes in air- and |
T111 |
4268-4312 |
Sentence |
denotes |
ozone-exposed normal and allergic animals at |
T112 |
4313-4361 |
Sentence |
denotes |
day 3, but had no effect on eosinophils in blood |
T113 |
4362-4381 |
Sentence |
denotes |
at this time point. |
T114 |
4382-4419 |
Sentence |
denotes |
This was one of the few statistically |
T115 |
4420-4464 |
Sentence |
denotes |
significant findings in the blood of exposed |
T116 |
4465-4486 |
Sentence |
denotes |
animals in the study. |
T117 |
4487-4489 |
Sentence |
denotes |
3. |
T118 |
4490-4542 |
Sentence |
denotes |
Anti-IL-5 reduced bronchoconstriction at day 3 after |
T119 |
4543-4581 |
Sentence |
denotes |
exposure of allergic animals to ozone. |
T120 |
4582-4594 |
Sentence |
denotes |
In contrast, |
T121 |
4595-4636 |
Sentence |
denotes |
bronchoconstriction was greatly increased |
T122 |
4637-4678 |
Sentence |
denotes |
in normal animals treated with anti-IL-5. |
T123 |
4679-4691 |
Sentence |
denotes |
Conclusions: |
T124 |
4692-4745 |
Sentence |
denotes |
Fryer and colleagues explored the airway and cellular |
T125 |
4746-4788 |
Sentence |
denotes |
responses in guinea pigs exposed to ozone. |
T126 |
4789-4792 |
Sentence |
denotes |
The |
T127 |
4793-4845 |
Sentence |
denotes |
HEI Review Committee, which conducted an independent |
T128 |
4846-4891 |
Sentence |
denotes |
review of the study, agreed that the findings |
T129 |
4892-4943 |
Sentence |
denotes |
supported the authors’ hypothesis (1) that exposure |
T130 |
4944-4997 |
Sentence |
denotes |
to ozone stimulates production of eosinophils in bone |
T131 |
4998-5053 |
Sentence |
denotes |
marrow, (2) that these newly formed eosinophils migrate |
T132 |
5054-5103 |
Sentence |
denotes |
to the lungs, and (3) that those eosinophils play |
T133 |
5104-5157 |
Sentence |
denotes |
a delayed but potentially beneficial role in reducing |
T134 |
5158-5210 |
Sentence |
denotes |
ozone-induced inflammation in the airways of healthy |
T135 |
5211-5266 |
Sentence |
denotes |
normal animals, but not in allergen-sensitized animals. |
T136 |
5267-5309 |
Sentence |
denotes |
The Committee also agreed that guinea pigs |
T137 |
5310-5366 |
Sentence |
denotes |
were a good model for studying responses to an allergen, |
T138 |
5367-5410 |
Sentence |
denotes |
because a major subtype of asthma (the high |
T139 |
5411-5466 |
Sentence |
denotes |
Th2 or allergic type) is associated with high levels of |
T140 |
5467-5492 |
Sentence |
denotes |
eosinophils in the blood. |
T141 |
5493-5545 |
Sentence |
denotes |
A novel finding was that the TNFa blocker etanercept |
T142 |
5546-5594 |
Sentence |
denotes |
decreased ozone-induced formation of eosinophils |
T143 |
5595-5636 |
Sentence |
denotes |
in the bone marrow and blocked eosinophil |
T144 |
5637-5677 |
Sentence |
denotes |
migration to the lung in normal animals. |
T145 |
5678-5686 |
Sentence |
denotes |
However, |
T146 |
5687-5748 |
Sentence |
denotes |
because injecting etanercept had little effect on eosinophils |
T147 |
5749-5792 |
Sentence |
denotes |
and did not decrease bronchoconstriction in |
T148 |
5793-5850 |
Sentence |
denotes |
allergic guinea pigs, the potential for treating patients |
T149 |
5851-5904 |
Sentence |
denotes |
with allergic asthma with TNFa blockers is uncertain. |
T150 |
5905-5957 |
Sentence |
denotes |
This is consistent with the poor performance of TNFa |
T151 |
5958-6007 |
Sentence |
denotes |
blockers in clinical studies of asthma treatment. |
T152 |
6008-6061 |
Sentence |
denotes |
Blocking the cytokine IL-5 with an anti-IL-5 antibody |
T153 |
6062-6108 |
Sentence |
denotes |
substantially decreased bronchoconstriction in |
T154 |
6109-6128 |
Sentence |
denotes |
sensitized animals. |
T155 |
6129-6167 |
Sentence |
denotes |
This suggests that therapies targeting |
T156 |
6168-6213 |
Sentence |
denotes |
IL-5 and eosinophils would be promising in at |
T157 |
6214-6241 |
Sentence |
denotes |
least some types of asthma. |
T158 |
6242-6265 |
Sentence |
denotes |
The Committee expressed |
T159 |
6266-6316 |
Sentence |
denotes |
caution toward experiments with cytokine blockers, |
T160 |
6317-6363 |
Sentence |
denotes |
both in animal models and humans, because such |
T161 |
6364-6421 |
Sentence |
denotes |
blockers are often not specific to a particular cell type |
T162 |
6422-6468 |
Sentence |
denotes |
and may differ at different sites in the body. |
T163 |
6469-6476 |
Sentence |
denotes |
Without |
T164 |
6477-6528 |
Sentence |
denotes |
further detailed confirmation of the effects of the |
T165 |
6529-6589 |
Sentence |
denotes |
blockers, interpreting these experiments can be challenging. |
T166 |
6590-6637 |
Sentence |
denotes |
The Committee concluded that the study by Fryer |
T167 |
6638-6693 |
Sentence |
denotes |
and colleagues raises several intriguing directions for |
T168 |
6694-6744 |
Sentence |
denotes |
future research, including exploring ways in which |
T169 |
6745-6794 |
Sentence |
denotes |
newly formed eosinophils differ from pre-existing |
T170 |
6795-6843 |
Sentence |
denotes |
ones, and how such findings apply to humans with |
T171 |
6844-6862 |
Sentence |
denotes |
allergy or asthma. |