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[(index)-331.9(of)-335.1(nasal)-334.7(\(hyper\)respon)10.1(siveness.)]TJ 0.999 -1.0559 TD [(The)-412.5(hyperrespon)11(siveness)-417.3(to)-411(histamine)-410.7(gradually)-414.4(developed)-416.5(with)-407.9(repeated)-404.1(pollen)]TJ -0.999 -1.0496 TD [(inhalation)-384.5(challenge,)-378.9(and)-381.3(the)-377.2(airway)-381.8(r)13.4(esponse)-381.2(at)-379.3(the)-383.5(20th)-376.9(and)-381.3(24th)-376.9(challenges)-383(was)]TJ 0 -1.0559 TD [(three)-293.5(to)-297.1(four)-288.1(orders)-299.5(of)-303.5(magnitude)-298.2(higher)-305.9(than)-299.6(that)-295.7(in)-303.5(nonsensitized)-305(animals.)-301.5(Similar)]TJ T* [(degree)11.7(s)-348.5(o)0(f)-347.7(hyperr)12.9(esponsiveness)-349.7(wer)11.3(e)-347(observed)-347.7(at)-341.4(10)-346.8(h)-345.9(and)-343.4(2)-347.3(days)-345.5(after)-346.7(a)-340.9(pollen)-346.4(in-)]TJ T* [(halation)-213.8(challenge,)-214.5(but)-211.6(the)-212.8(hyperr)12.9(esponsiveness)-216.9(had)-210.6(almost)-210.6(disappeared)-200.3(by)-212.6(day)-212(7.)-211.1(The)]TJ T* 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[(its)-338.3(detai)-9.4(ls)-335.1(are)-340.4(still)-338.9(unclea)-8.2(r)48.9(.)-330.4(The)-342.6(mechanism)-348(of)-333.2(upper)-341.6(air-)]TJ T* [(way)-234.2(h)-6.5(yperresponsi)-12.2(veness)-241.1(has)-231.5(mai)-8.2(nly)-232.3(been)-237.2(inves)-7.8(tigated)-240.9(in)]TJ 0 -1.0471 TD [(rhiniti)-10.8(s)-280.8(patients)-288.4([3\2616].)-286.2(However)24.2(,)-284.9(owing)-283.3(to)-282.7(the)-283.9(limitati)-12.5(ons)]TJ 0 -1.0528 TD [(of)-230.7(clin)-8.2(ical)-236.2(research)-12.1(,)-228(a)0(n)-235.2(adequate)-237.7(experi)-9.4(mental)-235.2(anim)-9(al)-231.9(mo-)]TJ T* [(del)-295.3(is)-295.3(indispens)-8.7(able)-296.5(for)-295.7(inves)-7.8(tigatin)-9.6(g)-291(the)-295.3(mecha)-8.2(nism)-294.3(that)]TJ T* [(bring)-7.8(s)-332(about)-336.6(the)-340.8(symptom)-339.6(of)-338.9(rhinitis.)]TJ 1.0015 -1.0471 TD 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[(pi)18.9(gs)-429.5(wa)16.9(s)-434.4(e)0(v)15.1(a)0(l)18.5(u)0(a)15.1(t)0(e)18.4(d)-433.3(2)-438.9(d)0(a)15.1(y)0(s)-423.8(a)0(f)13.5(t)13.9(er)-430.3(th)18.9(e)-439.3(2)0(0)21.2(t)0(h)-430.7(a)0(n)20.8(d)-438.9(th)18.9(e)-439.3(2)0(2)21.2(n)0(d)]TJ 0 -1.0471 TD [(ch)15.1(al)18.5(le)18.4(ng)15.5(es)19.6(,)-455.6(r)0(e)19.2(s)0(p)20(e)0(c)14.7(t)0(i)16.5(v)0(e)20.8(l)0(y)81.4(,)-455.6(in)-447.8(co)20.8(mp)18.1(ar)13.5(is)17.7(on)-445.4(wi)14.9(t)13.9(h)-456(th)18.9(at)-448.2(in)-442.1(th)13.2(e)]TJ 0 -1.0528 TD [(no)15.5(ns)20(en)15.1(si)17.7(t)13.9(i)0(z)12.8(e)0(d)-531.2(a)0(n)20.8(i)0(m)15.7(a)0(l)12.8(.)-535.3(Fu)16.3(rt)17.3(he)15.1(rm)16.5(or)19.6(e,)-530.8(th)13.2(e)-541.8(n)0(a)20.8(s)0(a)13.9(l)-538.1(hy)15.5(pe)20.8(rr)18(es)13.9(-)]TJ T* [(po)15.5(ns)20(iv)18.9(en)15.1(es)19.6(s)-218.2(t)0(o)-208.8(h)0(i)18.9(s)0(t)17.7(a)0(m)17.7(i)0(n)18.9(e)-217.4(an)15.1(d)-217(M)0(C)14.6(h)-217(w)12.4(a)0(s)-208(e)0(v)15.1(a)0(l)18.4(u)0(a)15.1(t)0(e)18.4(d)-217(10)-206.4(h)-217(a)0(n)15.1(d)]TJ 0 -1.0471 TD [(2)-291(a)0(n)15.1(d)-291(7)-296.7(d)0(a)20.8(y)0(s)-287.2(a)0(f)19.2(t)0(e)18.4(r)-298.3(th)18.9(e)-291.4(2)0(4)15.5(t)0(h)-282.7(a)0(n)15.1(d)-291(th)18.9(e)-297.1(2)0(6)21.2(t)0(h)-288.4(a)0(n)20.8(t)0(i)16.5(g)0(e)15.1(n)-291(pr)19.6(ov)15.5(oc)15.1(a-)]TJ 0 -1.0528 TD [(ti)16.5(on)21.2(,)-205.2(r)0(e)19.2(s)0(p)20(e)0(c)14.7(t)0(i)16.5(v)0(e)20.8(l)0(y)75.8(.)-199.6(In)-190.9(a)-200.3(s)0(e)13.9(p)0(a)20.8(r)0(a)13.5(t)0(e)-192.1(g)0(r)19.6(o)0(u)15.5(p)-199.9(of)-196.6(se)19.6(ns)20(it)16.5(iz)18.4(ed)-195.4(an)20.8(im)15.7(al)12.8(s,)]TJ 0 -1.0471 TD [(ti)16.5(me)17.7(-r)18(el)12.8(at)18.4(ed)-303.5(ch)15.1(an)20.8(ge)15.1(s)-314.9(i)0(n)-305.5(n)0(a)15.1(s)0(a)19.6(l)-316.1(re)19.2(sp)14.4(on)21.2(si)17.7(ve)15.1(ne)15.1(ss)-305.5(to)-305.5(hi)18.9(st)17.7(am)17.7(in)13.2(e)]TJ 0 -1.0528 TD [(du)15.5(ri)17.3(ng)-473.8(th)18.9(e)-490.6(c)0(o)20.8(u)0(r)13.9(s)0(e)-475.4(o)0(f)-481.1(r)0(e)19.2(p)0(e)15.1(t)0(i)16.5(t)0(i)22.2(v)0(e)-479.9(a)0(n)15.1(t)0(i)16.5(g)0(e)20.8(n)-490.2(i)13.9(n)0(h)15.5(a)0(l)18.4(a)0(t)18.4(i)0(o)13.2(n)-484.5(ch)15.1(al)18.4(-)]TJ 0 -1.0471 TD [(le)18.4(ng)15.5(es)-412.8(we)16.9(re)-413.2(in)18.9(ve)20.8(st)12(i)13.9(g)0(a)15.1(t)0(e)18.4(d)-421.9(us)20(in)13.2(g)-416.2(t)0(h)13.2(e)-422.3(an)20.8(im)15.7(al)18.5(s)-423.1(2)-421.9(da)20.8(ys)-412.4(af)13.5(te)18.4(r)]TJ 0 -1.0527 TD 0.3777 Tc [(t)377.7(h)396.6(er)377.7(e)391.2(s)377.7(p)397.7(e)377.7(c)392.4(t)377.7(i)399.9(v)377.7(e1)377.7(s)397.7(t)377.7(\261)396.6(2)377.7(0)393.2(t)377.7(hp)377.7(o)398.9(l)377.7(l)394.2(e)377.7(nc)377.7(h)398.5(a)377.7(l)396.1(l)377.7(e)390.5(n)377.7(g)398.9(e)377.7(s)391.6(.)-4(T)389.9(h)377.7(ee)377.7(f)408.3(f)377.7(e)396.9(c)377.7(t)390.5(s)0.2(o)377.7(f)]TJ 0 -1.0471 TD 0 Tc [(me)17.7(py)15.5(ra)19.2(mi)15.7(ne)-354.7(\(a)-356.3(hi)18.9(st)17.7(am)17.7(in)18.9(e)-365.4(r)0(e)19.2(c)0(e)14.7(p)0(t)18.9(o)0(r)-355.9(\()0(H)]TJ 7.472 0 0 6.641 207.95 377.688 Tm (1)Tj 9.963 0 0 9.963 211.635 379.332 Tm [(\))-360.9(a)0(n)15.1(t)13.9(ag)15.1(on)15.5(is)17.7(t\))17.3(,)-358.9(a)0(t)18.5(r)0(o)13.9(-)]TJ -15.3929 -1.0527 TD [(pi)18.9(ne)-400.3(\(a)-396.2(ch)15.1(ol)18.9(in)18.9(er)30.6(gi)13.2(c)-405.2(r)0(e)19.2(c)0(e)14.7(p)0(t)18.9(o)0(r)-395.8(a)0(n)15.1(t)0(a)18.4(g)0(o)15.5(n)0(i)18.9(s)0(t)17.7(\))-406.4(an)20.8(d)-410.5(n)0(a)20.8(p)0(h)15.5(a)0(z)20.4(o)0(l)18.9(i)0(n)13.2(e)]TJ 0 -1.0471 TD [(\(a)19.2(n)]TJ /F8 1 Tf 1.6275 0 TD (a)Tj /F3 1 Tf 0.626 0 TD [(-a)19.2(dr)19.6(en)15.1(er)24.9(gi)18.9(c\))-373.4(on)-377.1(na)20.8(sa)19.6(l)-384.4(h)0(y)15.5(p)0(e)20.8(r)0(r)12.4(e)0(s)19.6(p)0(o)15.5(n)0(s)20(i)0(v)18.9(e)0(n)15.1(e)0(s)19.6(s)-383.2(to)-373.8(hi)18.9(st)12(a-)]TJ -2.2535 -1.0528 TD [(mi)15.7(ne)-349.1(we)16.9(re)-350.7(ex)15.1(am)17.7(in)18.9(ed)-349.1(on)-348.7(th)18.9(e)-359.7(2)0(n)15.5(d)-359.3(da)20.8(y)-359.3(a)0(f)19.2(t)0(e)12.8(r)-355.2(th)18.9(e)-359.7(r)0(e)13.5(s)0(p)20(e)0(c)20.4(t)0(i)16.5(v)0(e)]TJ 0 -1.0471 TD [(22)15.5(nd)21.2(,)-250.8(2)0(4)15.5(t)0(h)-242.9(a)0(n)20.8(d)-251.2(26)15.5(th)-242.9(ch)20.8(al)18.4(le)12.8(ng)21.2(es)19.6(.)-250.8(T)0(h)17.1(e)-251.6(po)15.5(ss)18.9(ib)18.9(le)-243.3(pa)15.1(rt)17.3(ic)18.4(ip)18.8(at)18.4(io)13.2(n)]TJ 0 -1.0528 TD [(of)-304.7(na)15.1(sa)19.6(l)-316.1(v)0(a)20.8(s)0(c)13.9(u)0(l)18.9(a)0(r)-305.1(p)0(e)20.8(r)0(m)16.5(e)0(a)14.7(b)0(i)18.9(l)0(i)16.5(t)0(y)-305.5(i)0(n)-305.5(t)0(h)18.9(e)-314.2(hy)15.5(pe)20.8(rr)18(es)13.9(po)21.2(ns)14.4(iv)18.9(en)20.8(es)13.9(s)]TJ 0 -1.0471 TD [(to)-345.3(hi)13.2(st)17.7(am)17.7(in)18.9(e)-354(w)0(a)11.2(s)-354.8(al)18.5(so)-344.2(as)13.9(se)19.6(ss)18.9(ed)-349.1(by)-348.7(me)17.7(an)15.1(s)-354.8(o)0(f)-344.6(d)0(y)15.5(e)-354(le)18.4(ak)15.1(ag)15.1(e)]TJ 0 -1.0527 TD [(me)17.7(th)18.9(od)15.5(.)]TJ /F4 1 Tf 0 -2.612 TD [(Pr)27.3(eparation)-343.3(of)-334(Japanes)-7.3(e)-336.9(cedar)-335.9(polle)-9(n)-330.8(extra)-8.2(ct)]TJ /F3 1 Tf 1.0015 -1.8494 TD [(Th)17.1(e)-331.2(c)0(e)14.7(d)0(a)20.8(r)-332.4(po)15.5(ll)16.5(en)-320.6(ex)15.1(tr)17.3(ac)20.4(t)-333.2(u)0(s)14.4(e)0(d)-320.6(f)0(o)13.9(r)-332.4(th)18.9(e)-331.2(s)0(e)13.9(n)0(s)20(i)0(t)16.5(i)0(z)18.4(a)0(t)18.4(i)0(o)18.9(n)-336.5(w)12.4(a)0(s)]TJ -1.0015 -1.0527 TD [(pr)19.6(ep)15.1(ar)19.2(ed)-314.9(ac)20.4(co)15.1(rd)19.6(in)18.9(g)-319.4(t)0(o)-311.2(a)-325.5(pr)19.6(ev)20.8(io)13.2(us)20(ly)-311.2(de)15.1(sc)19.6(ri)17.3(be)15.1(d)-319.4(m)0(e)17.7(t)0(h)18.9(o)0(d)-308.8([)0(7)13.9(])0(.)]TJ 0 -1.0471 TD [(In)-441.3(brief,)-448.3(the)-437.6(po)-7.2(llen)-440.7(was)-446(suspende)-9.3(d)-438.9(a)0(t)-436.8(1)-6.5(00)-439.7(mg)]TJ /F10 1 Tf 19.3194 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD (mL)Tj 7.472 0 0 6.641 267.194 245.14 Tm (-1)Tj 9.963 0 0 9.963 277.739 240.718 Tm (in)Tj -22.0281 -1.0528 TD [(physi)-7.4(ological)-287.2(saline)-284.5(and)-275.8(allo)-8.2(wed)-279.8(to)-282.7(stand)-280.9(for)-278.6(18)-280.4(h)-279.6(a)0(t)-277.5(4)]TJ /F9 1 Tf 21.7436 0 TD (8)Tj /F3 1 Tf 0.387 0 TD (C)Tj -22.1305 -1.0471 TD [(with)-353.2(mild)-352.4(sti)-8.2(rring.)-351.2(The)-353.9(suspen)-7.4(sion)-353.7(was)-349.2(then)-353(centr)-8.6(ifuge)-8.2(d)]TJ 0 -1.0528 TD (\(1,700)Tj /F9 1 Tf 2.9022 0 TD (6)Tj /F4 1 Tf 1.3202 0 TD (g)Tj /F3 1 Tf 0.5008 0 TD [(,)-324.7(1)0(5)-325.9(min\),)-323.5(and)-327.1(the)-323.7(resul)-9.4(tant)-326.9(supern)-7.8(atant)-328.1(used)]TJ -4.7232 -1.0471 TD [(as)-259.2(the)-261.2(sensi)-9(tization)-266.8(anti)-8.2(gen;)-261.9(this)-259.4(was)-263.9(stor)-8.2(ed)-258(at)-260.4(-80)]TJ /F9 1 Tf 19.6722 0 TD (8)Tj /F3 1 Tf 0.387 0 TD [(C)-261.6(until)]TJ -20.0592 -1.0527 TD [(use.)-311.6(The)-314.1(prote)-8.2(in)-311.2(concent)-8.9(ration)-318.6(in)-311.2(the)-312.4(solut)-9.8(ion)-312(was)-315.1(quan-)]TJ T* [(tified)-355.2(according)-353.5(to)-345.3(the)-346.5(met)-8.2(hod)-343.7(of)-350.2(B)]TJ 6.974 0 0 6.974 202.904 177.902 Tm 0.0001 Tc [(ENSADO)-11.9(UN)]TJ 9.963 0 0 9.963 244.516 177.902 Tm 0 Tc [(and)-349.8(W)]TJ 6.974 0 0 6.974 271.672 177.902 Tm 0.0001 Tc (EIN-)Tj -30.5991 -1.4958 TD (STEIN)Tj 9.963 0 0 9.963 81.184 167.471 Tm 0 Tc [([9];)-338.7(it)-336.3(was)-337.9(estimated)-343.9(to)-334(be)-337.7(500)]TJ /F8 1 Tf 12.8379 0 TD (m)Tj /F3 1 Tf 0.5747 0 TD [(g)-336.5(protein)]TJ /F10 1 Tf 3.642 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD (mL)Tj 7.472 0 0 6.641 267.534 171.893 Tm (-1)Tj 9.963 0 0 9.963 273.657 167.471 Tm (.)Tj /F4 1 Tf -21.6184 -2.6177 TD [(Sensi)-7.8(tization)-341.2(and)-338(challenge)]TJ /F3 1 Tf 1.0015 -1.8494 TD [(As)-342.4(pr)19.6(ev)15.1(io)18.9(us)20(ly)-339.7(de)15.1(sc)19.6(ri)17.3(be)15.1(d)-347.9([)0(7)19.6(])0(,)-361.2(guinea)-7.8(-pigs)-361.8(wer)-8.2(e)-359.7(bilater-)]TJ -1.0015 -1.0471 TD [(ally)-361(intr)-9.4(anasally)-366.1(sensiti)-9.6(zed)-361.6(by)-360(instil)-9.6(lation)-364.9(with)-364.6(3)]TJ /F8 1 Tf 20.0023 0 TD (m)Tj /F3 1 Tf 0.5691 0 TD [(L)-363.4(per)]TJ 4.6264 66.1583 TD [(nostr)-9(il)-245.3(of)-242.1(cedar)-251.3(pollen)-248.7(extract)-251.9(adsorbed)-248.7(on)-246.2(Al\(OH\))]TJ 7.472 0 0 6.641 508.819 770.003 Tm (3)Tj 9.963 0 0 9.963 514.942 771.647 Tm [(gel)-244.1(at)]TJ -20.6396 -1.0471 TD (1)Tj /F8 1 Tf 0.717 0 TD (m)Tj /F3 1 Tf 0.5747 0 TD [(g)-211.3(prote)-8.2(in)]TJ /F10 1 Tf 3.5168 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD [(mg)-215.2(Al\(O)-9.2(H\))]TJ 7.472 0 0 6.641 405.411 759.515 Tm (3)Tj 0.5008 0.922 TD (-1)Tj /F10 1 Tf 9.963 0 0 9.963 415.332 763.2 Tm (.)Tj /F3 1 Tf 0.239 -0.1992 TD (10)Tj /F8 1 Tf 1.2121 0 TD (m)Tj /F3 1 Tf 0.5747 0 TD (L)Tj 7.472 0 0 6.641 441.581 765.638 Tm (-1)Tj 9.963 0 0 9.963 449.801 761.216 Tm [(tw)-7.8(ice)-216(daily)-219.5(for)-216(7)-211.3(days.)]TJ -14.1012 -1.0528 TD [(Prior)-520.8(to)-510.4(each)-510.7(sensi)-9(tization)-10.7(,)-506.8(the)-511.5(u)-6.5(pper)-511.5(airway)-519.8(mucosal)]TJ 0 -1.0471 TD [(surfa)-8.6(ce)-258.4(was)-258.2(topicall)-10.7(y)-256.8(anaestheti)-11.9(zed)-253.5(by)-257.6(subje)-7.8(cting)-259.4(the)-255.5(an)-7.6(i-)]TJ 0 -1.0528 TD [(mal)-497.6(to)-487.6(a)-490.6(2-mi)-10.2(n)-490.2(inhalation)-496(of)-492.5(a)-490.6(4)0(%)-493.3(lignoca)-10.9(ine)-488.8(hydro-)]TJ 0 -1.0471 TD [(chlor)-8.2(ide)-306.7(mist)-308.1(\(F)-8(ujisawa)-311.9(Pharm)-8.2(aceutical)-311.9(Co.)-308.2(Ltd.,)-311.1(Osaka,)]TJ 0 -1.0528 TD [(Japan\))-8.2(,)-341.8(whi)-8.6(ch)-343.4(was)-343.6(g)-6.5(enerated)]TJ /F4 1 Tf 12.0355 0 TD (via)Tj /F3 1 Tf 1.5535 0 TD [(an)-349.1(ultrasonic)-354.1(nebulizer)]TJ -13.589 -1.0471 TD [(\(NE-)-8.6(U12;)-493.1(Omron,)-490.9(Osa)-7.8(ka,)-486(Japan\))-8.2(.)-489.8(This)-488.8(procedu)-7.7(re)-492.9(was)]TJ 0 -1.0527 TD [(con)-8.4(ducted)-463(in)-459.2(order)-468.3(to)-459.2(obtain)-465(effective)-460.3(sensiti)-9.6(zation)-465.4(by)]TJ T* [(means)-543.9(of)-538(prolonge)-10.5(d)-530(reten)-8.6(tion)-537(of)-538(the)-540(antigen)-540.1(plus)-541.5(Al)]TJ 0 -1.0471 TD (\(OH\))Tj 7.472 0 0 6.641 330.123 665.405 Tm (3)Tj 9.963 0 0 9.963 336.586 667.049 Tm [(in)-277.1(the)-278.2(nasal)-275.7(cavit)-9.4(y:)-271.4(it)-279.4(has)-277(been)-277(reported)-279.9(that)-281.4(ligno-)]TJ -2.7372 -1.0528 TD [(caine)-269.2(reduces)-265.4(the)-261.2(ciliary)-265.3(beat)-262.3(freque)-8.6(ncy)-258.8(of)-264.9(the)-261.2(guinea-pig)]TJ 0 -1.0471 TD [(airw)-11.4(ay)]TJ /F4 1 Tf 2.9875 0 TD [(in)-294.1(vitr)24.7(o)]TJ /F3 1 Tf 3.1924 0 TD [([10])-296.5(and)-292.9(that)-298.4(topic)-9(al)-288.8(a)-6.9(naestheti)-10.7(c)-291.4(drugs)-296.8(do)]TJ -6.1799 -1.0527 TD [(not)-340.4(decreas)-9.7(e)-331.2(mucos)-8.6(al)-334.4(absorb)-7.8(ency)-339.6([1)31(1].)-339.2(Then,)-338(the)-335.1(sensit-)]TJ 0 -1.0471 TD [(ized)-233.9(anim)-9(als)-228.2(wer)-8.2(e)-223.1(bila)-8.2(terally)-236.8(intranasal)-13.1(ly)-225.8(chall)-9.4(enged)-232.3(once)]TJ 0 -1.0527 TD [(eve)-8.8(ry)-276.3(week)-280.9(by)-274.7(quantitat)-11.5(ive)-278.2(inhalati)-10.7(on)-274.7(of)-276.3(the)-278.2(cedar)-285.5(pollen)]TJ 0 -1.0471 TD [(at)-379.9(a)-371.1(dose)-380.2(of)-373(1.8)-377.5(mg)]TJ /F10 1 Tf 8.1887 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD (nostril)Tj 7.472 0 0 6.641 418.79 608.712 Tm (-1)Tj /F4 1 Tf 9.963 0 0 9.963 428.655 604.29 Tm (via)Tj /F3 1 Tf 1.582 0 TD [(a)-376.7(handma)-8.5(de)-371.8(inhal)-9(ation)]TJ -13.5606 -1.0528 TD [(app)-8.4(aratus)-260.9([12].)-262.7(When)-260.7(the)-261.2(pollen)-260.1(was)-258.2(appli)-9(ed)-258(to)-260(both)-255.8(nos-)]TJ 0 -1.0471 TD [(tri)-8.6(ls)-238.4(of)-242.1(spont)-7.4(aneousl)-9.7(y)-239.8(breathing)-247.3(guinea)-7.8(-pigs)-9(,)-239.4(almost)-247.4(all)-240.8(of)]TJ 0 -1.0527 TD [(the)-346.5(inhaled)-346.7(poll)-7.8(en)-343.4(was)-343.6(trapp)-8.2(ed)-337.7(in)-345.3(the)-346.5(upper)-341.6(airw)-11.4(ays;)-342.8(10)]TJ 0 -1.0471 TD [(and)-236(60)-234.8(min)-235.4(after)-243.5(the)-232.7(inhal)-9(ation,)-237(81)-234.8(and)-236(55%)-232.3(of)-236.4(the)-238.4(pollen,)]TJ 0 -1.0528 TD [(respec)-8.6(tive)-8.2(ly)64.4(,)-267.8(was)-263.9(found)-267.2(in)-265.7(the)-266.8(upper)-267.6(airwa)-12.5(y)61.8(,)-262.1(but)-266.4(less)-264.3(than)]TJ 0 -1.0471 TD [(0.00)-8.4(1%)-396.5(reached)-401.2(the)-392(low)-8.6(er)-396.2(airways)-402.2([12].)-399.3(The)-393.8(decreas)-9.8(ed)]TJ 0 -1.0527 TD [(amoun)-7.4(t)-316.1(o)0(f)-321.8(pollen)-322.7(in)-316.9(the)-318.1(upper)-324.5(airway)-320.6(wi)-7.8(th)-316.9(time)-324.3(after)-323.2(in-)]TJ 0 -1.0471 TD [(halat)-9.4(ion)-403(was)-400.5(mostly)-406.3(account)-8.9(ed)-400.3(for)-403.8(by)-399.9(poll)-7.8(en)-400.3(cell)-401.3(walls)]TJ 0 -1.0528 TD [(found)-341.2(in)-334(the)-335.1(oesopha)-7.3(g)-6.5(u)0(s)-332.8(and)-338.4(stomach.)]TJ 1.0015 -1.0471 TD [(Wh)14.4(en)-349.1(no)21.2(ns)14.3(en)20.8(si)17.7(ti)16.5(ze)14.7(d)-353.6(g)0(u)15.5(i)13.9(ne)15.1(a-)19.2(pi)13.2(gs)-344.2(we)16.9(re)-350.7(fo)19.6(rc)19.2(ed)-349.1(to)-345.4(in)13.2(ha)20.8(le)]TJ -1.0015 -1.0527 TD [(po)15.5(ll)16.5(en)20.8(,)-256.5(t)0(h)18.9(e)-257.2(gu)21.2(in)18.9(ea)14.7(-p)19.6(ig)13.2(s)-252.3(s)0(h)20(o)0(w)17.3(e)0(d)-246.6(n)0(o)-246.2(i)0(n)18.9(c)0(r)13.5(e)0(a)20.4(s)0(e)13.9(s)-252.3(in)-248.6(ei)18.5(th)18.8(er)-248.2(s)]TJ /F4 1 Tf 21.294 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 527.357 489.203 Tm (aw)Tj 9.963 0 0 9.963 309.316 478.772 Tm [(or)-316.1(re)13.5(sp)20(on)15.5(si)17.7(ve)20.8(ne)15.1(ss)-311.2(to)-316.9(hi)18.8(st)17.7(am)12(in)18.9(e)-325.5(\()0(d)19.6(a)0(t)18.5(a)-325.5(no)15.5(t)-321.8(s)0(h)20(o)0(w)11.6(n)0(\))19.6(.)]TJ /F4 1 Tf 0 -2.8794 TD [(Measu)-7.8(r)26.5(ement)-335.3(of)-339.6(specific)-340(airway)-343.3(r)32.2(esis)-8.2(tance)]TJ /F3 1 Tf 1.0015 -1.8551 TD (s)Tj /F4 1 Tf 0.3813 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 328.989 431.603 Tm (aw)Tj 9.963 0 0 9.963 340.724 431.603 Tm [(wa)16.9(s)-258(m)0(e)17.7(a)0(s)13.9(u)0(r)19.6(e)0(d)-252.3(b)0(y)-251.9(m)0(e)17.7(a)0(n)15.1(s)-258(of)-247.8(a)-262.9(t)0(w)14.9(o)0(-)19.6(c)0(h)15.1(a)0(m)17.7(b)0(e)20.8(r)0(e)13.5(d)-256.8(do)15.5(u-)]TJ -3.1526 -1.0471 TD [(bl)13.2(e-)19.2(fl)17.3(ow)-290(pl)13.2(et)18.4(hy)21.2(sm)16.9(og)15.5(ra)19.2(ph)15.5(ic)-288.8(sy)14.4(st)17.7(em)-289.6(ac)14.7(co)20.8(rd)13.9(in)18.8(g)-302.4(t)13.9(o)-302.4(t)0(h)18.8(e)-302.8(me)17.7(th)18.8(-)]TJ 0 -1.0528 TD [(od)-263.3(of)-264.9(P)]TJ 6.974 0 0 6.974 338.116 410.683 Tm 0.0001 Tc [(ENN)24.1(OC)18.4(K)]TJ /F4 1 Tf 9.963 0 0 9.963 369.468 410.683 Tm 0 Tc [(et)-266.1(al)18.9(.)]TJ /F3 1 Tf 2.2421 0 TD [([1)13.9(3].)-271(In)-282(brief)-9.8(,)-279.2(the)-283.9(anim)-9(al)-283.2(was)-281(placed)]TJ -8.2797 -1.0471 TD [(wi)-7.8(th)-396.6(its)-400.9(neck)-402.2(extending)-405.1(through)-402(the)-397.7(parti)-10.6(tion)-400.5(of)-395.8(a)-399.5(two-)]TJ 0 -1.0527 TD [(cha)-8.8(mbered)-448.3(box,)-440.8(and)-446.6(s)]TJ /F4 1 Tf 9.2585 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 407.565 389.764 Tm (aw)Tj 9.963 0 0 9.963 421.172 389.764 Tm [(was)-446(meas)-8.2(ured)-443.2(using)-445.6(a)-445(Data)]TJ -11.2275 -1.0471 TD [(ana)-8.8(lyser)-595.5(Pulmos-I)-601.3(\(Medical)-596.1(Inter)-9.8(face)-592(Pr)-8(oject)-595.5(Station,)]TJ 0 -1.0527 TD [(Osa)-7.8(ka,)-229.9(Japan\))-235.8(and)-236(a)-228.8(P)0(C)-233.1(9801)-230.7(F)68.3(A)-226.6(compu)-7.4(ter)-234.3(\(NEC,)-239.7(T)63.4(okyo,)]TJ 0 -1.0471 TD [(Japan\))-224.4(after)-226.4(moni)-8.6(toring)-221.5(the)-221.3(airflow)]TJ /F4 1 Tf 13.9475 0 TD (via)Tj /F3 1 Tf 1.4283 0 TD [(sensor)-9(s)-218.2(attached)-223(to)]TJ -15.3759 -1.0528 TD [(both)-341.2(the)-335.1(front)-339.4(and)-338.4(rear)-337.1(chamb)-7.8(ers.)]TJ /F4 1 Tf 0 -2.8794 TD [(Nas)-8.2(al)-612.8(r)32.2(espons)-7.4(ivenes)-9.4(s)-610.8(t)0(o)-612.8(histam)-8.8(ine)-614(and)-611.2(methac)-11.7(holine)]TJ 0 -1.0471 TD [(chlor)-7.8(ide)]TJ /F3 1 Tf 1.0015 -1.8494 TD [(In)-333.2(or)19.6(de)15.1(r)-338.1(t)0(o)-328.3(e)0(s)19.6(t)0(i)16.5(m)0(a)17.7(t)0(e)-328.7(t)0(h)18.9(e)-342.6(t)13.9(i)0(m)15.7(e)0(-)13.5(c)0(o)20.8(u)0(r)14(s)0(e)-327.5(o)0(f)-327.5(t)0(h)18.9(e)-336.9(re)13.5(sp)20(on)15.5(se)-327.5(to)]TJ -1.0015 -1.0528 TD [(hi)13.2(st)17.7(am)17.7(in)18.9(e)-257.2(i)0(n)-242.9(t)0(h)18.9(e)-257.2(na)20.8(sa)13.9(l)-253.5(a)0(i)18.5(r)0(w)15.7(a)0(y)77.7(,)-250.8(10)]TJ /F8 1 Tf 13.0541 0 TD (m)Tj /F3 1 Tf 0.5634 0 TD (L)Tj /F10 1 Tf 0.5975 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD [(ca)20.4(vi)18.8(ty)]TJ 7.472 0 0 6.641 477.184 284.315 Tm -0.0185 Tc (-1)Tj 9.963 0 0 9.963 485.405 279.893 Tm 0 Tc (10)Tj 7.472 0 0 6.641 495.212 284.315 Tm (-4)Tj 9.963 0 0 9.963 503.773 279.893 Tm 0.2588 Tc [(Mh)258.8(i)277.7(s)258.8(t)276.5(a)258.8(-)]TJ -19.5186 -1.0471 TD 0 Tc [(mi)15.7(ne)-235.2(wa)16.9(s)-241(i)0(n)18.9(s)0(t)17.7(i)0(l)16.5(l)0(e)12.8(d)-239.8(in)18.8(to)-231.5(bo)15.5(th)-231.5(na)15.1(sa)19.6(l)-242.2(c)0(a)14.7(v)0(i)18.9(t)0(i)16.5(e)0(s)-230.7(o)0(f)-236.4(t)0(h)18.8(e)-240.2(co)15.1(ns)20(ci)12.8(ou)21.2(s)]TJ 0 -1.0527 TD [(se)13.9(ns)20(it)16.5(iz)18.4(ed)-286.5(gu)15.5(in)18.9(ea)20.4(-p)14(ig)18.8(s)-292.2(2)-296.7(da)15.1(ys)-281.6(af)13.5(t)13.9(e)0(r)-288.1(t)0(h)18.9(e)-297.1(13)21.2(th)-288.4(po)15.5(l)13.9(l)0(e)12.8(n)-291(in)18.8(ha)15.1(la)18.4(-)]TJ 0 -1.0471 TD [(ti)16.5(on)-314.5(ch)15.1(al)18.4(le)18.4(ng)15.5(e,)-314.5(an)20.8(d)-325.1(t)0(h)18.9(e)0(n)-320.6(s)]TJ /F4 1 Tf 10.2487 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 417.316 248.542 Tm (aw)Tj 9.963 0 0 9.963 429.675 248.542 Tm [(wa)16.9(s)-326.3(m)0(o)18.1(n)0(i)18.9(t)0(o)18.9(r)0(e)13.5(d)-325.1(fo)19.6(r)-326.7(6)0(0)-314.5(m)0(i)15.7(n)0(.)]TJ -11.0795 -1.0528 TD -0.0177 Tc [(T)51.4(w)-17.7(o)-364.6(d)-17.7(ay)-17.7(s)-367.5(a)-17.7(ft)-17.7(er)-372.9(t)-17.7(h)1.2(e)-371.7(2)-17.7(0t)-17.7(h)-363(a)-17.7(nd)-371.3(t)-17.7(h)1.1(e)-371.7(2)-17.7(2n)-17.7(d)-360.7(i)-17.7(nh)-17.7(al)-17.7(at)-17.7(io)-17.7(n)-360.7(c)-17.7(ha)-17.7(l-)]TJ -1.0015 -1.0527 TD 0 Tc [(le)12.8(ng)21.2(es)13.9(,)-273.5(t)0(h)18.9(e)-280(ai)18.5(rw)15.7(ay)-269.4(re)19.2(sp)20(on)15.5(si)17.7(ve)15.1(ne)20.8(ss)-271.4(to)18.9(,)-273.5(r)0(e)13.5(s)0(p)20(e)0(c)14.7(t)0(i)22.2(v)0(e)15.1(l)0(y)81.4(,)-279.2(hi)18.9(st)17.7(am)17.7(-)]TJ 0 -1.0471 TD [(in)13.2(e)-285.7(a)0(n)15.1(d)-291(MC)20.3(h)-291(o)0(f)-282(t)0(h)18.9(e)-291.4(se)19.6(ns)20(it)16.5(iz)12.8(ed)-275.1(gu)15.5(in)18.9(ea)14.7(-p)19.6(ig)18.9(s)-292.2(w)0(a)16.9(s)-286.5(me)12(as)19.6(ur)19.6(ed)15.1(.)]TJ 0 -1.0527 TD [(Th)17.1(e)-325.5(t)0(i)16.5(m)0(e)12(-)0(c)19.2(o)0(u)21.2(r)0(s)12.8(e)-325.5(of)-316.1(ch)15.1(an)20.8(ge)15.1(s)-326.3(i)0(n)-316.9(n)0(a)20.8(s)0(a)13.9(l)-321.8(hy)15.5(pe)15.1(rr)18(es)19.6(po)15.5(ns)20(iv)18.9(en)15.1(es)19.6(s)]TJ 0 -1.0471 TD [(to)-254.3(hi)18.9(st)17.7(am)17.7(in)18.9(e)-262.9(a)0(n)20.8(d)-262.5(MC)14.6(h)-256.8(f)0(o)19.6(l)0(l)16.5(o)0(w)17.3(i)0(n)18.8(g)-262.5(an)20.8(ti)16.5(ge)15.1(n)-256.8(c)0(h)15.1(a)0(l)18.5(l)0(e)18.4(n)0(g)15.5(e)-257.2(in)-254.3(se)19.6(n-)]TJ 0 -1.0527 TD [(si)17.7(ti)16.5(ze)14.7(d)-302.4(g)0(u)21.2(i)0(n)18.9(e)0(a)14.7(-)0(p)19.6(i)0(g)13.2(s)-297.9(we)16.9(re)-293.7(ev)15.1(al)18.5(ua)15.1(te)18.4(d)-302.4(1)0(0)-291.7(h)-302.4(an)20.8(d)-302.4(2)-302.4(a)0(n)15.1(d)-296.7(7)-302.4(d)0(a)15.1(y)0(s)]TJ 0 -1.0471 TD [(af)13.5(te)18.4(r)-281.2(t)0(h)18.8(e)-285.7(24)15.5(t)13.9(h)-285.3(an)20.8(d)-285.3(2)0(6)15.5(t)13.9(h)-285.3(a)0(n)20.8(t)0(i)16.5(g)0(e)15.1(n)-279.6(pr)14(ov)21.2(oc)15.1(at)18.5(io)18.9(ns)14.4(,)-279.2(r)0(e)19.2(s)0(p)14.4(e)0(c)20.4(t)0(i)16.5(v)0(e)15.1(l)0(y)81.5(.)]TJ 1.0015 -1.0528 TD [(Th)17.1(e)-519(h)0(y)21.2(p)0(e)15.1(r)0(r)18(e)0(s)19.6(p)0(o)15.5(n)0(s)20(i)0(v)18.8(e)0(n)15.1(e)0(s)19.6(s)-514.1(te)12.8(st)17.7(s)-514.1(d)0(e)20.8(s)0(c)13.9(r)0(i)17.3(b)0(e)20.8(d)-512.9(ab)15.1(ov)15.5(e)-513.3(w)0(e)16.9(r)0(e)]TJ -1.0015 -1.0471 TD 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[(sa)19.6(cr)13.5(if)17.3(ic)18.4(ed)-462.9(by)-468.2(ex)20.8(sa)13.9(ng)21.2(ui)13.2(na)20.8(ti)16.5(on)-468.2(un)21.2(de)15.1(r)-474.7(p)0(e)20.8(n)0(t)18.9(o)0(b)15.5(a)0(r)19.2(b)0(i)13.2(t)13.9(al)-470.9(an)20.8(ae)14.7(s-)]TJ 0 -1.0584 TD [(th)18.9(es)13.9(ia)-385.6(\(4)19.6(0)-399.1(m)0(g)]TJ /F10 1 Tf 5.6052 0.1992 TD (.)Tj /F3 1 Tf 0.2731 -0.1992 TD (kg)Tj 7.472 0 0 6.641 126.595 388.346 Tm (-1)Tj 9.963 0 0 9.963 132.548 383.924 Tm (,)Tj /F4 1 Tf 0.6487 0 TD -0.0139 Tc [(i.)-13.9(v)75.6(.)]TJ /F3 1 Tf 1.0926 0 TD 0 Tc [(\).)-389.7(Th)17.1(e)-393.8(f)0(o)13.9(l)0(l)22.2(o)0(w)11.6(i)13.9(ng)-388.5(pr)19.6(oc)15.1(ed)15.1(ur)19.6(es)-384.4(we)11.2(re)]TJ -9.1959 -1.0527 TD [(ca)14.7(rr)18(ie)18.4(d)-205.6(o)0(u)21.2(t)-202.3(fo)13.9(r)-201.5(q)0(u)15.5(a)0(n)20.8(t)0(i)16.5(f)0(i)17.3(c)0(a)14.7(t)0(i)16.5(o)0(n)-189.3(o)0(f)-196.6(t)0(h)18.9(e)-206(dy)21.2(e)-206(t)0(h)18.9(a)0(t)-197.8(h)0(a)20.8(d)-205.6(le)18.4(ak)15.1(ed)-195.4(i)13.9(n)0(t)13.2(o)]TJ T* [(th)18.9(e)-297.1(l)0(u)18.9(m)0(i)15.7(n)0(a)15.1(l)-299.1(en)20.8(tr)17.3(y)-296.7(a)0(n)15.1(d)-296.7(la)18.4(mi)15.7(na)-286.5(pr)19.6(op)15.5(ri)17.3(a.)-286.1(T)69.1(o)-296.7(qu)21.2(an)15.1(ti)16.5(fy)-287.7(th)18.9(e)-297.1(d)0(y)15.5(e)]TJ 0 -1.0584 TD [(in)-203.1(th)18.9(e)-211.7(l)0(u)18.9(m)0(i)15.7(n)0(a)15.1(l)-213.7(en)20.8(tr)17.3(y)67.5(,)-210.9(t)13.9(h)0(e)-206.8(n)0(a)20.8(s)0(a)13.9(l)-208(ca)14.7(vi)18.9(ti)16.5(es)-202.3(we)16.9(re)-202.7(pe)15.1(rf)18(us)14.4(ed)-201.1(wi)14.9(th)-203.1(2)]TJ 0 -1.0528 TD (mL)Tj /F10 1 Tf 1.36 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD [(an)15.1(im)15.7(al)]TJ 7.472 0 0 6.641 100.743 346.337 Tm (-1)Tj 9.963 0 0 9.963 109.757 341.915 Tm [(sa)19.6(li)16.5(ne)-292.2(th)18.9(ro)13.9(ug)21.2(h)-296.7(t)0(h)13.2(e)-297.1(ph)15.5(ar)19.2(yn)21.2(x)-302.4(a)0(n)20.8(d)-302.4(th)18.9(e)-297.1(p)0(e)15.1(r)0(f)18(u)0(s)20(a)0(t)12.8(e)]TJ -5.167 -1.0527 TD [(wa)16.9(s)-286.5(c)0(o)20.8(l)0(l)16.5(e)0(c)14.7(t)0(e)18.4(d)0(.)-274.3(T)0(h)17.1(e)-285.7(pe)15.1(rf)18(us)20(at)12.8(e)-285.7(w)12.4(as)-276.3(ce)14.7(nt)18.9(ri)17.3(fu)13.9(ge)20.8(d)-285.3(\()0(1)13.9(,)0(7)21.6(0)0(0)]TJ /F9 1 Tf 20.7705 0 TD (6)Tj /F4 1 Tf 1.2861 0 TD (g)Tj /F3 1 Tf 0.4951 0 TD (,)Tj -22.5516 -1.0584 TD [(10)-286.1(mi)15.7(n\))19.6(,)-296.3(a)0(n)15.1(d)-296.7(th)18.9(en)-286.5(th)18.9(e)-297.1(a)0(m)12(o)0(u)21.2(n)0(t)-288.4(o)0(f)-287.6(E)0(v)17.1(a)0(n)20.8(s)-297.9(bl)18.9(ue)-292.2(in)-282.7(th)13.2(e)-297.1(s)0(u)20(p)0(e)15.1(r)20.4(-)]TJ 0 -1.0528 TD [(na)15.1(ta)18.4(nt)-225.8(me)17.7(as)13.9(ur)19.6(ed)-229.6(co)15.1(l)13.9(o)0(r)13.9(i)0(m)15.7(e)0(t)18.5(r)0(i)17.3(c)0(a)14.7(l)13.9(ly)-231.5(at)-226.2(62)15.5(0)-234.1(n)0(m)12.4(.)-233.7(T)69.1(o)-234.1(qu)15.5(al)18.4(if)17.3(y)-234.1(t)0(h)13.2(e)]TJ T* [(dy)15.5(e)-399.5(i)13.9(n)-399.1(t)0(h)13.2(e)-399.5(l)13.9(a)0(m)12(i)0(n)18.9(a)-399.5(pr)19.6(op)15.5(ri)17.3(a,)-388.5(th)18.9(e)-399.5(n)0(a)15.1(s)0(a)19.6(l)-401.5(mu)18.1(co)20.8(sa)13.9(l)-395.8(t)0(i)16.5(s)0(s)18.9(u)0(e)-394.6(w)12.4(as)]TJ 0 -1.0584 TD [(re)19.2(mo)12.4(ve)20.8(d)-313.7(a)0(f)13.5(t)0(e)18.4(r)-315.3(pe)15.1(rf)18(us)20(io)18.9(n)-319.4(o)0(f)-304.7(t)0(h)18.9(e)-314.2(he)15.1(ad)-309.2(w)12.4(i)0(t)16.5(h)-313.7(40)-308.8(mL)]TJ /F10 1 Tf 19.291 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD [(an)15.1(im)15.7(al)]TJ 7.472 0 0 6.641 279.383 293.783 Tm (-1)Tj 9.963 0 0 9.963 58.28 278.872 Tm [(sa)19.6(li)16.5(ne)-411.7(th)18.9(ro)19.6(ug)15.5(h)-416.2(t)0(h)18.9(e)-416.6(ca)14.7(ro)19.6(ti)16.5(d)-416.2(a)0(r)13.5(t)0(e)18.4(r)0(y)82.2(.)-415.8(Th)17.1(e)-416.6(t)0(i)16.5(s)0(s)18.9(u)0(e)-411.7(w)0(a)16.9(s)-417.4(tr)17.3(ea)20.4(te)12.8(d)]TJ 0 -1.0528 TD [(wi)14.9(th)-237.2(al)18.4(ka)15.1(li)-233.9(\(1)13.9(.2)-234.5(N)-249.4(K)0(O)13.4(H)12.4(,)-250.8(1)0(8)-234.8(h)-245.5(at)-237.6(37)]TJ /F9 1 Tf 13.663 0 TD (8)Tj /F3 1 Tf 0.3756 0 TD [(C,)-239.2(2)-245.5(m)0(L)]TJ /F10 1 Tf 3.2607 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD [(an)15.1(im)15.7(al)]TJ 7.472 0 0 6.641 259.54 272.806 Tm (-1)Tj 9.963 0 0 9.963 265.493 268.384 Tm [(\),)-236.1(th)13.2(e)]TJ -20.799 -1.0584 TD [(su)20(sp)14.4(en)20.8(si)17.7(on)-195(ce)14.7(nt)18.9(ri)17.3(fu)19.6(ge)15.1(d)-205.6(f)0(o)19.6(r)-201.5(10)-195(mi)15.7(n)-205.6(a)0(t)-192.1(1)0(,)15.9(7)0(0)15.5(0)]TJ /F9 1 Tf 16.6676 0 TD (6)Tj /F4 1 Tf 0.9902 0 TD (g)Tj /F3 1 Tf 0.7056 0 TD [(an)15.1(d)-199.9(t)0(h)18.9(e)-206(dy)15.5(e)]TJ -18.3634 -1.0527 TD [(in)-390.9(th)13.2(e)-399.5(s)0(u)20(p)0(e)15.1(r)0(n)19.6(a)0(t)12.8(a)0(n)20.8(t)-401.5(co)15.1(lo)18.9(ri)17.3(me)17.7(tr)17.3(ic)12.8(al)18.4(ly)-390.9(me)17.7(as)13.9(ur)19.6(ed)-394.6(at)-391.3(62)15.5(0)-399.1(n)0(m)12.4(,)]TJ T* [(ac)14.7(co)20.8(rd)13.9(i)13.9(n)0(g)-303.1(t)0(o)-305.5(t)0(h)18.9(e)-314.2(me)17.7(th)18.9(od)-303.1(of)-304.7(K)]TJ 6.974 0 0 6.974 175.805 236.863 Tm -0.1083 Tc [(AT)-24.6(A)-16.3(Y)0(A)-108.4(M)-90.5(A)]TJ /F4 1 Tf 9.963 0 0 9.963 211.465 236.863 Tm 0 Tc [(et)-305.9(al)18.9(.)]TJ /F3 1 Tf 2.3274 0 TD [([1)19.6(4].)-316.5(For)-321.8(the)]TJ -17.7033 -1.0584 TD [(contr)-8.2(ols,)-324.9(nonsens)-8.1(itized)-331.2(saline-in)-11.9(stilled)-329.4(and)-327.1(nonsens)-8.1(itized)]TJ 0 -1.0528 TD [(histami)-11.5(ne-insti)-10.7(lled)-338.3(groups)-337.4(were)-339.4(prepar)-8.6(ed.)]TJ /F4 1 Tf 0 -4.0517 TD [(Statist)-10.4(ical)-338.3(analyses)]TJ /F3 1 Tf 1.0015 -2.0998 TD [(St)19.6(at)12.8(is)17.7(ti)16.5(ca)20.4(l)-395.8(a)0(n)15.1(a)0(l)18.5(y)0(s)20(e)0(s)-384.4(w)0(e)16.9(r)0(e)-390.5(p)0(e)20.8(r)0(f)12.4(o)0(r)19.6(m)0(e)17.7(d)-393.4(by)-388.5(me)17.7(an)15.1(s)-394.6(o)0(f)-384.4(o)0(n)15.5(e)0(-)]TJ -1.0015 -1.0528 TD [(wa)16.9(y)-393.4(a)0(n)20.8(a)0(l)12.8(y)0(s)20(i)0(s)-386.4(o)0(f)-378.7(v)0(a)15.1(r)0(i)17.3(a)0(n)15.1(c)0(e)20.4(.)-393(If)-386(a)-388.1(s)0(i)17.7(g)0(n)15.5(i)0(f)17.3(i)0(c)18.4(a)0(n)15.1(t)-390.1(di)18.9(f)14.7(f)0(e)19.2(r)0(e)19.2(n)0(c)15.1(e)-393.8(wa)16.9(s)]TJ T* [(de)15.1(te)18.4(ct)18.4(ed)15.1(,)-353.2(t)0(h)18.9(e)-354(in)13.2(di)18.9(vi)18.9(du)15.5(al)-345.7(gr)19.6(ou)15.5(p)-353.6(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nc)15.1(e)-354(w)0(a)16.9(s)-354.8(de)15.1(te)18.4(rm)16.5(in)18.8(ed)]TJ 0 -1.0584 TD [(us)20(in)13.2(g)-512.9(B)0(o)16.5(n)0(f)19.6(e)0(r)13.5(r)0(o)19.6(n)0(i)]TJ /F9 1 Tf 6.8856 0 TD (')Tj /F3 1 Tf 0.2106 0 TD [(s)-514.1(m)0(u)12.4(l)13.9(ti)16.5(pl)13.2(e)-513.3(t)0(e)18.4(s)0(t)17.7(.)-518.2(A)-511.2(p)0(-)14(v)0(a)20.8(l)0(u)13.2(e)]TJ /F8 1 Tf 11.3982 0 TD (<)Tj /F3 1 Tf 0.5406 0 TD [(0.)15.9(05)-508(wa)16.9(s)]TJ -19.0349 -1.0528 TD [(co)15.1(ns)20(id)18.9(er)13.5(ed)-314.9(st)17.7(at)18.5(is)17.7(ti)16.5(ca)20.4(ll)16.5(y)-325.1(s)0(i)17.7(g)0(n)15.5(i)13.9(fi)11.6(ca)20.4(nt)18.9(.)]TJ /F6 1 Tf 35.0595 66.1583 TD [(Res)-7.8(ults)]TJ /F4 1 Tf -9.8617 -2.0998 TD [(T)51.2(i)0(m)-7.8(e-cour)-8.2(se)-617.7(of)-618.5(change)-620(in)-618.5(speci)-8.2(fic)-622(airway)-622.2(r)26.5(esistance)]TJ 0 -1.0471 TD [(afte)-8.2(r)-320.6(hist)-9(amine)-334.9(inst)-9(illation)]TJ /F3 1 Tf 1.0015 -2.0998 TD [(Fi)14(gu)21.2(re)-305.1(1)-308.1(show)-8.2(s)-314.9(the)-323.7(time-cou)-10.7(rse)-324.2(of)-321.8(the)-323.7(change)-324.5(in)-322.6(s)]TJ /F4 1 Tf 20.2754 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 527.301 719.376 Tm (aw)Tj 9.963 0 0 9.963 309.316 708.888 Tm [(after)-345.9(inst)-9(illation)-342.8(of)-344.6(10)]TJ 7.472 0 0 6.641 397.644 713.31 Tm (-4)Tj 9.963 0 0 9.963 407.168 708.888 Tm [(M)-338.5(histami)-11.5(ne)-337.7(into)-343.6(both)-341.2(nasal)-343.9(ca-)]TJ -9.8219 -1.0471 TD 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[(Effect)-11(s)-508.4(o)0(f)-504.7(mepy)-7.8(ramine)-513.2(and)-508.8(atr)28.3(opine)-513.1(on)-508(the)-511.5(incr)27.1(eased)]TJ 0 -1.0527 TD [(speci)-8.2(fic)-337.5(airway)-343.3(r)32.2(esistance)-345.3(induced)-338.6(by)-337.7(histamine)]TJ /F3 1 Tf 1.0015 -2.0998 TD [(Fi)14(gu)21.2(re)-236.8(6)-239.8(shows)-254.8(the)-255.5(eff)11.2(e)-6.9(cts)-251(of)-253.5(mepyrami)-11.5(ne)-252.3(and)-253.1(atropine)]TJ -1.0015 -1.0471 TD [(on)-331.6(nasal)-326.9(hyperr)-8.2(espons)-7.4(ivenes)-9(s)-326.3(t)0(o)-322.6(hist)-9(amine.)-329.2(Pretr)-9(eatment)]TJ 0 -1.0528 TD [(wi)-7.8(th)-436.4(10)-434(mg)]TJ /F10 1 Tf 4.9109 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD (kg)Tj 7.472 0 0 6.641 370.885 386.589 Tm (-1)Tj 9.963 0 0 9.963 381.373 382.167 Tm [(mepyr)-9(amine)-442.6(suppressed)-440.4(the)-437.6(hy)-7.2(perres-)]TJ -7.2327 -1.0471 TD [(pon)-8(siveness)-377.1(to)-379.5(a)-371.1(level)-379.3(sim)-9(ilar)-379.7(to)-373.8(that)-378.1(found)-375.3(in)-379.5(the)-375(non-)]TJ 0 -1.0527 TD [(sensi)-9(tized)-225.6(group.)-227.7(The)-223.1(inhi)-7.8(bitory)-227.2(acti)-8.6(on)-217.8(o)-6.5(f)-218.6(the)-227(drug)-226.6(against)]TJ 0 -1.0471 TD [(the)-272.5(respon)-7.8(ses)-266.8(induce)-7.8(d)-262.5(b)0(y)-269(both)-267.2(10)]TJ 7.472 0 0 6.641 442.091 355.238 Tm (-6)Tj 9.963 0 0 9.963 450.879 350.816 Tm [(and)-270.1(10)]TJ 7.472 0 0 6.641 477.864 355.238 Tm (-2)Tj 9.963 0 0 9.963 486.652 350.816 Tm [(M)-264.5(hist)-9(amine)]TJ -17.8 -1.0527 TD [(was)-434.6(significant.)-437.3(However)24.2(,)-427.2(pretr)-9.8(eatment)-435.6(with)-427.2(1)-427.6(m)0(g)]TJ /F10 1 Tf 20.9128 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD (kg)Tj 7.472 0 0 6.641 530.305 344.75 Tm (-1)Tj 9.963 0 0 9.963 309.316 329.839 Tm [(atrop)-8.2(ine)-335.1(had)-338.4(no)-337.3(inhibitory)-343.1(effect)-330(on)-337.3(the)-335.1(respon)-7.8(se.)]TJ ET 0 0 0 1 K 0 J 0 j 0.5 w 3.864 M []0 d /GS3 gs 1 i 220.699 234.679 m 220.699 222.93 l 193.53 219.43 m 193.53 209.555 l 166.155 219.18 m 166.155 206.305 l 138.78 223.305 m 138.78 213.18 l S [2 2 ]0 d 98.03 211.627 m 225.279 211.627 l S 0 0 0 0 k 3.864 M []0 d 111.711 211.614 m 111.711 212.891 112.747 213.926 114.024 213.926 c 115.301 213.926 116.336 212.891 116.336 211.614 c 116.336 210.337 115.301 209.301 114.024 209.301 c 112.747 209.301 111.711 210.337 111.711 211.614 c b 98.03 313.929 m 98.03 187.68 l 98.03 184.43 m 225.779 184.43 l 98.03 187.878 m 94.53 187.878 l 98.03 211.627 m 94.53 211.627 l 98.03 235.377 m 94.53 235.377 l 98.03 259.127 m 94.53 259.127 l 98.03 283.132 m 94.53 283.132 l 98.03 306.514 m 94.53 306.514 l S BT /F16 1 Tf 10 0 0 10 79.905 302.974 Tm 0 0 0 1 k /GS4 gs (1.2)Tj 0.0092 -2.3177 TD (0.9)Tj -0.0047 -2.3868 TD (0.6)Tj 0.0024 -2.4 TD (0.3)Tj 0.6432 -2.375 TD (0)Tj -0.9375 -2.3481 TD (-0.3)Tj ET /GS3 gs 110.53 184.555 m 110.53 181.93 l 124.853 184.35 m 124.853 181.725 l 138.836 184.144 m 138.836 181.519 l 166.195 184.314 m 166.195 181.689 l 193.383 184.371 m 193.383 181.746 l 220.572 184.428 m 220.572 181.803 l S BT 10 0 0 10 212.404 171.055 Tm /GS4 gs (10)Tj 8 0 0 8 221.524 173.323 Tm (-2)Tj 10 0 0 10 185.78 171.031 Tm (10)Tj 8 0 0 8 194.9 173.299 Tm (-4)Tj 10 0 0 10 159.03 171.055 Tm (10)Tj 8 0 0 8 168.15 173.323 Tm (-6)Tj 10 0 0 10 131.655 171.055 Tm (10)Tj 8 0 0 8 140.775 173.323 Tm (-8)Tj 10 0 0 10 122.53 171.055 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 132.03 165.555 m 226.904 165.555 l S BT 10 0 0 10 154.905 154.68 Tm /GS4 gs (Histamine M)Tj /F13 1 Tf 0 10 -10 0 69.28 216.555 Tm (D)Tj /F16 1 Tf 0.612 0 TD (s)Tj /F18 1 Tf 0.41 0 TD (R)Tj /F16 1 Tf 0 8 -8 0 69.28 232.694 Tm (aw)Tj 0 10 -10 0 69.28 241.078 Tm ( cmH)Tj 0 8 -8 0 71.548 262.488 Tm (2)Tj 0 10 -10 0 69.28 266.136 Tm (O\341s)Tj 10 0 0 10 61.28 306.429 Tm (a\))Tj ET 3.864 M /GS3 gs 109.364 213.999 4.75 -4.75 re B 122.614 222.249 4.75 -4.75 re B 136.613 232.499 4.75 -4.75 re B 163.613 234.749 4.75 -4.75 re B 190.613 260.624 4.75 -4.75 re B 217.988 308.499 4.75 -4.75 re B 0 0 0 0 k 3.864 M 124.086 214.489 m 124.086 215.766 125.122 216.801 126.399 216.801 c 127.676 216.801 128.711 215.766 128.711 214.489 c 128.711 213.212 127.676 212.176 126.399 212.176 c 125.122 212.176 124.086 213.212 124.086 214.489 c b 136.711 218.364 m 136.711 219.641 137.747 220.676 139.024 220.676 c 140.301 220.676 141.336 219.641 141.336 218.364 c 141.336 217.087 140.301 216.051 139.024 216.051 c 137.747 216.051 136.711 217.087 136.711 218.364 c b 163.961 213.864 m 163.961 215.141 164.996 216.176 166.274 216.176 c 167.551 216.176 168.586 215.141 168.586 213.864 c 168.586 212.587 167.551 211.551 166.274 211.551 c 164.996 211.551 163.961 212.587 163.961 213.864 c b 191.211 214.989 m 191.211 216.266 192.246 217.301 193.524 217.301 c 194.801 217.301 195.836 216.266 195.836 214.989 c 195.836 213.712 194.801 212.676 193.524 212.676 c 192.246 212.676 191.211 213.712 191.211 214.989 c b 218.586 228.614 m 218.586 229.891 219.621 230.926 220.898 230.926 c 222.176 230.926 223.211 229.891 223.211 228.614 c 223.211 227.336 222.176 226.301 220.898 226.301 c 219.621 226.301 218.586 227.336 218.586 228.614 c b 3.864 M 122.905 226.93 m 127.155 226.93 l 125.03 227.055 m 125.03 216.43 l 126.405 212.305 m 126.405 208.805 l 124.53 208.805 m 128.405 208.805 l 136.53 223.18 m 140.78 223.18 l 136.905 213.555 m 140.655 213.555 l 136.905 235.554 m 141.155 235.554 l 139.03 235.804 m 139.03 224.805 l 137.03 225.055 m 140.905 225.055 l 164.155 237.804 m 168.28 237.804 l 166.155 237.93 m 166.155 227.179 l 164.28 227.43 m 168.28 227.43 l 164.155 219.055 m 168.155 219.055 l 164.03 206.555 m 168.405 206.555 l 191.28 219.18 m 196.28 219.18 l 191.03 209.805 m 196.28 209.805 l 218.449 234.555 m 222.949 234.555 l 218.534 223.054 m 222.784 223.054 l 190.78 270.554 m 195.405 270.554 l 192.905 270.804 m 192.905 246.555 l 190.53 246.555 m 195.155 246.555 l 220.529 304.679 m 220.529 260.054 l 218.279 260.304 m 223.154 260.304 l S BT /F22 1 Tf 10 0 0 10 188.155 270.429 Tm 0 0 0 1 k /GS4 gs (**)Tj -2.4375 -3.225 TD (*)Tj ET /GS3 gs 115.28 213.555 m 124.03 219.18 l 126.905 220.93 m 138.53 230.179 l 139.78 230.805 m 165.78 232.555 l 115.905 212.43 m 124.03 213.93 l 128.405 215.055 m 136.78 217.93 l 141.155 218.305 m 163.961 213.864 l 167.78 234.429 m 193.28 258.429 l 168.405 213.43 m 191.03 214.805 l 195.654 215.68 m 218.779 228.304 l 194.28 260.054 m 219.404 305.304 l 502.403 223.429 m 502.403 213.43 l 529.778 242.43 m 529.778 229.93 l S 0 0 0 0 k 3.864 M 444.068 213.423 m 444.068 214.7 445.103 215.735 446.381 215.735 c 447.658 215.735 448.693 214.7 448.693 213.423 c 448.693 212.146 447.658 211.11 446.381 211.11 c 445.103 211.11 444.068 212.146 444.068 213.423 c b 430.844 216.093 m 430.844 217.37 431.879 218.405 433.157 218.405 c 434.434 218.405 435.469 217.37 435.469 216.093 c 435.469 214.815 434.434 213.78 433.157 213.78 c 431.879 213.78 430.844 214.815 430.844 216.093 c b 3.864 M [2 2 ]0 d 405.778 209.752 m 534.278 209.752 l S 3.864 M []0 d 418.969 209.593 m 418.969 210.87 420.004 211.905 421.282 211.905 c 422.559 211.905 423.594 210.87 423.594 209.593 c 423.594 208.315 422.559 207.28 421.282 207.28 c 420.004 207.28 418.969 208.315 418.969 209.593 c b 405.778 312.054 m 405.778 185.805 l 405.778 182.555 m 533.528 182.555 l 405.778 186.003 m 402.278 186.003 l 405.778 209.752 m 402.278 209.752 l 405.778 233.502 m 402.278 233.502 l 405.778 257.252 m 402.278 257.252 l 405.778 281.257 m 402.278 281.257 l 405.778 304.639 m 402.278 304.639 l 418.278 182.68 m 418.278 180.055 l 432.601 182.475 m 432.601 179.85 l 446.585 182.269 m 446.585 179.644 l 473.943 182.439 m 473.943 179.814 l 501.132 182.496 m 501.132 179.871 l 528.32 182.553 m 528.32 179.928 l S BT /F16 1 Tf 10 0 0 10 520.153 169.18 Tm 0 0 0 1 k /GS4 gs (10)Tj 8 0 0 8 529.273 171.448 Tm (-2)Tj 10 0 0 10 493.528 169.156 Tm (10)Tj 8 0 0 8 502.648 171.424 Tm (-4)Tj 10 0 0 10 466.778 169.18 Tm (10)Tj 8 0 0 8 475.898 171.448 Tm (-6)Tj 10 0 0 10 439.403 169.18 Tm (10)Tj 8 0 0 8 448.523 171.448 Tm (-8)Tj 10 0 0 10 430.278 169.18 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 439.778 163.68 m 534.653 163.68 l S BT 10 0 0 10 462.653 152.805 Tm /GS4 gs (Histamine M)Tj ET 3.864 M /GS3 gs 416.737 211.875 4.75 -4.75 re B 429.237 218.374 4.75 -4.75 re B 442.487 213.375 4.75 -4.75 re B 470.861 222.749 4.75 -4.75 re B 499.236 230.374 4.75 -4.75 re B 526.236 253.624 4.75 -4.75 re B 0 0 0 0 k 3.864 M 472.693 205.798 m 472.693 207.075 473.728 208.11 475.005 208.11 c 476.282 208.11 477.318 207.075 477.318 205.798 c 477.318 204.521 476.282 203.485 475.005 203.485 c 473.728 203.485 472.693 204.521 472.693 205.798 c b 500.193 218.923 m 500.193 220.2 501.228 221.235 502.505 221.235 c 503.782 221.235 504.818 220.2 504.818 218.923 c 504.818 217.646 503.782 216.61 502.505 216.61 c 501.228 216.61 500.193 217.646 500.193 218.923 c b 527.443 236.298 m 527.443 237.575 528.478 238.61 529.755 238.61 c 531.032 238.61 532.068 237.575 532.068 236.298 c 532.068 235.02 531.032 233.985 529.755 233.985 c 528.478 233.985 527.443 235.02 527.443 236.298 c b 3.864 M 526.278 259.304 m 530.278 259.304 l 528.278 259.554 m 528.278 242.929 l 526.278 242.929 m 530.153 242.929 l 528.028 242.304 m 531.653 242.304 l 527.278 230.055 m 531.903 230.055 l 499.778 233.179 m 504.153 233.179 l 501.761 233.304 m 501.761 223.68 l 499.502 223.727 m 504.127 223.727 l 500.528 223.18 m 504.528 223.18 l 500.528 213.43 m 504.653 213.43 l 471.278 229.93 m 475.528 229.93 l 473.403 229.93 m 473.403 211.055 l 471.403 211.305 m 475.153 211.305 l 473.403 214.18 m 476.528 214.18 l 474.778 214.18 m 474.778 208.11 l 475.005 203.485 m 475.005 197.805 l 473.153 197.93 m 477.278 197.93 l 443.075 220.429 m 447.2 220.429 l 445.16 220.68 m 445.16 215.805 l 445.217 215.805 m 445.217 202.68 l 443.12 202.68 m 447.495 202.68 l 446.381 215.735 m 446.381 219.43 l 448.028 219.43 m 444.778 219.43 l 448.528 208.555 m 446.028 208.555 l 446.552 208.68 m 446.552 211.555 l 431.528 218.055 m 431.528 221.805 l 433.403 221.929 m 429.903 221.929 l 431.528 218.805 m 431.528 210.93 l 433.278 211.055 m 429.778 211.055 l 431.528 220.93 m 434.778 220.93 l 433.278 221.055 m 433.278 210.43 l 434.778 210.555 m 431.528 210.555 l 422.528 211.43 m 430.778 215.18 l 422.903 211.055 m 430.153 214.555 l 435.469 216.093 m 444.153 214.43 l 435.278 216.18 m 442.653 212.68 l 448.528 213.18 m 471.403 219.555 l 448.778 213.805 m 472.778 206.305 l 475.278 220.93 m 501.153 228.304 l 476.903 207.18 m 500.193 218.923 l 503.153 229.68 m 527.903 250.679 l 504.153 220.429 m 527.528 235.68 l 279.246 232.305 m 279.246 204.555 l 281.463 219.805 m 281.463 207.68 l 294.63 223.305 m 294.63 213.055 l 320.904 219.304 m 320.904 210.68 l 347.029 224.43 m 347.029 216.93 l 374.029 244.179 m 374.029 229.429 l S [2 2 ]0 d 253.029 212.128 m 379.904 212.128 l S 3.864 M []0 d 265.923 212.331 m 265.923 213.608 266.958 214.643 268.235 214.643 c 269.512 214.643 270.548 213.608 270.548 212.331 c 270.548 211.054 269.512 210.018 268.235 210.018 c 266.958 210.018 265.923 211.054 265.923 212.331 c b 253.029 314.429 m 253.029 188.18 l 253.029 184.93 m 380.779 184.93 l 253.029 188.378 m 249.529 188.378 l 253.029 212.128 m 249.529 212.128 l 253.029 235.878 m 249.529 235.878 l 253.029 259.627 m 249.529 259.627 l 253.029 283.632 m 249.529 283.632 l 253.029 307.014 m 249.529 307.014 l 265.529 185.055 m 265.529 182.43 l 279.852 184.85 m 279.852 182.225 l 293.836 184.644 m 293.836 182.019 l 321.194 184.814 m 321.194 182.189 l 348.383 184.871 m 348.383 182.246 l 375.571 184.927 m 375.571 182.302 l S BT 10 0 0 10 367.404 171.555 Tm 0 0 0 1 k /GS4 gs (10)Tj 8 0 0 8 376.524 173.822 Tm (-2)Tj 10 0 0 10 340.779 171.531 Tm (10)Tj 8 0 0 8 349.899 173.799 Tm (-4)Tj 10 0 0 10 314.029 171.555 Tm (10)Tj 8 0 0 8 323.149 173.822 Tm (-6)Tj 10 0 0 10 286.654 171.555 Tm (10)Tj 8 0 0 8 295.774 173.822 Tm (-8)Tj 10 0 0 10 277.529 171.555 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 287.029 166.055 m 381.904 166.055 l S BT 10 0 0 10 309.904 155.18 Tm /GS4 gs (Histamine M)Tj ET 3.864 M /GS3 gs 263.738 214.749 4.75 -4.75 re B 276.738 221.124 4.75 -4.75 re B 290.238 234.624 4.75 -4.75 re B 316.113 234.624 4.75 -4.75 re B 342.362 264.624 4.75 -4.75 re B 368.987 305.499 4.75 -4.75 re B 0 0 0 0 k 3.864 M 279.048 214.331 m 279.048 215.608 280.083 216.643 281.36 216.643 c 282.637 216.643 283.673 215.608 283.673 214.331 c 283.673 213.054 282.637 212.018 281.36 212.018 c 280.083 212.018 279.048 213.054 279.048 214.331 c b 292.423 217.831 m 292.423 219.108 293.458 220.143 294.735 220.143 c 296.012 220.143 297.048 219.108 297.048 217.831 c 297.048 216.554 296.012 215.518 294.735 215.518 c 293.458 215.518 292.423 216.554 292.423 217.831 c b 318.673 215.456 m 318.673 216.733 319.708 217.768 320.985 217.768 c 322.262 217.768 323.298 216.733 323.298 215.456 c 323.298 214.179 322.262 213.143 320.985 213.143 c 319.708 213.143 318.673 214.179 318.673 215.456 c b 344.672 220.831 m 344.672 222.108 345.708 223.143 346.985 223.143 c 348.262 223.143 349.297 222.108 349.297 220.831 c 349.297 219.554 348.262 218.518 346.985 218.518 c 345.708 218.518 344.672 219.554 344.672 220.831 c b 371.797 237.081 m 371.797 238.358 372.833 239.393 374.11 239.393 c 375.387 239.393 376.422 238.358 376.422 237.081 c 376.422 235.804 375.387 234.768 374.11 234.768 c 372.833 234.768 371.797 235.804 371.797 237.081 c b 3.864 M 372.279 244.054 m 376.029 244.054 l 371.904 229.578 m 376.154 229.578 l 345.029 224.305 m 349.279 224.305 l 344.899 217.055 m 349.274 217.055 l 319.029 219.055 m 323.154 219.055 l 323.154 210.805 m 318.529 210.805 l 315.654 245.805 m 321.529 245.805 l 318.779 245.929 m 318.779 218.929 l 316.404 219.18 m 321.029 219.18 l 292.965 223.18 m 296.59 223.18 l 292.805 213.18 m 296.555 213.18 l 290.154 239.679 m 295.529 239.679 l 292.746 239.679 m 292.746 224.305 l 290.279 224.305 m 295.279 224.305 l 342.779 270.929 m 347.654 270.929 l 345.029 271.054 m 345.029 254.554 l 342.779 254.804 m 347.904 254.804 l 371.279 301.304 m 371.279 284.554 l 368.654 284.929 m 374.404 284.929 l S BT /F22 1 Tf 10 0 0 10 366.404 305.554 Tm 0 0 0 1 k /GS4 gs (**)Tj -2.625 -3.375 TD (**)Tj ET /GS3 gs 277.029 232.18 m 282.029 232.18 l 277.154 204.805 m 282.279 204.805 l 281.154 219.679 m 283.029 219.679 l 279.859 207.805 m 283.359 207.805 l 269.529 214.305 m 277.404 218.055 l 280.779 220.68 m 291.279 231.18 l 270.529 212.805 m 279.029 214.18 l 283.654 214.805 m 292.404 217.305 l 297.029 218.18 m 318.673 215.456 l 293.529 232.18 m 317.279 232.054 l 323.279 215.68 m 344.529 220.555 l 349.154 221.68 m 372.154 236.304 l 320.154 234.429 m 344.279 261.679 l 345.904 263.679 m 370.404 301.929 l S BT /F16 1 Tf 10 0 0 10 232.779 306.429 Tm /GS4 gs [(b\))-14721(c\))]TJ /F3 1 Tf 7.97 0 0 7.97 58.28 138.387 Tm 0 g /GS2 gs [(Fig.)-327.1(3.)-331.2(\261)-332.2(T)35(ime)-215.9(course)-214.4(of)-216.5(changes)-211.1(in)-218.7(nasal)-211.5(responsive)11(ness)-213.5(to)-218.7(histamine:)-215.6(a\))-215.5(10)-216.3(h;)-211.6(b\))-216.5(2)-218.4(days;)-212.6(and)-213.2(c\))-222.6(7)-211.3(days)-219.4(after)-210.7(the)-215.6(24th)-214.5(cedar)-214.2(pollen)-211.7(inhalation)-214.1(challenge)-209.4(in)]TJ 0 -1.067 TD [(sensitized)-262.9(\()]TJ /F5 1 Tf 4.4813 0 TD (&)Tj /F3 1 Tf 0.9958 0 TD [(\))-268.4(and)-270.1(nonsensitize)11.6(d)-275.3(\()]TJ /F19 1 Tf 8.2726 0 TD (s)Tj /F3 1 Tf 0.8322 0 TD [(\))-268.4(guinea-pig)11(s.)-275.5(Data)-264.8(are)-269.3(presented)-266.3(as)-273.4(mean\213)]TJ 5.579 0 0 5.579 311.131 129.883 Tm (SEM)Tj 7.97 0 0 7.97 324.737 129.883 Tm (\(n)Tj /F8 1 Tf 0.818 0 TD (=)Tj /F3 1 Tf 0.5477 0 TD [(12\).)-270.2(Specific)-267.4(airway)-267.8(resistance)10.6(s)-276.5(\()0(s)]TJ /F4 1 Tf 13.5221 0 TD (R)Tj /F3 1 Tf 6.376 0 0 6.376 448.214 129.883 Tm (aw)Tj 7.97 0 0 7.97 455.584 129.883 Tm [(\))-268.4(before)-270.2(saline)-268.7(instillation)]TJ -49.8489 -1.0599 TD [(\(B\))-247.7(were)-241.2(1.50\2130.13)-233.8(and)-241.6(1.88\2130.15)-233.8(cmH)]TJ 5.977 0 0 5.313 184.762 120.076 Tm (2)Tj 7.97 0 0 7.97 187.71 121.436 Tm (O)Tj /F10 1 Tf 0.7184 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD 0.2481 Tc (s\()Tj 5.579 0 0 5.579 203.187 121.436 Tm 0 Tc (NS)Tj 7.97 0 0 7.97 210.274 121.436 Tm [(\))-247.1(i)0(n)-247.2(nonsens)13.3(itized)-248.6(and)-241.7(sensitized)-234.4(animals)-245.6(\(a\),)-240.9(1.56\2130.13)-233.8(and)-248.8(1.36\2130.08)-233.8(cmH)]TJ 5.977 0 0 5.313 449.858 120.076 Tm (2)Tj 7.97 0 0 7.97 452.863 121.436 Tm (O)Tj /F10 1 Tf 0.7113 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD 0.2481 Tc (s\()Tj 5.579 0 0 5.579 468.283 121.436 Tm 0 Tc (NS)Tj 7.97 0 0 7.97 475.37 121.436 Tm [(\))-247.1(\(b\))-243(and)-248.8(1.71\2130.12)]TJ -52.3313 -1.0599 TD [(and)-327(1.64\2130.09)-326.3(cmH)]TJ 5.977 0 0 5.313 122.457 111.628 Tm (2)Tj 7.97 0 0 7.97 125.405 112.989 Tm (O)Tj /F10 1 Tf 0.7184 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD 0.3334 Tc (s\()Tj 5.579 0 0 5.579 141.562 112.989 Tm 0 Tc (NS)Tj 7.97 0 0 7.97 148.649 112.989 Tm [(\))-339.5(\(c\).)]TJ /F11 1 Tf 2.3189 0 TD (D)Tj /F3 1 Tf 0.6686 0 TD [(:)-327.5(change;)-326(S:)-337.4(saline)-325.7(instillation.)-324.9(*,**:)-334.4(p)]TJ /F8 1 Tf 15.4284 0 TD (<)Tj /F3 1 Tf 0.5477 0 TD [(0.05,)-325.9(p)]TJ /F8 1 Tf 2.8239 0 TD (<)Tj /F3 1 Tf 0.5548 0 TD [(0.01)-327(compared)-322(to)-332.5(the)-329.4(nonsensitized)-320.6(group.)]TJ ET /GS3 gs 277.892 705.631 m 277.892 692.881 l 242.142 686.256 m 242.142 679.881 l 206.581 685.131 m 206.581 676.506 l 170.609 686.506 m 170.609 676.131 l 152.767 686.381 m 152.767 669.381 l S [2 2 ]0 d 113.768 674.48 m 288.267 674.48 l S 0 0 0 0 k 3.864 M []0 d 131.83 674.245 m 131.83 675.523 132.865 676.558 134.142 676.558 c 135.42 676.558 136.455 675.523 136.455 674.245 c 136.455 672.968 135.42 671.933 134.142 671.933 c 132.865 671.933 131.83 672.968 131.83 674.245 c b 113.893 777.631 m 113.893 649.381 l 113.893 646.881 m 288.392 646.881 l 113.768 773.631 m 108.893 773.631 l 113.768 748.631 m 108.893 748.631 l 113.768 723.914 m 108.893 723.914 l 113.768 699.197 m 108.893 699.197 l 113.768 674.48 m 108.893 674.48 l 113.909 649.679 m 109.034 649.679 l S BT /F16 1 Tf 10 0 0 10 91.541 647.513 Tm 0 0 0 1 k /GS4 gs (-0.3)Tj 0.9101 2.3868 TD (0)Tj -0.6375 2.5125 TD -0.0009 Tc (0.3)Tj -0.0125 2.45 TD 0 Tc (0.6)Tj ET 3.864 M /GS3 gs 272.892 755.631 4.75 -4.75 re B BT 10 0 0 10 93.643 745.631 Tm /GS4 gs (0.9)Tj 0.075 2.475 TD (1.2)Tj /F13 1 Tf 0 10 -10 0 74.893 682.631 Tm (D)Tj /F16 1 Tf 0.612 0 TD (s)Tj /F18 1 Tf 0.41 0 TD (R)Tj /F16 1 Tf 0 8 -8 0 74.893 698.771 Tm (aw)Tj 0 10 -10 0 74.893 707.155 Tm ( cmH)Tj 0 8 -8 0 77.16 728.564 Tm (2)Tj 0 10 -10 0 74.893 732.212 Tm (O\341s)Tj 10 0 0 10 66.893 770.881 Tm (a\))Tj ET 3.864 M /GS3 gs 132.767 646.881 m 132.767 644.131 l 150.142 646.881 m 150.142 644.131 l 170.267 646.881 m 170.267 644.131 l 204.392 646.881 m 204.392 644.131 l 239.892 646.881 m 239.892 644.131 l 274.458 646.881 m 274.458 644.131 l S BT 10 0 0 10 266.392 632.881 Tm /GS4 gs (10)Tj 8 0 0 8 275.512 635.149 Tm (-2)Tj 10 0 0 10 231.267 632.881 Tm (10)Tj 8 0 0 8 240.387 635.149 Tm (-4)Tj 10 0 0 10 196.392 632.631 Tm (10)Tj 8 0 0 8 205.512 634.899 Tm (-6)Tj 10 0 0 10 161.517 632.631 Tm (10)Tj 8 0 0 8 170.637 634.899 Tm (-8)Tj 10 0 0 10 147.767 632.881 Tm (S)Tj -1.7125 0 TD (B)Tj ET /GS3 gs 162.517 628.506 m 288.267 628.506 l S BT 10 0 0 10 198.642 614.381 Tm /GS4 gs (Histamine M)Tj ET 3.864 M /GS3 gs 237.142 722.131 4.75 -4.75 re B 201.267 694.131 4.75 -4.75 re B 165.267 696.131 4.75 -4.75 re B 147.142 684.756 4.75 -4.75 re B 129.143 676.631 4.75 -4.75 re B 0 0 0 0 k 3.864 M 275.704 699.194 m 275.704 700.471 276.739 701.506 278.017 701.506 c 279.294 701.506 280.329 700.471 280.329 699.194 c 280.329 697.917 279.294 696.881 278.017 696.881 c 276.739 696.881 275.704 697.917 275.704 699.194 c b 239.829 682.944 m 239.829 684.221 240.865 685.256 242.142 685.256 c 243.419 685.256 244.454 684.221 244.454 682.944 c 244.454 681.667 243.419 680.631 242.142 680.631 c 240.865 680.631 239.829 681.667 239.829 682.944 c b 204.33 680.444 m 204.33 681.721 205.365 682.756 206.642 682.756 c 207.919 682.756 208.955 681.721 208.955 680.444 c 208.955 679.167 207.919 678.131 206.642 678.131 c 205.365 678.131 204.33 679.167 204.33 680.444 c b 168.33 681.318 m 168.33 682.596 169.365 683.631 170.642 683.631 c 171.919 683.631 172.955 682.596 172.955 681.318 c 172.955 680.042 171.919 679.006 170.642 679.006 c 169.365 679.006 168.33 680.042 168.33 681.318 c b 150.705 677.944 m 150.705 679.221 151.74 680.256 153.017 680.256 c 154.295 680.256 155.33 679.221 155.33 677.944 c 155.33 676.667 154.295 675.631 153.017 675.631 c 151.74 675.631 150.705 676.667 150.705 677.944 c b 3.864 M 146.642 693.881 m 152.017 693.881 l 149.267 694.006 m 149.267 670.631 l 146.767 670.756 m 151.892 670.756 l 150.142 686.256 m 155.142 686.256 l 150.392 669.53 m 155.267 669.53 l 164.642 701.381 m 170.142 701.381 l 167.392 701.631 m 167.392 686.131 l 164.767 686.381 m 169.267 686.381 l 168.892 686.381 m 173.392 686.381 l 168.267 676.256 m 173.517 676.256 l 201.142 703.381 m 206.267 703.381 l 203.517 703.381 m 203.642 679.881 l 204.267 684.881 m 209.267 684.881 l 204.017 676.506 m 209.392 676.506 l 239.932 686.216 m 244.932 686.216 l 239.944 679.78 m 244.694 679.78 l 275.267 705.381 m 280.392 705.381 l 275.267 693.001 m 280.392 693.001 l 272.767 772.506 m 278.267 772.506 l 275.392 772.63 m 275.392 733.131 l 272.42 733.256 m 277.92 733.256 l 236.904 729.397 m 242.154 729.397 l 239.392 729.631 m 239.392 710.506 l 236.767 710.756 m 242.017 710.756 l S BT /F22 1 Tf 10 0 0 10 225.892 718.006 Tm 0 0 0 1 k /GS4 gs (**)Tj 3.6125 3.3375 TD (**)Tj ET /GS3 gs 135.518 676.256 m 147.517 681.381 l 136.268 674.881 m 151.017 677.381 l 151.642 683.256 m 166.517 692.881 l 155.392 678.131 m 168.392 680.756 l 169.267 693.881 m 202.392 692.506 l 172.892 681.131 m 204.267 680.256 l 208.955 680.444 m 239.829 682.944 l 204.767 693.506 m 237.517 718.881 l 244.267 683.381 m 275.767 698.506 l 241.142 721.756 m 274.517 752.006 l 520.89 707.506 m 520.89 695.506 l 484.221 699.881 m 484.221 685.256 l 447.999 692.381 m 447.999 680.506 l 411.766 681.506 m 411.766 667.631 l 394.141 685.006 m 394.141 671.506 l S [2 2 ]0 d 354.87 674.912 m 529.015 674.912 l S 0 0 0 0 k 3.864 M []0 d 373.329 674.444 m 373.329 675.721 374.364 676.756 375.641 676.756 c 376.918 676.756 377.954 675.721 377.954 674.444 c 377.954 673.167 376.918 672.131 375.641 672.131 c 374.364 672.131 373.329 673.167 373.329 674.444 c b 354.891 777.381 m 354.891 649.131 l 354.891 646.631 m 529.39 646.631 l S BT /F16 1 Tf 10 0 0 10 372.58 632.881 Tm 0 0 0 1 k /GS4 gs 1.2716 Tc [(BS)643.6(1)1271.6(0)]TJ 8 0 0 8 411.636 635.149 Tm 0 Tc (-8)Tj 10 0 0 10 437.516 632.881 Tm (10)Tj 8 0 0 8 446.636 635.149 Tm (-6)Tj 10 0 0 10 473.391 632.631 Tm (10)Tj 8 0 0 8 482.511 634.899 Tm (-4)Tj 10 0 0 10 509.89 632.631 Tm (10)Tj 8 0 0 8 519.01 634.899 Tm (-2)Tj ET /GS3 gs 375.082 646.648 m 375.082 643.898 l 392.832 646.648 m 392.832 643.898 l 410.582 646.648 m 410.582 643.898 l 446.082 646.648 m 446.082 643.898 l 482.204 646.648 m 482.204 643.898 l 518.525 646.648 m 518.525 643.898 l 404.516 628.631 m 529.515 628.631 l S BT 10 0 0 10 449.025 614.131 Tm /GS4 gs (MCh M)Tj ET /GS3 gs 354.903 649.412 m 350.028 649.412 l 354.87 674.912 m 349.995 674.912 l 354.837 699.534 m 349.962 699.534 l 354.804 723.93 m 349.929 723.93 l 354.771 748.609 m 349.896 748.609 l 354.738 773.402 m 349.863 773.402 l S BT 10 0 0 10 330.767 770.881 Tm /GS4 gs -0.0163 Tc (b\))Tj ET 3.864 M /GS3 gs 370.641 676.756 4.75 -4.75 re B 388.391 687.631 4.75 -4.75 re B 406.266 686.881 4.75 -4.75 re B 442.016 694.506 4.75 -4.75 re B 478.391 705.881 4.75 -4.75 re B 515.515 717.881 4.75 -4.75 re B 0 0 0 0 k 3.864 M 518.64 701.444 m 518.64 702.721 519.676 703.756 520.953 703.756 c 522.23 703.756 523.266 702.721 523.266 701.444 c 523.266 700.167 522.23 699.131 520.953 699.131 c 519.676 699.131 518.64 700.167 518.64 701.444 c b 481.828 692.319 m 481.828 693.596 482.863 694.631 484.141 694.631 c 485.418 694.631 486.453 693.596 486.453 692.319 c 486.453 691.042 485.418 690.006 484.141 690.006 c 482.863 690.006 481.828 691.042 481.828 692.319 c b 445.703 685.818 m 445.703 687.096 446.739 688.131 448.016 688.131 c 449.293 688.131 450.328 687.096 450.328 685.818 c 450.328 684.541 449.293 683.506 448.016 683.506 c 446.739 683.506 445.703 684.541 445.703 685.818 c b 391.829 677.944 m 391.829 679.221 392.864 680.256 394.141 680.256 c 395.418 680.256 396.454 679.221 396.454 677.944 c 396.454 676.667 395.418 675.631 394.141 675.631 c 392.864 675.631 391.829 676.667 391.829 677.944 c b 409.453 674.694 m 409.453 675.971 410.489 677.006 411.766 677.006 c 413.043 677.006 414.078 675.971 414.078 674.694 c 414.078 673.417 413.043 672.381 411.766 672.381 c 410.489 672.381 409.453 673.417 409.453 674.694 c b 3.864 M 388.141 692.131 m 393.266 692.131 l 390.641 692.256 m 390.641 678.381 l 388.016 678.631 m 391.766 678.631 l 393.141 684.881 m 395.391 684.881 l 391.266 671.631 m 396.266 671.631 l 406.141 690.881 m 411.016 690.881 l 408.516 691.006 m 408.516 678.131 l 406.391 678.006 m 410.766 678.006 l 409.978 681.381 m 413.853 681.381 l 409.676 667.756 m 414.176 667.756 l 442.141 697.881 m 446.766 697.881 l 444.391 698.006 m 444.391 686.381 l 442.266 686.381 m 445.766 686.381 l 447.141 692.131 m 450.266 692.131 l 446.266 680.631 m 450.016 680.631 l 482.141 699.756 m 486.641 699.756 l 482.141 685.256 m 486.516 685.256 l 478.891 713.256 m 483.641 713.256 l 480.943 713.506 m 480.943 693.631 l 478.891 693.756 m 482.266 693.756 l 518.89 707.381 m 523.641 707.381 l 518.265 695.506 m 523.641 695.506 l 515.64 731.256 m 520.39 731.256 l 517.89 731.381 m 517.89 699.756 l 515.89 699.881 m 519.141 699.881 l 376.266 676.631 m 390.391 684.756 l 377.891 674.631 m 391.891 677.381 l 392.641 685.256 m 407.891 684.631 l 396.391 677.631 m 409.453 674.694 l 410.516 684.881 m 444.391 692.131 l 413.891 674.881 m 445.766 685.131 l 446.641 692.631 m 480.391 703.131 l 450.391 686.006 m 482.016 691.881 l 481.891 703.881 m 516.64 715.006 l 486.391 692.506 m 519.015 700.506 l S BT /F3 1 Tf 7.97 0 0 7.97 58.28 599.584 Tm 0 g /GS2 gs 0 Tc [(Fig.)-327.1(2.)-331.2(\261)-332.2(Nasal)-278.1(respons)13.2(iveness)-279.7(to:)-275.9(a\))-279.5(histamine;)-272.5(and)-277.2(b\))-273.4(methacholin)11.6(e)-281.4(\(MCh\))-271.1(in)-282.7(sensitized)-270(\()]TJ /F5 1 Tf 36.1916 0 TD (&)Tj /F3 1 Tf 1.003 0 TD [(\))-275.5(and)-277.2(nonsensiti)12.5(zed)-276.2(\()]TJ /F19 1 Tf 8.2939 0 TD (s)Tj /F3 1 Tf 0.8322 0 TD [(\))-275.5(guinea-pig)11(s)-283.6(2)-275.3(days)-276.3(after)-274.7(the)-279.6(20th)]TJ -46.3207 -1.0599 TD [(\(histamine\))-325.3(or)-330.3(the)-329.4(22nd)-325.9(cedar)-328.1(pollen)-325.5(inhalation)-327.9(challenge)-323.2(\(MCh\).)-326.9(Data)-328.8(are)-326.2(presented)-323.2(as)-330.3(mean\213)]TJ 5.579 0 0 5.579 364.422 591.137 Tm (SEM)Tj 7.97 0 0 7.97 378.482 591.137 Tm (\(n)Tj /F8 1 Tf 0.818 0 TD (=)Tj /F3 1 Tf 0.5548 0 TD [(12\).)-327.1(Specific)-324.3(airway)-324.7(resistances)-329.9(\(s)]TJ /F4 1 Tf 13.7568 0 TD (R)Tj /F3 1 Tf 6.376 0 0 6.376 503.886 591.137 Tm (aw)Tj 7.97 0 0 7.97 511.257 591.137 Tm [(\))-332.4(before)]TJ -56.8339 -1.067 TD [(saline)-261.6(instillation)-254.9(\(B\))-262(were)-262.5(1.76\2130.21)-248(and)-263(1.79\2130.09)-255.2(cmH)]TJ 5.977 0 0 5.313 241.455 581.329 Tm (2)Tj 7.97 0 0 7.97 244.403 582.633 Tm (O)Tj /F10 1 Tf 0.7184 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD 0.2623 Tc (s\()Tj 5.579 0 0 5.579 259.994 582.633 Tm 0 Tc (NS)Tj 7.97 0 0 7.97 267.137 582.633 Tm [(\))-261.3(for)-264.4(nonsens)13.3(itized)-262.8(and)-255.9(sensitized)-262.9(animals)-252.7(\(a\))-263.3(and)-263(1.81\2130.13)-248(and)-263(1.94\2130.17)-255.1(cmH)]TJ 5.977 0 0 5.313 522.595 581.329 Tm (2)Tj 7.97 0 0 7.97 525.543 582.633 Tm (O)Tj /F10 1 Tf 0.7184 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD (s)Tj -59.6152 -1.0599 TD (\()Tj 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355.476 227.942 m 355.476 211.067 l 366.226 228.192 m 366.226 216.067 l 378.476 229.442 m 378.476 215.067 l 390.601 229.317 m 390.601 215.192 l 402.476 228.317 m 402.476 213.692 l 425.976 222.567 m 425.976 208.192 l 461.499 223.817 m 461.499 203.942 l 497.317 231.692 m 497.317 217.942 l 532.85 224.067 m 532.85 214.692 l 341.976 328.316 m 341.976 198.567 l 341.976 195.567 m 514.225 195.567 l 518.225 195.567 m 537.975 195.567 l 513.43 192.942 m 515.18 197.942 l 517.35 192.881 m 519.1 197.88 l 532.6 195.817 m 532.6 192.817 l 497.35 195.567 m 497.35 192.817 l 461.476 195.567 m 461.476 192.817 l 426.476 195.567 m 426.476 192.817 l 402.101 195.567 m 402.101 192.817 l 390.726 195.567 m 390.726 192.817 l 378.412 195.567 m 378.412 192.817 l 366.226 195.567 m 366.226 192.817 l 354.351 195.567 m 354.351 192.817 l 414.226 195.567 m 414.226 192.817 l 438.476 195.567 m 438.476 192.817 l 450.976 195.567 m 450.976 192.817 l 473.226 195.567 m 473.226 192.817 l 485.975 195.817 m 485.975 193.067 l S BT /F16 1 Tf 10 0 0 10 352.226 182.067 Tm 0 0 0 1 k /GS4 gs 0.719 Tc [(12)-50(3)-62.5(4)-12.5(5)75(6)-12.5(7)]TJ 8.4375 -0.025 TD 0 Tc (8)Tj 1.225 0.025 TD 0.3815 Tc [(91)381.5(0)118.5(1)441.5(1)83.5(1)381.5(2)93.5(1)381.5(3)-2306.5(2)381.5(0)]TJ -4.3125 -2.1625 TD -0.0009 Tc -0.001 Tw (Allergen challenge No.)Tj /F13 1 Tf 0 10 -10 0 317.674 236.066 Tm 0 Tc 0 Tw (D)Tj /F16 1 Tf 0.612 0 TD (s)Tj /F18 1 Tf 0.41 0 TD (R)Tj /F16 1 Tf 0 8 -8 0 317.674 252.206 Tm (aw)Tj 0 10 -10 0 317.674 260.59 Tm ( cmH)Tj 0 8 -8 0 319.942 282 Tm (2)Tj 0 10 -10 0 317.674 285.648 Tm (O\341s)Tj ET /GS3 gs 341.976 198.85 m 339.226 198.85 l 341.976 212.1 m 339.226 212.1 l 341.976 226.475 m 339.226 226.475 l 341.976 239.975 m 339.226 239.975 l 341.976 254.1 m 339.226 254.1 l 341.976 267.6 m 339.226 267.6 l 341.976 281.725 m 339.226 281.725 l 341.976 295.595 m 339.226 295.595 l 341.976 309.691 m 339.226 309.691 l 341.976 323.788 m 339.226 323.788 l S BT 10 0 0 10 325.351 320.566 Tm /GS4 gs -0.0134 Tc (0.8)Tj 0 -1.45 TD -0.0009 Tc (0.7)Tj -0.025 -1.35 TD (0.6)Tj 0.025 -1.375 TD (0.5)Tj -0.0375 -1.3625 TD 0 Tc (0.4)Tj 0 -2.825 TD (0.2)Tj 0.175 -1.4375 TD -0.0196 Tc (0.1)Tj 0.4625 -1.35 TD 0 Tc (0)Tj -0.7774 -1.3056 TD (-0.1)Tj ET 0 0 0 0 k /GS3 gs 364.06 222.143 m 364.06 223.42 365.095 224.456 366.372 224.456 c 367.649 224.456 368.685 223.42 368.685 222.143 c 368.685 220.866 367.649 219.831 366.372 219.831 c 365.095 219.831 364.06 220.866 364.06 222.143 c b 0 0 0 1 k 3.864 M 351.497 242.779 4.75 -4.75 re B 364.372 249.154 4.75 -4.75 re B 376.122 247.654 4.75 -4.75 re B 388.122 254.029 4.75 -4.75 re B 399.122 253.529 4.75 -4.75 re B 423.747 260.404 4.75 -4.75 re B 459.247 270.029 4.75 -4.75 re B 495.496 286.778 4.75 -4.75 re B 531.371 297.904 4.75 -4.75 re B 0 0 0 0 k 3.864 M 353.06 219.268 m 353.06 220.545 354.095 221.581 355.372 221.581 c 356.649 221.581 357.685 220.545 357.685 219.268 c 357.685 217.991 356.649 216.956 355.372 216.956 c 354.095 216.956 353.06 217.991 353.06 219.268 c b 376.06 222.268 m 376.06 223.545 377.095 224.58 378.372 224.58 c 379.649 224.58 380.685 223.545 380.685 222.268 c 380.685 220.991 379.649 219.956 378.372 219.956 c 377.095 219.956 376.06 220.991 376.06 222.268 c b 388.185 222.018 m 388.185 223.295 389.22 224.331 390.497 224.331 c 391.774 224.331 392.809 223.295 392.809 222.018 c 392.809 220.741 391.774 219.706 390.497 219.706 c 389.22 219.706 388.185 220.741 388.185 222.018 c b 400.059 220.893 m 400.059 222.17 401.095 223.206 402.372 223.206 c 403.649 223.206 404.684 222.17 404.684 220.893 c 404.684 219.616 403.649 218.581 402.372 218.581 c 401.095 218.581 400.059 219.616 400.059 220.893 c b 423.684 215.518 m 423.684 216.795 424.72 217.831 425.997 217.831 c 427.274 217.831 428.309 216.795 428.309 215.518 c 428.309 214.241 427.274 213.206 425.997 213.206 c 424.72 213.206 423.684 214.241 423.684 215.518 c b 494.934 224.643 m 494.934 225.92 495.969 226.956 497.246 226.956 c 498.524 226.956 499.559 225.92 499.559 224.643 c 499.559 223.366 498.524 222.33 497.246 222.33 c 495.969 222.33 494.934 223.366 494.934 224.643 c b 530.559 219.268 m 530.559 220.545 531.594 221.581 532.871 221.581 c 534.148 221.581 535.183 220.545 535.183 219.268 c 535.183 217.991 534.148 216.956 532.871 216.956 c 531.594 216.956 530.559 217.991 530.559 219.268 c b 459.059 214.768 m 459.059 216.045 460.094 217.081 461.372 217.081 c 462.649 217.081 463.684 216.045 463.684 214.768 c 463.684 213.491 462.649 212.456 461.372 212.456 c 460.094 212.456 459.059 213.491 459.059 214.768 c b 530.862 224.027 m 535.362 224.027 l 530.6 214.942 m 535.1 214.942 l 495.725 231.567 m 499.475 231.567 l 495.225 217.942 m 499.6 217.942 l 459.584 223.817 m 463.959 223.817 l 459.601 204.067 m 463.851 204.067 l 423.976 222.317 m 428.226 222.317 l 423.851 208.317 m 427.851 208.317 l 400.601 228.067 m 404.601 228.067 l 400.351 214.067 m 404.476 214.067 l 388.726 229.192 m 392.601 229.192 l 388.601 215.317 m 392.476 215.317 l 376.476 229.317 m 380.601 229.317 l 376.476 215.317 m 380.351 215.317 l 364.351 228.067 m 368.101 228.067 l 364.476 216.192 m 368.226 216.192 l 354.101 227.817 m 357.601 227.817 l 353.476 211.192 m 356.851 211.192 l 351.976 254.191 m 355.851 254.191 l 353.976 254.317 m 353.976 226.317 l 352.101 226.317 m 355.476 226.317 l 364.851 254.816 m 368.476 254.816 l 366.601 254.941 m 366.601 238.316 l 364.726 238.316 m 368.351 238.316 l 376.351 253.942 m 379.851 253.942 l 377.976 254.191 m 377.976 236.942 l 376.226 236.942 m 380.101 236.942 l 388.351 258.691 m 392.226 258.691 l 390.226 258.817 m 390.226 244.316 l 388.351 244.442 m 392.476 244.442 l 399.726 262.567 m 403.726 262.567 l 401.726 262.691 m 401.726 240.067 l 399.726 240.191 m 403.851 240.191 l 423.601 269.441 m 428.101 269.441 l 425.976 269.566 m 425.976 246.692 l 423.726 246.941 m 428.726 246.941 l 459.475 274.691 m 463.851 274.691 l 461.601 274.816 m 461.601 261.067 l 459.475 261.191 m 464.1 261.191 l 495.225 294.441 m 499.85 294.441 l 497.6 294.566 m 497.6 274.441 l 495.475 274.691 m 499.975 274.691 l 531.6 321.191 m 535.85 321.191 l 533.6 321.316 m 533.6 270.691 l 531.225 270.566 m 536.1 270.566 l S BT /F22 1 Tf 10 0 0 10 493.35 295.066 Tm 0 0 0 1 k /GS4 gs (**)Tj 3.775 2.675 TD (*)Tj -7.4125 -4.625 TD (**)Tj -3.5875 -0.5625 TD (**)Tj -3.575 -1.1375 TD (**)Tj 1.3875 0.4125 TD (*)Tj ET 3.864 M [2 2 ]0 d /GS3 gs 341.976 212.1 m 514.725 212.1 l 518.225 211.942 m 537.1 211.942 l S 3.864 M []0 d 513.975 209.692 m 515.725 214.692 l 517.555 209.645 m 519.305 214.645 l S BT /F16 1 Tf 10 0 0 10 325.08 251.128 Tm /GS4 gs (0.3)Tj /F3 1 Tf 7.97 0 0 7.97 308.976 146.494 Tm 0 g /GS2 gs [(Fig.)-327.1(5.)-331.2(\261)-332.2(Changes)-231(in)-232.9(nasal)-232.9(responsive)11(ness)-234.8(to)-240(histamine)-229.5(\(10)]TJ 5.977 0 0 5.313 494.646 150.066 Tm (-4)Tj 7.97 0 0 7.97 499.578 146.494 Tm [(\))-232.8(during)-231.8(the)]TJ -23.9144 -1.0599 TD [(course)-249.9(of)-252.1(repetitive)-256(challenge)11.1(s)-255.2(i)0(n)-254.3(guinea-pig)11(s)-255.2(2)-254(days)-255(after)-253.4(the)-251.2(respective)]TJ T* [(pollen)-368.2(inhalatio)11.4(n)-374.9(challenge)11.1(s.)-367.9(Data)-371.5(are)-368.9(presented)-358.8(as)-373(mean\213)]TJ 5.579 0 0 5.579 498.331 129.6 Tm (SEM)Tj 7.97 0 0 7.97 512.674 129.6 Tm (\(n)Tj /F8 1 Tf 0.8251 0 TD (=)Tj /F3 1 Tf 0.5477 0 TD (12\).)Tj /F19 1 Tf -26.9303 -1.067 TD (s)Tj /F3 1 Tf 0.8322 0 TD [(:)-526.7(nonsens)13.4(itized;)]TJ /F5 1 Tf 6.9709 0 TD (&)Tj /F3 1 Tf 0.9958 0 TD [(:)-519.6(sensitized.)]TJ /F11 1 Tf 5.4487 0 TD (D)Tj /F3 1 Tf 0.6686 0 TD (s)Tj /F4 1 Tf 0.3841 0 TD (R)Tj /F3 1 Tf 6.376 0 0 6.376 435.685 121.096 Tm (aw)Tj 7.97 0 0 7.97 443.112 121.096 Tm [(:)-519.6(change)-517.8(in)-524.6(specific)-519.8(airway)]TJ -16.8297 -1.0599 TD [(resistance.)-329.7(*,**:)-327.2(p)]TJ /F8 1 Tf 7.3052 0 TD (<)Tj /F3 1 Tf 0.5477 0 TD [(0.05,)-325.9(p)]TJ /F8 1 Tf 2.8239 0 TD (<)Tj /F3 1 Tf 0.5548 0 TD [(0.01)-327(compared)-322(to)-332.5(the)-329.4(nonsensitized)-327.7(group.)]TJ ET /GS3 gs 140.929 689.506 m 140.929 674.131 l 154.054 682.631 m 154.054 670.631 l 180.804 696.256 m 180.804 684.006 l 207.053 707.256 m 207.053 687.756 l 233.053 711.256 m 233.053 696.381 l 298.565 689.131 m 298.565 676.506 l 324.018 693.131 m 324.018 682.381 l 375.383 711.256 m 375.383 699.756 l S 3.864 M [2 2 ]0 d 397.427 673.704 m 525.927 673.704 l S 3.864 M []0 d 397.427 776.005 m 397.427 649.756 l 397.427 646.506 m 525.177 646.506 l 397.427 649.954 m 393.927 649.954 l 397.427 673.704 m 393.927 673.704 l 397.427 697.454 m 393.927 697.454 l 397.427 721.204 m 393.927 721.204 l 397.427 745.209 m 393.927 745.209 l 397.427 768.591 m 393.927 768.591 l 409.927 646.631 m 409.927 644.006 l 424.25 646.426 m 424.25 643.801 l 438.234 646.221 m 438.234 643.596 l 465.592 646.391 m 465.592 643.766 l 492.781 646.448 m 492.781 643.823 l 519.969 646.504 m 519.969 643.879 l S BT /F16 1 Tf 10 0 0 10 511.802 633.131 Tm 0 0 0 1 k /GS4 gs (10)Tj 8 0 0 8 520.922 635.399 Tm (-2)Tj 10 0 0 10 485.177 633.108 Tm (10)Tj 8 0 0 8 494.297 635.376 Tm (-4)Tj 10 0 0 10 458.427 633.131 Tm (10)Tj 8 0 0 8 467.547 635.399 Tm (-6)Tj 10 0 0 10 431.052 633.131 Tm (10)Tj 8 0 0 8 440.172 635.399 Tm (-8)Tj 10 0 0 10 421.927 633.131 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 431.427 627.631 m 526.302 627.631 l S BT 10 0 0 10 378.927 770.38 Tm /GS4 gs (c\))Tj ET 0 0 0 0 k /GS3 gs 296.213 682.922 m 296.213 684.199 297.249 685.235 298.526 685.235 c 299.803 685.235 300.838 684.199 300.838 682.922 c 300.838 681.645 299.803 680.609 298.526 680.609 c 297.249 680.609 296.213 681.645 296.213 682.922 c b 3.864 M [2 2 ]0 d 255.1 674.186 m 381.975 674.186 l S 3.864 M []0 d 255.1 776.487 m 255.1 650.238 l 255.1 646.988 m 382.85 646.988 l 255.1 650.436 m 251.601 650.436 l 255.1 674.186 m 251.601 674.186 l 255.1 697.936 m 251.601 697.936 l 255.1 721.686 m 251.601 721.686 l 255.1 745.69 m 251.601 745.69 l 255.1 769.072 m 251.601 769.072 l 267.6 647.113 m 267.6 644.488 l 281.923 646.908 m 281.923 644.283 l 295.907 646.703 m 295.907 644.078 l 323.265 646.872 m 323.265 644.247 l 350.454 646.929 m 350.454 644.304 l 377.642 646.986 m 377.642 644.361 l S BT 10 0 0 10 369.475 633.613 Tm 0 0 0 1 k /GS4 gs (10)Tj 8 0 0 8 378.595 635.881 Tm (-2)Tj 10 0 0 10 342.85 633.59 Tm (10)Tj 8 0 0 8 351.97 635.857 Tm (-4)Tj 10 0 0 10 316.1 633.613 Tm (10)Tj 8 0 0 8 325.22 635.881 Tm (-6)Tj 10 0 0 10 288.725 633.613 Tm (10)Tj 8 0 0 8 297.845 635.881 Tm (-8)Tj 10 0 0 10 279.6 633.613 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 289.1 628.113 m 383.975 628.113 l S BT 10 0 0 10 234.851 768.487 Tm /GS4 gs (b\))Tj ET 0 0 0 0 k /GS3 gs 269.209 673.172 m 269.209 674.449 270.244 675.485 271.521 675.485 c 272.798 675.485 273.834 674.449 273.834 673.172 c 273.834 671.895 272.798 670.86 271.521 670.86 c 270.244 670.86 269.209 671.895 269.209 673.172 c b 178.834 690.422 m 178.834 691.699 179.87 692.735 181.147 692.735 c 182.424 692.735 183.459 691.699 183.459 690.422 c 183.459 689.145 182.424 688.109 181.147 688.109 c 179.87 688.109 178.834 689.145 178.834 690.422 c b 138.459 681.297 m 138.459 682.574 139.495 683.609 140.772 683.609 c 142.049 683.609 143.084 682.574 143.084 681.297 c 143.084 680.02 142.049 678.985 140.772 678.985 c 139.495 678.985 138.459 680.02 138.459 681.297 c b 3.864 M [2 2 ]0 d 110.601 674.186 m 237.851 674.186 l S 3.864 M []0 d 124.283 674.172 m 124.283 675.449 125.318 676.485 126.595 676.485 c 127.872 676.485 128.908 675.449 128.908 674.172 c 128.908 672.895 127.872 671.86 126.595 671.86 c 125.318 671.86 124.283 672.895 124.283 674.172 c b 110.601 776.487 m 110.601 650.238 l 110.601 646.988 m 238.351 646.988 l 110.601 650.436 m 107.101 650.436 l 110.601 674.186 m 107.101 674.186 l 110.601 697.936 m 107.101 697.936 l 110.601 721.686 m 107.101 721.686 l 110.601 745.69 m 107.101 745.69 l 110.601 769.072 m 107.101 769.072 l S BT 10 0 0 10 92.476 765.532 Tm 0 0 0 1 k /GS4 gs (1.2)Tj 0.0092 -2.3177 TD (0.9)Tj -0.0047 -2.3868 TD (0.6)Tj 0.0024 -2.4 TD (0.3)Tj 0.6432 -2.375 TD (0)Tj -0.9375 -2.3481 TD (-0.3)Tj ET /GS3 gs 123.101 647.113 m 123.101 644.488 l 137.424 646.908 m 137.424 644.283 l 151.408 646.703 m 151.408 644.078 l 178.766 646.872 m 178.766 644.247 l 205.954 646.929 m 205.954 644.304 l 233.143 646.986 m 233.143 644.361 l S BT 10 0 0 10 224.976 633.613 Tm /GS4 gs (10)Tj 8 0 0 8 234.096 635.881 Tm (-2)Tj 10 0 0 10 198.351 633.59 Tm (10)Tj 8 0 0 8 207.471 635.857 Tm (-4)Tj 10 0 0 10 171.601 633.613 Tm (10)Tj 8 0 0 8 180.721 635.881 Tm (-6)Tj 10 0 0 10 144.226 633.613 Tm (10)Tj 8 0 0 8 153.346 635.881 Tm (-8)Tj 10 0 0 10 135.101 633.613 Tm (S)Tj -1.4375 0 TD (B)Tj ET /GS3 gs 144.601 628.113 m 239.476 628.113 l S BT 10 0 0 10 178.976 617.238 Tm /GS4 gs (MCh M)Tj /F13 1 Tf 0 10 -10 0 74.351 678.113 Tm (D)Tj /F16 1 Tf 0.612 0 TD (s)Tj /F18 1 Tf 0.41 0 TD (R)Tj /F16 1 Tf 0 8 -8 0 74.351 694.252 Tm (aw)Tj 0 10 -10 0 74.351 702.636 Tm ( cmH)Tj 0 8 -8 0 76.619 724.046 Tm (2)Tj 0 10 -10 0 74.351 727.694 Tm (O\341s)Tj 10 0 0 10 65.929 770.131 Tm (a\))Tj ET 3.864 M /GS3 gs 121.935 676.558 4.75 -4.75 re B 135.31 686.808 4.75 -4.75 re B 149.56 686.932 4.75 -4.75 re B 175.81 692.683 4.75 -4.75 re B 201.434 706.182 4.75 -4.75 re B 227.934 720.432 4.75 -4.75 re B 266.434 675.558 4.75 -4.75 re B 279.809 687.183 4.75 -4.75 re B 293.059 685.933 4.75 -4.75 re B 318.934 697.432 4.75 -4.75 re B 344.434 706.057 4.75 -4.75 re B 370.184 716.682 4.75 -4.75 re B 0 0 0 0 k 3.864 M 152.084 676.797 m 152.084 678.074 153.12 679.11 154.397 679.11 c 155.674 679.11 156.709 678.074 156.709 676.797 c 156.709 675.52 155.674 674.485 154.397 674.485 c 153.12 674.485 152.084 675.52 152.084 676.797 c b 204.709 697.547 m 204.709 698.824 205.744 699.859 207.021 699.859 c 208.299 699.859 209.334 698.824 209.334 697.547 c 209.334 696.27 208.299 695.234 207.021 695.234 c 205.744 695.234 204.709 696.27 204.709 697.547 c b 230.834 704.297 m 230.834 705.574 231.869 706.609 233.146 706.609 c 234.424 706.609 235.459 705.574 235.459 704.297 c 235.459 703.02 234.424 701.984 233.146 701.984 c 231.869 701.984 230.834 703.02 230.834 704.297 c b 282.834 679.547 m 282.834 680.824 283.869 681.86 285.146 681.86 c 286.423 681.86 287.459 680.824 287.459 679.547 c 287.459 678.27 286.423 677.235 285.146 677.235 c 283.869 677.235 282.834 678.27 282.834 679.547 c b 321.833 687.922 m 321.833 689.199 322.869 690.235 324.146 690.235 c 325.423 690.235 326.458 689.199 326.458 687.922 c 326.458 686.645 325.423 685.61 324.146 685.61 c 322.869 685.61 321.833 686.645 321.833 687.922 c b 347.208 698.047 m 347.208 699.324 348.244 700.36 349.521 700.36 c 350.798 700.36 351.833 699.324 351.833 698.047 c 351.833 696.77 350.798 695.734 349.521 695.734 c 348.244 695.734 347.208 696.77 347.208 698.047 c b 373.083 705.672 m 373.083 706.949 374.119 707.984 375.396 707.984 c 376.673 707.984 377.708 706.949 377.708 705.672 c 377.708 704.395 376.673 703.36 375.396 703.36 c 374.119 703.36 373.083 704.395 373.083 705.672 c b 369.802 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[(in)13.2(st)17.7(il)16.5(l)13.9(a)0(t)12.8(i)0(o)18.9(n)-461.7(i)13.9(n)0(c)15.1(r)0(e)19.2(a)0(s)14(e)0(d)-451.5(w)0(i)20.6(t)0(h)-453.5(t)0(h)18.9(e)-462.1(nu)15.5(mb)18.1(er)-453.1(of)-447(an)15.1(ti)16.5(ge)20.8(n)-461.7(e)0(x)15.1(p)0(o)21.2(-)]TJ T* [(su)14.4(re)19.2(s,)-309.6(an)20.8(d)-319.4(n)0(a)20.8(s)0(a)13.9(l)-316.1(hy)21.2(pe)15.1(rr)18(es)13.9(po)21.2(ns)14.3(i)13.9(v)0(e)15.1(n)0(e)15.1(s)0(s)-305.5(w)0(a)16.9(s)-314.9(ev)15.1(id)18.9(en)15.1(t)-316.1(a)0(t)-305.9(1)0(0)-308.8(h)]TJ 0 -1.0698 TD [(an)15.1(d)-427.6(2)-421.9(da)15.1(ys)20(,)-427.2(b)0(u)15.5(t)-424.2(no)21.2(t)-429.9(a)0(t)-414(7)-427.6(da)15.1(ys)20(,)-427.2(f)0(o)19.6(l)0(l)16.5(o)0(w)17.3(i)0(n)18.8(g)-427.6(th)18.9(e)-428(i)0(n)18.9(h)0(a)15.1(l)0(a)18.4(t)0(i)16.5(o)0(n)]TJ 0 -1.0755 TD [(pr)13.9(ov)21.2(oc)15.1(at)18.4(io)18.9(n.)-365.3(In)-367.3(in)18.9(di)13.2(vi)18.9(du)21.2(al)12.8(s)-371.8(w)0(i)14.9(t)0(h)-368.1(p)0(o)21.2(l)0(l)16.5(i)0(n)18.8(o)0(s)14.4(i)13.9(s,)-366.5(in)-368.1(wh)17.3(om)-368.9(th)18.9(e)]TJ ET 0 0 0 1 K 0 J 0 j 0.5 w 3.864 M []0 d /GS3 gs 1 i 269.262 721.756 m 269.262 700.131 l 147.763 692.256 m 147.763 682.256 l 151.138 689.006 m 151.138 677.006 l 168.343 693.131 m 168.343 675.881 l 165.138 681.631 m 165.138 669.631 l 202.076 684.74 m 202.076 663.381 l 198.763 686.9 m 198.763 665.881 l 232.762 692.131 m 232.762 666.506 l 235.762 700.131 m 235.762 684.131 l 266.137 707.381 m 266.137 684.131 l S 0 0 0 0 k 196.437 678.251 m 196.437 679.528 197.472 680.564 198.75 680.564 c 200.027 680.564 201.062 679.528 201.062 678.251 c 201.062 676.974 200.027 675.939 198.75 675.939 c 197.472 675.939 196.437 676.974 196.437 678.251 c b 3.864 M 131.004 675.791 4.75 -4.75 re B [2 2 ]0 d 114.623 669.486 m 289.122 669.486 l S 3.864 M []0 d 114.248 776.966 m 114.248 648.717 l 114.248 646.217 m 288.747 646.217 l 114.123 772.966 m 109.248 772.966 l 114.123 731.649 m 109.248 731.649 l 114.123 710.99 m 109.248 710.99 l 114.123 690.332 m 109.248 690.332 l 114.123 669.447 m 109.248 669.447 l 114.264 649.014 m 109.389 649.014 l S BT /F16 1 Tf 10 0 0 10 91.146 647.099 Tm 0 0 0 1 k /GS4 gs (-0.3)Tj 0.9742 1.8868 TD (0)Tj -0.652 2.1625 TD -0.0009 Tc (0.3)Tj 0.0068 2.0146 TD 0 Tc (0.6)Tj -0.0189 2.0097 TD (0.9)Tj 0.014 2.1632 TD (1.2)Tj /F13 1 Tf 0 10 -10 0 72.748 681.967 Tm (D)Tj /F16 1 Tf 0.612 0 TD (s)Tj /F18 1 Tf 0.41 0 TD (R)Tj /F16 1 Tf 0 8 -8 0 72.748 698.106 Tm (aw)Tj 0 10 -10 0 72.748 706.49 Tm ( cmH)Tj 0 8 -8 0 75.016 727.9 Tm (2)Tj 0 10 -10 0 72.748 731.548 Tm (O\341s)Tj 10 0 0 10 63.888 770.38 Tm (a\))Tj ET /GS3 gs 133.123 646.217 m 133.123 643.467 l 150.498 646.217 m 150.498 643.467 l 170.623 646.217 m 170.623 643.467 l 204.747 646.217 m 204.747 643.467 l 240.247 646.217 m 240.247 643.467 l 274.813 646.217 m 274.813 643.467 l S BT 10 0 0 10 266.747 632.217 Tm /GS4 gs (10)Tj 8 0 0 8 275.867 634.485 Tm (-2)Tj 10 0 0 10 231.622 632.217 Tm (10)Tj 8 0 0 8 240.742 634.485 Tm (-4)Tj 10 0 0 10 196.747 631.967 Tm (10)Tj 8 0 0 8 205.867 634.235 Tm (-6)Tj 10 0 0 10 161.873 631.967 Tm (10)Tj 8 0 0 8 170.992 634.235 Tm (-8)Tj 10 0 0 10 148.123 632.217 Tm (S)Tj -1.7125 0 TD (B)Tj ET /GS3 gs 162.873 627.842 m 288.622 627.842 l S BT 10 0 0 10 198.997 613.717 Tm /GS4 gs (Histamine M)Tj 13.0125 15.6664 TD -0.0163 Tc (b\))Tj ET 0 0 0 0 k /GS3 gs 145.435 687.081 m 145.435 688.358 146.47 689.394 147.748 689.394 c 149.025 689.394 150.06 688.358 150.06 687.081 c 150.06 685.804 149.025 684.768 147.748 684.768 c 146.47 684.768 145.435 685.804 145.435 687.081 c b 0 0 0 1 k 3.864 M 127.867 675.751 4.75 -4.75 re B BT 10 0 0 10 94.473 769.673 Tm /GS4 gs 0 Tc (1.8)Tj ET 3.864 M /GS3 gs 114.623 752.308 m 109.748 752.308 l S 3.864 M 144.983 680.303 4.75 -4.75 re B 162.857 695.303 4.75 -4.75 re B 196.732 706.553 4.75 -4.75 re B 230.607 720.553 4.75 -4.75 re B 264.232 760.052 4.75 -4.75 re B 0 0 0 0 k 267.107 712.678 4.75 -4.75 re B 233.482 694.803 4.75 -4.75 re B 199.607 678.678 4.75 -4.75 re B 165.857 687.428 4.75 -4.75 re B 149.115 685.411 4.75 -4.75 re B 3.864 M 162.935 676.331 m 162.935 677.608 163.97 678.644 165.248 678.644 c 166.525 678.644 167.56 677.608 167.56 676.331 c 167.56 675.054 166.525 674.019 165.248 674.019 c 163.97 674.019 162.935 675.054 162.935 676.331 c b 230.685 680.456 m 230.685 681.733 231.72 682.769 232.997 682.769 c 234.274 682.769 235.31 681.733 235.31 680.456 c 235.31 679.179 234.274 678.144 232.997 678.144 c 231.72 678.144 230.685 679.179 230.685 680.456 c b 263.809 696.206 m 263.809 697.483 264.845 698.519 266.122 698.519 c 267.399 698.519 268.434 697.483 268.434 696.206 c 268.434 694.929 267.399 693.894 266.122 693.894 c 264.845 693.894 263.809 694.929 263.809 696.206 c b 264.137 770.005 m 269.262 770.005 l 266.512 770.255 m 266.512 745.63 l 264.387 745.381 m 269.137 745.381 l 230.512 732.006 m 235.512 732.006 l 232.887 732.131 m 232.887 703.881 l 230.512 704.131 m 235.387 704.131 l 267.012 721.506 m 271.887 721.506 l 267.012 700.131 m 272.262 700.131 l 268.012 707.256 m 264.385 707.256 l 268.887 684.256 m 264.137 684.256 l 233.262 700.131 m 238.137 700.131 l 233.262 684.381 m 237.887 684.381 l 230.387 692.006 m 233.512 692.006 l 230.512 666.506 m 235.137 666.506 l 196.388 713.881 m 201.762 713.881 l 198.887 714.131 m 198.887 694.006 l 196.262 694.256 m 201.887 694.256 l 196.513 687.006 m 201.387 687.006 l 197.012 665.881 m 200.762 665.881 l 199.803 684.881 m 205.052 684.881 l 200.576 663.381 m 204.451 663.381 l 162.638 697.756 m 167.638 697.756 l 165.013 697.881 m 165.013 688.006 l 163.013 688.006 m 167.263 688.006 l 167.138 693.006 m 170.638 693.006 l 167.388 675.881 m 170.138 675.881 l 162.638 681.756 m 167.138 681.756 l 163.263 669.631 m 166.763 669.631 l 145.513 692.006 m 150.388 692.006 l 146.263 682.381 m 149.513 682.381 l 149.388 688.881 m 153.513 688.881 l 153.638 677.256 m 149.638 677.256 l 145.638 682.006 m 148.763 682.006 l 147.263 682.006 m 147.263 671.131 l 147.279 672.756 m 147.279 668.131 l 145.263 668.256 m 149.263 668.256 l 133.388 675.756 m 145.763 685.881 l 135.638 674.756 m 149.263 682.381 l 135.763 674.381 m 145.638 677.131 l 153.763 683.256 m 164.763 692.381 l 153.763 683.256 m 165.888 684.631 l 153.763 682.631 m 163.138 677.506 l 167.388 693.506 m 200.637 704.756 l 170.513 684.381 m 196.437 678.251 l 167.263 676.881 m 196.262 678.006 l 200.888 678.756 m 230.685 680.456 l 204.263 676.631 m 233.637 691.756 l 200.012 704.881 m 231.512 717.256 l 238.137 693.631 m 267.262 709.631 l 235.012 681.381 m 263.762 695.631 l 234.512 719.631 m 265.637 756.756 l S BT /F22 1 Tf 10 0 0 10 264.262 722.131 Tm 0 0 0 1 k /GS4 gs (**)Tj -6.4646 -6.7125 TD (*)Tj ET /GS3 gs 408.886 679.545 m 408.886 672.545 l 388.731 676.188 m 378.011 671.347 l 394.387 682.58 m 378.761 670.955 l S 0 0 0 0 k 385.684 677.495 m 385.684 678.772 386.719 679.808 387.996 679.808 c 389.273 679.808 390.309 678.772 390.309 677.495 c 390.309 676.218 389.273 675.183 387.996 675.183 c 386.719 675.183 385.684 676.218 385.684 677.495 c b 511.136 699.545 m 511.136 681.045 l 476.761 684.67 m 476.761 671.92 l 442.136 681.17 m 442.136 665.795 l 481.528 700.92 m 481.528 690.67 l 407.761 690.67 m 392.636 680.795 l S 380.244 668.738 m 375.029 668.738 l 377.636 673.253 l 380.244 668.738 l b 3.864 M [2 2 ]0 d 358.225 671.166 m 532.371 671.166 l S 3.864 M []0 d 358.246 778.38 m 358.246 650.131 l 358.246 647.631 m 532.746 647.631 l S BT /F16 1 Tf 10 0 0 10 375.935 633.881 Tm 0 0 0 1 k /GS4 gs 1.2716 Tc [(BS)643.6(1)1271.6(0)]TJ 8 0 0 8 414.991 636.149 Tm 0 Tc (-8)Tj 10 0 0 10 440.871 633.881 Tm (10)Tj 8 0 0 8 449.991 636.149 Tm (-6)Tj 10 0 0 10 476.746 633.631 Tm (10)Tj 8 0 0 8 485.866 635.899 Tm (-4)Tj 10 0 0 10 513.246 633.631 Tm (10)Tj 8 0 0 8 522.366 635.899 Tm (-2)Tj ET /GS3 gs 378.437 647.648 m 378.437 644.898 l 396.187 647.648 m 396.187 644.898 l 413.937 647.648 m 413.937 644.898 l 449.437 647.648 m 449.437 644.898 l 485.56 647.648 m 485.56 644.898 l 521.88 647.648 m 521.88 644.898 l 407.871 629.631 m 532.871 629.631 l 358.258 650.412 m 353.383 650.412 l 358.225 671.077 m 353.35 671.077 l 358.192 691.742 m 353.317 691.742 l 358.159 712.407 m 353.284 712.407 l 358.126 733.072 m 353.251 733.072 l 358.093 774.401 m 353.218 774.401 l 358.593 753.736 m 353.718 753.736 l S 3.864 M 406.356 693.592 4.75 -4.75 re B 0 0 0 0 k 3.864 M 406.559 676.12 m 406.559 677.398 407.594 678.433 408.871 678.433 c 410.148 678.433 411.184 677.398 411.184 676.12 c 411.184 674.843 410.148 673.808 408.871 673.808 c 407.594 673.808 406.559 674.843 406.559 676.12 c b 0 0 0 1 k 3.864 M 372.481 673.375 4.75 -4.75 re B 388.024 681.137 4.75 -4.75 re B 441.481 688.262 4.75 -4.75 re B 474.481 703.387 4.75 -4.75 re B 509.981 759.636 4.75 -4.75 re B 0 0 0 0 k 3.864 M 518.993 773.539 m 513.779 773.539 l 516.386 778.055 l 518.993 773.539 l b 484.118 693.04 m 478.904 693.04 l 481.511 697.555 l 484.118 693.04 l b 415.868 681.915 m 410.654 681.915 l 413.261 686.43 l 415.868 681.915 l b 439.934 674.495 m 439.934 675.772 440.969 676.808 442.246 676.808 c 443.523 676.808 444.559 675.772 444.559 674.495 c 444.559 673.218 443.523 672.183 442.246 672.183 c 440.969 672.183 439.934 673.218 439.934 674.495 c b 474.433 677.745 m 474.433 679.023 475.469 680.058 476.746 680.058 c 478.023 680.058 479.058 679.023 479.058 677.745 c 479.058 676.468 478.023 675.433 476.746 675.433 c 475.469 675.433 474.433 676.468 474.433 677.745 c b 508.808 689.37 m 508.808 690.648 509.844 691.683 511.121 691.683 c 512.398 691.683 513.433 690.648 513.433 689.37 c 513.433 688.093 512.398 687.058 511.121 687.058 c 509.844 687.058 508.808 688.093 508.808 689.37 c b 396.636 683.545 m 411.011 682.67 l 414.761 684.17 m 446.261 695.545 l 448.761 695.295 m 480.386 695.545 l 511.011 757.795 m 477.386 702.67 l 475.511 699.545 m 445.261 687.795 l 442.011 686.795 m 410.011 691.92 l 391.762 676.045 m 406.511 676.545 l 411.136 676.295 m 439.934 674.495 l 444.511 674.045 m 474.511 677.545 l 478.761 678.17 m 508.886 688.545 l 509.386 776.794 m 514.386 776.794 l 511.886 777.045 m 511.886 730.92 l 509.261 730.92 m 514.886 730.92 l 516.511 773.794 m 516.511 739.045 l 513.761 739.045 m 518.886 739.045 l 474.761 707.67 m 479.386 707.67 l 477.023 707.795 m 477.023 692.795 l 475.181 693.045 m 478.806 693.045 l 479.386 690.795 m 483.636 690.795 l 481.511 697.555 m 515.636 773.545 l 479.749 700.795 m 483.249 700.795 l 509.148 699.42 m 513.397 699.42 l 474.886 684.42 m 479.636 684.42 l 474.886 672.045 m 479.011 672.045 l 440.205 680.92 m 444.705 680.92 l 440.011 665.92 m 443.886 665.92 l 509.261 680.92 m 513.511 680.92 l 393.136 684.92 m 389.011 684.92 l 391.261 685.17 m 391.261 671.67 l 393.262 671.795 m 389.887 671.795 l 389.996 675.183 m 389.996 670.42 l 388.511 670.42 m 391.511 670.42 l 389.636 680.17 m 389.636 683.545 l 391.136 683.42 m 387.886 683.42 l 391.95 692.42 m 395.7 692.42 l 393.672 692.67 m 393.672 678.92 l 395.705 679.153 m 392.705 679.153 l S 396.323 682.915 m 391.109 682.915 l 393.716 687.43 l 396.323 682.915 l b 406.66 701.231 m 411.035 701.231 l 408.761 701.42 m 408.761 680.045 l 410.851 680.045 m 407.037 680.045 l 413.136 682.17 m 413.136 679.295 l 411.136 679.295 m 415.261 679.295 l 413.136 686.387 m 413.136 692.262 l 410.761 692.609 m 415.386 692.609 l 407.136 679.42 m 410.636 679.42 l 407.011 672.67 m 410.761 672.67 l 442.235 692.545 m 445.985 692.545 l 444.011 692.42 m 444.011 679.17 l 442.256 679.403 m 446.006 679.403 l 447.478 701.67 m 447.478 689.17 l 449.136 689.42 m 445.761 689.42 l 446.136 701.875 m 449.261 701.875 l S 450.118 693.04 m 444.904 693.04 l 447.511 697.555 l 450.118 693.04 l b BT 10 0 0 10 448.496 615.217 Tm 0 0 0 1 k /GS4 gs (Histamine M)Tj /F3 1 Tf 7.97 0 0 7.97 58.28 599.584 Tm 0 g /GS2 gs [(Fig.)-327.1(6.)-331.2(\261)-332.2(E)0(f)15.6(fect)-276.7(of:)-273.7(a\))-279.5(mepyramin)10.7(e)-274.3(\()]TJ /F19 1 Tf 14.397 0 TD (h)Tj /F3 1 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5.313 78.463 586.205 Tm (-1)Tj 7.97 0 0 7.97 83.395 582.633 Tm [(\))-218.6(were)-219.9(administered)-215.3(orally)-219(1)-218.4(h)-225.5(prior)-219.9(to)-218.7(the)-222.7(saline)-219(instillation)8.3(.)-219.5(Data)-222.1(are)-219.5(presented)-216.5(as)-223.6(mean\213)]TJ 5.579 0 0 5.579 361.701 582.633 Tm (SEM)Tj 7.97 0 0 7.97 374.91 582.633 Tm (\(n)Tj /F8 1 Tf 0.818 0 TD (=)Tj /F3 1 Tf 0.5477 0 TD [(8\26112\).)-216.2(Specific)-217.6(airway)-218(resistances)-216.1(\(s)]TJ /F4 1 Tf 14.3187 0 TD (R)Tj /F3 1 Tf 6.376 0 0 6.376 504.737 582.633 Tm (aw)Tj 7.97 0 0 7.97 512.107 582.633 Tm [(\))-225.7(before)]TJ -56.9406 -1.0599 TD [(saline)-517.7(instillation)-518(\(B\))-518(were)-518.6(1.86\2130.10)15.1(,)-525.3(1.95\2130.12)-504.1(and)-519.1(2.04\2130.14)-511.2(cmH)]TJ 5.977 0 0 5.313 294.066 572.882 Tm (2)Tj 7.97 0 0 7.97 297.071 574.186 Tm (O)Tj /F10 1 Tf 0.7184 0.249 TD (.)Tj /F3 1 Tf 0.2703 -0.249 TD 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[(couple)-451.6(of)-452.7(weeks.)-454(Thus,)-452.6(the)-448.9(occurr)-8.6(ence)-448.1(and)-452.2(restorati)-13.5(on)]TJ 0 -1.0527 TD [(pattern)-331.2(of)-321.8(the)-323.7(h)-6.5(yperresponsi)-12.2(veness)-326.4(observ)-7.8(ed)-326.3(in)-322.6(the)-323.7(pres-)]TJ 0 -1.0471 TD [(ent)-511.5(model)-516.2(are)-511.2(rema)-8.6(rkably)-515.4(similar)-519.6(to)-510.4(those)-514.2(of)-509.6(clinical)]TJ 0 -1.0528 TD [(allergic)-408.7(rhinitis.)-411.4(Fu)-6.4(rthermor)-11.1(e,)-405.6(P)]TJ 6.974 0 0 6.974 187.37 656.56 Tm 0.0001 Tc (RIETO)Tj /F4 1 Tf 9.963 0 0 9.963 211.748 656.56 Tm 0 Tc [(et)-408.3(al.)]TJ /F3 1 Tf 2.5437 0 TD [([5])-409.5(report)-10.5(ed)]TJ -17.948 -1.0471 TD [(that)-298.4(nasal)-298.4(hyperr)-8.2(espons)-7.4(ivenes)-9(s)-292.2(i)0(n)-294.1(pati)-8.2(ents)-297.2(with)-296.3(perenni)-10.1(al)]TJ 0 -1.0527 TD [(allergic)-385.9(rhinitis)-388.3(is)-386.4(more)-389.5(eviden)-7.8(t)-384.4(than)-387.1(that)-389.5(in)-385.2(individua)-8.7(ls)]TJ T* [(with)-381.6(seasonal)-382(rhinitis,)-383(sugges)-7.4(ting)-377.7(that)-378.1(repetitive)-384.2(anti)-8.2(gen)]TJ 0 -1.0471 TD [(exposur)-8.5(e)-251.6(i)0(s)-255.5(a)0(n)-258(importan)-10.3(t)-253.5(factor)-255.6(in)-260(the)-255.5(acquisition)-264.6(of)-253.5(nasal)]TJ 0 -1.0527 TD [(hyperr)-8.2(espons)-7.4(iveness)-284.1(to)-277.1(stimul)-10.4(i.)-276.7(The)-280(exposur)-8.5(e)-280(freque)-8.6(ncy-)]TJ 0 -1.0471 TD [(dependen)-7.3(t)-247.8(incre)-8.6(ase)-249(in)-248.6(nasal)-252.9(hyperr)-8.2(espons)-7.4(iveness)-255.6(to)-248.6(hista-)]TJ 0 -1.0527 TD [(mine)-481.3(shown)-481.2(in)-476.2(the)-477.4(presen)-8.2(t)-475.5(study)-479.7(further)-479.5(indi)-7.8(cates)-480.9(the)]TJ 0 -1.0471 TD [(utility)-256.2(of)-253.5(the)-255.5(presen)-8.2(t)-247.8(alle)-8.6(rgic)-246.4(rhinitis)-257.4(model)-254.4(for)-255.9(inves)-7.8(tigat-)]TJ 0 -1.0527 TD [(ing)-505.4(the)-505.8(detailed)-509.5(mecha)-8.2(nism)-510.5(of)-503.9(the)-505.8(induction)-509.5(of)-503.9(nasal)]TJ 0 -1.0471 TD [(hyperr)-8.2(espons)-7.4(iveness.)]TJ 1.0015 -1.0527 TD [(Co)16.5(ns)20(id)13.2(er)19.2(in)18.9(g)-302.4(t)13.9(he)-292.2(pa)15.1(th)18.9(op)21.2(hy)15.5(si)17.7(ol)18.9(og)15.5(ic)18.4(al)-288.8(ac)14.7(ti)16.5(on)-286.1(of)-293.3(hi)18.9(st)17.7(am)17.7(in)13.2(e)]TJ -1.0015 -1.0471 TD [(on)-399.9(bl)18.9(oo)21.2(d)-410.5(v)0(e)20.8(s)0(s)13.2(e)0(l)18.4(s)-406([1)19.6(7,)-410.9(18],)-419.7(this)-418.7(ami)-8.2(ne)-417.3(may)-421.2(induce)-423.2(both)]TJ 0 -1.0527 TD [(dilatati)-13.1(on)-485.2(of)-486.8(the)-483.1(nasal)-491.9(resistanc)-11.1(e)-484.9(o)0(r)-486.8(capaci)-8.6(tance)-491.1(blood)]TJ 0 -1.0471 TD [(vessel)-10.1(s)-377.5(and)-384(incre)-8.6(ases)-381.8(in)-379.5(nasal)-389.5(capillary)-392.4(permeabil)-11.9(ity)61.2(.)-381.6(I)0(n)]TJ 0 -1.0528 TD [(the)-215.6(presen)-8.2(t)-208(study)55.2(,)-210.9(the)-215.6(histamine-i)-13.3(nduced)-215.9(elevat)-10.6(ion)-209.5(o)-6.5(f)-207.2(s)]TJ /F4 1 Tf 21.2713 0 TD 0 Tw (R)Tj /F3 1 Tf 7.97 0 0 7.97 276.264 499.634 Tm (aw)Tj 9.963 0 0 9.963 58.28 489.146 Tm [(was)-326.5(trans)-9.4(ient,)-327.3(wi)-7.8(th)-322.6(a)-325.5(peak)-328.2(at)-328.7(10)-325.9(min)-326.5(after)-334.6(stimul)-10.4(ation)-327.7(in)]TJ 0 -1.0471 TD [(sensiti)-9.6(zed)-486.8(guinea)-7.8(-pigs)-9(;)-486.8(naphazoline,)-498.8(a)-484.9(potent)-493.4(vasocon)-7.3(-)]TJ 0 -1.0528 TD [(stricti)-12.4(ve)]TJ /F8 1 Tf 3.659 0 TD (a)Tj /F3 1 Tf 0.6373 0 TD [(-adren)-8.6(ergic,)-481.3(n)-6.5(o)0(t)-487.6(only)-489.1(compl)-9.7(etely)-493.1(suppre)-7.8(ssed)]TJ -4.2964 -1.0471 TD [(the)-238.4(incre)-8.6(ase)-237.6(in)-237.2(s)]TJ /F4 1 Tf 6.3108 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 127.162 457.795 Tm (aw)Tj 9.963 0 0 9.963 138.671 457.795 Tm [(induce)-7.8(d)-234.1(b)0(y)-240.5(histamine)-246.8(but)-238(also)-234.7(furt)-8.6(her)]TJ -8.0692 -1.0528 TD [(potent)-9.7(ly)-368.1(lowered)-378.2(the)-375(spontaneous)-378.2(s)]TJ /F4 1 Tf 14.4483 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 208.233 447.307 Tm (aw)Tj 9.963 0 0 9.963 216.794 447.307 Tm [(,)-370.3(altho)-9(ugh)-366.5(not)-374.6(to)]TJ -15.9108 -1.0471 TD [(the)-318.1(extent)-323.1(seen)-318(in)-316.9(nonsens)-8.1(itized)-319.8(naphazol)-9.7(ine-treat)-12.7(ed)-314.9(ani-)]TJ 0 -1.0527 TD [(mals.)-426(The)-427.9(presen)-8.2(t)-424.2(experiment)-12.6(s)-423.1(regard)-8.6(ing)-425.8(plasma)-427.5(extra)-8.6(-)]TJ 0 -1.0471 TD [(vasat)-8.2(ion)-380.2(demon)-7.4(strated)-389.3(that)-383.8(histamine)-389(incre)-8.6(ases)-381.8(vascul)-9(ar)]TJ 0 -1.0527 TD [(perm)-8.2(eability)-232.7(into)-224.1(the)-227(lamina)-229.5(propri)-10.1(a)-223.1(and)-224.6(the)-227(luminal)-232.3(entry)]TJ 0 -1.0471 TD [(of)-344.6(sensitized)-348.4(guinea)-7.8(-pigs.)-345.1(This)-346.5(indicates)-346.5(that)-344(both)-346.9(blood)]TJ 0 -1.0528 TD [(vessel)-289(dila)-8.2(tion,)-287(to)-288.4(a)-285.7(lar)10.4(ge)-286.5(degree,)-292.3(and)-287.2(the)-289.6(oedematous)-294.4(re-)]TJ T* [(sponse)-7.4(,)-336.1(t)0(o)-339.7(a)-336.9(less)-8.2(er)-339.3(degree,)-343.5(contr)-8.2(ibute)-339(to)-339.7(the)-340.8(elevat)-10.6(ion)-340.4(of)]TJ 0 -1.0471 TD (s)Tj /F4 1 Tf 0.387 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 68.145 363.628 Tm (aw)Tj 9.963 0 0 9.963 80.674 363.628 Tm [(induce)-7.8(d)-330.8(b)0(y)-337.3(histami)-11.5(ne.)]TJ -1.2462 -1.0527 TD [(Th)17.1(e)-228.8(p)0(r)13.9(e)0(s)19.6(e)0(n)15.1(t)-230.8(na)20.8(sa)13.9(l)-230.8(h)0(y)21.2(p)0(e)15.1(r)0(r)18(e)0(s)19.6(p)0(o)15.5(n)0(s)20(i)0(v)18.9(e)0(n)15.1(e)0(s)19.6(s)-229.6(to)-225.8(hi)18.9(st)17.7(am)17.7(in)18.8(e)-234.5(w)0(a)16.9(s)]TJ -1.0015 -1.0471 TD -0.0143 Tc [(l)-14.3(a)4.1(r)6.1(g)-14.3(el)-14.3(y)-325.5(s)-14.3(u)5.7(p)-14.3(pr)-14.3(e)4.9(s)-14.3(se)-14.3(d)-323.5(b)-14.3(y)-323.1(t)-14.3(he)-334.1(H)]TJ 7.472 0 0 6.641 169.002 341.064 Tm 0 Tc (1)Tj 9.963 0 0 9.963 175.918 342.709 Tm [(an)15.1(ta)18.4(go)15.5(ni)18.9(st)-312.4(me)17.7(py)15.5(ra)19.2(mi)15.7(ne)20.8(,)-319.1(b)0(u)15.5(t)]TJ -11.8079 -1.0527 TD [(no)15.5(t)-464.1(b)0(y)-462.5(a)0(t)18.4(r)0(o)13.9(p)0(i)18.9(n)0(e)20.8(,)-472.7(w)12.4(h)0(i)13.2(c)0(h)-457.2(s)0(u)14.4(g)0(g)21.2(e)0(s)13.9(t)13.9(s)-474.3(t)13.9(h)0(a)15.1(t)-469.8(hi)18.9(st)17.7(am)17.7(in)13.2(e)-467.8(d)0(i)18.9(r)0(e)19.2(c)0(t)12.8(l)0(y)]TJ 0 -1.0471 TD [(st)17.7(im)15.7(ul)18.9(at)18.5(es)-304.7(H)]TJ 7.472 0 0 6.641 107.49 320.088 Tm (1)Tj 9.963 0 0 9.963 111.118 321.789 Tm [(-r)18(ec)14.7(ep)15.1(t)13.9(o)0(r)13.9(s)-309.2(on)-303.1(th)13.2(e)-308.5(b)0(l)13.2(o)0(o)21.2(d)-313.7(ve)20.8(ss)13.2(el)18.4(s)-309.2(i)0(n)13.2(d)0(u)21.2(c)0(i)18.4(n)0(g)-303.1(t)0(h)13.2(e)]TJ -5.3036 -1.0528 TD [(hy)15.5(pe)20.8(rr)18(es)13.9(po)21.2(ns)14.4(e)-553.2(w)0(i)14.9(t)13.9(ho)15.5(ut)-544.5(in)18.9(vo)15.5(lv)18.9(in)18.9(g)-552.8(t)0(h)13.2(e)-553.2(ch)20.8(ol)13.2(in)18.9(er)30.6(gi)13.2(c)-553.2(n)0(e)20.8(r)0(v)13.9(e)]TJ 0 -1.0471 TD [(re)19.2(fl)17.3(ex)15.1(.)-267.8(I)]TJ 6.974 0 0 6.974 88.838 300.869 Tm 0.0001 Tc [(RIY)23.4(O)0(S)18.2(H)0(I)]TJ /F4 1 Tf 9.963 0 0 9.963 119.225 300.869 Tm 0 Tc [(et)-260.4(al)18.9(.)]TJ /F3 1 Tf 2.2364 0 TD [([1)13.9(9])-270.6(demonstra)-10.3(ted)-283.9(increased)-286.8(expres)-8.2(-)]TJ -8.3537 -1.0528 TD [(sion)-467.6(of)-469.7(H)]TJ 7.472 0 0 6.641 99.439 288.737 Tm (1)Tj 9.963 0 0 9.963 107.83 290.381 Tm [(receptor)-473.8(messenger)-476.1(ribonuclei)-11.5(c)-462.1(acid)-472.9(in)-464.8(the)]TJ -4.9735 -1.0471 TD [(nasal)-378.1(mucos)-8.6(a)-371.1(o)0(f)-378.7(patients)-379.4(with)-381.6(allergic)-368.9(rhini)-10.2(tis.)-372.8(This)-380.6(has)]TJ 0 -1.0528 TD [(not)-414.4(yet)-414.8(been)-413.6(examined)-416.9(in)-413.6(the)-414.8(presen)-8.2(t)-407.2(model)-9.7(,)-410.1(but)-414.4(it)-410.3(re-)]TJ T* [(mains)-278.4(to)-271.4(be)-269.4(clari)-11(fied)-274.9(whether)-275.8(the)-272.5(hype)-9.1(rresponse)-280.7(is)-266.9(d)-6.5(u)0(e)-269.4(t)0(o)]TJ 0 -1.0471 TD [(the)-420.5(increased)-423.4(numbe)-7.4(r)-412.1(o)0(f)-418.5(H)]TJ 7.472 0 0 6.641 169.682 246.898 Tm (1)Tj 9.963 0 0 9.963 177.562 248.542 Tm [(recept)-9.8(ors,)-415.2(enhanc)-11.5(ed)-411.7(signa)-7.8(l)]TJ -11.9729 -1.0528 TD [(transd)-10.1(uction)-260.1(in)-254.3(the)-255.5(intracell)-13.5(ular)-257.8(events)-259.3(follow)-9.2(ing)-255.1(recept)-9.8(or)]TJ 0 -1.0471 TD [(stimul)-10.4(ation)-299.2(or)-293.3(o)-6.5(ther)-297.6(events)-9(.)-290.6(Con)-7(versely)57(,)-296.3(i)0(t)-296.5(i)0(s)-295.3(wel)-9(l)-293.4(know)-7(n)]TJ 0 -1.0528 TD [(that)-423.6(the)-420.5(accelerati)-13.1(on)-416.9(of)-418.5(serous)-424.4(secret)-11(ion)-420.1(by)-416.9(nasal)-423.6(glan-)]TJ 0 -1.0471 TD [(dular)-355.3(cell)-8.6(s)-349.1(i)0(s)-357.9(stimulated)-363.7(directly)-362.8(by)-348.7(cho)-8.4(linergic)-345.7(ago)-8.4(nists)]TJ 0 -1.0527 TD [(and)-526.2(indirectly)-531.7(by)-525.1(histamine)]TJ /F4 1 Tf 12.1664 0 TD (via)Tj /F3 1 Tf 1.7299 0 TD [(the)-528.6(cholinergic)-524.8(nerve)]TJ -13.8963 -1.0471 TD [(reflex)-11(.)-376(I)0(n)-384.4(the)-380.7(presen)-8.2(t)-378.7(model,)-385.7(it)-381.9(was)-383.4(observ)-7.8(ed)-377.5(that)-383.8(MC)-8.2(h)]TJ 0 -1.0527 TD [(induce)-7.8(d)-404.8(serous)-413(secret)-11(ion)-408.7(in)-407.9(not)-408.7(only)-415.2(sensitized)-416.7(guinea)-7.8(-)]TJ 0 -1.0471 TD [(pigs)-313.9(b)-6.5(u)0(t)-311.2(also)-320(nonsensit)-8.7(ized)-313.5(ones.)-318(The)-314.1(incre)-8.6(ased)-318(s)]TJ /F4 1 Tf 19.8657 0 TD (R)Tj /F3 1 Tf 7.97 0 0 7.97 262.205 164.863 Tm (aw)Tj 9.963 0 0 9.963 274.507 164.863 Tm (in-)Tj -21.7038 -1.0527 TD [(duced)-215.2(by)-212.1(nasal)-218.7(instil)-9.6(lation)-217(of)-213.7(MCh)-213.8(was)-218.4(almost)-218.9(completel)-12.7(y)]TJ T* [(blocke)-7.8(d)-211.3(b)0(y)-212.1(naphazoline,)-220(to)-214.5(a)-206(level)-219.9(similar)-218(to)-214.5(that)-213.1(observ)-7.8(ed)]TJ 0 -1.0471 TD [(when)-439.9(MC)-8.2(h-untreate)-11.1(d)-433.2(g)0(u)-7.2(inea-pigs)-442(wer)-8.2(e)-433.7(treat)-11(ed)-434.4(wi)-7.8(th)]TJ /F8 1 Tf 21.8403 0 TD (a)Tj 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[(15.)-1266.5(Iijima)-367.1(H,)-372.4(Ishii)-371.1(M,)-369.8(Y)92(amauchi)-366.7(K,)-372.4(Chao)-369.2(C-L,)]TJ /F4 1 Tf 20.5558 0 TD [(et)-367.9(al)]TJ /F3 1 Tf 1.8463 0 TD [(.)-369.6(Bron-)]TJ -19.8856 -1.1128 TD [(choalveolar)-290.1(lavage)-295.8(and)-289.1(histologic)-296.3(characterization)-298.9(of)-297.1(late)]TJ 27.9978 31.115 TD [(asthmatic)-441.2(response)-435.1(in)-437.7(guinea)-441.5(pigs.)]TJ /F4 1 Tf 14.7513 0 TD [(Am)-435.7(Rev)-437.8(Respir)-441.3(Dis)]TJ /F3 1 Tf -14.7513 -1.1128 TD [(1987;)-334.9(136:)-329.1(922\261929.)]TJ -2.5165 -1.1128 TD [(16.)-1266.5(Narita)-296.4(S,)-298.2(Asakura)-298.6(K,)-296.5(Kataura)-299.6(A.)-296.5(Effec)10.2(ts)-299.7(of)-297.1(thromboxane)]TJ 2.5165 -1.1065 TD (A)Tj 6.725 0 0 5.977 338.343 740.749 Tm (2)Tj 8.966 0 0 8.966 344.579 742.28 Tm [(receptor)-322(antagonist)-325.2(\(Bay)-319.6(u)-322(3405\))-320.9(on)-321.5(nasal)-316.7(symptoms)]TJ -1.4163 -1.1128 TD [(after)-266.9(antigen)-266.3(challenge)-264.8(in)-266.9(sensitized)-269.3(guinea)-264.4(pigs.)]TJ /F4 1 Tf 19.5631 0 TD [(Int)-267.4(Ar)27.9(ch)]TJ -19.5631 -1.1128 TD [(Aller)31.3(gy)-333.9(Immunol)]TJ /F3 1 Tf 7.069 0 TD [(1996;)-334.9(109:)-335.5(161\261166.)]TJ -9.5855 -1.1065 TD [(17.)-1266.5(Havas)-330.3(TE,)-325(Cole)-327.3(P)103.1(,)-325.4(Parker)-325.8(L,)-328.4(Oprysk)-331.2(D,)-321.8(A)79.4(yiomamitis)-331.6(A.)]TJ 2.5165 -1.1128 TD [(The)-248.3(effects)-247.9(of)-252.9(combined)-252.6(H)]TJ 6.725 0 0 5.977 427.011 700.894 Tm (1)Tj 8.966 0 0 8.966 432.623 702.425 Tm [(and)-251.2(H)]TJ 6.725 0 0 5.977 454.167 700.894 Tm (2)Tj 8.966 0 0 8.966 459.836 702.425 Tm [(histamine)-251.8(antagonists)]TJ -14.2708 -1.1128 TD [(on)-270.9(alterations)-277.3(in)-273.3(nasal)-272.5(airflow)-278.1(resistance)-280.3(induced)-270.3(by)-270.9(topi-)]TJ T* [(cal)-291.3(histamine)-289.7(provocation.)]TJ /F4 1 Tf 10.8438 0 TD [(J)-290.1(Aller)31.3(gy)-289.6(Clin)-292(Immunol)]TJ /F3 1 Tf 9.7057 0 TD (1986;)Tj -20.5495 -1.1065 TD [(78:)-336(856\261860.)]TJ -2.5165 -1.1128 TD [(18.)-1266.5(Arfors)-320.5(KE,)-324.8(Rutili)-321(G,)-321.8(Svensjo)-320.8(E.)-322(Microvascular)-323.5(transport)]TJ 2.5165 -1.1128 TD [(of)-436.2(macromolecules)-438.7(in)-431.3(normal)-438.2(and)-434.5(inflammatory)-442.5(condi-)]TJ T* (tions.)Tj /F4 1 Tf 2.5102 0 TD [(Acta)-332.4(Physiol)-334.4(Scand)-332.3(Suppl)]TJ /F3 1 Tf 10.8185 0 TD [(1979;)-334.9(463:)-329.1(93\261103.)]TJ -15.8452 -1.1065 TD [(19.)-1266.5(Iriyoshi)-282(N,)-283.9(T)60.2(akeuchi)-282.7(K,)-283.9(Y)104.7(uta)-285.2(A,)-283.9(Ukai)-281.6(K,)-283.9(Sakakura)-285.6(Y)123.6(.)-281.1(In-)]TJ 2.5165 -1.1128 TD [(creased)-427.6(expression)-430.1(of)-429.9(histamine)-428.8(H)]TJ 6.725 0 0 5.977 460.006 621.241 Tm (1)Tj 8.966 0 0 8.966 467.206 622.715 Tm [(receptor)-429.5(mRNA)-428.5(in)]TJ -15.0928 -1.1128 TD [(aller)9.9(gic)-335.8(rhinitis.)]TJ /F4 1 Tf 6.6454 0 TD [(Clin)-329.9(Exp)-336.9(Aller)31.3(gy)]TJ /F3 1 Tf 7.1196 0 TD [(1996;)-334.9(26:)-336(379\261385.)]TJ -16.2815 -1.1128 TD [(20.)-1266.5(Harg)10.6(reave)-408.7(FE,)-402.3(R)27.4(yan)-402.9(G,)-404(Thomson)-407.7(NC,)]TJ /F4 1 Tf 18.8929 0 TD [(et)-405.8(al)]TJ /F3 1 Tf 1.8842 0 TD [(.)-401.3(Bronchial)]TJ -18.2606 -1.1065 TD [(responsiveness)-379.7(to)-380.8(histamine)-378.2(or)-379.3(methacholine)-381.4(in)-374.4(asthma:)]TJ 0 -1.1128 TD [(measurement)-261(and)-263.8(clinical)-264(significance.)]TJ /F4 1 Tf 15.6555 0 TD [(J)-264.8(Aller)31.3(gy)-258(Clin)-260.4(Im-)]TJ -15.6555 -1.1128 TD (munol)Tj /F3 1 Tf 2.82 0 TD [(1981;)-334.9(68:)-336(347\261355.)]TJ -5.3365 -1.1065 TD [(21.)-1266.5(Cartier)-285.6(A,)-283.9(Thomson)-287.5(NC,)-288.1(Frith)-286.3(P)84.1(A)0(,)-283.9(Roberts)-283.7(R,)-285.3(Harg)10.6(reave)]TJ 2.5165 -1.1128 TD [(FE.)-440.2(Allergen-)7.7(induced)-441(increase)-442.2(in)-444(bronchial)-443.3(responsive-)]TJ T* [(ness)-411.1(to)-418.7(histamine:)-411.7(relationship)-422.4(to)-412.4(the)-411.6(late)-419.6(asthmatic)-415.9(re-)]TJ T* [(sponse)-561.8(and)-567.3(change)-565.3(in)-564.1(airway)-565.9(caliber)49.1(.)]TJ /F4 1 Tf 16.6735 0 TD [(J)-562(Aller)31.3(gy)-567.8(Clin)]TJ -16.6735 -1.1065 TD (Immunol)Tj /F3 1 Tf 3.8633 0 TD [(1982;)-334.9(70:)-329.6(170\261177.)]TJ -6.3798 -1.1128 TD [(22.)-1266.5(Gawin)-252.8(AZ,)-255.3(Baraniuk)-250.1(JN,)-253(Igarashi)-253.9(Y)123.6(,)-249.5(Kaliner)-257.9(MA.)-252.5(Effec)10.2(ts)]TJ 2.5165 -1.1128 TD [(of)-252.9(capsaicin)-259.7(desensitization)-258.7(on)-258.2(nasal)-253.5(mucosal)-260.7(secretion)-254.6(in)]TJ T* [(guinea)-334(pigs)]TJ /F4 1 Tf 4.9698 0 TD [(in)-330.2(vivo)]TJ /F3 1 Tf 2.7441 0 TD (.)Tj /F4 1 Tf 0.588 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F3 1 Tf 6.2786 0 TD [(1993;)-328.6(75:)-336(798\261804.)]TJ 6.2407 33.9414 TD (1375)Tj 7.472 0 0 7.472 198.198 797.499 Tm 0.0001 Tc 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