New frontiers in bryology - physiology, molecular biology and functional genomics. * Wood AJ, Oliver MJ, Cove DJ, eds. 2004. Dordrecht: Kluwer Academic Publishers. {pound}63 (hardback). 203 pp.

This book is a collection of papersfrom the major researchers involved in physiological, molecularand genomic research on bryophytes, mainly, although not exclusively,using the moss Physcomitrella patens. This is a growing areaof research and the book aims to provide ‘... a synopsisof the outstanding basic research being conducted using mossesas a model multi-cellular eukaryote’. Bryophytes (mosses, liverworts and hornworts) are an importantand often neglected group     

Synchrony, asynchrony, and temporally random mating: a new method for analyzing breeding synchrony

Much research has focused on understanding breeding synchronyin animals and its relationship to such issues as mating systemsand extrapair copulations in birds (Birkhead and Biggins, 1987;Emlen and Oring, 1977; Knowlton, 1979; Stutchbury and Morton,1995). To empirically examine synchrony, one needs an appropriatemeasure of the degree of synchrony in a population. Kempenaers(1993) presented an index of breeding synchrony (modified fromBjörklund and Westman, 1986) that has gained wide use asa simple representation of the degree to which breeding is synchronizedamong animals. This synchrony index (SI) is calculated as follows:

where F is the totalnumber of breeding females in the population; f_i,p is the numberof fertile females, excluding     

Distinct domains of the voltage-gated K+ channel Kvbeta 1.3 beta -subunit affect voltage-dependent gating

The Kv1.3 subunit confers a voltage-dependent, partialinactivation (time constant = 5.76 ± 0.14 ms at +50 mV), anenhanced slow inactivation, a hyperpolarizing shift in the activationmidpoint, and an increase in the deactivation time constant of theKv1.5 delayed rectifier. Removal of the first 10 amino acids fromKv1.3 eliminated the effects on fast and slow inactivation but notthe voltage shift in activation. Addition of the first 87 amino acids of Kv1.3 to the amino terminus of Kv1.5 reconstituted fast and slowinactivation without altering the midpoint of activation. Although aninternal pore mutation that alters quinidine block (V512A) did notaffect Kv1.3-mediated inactivation, a mutation of the external mouthof the pore (R485Y) increased the extent of fast inactivation whilepreventing the enhancement of slow inactivation. These data suggestthat 1) Kv1.3-mediated effects involve at least two distinct domains of this -subunit,2) inactivation involves openchannel block that is allosterically linked to the external pore, and3) the Kv1.3-induced shift in theactivation midpoint is functionally distinct from inactivation.

     

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise

Barstow, Thomas J., Andrew M. Jones, Paul H. Nguyen, andRichard Casaburi. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.J. Appl. Physiol. 81(4):1642-1650, 1996.We tested the hypothesis that the amplitude ofthe additional slow component ofO₂ uptake(O₂) during heavy exerciseis correlated with the percentage of type II (fast-twitch) fibers inthe contracting muscles. Ten subjects performed transitions to a workrate calculated to require aO₂ equal to 50% betweenthe estimated lactate (Lac) threshold and maximalO₂ (50%).Nine subjects consented to a muscle biopsy of the vastus lateralis. Toenhance the influence of differences in fiber type among subjects,transitions were made while subjects were pedaling at 45, 60, 75, and90 rpm in different trials. Baseline O₂ was designed to besimilar at the different pedal rates by adjusting baseline work ratewhile the absolute increase in work rate above the baseline was thesame. The O₂ response after the onset of exercise was described by a three-exponential model. Therelative magnitude of the slow component at the end of 8-min exercisewas significantly negatively correlated with %type I fibers at everypedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore,the gain of the fast component forO₂ (asml ^· min^{1 ·} W¹)was positively correlated with the %type I fibers across pedal rates(r = 0.69-0.83). Increase inpedal rate was associated with decreased relative stress of theexercise but did not affect the relationships between%fiber type and O₂parameters. The relative contribution of the slow component was alsosignificantly negatively correlated with maximalO₂(r = 0.65), whereas the gainfor the fast component was positively associated(r = 0.68-0.71 across rpm). Theamplitude of the slow component was significantly correlated with netend-exercise Lac at all four pedal rates(r = 0.64-0.84), but Lac was notcorrelated with %type I (P > 0.05).We conclude that fiber type distribution significantly affects both thefast and slow components ofO₂ during heavy exerciseand that fiber type and fitness may have both codependent andindependent influences on the metabolic and gas-exchange responses toheavy exercise.

     

Plant ecology. * Schulze ED, Beck E, Muller-Hohenstein K. 2005. Berlin/Heidelberg: Springer. $89{middle dot}95 (hardback). 702 pp.

This book (a translation fromSchulze et al., 2002) is one of the most comprehensive textbooksof plant ecology so far. The authors aim to ‘for the firsttime bring together and clearly organize the large subdisciplinesof plant ecology’ and, to a large extent they have succeeded.The book is well written, and its more than 500 illustrationsare beautifully laid out and well chosen to help the readerunderstand the theory. It is clearly suitable not only     

Comparison of energy expenditure elevations after submaximal and supramaximal running

Laforgia, J., R. T. Withers, N. J. Shipp, and C. J. Gore.Comparison of energy expenditure elevations after submaximal andsupramaximal running. J. Appl.Physiol. 82(2): 661-666, 1997.Although exerciseintensity has been identified as a major determinant of the excesspostexercise oxygen consumption (EPOC), no studies have compared theEPOC after submaximal continuous running and supramaximal intervalrunning. Eight male middle-distance runners [age = 21.1 ± 3.1 (SD) yr; mass = 67.8 ± 5.1 kg; maximal oxygen consumption(O_{2 max}) = 69.2 ± 4.0 ml ^· kg^{1 ·} min¹] thereforecompleted two equated treatments of treadmill running (continuousrunning: 30 min at 70%O_{2 max}; intervalrunning: 20 × 1-min intervals at 105%O_{2 max} withintervening 2-min rest periods) and a control session (no exercise) ina counterbalanced research design. The 9-h EPOC values were 6.9 ± 3.8 and 15.0 ± 3.3 liters (t-test:P = 0.001) for the submaximal andsupramaximal treatments, respectively. These values represent 7.1 and13.8% of the net total oxygen cost of both treatments. Notwithstanding the higher EPOC for supramaximal interval running compared with submaximal continuous running, the major contribution of both to weightloss is therefore via the energy expended during the actual exercise.

     

Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitiveisometric tetanic contractions (1/s) of the caninegastrocnemius-plantaris muscle were studied either at optimal length(L_o) or shortlength (L_s;~0.9 · L_o),to determine the effects of initial length on mechanical and metabolicperformance in situ. Respective averages of mechanical and metabolicvariables were(L_o vs.L_s, allP < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension(P_o) = 544 vs. 174 (0.38 · P_o)g/g, maximal blood flow () = 2.0 vs. 1.4 ml · min¹ · g¹,and maximal oxygen uptake(O₂) = 12 vs. 9 µmol · min¹ · g¹.Tension at L_odecreased to0.64 · P_o over20 min of repetitive contractions, demonstrating fatigue; there were nosignificant changes in tension atL_s. In separatemuscles contracting atL_o, was set to that measured atL_s (1.1 ml · min¹ · g¹),resulting in decreased O₂(7 µmol · min¹ · g¹),and rapid fatigue, to0.44 · P_o. Thesedata demonstrate that 1)muscles at L_ohave higher andO₂ values than those at L_s;2) fatigue occurs atL_o with highO₂, adjusting metabolic demand (tension output) to match supply; and3) the lack of fatigue atL_s with lowertension, , andO₂ suggestsadequate matching of metabolic demand, set low by shortmuscle length, with supply optimized by low preload. Thesedifferences in tension andO₂ betweenL_o andL_s groupsindicate that muscles contracting isometrically at initial lengthsshorter than L_oare working under submaximal conditions.

     

Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture

Oxygen consumption, glucose, lactate, andATP concentrations, as well as glucose and lactate turnover rates, havebeen studied in a three-dimensional carcinogenesis model of differentlytransformed rat embryo fibroblasts (spontaneously immortalized Rat1 andmyc-transfected M1, and the ras-transfected,tumorigenic descendants Rat1-T1 and MR1) to determine metabolicalterations that accompany tumorigenic conversion. Variousbioluminescence techniques, thymidine labeling, measurement ofPO₂ distributions withmicroelectrodes, and determination of cellular oxygen uptake rates(c_O2)have been applied. In the ras-transfected, tumorigenic spheroidtypes, the size dependencies of some of the measured parametersexhibited sharp breaks at diameters of ~830 µm for Rat1-T1 and~970 µm for MR1 spheroids, respectively, suggesting that somefundamental change in cell metabolism occurred at these characteristicdiameters (denoted as "metabolic switch").c_O2decreased and lactate concentration increased as functions of sizebelow the characteristic diameters. Concomitantly, glucose and lactateturnover rates decreased in MR1 spheroids and increased inRat1-T1. Spheroids larger than the characteristic diameters (exhibitingcell quiescence and lactate accumulation) showed an enhancement ofc_O2with size. Systematic variations in the ATP and glucose levels in theviable cell rim were observed for Rat1-T1 spheroids only. Proliferativeactivity, c_O2,and ATP levels in small, nontumorigenic Rat1 and M1aggregates did not differ systematically from those recorded in thelargest spheroids of the corresponding ras transfectants.Unexpectedly, respiratory activity was present not only in viable butalso in the morphologically disintegrated core regions of M1aggregates. Our data suggest that myc but not rastransfection exerts major impacts on cell metabolism. Moreover, somekind of switch has been detected that triggers profound readjustment oftumor cell metabolism when proliferative activity begins tostagnate, and that is likely to initiate some other, yetunidentified energy-consuming process.

     

Interactive flora of the British Isles: a digital encyclopedia. * Stace C, van der Meijden R, Kort I. 2004. * University of Amsterdam: ETI(Expert Center for TaxonomicIdentification). {pound}37.50 (DVD-ROM).

This DVD-ROM isa computerized version of Clive Stace's New Flora of the BritishIsles (1997, Cambridge University Press), with distributionmaps from the New Atlas of the British and Irish Flora (Prestonet al., 2002, Oxford University Press). In addition, the DVDhas more than 6500 colour photographs by 100 different photographersand over 2000 line drawings, mostly from the flora but alsofrom BSBI Handbooks, Watsonia and BSBI News (all publicationsof the Botanical Society of the British Isles). All the vascularplants (pteridophytes, gymnosperms and angiosperms) in the regionare covered, i.e. 3525 species in 166 families. The DVD enablesthe user to identify virtually any plant growing in     

A comparison of net and gross rates of oxygen production as a function of light intensity in some natural plankton populations and in a Synechococcus culture

In vitrorates of gross and net oxygen production were measuredas a function of light intensity in some plankton communitiescollected from Bedford Basin, Nova Scotia, and in a monoclonalculture of Synechococcus. The rate of gross oxygen productionwas measured by a technique in which the stable oxygen isotope,¹⁸O, serves as a photosynthetic tracer Net oxygen productionwas measured by automated Winkler technique. The rate of communityrespiration in the light was then determined by the differencebetween gross and net rates of oxygen production. In the naturalpopulations examined, neither gross nor net oxygen productionrates were significantly inhibited at the highest light intensitymeasured (500–800 µE m^–2 s^–1) In a samplein which the dark respiration rate was small relative to themaximal rate of production [P_max;sensu Platt et al (1980) JMar. Res., 38, 687–701] the rates of ‘light’respiration were 3 times greater. In two other communities,with high rates of dark respiration relative to P_maxthe ratesof ‘light’ respiration were closer to rates of darkrespiration. In the Synechococcus clone, both gross and netoxygen production rates were inhibited at high light intensities.Rates of ‘light’ respiration were found to varyas a function of light intensity. The greatest rates of respirationwere measured in samples incubated at light intensities thatwere just saturating (100 µE m^–2 s^–1). Therates of ¹⁴C production were also measured as a function oflight intensity The photosynthetic quotients, based on ¹⁴C productionrates and gross oxygen production rates, average 1 9     

The opt1 gene of Drosophila melanogaster encodes a proton-dependent dipeptide transporter

We have cloned andcharacterized the opt1 gene ofDrosophila melanogaster. This geneencodes a protein with significant similarity to the PTR family ofoligopeptide transporters. The OPT1 protein is localized to the apicalepithelial membrane domains of the midgut, rectum, and femalereproductive tract. The opt1 message is maternally loaded into developing oocytes, and OPT1 is found in the-yolk spheres of the developing embryo. It is also found throughoutthe neuropil of the central nervous system, with elevated expressionwithin the - and -lobes of the mushroom bodies. Transport activity was examined in HeLa cells transiently expressing OPT1. Thisprotein is a high-affinity transporter of alanylalanine; theapproximate K_mconstant is 48.8 µM for this substrate. OPT1 dipeptide transportactivity is proton dependent. The ability of selected -lactams toinhibit alanylalanine transport suggests that OPT1 has a broadspecificity in amino acid side chains and has a substrate requirementfor an -amino group. Together these data suggest an important rolefor OPT1 in regulating amino acid availability.

     

Prolonged fasting significantly changes nutrient oxidation and glucose tolerance after a normal mixed meal

The aim of this study wasto establish the experimental paradigm of fasting, followed byrefeeding, to investigate individual differences in nutrientpartitioning. Eight nonobese men were fed a normal meal (25% ofdaily energy requirements) on two occasions, after an overnight (13-h)fast and after a prolonged (72-h) fast. During the entire fastingperiod, subjects were resident in a whole room indirect calorimeter,and blood samples were drawn periodically. Because no other food wasconsumed over the 12 h after either meal, negative energy balancewas observed after the overnight and prolonged fast. Postprandialcarbohydrate oxidation was significantly reduced after the 72- vs. 13-hfast (P < 0.0001), whereas fat oxidation wassignificantly increased (P < 0.0001). Interestingly,carbohydrate balance was positive after the prolonged fast but negativeafter the overnight fast (24 ± 17 vs. 57 ± 16 g/12 h,respectively; P < 0.001), whereas fat balance wasnegative under both conditions (78 ± 7 vs. 47 ± 8 g/12h, respectively; P < 0.002). With 72 h offasting, the glucose and insulin excursions in response to the mixedmeal were significantly greater compared with the 13-h fast(P < 0.001). In conclusion, prolonged fasting resulted in a significant decrease in carbohydrate oxidation and anincrease in fat oxidation, after a normal mixed meal, in healthy men.This was associated with a significant decrease in glucose tolerance.Because circulating free fatty acids were greatly elevated at all timesafter the prolonged fast, these may be mediating some of the changes inpostprandial metabolism.

     

Mechanisms of Inhibition of Water Movement in Anaerobically Treated Roots of Zea mays L.

Changes in water flux (Jv) across detopped, 7-d-old, maize rootswere characterized during the initial 24 h of being made anoxicby exposure to an anaerobic nutrient solution. Suction (50 kPa)was applied to the xylem and samples of the xylem sap were collectedat intervals and the osmolality and ionic content were measured. Values of Jv through anoxic roots fell below those of aerobiccontrols 1 h after the equilibrium oxygen partial pressure inthe bathing medium dropped below 20 kPa (air = 20.6 kPa). Thereduction in Jv was due primarily to a nullification of thediurnal rhythm in hydraulic conductivity (Lp) that was measuredin aerobic roots. However, about one-quarter of the reductionin Jv could be accounted for by a smaller osmotic componentof the driving force () on water movement. The significance of changes in Jv in anoxic roots is discussedin terms of the reliability of estimates of Lp, the reflectioncoefficient () and . Key words: Anaerobiosis, hydraulic conductivity, osmotic potential, water     

Cholecystokinin induction of mob-1 chemokine expression in pancreatic acinar cells requires NF-kappa B activation

Inflammatory mediators are involved in the early phase of acutepancreatitis, but the cellular mechanisms responsible for theirgeneration within pancreatic cells are unknown. We examined the role ofnuclear factor-B (NF-B) in cholecystokinin octapeptide (CCK-8)-induced mob-1 chemokineexpression in pancreatic acinar cells in vitro. Supraphysiological, butnot physiological, concentrations of CCK-8 increased inhibitory B(IB-) degradation, NF-B activation, andmob-1 gene expression in isolatedpancreatic acinar cells. CCK-8-induced IB- degradation wasmaximal within 1 h. Expression ofmob-1 was maximal within 2 h. Neitherbombesin nor carbachol significantly increasedmob-1 mRNA or induced IB-degradation. Thus the concentration, time, and secretagogue dependenceof mob-1 gene expression and IB-degradation were similar. Inhibition of NF-B with pharmacologicalagents or by adenovirus-mediated expression of the inhibitory proteinIB- also inhibited mob-1 geneexpression. These data indicate that the NF-B signaling pathway isrequired for CCK-8-mediated induction ofmob-1 chemokine expression inpancreatic acinar cells. This supports the hypothesis that NF-Bsignaling is of central importance in the initiation of acute pancreatitis.

     

ATP stimulation of Na+/Ca2+ exchange in cardiac sarcolemmal vesicles

In cardiacsarcolemmal vesicles, MgATP stimulatesNa⁺/Ca²⁺exchange with the following characteristics:1) increases 10-fold the apparentaffinity for cytosolic Ca²⁺;2) a Michaelis constant for ATP of~500 µM; 3) requires micromolar vanadate while millimolar concentrations are inhibitory;4) not observed in the presence of20 µM eosin alone but reinstated when vanadate is added;5) mimicked by adenosine5'-O-(3-thiotriphosphate), without the need for vanadate, but not by ,-methyleneadenosine 5'-triphosphate; and 6) notaffected by unspecific protein alkaline phosphatase but abolished by aphosphatidylinositol-specific phospholipase C (PI-PLC). The PI-PLCeffect is counteracted by phosphatidylinositol. In addition, in theabsence of ATP,L--phosphatidylinositol4,5-bisphosphate (PIP₂) was ableto stimulate the exchanger activity in vesicles pretreated with PI-PLC.This MgATP stimulation is not related to phosphorylation of thecarrier, whereas phosphorylation appeared in the phosphoinositides,mainly PIP₂, thatcoimmunoprecipitate with the exchanger. Vesicles incubated with MgATPand no Ca²⁺ show a markedsynthesis ofL--phosphatidylinositol4-monophosphate (PIP) with little production ofPIP₂; in the presence of 1 µM Ca²⁺, the net synthesis of PIP issmaller, whereas that of PIP₂increases ninefold. These results indicate thatPIP₂ is involved in the MgATPstimulation of the cardiacNa⁺/Ca²⁺exchanger through a fast phosphorylation chain: aCa²⁺-independent PIP formationfollowed by a Ca²⁺-dependentsynthesis of PIP₂.

     

Photosynthesis and Light Activation of Ribulose 1, 5-bisphosphate Carboxylase in the Presence of Starch

Owing to a typographical error three equations were omittedfrom page 1294. The correct paragraphs are set out below. The component K₁ corrected for the difference in temperaturebetween the enzyme assay and the leaf and was calculated accordingto the Arrhemus equation. where v10 and v18 are the reaction velocities of carboxylationat 10?C and 18?C, respectively and A is the activation energy(A = 90 kJ mol^–1, as determined for purified wheat RuBPCOby M?chler, Keys and Cornelius, 1980) The components K2 corrected for the difference in CO₂ partialpressure between enzyme assay and leaf and for competitive inhibitionof carboxylation by O₂ and was calculated according to the modifiedMichaelis Menten equation where v_c, is the carboxylation velocity under leaf conditions,V_c. is the maximum carboxylation velocity as determined in theenzyme assay, K_c, and K_o are the Michaelis constants for carboxylationand oxygenation, respectively (K_o = 159 Pa CO₂. K_o = 35.3 kPaO₂, as interpolated for 18?C from spinach data as determinedby Jordan and Ogren, 1984), O is oxygen partial pressure inair and C₁ is intercellular CO₂ partial pressure in leaves (C₁= 29.1 ? 0.8 Pa (? s c , n = 15)) The component K3 corrected for the decrease in CO₂ fixationin leaves due to photorespiration and was calculated accordingto equation 3 Equation 3 is denved from the equation for the substrate specificityof RuBPCO, S= v_c/v_oC (Laing, Ogren, and Hageman, 1974), andfrom the equation for the stoichiometry of photorespiratoryCO₂ release, F=v_c–1/2 v_o, where v_c, and v_c are reactionvelocities of carboxylation and oxygenation, O and C are partialpressures of 02 and intercellular CO₂, F is net photosynthesisand S is the substrate specificity of RuBPCO (S= 3061 Pa/Pa,as interpolated for 18?C from spinach data as determined byJordan and Ogren, 1984)     

Ethanol sensitivity of BK(Ca) channels from arterial smooth muscle does not require the presence of the beta 1-subunit

Ethanol inhibition of large-conductance,Ca²⁺-activated K⁺ (BK_Ca) channelsin aortic myocytes may contribute to the direct contraction of aorticsmooth muscle produced by acute alcohol exposure. In this tissue,BK_Ca channels consist of pore-forming (bslo) and modulatory () subunits. Here, modulation of aortic myocyteBK_Ca channels by acute alcohol was explored by expressingbslo subunits in Xenopus oocytes, in the absenceand presence of ₁-subunits, and studying channelresponses to clinically relevant concentrations of ethanol in excisedmembrane patches. Overall, average values of bslo channelactivity (NP_o, with N = no. ofchannels present in the patch; P_o = probability of a single channel being open) in response to ethanol(3-200 mM) mildly decrease when compared with pre-ethanol,isosmotic controls. However, channel responses show qualitativeheterogeneity at all ethanol concentrations. In the majority of patches(42/71 patches, i.e., 59%), a reversible reduction inNP_o is observed. In this subset, the maximaleffect is obtained with 100 mM ethanol, at whichNP_o reaches 46.2 ± 9% of control. Thepresence of ₁-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17-estradiol, fails to modifyethanol action on bslo channels. Ethanol inhibition of bslo channels results from a marked increase in the meanclosed time. Although the voltage dependence of gating remainsunaffected, the apparent effectiveness of Ca²⁺ to gate thechannel is decreased by ethanol. These changes occur withoutmodifications of channel conduction. In conclusion, a new molecularmechanism that may contribute to ethanol-induced aortic smooth musclecontraction has been identified and characterized: a functionalinteraction between ethanol and the bslo subunit and/or itslipid microenvironment, which leads to a decrease in BK_Cachannel activity.

     

Roots: the dynamic interface between plants and the Earth. * Abe J, ed. 2003. * Dordrecht: Kluwer Academic Publishers. * {euro}165 (hardback). 460 pp

All but five of the 46 contributionsin this symposium volume have been published already as a specialissue in Volume 255 of Plant and Soil in 2003. They are reproducedin exactly the same format and with the same pagination as inthe journal. To anyone who has access to Plant and Soil thisbook would therefore not be a sensible purchase. This is allthe more true because the editor has not provided any commentaryon the papers or subdivided them     

Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis

Welty-Wolf, Karen E., Steven G. Simonson, Yuh-Chin T. Huang,Stephen P. Kantrow, Martha S. Carraway, Ling-Yi Chang, James D. Crapo, and Claude A. Piantadosi. Aerosolizedmanganese SOD decreases hyperoxic pulmonary injury in primates. II.Morphometric analysis. J. Appl.Physiol. 83(2): 559-568, 1997.Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygenspecies that exceeds antioxidant defenses. We hypothesized thataerosolized human recombinant manganese superoxide dismutase (rhMnSOD)would augment extracellular antioxidant defenses and attenuateepithelial injury in the lung during hyperoxia in primates. Twenty-fouradult male baboons were anesthetized and mechanically ventilated with100% oxygen for 96 h. The baboons were divided equally into fourgroups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg · kg¹ · day¹were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg · kg¹ · day¹to study dose effects and toxicity. Quantitative morphometry showedprotection of alveolar epithelium from hyperoxia by 3 mg · kg¹ · day¹rhMnSOD (P < 0.05). In addition,interstitial fibroblast volumes were increased in the treatment group(P = 0.06). This effect appearedgreater at the two higher doses of the rhMnSOD. The aerosolized drugwas localized to the surface of airways and air spaces and macrophagesby immunolabeling studies, suggesting efficacy via physicochemicalproperties that localize it to cell surfaces or by effects on alveolarmacrophage function.