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Fold recognition by combining sequence profiles derived from evolution and from depth-dependent structural alignment of fragments.

Recognizing structural similarity without significant sequence identity has proved to be a challenging task. Sequence-based and structure-based methods as well as their combinations have been developed. Here, we propose a fold-recognition method that incorporates structural information without the need of sequence-to-structure threading. This is accomplished by generating sequence profiles from protein structural fragments. The structure-derived sequence profiles allow a simple integration with evolution-derived sequence profiles and secondary-structural information for an optimized alignment by efficient dynamic programming. The resulting method (called SP(3)) is found to make a statistically significant improvement in both sensitivity of fold recognition and accuracy of alignment over the method based on evolution-derived sequence profiles alone (SP) and the method based on evolution-derived sequence profile and secondary structure profile (SP(2)). SP(3) was tested in SALIGN benchmark for alignment accuracy and Lindahl, PROSPECTOR 3.0, and LiveBench 8.0 benchmarks for remote-homology detection and model accuracy. SP(3) is found to be the most sensitive and accurate single-method server in all benchmarks tested where other methods are available for comparison (although its results are statistically indistinguishable from the next best in some cases and the comparison is subjected to the limitation of time-dependent sequence and/or structural library used by different methods.). In LiveBench 8.0, its accuracy rivals some of the consensus methods such as ShotGun-INBGU, Pmodeller3, Pcons4, and ROBETTA. SP(3) fold-recognition server is available on http://theory.med.buffalo.edu.

Algorithms↗

Diversity and phylogenetic implications of CsCl profiles from rodent DNAs.

Buoyant density profiles of high-molecular-weight DNAs sedimented in CsCl gradients, i.e., compositional distributions of 50- to 100-kb genomic fragments, have revealed a clear difference between the murids so far studied and most other mammals, including other rodents. Sequence analyses have revealed other, related, compositional differences between murids and nonmurids. In the present study, we obtained CsCl profiles of 17 rodent species representing 13 families. The modal buoyant densities obtained for rodents span the full range of values observed in other eutherians. More remarkably, the skewness (asymmetry, mean - modal buoyant density) of the rodent profiles extends to values well below those of other eutherians. Scatterplots of these and related CsCl profile parameters show groups of rodent families that agree largely with established rodent taxonomy, in particular with the monophyly of the Geomyoidea superfamily and the position of the Dipodidae family within the Myomorpha. In contrast, while confirming and extending previously reported differences between the profiles of Myomorpha and those of other rodents, the CsCl data question a traditional hypothesis positing Gliridae within Myomorpha, as does the recently sequenced mitochondrial genome of dormouse. Analysis of CsCl profiles is presented here as a rapid, robust method for exploring rodent and other vertebrate systematics.

Animals↗

Pressure profile of esophageal peristalsis in normal humans as measured by direct intraesophageal transducers.

The pressure profile of esophageal peristalsis was studied in healthy young adult males using an intraesophageal transducer assembly. The amplitude of peristaltic contractions following wet swallows was determined at intervals along the esophagus from the lower esophageal sphincter (LES) to the upper esophageal sphincter (UES). The amplitude profile revealed a trough of significantly decreased (P less than 0.05) amplitude at 17.5-20.0 cm above the LES. The change in pressure per unit time (dp/dt) produced a profile also with a significant decrease (P less than 0.01) in the upper esophagus, having good correlation (r = 0.91, P less than 0.001) with the amplitude profile. Mean velocity of the peristaltic wave in the upper esophagus varied from 2.92 +/- 0.19 (+/- SEM) to 3.29 +/- 0.36 cm/sec. In the distal esophagus, mean velocity increased significantly (P less than 0.01) to 4.98 +/- 0.38 cm/sec at 7.5 cm above the LES, and then fell significantly (P less than 0.05) to 2.15 +/- 0.27 cm/sec at 2.5 cm above the LES. This report establishes amplitude and velocity profiles in the human esophagus. The profile of the first derivative of the primary peristaltic wave (dp/dt) is also described, and its possible importance discussed.

Adult↗

Human gut hormone profiles in patients with short bowel syndrome.

We have studied gut hormone profiles in a small number of patients on treatment with home parenteral nutrition following near-total enterectomy who had no evidence of inflammatory bowel disease and who were otherwise healthy. These and age- and sex-matched controls had gut hormone profiles measured after an overnight fast and a standard test meal. Circulating pancreatic glucagon concentrations and profiles were the same in both groups as were the neurotensin and VIP. Peptide YY (PYY) concentrations and profiles were markedly raised in the short bowel group. It is suggested that the normal glucagon responses reflect the integrity of the remaining duodenum and pancreas. Circulating neurotensin and VIP originate largely from outside the bowel and so the removal of the gut source does not significantly affect their profiles. Enteroglucagon and PYY are secreted from terminal ileum and colon in response to unabsorbed food residues. The elevated circulating levels and profiles are consistent with those observed by others in patients with jejunoileal bypass or major resections in whom unabsorbed nutrients reach the colon.

Adolescent↗

LH isoform profiles during short-term pulsatile LHRH administration in elderly men.

LH isoform profiles were analyzed in sera resolved with isoelectrofocusing from 5 elderly men (age 70.6 +/- 2.95) and 5 young adult men (age 28.2 +/- 1.24), by using polyclonal antibodies (RIA), monoclonal antibodies directed against the beta-subunits (IRMA) and in vitro LH bioassay. Despite the fact that the elderly had lower testosterone levels than the young (293 +/- 38 vs 512 +/- 77 ng/dl, p < 0.05), no differences were noted in the isoforms detected by any of the assays, although each assay yielded a characteristic profile. Indeed, RIA showed most LH in the acidic range, while IRMA revealed LH profiles with a major peak in the basic range, thus resembling the profiles determined by means of the bioassay. In the elderly, the profiles were also analyzed on day 7 and day 14 of short-term pulsatile sc LHRH administration (150 ng/bw/120 min). Only the LH bioassay detected an LHRH-induced shift to more basic and bioactive forms; these changes accompanied an increased in testosterone levels on day 7 (396 +/- 83 ng/dl, p < 0.05 vs day 0) and on day 14 (320 +/- 58 ng/dl NS vs day 0). Our data suggest that: 1) the profiles obtained in young and elderly subjects are similar, irrespective of the antisera used; 2) as a result of treatment with LHRH in the elderly an increase in T levels occurs, possibly due to the observed changes in LH bioactivity; 3) the in vitro LH bioassay appears to be the most sensitive assay in detecting such changes, which consisted of an enrichment in more basic and bioactive glycoforms.

Adult↗

Natural populations of chickpea rhizobia evaluated by antibiotic resistance profiles and molecular methods.

The aims of this study were to investigate the hypothesis that intrinsic antibiotic resistance (IAR) profiles of chickpea rhizobia are correlated with the isolates site of origin, and to compare the discriminating power of IAR profiles with molecular approaches in rhizobial strain identification and differentiation. Rhizobial diversity from five Portuguese soils was assessed by IAR profiles and molecular methods [16S rDNA restriction fragment length polymorphism (RFLP) analysis, direct amplified polymorphic DNA (DAPD) fingerprinting, and SDS-PAGE analysis of protein profiles]. For each analysis, a dendrogram was generated using the software BioNumerics. All three molecular methods generated analogous clustering of the isolates, supporting previous results on 16S rDNA sequence-based phylogeny. Clusters obtained with IAR profile are similar to the species groups generated with the molecular methods used. IAR groups do not correlate significantly with the geographic origin of the isolates. These results may indicate a chromosomal location of antibiotic resistance genes, and suggest that IAR is species related. DAPD and IAR profiles proved to be the most discriminating approaches in strain differentiation and can be used as fast methods to screen diversity in new isolates.

Anti-Bacterial Agents↗

Stable carbon and nitrogen isotope ratio profiling of sperm whale teeth reveals ontogenetic movements and trophic ecology.

Teeth from male sperm whales (Physeter macrocephalus) stranded in the North-eastern Atlantic were used to determine whether chronological profiles of stable isotope ratios of C (delta(13)C) and N (delta(15)N) across dentine growth layers could be used to detect known ontogenetic benchmarks in movements and trophic ecology. Profiles showed a general decrease in delta(13)C (median = 1.91 per thousand) and an increase in delta(15)N (median = 2.42 per thousand) with age. A marked decline in delta(13)C occurred for all 11 teeth around 9-10 years and again for six individuals around 20 years. After the early twenties the delta(13)C continued to decline with age for all teeth. These results are consistent with males segregating from natal groups in low latitudes with the onset of puberty between 4 and 15 years and gradually dispersing pole-ward into (13)C-depleted temperate waters. Penetration into further depleted, productive high latitudes after the age of 20 might facilitate the spurt of accelerated growth rate observed around this age. Breeding migrations back to lower latitudes were not reflected in the delta(13)C profiles possibly due to being short compared to the time spent feeding in high latitudes. The timings of marked isotopic change in the delta(15)N profiles reflect those of the delta(13)C profiles, suggesting a link between dietary changes and movements. The observed increase in delta(15)N with age is likely to be caused by a trophic level increase as males grow in size, probably feeding on larger prey. An additional explanation could be that, in the higher latitudes of the North Atlantic, the main prey source is the high trophic level squid Gonatus fabricii. Also, the lower latitudes from where males disperse are depleted in basal (15)N. Profiles of delta(13)C and delta(15)N in sperm whale teeth gathered from different regions, sexes, and periods in time, could provide a unique way to understand the ecology of this species across different oceans.

Age Factors↗

The abnormal fetal biophysical profile score. V. Predictive accuracy according to score composition.

The relationship between last abnormal biophysical profile score, in total and by variable composition, and a spectra of abnormal perinatal outcome end points was examined in 525 fetuses. Highly significant inverse relationships between last test score and outcome were observed; relationships were linear for most end points and exponential for perinatal mortality end points. For biophysical profile scores less than or equal to 6, 25 of the 26 possible variable combinations were observed, at varying frequencies. For a biophysical profile score of 6, the positive predictive accuracy for some end points was significantly higher with either nonreactive nonstress test/fetal tone absent or nonreactive nonstress test/absent fetal breathing movement, and significantly lower with absent fetal breathing movement and decreased amniotic fluid volume. For a biophysical profile score of 4, the positive predictive accuracy for some end points was significantly higher with nonreactive nonstress test/absent fetal breathing movement/decreased amniotic fluid and was significantly lower with absent fetal movement/fetal breathing movement/fetal tone. No significant variation was observed for a biophysical profile score of 2. These data indicate that not all abnormal biophysical profile scores are equal.

Apgar Score↗

The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in preterm premature rupture of the membranes.

The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in 44 consecutive patients with preterm premature rupture of the membranes were determined. All patients were followed up with daily fetal biophysical profiles and systolic/diastolic ratios. After delivery, placental pathologic examination for histologic evidence of infection (umbilical vasculitis) was performed in all cases according to a standard protocol. The longitudinal trends of fetal biophysical profile scores and systolic/diastolic ratios were analyzed for patients with and without umbilical vasculitis. Analysis of the longitudinal trend during the period of 2 to 7 days before delivery showed that there were no differences of biophysical scores of systolic/diastolic ratios in either group. However, in the last examination, within 24 hours of delivery, patients with umbilical vasculitis had higher systolic/diastolic ratios and lower biophysical profile scores as compared with previous examinations. In addition, the biophysical profile score of the last examination 24 hours before delivery in patients with umbilical vasculitis was found to be significantly lower as compared with patients without umbilical vasculitis (mean +/- SD, 6.6 +/- 2.3 versus 8.2 +/- 2.4, respectively). These data suggest that subclinical stages of infection are associated with biophysical alterations of the fetoplacental unit (i.e., simultaneous decrease in fetal biophysical activities and increase in systolic/diastolic ratios). Daily umbilical artery systolic/diastolic ratios, in conjunction with biophysical profiles, may be useful to follow up patients with preterm premature rupture of the membranes.

Blood Flow Velocity↗

Outcome profiles in the treatment of unipolar depression.

Treatment efficacy is typically evaluated by examining group means and pre-post change scores. Although informative, such analyses may obscure individual or subgroup differences in response (outcome profiles). The present study used two different methods to define treatment outcome profiles--rationally-derived criteria (Frank et al., Archives of General Psychiatry 48, 851-855, 1991) and dynamic clustering--to evaluate four treatments of unipolar depression: behaviour therapy, amitriptyline, psychodynamic psychotherapy and relaxation training (attention placebo). The profiling methods yielded similar results. Regardless of treatment, the majority of patients displayed either a recovery or nonremission outcome profile, with relatively few instances of remission followed by a recurrence of depression. These findings challenge the view that any of the treatments are associated with a strong tendency to relapse, at least over the 3-month follow-up period. To further characterize the major outcome profiles, discriminant analysis was performed. Results indicated that recovery and nonremission profiles differed in that the latter was associated with a longer and more severe index episode and greater neuroticism. A number of variables, including family history of depression and therapists' prediction of outcome, failed to distinguish recovered from unremitted patients.

Adult↗

A blood vessel model based on velocity profiles.

A simple model of pressure-flow relationship in blood vessels was developed. The calculation of the model components was based on velocity profiles in the vessels. The flat velocity profile in the entrance of the vessel was considered. By using mean pressure over the cross-section and assuming a polynomial approximation of the velocity profile, it is shown that the resistance of a vessel segment increases with increased flatness of the velocity profile. Moreover, the analysis provides a means to calculate the resistance of a vessel segment based on the shape of the velocity profiles in that segment. The analysis shows that the inertance element of the segment is not affected by the shape of the velocity profile.

Animals↗

REE chemistry and Sm-Nd systematics of late Archean weathering profiles in the Fortescue Group, Western Australia.

Two weathering profiles, each consisting of an upper, sericite-rich zone and a lower, chlorite-rich zone, are preserved between flows of the Mt. Roe Basalt in the Fortescue Group, Hamersley Basin, Western Australia. REE concentrations in samples from these two profiles, which originally developed ca 2,760 Ma, show large variations depending on stratigraphic position. LREE abundances and (La/Yb)N are greatest at depths of 3-6 m below the paleosurface of the Mt. Roe #1 profile and are somewhat lower in samples above this level. The LREEs reach concentrations 6-9 times greater than in the underlying basalt, and thus appear to have been mobilized downward in the paleosol and concentrated in its middle part. LREE concentrations in the #2 profile show a similar distribution but with a sharp increase in all REE concentrations within 50 cm of the paleosurface. The distinction between the REE profiles in the two paleosols may be related to the difference in the overlying material. The #1 paleosol is overlain by a few meters of sediments and then by basalt, whereas the #2 paleosol is directly overlain by basalt. The LREEs appear to have been mobilized both during chemical weathering of the parental basalt and during later lower-greenschist-facies metamorphism and metasomatism of the paleosols. Remobilization of the REEs during the regional metamorphism of the Fortescue Group is confirmed by a whole-rock Sm-Nd reference isochron of Mt. Roe #1 samples with an age of 2,151 +/- 360 Ma. Variable initial 143Nd/144Nd values of unweathered basalt samples which may represent the paleosol protolith prevents a confident determination of the magnitude of LREE mobility. Both the initial mobilization of the REEs during weathering and the metasomatic remobilization appear to have taken place under redox conditions where Ce was present dominantly as Ce3+, because Ce anomalies are not developed within the sericite zone samples regardless of concentration. Europium anomalies in the paleoweathering profile are somewhat variable and were probably modified by mobilization of Eu2+ at metamorphic conditions. In all samples, the HREEs appear to have been relatively immobile and correlate with Al, Ti, Cr, V, Zr, and Nb. Sm-Nd systematics and REE patterns of four unweathered basalt samples indicate derivation of the Mt. Roe Basalts from a heterogeneous and enriched source having epsilon Nd between -4.0 and -7.4. Initial 143Nd/144Nd values of these basalts are even lower than those reported by NELSON et al. (1992) for Fortescue Group basalts and indicate a substantial crustal component in the generation of Mt. Roe Basalts.

Atmosphere↗

An angular velocity profile in cycling derived from mechanical energy analysis.

The contributions of this article are twofold. One is procedure for determining the angular velocity profile in seated cycling that maintains the total mechanical energy of both legs constant. A five-bar linkage model (thigh, shank, foot, crank and frame) of seated (fixed hip) cycling served for the derivation of the equations to compute potential and kinetic energies of the leg segments over a complete crank cycle. With experimentally collected pedal angle data as input, these equations were used to compute the total combined mechanical energy (sum of potential and kinetic energies of the segments of both legs) for constant angular velocity pedalling at 90 rpm. Total energy varied indicating the presence of internal work. Motivated by a desire to test the hypothesis that reducing internal work in cycling will reduce energy expenditure, a procedure was developed for determining the angular velocity profile that eliminated any change in total energy. Using data recorded from five subjects, this procedure was used to determine a reference profile for an average equivalent cadence of 90 rpm. The phase of this profile is such that highest and lowest angular velocities occur when the cranks are near vertical and horizontal respectively. The second contribution is the testing of the hypothesis that the reference angular velocity profile serves to effectively reduce internal work for the subjects whose data were used to develop this profile over the range of pedalling rates (80-100 rpm) naturally preferred. In this range, the internal work was decreased a minimum of 48% relative to the internal work associated with constant angular velocity pedalling. The acceptance of this hypothesis has relevance to the protocol for future experiments which explore the effect of reduced internal work on energy expenditure in cycling.

Anthropometry↗

A model study of flow dynamics in human central airways. Part I: axial velocity profiles.

We measured detailed steady inspiratory and expiratory velocity profiles in a 3:1 scale model of the human central airways. The model was constructed out of acrylic plastic, mounted vertically, and connected to a specially designed steady-flow system. Laterally introduced hot-wire anemoneter probes were used to record axial velocities along 4 diameters at each of the 12 pre-drilled stations of measurement; the flow distribution among the five lobar bronchi was controlled by distally positioned linear resistors. Whether with a flat entrance profile or entering as a narrow jet, the inspiratory flow velocity profiles in the frontal plane showed a high degree of asymmetry in all branches, with peak velocities near the inner wall of the bifurcation. In the sagittal plane the velocity profiles were nearly symmetric, exhibiting a single peak near the center in the frontal plane and almost flat in the sagittal plane. Overall, the velocity profiles were more sensitive to airway geometry than to flow rate. The only site of flow separation was observed in the right upper lobar bronchus. The most evident modification of axial velocity profiles in a single branch was found in the left main bronchus during expiratory flow.

Humans↗

Urinary porphyrin profiles as biomarkers of trace metal exposure and toxicity: studies on urinary porphyrin excretion patterns in rats during prolonged exposure to methyl mercury.

Studies were conducted to define the specific changes in the urinary porphyrin excretion pattern (porphyrin profile) and the time course of those changes in rats exposed to mercury as methyl mercury hydroxide (MMH) at 5 or 10 ppm in the drinking water for up to 30 weeks. The urinary porphyrin profile elicited by MMH is uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins, and of a third atypical porphyrin with as yet undetermined chemical characteristics. Changes in the porphyrin profile were observed as early as 1 or 2 weeks following initiation of exposure to MMH at 10 or 5 ppm, respectively, and were sustained as long as 40 weeks following cessation of MMH treatment. The magnitude of the urinary porphyrin profile at either MMH dose level increased progressively during the course of mercury treatment and was highly correlated with the renal mercury concentration. A subsequent decline in the magnitude of the urinary porphyrin profile in animals exposed to 10 ppm MMH for more than 10 weeks was associated with the accumulation of high levels of Hg2+ in kidney cells and loss of renal functional status. These findings demonstrate that mercury elicits a unique change in the urinary porphyrin excretion pattern which is related to the dose and duration of mercury treatment. The association of urinary porphyrin excretion rates with renal mercury content and functional status suggests that urinary porphyrin profiles may serve as a useful biomarker of mercury accumulation and nephrotoxicity during prolonged mercury exposure.

Animals↗

Prostaglandin profile and synthetic capacity of the colon: comparison of tissue sources and subcellular fractions.

Although there has been intense interest in the physiology and pathophysiology of prostaglandins (PGs) synthesized in the colon, little is known about the PG profile and synthetic capacity of different tissue sources and subcellular fractions as enzyme sources. Subcellular fractions prepared from the mucosa and muscle layer of rat colon were incubated with or without exogenous arachidonic acid ([3H]20:4n-6) for 30 min. In experiments with exogenous [3H]20:4n-6, the prostaglandin synthetic capacity of the colonic muscle layer was significantly higher than that of the mucosa. Among the subcellular fractions, microsomes had the highest PG synthetic capacity in both mucosa and muscle. The major PG product was PGI2 and PGD2 in the mucosal microsomes and PGI2 and PGE2 in the muscularis microsomes. However, production of PGI2 in the mucosa and PGE2 in the muscle was significantly reduced in the fractions containing both cytosol and microsome, resulting in an alteration of the PG profile. Substrate availability (exogenous vs endogenous supply) appears to influence the PG profile of the colon. In the colonic mucosa with exogenous [3H]20:4n-6, the production of PGI2 was 5 times higher than that of PGE2, whereas the production of PGE2 was twice higher than that of PGI2 in experiments with endogenous 20:4n-6. These observations indicate: 1) different PG profile and synthetic capacity of tissue sources and subcellular fractions; 2) alteration of PG profile due to the variation of 20:4n-6 availability. Thus, the outcome of experiments on the physiological role of PG in the colon may be determined, in part, by the tissue source and subcellular fraction selected for analysis. The present study also suggests that the variation of substrate availability in physiological and pathophysiological processes may affect the PG profile of the colon.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Isoelectric focusing using non-amphoteric buffers in free solution: I. Determination of stable concentration profiles.

For large-scale separations of proteins, the use of simple non-amphoteric buffers in free solution and in multicompartment electrolyzers seems promising for industrial applications. The stabilization of a pH profile with this type of buffer requires the strict observation of two conditions: choice of an adequate buffer; stationary profiles of concentrations. During electrolysis in free solution, the ions of the buffer are displaced across the compartments by migration and by diffusion. To keep a stationary composition, the inflow and outflow of all individual ionic species through each compartment must be identical. At high current, diffusion may be neglected against migration and the ionic flows will be identical if the transport number of each ion is constant at each location within the cell. In these conditions, stationary compositions will be independent of the electric current. This condition of constant transport numbers implies the use of profiles of buffer concentrations different from those published up to now. The new equations for these profiles of concentrations are given in the present paper. The constant migration of the ions must be compensated in the end compartments of the isoelectric focusing cell to provide a stable steady state. Two methods are proposed in the literature: the buffer renewal method and the external recycling method (rheoelectrolysis). Here modified buffer renewal method is proposed. Using stationary mass balances, analytical equations are given to calculate the flows and the composition of the solutions to be recycled or added. Using these equations and the profiles of concentrations to keep constant transport numbers, it is demonstrated that only a renewal of the buffers in the end compartments may lead to stable pH profiles and thus to valid conditions of separation.

Buffers↗

Usefulness of bronchoalveolar cell profile in early detection of canine lung allograft rejection.

To evaluate the value of a bronchoalveolar cell profile in the early detection of canine lung allograft rejection, bronchoalveolar lavages were done serially in mongrel dogs before and after single lung transplantation. The dogs were divided into 3 groups. In group 1, neither donor nor recipient dogs were treated with cyclosporine. In group 2, only donors were treated with cyclosporine, orally at a single dose of 20 mg/kg/day for 3 days prior to single lung transplantation. In group 3, only recipients were treated with cyclosporine (20 mg/kg/day) for 9 days after single lung transplantation. A marked increase in the number of bronchoalveolar cells and their cell differentials, and of major histocompatibility complex (MHC) class II-positive cells obtained from the grafted lungs after lung transplantation, was seen in groups 1 and 2. The changes in bronchoalveolar cell profile obtained from the rejecting grafted lungs were significantly different from those obtained from the normal and native lungs (P less than 0.05). In group 3, the bronchoalveolar cell profile obtained from the grafted lungs did not significantly differ from those present in normal and native lungs during the period of cyclosporine treatment after lung transplantation. On various days after withdrawal of cyclosporine treatment, bronchoalveolar cell profiles obtained from the grafted lungs showed similar changes to those observed in groups 1 and 2. Abnormal changes in bronchoalveolar cell profiles obtained from the grafted lungs heralded the appearance of abnormalities detected by chest X-ray films. Our results indicate that serial measurements of bronchoalveolar cell profile may serve as a useful means for early detection of canine lung allograft rejection.

Animals↗