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Pyridalyl is a recently discovered insecticide that exhibits high insecticidal activity against Lepidoptera and Thysanoptera. Pyridalyl action requires cytochrome P450 activity, possibly for production of a bioactive derivative, Pyridalyl metabolism being prevented by general P450 inhibitors. Apoptosis is apparently not involved in the cytotoxicity. Continuous culture of Spodoptera frugiperda Sf21 cells in sub-lethal doses of Pyridalyl, results in a Pyridalyl-resistant cell line. Probing the molecular action of Pyridalyl by comparison of the proteomes of Pyridalyl-resistant and –susceptible cell lines, revealed differential expression of a number of proteins, including the up-regulation of thiol peroxiredoxin (TPx), in the resistant cells. Treatment of Bombyx mori larvae with Pyridalyl, followed by comparison of the midgut microsomal sub-proteome, revealed the up-regulation of three proteasome subunits. Such subunits, together with Hsp70 stress proteins, glyceraldehyde 3-phosphate dehydrogenases (GAPDHs) and thiol peroxiredoxin (TPx) were also up-regulated in the whole proteome of B. mori BM36 cells following treatment with the insecticide. The foregoing results lead to the hypothesis that cytochrome P450 action leads to an active Pyridalyl metabolite, which results in production of reactive oxygen species (ROS), that leads to damage to cellular macromolecules (e.g., proteins) and enhanced proteasome activity leads to increased protein degradation and necrotic cell death.

IN studying photographic plates exposed to the cosmic rays, we have found a number of multiple disintegrations each of which appears to have been produced by the entry of a slow charged particle into a nucleus. Mosaics of photomicrographs of three of these events are given in Figs. 1, 2 and 3. The edges of the individual photographs have not been trimmed so that the components of the mosaics can be distinguished. Three grains of a track in Fig. 1, indicated by three arrows, which were out of focus in the original negatives, have been blackened with ink, but the photographs are otherwise completely unretouched. 1947 was the year of the pion - flick through Nature volumes 159 and 160 and watch the story unfold. In February of that year, Cecil Powell and Giuseppe Occhialini reported the observation of six star-like patterns in emulsions exposed to cosmic rays. Powell’s group had finally found the Yukawa particle, predicted in 1935 to be the carrier of strong force inside the atomic nucleus. In fact, Don Perkins pipped them to the post with the publication of a single, similar star-like event just two weeks earlier [Perkins, D. H. Nature 159, 126–127 (1947)]. Later in the year, another paper from Powell’s group announced the first observation of pion decay to a muon - the particle picture was beginning to take shape.

Introduction. In recent experiments, it has M. been shown that charged mesons, brought to rest A in photographic emulsions, sometimes lead to the production of secondary mesons. We have now extended these observations by examining plates exposed in the Bolivian Andes at a height of 5,500 m., and have found, in all, forty examples of the process leading to the production of secondary mesons. In eleven of these, the secondary particle is brought to rest in the emulsion so that its range can be determined. In Part 1 of this article, the measurements made on these tracks are described, and it is shown that they provide evidence for the existence of mesons of different mass. In Part 2, we present further evidence on the production of mesons, which allows us to show that many of the observed mesons are locally generated in the ‘explosive’ disintegration of nuclei, and to discuss the relationship of the different types of mesons observed in photographic plates to the penetrating component of the cosmic radiation investigated in experiments with Wilson chambers and counters. 1947 was the year of the pion — flick through Nature volumes 159 and 160 and watch the story unfold. In February of that year, Cecil Powell and Giuseppe Occhialini reported the observation of six star-like patterns in emulsions exposed to cosmic rays. Powell's group had finally found the Yukawa particle, predicted in 1935 to be the carrier of strong force inside the atomic nucleus. In fact, Don Perkins pipped them to the post with the publication of a single, similar star-like event just two weeks earlier [Perkins, D. H. Nature 159, 126–127 (1947)]. Later in the year, another paper from Powell's group announced the first observation of pion decay to a muon — the particle picture was beginning to take shape.

During shipping, ornamental fish can be stressed due to handling, high stocking densities, and deteriorating water quality. Adding sedatives, such as metomidate hydrochloride, to shipping water may improve fish survival rates and the percentage of fish in saleable condition. Although the effects of metomidate hydrochloride on the stress response in fish have been studied, its application as a shipping additive has not been well investigated, particularly for tropical ornamental fishes shipped under industry conditions. Convict cichlids Cichlasoma nigrofasciatum and black mollies Poecilia sphenops were evaluated for 7 d after a 24-h period of exposure (including ground and air transport) to one of four metomidate hydrochloride concentrations: 0.0, 0.2, 0.5, and 1.0 mg/L. Immediate posttransport and cumulative mortality data, as well as 12-h and 7-d posttransport appearance and behavior scores, were generated. In convict cichlids, the highest dose of metomidate hydrochloride (1.0 mg/L) reduced mortality (0% compared with cumulative means of 5.5-9.2% in other groups) and increased the percentage of saleable fish (91.7% were immediately saleable compared with 12.5-50% in other groups). No effect was detected in black mollies at any concentration tested. Metomidate hydrochloride showed promise as a shipping additive for convict cichlids, but further studies are warranted to evaluate species-specific responses in other ornamental species.

The financial industry, like many others, is powered by information and data. A number of government agencies, quasi-government agencies, and private companies collect, process, use, and distribute information about a variety of players in the financial world. While the subjects of the data (balance sheet items or counterparty information, for example) may vary dramatically by agency and use, they all describe a particular financial institution or legal entity. Yet a standard way to uniquely identify one financial entity from another does not currently exist. A Social Security number distinguishes one John Smith from another John Smith, but at present no single identifier distinguishes one First National Bank from another. Several private companies have developed proprietary identifiers created for their own purposes but none of those identifiers are industry-wide, universal, or strictly focused on identifying a specific institution. A diverse group of analysts from the Board of Governors of the Federal Reserve System, Federal Reserve Bank of New York, Commodity Futures Trading Commission (CFTC), Federal Deposit Insurance Corporation (FDIC), Financial Industry Regulatory Authority (FINRA), Securities and Exchange Commission (SEC), and Treasury have developed guidelines detailing the best way the industry might create, develop, and maintain such a crucial identifier. The paper summarizes the current environment of entity identification and the problems that are currently encountered in both the private and public sectors by the lack of an industry-wide identifier. The paper identifies the key components that should be incorporated into the LEI such as uniqueness, persistence, and public availability. The paper identifies possible alternative approaches to solving the LEI problem and supports a collaborative public and private sector approach. The paper also considers the need for an international solution, as financial markets grow ever more interconnected across the globe.

The justification for a pediatric satellite pharmacy is described. Of the 742 inpatient beds in a tertiary-care medical center, 150 are dedicated to pediatric patients. The pharmacy department provides services to both adult and pediatric patients from a central pharmacy. However, unit dose drug distribution services are not provided to the nurseries. Furthermore, the department lacks a core of pharmacists specializing in pediatric practice. As a result, the ability of the pharmacy to support pediatric drug use has been compromised, and medication errors and infection control problems have occurred that can be attributed to this situation. A pediatric satellite pharmacy was proposed to improve the quality of pediatric care. Service objectives were established, and benefits were identified. A financial analysis was included in the proposal that documented a total gain attributable to a pediatric satellite pharmacy of approximately $285,000 over five years. The satellite pharmacy was approved by hospital administration. The pharmacy department's quality assurance committee will monitor the satellite's impact. The justification for a proposed pediatric satellite pharmacy included indications that the satellite could correct medication-related problems and improve pediatric care and that implementation would have a positive effect on finances.

Degradation kinetics for several peptides that bind to the major histocompatibility complex on antigen-presenting cells were determined in both human serum (HS; 25%) and synovial fluid (SF; 25%) from patients with rheumatoid arthritis to test whether therapeutic intervention of rheumatoid arthritis by direct intrasynovial injection is feasible (at least in terms of peptide stability). Controls consisted of enzymatically immature 10% fetal calf serum and peptidase-rich 5% liver homogenate (all diluted with RPMI-1040 tissue culture medium). Peptide half-lives ranged from approximately 4 to greater than 10,000 min, with most peptides showing half-lives of approximately 10-100 min. These studies show that, even though the populations of inflammatory and other cell types in SF and HS are different (and may, therefore, generate different peptidase profiles), the observed peptide stabilities in SF and HS are similar. This finding indicates that the effect of SF on peptide stability is similar to that of HS.

Heat-treated high chromium and Cr-Ni white cast irons are widely used by the mining and mineral industries for impact and abrasion resistance. With certain heat treatments, Fe-Cr carbides are precipitated within the chromium- and carbon-rich austenitic matrix, thereby destabilizing the austenite which transforms substantially to martensite on subsequent cooling. The crystal structures of these carbides were determined indirectly by referring electron microprobe analyses of the austenitic matrix to the appropriate isothermal solid-state sections of the Fe-Cr-C phase diagram and directly by microprobe analyses of exposed secondary carbides. The nucleation, growth and morphology of these carbides were studied by a combination of selective removal of the austenitic matrix and subsequent scanning electron microscopy of the exposed carbides.

To date there has been little research in the UK on farmer adoption of biosecurity measures to control food-borne zoonoses that have little or no impact on animal health or production but which threaten public health. Campylobacteriosis and salmonellosis are the two most common causes of food-borne infectious intestinal disease in people in Great Britain, causing approximately 57,000 and 13,000 reported cases in 2007 respectively (Anon 2008a) with an important cost to society. Poultry are an important source of both infections, while pigs may also contribute to human salmonellosis. However, these infections in poultry and pigs seldom cause disease. Research has shown that improved farm biosecurity may reduce the prevalence of these infections in livestock and if the majority of farmers were prepared to enhance biosecurity then there could be an important impact on public health. This article reports on the findings of two studies of farmer attitudes to and cost of the adoption of on-farm biosecurity measures to reduce the risk of animal diseases and therefore enhance food safety. One study, of Campylobacter infection among broiler flocks, is based on a survey of farmers faced with a hypothetical biosecurity intervention, while the other study, of Salmonella infection among pigs, is based on the participation of a group of farmers in an intervention study. In both cases, the results show a clear inverse relationship between the willingness of farmers to adopt a biosecurity measure and its estimated cost. This finding has implications for the success of on-farm biosecurity-enhancement policies based on voluntary adoption by farmers. In particular, financial inducements or penalties to farmers could be necessary to facilitate adoption of these measures.

Magnetic resonance imaging (MRI) is recognised as the "Gold Standard" investigation for symptoms pertaining to the inner ear and detection of retro-cochlear pathology. There is still no accurate clinical predictor for cerebellopontine angle lesions and increasingly more normal scans are being performed. With constantly increasing demands on ENT outpatient clinics, our aim was to investigate whether all patients referred for MRI of their internal auditory meatus (IAM) require follow-up in ENT clinics. A retrospective study was carried out in a tertiary referral centre referring patients for MRI IAM from ENT clinics and neurotology clinics on 153 patients referred for MRI IAM performed over a 4-month period. The MRI reports and the case notes of the patients were reviewed. MRI results and patient symptoms with patient follow-up schedule and follow-up situation for at least 6 months post-scan were compared. There were two patient groups, those referred from main outpatients (81) and those referred by the audiological physicians (72). Of the total number of scans, 101 were reported as normal, 45 had incidental findings, and 7 showed pathology of the cerebellopontine angle. The presenting complaints of the patients, the scan results and the follow-up since were compared. Six months later 63% of those referred from outpatients were no longer being followed up in clinic. We suggest that 56.8% of patients referred for MRI IAM do not require ENT follow-up. Their symptoms and concerns could be dealt with at the first consultation where onward referral could be made if necessary. Once checked by the requesting clinician, uncomplicated scan results could be sent to the patients and general practitioners by post or email. This would reduce the burden on general otolaryngology outpatient clinics and improve resource utilisation.

The near-nozzle structure of several nonevaporating biodiesel-blend sprays has been studied using X-ray radiography. Radiography allows quantitative measurements of the fuel distribution in sprays to be made with high temporal and spatial resolution. Measurements have been made at different values of injection pressure, ambient density, and with two different nozzle geometries to understand the influences of these parameters on the spray structure of the biodiesel blend. These measurements have been compared with corresponding measurements of Viscor, a diesel calibration fluid, to demonstrate the fuel effects on the spray structure. Generally, the biodiesel-blend spray has a similar structure to the spray of Viscor. For the nonhydroground nozzle used in this study, the biodiesel-blend spray has a slightly slower penetration into the ambient gas than the Viscor spray. The cone angle of the biodiesel-blend spray is generally smaller than that of the Viscor spray, indicating that the biodiesel-blend spray is denser than the Viscor spray. For the hydroground nozzle, both fuels produce sprays with initially wide cone angles that transition to narrow sprays during the steady-state portion of the injection event. These variations in cone angle with time occur later for the biodiesel-blend spray than for the Viscor spray, indicating that the dynamics of the injector needle as it opens are somewhat different for the two fuels.

The mechanisms by which the pituitary gland, and growth hormone (GH) in particular, affect growth hormone-releasing factor (GRF) gene expression have been addressed using the technique of in situ hybridization. Anatomically matched sections through the mediobasal hypothalamus of control and hypophysectomized male rats, with or without GH hormone replacement, were analysed to obtain information on GRF mRNA levels within the arcuate nucleus and around the ventromedial hypothalamus. Hypophysectomy resulted in a 70% increase in the amount of GRF mRNA per cell (P

The internal structure of diesel fuel injectors is known to have a significant impact on the steady-state fuel distribution within the spray. However, little experimental or computational work has been performed on the dynamics of fuel injectors. Recent studies have shown that it is possible to measure the three-dimensional geometry of the injector nozzle, and to track changes in that geometry as the needle opens and closes in real time. This has enabled the dynamics of the injector to be compared with the dynamics of the spray, and allows CFD simulations to use realistic time-dependent flow passage geometries. In this study, x-ray phase-enhanced imaging has been used to perform time-resolved imaging of the needle seat area in several common-rail diesel injection nozzles. The fuel distributions of the sprays emitted by these injectors were also studied with fast x-ray radiography. Correlations between eccentric motions of the injector needle valve and oscillations in the fuel density as it emerges from the nozzle are examined. CFD modeling is used to interpret the effect of needle motion on fuel flow.

Allergic (immune-mediated) reactions to cow milk and other dietary proteins encountered during infancy are responsible for some of the adverse symptoms and syndromes observed in infants intolerant to cow milk, infant formulas and occasionally human milk. Iron deficiency anemia associated with gastrointestinal blood loss, protein losing enteropathy, enterocolitis, colitis, and malabsorption syndrome are examples of putative allergic reactions to dietary antigens which occur in infancy. A number of symptoms referable to the gastrointestinal tract such as, vomiting, colic and chronic non-specific diarrhea occur in infants both with and without immune-mediated reactions to dietary antigens. Verification of adverse reactions to dietary antigens, including allergic reactions, should be accomplished through the use of double-blind, placebo-controlled food challenge, with the dietary antigen to be tested presented in a liquid vehicle or, in older children, in capsule form. Approximately 8%–25% of children with immediate hypersensitivity to cow milk have been found to be allergic to soy products. Soy and other intact protein substitutes for cow milk, such as beef and lamb based formulas, have produced anaphylactic reactions both in human infants and in animal models. Hypoallergenic formulas should have a chemically modified protein base which demonstrates significant reduction in anti-genicity when tested in the laboratory both in vitro and in vivo. Such formulas should meet rigorous standards for hypoallergenicity in clinical testing in human allergic infants or infants at high risk for developing allergy before being labelled hypoallergenic.

We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+ aH+ + ko + kHO-aHO− and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater than 2 years. Compound 4 reacts significantly slower than ganciclovir in acidic media, even though the adamantyl esters provide additional reaction sites (which would be expected to increase the rate of degradation) that are distally removed from the guanine ring system, offering negligible steric or electronic substituent effects. Both 3 and 4 hydrolyzed in tissue homogenate, where kobs followed liver > intestine ≫ skin. Based on these findings of chemical stability, lipophilicity, and acceptable rate of enzymatic cleavage by skin es-terases, 4 meets several of the criteria required for the topical sustained delivery of ganciclovir.

The degradation of native LHRH in aqueous buffers of pH ∼1–10 obeyed the rate equation, kobs = kH+aH+ + ko + kHO-(aHO-)x, where x at 60–100°C was ∼0.64 and temperature independent. Extrapolation to 25°C using the Arrhenius equation and secondary rate constants showed that native LHRH is reasonably stable at pH 5.4, giving a shelf life (t90) of approximately 5 years. Regarding physical properties, hydrophobic LHRH analogues nafarelin and detirelix were found to be surface active as demonstrated by a decrease in apparent surface tension with increased peptide concentration. The CMC for detirelix at pH 7.4 was determined to be 5.3 × 10−4M (0.88 mg/ml), and that for nafarelin, >2 mg/ml. At higher concentrations (∼4–8 mg/ml), nafarelin and detirelix formed nematic liquid crystals of undulose extinction (birefringence

We investigated the associations between Campylobacter colonisation and management practices and farm characteristics in 603 housed broiler batches originating from 137 farms in Great Britain. All study batches were the initial batch slaughtered from the selected house on enrolled farms. Between 1 and 15 batches were sampled from each farm throughout the study. A total of 34.2% of the batches was Campylobacter positive and multivariable multilevel logistic regression revealed that the risk of Campylobacter colonisation was highest in July (OR=3.4, CI95%:1.8; 6.4), August (OR=3.4, CI95%:1.9; 6.2) and September (OR=3.7, CI95%:1.9; 7.1). Cattle on or adjacent to the farm increased the risk (OR=1.7, CI95%:1.1; 2.7), whereas chlorinated drinking water reduced it (OR=0.5, CI95%:0.2; 0.9). If the first removed batch from the previous flock in the house had been Campylobacter positive, the first batch of the following flock was also more likely to be colonised (OR=3.2, CI95%:2.1; 4.9). This association was more likely due to a persistent risk practice or source of Campylobacter on the farm than a direct carry-over from previous flock.

The variability of diesel jet structure, both as a function of time and between individual injection events, has important implications on the breakup and mixing of the jet. It is accepted that diesel jets become unstable due to interactions with the ambient gas, leading to breakup of the jet. This concept is the principle behind the Kelvin–Helmholtz and Rayleigh–Taylor models of diesel atomization. Very little information regarding diesel jet variability is available, however, in the near-nozzle region of the diesel jet, where primary breakup of the jet occurs. This is due to the presence of many small droplets, which strongly scatter visible light and render the spray opaque. X-ray radiography has been successfully used in recent years to probe the structure of diesel sprays with high spatial and temporal resolutions. All of these previous measurements, however, were ensemble averaged, measuring only persistent features of the spray. In the current study, measurements are performed at individual measurement points of single diesel injection events. These measurements are taken at several points near the injector exit for a nonhydroground nozzle with a single axial hole at two injection pressures (500bars and 1000bars). The variability of the start of injection, end of injection, and the time history of the spray density during the injection event are examined, as well as how these quantities change for different transverse positions across the jet.

X-ray radiography was used to measure the behavior of four fuel sprays from a light-duty common-rail diesel injector. The sprays were at 250 bar injection pressure and 1 bar ambient pressure. Injection durations of 400 {micro}s and 1000 {micro}s were tested, as were axial single-hole nozzles with hydroground and nonhydroground geometries. The X-ray data provide quantitative measurements of the internal mass distribution of the spray, including near the injector orifice. Such measurements are not possible with optical diagnostics. The 400 {micro}s sprays from the hydroground and nonhydroground nozzles appear qualitatively similar. The 1000 {micro}s spray from the nonhydroground nozzle has a relatively consistent moderate width, while that from the hydroground nozzle is quite wide before transitioning into a narrow jet. The positions of the leading- and trailing-edges of the spray have also been determined, as has the amount of fuel residing in a concentrated structure near the leading edge of the spray.

Streptococcus mutans, the primary causative agent of human dental caries, grows as a biofilm on the tooth surface, where it metabolizes dietary carbohydrates and generates acid byproducts that demineralize tooth enamel. A drop in plaque pH stimulates an adaptive acid-tolerance response (ATR) in this oral pathogen that allows it to survive acid challenge at pHs as low as 3.0. In the present study, we describe the growth of an S. mutans mutant, GMS901, that harbours an insertion–deletion mutation in gcrR, a gene that encodes a transcriptional regulatory protein. The mutant is acid-sensitive and significantly compromised in its ATR relative to the UA159 wild-type progenitor strain. Consistent with these findings are the results of real-time quantitative RT-PCR (qRT-PCR) experiments that support the GcrR-regulated expression of known ATR genes, including atpA/E and ffh. Although we observed gcrR transcription that was not responsive to acidic pH, we did note a significant increase in gcrR expression when S. mutans cells were grown in a manganese-restricted medium. Interestingly, the results of gel mobility shift assays indicate that the S. mutans SloR metalloregulatory protein is a potential regulator of gcrR by virtue of its manganese-dependent binding to the gcrR promoter region, and expression studies support the hypothesis that sloR transcription is responsive to manganese deprivation and acidic pH. Taking these results together, we propose that SloR–Mn modulates S. mutans gcrR expression as part of a general stress response, and that GcrR acts downstream of SloR to control the ATR.

The near-nozzle structure of several non-evaporating biodiesel blend sprays has been studied using x-ray radiography. Radiography allows quantitative measurements of the fuel distribution in sprays to be made with high temporal and spatial resolution. Measurements have been made at different values of injection pressure, ambient density, and with two different nozzle geometries to understand the influences of these parameters on the spray structure of the biodiesel blend. These measurements have been compared to corresponding measurements of Viscor, a diesel calibration fluid, to demonstrate the fuel effects on the spray structure. Generally, the biodiesel blend spray has a similar structure to the spray of Viscor. For the nonhydroground nozzle used in this study, the biodiesel blend spray has a slightly slower penetration into the ambient gas than the Viscor spray. The cone angle of the biodiesel blend spray is generally smaller than that of the Viscor spray, indicating that the biodiesel blend spray is denser than the Viscor spray. For the hydroground nozzle, both fuels produce sprays with initially wide cone angles that transition to narrow sprays during the steady-state portion of the injection event. These variations in cone angle with time are timed later for the biodiesel blend spray than for the Viscor spray, indicating that the dynamics of the injector needle as it opens are somewhat different for the two fuels.

The beginning of the seventy-sixth poem of Catullus appears to cause some modern readers considerable dismay. One may instance the reactions of R. O. A. M. Lyne: ‘Our first reaction to the beginning of this poem may be one of incredulity’ (The Latin Love Poets [Oxford, 1980], p. 31); ‘The effect of such language is to imply an outrageous and implausible self-righteousness’ (ibid. 32); of K. Quinn: ‘a self-righteousness that makes us feel a little uncomfortable’ (The Catullan Revolution [Melbourne, 1959], p. 77); or of G. Williams: ‘this is sheer melodrama, a deft and surprising reversal of “count your blessings”’(Tradition and Originality in Roman Poetry [Oxford, 1968], p. 410); and, further down, on ‘si vitam puriter egi’: ‘This could be simply priggish or outrageous or both, but he does not mean it as a general statement’ (ibid.)

The identification of a core region for OVA 323-339, which is critical in determining binding to IAd, has enabled us to generate a series of analog peptides in which this core region was extended at both the N and C termini with different amino acid residues. When assessed for binding capacity, several peptides were shown to have increased affinity for IAd compared with the parent sequence, and in addition, some peptides had acquired binding specificities for class II MHC haplotypes not present for OVA 323-339. These peptides were next examined for their ability to inhibit T cell responses in vitro and in vivo. The correlation between binding and the ability to inhibit T cell activation in vitro was good. However, when assessed in vivo, it was clear that high Ia binding was not sufficient in itself to define the inhibitory capacity of a given peptide. That this discrepancy was due to differences in degradation of the core-extended peptides was suggested by 1) results from an inhibition of Ag presentation assay, in which the pulse period with Ag and inhibitor was extended to 20 h; and 2) direct analysis of peptide stability by using reverse phase HPLC. Finally, by protecting the peptide from degradation with N- and C-terminal substitutions of D-amino acids, the inhibitory capacity of an unstable core-extended peptide in vitro could be greatly enhanced. These data indicate that the core extension approach may be one method by which antagonists for MHC class II molecules may be generated.

Rates of loss of tritium from p-nitrophenylnitromethane-α-t in toluene solution catalyzed by a series of amine bases show that hydrogen exchange in this system occurs at the same rate as ionization of the carbon acid, and that internal return is not taking place. This substantiates a previous suggestion that very large deuterium isotope effects reported for some of these reactions and attributed to extensive tunnelling were determined under conditions where the isotopic label was being lost and are therefore artifacts. This study provides isotope effects which are generally much smaller than those reported previously, but some tunnelling may still be taking place in some of these reactions.

Cell and cytokine responses during the development of foot pad dermatitis (FPD) in growing turkeys were studied in a model system. The objective was to evaluate the hypothesis that FPD is an allergic response to the environmental materials. Hybrid female turkeys at 28 days of age were exposed to wet litter for 48 h in a randomized block experiment. Expression levels of pro-inflammatory (interleukin (IL)-1 beta, IL-6, and CXCLi2) and signature Th1 (interferon-gamma), Th2 (IL-13) and Treg (IL-10) cytokines were measured in the foot pad tissues using real-time quantitative reverse transcriptase-polymerase chain reaction. Sections of foot pad tissue were stained for CD4+ and CD8+ T lymphocytes, B lymphocytes and macrophages using antibodies that specifically recognize the relevant cell types in the turkey. In the footpads of birds suffering from FPD, there were large fold increases in mRNA expression levels for the pro-inflammatory cytokines IL-1 beta (+635), IL-6 (+65), and CXCLi2 (+1924), and interferon-gamma (+32), whereas there was only a small increase in IL-13 mRNA (+2) and no change in IL-10 mRNA expression levels. CD4+ and CD8+ T lymphocytes were present in the footpads of more than 90% of birds housed on wet litter compared with 25% or less on dry litter. Macrophages were observed in the footpads of approximately 85% of birds housed on wet litter compared with none in birds housed on dry litter. B lymphocytes were not detected in tissue from any of the birds. The data suggest that FPD is associated with a rapidly occurring inflammatory response, rather than a Th2-mediated allergic reaction.