Search

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK. Methods: Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C‐reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death. Results: Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785–0.810), sensitivity was 70% (95% CI 67–72) and specificity was 75% (95% CI 74–76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747–0.768), sensitivity was 73% (95% CI 71‐74) and specificity was 66% (95% CI 65–67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711–0.761), sensitivity was 63% (95% CI 59–68) and specificity was 69% (95% CI 67–72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham. Conclusions: The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess clinical utility is needed. [ABSTRACT FROM AUTHOR]

The ability of transposons to mobilize to new places in a genome enables them to introgress rapidly into populations. The piRNA pathway has been characterized recently in the germ line of the fruit fly, Drosophila melanogaster, and is responsible for downregulating transposon mobility. Transposons have been used as tools in mosquitoes to genetically transform a number of species including Anopheles stephensi, a vector of human malaria. These mobile genetic elements also have been proposed as tools to drive antipathogen effector genes into wild mosquito populations to replace pathogen-susceptible insects with those engineered genetically to be resistant to or unable to transmit a pathogen. The piRNA pathway may affect the performance of such proposed genetic engineering strategies. In the present study, we identify and describe the An. stephensi orthologues of the major genes in the piRNA pathway, Ago3, Aubergine ( Aub) and Piwi. Consistent with a role in protection from transposon movement, these three genes are expressed constitutively in the germ-line cells of ovaries and induced further after a blood meal. [ABSTRACT FROM AUTHOR]

To assess how flow affects school structure and threat detection, startle response rates of solitary and small groups of giant danio Devario aequipinnatus to visual looming stimuli were compared in flow and no-flow conditions. The instantaneous position and heading of each D. aequipinnatus was extracted from high-speed videos. Behavioural results indicate that (1) school structure is altered in flow such that D. aequipinnatus orient upstream while spanning out in a crosswise direction, (2) the probability of at least one D. aequipinnatus detecting the visual looming stimulus is higher in flow than no flow for both solitary D. aequipinnatus and groups of eight D. aequipinnatus; however, (3) the probability of three or more individuals responding is higher in no flow than in flow. These results indicate a higher probability of stimulus detection in flow but a higher probability of internal transmission of information in no flow. Finally, results were well predicted by a computational model of collective fright response that included the probability of direct detection (based on signal detection theory) and indirect detection ( i.e. via interactions between group members) of threatening stimuli. This model provides a new theoretical framework for analysing the collective transfer of information among groups of fishes and other organisms. [ABSTRACT FROM AUTHOR]

Aim Accurate assessment of missed discharge codes for diabetes is critical for effective planning of hospital diabetes services. We wished to estimate the frequency of missed discharge diagnostic codes for diabetes and the impact missed codes would have on diabetes-related payments to the hospital. Methods We linked Patient Administration System data to the Prescribing Information and Communication System. We defined diabetes as those having a discharge code for diabetes in the Patient Administration System and those on anti-diabetic medication in the Prescribing Information and Communication System. Based on the two sources, we calculated the estimated missed discharge codes for diabetes using the capture-recapture technique. We generated the Healthcare Resource Group for a given admission before and after correction for the missed code to estimate the impact that correction would make on payments to the hospital. Results Among the 171 067 admissions linked, 22 412 (13.1%) had a code for diabetes at discharge. An additional 2706 admissions were classified as having diabetes based on prescription data. The capture-recapture technique estimated there were 4588 (2.7% of all admissions) admissions with diabetes missed by current coding, of which 2706 (60%) would be obtained from prescription data. After adding a diabetes diagnostic code, 12.8% of the missed admissions with diabetes resulted in a change to the Healthcare Resource Group tariff code and payment. Conclusion The use of electronic prescription data is a simple solution to correct for missed discharge diagnostic codes. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 698-708 (2012) Abstract Background Computerized clinical decision support systems have been claimed to reduce prescription errors and improve patient care. They may play an important role in the care of hospitalized patients with diabetes. Aim To collate evidence for the use of clinical decision support systems in improving the care of hospitalized patients with diabetes in a non-critical care setting and to assess their effectiveness. Methods We searched four databases from 1980 to 2010 without language restrictions. All types of studies other than case reports were included. Data extraction and quality assessment were carried out based on the Centre for Review and Dissemination guidance. A narrative synthesis was conducted. Results Fourteen studies met the inclusion criteria, including two cluster randomized controlled trials, eight before-and-after studies and four other descriptive studies. Generally, the quality of the studies was not very high. Nine out of 10 studies reported reduction in mean blood glucose or similar measures (patient-day-weighted mean blood glucose) during inpatient stay. The reduction using computerized physician order entry system in patient-day-weighted mean blood glucose ranged from 0.6 to 0.8 mmol/l (10.8-15.6 mg/dl). Other beneficial effects during inpatient stay included reduced use of sliding scale insulin and greater use of basal-bolus insulin regimen. Only one study found a significant increase in hypoglycaemic events. Conclusions Clinical decision support systems have been used, often as part of a complex programme, to improve the care of hospitalized patients with diabetes. There is some evidence that they may have a beneficial effect, but this needs further confirmation. [ABSTRACT FROM AUTHOR]

The late spring/early summer flooding that occurred in the American Midwest between May and June 2008 resulted from a combination of large-scale atmospheric circulation patterns that supported a steady influx of moisture into the area. A low pressure system centered over the central-western United States steered a strong jet and associated storms along its eastern edge from the west to southwest and an anomalously strong Great Plains Low Level Jet brought continuous warm and moist air into the area from the Gulf of Mexico into the area. We examine and quantify here the impact these circulation patterns had on the hydroclimatology of the Midwest highlighting the magnitude, frequency, geographic distribution, and temporal evolution of precipitation that ultimately magnified the flooding. Historical precipitation records were used to assess the regional rainfall characteristics at various geographic and time scales. Five distinct hydroclimatic characteristics contributed to the definition of the 2008 flood including persistent high surface soil moisture conditions prior to flooding exasperated by anomalously high rainfall, extreme rainfall totals covering extensive areas, increased frequency of shorter-term, smaller-magnitude events, persistent multiday heavy precipitation events, and extreme flood-producing rain storms. The major flooding lasted for approximately 24 days and most greatly impacted the state of Iowa, southern Wisconsin, and central Indiana. Its occurrence during the May-June period makes the event especially unusual for this region. [ABSTRACT FROM AUTHOR]

Microbial adaptations associated with extreme growth environments, including high temperatures and low pH, are of interest to astrobiologists and origin of life researchers. As part of a survey of microbial lipids present in terrestrial geothermal settings, we examined four silica sinters associated with three different hot spring areas of the Taupo Volcanic Zone (TVZ), New Zealand. Dominant bacterial lipids include free fatty acids, 1,2-diacylglycerophospholipids, 1,2-di- O-alkylglycerols, 1- O-alkylglycerols, wax esters, alkanols, alkan-1,2-diols and various hopanoids, whereas dominant archaeal lipids include both archaeol and glycerol dialkyl glycerol tetraethers. Although many of these compounds occur in other settings, in the TVZ sinters their distributions (with high abundances of β-OH fatty acids and high-molecular-weight (> C18) fatty acyl components) and carbon isotopic compositions (ranging from −40 to +4, with up to 25 variability in a single sample) are unusual. In addition, we have identified a range of unusual compounds, including novel macrocyclic diethers and hopanoids. The distributions of these compounds differ among the study sites, suggesting that, where preserved in ancient sinters, they could serve as an important tool in studying past hydrothermal environments. [ABSTRACT FROM AUTHOR]

Monitoring describes the prospective supervision, observation, and testing of an ongoing process. The result of monitoring provides reassurance that the goal has been or will be achieved, or suggests changes that will allow it to be achieved. In therapeutics, most thought has been given to Therapeutic Drug Monitoring, that is, monitoring of drug concentrations to achieve benefit or avoid harm, or both. Patients and their clinicians can also monitor the progress of a disease, and adjust treatment accordingly, for example, to achieve optimum glycaemic control. Very little consideration has been given to the development of effective schemes for monitoring for the occurrence of adverse effects, such as biochemical or haematological disturbance. Significant harm may go undetected in controlled clinical trials. Even where harm is detected, published details of trials are usually insufficient to allow a practical monitoring scheme to be introduced. The result is that information available to prescribers, such as the Summary of Product Characteristics, frequently provides advice that is incomplete or impossible to follow. We discuss here the elements of logical schemes for monitoring for adverse drug reactions, and the possible contributions that computerized decision support can make. We should require evidence that if a monitoring scheme is proposed, it can be put into practice, will prove effective, and is affordable. [ABSTRACT FROM AUTHOR]

Objective. The relation between being deprived of a food and intake and craving for that food was investigated in restrained and unrestrained eaters.Method. For 1 week, 103 female undergraduate students were assigned to be chocolate deprived, vanilla deprived, or nondeprived. Only chocolate deprivation was expected to elicit cravings, as chocolate is not easily substituted, whereas vanilla is.Results. The main effect of chocolate deprivation on consumption was qualified by an interaction with restraint. Chocolate-deprived restrained eaters consumed more chocolate food than did any other group. Restrained eaters experienced more food cravings than did unrestrained eaters and were more likely to eat the craved food. Moreover, restrained eaters deprived of chocolate spent the least time doing an anagram task before a 'task-rating task' in which they expected that chocolate foods might be available.Conclusion. Converging measures of craving indicate that deprivation causes craving and overeating, but primarily in restrained eaters. [ABSTRACT FROM AUTHOR]

This article studies the critical purpose of home economics postsecondary education as preparation for social reform, focusing on the role that founders expected homemakers to play in ameliorating social problems. For them, the goal of home economics was a better world. The means to this improved society was scientific knowledge applied to the family and the community by home economists and home economics-trained homemakers. Yet, by the 1920s, it was clear that the social responsibility of homemakers, as envisioned by the first leaders of the discipline, had virtually disappeared from the rhetoric of home economics. Although no one factor explains the silencing of calls for civic involvement on the part of homemakers, factors external of the discipline, including federal legislation and directed appropriations, developing education theories, a growing emphasis on professional specialization, increased employment opportunities for women, and a redefinition of women's familial role, served to redirect the focus of the field.

Provides information on a study that assessed the enriched apoplastic extracts of Arabidopsis thaliana, Triticum aestivum and Oryza sativa, using proteomic approaches. Methodology of the study; Results and discussion on the study.

Summary 1. The accidental or deliberate release of alien species may be very disruptive to native biota, principally through competition or predation. Naturalized populations of mute swans Cygnus olor in western Europe and North America have overgrazed native aquatic vegetation, competed with other waterbirds, and damaged arable and fodder crops. Numbers may be controlled by destroying or oiling a proportion of eggs in each clutch to prevent hatching (clutch reduction). 2. A difference equation model was used to examine the effectiveness of clutch reduction on a mute swan population in the Wylye Valley, Wiltshire, UK. Model parameters were derived mainly from a long-term study of individually marked birds. Survival and emigration were parameterized as a combined function. The model focused on the non-breeding subpopulation, considered to have a negative impact on local fisheries by overgrazing aquatic macrophytes. 3. The model was also parameterized for another swan population in the West Midlands, UK. This population was characterized by rapid growth in a much larger area, compared with the smaller, comparatively stable population in the Wylye Valley. There were insufficient data available to parameterize accurately the model for other areas. 4. Annual survival rates were high in both populations, ranging between 68% and 73% for juveniles, first-years and non-breeding adults, and between 72% and 90% for breeding adults. Immigration was an important factor in the dynamics of both populations. 5. The effects of different levels of clutch reduction on the Wylye Valley mute swan population were simulated. Reducing clutches to two eggs per clutch lowered non-breeding numbers by 30% over a 10-year period. Total destruction of all eggs in each clutch stabilized the non-breeding subpopulation but did not eradicate it. The effects of clutch reduction were offset by high survival rates and immigration. 6. In the West Midlands, the simulated restriction of clutches to two... [ABSTRACT FROM AUTHOR]

Abstract Aims To determine the views of teachers, general practitioners (GPs) and paediatricians about whether there has been a recent change in the timing of the onset of puberty in children in the UK and in the timing of menarche in girls. Design Questionnaires were sent to a stratified random sample of each professional group. Results In relation to girls, almost 80% of teachers believe that the onset of puberty is occurring earlier, and 73% feel that the menarche is occurring earlier. Those who had been working for longer than 10 years were more likely to say that the age of onset of puberty had decreased. GPs feel that both puberty and menarche are starting earlier, whereas paediatricians were evenly divided between those who thought puberty was starting earlier and those who thought that the timing had not changed. In boys, professionals generally believe that the timing of the onset of puberty has not altered significantly. Conclusion Further study is required to determine whether puberty is really occurring earlier in girls. [ABSTRACT FROM AUTHOR]

Background: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion. Methods: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti-CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP-allergic donors. Results: Anti-CD3 stimulated T cells supported BP-specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP-allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP-allergic donors failed to produce BP-specific IgE in vitro , when cultured in the presence of allergen. Conclusions: An allergen specific immune response is readily generated in vitro . The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre-exposure to this allergen in vivo . [ABSTRACT FROM AUTHOR]

Summary This study used an environmentally controlled plant growth facility, EcoCELLs, to measure canopy gas exchanges directly and to examine the effects of elevated [CO2] on canopy radiation- and water-use efficiencies. Sunflowers (Helianthus annus var. Mammoth) were grown at ambient (399 μmol mol-1) and elevated [CO2] (746 μmol mol-1) for 53 days in EcoCELLs. Whole canopy carbon- and water-fluxes were measured continuously during the period of the experiment. The results indicated that elevated [CO2] enhanced daily total canopy carbon- and water-fluxes by 53% and 11%, respectively, on a ground-area basis, resulting in a 54% increase in radiation-use efficiency (RUE) based on intercepted photosynthetic active radiation and a 26% increase in water-use efficiency (WUE) by the end of the experiment. Canopy carbon- and water-fluxes at both CO2 treatments varied with canopy development. They were small at 22 days after planting (DAP) and gradually increased to the maxima at 46 DAP. When canopy carbon- and water-fluxes were expressed on a leaf-area basis, no effect of CO2 was found for canopy water-flux while elevated [CO2] still enhanced canopy carbon-flux by 29%, on average. Night-time canopy carbon-flux was 32% higher at elevated than at ambient [CO2]. In addition, RUE and WUE displayed strong diurnal variations, high at noon and low in the morning or afternoon for WUE but opposite for RUE. This study provided direct evidence that plant canopy may consume more, instead of less, water but utilize both water and radiation more efficiently at elevated than at ambient [CO2], at least during the exponential growth period as illustrated in this experiment. [ABSTRACT FROM AUTHOR]

SummaryPlant responses to elevated atmospheric CO2 have been characterized generally by stomatal closure and enhanced growth rates. These responses are being increasingly incorporated into global climate models that quantify interactions between the biosphere and atmosphere, altering climate predictions from simpler physically based models. However, current information on CO2 responses has been gathered primarily from studies of crop and temperate forest species. In order to apply responses of vegetation to global predictions, CO2 responses in other commonly occurring biomes must be studied. A Free Air CO2 Enrichment (FACE) study is currently underway to examine plant responses to high CO2 in a natural, undisturbed Mojave Desert ecosystem in Nevada, USA. Here we present findings from this study, and its companion glasshouse experiment, demonstrating that field-grown Ephedra nevadensis and glasshouse-grown Larrea tridentata responded to high CO2 with reductions in the ratio of transpirational surface area to sapwood area (LSR) of 33% and 60%, respectively. Thus, leaf-specific hydraulic conductivity increased and stomatal conductance remained constant or was increased under elevated CO2. Field-grown Larrea did not show a reduced LSR under high CO2, and stomatal conductance was reduced in the high CO2 treatment, although the effect was apparent only under conditions of unusually high soil moisture. Both findings suggest that the common paradigm of 20–50% reductions in stomatal conductance under high CO2 may not be applicable to arid ecosystems under most conditions. [ABSTRACT FROM AUTHOR]

SummaryIncreased atmospheric carbon dioxide supply is predicted to alter plant growth and biomass allocation patterns. It is not clear whether changes in biomass allocation reflect optimal partitioning or whether they are a direct effect of increased growth rates. Plasticity in growth and biomass allocation patterns was investigated at two concentrations of CO2 ([CO2]) and at limiting and nonlimiting nutrient levels for four fast- growing old-field annual species. Abutilon theophrasti, Amaranthus retroflexus, Chenopodium album, and Polygonum pensylvanicum were grown from seed in controlled growth chamber conditions at current (350 μmol mol-1, ambient) and future- predicted (700 μmol mol-1, elevated) CO2 levels. Frequent harvests were used to determine growth and biomass allocation responses of these plants throughout vegetative development. Under nonlimiting nutrient conditions, whole plant growth was increased greatly under elevated [CO2] for three C3 species and moderately increased for a C4 species (Amaranthus). No significant increases in whole plant growth were observed under limiting nutrient conditions. Plants grown in elevated [CO2] had lower or unchanged root:shoot ratios, contrary to what would be expected by optimal partitioning theory. These differences disappeared when allometric plots of the same data were analysed, indicating that CO2-induced differences in root:shoot allocation were a consequence of accelerated growth and development rates. Allocation to leaf area was unaffected by atmospheric [CO2] for these species. The general lack of biomass allocation responses to [CO2] availability is in stark contrast with known responses of these species to light and nutrient gradients. We conclude that biomass allocation responses to elevated atmospheric [CO2] are not consistent with optimal partitioning predictions. [ABSTRACT FROM AUTHOR]

ABSTRACTSolute transport systems are one of the major ways in which organisms interact with their environment. Typically, transport is catalysed by integral membrane proteins, of which one of the largest groups is the ATP-binding cassette (ABC) proteins. On the basis of sequence similarities, a large family of ABC proteins has been identified in Arabidopsis. A total of 60 open reading frames (ORFs) encoding ABC proteins were identified by BLAST homology searching of the nuclear genome. These 60 putative proteins include 89 ABC domains. Based on the assignment of transmembrane domains (TMDs), at least 49 of the 60 proteins identified are ABC transporters. Of these 49 proteins, 28 are full-length ABC transporters (eight of which have been described previously), and 21 are uncharacterized half-transporters. Three of the remaining proteins identified appear to be soluble, lacking identifiable TMDs, and most likely have non-transport functions. The eight other ORFs have homology to the nucleotide-binding and transmembrane components of multi-subunit permeases. The majority of ABC proteins found in Arabidopsis can, on the basis of sequence homology, be assigned to subfamilies equivalent to those found in the yeast genome. This assignment of the Arabidopsis ABC proteins into easily recognizable subfamilies (with distinguishable subclusters) is an important first step in the elucidation of their functional role in higher plants. [ABSTRACT FROM AUTHOR]

AbstractThe gene encoding sialokinin I, the principal vasodilatory peptide of Aedes aegypti, has been isolated and characterized. Degenerate oligonucleotide primers based on peptide amino acid sequence were used to amplify a gene fragment from messenger RNA (mRNA) isolated from female salivary glands. The amplification product was used to probe a salivary gland complementary DNA (cDNA) library, and a number of corresponding cDNAs were isolated and their primary sequence determined. Analysis of the conceptual translation product of a 406-bp cDNA indicates that sialokinin I is expressed as a preprosialokinin and is subsequently post-translationally processed to the active peptide. Northern analysis revealed a 490-bp transcription product expressed exclusively in female salivary glands, and hybridization in situ of probes to RNA in whole tissues localized gene expression to the medial lobe of female salivary glands. Screening of an Ae. aegypti genomic library with the cDNA resulted in the isolation of a clone containing the gene, designated Sialokinin I (Sia I). Comparison of the cDNA with the genomic clone reveals two introns of 62 bp and 833 bp. Primer extension analysis showed that several transcription initiation sites are present. Southern analysis of genomic DNA shows that Sia I is most probably a single-copy gene. Similarities of the Sia I gene product with other genes are confined to the region encoding the active decapeptide. [ABSTRACT FROM AUTHOR]

Mast cells obtained by fragmentation of human lung tissue retained the capacity to bind IgE and to respond to immunological challenge. Direct binding studies with radiolabelled IgE enabled quantification of binding parameters of the reaction between IgE and its receptor on human mast cells. The average equilibrium constant was estimated as 1.0 × 108 M-1 and the average number of IgE receptors per mast cell as 1.3 × 105. [ABSTRACT FROM AUTHOR]

Mitochondria were isolated from beech mycorrhizas, by disruption of the tissue in a medium containing PVP and reducing agents, to counteract the enzyme denaturing actions of endogenous phenols, tannins and the products of phenoloxidase activity. Electron microscopic examination of the isolated mitochondria showed that they were structurally intact, and spectral analysis revealed that their cytochrome composition was marked by a particularly high content of cytochrome b557. The mitochondria actively respired with the Krebs cycle intermediates α-ketoglutarate, malate + pyruvate and succinate, and with exogenous NADH. In each case the oxidation was tightly coupled to phosphorylation, and ADP:O ratios were obtained which indicated that three sites of oxidative phosphorylation were associated with the respiration of the NAD-linked substrates α-ketoglutarate and malate + pyruvate, and two sites with the respiration of succinate and exogenous NADH. The inhibitors rotenone, antimycin A and cyanide blocked electron flow at the known sites of action in the electron transport chain. Rotenone completely inhibited the oxidation of both α-ketoglutarate and malate + pyruvate, but had no effect on the oxidation of succinate or NADH. Oxidation of the four substrates was found to be partially sensitive to antimycin and to cyanide which caused a maximal inhibition of 50-60% in the rate of respiration. The antimycin- and cyanide-insensitive respiration was abolished by mCLAM. It was concluded that there was at least one fraction of the mitochondrial population which had a cyanide-insensitive pathway of respiration, and that the respiratory system of the mitochondria in this fraction could best be explained by a model in which the respiratory chain is branched from substrate to oxygen, one branch via cyanide-sensitive cytochrome oxidase and the other via a cyanide-insensitive alternate oxidase. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated increased production of interleukin-4 (IL-4) and reduced production of interferon (IFN)-γ in stimulated peripheral blood mononuclear cell cultures from children and adults with atopic dermatitis, however, it is unclear whether such an imbalance of cytokine production relates to other childhood atopic diseases such as asthma, and in particular to the presence of the atopic state per se. The production of IL-4 and IFNγ in phytohaemagglutin- (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from atopic and non-atopic children with moderately severe chronic persistent asthma, and a group of age-matched non-atopic controls who did not have asthma was examined. Atopic children with asthma produced significantly more IL-4 and less IFNγg than non-atopic children with asthma and non-atopic controls who did not have asthma. There was no significant difference in IL-4 or IFNγ production between non-atopic children with asthma and controls. These findings demonstrate that an imbalance of IL-4 and IFNγ production is present in atopic asthma as previously documented in atopic dermatitis, therefore suggesting that it is a feature of the atopic state per se. [ABSTRACT FROM AUTHOR]

The article provides information on adverse reactions to drugs, which constitute a common problem in clinical practice. They can be divided broadly into those that can be accounted for by the known pharmacological and chemical properties of the drug and those that appear to depend rather on some abnormality of host responsiveness. Allergic drug reactions may be directed against the drug itself or towards new antigenic determinants generated on self proteins as a result of chemical interaction with the drug. Alternatively, native determinants may no longer be recognized as self as a result of chemical modification of adjacent structures leading to by-pass of immune suppression. To establish that a drug induces adverse reactions via an allergic mechanism, evidence must be obtained for a population of antibodies or lymphocytes in the blood of affected patients that recognize the drug or a drug-derived antigen in a relatively specific way.

We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interferon-γ (IFN-γ). Unstimulated PMC expressed detectable mRNA for TNF-α but not for the other four cytokines. incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10-6 M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-α. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Mice primed with the anti-arthritic drug D-penicillamine (DP) developed DP-specific T cells in the draining lymph nodes (DLN) which responded to drug-haptenated stimulator cells, but not to untreated control cells nor to free drug, in in vitro proliferation assays. The responder cells were CD4+ and the response was major histocompatibility complex (MHC) class II restricted. The conditions required to generate efficient stimulator cells for in vitro proliferation assays were investigated. Drug-haptenated syngeneic spleen cells, but not thymocytes, were able to stimulate T cells from DP-sensitized mice. However, prolonged incubations of spleen cells with DP were required to generate the drug-derived T-cell antigen. Further experiments revealed that the generation of a DP-derived antigenic determinant for T cells did not require intracellular processing, as stimulator cells pretreated with fixative or lysosomotropic agents before drug haptenation were as effective as untreated DP-haptenated cells in stimulating the responder cells to proliferative in vitro. These findings show that the protein-reactive drug DP can generate a cellular antigen that is capable of stimulating a T-cell response. Furthermore, the generation of this antigen appears to bypass conventional antigen processing, suggesting perhaps a direct chemical modification of cell surface molecules that are involved in immune recognition. This process may underlie adverse reactions to DP that are believed to be mediated by the cellular immune system. [ABSTRACT FROM AUTHOR]

Conditioned medium (CM) from concanavalin A (Con A)stimulated murine spleen cells inhibited release of histamine and 5-HT from murine peritoneal mast cells sensitized with monoclonal IgE anti- DNP antibody and challenged with DNP-human serum albumin (HSA) antigen. Inhibition was seen when the CM was added to the mast cells either 24 hr before or simultaneous with, but not 24 hr subsequent to, the IgE, thus showing that inhibition was at the IgE-dependent stage of mast cell sensitization. Unconditioned medium, prepared in the same way as CM but not exposed to spleen cells was without activity, demonstrating that inhibition was due to a spleen cell-derived factor. CM from unstimulated spleen cells was likewise without activity. The sensitization inhibitory factor appears to be a protein, since it was retained upon dialysis, and destroyed by heating at 700 and above. The factor does not appear to be IgE, since it was stable at 56°, and is not IL-1 or IL-2, since recombinant human IL-lα and IL-lβ, and recombinant mouse IL-lα and IL-2 were without inhibitory activity. The active CM and all recombinant IL-I and IL-2 preparations did not release histamine or 5-HT directly from mast cells during 48 hr of culture, and did not modulate the histamine content of these cells, nor their capacity to incorporate [3H]5-HT. [ABSTRACT FROM AUTHOR]

Incubation of murine peritoneal cells with monoclonal IgE anti-DNP antibody in vitro led to sensitization of mast cells, measured as release of 5-HT upon challenge with DNPHSA antigen. Sensitization was maximal at 0.3-30 μg/ml of IgE anti-DNP and declined above and below this concentration range. In kinetic studies, the time-course of sensitization was clearly divisible into an early slow phase of approximately 4 hr, followed by a more rapid linear phase from 4 to 48 hr. The early slow phase was more pronounced at lower concentrations of IgE anti-DNP (within the range 005-50 μg/ml). The degree of sensitization obtained after incubation of peritoneal cells with IgE anti-DNP for fixed periods (2, 4 and 8 hr) was markedly increased when the cells were washed and recultured in IgE-free medium, thus demonstrating that sensitization proceeds subsequent to an early stage of binding of IgE to receptors. Sensitization with IgE anti-DNP was blocked by addition of excess rat myeloma IgE, but only to a marked extent (>50%) when the blocking immunoglobulin was added during the first 2 hr. thus providing further evidence that the major part of binding of the IgE antibody took place during this early stage, that is, prior to the phase of greatest sensitization. These findings indicate a period of delay between binding of IgE to teceptors and functional sensitization, measured as mediator release in response to antigen. [ABSTRACT FROM AUTHOR]

Monochlorobimane (BmCl), a non-fluorescent cell-permeant compound that reacts with glutathione to yield a strong blue fluorescent conjugate bimane-glutathione (Bm-SG), was used to trace the glutathione-dependent detoxification of xenobiotics in plant cells and protoplasts. In BmCl-labelled cells and protoplasts, fluorescence developed rapidly and was quickly concentrated in the vacuole. The rate of fluorescence development was dependent on the concentration of BmCl and the only metabolite formed was the conjugate Bm-SG. The formation of Bm-SG was correlated with a decrease in the amount of intracellular GSH. Compounds which reduced the intracellular levels of GSH severely reduced the formation of Bm-SG. Bm-SG was shown to be transported into isolated vacuoles by an ATP-dependent vanadate-sensitive mechanism. Kinetic analysis of cellular Bm-SG formation implicated both spontaneous conjugation and enzyme catalysis. Our results demonstrate a cellular pathway for xenobiotic detoxification in plants, starting with conjugation to glutathione in the cytoplasm, followed by the transport of the conjugates into the vacuole. This pathway is used to counter the toxic effects of some herbicides and environmental pollutants and overlaps with or parallels the pathway used for the biosynthesis of anthocyanins. [ABSTRACT FROM AUTHOR]

Differential screening of a cDNA library constructed from root mRNA from jack pine (Pinus banksiana Lamb.) seedlings exposed to two cycles of drought conditioning identified a S-adenosylmethionine synthetase (sam-s) cDNA. A cDNA encoding the entire open reading frame of sam-s was identified and characterized. Analysis of the full-length sam-s cDNA revealed that it was 1675 bp, encoded an open reading frame of 393 ammo acids and had a predicted protein mass of 43 kDa. jack pine sam-s was found to he highly similar to several other plant sam-s genes RNA gel blot analysis showed that sam-s mRNA abundance increased following two cycles of drought conditioning and remained abundant after 3 d of rewatering Expression of this gene appears to be root-specific. Quantitative slot blot analysis showed that two cycles of drought conditioning caused a 6-fold increase in sam-s mRNA abundance whereas heat shock, cold stress anti, anoxia did not result in the accumulation of sam-s mRNA. sam-s enzyme activity increased 2-fold following two cycles of drought conditioning. The increase in the rate of SAM-s enzyme was also cerrelated with changes in rates of ethylene and betaine synthesis, biosynthetic pathways that utilize SAM as a substrate. Ethylene evolution and betaine abundance increased following two cycles of drought conditioning. [ABSTRACT FROM AUTHOR]

The supply of dissolved inorganic carbon for photosynthesis in the aquatic environment is much more variable than that experienced by terrestrial plants. In response to this variability, cyanobacteria and many species of microalgae acclimate to rapid changes in the availability of dissolved inorganic carbon by the induction of high affinity/high capacity C02-concentrating systems (CCMs). Biochemical and molecular analyses of the acclimation response have recently identified several components that are required for efficient operation of the CCMs and CO2 assimilation. This has been accomplished using in vivo labelling studies, and characterization of high inorganic carbon (Ci) requiring cyanobacterial and algal mutants. The identification and regulation of expression of polypeptides synthesized in response to limiting Ci concentrations, and the proposed role of the carboxysome and the pyrenoid in the functioning of the CCMs are examined. [ABSTRACT FROM AUTHOR]

Elevated levels of Co2 in the atmosphere are expected to affect plant performance and may alter global temperature patterns. Changes in mean air temperatures that might be induced by rising levels of CO2 and other greenhouse gases could also be accompanied by increased variability in daily temperatures such that acute increases in air temperature may be more likely than at present. Consequently, we investigated whether plants grown in a CO2 enriched atmosphere would be differently affected by a heat shock than plants grown at ambient CO2 levels. Plants of a C3 annual (Abutilon theophrasti), a C3 annual crop (Sinapis alba) and a C4 annual (Amaranthus retroflexus) were grown from seed in growth chambers under either 400 or 700cm ³ m-3 CO2, and were fertilized with either a high or low nutrient regime. Young seedlings of S. alba, as well as plants of all species in either the vegetative or reproductive phase of growth were exposed to a 4-h heat chock in which the temperature was raised an additional 14-23°C (depending on plant age). Total biomass and reproductive biomass were examined to determine the effect of CO2, nutrient and heat shock treatments on plant performance heat shock, CO2, and nutrient treatments, all had sonic significant effects on plant performance, but plants from both CO2 treatments responded similarly to heat shocks. We also found, as expected, that plants grown under high CO2 had dramatically decreased tissue N concentrations relative to plants grown under ambient conditions. We predicted that high-CO2-grown plants would be more susceptible to a heat shock than ambient-CO2-grown plants, because the reduced N concentrations of high-CO2 grown plants could result in the reduced synthesis of heat shock proteins and reduced thermotolerance. Although we did not examine heat shock proteins, our results showed little relationship between plant nitrogen status and the ability of a plant to tolerate an acute increase in temperature. [ABSTRACT FROM AUTHOR]

Coated vesicles are organelles frequently encountered in many plant cell types often in association with the plasma membrane, Golgi apparatus, partially coated reticulum and multivesicular bodies. They are readily identified by a characteristic cage or basket composed of interlocking triskelions of the protein clathrin which are bound to the surface of the vesicle membrane. Although their transport function has been well studied and characterized in mammalian systems, the possible importance of coated vesicles as transport organelles in plant cells is only just beginning to be explored. In this review, the authors describe the structure of higher plant coated vesicles and discuss their possible involvement in the endocytosis of marcromolecules, in exocytosis and in the intracellular transport of material between cytoplasmic compartments. Their possible role in maintaining the macromolecular composition of the plasma membrane whilst allowing recycling of excess lipid bilayer and their potential application as vehicles for the introduction of foreign macromolecules into plant cells are discussed. [ABSTRACT FROM AUTHOR]

Cells of the blue-green alga Coccochloris peniocystis, grown at air levels of CO2, were exposed to [14C]bicarbonate in the light for periods of 0.5 to 2.0 s followed by exposure to unlabelled bicarbonate for longer periods of time in the light. The kinetics of tracer movement during these pulse-chase experiments demonstrate that the principal mechanism of CO2 fixation in this alga is the C3-pathway although an appreciable amount of the C4 acid aspartate is found as one of the initial products of photosynthesis. Degradation of the labelled aspartate revealed that after 20 s of illumination, over 95% of the radioactivity was located in the β-carboxyl of this C4 acid. This alga possesses little, if any, capacity for either the enzymatic decarboxylation of C4 acids or the regeneration of phosphoenolpyruvate (PEP) from pyruvate mediated by the enzyme pyruvate, Pi dikinase. These data further demonstrate the lack of a functional C4-pathway in this alga. [ABSTRACT FROM AUTHOR]

We report that stem-cell factor (SCF), the ligand of the receptor encoded by the c-kit proto-oncogene, is a potent activator of degranulation of rat peritoneal mast cells in vitro and in vivo. Freshly isolated, purified mast cells were relatively unresponsive to SCF (4–500ng/ml) but progressively acquired responsiveness to this agent, assessed as serotonin (5-HT) release, during 48 hr culture in vitro. The cells showed a similar kinetic pattern of acquisition of responsiveness to anti-IgE but responded fully to calcium ionophore A23187 or compound 48/80 regardless of time in culture. Acquisition of mast cell responsiveness to SCF or anti-IgE was not due to serum factors or to recovery from the Percoll purification procedure. During culture, mast cell expression of the SCF receptor (SCFR) increased, and this may explain in part the increased responsiveness to SCF. However, surface IgE expression remained constant, and the increased responses to anti-IgE therefore must reflect changes in components of the secretion-coupling pathway that are activated subsequent to IgE cross-linking. The unresponsiveness of freshly isolated peritoneal mast cells to SCF or anti-IgE does not reflect a state of in vivo unresponsiveness, as peritoneal mast cells degranulated in vivo in response to these agents. We conclude that in terms of their responsiveness to SCF or anti-IgE, cultured tissue mast cells may be more representative than freshly isolated mast cells of secretory function in vivo, and therefore may be more appropriate for physiological or pharmacological studies of SCF- or IgE-dependent secretory responses. [ABSTRACT FROM AUTHOR]

This study demonstrates an essential role for interleukin-4 (IL-4) in the delayed hypersensitivity reaction, as illustrated by contact sensitivity (CS) to trinitrochlorobenzene (TNCB). Injection of mice with monoclonal antibody to IL-4, but not with control antibody, reduced CS after active immunization by 75%, as judged by ear swelling. The histological alterations of CS were also reduced. IL-4 was essential to the effector stage, as inhibition of its production or action blocked the passive transfer of CS. In particular, treatment of immune lymph node cells with antisense oligonucleotide to IL-4 inhibited the systemic transfer of CS. Transfer was also inhibited by monoclonal antibody to IL-4 given to the recipient. The present results indicate that IL-4 is an essential cytokine at the effector stage of the CS reaction. [ABSTRACT FROM AUTHOR]

We have examined the interactions between interferon-γ (IFN-γ), interleukin-3 (IL-3) and interleukin-4 (IL-4) in the regulation of IgE/antigen-induced secretory responses of mouse peritoneal mast cells. The cytokines were added either alone or in various combinations to cultured mast cells sensitized passively with IgE antibody. In experiments with unfractionated peritoneal cells (containing approx. 1% mast cells), IL-3 and IL-4 enhanced in an additive manner antigen-induced release of serotonin (5-HT), while IFN-γ inhibited release regardless of whether IL-3 and/or IL-4 were present. In experiments employing mast cells purified to >90%, IL-3 and IL-4 retained their enhancing activities whereas the inhibitory effect of IFN-γ was considerably diminished. Nevertheless, IFN-γ still inhibited significantly IL-4-enhanced secretion. The effects of IL-3 and IL-4 ± IFN-γ, on arachidonate release were identical to those seen for 5-HT release, indicating that the secretion of both preformed mediators and newly synthesized eicosanoids is regulated in a similar way by these cytokines. [ABSTRACT FROM AUTHOR]

Induction of an auto-anti-IgE (auto-aIgE) response in the rat inhibits both total and specific IgE production and alters the distribution of mast cell (MC) subpopulations identified by differential Alcian blue/safranin staining. We have extended these observations by characterizing the auto-aIgE antibodies and determining their effects on MC degranulation in vitro and in vivo. An auto-aIgE response was induced in bacillus Calmette-Guérin (BCG)-primed rats by injecting a conjugate of highly purified rat IgE myeloma (IR2) coupled to tuberculin-derived purified protein derivative (PPD). Anti-IgE autoantibodies were almost exclusively IgG2a. The intradermal injection of autos aIgE into untreated rats induced local MC degranulation as shown by a strong immediate skin response. Histologically there was evidence of significant degranulation of safranin staining connective tissue MC (SMC) in the skin but not of the Alcian blue staining MC (ABMC) in the subepidermal region. The induced degranulation was ∊-chain specific; immunopurified anti-idiotypic antibodies raised to the IgE IR2 myeloma had no MC degranulating activity. When administered locally, auto-aIgE inhibited a subsequent passive cutaneous anaphylaxis (PCA) response elicited by anti-ovalbumin IgE. In addition, the PCA response was significantly decreased in animals with an ongoing auto-aIgE response. Immunopurified auto-aIgE also induced histamine release in vitro from rat peritoneal MC. These results are discussed in the context of naturally occurring autoantibodies to IgE present in patients with allergic disease. [ABSTRACT FROM AUTHOR]