Preterm infants have deficient monocyte and lymphocyte cytokine responses to Group B Streptococcus

Group B streptococcus GBS) is an important cause of early-and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS HKGBS) of preterm infants gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants GA, < 30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection

How do enamelysin and kallikrein 4 process the 32-kDa enamelin?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74876/1/j.1600-0722.2006.00281.x.pd

Establishment of porcine pulp-derived cell lines and expression of recombinant dentin sialoprotein and recombinant dentin matrix protein-1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72436/1/j.1600-0722.2007.00426.x.pd

Proteomic analysis of enamel matrix using a two-dimensional protein fractionation system

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72560/1/j.1600-0722.2006.00279.x.pd

Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis

Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens

Surrogate cloud fields generated with the Iterative Amplitude Adapted Fourier Transform algorithm

A new method of generating two-dimensional and three-dimensional cloud fields is presented, which share several important statistical properties with real measured cloud fields.Well-known algorithms such as the Fourier method and the Bounded Cascade method generate fields with a specified Fourier spectrum. The new iterative method allows for the specification of both the power spectrum and the amplitude distribution of the parameter of interest, e.g. the liquid water content or liquid water path. As such, the method is well suited to generate cloud fields based on measured data, and it is able to generate broken cloud fields. Important applications of such cloud fields are e.g. closure studies. The algorithm can be supplied with additional spatial constraints which can reduce the number of measured cases needed for such studies. In this study the suitability of the algorithm for radiative questions is evaluated by comparing the radiative properties of cloud fields from cloud resolving models of cumulus and stratocumulus with their surrogate fields at nadir, and for a solar zenith angle of 0◦ and 60◦. The cumulus surrogate clouds ended up to be identical to the large eddy simulation (LES) clouds on which they are based, except for translations and reflections. The root mean square differences of the stratocumulus transmittance and reflectance fields are less than 0.03% of the radiative budget. The radiances and mean actinic fluxes fit better than 2%. These results demonstrate that these LES clouds are well described from a radiative point of view, using only a power spectrum together with an amplitude distribution

Composition of early life leukocyte populations in preterm infants with and without late-onset sepsis

Background Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. Study design Single-centre prospective observational cohort study. Participants Infants born <30 weeks gestational age (GA). Outcome measures Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. Results Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6–26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. Conclusion Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression

Assimilation of 3D radar reflectivities with an ensemble Kalman filter on the convective scale

An ensemble data assimilation system for 3D radar reflectivity data is introduced for the convection-permitting numerical weather prediction model of the COnsortium for Small-scale MOdelling (COSMO) based on the Kilometre-scale ENsemble Data Assimilation system (KENDA), developed by Deutscher Wetterdienst and its partners. KENDA provides a state-of-the-art ensemble data assimilation system on the convective scale for operational data assimilation and forecasting based on the Local Ensemble Transform Kalman Filter (LETKF). In this study, the Efficient Modular VOlume RADar Operator is applied for the assimilation of radar reflectivity data to improve short-term predictions of precipitation. Both deterministic and ensemble forecasts have been carried out. A case-study shows that the assimilation of 3D radar reflectivity data clearly improves precipitation location in the analysis and significantly improves forecasts for lead times up to 4 h, as quantified by the Brier Score and the Continuous Ranked Probability Score. The influence of different update rates on the noise in terms of surface pressure tendencies and on the forecast quality in general is investigated. The results suggest that, while high update rates produce better analyses, forecasts with lead times of above 1 h benefit from less frequent updates. For a period of seven consecutive days, assimilation of radar reflectivity based on the LETKF is compared to that of DWD's current operational radar assimilation scheme based on latent heat nudging (LHN). It is found that the LETKF competes with LHN, although it is still in an experimental phase