Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

1. Download : Download high-res image (202KB)
2. Download : Download full-size image

     

Effect of lymphocyte mediators on macrophages in vitro. A correlation of morphological and cytochemical changes

Sephadex purified PPD and Con A induced mediator rich fractions (MRF) were applied to guinea-pig macrophages cultured in vitro. At varying times after the addition of the MRF, cells were removed from culture for morphological study and for cytochemical tests. Respiratory enzyme activity and lysosomal acid phos-phatase activity were estimated and the former was quantitated using an integrating microdensitometer. Early changes, 1 hr after MRF contact, were observed and subsequent alterations in activity up to 48 hr after the addition of MRF were also seen. These changes have been related to the inhibition of migration and subsequent `activation' of the macrophages which has been observed morphologically at times up to 3 weeks after MRF addition.

It is suggested that alterations in the cytochemistry of the macrophages after MRF contact could help explain changes in the behaviour of the cells under these experimental conditions.

     

Mast cell–derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

1. Download : Download high-res image (242KB)
2. Download : Download full-size image

     

Linkage analysis of SLE susceptibility: confirmation of SLER1 at 5p15.3

We detected a novel susceptibility gene, SLER1, for systemic lupus erythematosus (SLE) at 5p15.3.(1) This finding was based on a selected subgroup of SLE families, where two or more family members have had alleged rheumatoid arthritis (SLE-RA). The main objective of this study was to replicate the linkage at 5p15.3 based on an independent data set of 88 SLE-RA families. Heterogeneity in the genetic model led us to use a nonparametric allele-sharing method. Since our a priori hypothesis of linkage at 5p15.3 was fixed, we genotyped six markers at the linked region. Our new results replicate the initial linkage at 5p15.3 (Zlr=2.58, P<0.005, LOD=1.45). Moreover, evidence of linkage was sustained when analysis was restricted to the subset of SLE families who had 3 or more individuals with alleged RA (Zlr=3.32, P=0.008, LOD=2.40) The results of our previous findings, together with these new results, confirm the SLER1 linkage at 5p15.3. Our results also demonstrate the utility of clinically defined subgroup analysis for detecting susceptibility loci for complex genetic diseases, such as SLE.     

Comparison of inhomogeneity correction algorithms in small photon fields

Algorithms such as convolution superposition, Batho, and equivalent pathlength which were originally developed and validated for conventional treatments under conditions of electronic equilibrium using relatively large fields greater than 5 x 5 cm2 are routinely employed for inhomogeneity corrections. Modern day treatments using intensity modulated radiation therapy employ small beamlets characterized by the resolution of the multileaf collimator. These beamlets, in general, do not provide electronic equilibrium even in a homogeneous medium, and these effects are exaggerated in media with inhomogenieties. Monte Carlo simulations are becoming a tool of choice in understanding the dosimetry of small photon fields as they encounter low density media. In this study, depth dose data from the Monte Carlo simulations are compared to the results of the convolution superposition, Batho, and equivalent pathlength algorithms. The central axis dose within the low-density inhomogeneity as calculated by Monte Carlo simulation and convolution superposition decreases for small field sizes whereas it increases using the Batho and equivalent pathlength algorithms. The dose perturbation factor (DPF) is defined as the ratio of dose to a point within the inhomogeneity to the same point in a homogeneous phantom. The dose correction factor is defined as the ratio of dose calculated by an algorithm at a point to the Monte Carlo derived dose at the same point, respectively. DPF is noted to be significant for small fields and low density for all algorithms. Comparisons of the algorithms with Monte Carlo simulations is reflected in the DCF, which is close to 1.0 for the convolution-superposition algorithm. The Batho and equivalent pathlength algorithms differ significantly from Monte Carlo simulation for most field sizes and densities. Convolution superposition shows better agreement with Monte Carlo data versus the Batho or equivalent pathlength corrections. As the field size increases the DCF's for all algorithms converge toward 1.0. The largest differences in DCF are at the interface where changes in electron transport are greatest. For a 6 MV photon beam, electronic equilibrium is restored at field sizes above 3 cm diameter and all of the algorithms predict dose in and beyond the inhomogeneous region equally well. For accurate dosimetry of small fields within and near inhomogeneities, however, simple algorithms such as Batho and equivalent pathlength should be avoided.     

Dose rate constant and energy spectrum of interstitial brachytherapy sources

In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125I and 103Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S(K)) standard for 125I seeds and has also established an S(K) standard for 103Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (inverted V) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of dose rate constant and to develop a simple method for a quick and accurate estimation of dose rate constant. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that dose rate constant may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S(K) and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for dose rate constant was derived for point sources with known photon energy spectra. This approach enabled a systematic study of dose rate constant as a function of energy. Using the measured energy spectra, the calculated dose rate constant for 125I model 6711 and 6702 seeds and for 192Ir seed agreed with the AAPM recommended values within +/-1%. For the 103Pd model 200 seed, the agreement was 5% with a recently measured value (within the +/-7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for dose rate constant proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known.