Mechanism of suppression of cell-mediated immunity by measles virus

The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular immune responses.     

Purification and some properties of maleylpyruvate hydrolase and fumarylpyruvate hydrolase from Pseudomonas alcaligenes

Hydrolysis of the gentisate ring-cleavage product, maleylpyruvate (cis-2,4-diketohept-5-enedioic acid), was shown to be catalyzed by an enzyme, maleylpyruvate hydrolase 11, in Pseudomonas alcaligenes (P25X1) after growth with 3-hydroxybenzoate. This activity was separated from fumarylpyruvate hydrolase activity during the course of its purification which accomplished an approximately 50-fold increase in specific activity. An apparent molecular weight of 77,000 was assigned on the basis of Sephadex G-200 chromatography. Despite the presence of up to three similarly migrating bands of protein on polyacrylamide-gel electrophoresis of the purified enzyme, at least two of these bands possessed maleylpyruvate hydrolase activity. Electrophoresis on sodium dodecyl sulfate-polyacrylamide before and after reduction with mercaptoethanol gave a principal band of molecular weight of 33,000 (and a minor band of molecular weight 50,000). A number of substituted maleylpyruvates also served as substrates for maleylpyruvate hydrolase 11, but maleylacetoacetate and fumarylpyruvate were not attacked. Fumarylpyruvate hydrolase was purified approximately 40-fold to give a single band on polyacrylamide gels and with an apparent molecular weight of 73,000 by Sephadex G-200 chromatography. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis before or after reduction with mercaptoethanol, a subunit molecular weight of 25,000 was obtained. Neither maleylpyruvate nor fumarylacetoacetate served as substrates for fumarylpyruvate hydrolase. The activities of both maleyl- and fumarylpyruvate hydrolases were stimulated by Mn(2+) ions. Reasons are discussed for the presence of both enzyme activities, one of which appears to be redundant.     

Anomalous double blood supply to the lung

We report an unusual case in which an apparently normal upper lobe of the right lung was supplied by major systemic arterial and pulmonary arterial vessels. The anomalous artery arose from the descending aorta. Following interruption of this vessel, the machinery-like murmur previously present disappeared.     

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

The role of epidemiology in cancer prevention

1. ISA Brown and Shaver 288 pullets were changed from 8 h to 8, 10, 13 or 16 h photoperiods at 42, 63, 84, 105, 126 or 142 d of age. 2. Age at first egg (AFE) was curvilinearly affected by the size and timing of the change in photoperiod. AFE was advanced most by a photoperiod change from 8 to 13 h made at 63 or 84 d. ISA birds were generally more responsive than Shaver to the photoperiod changes. 3. Longer photoperiods significantly increased survivors' egg production, but decreased liveability to 504 d. so that eggs per hen housed were unaffected. Retarding AFE by 10 d reduced survivors' egg numbers by 7.0, but increased mean egg weight by 1.26 g. Egg output by Shaver birds was unaffected by AFE, but that of ISA was curvilinearly affected, with an apogee at an AFE of 135 d. In both breeds, egg weight and egg output were greater following an early or late, rather than a mid-term photostimulation. 4. Photoperiod significantly increased mean daily food intake during lay by 1.26 g/h. A 10 d retardation in AFE resulted in a reduction in food intake of 1 g/d. Efficiency of food conversion deteriorated according to the square of the photoperiod, and changed curvilinearly according to age at photostimulation. Food conversion efficiency improved by 0.05 g/g for each 10 d delay in AFE. 5. Shell quality was unaffected by AFE, but deteriorated with increasing photoperiod and was curvilinearly affected by age at photostimulation with the smallest shell weights associated with photostimulation at 63 d. The incidence of double-yolked (DY) egg production increased with photoperiod and decreased with delayed photostimulation. There was an exponential regression of DY eggs on AFE. 6. Body weight at first egg increased by 75 g/d delay in AFE, but body weight at 504 d of age was unaffected by AFE, photoperiod or age at photostimulation. Body weight gain during lay increased by 15 g/h increase in photoperiod, decreased by 6 g per 10 d delay in photostimulation and by 40 g per 10 d delay in AFE. Fat content at 504 d increased by about 10 g/kg and by 23 g/bird for each 10 d delay in AFE. 7. Mortality in lay increased by 0.8%/h increase in photoperiod, but was unaffected by either age at photostimulation or AFE.