Human blood eosinophils produce and secrete interleukin 4

Interleukin 4 (Il-4) is an immunoregulatory cytokine which induces T-cell proliferation and differentiation into a Th2 phenotype, and is of particular importance for the induction of IgE synthesis. In the present study, the capability of human peripheral blood eosinophils from allergic and non-allergic donors to produce Il-4 was examined. Using reverse transcribed polymerase chain reaction (RT-PCR), it was shown that highly purified eosinophils from allergic patients express mRNA for Il-4. Resting eosinophils also gave specific immunoreactivity with anti-Il-4 antibodies, consistent with translation of Il-4 mRNA. Light and electron microscopic immunocytochemistry revealed that Il-4 was prestored in the eosinophilic granules. These results were confirmed by Il-4 specific ELISA which showed that Il-4 production could be upregulated in the eosinophils and released from the eosinophils following stimulation with the calcium ionophore A23187. These data indicate that eosinophils may be an important source of Il-4 at sites of allergic inflammation. Thus, eosinophils may act as immunomodulatory cells enhancing the allergic response through formation of Th2-cells and inducing the isotype switching to IgE in human B-cells.     

Coupled activation of the donor and the acceptor side of photosystem II during photoactivation of the oxygen evolving cluster

Photoactivation of photosystem II has been studied in the FUD 39 mutant of Chlamydomonas reinhardtii that lacks the 23 kDa extrinsic subunit of photosystem II. We have taken advantage of the slow photoactivation rate of FUD 39, earlier demonstrated in Rova, E. M., et al. [(1996) J. Biol. Chem. 271, 28918-28924], to study events in photosystem II during intermediate stages of the process. By measuring the EPR multiline signal, the decay of the variable fluorescence after single flashes, and electron transfer from water to the QB site, we found a good correlation between the building of a tetrameric Mn cluster, longer recombination times between QA- and the donor side of photosystem II, and the achievement of water splitting ability. An increased rate of electron transfer from QA- to the QB site on the acceptor side of photosystem II, mainly due to enhanced efficiency of binding of QB to its site, was found to precede the building of the Mn cluster. We also showed that TyrD was oxidized simultaneously with this increase in electron-transfer rate. Thus, it appears that photoactivation is sequential, with an increased rate of electron transfer on the acceptor side occurring together with the oxidation of TyrD in the first step, followed by the assembly of the Mn cluster. We suggest that a conformational change of photosystem II is induced early in the photoactivation process facilitating electron transfer from the primary donor to the acceptor side. As a consequence, TyrD, an auxiliary electron donor to P680+/TyrZ*, is oxidized. That this occurs before the Mn cluster is fully functional serves to protect photosystem II against donor side induced photodamage.     

Differential effects of preterm birth and small gestational age on cognitive and motor development

AIMS: To determine the differential effects of preterm birth and being small for gestational age on the cognitive and motor ability of the child. METHODS: A longitudinal cohort of all infants of gestational age < or = 32 weeks born to mothers resident in the counties of Cheshire and Merseyside in 1980-1 was studied. The children were assessed at the age of 8 to 9 years using the Wechsler Intelligence Scale for Children, the Neale analysis of reading ability, and the Stott-Moyes-Henderson test of motor impairment. Adequacy of fetal growth was determined by the birthweight ratio--that is, the ratio of the observed birthweight to the expected birthweight for a given gestational age. Children with clinically diagnosed motor, learning or sensory disabilities were excluded. Information on social variables was obtained by a questionnaire completed by the parents. Of the 182 children, 158 were assessed. RESULTS: IQ was positively correlated with birthweight ratio but not with birthweight or gestational age. Motor ability was associated with birthweight, gestational age, and birthweight ratio. Reading comprehension was associated with birthweight ratio, but reading rate and accuracy were best explained by social variables and sex. IQ remained associated with birthweight ratio, after adjusting for maternal education, housing status, and number of social service benefits received. Reading ability was related to these social variables but motor ability was not. CONCLUSIONS: The effects of SGA and preterm birth differed: SGA was associated with cognitive ability, as measured by IQ and reading comprehension; motor ability was additionally associated with preterm birth. Reading rate and accuracy were not associated with SGA or preterm birth but were socially determined.     

Deep vein thrombosis and pulmonary embolism in the general population. 'The Study of Men Born in 1913'

BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common public health problems. Still, little is known about the epidemiology and the natural history of venous thromboembolism. METHODS: In the Study of Men Born in 1913, 855 men were followed up prospectively from the age of 50 years to the age of 80 years. Several cross-sectional samples, also of men born in 1913, were studied at the ages of 50, 54, 60, 67, 75, and 80 years. Objective methods were used to ascertain a diagnosis of DVT or PE, and all were confirmed by hospital records or autopsy reports. The follow-up rate in the longitudinal study was 98.2%. RESULTS: In the longitudinal study, the incidence of DVT was 182 per 100,000 observation-years. Corresponding incidence rates were 98 for nonfatal PE, 107 for fatal PE, and 387 for all thromboembolic events. The cumulative probability for a venous thromboembolic event at different ages was estimated to be 0.5% by the age of 50 years and 10.7% by the age of 80 years. In the cross-sectional studies, a history of confirmed venous thromboembolism was found in 0.5% of the men at age 50 years, 0.9% at age 54 years, 1.3% at age 60 years, 2.0% at age 67 years, 4.5% at age 75 years, and 3.8% at age 80 years. CONCLUSIONS: The results indicate a high incidence of DVT and PE in the general population. The incidence of thromboembolic events increases with age. The rate of fatal PE seems to be higher than estimated before, and PE constitutes almost 5% of all deaths during follow-up.