Identification, purification, and characterization of a soluble interleukin (IL)-13-binding protein. Evidence that it is distinct from the cloned Il-13 receptor and Il-4 receptor alpha-chains

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are structurally and functionally related cytokines which play an important role in the regulation of the immune response to infection. The functional similarity of IL-4 and IL-13 can be explained, at least in part, by the common components that form their cell surface receptors, namely the IL-4 receptor alpha-chain (IL-4Ralpha) and the IL-13 receptor alpha-chain (IL-13Ralpha). Soluble forms of the IL-4Ralpha have also been described and implicated in modulating the effect of IL-4. In this paper we describe the presence of a 45,000-50,000 Mr IL-13-binding protein (IL-13BP) in the serum and urine of mice. This protein binds IL-13 with a 100-300-fold higher affinity (KD = 20-90 pM) than does the cloned IL-13Ralpha (KD = 3-10 nM). In addition to this functional difference, the IL-13BP appears to be structurally and antigenically distinct from the IL-13Ralpha. Finally, unlike the cloned receptor, the IL-13BP acts as a potent inhibitor of IL-13 binding to its cell surface receptor, raising the possibility that it may be used to modulate the effects of IL-13 in vivo.     

Mammography of breasts in which catheter cuffs have been retained: normal, infected, and postoperative appearances

OBJECTIVE: The purpose of this report is to show that Dacron (DuPont, Wilmington, DE) cuffs retained in breasts after the removal of Hickman catheters may result in complications requiring radiographic evaluation for subsequent management. We also describe potential complications, including infection, associated with a retained cuff and changes after the removal of a retained cuff. CONCLUSION: Because of the increased use of Hickman catheters for central vein access, Dacron cuffs more frequently are retained in breasts and are likely to be seen on mammograms. Radiologists need to be aware of the mammographic findings of a normal cuff, infected cuff, and the site of a surgically excised cuff.     

Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association

MSL-2 is required for the male-specific assembly of a dosage compensation regulatory complex on the X chromosome of Drosophila melanogaster. We found that MSL-2 binds in a reproducible, partial pattern to the male X chromosome in the absence of MLE or MSL-3, or when ectopically expressed at a low level in females. Moreover, the pattern of MSL-2 binding corresponds precisely in each case to that of MSL-1, suggesting that the two proteins function together to associate with the X. Consistent with this hypothesis, we isolated EMS-induced loss of function msl-1 and msl-2 alleles in a screen for suppressors of the toxic effects of MSL-2 expression in females. We also used site-directed mutagenesis to determine the importance of the MSL-2 RING finger domain and second cysteine-rich motif. The mutations, including those in conserved zinc coordinating cysteines, confirm that the RING finger is essential for MSL-2 function, while suggesting a less stringent requirement for an intact second motif.     

Ontogeny of cation-Cl- cotransporter expression in rat neocortex

A direct investigation into the grammatical abilities of Broca's and Wernicke's aphasics sought to obtain critical evidence for a revised model of the functional neuroanatomy of language. We examined aphasics' ability to make grammaticality judgments on a set of theoretically selected, highly complex syntactic structures that involve, most prominently, fine violations of constraints on syntactic movement. Although both groups have been thought to possess intact abilities in this domain, we discovered severe deficits; Broca's and Wernicke's aphasics (whose performances differed) exhibited clear, delineated, and grammatically characterizable deficits - they follow from the Trace-Deletion Hypothesis, which is motivated by independent comprehension results. These conclusions have both linguistic and neurological implications; Linguistically, they show that the aphasic deficit interacts with more than one module of the grammar. Namely, it manifests not only when the thematic module is called for in interpretive tasks but also when constraints on syntactic movement are tapped in a study of judgment. Neurologically, the results support a view of receptive grammatical mechanisms in the left cortex, which is functionally more restrictive than currently assumed; neuroanatomically, however, it is more distributed.     

Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity

Dominant optic atrophy, Kjer type, is an autosomal dominant disorder causing progressive loss of visual acuity and colour vision from early childhood. The gene (OPA1) has variable expressivity, a penetrance of 0.98, and the locus has been localised to 3q28-29. We have genotyped nine British families with the disease using 12 polymorphic microsatellite markers from this region. Linkage and haplotype analysis shows the OPA1 gene to be located in a 2.3 cM interval between markers D3S1601 and D3S2748. One family showed no evidence of linkage with the chromosome 3 markers, suggesting for the first time that locus heterogeneity for this disease may exist, although exclusion for linkage is based on unaffected subjects. In addition, analysis of recombinants has enabled us to order the 12 markers along chromosome 3.     

Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin-like growth factor 1 signaling

The ability of ethanol to interfere with insulin-like growth factor 1 (IGF-1)-mediated cell survival was examined in primary cultured cerebellar granule neurons. Cells underwent apoptosis when switched from medium containing 25 mM K+ to one containing 5 mM K+. IGF-1 protected granule neurons from apoptosis in medium containing 5 mM K+. Ethanol inhibited IGF-1-mediated neuronal survival but did not inhibit IGF-1 receptor binding or the neurotrophic action of elevated K+, and failed to potentiate cell death in the presence of 5 mM K+. Inhibition of neuronal survival by ethanol was not reversed by increasing the concentration of IGF-1. Significant inhibition by ethanol (15-20%) was observed at 1 mM and was half-maximal at 45 mM. The inhibition of IGF-1 protection by ethanol corresponded to a marked reduction in the phosphorylation of insulin receptor substrate 1, the binding of phosphatidylinositol 3-kinase (PI 3-kinase), and a block of IGF-1-stimulated PI 3-kinase activity. The neurotrophic response of IGF-1 was also inhibited by the PI 3-kinase inhibitor LY294002, the protein kinase C inhibitor chelerythrine chloride, and the protein kinase A inhibitor KT5720, but unaffected by the mitogen-activated protein kinase kinase inhibitor PD 98059. These data demonstrate that ethanol promotes cell death in cerebellar granule neurons by inhibiting the antiapoptotic action of IGF-1.     

Phosphorylation of myosin regulatory light chain eliminates force-dependent changes in relaxation rates in skeletal muscle

The rate of relaxation from steady-state force in rabbit psoas fiber bundles was examined before and after phosphorylation of myosin regulatory light chain (RLC). Relaxation was initiated using diazo-2, a photolabile Ca2+ chelator that has low Ca2+ binding affinity (K(Ca) = 4.5 x 10(5) M(-1)) before photolysis and high affinity (K(Ca) = 1.3 x 10(7) M(-1)) after photolysis. Before phosphorylating RLC, the half-times for relaxation initiated from 0.27 +/- 0.02, 0.51 +/- 0.03, and 0.61 +/- 0.03 Po were 90 +/- 6, 140 +/- 6, and 182 +/- 9 ms, respectively. After phosphorylation of RLC, the half-times for relaxation from 0.36 +/- 0.03 Po, 0.59 +/- 0.03 Po, and 0.65 +/- 0.02 Po were 197 +/- 35 ms, 184 +/- 35 ms, and 179 +/- 22 ms. This slowing of relaxation rates from steady-state forces less than 0.50 Po was also observed when bundles of fibers were bathed with N-ethylmaleimide-modified myosin S-1, a strongly binding cross-bridge derivative of S1. These results suggest that phosphorylation of RLC slows relaxation, most likely by slowing the apparent rate of transition of cross-bridges from strongly bound (force-generating) to weakly bound (non-force-generating) states, and reduces or eliminates Ca2+ and cross-bridge activation-dependent changes in relaxation rates.     

Characterization of the tyrosine phosphorylation and distribution of dystrobrevin isoforms

While level of school education has been related to prevalence of cigarette smoking in a number of studies, less information is available on the role of vocational education and related occupational contexts. This study analyses the relative contribution of different types of educational experience to explaining prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees in Germany. A standardized questionnaire on smoking behaviour and educational performance was applied in 27 educational centers across the country, covering a total of 20,527 respondents (77.3% of the original sample; women: 59.5%, men: 40.5%). Bivariate analysis revealed a high prevalence of current smokers among vocational trainees, both men (51.2%) and women (49.4%). Men were more likely to be heavy smokers, especially with increasing age. In both sexes, prevalence of smoking was particularly high in the following occupational groups: hairdressers, butchers, painters, service personnel (hotels, restaurants), shop assistants/sellers and cooks. Multivariate analysis taking educational level, type of vocational training (occupation), age, sex and urban-rural background into account revealed the highest prevalence odds ratios (POR) of smoking in subjects with the lowest educational level (POR = 5.19 for men and 4.56 for women). Even stronger effects were observed with smoking intensity (> or = 20 cigarettes/day): in men with the lowest educational level the risk of being a heavy smoker was 8.92, and in women 13.54 compared to subjects with a high-school leaving qualification. Poor school education must be considered the relatively strongest predictor of prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees. Preventive efforts should be directed at specific target groups such as those identified by this study.