Risk factors for repeat attendance at hospital emergency departments among adults and children with asthma

Protein phosphorylation is a well-known mechanism by which extracellular molecules or factors transduce their signals into intracellular effects. In the context of myelin assembly, phosphorylation of major myelin proteins affects the electrostatic repulsion between adjacent proteins within myelin structure and therefore constitutes one of the mechanisms by which myelin stability is regulated. We report here that arachidonic acid (AA) decreases the phosphorylation of myelin basic protein (MBP) both in the absence and in the presence of phorbol esters in cultured rat oligodendrocytes (OLGs). The effect of AA on MBP phosphorylation is not mediated by cyclooxygenase products, though the possibility that leukotrienes or other epoxides may have a role cannot be excluded. AA did not act by inactivation of protein kinase C. Based on our findings from gadolinium and low K+ experiments, we conclude that inhibition of MBP phosphorylation is not dependent on AA-induced increases in OLG Ca(i), but rather on its depolarizing action. We have thus demonstrated that a brief exposure to AA, which either acts as a diffusible paracrine signal to OLGs or as a signal transducer, can trigger changes in protein phosphorylation in OLGs/myelin via ionic signaling events at the plasma membrane.     

Follicular vascularity--the predictive value of transvaginal power Doppler ultrasonography in an in-vitro fertilization programme: a preliminary study

The glnA gene from the human pathogen Streptococcus agalactiae was cloned from a genomic library prepared with the lambda phage vector lambdaDASHII. A 4.6-kb DNA fragment of one of the recombinant phages was subcloned in pUC18. This Escherichia coli clone expressed a 52-kDa protein encoded by a 1,341-bp open reading frame. The nucleotide sequence of the open reading frame and the deduced amino acid sequence shared a significant degree of homology with the sequences of other glutamine synthetases (GS). The highest homology was between our deduced protein and GS of gram-positive bacteria such as Bacillus subtilis, Bacillus cereus, and Staphylococcus aureus. Plasmids with the cloned streptococcal glnA were able to complement E. coli glnA mutants grown on minimal media. Rabbit antisera to streptococcal GS recombinant protein recognized not only the recombinant protein but also a similar-sized band in mutanolysin extracts of all group B streptococcal strains tested, regardless of polysaccharide type or surface protein profile. The amino acid sequence of the deduced protein had similarities to other streptococcal cell-surface-bound proteins. The possible functional role of the immunological features of streptococcal GS is discussed.     

Temporal expression of PTHrP during endochondral bone formation in mouse and intramembranous bone formation in an in vivo rabbit model

Expression of parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) and protein was investigated throughout the developmental progression of endochondral bone formation in mouse and intramembranous bone formation in an in vivo model in rabbit, using in situ hybridization and immunohistochemistry. Endochondral bone formation was investigated in a developing embryo, newborn, and adult mouse. In fetal long bones through to newborn (day 7), PTHrP mRNA and protein were consistently expressed in chondrocytes within the proliferative, transitional, and hypertrophic zones. In addition, high levels of PTHrP were also detected in osteoblasts on the surface of trabecular bone surfaces. Similarly, at the adult stage (week 7), PTHrP mRNA and protein were consistently expressed in chondrocytes at epiphyseal ends of the subarticular cartilage, within cortical periosteum, as well as in osteoblasts located at the metaphyseal trabecular bone surfaces. Using an in vivo intramembranous bone formation model in rabbits, expression of PTHrP mRNA and protein was demonstrated in preosteoblasts prior to trabecular bone formation (1-week bone harvest). As bone formed (2-, 3-, and 4-week bone tissue harvests), PTHrP mRNA and protein were highly expressed in actively synthesizing osteoblasts and in those osteocytes embedded within the superficial layers of the bone matrix. Lining osteoblasts and osteocytes buried deeply in the bone matrix displayed weak or no signal for PTHrP. The pattern of spatial and temporal expression of PTHrP demonstrated in cartilage cells and osteoblasts in the two systems suggests an important role of PTHrP in both endochondral and intramembranous bone formation.     

Prognostic significance of tumour markers in endometrial cancer

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.     

Molecular characterization of human and mouse fatty acid amide hydrolases

Recently, we reported the isolation, cloning, and expression of a rat enzyme, fatty acid amide hydrolase (FAAH), that degrades bioactive fatty acid amides like oleamide and anandamide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Here, we report the molecular characterization of both a mouse and a human FAAH and compare these enzymes to the rat FAAH. The enzymes are well conserved in primary structure, with the mouse and rat FAAHs sharing 91% amino acid identity and the human FAAH sharing 82% and 84% identity with the rat FAAH and mouse FAAH, respectively. In addition, the expressed human and rat FAAHs behave biochemically as membrane proteins of comparable molecular size and show similar, but distinguishable, enzymological properties. The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid amides in mammalian biology.     

Press coverage of public expenditure of Master Settlement Agreement funds: how are non-tobacco control related expenditures represented?

Objective: To examine newspaper reports of Master Settlement Agreement (MSA) allocation decisions outside of tobacco control, focusing on the arguments being put forth in favour of competing claims on MSA funds. The major aims were to identify newsworthy non-tobacco control areas for which MSA funds have been applied and to examine how non-tobacco control spending has been presented through the US press.

Design: A qualitative textual analysis was performed on 94 articles taken from a sample of 322 newspapers over a 12 month period (October 2000 through September 2001) that related to the allocation of MSA funds to non-tobacco control causes. Articles were coded for general content areas of MSA allocation as well as for rhetorical and framing devices employed to explain and justify allocation decisions.

Main outcome measures: (1) Areas of non-tobacco control allocation; (2) rhetorical devices and framing techniques employed in the articles to discuss the allocation.

Results: The analysis identified a wide variety of issues for which MSA funds were being appropriated. Three main frames emerged in relation to justifying or appealing for particular spending decisions: (1) funds should be allocated to the needy and/or the deserving; (2) funds should be spent on state development; (3) funds should be put towards helping the state weather a crisis. Claims for each such issue were made using strategies such as presenting the MSA funds as a "windfall", focusing coverage on the merits of the cause rather than the issue of resource allocation, and stressing links between the particular claim and the stated objectives of the MSA.

Conclusions: Press coverage of MSA non-tobacco control spending suggests that the funds have been quickly formulated as fodder for state spending, rather than to support tobacco control efforts. Thus, caution is required in pursuing settlements with the industry where the objective is better funding for tobacco control efforts, particularly in light of the possibility that press coverage of MSA allocation may actually serve as positive publicity for the tobacco industry.

     

Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene

Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat, is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK). Whether IB1 and JIP-1 are present in humans was not known. We report the sequence of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94% identical to rat IB1. The tissue-specific expression of IB1 in human is similar to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome 11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found in the human genome. Our data indicate that the sequence and expression pattern of IB1 are highly conserved between rodent and human and provide the necessary tools to investigate whether IB1 is involved in human diseases.