Nucleic acid synthesis during larval development of Rhynchosciara.
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Biomedical subjects
Publications and source records attributed to C Parker.
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Patients with chronic respiratory insufficiency resulting from paralysis of respiratory muscles have been supported most commonly by mechanical ventilation via a tracheostomy. Acute and long-term morbidity and mortality have been associated with tracheostomy. Noninvasive alternatives for providing mechanical respiratory support include negative pressure "body ventilators" and positive pressure ventilation via a nasal, oral, or oronasal interface. Intermittent positive pressure ventilation via the nose, mouth, or oronasal combination is effective and convenient for the majority of patients when the interface is sufficiently airtight and comfortable to permit effective long-term use. Construction of custom-fabricated interfaces for the administration of assisted ventilation is presented. These interfaces provide better fit for greater interface seal and comfort than commercial masks. They allow more patients to benefit from assisted positive pressure ventilation in the home without resorting to a tracheostomy.
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This study was conducted to assess the long-term safety of fluticasone propionate 50 micrograms twice daily (100 micrograms/day) or 100 micrograms twice daily (200 micrograms/day) administered via a dry powder inhaler in children aged 4-17 years with moderately severe asthma. A total of 257 patients received open treatment for 12 months. Of these, 110 had not received treatment with fluticasone propionate in any prior study. The remaining 147 patients had completed one of two previous short-term inhaled fluticasone propionate studies. In all, 132 patients (51%) reported 273 adverse events, the pattern of which was as expected in an atopic population with asthma; only 26 (10%) of these reports were considered either certainly, probably or possibly related to study treatment. The events most commonly reported either as a single or multiple diagnosis were: asthma and related events (25%), upper respiratory tract infection (13%), and rhinitis (6%). For most patients who reported a worsening of asthma, additional therapy was all that was required to control symptoms, and they continued in the study. There was a low incidence (2%) of pharmacologically predictable adverse events. Eight patients (3%) withdrew from the study because of an adverse event, five of which events (one each of hypertension, hoarseness and asthma and two of oral candidiasis) were recorded as being possibly or probably drug-related. Sixteen adverse events reported by 15 patients (6%) were classified as serious but none was considered to be related to the study drug. Of these reports 10 ( patients; 4%) were exacerbations of asthma requiring hospital admission; the other six adverse events were unrelated to asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
The nm23 and mts1 genes are associated with the expression of the metastatic phenotype. We have shown previously that modulation of metastatic behaviour produces parallel changes in the expression of these genes and that the expression of the two genes is co-regulated. Here we show that modulation of gene expression affects the process of tubulin polymerisation. B16 melanoma cell lines F1 and ML8 were treated with alpha melanocyte stimulating hormone (MSH) and all-trans retinoic acid (RA) respectively. MSH reduced the proportion of nm23+ and increased mts1+ F1 cells, with a 55% decrease in the ratio nm23:mts1. In parallel, MSH increased the expression of depolymerised form of tubulin in these cells. Treatment of ML8 cells with RA decreased mts1 positivity to a greater extent that nm23 positivity and the nm23:mts1 ratio increased by 70% and, in parallel, reduced the expression of depolymerised form of tubulin. These data suggest that nm23 and mts1 gene expression regulates the biological behaviour of the tumour cell and confer on it invasive and metastasizing properties by affecting the state of tubulin polymerisation.
CD44 is a transmembrane cell adhesion-mediating protein which occurs as alternatively spliced isoforms in a variety of cell types. CD44 isoforms have been reported to be differentially expressed in cancers and the isoform CD44v6 has often been associated with metastatic potential. The 18A2/mts1 gene, which codes for a Ca(2+)-binding protein of the S-100 family, is a metastasis associated gene and its expression has been shown to be related to cell proliferation, cancer metastasis and invasion. The association of 18A2/mts1 expression with invasion has been attributed to its ability to promote depolymerisation of cytoskeletal elements and it appears to also participate in the remodelling of the extracellular matrix. Here we have examined the expression of CD44v6 in metastatic variants of the B16 melanoma with different levels of 18A2/mts1 expression. We found that metastatic potential was not related to the overall CD44 expression as detected by immunostaining; the high metastasis variant ML8 showed reduced CD44v6 positivity as compared with the low metastasis variant F1. Up-regulation of 18A2/mts1 expression in F1 cells by a-melanocyte stimulating hormone (MSH) and its down-regulation in ML8 cells by RA reduced the numbers of CD44v6 staining cells. In F1 cells the glycoprotein was found to be uniformly associated with the cell membrane. But in F1 cells treated with a-MSH where 18A2/mts1 expression was up-regulated, CD44v6 showed redistribution into a patchy focal pattern. This patchy focal distribution of CD44v6 also occurred in ML8 cells which express 18A2/mts1 at a high level. It is suggested that the patching of CD44v6 molecules is a consequence of the changes in cytoskeletal dynamics brought about by 18A2/mts1 expression, that are conducive to aggregation and patching of these transmembrane glycoproteins. It is postulated that this induction of patching could provide discrete and strong adhesive foci promoting cell adhesion and invasive behaviour.