PubMed Health⌕ Search

Biomedical subjects

A Fleetwood

Publications and source records attributed to A Fleetwood.

8 recordsLinked to original sources

Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma.

Basic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We have investigated the FGF dual receptor mechanism in a novel model of the transformation from human colon adenoma to carcinoma in vitro. Reverse transcription-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytochemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition and sequence of human colon adenoma and carcinoma heparan sulphate (HS) differ in a defined and specific manner. The functional significance of these changes was assessed by affinity co-electrophoresis, which showed that the affinity of adenoma HS for bFGF was 10-fold greater than that of the carcinoma HS (Kd 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core protein expression was reduced significantly in the carcinoma cells. These findings were associated with a reduced biological response to bFGF in the carcinoma cells that could be partially reversed by the addition of exogenous heparin, suggesting that both the proteoglycan and signal transducing receptor control the cells' response to bFGF.

Adenoma↗

Control of morphology, cytoskeleton and migration by syndecan-4.

Syndecan-4 is a widely expressed transmembrane heparan sulfate proteoglycan which localizes to focal adhesions. Previous studies showed that the syndecan-4 cytoplasmic domain can associate with and potentiate the activity of protein kinase C, which is required for focal adhesion formation. To examine further the role of syndecan-4 in cell adhesion, we expressed syndecan-4 cDNA constructs in CHO-K1 cells. Syndecan-2 transfection was used to confirm effects seen were specific for syndecan-4. Cells overexpressing full length syndecan-4 core protein exhibited a more flattened, fibroblastic morphology, with increased focal adhesion formation and decreased cell motility. Expression of a syndecan-4 core protein with either a partial or complete deletion of the cytoplasmic domain or of an antisense construct led to markedly decreased spreading and focal adhesion formation, a more epithelioid morphology, and decreased motility. Overexpression of syndecan-2 changed the adhesive phenotype, but did not markedly alter focal adhesion and microfilament bundle formation. The data suggest that syndecan-4 is a regulator of focal adhesion and stress fiber formation, and influences both morphology and migration.

Amino Acid Sequence↗

Farm visits and zoonoses.

Recent reports of outbreaks of gastrointestinal illness, such as cryptosporidiosis, associated with visits to farms have drawn attention to the possible risks of acquiring zoonotic infections through contact with farm animals. These risks seem to be small, but it is important that people who work in urban and rural farms, and such establishments as animal sanctuaries where the general public can come into close contact with farm livestock and other animals, should be alerted to the simple precautions needed to prevent transmission of infections.

Adult↗

Evaluation of albumin as a reference marker of dilution in bronchoalveolar lavage fluid from asthmatic and control subjects.

BACKGROUND: Standardised expression of results of bronchoalveolar lavage (BAL) is problematical in the absence of a validated "denominator" of epithelial lining fluid dilution. The suitability of albumin in BAL fluid has been investigated in groups of clinically stable asthmatic and control subjects. METHODS: Absolute levels of albumin in BAL fluid were measured in a preliminary study of 21 asthmatic and 10 control subjects. In a more complex study designed to investigate the origin of albumin sampled at BAL in nine asthmatic and seven control subjects, radiolabelled albumin was injected intravenously five minutes before BAL. RESULTS: In the preliminary study levels of albumin in BAL fluid were very similar, with a geometric mean value of 44 (95% CI 35-54) micrograms/ml BAL supernatant for the asthmatic subjects and 41 (95% CI 33-52) micrograms/ml for the controls. The majority of control and asthmatic subjects in the radiolabel study exhibited minimal flux of albumin from the circulation into the BAL aspirate. This finding was not uniform, however, and in a third of the asthmatic subjects an albumin flux equivalent to > 20% of the measurable albumin was found in two or more aliquots of a 3 x 60 ml lavage. CONCLUSIONS: The results of this investigation into the source of albumin sampled at BAL suggest that, in general, albumin would be a reasonable reference solute for normalising the degree of dilution of BAL fluid in the groups studied. The origin of albumin was not always restricted to the bronchopulmonary segment under investigation, however, with significant leakage from the blood compartment in some individuals despite the consistency of absolute levels observed in the preliminary study.

Adult↗

Plasma albumin and total protein in preterm babies from birth to eight weeks.

We have measured albumin and total protein concentrations over the first eight weeks of life in a group of preterm babies. The albumin concentration in newborn babies rose from about 20 g/l in 28 weeks gestation babies to about 30 g/l in term babies. The total protein concentration in newborn babies rose from about 40 g/l in 28 week gestation babies to about 60 g/l in term babies. In babies of postnatal age up to 8 weeks the albumin concentration continues to rise at the same rate as the in utero rise in concentration with increasing gestation, regardless of the clinical state of the baby. The total protein concentration, however, remains about the same as at birth. These results allow better clinical interpretation of albumin and total protein concentration in "older" preterm babies.

Blood Proteins↗

Fluid dynamics during bronchoalveolar lavage.

A series of related studies were designed to investigate and quantify the degree of fluid exchange between the lung segment and the interstitium or pulmonary circulation that occurred during a standardized bronchoalveolar lavage (BAL). In 5 subjects undergoing a 3 x 60 ml BAL, the dilution of introduced fluid was calculated at approximately 25% using both technetium colloid and methylene blue. Thus, there was a total dilution volume of about 225 ml. In the same experiment, tritiated water was incorporated into the introduced fluid, and the degree of dilution of tritium in the aspirate was compared with that of the other 2 markers. The dilution of tritium was greater than anticipated, suggesting that around 55 ml of water had effluxed from the lung segment during BAL. The total fluid gain by the segment during BAL was thus approximately 100 ml (44% of the dilution volume), although the contribution of fluid resident in the lung prior to BAL to this volume was not known. The 3 x 60 ml BAL procedures were performed in a further 5 patients 12 h after they had received tritiated water orally. The concentration of urea, a putative "endogenous marker" of dilution, was assayed simultaneously in plasma and aspirate. From these values the fluid normally resident in the lung segment was calculated to contribute at most about 2% to the total aspirated volume. A median of 39% of the 85 ml aspirated was calculated to have come from the circulation or surrounding interstitium by simultaneous measurements of the concentrations of tritium in plasma and lavage aspirate.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗