PubMed Health⌕ Search

Biomedical subjects

S F Smith

Publications and source records attributed to S F Smith.

At least 19 recordsLinked to original sources
PubMed1999

Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids.

Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 microgramgs twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 ng/10(6) AMs; 4.4 ng/10(6) ATII cells) and secreted (1. 4 ng/10(6) AMs; 1.8 ng/10(6) ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10(-7) M dexamethasone but at 10(-3) M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.

Administration, Inhalation↗
PubMed1998

Reduction of nitric oxide release from alveolar macrophages by a lipocortin peptide.

Nitric oxide (NO), produced by alveolar macrophages (AM) is used as a marker of respiratory tract inflammation. Lipocortin 1 (Lc-1) is an anti-inflammatory, glucocorticoid-inducible protein. The current aims were to determine whether (a) an Lc-1-derived peptide, Ac2-26, inhibited lipopolysaccharide (LPS)-induced NO release by primary AM in vitro and (b) the inhibitory action of dexamethasone was Lc-1-dependent. LPS treatment stimulated NO release from rat AM. Ac2-26 had little effect on unstimulated release, but suppressed LPS-stimulated release at concentrations > or =320 nM (320 nM, 10 +/- 3%; 3.2 microM, 15 +/- 3%; 32 microM, 27 +/- 4% NO inhibited, mean +/- SEM, n = 6). Inhibition by dexamethasone of NO release was unaffected by neutralizing anti-Lc-1 indicating that this action is Lc-1-independent in primary AM. Nevertheless inhibition of NO release by Ac2-26 (80 microM) was similar to that of 1 microM dexamethasone (Ac2-26, 40 +/- 6%; dexamethasone, 48 +/- 6% NO inhibited, mean +/- SEM, n = 6).

Animals↗
PubMed1996

Compromised inhibition of human lung lavage cell elastases.

Increased elastinolytic activity has been correlated with the degree of lung damage occurring in a variety of lung diseases including cystic fibrosis; serine proteinase inhibitors are currently on trial for the treatment of some lung disorders. However, human lung lavage cells also secrete metallo-dependent elastases. Here we show, for the first time, that whilst these are readily inhibited by EDTA, inhibition of serine elastases using serpins (serine proteinase inhibitors) is not always possible. This may reflect inactivation of serpins by uninhibited metalloproteinases and oxidants in a low protein milieu. Thus, the therapeutic inhibition of excessive elastinolytic activity may require a combination of inhibitors to work efficiently.

Adult↗
PubMed1996

Lipocortin 1: glucocorticoids caught in the act?

Glucocorticoids (glucocorticosteroids, corticosteroids) have an important place in the treatment of many inflammatory conditions including those of the respiratory tract. Their mechanisms of action include both the suppression of proinflammatory mediators and the upregulation of at least one anti-inflammatory protein, lipocortin 1 (also known as annexin 1). Lipocortin 1 has been convincingly demonstrated to mediate the anti-inflammatory effects of glucocorticoids in a variety of in vivo and in vitro models of inflammation. The actions of lipocortin 1 in the lung have not been fully elucidated. If, as initial studies suggest, its effects in the respiratory tract are shown to be anti-inflammatory, it is possible that administration of lipocortin 1 peptides, or other drugs based on the active site of lipocortin 1, might prove to be useful agents for the control of respiratory tract inflammation.

Annexin A1↗
PubMed1996

Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Lipocortin-1 distribution in bronchoalveolar lavage from healthy human lung: effect of prednisolone.

Lipocortin-1 (LC-1; annexin-1) may mediate some anti-inflammatory actions of the glucocorticoids, probably after binding to specific cell surface binding sites. We have quantified LC-1 levels in bronchoalveolar lavage (BAL) fluid and cells collected from seven healthy volunteers before and after 7 days of treatment with an oral glucocorticoid, prednisolone (30 mg/day). Extracellular BAL LC-1 was higher and cellular LC-1 was lower after prednisolone than before [extracellular: before, median 98 ng/mg albumin (range 48-350 ng/mg albumin); after, 236 ng/mg albumin (19-414 ng/mg albumin); P < 0.05. Cellular: before, 23.3 ng/10(6) cells (14.6-26.9 ng/10(6) cells); after, 18.0 ng/10(6) cells (122-268 ng/10(6) cells); P < 0.05]. The distribution of LC-1 within BAL cells ex vivo (cell surface = 25%, cytosol = 50%, membrane = 25%) was unaffected by prednisolone treatment. However, in adherent cells that had been cultured for 4 h, 70-80% of the LC-1 was on the cell surface. In summary, prednisolone appears to promote cellular release of LC-1. The difference in distribution of cellular LC-1 in BAL cells ex vivo and in vitro may reflect adherence and/or activation.

Adult↗
PubMed1995

Flexible protocols improve parallel experimentation throughput.

Advanced chemical workstations offer the potential to substantially improve the productivity of experimental research. To fully exploit such technologies, effective scheduling of experiments is crucial. Chemists tend to define experimental protocols with rigid time constraints, although often the scientific objectives can be achieved without adhering to such constraints. Investigation of a scheduling algorithm that allows flexible time constraints shows that improvements in workstation throughput as great as 50% can be reached by modest flexibility in the timing of operations in the experiments. Several heuristics that might be used with the scheduling algorithm were tested; a heuristic that schedules long experiments while first keeping the workstation busy was shown to be a good general choice.

Algorithms↗
PubMed1994

[Induced abortion].

Explore the source record for details and available documents.

Abortion, Induced↗
PubMed1993

Comparison of bone volume and strength as measures of skeletal integrity in caged laying hens with access to perches.

Fractures in spent laying hens are now recognised as a major welfare problem; the objective of this work was to determine whether provision of perches for caged layers would increase bone strength, bone volume or both. Sixteen ISA Brown hens were housed from 18 to 72 weeks old in cages with perches and 16 in similar cages without perches. At the end of lay the birds' tibiotarsi were examined for strength by a three-point loading test and their tarsometatarsi for bone volume by histomorphometry. There was no significant effect of perches on tibiotarsal breaking strength. Hens from both groups showed evidence of osteoporosis, but it was more severe in the birds from conventional cages: tarsometatarsal trabecular bone volume was greater in the hens which had access to perches. A positive correlation was found between trabecular bone volume and the degree of day-time perch usage by individual hens. Provision of perches can have a slight but significant beneficial effect, at least for the leg bones, in increasing the bone volume of caged laying hens.

Animals↗
PubMed1993

Effects of perches on trabecular bone volume in laying hens.

Trabecular bone remodelling is known to be affected by loading or exercise, and thus exercise may effect the trabecular bone loss associated with osteopenia in laying hens. Sixteen ISA Brown hens were housed from 18 to 72 weeks old in cages with perches and 16 in similar cages without perches to examine the effects of the exercise afforded by perch provision on trabecular bone volume. At 72 weeks, mean trabecular bone volume in the proximal tarsometatarsus of birds with access to perches was significantly greater than in control birds, while medullary bone volume was not significantly different in the two groups. However, all the birds were considered osteoporotic, though to varying degrees, and the beneficial effects of perches were relatively minor. It was concluded that while trabecular bone loss may be reduced by perch provision, other factors are probably more influential in the development of the osteoporosis typical of laying hens.

Animals↗
PubMed1993

Antibodies to human recombinant lipocortin-I in inflammatory bowel disease.

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Nesting, dust bathing and perching by laying hens in cages: effects of design on behaviour and welfare.

1. Laying hens (192 ISA Brown medium hybrids) were housed from 18 to 72 weeks as groups of 4 in conventional or experimental cages. The main area of all cages provided 675 cm2/hen. All experimental cages had perches, dust baths and nest boxes, which were of three types: litter (L), artificial turf (A) or plastic rollaway (P). These facilities provided an additional 375 to 480 cm2/hen. The nest boxes and dust baths occupied either high or low positions. Behaviour, physical condition and production of the birds were regularly recorded. 2. Mortality was low (1.6% overall) and egg production very good in all treatments. The proportion of cracked and dirty eggs was slightly (but not significantly) higher in the experimental cages. In the experimental cages 90% of eggs were laid overall in the nest boxes and 3% in the dust baths. The proportion laid in the nest boxes was lower early in the laying cycle and increased with time, reaching 99% in A. 3. The facilities were heavily used. Birds spent about 25% of day time on the perches and 10-15% in or near the nest box and dust bath. At night, the majority of birds (90 to 94%) roosted on perches, but most of the remainder were on the lips of the nest box or dust bath, fouling the interiors. 4. Pre-laying behaviour was much more settled in the experimental cages (45 min spent in the eventual laying position) than in the conventional ones (20 min) and total duration varied from 68 min in A to 87 min in P. The number of nest entries varied from 3.0 (A and P) to 4.3 (L); disturbance to sitting birds was correspondingly greater in L. 5. Dust bathing in the experimental cages generally took place during the afternoon in a single bout of about 5 min duration, whereas in the conventional cages it was brief and fragmented (3 bouts of 10 s each). The dust bath was also used for foraging behaviour (pecking and scratching). The treatments with small dust baths (A and P) caused problems for the birds. 6. Feather, foot and claw damage all tended to be less in the experimental than in the conventional cages, though only in the last case was the difference significant. Keel bone depressions appeared to be associated with perches; they were present in 43% of hens in the experimental cages but only 4% in conventional cages.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Welfare↗
PubMed1992

Individual perching behavior of laying hens and its effects in cages.

1. ISA Brown hens were housed, from 18 to 71 weeks of age, as groups of 4 in cages with 675 cm2/bird. There were 7 treatments: control cages and 6 treatments with perches fitted across the rear of the cage. Five treatments had 450 mm wide cages, with perches made from hardwood, textured metal, smooth plastic, softwood and padded vinyl, and one treatment had a 600 mm wide cage, with a softwood perch. There were 4 cages in each of the first 6 treatments and 6 in the last. 2. Overall, birds spent about 25% of the day time on perches. Most time (28 to 41%) was spent perching on the 600 mm softwood perches. Among 450 mm perches, most time (25 to 30%) was spent on the softwood perch and least (13 to 23%) on the plastic; the results suggested that a slightly rough surface was preferred. Individual birds varied considerably in the proportion of day time they spent perching; this variation was relatively consistent over time. 3. Overall, the proportion of birds roosting on the perches at night was 85% in period 1; declined to 76% by period 6, probably because increased body size made it almost impossible for 4 birds to perch in the 450 mm cages. Birds roosting on the floor tended always to be the same individuals. 4. Damage to the soles of the feet was less in all treatments with perches than in control cages. It was least in 600 mm wide cages and showed a negative correlation with time spent perching, both within and between treatments. Long or twisted claws, in contrast, tended to be slightly worse in treatments where there was most perching. 5. Downgraded eggs tended to be slightly more frequent in cages with perches; the greatest proportion (cracked 1.4%, dirty 3.6%) was from the 600 mm wide cages, as a result of hens laying from the perch and a build-up of manure behind it. 6. Although problems remain the findings suggest that provision of perches is important for the welfare of hens; perch space should be sufficient to allow all birds to perch simultaneously.

Age Factors↗
PubMed1992

Cholesterol-lowering effects of psyllium-enriched cereal as an adjunct to a prudent diet in the treatment of mild to moderate hypercholesterolemia.

Psyllium hydrophilic mucilloid, rich in soluble fiber, significantly lowers serum cholesterol concentrations. To investigate the lipid-lowering effects of a ready-to-eat cereal enriched with psyllium, we studied 44 hypercholesterolemic ambulatory individuals for 7 wk, using a randomized, double-blind, parallel design. After a 1-wk baseline period, subjects were randomly assigned to consume 114 g/d of a psyllium-flake or wheat-bran-flake cerearl for 6 wk adjunctive to an American Heart Association Step I diet. Serum high-density-lipoprotein cholesterol and triglycerides remained unchanged throughout the study; however, serum cholesterol and low-density lipoprotein (LDL) concentrations were significantly lower on psyllium than on wheat-bran cereal. Additionally, serum total and LDL cholesterol values were significantly lower than baseline values in the psyllium group. The dietary nutrient intake of the two groups did not differ except for soluble fiber. Adding psyllium-enriched cereal to a prudent low-fat diet may enhance dietary management of hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1991

Lipid responses of hypercholesterolemic men to oat-bran and wheat-bran intake.

The hypocholesterolemic effects of oat bran (OB) have been recently challenged. To carefully document the hypocholesterolemic effects of OB, 20 hypercholesterolemic men admitted to a metabolic ward were randomly allocated to either OB or wheat bran (WB) for 21 d after a 7-d control-diet period. Control and treatment diets were designed to be identical in energy content and nutrients, differing only in the amount of soluble fiber. After 21 d, OB significantly decreased total cholesterol by 12.8% (P less than 0.001), low-density-lipoprotein cholesterol by 12.1% (P less than 0.004), and apolipoprotein B-100 by 13.7% (P less than 0.001) whereas WB had no significant effect. High-density-lipoprotein cholesterol and apolipoprotein A-I did not change significantly in either group. Serum triglycerides decreased by 10% in both groups but the decrease was only significant (P less than 0.04) in WB subjects. OB but not WB significantly reduced total cholesterol and other atherogenic lipoprotein fractions independent of other dietary changes.

Adult↗
PubMed1990

An assay for the assessment of lipocortin 1 levels in human lung lavage fluid.

The physiological function of the lipocortins, proteins which are thought to be glucocorticoid-regulated, is unclear. An improved assay for lipocortins might help to elucidate their role. A rapid and specific sandwich enzyme-linked immunosorbent assay (ELISA) for lipocortin 1 with a working range of 1-2000 ng/ml and an interrun coefficient of variation of less than 10% is described and used in this pilot study to quantify human lipocortin 1 for the first time in acellular bronchoalveolar lavage fluid (BALF), and in media conditioned by BAL cells, from control patients and those with pulmonary sarcoidosis. Using this assay a statistically significant relationship, not previously observed in man, has been demonstrated between concentrations of lipocortin 1/ml of BALF and serum cortisol levels (n = 10, rs = 0.6939, P less than 0.05). Although lipocortin 1 levels in acellular BALF were the same in control and sarcoid patients, significantly more lipocortin 1 was released from sarcoid BAL cells in culture (median 21.6, range 8.1-45.4 ng lipocortin/10(6) cells/h in culture) than from control cells (2.5, 1.5-7.6 ng lipocortin/10(6) cells/h in culture). The possible clinical significance of these data is discussed, but remains to be established.

Annexins↗