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Biomedical subjects

L Armstrong

Publications and source records attributed to L Armstrong.

At least 55 records · Page 3Linked to original sources
PubMed1997

Relative production of tumour necrosis factor alpha and interleukin 10 in adult respiratory distress syndrome.

BACKGROUND: The adult respiratory distress syndrome (ARDS) may be regarded as an example of an uncontrolled or excessive inflammatory response in which tumour necrosis factor alpha (TNF-alpha) has been proposed to play a central role. Interleukin 10 (IL-10) has been identified as an important regulator of this response. The potential role for IL-10 in this context was investigated by measuring the relative production of IL-10 and TNF-alpha protein in the plasma, bronchoalveolar lavage (BAL) fluid, and alveolar macrophage culture supernatants of patients with, or at risk of developing, ARDS. METHODS: Twenty six patients were studied from three groups at risk of or with ARDS: sepsis (n = 12), multiple trauma (n = 8), and perforated bowel (n = 6). Ten patients had ARDS. Bronchoalveolar lavage and venepuncture were performed within 24 hours of arrival on the intensive therapy unit or of diagnosis of ARDS. IL-10 and TNF-alpha protein were detected in the plasma, BAL fluid, and alveolar macrophage supernatants by sandwich enzyme linked immunoabsorbent assays. RESULTS: The median IL-10 concentrations in the plasma and BAL fluid of patients with ARDS were significantly lower than the concentrations detectable in the plasma (median difference-17.5, 95% CI -52.4 to 1.31, p < 0.05) and BAL fluid of at risk patients (median difference -32.1, 95% CI -47.5 to 2.3, p < 0.05). There was a tendency towards enhanced concentrations of TNF-alpha detectable in the alveolar macrophage supernatants and the BAL fluid of patients with ARDS compared with at risk patients, although this did not reach statistical significance. No difference was observed in the plasma concentrations of TNF-alpha between the two groups. The ratios of TNF-alpha to IL-10 protein in the BAL fluid of patients with ARDS and at risk patients were 3.52 and 0.85, respectively (median difference 1.44, 95% CI 0.07 to 5.01, p < 0.01). There was no difference in alveolar macrophage production of IL-10 between the two groups. CONCLUSIONS: This study highlights the potential importance of the pro-inflammatory versus the anti-inflammatory imbalance in ARDS which may be reflected by the ratio of IL-10 and TNF-alpha in the lung.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Differential effects of stimulus context on perceived length: implications for the horizontal-vertical illusion.

Six experiments examined orientation-specific effects of stimulus context on the visual perception of horizontal and vertical lengths: Using a paired-comparison method, Experiments 1-5 showed that the probability of judging a given vertical line to be longer than a given horizontal line was relatively great when the stimulus set comprised relatively long horizontals and short verticals, and relatively small when the stimulus set comprised short horizontals with long verticals. To the extent that stimulus context exerts orientation-specific effects on perceived length, it thereby modulates the degree to which verticals appear longer than physically equivalent horizontals: the horizontal-vertical illusion (HVI). Under various contextual conditions, the HVI was as small as 3% (horizontals had to be 3% greater than verticals to be perceived as equally long) and as great as 15%, equaling about 12% in a "neutral" context. In Experiment 6, subjects judged the absolute physical length of each stimulus, and the results indicated that stimulus context acted largely by decreasing perceived lengths. The results are consistent with the hypothesis that differential effects of context reflect a process of stimulus-specific perceptual attenuation.

Adolescent↗
PubMed1997

Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor.

Echistatin is a 49-amino-acid peptide belonging to the family of disintegrins that are derived from snake venoms and are potent inhibitors of platelet aggregation and cell adhesion. Integrin alphavbeta3 receptor plays a critical role in several physiological processes such as tumor-induced angiogenesis, tumor cell metastasis, osteoporosis and wound repair. In this study, we have characterized the binding of echistatin to purified integrin alphavbeta3 receptor and the form expressed on human embryonic kidney 293 cells. We show that both purified and membrane-bound integrin alphavbeta3 binds to echistatin with a high affinity, which can be competed efficiently by linear and cyclic peptides containing the RGD sequence. Previous studies have shown that alphavbeta3 binds to vitronectin in a nondissociable manner, whereas an RGD-containing peptide derived from vitronectin binds in a dissociable manner with a Kd of 9.4 x 10(-7) M. Our studies indicate that radiolabeled echistatin binds to alphavbeta3 in a nondissociable manner, similar to native echistatin. However, echistatin does not support the adhesion of 293 cells expressing alphavbeta3 receptor because of poor binding to plastic dishes and is a potent antagonist of the adhesion of these cells to vitronectin. These studies demonstrate that echistatin binding to alphavbeta3 is of high affinity and irreversible similar to vitronectin and provides an alternate ligand for high-throughput screening for alphavbeta3 antagonists.

Cell Adhesion↗
PubMed1996

Evaluation of cyclohexenoesculetin-beta-D-galactoside and 8-hydroxyquinoline-beta-D-galactoside as substrates for the detection of beta-galactosidase.

We describe the synthesis of two new substrates for the detection of beta-galactosidase and evaluate their performance in comparison with that of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). Of 171 Enterobacteriaceae strains that were able to hydrolyze X-Gal, 166 (97.1%) also hydrolyzed cyclohexenoesculetin-beta-D-galactoside whereas only 96 (56.1%) showed evidence of hydrolysis of 8-hydroxyquinoline-beta-D-galactoside. No false-positive results were observed with either substrate.

Enterobacteriaceae↗
PubMed1996

Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes.

BACKGROUND: Regulation of the inflammatory response within the human lung is essential to prevent this important part of the normal host defence response becoming a pathological process. Tumour necrosis factor alpha (TNF-alpha) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis in many organ systems including the lung. Interleukin 10 (IL-10) has been proposed as having an inhibitory effect on the production of several inflammatory cytokines including TNF-alpha. METHODS: The effect of IL-10 administration on TNF-alpha production was explored in human alveolar macrophages and peripheral blood monocytes from matched individuals. The effects of IL-10 on TNF-alpha protein production were determined by sandwich enzyme linked immunosorbant assay (ELISA), whereas the TNF-alpha mRNA response was established by Northeren blotting using a TNF-alpha specific oligonucleotide probe. The protein synthesis inhibitors actinomycin D and cyclohexamide were utilised to monitor IL-10 effects on mRNA degradation and de novo protein synthesis, respectively. RESULTS: The lipopolysaccharide-mediated TNF-alpha production in alveolar macrophages was reduced from 3.508 (0.629) to 2.035 (0.385) ng/ml by 100 U/ml IL-10. Lipopolysaccharide-induced TNF-alpha production in peripheral blood monocytes was reduced from 2.035 (0.284) to 0.698 (0.167) ng/ml. TNF-alpha gene expression was also inhibited in both alveolar macrophages and peripheral blood monocytes; lipopolysaccharide-induced TNF-alpha mRNA was reduced by 47.8 (15.2)% and 83.1 (4.2)%, respectively, by IL-10. The IL-10 mediated suppression of TNF-alpha mRNA was unaffected by addition of cyclohexamide, suggesting that de novo protein synthesis was not required for TNF-alpha inhibition. mRNA stability experiments indicated no acceleration in lipopolysaccharide-induced TNF-alpha mRNA degradation in response to IL-10. CONCLUSIONS: These findings suggest that IL-10 is a potent inhibitor of TNF-alpha expression and release from alveolar macrophages and peripheral blood monocytes, and thus it may have an important role in the cytokine network of the pulmonary immune response.

Adult↗
PubMed1996

Using a quantitative measure of communicative environment to compare two psychogeriatric day care settings.

The importance of the relationship between the physical and interpersonal environment and the maintenance and enhancement of communication in the ageing institutionalised population is well-documented in the literature. This study aimed to evaluate the communicative environment in two different day care settings for people with dementia by the recording and structuring of observations made of sampled conversations. The data collected were considered quantitatively in order to compare the two settings. The findings of the study can be applied to clinical and everyday practice, through the suggestion of practical ideas for physical and/or social environmental modification.

Aged↗
PubMed1996

A content analysis of the professional journal of the British Society of Speech Therapists. I: The first 10 years. Spotlight on 'Speech' 1935-1945.

The 24 editions of the professional journal 'Speech' published between 1935-1945 were examined by use of content analysis. The use of this approach enabled an in-depth survey of the professional, clinical and political issues of the period which saw the beginning of speech and language therapy as a profession. Two main areas were focused upon: the development of the professional body and the authored papers which appeared in the journal. 'Speech' at that time can be viewed as a blend of today's 'European Journal of Disorders of Communication' with today's 'Bulletin'.

Bibliometrics↗
PubMed1996

Use of the Arizona Battery for Communication Disorders of Dementia in the UK.

The Arizona Battery for Communication Disorders of Dementia (ABCD) (Bayles & Tomoeda, 1993) was given to groups of young and old normal subjects and to subjects with moderate Alzheimer's disease in the UK. Very few significant differences were found between their raw scores and those of the original standardisation sample in the USA, which makes the ABCD an appropriate test to use in the UK. Although some subjects commented on several of the test stimuli, cultural differences in pictures and vocabulary did not produce notable effects on test performance and so alterations to test materials are not required for the test to be used in the UK.

Adult↗
PubMed1995

SCH 51344 inhibits ras transformation by a novel mechanism.

A pyrazolo-quinoline compound, 6-methoxy-4-[2-[(2-hydroxyethoxyl)-ethyl]amino]-3-methyl-1M-pyrazo lo [3,4-b]quinoline (SCH 51344), was identified based on its ability to derepress human smooth muscle alpha-actin promoter activity in ras-transformed cells. In this study, we show that SCH 51344 reverts several key aspects of ras transformation, such as morphological changes, actin filament organization, and anchorage-independent growth, and also inhibits Val-12 Ras-induced maturation of Xenopus oocytes. SCH 51344 is also a potent inhibitor of the anchorage-independent growth of human tumor lines known to contain multiple genetic alterations in addition to activated ras genes. We have sought to determine whether SCH 51344 disrupts the signaling pathway that activates mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) in normal and ras-transformed fibroblast cells. NIH 3T3 cells transformed by different oncogenes, which have products that participate at different steps of the Ras signaling pathway, were tested in a soft-agar colony formation assay to determine which step of the pathway is inhibited by SCH 51344. Our results indicate that SCH 51344 inhibits the ability of v-abl, v-mos, H-ras, v-raf, and mutant active MAP kinase kinase-transformed NIH 3T3 cells to grow in soft agar. Only v-fos-transformed cells were found to be resistant to the treatment of SCH 51344. SCH 51344 treatment had very little effect, if any, on the activation of MAP kinase kinase, MAP kinase, and p90RSK activity in response to growth factor stimulation. Treatment of ras-transformed cells with SCH 51344 led to stimulation of serum response factor DNA binding activity and activation of serum response element-dependent gene transcription, accounting for its ability to activate alpha-actin promoter activity in ras-transformed cells. Our results indicate that SCH 51344 inhibits ras transformation by a novel mechanism and acts at a point either downstream or parallel to extracellular signal-regulated kinase-dependent Ras signaling pathway.

3T3 Cells↗
PubMed1995

Activation of smooth muscle alpha-actin promoter in ras-transformed cells by treatments with antimitotic agents: correlation with stimulation of SRF:SRE mediated gene transcription.

Smooth muscle alpha-actin promoter is repressed in ras-transformed fibroblast cells and derepressed in revertant cells. We have recently shown that serum response factor (SRF) which can bind to the serum response elements (SREs) present in the alpha-actin promoter, can activate alpha-actin promoter activity in ras-transformed cells and suppress transformation by ras. Agents that stimulate SRF expression and alpha-actin promoter activity in ras-transformed cells are expected to be potential candidates as antitumor agents. In this study, we show that treatment of ras-transformed cells with antitumor agents such as taxol, vincristine, vinblastine, colchicine, and nocodazole leads to 5- to 7-fold activation of alpha-actin promoter driven CAT activity, whereas there was very little effect on thymidine kinase promoter driven CAT activity. This activation occurred at subcytotoxic concentrations of these agents and correlated with inhibition of cell cycle progression. Furthermore, these agents stimulated SRF expression in ras-transformed cells, as measured by its SRE binding activity. The increase in alpha-actin expression is accompanied by the restoration of actin filaments into organized bundles. These results suggest a novel mechanism by which antimitotic agents suppress the ras-transformed phenotype.

Actin Cytoskeleton↗
PubMed1995

Do mothers and fathers interact differently with their child or is it the situation which matters?

This study aimed to test the Differential Experience Hypothesis which suggests mothers and fathers interact differently with their child. The forms and functions of parents' language in interaction with their 2-2.5-year-old child were investigated across four different interactional settings within the home and for each parent separately. The results, supporting the differential experience hypothesis, suggest that differences do exist between mothers' and fathers' conversational styles. However, the findings indicate that gender is not the only influencing factor. The situations in which interaction occurs also appear to have an effect on the style of interaction irrespective of the sex of the parent (context hypothesis).

Child, Preschool↗
PubMed1995

Strategy for developing transgenic assays for screening antineoplastic drugs that affect tubulin polymerization.

In this study we evaluated the antitumor efficacy of taxol in four solid tumor models derived from wap-ras line 69 transgenic mice. Taxol inhibited the growth of spontaneous salivary and mammary gland adenocarcinomas in wap-ras mice. In nude mice it was also effective against solid tumors caused by WR21 cells derived from a wap-ras salivary gland tumor. Taxol was not able to prevent tumor emergence in wap-ras/F mice, a subline of the wap-ras strain in which all males develop palpable mammary gland tumors between 1.5 and 3.0 months of age. Our data indicate the range of results that can be expected when this panel of related transgenic tumor models is used to study the antitumor effects of taxol and other therapeutic drugs that act by affecting tubulin polymerization. These models of ras-mediated neoplasia should prove useful for testing anticancer compounds with taxol-like mechanisms of action.

Animals↗
PubMed1994

Preliminary evidence on the question of gender differences in language testing of older people.

The effect of gender on the outcomes of language assessments in older people is relatively unknown. This study compared the performance of groups of normal older men and women on three different batteries of language and memory tests. No significant mean score difference was found. All three batteries therefore show no strong quantitative gender bias and can be applied equally to older men and women with communication difficulties. Although no quantitative gender difference was found, the data suggested two possible areas for further investigation (error types and interpersonal styles) which may have clinical implications.

Aged↗
PubMed1993

Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass.

Multiorgan dysfunction still occurs after cardiopulmonary bypass and remains a major cause of morbidity and mortality, especially in the pediatric age group. This is consequent upon the so-called systemic inflammatory response to bypass with an increase in inflammatory mediators. Hemofiltration may be able to attenuate the effects of this response by elimination of some or all of these mediators. We undertook a prospective, randomized study to investigate the effect of hemofiltration on plasma levels of the cytokines tumor necrosis factor alpha, interleukin-8, and interleukin 6 in 18 infants and children undergoing deep hypothermic bypass. Serial plasma samples were taken before, during, and after bypass. Assay of the plasma samples revealed presence of the cytokines in a number of subjects in both groups, in some cases before operation. There were significant reductions in levels of tumor necrosis factor after hemofiltration, with no reduction noted in the group not undergoing hemofiltration. A similar difference (p < 0.05) was detected in the levels of interleukin-6 between the two groups after bypass, although this was largely due to changes in 2 subjects. Interleukin-8 was detected in a small number of subjects insufficient for statistical analysis, but with higher values in the group undergoing hemofiltration. We conclude that hemofiltration has the potential to remove cytokines from the circulation, with consequent beneficial effects.

Cardiopulmonary Bypass↗
PubMed1992

Predisposition to and late onset of upper airway obstruction following angiotensin-converting enzyme inhibitor therapy.

Angioedema of the face and neck is a rare but potentially fatal complication of angiotensin-converting enzyme inhibitor (ACEI) use. We retrospectively reviewed five cases of ACEI angioedema seen at our institution over the past 2 1/2 years. Four of the cases occurred with enalapril and one with lisinopril. Onset of symptoms varied from two days to ten months. Importantly, three of the five patients had been receiving medication three months or longer, suggesting clinicians must consider this complication during long-term administration of these agents. Three of the five patients were markedly obese, had a history of previous face and neck surgery, or had been intubated in the past. Thus, we propose that previous manipulation or trauma of the upper airway, perhaps resulting in airway narrowing, may represent a risk factor for upper airway obstruction secondary to ACEI-induced angioedema.

Adult↗