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Biomedical subjects

A Stewart

Publications and source records attributed to A Stewart.

At least 127 records · Page 7Linked to original sources

Influence of hypoxia and glucose deprivation on tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor expression in human cultured monocytes.

Ischaemia in wounds may modulate the expression of tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The release of these and other cytokines by stimulated macrophages influences wound healing. Our aim was to examine the separate and combined effects of hypoxia and glucose deprivation on TNF-alpha and GM-CSF mRNA levels in human monocytes isolated from peripheral blood by density gradient centrifugation and purified by adherence. Cells were incubated for a 16-hour period in a hypoxic (3% O2) or normoxic (21% O2) environment in the presence or absence of glucose followed by a further 4 h under normoxic conditions in the presence or absence of lipopolysaccharide (LPS, 100 pg/ml). These different incubation conditions had no effect on cell viability, cell number, lactate dehydrogenase release or superoxide anion generation (n = 5, p > 0.05, paired t test). However, Northern hybridisation showed that hypoxia decreased the expression of GM-CSF mRNA in LPS-stimulated human monocytes by 46% (n = 9, p < 0.05, paired t test) and increased the expression of TNF-alpha by 102% (n = 7, p < 0.05, paired t test). The increase in the level of immunoreactive TNF-alpha in the cell supernatants paralleled the increase in TNF-alpha mRNA. The combination of glucose deprivation and hypoxia decreased the expression of both GM-CSF and TNF-alpha mRNA in LPS-stimulated human monocytes. Similarly, a decrease in the level of TNF-alpha in the cell supernatants was observed (n = 3-5, p < 0.05, two-way ANOVA). These data suggest that incubation conditions simulating ischaemia reduce LPS-induced cytokine expression.

Cell Count↗

Cultural diversity in Florida nursing programs: a survey of deans and directors.

To determine how nursing programs in the state of Florida promote and integrate cultural diversity, a survey of deans and directors was conducted. Of 90 deans and directors surveyed, 46 (51%) responded. The ethnic composition of students and faculty in the respondents' programs was examined in comparison with that of the Florida population. Hispanics, Blacks, and Asians were found to be underrepresented in nursing faculty as compared with their proportion in the state population. The majority of deans and directors ranked the goal of promoting cultural diversity of moderate importance. The two most critical issues perceived by the respondents were the lack of cultural knowledge, sensitivity, and awareness, and the academic problems and educational deficits of minority students. In 50% of the programs surveyed, culture content was integrated throughout the curriculum. Other programs either integrated culture content in specific classes or offered a course in transcultural nursing. Although numerous approaches are currently being employed to recruit ethnically diverse faculty and students, the data suggest that more extensive and innovative efforts are needed to overcome existing barriers. As nursing faces the challenge of caring for a multicultural society in the 21st century, nursing leaders and organizations must collaborate to resolve the issues and problems revealed in this survey.

Cultural Diversity↗

Inhibition of phospholipid signalling and proliferation of Swiss 3T3 cells by the wortmannin analogue demethoxyviridin.

Growth factors and certain oncogenes activate a range of phospholipid-mediated signal transduction pathways resulting in cell proliferation. Demethoxyviridin (DMV), a structural analogue of wortmannin and recently reported as a potent inhibitor of phosphoinositide-3-kinase, inhibited bombesin plus insulin-stimulated increase in cell number in Swiss 3T3 cells, a model of cell proliferation. The drug produced cytostatic effects at concentrations below 1 microM and cytotoxic effects at 10 microM. In intact Swiss 3T3 cells DMV inhibited insulin-stimulated PI 3- and 4-kinases and bombesin-stimulated phospholipases C, D and A2 in the nanomolar range. DMV also inhibited bombesin-stimulated tyrosine phosphorylation of a range of proteins at nM concentrations. This study shows that DMV inhibited multiple stimulated signalling pathways which lead to increased Swiss 3T3 cell proliferation. A stable analogue of DMV may have chemotherapeutic potential.

3T3 Cells↗

The regulation by phosphorylation of 'priming' of phospholipase A2 activity in the neutrophil model system, differentiated HL60 cells.

1 Differential HL60 cells have been utilized as a model system to examine the 'priming' of neutrophil phospholipase A2 activity. In control cells activation of phospholipase A2 by a 5 min stimulation with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (100 nM) was essentially undetectable. When cells were primed by preincubation with 5 microns cytochalasin B for 5 min arachidonate release, a measure of phospholipase A2 activation, was observed within 20 s. 2 Priming by cytochalasin B did not involve or require a change in intracellular free calcium concentration. 3 Priming was associated with an increase in general protein tyrosine phosphorylation and could also be induced by the receptor tyrosine kinase agonist granulocyte macrophage colony-stimulating factor (GM-CSF, 20 ng ml-1) and be mimicked by treatment with the phosphotyrosine phosphatase inhibitor perhydrovanadate (0.5 mM). However, increase in MAP kinase activity was not involved in the priming process. 4 Western blot analysis demonstrated that phospholipase A2 was phosphorylated in both control and primed cells, but that an increase in the amount of membrane associated enzyme was found in the primed cells. 5 Thus priming appears to be due to membrane association of the phospholipase and this may be regulated by tyrosine kinase activities.

Arachidonic Acid↗

Activation of gammadelta T cells in malaria: interaction of cytokines and a schizont-associated Plasmodium falciparum antigen.

A soluble Plasmodium falciparum antigen that specifically stimulates gammadelta T cells has been found associated predominantly with schizonts rather than ring forms, trophozoites, or gametocytes. This schizont-associated antigen (SAA) is resistant to protease digestion, is anionic at pH 8.5, is heat- and pH-resistant, and contains a phosphate group(s) that is crucial for biologic activity. Partially purified SAA induced proliferative responses and interferon-gamma production by gammadelta T cells. These stimulatory effects were greatly enhanced by monocyte-derived cytokines, interleukin (IL)-10, IL-12, and IL-1beta, but not by tumor necrosis factor-alpha. Taken together, these results suggest that concurrent stimulation of gammadelta T cells by SAA and by cytokines released from activated monocytes (IL-10, IL-12, IL-1beta) may represent the major mechanism underlying the selective activation of gammadelta T cells that is consistently observed in clinical cases of P. falciparum infection.

Adult↗

A common strategic language for clinicians and senior managers.

Effective strategic analysis of existing and potential services requires a framework which is relevant and understandable to both clinicians and senior managers. Our work with NHS trusts has developed a framework based on analysis of services into four principal service streams--emergency general hospital, non-emergency general hospital, specialist general hospital and tertiary. Relating service streams to clinical specialties provides a matrix which can provide a basis for an initial analysis of the current and prospective clinical services portfolio, allowing drilling down into the detail and back up to the overall picture. Portfolio effectiveness is assessed by considering overall viability consisting of three interrelated elements--clinical, market and financial viability. The interrelationship of service streams, clinical specialties and viability allows the trust board and key clinicians to share insights into the current and potential systemic linkages between these three elements and to develop a vision of future strategic direction.

Communication↗

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. METHODS: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. RESULTS: The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions. CONCLUSION: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.

Adolescent↗

Activation of the L-arginine nitric oxide pathway in severe sepsis.

AIMS: To determine in children with sepsis syndrome and septic shock the time course of nitric oxide metabolites: nitrate and nitrite (nitrogen oxides). To determine whether serum concentrations of nitrogen oxides distinguished those children who died from sepsis from those who survived; those who required prolonged inotropic support compared with those who did not; and whether there was any relationship of the levels of nitrogen oxides to markers of tissue perfusion. METHODS: Nitrogen oxides were measured in 30 children with sepsis syndrome or septic shock at admission, 12, 24, and 48 hours. A non-septic control group had serum nitrogen oxides measured at admission. Markers of haemodynamics and tissue perfusion measured were mean arterial pressure, blood lactate, base deficit, gastric intramucosal pH, and deltaCO2 (DCO2: the difference between arterial and gastric intraluminal carbon dioxide tensions). Inotrope doses, number of organ systems failing at 48 hours, and outcome as survival were recorded. RESULTS: Children with sepsis had increased nitrogen oxide concentrations at presentation compared with a group of non-septic controls. Children with organ failure at 48 hours had higher serum nitrogen oxide concentrations than those with sepsis uncomplicated by organ failure at 48 hours. There was no difference in nitrogen oxide when patients were subgrouped according to the receipt of inotropes at 48 hours, and no association with markers of tissue perfusion, or survival. CONCLUSIONS: While this study shows that nitric oxide production is increased in sepsis in children, there was a limited relationship with clinically important markers of illness severity and no relationship to survival.

Adolescent↗

The effect on risk estimates of excluding cases from a case-control study of ischemic stroke.

There is limited information about the effect on stroke risk estimates of excluding cases who are unable to respond to interviews. A case-control study of ischemic stroke between 1988 and 1990 in Shreveport, La., USA, provided a basis for studying this question. Of 197 consecutively admitted cases of ischemic stroke, 77 were excluded due to dementia, aphasia or impaired consciousness. Information about risk factors and stroke characteristics was obtained from hospital records. Excluded cases had more left hemispheric (52 versus 19%) and fewer vertebrobasilar (12 versus 29%) and lacunar (5 versus 13%) infarcts than included cases. Excluded cases were also older (p < 0.01), and they had larger infarcts (p < 0.01), multiple strokes (p < 0.01) and congestive heart failure (p < 0.01) more often than included cases. Cases were matched to hospital controls by age, sex, race, and date of admission. Odds ratios (ORs) were higher for excluded cases for 5 of 6 exposures with a significantly higher OR for congestive heart failure (p < 0.01). The ORs changed by as much as 63% when excluded cases were added. These results emphasize the importance of acquiring information about excluded cases and considering selection bias when interpreting stroke studies that exclude cases who are unable to respond to interviews.

Adult↗