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Biomedical subjects

J J Powell

Publications and source records attributed to J J Powell.

At least 19 recordsLinked to original sources
PubMed2006

Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.

OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.

Adult↗
PubMed2006

Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

Alcohol Drinking↗
PubMed2006

Immunolocalization of duodenal cytochrome B: a relationship with circulating markers of iron status.

BACKGROUND: The brush border ferric reductase (Dcytb) is critical for the absorption of dietary iron and appears to be expressed on the duodenal enterocyte brush border. The Dcytb expression is increased in severe iron-deficient anaemia, but the situation in a more typical mild iron deficiency is unclear. This study investigated Dcytb expression in patients with normal iron status or mild iron deficiency and its relationships with enterocyte iron status. MATERIALS AND METHODS: Duodenal biopsy specimens and blood samples were obtained from 32 patients undergoing routine upper gastrointestinal endoscopy. Twenty-three specimens (six iron-deficient and 17 iron-replete) were processed for light-microscopy (LM) and for immunohistochemistry with antibodies against Dcytb and heavy/light chain ferritin subunits. The nine remaining biopsies (three iron-deficient and six iron-replete) were processed for electron microscopy (EM). Immunolocalization of Dcytb and intracellular ferritin was performed with appropriate primary antibodies followed by 10-nm gold conjugate labels. RESULTS: The LM process showed a strong negative correlation between immunolabelling intensity of Dcytb on the enterocyte brush border and serum iron saturation (P < 0.001), but only a weak negative correlation between this antigen and haemoglobin (P = 0.08) or serum ferritin concentrations (P = 0.4). EM confirmed anti-Dcytb preferential labelling of microvilli rather than enterocyte cytoplasm (P = 0.001), but preferential antiferritin labelling of cytoplasm (P < 0.02). There was no correlation with enterocyte cytoplasmic ferritin labelling (i.e. enterocyte iron status and Dcytb expression). CONCLUSIONS: Enterocyte Dcytb brush border expression is increased even in mild iron deficiency and may be related to serum iron saturation. The lack of correlation with enterocyte ferritin expression deserves further study with direct measurement of intracellular iron.

Biomarkers↗
PubMed2006

The association between metal ions from hip resurfacing and reduced T-cell counts.

We have studied the relationship between metal ion levels and lymphocyte counts in patients with metal-on-metal hip resurfacings. Peripheral blood samples were analysed for lymphocyte subtypes and whole blood cobalt and chromium ion levels in 68 patients (34 with metal-on-metal hip resurfacings and 34 with standard metal-on-polyethylene total hip replacements). All hip components were radiologically well-fixed and the patients were asymptomatic. Cobalt and chromium levels were significantly elevated in the patients with metal-on-metal hip resurfacings, compared with the patients with standard metal-on-polyethylene designs (p < 0.0001). There was a statistically significant decrease in the level of CD8(+) cells (T-cytotoxic/suppressor) (p = 0.005) in the metal-on-metal hip resurfacing group. A threshold level of blood cobalt and chromium ions was associated with reduced CD8(+) T-cell counts. We have no evidence that our patients suffered as a result of this reduced level of CD8(+) T-cells.

Adult↗
PubMed2005

Effect of humic acid on water chemistry, bioavailability and toxicity of aluminium in the freshwater snail, Lymnaea stagnalis, at neutral pH.

The influence of humic acid on the water chemistry of environmentally relevant concentrations of Al at neutral pH was studied, together with its effect on the bioavailability and toxicity of Al in Lymnaea stagnalis. Humic acid significantly reduced the loss of Al from the water and increased the fraction of filterable Al, although this was a relatively small fraction of total Al. Filterable Al concentration in the presence or absence of humic acid was independent of initial Al concentration. Humic acid only partly reduced toxicity, as observed by a reduction in behavioural suppression, and had no effect on the level of Al accumulated in tissues. These results suggest that humic acid maintains Al in a colloidal form that is bioavailable to L. stagnalis. However, these colloidal Al-humic acid species were less toxic since behavioural toxicity was reduced. Humic acid may play an important role in limiting the toxicity of Al to freshwater organisms.

Aluminum↗
PubMed2005

A provisional database for the silicon content of foods in the United Kingdom.

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma-optical emission spectrometry following microwave-assisted digestion with nitric acid and H(2)O(2). The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.

Beverages↗
PubMed2005

Dietary silicon intake in post-menopausal women.

Si has been suggested as an essential element, and may be important in optimal bone, skin and cardiovascular health. However, there are few estimates of dietary Si intakes in man, especially in a UK population. Following the development of a UK food composition database for Si, the aim of the present study was to investigate dietary intakes of Si amongst healthy women aged over 60 years and to identify important food sources of Si in their diet. Healthy, post-menopausal female subjects (>60 years of age; n 209) were recruited from the general population around Dundee, Scotland as part of an unrelated randomised controlled intervention study where dietary intake was assessed using a self-administered, semi-quantitative food-frequency questionnaire at five time-points over a 2-year period. Food composition data on the Si content of UK foods was used to determine the Si content of food items on the food-frequency questionnaire. Mean Si intake was 18.6 (sd 4.6) mg and did not vary significantly across the 2 years of investigation. Cereals provided the greatest amount of Si in the diet (about 30 %), followed by fruit, beverages (hot, cold and alcoholic beverages combined) and vegetables; together these foods provided over 75 % about Si intake. Si intakes in the UK appear consistent with those reported previously for elderly women in Western populations, but lower than those reported for younger women or for men.

Aged↗
PubMed2004

Functional interactions between mucosal IL-1, IL-ra and TGF-beta 1 in ulcerative colitis.

OBJECTIVE: Studies aiming to define key cytokines in inflammatory bowel disease have been restricted to gene expression or protein quantitation but lack functional information on cytokine interactions. Some of the major cytokines that govern the extent and duration of the inflammatory process in ulcerative colitis (UC), appear to be interleukin 1 (IL-1), its natural inhibitor IL-1 receptor antagonist (IL-1ra) and transforming growth factor beta1 (TGF-beta 1). Indeed, as a predictor of inflammation, the mucosal status of IL-1, depicted as a ratio of IL-1ra/IL-1, has often been used. METHODS: Using an IL-1 bioassay and specific anti-cytokine antibodies we have identified the functional role of these cytokines and their interactions in mucosal biopsy samples taken from patients with UC. RESULTS: Compared with control specimens, the secreted and tissue levels of IL-1 were consistently raised in UC samples. Levels of IL-1, rather than IL-1ra or the ratio of IL-1ra/IL-1, most closely mirrored the severity of inflammation. Using specific antibodies we showed that IL-1ra and TGF-beta 1 appear to modulate the degree of inflammation at different stages of the inflammatory process. Only in severely inflamed tissue, when IL-1 levels were high did IL-1ra inhibit IL-1-induced activity. In contrast, the levels of TGF-beta 1, and its effect in controlling inflammation, was most marked in mild but not severe UC. CONCLUSIONS: The functional roles of these cytokines in the inflammatory process can now be more carefully elucidated using a bioassay and specific neutralising antibodies.

Adolescent↗
PubMed2004

Competition between IL-1, IL-1ra and TGF-beta 1 modulates the response of the ELA4.NOB-1/CTLL bioassay: implications for clinical investigations.

OBJECTIVE: The use of ELISA techniques to measure cytokine levels in clinical samples has chiefly replaced more labour intensive bioassays. ELISA measurements, however, do not reflect the functional activity of a cytokine within a sample; interleukin-1 (IL-1), for example, has two agonist isoforms (IL-1 alpha and IL-1 beta) and a competitive receptor antagonist (IL-1ra), and can be regulated by transforming growth factor beta1 (TGF-beta 1). The net effect of these cytokines, rather than IL-1 levels, are frequently suggested to regulate tissue inflammation, but confirming this has been difficult. METHODS: We used the ELA4.NOB-1/CTLL co-culture IL-1 bioassay to investigate whether IL-1 activity was inhibited by IL-1ra and TGF-beta 1 in a predictable manner. RESULTS: Thymidine incorporation into CTLL cells, induced by IL-1, was reduced dose dependently by IL-1ra and TGF-beta 1. With optimal levels of IL-1 CTLL responsiveness was reduced by 90% by 1 ng/ml TGF-beta 1 and completely abolished by 100 ng/ml IL-1ra. As expected, TGF-beta 1 and IL-1ra had independent mechanisms of action on the bioassay cell lines, and, in combination, they caused an additive, but not synergistic, effect. Importantly, the effect of these cytokines could be completely abolished in the presence of neutralising antibodies. CONCLUSIONS: Bioassay should provide specific functional information on the net IL-1 activity of clinical samples, while the use of specific antibodies could ascertain the contribution of individual cytokines within such samples.

Animals↗
PubMed2004

Does treatment of vulvar lichen sclerosus influence its prognosis?

OBJECTIVE: To record the clinical features, symptomatic response to topical steroids, and resolution of clinical signs in a large cohort of female patients with vulvar lichen sclerosus. DESIGN: Descriptive cohort study with a mean follow-up of 66 months. SETTING: The vulvar clinics of a teaching hospital and of a district general hospital in Oxfordshire, England. PATIENTS: Three hundred twenty-seven patients (74 girls and 253 women) with a definite clinical diagnosis of vulvar lichen sclerosus. Interventions The patients received topical steroids as part of their normal care. MAIN OUTCOME MEASURES: Symptomatic response to treatment (good, partial, or poor); response of the vulvar signs (total, partial, minor, or poor); and the presence or absence of moderate or severe scarring. RESULTS: The mean age at onset was 5.4 years in girls and 55.1 years in women and first-choice therapy was an ultrapotent topical steroid for 50% of the girls and 89% of the women. Response to treatment was recorded in 255 patients. In 244 patients (96%) symptoms improved with treatment, as 168 (66%) became symptom free and 76 (30%) showed partial response; 11 (4%) had poor response. Among the 253 patients in whom a response of the vulvar signs to topical steroid was recorded, 58 (23%) showed total response, with return to normal skin texture and color; and 173 (68%) showed partial, 18 (7%) showed minor, and 4 (2%) showed poor response. Moderate or severe scarring occurred less often in girls (P<.001). Squamous cell carcinoma developed in 6 women (2.4%). CONCLUSION: Topical ultrapotent steroid is an effective treatment for vulvar lichen sclerosus, giving relief of symptoms in most and completely reversing the skin changes in approximately one fifth of patients.

Administration, Cutaneous↗
PubMed2004

Role of exogenous and endogenous silicon in ameliorating behavioural responses to aluminium in a freshwater snail.

Aluminium accumulation by the freshwater snail Lymnaea stagnalis is correlated with behavioural depression which is ameliorated by addition of orthosilicic acid. We hypothesised that Si is relocated to the digestive gland in response to Al, leading to the formation of non-toxic hydroxyaluminosilicates (HAS). Exposure to 500 microg l(-1) Al for 30 days was associated with an initial period of behavioural depression, followed by apparent tolerance and subsequent depression, suggesting saturation of the cellular detoxification pathway during prolonged exposure. Exogenous Si (7.77 mg l(-1)) completely ameliorated all behavioural effects of Al but did not prevent its accumulation. In the presence of added Al, significantly more of this Si was accumulated by the tissues, compared to controls and snails exposed to Si alone. In snails exposed to Al plus Si, Al and Si concentrations were significantly correlated, with a ratio around 3:1 Al:Si, consistent with the presence of the non-toxic HAS protoimogolite.

Aluminum↗
PubMed2004

Interferon-gamma polymorphisms correlate with duration of survival in pancreatic cancer.

Despite progress in diagnosis and staging, pancreatic cancer still has a poor prognosis and it remains difficult to predict duration of survival in advanced pancreatic cancer. Nutritional decline, or cachexia, is a contributory factor to decreased survival in advanced pancreatic carcinoma, and it has been demonstrated that proinflammatory cytokines give rise to cachexia. Interferon (IFN)-gamma is a proinflammatory cytokine whose administration increases survival outcomes in a variety of cancers. The human IFN-gamma gene has a variable length CA-repeat sequence, the length that has been shown to influence IFN-gamma production. The current study was performed to ascertain whether polymorphisms of the IFN-gamma gene would influence survival of individuals with advanced pancreatic cancer. The study demonstrated that the presence of allele 2 (12 CA repeats) was consistently associated with increased duration of survival after confirmation of nonresectable pancreatic carcinoma. We therefore propose that the presence of allele 2 may be a useful marker for patient outcome.

Adult↗
PubMed2003

Bioavailability and toxicity of freshly neutralized aluminium to the freshwater crayfish Pacifastacus leniusculus.

Freshly neutralized aluminium (Al) is toxic to a variety of freshwater organisms despite its insolubility at circumneutral pH. Insoluble Al acts exogenously--for example, on the fish gill--thereby impairing respiratory function, and endogenously in grazing and filter-feeding invertebrates following ingestion during drinking and feeding. This paper examines the bioavailability and behavioral toxicity of freshly neutralized Al to the freshwater crayfish Pacifastacus leniusculus exposed to 500 microg L(-1) added Al for 20 days under controlled conditions. We test the hypothesis that aqueous Al is toxic to the crayfish and that this is largely due to the metal's association with the gill rather than following accumulation in the body. Little Al was accumulated in the digestive gland (hepatopancreas) or flexor muscle, but large amounts were associated with the gills, resulting in concentration factors of up to 1 x 10(4). Histochemistry showed that much of this metal was extracellular to the gill epithelium and associated with the mucus layer. Behavioral dysfunction was observed following exposure to Al for five days. Reduction in the amount of Al in the water column, due to binding to snail trail mucus attached to the substrate, reduced the amount of Al associated with the gill and delayed the onset of behavioral dysfunction. We conclude that freshly neutralized Al is toxic to the crayfish and that main site of Al action is the gill.

Aluminum↗
PubMed2003

Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro.

Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in plasma are 5-20 microM. The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 microM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively, P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 microM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold, P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 microM, respectively, P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.

Adolescent↗
PubMed2003

A simplified method for computed tomographic estimation of prognosis in acute pancreatitis.

BACKGROUND: Computed tomography is valuable for the diagnosis of acute pancreatitis. Although CT-based prognostic scoring systems are available, they are complex and impractical for routine clinical use. We examined the validity of a simplified CT-based scoring system in a cohort of patients with acute pancreatitis. METHOD: Observational study based on correlation of CT findings with clinical outcomes. Seventy patients admitted to the Royal Infirmary of Edinburgh from January 1991 to December 1997 with a diagnosis of acute pancreatitis and undergoing CT with intravenous contrast during the first 3 to 10 days after admission were included in the study. RESULTS: Multivariate logistic regression analysis demonstrated that the finding of mesenteric oedema and free peritoneal fluid on CT were independent early predictive factors of adverse outcome. Allocating one point each for either mesenteric oedema (MO) or peritoneal fluid (P) (giving a maximum score of 2), a simple MOP score was derived. Compared with the Glasgow and APACHE multiple-factor scoring systems and the Helsinki and Balthazar CT-based scoring systems areas under ROC curves were: admission Apache II 0.57, admission Glasgow 0.62. Balthazar score 0.79, Helsinki score 0.85 and MOP score 0.87. CONCLUSIONS: The presence of mesenteric oedema or peritoneal fluid on CT appears to be a simple and widely applicable predictor of disease severity in acute pancreatitis.

Acute Disease↗
PubMed2002

Influence of oligomeric silicic and humic acids on aluminum accumulation in a freshwater grazing invertebrate.

This study examined the influence of oligomeric silicic acid and humic acid on aluminum in the water column and its accumulation in the freshwater snail Lymnaea stagnalis. Forty-eight hours after addition of Al (500 microg L(-1)), 83% of the metal was lost from the water column. This loss was reduced by oligomeric silica (20 mg L(-1)) and by humic acid (10 mg L(-1)). Aluminum accumulated in the digestive gland and, to a lesser extent, in the remaining soft tissues, and this accumulation was reduced by oligomeric silica. In the presence of humic acid, Al accumulation in the digestive gland was unaffected, though less was accumulated in the remaining tissues. Snails accumulated Si preferentially in the digestive gland and this accumulation was increased in the presence of added Al. Thus, both oligomeric silica and humic acid influence Al bioavailability and Si is upregulated in the digestive gland in the presence of Al.

Aluminum↗
PubMed2002

Analysis of aluminosilicate particles in biological matrices using histochemistry and X-ray microanalysis.

Aluminosilicates are a group of ubiquitous environmental particles that, in some cases, have been implicated in human disease. Characterisation of aluminosilicates in tissue samples requires, first, their in situ identification and, secondly, analysis of their aluminium and silicon content or, at least, aluminium:silicon ratio. Here, histochemical staining, microscopy and X-ray microanalysis were investigated as potential methods for the detection of aluminosilicates in biological samples. In contrast to aluminium phosphate or hydroxide, aluminosilicates were refractory to histochemical staining for aluminium. However, using electron microscopy, back scattered electrons allowed identification of aluminosilicates in tissue-like (gelatine) sections. X-ray microanalysis, using conventional peak:background ratios, did not provide a sufficiently accurate assessment of the aluminium content of various standard aluminosilicates to allow their identification. However, the similar spectral energies of aluminium and silicon allowed spectral peak heights to be directly compared and, using simple standards, aluminium:silicon ratios were found for a range of reference particles. Application of this technique should allow the localisation and identification of aluminosilicates in biological samples.

Aluminum Silicates↗