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Biomedical subjects

A Flynn

Publications and source records attributed to A Flynn.

At least 55 records · Page 3Linked to original sources
PubMed2000

The effect of high intakes of casein and casein phosphopeptide on calcium absorption in the rat.

The effect of the level or source of dietary protein or protein-derived peptides on Ca absorption is not well understood. We determined, therefore, the influence of habitual dietary casein level, meal casein and meal casein phosphopeptide (CPP) on Ca absorption in the rat. True fractional Ca absorption was investigated in male 7-week-old rats, Wistar strain, in three separate studies using a faecal 47Sc: 47Ca ratio method. In studies A and C, rats (n 8 per group) were fed on a purified diet containing 200 g casein/kg for 2 weeks. Rats were then given a 47Ca-labelled meal (10 g) containing (per kg) either 0, 100, 200, or 300 g casein (study A) or 0, 100, 200, 350 or 500 g CPP (study C). In study B, rats (n 24 per group) were fed on a purified diet containing (per kg) either 200, 350 or 500 g casein for 2 weeks. Each group was then further randomized into three groups (n 8 per group) and given a 47Ca-labelled meal (10 g of the same diet) containing (per kg) either 200, 350 or 500 g casein. Ca absorption from a meal was unaffected by increasing meal casein concentration from 0 to 300 g/kg (study A), but was increased with a meal casein content of 500 g/kg (study B). Fractional Ca absorption decreased with increasing usual dietary casein intake in the range 200-500 g/kg (study B), suggesting intestinal adaptation. Ca absorption was unaffected by inclusion of 100 g CPP/kg in a single meal but was significantly (P < 0.001) reduced by 200, 350 and 500 g CPP/kg meal, with no evident dose-relationship. Thus, while Ca absorption was enhanced by high-casein meals, the mechanism remains unclear.

Animals↗
PubMed2000

A study of the knowledge that school rugby coaches have in the management and prevention of serious neck injury.

The following study is an analysis of the knowledge school rugby coaches responsible for Senior Cup Team in Leinster, have in the area of neck injury prevention and management. When serious neck injuries affect schoolboys it is particularly tragic and deserves special attention. The study targeted all the coaches of Senior Cup Teams in Leinster. Results showed that coaches lack vital knowledge in the area of neck injury prevention, recognition and management. Only 50% (n = 18) of coaches have a first aid qualification and only 47% (n = 17) carry first aid equipment to deal with neck injuries to matches. More than half of the schools in the study sample do not have neck collars available and a staggering 83% (n = 30) of schools do not have a stretcher available to SCT players. The study highlights the need to provide better first aid facilities in schools and demonstrates the need for further education of school rugby coaches.

Cervical Vertebrae↗
PubMed1999

The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat.

Forty 3-week-old male rats, Wistar strain, average weight 59 g, were randomized by weight into five groups of eight rats each. Three groups were fed ad libitum on a semi-purified diet containing (per kg) 400 (adequate), 200 (moderately Mg-restricted) or 20 (severely Mg-restricted) mg Mg for 3 weeks while two groups were pair-fed with the Mg-adequate diet in the same quantities as those consumed by the two Mg-restricted groups respectively. While weight gains and food conversion efficiency values for the Mg-restricted groups were similar to those of the corresponding pair-fed control groups, serum and kidney Mg, and femoral dry weight were reduced by 70, 7 and 9% respectively in the severely Mg-restricted group and were unaffected in the moderately Mg-restricted group. Significant reductions were observed in urinary pyridinoline (Pyr) (by 44 and 34%) and deoxypyridinoline (Dpyr) levels (by 40 and 33%) (markers of bone resorption), serum osteocalcin levels (by 46 and 28%) (marker of bone formation), femoral Mg levels (by 52 and 14%) and osteocalcin mRNA levels (by 46 and 22%) compared with the corresponding pair-fed controls, in the severely and moderately Mg-restricted groups respectively, and these reductions, except for those in urinary Pyr and Dpyr, were more marked in the severely Mg-restricted group. Femoral Ca and P concentrations were unaffected by dietary Mg restriction. These results show that not only severe but also moderate dietary restriction of Mg over 21 d results in qualitative changes in bone (i.e. reduced Mg concentration) as well as in aberrant bone turnover in young growing rats (i.e. severely depressed rates of bone formation and bone resorption), which may impair bone development and bone strength.

Amino Acids↗
PubMed1999

Optimal nutrition: calcium, magnesium and phosphorus.

In the past, a major challenge for nutrition research was in defining indicators of nutritional adequacy. More recently, the research base related to the role of nutrition in chronic disease has expanded sufficiently to permit moving beyond deficiency indicators to other indicators with broader functional significance. Thus, nutrition research is faced with the new challenge of defining 'optimal nutrition'. One definition of optimal nutrition with respect to any particular nutrient could be when a functional marker reaches an 'optimal value' or plateau beyond which it is not longer affected by intake or stores of the nutrient. A functional marker of nutrient status could be defined as a physiological or biochemical factor which (1) is related to function or effect of the nutrient in target tissue(s) and (2) is affected by dietary intake or stores of the nutrient (which may include markers of disease risk). Examples of such indicators or markers are those related to risk of chronic diseases such as osteoporosis, CHD, or hypertension. The present review focuses on the concept of optimal nutrition with respect to three nutrients, Ca, Mg and P. However, for P and Mg there are as yet no functional indicators which respond to dietary intake, and in such cases nutrient requirements are established using more traditional approaches, e.g. balance data. For Ca, there has been interest in using maximal Ca retention, which is based on balance data, bone mass measurements and biomarkers of bone turnover as useful functional indicators of the adequacy of Ca intake.

Adolescent↗
PubMed1999

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome.

Proteins control cell function and measurement of their concentration is crucial for understanding their roles in health and disease. However, current methods for their detection in tissue sections are not quantitative. Radioimmunoluminography (RILG) is a system for direct measurement of quantity and distribution of protein in histological sections. Histological carcinomas were reacted with antigen-saturating concentrations of 125I-antibody to carcinoembryonic antigen (CEA). Antibody distribution and concentration was mapped by phosphor imaging. Radioactivity in each pixel of the digital image was proportional to antigen concentration, calculated from a standard line generated from a nitrocellulose CEA dot-blot assay. RILG gave a linear correlation with standards of known CEA concentration (r = 0.999). Six tumour xenografts with differing CEA concentrations by radioimmunoassay (RIA) were studied by RILG and immunohistochemistry (IHC). RILG gave a linear correlation with CEA by RIA (r = 0.994) but IHC failed to do so (r = 0.42). CEA levels measured by RILG, in cryostat (n = 15) and paraffin (n = 19) sections from colorectal cancer patients showed a range of CEA concentration (38.9-594 ng g(-1) and 22.5-212.5 ng g(-1) respectively). Tumour CEA concentration by RILG was significantly correlated with dose of antibody (% injected radioactivity kg(-1)) localized in tumour (P = 0.04 and P < 0.02 respectively), in patients receiving radioimmunoguided surgery. Clinical relevance of RILG is illustrated by identifying patients with high tumour CEA, most likely to benefit from antibody targeted therapy. Knowledge of the pathophysiology of many diseases may be enhanced by quantitative estimation of antigen concentration related to tissue morphology.

Adenocarcinoma↗
PubMed1999

The effect of magnesium supplementation on biochemical markers of bone metabolism or blood pressure in healthy young adult females.

OBJECTIVES: To investigate the effects of increasing Mg intakes, above the usual dietary intake, on blood pressure and on biomarkers of bone metabolism in healthy young adult females. DESIGN: A double-blind, placebo-controlled, randomised crossover Mg intervention trial. SETTING: The study was conducted in the Department of Nutrition, University College, Cork, Ireland. SUBJECTS: Twenty-six healthy (normotensive) adult females aged 20-28 y were recruited from University College, Cork. INTERVENTION: Subjects were randomly assigned to their self-selected diets (approximately 11 mmol Mg/d) or their self-selected diet with a 10 mmol/d Mg supplement as Mg(OH)2 (approximately 22 mmol Mg/d) for 28 d followed by cross-over to the alternative diet for a further 28 d. During each dietary period urines (last 3 d) and blood (morning of 27 d) were collected and blood pressure was measured on the morning of 28 d. RESULTS: Increasing Mg intake from the usual level (11 mmol/d) to 22 mmol/d for 28d increased urinary excretion of Mg by 36% and erythrocyte Mg content by 5% but had no effect on serum Mg, Ca, PTH, osteocalcin or bone-specific alkaline phosphatase (biomarkers of bone formation), urinary pyridinium crosslinks of collagen (biomarkers of bone resorption), or on blood pressure. CONCLUSION: Increasing the mean Mg intake in healthy young adult females above the usual dietary intake, which is currently above the US EAR (estimated average requirement), but below the US RDA for Mg, does not affect blood pressure or the rate of bone turnover.

Adult↗
PubMed1999

Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males.

OBJECTIVE: To investigate the effects of changing from a medium (1.6 mg Cu/d) to a low (0.7 mg Cu/d) or a high (6.0 mg/d) Cu intake on biochemical indices of bone turnover in healthy adult males. DESIGN: A longitudinal intervention trial. SETTING: The study was conducted at the Institute of Food Research, Norwich, UK. SUBJECTS: Eleven healthy adult males aged 20-59 y were recruited from Norwich Research Park. INTERVENTION: Subjects were given medium (1.6 mg/d), low (0.7 mg/d) and high (6.0 mg/d) intakes of Cu, in that order, over consecutive 8 week periods with a minimum of 4 week washout periods. On the last d of each dietary period fasting first void urine and blood were collected. RESULTS: Serum caeruloplasmin or Cu (indices of Cu status), serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) were unaffected by dietary Cu intake. Urinary Pyr/Cr and Dpyr/Cr (biomarkers of bone resorption) were significantly increased (P < 0.05) (by 30% and 25%, respectively), when subjects were switched from the medium to the low Cu diet and were significantly decreased (P < 0.05) (by 30%) and 22% respectively), when subjects were switched from the low to the high Cu diet. CONCLUSION: The findings of the present study could have implications for bone health in individuals with marginal Cu intakes. Thus, further studies are warranted to better define the relationship of marginal Cu intakes to bone health.

Adult↗
PubMed1999

Personal hormone monitoring for contraception.

OBJECTIVE: To determine the effectiveness and acceptability of personal hormone monitoring for contraception. DESIGN: A large prospective study was carried out on personal hormone monitoring for contraception when used with abstinence during the identified fertile days. SETTING: Three country study under the auspices of the departments of Obstetrics and Gynaecology of the Universities of Birmingham, Dublin and Dusseldorf SUBJECTS: Seven hundred and ten women, median age 30, were recruited from the general population. They were required to have regular menstrual cycles (23-35 days) and to be delaying their next pregnancy. INTERVENTIONS: Personal hormone monitoring consists of a hand held monitor and disposable test sticks which measure changes in urinary concentrations of oestrone-3-glucuronide and luteinising hormone. An algorithm estimated the fertile days which were displayed by a red light. OUTCOME MEASURES AND RESULTS: One hundred and sixty two pregnancies occurred in 7209 cycles of use, of which 67 were method related pregnancies. The 13 cycle life-table method pregnancy rate (95 per cent CI) was 12. 1 per cent (9.3-14.8). The system allowed analysis of the effect of changes to the algorithm to modify the defined fertile period. As a result the algorithm was changed to increase the median warning of the luteinising hormone surge to six days. With the revised algorithm, half of the method pregnancies would have been prevented giving a calculated method pregnancy rate of 6.2 per cent (4.2-8.3) and method efficacy of 93.8 per cent. The continuation rate after 13 cycles was 78 per cent. CONCLUSION: Personal hormone monitoring proved simple to use and will be of value to women who do not want to use other methods of contraception.

Adolescent↗
PubMed1999

No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults.

The influence of Cu supplementation of the usual diet for 6 weeks on biochemical markers of bone turnover and on putative indices of Cu status was investigated in healthy adults (twelve male and twelve female) aged 22-46 years, who participated in a double-blind placebo-controlled repeated crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate (CuGC), and 6 mg CuGC, each separated by placebo periods of equal length. During baseline and on the last day of each dietary period, fasting morning first-void urine and fasting blood serum, plasma and erythrocytes were collected. The habitual dietary Cu intakes in males and females were approximately 1.4 and 1.1 mg/d respectively. Females had significantly higher (50%) plasma caeruloplasmin (Cp) protein concentrations than males at baseline. Cu supplementation had no effect on erythrocyte superoxide dismutase (SOD, EC 1.15.1.1) activity or plasma Cp protein (putative indices of Cu status) in the total group. Similarly, serum osteocalcin (a marker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline: Cr or deoxypyridinoline: Cr excretion (markers of bone resorption) were unaffected in either the total group or in males and females separately, by any Cu supplementation regimen. It is concluded that Cu supplementation of the usual diet in healthy adult males and females had no effect on biochemical markers of bone formation or bone resorption over 6-week periods.

Adult↗
PubMed1998

The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways.

Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.

Animals↗
PubMed1998

Inter and intra-individual variations in urinary excretion of pyridinium crosslinks of collagen in healthy young adults.

OBJECTIVES: To investigate the inter- and intra-individual variation in the excretion of pyridinium crosslinks of collagen in first morning void urine samples in healthy young adults. DESIGN: An observational study in which urinary pyridinium crosslinks of collagen were measured in fasting first void urine samples over five consecutive days. SETTING: The study was conducted in the Department of Nutrition, University College, Cork, Ireland. SUBJECTS: A total of 17 healthy young adults (11 females and 6 males) aged 22-26 y were recruited from University College, Cork. The subjects were without any history of bone or articular disease, and with no intake of medicine that could affect bone or cartilage metabolism. RESULTS: There were large intra-individual variations in the excretion of both pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in first morning void urine samples and the ratios of intra- to inter-individual variation were high. In comparison, inter-individual variation in excretion of crosslinks was relatively low. No significant day-to-day variation was observed either in Pyr or Dpyr excretion when either five, four or three consecutive days or four or three non-consecutive days of urine sampling were used. However, there were significant differences between any two consecutive or non-consecutive days in both Pyr and Dpyr excretion. CONCLUSIONS: The relatively large day-to-day variation in urinary excretion of the pyridinium crosslinks emphasises the need to use multiple samples to characterise the crosslink excretion of an individual. The present study demonstrates that urine sampling for these crosslinks necessitates at least a 3 d collection to ensure that day-to-day effects are not a significant source of variation included in the data analysis.

Adult↗
PubMed1998

The effect of dietary sodium intake on biochemical markers of bone metabolism in young women.

To investigate the effect of a low (80 mmol/d) or high (180 mmol/d) Na intake for 14d on biochemical markers of bone turnover in Na-sensitive and Na-non-sensitive healthy young women, twenty-nine subjects were screened for responsiveness of urinary Ca excretion to increasing dietary Na intake (40, 80, 120 and 200 mmol/d for 7 d). In a crossover study, the eight Na-sensitive and eight of the twenty-one Na-non-sensitive subjects were randomly assigned to diets containing either 80 or 180 mmol Na/d for 14d followed by crossover to the alternative diet for a further 14 d. Dietary Ca was restricted to 12.5 mmol/d throughout. During each dietary period, fasting morning first void urine samples (last 3 d) and fasting blood serum samples (morning of twelfth day) were collected. Increasing Na intake from 80 to 180 mmol/d increased urinary Na about twofold in both the Na-sensitive and Na-non-sensitive groups and increased urinary Ca excretion (by 73%) in the Na-sensitive group only. Biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline) and bone formation (serum osteocalcin and bone-specific alkaline phosphatase; EC 3.1.3.1) were unaffected by increasing dietary Na in either group. It is concluded that the Na-induced calciuria observed in the Na-sensitive healthy young women did not result in increased bone resorption or turnover and, despite restricted Ca intake, adaptation of dietary Ca absorption may have compensated for the increased urinary Ca loss.

Adult↗
PubMed1998

Effect of myofibrillar muscle proteins on the in vitro bioavailability of non-haem iron.

It is well established that the bioavailability of non-haem iron from foods is enhanced by the presence of meat. However, the nature of the promoter in meat has not yet been characterised. The present study was designed to compare the effects of the myofibrillar protein fractions on the bioavailability of non-haem iron in an attempt to identify the 'meat factor'. Rabbit skeletal muscle was fractionated and whole muscle, myofibrillar protein, myosin and actin were isolated. Myosin was subjected to selective proteolysis with chymotrypsin and the heavy meromyosin, light meromyosin, rod region and head region were prepared. Protein fractions (1 g) were incorporated into 100 g semi-synthetic liquid meal and the in vitro dialysability of iron was determined. Egg albumin was used as a reference protein. When compared with egg albumin, all protein fractions significantly enhanced iron dialysability, except for light meromyosin which was inhibitory. Myosin had a greater enhancing effect than actin and, within myosin, the enhancing effect was greatest for the heavy meromyosin fraction. The enhancement appeared to coincide with the known distribution of cysteine residues in the myofibrillar proteins. The presence of the sulphydryl blocking agent, N-ethylmaleimide (NEM), in meals containing myosin reduced iron dialysability in a dose-related manner, but NEM had only a small effect in meals containing actin. Meanwhile, incorporation of cysteine into meals containing actin increased iron dialysability. The present results suggest that the enhancement of non-haem iron dialysability by meat is associated with myosin, in particular, with the heavy meromyosin region. Peptide fractions rich in cysteine residues, probably constitutes the 'meat factor'.

Actins↗
PubMed1998

The effect of short-term calcium supplementation on biochemical markers of bone metabolism in healthy young adults.

The influence of Ca supplementation of the usual diet for 14 d on biochemical markers of bone turnover was investigated in healthy young adults aged 21-26 years. In a crossover study, eighteen subjects (five male and thirteen female) were randomly assigned to their self-selected diet (about 22 mmol Ca/d) or their self-selected diet with a 20 mmol/d Ca supplement (about 40 mmol Ca/d) for 14 d followed by crossover to the alternative diet for a further 14 d. During each dietary period fasting morning first void urine samples (last 3 d) and fasting blood serum samples (morning of twelfth day) were collected. Ca supplementation reduced urinary excretion of pyridinoline (14%) and deoxypyridinoline (16%) (biochemical markers of bone resorption) but had no effect on biochemical markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase; EC 3.1.3.1). It is concluded that Ca supplementation of the usual diet in young adults suppresses bone resorption over a 2-week period. If sustained, this could result in suppression of the bone remodelling rate and an increase in bone mass over time. The findings of this short-term study with a relatively small number of young adults highlight the need for a longer-term intervention study of the effect of increased Ca intake on bone mass in this age group.

Adult↗
PubMed1997

Heat shock increases the association of binding protein-1 with initiation factor 4E.

The effects of heat shock on the regulation of the cap-binding initiation factor 4E (eIF4E) and its inhibitory binding protein, 4E-BP1, have been examined in Chinese hamster ovary cells and in cardiac myocytes. Heat shock increased the association between eIF4E and 4E-BP1, and this was associated with a dephosphorylation of 4E-BP1. These effects did not appear to be due wholly to decreased activity of the p70 S6 kinase pathway, which is implicated in the control of 4E-BP1, and they were not mediated by the stress-activated p38 microtubule-associated protein kinase pathway. Increased binding of 4E-BP1 to eIF4E correlated with a decrease in the amount of eIF4G which co-purified with the latter. This could account for the previously observed impairment of eIF4F function during heat shock, and, since heat shock protein mRNAs are believed to be relatively cap-independent, could provide a mechanism for the selective up-regulation of the synthesis of heat shock proteins and other stress proteins during heat shock.

Animals↗
PubMed1997

Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2.

Mitogen-activated protein (MAP) kinases bind tightly to many of their physiologically relevant substrates. We have identified a new subfamily of murine serine/threonine kinases, whose members, MAP kinase-interacting kinase 1 (Mnk1) and Mnk2, bind tightly to the growth factor-regulated MAP kinases, Erk1 and Erk2. MNK1, but not Mnk2, also binds strongly to the stress-activated kinase, p38. MNK1 complexes more strongly with inactive than active Erk, implying that Mnk and Erk may dissociate after mitogen stimulation. Erk and p38 phosphorylate MNK1 and Mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor-4E (eIF-4E). Initiation factor eIF-4E is a regulatory phosphoprotein whose phosphorylation is increased by insulin in an Erk-dependent manner. In vitro, MNK1 rapidly phosphorylates eIF-4E at the physiologically relevant site, Ser209. In cells, Mnk1 is post-translationally modified and enzymatically activated in response to treatment with either peptide growth factors, phorbol esters, anisomycin or UV. Mitogen- and stress-mediated MNK1 activation is blocked by inhibitors of MAP kinase kinase 1 (Mkk1) and p38, demonstrating that Mnk1 is downstream of multiple MAP kinases. MNK1 may define a convergence point between the growth factor-activated and one of the stress-activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in cells.

3T3 Cells↗