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Biomedical subjects

A White

Publications and source records attributed to A White.

At least 55 records · Page 3Linked to original sources
PubMed2002

IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte.

IGF action in vivo is acutely regulated by IGF-binding protein-1 (IGFBP-1) and its phosphorylation state is implicated in modulating these effects. Since IGFs have an important regulatory role in adipocyte function, we investigated the effects of phosphorylated IGFBP-1 (pIGFBP-1) and non-phosphorylated IGFBP-1 (npIGF BP-1) on 3T3-L1 preadipocyte proliferation and adipocyte metabolism. IGFs stimulated clonal expansion of 3T3-L1 cells (IGF-I more potently than IGF-II (EC(50): 30 nM and 50 nM)). npIGFBP-1 inhibited IGF-I (50 nM) clonal expansion at a 5:1 molar ratio (P<0.01), whereas pIGFBP-1 (purified from HepG2 cell medium) abolished clonal expansion at a 1:1 molar ratio (P<0.005). In contrast, IGF-II-induced clonal expansion was inhibited 100% at a 1:1 molar ratio of npIGFBP-1. In mature adipocytes, IGF-I was equipotent with insulin in stimulating glucose uptake (EC(50): 10 nM) and inhibiting isoproterenol-induced lipolysis (EC(50): 15 nM). npIGFBP-1 completely reversed IGF-I effects at a 1:1 molar ratio (P<0.01). In summary, IGFs rather than insulin are potent regulators of clonal expansion in 3T3-L1 preadipocytes. Importantly, IGFs are equipotent with insulin in regulating adipocyte metabolism. IGFBP-1 inhibits IGF effects on preadipocyte proliferation and adipocyte metabolism, with pIGFBP-1 being more potent than npIGFBP-1 at inhibiting mitogenic actions. Since IGFBP-1 is acutely regulated by insulin, this could have important consequences in hyperinsulinaemic and insulin-resistant states.

3T3 Cells↗
PubMed2001

Epidemiology of the insulin-like growth factor system in three ethnic groups.

The insulin-like growth factor (IGF) system, comprising insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and their binding proteins (IGFBPs), is linked to cell growth, the development of cardiovascular disease, and several cancers. Little is known about its epidemiology. The authors studied relations of the IGF system to anthropometric and metabolic variables in three population-based ethnic groups in Manchester, England, in 1994-1998 with differing disease risks: African Caribbean (n = 193), Pakistani (n = 130), and local Europeans(n = 142). Standardized anthropometry, glucose tolerance tests, and serum assays were performed. Body mass indices (BMIs) were high in all groups. IGF-I levels were highest in normoglycemic African Caribbeans and declined with age (r = -0.28). IGF-II levels were greatest in Europeans. IGFBP-1 concentrations increased with age in Pakistanis (r = 0.20) and Europeans (r = 0.29), but not in African Caribbeans (r = 0.06), and were inversely related to BMI (r = -0.37). Age- and sex-adjusted IGFBP-1 was inversely related to fasting insulin and proinsulin in all groups; participants with newly detected diabetes were relatively insulinopenic but had higher IGFBP-1 concentrations. Nonesterified (free) fatty acid (NEFA) concentrations increased with declining glucose tolerance. In multiple regression analysis, IGFBP-1 was independently and negatively related to fasting insulin, BMI, and African-Caribbean compared with European ethnicity but positively related to age, fasting glucose, and NEFA. IGF-I was inversely related only to age, NEFA, and Pakistani ethnicity. IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples.

Adult↗
PubMed2001

alpha 2-Macroglobulin: a new component in the insulin-like growth factor/insulin-like growth factor binding protein-1 axis.

Insulin-like growth factors (IGFs) are crucial for many aspects of development, growth, and metabolism yet control of their activity by IGF-binding proteins (IGFBPs) remains controversial. The effect of IGFBP-1 depends on its phosphorylation status; phosphorylated IGFBP-1 inhibits IGF actions whereas the nonphosphorylated isoform is stimulatory. In order to understand this phenomenon, we purified phosphorylated IGFBP-1 from normal human plasma by immunoaffinity chromatography. Unexpectedly, the resulting preparation enhanced IGF-stimulated 3T3-L1 fibroblast proliferation, due to the presence of a co-purified protein of approximately 700 kDa. Matrix-assisted laser desorption ionization-mass spectrometry and Western immunoblotting analysis identified this co-purified protein as alpha(2)-macroglobulin (alpha(2)M). Anti-alpha(2)M antibodies co-immunoprecipitated IGFBP-1 from human plasma and from (125)I-IGFBP-1.alpha(2)M complexes formed in vitro. The (125)I-IGFBP-1/alpha(2)M association could be inhibited with excess unlabeled IGFBP-1. Surface plasmon resonance analysis indicated that alpha(2)M preferentially associates with the phosphorylated isoform of IGFBP-1 and that when complexed to alpha(2)M, IGFBP-1 can still bind IGF-I. These findings have functional significance since alpha(2)M protects IGFBP-1 from proteolysis and abrogates the inhibitory effect of phosphorylated IGFBP-1 on IGF-I stimulated 3T3-L1 cell proliferation. We conclude that alpha(2)M is a binding protein of IGFBP-1 which modifies IGF-I/IGFBP-1 actions resulting in enhanced IGF effects. In line with its role in regulating the clearance and activity of other growth factors, we predict that alpha(2)M has a novel and important role in controlling the transport and biological activity of IGFs.

3T3 Cells↗
PubMed2001

Expression in hematological malignancies of a glucocorticoid receptor splice variant that augments glucocorticoid receptor-mediated effects in transfected cells.

Glucocorticoids play an important role in the treatment of a number of hematological malignancies, such as multiple myeloma. The effects of glucocorticoids are mediated through the glucocorticoid receptor alpha, the abundance of which can be modulated by alternative splicing of the glucocorticoid receptor mRNA. Two splice variants of the glucocorticoid receptor mRNA have been described: glucocorticoid receptor beta, which reportedly has a dominant negative effect on the actions of the glucocorticoid receptor alpha, and glucocorticoid receptor P, of which the effects are unknown. In this study, we have investigated the expression levels of these two splice variants at the mRNA level in multiple myeloma cells and in a number of other hematological tumors. Although the glucocorticoid receptor beta mRNA was, if at all, expressed at very low levels, considerable amounts (up to 50% of the total glucocorticoid receptor mRNA) glucocorticoid receptor P mRNA was present in most hematological malignancies. In transient transfection studies in several cell types and in multiple myeloma cell lines, the glucocorticoid receptor P increased the activity of the glucocorticoid receptor alpha. These results suggest that the relative levels of the glucocorticoid receptor alpha and the glucocorticoid receptor P may play a role in the occurrence of glucocorticoid resistance in tumor cells during the treatment of hematological malignancies with glucocorticoids.

Alternative Splicing↗
PubMed2001

Investigation of novel polymorphisms within the 3' region of the IL-6 gene in patients with rheumatoid arthritis using Genescan analysis.

A highly polymorphic AT rich repeat exists in the 3' flanking region of the IL-6 gene. Using Genescan analysis we studied this region of the IL-6 gene in 55 normals and 95 patients with rheumatoid arthritis (RA). The influence of alleles on need for early major joint surgery in RA patients was assessed. We identified nine alleles of which, G8, G7 and G4 were the most common (37% vs 36% vs 13%). RA surgery patients had an increase in the frequency of G7 compared to non-surgery and control populations (46% vs 27% vs 34%, respectively) and a decrease in G8 (22% vs 46% vs 43%, respectively). RA patients homozygous for G8 had a lower ESR than those homozygous for G7 (23 mm/h vs 36 mm/h) although this was not significant. We have determined these alleles and their distribution in a normal and RA population. Initial findings suggest G8 may be associated with lower erythrocyte sedimentation rate (ESR) and less severe RA. Although trends in allele distribution were observed, further studies in larger cohorts are required.

Alleles↗
PubMed2001

Acupuncture for idiopathic headache.

BACKGROUND: Acupuncture is widely used for the treatment of headache, but its effectiveness is controversial. OBJECTIVES: To determine whether acupuncture is: - more effective than no treatment - more effective than 'sham' (placebo) acupuncture - as effective as other interventions used to treat idiopathic (primary) headaches. SEARCH STRATEGY: Electronic searches were performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the database of the Cochrane Field for Complementary Medicine. We also contacted researchers in the field and checked the bibliographies of all articles obtained. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials comparing acupuncture with any type of control intervention for the treatment of idiopathic (primary) headaches were included. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, methods, and results was extracted by at least two independent reviewers using a pre-tested standard form. Results on headache frequency and intensity were summarized descriptively. Responder rate ratios (responder rate in treatment group/responder rate in control group) were calculated as a crude indicator of results for sham-acupuncture-controlled trials. Quantitative meta-analysis was not possible due to trial heterogeneity and insufficient reporting. MAIN RESULTS: Twenty-six trials including a total of 1151 patients (median, 37; range, 10-150) met the inclusion criteria. Sixteen trials were conducted among patients with migraine, six among patients with tension-type headache, and four among patients with various types of headaches. The majority of trials had methodological and/or reporting shortcomings. In eight of the 16 trials comparing true and sham (placebo) acupuncture in migraine and tension-type headache patients, true acupuncture was reported to be significantly superior; in four trials there was a trend in favor of true acupuncture; and in two trials there was no difference between the two interventions. (Two trials were uninterpretable.) The 10 trials comparing acupuncture with other forms of treatment yielded contradictory results. REVIEWER'S CONCLUSIONS: Overall, the existing evidence supports the value of acupuncture for the treatment of idiopathic headaches. However, the quality and amount of evidence are not fully convincing. There is an urgent need for well-planned, large-scale studies to assess the effectiveness and cost-effectiveness of acupuncture under real-life conditions.

Acupuncture Therapy↗
PubMed2001

Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.

AIMS/HYPOTHESIS: Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus. METHODS: In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA). RESULTS: Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009) and logistic regression indicated a 40% reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease.

Blood Glucose↗
PubMed2001

Effect of acupuncture on nausea of pregnancy: a randomized, controlled trial.

OBJECTIVE: To compare acupuncture with sham (placebo) acupuncture for treatment of nausea of pregnancy. METHODS: In a subject- and observer-masked, randomized, controlled trial in the maternity unit at Exeter Hospital, we gave 55 women between 6 and 10 weeks' gestation genuine, traditional-style acupuncture or sham treatment with a cocktail stick on three or four occasions over 3 weeks. The main outcome measure was nausea score, as determined by subject report on a visual analogue scale in a daily diary. Anxiety and depression also were assessed. RESULTS: Nausea scores decreased from a median of 85.5 (interquartile range 71.25-89.75) to 47.5 (interquartile range 29.25-69.5) in the acupuncture group and from 87.0 (interquartile range 73.0-90.0) to 48.0 (interquartile range 14.0-80.0) in the sham treatment group. There was strong evidence of a time effect (P <.001) but no evidence of a group effect (P =.9) or a group-time interaction (P =.8). Similarly, there was evidence of time effects in scores for anxiety and depression but no group differences. The study had a power of 95% to detect significant differences in nausea scores. CONCLUSION: Acupuncture was as effective in treating nausea of pregnancy as a sham procedure.

Acupuncture Therapy↗
PubMed2001

Role of exercise and ascorbate on plasma antioxidant capacity in thoroughbred race horses.

During exercise, the oxygen consumption and the production of free radicals increase and can lead to oxidative stress with a deleterious effect on cellular structures involved in physical activity. To evaluate the oxidative stress produced by exercise and the role of ascorbate as an antioxidant, venous blood samples were obtained from 44 thoroughbred racehorses, before and after a 1000+/-200-m race at maximum velocity. Fourteen of these horses were treated intravenously with 5 g of ascorbate before running. Antioxidant capacity (PAOC), endogenous and exogenous ascorbate concentration, total antioxidant reactivity (TAR), urate concentration, creatine kinase activity, protein concentration and thiobarbiturate reactive substances (TBAR) as oxidative stress indicators were measured in the plasma of some of these horses. PAOC, TAR and TBAR increased after the race, while plasma ascorbate and urate concentrations remained unchanged. Total plasma protein (TPP) concentrations increased in line with antioxidant capacity. As predicted, both the plasma ascorbate concentration and PAOC increased immediately after ascorbate administration, but was not modified after the race, such as TBAR. However, in both groups plasma creatine kinase activity increased after the race. These results would suggest that the administration of ascorbate could nullify the oxidative stress produced by exercise in thoroughbred racehorses, but could not prevent muscular damage.

Animals↗
PubMed2001

Surveillance of antimicrobial resistance--what, how and whither?

OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.

Animals↗
PubMed2001

Arguments for 'British Pluralism' in qualitative health research.

AIMS OF THE STUDY: This paper examines the argument that certain qualitative research methods can be used in 'pure' forms. Whilst rigid adherence to particular published procedures might be possible, we argue that in many cases this is neither necessary nor more likely to increase the validity of the research outcome. METHODOLOGICAL PURITY: In examining the works of well-known claimants to particular research approaches such as grounded theory and phenomenology we show that purity of method is uncommon. In particular it is possible to demonstrate that all published qualitative methods are subject to their own underlying relativist philosophy. The implication of this is that all are social constructions and that their execution will necessarily be negotiated in time and context. CONCLUSION: We conclude that analysis of varied examples of qualitative research shows methods to be more flexible than is often admitted. What we describe as 'British Pluralism' is an attempt to accept this reality whilst maintaining rigour through integrity, clear accounts, reflexivity and constructive critique of one's own work and that of others.

Bias↗
PubMed2001

Is the defect in pro-hormone processing in Type 2 diabetes mellitus restricted to the beta cell?

AIMS: To investigate whether the defect in pro-hormone processing in people with Type 2 diabetes mellitus is restricted to the pancreatic beta cell or whether there is evidence of a more generalized abnormality. METHODS: Ten Indian subcontinent Asian women with diet-controlled Type 2 diabetes were compared with a control group of nine non-diabetic Asian women who were matched for body mass index. All subjects underwent a standard 75 g oral glucose tolerance test during which plasma glucose, insulin, proinsulin and 32,33 split proinsulin were measured. Subjects in both groups then underwent an intravenous corticotrophin-releasing hormone (CRH) test with 100 microg human CRH. Plasma cortisol, adrenocorticotrophic hormone (ACTH) and ACTH precursors were measured. RESULTS: Basal levels of insulin were lower in diabetic subjects (32.5 (12.5-52) pmol/l) than in the control group (42.2 (21.4-63.0) pmol/l); normalized geometric mean (95% confidence interval), P<0.05; as were the levels at 30 min (29.5 (3.7-55.3) pmol/l) and (34.4 (10.7-58.2) pmol/l), P<0.05. The levels at 60 min were (26.7 (6.4-47.0) pmol/l) in subjects with diabetes and (13.6 (-11.3-38.5) pmol/l) in controls, P<0.05 and at 90 min these were (43.4 (19.4-67.4) pmol/l) and (19.3 (-4.6-43.3) pmol/l), P<0.05, respectively, after the 75-g oral glucose load. The acute insulin response was markedly reduced in the subjects with diabetes (1.8 (0.60-3.1) pmol insulin/ mmol glucose), compared with the control group (31.4 (8.0-54) pmol/l insulin/mmol glucose), P<0.005. Intact proinsulin was much higher in the diabetic subjects (23.9 (10.1-37) pmol/1) than in the control group (7.2 (3.9-10) pmol/1), P<0.002, as was the percentage of proinsulin-like molecules (28 (14-42) and 12 (8-17)%), respectively, P<0.01. There were no differences between basal or stimulated levels of ACTH precursors, ACTH or cortisol between the diabetic subjects and the controls. CONCLUSIONS: The defect in insulin secretion in Indian subcontinent Asian women with Type 2 diabetes is similar to that described in other populations with an increased prevalence of Type 2 diabetes. The absence of any defect in the processing of cortisol precursors in the women with Type 2 diabetes suggests that they do not have a generalized defect of hormone processing.

Adrenocorticotropic Hormone↗