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Biomedical subjects

F Green

Publications and source records attributed to F Green.

At least 37 records · Page 2Linked to original sources
PubMed1995

Market testing specialist health promotion services--a test case for an imaginative public health presence in purchasing.

This paper focuses on the current pressure being imposed upon health promotion services in the 'North West' Region in the form of 'market testing'. It suggests that this is not only of concern to those services themselves, but may also act as a 'test case' for the examination of the range of competing perspectives that inform a purchasing function. The tensions between the views that respectively support or question the application of market values is thus examined in relation to the role of public health specialists within purchasing organizations. The paper concludes that although there is some potential to 'sharpen up' services, caution is required in avoiding unrestricted market values leading to superficial and fragmented health promotion provision. It is admitted that there are consequences relating to health promotion specialists. However, because of the close affinity between promotion and public health, failure to protect health promotion from the harshness of the market and ensure a broad-based approach will not only be a set-back for health promotion but will also harm the status of 'public health perspectives' in the broader purchasing context.

Contract Services↗
PubMed1995

Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator inhibitor 1 gene.

Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their excess risk of cardiovascular disease. We examined the determinants of PAI-1 activity in 146 NIDDM subjects by using specific assays of insulin and intact and des-31,32-proinsulin and measures of insulin resistance, relating these measurements to serum lipids, hypoglycemic therapy, and a common 4G/5G polymorphism in the promoter region of the PAI-1 gene. Subjects were treated with insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In the whole group, PAI-1 activity correlated significantly with serum triglycerides (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in subjects not on insulin (n = 110), with insulin sensitivity (r = -0.42, P < 0.001). There was a significant difference in PAI-1 activity among the three genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1 activity correlated significantly with triglyceride levels (r = 0.65, P < 0.0001). There was no significant difference in PAI-1 activity in the different treatment groups despite a significant difference in concentrations of intact and des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the interaction between PAI-1 4G/5G genotype and triglyceride were the strongest determinants of PAI-1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Genetic determination of coagulation factor VIIc levels among healthy middle-aged women.

A recent study (1) reported variation among men in clotting factor VIIc levels is associated with a genetic polymorphism detected by the restriction enzyme Msp I. The present study determined the Msp I genotype (Arg353, Gln353 alleles) for 189 women (mean age 53) who were subjects in the Healthy Women Study, a population study of CHD risk factor change at menopause. Women with the Arg/Arg genotype (n = 147) had an 16% higher (geometric) mean FVIIc level than those with the Arg/Gln (n = 41) genotype (1.21 vs 1.04 U/ml, p < 0.01), while the one subject with the Gln/Gln genotype had an FVIIc level of 1.00 U/ml. These results are consistent with those previously found in healthy men (1). In addition, women carrying the Gln allele did not exhibit the elevation in FVIIc with menopause and use of hormone therapy found among those with the Arg allele, suggesting that genotype may modify the observed rise in factor VIIc at menopause. Possibly because of the small sample size this interaction did not reach conventional levels of statistical significance. Results of multiple linear regression analyses controlling for age, hormone use, obesity, (ln) triglyceride levels, and family history of CHD found FVIIc levels to be significantly (p < 0.001) related to genotype. Thus, genotype appears to be a major determinant of FVIIc levels among women.

Adult↗
PubMed1994

Phase II trial of PALA and 6-methylmercaptopurine riboside (MMPR) in combination with 5-fluorouracil in advanced pancreatic cancer.

The biochemical modulators PALA, an inhibitor of aspartate transcarbamylase which depletes uridine nucleotide pools, and 6-methylmercaptopurine riboside (MMPR) which inhibits purine metabolism, selectively potentiate the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Based on a phase I trial of this combination, we performed a phase II trial in patients with advanced pancreatic cancer. PALA 250 mg/m2 was administered i.v. on day 1, followed 24h later by MMPR 150 mg/m2 as a bolus i.v. injection, and 5-FU 2300 mg/m2 by 24h infusion. Treatments were repeated weekly. Seventeen patients, all previously untreated with chemotherapy, were entered, of whom 14 are evaluable for response. Toxicity > or = grade 2 included nausea (6/17), vomiting (4/17), diarrhea (3/17), stomatitis (5/17), and neurotoxicity (2/17). Among 14 evaluable patients there were no partial responses, and two patients with stable disease. Pretreatment with PALA and MMPR is insufficient to enhance the activity of 5-FU in pancreatic cancer.

Adenocarcinoma↗
PubMed1994

Genetic determinants of arterial thrombosis.

This chapter describes examples of genetic variation determining plasma levels of three independent risk factors for arterial thrombotic disease, namely fibrinogen, coagulation factor VII and plasminogen activator inhibitor type 1, together with a discussion of the underlying molecular mechanisms. In each case, the data suggest that there is interaction between genotype and environment in determination of the relevant plasma level, providing a possible explanation for the differential response of different individuals to their environment.

Afibrinogenemia↗
PubMed1994

Partial reversal of established bleomycin-induced pulmonary fibrosis by rh-urokinase in a rat model.

Pulmonary fibrosis was induced in male Sprague-Dawley rats by intratracheal instillation of bleomycin. By 30 d post-bleomycin, the lungs exhibited elevated interstitial collagen levels. Thirty d after exposure to bleomycin, animals were further treated by intratracheal administration of phosphate-buffered saline (PBS) or 12,500 units of recombinant human urokinase (rh-UK). Three days later, the animals were sacrificed and the lungs fixed, sectioned, and assessed for fibrosis. The presence of interstitial collagen was quantitated using a BioQuant Image Analysis System (R and M Biometrics, Inc., Nashville, TN). Urokinase treatment of animals with established pulmonary fibrosis induced by exposure to 0.5 units of bleomycin was found to diminish the collagen content of lungs to near control levels by 3 d post-UK treatment. By 36 d post-UK treatment (66 d post-bleomycin), values for interstitial collagen were again partially elevated, indicating that UK treatment interfered with established fibrosis but did not stop the bleomycin-mediated process. However, the extent of fibrosis was less than that observed in lungs from non-UK treated animals 66 d post-bleomycin. UK treatment initiated 63 d post-bleomycin exposure again revealed a decline in the extent of fibrosis, but the values did not return to baseline levels. A repeat of the short-term experiment with a higher dose of bleomycin (0.85 units) again revealed that UK treatment was effective in diminishing the extent of fibrosis from 22% to 12% collagen. These results indicate that exogenous UK may be an effective therapeutic modality in the treatment of pulmonary fibrosis induced by some stimuli or developing in association with diseases such as scleroderma.

Animals↗
PubMed1994

Elevated levels of factor VII activity in the postprandial state: effect of the factor VII Arg-Gln polymorphism.

A genetic polymorphism (Arg/Gln353) of coagulation factor VII was recently identified and shown to be associated with differences in basal factor VII coagulant activity. Postprandial lipaemia seems to exert an acute but evanescent effect on the activity of factor VII, and the influence of the Arg/Gln353 polymorphism on factor VII activation during postprandial lipaemia was therefore studied in male post-infarction patients [age 48.8 +/- 3.3 years (mean +/- SD)] with Arg/Arg (n = 23) and Arg/Gln (n = 8) genotypes. Factor VII antigen (VIIag) and activity along with plasma lipoproteins were determined before and after intake of a mixed meal-type of oral fat load. Patients with the Arg/Gln genotype had basal VIIag and activated factor VII (VIIa) levels 75% and 48%, respectively, of those of patients homozygous for the Arg allele. In absolute terms, VIIa increased more in homozygotes for the Arg allele (delta 0-6 h VIIa 1.76 +/- 1.48 ng/ml) than in heterozygotes (0.60 +/- 0.27 ng/ml) in response to fat intake, but the percentage increase in VIIa molecules did not differ significantly between subjects with Arg/Arg and Arg/Gln genotypes (37 +/- 32% versus 27 +/- 15%). This suggests that the influence of the Arg/Gln polymorphism on factor VII activity is mainly accounted for by differences in the basal factor VII protein level between genotypes. Since most of our lives are spent in the postprandial state, possession of the factor VII-Gln353 allele is likely to confer protection against coronary heart disease by reducing the amount of VIIa produced in response to fat intake.

Arginine↗
PubMed1993

The role of beta-fibrinogen genotype in determining plasma fibrinogen levels in young survivors of myocardial infarction and healthy controls from Sweden.

Beta-fibrinogen G/A-455 polymorphism genotype was determined in 123 young survivors of myocardial infarction and 86 healthy controls from Sweden. Frequency of the A-455 allele was 0.25 (95% Confidence Interval 0.21-0.29) in both patients and controls, significantly higher than that reported previously (0.19, 95% CI 0.16-0.22) in 292 men from the UK. Mean plasma fibrinogen level was significantly higher in patients (3.6 g/l) than in controls (3.1 g/l), with p < 0.001. Genotype was significantly associated with (adjusted) plasma fibrinogen level in controls (p = 0.003). This effect was confined to the smokers (n = 50) where mean fibrinogen level was significantly (p = 0.001) higher in G/A-455 and A/A-455 individuals (3.5 g/l) compared with G/G-455 homozygotes (2.9 g/l). There was a significant interaction between smoking status and genotype in determining plasma fibrinogen levels in the controls. These data provide independent confirmation of the association between beta-fibrinogen G/A-455 genotype and plasma fibrinogen levels previously observed in healthy men from the UK.

Adult↗
PubMed1993

The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells.

We have detected a common (allele frequency 0.53/0.47) single base pair insertion/deletion polymorphism 675 base pairs upstream from the start of transcription of the plasminogen activator inhibitor-1 (PAI-1) gene, using the chemical cleavage mismatch analysis. "Band shift assays" suggest that the allele with the single base pair insertion contains an additional protein binding site which is not present in the del allele. Competition experiments confirmed that the binding was specific to the sequence of the ins allele and suggest that proteins bound to this site may be NF-kB-like proteins. Analysis of chloramphenicol acetyltransferase (CAT) mRNA produced by constructs containing the PAI-1 promoter (-805 to +83) showed that the deletion allele produced six times more mRNA than the insertion allele in response to interleukin-1 (p < 0.001). In a sample of 107 young patients with previous myocardial infarction and 95 healthy population-based subjects, the del allele was associated with increased PAI-1 levels, 21% higher than the sample mean in the del homozygotes (p < 0.05). This study also suggested that individuals homozygous for the del allele may have an altered response to the acute phase stimulus. Taken together these results suggest that the insertion/deletion polymorphism in the PAI-1 promoter is of functional importance in regulating the expression of the PAI-1 gene.

Adult↗
PubMed1993

Natural antibodies to avidin in human serum.

Human serum was found to contain natural antibodies to the egg-white glycoprotein avidin. Of 270 samples tested, all contained antibodies to different extents, mainly of the IgG and IgM classes. Anti-avidin antibodies could be isolated by affinity chromatography.

Avidin↗
PubMed1993

Use of jacalin as a solid phase in ABO reverse grouping.

A major problem of using red cells as the solid phase in assay systems is the difficulty to bind them strongly to appropriate surfaces. We report here on a number of lectins of different specificities which were examined for their ability to bind red cells to polystyrene 96-well microtitre plates. The use of the Thomsen-Friedenreich antigen-specific lectins, jacalin, mushroom and Maclura pomifera agglutinin proved the most useful for ABO reverse grouping. Jacalin-coated plates were also compared with plates coated with poly-L-lysine and bovine serum albumin/glutaraldehyde for the binding of erythrocyte membranes and were found to be superior. We also describe the colorimetric detection of the solid phase red cell antibody reaction by using an indicator erythrocyte and peroxidase chromogenic substrate.

ABO Blood-Group System↗