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Biomedical subjects

A Douglas

Publications and source records attributed to A Douglas.

At least 19 recordsLinked to original sources
PubMed1992

Social effects of wheeze in childhood: a 25 year follow up.

OBJECTIVES: To determine the outcome of childhood wheeze in terms of education, employment, housing, and social class. DESIGN: 25 year follow up study. SETTING: Community study based at the department of thoracic medicine, Aberdeen Royal Infirmary. PARTICIPANTS: Three groups of subjects who had been identified in a random community survey in 1964: those who had had asthma in childhood (n = 97), those who had wheezed only in the presence of upper respiratory tract infections (n = 132), and a comparison group who had had no respiratory symptoms as children (n = 131). Subjects were aged 34 to 40 years at the time of the current study. MAIN OUTCOME MEASURES: Interview and questionnaire data on education, employment, housing and social class, ventilatory function, and peak flow rate. RESULTS: Pulmonary function testing showed that only the "asthmatic" group had airways obstruction; this group showed greater peak flow variation than the "wheezy" group, which did not differ from the comparison group. The asthmatic subjects were more likely to have experienced respiratory problems during their school years and associated with their work. Despite these problems, educational attainment, employment, housing, and eventual social class were similar for all three groups. CONCLUSION: Childhood wheeze did not adversely affect education, employment, housing, or social class in this population.

Asthma↗
PubMed1992

Description of the deformation of the left ventricle by a kinematic model.

A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation.

This double-blind study was designed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease. Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened, matched, and randomly allocated to take either 15 g/d fish oil or olive oil for 4 weeks. Fish oil reduced serum triglyceride levels by 26%, but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-2 cholesterol (HDL2-C). There was a nonsignificant decrease in HDL3-C levels. Olive oil reduced total cholesterol levels, accountable to a significantly decrease in LDL-C levels. Serum thromboxane B2 (TXB2) levels remained unchanged following fish oil, but were significantly increased by olive oil. Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement. Platelet aggregation, which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor (PAF), was significantly reduced after fish oil, but was increased by olive oil. Following fish oil, there was a significant increase in eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) levels and a decrease in arachidonic acid content of platelet phospholipids. The platelet fatty acid composition after olive oil was unchanged. Fish oil decreased neutrophil leukotriene B4 (LTB4) generation following calcium ionophore stimulation by 33%, while leukotriene B5 levels increased significantly. Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Gene expression in clonally derived cell lines produced by in vitro transformation of rat fetal hepatocytes: isolation of cell lines which retain liver-specific markers.

The pattern of gene expression in fetal hepatocytes transformed in culture with a hepatocarcinogen (FRL cells) is studied with respect to a range of markers which are either developmentally regulated and/or shown to be expressed at high levels in hepatoma cells. The relative abundance of the respective mRNAs is determined and immunocytochemistry is used to detect the respective proteins in cultured cells. When compared with its normal counterpart, FRL cells retain the expression of transferrin, alpha 1-acid glycoprotein, gamma-glutamyltranspeptidase, and tyrosine aminotransferase at near normal levels, while expression of the liver-specific isoenzymes of pyruvate kinase (L form) and aldolase (B form) is reduced. The cell lines are different in that they fail to express albumin, alpha-fetoprotein, thiostatin and alpha 2-macroglobulin, and they express high levels of M2-pyruvate kinase and aldolase A, markers often found in abundance in hepatoma cells. Therefore transformation has resulted in different effects on different genes. Furthermore, it is of interest to find that the cells coexpress both forms of the pyruvate kinase isoenzymes which does not occur in the normal developing hepatocyte. These results indicate that it is possible to use this model to study changes which accompany transformation of fetal rat hepatocytes. The resulting cell lines have a stable phenotype and retain the changes which result from transformation even after extended passaging. This facilitates comparisons between the precursor cell and the tumor cell, both of which can be maintained under controlled conditions which exist in culture.

Animals↗
PubMed1990

In vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by lung cells isolated from Syrian golden hamster.

The nicotine derived N-nitrosamine, 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK), is a potent respiratory carcinogen in the Syrian golden hamster. The in vitro metabolism of NNK by three enriched lung cell populations were compared. Clara cells had more than ten times higher capacity to activate NNK by alpha-carbon hydroxylation than alveolar macrophages and fibroblasts. In the former cell types, levels of deactivation of NNK by pyridine N-oxidation were ten times lower than those of alpha-carbon hydroxylation. In alveolar macrophages, carbonyl reduction was the major metabolic pathway. Our results suggest that DNA damages induced by NNK in hamster lung is more likely to occur in Clara cells than in macrophages or fibroblasts.

Animals↗
PubMed1990

Blocking-ELISA for detection of specific antibodies to the glycoproteins of the human immunodeficiency virus type 1 (HIV-1).

A blocking ELISA was developed to confirm the specificity of screening tests for anti-HIV-1 antibodies. A murine monoclonal antibody (McAb) raised against recombinant gp160 was used in combination with a commercial technique (ELA-VIA-1). After determining the optimal experimental conditions, the assay was applied to 92 samples presenting different reactivities by Western blot (WB) analysis. All the sera containing antibodies to gp160/gp120 (53) were positive in our assay. The six patients who sero converted showed a low positivity by ELAVIA-1 (optical density near the cutoff value) reacted by blocking-ELAVIA-1 with an McAb binding inhibition greater than 85%. By contrast, negative samples (29) and specimens that exhibited reactivity only against gag-proteins (10) were not detected (McAb binding inhibition smaller than 15%). This sensitive and specific blocking-ELAVIA-1 represents a convenient alternative to WB as a confirmatory test. The technique is time-saving and inexpensive and can easily be integrated with a screening test for diagnostic or epidemiologic studies on HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Transformation of cultured fetal rat liver cells by MDAB and phenobarbital. Morphological, biochemical and immunocytochemical characterization of cell lines.

Fetal rat liver cells derived from 19-day gestation rats were exposed in culture to the carcinogen, 3'-methyl-4-dimethyl-aminoazobenzene (MDAB) for 3 days and then maintained in medium supplemented with the tumor promoter, phenobarbital (PB). Tumors developed in immunodeficient mice inoculated with cells derived from cultures which had been maintained for more than 8 weeks. Histologically, three types of tumors could be distinguished. One contained epithelial-like cells, which resembled what has previously been described as 'clear' epithelial cells. The second contained cells which were more basophilic, with prominent nuclei and closely resembled the hepatoma cell line Mc-A-R-777. The third group of tumors possessed cells of both varieties. Cell lines derived from these tumors were then characterized by determining their capacity to synthesize and secrete alpha-fetoprotein, albumin and transferrin by measuring the incorporation of 35S-methionine into immunoprecipitates obtained by reaction with the respective specific antibodies and the content of the respective mRNAs were determined by hybridization to cDNAs. The activity of gamma-glutamyl-transpeptidase (GGT) and the liver specific enzyme tyrosine aminotransferase (TAT), as well as the induction of TAT by dexamethasone was also evaluated. The presence of these markers in some of the cell lines strongly suggests that they are derived from parenchymal cells. In contrast, other cell lines which morphologically resemble 'clear' epithelial cells are negative, suggesting that they may be derived from non-parenchymal epithelial cells which exist in the original culture. However, some epithelial-like cell lines derived from tumors of mixed morphology appear different to those established from tumors which contained only epithelial-like cells. These express low levels of transferrin and tyrosine aminotransferase suggesting that they may be more closely related to hepatocytes than those cells which are derived from tumors which originally comprised only epithelial cells. The absence or presence of liver markers correlates with the morphology of the respective cell lines since transferrin and TAT are only present in significant levels in those lines which comprise cells with a morphology resembling hepatoma cell lines. In cell lines which show mixed morphology, immunocytochemistry reveals that significant amounts of transferrin are only present in the parenchymal-like population. Growth rate measurements show that the faster growing cell lines generally possessed lower levels of transferrin and TAT expression. It can be concluded from these studies that it is possible to transform cells derived from fetal rat liver in culture using a hepatocarcinogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Comparative analysis of ELISAs employing repetitive peptides to detect antibodies to Plasmodium falciparum sporozoites.

In the last few years, a number of different recombinant and synthetic peptides consisting of the repetitive sequence of the Plasmodium falciparum circumsporozoite protein (NANP)n have been produced and used to develop immunoassays for the detection of antibodies against P. falciparum sporozoites in human sera. A comparative study of three enzyme-linked immunosorbent assays (ELISAs) that employed different (NANP)n peptides (the synthetic peptides (NANP)3 and (NANP)40 as well as the recombinant peptides R32tet32 and R32LR) was carried out using serum samples from individuals who were living in different malaria-endemic areas. The results obtained for these peptide-based ELISAs were compared with those obtained for an immunofluorescence assay (IFA) that used glutaraldehyde-fixed sporozoites. All the methods tested exhibited 100% specificity on sera from persons not exposed to malaria, good reproducibility (coefficients of variation ranged from 3% to 15% for peptide-based ELISAs), and good sensitivity. Reproducibility and sensitivity were lower for the IFA than for the peptide-based ELISAs, perhaps because of the subjective element in the interpretation of the results which is inherent in the IFA method. ELISAs based on peptides that contain a higher number of (NANP) repeats, i.e., (NANP)40 and R32tet32 or R32LR, gave results which correlated better with each other than with those obtained with the ELISA that employed a shorter (NANP)3 peptide. (NANP)n-based ELISAs are relatively simple and inexpensive methods for the detection of anti-P. falciparum sporozoite antibodies and can readily be used in epidemiological research in the field. These assays could contribute to a better understanding of the natural history of the host-parasite relationship in malaria research.

Animals↗
PubMed1987

The acute haemodynamic effects of intravenous verapamil in patients with chronic obstructive airways disease.

The haemodynamic effects of a single intravenous dose of verapamil have been investigated in patients with chronic obstructive airways disease both during an acute exacerbation and when in a stable clinical condition and compared with the effects of oxygen administered by nasal cannulae. In five patients studied during an episode of acute on chronic hypoxaemia (mean PaO2 = 5.4 kPa) there was a significant fall in pulmonary vascular resistance (p less than 0.03) following intravenous verapamil (10 mg) without any reduction in PaO2, cardiac index or oxygen delivery. Subsequent administration of oxygen by nasal cannulae at 2 l/min for 30 min produced similar pulmonary haemodynamic changes: pulmonary vascular resistance fell by 17 +/- 3 per cent following oxygen and by 22 +/- 4 per cent following verapamil. In a similar group of five patients in a stable clinical condition (mean PaO2 = 7.3 kPa) neither oxygen nor verapamil administered during acute exacerbations produced any significant changes in pulmonary vascular resistance, cardiac index or oxygen delivery.

Acute Disease↗
PubMed1986

Fever during treatment of infective endocarditis.

In 83 episodes of culture-positive infective endocarditis (IE) of a native valve, fever persisted or recurred in 42 (50%) despite appropriate bactericidal antibiotics. The commonest cause of fever was extensive infection of the valve ring and adjacent structures, even when the infecting organisms were viridans streptococci; urgent surgery was required. Less frequent causes were systemic and pulmonary emboli and drug hypersensitivity. Infected intravenous access sites were seldom responsible. In no case was fever due to antibiotic resistance of the infecting organism. In patients with a definite microbiological diagnosis who have been given appropriate antibiotics, the temptation to alter antibiotic therapy because of persistent or recurrent fever should be resisted unless there are features of drug hypersensitivity. When fever persists or recurs during treatment of IE, the opinions of a cardiologist and cardiac surgeon should be obtained as soon as possible; delay in valve replacement may prove fatal in patients with extensive infection.

Acute Disease↗
PubMed1986

Cohort study analysis with a FORTRAN computer program.

We describe the analysis of cohort study data with a standard FORTRAN program which should run on most computers. It provides a summary measure of the mortality (or incidence) rate ratio between the study cohort and some standard population, based either on person-years at risk or on proportional mortality, and adjusted for age, sex and calendar period; a test of the statistical significance of the ratio; and a set of observed death rates in the study cohort. Results may also be produced in a form suitable for use with GLIM. The analysis may be subdivided into a range of time intervals since each subject was first exposed to risk. The program provides for movement of subjects between different 'level-of-exposure' subgroups within the cohort, and for various methods of censoring. It allows considerable flexibility in data management, and is available with complete documentation and a worked example. The program should enable epidemiologists with little computing experience to carry out formal analysis of cohort studies.

Adolescent↗
PubMed1986

Long-term culture of fetal rat hepatocytes in media supplemented with fetal calf-serum Ultroser SF or Ultroser G.

Fetal hepatocytes cultured in medium supplemented with fetal calf serum (FCS) or Ultroser SF do not maintain production of albumin or transferrin beyond one week of culture. When dexamethasone (10(-7) M) is present, secretion of albumin and transferrin can be extended to two weeks, however, levels are extremely low. By three weeks, neither plasma protein can be detected in the culture medium in either conditions of culture. In contrast, hepatocytes maintained in medium supplemented with Ultroser G continue to produce albumin and transferrin at high levels for the entire three week period of this study. The morphology of the cultures are different. In FCS and Ultroser SF supplemented medium there are many more fibroblast and epithelial-like cells and relatively fewer cells which are distinctly hepatocytes when compared with Ultroser G supplemented medium. The level of tyrosine aminotransferase, which is a dexamethasone inducible enzyme, is found to be much higher in Ultroser G cultures, with no further increase demonstrable by addition of dexamethasone. In contrast, dexamethasone induces the enzyme by about eight-fold in cultures maintained in FCS supplemented medium. Therefore it appears that Ultroser G already contains sufficient steroid activity to maximize the level of tyrosine aminotransferase. A comparison between Ultroser C and SF (steroid-free) suggests that the mixture of steroid and steroid derivatives in the G formulation must be important in the maintenance of differentiated functions of hepatocytes in culture. However, supplementation of FCS cultures with dexamethasone, which is known to be present in Ultroser G, does not allow hepatocytes to retain their differentiated functions over an extended period. Therefore it is concluded that other components besides dexamethasone must be important.

Animals↗
PubMed1977

Gonadal karyotyping in women with and without ovarian activity.

Results of gonadal karyotyping on 26 patients with cyclic or acyclic ovarian activity and hypogonadotropic or hypergonadotropic hypogonadism are presented. Gonadal culture growth, with the exception of tissue from polycystic ovaries, was usually successful. With one exception, leukocytic and gonadal karyotypes were concordant. Normal ovarian function did not appear to be limited to ovaries of the 46,XX karyotype.

Adolescent↗
PubMed1977

A study of events in chick cells infected with human adenovirus type 5 and their relationship to the induction of interferon.

In an attempt to define the molecular events involved in induction of interferon, various parameters of chick cells infected with human adenovirus type 5 were analysed. It was shown by digestion with various proteolytic enzymes and by disruption of the purified virus that induction of interferon requires the interaction of infectious virus with the chick cells. Analysis of adenovirus-infected chick cells by immunological and biochemical techniques indicated that most of the cells produce some virus-specific components, and that temperature sensitive mutants which fail to induce interferon at the restrictive temperature fail to synthesize late components at that temperature. However, since it has been shown that interferon can be induced in the absence of DNA synthesis, these studies conclude that interferon induction results from an early interaction between virus (or virus product) and chick cells and moreover that this interaction is also necessary for the synthesis of virus DNA in this system.

Adenoviruses, Human↗