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Biomedical subjects

C Hart

Publications and source records attributed to C Hart.

At least 37 records · Page 2Linked to original sources
PubMed2000

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.

The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.

Animals↗
PubMed2000

Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality.

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting in--or being associated with--shorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers.

Body Height↗
PubMed1999

An evaluation of worker lead exposures and cleaning effectiveness during removal of deteriorated lead-based paint.

We evaluated worker lead exposures and cleaning effectiveness during initial cleanup of 19th-century buildings with highly deteriorated lead-based paint. Eighteen rooms of similar size and condition in two university-owned buildings were selected for a pilot project to compare three methods for removing loose paint, paint chips, and dust. The methods used were: dry scraping followed by dry sweeping (no engineering or work practice controls); wet scraping and high-efficiency particulate air (HEPA) vacuuming; and the latter method with the addition of a portable HEPA-filtered exhaust fan in the room providing about 40 air changes per hour. The final step for all methods was wet-mopping once with tri-sodium phosphate solution. During a single day 18 rooms were cleaned; each of three two-person work crews cleaned six rooms, two with each method. Air and surface samples were collected before, during, and after cleaning. All of the methods were potentially hazardous to workers: 44 percent of the method-based exposures (range: 5.0-360 micrograms/m3) and one of five full-shift exposures exceeded the OSHA PEL (range 9.4-110 micrograms/m3). Lowest worker exposures were during the wet scraping and vacuuming method (mean: 24 micrograms/m3). Providing general ventilation in rooms did not reduce worker exposures and appeared to increase them (mean: 73 micrograms/m3). Overall, the mean floor surface lead levels were reduced 50 percent after cleaning (from 2,600 to 1,300 micrograms/ft2), but the effectiveness of the three methods in reducing floor lead levels did not differ significantly. Overall, the method, mean paint lead concentration, pre-cleaning surface lead concentration, and work crew were significantly associated with the mean worker exposures during cleaning (p = 0.023), but not with the post-cleaning surface lead concentrations (p = 0.13).

Air Pollutants↗
PubMed1998

Adverse socioeconomic conditions in childhood and cause specific adult mortality: prospective observational study.

OBJECTIVE: To investigate the association between social circumstances in childhood and mortality from various causes of death in adulthood. DESIGN: Prospective observational study. SETTING: 27 workplaces in the west of Scotland. SUBJECTS: 5645 men aged 35-64 years at the time of examination. MAIN OUTCOME MEASURES: Death from various causes. RESULTS: Men whose fathers had manual occupations when they were children were more likely as adults to have manual jobs and be living in deprived areas. Gradients in mortality from coronary heart disease, stroke, lung cancer, stomach cancer, and respiratory disease were seen (all P<0.05), generally increasing from men whose fathers had professional and managerial occupations (social class I and II) to those whose fathers had semiskilled and unskilled manual occupations (social class IV and V). Relative rates of mortality adjusted for age for men with fathers in manual versus non-manual occupations were 1.52 (95% confidence interval 1.24 to 1.87) for coronary heart disease, 1.83 (1.13 to 2. 94) for stroke, 1.65 (1.12 to 2.43) for lung cancer, 2.06 (0.93 to 4. 57) for stomach cancer, and 2.01 (1.17 to 3.48) for respiratory disease. Mortality from other cancers and accidental and violent death showed no association with fathers' social class. Adjustment for adult socioeconomic circumstances and risk factors did not alter results for mortality from stroke and stomach cancer, attenuated the increased risk of coronary heart disease and respiratory disease, and essentially eliminated the association with lung cancer. CONCLUSIONS: Adverse socioeconomic circumstances in childhood have a specific influence on mortality from stroke and stomach cancer in adulthood, which is not due to the continuity of social disadvantage throughout life. Deprivation in childhood influences risk of mortality from coronary heart disease and respiratory disease in adulthood, although an additive influence of adulthood circumstances is seen in these cases. Mortality from lung cancer, other cancer, and accidents and violence is predominantly influenced by risk factors that are related to social circumstances in adulthood.

Accidents↗
PubMed1998

A novel method for quantitative analysis of recombinant secreted proteins using two-dimensional electrophoresis.

We describe a two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)-based approach for detecting and quantifying secreted recombinant proteins in media conditioned by baby hamster kidney (BHK) cells. Seven secreted proteins were analyzed in this system: leptin, thrombopoietin, thrombin, glycoprotein 130, soluble interleukin-2 receptor, and two novel sequences obtained from sequence database searches. BHK cells transfected with plasmids encoding each of these proteins, and cells transfected with empty plasmids (control cells), were metabolically labeled and the resulting conditioned media were analyzed by 2-D PAGE. Gel images derived from cells expressing recombinant proteins were compared with images from control cells in order to identify spots corresponding to the expressed proteins. All seven of the test proteins were successfully detected using this method. The sensitivity of the system was evaluated by diluting samples derived from high-expressing clones with conditioned media from control cells. The sensitivity of detection was protein-dependent, but recombinant proteins expressed at levels as low as 10 ng/mL could be detected. Quantification of recombinant protein levels was achieved by measuring spot intensities using phosphorimager analysis. The intensity of spots corresponding to recombinant proteins were compared with the spot intensity of an endogenous BHK protein which had been calibrated to a known standard. Estimates of the levels of expressed protein determined using this technique correlated with the levels determined using standard affinity assays. We conclude that this system provides a reliable method for quantifying levels of protein expression when specific assays are unavailable.

Animals↗
PubMed1998

CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors.

The AC133 antigen is a novel antigen selectively expressed on a subset of CD34+ cells in human fetal liver, bone marrow, and blood as demonstrated by flow cytometric analyses. In this study, we have further assessed the expression of AC133 on CD34+ cells in hemopoietic samples and found that there was a highly significant difference between normal bone marrow and cord blood versus aphereses (p <0.0001) but not between bone marrow and cord blood. Most of the clonogenic cells (67%) were contained in the CD34+AC133+ fraction. Compared with cultures of the CD34+AC133- cells, generation of progenitor cells in long-term culture on bone marrow stroma was consistently 10- to 100-fold higher in cultures initiated with CD34+AC133+ cells and was maintained for the 8-10 weeks of culture. Only the CD34+AC133+ cells were capable of repopulating NOD/SCID mice. Human cells were detectable as early as day 20, with increased levels (67%) apparent 40 days post-transplantation. Five thousand CD34+AC133+ cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted with up to 1.2 x 10(5) CD34+AC133- cells. The CD34+AC133+ population was also enriched (seven-fold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymphocyte reaction assay. AC133+ cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic cells.

AC133 Antigen↗
PubMed1998

Education and occupational social class: which is the more important indicator of mortality risk?

STUDY OBJECTIVES: In the UK, studies of socioeconomic differentials in mortality have generally relied upon occupational social class as the index of socioeconomic position, while in the US, measures based upon education have been widely used. These two measures have different characteristics; for example, social class can change throughout adult life, while education is unlikely to alter after early adulthood. Therefore different interpretations can be given to the mortality differentials that are seen. The objective of this analysis is to demonstrate the profile of mortality differentials, and the factors underlying these differentials, which are associated with the two socioeconomic measures. DESIGN: Prospective observational study. SETTING: 27 work places in the west of Scotland. PARTICIPANTS: 5749 men aged 35-64 who completed questionnaires and were examined between 1970 and 1973. FINDINGS: At baseline, similar gradients between socioeconomic position and blood pressure, height, lung function, and smoking behaviour were seen, regardless of whether the education or social class measure was used. Manual social class and early termination of full time education were associated with higher blood pressure, shorter height, poorer lung function, and a higher prevalence of smoking. Within education strata, the graded association between smoking and social class remains strong, whereas within social class groups the relation between education and smoking is attenuated. Over 21 years of follow up, 1639 of the men died. Mortality from all causes and from three broad cause of death groups (cardiovascular disease, malignant disease, and other causes) showed similar associations with social class and education. For all cause of death groups, men in manual social classes and men who terminated full time education at an early age had higher death rates. Cardiovascular disease was the cause of death group most strongly associated with education, while the non-cardiovascular non-cancer category was the cause of death group most strongly associated with adulthood social class. The graded association between social class and all cause mortality remains strong and significant within education strata, whereas within social class strata the relation between education and mortality is less clear. CONCLUSIONS: As a single indicator of socioeconomic position occupational social class in adulthood is a better discriminator of socioeconomic differentials in mortality and smoking behaviour than is education. This argues against interpretations that see cultural--rather than material--resources as being the key determinants of socioeconomic differentials in health. The stronger association of education with death from cardiovascular causes than with other causes of death may reflect the function of education as an index of socioeconomic circumstances in early life, which appear to have a particular influence on the risk of cardiovascular disease.

Adult↗
PubMed1998

Individual social class, area-based deprivation, cardiovascular disease risk factors, and mortality: the Renfrew and Paisley Study.

OBJECTIVE: To investigate the associations of individual and area-based socioeconomic indicators with cardiovascular disease risk factors and mortality. DESIGN: Prospective study. SETTING: The towns of Renfrew and Paisley in the west of Scotland. PARTICIPANTS: 6961 men and 7991 women included in a population-based cardiovascular disease screening study between 1972 and 1976. MAIN OUTCOME MEASURES: Cardiovascular disease risk factors and cardiorespiratory morbidity at the time of screening: 15 year mortality from all causes and cardiovascular disease. RESULTS: Both the area-based deprivation indicator and individual social class were associated with generally less favourable profiles of cardiovascular disease risk factors at the time of the baseline screening examinations. The exception was plasma cholesterol concentration, which was lower for men and women in manual social class groups. Independent contributions of area-based deprivation and individual social class were generally seen with respect to risk factors and morbidity. All cause and cardiovascular disease mortality rates were both inversely associated with socioeconomic position whether indexed by area-based deprivation or social class. The area-based and individual socioeconomic indicators made independent contributions to mortality risk. CONCLUSIONS: Individually assigned and area-based socioeconomic indicators make independent contributions to several important health outcomes. The degree of inequalities in health that exist will not be demonstrated in studies using only one category of indicator. Similarly, adjustment for confounding by socioeconomic position in aetiological epidemiological studies will be inadequate if only one level of indicator is used. Policies aimed at reducing socioeconomic differentials in health should pay attention to the characteristics of the areas in which people live as well as the characteristics of the people who live in these areas.

Cardiovascular Diseases↗
PubMed1998

Reversible male sterility: a novel system for the production of hybrid corn.

Hybrid corn seed is traditionally produced using either mechanical/hand detasseling or cytoplasmic male sterility, or a combination of both. In recent years, the development of transgenic systems to produce hybrid seed in several crops has attracted much attention. Here we describe a transgenic mechanism for production of hybrid corn, reversible male sterility (RMS), in which the action of the cytotoxic gene used to introduce male sterility is suppressed by the application of a chemical to the plant. Reversion of the sterility allows the RMS parent to be self-fertilized, a step which overcomes the need to remove fertile sib plants prior to making the hybrid cross. The key enabling technology in RMS is the use of a plant gene promoter which is specifically induced by chemical application. We have exemplified RMS in transgenic corn plants and believe that it provides specific benefits in the production of hybrid corn seed.

Hybridization, Genetic↗
PubMed1997

Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study.

OBJECTIVE: To investigate the association between birth weight of offspring and mortality among fathers and mothers in the west of Scotland. DESIGN: Prospective observational study. PARTICIPANTS: 794 married couples in Renfrew district of the west of Scotland. MAIN OUTCOME MEASURES: Mortality from all causes and from cardiovascular disease over 15 year follow up. RESULTS: Women who had heavier babies were taller, had higher body mass index and better lung function, and were less likely to be smokers than mothers of lighter babies. Fathers of heavier babies were taller and less likely to be smokers than fathers of lighter babies. Mortality was inversely related to offspring's birth weight for both mothers (relative rate for a 1 kg lower birth weight 1.82 (95% confidence interval 1.23 to 2.70)) and fathers (relative rate 1.35 (1.03 to 1.79)). For mortality from cardiovascular disease, inverse associations were seen for mothers (2.00 (1.18 to 3.33)) and fathers (1.52 (1.03 to 2.17)). Adjustment for blood pressure, plasma cholesterol, body mass index, height, social class, area based deprivation category, smoking, lung function, angina, bronchitis, and electrocardiographic evidence of ischaemia had little effect on these risk estimates, although levels of statistical significance were reduced. CONCLUSIONS: Birth weight of offspring was related inversely to mortality, from all causes and cardiovascular disease, in this cohort. The strength of this association was greater than would have been expected by the degree of concordance of birth weights across generations, but an extensive range of potential confounding factors could not account for the association. Mortality is therefore influenced by a factor related to birth weight that is transmissible across generations.

Birth Weight↗
PubMed1997

Lifetime socioeconomic position and mortality: prospective observational study.

OBJECTIVES: To assess the influence of socioeconomic position over a lifetime on risk factors for cardiovascular disease, on morbidity, and on mortality from various causes. DESIGN: Prospective observational study with 21 years of follow up. Social class was determined as manual or non-manual at three stages of participants' lives: from the social class of their father's job, the social class of their first job, and the social class of their job at the time of screening. A cumulative social class indicator was constructed, ranging from non-manual social class at all three stages of life to manual social class at all three stages. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 at the time of examination. MAIN OUTCOME MEASURES: Prevalence and level of risk factors for cardiovascular disease; morbidity; and mortality from broad causes of death. RESULTS: From non-manual social class locations at all three life stages to manual at all stages there were strong positive trends for blood pressure, body mass index, current cigarette smoking, angina, and bronchitis. Inverse trends were seen for height, cholesterol concentration, lung function, and being an ex-smoker. 1580 men died during follow up. Age adjusted relative death rates in comparison with the men of non-manual social class locations at all three stages of life were 1.29 (95% confidence interval 1.08 to 1.56) in men of two non-manual and one manual social class; 1.45 (1.21 to 1.73) in men of two manual and one non-manual social class; and 1.71 (1.46 to 2.01) in men of manual social class at all three stages. Mortality from cardiovascular disease showed a similar graded association with cumulative social class. Mortality from cancer was mainly raised among men of manual social class at all three stages. Adjustment for a wide range of risk factors caused little attenuation in the association of cumulative social class with mortality from all causes and from cardiovascular disease; greater attenuation was seen in the association with mortality from non-cardiovascular, non-cancer disease. Fathers having a manual [corrected] occupation was strongly associated with mortality from cardiovascular disease: relative rate 1.41 (1.15 to 1.72). Participants' social class at the time of screening was more strongly associated than the other social class indicators with mortality from cancer and from non-cardiovascular, non-cancer causes. CONCLUSIONS: Socioeconomic factors acting over the lifetime affect health and risk of premature death. The relative importance of influences at different stages varies for the cause of death. Studies with data on socioeconomic circumstances at only one stage of life are inadequate for fully elucidating the contribution of socioeconomic factors to health and mortality risk.

Adult↗