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Biomedical subjects

C J Duncan

Publications and source records attributed to C J Duncan.

At least 19 recordsLinked to original sources
PubMed2001

Protection against cellular damage in the rat heart by iodoacetate.

In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O2 paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca2+o depletion or anoxia; stage 1) and subsequent full activation (Ca2+o repletion, caffeine or reoxygenation; stage 2) of the damage system of the sarcolemma. Iodoacetate (1 mM) provided complete protection in the O2 paradox and over 80% protection in the Ca2+ paradox and caffeine protocols against creatine kinase release when present throughout the experiment (P < 0.001). Almost identical protection was found when iodoacetate was present only in stage 2 (P < 0.001). However, it was concluded that iodoacetate had limited protective effects when present only in stage 1 in any of the three protocols and that its action is to inhibit the activity of the transsarcolemma damage system in stage 2 when it has been activated in stage 1. It is suggested that iodoacetate interacts with thiol groups on the damage system of the sarcolemma.

Animals↗
PubMed2000

A new indanone from the marine cyanobacterium Lyngbya majuscula that inhibits hypoxia-induced activation of the VEGF promoter in Hep3B cells.

A new indanone (1) has been isolated from the filamentous marine cyanobacterium Lyngbya majuscula, and its structure determined spectroscopically. Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis. Compound 1 inhibits hypoxia-induced activation of the VEGF gene promoter in Hep3B human liver tumor cells, in vitro.

Cell Hypoxia↗
PubMed2000

Modelling the dynamics of scarlet fever epidemics in the 19th century.

Annual deaths from scarlet fever in Liverpool, UK during 1848-1900 have been used as a model system for studying the historical dynamics of the epidemics. Mathematical models are developed which include the growth of the population and the death rate from scarlet fever. Time-series analysis of the results shows that there were two distinct phases to the disease (i) 1848-1880: regular epidemics (wavelength = 3.7 years) consistent with the system being driven by an oscillation in the transmission coefficient (deltabeta) at its resonant frequency, probably associated with dry conditions in winter (ii) 1880-1900: an undriven SEIR system with a falling endemic level and decaying epidemics. This period was associated with improved nutritive levels. There is also evidence from time-series analysis that raised wheat prices in pregnancy caused increased susceptibility in the subsequent children. The pattern of epidemics and the demographic characteristics of the population can be replicated in the modelling which provides insights into the detailed epidemiology of scarlet fever in this community in the 19th century.

Adult↗
PubMed2000

Interacting effects of nutrition and social class differentials on fertility and infant mortality in the pre-industrial population.

Inadequate nutrition of both the mother and her offspring at each stage of its development - before pregnancy, in the womb, in infancy and during early childhod - played an important role in the patterns of subfertility and infant mortality in a saturated, marginal, preindustrial community. It is suggested that the three social classes had different diets but all were deficient in some essential constituents. Differences in nursing practices in the social groups contributed to differential exogenous mortality and to malnourishment and maternal depletion in the subsistence and (paradoxically) in the elite classes, producing an interacting web of effects and generating a vicious circle from which they could not escape for 150 years. Although the population apparently preferred daughters, the persistent generation effect of low birthweight girls bearing low birthweight daughters probably contributed to the steady-state conditions in this compromised community.

England↗
PubMed1999

Protection against cellular damage in the rat heart by hyperosmotic solutions.

In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O(2) paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca(2+)(0) depletion or anoxia; stage 1) and subsequent full activation (Ca(2+)(0) repletion, caffeine or reoxygenation; stage 2) of the damage system of the sarcolemma. Creatine kinase release in stage 2 was completely inhibited (P < 0.001) in all three protocols when 420 mOsm was added to the perfusion medium throughout the experiments, or only during stage 1, or only during stage 2. Increasing the perfusion pressure in the Ca2+ paradox significantly (P < 0.001) exacerbated creatine kinase release, although this was still completely inhibited at 28 degrees C. Amiloride (1 mM) inhibited creatine kinase release completely at 40 cm of water pressure but only some 50% at 80 cm of water pressure. It is suggested that the transmembrane damage system needs to be uncoupled or deactivated by modifying its relationship with the cytosol or with the underlying cytoskeleton by hyperosmotic cell shrinkage for only one of the stages in all three protocols to block the damage pathway. Increased perfusion pressure has the opposite effect and exacerbates damage.

Animals↗
PubMed1999

Nutrition, fertility and steady-state population dynamics in a pre-industrial community in Penrith, northern England.

The effect of nutrition on fertility and its contribution thereby to population dynamics are assessed in three social groups (elite, tradesmen and subsistence) in a marginal, pre-industrial population in northern England. This community was particularly susceptible to fluctuations in the price of grains, which formed their basic foodstuff. The subsistence class, who formed the largest part of the population, had low levels of fertility and small family sizes, but women from all social groups had a characteristic and marked subfecundity in the early part of their reproductive lives. The health and nutrition of the mother during pregnancy was the most important factor in determining fertility and neonatal mortality. Inadequate nutrition had many subtle effects on reproduction which interacted to produce a complex web of events. A population boom occurred during the second half of the 18th century; fertility did not change but there was a marked improvement in infant mortality and it is suggested that the steadily improving nutritional standards of the population, particularly during crucial periods in pregnancy (i.e. the last trimester), probably made the biggest contribution to the improvement in infant mortality and so was probably the major factor in triggering the boom.

Adolescent↗
PubMed1998

Normal adaptive function with learning disability in duplication 8p including band p22.

Duplication 8p usually results in a syndrome characterized by profound mental retardation, mild facial anomalies, and malformations of hand, heart, and brain. We report on a large kindred segregating a Y;8 translocation in whom several individuals have duplication 8p22-->8pter. These individuals have normal adaptive function despite their unbalanced karyotype. The family was studied with G-banding and fluorescent in situ hybridization (FISH) using probes to chromosomes 8 and Y. Comparison of this family with other reported cases defines a mild clinical outcome for trisomy 8p22-->8pter in contrast to the severe findings when the duplication involves a longer, more proximal segment.

Adaptation, Physiological↗
PubMed1998

Migration to the New South Wales North Coast 1986-1991: lifestyle motivated counterurbanisation.

"Some of [Australia's] most rapid population growth rates have been recorded on the North Coast of New South Wales. The paper sets this migration flow in an international context and looks in detail at the profile, decision-making, and experience of 150 households who moved to the North Coast in the 1986-1991 intercensal period. Results corroborate earlier findings that many coastal migrants are motivated by non-economic considerations. ¿Pull' factors are much more important than ¿push' factors, with the influence of the physical environment, climate and relaxed lifestyle dominant."

Australia↗
PubMed1998

The interacting effects of prices and weather on population cycles in a preindustrial community.

The exogenous cycles and population dynamics of the community at Penrith, Cumbria, England, have been studied (1557-1812) using aggregative analysis, family reconstitution and time series analysis. This community was living under marginal conditions for the first 200 years and the evidence presented is of a homeostatic regime where famine, malnutrition and epidemic disease acted to regulate the balance between resources and population size. This provides an ideal historic population for an investigation of the direct and indirect effects of malnutrition. Throughout the period studied, a short wavelength oscillation in grain prices was apparently the major external factor that drove exogenous cycles in mortality, birth rate, and migration. In particular, the different responses of children to variations in food supply are emphasised; fluctuations in poor nutrition correlated significantly with the variations in mortality rates for infants (probably indirectly during pregnancy and directly during the first year of life) and for young children (via susceptibility to lethal infectious diseases). Migratory movements contributed to the maintenance of homeostasis in the population dynamics. A medium wavelength cycle in low winter temperatures was associated with a rise in adult mortality which, in turn, promoted an influx of migrants into this saturated habitat. A model incorporating these interacting associations between vital events and exogenous cycles is presented: grain prices were an important density-dependent factor and constituted the major component of the negative feedback of this population and drove the exogenous, short wavelength mortality cycles. Cycles of births and immigration provide a positive feedback for the build-up of susceptibles and the initiation of smallpox epidemics and increased population size.

Commerce↗
PubMed1998

The effects of population density and malnutrition on the dynamics of whooping cough.

Liverpool, a seaport in NW England, suffered severely from lethal infectious diseases in the second half of the 19th century: the population was densely crowded and malnourished and life expectancy was low. Time-series analysis shows that the epidemics of whooping cough (i) had an interepidemic interval of 2.9 years, 1863-85, which lengthened to 3.4 years, 1885-1900 (ii) were strongly coherent with wheat prices (P < 0.001) and (iii) also correlated with cycles of seasonal weather conditions. It is suggested from mathematical modelling that the epidemics in this compromised population were maintained (i.e. the system was driven) by an oscillation of malnutrition and by seasonal weather conditions. A model that incorporates both the dynamics of whooping cough and the demographic characteristics of the population is presented. It has been shown to replicate the dynamics of the epidemics and has been used to predict the changes with time of (i) the force of the infection and (ii) the proportion of those infected with whooping cough who died.

Disease Outbreaks↗
PubMed1997

Protection against cellular damage in the perfused rat heart by lowered pH.

In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O2 paradox and with 20 mM caffeine. Each protocol involved an initial priming (Ca2+(o) depletion or anoxia; stage 1) and subsequent full activation (Ca2+(o) repletion or reoxygenation; stage 2) of the damage system of the sarcolemma. Creatine kinase release in stage 2 was completely inhibited (P < 0.001) in all three protocols when pH was reduced to 6.5 throughout the experiments, or only during stage 1, or only during stage 2. The inhibitor of the Na+/H+ antiporter, amiloride (1 mM), completely prevented creatine kinase release in the Ca2+ paradox (P < 0.001) and markedly reduced damage in the caffeine protocol. Amiloride had no significant effect on creatine kinase release in the O2 paradox. The possible role of Na+(i) was studied in the caffeine protocol: ouabain (5 x 10(-6) M) had little effect whereas substitution of choline for Na+ in the perfusion medium reduced creatine kinase release by about 50%. It is suggested that the same damage system is activated in stage 1 in all three protocols and that a key event is the intracellular production of H+ which are exported via Na+(o)/H(i) exchange. Prevention of H+ efflux by lowered pH(o), even during stage 2, protected against creatine kinase release. The possible role of Na+ movements in the genesis of sarcolemma damage is discussed.

Amiloride↗
PubMed1997

The dynamics of measles epidemics.

The interepidemic interval (T) of measles in London from 1647 to 1837 evolved progressively from 5-yearly to 2-yearly by 1800. Measles mortality was significantly ( p<0.001) cross-correlated with the annual wheat prices, a good index of nutrition although at a 2-year lag. Epidemics correlated with low autumn temperatures (p<0. 001). A linearised model of the dynamics of epidemics shows that T is determined by the product of population (N) and susceptibility (beta) and that the system will settle at its steady state unless the epidemics are driven. It is suggested that (i) the progressive change in T was caused by a rise in population size (N) and an increased susceptibility (beta) related to malnutrition and (ii) epidemics were driven by oscillations in low autumn temperature (p<0. 001) and by cycles of susceptible young children produced by malnutrition during pregnancy.

Child↗
PubMed1997

Interacting factors affecting illegitimacy in preindustrial northern England.

Illegitimacy in a historic, single community at Penrith, Cumbria (1557-1812), has been studied using aggregative analysis, family reconstitution and time series analysis. This population was living under extreme conditions of hardship. Long, medium and short wavelength cycles in the rate of illegitimacy have been identified by time series analysis; each represents a different response to social and economic pressures. In a complex interaction of events, the peaks of the cycles in wheat prices were associated with rises in adult mortality which promoted an influx of migrants and a concomitant rise in illegitimacy. The association between immigration and illegitimacy was particularly noticeable after the mortality crises of the late sixteenth and early seventeenth centuries. Children of immigrant families also tended to produce illegitimate offspring. Native and immigrant families responded differently to extrinsic fluctuations, and variations in their reproductive behaviour were probably related to access to resources.

Emigration and Immigration↗
PubMed1996

Oscillatory dynamics of smallpox and the impact of vaccination.

The evolution of smallpox epidemics in London, 1647-1893, was studied by time series analysis of deaths from the disease in the Bills of Mortality. The interepidemic interval (T) evolved progressively from 4 years to 2 years at 1800. The dynamics of epidemics during 1647-1800 are explicable in terms of the transmission of viral diseases which shows that (i) T is determined by the product of population size (N) and susceptibility (beta), (ii) T determines the mean age of catching the disease, (iii) the system will settle at its steady-state, endemic level unless the epidemics are driven. It is suggested that (i) the progressive change in T was initially caused by a rise in N and later by an increased beta related to malnutrition and (ii) the epidemics were driven by an oscillation in delta beta associated with seasonal dry conditions. The effects of variolation and vaccination became apparent after 1800: the endemic level fell progressively, the epidemics were reduced in amplitude and they were not driven. The dynamics of the disease can now be described by an SEIR model: severe outbreaks of smallpox are followed by decaying epidemics. Endemic smallpox mortality also interacts with the dynamics of the population so that a long wavelength oscillation (associated with recovery after the plague) and a 5/6 year (associated with immigration) oscillation are generated.

Disease Outbreaks↗
PubMed1996

Extracellular K+ and protection against cellular damage in the rat heart.

Rat hearts were perfused at 37 degrees C with three clearly-defined protocols: the Ca2+ paradox, the O2 paradox and with 20 mM caffeine. Each protocol involved an initial priming (stage 1) and a subsequent full activation (stage 2) of the damage system of the sarcolemma. Raising [K+]o from 5.4 to 6.5 mM in the Ca2+ paradox had no significant effect, but creatine kinase release was significantly inhibited (P < 0.001) at 7.5, 10.8 or 16.2 mM. Raising [K+]o to 16.2 mM only during stage 1 or only during stage 2 also inhibited creatine kinase release (P < 0.001); protection was greater than when 16.2 mM [K+]o was present throughout. [K+]o at 10.8 mM exacerbated creatine kinase release in the O2 paradox (P < 0.001) and also when present only during stage 1. However, significant protection was provided when [K+]o was raised only during stage 2 (P < 0.001). Creatine kinase release in the caffeine protocol was significantly inhibited (P < 0.001) at 10.8 mM [K+]o and when [K+]o was raised only during stage 1 or stage 2. It is concluded that raised [K+]o has two opposing effects: prevention of the activation of the membrane damage system and an exacerbation of damage via an increased Ca2+ influx.

Animals↗
PubMed1996

Whooping cough epidemics in London, 1701-1812: infection dynamics, seasonal forcing and the effects of malnutrition.

Time series analysis of the London Bills of Mortality, 1701-1812, reveals that whooping cough appeared as a lethal endemic disease after 1700 with epidemics of progressively increasing amplitude after 1720. The interepidemic period changed from 5 years (1720-1750) to 3 years (1750-1785) before returning to 5 years during 1785-1812. The epidemiology of whooping cough can be described by the mathematics of linearized dynamic systems and the interepidemic interval is determined by population size and susceptibility. The latter was governed by fluctuating levels of malnutrition, which were directly associated with oscillations in the wheat prices. It is suggested that the epidemics were driven in 1720-1785 by fluctuating seasonal temperatures which interacted with oscillations in wheat prices to produce an oscillation in susceptibility, but after 1785 the dynamics escaped from the pattern predicted by mathematical theory and the epidemics were apparently driven only by the wheat prices which generated a regular oscillation in susceptibility. The results emphasize the importance of an adequate nutritive level in combating whooping cough in the Third World today where it remains a lethal disease in children because of immunodeficiency linked to fluctuating and severe malnutrition which is often a consequence of crop cycles.

Agriculture↗