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Biomedical subjects

J H Koeslag

Publications and source records attributed to J H Koeslag.

At least 19 recordsLinked to original sources
PubMed1999

The chromogranins and the counter-regulatory hormones: do they make homeostatic sense?

1. The chromogranins are ubiquitous proteins which are co-stored and co-secreted with many peptide hormones. All appear to be powerful inhibitors of endocrine secretions. This poses a problem. 2. When endocrine glands are involved in the efferent limbs of homeostatic loops, they are message transmitters. The self-inhibition caused by the co-secretion of a chromogranin will, on the face of it, erase the message. 3. Pairs of counter-regulatory homeostatic hormones also present a problem. 4. If both members of the pair have clearly defined set points, as suggested by their 'time integral' (or 'growth with time') responsiveness to deviations from set point, then, if the two set points are not exactly the same, one or other member will always register an error, leading, eventually, to an overwhelmingly large and unnecessary response. 5. Our model eliminates both paradoxes, and emphasizes the importance of counter-regulation and the co-secretion of chromogranins in 'zero steady-state error' (ZSSE) homeostasis. 6. If hormone A is secreted into the blood in progressively increasing amounts when [Q], the plasma concentration of substance Q, is low, and in decreasing amounts when [Q] is high; and hormone B responds in the opposite manner, then there will be a [Q], designated [Q]p, at which the secretory rate increase, or decrease, of the two hormones is exactly the same. 7. If, in addition, the secretion of both hormones is stimulated by low plasma chromogranin levels, [Cg], but inhibited by high [Cg] then there will be a different [Q]p for every chromogranin concentration in the blood. 8. At one of these points (at a unique [Q] and [Cg]) the concentration of neither hormone will increase or decrease. This is the equilibrium point to which, according to our model, the system always returns regardless of disturbances within physiological limits. 9. This is robust ZSSE control.

Animals↗
PubMed1999

A computer simulation of free-range exercise in the laboratory.

We present a technique for simulating dynamic field (free-range) exercise, using a novel computer-controlled cycle ergometer. This modified cycle ergometer takes into account the effect of friction and aerodynamic drag forces on a 70-kg cyclist in a racing position. It also affords the ability to select different gear ratios. We have used this technique to simulate a known competition cycle route in Cape Town, South Africa. In an attempt to analyze the input stimulus, in this case the generated power output of each cyclist, eight subjects cycled for 40 min at a self-selected, comfortable pace on the first part of the simulated route. Our results indicate that this exercise input excites the musculocardiorespiratory system over a wide range of power outputs, both in terms of amplitude and frequency. This stimulus profile thereby complies with the fundamental requirement for nonlinear (physiological) systems analysis and identification. Through a computer simulation, we have devised a laboratory exercise protocol that not only is physiologically real but also overcomes the artificiality of most traditional laboratory exercise protocols.

Computer Simulation↗
PubMed1998

Integral rein control in physiology.

We propose that blood glucose is regulated by a principle which we call integral rein control, in which under most conditions both glucagon and insulin are produced and control is achieved by altering the balance between the two. Like other integral control systems, the mechanism achieves zero steady-state error, which explains how the blood glucose level can remain very nearly constant over a wide range of input and demand. In addition, the use of two hormones makes the system stable against relatively large perturbations in either direction. An important feature of the model is that the set point is not fixed by an external reference but arises out of the dynamics, in particular out of the relation between the rates of production of the two hormones. The model therefore predicts that the consequence of an inability to produce insulin will be not just that the control will be less effective but that the set point will be shifted. This allows us to explain why patients with untreated Type I diabetes mellitus have high blood glucose levels even under conditions of low glucose input, and why it is difficult to maintain the normal level of 5 mmol/1 in patients who are being treated with insulin. It also explains why Type II diabetes is easier to treat.

Blood Glucose↗
PubMed1997

Sex, the Prisoner's Dilemma Game, and the evolutionary inevitability of cooperation.

It will be a universal feature of sexual populations that individuals prefer mates with typical rather than rare characteristics--essentially because most mutations reduce fitness. This is termed koinophilia. Koinophilia will also apply to behaviour. In particular, individuals will prefer mates that behave in social interactions that follow whatever rules are common in that population. Suppose that individuals interact in situations which can be represented by the Iterated Prisoner's Dilemma Game (IPD). If koinophilia is ignored, previous authors have shown that it is hard to find an evolutionarily stable strategy, and that strategies cycle indefinitely. However, if koinophilia is included, it has the effect of increasing the fitness of whatever happens to be the common strategy. This, in turn, has the effect of stabilizing almost any strategy (that has, for whatever reason, become the local norm) in the IPD. Different, partially isolated groups will thus become evolutionarily trapped in different behaviours, which are defended against alternative strategies originating through mutation or immigration. Groups that happen, by chance, to reach a cooperative strategy will be fitter, as groups, than those that reach defection (even though, in one-to-one encounters, it is the selfish individual who always wins). The ultimate result will be the replacement of selfish groups by cooperative groups.

Animals↗
PubMed1997

Glucose homeostasis with infinite gain: further lessons from the Daisyworld parable?

A major unresolved physiological problem is how the rate of hepatic glucose production is increased to match the increased rate of glucose utilization during exercise without a change in arterial blood glucose level. A homeostat with such capabilities is said to have infinite gain. Daisyworld is an imaginary planet orbiting a variable star. The only life is black and white daisies. Black daisies retain heat, slightly warming the planet; white daisies cool it. When the two types of daisies grow best at slightly different temperatures, variations in solar luminosity (over a wide range) cause the ratio of white:black daisies to vary in a manner that keeps the planetary temperature constant. This model therefore achieves infinite gain by having two opposing but interdependent controllers. Here we suggest that the pancreatic islet alpha- and beta-cells might act as black and white daisies. For the analogy to apply, glucagon and insulin must not only have opposing effects on the blood sugar concentration, but the secretion of the one has, at some quantum level, to be at the expense of the other. Electrical coupling between heterocellular groups of alpha- and beta-cells within the pancreatic islets suggests that this might indeed be the case. alpha-Cell activity must, furthermore, promote secretory activity in other alpha-cells; similarly with beta-cells. This is probably mediated via pancreastatin and gamma-amino butyric acid (GABA) which are paracrinically co-secreted with glucagon and insulin, respectively. alpha-Cell activity spreads (at the expense of beta-cell activity) when the blood glucose level is below set point, while beta-cell activity progressively replaces alpha-cell activity above set point. At set point changes in the ratio of alpha:beta-cell activity are inhibited.

Chromogranin A↗
PubMed1994

Koinophilia replaces random mating in populations subject to mutations with randomly varying fitnesses.

Koinophilia, the avoidance of sexual mates bearing strange phenotypic features, or displaying odd behaviour, would, if it evolved, profoundly influence the evolutionary process. A stochastic computer model was therefore devised to investigate the evolution of an initially rare koinophilic trait in panmictic populations, subject to mutations with randomly varying fitnesses. Individual genomes consisted of 50 genes. Mutations occurred at a rate of 0.005, 0.01 or 0.02 per gene per generation. The mean and maximum fitness of mutations could be varied, as could the proportion of beneficial mutations. The carriers of the koinophilic trait avoided, with adjustable degrees of intensity, mates displaying unusual phenotypic features (traits with population frequencies < 0.5); panmictic individuals mated randomly. The results show that koinophilia tends to replace panmixis whenever the preference for common phenotypic traits is strongly expressed, when few mutations are beneficial (1% instead of 10%), or when the maximum fitness of mutations is low (1.2 instead of 2.0). The mutation rate and mean fitness of mutations had only minor effects on the relative advantage of koinophilia.

Animals↗
PubMed1994

Koinophilia.

This paper is concerned with the evolution of the species phenotype (morphology and behaviour) when sexual organisms identify mutant traits by their unusual (or rare) appearance. Mate-seeking individuals are assumed, however, to have no means of distinguishing the occasional beneficial mutation from the others. We show that the resulting preference for mates with predominantly common traits (koinophilia) transforms the prevailing phenotype (as perceived by conspecifics) into an evolutionary stable strategy (ESS), as defined by Maynard-Smith (1974). This has far reaching evolutionary implications, permitting, in particular, the evolution of true "group adaptations". A subsidiary finding shows that koinophilia always has a substantial, immediate, selective advantage over panmixis, rendering koinophilia, itself, an ESS with respect to panmixis. This is particularly pronounced when the mutation rate is high, but beneficial mutations with high fitnesses are rare. The mean fitness of mutations has only a minor effect on the relative advantage of koinophilia.

Adaptation, Physiological↗
PubMed1994

Koinophilia stabilizes bi-gender sexual reproduction against asex in an unchanging environment.

Koinophilia, the tendency to choose mates with predominantly common phenotypic features, may be favourable because maladapted traits tend to have low frequencies. We used computer simulations to study competition between asexual and sexual reproduction, with and without koinophilia. The mutation process created new alleles, most of which were deleterious, but some small fraction was beneficial. With random mating, genderless sex (which does not suffer the two-fold cost of producing males) had a modest advantage over asex, while bi-gender sex was rapidly replaced by asex. In contrast, koinophilia allowed sex to persist, even when males represented half the population. The advantage of koinophilia was greatest when populations were large, the incidence of mildly disadvantageous mutations was high, and beneficial mutations were rare. Under these circumstances koinophilic bi-gender sexual reproduction resisted replacement by asexuals for over 10,000 generations, even when one sexual mutated into a parthenogen every generation. Thus, koinophilia may be an important factor maintaining sexual reproduction.

Animals↗
PubMed1994

Enhanced adipose tissue lipoprotein lipase activity in detrained rats: independent of changes in food intake.

Short-term detraining has been characterized by increased body mass and rapid body fat accretion. However, detraining has also been associated with increased food intake, especially in rats genetically predisposed to obesity. Thus, it has been difficult to separate refeeding effects from alterations resulting from the cessation of exercise training. In the present study, the in vitro activity of adipose tissue lipoprotein lipase (ATLPL) was measured in freely running wheel-trained rats and rats that had stopped training for 1, 2, or 3 days or 1 or 2 wk, respectively. Heparin-releasable ATLPL activity was measured at rest and after acute exhaustive exercise. Feeding efficiency (change in body mass/kJ ingested energy), fat pad mass, and adipocyte size were also measured. The rate of weight gain in 1- and 2-wk detrained rats was significantly higher than that of sedentary control or trained rats (P < 0.05). Feeding efficiency was also higher in 1-wk detrained rats than in all other groups (P < 0.005). However, food energy intake was not different between trained rats, 1- and 2-wk detrained rats, or sedentary control rats. ATLPL activity in all groups was highest after acute exhaustive exercise. ATLPL activity in 1-wk detrained rats was nearly threefold higher compared with that in trained rats (P < 0.005) and was not different from that of sedentary control rats. These results suggest that the cessation of exercise training causes an enhanced capacity for lipogenesis independent of changes in food energy intake or the acute effects of the last bout of exercise.

Adipocytes↗
PubMed1993

What is normal?

The distinction between normality and abnormality forms the basis of medical practice. However, these words appear to have no more precise meanings in medicine than they do in conversational English. At least five contradictory definitions are described in the literature, and are in simultaneous use in everyday practice. The apparently arbitrary manner in which these definitions are chosen to evaluate different phenomena effectively means that medicine operates without a definition: certain phenomena are normal (by decree, as it were), and others are not. Actions based on such an arbitrary system are, of necessity, haphazard. The adoption of a precise, rigorously acultural definition of normality would unquestionably admit medicine to full membership of the family of objective sciences.

Diagnosis↗
PubMed1992

No persistent effect of preweaning nutrition on postweaning food intake, feeding efficiency, or body energy stores in Long-Evans rats.

The purpose of this study was to determine the relative importance of pre- and postweaning nutrition on body mass, body fat, and feeding efficiency in Long-Evans rats up to a period of 18 weeks following weaning. Female rats were bred and pups were redistributed to form large (14-19 pups), normal (11-13 pups) and small (4 pups) litter groups. Weaned rats were housed as pairs (40 pairs) or singletons (n = 16) and fed either a mixed-fat diet (36.6% fat) or a standard chow diet (13.5% fat). Food intake, body mass, and feeding efficiency were measured at 4, 8, 12, and 18 weeks postweaning. Total body fat and depot fat pad mass were also measured at 18 weeks postweaning. At weaning, pups from small litters were fatter (p less than 0.001), and had a greater mass (p less than 0.03) than pups from large litters. There were no persistent effects of preweaning litter size after covarying for preweaning mass on body mass, and postweaning growth, food intake, feeding efficiency, or body fat accretion. Male rats ingesting the mixed-fat diet had a greater body mass (p less than 0.05), greater body fat accretion (p less than 0.008) and a higher feeding efficiency (p less than 0.001) than their chow-fed counterparts, despite an overall lower energy intake (p less than 0.05). Female rats ingesting the mixed-fat diet had a lower food energy intake (p less than 0.005) and a greater feeding efficiency (p less than 0.001) than chow-fed rats during the early postweaning period, only. Thus, postweaning nutrition may play a more important role in postweaning adult mass and depot fat in freely eating rats than early nutritional experiences.

Adipose Tissue↗
PubMed1991

Metabolic response to localized surgical fat removal in nonobese women.

Although suction lipectomy and dermolipectomy are common surgical procedures, the body's response to localized removal of fat and the long-term efficacy of these procedures remain controversial. Seven women who underwent liposuction or abdominoplasty were studied prior to surgery and between one and two months postoperatively. All patients were weight-stable prior to surgery and the reported daily food intake and nutrient composition of the diet did not change. The following parameters were measured: resting oxygen uptake (VO2), glucose-induced increment in VO2, anthropometry, and site-specific fat cell size. Fat samples were taken by needle aspiration from abdominal and femoral regions. Resting energy expenditure and the response to glucose feeding were not significantly different postoperatively. Furthermore, site-specific fat cell size did not change, nor were there any significant differences in the sum of four skinfold thicknesses. These results suggest that energy balance was not altered as a result of localized fat removal in previously weight-stable women. Thus, short-term follow-up suggests that surgical fat removal does not result in a compensatory change in metabolic efficiency or fat cell size and distribution in these weight-stable women. Therefore, this technique may prove effective for body contouring in nonobese women.

Abdomen↗
PubMed1991

Self-planned experimentation (SPEX) practical classes in physiology.

A new form of undergraduate physiology practical experience is described. Students make their acquaintance with the physiological apparatus in the usual manner. At the end of the afternoon each group of four students is allocated an item of equipment with which to perform a true investigative experiment of their own choice, in their own time, the results of which are to be presented 2 weeks later by a randomly chosen member of the group. Students may investigate any question that can be answered using the resources available to them without endangering themselves or their subjects. Marks are awarded for the planning of the experiment (i.e. choice of controls, etc.), the correctness of graphical presentation of the results, the appropriateness of the statistical analysis, and for the discussion. There are no penalties for negative or unexpected results.

Education, Medical, Undergraduate↗
PubMed1990

Koinophilia groups sexual creatures into species, promotes stasis, and stabilizes social behaviour.

In a population whose members' genomes are subject to degradation by random mutations, the heritable vigour of the most common phenotypes is unquestionable (though not necessarily optimal), and that of fringe individuals is always suspect. Natural selection will therefore support the evolution of an affinity for modal mates (i.e. koinophilia). The population's genetic make-up can then not readily be invaded by non-cryptic mutations. This imposes considerable phenotypic conservatism on sexually reproducing creatures, and inexorably canalizes them into sexually isolated, phenotypically distinct species. The model predicts, and the empiric data confirms, that the phenotypic gaps between largely monomorphic sexual species do not characterize the taxonomy of longstanding apomicts, where variation below the genus level is often continuous. The bias against the propagation of all forms of phenotypic novelty and non-conformity stabilizes social animals against selfish mutants, thus removing the barriers to the evolution of "group adaptations".

Adaptation, Biological↗
PubMed1990

Social mechanisms in the population genetics of Tay-Sachs and other lethal autosomal recessive diseases: a computer simulation model.

A computer simulation model was developed to study the effects of various feudal social customs on the incidence of lethal autosomal recessive genes. Populations of 500 individuals were created in which each person was characterized by sibship, genotype, and sex. The numbered sibships were sorted into numerical order. Each individual then sought a mate from 6 or 12 sibships on either side of his or her own sibship. The resulting couples were sorted in order of the husband's sibship number, after which the couples produced children in accordance with the prevailing birth rate. This ordering of sibships made the probability of a gene remaining in one locality higher than the probability of it drifting to distant localities. A lethal autosomal recessive gene was introduced into populations at a starting carrier rate of 10%. This fell after 20 generations to 2.54 +/- 0.17% (SEM) which was significantly less than the 5.00% carrier rate predicted by a deterministic model in which random mating occurred in an infinite population. The excessive loss of the lethal gene was caused by the high incidence of consanguineous marriages and by the occurrence of random inequalities in the distribution of the gene. The avoidance of sib marriages raised the final carrier frequency (3.28 +/- 0.19%) as did reproductive compensation (4.33 +/- 0.26%). The combination of the incest taboo and reproductive compensation raised the final carrier rate to 5.05 +/- 0.28%. It is concluded that the social factors which may have operated over a period of many centuries in the past have had a significant effect on the population genetics of lethal autosomal recessive genes.

Computer Simulation↗