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Biomedical subjects

H M Lacker

Publications and source records attributed to H M Lacker.

8 recordsLinked to original sources

A gastric acid secretion model.

A theory of gastric acid production and self-protection is formulated mathematically and examined for clinical and experimental correlations, implications, and predictions using analytic and numerical techniques. In our model, gastric acid secretion in the stomach, as represented by an archetypal gastron, consists of two chambers, circulatory and luminal, connected by two different regions of ion exchange. The capillary circulation of the gastric mucosa is arranged in arterial-venous arcades which pass from the gastric glands up to the surface epithelial lining of the lumen; therefore the upstream region of the capillary chamber communicates with oxyntic cells, while the downstream region communicates with epithelial cells. Both cell types abut the gastric lumen. Ion currents across the upstream region are calculated from a steady-state oxyntic cell model with active ion transport, while the downstream ion fluxes are (facilitated) diffusion driven or secondarily active. Water transport is considered iso-osmotic. The steady-state model is solved in closed form for low gastric lumen pH. A wide variety of previously performed static and dynamic experiments on ion and CO2 transport in the gastric lumen and gastric blood supply are for the first time correlated with each other for an (at least) semiquantitative test of current concepts of gastric acid secretion and for the purpose of model verification. Agreement with the data is reported with a few outstanding and instructive exceptions. Model predictions and implications are also discussed.

Animals↗

Follicular development and ovulation in the marmoset monkey as determined by repeated laparoscopic examination.

This paper describes the course of follicular development in vivo in the marmoset monkey, the only anthropoid primate with a relatively high (2-4) and variable ovulation number. Results are presented in relation to predictions from a mathematical model of control of follicle selection and ovulation number. Repeated laparoscopic examinations during the follicular phase were conducted for 14 cycles. Ovulatory follicles were 1.0 mm (median) in diameter at Day 6 and could be distinguished from nonovulatory follicles by Day 8, at which point they were 2.0 mm in diameter. Ovulations were not synchronous; the most common observation 1-2 days after the estradiol peak was ovulation of one follicle but not the other. Examination of the course of follicular development within a cycle and the distribution of ovulation sites both supported predictions stemming from a mathematical model of follicle selection developed by Lacker et al. [Biol Reprod 1987; 37:570-580]. Specific findings were the following: 1) Variations in patterns of follicle growth within a cycle resembled those generated by the model; in 64% of cycles, the 2-3 ovulatory follicles grew at similar rates. However, in 36% of cycles, ovulatory follicles displayed disparate rates of growth. 2) An examination of the distribution of ovulation sites (right versus left) revealed no significant difference from a binomial distribution, suggesting the likelihood that interovarian (rather than intraovarian) factors control this distribution.

Animals↗

A "give" in tension and sarcomere dynamics in cardiac muscle relaxation.

Isometric relaxation in cardiac sarcomeres is characterised by an early, very slow phase of tension fall which is terminated by a 'give' in tension. A 'give' which occurs during relaxation in cardiac muscle can not be attributed to decrease in myofilament overlap. After the 'give' asynchronous motion occurs between sarcomeres, but the duration and extent of their displacement is limited. Intriguingly, the effect of isotonic displacements on the early fall in the velocity of sarcomere shortening indicates that an internal resistance increases near the peak of contraction. The complex shape of the sarcomere's complete force-velocity relation, with lengthening motions in particular, was consistent with an idealized model of cross-bridge cycling. The sarcomere's resistance to stretch is high at low velocity, but it diminishes to reveal yielding at larger velocities. Relative to tension, the resistance to yielding does not decrease during relaxation, and it may actually increase. The decay of isometric tension after a controlled stretch also slows during relaxation. Consequently, cycling slows in those cross-bridges which form (or persist but produce less force) later in contraction. Changes in cross-bridge properties may restrict sarcomere shortening, prolong activation, but promote a disequilibrium which favors rapid relaxation in cardiac muscle.

Animals↗

A theory of follicle selection: I. Hypotheses and examples.

A theory of follicle selection is developed in which all follicles, ovulatory and atretic, inherit the same developmental plan for responding to circulating concentrations of estradiol and gonadotropins. In the model, this plan is represented by a maturation surface that determines the rate of follicle growth as a function of follicle maturity and circulating hormone concentration. Examples of maturation surfaces are constructed for single and multiple spontaneous ovulators. When model follicles are activated from the reserve pool at random times, spontaneous and coordinated cycles of maturation develop in which the number of ovulatory follicles is controlled within a small and predictable range. For a given maturation surface, this range is nearly independent of the number of follicles in the interacting population, their activation times, and their initial maturities. The theory is therefore consistent with Lipschütz's Law of Follicular Constancy. The theory can account for certain statistical effects that occur with age on the timing of ovulation and the control of ovulation number. Maturation surfaces are also constructed that exhibit spontaneous transitions from cyclic to steady anovulatory behavior. The theory predicts an important regulatory role for atretic follicles in controlling both the timing of maturation and the number of follicles that reach ovulatory maturity.

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A theory of follicle selection: II. Computer simulation of estradiol administration in the primate.

A theory of follicle selection (Lacker, 1981) is tested in the primate by simulating the effects of estradiol administration at different times, strengths, and durations during the follicular phase of the menstrual cycle (Clark et al., 1981; Zeleznik, 1981; Dierschke et al., 1985). The theory can account for the observed atretogenic effects of circulating estradiol on follicle development including full, partial, and delayed atresia of the dominant follicle (Dierschke et al., 1985) and can explain why similar estradiol doses achieve different qualitative effects when given at different times during the cycle. The theory predicts that recovery from early atresia may be possible, and it can also account for the loss of control in the number of maturing follicles that has been observed when estradiol antibodies are given in the midfollicular phase (Zeleznik et al., 1985). These results support the hypothesis that the selection mechanism in the primate is a consequence of feedback involving an essentially equipotent follicle population interacting through circulating estradiol and pituitary gonadotropins. A quantitative test of the theory awaits experimental identification of the maturation surfaces that are predicted by it. An experimental design for this purpose is proposed.

Animals↗

Experimental evidence supporting a mathematical theory of the physiological mechanism regulating follicle development and ovulation number.

In higher vertebrates, follicular development is regulated so that the number of follicles that periodically mature and ovulate is controlled within a narrow range. Lacker has proposed a simple mathematical model of follicle development that can account for the regulation of ovulation number. To support the assumption of the theory that follicle interactions are mediated by estradiol acting as a chemical messenger to communicate follicular maturity to the pituitary and other follicles, we have presented data to demonstrate that in the rabbit physiological concentrations of circulating estradiol inhibit follicle maturation. Implants containing estradiol were placed subcutaneously after surgical rupture of the existing follicles that were 1 mm in diameter or larger. Serum estradiol concentrations were maintained near physiological concentrations by the implants. Concentrations of circulating estradiol were 74 +/- 5.7 pg/ml in the untreated groups, whereas the concentrations with the implants were increased by approximately 50 pg/ml/implant over this basal concentration with a range of 100-300 pg/ml. In the control groups, the average number of follicles before surgical rupture was 27 +/- 2.9 and there was no significant difference (p greater than 0.05) in the number of follicles, 26 +/- 1.9, three days after follicle rupture. The follicles ranged in size from 1 mm to 4 mm, and only those over 3 mm were considered mature. In the first group of animals with implants, the total number of follicles before surgery was 19 +/- 3; three days after follicle rupture, the number of follicles was only 9 +/- 1.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of ovulation number in mammals. A follicle interaction law that controls maturation.

The assumption that developing follicles communicate through circulating hormones has been used to obtain a class of interaction laws that describe follicle growth. A specific member of this class has been shown to control ovulation number. Although all interacting follicles obey the same growth law and are given initial maturities that are chosen at random from a uniform distribution, ovulatory and atretic follicles emerge. Changing the parameters in the growth law can alter the most probable ovulation number values, anovulatory states are also admitted as possible solutions of the growth law. The behavior of the model is examined for interacting follicle populations of different size. Methods are suggested for identifying growth laws in particular mammals. These can be used to test the model from experimental data.

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