PubMed Health⌕ Search

Biomedical subjects

M Witten

Publications and source records attributed to M Witten.

At least 37 records · Page 2Linked to original sources
PubMed1989

Modeling of the aging-cancer interface: some thoughts on a complex biological dynamics.

Major US demographers predict that, by the year 2010, the United States will have attained zero population growth. They further predict that, by that time, more than half the U.S. population will be over the age of 40. Along with this dynamic change in the underlying age structure of the population comes an increasing body of evidence which supports the correlation between chronological age of the host and incidence of a variety of human cancers. Not only does cancer affect the older age group in a disproportionate manner but, as we have already noted, our nation's number of older individuals is increasing. In 1900, the number of individuals over 65 years of age was 3.1 million. By 2030 this number is expected to reach 55 million. Hence, there will be an increasing need for cancer treatment and cancer care among the older segment of the population. This chapter addresses some of the issues of the modeling and the simulation of the interplay of aging normal tissues and cancer processes. We will illustrate some simply preliminary results and will show how these might be extended to address some of the more complex questions arising in this intriguing interface.

Aging↗
PubMed1988

A return to time, cells, systems, and aging: V. Further thoughts on Gompertzian survival dynamics--the geriatric years.

In this paper, I attempt to address the problem of how to model the survival curve in the later lifespan years; the geriatric years. I present a new general model for a three group population in which the first group represents early life failure (neonatal failure), the second group represents the classical "Gompertzian failure", and the third group represents the later life failure or geriatric failure. Theoretical results are compared to the known biological data. It is demonstrated that this three group model embeds, within itself, a greater variety of the known biological survival dynamics. In particular, this new model resolves some of these issues concerning the failure of the pure Gompertzian to model the later life (geriatric) survival distribution.

Adolescent↗
PubMed1986

A return to time, cells, systems, and aging: IV. Further thoughts on Gompertzian survival dynamics--the neonatal years.

In this paper, I attempt to address the problem of how to model the survival curve in the early lifespan years; the neonatal years. I present a general model for a two group population in which the first group represents early stage failure and the second group represents the classical Gompertzian failure. After calculating the instantaneous failure rate for this population, I compare it to the single group Gompertzian with log-linear instantaneous failure rate. The theoretical results are then compared to the known biological data. It is demonstrated that this new model embeds, within itself, a variety of the known biological survival dynamics.

Adolescent↗
PubMed1985

A return to time, cells, systems, and aging: III. Gompertzian models of biological aging and some possible roles for critical elements.

In this paper, I continue my investigation into the modeling of senescence in biological hierarchies. Making use of my previous discussion on non-reestablishable biological components, I derive a mathematical model which has Gompertzian-like dynamics. I show how this model may be approximated, in certain instances, by a Gompertzian equation. I then demonstrate how our approach yields a biological interpretation for the parameters in the Gompertzian equation. I then demonstrate how changes in the parameter values may be interpreted in light of the biology. Subsequently, I review the literature on the allometry of aging, and I demonstrate how my reliability model may be used to obtain--in a qualitative manner--some of the lifespan curves found in the literature. I close my discussion by constructing a more complex reliability model which incorporates the deterministic failure of biological components with stochastic aspects of senescence.

Aging↗
PubMed1984

Biological populations obeying difference equations: the effects of stochastic perturbation.

We consider the effects of stochastic perturbation in various components of a finite difference model arising in population biology. In particular, we examine how fluctuation in the net reproductive rate can effect the population dynamics of the system. Computer simulation and some elementary analyses bear out the result that, in the mean, the stochastic dynamics will behave like the deterministic dynamics. This study also answers a currently unanswered conjecture published by the first author in 1977.

Animals↗
PubMed1984

A return to time, cells, systems and aging: II. Relational and reliability theoretic approaches to the study of senescence in living systems.

In this paper, we approach the problem of attempting to understand senescence by understanding the complexity and hierarchical structure of mammalian organisms. To do this, we make use of some concepts from abstract relational biology; in particular, graph theory. We subsequently utilize these concepts to develop the idea of an irreplaceable element in a mammalian system. We then make use of these elements, and some concepts from reliability theory, to show how senescence processes in mammalian systems may be related to the failure of a critical number of irreplaceable elements. Finally, we show how we may derive formulas for the expected number of elements which fail by a given time, and how this time is related to actual lifespan and expected lifespan of the organism. In particular, we relate this to some recent work by Cutler on the evolution of longevity.

Aging↗
PubMed1982

DNA and protein synthesis in normal and transformed lymphocytes exposed to abrin.

The dose dependent effects of abrin, a toxic D-galactose binding plant lectin, on 3H-TdR and 14C-leucine uptake are studied in normal and Epstein Barr Virus (EBV) transformed lymphocyte cultures. Results show that while abrin is highly toxic to both the DNA and protein synthesis in EBV lymphocytes, some toxicity to the normal cells is also seen. It is postulated that lymphocyte DNA synthesis is affected by ribosomal shutdown induced by the abrin.

Abrin↗
PubMed1982

Studies on the toxicity and binding kinetics of abrin in normal and Epstein-Barr virus-transformed lymphocyte culture-I. Experimental results - 4.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein-Barr virus (EBV)-transformed lymphocytes have been previously investigated. Using data on EBV-transformed lymphocyte cell density as a function of both time and dose of abrin, the authors introduced the concept of self- and cross-coupling metabolic variables as a means of understanding how abrin affected DNA and protein uptake. In this paper, the self-coupling constant is studied in more detail and the relationship between DNA and protein synthesis is further expanded. We find that there is a significant linear relationship between DNA and protein synthesis in normal lymphocyte culture as measured by abrin interaction in the culture. We further find that there is a much stronger relationship between these variables in EBV-transformed lymphocyte culture. This relationship is further examined, and possible analytic equations are expressed.

Abrin↗
PubMed1981

Modeling cellular systems and aging processes: I. Mathematics of cell system models-a review.

A review of the literature on mathematical models of populations of cellular systems is presented. Continuous, discrete, and stochastic models are presented in a semihistorical manner as a prelude to answering the question of how to model an asynchronously dividing cellular system. This analysis is then broadened, in an attempt to broach the more general question of modeling the distribution of a set or collection of cell properties through an asynchronously dividing cellular system. Such properties might be cell motility, cell cycle length, time to mitosis, or number of epigenetic particles. It is shown that one fruitful approach to this modeling question is a coupled continuous-probabilistic model. The ramifications of this type of formalism are discussed.

Aging↗
PubMed1981

The role of dietary carbohydrates in muscle glycogen resynthesis after strenuous running.

This study examined the effect of the type, amount, and the frequency of feeding of carbohydrates on muscle glycogen resynthesis after running. Trained male runners performed a 16.1 km run at 80% VO2 max to decrease gastrocnemius glycogen levels. A complex or simple carbohydrate diet (approximately 3000 kcal) resulted in similar muscle glycogen levels 24 h after exercise. Forty-eight hours after exercise the complex carbohydrate diet resulted in significantly higher (p less than 0.05) muscle glycogen levels. Consuming increasing amounts of carbohydrate, between 88 to 648 g carbohydrate/day, resulted in increasingly larger amounts of muscle glycogen resynthesis (24 h) after exercise. Frequent feedings of a high carbohydrate diet did not enhance muscle glycogen synthesis when compared to equal amounts of carbohydrates in two meals. It appears that muscle glycogen can be normalized between daily strenuous running activity.

Adult↗
PubMed1981

Studies on the toxicity and binding kinetics of abrin in normal and Epstein Barr virus-transformed lymphocyte culture-I: experimental results - 1.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein Barr virus-transformed lymphocytes have been investigated. Activation, stimulation and relative toxicity factor indices are studied as well as possible relationships between the DNA and protein synthesis rates, as measured by simultaneous 3H-TdR and 14C-leucine uptake.

Abrin↗
PubMed1981

Studies on toxicity and binding kinetics of abrin in normal and Epstein Barr virus-transformed lymphocyte culture-I: experimental results - 2.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein Barr virus-transformed lymphocytes have been investigated. Studies of activation and stimulation indices, as well as two new indices; the metabolic self and cross-coupling indices, lead to the prediction that there are three morphologically distinct subpopulations of EBV-transformed lymphocytes with different abrin binding site numbers. This conclusion is supported by SEM morphological differences.

Abrin↗
PubMed1981

Studies on the toxicity and binding kinetics of abrin in normal and Epstein Barr virus-transformed lymphocyte culture-I: experimental results - 3.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA and protein synthesis of normal and Epstein Barr virus-transformed lymphocytes have been investigated. Using data on EBV-transformed lymphocyte cell density as a function of time and dose of abrin, one can demonstrate that the mean number of sites bound/EBV-lymphocyte needed to exert a biological influence upon the cell DNA synthesis lies between 59,264 and 370,000 sites/cell. Using a simple packing model, one can demonstrate that a theoretical estimate places the number of binding sites between 57,600 and 360,000 sites/cells.

Abrin↗