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M Witten

Publications and source records attributed to M Witten.

45 records · Page 3Linked to original sources
PubMed1981

On the dynamics of abrin binding to receptor sites in normal and Epstein Barr Virus transformed lymphocyte cell cultures.

The effects of treatment with varying doses of abrin, a D-galactose binding lectin, on DNA an protein synthesis of normal and Epstein Barr Virus transformed lymphocytes has been investigated. Activation, stimulation, and relative toxicity factor indices are studied, as well as possible relationships between DNA and protein synthesis rates, as measured by simultaneous tritiated thymidine (3H-TdR) and 14C-leucine uptake. Studies of the 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 receptor site concentrations. This prediction is supported by SEM morphological differences. 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 receptors bound-EBV-lymphocyte needed to exert a biological influence lies in the interval 59,264 receptors/cell to 370.040 receptors/cell. Using a simple packing model, one can demonstrate that a theoretical estimate places the number of binding sites between 57,600 receptors/cell and 360,000 receptors/cell.

Abrin↗
PubMed1980

Some mathematics of recombination: evolution of complexity and genotypic modification in somatic cells - a possible model for aging and cancer effects.

A plausible discrete time model is proposed, in an effort to explain genotypic modificaton via genetic recombination. The model is used in an effort to explain the evolution of macromolecular complexity. By macromolecular complexity we mean the evolution of a more complex form of a given protein or enzyme from its less-complex ancestors. The model is also used to draw some conclusions concerning the utility of recombination events in aging and carcinogenesis.

Aging↗
PubMedDate not supplied

How square is the survival curve of a given species?

An investigator-independent parameter, the prolate rectangularity index kappa for describing the so-called rectangularity of biological population survival curves, is introduced, developed, and applied to realworld survival datasets. This new rectangularity parameter is constructed using an intrinsic time scaling that places the intrinsic inflection point time at a value of unity so that species populations may be compared independently of their extrinsic life span distributions. The analytical expressions for the prolate rectangularity index of the theoretical Gompertz and Weibull continuous models are obtained, as are numerical values of this index for discrete experimental population survival data sets from two dissimilar species with orders of magnitude difference in extrinsic life span range. The values of the parameter are also compared for populations of a single species having differing dietary regimens, and for human demographic populations at decade intervals in extrinsic chronological time during the current century. It is found that scaling time, using the survival inflection point, appreciably collapses extrinsic survival profile dispersion among similar populations and allows a more meaningful comparison of profiles among dissimilar populations. Using this method of scaling, demographic populations within the United States are seen to have rectangularity parameter values that have been slowly drifting during this century toward values indicating a higher degree of rectangularity. In recent decades, however, the trend appears to be stabilizing with kappa values indicating no approach towards the theoretical maximum rectangularity. This apparent submaximal stabilization of kappa supports a hypothesis of no genetically pre-determined maximum life span in human populations. Or, if such a maximum exists, we are not currently near it.

Animals↗
PubMedDate not supplied

Immunotoxicological effects of JP-8 jet fuel exposure.

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed (3-5). Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (e.g., physiology, cardiology, respiratory, etc.); e.g., the immune system. Significant changes in immune consequences, even if short-lived, may have serious consequences for the exposed host that may impinge affect susceptibility to infectious agents. Major alterations in immune function that are long-lasting may result in an increased likelihood of development and/or progression of cancer, as well as autoimmune diseases. In the current study mice were exposed for 1h/day for 7 days to varying concentrations of aerosolized JP-8 jet fuel to simulate occupational exposures. Twenty-four hours after the last exposure the mice were analyzed for effects on their immune systems. It was observed that even at exposure concentrations as low as 100 mg/m3 detrimental effects on the immune system occurred. Decreases in viable immune cell numbers and immune organ weights were found. Jet fuel exposure resulted in losses of different immune cell subpopulations depending upon the immune organ being examined. Further, JP-8 exposure resulted in significantly decreased immune function, as analyzed by mitogenesis assays. Suppressed immune function could not be overcome by the addition of exogenous growth factors known to stimulate immune function. Thus, short-term, low concentration exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure, as effects were seen at concentrations of jet fuel that did not evidence change in other biological systems. Such changes may have significant effects on the health of the exposed individual.

Administration, Inhalation↗
PubMedDate not supplied

Short-term exposure to JP-8 jet fuel results in long-term immunotoxicity.

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed. Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (i.e., physiology, cardiology, respiratory, etc.); e.g., the immune system. Previous studies have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system, which should have serious consequences for the exposed host in terms of susceptibility to infectious agents. If these alterations in immune function were long-lasting, it might also result in an increased likelihood of development and/or progression of cancer, as well as autoimmune disease. In the current study, mice were exposed for 1 h/day for 7 days to a moderate (1000 mg/m3) and a high (2500 mg/m3) concentration of aerosolized JP-8 jet fuel to stimulate occupational exposures. One to 28 days after the last exposure the mice were analyzed for effects of the exposure on their immune systems. It was observed that decrease in viable immune cell numbers and immune organ weights found at 24 h after exposure persisted for extended periods of time. Further, JP-8 exposure resulted in significantly decreased immune infection, as analyzed by mitogenesis assays, which persisted for up to 4 weeks post-exposure. Thus, short-term exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system, which were long-lasting and persistent. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure. Such long-term changes in immune status may have significant effects on the health of the exposed individual.

Aircraft↗
PubMedDate not supplied

Protection from JP-8 jet fuel induced immunotoxicity by administration of aerosolized substance P.

Chronic exposure to jet fuel has been shown to cause human liver dysfunction, emotional dysfunction, abnormal electroencephalograms, shortened attention spans, and decreased sensorimotor speed. The United States Air Force has decided to implement the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Exposure to potential environment toxicants such as JP-8 may have significant effects on host physiology. Previous studies in mice have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system; e.g., decreased viable immune cell numbers, decreased immune organ weights, and loss on immune function that persisted for extended periods of time (i.e., up to 4 weeks post-exposure). Previous studies have shown that JP-8 induced pulmonary dysfunction was associated with a decrease in levels of the neuropeptide substance P (SP) in lung lavage fluids. It was found that administration of aerosolized SP was able to protect exposed animals from such JP-8 induced pulmonary changes. In the current study, aerosolized SP was analyzed for its effects on JP-i induced immunotoxicity in exposed mice. It was observed that SP administration could protect JP-8 exposed animals from losses of viable immune cell numbers, but not losses in immune organ weights. Further, exposure of animals to SP inhibitors generally increased the immunotoxicity of JP-8 exposure. SP appeared to act on all immune cell populations equally as analyzed by flow cytometry, as no one immune cell population appeared to be preferentially protected by SP. Also, SP administration was capable of protecting JP-8 exposed animals from loss of immune function at all concentrations of JP-8 utilized (250-2500 mg/m3). Significantly, SP only needed to be administered for 15 minutes after JP-8 exposure, and was active at both 1 microM and 1 nM concentrations. Thus, SP administration appears to be a relatively simple and efficient means to reverse the immunotoxicity due to hydrocarbon exposure.

Aerosols↗
PubMedDate not supplied

Quantifying the concepts of rate and acceleration/deceleration of aging.

In this paper, we shall attempt to quantify the rather abstractly and ambiguously used concepts of acceleration of aging and rate or velocity of aging. The use of the phrase "rate of aging", in the gerontological literature, requires that we formalize the concepts so that they may be discussed in a uniform manner. We shall perform this formalization by means of an analogy with various similar concepts from the discipline of physics. This set of analogies leads, quite naturally, to some practical ways in which we may discuss the acceleration of aging. Additionally, these analogies allow us to introduce two forms of acceleration of aging; uniform and non-uniform acceleration. By uniform acceleration, we shall see that we mean an acceleration which is independent of the age of the individual in the population. That is, every individual in the population feels the same magnitude of acceleration, no matter what his age. Non-uniform acceleration is an acceleration which is age-dependent. We shall introduce the concepts of relative acceleration and fraction relative acceleration as a means of deciding whether a population is undergoing uniform or non-uniform acceleration. Finally, these new developments will be applied to C. elegans, to rat, and to C57BL/6J mouse experimental data.

Aging↗