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Biomedical subjects

J D Murray

Publications and source records attributed to J D Murray.

At least 19 recordsLinked to original sources
PubMed1992

Continuum model of fibroblast-driven wound contraction: inflammation-mediation.

We propose a mathematical model to aid the understanding of how events in wound healing are orchestrated to result in wound contraction. Ultimately, a validated model could provide a predictive means for enhancing or mitigating contraction as is appropriate for managing a particular wound. The complex nature of wound healing and the lack of a modeling framework which can account for both the relevant cell biology and biomechanics are major reasons for the absence of models to date. Here we adapt a model originally proposed by Murray and co-workers to show how cell traction forces can result in spatial patterns of cell aggregates since it offers a framework for understanding how traction exerted by wound fibroblasts drives wound contraction. Since it is a continuum model based on conservation laws which reflect assumed cell and tissue properties, it is readily extended to account for emerging understanding of the cell biology of wound healing and its relationship to inflammation. We consider various sets of assumed properties, based on current knowledge, within a base model of dermal wound healing and compare predictions of the rate and extent of wound contraction to published experimental results.

Extracellular Matrix↗
PubMed1992

Modelling coccidial infection in chickens: emphasis on vaccination by in-feed delivery of oocysts.

Trickle immunization of poultry by incorporating wildtype strains of coccidia in the feed has been shown to be an effective and practical means of controlling coccidiosis. Here we develop a mathematical model of the life cycle of Eimeria tenella and estimate the model parameters from extant experimental studies. Numerical solutions of the model compare well with experiment. The model provides quantitative estimates of the required trickle immunization hitherto only available after extensive time-consuming trials.

Animal Feed↗
PubMed1992

Analysis of dynamic and stationary pattern formation in the cell cortex.

We study a sol-gel mechanochemical model for cellular cytoplasm. Using conservation equations and a force balance equation, we derive equations for the sol-gel dynamics. Regular perturbation analysis suggests the growth of patterns which may be either dynamic or stationary, depending on parameter values. Nonlinear analysis, which indicates that these patterns remain bounded, is confirmed by numerically solving the mechanochemical equations. We use these analytical and numerical results to model two different biological problems: the dynamic formation of filopodia in nerve growth cones, and the growth of microvilli in epithelial cells.

Actins↗
PubMed1992

Mathematical models of wound healing in embryonic and adult epidermis.

Epidermal wound healing occurs by quite different mechanisms in embryos and adults. In the latter case, it has long been known that cells crawl inwards via lamellipodia to close the defect. In the embryonic system, recent evidence suggests that healing may be caused by a quite different mechanism, namely the contraction of a cable of filamentous actin at the wound edge. The authors use mathematical modelling to investigate both systems. A mechanical model for the initial formation of the actin cable in embryonic epidermal wounds is presented, which incorporates the important phenomenon of stress-induced microfilament alignment. Also discussed is a reaction-diffusion model for the healing of adult wounds subject to autoregulation of cell division. In both cases, the results suggest possible biological mechanisms for key aspects of the healing process.

Actins↗
PubMed1992

Sequential pattern formation in a model for skin morphogenesis.

During morphogenesis regular patterns often develop behind a frontier of pattern formation which travels across the prospective tissue. Here the authors consider the propagating patterns exhibited in a two-dimensional domain by a tissue interaction mechanochemical model for skin pattern formation. It is shown that the model can exhibit travelling waves of complex spatial pattern formation. Two alternative mechanisms that can produce such sequential patterning are presented. In particular, it is demonstrated that the specification of a simple quasi-one-dimensional pattern is all that is required to determine a complex two-dimensional pattern. Finally, the model solutions are related to actual pattern propagation during chick feather primordia initiation.

Animals↗
PubMed1992

Linear bone growth of oMT1a-oGH transgenic male mice.

Linear bone growth was studied in male mice possessing a controlled ovine metallothionein 1a promoter-ovine growth hormone (oMT1a-oGH) transgene. Transgene expression was activated at weaning by the addition of 25 mM zinc sulfate to drinking water; transgenic and control mice received the zinc supplementation. The ulna, humerus, and tibia were excised at 10-day intervals until 130 days from control and from mice hemizygous for oMT1a-oGH. Bones from mice overexpressing growth hormone (GH) were 11-20% longer than those from controls (P less than 0.01) at 130 days. Transgenic mice exhibited both an enhanced rate of bone growth and a growth period of greater duration, i.e., the ulna, tibia, and humerus from oMT1a-oGH mice grew at an accelerated rate for an additional 20-40 days relative to the same bones from control mice. The bones from both groups were characterized by isometric growth patterns. Genetic size scaling revealed that the observed differences in bone growth were directly related to the mature size of the bone, suggesting that the bones possess an inherent growth pattern that is followed even in the presence of elevated GH.

Aging↗
PubMed1992

Epidermal wound healing: the clinical implications of a simple mathematical model.

The role of biochemical regulation in the healing of epidermal wounds remains the subject of much biological debate. We have previously developed a mathematical model which focuses on the role of mitogenic autoregulation in reepithelialization (23-25). Here, we discuss some predictions of our model and their clinical relevance. We investigate both the effects of adding mitotic regulators to healing wounds and the dependence of healing time on wound shape. The latter study suggests a possible mechanism for the control of changes in wound shape during healing. The predictions we make are amenable to experimental verification, and suggest new ideas for experimental research.

Animals↗
PubMed1992

Effect of increased production of growth hormone on body composition in mice: transgenic versus control.

The body composition (water, fat, protein and ash) of male and female transgenic mice which had a sheep metallothionein 1a-sheep growth hormone fusion gene and their non-transgenic controls was determined at intervals from birth to 21 days of age (weaning) in 66 mice of each group, and in an additional 64 mice over the period 25 to 98 days of age. Overall 520 mice were analysed. Weaned mice were starved overnight prior to slaughter. Food was available ad libitum. and, after weaning, a zinc sulphate supplement was added to the drinking water to initiate expression of the transgene. Growth and body composition were similar in all groups before weaning. From 39 days of age, transgenic females became progressively heavier than corresponding controls, being 60% heavier at the end of the experiment. They contained less fat, more water and slightly less ash than did controls of the same live weight but similar amounts of protein. When examined on a fat-free basis, they had less protein and ash and more water than corresponding controls. Appropriate linear and quadratic regression equations are presented to describe the above relationships. Growth and body composition were more variable in transgenic males but, on average, similar to controls.

Adipose Tissue↗
PubMed1991

Pigmentation pattern formation on snakes.

We consider a cell-chemotaxis model mechanism for generating some of the common, simple and complex, patterns found on the skin of snakes. By investigating the pattern generation potential of the model we show that many of the more complex patterns might result from growth of the integument during the pattern formation process. We suggest that many of the diverse elaborate patterns on snakes, and other species, can be generated by a single mechanism if the time scale of the pattern process is commensurate with the time scale associated with significant embryonic growth.

Animals↗
PubMed1991

Mathematical analysis of a basic model for epidermal wound healing.

The stimuli for the increase in epidermal mitosis during wound healing are not fully known. We construct a mathematical model which suggests that biochemical regulation of mitosis is fundamental to the process, and that a single chemical with a simple regulatory effect can account for the healing of circular epidermal wounds. The numerical results of the model compare well with experimental data. We investigate the model analytically by making biologically relevant approximations. We then obtain travelling wave solutions which provide information about the accuracy of these approximations and clarify the roles of the various model parameters.

Animals↗
PubMed1991

Bifurcating spatially heterogeneous solutions in a chemotaxis model for biological pattern generation.

We consider a simple cell-chemotaxis model for spatial pattern formation on two-dimensional domains proposed by Oster and Murray (1989, J. exp. Zool. 251, 186-202). We determine finite-amplitude, steady-state, spatially heterogeneous solutions and study the effect of domain growth on the resulting patterns. We also investigate in-depth bifurcating solutions as the chemotactic parameter varies. This numerical study shows that this deceptively simple-chemotaxis model can produce a surprisingly rich spectrum of complex spatial patterns.

Animals↗
PubMed1991

Psychology and rural America. Current status and future directions.

Rural people constitute about one fourth of the U.S. population, and their special mental health needs have been largely neglected. For a variety of reasons psychologists have focused little attention on this group. Recent economic developments affecting agriculture, farm families, and rural communities have increased awareness of problems facing rural areas. Psychologists can respond to the unique challenges created by rural mental health needs through research on stress, psychopathology, and community well-being. Training programs should be encouraged to recognize rural concerns. Psychologists are needed to practice in rural areas and to help develop effective rural service models. They can also support the development of state and federal policies that address rural needs.

Community Mental Health Centers↗
PubMed1991

Synaptonemal complex analysis of hybrid cattle. II. Bos indicus x Bos taurus F1 and backcross hybrids.

The levels of meiotic chromosome pairing abnormalities observed in six Australian F1 Bos indicus x Bos taurus cattle crosses (mean = 23%) were significantly higher than those of the full-blood breeds (9%). The abnormal configurations in the F1 hybrids included partial pairing failure, multivalents, interlocks, and inversion pairing. Abnormal configurations were also present, but at lower frequency, in backcross hybrid bulls. The main types of abnormal configurations and the levels of XY-autosomal associations and autosomal asynapsis observed were unlikely to cause significant fertility problems in the hybrids.

Aneuploidy↗
PubMed1991

Synaptonemal complex analysis of hybrid cattle. III. Meiotic pairing mechanisms in F1 Brahman x Hereford hybrids.

The mechanisms of homologous chromosome pairing were studied in synaptonemal complex (SC) spreads of F1 Brahman (Bos indicus) x Hereford (Bos taurus) cattle. The most common SC abnormalities were bivalents with partial pairing failure and interlocks. While C-band polymorphisms could underlie most of the SC abnormalities observed in the full-blood cattle, other causes seem also to be contributing in the hybrids. The pattern of the abnormalities indicates that genic differences between the species were probably involved. Pachytene substaging data suggest that in some spreads, early pachytene bivalents with partial pairing failure may achieve complete synapsis or may be converted to interlocks by late pachytene.

Animals↗
PubMed1990

On the kinetics of suicide substrates.

We consider a realistic suicide substrate reaction which can be represented by four rate equations for the concentrations of the various molecules as functions of time. We present a general procedure to obtain accurate, approximate solutions analytically in terms of the rate equation parameters. This systematic technique provides more accurate approximations to the exact (numerical) solutions than other approximate methods which have been proposed based on a pseudo-steady state hypothesis.

Enzyme Inhibitors↗
PubMed1990

Models of epidermal wound healing.

The spreading of cells across the surface of an epidermal wound enables epidermal migration to be studied independently of the wound contraction that occurs in deeper wounds. In particular, the stimulus for the increase in epidermal mitosis during would healing is uncertain. Our modelling suggests that biochemical regulation of mitosis is fundamental to the process, and that a single chemical with a simple regulatory effect can account for the healing of circular epidermal wounds. The model results compare well with experimental data.

Cell Movement↗
PubMed1990

Size-dependent pigmentation-pattern formation in embryos of Alligator mississippiensis: time of initiation of pattern generation mechanism.

The pigmentation pattern of Alligator mississippiensis was examined. The number of white stripes on the dorsal side of embryos (stages 21-28) and hatchlings from eggs incubated at 30 degrees C (100% females) and 33 degrees C (100% males) was recorded. Total length, nape-rump length and tail length were recorded for each embryo and hatchling. The number of white stripes was affected by incubation temperature but not sex; hatchlings incubated at 33 degrees C had two more white stripes than those at 30 degrees C, despite being the same length. Five female hatchlings produced at 33 degrees C by manipulation of the temperature, had the same number of stripes as males that developed under the same incubation temperatures. The appearance of the pigmentation was accelerated in embryos incubated at 33 degrees C, occurring eight days earlier than at 30 degrees C. At the time just before the first signs of pigment deposition, embryos from 33 degrees C were longer than those at 30 degrees C. If the stripe formation is size dependent this explains why hatchlings at 33 degrees C have more stripes than hatchlings from 30 degrees C. The mechanism that produces the stripe patterns is unknown. We describe key elements a pattern formation mechanism must possess to produce such stripes and suggest a possible mechanism, based on cell movement driven by chemotaxis. We apply the mathematical model to dorsal patterning on A. mississippiensis. We show how length at pattern formation is the prime factor in determining stripe number and how the pattern can be formed in the observed anterior-posterior sequence. We present numerical simulations and show that the qualitative behaviour is consistent with the experimental results.

Alligators and Crocodiles↗