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Biomedical subjects

R B Martin

Publications and source records attributed to R B Martin.

At least 19 recordsLinked to original sources
PubMed1992

Cooperative proton and calcium binding by sarcoplasmic reticulum ATPase.

The classic work on binding of calcium to CaATPase is analyzed by an objective non-linear least squares procedure of 74 data points over six pH values. Binding of two calciums to the basic form of the sites occurs with an equilibrium stability constant product of log K1K2 = 13.2. Owing to competition from protons, this value drops in acidic and neutral solutions, becoming, for example, 11.9 at pH 6.8. Binding of the two calciums is so strongly cooperative that its extent is difficult to estimate reliably; there is very little of the one calcium species. Two protons are also bound cooperatively to the calcium sites. In solutions of calcium free protein, at pH less than 7.6 the predominant species holds two protons at the calcium sites, while at greater pH the dominant species bears no protons; there is very little of the intermediate one proton species. The analysis also reveals the likely presence of a small, less than statistical, amount of a ternary complex bearing one calcium and one proton.

Adenosine Triphosphatases↗
PubMed1992

Aluminium speciation in biology.

Before we can understand the role of Al3+ in living organisms we need to learn how it interacts with molecules found in biological systems. The only aluminium oxidation state in biology is 3+. In aqueous solutions there are only two main Al(III) species: the hexahydrate Al3+ at pH < 5.5 and the tetrahedral aluminate at pH > 6.2. In the blood plasma, citrate is the main small molecule carrier and transferrin the main protein carrier of Al3+. In fluids where the concentrations of these two ligands are low, nucleoside di- and triphosphates become Al3+ binders. Under these conditions Al3+ easily displaces Mg2+ from nucleotides. When all three classes of ligands are at low concentrations, catecholamines become likely Al3+ binders. Double-helical DNA binds Al3+ weakly and under no conditions should it compete with other ligands. Al(III) in the cell nucleus probably binds to nucleotides or phosphorylated proteins. Al3+ undergoes ligand exchange much more slowly than most metal ions: 10(5) times slower than Mg2+.

Aluminum↗
PubMed1992

Optimal control of tumor size used to maximize survival time when cells are resistant to chemotherapy.

The high failure rates encountered in the chemotherapy of some cancers suggest that drug resistance is a common phenomenon. In the current study, the tumor burden during therapy is used to slow the growth of the drug-resistant cells, thereby maximizing the survival time of the host. Three types of tumor growth model are investigated--Gompertz, logistic, and exponential. For each model, feedback controls are constructed that specify the optimal tumor mass as a function of the size of the resistant subpopulation. For exponential and logistic tumor growth, the tumor burden during therapy is shown to have little impact upon survival time. When the tumor is in Gompertz growth, therapies maintaining a large tumor burden double and sometimes triple the survival time under aggressive therapies. Aggressive therapies aim for a rapid reduction in the sensitive cell subpopulation. These conclusions are not dependent upon the values of the model constants that determine the mass of resistant cells. Since treatments maintaining a high tumor burden are optimal for Gompertz tumor growth and close to optimal for exponential and logistic tumor growth, it may no longer be necessary to know the growth characteristics of a tumor to schedule anticancer drugs.

Animals↗
PubMed1992

Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells.

Recent clinical trials have shown that for some cancers, high-intensity alternating chemotherapy does not significantly improve either survival times or response rates compared with nonalternating therapy. The current study uses optimal control to determine the best way to treat a tumor that contains drug-resistant cells that cannot be destroyed. The delivery of two non-cross-resistant chemotherapeutic agents is limited by bounds on the drug concentration and the dose intensity. This ensures that the drug toxicity stays within a tolerable range. The aim of the therapy is to maximize the host survival time, defined as the time over which the tumor burden can be kept below a fixed bound. The model is posed as a free terminal time, optimal parameter selection problem in which the constraints are continuously parametrized by time and the number of courses of therapy is free to vary. New theory is developed so that the optimal parameter selection problem can be solved as a sequence of fixed terminal time problems using existing optimal control software. Numerical simulations of Gompertz tumor growth showed that a treatment maintaining a high tumor burden doubled and sometimes tripled with survival time under aggressive therapy. When these simulations were repeated using exponential and logistic tumor growth models, the tumor burden during treatment had little influence upon survival time. In all simulations, survival time was not extended by delivering the anticancer drugs concurrently instead of staggering the treatment arms.

Animals↗
PubMed1992

A worst-case optimal parameter selection model of cancer chemotherapy.

An optimal parameter selection model of cancer chemotherapy in which two system parameters are unknown is formulated as a worst-case optimal parameter selection model. The model assumes that the unknown parameters lie within a known set. The system constraints must be satisfied over this entire set, and the objective function minimized in the worst case. The continuous dependence of the objective function and the system constraints upon the unknown parameters can be removed, making a numerical solution tractable. For the data considered it is proven that a cure is impossible no matter what the values of the unknown parameters in the parameter set. The optimal policy is shown to be relatively low dose intensity for the majority of the treatment, with the remaining drug delivered towards the end of the treatment interval.

Humans↗
PubMed1992

Histological features of the dorsal cortex of the third metacarpal bone mid-diaphysis during postnatal growth in thoroughbred horses.

The dorsal cortex of the equine third metacarpal mid-diaphyseal bone was characterised during growth by the histological and microradiographic examination of specimens from 30 horses ranging in age from 2 months to 8 y. Bone from horses aged less than 6 months was characterised by rapid periosteal apposition of circumferential trabeculae of woven bone that were next connected by radial trabeculae to the parent cortex. Deposition of lamellar bone on the inner trabecular surfaces resulted in rows of primary osteons. Replacement of primary bone occurred only after 4 months of age and preferentially in the woven interstitial bone separating rows of primary osteons formed in the postnatal periosteal cortex. Resorption cavities and incompletely filled secondary osteons characterised bone of 1 and 2-y-old horses. Bone from horses older than 3 y contained several generations of secondary osteons, fewer resorption spaces and incompletely filled osteons, and had a greater portion of circumferentially oriented collagen fibres than bone from younger horses. Bone from horses older than 5 y had large resorption cavities characterised by irregular boundaries. We propose that the process of periosteal bone tissue apposition observed in growing foals be called 'saltatory primary osteonal bone formation' and that this process results in faster cortical expansion and larger total surface area for bone deposition than circumferential lamellar, simple primary osteonal, and plexiform mechanisms of periosteal bone formation. We speculate that bone from 1 and 2-y-old horses would be more susceptible to fatigue microdamage resulting from compressive loads because of high porosity, few completed secondary osteons and low proportion of circumferentially oriented collagen fibres.

Aging↗
PubMed1991

The assessment of involvement in role playing.

Two experiments (N = 169) focused on involvement in role playing. Subjects rated their level of involvement after each enactment; in addition, a probe procedure was used with prompts, increasingly disparate from the content of the role play. In the first experiment, subjects role played an anger of sad scenario; both measures of involvement correlated with emotional response, but were not correlated with each other. In the second experiment, involvement was manipulated experimentally; both measures varied as expected with the manipulation.

Adult↗
PubMed1991

Determinants of the mechanical properties of bones.

The mechanical properties of bones are governed by the same principles as those of man-made load-bearing structures, but the organism is able to adapt its bone structure to changes in skeletal loading. In this overview of the determinants of the strength and stiffness of bone, a continuum approach has been taken, in which the behavior of a macroscopic structure depends on its shape and size, and on the mechanical properties of the material within. The latter are assumed to depend on the composition (porosity and mineralization) and organization (trabecular or cortical bone architecture, collagen fiber orientation, fatigue damage) of the bone. The effects of each of these factors are reviewed. Also, the possible means of non-invasively estimating the strength or other mechanical properties of a bone are reviewed, including quantitative computed tomography, photon absorptiometry, and ultrasonic measurements. The best estimates of strength have been obtained with photon absorptiometry and computed tomography, which at best are capable of accounting for 90% of the strength variability in a simple in vitro test, but results from different laboratories have been highly variable.

Animals↗
PubMed1991

Relationships between marrow fat and bone turnover in ovariectomized and intact rats.

It is known that marrow fat content increases in a variety of osteoporoses. This study sought to clarify this phenomenon by combining bone and marrow histomorphometry, and to determine (1) whether the marrow fat increase follows or precedes diminishment of bone volume, and (2) whether the increase in fat volume is due to adipocyte growth or proliferation. The relationship between marrow fat content and bone turnover was studied in the metaphysis and epiphysis of the proximal tibia in 20 ovariectomized and 20 intact 200 gm Sprague-Dawley rats. The results were examined after one and three months. The epiphysis had greater trabecular bone volume than the metaphysis. The metaphysis exhibited a decrease in bone volume with time; the epiphysis did not. Following ovariectomy, the bone volume diminished twice as much in the metaphysis as in the epiphysis. In the epiphysis, as bone volume fraction fell following ovariectomy, the vacated space was filled by both hemopoietic and adipose tissue. In the metaphysis, space-filling was time-dependent: hemopoietic tissue at one month and adipose tissue at three months. Marrow fat content increased with both time and ovariectomy in the metaphysis, but only with time in the epiphysis. Thus, marrow fat increased after bone volume began to decline in the metaphysis, and not at all in the epiphysis. Ovariectomy increased erosion surface in both the epiphysis and the metaphysis, but bone formation rate was increased only in the epiphysis. There was a reciprocal relationship between marrow fat content and bone formation rate.

Adipose Tissue↗
PubMed1991

On the significance of remodeling space and activation rate changes in bone remodeling.

This paper quantifies the relative contributions of the remodeling space and the accumulation of Haversian canals to bone porosity at various ages. It also examines the importance of variations in the rate of bone remodeling that occur during growth and aging, and as a result of trauma and disease. The dependence of the remodeling space (cavities due to resorbing, reversing, and refilling BMUs) and the Haversian canal components of porosity on the Basic Multicellular Unit (BMU) activation frequency are mathematically formulated. A graph is developed using data for the cortex of the human rib which shows the extent to which porosity is primarily due to the remodeling space in children, and to accumulated Haversian canals in adults. It is shown that the diminution of activation frequency between birth and age 35 contributes to the concurrent increase in bone volume fraction, and the increase in activation frequency after age 35 contributes to the subsequent decline of bone volume fraction. An equation is derived for determining the time rate of change of activation frequency using two fluorochrome labels.

Aging↗
PubMed1991

Biomechanical testing of new and old fixation devices for vertical shear fractures of the pelvis.

Malgaigne fractures of the pelvis have been treated with many different methods of fixation. We developed a plate for use on the anterior aspect of the sacroiliac (SI) joint using information obtained from cadaveric dissections and computed tomography (CT) scans of male (50) and female (50) pelvises. We tested each of six pelvises in the Instron, with five different fixation systems. Our results showed that the weakest system was the anterior quadrilateral frame plus two symphyseal plates. When comparing three posterior screws with the SI joint plate, the difference was not statistically significant. However, in both of these systems, a second symphyseal plate added to the overall stability.

Biomechanical Phenomena↗
PubMed1990

Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs.

It was previously shown that 11 months after ovariectomy the volume fraction of trabecular bone in the spine and 11th rib medullary canal of Beagle dogs (6 control, 9 ovariectomized) was significantly reduced. In this paper it is shown that these changes are accompanied by increased marrow fat volume in the 11th rib (59.0 +/- 9.5% vs. 44.3 +/- 10.0%). Conversely, the volume fraction of functional (hematopoietic) cells in the marrow was reduced by ovariectomy. Additionally, variations in marrow fat volume were tested for correlation with 22 other variables pertinent to bone physiology. Marrow fat volume was significantly positively correlated with serum osteocalcin, rib trabecular bone porosity, rib cross-sectional area, and gains in body weight. It was negatively correlated with serum estrogen concentrations and the extent of rib trabecular surfaces labeled with tetracycline.

Adipose Tissue↗
PubMed1990

Linear calibration of radiographic mineral density using video-digitizing methods.

Radiographic images can provide quantitative as well as qualitative information if they are subjected to densitometric analysis. Using modern video-digitizing techniques, such densitometry can be readily accomplished using relatively inexpensive computer systems. However, such analyses are made more difficult by the fact that the density values read from the radiography have a complex, nonlinear relationship to bone mineral content. This article derives the relationship between these variables from the nature of the intermediate physical processes, and presents a simple mathematical method for obtaining a linear calibration function using a step wedge or other standard.

Animals↗
PubMed1990

A mathematical model of cancer chemotherapy with an optimal selection of parameters.

An optimal parameter selection model of cancer chemotherapy is presented which describes the treatment of a tumor over a fixed period of time by the repeated administration of a single drug. The drug is delivered at evenly spaced intervals over the treatment period at doses to be selected by the model. The model constructs a regimen that both minimizes the tumor population at the end of the treatment and satisfies constraints on the drug toxicity and intermediate tumor size. Numerical solutions show that an optimal regimen withholds the bulk of the doses until the end of the treatment period. When a drug used is of either moderate or low effectiveness, an optimal regimen is superior to a schedule that delivers all of the drug at the beginning of the treatment. This study questions whether the current method for the administration of chemotherapy is optimal and suggests that alternative regimens should be considered.

Antineoplastic Agents↗
PubMed1990

Interlocking femoral components for revision arthroplasty with allografts.

The use of interlocking screws has been advocated to fix major proximal femoral allografts to femoral prostheses. This study examines the effect of interlocking screws on strength of the component. Model femoral components were tested in axial compression. Drilling one hole diagonally (lateral to medial), drilling one hole anterior to posterior, or drilling one diagonal hole plus one anterior-to-posterior hole did not significantly decrease failure load compared to controls with no holes. However, two diagonal holes or horizontal, medial-to-lateral holes were weaker. Four cases have been done with proximal femoral allografts fixed to porous-coated femoral components with proximal and distal interlocking screws. Initial results in these cases are good.

Adult↗
PubMed1990

Emotional coping, age, and physical disorder.

Traditional ideas suggest that emotional expression is healthy, but empirical support for this position is mixed. Adult subjects participated in a telephone interview to examine the relationships among age, emotional coping (ie, laughter and crying), physical disorder, sex, and income level. Results indicated that cry-coping in women and in low-income participants was associated with increased disorder as age increased. Humor-coping had no relationship to physical disorder across the adult lifespan. These results indicate that emotional weeping does play a role in the prediction of physical disorder, especially in certain groups. In the future, researchers need to concentrate on more subtle physiological effects as well as on the psychological and social consequences of emotional expression.

Adaptation, Psychological↗
PubMed1990

The physiological and psychological effects of the expression and inhibition of emotion.

Previous work has indicated that humor enhances immunity, but the immunological effects of overt crying have not been studied. Thirty-nine women viewed sad and humorous videotapes and either inhibited or expressed overt expressions of laughter and weeping; these were observed and timed. Moods and immunity (S-IgA) were repeatedly measured. The humorous stimulus resulted in improved immunity, regardless of the overt laughter expressed; overt crying was immunosuppressive, whereas the inhibition of weeping in the context of the same sad stimulus was not. Moods were more negative following the sad stimulus and in the expression condition. The results with respect to humor are consistent with previous research; the immunosuppressive effect of overt crying is discussed in the context of various types of crying that may have different effects.

Adaptation, Psychological↗