Biomedical subjects

T E Orr

Publications and source records attributed to T E Orr.

At least 19 recordsLinked to original sources

PubMed1992

Skeletal development and bone functional adaptation.

The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The results of many previous computer models for endochondral ossification and bone modeling and remodeling are reviewed. These studies support the view that simple stress-related mathematical algorithms or "construction rules" can be used to emulate normal skeletal development and architectural construction. Such mathematical rules presumably represent the net result of biophysical phenomena influencing cell metabolism and biosynthetic activity. These rules are also successful in describing the adaptation of adult bone to changes in tissue stresses. The findings suggest that stress-related functional adaptation in mature bones may be merely the adult manifestation of the same mechanical construction rules that guide and constrain normal development.

Adaptation, Physiological↗

PubMed1992

Role of glucocorticoids in the stress-induced suppression of testicular steroidogenesis in adult male rats.

We have examined the role of glucocorticoids in the stress-induced inhibition of testicular steroidogenesis. Immobilization (3 hr) reduced plasma testosterone (T) levels to 24% of control values but did not affect plasma LH levels. This reduction was partially reversed by in vivo injections of the antiglucocorticoid, RU486, prior to the stress session at a dose of 10 mg/kg BW, but not at 1.0 or 50 mg/kg BW. Stressed rats that were treated with 10 mg/kg BW RU486 had twofold higher plasma T levels than vehicle-treated stressed animals. Injections of RU486 did not affect plasma LH levels in control or stressed rats and did not affect T levels of unstressed rats. Stressed rats had eightfold higher plasma corticosterone levels than controls, and RU486 had no effect on control or stress levels of corticosterone. The possible role of glucocorticoids in mediating the effect of stress on testicular T production was investigated also in vitro by incubating testicular interstitial cells from unstressed rats for 3 hr with corticosterone (0, 0.01, 0.1, or 1.0 microM) or dexamethasone (0, 0.001, 0.01, or 0.1 microM), followed by an additional 2 hr with hCG (0, 25, 50, or 100 microIU). Both corticosterone and dexamethasone inhibited hCG-stimulated T production in a dose-dependent manner. Cells incubated with the highest concentration of either of the glucocorticoids showed significantly reduced responses to hCG stimulation. In the absence of hCG, in vitro T production was not affected by dexamethasone or 0.01 and 0.1 microM corticosterone. However, the highest dose of corticosterone (1.0 microM) produced a 63% elevation in basal T production. Coincubation of testicular interstitial cells with corticosterone (1.0 microM) or dexamethasone (0.1 microM) and RU486 (0.01, 0.1, and 1.0 microM) reversed the glucocorticoid-induced suppressions of T production in a dose-dependent manner. Our results suggest that during stress increases in plasma levels of glucocorticoids in male rats act via glucocorticoid receptors on testicular interstitial cells to suppress the testicular response to gonadotropins, and that the decline of testosterone production during immobilization stress is in part mediated by a direct action of glucocorticoids on the testis.

Animals↗

PubMed1992

Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats.

This report updates the bidirectional selective breeding of taste aversion (TA) prone (TAP) and TA resistant (TAR) rat lines from the 8th through the 22nd generations. A palatable saccharin solution and the aversive consequences of a cyclophosphamide injection are the respective conditioned stimulus (CS) and unconditioned stimulus (US) of line development. Nonsibling matings within each of the two extremes of TA conditionability have produced TAP and TAR lines having markedly different TA propensities. As previously reported, the substitution of a rotational (i.e., motion sickness) US for cyclophosphamide during TA conditioning also produced characteristic line differences in conditioned taste aversion acquisition. The present report extends the effective line separating USs to include injections of lithium chloride, emetine hydrochloride, and EtOH. A range of EtOH dose levels produced dose-dependent TAs within TAP rats but failed to induce TAs in TAR rats. Following the conclusion of TA testing, the administration of a hypnotic EtOH dose produced equivalent loss of righting capability and equivalent hypothermia in both TAP and TAR rats. The line differences in EtOH induced TA conditionability therefore do not reflect general line differences in EtOH sensitivity. The lines may be useful within studies of biological bases of TA conditionability and animal analog studies of prevention and treatment of alcohol dependence.

Alcohol Drinking↗

PubMed1991

Musculoskeletal ontogeny, phylogeny, and functional adaptation.

Physical forces applied to connective tissues may cause significant changes in cell metabolism and gene expression. Theoretical investigations indicate that mechanical loading histories beginning very early in skeletal development may guide endochondral ossification patterns and the initial architectural construction of bones. Developmental patterns and structures of bones can be emulated using mathematical algorithms or "rules of construction" which relate developmental processes to tissue stress (or strain) histories. Skeletal forms and tissues are well-designed for their mechanical function primarily because their histomorphological construction has been guided by mechanical loading during growth and development. Construction rules of developmental mechanics can also be used to describe many of the histological and morphological adaptations of mature skeletal tissues to changes in customary physical activity. Over many generations, changes in the heritable genetic information occurs by mutation and genetic variability. The range of skeletal forms that are possible in evolution due to such variations, however, is constrained by the developmental rules of construction that reflect biophysical processes associated with the tissue mechanical loading.

Adaptation, Physiological↗

PubMed1990

An approach for time-dependent bone modeling and remodeling--theoretical development.

A time-dependent approach for emulating bone modeling and remodeling in response to the daily loading history is presented. We postulate that genotype, systemic metabolic conditions, and local tissue interactions establish the level of local tissue mechanical stimulation (attractor state) appropriate for the maintenance of bone tissue. The net daily rate of apposition or resorption on a bone surface is determined by the difference between the actual stimulus and the tissue attractor state and can be modulated by other biologic factors. In calculating the net change in local bone apparent density, the technique takes into account the bone surface area available for osteoblastic and osteoclastic activity. Endosteal, periosteal, haversian, and cancellous bone modeling and remodeling are thereby treated in a consistent, unified fashion.

Animals↗

PubMed1990

An approach for time-dependent bone modeling and remodeling-application: a preliminary remodeling simulation.

In a companion paper, we presented a time-dependent theory for bone modeling and remodeling in response to a daily loading history. This paper represents a preliminary attempt to use the theory to determine the distribution of bone density within the adult proximal femur under an assumed normal loading history. Subsequent functional adaptation of the internal structure due to changes in the loading history are then determined. Throughout this preliminary study, the external geometry of the proximal femur is considered to be fixed, i.e., changes in the external shape are neither stimulated nor allowed. Linear and trilinear (dead-zone nonlinearity) rate remodeling laws were compared. Computer emulations using two-dimensional finite element models were successful in creating a normal-appearing distribution of bone tissue when remodeling was initiated from a solid structure of homogeneous bone density. Subsequent reduction in the loading history caused regional bone atrophy. Reinstatement of the normal loading history caused a generalized increase in bone mass but resulted in a slightly different bone distribution than was calculated for a constant loading history. These results demonstrate the utility of the remodeling theory and are consistent with the hypothesis that similar stress-related phenomena are responsible for both normal morphogenesis and functional adaptation in response to changes in the bone loading.

Animals↗

PubMed1990

Effects of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/hCG receptors, and in vitro testicular steroidogenesis in adult rats.

We examined the effect of restraint stress (3 hr) on plasma LH and testosterone levels, on the Leydig cell LH/hCG receptor, and on the activity of enzymes in the testicular steroidogenic pathway of the adult rat. Restraint stress caused a 47% reduction in plasma testosterone concentrations, but had no effect on plasma LH levels. The binding capacity and affinity of Leydig cell LH/hCG receptors were not affected by restraint. Stress did not affect the testicular activity of 20,22 desmolase or 3 beta-hydroxysteroid dehydrogenase, but testicular interstitial cells of stressed rats incubated in vitro with progesterone as a substrate produced more 17 alpha-hydroxyprogesterone but less testosterone than control cells, and when incubated with 17 alpha-hydroxypregnenolone, produced 39% less androstenedione and 40% less testosterone than control cells. These results suggest that restraint stress inhibited 17,20 desmolase but not 17 alpha-hydroxylase activity. When the delta 4 pathway was blocked with cyanoketone (3 beta-HSD inhibitor), stress did not alter the production of pregnenolone or 17 alpha-hydroxypregnenolone, but the production of dehydroepiandrosterone by cells from stressed rats was subnormal, suggesting again a reduction of 17,20 desmolase activity. The data suggest that a major site of the inhibitory action of restraint stress on testicular steroidogenesis is the 17,20 desmolase step. The disruption of androgen production by restraint appears to be LH independent since stress did not affect plasma LH levels, the binding capacity or affinity of LH/hCG receptors, or the activity of 20,22 desmolase.

3-Hydroxysteroid Dehydrogenases↗

PubMed1990

Effect of restraint stress on gonadal proopiomelanocortin peptides and the pituitary-testicular axis in rats.

We examined the effect of restraint on testicular interstitial fluid (TIF) concentrations of ACTH, beta-endorphin-lipotropin (beta-E-LI) and testosterone and correlated those changes with plasma concentrations of ACTH, beta-E-LI, corticosterone, LH and testosterone in adult rats. Animals were subjected to 1, 2, or 3 h of restraint and were killed immediately following the stress period. Plasma values of ACTH and beta-E-LI were elevated above control values after 1 and 2 h, but not after 3 h of restraint. Plasma corticosterone showed a similar response to restraint except that concentrations were also elevated after 3 h. Plasma testosterone concentrations were elevated after 1 h of restraint, but after 3 h of restraint had fallen below control values. Restraint reduced plasma testosterone concentrations without altering plasma LH concentrations. The decline in plasma testosterone during restraint was associated with a parallel decrease in testosterone in the TIF. Concentrations of ACTH and beta-E-LI were 6- and 3-fold greater in TIF than in the plasma. While 1 or 2 h of restraint did not affect ACTH and beta-E-LI in TIF, values of these hormones were elevated in rats exposed to 3 h of restraint. These data, coupled with recent reports that testicular proopiomelanocortin (POMC)-derived peptides may modulate testicular steroidogenesis, suggest that these factors may play an autocrine or paracrine role in mediating stressor-induced changes in testicular function.

Adrenocorticotropic Hormone↗

PubMed1990

Hyperresponsiveness of the rat neuroendocrine system due to repeated exposure to stress.

Sequential exposure to stressors may elicit a period of endocrine hyperresponsiveness during which plasma hormone concentrations reach higher levels after repeated exposure to a stressor compared to levels after initial exposure. The present study was designed to further characterize hyperresponsiveness to repeated stress and determine if hyperresponsiveness is dependent upon repeated exposure to the same stressful stimuli. In Experiment 1, rats were stressed by inescapable tailshock, immobilization or exposure to shock chamber without shock for one, two, three, four or five consecutive days (15 min/day). In rats exposed to tailshock, corticosterone (CS) levels in plasma collected on days 2, 3, 4 and 5 were higher than CS levels following acute tailshock on day 1, demonstrating hyperresponsiveness to repeated tailshock. Hyperresponsiveness of CS secretion also occurred in groups of rats restrained for four or five days. No changes occurred in the CS response of animals repeatedly exposed to immobilization. Prolactin (PRL) levels were not affected by repeated exposure to the stressors. However, PRL values were different between the stress conditions and indicated that the order of stressor severity was tailshock greater than immobilization greater than exposure to shock chamber without shock. In Experiment 2, rats were exposed to either one or two consecutive days of tailshock or immobilization. Other rats were exposed to either tailshock or immobilization on the first day, then switched to the other stressor on the next day. Hyperresponsiveness to repeated tailshock, but not immobilization, was reflected in plasma levels of CS and adrenocorticotropic hormone (ACTH), but not PRL. Hyperresponsiveness of CS and ACTH secretion also was found in rats first stressed by immobilization then switched to tailshock, demonstrating that hyperresponsiveness is not dependent upon reexposure to familiar stressful stimuli. However, hyperresponsiveness did not occur in rats first exposed to tailshock then switched to immobilization. The data suggest that both immobilization and tailshock primed the organism to hyperrespond, but only the more severe stressor (tailshock) elicited hyperresponsiveness of the neuroendocrine system.

Adrenocorticotropic Hormone↗

PubMed1990

Computer predictions of bone remodeling around porous-coated implants.

Computer simulations of bone remodeling in response to mechanical stresses can be used to understand normal growth and development of the skeleton or to predict the remodeling of bone in response to prosthetic devices. Using a previously derived bone maintenance theory, a technique for computing bone density distributions was applied to the proximal femur and tibia using two-dimensional, multiple-loading finite element models. The models initially represented solid, homogeneous structures. Using an iterative bone remodeling technique that relates bone apparent density to loading history, the internal distributions of apparent density and elastic modulus for the normal bones were predicted. The finite element models were then modified to represent bones in which porous-coated femoral surface replacements and tibial tray components had been implanted. The same iterative remodeling method was then applied to predict the distribution of bone around these components. The predicted bone density distributions for the natural femur and tibia agree with previously documented normal bone morphology. The predicted bone density distributions around various implanted prostheses were characteristic of the component under investigation and were consistent with clinical and experimental findings of other investigators. In the femoral head, stress shielding occurred underneath the metal surface replacement cup, resulting in lower densities in the femoral head. The addition of a central femoral cup fixation peg caused bone hypertrophy around the peg. In the tibia, the stress concentrations around the pegs also resulted in denser bone, with a concomitant decrease in bone density at more peripheral locations underneath the prosthetic tray. This remodeling technique has the potential to be an important tool in predicting the possible remodeling consequences of new implant design features.

Biomechanical Phenomena↗

PubMed1989

Relationships between loading history and femoral cancellous bone architecture.

A theory relating bone maintenance to mechanical loading history has been applied to successfully predict the distribution of bone density and trabecular orientation in the adult proximal femur. The loading history was simulated by determining the stress fields in a two-dimensional finite element model exposed to various discrete loading cases and making assumptions about the relative number of loading cycles associated with each load case. The total stimulus to bone maintenance was then calculated by a linear superposition of the stimulus of each loading case. Based on the calculated total stimulus, the apparent density and material properties of each element were changed and the stress solutions were again determined. Using this iterative technique, the bone apparent density and orientation characteristics were predicted. The results indicate that the trabecular morphology of the femur can only be explained by considering the joint loadings from multiple directions. Contrary to the 'trajectorial theory' promoted by Wolff (The Law of Bone Remodelling, 1892), trabecular orientations predicted from our multiple-load analyses are not necessarily perpendicular and do not correspond to the principal stress directions of any one loading condition. Our predicted orientations correspond better to the drawing of bone trabecular morphology by von Meyer (Archs Anat. Physiol. wiss. Med. 34, 615-628, 1867) than to the classic drawing by Wolff and suggest that further study of the trajectorial theory is warranted.

Animals↗

PubMed1989

Evaluation of the possible direct effects of gonadotrophin-releasing hormone analogues on the monkey (Macaca mulatta) testis.

In Exp. 1, the effect of treatment with a GnRH agonist on basal concentrations of serum testosterone and peak values of serum testosterone after administration of hCG was determined. One group of adult male monkeys was treated with a low dose (5-10 micrograms/day) and a second group with a high dose (25 micrograms/day) of a GnRH agonist for 44 weeks. Basal and peak testosterone concentrations were both significantly reduced by GnRH agonist treatment in all groups compared to untreated control animals, but the % rise in serum testosterone above basal values in response to hCG administration was unchanged by agonist treatment. In Exp. 2, the GnRH agonist (100 or 400 ng) or a GnRH antagonist (4 micrograms) was infused into the testicular arteries of adult monkeys. The agonist did not alter testosterone concentrations in the testicular vein or testosterone and LH values in the femoral vein. In Exp. 3, testicular interstitial cells from monkeys were incubated with three concentrations (10(-9), 10(-7) and 10(-5)M) of the GnRH agonist or a GnRH antagonist with and without hCG. After 24 h, neither basal nor hCG-stimulated testosterone production was affected by the presence of the GnRH agonist or antagonist. The results from all 3 experiments clearly suggest that GnRH agonist treatment does not directly alter steroid production by the monkey testis.

Animals↗

PubMed1988

Stresses in plated long-bones: the role of screw tightness and interface slipping.

Using a three-dimensional finite element model of a plated long bone, we studied the influence of screw tightness, sliding frictional interfaces, and loading magnitude on the stresses within the plated bone. The model incorporated frictional interface elements that allowed stress-free separation under tensile loading to occur between the plate and bone and between the screw heads and the plate. The applied loading stimulated both static preloads created by tightening the screws that secure the plate to the bone and physiologic loads created by activity. Initial screw tightening with plate application created regions of bone hydrostatic compressive stress that may be partly responsible for ischemia under the plate. The inclusion of frictional interfaces resulted in a nonlinear relationship between physiologic loan and bone strain that was dependent on screw tightness. This nonlinear response correlated well with the results of previous in vitro studies showing that slippage between the plate and the bone can occur at physiologic load levels. The results showed that the effect of such slippage can be at least as important as plate material, rigidity, and placement in determining the degree of stress shielding. The results also indicated that previous plated bone models that assumed tight interfaces may have overestimated the extent of mechanical stress shielding.

Biomechanical Phenomena↗

PubMed1988

Stress analyses of glenoid component designs.

Metal backing of glenoid components for total shoulder replacements and the use of bony ingrowth surfaces on these components have recently been introduced. In this study, finite element analyses were performed to determine the stress fields in the natural glenoid and to calculate the change in bone stresses after implantation of glenoid components of various designs. The effects of metal backing, keel geometry, and superior constraint on bone stresses indicate that stress distributions on the natural glenoid corresponded to bone morphology. Metal-backing the glenoid component may cause slight improvement in stress transfer to cortical bone. Altered fin geometry better stabilized the glenoid component. Superior restraints on the component intending to prevent subluxation increase stresses and may cause earlier loosening than encountered with unconstrained components.

Humans↗

PubMed1987

Influences of mechanical stress on prenatal and postnatal skeletal development.

A new theory is introduced to describe some of the influences of mechanical stresses on chondroosseous biology. It is proposed that degeneration and ossification is a normal process for all cartilage in the appendicular skeleton, which is accelerated by intermittently applied shear stresses (or strain energy), and inhibited or prevented by intermittently applied hydrostatic pressure. These concepts were applied using finite element computer models in an effort to predict the ossification pattern of the prenatal and postnatal femoral anlage. The theoretical calculations successfully predicted the key features of skeletal morphogenesis including the development of the primary ossification site, a tubular diaphysis and marrow cavity, metaphyseal and epiphyseal trabecular bone, the location and geometry of the growth plate, the appearance and location of the secondary ossific nucleus, and the existence and thickness distribution of articular cartilage. The results suggest that degenerative joint disease in immobilized or nonload-bearing mature joints may be a manifestation of the final stage in the ossification of the anlage. In nonfunctional joints, the absence or reduction of intermittent hydrostatic pressure in the articular cartilage permits cartilage degeneration and the progressive advance of the ossification front toward the joint surface until the articular cartilage has been ossified.

Cartilage, Articular↗

PubMed1985

Stress analyses of joint arthroplasty in the proximal humerus.

Finite element stress analyses were performed on the proximal humerus before and after the simulated implantation of stemmed, metallic prosthetic components with porous sintered surfaces for direct bony attachment. Design geometries with surfaces at the prosthetic head/bone interface that were (a) convex, (b) flat, and (c) concave were studied. Analyses for each of the three geometries were conducted to reflect (a) bone ingrowth on all the prosthesis/bone surfaces and (b) bone ingrowth only along the underside of the prosthetic humeral head (assuming the stem was not coated with a porous material). Three loading conditions were used to model various degrees of abduction of the arm. Results indicated that in the normal humerus the compressive joint forces are transmitted from the articular surface through cancellous bone to the inferior cortical shell. Contraction of the rotator cuff muscles created tensile stresses in the superolateral cancellous bone and the superior cortical shell of the humerus. Results of the implanted humeral component models indicated that the use of a prosthesis with bone ingrowth along the stem would cause marked stress shielding proximally whereas the use of implants with porous ingrowth only on the underside of the humeral head replacement produced stress fields more similar to the normal humerus. The convex, flat, and concave surfaces provided similar load transfer from the component to the underlying bone in all loading cases. Other prosthetic head designs that may offer better initial stability produced stress fields similar to those of existing prostheses.

Biomedical Engineering↗

PubMed1971

Interaction of Pseudomonas bacteriophage 2 with the slime polysaccharide and lipopolysaccharide of Pseudomonas aeruginosa strain B1.

Purified slime polysaccharide B and lipopolysaccharide of Pseudomonas aeruginosa strain BI were shown to possess receptor-like properties in inactivating Pseudomonas phage 2, whereas lipoprotein and glycopeptide fractions were devoid of activity. On a weight basis, slime polysaccharide B was more effective than lipopolysaccharide in inactivating phage. The specificity of the reaction with slime polysaccharide B was indicated by the fact that slime polysaccharide A of P. aeruginosa strain EI failed to inactivate phage 2. Electron micrographs showed phage 2 in typical, tail-first position of attachment on intact cells of strain BI, slime polysaccharide B, and lipopolysaccharide. Tail fibers were discernible during phage attachment.

Adsorption↗

PubMed1969

Origin of polysaccharide depolymerase associated with bacteriophage infection.

Analyses, by construction of phage growth curves, indicated that the polysaccharide depolymerase was synthesized by Pseudomonas aeruginosa strains B and BI after infection with phage 2. The kinetics of biosynthesis of the depolymerase were found to parallel closely the rate of formation of phage-directed virions, and alterations in the experimental conditions of infection were reflected by alterations in the production of enzyme. Infection with other Pseudomonas phages, 84 and 1197, did not result in the synthesis of depolymerase. The enzyme was not detectable in uninfected cultures, and no evidence was obtained for the existence of inhibitors or activators of enzyme activity in extracts of uninfected or infected cells. The results of experiments employing chloramphenicol or an auxotorphic mutant (BI arg(-)) suggested that protein synthesis de novo was essential for production of the enzyme. Various mutants of phage 2 (pdp(1), pdp(2)), which alter the synthesis of the polysaccharide depolymerase, have been isolated. These experimental results strongly support the role of the phage genome in the synthesis of this enzyme.

Arginine↗