Biomedical subjects
Publications and source records attributed to R B Ashman.
The yeast Candida albicans is a recognized, though uncommon, cause of osteomyelitis in humans. In a mouse model of systemic candidiasis, osteomyelitis has been found to occur in the vicinity of the inner ear, and to persist for at least 6 months after the initial infection.
The beige mutation in mice has a pervasive effect on mechanisms of host resistance to infectious agents. Best characterized are defects in granulocyte chemotaxis and phagocytosis, which are associated with increased susceptibility to bacteria, and a deficiency in the levels of natural killer (NK) cells, which has been linked to decreased resistance to both murine cytomegalovirus and the yeast Cryptococcus neoformans. The objective of the present experiments was to explore the cellular basis of the enhanced susceptibility of beige mice to systemic infection with the yeast Candida albicans. In contrast to murine cytomegalovirus and C. neoformans, infection with C. albicans did not induce any detectable NK cell activity in the spleen of bg/bg or bg/+ mice. Unfractionated bone marrow (BM) displayed some candidacidal activity, mediated by both phagocytic and nonphagocytic cells; however, there was no difference between homozygous and heterozygous mice in the effector function of normal BM cells or mononuclear cells derived from either short- or long-term BM cultures. On the other hand, peritoneal granulocytes from bg/bg mice were significantly more effective than those from bg/+ mice in killing Candida blastoconidia in vitro. A similar comparison of granulocytes from short-term BM cultures showed that the activities of cells from bg/bg and bg/+ mice were equivalent, indicating that the granulocytes derived from the peritoneal cavity of bg/bg mice had probably been exposed to some form of nonspecific stimulation in vivo. Somewhat surprisingly, long-term BM cultures did not support the continual growth of bg/bg granulocytes, and it is possible that the beige mutation may be associated with a lesion in the differentiation pathway that leads to the production of granulocytes. Taken together, the data indicate that, in beige mice, granulocytes rather than NK cells are a major determinant of natural resistance to C. albicans infections.
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It has been proposed that the orthotropic elastic constants of cancellous bone depend upon a tensorial measure of anisotropy called fabric as well as the tissue's structural density. Cowin (1985, Mechanics Mater, 4, 137-147; 1986, J. biomech. Engng 108, 83-88) developed explicit relationships for the elastic constant, structural density and fabric relationship. In this study the orthotropic elastic moduli, structural density, and fabric components were measured for 11 cancellous bone specimens from five bovine femora and for 75 specimens from three human proximal tibiae and fitted to these relationships using a least squares analysis. The relationships explained between 72 and 94% of the variance in the elastic constants. The relationships between the elastic constants and squared or cubed power functions of structural density had better predictive value over the entire distribution of the data than did expressions with linear functions of structural density.
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Despite extensive investigation, the mechanisms of host resistance against C. albicans infection remain poorly understood. Granulocytes and macrophages are the major effector cell types; however, their intrinsic candidacidal activity is rather limited, and its full expression requires augmentation by components of the T cell-initiated lymphokine cascade. Consequently, susceptibility to recurrent mucocutaneous infections may be associated with aberrant T cell function. In contrast, protection from systemic infection appears to be mediated by candida-specific antibodies.
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Cell-mediated immune responses were evaluated after immunization in two inbred mouse strains, CBA/H and BALB/c, that are respectively susceptible and resistant to infection with the yeast Candida albicans. Local immune responses, as measured by leucocytic infiltration into the draining lymph node, were similar; however, both delayed-type hypersensitivity responses and candida-specific lymphocyte proliferation in vitro were significantly stronger in the resistant strain. The response was controlled by genes mapping outside the major histocompatibility complex. A possible explanation for the down regulation of the immune response in CBA/H mice is discussed.
Antibody to an immunodominant antigen of approximately 48 kDa is found in a high proportion of patients with mucocutaneous or systemic infections of the yeast Candida albicans. A cDNA encoding part of the 48 kDa antigen has been isolated. From the deduced amino acid sequence of the cDNA clone, the 48 kDa antigen shows homology to the enzyme enolase.
Inbred mice can be classified as susceptible or resistant to systemic infection with the yeast Candida albicans by histopathological evaluation of tissue lesions. Candida-specific memory T cell responses generated by resistant BALB/c mice are vigorous and sustained, whereas those displayed by susceptible CBA/H mice are weak. When spleen cells from immune mice were activated by culture with candida antigens in vitro, and injected into syngeneic and allogeneic recipients in the absence of further antigenic stimulation, cells from CBA/H mice induced a specific inflammatory response only in CBA/H recipients. In contrast, cells from immune BALB/c mice showed no specific activity. The effector cells were identified as T cells of the cytotoxic/suppressor subclass (CD4-, CD8+); and analysis in various F1 hybrid mice showed that reactivity was expressed only in animals carrying CBA/H genes. The data thus indicate that susceptibility to C. albicans infection is associated with the induction of a T cell subpopulation that has the potential to react specifically against unmodified self antigens expressed by the susceptible strain.
The relationship between initial spinal construct stiffness and the stiffness of the resulting fusion mass was studied by performing standardized 10-segment posterior spinal fusions in goats. Animals were divided into 5 groups based on type of spinal construct, using rods of different diameters (3.2 mm, 4.8 mm, 6.4 mm) with or without rigid crosslinking to produce constructs of different stiffnesses. Stiffness data on 28 animals were obtained by removing the spines en bloc, at 6 or 12 weeks postoperatively, and performing load-deformation testing in axial and torsional loading to determine the stiffness of the fusion masses (rods removed). The initial construct stiffnesses were also compared by ex vivo testing on spine specimens to correlate initial construct stiffness with eventual fusion mass stiffness. In axial testing, results showed stiffer fusion masses from larger diameter rod constructs compared with smaller rod constructs. This was similar to results of control testing on spine specimens ex vivo. Rigid crosslinking did not produce stiffer fusions in axial testing, due to a technical limitation of the button-wire implants used to segmentally fix the rods at each vertebra. In torsional testing, stiffer fusion masses resulted from using larger rods, and rigid Crosslinking also produced the stiffest fusion masses, which was consistent with ex vivo testing. In general, larger diameter (stiffer) rods produced stiffer fusion masses, and no evidence of stress shielding was found.
In the Cotrel-Dubousset and Texas Scottish Rite Hospital spinal implants systems, the upper hook on the convex rod is usually clawed to prevent posterior pull out. A transverse process hook and an upwardly directed pedicle hook are usually inserted on the same lamina level. However, clawing two levels instead of one is a simpler surgical procedure. We biomechanically compared the posterior pull-out strength of a one-level versus two-level construct. The average load of failure of the double-level construct was significantly greater (p less than 0.05) as compared with the single level. Thus, the two-level construct is not only easier to insert, it is also stronger.
The effects of mechanical vibration on bone ingrowth into porous hydroxyapatite implants and fracture healing were examined radiographically, histomorphometrically, and biomechanically in a rabbit model. Fifty-three female NZW rabbits were used in this study. These rabbits were divided into four separate studies to assess the effects of 20 and 60 min of vibration/day in both implant and osteotomy models as compared with the respective non-vibrated controls. For the implant model, coral hydroxyapatite goniopora rods were implanted bilaterally into tibiae and for the osteotomy model, bilateral fibulae were osteotomized. A resonant frequency of 25 Hz mechanical vibration was used. After periods of 2, 3, 4, and 6 weeks of vibration, the rabbits were killed and examined. For the implant model, there was no significant difference between control, 20, or 60 min of vibration/day with respect to the rate or amount of new bone ingrowth. For the fracture model, 60 min of vibration/day produced a significantly larger callus as compared with the non-vibrated controls (p less than 0.05), whereas 20 min of vibration/day did not. Although biomechanical testing demonstrated a general trend for increased strength in the vibrated animals, it failed to reach significance. These results suggest that the mechanical vibration used in the present study had a beneficial effect on callus volume, possibly due to the stimulation of secondary bone healing processes, but does not appear to promote bone ingrowth into a porous hydroxyapatite implant.
The anatomical variation of orthotropic elastic moduli of the cancellous bone from three human proximal tibiae was investigated using an ultrasonic technique. With this technique, it was possible to measure three orthogonal elastic moduli and three shear moduli from cubic specimens of cancellous bone as small as 8 mm per side. Correlation with mechanical tensile testing has shown this technique to offer a precise measure of cancellous modulus (Eten = 0.94Eult + 144.6 MPa, r2 = 0.96, n = 34). The cancellous bone of the proximal tibia was found to be very inhomogeneous, with the axial modulus ranging between 340 and 3350 MPa. A course map is presented, showing measured Young's moduli as a function of anatomical position. The anisotropy of the cancellous bone, determined by the relative differences between the three orthogonal moduli, was shown to be relatively constant over the entire range of cancellous densities tested. The relationship between the axial elastic modulus and the apparent density was found to be approximately linear, as reported by others for proximal tibial cancellous bone.
Five different spinal implants, all using pedicle screw attachment to vertebrae, were examined in a one above/one below corpectomy model, to determine 1) the relative stiffness of each construct, 2) the stresses generated in the implant during loading, and 3) the relative fatigue susceptibility of each implant. Results indicated that the relative axial and torsional stiffnesses were similar for all the implants tested (DKS/Zielke, VSP/Steffee, AO Fixator Interne, Luque plate, AO Notched plate). Hence, each of the devices impart approximately the same stability to the spine in this highly unstable model. Stresses measured at the root of the pedicle screws were found to exceed the endurance limit of stainless steel in those systems in which the pedicle screws were attached rigidly to the plates (VSP/Steffee, AO Fixator Interne). Good agreement was found between the measured stresses and stresses derived from static calculations. Comparisons between the stresses from each implant gave a relative measure of fatigue susceptibility that was validated by in vitro cyclic testing. Implants with stresses exceeding the endurance limit failed during the cyclic test.
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Mechanical testing protocols and test methods used to evaluate spinal implants have varied widely. Use of different test methods would not present a problem except that multicomponent mechanical systems, such as the spine and spinal implant constructs, yield different mechanical properties when subjected to different test methods. The goal of this article is to outline considerations specific to the mechanical assessment of spinal implants. With standard test methods and treatment of results, redundancy between testing programs will be reduced and comparison of results will be facilitated.
Chronic vaginal candidosis is a significant cause of morbidity in women, but its causes are not yet understood. We propose that in genetically susceptible women a candidal infection elicits responses that cross-react with self-antigens. Control of these deleterious responses may compromise the normal mechanisms of resistance and predispose to recurrent infection. Furthermore, the local inflammation caused by these autoreactive cells may contribute to other forms of vaginitis.