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Biomedical subjects

H B Skinner

Publications and source records attributed to H B Skinner.

At least 55 records · Page 3Linked to original sources

SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast.

Mutations in the SAC1 gene exhibit allele-specific genetic interactions with yeast actin structural gene defects and effect a bypass of the cellular requirement for the yeast phosphatidylinositol/phosphatidylcholine transfer protein (SEC14p), a protein whose function is essential for sustained Golgi secretory function. We report that SAC1p is an integral membrane protein that localizes to the yeast Golgi complex and to the yeast ER, but does not exhibit a detectable association with the bulk of the yeast F-actin cytoskeleton. The data also indicate that the profound in vivo effects on Golgi secretory function and the organization of the actin cytoskeleton observed in sac1 mutants result from loss of SAC1p function. This cosuppression of actin and SEC14p defects is a unique feature of sac1 alleles as mutations in other SAC genes that result in a suppression of actin defects do not result in phenotypic suppression of SEC14p defects. Finally, we report that sac1 mutants also exhibit a specific inositol auxotrophy that is not exhibited by the other sac mutant strains. This sac1-associated inositol auxotrophy is not manifested by measurable defects in de novo inositol biosynthesis, nor is it the result of some obvious defect in the ability of sac1 mutants to utilize inositol for phosphatidylinositol biosynthesis. Thus, sac1 mutants represent a novel class of inositol auxotroph in that these mutants appear to require elevated levels of inositol for growth. On the basis of the collective data, we suggest that SAC1p dysfunction exerts its pleiotropic effects on yeast Golgi function, the organization of the actin cytoskeleton, and the cellular requirement for inositol, through altered metabolism of inositol glycerophospholipids.

Actins↗

Complications related to modularity of total hip components.

We report complications from the use of modular components in 20 hip replacements in 18 patients. Fifteen complications (in 13 patients) were related to failure of a modular interface after operation. Femoral head detachment from its trunnion was seen in 6 hips from trauma (3), reduction of a dislocation (2), and normal activity (1). In one case the base of the trunnion fractured below an extra-long modular head. In seven other hips the modular polyethylene liner dislodged from its shell, causing severe damage to the shell in four cases with extensive metallosis. In one other hip an asymmetrical polyethylene liner rotated, resulting in impingement of the femoral component and recurrent dislocation. Operative errors were seen in five cases: implantation of a trial acetabular component in one; and mismatching between the size of the femoral head and the acetabular component in the others. Surgeons who use hip replacements with modular components should be aware of the potential for operative error and of the importance of early treatment for postoperative mechanical failure.

Adult↗

Ankle weight effect on gait: orthotic implications.

Oxygen consumption during ambulation was measured in 10 normal subjects wearing ankle weights of 0.91 kg, 1.82 kg, and 2.73 kg, either on the right ankle or bilaterally. Subjects walked at self-selected speeds and oxygen consumption was measured over 1-minute intervals during steady-state walking. Oxygen consumption per unit distance and oxygen consumption rate demonstrated significant positive linear correlations with added weight (P = .001, P = 0.007, respectively). Velocity demonstrated a significant decrease when correlated with added weight (P = 0.03). Multiple regression analysis was used to relate these measures of oxygen consumption rates to velocity, age, and added weight, yielding predictive relationships. Based on these results, the weight of orthoses should be minimized in order to maximize walking velocity and minimize oxygen consumption per unit distance. The advantage of a light-weight, molded plastic ankle-foot orthosis (AFO) over heavier AFO designs is demonstrated by this study.

Adult↗

Effects of variation of cement thickness on bone and cement stress at the tip of a femoral implant.

With the resurgence of the use of bone cement in total hip arthroplasty, a renewed concern in techniques or designs that may reduce cement fixation failure has arisen. Analysis of the stresses at the tip of the prosthesis may suggest strategies to reduce loosening. Using a three-dimensional finite element model this study analyzed stresses in the bone, cement, and prosthesis near the tip of a femoral component as a function of cement thickness. A section of an idealized circular femoral shaft with implant prosthesis and cement was modeled with loading conditions representing the stance phase of gait. Increasing cement thickness is predicted to significantly reduce stress in the cement mantle of a femoral implant. Tensile stress is reduced by fifty percent while shear stress is reduced at least twelve percent. Peak tensile stresses occur on the medial side at the tip of the prosthesis in a transverse direction, indicating likelihood of failure due to debonding. Local shear stress peaks also occur at the tip. Shear stresses in the cement mantle are in the same range as the tensile stresses and must be considered when analyzing the possible modes of failure. However, the mode of failure in shear is complex, and shear strength of the stem-cement interface is unknown at present.

Bone Cements↗

Pathokinesiology and total joint arthroplasty.

Gait analysis data relating to total joint arthroplasty were reviewed to assess their impact on the evolution of prosthetic design. Although joint replacement designs have led to clinical improvement, they do not yet permit the restoration of normal gait. Normal function may be difficult to attain in patients with arthritic destruction, because of a proprioceptive defect. Arthroplasty improves gait by relieving pain, but other factors (previous gait patterns, prosthetic design, muscle weakness, balance, and proprioception) seem to prevent most patients from regaining normal gait.

Evaluation Studies as Topic↗

Total elbow arthroplasty. An 18-year experience.

In 34 primary and 18 revision total elbow arthroplasties (TEAs), rheumatoid arthritis (RA) was the most common indication, with traumatic arthritis next most common. The indications were primarily pain and decreased range of motion. Follow-up time averaged 7.6 years for index arthroplasties. Complication rates of primary arthroplasties were high, with 40% neural problems, 9.3% aseptic loosening, and 13.3% early postoperative infection. Overall function was satisfactory in 68% of patients with RA. In agreement, the rates of revision were high. Overall satisfaction was good, and function was fair in patients with TEA.

Adult↗

Use of hot wire anemometry to measure velocity of the limb during human movement.

Hot film anemometry, x-configuration probes were used in two experiments to evaluate their effectiveness at measurement of limb velocity. Data from tests with a probe attached to the end of a pendulum establish that the hot films measure velocity in the swing phase within 0.098 ms-1. The kinetic energy per unit mass of the pendulum was predicted within +/- 0.005 m2 s-2, from the measured velocity. In gait experiments with one human subject at speeds greater than 0.25 ms-1, the hot film anemometer and a video system predicted speeds within 0.083 ms-1. The hot film data are electronic signals that are easily stored and processed. The results from these experiments demonstrate that hot film anemometry is an effective and efficient method for direct measurement and analysis of the limb velocity.

Biophysical Phenomena↗

Three-dimensional finite element modelling of bone: effects of element size.

This study quantifies the effects of element size on the stress/strain results of finite element (FE) models of bone that are generated with a previously described automated method. This method uses cube-shaped hexahedral elements, which enabled element shape and aspect ratio to be held constant while the effects of element size were studied. Three models of a human proximal femur, each with a different element size (3.1 mm, 3.8 mm and 4.8 mm), were analysed. Convergence in strain energy of the models had been verified in previous work. The stresses and strains predicted by the models were compared on a pointwise basis using linear regression analysis. There was a general decrease in the level of stress and strain when element size was increased, even though convergence in strain energy had been achieved. An increase in element width from 3.1 mm to 3.8 mm decreased the predicted stresses by 13% to 29% overall; the predicted strains decreased by 4% to 20% for the same increase in element size. These results indicate that linear cube-shaped hexahedral elements must be very small (3 mm on a side or smaller) to represent the sharp variations in mechanical properties that exist in bone, and that use of larger elements decreases the predicted stresses and strains. The elements used in this study are similar to those typically used to represent trabecular bone in conventional (non-automated) FE modelling methods. Therefore, the sensitivity of the stress/strain results to element size that was found for trabecular bone also applies to conventional modelling of such bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanistic insights relevant to protein secretion in yeast.

During the past year, a powerful combination of genetic and biochemical approaches has yielded fascinating information with respect to the question of how proteins cross membranes and subsequently traffic between intracellular compartments of the yeast secretory pathway. Fundamental advances have been made in two specific areas. These include experiments that have provided new perspectives with respect to the nature of the soluble machinery involved in facilitating protein traffic from the cytoplasm to the lumen of the endoplasmic reticulum, and work that has provided a biochemical description of what may in effect represent a membranous ligand-gated channel that is required for protein translocation into the endoplasmic reticulum lumen.

Biological Transport↗

Compressive mechanical properties of human cancellous bone after gamma irradiation.

The effect of gamma irradiation on the mechanical properties of human bone was examined. Specimens of cancellous bone were cut from the proximal epiphyseal region of fresh-frozen tibiae and divided into control and irradiated groups according to anatomical region. The irradiated groups were exposed to 10,000, 31,000, 51,000, or 60,000 gray (1.0, 3.1, 5.1, or 6.0 megarad). The specimens were tested in compression to failure to determine failure stress, strain to failure, and elastic modulus. Failure stress and elastic modulus were found to be proportional to the square of the density and were normalized with respect to this property. Significant differences in normalized failure stress (p less than 0.001) and normalized elastic modulus (p = 0.003), when compared with the values for matched control specimens, were found only for the specimens that had been irradiated with 60,000 gray (6.0 megarad).

Aged↗

The effect of ankle constraint on the torsional laxity of the knee during internal-external rotation of the foot.

The in vivo torsional laxity and stiffness of the knee joint are usually determined by rotating the foot and measuring the torque generated at the knee. However, when rotation is applied to the foot, significant three-dimensional forces and moments are produced at the knee. These forces and moments depend upon the external constraint of the ankle complex, and as a result, the observed laxity of the knee also depends on the ankle constraint. Tests are conducted with the foot of a subject in a shoe, with and without the ankle taped, and in a buckled and unbuckled (ski) boot that can effectively constrain ankle rotation. The average laxity of the primary (linear) region of the axial moment vs internal-external rotation is 30% greater when the ankle is constrained by the buckled boot than it is in three other cases of lesser ankle constraint.

Adult↗

Subtrochanteric osteotomy in total hip revision. Report of two cases.

Revision of the femoral component in a failed total hip arthroplasty can be difficult, tedious, and destructive to the patient's femur. This is particularly true in cases of severe osteolysis or revision of previous revisions. A technique is described whereby visualization of the femoral canal is obtained by subtrochanteric osteotomy. This technique may be useful in selected cases of hip revision.

Femur↗

A finite helical axis as a landmark for kinematic reference of the knee.

Reference coordinates based on the finite helical axis for flexion of the knee from 0 to 90 deg are proposed. Six degree-of-freedom tracking allows the use of such a helical axis as a kinematic landmark for knee motion representation. Data from five human subjects in vivo are presented as a path of finite helical axes for flexion of the knee from 20 to 80 deg. The finite helical axis rotates by an average of 11.4 deg, the centrode translates an average of 19.8 mm, and the total axial translation averages 0.1 mm during flexion from 20 to 80 deg. Error due to the transducer was measured on a fixed-pivot pendulum and found to be 1.0 deg and 1.9 mm rms for the helical axis orientation and position, respectively, and 0.1 mm for the axial translation. Reproducibility and soft tissue effects on the measurements were repeatable to 4.0 deg and 2.7 mm rms in orientation and position, respectively, and 0.1 mm for the axial translations. Soft tissue errors averaged 4.9 deg and 3.6 mm in position and orientation, and 0.3 mm in the axial translations.

Adult↗

Analysis of a below-knee patellar tendon-bearing prosthesis: a finite element study.

In this study, a finite element (FE) model of a below-knee prosthesis of patellar tendon-bearing (PTB) design, and several altered variations of the model have been constructed. A load of approximately 1.5 times normal body weight (984 N) was applied at the heel of the model to simulate heelstrike conditions. The "base" model was then analyzed and revised iteratively until a model which provided consistency between soft tissue elastic modulus and socket displacement was developed. The interface normal and shear stresses obtained from the analysis of this revised base model were highest (about 961, and 463 KPa, respectively) at the distal anterior tip of the socket/stump. Proximally, higher normal stresses (72-78 KPa) were found medially and posteriorly. Proximal shear stresses were highest posteriorly (79 KPa), although shear stresses medially (51 KPa), and laterally (43 KPa), were also much higher than anteriorly (10 KPa). FE analyses were performed on the altered models to determine the relative effects on socket/stump interface stresses of altering the FE model of the prosthesis. Results of the analysis indicate that fabricating the prosthesis from a material with an elastic modulus ten times lower than that of the revised base model can produce reductions in the maximum pressure of up to 14 percent. Large decreases in maximum pressures (71 percent) resulted from the use of a suction socket rather than a conventional socket. Small changes in stump length (2 cm) caused relatively large pressure changes (16 to 18 percent).

Amputation, Surgical↗

Isoelasticity and total hip arthroplasty.

Important parameters in designing an "isoelastic" prosthesis that transfers stress in a more physiologic manner are explored. The effect of material properties and geometry on the mechanical properties of a femoral component are discussed. The bending "stiffnesses" of cortical bone, metal prosthese, and composite prostheses are compared, and the bending rigidities of prosthesis and bone as they might vary with surgical technique are explained. It is shown that the flexural rigidity of a prosthesis stem as presently designed is close to the flexural rigidity of cortical bone, but 200 to 400 times greater than that of the material it replaces, ie, cancellous bone and fatty marrow.

Bone and Bones↗

Automated three-dimensional finite element modelling of bone: a new method.

Three-dimensional finite element stress analysis of bone is a key to understanding bone remodelling, assessing fracture risk, and designing prostheses; however, the cost and complexity of predicting the stress field in bone with accuracy has precluded the routine use of this method. A new, automated method of generating patient-specific three-dimensional finite element models of bone is presented--it uses digital computed tomographic (CT) scan data to drive the geometry of the bone and to estimate its inhomogeneous material properties. Cubic elements of a user-specified size are automatically defined and then individually assigned the CT scan-derived material properties. The method is demonstrated by predicting the stress, stain, and strain energy in a human proximal femur in vivo. Three-dimensional loading conditions corresponding to the stance phase of gait were taken from the literature and applied to the model. Maximum principal compressive stresses of 8-23 MPa were computed for the medial femoral neck. Automated generation of additional finite element models with larger numbers of elements was used to verify convergence in strain energy.

Adult↗

Alternatives in the selection of allograft bone.

Many orthopedic surgeons are unfamiliar with the various types of commercially available allograft bones, despite their frequent use in reconstructive and tumor surgery. This report summarizes the mechanical, osteoinduction, and safety data for sterile fresh-frozen, secondarily sterilized, and freeze-dried bone. The orthopedic surgeon can make informed choices about bone alternatives based on the risks and benefits of each type. Data have shown that fresh-frozen sterile-collection bone is the optimal substitute for autogenous bone in most applications.

Biomechanical Phenomena↗