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Biomedical subjects

H B Skinner

Publications and source records attributed to H B Skinner.

At least 19 recordsLinked to original sources
PubMed1997

Free and protein-associated nitrotyrosine formation following rat liver preservation and transplantation.

Nitrotyrosine in human and animal tissues has been associated with pathologic conditions such as atherosclerosis, renal failure, and acute lung disease. In this study, free and protein-associated nitrotyrosine were determined in plasma and tissue samples using a dual-channel electrochemical detection method. Free nitrotyrosine was quantified in acetonitrile-extracted samples while protein-associated nitrotyrosine was determined in proteinase K-digested samples. In human plasma, total nitrotyrosine increased from 2.3 to 4.3 and 13.2 mumol/mol Tyr following addition of 0, 0.5, and 1 mM ONOO-. To determine if nitrotyrosine was produced during ex vivo hypothermic preservation, rat livers were stored in University of Wisconsin solution (UW) for 0, 6, or 8 h and reperfused for 3 h. Total nitro-tyrosine increased 359 and 908% after 6 and 8 h preservation compared to 0 h. To determine if nitrotyrosine was produced in vivo following hepatic ischemia, a rat preservation-transplantation model was utilized in which livers were flushed with cold UW (0-h group) or transplanted following 6 h hypothermic preservation in UW. Free nitrotyrosine increased from 15.7 +/- 0.3 in the 0-h group to 23.6 +/- 2.5 mumol/mol Tyr, 24 h posttransplant of 6-h preserved livers. Protein-associated nitrotyrosine increased from 9.5 +/- 1.1 in the 0-h group to 27.5 +/- 0.7 mumol/mol Tyr in the 6-h preservation-transplantation group. Protein-associated nitrotyrosine provides an integrative determination of nitration. Detection of free and protein-associated nitrotyrosine in biologic samples may allow insight into the role of .NO-derived oxidants in tissue injury associated with various pathologic conditions.

Animals↗
PubMed1996

Postfailure compressive behavior of tibial trabecular bone in three anatomic directions.

To obtain information describing the postfailure behavior of human proximal tibial trabecular bone, cube specimens of bone were mechanically tested in compression beyond the point of failure. Tests were performed in the three anatomic directions, plots of stress versus strain were obtained, and measures to describe the stress-strain relations before, during, and after failure were defined. These measures included elastic modulus, strength, postfailure slope, strain during maximum stress, and first postfailure minimum stress. For each anatomic direction, analyses were performed to correlate these parameters with ash density. Each of these measures was significantly correlated with ash density at the p < 0.05 level for all test directions, except for postfailure slope, which was correlated in the mediolateral and superior-inferior directions, and strain during maximum stress, which was correlated only in the superior-inferior direction. The data from this study enable trilinear stress-strain relations to be estimated for proximal tibial trabecular bone of various densities, and can serve as a first step toward modeling the behavior of trabecular bone before, during, and after failure.

Adult↗
PubMed1996

Medial compartment arthrosis of the knee.

When the resultant forces on the tibial plateau are displaced medially, compressive stresses cause apposition of bony tissue, thus thickening the dense subchondral bone underlying the medial plateau. Loss of the articular cartilage and an increase in subchondral bone density facilitate the progression of osteoarthrosis. Surgical management is dependent on the presence of a varus deformity; patients with medial compartment disease and varus alignment should be considered for high tibial osteotomy (HTO) or unicondylar or total knee arthroplasty (TKA), depending on their age and activity level. Patients without varus deformity and with mechanical symptoms, only mild joint-space narrowing, and pain less than 1 year are likely to benefit from arthroscopic débridement. Patients without varus alignment but with chronic pain associated with loading and more pronounced joint-space loss should be considered for HTO, or unicondylar or TKA.

Arthrodesis↗
PubMed1995

Mutant rat phosphatidylinositol/phosphatidylcholine transfer proteins specifically defective in phosphatidylinositol transfer: implications for the regulation of phospholipid transfer activity.

The mammalian phosphatidylinositol/phosphatidylcholine transfer proteins (PI-TPs) catalyze exchange of phosphatidylinositol (PI) or phosphatidylcholine (PC) between membrane bilayers in vitro. We find that Ser-25, Thr-59, Pro-78, and Glu-248 make up a set of rat (r) PI-TP residues, substitution of which effected a dramatic reduction in the relative specific activity for PI transfer activity without significant effect on PC transfer activity. Thr-59 was of particular interest as it is a conserved residue in a highly conserved consensus protein kinase C phosphorylation motif in metazoan PI-TPs. Replacement of Thr-59 with Ser, Gln, Val, Ile, Asn, Asp, or Glu effectively abolished PI transfer capability but was essentially silent with respect to PC transfer activity. These findings identify rPI-TP residues that likely cooperate to form a PI head-group binding/recognition site or that lie adjacent to such a site. Finally, the selective sensitivity of the PI transfer activity of rPI-TP to alteration of Thr-59 suggests a mechanism for in vivo regulation of rPI-TP activity.

Androgen-Binding Protein↗
PubMed1995

The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity.

The Saccharomyces cerevisiae protein SEC14p is required for Golgi function and cell viability in vivo. This requirement is obviated by mutations that specifically inactivate the CDP-choline pathway for phosphatidylcholine biosynthesis. The biochemical basis for the in vivo relationship between SEC14p function and the CDP-choline pathway has remained obscure. We now report that SEC14p effects an in vivo depression of CDP-choline pathway activity by inhibiting choline-phosphate cytidylyltransferase (CCTase; EC 2.7.7.15), the rate-determining enzyme of the CDP-choline pathway. Moreover, this SEC14p-mediated inhibition of CCTase was recapitulated in vitro and was saturable. Finally, whereas the SEC14p-dependent inhibition of CCTase in vitro was markedly reduced under assay conditions that were expected to increase levels of phosphatidylinositol-bound SEC14p, assay conditions expected to increase levels of phosphatidylcholine-bound SEC14p resulted in significant potentiation of CCTase inhibition. The collective data suggest that the phosphatidylcholine-bound form of SEC14p effects an essential repression of CDP-choline pathway activity in Golgi membranes by inhibiting CCTase and that the phospholipid-binding/exchange activity of SEC14p represents a mechanism by which the regulatory activity of SEC14p is itself controlled.

Carbon Radioisotopes↗
PubMed1995

Knee joint proprioception in below-knee amputees.

This study determined knee joint proprioception in below-knee amputees using two methods of measurement of knee joint proprioception. The threshold for detection of passive motion and the ability to reproduce specific limb positions were recorded in nine below-knee amputees. A significant difference was observed between the prosthetic and sound limbs in the amputees in the threshold of detection test. The large angles (5 degrees to 25 degrees) involved in position reproduction tests may have provided cues through the cuff suspension. Different strategies are used by below-knee amputees to discern large and small movements of the knee.

Aged↗
PubMed1995

Gait initiation of persons with below-knee amputation: the characterization and comparison of force profiles.

The purpose of this study was to characterize gait initiation of persons with leg amputation and determine whether prosthetic alignment was a critical parameter in the initiation process. Gait initiation was chosen for study because of the difficult neuromuscular demands placed on the body in negotiating the transition from stance to ambulation. In this investigation, ground reaction force data were collected on seven persons with below-knee amputation. These subjects underwent a series of gait initiation trials while varying prosthetic alignment. An analysis of the data demonstrated key elements in the gait initiation process, including the motion of the center of gravity in preparation for steady-state walking. Significant asymmetries in the force profiles of the residual and nonamputated limbs were also found; gait initiation forces were consistently higher for the prosthetic limb and the timings of maxima and minima were indicative of an intact limb preference. Relatively small changes in prosthesis alignment proved not to have statistically significant effects on generalized force parameters. This result is consistent with the findings of other studies that gait initiation is a motor program with certain invariant characteristics.

Aged↗
PubMed1995

The prediction of metabolic energy expenditure during gait from mechanical energy of the limb: a preliminary study.

Measurements of metabolic energy consumption and free-walking velocity were recorded for four persons with trans-femoral amputation with variations of prosthesis mass and mass distribution. Hot-film anemometers, rate gyroscopes, and a force platform were used to measure prosthetic limb segment velocities and ground reaction forces. Metabolic energy consumption for the nine configurations of mass and mass distribution averaged 1.177 cal/kg/m with a standard deviation of +/- 0.052 cal/kg/m. Two measures of mechanical work of the amputated extremity, one based on power developed across joints (W1) and the other based on changes in energy of the body segments (W2), were computed to be 0.162 +/- 0.014 and 0.175 +/- 0.025 cal/kg/m, respectively. A linear regression model led to rejections of both W1 and W2 as predictors of metabolic energy expenditure of the amputee at a significance level of 0.05.

Aged↗
PubMed1994

Effects of variation of prosthesis size on cement stress at the tip of a femoral implant.

With the resurgence of the use of bone cement in total hip arthroplasty, a renewed interest 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. This study analyzed stresses in the cement near the tip of a femoral component as a function of cement thickness, using a three-dimensional finite element model. A section of an idealized circular femoral shaft with implanted prosthesis and cement was modeled with loading conditions representing the stance phase of gait. Increasing cement thickness from 2 to 5 mm by reducing the prosthesis diameter from 15 to 9 mm is predicted to reduce stress significantly in the cement mantle of a femoral implant. Peak tensile stresses are reduced 45%, whereas peak von Mises and shear stresses are reduced 40%. Such a reduction in stress can increase fatigue life by an order of magnitude. Peak interface tensile stresses occur on the medial side at the tip of the prosthesis in a transverse direction, indicating likelihood of failure due to debonding. The shear and tensile stresses predicted by our model greatly exceed the fatigue endurance limit values for both bulk cement and the cement-prosthesis interface, indicating the likelihood of premature fatigue failure, even allowing for considerable uncertainty. These analytical results suggest that the surgeon should adopt a strategy of selecting a prosthesis that permits a 5-mm cement mantle near the tip of the prosthesis.

Bone Cements↗
PubMed1994

Correlations between orthogonal mechanical properties and density of trabecular bone: use of different densitometric measures.

To compare the numerous modulus-density and strength-density relations that have been found for human trabecular bone from the proximal tibia, correlations between various measures of density were sought. Hydrated and dry apparent density, ash density, and density from quantitative computed tomography (QCT) were determined for cubic trabecular specimens taken from the proximal portion of human tibiae, and correlations between these measures were found (r > 0.99, P < .001). Orthogonal moduli and strengths of the specimens were measured mechanically, and were significantly correlated with ash density according to power relations (r > or = 0.85, P < .001). The strong correlation between density from QCT and ash density indicates that these measures can be used with nearly equal precision in estimating modulus and strength of tibial trabecular bone. Equations between mechanical properties and density reported in previous studies were converted to use a common density measure and, after considering the effects of specimen size, were in general agreement with results of the present study.

Adult↗
PubMed1994

Femoral prosthesis implantation induces changes in bone stress that depend on the extent of porous coating.

The objective of this study was to evaluate the effect of implantation of porous-coated anatomic medullary fitting prostheses on stress in the proximal femur. Three-dimensional finite element models of a cadaveric femur before and after implantation were used to evaluate the resulting changes in stress in the bone. Models of the femur were generated automatically from computed tomographic scan data with use of an innovative mesh-generation technique. The models were analyzed for three levels of porous coating (proximal, 5/8, and full), with the assumption of ideal ingrowth (perfect bonding) over porous areas and a frictionless, tension-free surface on smooth areas. All models were loaded and restrained to represent conditions of normal gait. The stresses predicted in the implanted femur are consistent with clinical observations of proximal cortical atrophy (normal stress reduced to 6-9% of normal at the calcar and 50-55% at mid-prosthesis) and of hypertrophy at the porous coating junctions (normal stress at the 5/8-coating junction, 123% of stress proximal to the junction) and hypertrophy near the distal tip of the prosthesis (anterior and posterior normal stresses 200-800% of normal). The fully coated prosthesis induced stresses in the bone near the tip of the prosthesis that were most like stresses in the normal femur (medial and lateral normal stress 105 and 102% of the stress in the normal femur). Below the collar, the normal stress associated with the proximally coated prosthesis was 6% greater than that produced with the other two levels of coating but still was only 2% of normal. The 5/8-coated prosthesis appeared to combine the worst features of the fully coated and proximally coated prostheses--greater stress-shielding at the calcar and higher stress near the tip of the prosthesis.

Artificial Limbs↗
PubMed1994

Constrained acetabular components.

Between May 1987 and October 1990, 21 constrained acetabular components were used in revision total hip arthroplasty at the University of California, San Francisco. In 18 patients, the device was placed for a chronically dislocating total hip arthroplasty. In the remaining three, intraoperative instability during revision total hip arthroplasty necessitated its use. At the minimum 2-year follow-up evaluation (average, 31 months; range, 24-64 months), 15 patients (71%) experienced no further dislocations or subluxations. There were eight dislocations in the remaining six patients (29%). The average Harris hip score at the follow-up evaluation was 76 points (range, 32-100 points). For those patients who redislocated (n = 6), an increased acetabular abduction angle of the metallic acetabular cup, averaging 70 degrees, was the only predictive factor of failure of the constrained cup (P < .05). No radiographic or clinical evidence of loosening in the 19 porous ingrowth acetabular component was observed. This device will relieve the complication of severe hip instability in the majority of patients, but is not universally successful.

Acetabulum↗
PubMed1994

A phosphatidylinositol transfer protein controls the phosphatidylcholine content of yeast Golgi membranes.

SEC14p is required for protein transport from the yeast Golgi complex. We describe a quantitative analysis of yeast bulk membrane and Golgi membrane phospholipid composition under conditions where Golgi secretory function has been uncoupled from its usual SEC14p requirement. The data demonstrate that SEC14p specifically functions to maintain a reduced phosphatidylcholine content in Golgi membranes and indicate that overproduction of SEC14p markedly reduces the apparent rate of phosphatidylcholine biosynthesis via the CDP-choline pathway in vivo. We suggest that SEC14p serves as a sensor of Golgi membrane phospholipid composition through which the activity of the CDP-choline pathway in Golgi membranes is regulated such that a phosphatidylcholine content that is compatible with the essential secretory function of these membranes is maintained.

Carrier Proteins↗
PubMed1994

A phosphatidylinositol/phosphatidylcholine transfer protein is required for differentiation of the dimorphic yeast Yarrowia lipolytica from the yeast to the mycelial form.

The SEC14SC gene encodes the phosphatidylinositol/phosphatidylcholine transfer protein (PI/PC-TP) of Saccharomyces cerevisiae. The SEC14SC gene product (SEC14pSC) is associated with the Golgi complex as a peripheral membrane protein and plays an essential role in stimulating Golgi secretory function. We report the characterization of SEC14YL, the structural gene for the PI/PC-TP of the dimorphic yeast Yarrowia lipolytica. SEC14YL encodes a primary translation product (SEC14YL) that is predicted to be a 497-residue polypeptide of which the amino-terminal 300 residues are highly homologous to the entire SEC14pSC, and the carboxyl-terminal 197 residues define a dispensible domain that is not homologous to any known protein. In a manner analogous to the case for SEC14pSC, SEC14pYL localizes to punctate cytoplasmic structures in Y. lipolytica that likely represent Golgi bodies. However, SEC14pYL is neither required for the viability of Y. lipolytica nor is it required for secretory pathway function in this organism. This nonessentiality of SEC14pYL for growth and secretion is probably not the consequence of a second PI/PC-TP activity in Y. lipolytica as cell-free lysates prepared from delta sec14YL strains are devoid of measurable PI/PC-TP activity in vitro. Phenotypic analyses demonstrate that SEC14pYL dysfunction results in the inability of Y. lipolytica to undergo the characteristic dimorphic transition from the yeast to the mycelial form that typifies this species. Rather, delta sec14YL mutants form aberrant pseudomycelial structures as cells enter stationary growth phase. The collective data indicate a role for SEC14pYL in promoting the differentiation of Y. lipolytica cells from yeast to mycelia, and demonstrate that PI/PC-TP function is utilized in diverse ways by different organisms.

Amino Acid Sequence↗
PubMed1994

Three-dimensional finite element modeling of a cervical vertebra: an investigation of burst fracture mechanism.

Finite element modeling was used to study the mechanical behavior of a cervical vertebra under axial compressive loading. A three-dimensional (3-D) finite element (FE) model of a mid-cervical vertebra using inhomogeneous material properties was generated from quantitative computed tomographic (CT) scan data. This model improved upon previous vertebral FE models by using a highly refined mesh to represent the 3-D variation in material properties of vertebral bone. Traumatic loading of the vertebra was simulated by applying an axial compressive displacement through linear spring elements. Bone strength was computed from the CT scan data and compared with predicted stress. Based on the maximum shear stress theory of failure, the model predicts initiation of failure in the central cancellous region of the vertebral body. The type of fracture pattern predicted by the model is consistent with the typical cervical burst fracture that is seen clinically after compressive loading of the cervical spine. As such, we have developed a tool that can be useful for validating proposed fracture mechanisms in the cervical spine.

Cervical Vertebrae↗
PubMed1994

Functional redundancy of CDP-ethanolamine and CDP-choline pathway enzymes in phospholipid biosynthesis: ethanolamine-dependent effects on steady-state membrane phospholipid composition in Saccharomyces cerevisiae.

It has been established that yeast membrane phospholipid content is responsive to the inositol and choline content of the growth medium. Alterations in the levels of transcription of phospholipid biosynthetic enzymes contribute significantly to this response. We now describe conditions under which ethanolamine can exert significant influence on yeast membrane phospholipid composition. We demonstrate that mutations which block a defined subset of the reactions required for the biosynthesis of phosphatidylcholine (PC) via the CDP-choline pathway cause ethanolamine-dependent effects on the steady-state levels of bulk PC in yeast membranes. Such an ethanolamine-dependent reduction in bulk membrane PC content was observed for both choline kinase (cki) and choline phosphotransferase (cpt1) mutants, but it was not observed for mutants defective in cholinephosphate cytidylyltransferase, the enzyme that catalyzes the penultimate reaction of the CDP-choline pathway for PC biosynthesis. Moreover, the ethanolamine effect observed for cki and cpt1 mutants was independent of the choline content of the growth medium. Finally, we found that haploid yeast strains defective in the activity of both the choline and ethanolamine phosphotransferases experienced an ethanolamine-insensitive reduction in steady-state PC content, an effect which was not observed in strains defective in either one of these activities alone. The collective data indicate that specific enzymes of the CDP-ethanolamine pathway for phosphatidylethanolamine biosynthesis, while able to contribute to PC synthesis when yeast cells are grown under conditions of ethanolamine deprivation, do not do so when yeast cells are presented with this phospholipid headgroup precursor.

Carrier Proteins↗