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Biomedical subjects

J D Clausen

Publications and source records attributed to J D Clausen.

16 recordsLinked to original sources
PubMed2003

ATP binding residues of sarcoplasmic reticulum Ca2+-ATPase.

ATP-binding residues in the N and P domains of sarcoplasmic reticulum Ca-ATPase have been investigated using mutagenesis in combination with a binding assay based on the photolabeling of Lys(492) with [g-(32)P] 2',3'-O-(2,4,6 trinitrophenyl)-8-azido-ATP and competition with nucleotide. In the N domain, mutations to several residues in conserved motifs, (438)GEATE, (487)FSRDRK, (515)KGAPE, and (560)RCLALA produce nucleotide-binding defects. Key residues include Thr(441), Glu(442), Phe(487), Arg(489), Lys(492), Lys(515), Arg(560), and Leu(562). In the absence of Mg(2+), Arg(489), Lys(492), and Arg(560) are most important, whereas in its presence Thr(441) and Glu(442) also play a crucial role. In the P domain, Asp(351) is striking for its strong electrostatic repulsion of the gamma-phosphate, especially in the presence of Mg(2+). Lys(352) is a key residue, and Asp(627) and Lys(684) must come close to the nucleotide. Thr(353), Asn(359), Asp(601), and Asp(703) interact only in the presence of Mg(2+). Asn(706) and Asp(707) are unimportant for nucleotide binding. The results identify several ATP binding residues in the N and P domains and suggest that Mg(2+) changes the nucleotide/protein interaction in both. Models of bound ATP and MgATP are presented.

Adenosine Triphosphate↗
PubMed2001

Importance of Thr-353 of the conserved phosphorylation loop of the sarcoplasmic reticulum Ca2+-ATPase in MgATP binding and catalytic activity.

Mutants in which Thr-353 of the Ca(2+)-ATPase of sarcoplasmic reticulum had been replaced with alanine, serine, glutamine, cysteine, valine, aspartate, or tyrosine were analyzed functionally. All the mutations severely affected MgATP binding, whereas ATP binding was close to normal in the alanine, serine, glutamine, and valine mutants. In the serine and valine mutants, the maximum rate of phosphorylation from MgATP was 8- and 600-fold lower, respectively, compared with wild type. Replacement of Mg(2+) with Mn(2+) led to a 1.5-fold enhancement of the maximum phosphorylation rate in the valine mutant and a 5-fold reduction in the wild type. The turnover of the phosphoenzyme formed from MgATP was slowed 1-2 orders of magnitude relative to wild type in the alanine, serine, and valine mutants, but was close to normal in the aspartate and cysteine mutants. Only the serine mutant formed a phosphoenzyme in the backward reaction with P(i), and the hydrolysis of this intermediate was greatly enhanced. Analysis of the functional changes in the mutants in the light of the recent high resolution structure of the Ca(2+)-ATPase crystallized without the MgATP substrate suggests that, in the native activated state of the enzyme, the side chain hydroxyl of Thr-353 participates in important interactions with nucleotide and phosphate, possibly in catalysis, whereas the main chain carbonyl of Thr-353, but not the side chain, may coordinate the catalytic Mg(2+).

Adenosine Triphosphate↗
PubMed2001

A new semirigid implant for instrumentation of scoliosis: preliminary report.

A new set of pedicle screws, lamina and pedicle hooks, longitudinal rods and a titanium cable was developed to overcome the increasingly obvious hazards of overly rigid spinal instrumentation. Results of the first 12 consecutive scoliosis patients with this new system are reported, with an average follow-up time of 18 months. No major complications occurred. The average correction of the deformity was well within the range of more rigid systems. The new Dorsal Dynamic Spondylodesis (DDS) system proved to be easy to use, fast, powerful, safe, versatile, and biomechanically sound. Reduction of stress-shielding effects and protection of adjacent segments can be expected, and the system warrants future application in selected prospective cases with long-term follow-up.

Equipment Design↗
PubMed1998

Prediction of load sharing among spinal components of a C5-C6 motion segment using the finite element approach.

STUDY DESIGN: A finite element model of the ligamentous cervical spinal segment was used to compute loads in various structures in response to clinically relevant loading modes. OBJECTIVE: To predict biomechanical parameters, including intradisc pressure, tension in ligaments, and forces across facets that are not practical to quantify with an experimental approach. SUMMARY OF BACKGROUND DATA: Finite element models of the cervical spine in their present form, because of inherent assumptions and simplifications, are not entirely satisfactory for studying the biomechanics of the intact, injured, and stabilized cervical spinal segment. METHODS: A three-dimensional finite element model of a C5-C6 motion segment was developed from serial computed tomographic scans of a ligamentous cervical spinal segment. This model included nonlinear ligament definition, fully composite intervertebral disc, fluid nucleus, and Luschka's joints. The model-based displacement predictions were in agreement with the experimental data. This model was used to predict load sharing and other related parameters in spinal elements in response to various loading modalities. RESULTS: In axial compression, 88% of the applied load passed through the disc. The interspinal ligament experienced the most strain (29.5%) in flexion, and the capsular ligaments were strained the most (15.5%) in axial rotation. The maximum intradisc pressure was 0.24 MPa in the flexion with axial compression mode (1.8 Nm + 73.6 N). The anterior and posterior disc bulges increased with the increase in axial compression (up to 800 N). CONCLUSIONS: The results provide new insight into the role of various elements in transmitting loads. The model represents significant and essential advancement in comparison with previous finite element models, making it possible for such models to be used in investigating a broad spectrum of clinically relevant issues.

Biomechanical Phenomena↗
PubMed1997

Uncinate processes and Luschka joints influence the biomechanics of the cervical spine: quantification using a finite element model of the C5-C6 segment.

A fully three-dimensional finite element model of a C5-C6 motion segment of the human spine was developed and validated for the purpose of investigating the biomechanical significance of uncinate processes and Luschka joints. The original intact cervical model was modified to create two additional models. The first simulated the absence of Luschka joints by replacing the fissures with continuous annulus fibrosus and leaving the uncinate processes intact. The second model simulated a surgical resection of the uncinate processes, while leaving the Luschka joints intact. The results of these two models were compared with the intact model, which served as a baseline; thus, the relative contributions of these two structures to cervical motion were established. With use of our model, it was possible, for the first time, to provide quantitative data concerning the source of coupled motions in the lower cervical spine. In principle, the results from this model support the hypothesis of Penning and Wilmink. Our results indicate that the facet joints and Luschka joints are the major contributors to coupled motion in the lower cervical spine and that the uncinate processes effectively reduce motion coupling and primary cervical motion (motion in the same direction as load application), especially in response to axial rotation and lateral bending loads. Luschka joints appear to increase primary cervical motion, showing an effect on cervical motion opposite to that of the uncinate processes. Surgeons should be aware of the increase in motion accompanied by resection of the uncinate processes.

Biomechanical Phenomena↗
PubMed1997

Chlamydia trachomatis utilizes the host cell microtubule network during early events of infection.

The host cell cytoskeleton is known to play a vital role in the life cycles of several pathogenic intracellular microorganisms by providing the basis for a successful invasion and by promoting movement of the pathogen once inside the host cell cytoplasm. McCoy cells infected with Chlamydia trachomatis serovars E or L2 revealed, by indirect immunofluorescence microscopy, collocation of microtubules and Chlamydia-containing vesicles during the process of migration from the host cell surface to a perinuclear location. The vast majority of microtubule-associated Chlamydia vesicles also collocated with tyrosine-phosphorylated McCoy cell proteins. After migration, the Chlamydia-containing vesicles were positioned exactly at the centre of the microtubule network, indicating a microtubule-dependent mode of chlamydial redistribution. Inhibition of host cell dynein, a microtubule-dependent motor protein known to be involved in directed vesicle transport along microtubules, was observed to have a pronounced effect on C. trachomatis infectivity. Furthermore, dynein was found to collocate with perinuclear aggregates of C. trachomatis E and L2 but not C. pneumoniae VR-1310, indicating a marked difference in the cytoskeletal requirements for C. trachomatis and C. pneumoniae during early infection events. In support of this view, C. pneumoniae VR-1310 was shown to induce much less tyrosine phosphorylation of HeLa cell proteins during uptake than that seen for C. trachomatis.

Animals↗
PubMed1997

A protocol to evaluate semi-rigid pedicle screw systems.

The objective of the current study was to develop an in vitro testing protocol to evaluate semi-rigid pedicle screw devices. A corpectomy model protocol exists to evaluate rigid spinal implants; however, semi-rigid devices are contraindicated for this condition. This paper describes a technique that simulates more closely the conditions a semi-rigid device would see in vivo. Finally, the new testing protocol is used to evaluate the DDS pedicle screw-cable system. Benefits and shortcomings of the new protocol are discussed.

Bone Screws↗
PubMed1996

Cervical spine motion with direct laryngoscopy and orotracheal intubation. An in vivo cinefluoroscopic study of subjects without cervical abnormality.

BACKGROUND: Cervical spine kinetics during airway manipulation are poorly understood. This study was undertaken to quantify the extent and distribution of segmental cervical motion produced by direct laryngoscopy and orotracheal intubation in human subjects without cervical abnormality. METHODS: Ten patients without clinical or radiographic evidence of cervical spine abnormality underwent laryngoscopy using a #3 Macintosh blade while under general anesthesia and neuromuscular blockade. Cervical motion was recorded with continuous lateral fluoroscopy. The intubation sequence was divided into distinct stages and the corresponding fluoroscopic images were digitized. Segmental motion, occiput through C5, was calculated for each stage using the digitized data. RESULTS: During exposure and laryngoscope blade insertion, minimal displacement of the skull base and rostral cervical vertebral bodies was observed. Visualization of the larynx created superior rotation of the occiput and C1 in the sagittal plane, and mild inferior rotation of C3-C5. C2 maintained nearneutral posture. This pattern of displacement resulted in extension at each motion segment, with the most significant motion produced at the occipitoatlantal and atlantoaxial joints (mean = 6.8 degrees and 4.7 degrees, respectively). Intubation created slight additional superior rotation at the occiput and C1, without substantial alteration in the posture of C2-C5. After laryngoscope removal, position trended toward baseline at all levels, although exact neutral posture was not regained. CONCLUSIONS: This investigation quantifies the behavior of the normal cervical spine during direct laryngoscopy with a Macintosh blade. With this maneuver, the vast majority of cervical motion is produced at the occipitoatlantal and atlantoaxial joints. The subaxial cervical segments (C2-C5) are displaced only minimally. This study establishes a highly reliable and reproducible method for analyzing cervical motion in real time.

Adult↗
PubMed1996

Biomechanical evaluation of Caspar and Cervical Spine Locking Plate systems in a cadaveric model.

There exist two markedly different instrumentation systems for the anterior cervical spine: the Cervical Spine Locking Plate (CSLP) system, which uses unicortical screws with a locking hub mechanism for attachment, and the Caspar Trapezial Plate System, which is secured with unlocked bicortical screws. The biomechanical stability of these two systems was evaluated in a cadaveric model of complete C5-6 instability. The immediate stability was determined in six loading modalities: flexion, extension, right and left lateral bending, and right and left axial rotation. Biomechanical stability was reassessed following fatigue with 5000 cycles of flexion-extension, and finally, the spines were loaded in flexion until the instrumentation failed. The Caspar system stabilized significantly in flexion before (p < 0.05) but not after fatigue, and it stabilized significantly in extension before (p < 0.01) and after fatigue (p < 0.01). The CSLP system stabilized significantly in flexion before (p < 0.01) but not after fatigue, and it did not stabilize in extension before or after fatigue. The moment needed to produce failure in flexion did not differ substantially between the two plating systems. The discrepancy in the biomechanical stability of these two systems may be due to differences in bone screw fixation.

Adult↗
PubMed1995

Assessment of unicortical and bicortical fixation in a quasistatic cadaveric model. Role of bone mineral density and screw torque.

STUDY DESIGN: The stabilizing potential of the Caspar Trapezial Osteosynthetic Plate was studied using unicortical and bicortical screw placement in cadaveric cervical spines. OBJECTIVE: To determine if Caspar plates secured with unicortical screws provide the same degree of stability as those anchored with unlocked bicortical screws. SUMMARY OF BACKGROUND DATA: Previous work has demonstrated that bicortical cervical vertebral screws are superior to unicortical screws in terms of pullout strength and decreased wobble. However, these two methods of plate fixation have not been directly compared in a clinically relevant cadaveric model. METHODS: The immediate and post-fatigue stabilizing potential of Caspar plates secured with unicortical or bicortical screws was assessed using a model of complete segmental instability. RESULTS: Unicortical screw placement resulted in inadequate stabilization in half of the cervical specimens. CONCLUSIONS: Our results suggest that, for the Caspar screw, bicortical fixation provides greater flexion-extension stability.

Biomechanical Phenomena↗
PubMed1995

Finite element methods in spine biomechanics research.

The finite element method has been used in spine biomechanics research for nearly a quarter of a century. Recent developments have made it possible to simulate a variety of clinically relevant situations in an increasingly realistic manner, elevating the finite element method into a fully complementary partnership with experimental approaches for the investigation of clinical problems in the spine. These new developments are presented in a historical context to evaluate their potential impact on future spine biomechanics research.

Age Factors↗
PubMed1995

Biomechanical analysis of bone mineral density, insertion technique, screw torque, and holding strength of anterior cervical plate screws.

The bone mineral density (BMD) of 99 cadaveric cervical vertebral bodies (C3-7) was determined using dual x-ray absorptiometry. The vertebral bodies were randomly assigned to receive either a unicortical (51 bodies) or bicortical (48 bodies) Caspar cervical plating screw. The initial insertion torque was measured using a digital electronic torque wrench, and the force required to withdraw the screw from the vertebral body was determined. The mean BMD for the total group of 99 was 0.787 +/- 0.154 g/cm2, the mean insertion torque was 0.367 +/- 0.243 newton-meters, and the mean pullout force was 210.4 +/- 158.1 newtons. A significant correlation was noted between BMD and torque (p < 0.0001, r = 0.42), BMD and pullout force (p < 0.0001, r = 0.54), and torque and pullout force (p < 0.0001, r = 0.88). Although the BMD of the unicortical and biocortical groups was equivalent (p = 0.92), the insertion torque and pullout force differed significantly (p = 0.02 and p = 0.008, respectively) for the unicortical and bicortical groups. A holding index for each screw and insertion technique was defined as the product of the BMD and insertion torque. The calculated holding index and resultant pullout force were significantly correlated for both techniques of screw insertion (r = 0.92), and a significant difference in holding index was observed with unicortical versus bicortical screw placement (p = 0.04). The determination of BMD and measurement of insertion torque to create a unique holding index provides an assessment of bone-screw interaction and holding strength of the screw, both of which impact on the resultant stability of cervical instrumentation. As the number of cervical plating systems increases, the determination of a holding index for various screws and insertion techniques may assist in the comparison of cervical instrumentation.

Absorptiometry, Photon↗
PubMed1994

Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures.

In an experimental study with 18 minipigs, we have tried to establish a model for the standardized evaluation of mechanical, histological and radiological phenomena of degenerative and reparative processes within the lumbar motion segment. Comparing different operative techniques revealed that the intradiscal application of hyaluronic acid into the nuclear defect is likely to enhance the regeneration process. Using the measurement of disc compliance, a semiautomatic picture analyzer and a new semiquantitative disc score could make future studies more comparable. From this basis, the intradiscal application of hyaluronic acid deserves further evaluation.

Animals↗
PubMed1980

Relationship of dietary regimens to success, efficiency, and cost of weight loss.

One hundred twenty-five subjects in a behaviorally oriented, weight loss program that used several dietary patterns were retrospectively grouped according to the percentage of time they followed one of four dietary regimens: (a) Group 1--partial fasting, 400 kcal; (b) group 2--600 kcal; (c) group 3--1,200 to 1,500 kcal; and (d) group 4--failure to diet. The groups were described and compared regarding program completion, i.e., success and cost of weight loss. Groups 1 and 2 did significantly better than the other two in nearly all respects. Group 1 did better than Group 2 on program completion; the reverse was true when success of those completing 75 and 100 per cent of the program was compared. Groups 1 and 2 did not differ significantly on success variables.

Adult↗
PubMedDate not supplied

Characterization of Chlamydia trachomatis l2-induced tyrosine-phosphorylated HeLa cell proteins by two-dimensional gel electrophoresis.

Chlamydia trachomatis is an obligate intracellular bacteria, inducing its own uptake in nonprofessional phagocytes either by phagocytosis or pinocytosis. We have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of eukaryotic proteins upon their entry by phagocytosis. In this paper we characterize the tyrosine-phosphorylated proteins by two-dimensional gel electrophoresis. In immunoblotting with anti-phosphotyrosine antibodies of C. trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to 5.2. In addition, a single spot of 100 kDa and pI 6.2 was observed.

Animals↗