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Biomedical subjects

R E Hughes

Publications and source records attributed to R E Hughes.

At least 19 recordsLinked to original sources
PubMed2001

Altered transcription in yeast expressing expanded polyglutamine.

Expanded polyglutamine tracts are responsible for at least eight fatal neurodegenerative diseases. In mouse models, proteins with expanded polyglutamine cause transcriptional dysregulation before onset of symptoms, suggesting that this dysregulation may be an early event in polyglutamine pathogenesis. Transcriptional dysregulation and cellular toxicity may be due to interaction between expanded polyglutamine and the histone acetyltransferase CREB-binding protein. To determine whether polyglutamine-mediated transcriptional dysregulation occurs in yeast, we expressed polyglutamine tracts in Saccharomyces cerevisiae. Gene expression profiles were determined for strains expressing either a cytoplasmic or nuclear protein with 23 or 75 glutamines, and these profiles were compared to existing profiles of mutant yeast strains. Transcriptional induction of genes encoding chaperones and heat-shock factors was caused by expression of expanded polyglutamine in either the nucleus or cytoplasm. Transcriptional repression was most prominent in yeast expressing nuclear expanded polyglutamine and was similar to profiles of yeast strains deleted for components of the histone acetyltransferase complex Spt/Ada/Gcn5 acetyltransferase (SAGA). The promoter from one affected gene (PHO84) was repressed by expanded polyglutamine in a reporter gene assay, and this effect was mitigated by the histone deacetylase inhibitor, Trichostatin A. Consistent with an effect on SAGA, nuclear expanded polyglutamine enhanced the toxicity of a deletion in the SAGA component SPT3. Thus, an early component of polyglutamine toxicity, transcriptional dysregulation, is conserved in yeast and is pharmacologically antagonized by a histone deacetylase inhibitor. These results suggest a therapeutic approach for treatment of polyglutamine diseases and provide the potential for yeast-based screens for agents that reverse polyglutamine toxicity.

Amino Acid Sequence↗
PubMed2001

The effect of wearing a back belt on spine kinematics during asymmetric lifting of large and small boxes.

STUDY DESIGN: A crossover design was used to evaluate kinematic measurements collected with an infrared-based motion measurement system. OBJECTIVES: To evaluate belt effects on spine kinematics during asymmetric lifting of large and small boxes and to test for carryover effects between trials from belts. SUMMARY OF BACKGROUND DATA: Conflicting evidence in the literature exists regarding whether belts are beneficial or detrimental to manual material handlers. Studies have not examined belt effects when lifting different sized boxes, nor carryover effects from belts. METHODS: Twenty-eight subjects with manual-handling experience (17 male and 11 female) were randomly assigned to lift either a large or small box (weighing 9.4 kg), from a sagittally symmetric origin at pallet height to a 79 cm height, 60 degrees to the right. Spine flexion, lateral bending and twisting, hip and knee flexion, and angular velocity measurements of the torso with respect to the pelvis were collected for each of three lifting periods, 50 lifts each at 3 lifts per minute, with 18-minute breaks between periods. RESULTS: Belts significantly reduced maximum spine flexion, spine flexion and extension angular velocities, and torso left lateral bending angular velocity, and increased hip and knee flexion, regardless of box size. When lifting large boxes, belts significantly reduced torso right lateral bending and torso left twisting. No significant differential carryover effects were detected from belts. CONCLUSIONS: Subjects with belts lifted more slowly and used more of a squat-lift technique, regardless of box size. Belts reduced more torso motions while lifting large boxes.

Adolescent↗
PubMed2001

Therapeutic opportunities in polyglutamine disease.

Polyglutamine diseases comprise a class of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine tracts. Great progress has been made in elucidating the molecular mechanisms contributing to polyglutamine pathology, and in identifying potential drug targets. Although much remains to be learned, these advances provide an opportunity for rational approaches to target-based drug discovery.

Animals↗
PubMed2001

The relationship between Parson's tubercle and the insertion of the anterior horn of the medial meniscus.

PURPOSE: The purpose of this investigation was to correlate the anatomic characteristics of the third intercondylar tubercle of Parsons (TITP) with the insertional variations of the anterior horn of the medial meniscus using precise measurements in an anatomic cadaver study. Our hypothesis was that the height of the TITP would correlate with the degree of inferior insertion of the medial meniscus. TYPE OF STUDY: A cadaver study using a convenience sample. METHODS: Twenty unpaired proximal tibia specimens without advanced arthritis were analyzed with a coordinate measuring machine using a 0.479-mm diameter probe. A reference plane was created using 3 reproducible points on the tibial surface. Measurements from the TITP included another reference plane through its base, which was used to calculate its absolute height. The locations of the anterior- and inferior-most insertional points of the anterior horn of the medial meniscus were also determined. Correlations between the height of the TITP and age were also made. RESULTS: The overall height of the TITP was found to correlate with the degree of inferior insertion of the anterior horn of the medial meniscus (r =.52, P =.019). No correlation was found with the anterior placement of the meniscus (r =.12, P =.629) or with the age of the specimen (r =.14, P =.592). CONCLUSIONS: This absolute height of the TITP correlates with the inferior location of the insertion of the anterior horn of the medial meniscus. This association suggests a developmental relationship between 2 anatomic structures within the knee.

Adult↗
PubMed2000

Effect of optimization criterion on spinal force estimates during asymmetric lifting.

Optimization-based muscle force prediction models of the lumbar region are used in research and ergonomic practice, usually as a subroutine of a job analysis software package. Various optimization criteria have been put forward for use in rationally selecting a set of muscle forces to satisfy moment equilibrium, including the sum of cubed muscle contraction intensities and a double linear programming procedure for minimizing the spinal compression force and maximum muscle contraction intensity. A laboratory study was conducted to determine whether these two model formulations produce significantly different estimates of spinal forces for a dynamic asymmetric lift. Although statistically significant differences were found between the predictions of the two models, the difference in peak spinal compression force was only 1.1%.

Adult↗
PubMed2000

Systematic and large-scale two-hybrid screens.

The increasing rate at which complete genome sequences become available necessitates rapid and robust methods for investigating the functions of their encoded proteins. Efforts have been made to study protein function by systematically screening large sets of proteins using the two-hybrid method. Analyses of the complete proteomes of baceriophage T7, the mammalian viruses hepatitis C and vaccinia, as well as of several protein complexes including RNA splicing proteins and RNA polymerase III from yeast, have been undertaken. Saccharomyces cerevisiae has been studied extensively by two-hybrid methods, with more than 2500 protein-protein interactions described. Systematic studies on metazoan proteomes are, however, still in their infancy.

Animals↗
PubMed1999

Normative values of agonist-antagonist shoulder strength ratios of adults aged 20 to 78 years.

OBJECTIVE: To determine normative values for isometric flexion/extension, abduction/adduction, and external/internal rotation strength ratios about the shoulder and to determine if these ratios are affected by age or gender. STUDY DESIGN: A cross-sectional study of 120 healthy volunteers (60 men, 60 women) aged 20 to 78 years. SETTING: Orthopedic research laboratory. METHODS: Flexion and extension strengths were measured isometrically using a Cybex II dynamometer at arm flexion angles of 30 degrees, 60 degrees, and 90 degrees. Abduction and adduction strengths were measured at 30 degrees, 60 degrees, and 90 degrees abduction. Internal and external rotation strengths were measured (1) with the arm abducted 15 degrees and neutral external/internal rotation and (2) with the arm abducted 90 degrees and externally rotated 30 degrees above the transverse plane. OUTCOME MEASURES: Isometric strength ratios for flexion/extension, abduction/adduction, and external/internal rotation. RESULTS: No statistically significant differences in agonist/antagonist strength ratios were found between dominant and nondominant sides or between genders. Age was associated with changes in strength ratios for measurements taken with the arm flexed or abducted 90 degrees. Posture was found to affect strength ratios. CONCLUSIONS: These data can serve as a normative reference for clinical use.

Adult↗
PubMed1999

Abduction moment arm of transposed subscapularis tendon.

OBJECTIVE: The purpose of this study was to analyze the effects of the procedure of superior transposition of the subscapularis on the biomechanics of glenohumeral abduction. DESIGN: The abduction moment arms of the subscapularis muscle for the normal attachment and transposed tendon were measured on 10 cadaver shoulders and compared to that for the normal supraspinatus tendon for which it is intended to substitute. BACKGROUND: Superior transposition of the subscapularis tendon has been recommended for surgical repair of massive tears of the rotator cuff, but the effect of this procedure on shoulder biomechanics has not been reported. METHODS: The moment arm about an instantaneous center of rotation was derived, based on the slope of tendon excursion-glenohumeral angle curve. To simulate the insertion of the transposed subscapularis tendon, pseudo-insertion sites were created. RESULTS: Superior transposition of the subscapularis tendon significantly increased its abduction moment arm. The effect was optimal when the simulated insertion site was lateral rather than medial and, to a lesser extent, anterior versus posterior. CONCLUSIONS: The results provided a biomechanical rationale for subscapularis tendon transposition in restoring the loss of abduction strength of the shoulder in a massive cuff tear.

Adult↗
PubMed1999

Identification of optimal strategies for increasing whole arm strength using Karush-Kuhn-Tucker multipliers.

OBJECTIVE: The purpose of this study was to develop a computer model for identifying muscles critical to improving functional upper extremity strength. DESIGN: A three-dimensional biomechanical model of the upper extremity was developed, and the predictions were compared to maximal arm strength data collected from healthy volunteers. BACKGROUND: Although several optimization-based mathematical models of the shoulder have been developed, none have utilized the mathematical properties of the Karush-Kuhn-Tucker multipliers to efficiently estimate the effect of strengthening individual muscles on functional strength of the whole arm. METHODS: A static three-dimensional biomechanical model of the glenohumeral, radio-humeral, ulno-humeral and wrist joints was developed for predicting maximal hand exertion forces. The model was formulated as a linear program. Constraints consisted of moment equilibrium conditions and limits on maximum and minimum allowable muscle forces. Predicted arm strengths were compared to maximal pull strength measurements made on 10 subjects (5 male; 5 female). The task involved pulling toward the mid-sagittal plane of the body with the arm flexed 45 degrees. The Karush-Kuhn-Tucker variables associated with the maximal limits on muscle force were computed to estimate the effect of altering the strength of individual muscles on functional arm strength. RESULTS: Maximum pull strengths were predicted well by the model. Karush-Kuhn-Tucker values ranged from 0 (for muscles not at their upper force limits) to 0.11 for the flexor carpi radialis and pectoralis major muscles. Karush-Kuhn-Tucker multipliers were found to be insensitive to the assumed specific tension of muscle. CONCLUSIONS: Upper extremity strength can be predicted from musculoskeletal geometry and physiology using linear programming. RELEVANCE: Karush-Kuhn-Tucker multipliers associated with the muscle force upper limits give insight into the effect of strengthening individual muscles on whole arm exertion strength. Such an analysis may provide insight into the development of optimal rehabilitation protocols.

Adult↗
PubMed1998

Ca2+-dependent conformational changes in bovine GCAP-2.

GCAP-2, a mammalian photoreceptor-specific protein, is a Ca2+-dependent regulator of the retinal membrane guanylyl cyclases (Ret-GCs). Sensing the fall in intracellular free Ca2+ after photo-excitation, GCAP-2 stimulates the activity of Ret-GC leading to cGMP production. Like other members of the recoverin superfamily, GCAP-2 is a small N-myristoylated protein containing four EF-hand consensus motifs. In this study, we demonstrate that like recoverin and neurocalcin, GCAP-2 alters its conformation in response to Ca2+-binding as measured by a Ca2+-dependent change in its far UV CD spectrum. Differences in the conformation of the Ca2+-bound and Ca2+-free forms of GCAP-2 were also observed by examining their relative susceptibility to V8 protease. In contrast to recoverin, we do not observe proteolytic cleavage of the myristoylated N-terminus of Ca2+-bound GCAP-2. NMR spectra also show that, in contrast to recoverin, the chemical environment of the N-terminus of GCAP-2 is not dramatically altered by Ca2+ binding. Despite the similarity of GCAP-2 and recoverin, the structural consequences of Ca2+-binding for these two proteins are significantly dissimilar.

Amino Acid Sequence↗
PubMed1998

Comparison of two methods for computing abduction moment arms of the rotator cuff.

Biomechanical models of the shoulder mechanism require estimates of muscle moment arm magnitude. Some shoulder models have estimated muscle moment arms by assuming an idealized minimum distance path from the origin to insertion that passes around the bony geometry. Alternatively, the principle of virtual work can be used to estimate moment arms from tendon excursion and joint-angle data. The purpose of this study was to determine if these two methods give different estimates of abduction moment arms for the supraspinatus, infraspinatus, and subscapularis muscles. Muscle moment arms were estimated for these muscles on ten fresh frozen cadaver specimens. The results showed a significant difference between the two estimation methods. Average differences were 3.1 mm (10.6%), 3.9 mm (43.9%), and 7.2 mm (70.3%) for the supraspinatus, subscapularis, and infraspinatus muscles, respectively. These results suggest that shoulder models based on the origin-insertion method may give higher rotator cuff muscle force estimates than methods using the slope of the tendon excursion vs joint angle relationship.

Adult↗
PubMed1998

Torso loading via a harness method activates trunk muscles less than a hand loading method.

There is a need for data comparing muscle activity under equivalent moments at the torso using different loading methods. In torso biomechanics, it is often necessary to apply moments to people and then measure or predict the muscle activity in response to the external load. Alternative methods exist to generate moments including applying forces by a chest harness and loads held in the hands. The limitation of previous research has been to use only one of the loading methods, generally harness loading, assuming it produces muscle activity equal to when loads are held in the hands. The objective of the this study was to test if equivalent moments at L3/L4 applied to subjects through two loading methods resulted in the same muscle activity. Subjects maintained a static posture while attempting a combination of flexion/extension, lateral bending, and torsion to counter the external loads applied via hand and harness loading methods. Hand and harness loading did not result in equal muscle activity as measured by electromyographic techniques. The left and right latissimus dorsi had increases in activity (16-25%) when loads were held with the hands instead of applied via the harness. Increased activity for hand loading was also found for the left and right rectus abdominis (13-17%) and left external oblique (24%). The left and right erector spinae and right external oblique exhibited the same activity for both loading methods. The current findings indicate that studies of torso loading using a shoulder harness to create torso moments may be lowering activity of some torso muscles.

Adult↗
PubMed1998

Mechanical advantage of the thumb muscles.

The purpose of this study was to measure the moment arms of four extrinsic muscles (flexor pollicis longus, extensor pollicis longus, extensor pollicis brevis, and abductor pollicis longus) and four intrinsic muscles (flexor pollicis brevis, abductor pollicis brevis, adductor pollicis, and opponents pollicis) of the thumb at the interphalangeal, the metacarpophalangeal, and the carpometacarpal joints in the same cadaver specimens and to examine the specific role of each muscle. Measurements were made on seven fresh frozen cadaver hands. The moment arms were measured during flexion/extension of the interphalangeal joint, flexion/extension and adduction/abduction of the metacarpophalangeal joint, and flexion/extension and adduction/abduction of the carpometacarpal joint. Moment arms were computed using the slope of the tendon excursion joint angle relationship. The specific function of each muscle was determined by multiplying the measured moment arms by the maximum force that each muscle can generate. It was found that the flexor pollicis longus was a pure flexor while flexor pollicis brevis was an adductor as well as a flexor, the extensor pollicis longus was an extensor and an adductor, extensor pollicis brevis was an extensor and a mild abductor, the abductor pollicis longus was an extensor as well as an abductor, the abductor pollicis brevis was mainly an abductor, the adductor pollicis was a major flexor as well as an adductor, and the opponents pollicis was a flexor and an abductor.

Aged↗
PubMed1998

Biomechanical effect of medial advancement of the supraspinatus tendon. A study in cadavera.

During the repair of some rotator-cuff tears, the torn tendon cannot be freed up adequately to permit reattachment at its original anatomical site of insertion. An option is to advance the site of insertion medially and reattach the tendon to a trough in the sulcus or to the humeral head. The biomechanical effects of such medial advancement on the moment arm of the supraspinatus muscle during glenohumeral elevation were studied in ten fresh-frozen shoulders from cadavera. Medial advancement of the site of insertion of the supraspinatus tendon was simulated by the placement of suture anchors in the sulcus of the proximal part of the humerus at points three, ten, and seventeen millimeters medial to the junction of the supraspinatus tendon and the bone. These distances were chosen not because they represent clinical options but because the large range allowed biomechanical study of medial advancement. Nylon lines were attached to the suture anchors and were passed back through an eyehook at the midpoint of the supraspinatus muscle. The excursion of each line was measured as the humerus was elevated, and the moment arm was estimated from the joint angle and excursion data with use of the principle of virtual work. Three and ten millimeters of medial advancement of the tendon (attachment in the sulcus) had a minimum (non-significant) effect on the moment arm during elevation compared with the value determined for the intact condition. However, seventeen millimeters of medial advancement was found to reduce the moment arm significantly (p < 0.05).

Adult↗
PubMed1997

Calcium binding, but not a calcium-myristoyl switch, controls the ability of guanylyl cyclase-activating protein GCAP-2 to regulate photoreceptor guanylyl cyclase.

Guanylyl cyclase-activating protein 2 (GCAP-2) is a recoverin-like calcium-binding protein that regulates photoreceptor guanylyl cyclase (RetGC) (Dizhoor, A. M., and Hurley, J. B. (1996) J. Biol. Chem. 271, 19346-19350). It was reported that myristoylation of a related protein, GCAP-1, was critical for its affinity for RetGC (Frins, S., Bonigk, W., Muller, F., Kellner, R., and Koch, K.-W. (1996) J. Biol. Chem. 271, 8022-8027). We demonstrate that the N terminus of GCAP-2, like those of other members of the recoverin family of Ca2+-binding proteins, is fatty acylated. However, unlike other proteins of this family, more GCAP-2 is present in the membrane fraction at low Ca2+ than at high Ca2+ concentrations. We investigated the role of the N-terminal fatty acyl residue in the ability of GCAP-2 to regulate RetGCs. Myristoylated or nonacylated GCAP-2 forms were expressed in Escherichia coli. Wild-type GCAP-2 and the Gly2 --> Ala2 GCAP-2 mutant, which is unable to undergo N-terminal myristoylation, were also expressed in mammalian HEK293 cells. We found that compartmentalization of GCAP-2 in photoreceptor outer segment membranes is Ca2+- and ionic strength-sensitive, but it does not require the presence of the fatty acyl group and does not necessarily directly reflect GCAP-2 interaction with RetGC. The lack of myristoylation does not significantly affect the ability of GCAP-2 to stimulate RetGC. Nor does it affect the ability of the Ca2+-loaded form of GCAP-2 to compete with the GCAP-2 mutant that constitutively activates RetGC. We conclude that while Ca2+ binding plays a major regulatory role in GCAP-2 function, it does not operate through a calcium-myristoyl switch similar to the one found in recoverin.

Animals↗
PubMed1997

Risk factors for work-related musculoskeletal disorders in an aluminum smelter.

A cross-sectional study of selected jobs in an aluminum smelter was conducted to assess the prevalence of work-related musculoskeletal disorders (WMDs), and to estimate their association with physical and psychosocial characteristics of the jobs. A structured interview and physical exam were used to assess the musculoskeletal health status of the participants, and a self-administered questionnaire was used to assess the psychosocial factors. Observational job analysis was conducted to evaluate 37 potential physical risk factors. Complete data were available for 104 subjects. The prevalence of WMDs on interview and physical exam were 0.8%, 14.9%, 11.6%, 14.9%, and 17.4% for the neck, shoulder, elbow/forearm, hand/wrist, and low back regions, respectively. Unconditional multiple logistic regression was used to model the relationship between physical and psychosocial factors and health status. Years of forearm twisting were found to be a significant predictor for hand/wrist disorders on interview (OR = 17, 95% CI = 2.9-106); for elbow/forearm disorders on physical exam and interview (OR = 37, 95% CI = 3.0-470); and for shoulder disorders on interview (OR = 92, 95% CI = 7.3-infinity) and on interview and physical exam (OR = 46, 95% CI = 3.8-550). Low decision latitude was also found to be significant for the shoulder on interview (OR = 4.5, 95% CI = 1.3-16). High job satisfaction (OR = 5.9, 95% CI = 1.4-25) and low social support (OR = 5.3, 95% CI = 1.3-22) were associated with low back pain report on interview; only high job satisfaction (OR = 5.3, 95% CI = 1.1-26) was associated with low back pain on both interview and physical exam.

Cross-Sectional Studies↗