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Biomedical subjects

B R Jensen

Publications and source records attributed to B R Jensen.

At least 19 recordsLinked to original sources
PubMed2005

An 18-month follow-up study on vibrotactile sense, muscle strength and symptoms in computer users with and without symptoms.

OBJECTIVES: The aim was to explore whether symptoms, sensory perception and muscle strength among computer users with and without symptoms in forearm or hand had changed after 18 months. METHODS: Twenty-six out of 30 females, experienced computer users, from a baseline study participated in the follow-up. In addition, five control subjects participated. The subjects completed a questionnaire regarding exposure to computer work, prevalence and severity of symptoms, health status and physical activity. Perceived thresholds for vibration were measured twice with 3 h in between on the right hand on four different sites innervated by the radial, median or ulnar nerve. Furthermore, sensory perception was measured on the left hand on two sites innervated by the median and ulnar nerve, respectively. Skin temperature was measured at each site prior to sensory perception measurements. Maximal handgrip strength and maximal pinch-grip strength were measured for both hands. RESULTS: Eighty-three percent of the subjects who had symptoms at baseline still had symptoms and 21% of the subjects who did not have symptoms at baseline experienced symptoms at follow-up. The first and the second sensory perception measurement were highly correlated. Vibrotactile sensory threshold representing the radial nerve was increased since baseline among the subjects who originally had symptoms. At follow-up, the vibrotactile sense for the computer users who reported symptoms in forearm or hand at baseline was deteriorated for the sites representing the median, ulnar and radial nerves compared to the control group. Among the original symptom free subjects with intensive computer work increases in vibrotactile perception thresholds were found for the sites representing the median and ulnar nerves. Handgrip muscle strength remained unchanged for all groups. CONCLUSIONS: The study indicates that sensory dysfunctions as well as symptoms in forearm and hand among computer users to a high degree are persistent. Muscle strength seems to be well maintained.

Adult↗
PubMed2005

Effect of computer mouse gain and visual demand on mouse clicking performance and muscle activation in a young and elderly group of experienced computer users.

The present study evaluated the specific effects of motor demand and visual demands on the ability to control motor output in terms of performance and muscle activation. Young and elderly subjects performed multidirectional pointing tasks with the computer mouse. Three levels of mouse gain and three levels of target size were used. All subjects demonstrated a reduced working speed and hit rate at the highest mouse gain (1:8) when the target size was small. The young group had an optimum at mouse gain 1:4. The elderly group was most sensitive to the combination of high mouse gain and small targets and thus, this age group should avoid this combination. Decreasing target sizes (i.e. increasing visual demand) reduced performance in both groups despite that motor demand was maintained constant. Therefore, it is recommended to avoid small screen objects and letters. Forearm muscle activity was only to a minor degree influenced by mouse gain (and target sizes) indicating that stability of the forearm/hand is of significance during computer mouse control. The study has implications for ergonomists, pointing device manufacturers and software developers.

Adult↗
PubMed2004

Physical workload during use of speech recognition and traditional computer input devices.

Musculoskeletal symptoms among computer users are frequently found. The aim was to investigate the musculoskeletal workload during computer work using speech recognition and traditional computer input devices (keyboard/mouse). Ten experienced computer users (nine female, one male) participated. They performed three different computer tasks: (1). text entry and (2). text editing of a standard text and (3). a self-selected work task. These tasks were performed twice using speech recognition and traditional computer input devices (keyboard/mouse). Additionally, a task consisting of reading aloud of the standard text was performed. Surface EMG from the forearm (m. extensor carpi ulnaris, m. extensor carpi radialis), the shoulder (m. trapezius) and the neck extensor muscles was recorded, in addition to the voice-related muscles (m. scalenii, m. cricothyroideus). Using speech recognition during text entry and text editing reduced the static muscle activity of the forearm, neck and to some extent the shoulder muscles. Furthermore, tendencies to longer periods of muscle activity pause (relative time with EMG gaps) in the forearm and shoulder muscles were found. This was seen at the expense of a tendency to an increased static activity and a decreased relative time with EMG gaps in m. cricothyroideus. Finally, during use of speech recognition the hand was tied to the keyboard/mouse for a shorter period of time, while the eyes were viewing the screen for a longer period of time compared to the condition with traditional computer input devices. It is recommended to use speech recognition as a supplementary tool to traditional computer input devices.

Computer Peripherals↗
PubMed2002

Vibrotactile sense and mechanical functional state of the arm and hand among computer users compared with a control group.

OBJECTIVES: To measure sensory perception and mechanical muscle function of the arm among experienced female computer users with (+sPC) and without (-sPC) symptoms compared with a control group (ctrl). METHODS: Group +sPC had severe symptoms in the hand/wrist and/or the forearm/elbow region. They worked with the computer 75% and used a computer mouse 50% of the working day. Group -sPC had no or minimal symptoms. They used the computer 80% and a computer mouse 58% of the working day. The control group had no symptoms and worked with the computer for 2 h or fewer per day. Sensory perception threshold was measured using vibrotactilometry at five sites on the right hand representing nn. medianus, ulnaris and radialis. Mechanical muscle function was assessed by measuring muscle strength, wrist extension endurance, hand-eye co-ordination, and range of motion. Furthermore, performance was measured during standardized computer work. RESULTS: The perception thresholds for +sPC were greater in the areas innervated by n. medianus and n. ulnaris than for non-symptomatic groups, indicating that nerve compression is involved. For n. radialis, no differences were found between groups. No difference in isometric muscle strength was found for hand-grip, wrist extension, vertical pinch-grip and knee extension. However, for horizontal pinch-grip (pronated forearm) lower values were obtained for the +sPC group than for non-symptomatic groups. At the end of the endurance task, the perceived exertion was highest for +sPC. Furthermore, slower recovery was found for +sPC. No differences in range of motion, hand-eye co-ordination, and error rate during computer work were found between groups. CONCLUSIONS: Increased perception threshold values indicating entrapment of n. medianus and n. ulnaris were found for +sPC. Only few differences in mechanical muscle performance were found among the groups. The +sPC group had lower pinch-grip strength when measured in the pronated hand position, and the results indicated shorter muscle endurance for +sPC than for -sPC and ctrl.

Adult↗
PubMed2001

Performance and muscle activity during computer mouse tasks in young and elderly adults.

The influence of age on performance and muscle activity was studied during computer mouse tasks designed to induce high demands on motor control. Eight young (mean age 25 years) and nine elderly (mean age 63 years) women participated. When the speed was self-determined, the elderly subjects performed 13%-18% slower than did the young. When speed was predefined, the error rate was higher in the elderly subjects than in the young ones (medium precision 7.8% compared to 2.5%, high precision 16.5% compared to 7.9%, respectively). The highest error rate was found for double-clicking (32.9% compared to 13.5%, respectively). The reduced performance in the elderly subjects was hypothesised to be a combined effect of deteriorated proprioception, increased motor unit size, and changes in the central nervous system. Electrical activity (EMG) was recorded from the forearm, shoulder and neck muscles. Higher levels of EMG activity were found in the elderly compared to the young. A likely explanation is that the impaired motor control necessitated an increased muscle activity. The highest levels of EMG activity and lack of EMG gaps were found for the forearm extensor muscles, especially the extensor digitorum muscle (mean EMG activity 10.4% compared to 8.1% of maximal electrical activity, EMGmax) whereas lower EMG activity levels were found for the shoulder region (e.g. right trapezius muscle mean EMG 2.8% compared to 1.1% EMGmax, respectively). The latter was possibly due to a relieving effect of the forearm support. Differences in muscle activity among the tasks were found, however they were minor for the shoulder and neck muscles. Consideration of the demands on motor control when designing user interfaces is recommended, to the benefit of both the young and the elderly.

Adult↗
PubMed2001

Dynamic loads on the upper extremities during two different floor cleaning methods.

BACKGROUND: Biomechanical models have been used frequently to estimate the load on the low back and the lower extremities during occupational work tasks. The shoulder region has received much less attention although this area is a common site of work-related musculoskeletal disorders. OBJECTIVE: The aim of the present study was to evaluate the mechanical loading of the upper extremities during floor cleaning performed with different techniques. DESIGN: A comparative study of six subjects performing floor cleaning with two different techniques (mopping and scrubbing) in a laboratory setting. METHODS: A "force handle" equipped with two force dynamometers was used for continuous measurement of three-dimensional forces on each hand, separately, during this two handed asymmetrical task. A link segment model of the upper extremities was used to calculate the mechanical loading of the elbows and shoulders. Electromyograms were recorded from six shoulder muscles. RESULTS: Despite differences in movement patterns between mopping and scrubbing, only small differences were found in the moments of force. In accordance similar levels of electromyograms were found. CONCLUSION: In preventive strategies, changing the cleaning tool may not be sufficient to change the load on the shoulder muscles. RELEVANCE: Combined three-dimensional video recording and force measurements on the hands during a two-handed asymmetric work tasks allow calculation of the mechanical load on the elbow and shoulder. Thus it is possible to evaluate physiologically, new equipment designed to prevent work-related musculoskeletal disorders. Before introducing such equipment in large scale interventions it may be evaluated if the changes in force requirements are sufficient to predict prevention of musculoskeletal disorders.

Adult↗
PubMed2001

Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver.

The apparent anticarcinogenic effect of cruciferous vegetables found in numerous epidemiological and experimental studies has been associated with their influence on phase I and phase II metabolising enzymes as well as on the antioxidant status. In the present study we investigated the effect of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTpi)], all previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and gamma-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx and catalase activity was also assessed in the kidneys. In order to examine a possible effect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P < 0.05) and the activity of QR 2.6-fold in rat liver (P < 0.05). No significant differences were seen in the expression of the phase I enzymes. No differences in antioxidant enzyme activity/expression or OGG1 activity were observed. In a second experiment, administration of the Brussels sprouts extract for 3 or 7 days was found to increase the level of 8-oxodG in rat liver from 0.75 to 0.97 per 10(5) dG and from 0.81 to 0.97 per 10(5) dG, respectively (P < 0.05). No effects on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion of cruciferous vegetables is beneficial.

Animals↗
PubMed2001

Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients.

BACKGROUND: The purpose of this study was to assess whether long-term (8 years) inhibition of angiotensin-converting enzyme (ACE) protects kidney function in normotensive type 1 diabetic patients with diabetic nephropathy. METHODS: We performed an open randomized follow-up study of normotensive type 1 diabetics with nephropathy either treated (N = 15) or not (N = 17) with captopril twice per day (average 74, range 12.5 to 125 mg/day). The main outcome measures were arterial blood pressure, albuminuria, and glomerular filtration rate (GFR; 51Cr-EDTA plasma clearance, twice yearly). RESULTS: Arterial blood pressure (mm Hg) was kept constant in the captopril group, at baseline (mean, SEM), 128/78 (3/2) and during follow-up 129/77 (4/1) but increased significantly in the control group from 127/79 (2/1) to 137/84 (5/2) (P < 0.01). Furthermore, 8 out of the 17 control subjects required treatment with blood pressure-lowering drugs because they developed hypertension. The fractional albumin clearance (x10-5) remained unchanged in the captopril group: baseline [10.8 (1.25) geometric mean and antilog (SEM)] during the eight years [11.8 (1.47)], while a significant rise occurred in control patients: 13.3 (1.23) to 26.2 (1.42) (P < 0.05). Baseline GFR was nearly identical: 111 (6) and 115 (4) mL/min/1.73 m2 in the captopril and control group, respectively. The median (range) rate of decline in GFR (mL/min/year) was 1.7 (10.7 to -2.0) in the captopril group versus 2.8 (17.7 to -2.6) in the control group (P = NS). CONCLUSIONS: The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.

Adult↗
PubMed2000

Motor unit recruitment and rate coding in response to fatiguing shoulder abductions and subsequent recovery.

The purpose of the present study was to investigate motor unit (MU) recruitment and firing rate, and the MU action potential (MUAP) characteristics of the human supraspinatus muscle during prolonged static contraction and subsequent recovery. Eight female subjects sustained a 30 degrees shoulder abduction, requiring 11-12% of maximal voluntary contraction (MVC), for 30 min. At 10 and 30 min into the recovery period, the shoulder abduction was repeated for 1 min. The rating of perceived exertion for the shoulder region increased to "close to exhaustion" during the prolonged contraction, and the surface electromyography (EMG) recorded from the deltoid and trapezius muscles showed signs of local muscle fatigue. From the supraspinatus muscle, a total of 23,830 MU firings from 265 MUs were identified using needle electrodes. Of the identified MUs, 95% were continuously active during the 8-s recordings, indicating a low degree of MU rotation. The mean (range) MU firing rate was 11.2 (5.7-14.5) Hz, indicating the relative force contribution of individual MUs to be larger than the overall mean shoulder muscle load. The average MU firing rate remained stable throughout the prolonged abduction, although firing rate variability increased in response to fatigue. The average concentric MUAP amplitude increased by 38% from the beginning (0-6 min) to the end (24-29 min) of the contraction period, indicating recruitment of larger MUs in response to fatigue. In contrast, after 10 min of recovery the average MU amplitude was smaller than seen initially in the prolonged contraction, but not different after 30 min, while the MU firing rate was higher during both tests. In conclusion, MU recruitment plays a significant role during fatigue, whereas rate coding has a major priority during recovery. Furthermore, a low degree of MU rotation in combination with a high relative load at the MU level may imply a risk of overloading certain MUs during prolonged contractions.

Action Potentials↗
PubMed2000

Consistency of motor-unit identification during force-varying static contractions.

Due to inter-operator variability, two operators were used to assess the consistency of motor unit (MU) identification during ramp contractions, by the comparison of semi-automatic decompositions of the same recordings. Static shoulder abduction was performed against a force transducer in a position with the upper arms vertical and elbows flexed to 90 degrees. The subjects followed an 8-s force trajectory: 30% maximum voluntary contraction (MVC, 2 s), a reduction in force from 30% to 0% MVC (2 s), 0% MVC (1 s), an increase in force from 0 to 30% MVC (2 s), and 30% MVC (1 s). Muscle activity was recorded from the supraspinatus muscle with a quadripolar needle. From six recordings of 8 s duration, a total of 2527 MU firings were identified by both operators, and 93% of these were identified identically into 31 MUs. Both operators identified 8 of these MUs as continuously firing, 5 as only being active either before or after the 1 s at 0% MVC, and 18 as being de-recruited during force decreases and recruited during force increases. Both operators agreed that 16 of these 18 MUs were de-recruited at a higher force level than that at which they were recruited, which may be due to the electromechanical delay. The coefficient of variation for double determination of the results obtained by operators A and B was 8.5% for the number of MU firings, 4.5% for the MU mean firing rate, and 8.4% for the MU action potential (MUAP) amplitude. Therefore, the operator interactive decomposition method was considered to be valid for studying recruitment and de-recruitment as well as firing rate and MUAP amplitude during static, force-varying ramp contractions.

Adult↗
PubMed2000

Quantitative ultrasound image analysis of the supraspinatus muscle.

OBJECTIVE: To develop and validate a method, based on quantitative ultrasound image analysis, to objectively analyse and characterize the ultrasound images of m. supraspinatus. DESIGN: Quantitative ultrasonography was performed on the supraspinatus muscle of 14 healthy subjects. METHODS: A computerized analysis using first-order grey-scale statistics to evaluate the muscle tissue composition was developed and validated. RESULTS: Data from one scanning site were not representative for the whole muscle due to muscle inhomogenity. Using first-order grey-scale statistics the scanning direction was of no importance. By using a scanning session consisting of three different scanning sites along the muscle in two directions, longitudinally and transversely, to characterize the tissue composition of the muscle, a high day-to-day reproducibility was obtained. CONCLUSION: The described scanning session is a relatively sensitive and reproducible method for studying the muscle tissue composition. RelevanceQuantitative ultrasonography seems to be a potential clinical and occupational examination method to detect tissue composition of myalgic muscles compared to healthy muscles.

Adult↗
PubMed2000

Aspects of shoulder function in relation to exposure demands and fatigue - a mini review.

OBJECTIVE: To discuss the literature on control and function of multiple muscle systems with special focus on shoulder and upper extremity under submaximal conditions. DESIGN: The paper is a mini review based on 31 studies. BACKGROUND: Control mechanisms underlying the recruitment and gradation of muscle activity in complex multiple muscle systems during various voluntary exertions is still not fully understood. Load sharing principles may be influenced by several factors like work demand, fatigability, metabolic factors etc. METHODS: Several methods, e.g., electromyography, intramuscular pressure, and tissue oxygenation are used. The definition of fatigue is discussed. RESULTS AND CONCLUSION: A relatively fixed load sharing of the shoulder muscles has been found at low load levels, submaximal speeds and with a limited range of movements of the arms for healthy subjects. However, the load sharing of the shoulder muscles can be changed to some extent in response to fatigue, mental demands, visual feedback and in patients suffering from disorders in the upper extremities. It is hypothesized that lack of ability to redistribute muscle activation pattern in the shoulder region or the upper extremity increases the risk of development of work related symptoms.

Biomechanical Phenomena↗
PubMed2000

Shoulder muscle activity in young and older people during a computer mouse task.

OBJECTIVE: Assessment of the age effect in relation to computer work. BACKGROUND: Increasingly, more older people are using computers, while hardware and software are not designed with special consideration of their needs. METHODS: Eight young and nine older females performed different computer mouse tasks. Shoulder muscle activity was recorded from the right deltoid muscle, right and left upper trapezius muscle, and the neck extensor muscles. RESULTS: Mean trapezius muscle activity was significantly higher in the older people (2.8%/3.7% EMG(max) for R/L) compared to the young (1.1%/1.2% EMG(max)). There was a tendency to a higher activity in the older people for the deltoid muscle and the neck extensor muscles. There were small differences in shoulder muscle activation levels between mouse actions, target directions, and between precision demands. CONCLUSIONS: Shoulder muscle activity during computer work is affected by age, but only to a minor extent by the type of computer mouse task. The deltoid and the trapezius muscle activities are low during computer mouse use when there is efficient forearm support by the table. RelevanceAn increasing number of people use computers for hours every day. Intensive use of computers increases the risk of development of work-related musculoskeletal symptoms in the shoulder region.

Adult↗
PubMed2000

Lack of impact of low-dose acetylsalicylic acid on kidney function in type 1 diabetic patients with microalbuminuria.

OBJECTIVE: High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with microalbuminuria and macroalbuminuria. This effect may lead to an incorrect classification of albuminuria (normo-, micro-, and macroalbuminuria) and jeopardize the monitoring of antiproteinuric treatment (e.g., ACE inhibition). Whether similar difficulties exist using low-dose acetylsalicylic acid (ASA), now widely recommended for primary and secondary prevention of cardiovascular events in type 1 diabetic patients with micro- and macroalbuminuria, remains to be elucidated. RESEARCH DESIGN AND METHODS: We performed a randomized double-blind crossover trial in 17 type 1 diabetic patients with microalbuminuria (urinary AER 30-300 mg/24 h). Patients were given ASA (150 mg/daily) for 4 weeks followed by placebo for 4 weeks with at least a 2-week washout period in random order. At the end of each treatment period, AER (enzyme-linked immunosorbent assay), glomerular filtration rate (GFR) (plasma clearance of 51Cr-EDTA), blood pressure (BP) (Hawksley), and HbA1c (by high-performance liquid chromatography) were measured. Patients were advised to follow a normal diabetes diet without sodium restriction and received their usual antihypertensive treatment during the investigation. RESULTS: During the study (ASA vs. placebo), urinary AER (geometric mean 64 [95% CI 39-105] vs. 59 [40-87] mg/24 h), GFR (mean 106 [93-118] vs. 104 [90-117] ml x min(-1) x 1.73 m(-2)), systolic BP (mean 130 [119-141] vs. 130 [119-142] mmHg), diastolic BP (mean 71 [65-78] vs. 71 [64-78] mmHg), and HbA1c (mean 8.4% [8.0-9.0] vs. 8.5% [8.1-9.0]) remained unchanged. CONCLUSIONS: Treatment with 150 mg ASA daily does not have any impact on AER or GFR in type 1 diabetic patients with microalbuminuria. Consequently, primary and secondary prevention of cardiovascular events with low-dose ASA does not interfere with the classification of AER or monitoring of antiproteinuric treatment in such patients.

Adult↗
PubMed2000

Antioxidants, DNA damage and gene expression.

Reactive oxygen species (ROS) are generated from incomplete reduction in the respiratory chain. On one hand they pose a serious threat of deleterious effects on important macromolecules, among which DNA is considered most important since it carries the genetic information and changes will be carried on to future generations, or will fundamentally change the behaviour of the cells. On the other hand, it is becoming evident that there are important changes in the cells in response to redox changes. This review summarises the genes, the intracellular signalling elements and molecules that presently are known to be regulated by oxidative stress. It is now clear that both oxidants and antioxidants can regulate a multitude of different cellular functions, signal transduction pathways and gene expression. However, the quantitative importance is unknown and as of yet there are no examples of regulation exclusively by oxidative stress. Also the response to oxidative stress is variable, can be up-regulation as well as down-regulation, and different responses to dose or magnitude of the oxidative stress can be demonstrated. The effect from supplementation with an antioxidant is difficult to predict, and ultimately must be assessed in clinical trials.

Animals↗
PubMed1999

Physiological response to submaximal isometric contractions of the paravertebral muscles.

STUDY DESIGN: Brief (30-second) isometric trunk extensions at 5%, 20%, 40%, 60%, and 80% of maximal voluntary contraction (MVC) and 3 minutes of prolonged trunk extension (20% MVC) in erect position were studied in nine healthy male subjects. OBJECTIVES: To investigate the intercorrelation between intramuscular pressure and tissue oxygenation of the paravertebral muscles during submaximal isometric contractions and further, to evaluate paravertebral electromyogram and intramuscular pressure as indicators of force development. SUMMARY OF BACKGROUND DATA: Local physiologic responses to muscle contraction are incompletely understood. METHODS: Relative oxygenation was monitored with noninvasive near-infrared spectroscopy, intramuscular pressure was measured with a transducer-tipped catheter, and surface electromyogram was monitored at three recording sites. RESULTS: The root mean square amplitudes of the paravertebral electromyogram (L4, left and right; T12, right) and intramuscular pressure measured in the lumbar multifidus muscle at L4 increased with greater force development in a curvilinear manner. A significant decrease in the oxygenation of the lumbar paravertebral muscle in response to muscle contraction was found at an initial contraction level of 20% MVC. This corresponded to a paravertebral intramuscular pressure of 30-40 mm Hg. However, during prolonged trunk extension, no further decrease in tissue oxygenation was found compared with the tissue oxygenation level at the end of the brief contractions, indicating that homeostatic adjustments (mean blood pressure and heart rate) over time were sufficient to maintain paravertebral muscle oxygen levels. CONCLUSION: At a threshold intramuscular pressure of 30-40 mm Hg during muscle contraction, oxygenation in the paravertebral muscles is significantly reduced. The effect of further increase in intramuscular pressure on tissue oxygenation over time may be compensated for by an increase in blood pressure and heart rate. Surface electromyogram amplitudes and intramuscular pressure can be used as indicators of paravertebral muscle force.

Adult↗
PubMed1999

Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell extracts.

Base excision repair (BER) pathway is the major cellular process for removal of endogenous base lesions and apurinic/apyrimidinic (AP) sites in DNA. There are two base excision repair subpathways in mammalian cells, characterized by the number of nucleotides synthesized into the excision patch. They are the "single-nucleotide" (one nucleotide incorporated) and the "long-patch" (several nucleotides incorporated) BER pathways. Proliferating cell nuclear antigen (PCNA) is known to be an essential factor in long-patch base excision repair. We have studied the role of replication protein A (RPA) in PCNA-dependent, long-patch BER of AP sites in human cell extracts. PCNA and RPA were separated from the other BER proteins by fractionation of human whole-cell extract on a phosphocellulose column. The protein fraction PC-FII (phosphocellulose fraction II), which does not contain RPA and PCNA but otherwise contains all core BER proteins required for PCNA-dependent BER (AP endonuclease, DNA polymerases delta, beta and DNA ligase, and FEN1 endonuclease), had reduced ability to repair plasmid DNA containing AP sites. Purified PCNA or RPA, when added separately, could only partially restore the PC-FII repair activity of AP sites. However, additions of both proteins together greatly stimulated AP site repair by PC-FII. These results demonstrate a role for RPA in PCNA-dependent BER of AP sites.

Base Sequence↗