Biomedical subjects

A P Hollander

Publications and source records attributed to A P Hollander.

At least 19 recordsLinked to original sources

PubMed1996

Activation and inhibition of endogenous matrix metalloproteinases in articular cartilage: effects on composition and biophysical properties.

Bovine cartilage explants were cultured with 1 mM 4-aminophenylmercuric acetate (APMA) to activate endogenous matrix metalloproteinases (MMPs) and changes in biochemical, biomechanical, and physicochemical properties were assessed. Additionally, graded levels of either rhTIMP-1 (recombinant human tissue inhibitor of metalloproteinases-1) or L-696-418 (a synthetic metalloproteinase inhibitor) were used to inhibit degradation induced by APMA. Treatment with APMA resulted in as much as 80% loss in tissue GAG content, a greater than threefold increase in denatured type II collagen as determined by the presence of CB11B epitope, and complete loss of biosynthetic activity after 3 days in culture. Physicochemical studies revealed that APMA treatment resulted in a significant increase in tissue swelling response, consistent with damage to the collagen network. Activation of MMPs by APMA also resulted in > 80% decrease in equilibrium modulus, dynamic stiffness, and streaming potential and > 50% decrease in electrokinetic coupling coefficient. The addition of 4 microM, 400 nM, and 40 nM TIMP inhibited PG loss by 95, 50, and 20%, respectively, and all doses effectively inhibited swelling response. The addition of 4 microM and 400 nM L-696-418 inhibited PG loss by 95% while 40 nM L-696-418 inhibited PG loss by 60%, and all doses effectively inhibited swelling response. The inhibition of APMA-induced GAG loss by 4 microM TIMP was accompanied by maintenance of streaming potential, electrokinetic coupling coefficient, dynamic stiffness, and equilibrium modulus.

Animals↗

PubMed1996

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.

Adult↗

PubMed1996

Enhanced denaturation of the alpha (II) chains of type-II collagen in normal adult human intervertebral discs compared with femoral articular cartilage.

The mechanical strength of connective tissues is dependent on the integrity of their fibrillar collagen frameworks. The objective of the present study was to assess type-II collagen damage (denaturation) in the adult human intervertebral disc compared with articular cartilage, in order to determine whether damage to this molecule may vary in different anatomical sites in the same person. A new immunochemical assay was used to measure the amounts of denatured and total type-II collagen in the annulus fibrosus and nucleus pulposus of the L5-S1 disc and in cartilage from the femoral condyles of the same individuals (n = 7). Denaturation of type-II collagen was significantly higher in both the annulus fibrosus and the nucleus pulposus than in articular cartilage. Such increased damage to type-II collagen in the adult disc may have relevance to the more pronounced degenerative changes observed in this tissue compared with articular cartilage.

Adult↗

PubMed1996

Effects of growth factors and interleukin-1 alpha on proteoglycan and type II collagen turnover in bovine nasal and articular chondrocyte pellet cultures.

The aim of this study was to investigate the effects of insulin-like growth factor-I, transforming growth factor-beta (TGF-beta), and interluekin-1 alpha (IL-1 alpha) on the deposition and degradation of a cartilage-like matrix in high-density pellet cultures of adult bovine chondrocytes. Proteoglycan was determined by toluidine blue staining and colorimetric assay. Type II collagen was determined by immunohistochemical staining and its unwinding in situ by a recently developed immunoassay. Bovine nasal chondrocytes cultured as pellets deposited a well-organized extracellular matrix of proteoglycan and type II collagen. Insulin-like growth factor-I (2-10 ng/ml) increased the synthesis and incorporation into the matrix of both these proteins. TGF-beta (2-10 ng/ml) also increased proteoglycan synthesis. However it inhibited proteoglycan deposition, presumably through increased degradation of the molecule, as shown by increased release of aggrecan fragments into the tissue culture medium. TGF-beta had no effect on type II collagen deposition. In pellet cultures of bovine nasal or articular chondrocytes, 20 ng/ml IL-1 alpha induced a significant degradation of both proteoglycan and type II collagen. The effect on collagen clearly involved proteolytic cleavage of its triple helix because there was an increase in the proportion of unwound type II collagen in the matrix, as well as a loss of total type II collagen. In explant cultures of intact bovine articular cartilage, incubation with 50 ng/ml IL-1 alpha stimulated significant degradation of the proteoglycan but no degradation of the type II collagen. These results demonstrate that although the articular chondrocytes are capable of degrading type II collagen when isolated, they do not do so in situ, presumably because of some inherent property of the mature extracellular matrix. This study demonstrates the utility of pellet cultures when investigating chondrocyte-mediated turnover of cartilage matrix and its modulation by cytokines and growth factors.

Animals↗

PubMed1995

Hydrodynamic drag and lift forces on human hand/arm models.

Forces acting on the forearm and hand during swimming can be decomposed into drag forces and lift forces. In this study drag and lift forces were measured on two models of a human hand and forearm when towed in a towing tank. To compare the results of models with different size at different velocities force data were normalized to drag and lift coefficients (Cd and Ct). Influence of the orientation of the model with respect to the flow, velocity, size of the model and the relative contribution of the hand and forearm on Cd and Ct were studied. The orientation of the model with respect to the line of motion was varied by rotating the models around three axes, and quantified using the angle of pitch (AP: the angle between the hand plane and flow) and the sweep-back angle (SB: the orientation of the flow vector when projected on the hand plane). Cd was maximal when the palm of the hand is almost perpendicular to the flow (AP = 65 degrees, SB = 342 degrees). Ct shows maximal values at two different orientations: with the hand in a thumb-leading position, AP = 31 degrees, SB = 358 degrees, and with the hand in a little finger-leading position, AP = 48 degrees, SB = 193 degrees. The orientation of the hand was very critical in generating lift forces. By contrast, the influence of velocity and size of the model on the values of Cd and Ct was limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗

PubMed1995

Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration.

Enhanced denaturation of type II collagen fibrils in femoral condylar cartilage in osteoarthritis (OA) has recently been quantitated immunochemically (Hollander, A.P., T.F. Heathfield, C. Webber, Y. Iwata, R. Bourne, C. Rorabeck, and A.R. Poole. 1994. J. Clin. Invest. 93:1722-1732). Using the same antibody that only reacts with denatured type II collagen, we investigated with immunoperoxidase histochemistry (results were graded for analysis) the sites of the denaturation (loss of triple helix) of this molecule in human aging (at autopsy, n= 11) and progressively degenerate (by Mankin grade [MG]) OA (at arthroplasty, n= 51) knee condylar cartilages. Up to 41 yr, most aging cartilages (3 of 4) (MG 0-4) showed very little denaturation. In most older cartilages, (4 of 7) (MG 2-4), staining was observed in the superficial and mid zones. This pattern of collagen II denaturation was also seen in all OA specimens with increased staining extending to the deep zone with increasing MG. Collagen II staining correlated directly both with MG and collagen II denaturation measured by immunoassay. Cartilage fibrillation occurred in OA cartilages with increased penetration of the staining for collagen II denaturation into the mid and deep zones and where denaturation was more pronounced by immunoassay. Thus in both aging and OA the first damage to type II collagen occurs in the superficial and upper mid zone (low MG) extending to the lower mid and deep zones with increasing degeneration (increasing MG). Initial damage is always seen around chondrocytes implicating them in the denaturation of type II collagen.

Adult↗

PubMed1994

Relationship between physical strain during standardised ADL tasks and physical capacity in men with spinal cord injuries.

To describe physical strain during activities of daily living (ADL), 44 men with spinal cord injuries (C4-L5) performed a set of standardised tasks. The physical strain was defined as the highest heart rate response expressed as a percentage of the individual heart rate reserve (%HRR). The physical strain averaged over the subjects who performed all tasks (n = 24) was (mean +/- SD): 20.2 +/- 7.2 %HRR (washing hands), 20.4 +/- 7.3 %HRR (passing a side-hung door), 28.8 +/- 10.8 %HRR (transfer to a toilet), 31.2 +/- 13.1 %HRR (ascending an 8 cm curb). 33.9 +/- 12.0 %HRR (transfer to a shower seat), 35.1 +/- 10.5 %HRR (transfer to bed), 36.4 +/- 13.3 %HRR (preparing lunch), 37.1 +/- 12.0 %HRR (washing up), 38.7 +/- 14.9 %HRR (ascending a ramp), 39.8 +/- 15.6 %HRR (transfer to a shower wheelchair), 41.4 +/- 12.1 %HRR (changing sheets), and 45.9 +/- 10.4 %HRR (entering a car). Physical strain could be notably high, but large variations among subjects were present. During all tasks, subjects with tetraplegia had significantly higher levels of strain than subjects with low (T6-L5) lesions. Physical strain was inversely related to parameters of physical capacity: isometric strength (r: -0.34 to -0.72), sprint power (r: -0.34 to -0.69), peak oxygen uptake (r: -0.41 to -0.81) and maximal power output (r: -0.52 to -0.82). Parameters of physical capacity were better predictors of physical strain than was the lesion level, and explained 37-71% of the variance in strain during ADL. It was also concluded that the method used in this study provides a quantitative and objective estimation of physical strain and may therefore be a useful tool to identify task difficulty during rehabilitation and to evaluate the results of task and physical training on the physical strain during ADL.

Activities of Daily Living↗

PubMed1994

Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay.

A new immunoassay was developed to detect denaturation of type II collagen in osteoarthritis (OA). A peptide, alpha 1 (II)-CB11B, located in the CB11 peptide of type II collagen, was synthesized and used to produce a monoclonal antibody (COL2-3/4m) of the IgG1 (kappa) isotype. This reacts with a defined epitope in denatured but not native type II collagen and the alpha 3 chain of type XI collagen. The latter is present in very small amounts (about 1% wt/wt) in cartilage relative to the alpha 1 (II) chain. By using an enzyme-linked immunosorbent assay, type II collagen denaturation and total type II collagen content were determined. The epitope recognized by the antibody was resistant to cleavage by alpha-chymotrypsin and proteinase K which were used to extract alpha 1 (II)-CB11B from the denatured (alpha-chymotrypsin soluble) and residual native (proteinase K soluble) collagen alpha-chains, respectively, present in human femoral articular cartilage. Type II collagen content was significantly reduced from a mean (range) of 14% (9.2-20.8%) of wet weight in 8 normal cartilages to 10.3% (7.4-15.0%) in 16 OA cartilages. This decrease, which may result in part from an increased hydration, was accompanied by an increase in the percent denaturation of type II collagen in OA to 6.0% of total type II collagen compared with 1.1% in normal tissue. The percent denaturation was ordinarily greater in the more superficial zone than in the deep zone of OA cartilage.

Adult↗

PubMed1994

Physical strain in daily life of wheelchair users with spinal cord injuries.

Forty-three men (age 33 +/- 9 yr) with spinal cord injuries (SCI) were observed during a normal workday while heart rate was recorded continuously. Physical strain was estimated using the heart rate response expressed relative to the individual heart rate reserve (%HRR). The mean physical strain during the day for group I (C4-C8, N = 9), II (T1-T5, N = 6), III (T6-T10, N = 15), and IV (T10-L5, N = 13) was 38 +/- 8, 29 +/- 12, 22 +/- 8, and 23 +/- 5%HRR, respectively. Prolonged periods (> 15 min) of high strain (> 60%HRR) that might maintain or improve physical capacity were not identified during activities of daily life (ADL), but only during sports activities. The analysis of activity-related strain revealed that specific ADL such as making transfers, entering/leaving car, and negotiating environmental barriers, provoked high levels of strain, especially in those with quadriplegia. Periods of peak strain (> 60%HRR, < 3 min) occurred frequently, also predominantly in those with quadriplegia. It was concluded that the physical strain during ADL is related to the level of lesion and is not of a magnitude and duration that would maintain or improve physical capacity. The periods of peak strain might restrict the mobility and independence of persons with SCI, and, therefore, reduce their quality of life.

Activities of Daily Living↗

PubMed1994

Energetics of competitive swimming. Implications for training programmes.

An analysis of the mechanics and energetics of swimming reveals that different factors play key roles in success in competitive swimming events. Knowledge of these performance factors will help the development of optimal training programmes, especially when their relative importance can be identified. One approach to doing this is to evaluate the energy cost of swimming and the energy generating systems that cover these costs. It appears that the rate of energy expenditure is related to the velocity, the gross efficiency, the propelling efficiency and a drag factor. Energy is generated by aerobic and anaerobic processes. A balance should exist between the energy necessary to swim a distance in a certain time and the total energy available in this time from the energy producing system. This balance was used to predict the performance times over difference distances and to predict the effect of a 10% increase in the aerobic capacity, the anaerobic capacity or the propelling efficiency on the performance times, while keeping all other factors constant. The 10% increase in propelling efficiency resulted in both a reduction in time over the short distance as well as an improvement in performance over the long distance which was superior to the gains found when increasing the maximal aerobic or anaerobic power by 10%. It is concluded that for an optimal use of training time and for an optimal use of the capacities of the swimmer, it seems important to determine both the mechanical parameters (technique, drag) and the parameters describing the energy production. By determining the weak and strong points of competitive swimmers, the optimal training distances and what performance factors are the weakest and most likely to improve with training can be determined.

Aerobiosis↗

PubMed1994

Reliability of heart rate responses to non-steady-state activities of daily living in men with spinal cord injuries.

The reliability of heart rate responses to non-steady-state tasks among 37 men with spinal cord injuries (lesion level: C4/5-L5) was examined with a simple heart rate recording device (Sport Tester PE3000). Three identical trials of 6 different transfers and an 8-cm curb ascent were performed on one day (Trial 1 and 2; n = 37) and one week later (Trial 3; n = 12). Pearson's r and intraclass correlations for the highest and the mean heart rate provoked during Trial 1 and 2 ranged from 0.73 to 0.97 for the transfers and from 0.92 to 0.97 for the curb ascent. Correlations were somewhat lower for Trial 1 versus Trial 3. A paired t-test revealed lower heart rate responses to Trial 2 and 3, suggesting a moderate learning effect and/or a reduction in psychological stress. It was concluded that heart rate responses to non-steady-state tasks, as recorded by a Sport Tester PE3000, are reproducible in men with spinal cord injuries.

Activities of Daily Living↗

PubMed1993

Responses of subjects with spinal cord injuries to maximal wheelchair exercise: comparison of discontinuous and continuous protocols.

Six male subjects with spinal cord injuries (SCI) participated in this investigation to compare peak values of oxygen uptake (VO2), heart rate (fc), ventilation (VE), respiratory exchange ratio (R) and power output (W) obtained using a discontinuous (DP) and a continuous jump max protocol (JMP) in a maximal wheelchair exercise test on a treadmill. The W increments were achieved by imposing an extra mass upon the wheelchair through a pulley system. The DP involved exercise periods of 3 min separated by 2-min intervals at relative rest. Increments in W consisted of 0.10 or 0.15 W.kg-1 total mass. During the rest intervals no mass was imposed on the wheelchair. The JMP involved an increase in W each minute. Increments and velocity in the JMP were the same as during the exercise periods for DP. Mean peak values for W [99.5 (SD 13.6) W], VO2 [2.13 (SD 0.27) l.min-1, standard temperature and pressure, dry], R [1.25 (SD 0.16)] and VE [82.8 (SD 11.2) l.min-1, body temperature and pressure, saturated] in DP were not different from values observed for W [103.5 (SD 13.1)], VO2 [2.18 (SD 0.31) l.min-1], R [1.17 (SD 0.16)] and VE [78.9 (SD 16.0) l.min-1] in the JMP. The only significant difference was observed for fc: 198 (SD 11) beats.min-1 in DP and 187 (SD 11) beats.min-1 in JMP. The higher values for fc elicited using DP have been discussed. It was concluded that both a DP and a JMP seem to be equally appropriate in determining peak VO2 and peak W in SCI persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Isometric strength, sprint power, and aerobic power in individuals with a spinal cord injury.

This study investigated in rather specific wheelchair tests the relationships among estimates of isometric upper-body strength (Fiso), sprint power (P30), aerobic power (VO2peak), and maximal power output (POaer) in a group of 44 men (age 34 +/- 12 yr) with longstanding spinal cord injuries ranging from C4/C5 to L5. Fiso was defined as the maximum force that could be exerted on the blocked rims of a stationary wheelchair ergometer. The estimation of P30 involved the measurement of the mean power during a 30-s all-out sprint test on the same wheelchair ergometer. VO2peak and POaer were determined as the peak oxygen uptake and highest sustained power output during a discontinuous progressive maximal exercise test on a motorized treadmill, while subjects used their own daily use wheelchair. Fiso ranged from 1.5 N.kg-1 (mean of both arms) in the group with quadriplegia to 3.4 N.kg-1 in the group with lowest-lesions, and P30 ranged from 0.5 to 1.5 W.kg-1 among the subjects. VO2peak ranged from 13.6 ml.kg-1.min-1 in the group with quadriplegia to 31.3 ml.kg-1.min-1 in the group with lowest-lesions, and POaer ranged from 0.4 to 1.1 W.kg-1. Strong positive relationships (r = 0.81-0.92) were demonstrated among all variables. Regression equations among variables were calculated: P30 = 0.51 Fiso - 0.18 (R2 = 0.75); POaer = 0.34 Fiso - 0.02 (R2 = 0.66); POaer = 0.67 P30 + 0.11 (R2 = 0.81); VO2peak = 6.52 Fiso + 4.15 (R2 = 0.76); VO2peak = 12.03 P30 + 7.43 (R2 = 0.77); VO2peak = 16.81 POaer + 6.44 (R2 = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Hypothesis: cartilage catabolic cofactors in human arthritis.

Cartilage degradation in rheumatoid arthritis (RA) and osteoarthritis (OA) is commonly thought to be mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF). However, recent new evidence suggests that IL-1 and TNF on their own do not mediate all the cartilage changes seen in RA and OA. We propose that cartilage degradation is mediated by a complex network of cytokines, including IL-1, TNF and at least one cofactor present in synovial fluid.

Arthritis, Rheumatoid↗

PubMed1992

Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity?

The influence of maximum exercise has been studied in 10 patients with primary fibromyalgia syndrome (PFS) and 10 healthy sedentary control persons. The exercise consisted of a bicycle ergometertest and a steptest, both till exhaustion. In both tests, the mean maximum workload of the PFS patients was lower than that of the controls. Significantly lower values of serum creatinekinase, myoglobin, cortisol, epinephrine and norepinephrine were found in PFS patients. A striking finding was a lower heart rate in PFS patients compared to the controls under the same workload. The lower (nor)epinephrine concentration together with the lower heart rate suggests a disturbance of the sympathetic activity in PFS patients. The preliminary conclusion is that there is a disturbed reactivity of the sympathetic system as well as of the HPA axis in PFS.

Adolescent↗

PubMed1992

Energy expenditure during walking in subjects with tibial rotationplasty, above-knee amputation, or hip disarticulation.

The surgical treatment of osteosarcoma with a tibial rotationplasty seems to offer functional advantages in comparison with an above-knee amputation. It has not been established whether the functional advantages are accompanied by a lower rate of energy expenditure during walking. In children with a tibial rotationplasty (n = 15), an above-knee amputation (n = 6), or a hip disarticulation (n = 5), energy expenditure was measured during treadmill walking at various walking velocities. The subjects with a tibial rotationplasty were able to walk faster, but there were no differences between the groups in energy expenditure per unit time or per unit distance. Correction for confounding variables including age, sex, height, time since operation, level of activity, and support during walking in a multiple linear regression model did not reveal any significant differences in energy expenditure during walking between groups. 1992 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.

Adolescent↗

PubMed1991

Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by recombinant cytokines in vitro.

Rheumatoid arthritis (RA) synovial fluid (SF) stimulated significant loss of glycosaminoglycans (GAG) from normal and pathological human cartilage biopsies over 2 days as compared with normal human serum. By contrast, 15 RA SFs failed to degrade killed normal cartilage, and degraded killed RA cartilage less effectively than living RA cartilage. Four RA SFs were treated with neutralizing anti-cytokine antisera prior to incubation with normal cartilage. The degrading effects of two of the fluids were reversed by anti-interleukin-1 alpha (IL-1 alpha) while degradation by the third and fourth fluids were reversed by anti-interleukin-1 beta (IL-1 beta) and anti-tumour necrosis factor-alpha (TNF-alpha), respectively. However, recombinant human IL-1 alpha, IL-1 beta, TNF alpha or a combination of all three cytokines had no degrading effect in this 2-day culture system. It is concluded that RA SF degrades cartilage by a mechanism involving a synergistic interaction between cytokines and some other component of SF.

Arthritis, Rheumatoid↗

PubMed1991

Differential responses of human and rat cartilage to degrading stimuli in-vitro.

Human cartilage biopsies incubated for 2 days in-vitro with 15% synovial fluid from rheumatoid arthritis patients contained less glycosaminoglycans (GAG) than control biopsies. Recombinant human (rHu)-interleukin-1 alpha (IL-1 alpha) and IL-1 beta at 10 or 100 ng mL-1 had no effect on human cartilage GAG levels. Similarly, GAG loss from human cartilage biopsies into medium over 5 days was significantly increased by synovial fluid but unaffected by 100 ng mL-1 IL-1 alpha or IL-1 beta compared with controls. However, when rat femoral head cartilage samples were incubated with 100 ng mL-1 rHu-IL-1 alpha or IL-1 beta for 5 days there was a significant increase in GAG loss from the cartilage into medium, whilst human synovial fluid significantly decreased the loss of GAG from rat cartilage into medium, compared with controls. The results demonstrate that human and rat cartilage differ from each other in their responses to degrading stimuli and suggest that animal cartilage may have limited application for the screening of drugs intended for the treatment of human arthritides.

Animals↗