Proportion versus absolute counts of B cell populations in the assessment of immunological profiles of kidney transplant recipients.

Immunophenotyping lymphocytes in kidney transplant recipients often raises questions as to whether proportions or absolute counts should be considered, especially for longitudinal assessment. Several studies conclude the pathophysiology of rejection based on proportions of naive and memory B cells. We compared the two analytical methods for B cells sampled from 82 clinically stable, adult kidney transplant recipients. Time post-transplant was analyzed both as a continuous variable and as tertiles (<1.5 years, 1.5-8 years, and > 8 years). B cells were stained for CD38 and IgD and were classified according to mature B cells (Bm) classification. The proportion of cells in the naive Bm2 compartment decreased by more than half in the late versus the early tertile, whereas the percentages of memory early Bm5 tripled and that of memory Bm5 cells doubled. In contrast, we observed a substantial reduction in naive B cell counts, but very stable memory B cell counts. Linear regressions showed that the absolute reduction in the Bm2 cell compartment was independent of age, sex, graft function, immunosuppression scheme, and rejection occurrence. In conclusion, the physiological reservoir of naive cells decreases over time post-transplant in kidney recipients, whereas that of memory B cells remains stable. Peripheral B subset percentages should be interpreted cautiously when analyzing pathophysiological processes.

Tacrolimus prevents von Willebrand factor secretion by allostimulated human glomerular endothelium.

Little is known about the endothelial injury caused directly by circulating donor-specific antibodies (DSAs) during antibody-mediated rejection. von Willebrand factor (vWF) is a highly thrombotic glycoprotein stored in Weibel-Palade bodies in endothelial cells. It has been shown that its secretion is triggered by allostimulation. Calcineurin-like phosphatases regulate pathways involved in vWF secretion. Therefore, we hypothesized that tacrolimus would prevent alloantibody-induced glomerular lesions, in part via inhibition of vWF secretion from endothelial cells. Here, we used a human in vitro model of glomerular endothelium expressing HLA class I and II antigens and demonstrated that anti-HLA class II antibodies elicit a higher endothelial release of vWF than do anti-HLA class I antibodies in cell supernatants. We observed that tacrolimus treatment decreased vWF secretion after stimulation with both classes of anti-HLA antibodies and decreased platelet adhesion on allostimulated endothelial cells in a microfluidic chamber. In kidney recipients, tacrolimus trough levels were negatively associated with vWF blood levels. These results indicate that direct disruption of hemostasis via vWF secretion is a potential mechanism of antibody-mediated injury in patients with DSAs. Our results further suggest that the targeting of microcirculation hemostasis may be beneficial to prevent the development of microangiopathic lesions in antibody-mediated rejection.

Effects of alloantibodies to human leukocyte antigen on endothelial expression and serum levels of thrombomodulin.

Essentials The effect of alloantibodies on the endothelial expression of thrombomodulin is unknown. Thrombomodulin was quantified in stimulated endothelial cells and measured in serum samples. Anti-human leukocyte antigen (HLA) I vs. II antibodies have different effects on thrombomodulin. Anti-HLA II antibodies may promote a prothrombotic state and contribute to microangiopathy. SUMMARY: Rationale Thrombomodulin (TBM) is an anticoagulant and anti-inflammatory transmembrane protein expressed on endothelial cells. Donor-specific alloantibodies, particularly those against human leukocyte antigen (HLA) class II, are associated with microvascular endothelial damage in solid allografts. Objective Our aim was to characterize the effects of anti-HLA antibodies on endothelial expression of TBM, and in particular, the differential effects of anti-HLA class I compared with those of anti-HLA class II. Methods We used human glomerular microvascular endothelial cells to examine TBM expression on anti-HLA-treated cells, and we tested sera from transplant recipients for soluble TBM. Results We found that whereas membrane TBM expression increased in a dose-dependent manner in the presence of anti-HLA class I antibodies, treatment with anti-HLA class II led to minimal TBM expression on the endothelial surface but to a cytosolic accumulation. Platelet adhesion studies confirmed the functional impact of anti-HLA class II. Quantitative densitometry of the membrane lysates further suggested that anti-HLA class II impairs TBM glycosylation. Furthermore, we found a significant association between the presence of circulating anti-HLA class II antibodies in transplant recipients and low serum levels of TBM. Conclusion These results indicate that ligation of anti-HLA class I and II antibodies produces different effects on the endothelial expression of TBM and on serum levels of TBM in transplant recipients. Anti-HLA class II antibodies may be associated with a prothrombotic state, which could explain the higher occurrence of microangiopathic lesions in the allograft and the poor outcomes observed in patients with these alloantibodies.

Temporal changes in hematologic markers after splenectomy, splenic embolization, and observation for trauma.

INTRODUCTION: The spleen is one of the most commonly injured abdominal solid organs during blunt trauma. Modern management of splenic trauma has evolved to include non-operative therapies, including observation and angioembolization to preclude splenectomy in most cases of blunt splenic injury. Despite the shift in management strategies, relatively little is known about the hematologic changes associated with these various modalities. The aim of this study was to determine if there are significant differences in hematologic characteristics over time based on the treatment modality employed following splenic trauma. We hypothesized that alterations seen in hematologic parameters would vary between observation (OBS), embolization (EMB), and splenectomy (SPL) in the setting of splenic injury. METHODS: An institutional review board-approved, retrospective study of routine hematologic indices examined data between March 2000 and December 2014 at three academic trauma centers. A convenience sample of patients with splenic trauma and admission lengths of stay >96 h was selected for inclusion, resulting in a representative sample of each sub-group (OBS, EMB, and SPL). Basic demographics and injury severity data (ISS) were abstracted. Platelet count, red blood cell (RBC) count and RBC indices, and white blood cell (WBC) count with differential were analyzed between the time of admission and a maximum of 1080 h (45 days) post-injury. Comparisons between OBS, EMB, and SPL groups were then performed using non-parametric statistical testing, with statistical significance set at p < 0.05. RESULTS: Data from 130 patients (40 SPL, 40 EMB, and 50 OBS) were analyzed. The median age was 40 years, with 67 % males. Median ISS was 21.5 (21 for SPL, 19 for EMB, and 22 for OBS, p = n/s) and median Glasgow Coma Scale (GCS) was 15. Median splenic injury grade varied by interventional modality (grade 4 for SPL, 3 for EMB, and 2 for OBS, p < 0.05). Inter-group comparisons demonstrated no significant differences in RBC counts. However, mean corpuscular volume (MCV) and RBC distribution width (RDW) were elevated in the SPL and EMB groups (p < 0.01). Similarly, EMB and SPL groups had higher platelet counts than the OBS group (p < 0.01). In aggregate, WBC counts were highest following SPL, followed by EMB and OBS (p < 0.01). Similar trends were noted in neutrophil and monocyte counts (p < 0.01), but not in lymphocyte counts (p = n/s). CONCLUSION: This study describes important trends and patterns among fundamental hematologic parameters following traumatic splenic injuries managed with SPL, EMB, or OBS. As expected, observed WBC counts were highest following SPL, then EMB, and finally OBS. No differences were noted in RBC count between the three groups, but RDW was significantly greater following SPL compared to EMB and OBS. We also found that MCV was highest following OBS, when compared to EMB or SPL. Finally, our data indicate that platelet counts are similarly elevated for both SPL and EMB, when compared to the OBS group. These results provide an important foundation for further research in this still relatively unexplored area.

2013 Banff Criteria for Chronic Active Antibody-Mediated Rejection: Assessment in a Real-Life Setting.

Significant changes in the criteria for chronic active antibody-mediated rejection (CAABMR) were made in the Banff 2013 classification. These modifications expanded the number of patients diagnosed with CAABMR, with undetermined clinical significance. We compared the 2007 and 2013 criteria for the composite end point of death-censored graft failure or doubling of serum creatinine in 123 patients meeting the criterion related to the morphologic evidence of chronic tissue injury. In all, 18% and 36% of the patients met the 2007 and 2013 criteria, respectively. For the criterion related to antibody interaction with endothelium, only 25% were positive based on the 2007 definition compared with 82% using the 2013 definition. Cox modeling revealed that a 2013 but not a 2007 diagnosis was associated with the composite end point (adjusted hazard ratio 2.5 [95% confidence interval (CI) 1.2-5.2] vs. 1.6 [95% CI 0.7-3.8], respectively). The 2013 criterion based on both the C4d score and the glomerulitis plus peritubular capillaritis score (g+ptc) was more strongly associated with the end point than the 2007 criterion based only on C4d; however, when dissected by component, only the C4d component was significant. The association with clinical outcomes improved with the 2013 criteria. This is related to the new C4d threshold but not to the g+ptc ≥2 component.

Determination of optimal incubation time for the production of acute phase cytokines ex vivo by peripheral blood mononuclear cells from renal transplant recipients.

Levels of acute phase cytokines secreted ex vivo by peripheral blood mononuclear cells (PBMCs) have been shown to be associated with clinical conditions or histologic lesions in renal transplant recipients. One of the limiting factors for the potential use of this assay as a diagnostic tool is the incubation time needed to measure adequate cytokine levels. Here, we validated that shorter time periods than the usual 48 h are sufficient for the production of acute phase cytokines. Cytokine levels were measured with the Luminex platform. We observed that, in contrast to cytokines associated with adaptive immunity, cytokines such as IL-1ß, IL-6 and TNF-α are measurable as early as 2 h following incubation at a concentration of 1.5 million PBMC/150 µL. Levels obtained in the 2 h cultures have good correlations with the levels obtained after 48 h of culture for IL-1ß and TNF-α (R=0.79, P=0.004 and R=0.92, P<0.001 respectively). We conclude that same-day incubation of PBMCs and measurement of these cytokines following blood collection in transplant recipients is feasible. It provides a rationale for further studies using shorter incubation times for ex vivo cellular assay measuring acute phase cytokine levels.

Supramolecular-directed chiral induction in biaryl derivatives.

A thermodynamically controlled resolution has allowed for the generation of diastereomerically enriched complexes, by chirality transfer from an enantiopure building block to a dynamically racemic biaryl derivative. A switchable sense of induction could be achieved depending on the substituents of the chiral block.

Gadolinium-enhanced small-animal TOF magnetic resonance angiography.

So far, magnetic resonance angiography (MRA) of rodents has only been performed by using time-of-flight (TOF) MRI techniques. This is because applications of first-passage contrast agents as in humans are hampered by pronounced physiologic differences (blood volume and heart beat rate). Here we describe the use of low-dose Gd-DOTA to enhance the performance of TOF MRA in rat brain. While no improvement in contrast was achieved, the measuring time could be reduced by almost a factor of three. This decrease in total acquisition time has been used to study the impact of a model of ligatured common carotid on the upper part of the blood system of the rat.

Lactate involvement in neuron-glia metabolic interaction: (13)C-NMR spectroscopy contribution.

Glucose is commonly admitted to be the main substrate for brain energy requirement. However, it has been recently proposed that lactate, generated from glucose via glycolysis, would be the oxidative substrate for neurons, particularly during neuronal activation, according to a mechanism called the astrocyte-neuron lactate shuttle hypothesis (ANLSH). In that mechanism, glutamate released in the synaptic cleft during brain activation is taken up by astrocytes. This uptake, via the glutamate/Na(+) transporter, induces the entry of sodium, which is then excluded from the astrocytes via the Na(+)/K(+) ATPase. This exclusion consumes ATP, which stimulates glycolysis and thus lactate formation in astrocytes. This lactate is then transferred to neurons where it is utilized as oxidative substrate. This review tries to gather the recent evidences that support this hypothesis and presents the contribution of NMR to this matter.

Stretch and H reflexes in triceps surae are similar during tonic and rhythmic contractions in high decerebrate cats.

During locomotion in decerebrate and spinal cats the group Ia afferents from hind leg muscles are depolarized rhythmically. An earlier study concluded that this locomotor-related primary afferent depolarization (PAD) does not contribute to modulation of monosynaptic reflex pathways during locomotion. This finding indicated that the neural network generating the locomotor rhythm, the central pattern generator (CPG), does not presynaptically inhibit monosynaptic reflexes. In this investigation we tested this prediction in decerebrate cats by measuring the magnitude of reflexes evoked in ankle extensor muscles during periods of tonic contractions and during sequences of rhythmic contractions. The latter occurred when the animal was induced to walk on a treadmill. At the similar levels of activity in the soleus muscle there was no significant difference in the magnitude of the soleus H reflex in these two behavioral situations. Similar results were obtained for reflexes evoked by brief stretches of the soleus muscle. We also examined the reflexes evoked by ramp-and-hold stretches during periods of rhythmic and tonic activity of the isolated medial gastrocnemius (MG) muscle. At similar levels of background activity, the reflexes evoked in the MG muscle were the same during rhythmic and tonic contractions. Our failure to observe a reduction in the magnitude of H reflexes and stretch reflexes during rhythmic contractions, compared with reflexes evoked at the same level of background activity during tonic contractions, is consistent with the notion that the CPG for stepping does not presynaptically inhibit monosynaptic reflexes during the extension phase of locomotor activity. Our results indicate that presynaptic inhibition of the monosynaptic reflex associated with normal locomotion in cats or humans arises from sources other than the extensor burst generating system of the central pattern generator.

Endograft planning without preoperative arteriography: a clinical feasibility study.

PURPOSE: To investigate an alternative method of preprocedural planning for aortic endografting based solely on spiral computed tomography (CT) with 3-dimensional (3D) reconstruction without preoperative arteriography. METHODS: From August 1997 to April 1998, 25 consecutive patients with abdominal aortic aneurysms (AAA) were evaluated for endovascular repair by spiral CT scans (2-mm slice thickness) and computerized 3D model construction. No additional imaging for planning was performed. The aortoiliac dimensions, thrombus load, calcification, and vessel tortuosity were measured and evaluated from the 3D model of the aortoiliac segment. These data were used for selecting the patients; the configuration, diameter, and length of the endograft; and the attachment sites for deployment. RESULTS: Primary procedural success was 92% (23/25). All endografts were deployed as planned, and there were no conversions to open repair. Six patients required adjunctive procedures for delivery system access or for iliac aneurysm exclusion, as predicted by the 3D model. Mean procedural time was 91 minutes (range 24 to 273). Two (8%) type II (side branch) endoleaks both sealed spontaneously within 1 month. No graft-related complications or death occurred, for a 30-day technical success rate of 100%. CONCLUSIONS: This computerized 3D model provided accurate data for preoperative evaluation of the aortoiliac segment for endovascular AAA repair. Satisfactory technical outcomes for aortic endografts can be achieved without the use of preprocedural invasive imaging.

Older adults can maximally activate the biceps brachii muscle by voluntary command.

Because some of the decline in strength with age may be explained by an impairment of muscle activation, the purpose of this study was to determine the activation level achieved in biceps brachii by older adults during a maximum voluntary contraction (MVC). This capability was assessed with two superimposition techniques: one calculated the activation level that was achieved during an MVC, and the other provided an estimate of the expected MVC force based on extrapolation with submaximal forces. The activation level in biceps brachii was incomplete (< 100%) for the young (n = 16) and elderly (n = 16) subjects, with the elderly subjects exhibiting the greater deficit. In contrast, there was no difference between the measured and expected MVC forces for either group of subjects, whether the extrapolation involved a third-order polynomial or linearization of the data. Because of the lower signal-to-noise ratio associated with the measurement of activation level and the greater number of measurements that contributed to the estimate of the expected MVC force, we conclude that the older adults were able to achieve complete activation of the biceps brachii muscle during an MVC.

Gain of the triceps surae stretch reflex in decerebrate and spinal cats during postural and locomotor activities.

1. The triceps surae (TS) stretch reflex was measured in decerebrate cats during crossed extensor stimulation and after spinalization during rhythmic locomotor activity induced by clonidine and manual perineal stimulation. The TS force in response to sinusoidal stretch was measured at a given contraction level before and after deafferentation, and the 'reflex force' was computed by subtracting these two responses. Reflex 'gain' was computed as the ratio of the reflex and deafferented force responses (a unitless estimate of the open loop feedback gain). 2. Prior to locomotion the spontaneous muscle activity was low (less than 15% of maximum), but the reflex gain was relatively high (close to 1.0 with a 5 Hz stretch). When locomotion commenced the reflex gain was markedly lowered when measured at the same contraction level as before locomotion (25% of the gain prior to locomotion). At higher contraction levels the reflex gain was not significantly increased. The reflex force and EMG responses to stretch increased with the contraction level, but their effect on the total reflex gain was cancelled by an associated increase in the intrinsic muscle stiffness. 3. In the decerebrate cat, during weak tonic contractions (spontaneous), the reflex gain was high and comparable with the gain in the resting spinal cat. However, with increased tonic contractions produced by crossed extensor stimulation the reflex gain dropped. At higher contraction levels the gain was not significantly different from the gain during spinal locomotion. 4. When the frequency of stretch was increased from 3 to 20 Hz, EMG responses to stretch increased, but the reflex force decreased, since a more fused contraction developed with the more frequent reflex activations. Overall, the reflex gain decreased with frequency in both spinal and decerebrate cats. The phase lag of the reflex force, relative to the intrinsic muscle force, increased with increasing frequency, due to reflex delays, with a 180 deg lag occurring between 12 and 18 Hz (tremor frequencies). The mean gain was significantly lower and the phase lag was significantly greater during locomotion than during tonic crossed extensor contractions, suggesting different reflex mechanisms. 5. In conclusion, during locomotion in spinal cats afferent feedback from low frequency ankle movements, similar to those occurring during the normal step cycle, reflexly produces a small but significant fraction of the extensor force (about a quarter of the stretch-related force modulation). This fraction is remarkably constant at the different contraction levels of the step cycle. Afferent feedback during higher frequency movement is less effective, minimizing the chance of instability and tremor. In contrast during tonic contractions afferent feedback produces half of the total muscle force during perturbations, clearly contributing to the maintenance of posture.

Regulation of soleus muscle spindle sensitivity in decerebrate and spinal cats during postural and locomotor activities.

1. In order to study fusimotor control in reduced preparations, soleus muscle spindle afferents were recorded in premammillary decerebrate cats (n = 15) during crossed extensor reflexes and, after spinalization, during locomotion produced by either clonidine or L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The soleus muscle was oscillated sinusoidally (0.25 mm, 4 Hz) and the afferent mean firing rate and modulation were calculated. An increase in firing rate was assumed to arise from activity in dynamic gamma-motoneurones (dynamic gamma-drive) when associated with an increase in modulation to stretching, and in static gamma-motoneurones (static gamma-drive) when modulation decreased. 2. At rest in all preparations the firing rate and modulation in primary muscle spindle afferents were generally much higher than after de-efferentation (ventral root section), suggesting a predominant dynamic gamma-drive. Clonidine decreased and even eliminated this presumed resting gamma-drive in many afferents, both in the decerebrate (7 of 8) and the spinal (6 of 18) state. This effect on gamma-drive may account, at least in part, for its suppressive effect on spasticity in humans. 3. When locomotion commenced in clonidine-treated spinal cats, primary afferents generally fired with much higher mean rates (+121%) and lower sensitivities (-32%), suggesting a large increase in static gamma-drive (possibly accompanied by a small decrease in dynamic gamma-drive). These high rates were usually maintained tonically throughout the step cycle. However, a third of the afferents were silenced during locomotor contractions, and de-efferentation had no significant effect on their firing rates. Thus, for some spindles alpha-activity can occur without significant gamma-drive. 4. During locomotion in L-DOPA-treated spinal cats the inferred static gamma-drive only occurred phasically, coactivated with the EMG, though it could precede the EMG by 100-500 ms. In the flexion phase both the afferent rate and modulation were lower than before locomotion, suggesting a lack of effective gamma-drive. 5. Crossed extensor reflexes in decerebrate cats also produced a substantial increase in primary afferent firing rate (+187%) and decrease in sensitivity (-37%), again suggesting increased static gamma-drive (n = 18). This gamma-drive was largely independent of EMG activity and often occurred without alpha-activity. The mean firing rate of secondary muscle spindle afferents increased significantly during locomotion (with L-DOPA) and crossed extensor reflexes, again indicating increased static gamma-drive. Clonidine reduced or eliminated the gamma-drive in seven of eight afferents during crossed extensor reflexes. 6. In conclusion, although there are some common features, such as a predominant static gamma-drive in all walking preparations, the pattern of static and dynamic gamma-drive is not closely linked to alpha-activity under the conditions studied. As well as gamma-drive without alpha-activity, we have shown for the first time that alpha-motoneurones can be activated without significant gamma-drive to many spindles during behavioural tasks.

Mechanism for reflex reversal during walking in human tibialis anterior muscle revealed by single motor unit recording.

1. A reversal in the sign of a cutaneous reflex during walking was recently described in the human. Such reversals were most clearly seen in muscles that were active in two parts of the step cycle, such as the tibialis anterior (TA). The current study determined whether the reversal resulted from differential activation of a single group of motor units. 2. Single motor units were recorded from the TA muscle of healthy human subjects while they walked on a treadmill with a splint that limited motion of the ankle joint. The majority of motor units from which recordings were made (43 out of 46) were active in both the swing phase and the transition from swing to stance, indicating that the two bursts of activity from the TA muscle do not represent the activity of two separate populations of motor units. 3. The firing behavior of three motor units was observed during walking steps when stimuli were applied to the posterior tibial nerve during either the swing phase or the transition from swing to stance. The post-stimulus time histograms indicated that the same motor unit was excited during the swing phase, and inhibited during the transition from swing to stance. 4. The results support the hypothesis that there are parallel excitatory and inhibitory pathways from cutaneous afferents to single motoneurones of the TA muscle. A shift in balance between the two pathways as a function of the step cycle most probably generates the reflex reversal observed.

Effects of TENS and topical skin anesthesia on soleus H-reflex and the concomitant influence of skin/muscle temperature.

The purpose of this study was to determine, in ten healthy subjects, the extent of soleus motoneuronal excitability during conditions of increased (transcutaneous electrical nerve stimulation [TENS]), decreased (Xylocaine [lidocaine]a anaesthesia) and normal (placebo anaesthesia) cutaneous inputs. Increased cutaneous activity was evoked using a TENS unit, with the two pairs of electrodes placed respectively over the Achilles (S2 dermatome) and tibialis anterior (L5 dermatome) tendons. Experimental and placebo topical anaesthesia were obtained after rubbing Xylocaine (5%) and Vaselineb ointment, respectively, on the skin surface overlying the Achilles tendon. Sets of ten H-responses (Hmax/2) were evoked at a frequency of 1 shock/30s and averaged at regular time intervals before, during and after the testing conditions. The results showed a gradual increase (up to 40% after 20 minutes) of H-reflex amplitude during TENS regardless of whether it was applied on the L5 or S2 dermatome. Furthermore, placebo anesthesia (Vaseline) caused the same gradual facilitatory response (up to 100% after 50 minutes) as that obtained during Xylocaine anaesthesia. Power spectral analysis of the H-responses obtained over time showed that the increase in the peak-to-peak H-response value was accompanied by a shift of the spectral content toward low frequencies. This shift occurred concomitantly with a cooling of the skin overlying the soleus muscle.

Effect of pronation and supination tasks on elbow flexor muscles.

The aim of this study was to verify the presence of modulatory effects of pronation (P) and supination (S) on biceps brachii (BB) and brachioradialis (BR) electromyographic (EMG) signals while performing isometric elbow flexions at different angles (50, 90, and 130°). The EMG activity of BB and BR was recorded for normal subjects (N = 6) with surface electrodes during an isometric ramp contraction of elbow flexion (F) that was combined with 20% of maximal voluntary contraction (MVC) in pronation or in supination. The results indicate that (a) the BB muscle presents an increased EMG activity in the combined task of S-F and a decreased EMG activity in the combined task of P-F (Friedman ANOVA, p < 0.01); (b) the EMG activity of the BR is not significantly influenced by the different tasks (Friedman's ANOVA, p > 0.05); and (c) the modulation of the BB occurs only at a midrange angle of flexion. This study partly supports results that were previously reported by other authors, suggesting that a combined task can modulate the EMG activity of elbow flexor muscles. However, this modulation, observed especially for the BB, appears to be limited to elbow flexion angles that are close to 90°.

Cocontraction of the elbow muscles during combined tasks of pronation-flexion and supination-flexion.

The aim of this study was to determine if the antagonist activity of the triceps brachii (TB) and anconeus (AN) muscles is modulated when the activity of the biceps brachii (BB) and brachioradialis (BR) is modulated by the performance of combined tasks and to verify if this behavior is similar at different elbow angles. Electromyographic (EMG) activity of BB, BR, AN and TB was recorded for normal subjects (N = 6) with surface electrodes during a ramp isometric contraction in elbow flexion (F) which was performed alone or combined with 20% of maximal voluntary contraction (MVC) in pronation (P) or in supination (S). Two cocontraction ratios, using the EMG root mean square (rms) values of each muscle and identified as BB/TB and BR/AN were calculated. The results indicate that for low flexion torque levels, the BB/TB ratio is higher for the S-F condition while the BR/AN ratio is higher during the pure flexion task. Variations of the EMG activity across tasks were significant only for BB (Friedman ANOVA, p less than .01) whereas there was no significant change in EMG activity (rms) for TB, BR and AN (Friedman ANOVA, p greater than .01). Furthermore, the behavior of both ratios across tasks was similar at 50 degrees, 90 degrees and 130 degrees of elbow flexion. Thus, for isometric conditions, there appears to be no evidence of modulation of EMG activity of elbow extensors while performing combined tasks of S-F and P-F. In addition, cocontraction activity during these tasks tends to be similar across elbow angles.