Biomedical subjects

P Boissy

Publications and source records attributed to P Boissy.

8 recordsLinked to original sources

PubMed2007

Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?

AIMS/HYPOTHESIS: Post-translational modifications, such as isomerisation of native proteins, may create new antigenic epitopes and play a role in the development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises and repairs isomerised Asn and Asp residues in proteins. The aim of this study was to assess the role of PIMT in the development of type 1 diabetes. MATERIALS AND METHODS: Immunohistochemical analysis of 59 normal human tissues was performed with a monoclonal PIMT antibody. CGP3466B, which induces expression of Pcmt1, was tested on MIN6 and INS1 cells, to assess its effect on Pcmt1 mRNA and PIMT levels (RT-PCR and western blot) and apoptosis. Forty-five diabetes-prone BioBreeding (BB) Ottawa Karlsburg (OK) rats were randomised to receive 0, 14 or 500 microg/kg (denoted as the control, low-dose and high-dose group, respectively) of CGP3466B from week 5 to week 20. RESULTS: A high level of PIMT protein was detected in beta cells. CGP3466B induced a two- to threefold increase in Pcmt1 mRNA levels and reduced apoptosis by 10% in MIN6 cells. No significant effect was seen on cytokine-induced apoptosis or PIMT protein levels in INS1 cells. The onset of diabetes in the BB/OK rats was significantly delayed (85.6+/-9.0 vs 84.3+/-6.8 vs 106.6+/-13.5 days, respectively; p<0.01 for high-dose vs low-dose and control groups), the severity of the disease was reduced (glucose 22.2+/-3.2 vs 16.9+/-2.6 vs 15.8+/-2.7 mmol; p<0.01 for high- and low-dose groups vs control group) and residual beta cells were more frequently identified (43% vs 71% vs 86%; p<0.05 for high-dose vs control group) in the treated animals. CONCLUSIONS/INTERPRETATION: The results support a role for post-translational modifications and PIMT in the development of type 1 diabetes in the diabetes-prone BB rat, and perhaps also in humans.

Animals↗

PubMed2007

Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?

A major clinical manifestation of bone cancers is bone destruction. It is widely accepted that this destruction is not caused by the malignant cells themselves, but by osteoclasts, multinucleated cells of monocytic origin that are considered to be the only cells able to degrade bone. The present study demonstrates that bone-resorbing osteoclasts from myeloma patients contain nuclei with translocated chromosomes of myeloma B-cell clone origin, in addition to nuclei without these translocations, by using combined FISH and immunohistochemistry on bone sections. These nuclei of malignant origin are transcriptionally active and appear fully integrated amongst the other nuclei. The contribution of malignant nuclei to the osteoclast population analysed in this study was greater than 30%. Osteoclast-myeloma clone hybrids contained more nuclei than normal osteoclasts and their occurrence correlated with the proximity of myeloma cells. Similar hybrid cells were generated in myeloma cell-osteoclast co-cultures, as revealed by tracing myeloma nuclei using translocations, bromo-deoxyuridine, or the Y chromosome of male myeloma cells in female osteoclasts. These observations indicate that hybrid cells can originate through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells participate directly. The possibility that malignant cells corrupt host cells by the transfer of malignant DNA may have been underestimated to date in cancer research.

Acid Phosphatase↗

PubMed2001

RANKL induces formation of avian osteoclasts from macrophages but not from macrophage polykaryons.

We have shown that chick macrophages express RANK at their surface and human RANKL (hRANKL) triggers the formation of osteoclasts able to degrade dentine. As described for mammalian osteoclasts, hRANKL also stimulates the resorbing activity of chick bone-derived osteoclasts. In other hands, in culture, chick macrophages spontaneously form polykaryons sharing most of the osteoclast markers but unable to resorb bone. Since both bone-resorbing osteoclasts and macrophage polykaryons found in inflammatory tissues are multinucleated cells deriving from the fusion of macrophages, we examined whether macrophage polykaryons could be induced toward bone-resorbing osteoclasts. Long-term exposure of macrophage polykaryons to hRANKL failed to activate any resorbing activity, indicating that although deriving from the same precursors macrophage polykaryons and osteoclasts are independent cell types and polykaryons are not immature osteoclasts.

Animals↗

PubMed2000

Effects of upper and lower limb static exertions on global synkineses in hemiparetic subjects.

OBJECTIVES: Global synkineses are nonpurposive pathological involuntary muscle activities or movements elicited at several or all of the joints of the affected limb or limbs during voluntary forceful resisted contractions. The purpose of this study was to assess the effect of upper and lower limb exertions on manifestations of upper limb global synkineses in hemiparetic subjects. DESIGN: Involuntary muscle activities on the affected upper limb of 11 hemiparetic subjects and on the left or right upper limb of 10 control subjects were recorded using surface electromyography during successive bilateral maximal ankle exertions and during contralateral grips. RESULTS: Significant differences in the level of involuntary electromyography (EMG) activities were observed between experimental conditions (ANOVAs, p < 0.05). EMG levels in hemiparetic subjects were significantly higher during contralateral grip tasks than during the ankle exertions. CONCLUSION: These results suggest that upper limb global synkinases are more prevalent in specific tasks and that this task specificity may reflect the neurophysiological mechanisms involved in the generation of global synkinases.

Adult↗

PubMed1999

Maximal grip force in chronic stroke subjects and its relationship to global upper extremity function.

OBJECTIVES: Previous studies have shown that recovery of recordable grip strength in acute stroke subjects is one of the most sensitive assessments of initial upper limb recovery and a good prognostic factor for latter recovery. The objectives of this study were to test the reliability of maximal voluntary grip force (MVGF) measures and evaluate the relationship between paretic grip strength deficit and paretic upper extremity function in chronic stroke subjects. DESIGN: Over a three-week period, bilateral MVGF was assessed three times with a modified strain gauge dynamometer in 15 chronic stroke subjects and 10 control subjects. The paretic MVGF deficit was expressed in relation to the MVGF of the nonaffected hand. OUTCOME MEASURES: Upper extremity function in stroke subjects was measured using the Fugl-Meyer, the upper extremity performance test for the elderly (TEMPA), Box and Block and finger-to-nose tests. RESULTS: MVGF measures in both groups of subjects demonstrated good reliability (intraclass correlation, ICC >0.86) and low standard error measurements (SEM). The paretic MVGF of the stroke subjects was greatly impaired in comparison to the control subjects. Results of linear and quadratic regressions analyses show that this impairment was significantly correlated (p <0.01) with the performance of the stroke subjects on the four upper extremity function tests. The percentages of variances explained by the MVGF deficit on all four upper extremity tests varied from 62% to 78% for the linear regressions and from 72% to 93% for the quadratic regressions. CONCLUSIONS: These results suggest that the paretic maximal grip strength, normalized with the maximal grip strength on the nonaffected side, appears to be a valuable outcome measure of upper extremity function in chronic stroke subjects.

Adult↗

PubMed1998

A static dynamometer measuring simultaneous torques exerted at the upper limb.

The majority of available dynamometers are designed to measure force or torque in one specific direction, one joint at a time. For the quantification of motor incoordination in neurological patient populations, these dynamometers provide limited information about the global behavior of the limb under investigation. This report describes the potential use and function of a static dynamometer measuring torques exerted simultaneously at the shoulder (flexion-extension, abduction-adduction, internal-external rotation), elbow (flexion-extension), and forearm (pronation-supination). Orthogonal forces were measured at the arm and wrist using strain gauge transducers interfaced with a laboratory computer. The lever arms were specified to a software program and the joint torques were calculated in real time according to static equilibrium equations. The use of the dynamometer is illustrated by characterizing for one hemiparetic subject, the joints torques recorded at the shoulder, elbow, and forearm during isolated submaximal grip exertions at different force levels on both sides. The torques generated at the shoulder, elbow and forearm during the hand grip tasks on the affected side were significantly higher than those obtained on the nonaffected side and increased with the grip force level. These differences probably reflect the loss of movement selectivity observed following a lesion in the central nervous system. Further studies are currently being undertaken in neurological patient populations to characterize and quantify motor deficits using this dynamometer. As a long term goal, we hope that the method and technologies described here will contribute to the evaluation and rehabilitation of these populations.

Biofeedback, Psychology↗

PubMed1998

Aggregation of mononucleated precursors triggers cell surface expression of alphavbeta3 integrin, essential to formation of osteoclast-like multinucleated cells.

Alphavbeta3 is a key integrin mediating adhesion of multinucleated osteoclasts during bone resorption. 1, 25-dihydroxyvitamin D3 upregulates alphavbeta3 integrin expression in mononucleated osteoclast precursors and concomitantly stimulates their differentiation into osteoclasts. This suggests that this integrin could play a major role during osteoclast differentiation. We have developed an in vitro model, in which 1, 25-dihydroxyvitamin D3 sequentially modifies the behavior of macrophages: It first induces rounding up of these cells, then their subsequent aggregation and spreading, which finally leads to cell fusion and the formation of osteoclast-like multinucleated giant cells. We show that, while 1,25-dihydroxyvitamin D3 stimulates the de novo synthesis of alphavbeta3 in macrophages early in this process, its accumulation on the surface is triggered by cell aggregation. A high level of integrin alphavbeta3 cell surface expression correlates with macrophage spreading preceding fusion. This was confirmed by means of novel cell permeable peptides containing the C-terminal sequence of the integrin beta3 tail to specifically block (alphavbeta3 function. Although this peptide has no effect on the aggregation step, it disrupts the spreading of osteoclast precursors and consequently inhibits their fusion. These findings suggest a novel role of the integrin alphavbeta3 in a discrete step of osteoclast differentiation.

Amino Acid Sequence↗

PubMed1997

Characterization of global synkineses during hand grip in hemiparetic patients.

OBJECTIVE: Global synkineses are defined as nonpurposive associated movements on the involved side of hemiparetic subjects that are triggered during a voluntary movement. The purpose of this study was to characterize the intensity and pattern of upper limb global synkineses in hemiparetic subjects with a static biarticular dynamometer and electromyography during maximal progressive hand grip on the unaffected side. DESIGN: Survey, convenience sample. SETTINGS: University secondary care rehabilitation center. DATA SET: Global synkineses (ie, torques and electromyographic activities) in patients with severe (n = 8) and moderate (n = 7) deficits in motor performance, as evaluated by the Fugl-Meyer assessment, were compared with those obtained in a group of healthy subjects (n = 11). Clinically the subjects from the severe deficit group were more spastic and showed less strength at the elbow than the subjects from the moderate deficit group. RESULTS: Results of analyses of variance showed significant increases of shoulder torque in flexion and internal rotation, and elbow torque in flexion, with increasing force exertion during contralateral hand grip in subjects with severe deficits (p < .05). Furthermore, in these subjects increases of electromyographic activity were also observed in biceps brachii, brachioradialis, and triceps brachii muscles with increasing hand grip force levels. In contrast, no significant torques or electromyographic increases were observed in subjects with moderate deficits and in control subjects during contralateral hand grip exertions. CONCLUSION: These results provide a quantitative assessment of the kinematic and electromyographic patterns of global synkineses and their correlates with clinical observations. Within the limits of the experimental results presented in this study, it is suggested that global synkineses result from contralateral overflow of the voluntary command to hyperexcitable motoneuron pools.

Adult↗