Microtubule motors involved in nuclear movement during skeletal muscle differentiation.

Nuclear positioning is a determining event in several cellular processes, such as fertilization, cell migration, and cell differentiation. The structure and function of muscle cells, which contain hundreds of nuclei, have been shown to rely in part on proper nuclear positioning. Remarkably, in the course of muscle differentiation, nuclear movements along the myotube axis might represent the event required for the even positioning of nuclei in the mature myofiber. Here we analyze nuclear behavior, time in motion, speed, and alignment during myotube differentiation and temporal interference of cytoskeletal microtubule-related motors. Using specific inhibitors, we find that nuclear movement and alignment are microtubule dependent, with 19 microtubule motor proteins implicated in at least one nuclear behavior. We further focus on Kif1c, Kif5b, kif9, kif21b, and Kif1a, which affect nuclear alignment. These results emphasize the different roles of molecular motors in particular mechanisms.

Overexpressed transglutaminase 5 triggers cell death.

Transglutaminases are a class of nine different proteins involved in many biological phenomena such as differentiation, tissue repair, endocytosis. Transglutaminase 5 was originally cloned from skin keratinocytes, and a partial biochemical characterization showed its involvement in skin differentiation. Here we demonstrate that transglutaminase 5 is able to induce cell death when intracellularly overexpressed. Transfected cells show enzymatic activity, as demonstrated by fluoresceincadaverine staining. Transfected cells died due to the formation of hypodiploid DNA content, indicating the induction of cell death under these pharmacological conditions. We also show that the primary sequence of transglutaminase 5 contains GTP binding domains which are similar to those in transglutaminase 2. This raises the possibility that transglutaminase 5 is regulated by GTP in a similar fashion to transglutaminase 2.

Patterns of specific genomic alterations associated with poor prognosis in high-grade renal cell carcinomas.

A series of 13 sporadic renal cell carcinomas was analyzed for the specific chromosome rearrangements after serial xenografting into immunodeficient mice. Seven tumors displayed genetic traits of the conventional subtype and 5 showed genetic features of the papillary subtype. In all the xenografted conventional tumors, we observed loss of 3p, as well as loss of the 9p21 region and of the long arm of chromosome 14, both considered as markers of a poor prognosis. In the xenografted papillary tumors, a duplication of chromosome arm 8q was observed concomitant with the duplication of the 7q31 region. The association of the 7q31 and 8q22 approximately qter duplicated regions was also observed for one conventional tumor. The latency of tumor take was found to be reduced and the median time to passage statistically shorter for all tumors which presented the associated duplication of the 7q31 and 8q22 approximately qter regions. The proto-oncogene NOV (nephroblastoma overexpressed gene) maps to 8q24.1 and is overexpressed in some Wilms tumors. It could be an interesting candidate gene, since its level of expression and release in the culture medium was found to be increased in all of the fast growing tumors analyzed.

Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues.

AIMS: To investigate the expression of the human ccn3 (hccn3; nov) proto-oncogene, a member of the CCN family of proteins, in prostate epithelial cells and prostate tissue samples. METHODS: Normal adult prostate luminal epithelial cells immortalised by SV40 large T (PNT1A and PNT1B), metastatic tumours (LNCaP, DU-145, and PC-3), and prostate tissue samples from patients with benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma were used. hccn3 (nov) mRNA was measured by the reverse transcription polymerase chain reaction (RT-PCR) and hCCN3 (NOV) protein expression was determined by immunochemistry. RESULTS: hccn3 (nov) RNA values were higher in PC-3 cells than in the other prostate cell lines. The immortalised normal cell lines either did not express hccn3 (nov) RNA (PNT1B) or expressed very low amounts (PNT1A). BPH samples expressed variable amounts of hccn3 (nov) RNA. With the use of immunocytochemistry, all cell lines except PNT1A and PNT1B were shown to contain hCCN3 (NOV) protein. hCCN3 (NOV) was localised mainly in the epithelial compartment of BPH and adenocarcinoma samples, and there was evidence of luminal secretion. CONCLUSION: The overexpression of hccn3 (nov) RNA in cancer cell lines compared with other cell lines and its epithelial localisation in human prostate samples are consistent with a role for hCCN3 (NOV) in prostatic tumorigenesis.

Histomorphometry of the ulnar nerve and of its branches.

A morphometric study has shown that 10% of the fibers of the ulnar nerve should suffice to reinnervate the biceps muscle in brachial plexus palsies. The aim of this study was to evaluate, by a morphometric study using computerized microanalysis, the cross-sectional surface areas of the different collateral and terminal branches of the ulnar nerve. This was expressed in terms of percentage of the cross-sectional surface area of the main trunk of the ulnar nerve. The study revealed that the branch to the flexor digitorum profundus bellies to the ring and little fingers formed 9.5% of the cross-sectional area of the ulnar nerve. Thus use of these fascicles destined for the flexor digitorum profundus, identified by intra-operative nerve stimulation, at the level of the arm would be sufficient for neurotisation of the nerve to the biceps. This has been confirmed by the initial clinical results in patients operated upon using this technique.

Anatomical and biomechanical studies of the pathogenesis of trapeziometacarpal degenerative arthritis.

An anatomical and biomechanical study of the stabilizing ligaments of the thumb trapeziometacarpal joint was conducted on 32 hand specimens. Five main ligamentous structures could be identified. The mechanical properties (in particular, strength) of the five ligaments using a strain-rate failure test were determined and evaluated quantitatively. The maximum tensile strength of each ligament was correlated with the condition of the trapeziometacarpal articular cartilage. In studying the anterior oblique ligament, maximum strength decreased from Grade 0 to Grade 1 by 51%. With the first intermetacarpal ligament, the drop from Grade 1 to Grade 2 was 53%. With the posterior oblique ligament, the decrease was closely related to the grade of the deterioration of the trapeziometacarpal articular surface. These three ligaments also significantly decreased in strength with age. Our results may suggest that the anterior oblique ligament, intermetacarpal ligament and posterior oblique ligament play a large role in stabilizing the trapeziometacarpal joint and that the decrease in their strength is related to the pathogenesis of trapeziometacarpal osteoarthritis.

[Fractures of the wrist with cartilage rupture in young adults. Apropos of 18 cases]. / Les fractures du poignet avec enfoncement cartilagineux de l'adulte jeune. A propos de dix-huit cas.

Distal radius impaction fractures are not rare. They present a dual problem for the surgeon: the difficulty of establishing the exact pathological anatomy of the fracture, and of obtaining stable anatomic reduction. The authors report their experience of 18 distal radius impaction fractures in young patients after violent trauma (motor vehicle accident). We subdivided these fractures using Kapandji and Müller's classifications: 12 type 9 or C3, 4 type 5 or B1 and 2 type 4 or C1. The mean depth of impaction of the scaphoid fossa or lunate fossa ("die punch fracture"), or centrally was measured at 5 mm on preop X-rays or on CT scan. After radiographs of the wrist in traction under anaesthesia, open reduction was performed in 14 cases (78%). A volar approach with plate fixation was performed in 3 cases. A dorsal approach with internal fixation with k-wires and an external fixator was performed in the other 11 cases. A bone graft was necessary in 10 cases when the bone defect was significant. The four remaining patients were treated with percutaneous k-wires and external fixation. We reviewed these 18 patients after a mean follow-up of 27 months. The mean age at the time of the accident was 37 years. The results were graded on the Green and O'Brien scale. Results were excellent in 1 case, good in 11 cases, fair in 5 cases, and poor in 1 case. We believe that impaction fractures always require open reduction with or without the addition of bone graft depending on the degree of the impaction. This is because of the risk of arthritic degeneration with this kind of fracture, with articular incongruence (more than 2 mm), and with chondral injuries on the radial or the carpal aspect of the wrist joint. Also, when there is a distal radio-ulnar joint injury (D.R.U.J. dislocation or distal head ulna fracture), the joint must always be stabilized to avoid secondary displacement.

[Resection of the fourth ray for annular lesions: amputations of the fourth ray of the hand]. / Résection du quatrième rayon pour lésions de l'annulaire: les amputations du quatrième rayon de la main.

INTRODUCTION: Several procedures have been reported for amputation of the fourth ray of the hand. Most surgeons recommend translocation of the fifth finger on the proximal end of the fourth metacarpal bone. Others prefer to perform a resection of the fourth metacarpal bone combined with intracarpal osteotomy. MATERIAL AND METHODS: The authors' choice was to perform a resection of the fourth metacarpal bone with conservation of its proximal end. They emphased on two technical details: resection of the interosseous muscles and reconstruction of the intermetacarpal ligament. The present series includes 8 patients operated on with this technique. Results were assessed with an average follow-up of 47 months. Evaluation of the result was based on a personal rating score including 9 clinical scores and on 1 radiological measurement of the hand width. RESULTS: Mobility of the adjacent digits was normal in all cases except one with a retractile scar. In 7 cases out of 8, the aesthetic result was satisfactory. Grip strength was 65 per cent of the contralateral side. Diminution of the hand width was of 12 per cent. Five results were excellent and three were good. DISCUSSION: Translocation with intracarpal osteotomy can produce impairement of carpus function, especially with apparition of pain, but also some rotational malposition. Translocation of the fifth digit on the fourth metacarpal bone can also procedure an imbalance of the extrinsic muscles, but also a rotational malposition. CONCLUSION: Transmetacarpal amputation of the fourth ray has the advantage to be an easy anatomic procedure, and is particularly reliable and reproductible regarding to the results. This procedure does not produce any specific complication comparing with other techniques.

Median nerve suture in the distal part of the forearm. MRI evaluation.

The aim of the study was to assess MR images of median nerve suture in the distal part of the forearm on fresh cadavers and injured patients. The median nerve was dissected in the distal one-third of the forearm in four fresh cadaveric specimens, divided and repaired in three of them in two cases with 3/0 nylon (one with well-apposed edges and the other with a lateral gap) and, in the third specimen, with 9/0 nylon with well apposed edges. The course of the median nerve was then studied on MR imaging in different planes and the quality of the nerve repair was evaluated. A good correlation was found between the MR images and the type of nerve suture. These findings were applied in management of two clinical cases in whom reexploration and revision of the median nerve repair was carried out.

[Reconstruction of the loss of bone substance of the forearm by cubitalization of the radius (one bone forearm). Apropos of 6 cases]. / La reconstruction des pertes de substance osseuse de l'avant-bras par cubitalisation du radius (one bone forearm). A propos de six observations.

Extensive forearm bone loss, whatever its etiology, presents a difficult reconstruction problem. This is mainly the case in the presence of lesions of the interosseous membrane associated with the radio-ulnar joint. When preservation of forearm rotation is not possible, cubitalization of the radius and reconstruction of the forearm by creation of a "one bone forearm" seems to be an excellent salvage technique both functionally and cosmetically. Our experience concerns six clinical cases; two of these cases are original and give the authors the opportunity to describe a new reconstructive technique of the distal humerus and elbow by vascularized transfer of the radius onto the radial artery (with a cutaneo-osseous transfer in one case). The etiology of the bone defect included severe trauma in three cases, and a Volkman's syndrome complicated by osteomyelitis in one case. Two cases represent an original technique of reconstruction of the distal humerus by a vascularised transfer of the radius onto the radial artery. Forearm reconstruction is performed by cubitalization of the radius. The etiology was traumatic in one case and neoplastic in another, and a cutaneo-osseous transfer was performed in the latter case. In this difficult problem of bone reconstruction, a favorable functional and cosmetic result was obtained in our series.

[New metacarpal osteotomy: metacarpal cervicocapital shortening osteotomy of the rheumatoid hand]. / Nouvelle ostéotomie métacarpienne: l'ostéotomie cervico-capitale d'accourcissement métacarpien dans la main rhumatismale.

Volar dislocation of the four long fingers is a common situation in rheumatoid hands. Surgical reduction is rather difficult because of soft tissue retraction, especially interosseous muscles, and requires large releases. The authors propose the use of Weil's osteotomy, initially described in foot surgery. This is an oblique cervico-capital osteotomy which shortens the metacarpal bone, fixed by two screws. This makes soft tissue release less extensive and facilitates relocation of the extensor tendon. Two cases are reported.

[The middle third of the face in facial lift: lipopexy of the premalar fatty pad]. / L'étage moyen de la face dans le lifting: lipopexie du coussinet adipeux pré-malaire.

UNLABELLED: The technique proposed tries to resolve an irritating problem which has been incompletely and illogically resolved until now: the restoration of the natural relief of the middle third of the face. An anatomical study shows that the malar region is an eminence composed of a double structure, bony and fatty. The ptosis of what the authors propose to call "the premalar fatty pad" is probably the earliest sign of ageing in the face. It give a skeletal appearance and fills the canine fossa which become a heavy fold and increases the apparent depth of the naso genio labial sulcus. The aim of this technique is to restore a normal appearance by restoration of the true anatomical structures. The technique consists of extensive undermining behind the ptotic fatty pad, in front of the malar bone and SMAS as fas as the orbital rim which allow displacement upwards and backwards. Resorbable sutures and an accurate skin tension ensure the new premalar position of the fatty pad. Posterior fibrosis, in the undermining, will be the essential means of late fixation. 70 such operations with sufficient follow up have been carried out. The result is stable in 58 of them and insufficient but appreciable in all of the others. Fatty faces give poor results due to the poor quality of the skin. CONCLUSIONS: it is a simple, logical and efficient procedure, more often performed in association with the treatment of frontal and cervicofacial level of the face. No complications related to this procedure have been observed.