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Biomedical subjects

J P Simon

Publications and source records attributed to J P Simon.

At least 19 recordsLinked to original sources

A semi-active milling procedure in view of preparing implantation beds in robot-assisted orthopaedic surgery.

Bone cutting in total joint reconstructions requires a high accuracy to obtain a well-functioning and long-lasting prosthesis. Hence robot assistance can be useful to increase the precision of the surgical actions. A drawback of current robot systems is that they autonomously machine the bone, in that way ignoring the surgeon's experience and introducing a safety risk. This paper presents a semi-active milling procedure to overcome that drawback. In this procedure the surgeon controls robot motion by exerting forces on a force-controlled lever that is attached to the robot end effector. Meanwhile the robot constrains tool motion to the planned motion and generates a tool feed determined by the feed force that the surgeon executes. As a case study the presented milling procedure has been implemented on a laboratory set-up for robot-assisted preparation of the acetabulum in total hip arthroplasty. Two machining methods have been considered. In the first method the surgeon determines both milling trajectory and feed by the forces that he/she executes on the force-controlled lever. In the second method the cavity is machined contour by contour, and the surgeon only provides the feed. Machining experiments have shown that the first method results in large surface irregularities and is not useful. The second method, however, results in accurate cavity preparation and has therefore potential to be implemented in future robot systems.

Acetabulum↗

Posterior transosseous capsulotendinous repair in total hip arthroplasty : a cadaver study.

BACKGROUND: While recent clinical articles have reported a dramatic reduction in rates of total hip dislocation after posterior transosseous repair, we are not aware of any published biomechanical data to support this finding. The objectives of this study were to investigate the functional anatomy of the posterior transosseous repair and its effect on stability after total hip replacement. METHODS: Six total hip prostheses were implanted into three fresh cadavera. Three different repair situations (no repair, soft-tissue repair, and transosseous fixation) were then consecutively tested on each hip. Values for torque resistance and the angular range of motion at dislocation were recorded. Each repair was tested twice, yielding a total of thirty-six torque values and thirty-six angles of rotation. RESULTS: The transosseous repair was superior with regard to both torsion strength (four times stronger than that after no repair [p = 0.0002] and more than twice as strong as that after soft-tissue repair [p = 0.002]) and the magnitude of the angle of rotation observed prior to dislocation (an increase of 83% in comparison with that after no repair [p = 0.0005] and an increase of 46% in comparison with that after soft-tissue repair [p = 0.004]). CONCLUSIONS: In a cadaver model, posterior transosseous repair provides superior stability of a total hip replacement. Optimal surgical technique with a slightly modified approach allows greater retention of capsule and tendon length and a more anatomical reinsertion of the soft tissues.

Arthroplasty, Replacement, Hip↗

One-stage bilateral total hip replacement: a retrospective study of 70 patients.

In this study, we retrospectively reviewed 70 patients who had a one-stage bilateral total hip replacement in our institution, between 1992 and 1998. Different variables were considered such as gender, age, length of hospital stay, pre-operative diagnosis, duration of the operation and anesthesia, type of prosthesis, complications and amount of blood loss, pre- and postoperative range of motion, incidence of periarticular heterotopic ossifications and postoperative pain and walking distance. In our group of patients one-stage bilateral total hip replacement was found to have resulted in good objective results. Patients with a rheumatoid condition had the highest gain in postoperative hip mobility. In comparison with existing literature there were no more intra- or postoperative complications, making one-stage bilateral total hip replacement a safe procedure in well-selected cases.

Adolescent↗

Parsonage-Turner syndrome after total-hip arthroplasty.

A 68-year-old patient developed Parsonage-Turner syndrome after total hip arthroplasty. There was an acute onset of intense pain in the shoulder 48 hours after surgery followed by complete paralysis of the shoulder and almost complete loss of strength in the arm. Recovery was slow, and mild weakness persisted 7 years after the operation. Parsonage-Turner syndrome has been associated with various surgical procedures but has not been reported after total hip arthroplasty. For medicolegal reasons, it should be distinguished from a traction injury of the brachial plexus or compression of the radial or ulnar nerve resulting from positioning of the patient. Parsonage-Turner syndrome should be considered in the differential diagnosis when a patient describes pain or weakness in the shoulder after joint arthroplasty.

Aged↗

In vitro generation from the trans-Golgi network of coatomer-coated vesicles containing sialylated vesicular stomatitis virus-G protein.

We describe an in vitro system in which post-Golgi vesicles containing metabolically labeled, sialylated, vesicular stomatitis virus (VSV) G protein molecules (VSV-G) are produced from the trans-Golgi network (TGN) of an isolated Golgi membrane fraction. This fraction is prepared from VSV-infected Madin-Darby canine kidney (MDCK) cells in which the (35)S-labeled viral envelope glycoprotein was allowed to accumulate in the trans-Golgi network during a prolonged incubation at 20 degrees C. The vesicles produced in this system are separated from the remnant Golgi membranes by differential centrifugation or by velocity sedimentation in a sucrose gradient. Vesicle production, quantified as the percentage of labeled VSV-G released from the Golgi membranes, is optimal at 37 degrees C and does not occur below 20 degrees C. It requires GTP and the small GTP-binding protein Arf (ADP-ribosylation factor), as well as coat protein type I (COPI) coat components (coatomer) and vesicle scission factors-one of which corresponds to the phosphatidylinositol transfer protein (PITP). Formation of the vesicles does not require GTP hydrolysis which, however, is necessary for their uncoating. Thus, vesicles generated in the presence of the nonhydrolyzable GTP analogs, GTPgammaS or GMP-PNP, retain a coatomer coat visible in the electron microscope, sediment more rapidly in sucrose density gradients than those generated with ATP or GTP, and can be captured with anticoatomerantibodies. The process of coatomer-coated vesicle formation from the TGN can be dissected into two distinct sequential phases, corresponding to coat assembly/bud formation and vesicle scission. The first phase is completed when Golgi fractions are incubated with cytosolic proteins and nonhydrolyzable GTP analogs at 20 degrees C. The scission phase, which leads to vesicle release, takes place when coated Golgi membranes, recovered after phase I, are incubated at higher temperatures in the presence of cytosolic proteins. The scission phase does not take place if protein kinase C inhibitors are added during the first phase, even though these inhibitors do not prevent membrane coating and bud formation. The phosphorylating activity of a protein kinase C, however, plays no role in vesicle formation, since this process does not require ATP.

ADP-Ribosylation Factors↗

Functional role of transmembrane helix 7 in the activation of the heptahelical lutropin receptor.

A member of the G protein-coupled receptor superfamily, the LH receptor (LHR), and the two other glycoprotein hormone receptors are distinguished from the other members by the presence of a relatively large N-terminal extracellular domain that is responsible for high-affinity ligand binding. Transmembrane helix (TMH) 7 of LHR is amphipathic, with an extended face containing only hydrophobic side chains and another containing both hydrophobic and polar side chains with potential hydrogen bond donor and acceptor functions. Since several reports have shown the importance of this helix in ligand-mediated signaling, we have used Ala scanning mutagenesis to study eight amino acid residues of rat LHR that are invariant in the three glycoprotein hormone receptors, Leu586, Val587, Asn593, Ser594, Cys595, Asn597, Phe604, and Thr605. The wild type (WT) and mutant cDNAs were transiently transfected into COS-7 cells for characterization by human CG (hCG) binding and cAMP production. No differences were detected in dissociation constants (K(d)S) or basal cAMP production relative to WT LHR, but three categories of LHR mutants were distinguished from WT LHR based upon their expression levels and responsiveness to hCG: 1) comparable or higher expression but reduced ligand responsiveness (N593A and C595A), 2) reduced expression and ligand responsiveness (N597A and T605A), and 3) comparable expression and responsiveness (L586A, V587A, S594A, and F604A). Three other mutants, C595M, F604Y, and T605Y, were comparable to WT LHR in ligand responsiveness. To provide more information on Asn593 and Asn597, a total of 12 replacements were investigated. Of considerable interest and potential significance was the finding that many of the replacements in LHR resulted in either loss of function (N593A, Q, S; N597R) or gain of function (N593R and N597Q), this being the first evidence of a position in LHR that, depending upon the nature of the amino acid residue, can result in constitutive activation and/or diminished responsiveness to ligand. The results of molecular modeling and energy minimization of TMHs 6 and 7, based on a postulated interaction between Asp556 (TMH 6) and Asn593/Asn597 (TMH 7), indicated that, while there is not a correlation between function and predicted energies of WT LHR and the mutants, reorientation of one or both helices is responsible for the functional changes observed. Possible interactions of TMHs 3 and 4 and of 5 and 6 were suggested by molecular modeling. Ten mutants were prepared of two amino acid residues that are invariant in the glycoprotein hormone receptors and have side chain hydrogen bond donor and acceptor function, Glu429 in TMH 3 and Asn513 in TMH 5. Expression levels and hCG-mediated signaling were reduced in most of the LHR mutants, but none of these exhibited constitutive receptor activation. We conclude that Glu429 is not critical for receptor function, while Asn513 appears to be particularly important in receptor folding and/or trafficking. The results reported herein indicate an important role for TMH 7, and particularly Asn593 and Asn597, in the process of receptor activation. Moreover, these two asparagines, although in close proximity to each other in TMH 7, are quite distinct in function as evidenced by certain replacements that can lead to loss of function in one and gain of function in the other.

Amino Acid Sequence↗

Bifocal pubic stress fracture after ipsilateral total knee arthroplasty in rheumatoid arthritis. A case report.

We present the case of a 78-year-old rheumatoid patient with a bifocal stress fracture of the pubic rami after ipsilateral total knee arthroplasty. Many risk factors that may cause insufficiency fractures are combined in rheumatoid arthritis. These patients are used to chronic pain, and therefore the diagnosis is often made late. When a patient suffering from rheumatoid arthritis presents with recent pain in the pelvic or hip region after hip or knee arthroplasty, a stress fracture should always be suspected. A standard pelvic radiograph and skeletal scintigraphy establish the diagnosis. CT-scan may be useful in the differential diagnosis with less benign pathology. Rest and analgesic drugs are sufficient to let the fracture heal. Nonunion has never been reported for these fractures.

Aged↗

Identification of a new Pyk2 target protein with Arf-GAP activity.

Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence experiments demonstrate that Pap is localized in the Golgi apparatus and at the plasma membrane, where it is colocalized with Pyk2. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured cells reduced the constitutive secretion of a marker protein. We propose that Pap functions as a GAP for Arf and that Pyk2 may be involved in regulation of vesicular transport through its interaction with Pap.

ADP-Ribosylation Factor 1↗

D2AM, a beamline with a high-intensity point-focusing fixed-exit monochromator for multiwavelength anomalous diffraction experiments.

D2AM is a french CRG beamline installed at the ESRF (European Synchrotron Radiation Facility) in Grenoble, with half of the time dedicated to biological macromolecule crystallography and half to materials science studies (diffraction, wide-angle and small-angle scattering). It is constructed at the front-end BM02 of the ESRF storage ring, using the X-ray beam from a 0.8 T bending magnet. D2AM entered into routine operation at the end of 1994, and is used either for single-wavelength or for multiwavelength anomalous diffraction studies. The beam is monochromated by an Si[111] two-crystal monochromator with a resolution of about 2 x 10(-4). The first crystal is water cooled. The X-ray photon energy covers the range between 6.5 keV (lambda approximately 1.9 A) and 17 keV (lambda approximately 0.7 A), a domain of energy with many K or L absorption edges of heavy atoms of interest for biological macromolecules studies and in materials science. The X-ray beam is focused in the vertical plane by two long curved mirrors and in the horizontal plane by the second crystal of the monochromator which is given an adjustable sagittal curvature. A spot size of 0.3 x 0.1 mm (FWHM) is measured at the sample position. Both mirrors are cut out of a 6"-diameter 1.1 m-long Si single crystal, polished and coated with a 400 A Pt thin film. The rugosity is better than 4 A r.m.s. and the longitudinal slope error is better than 5 x 10(-6) rad r.m.s. The first mirror is water cooled, the second is not. The beam intensity on the sample is about 10(11) photon s(-1) on a 0.3 x 0.3 mm focus area at 100 mA in the storage ring of the ESRF. The harmonic rejection ratio obtained with the two mirrors is better than 10(-5) for lambda/3. The combined optical system, mirror/monochromating-crystals/mirror, used on D2AM constitutes altogether a high-intensity point-focusing fixed-exit monochromator, which has the additional property that the energy resolution is not dependent on the beam divergence in use. Its stability and resolution are perfectly adapted to multiwavelength anomalous diffraction studies. The alignment of the mirrors and the monochromator is fully automated, taking 5 min, with the exception of the adjustment of the sagittal focusing. During multiwavelength diffraction experiments the wavelength is changed by a fast single monochromator rotation. Neither realignment of the mirrors nor readjustment of the beam focusing are necessary. The stability and reproducibility of the selected X-ray photon energy is better than 0.5 eV.

Journal Article↗

Coherent small-angle scattering on a bending-magnet beamline at the ESRF.

A coherent X-ray beam is obtained from the D2AM bending-magnet beamline (BM2) of the European Synchrotron Radiation Facility. As this line has permanent convergent optics, monochromated by an Si(111) double monochromator, coherence conditions are satisfied by selecting a part of the beam close to the focal point. Low intensity (10(6) X-rays s(-1)) is partially compensated by a high degree of coherence and by the use of a high-resolution direct-illumination CCD area detector. The stability of the small-angle set-up makes quantitative analysis possible. The calculated and measured degrees of coherence are compared. The distributions of speckle intensities are explained by a beam composed of two-thirds coherent and one-third incoherent parts. This incoherent component is caused by Kapton windows, which will be removed in future experiments.

Journal Article↗

An essential role for the phosphatidylinositol transfer protein in the scission of coatomer-coated vesicles from the trans-Golgi network.

We identified the phosphatidylinositol transfer protein (PITP) as being responsible for a powerful latent, nucleotide-independent, Golgi-vesiculating activity that is present in the cytosol but is only manifested as an uncontrolled activity in a cytosolic protein subfraction, in which it is separated from regulatory components that appear to normally limit its action to the scission of COPI-coated buds from trans-Golgi network membranes. A specific anti-PITP antibody that recognizes the two mammalian PITP isoforms fully inhibited the capacity of the cytosol to support normal vesicle generation as well as the uncontrolled vesiculating activity manifested by the cytosolic protein subfraction. The phosphatidylinositol- (PI) loaded form of the yeast PITP, Sec14p, but not the phosphatidylcholine- (PC) loaded form of the protein, was capable of substituting for the cytosolic subfraction in promoting the scission of coated buds from the trans-Golgi network. At higher concentration, however, Sec14p, when loaded with PI, but not with PC or phosphatidylglycerol, caused by itself an indiscriminate vesiculation of uncoated Golgi membranes that could be suppressed by PC-Sec14p, which also suppresses the uncontrolled vesiculation caused by the cytosolic subfraction. We propose that, by delivering PI to specific sites in the Golgi membrane near the necks of coated buds, PITP induces local changes in the organization of the lipid bilayer, possibly involving PI metabolites, that triggers the fusion of the ectoplasmic faces of the Golgi membrane necessary for the scission of COPI-coated vesicles.

Animals↗

Coatomer, but not P200/myosin II, is required for the in vitro formation of trans-Golgi network-derived vesicles containing the envelope glycoprotein of vesicular stomatitis virus.

Using a cytosol and nucleotide dependent assay that we previously developed, we have investigated the requirement for coat proteins in the in vitro production of trans-Golgi network (TGN)-derived vesicles from a Madin-Darby canine kidney (MDCK) cell Golgi fraction that contains the 35S-labeled, terminally glycosylated, envelope glycoprotein of vesicular stomatitis virus (VSV-G) accumulated in the TGN. We found that the TGN-derived vesicles, like those involved in intra-Golgi transport and in retrograde transport to the endoplasmic reticulum, contain a coatomer coat and that coatomer is required for their formation. Thus, after they are produced with GTPgammaS, the coated vesicles could be captured on beads containing anticoatomer antibody. Moreover, a cytosolic protein fraction depleted of coatomer could not support vesicle formation but it did so after purified coatomer was added. We also determined that P200/myosin II does not play an essential role in the in vitro generation of TGN-derived vesicles. Thus, removal of this protein from the cytosol, by differential salt precipitation or binding to phalloidin-induced actin filaments, had no effect on vesicle generation. Nevertheless, immunodepletion of cytosol using the anti-P200/myosin II AD7 antibody abolished vesicle generation and that antibody was capable of effectively immunocapturing coated vesicles, even when these were generated in the absence of P200/myosin II. These effects, however, are explained by the unexpected finding that the AD7 antibody interacts with undenatured coatomer.

Animals↗

Ganglia of the superior tibiofibular joint: report of three cases and review of the literature.

Ganglion cysts that compress the common peroneal nerve frequently arise from the proximal tibiofibular joint. We report three cases of such ganglia. In one case the ganglion cyst arises from the proximal tibiofibular joint, finds its course along the common peroneal nerve causing pain, but no neurological deficit. In the two other cases the cysts have the same origin but they are the cause of a progressive peroneal nerve palsy. Treatment in these three cases was successful resection of the cyst with non mutilating surgery for the nerve and ligation of the stalk connecting the ganglion to the proximal tibiofibular articulation. A review of the controversial pathogenesis of the intra- and extraneural ganglia is exposed, and the anatomy, the diagnosis, the surgical treatment and the prognosis is discussed in light of relevant literature.

Adult↗

[Primary adrenal lymphoma with latent adrenal insufficiency: a case report and literature review].

We report a new case of primary adrenal lymphoma with latent adrenal insufficiency and long-term remission after hydrocortisone replacement therapy. We have analyzed 29 other cases described in the literature. This disease with poor prognosis can be revealed by an incidentally discovered, frequently bilateral, adrenal mass. Adrenal insufficiency may be latent and the diagnostic procedure should include both cortisol and ACTH determination with an additional ACTH stimulation test if appropriate. Early adrenal substitution can improve patient survival.

Adrenal Gland Neoplasms↗

Core decompression for avascular necrosis of the femoral head.

The results of core decompression as the sole treatment for Ficat stages 1, 2 and 3 avascular necrosis of 51 femoral heads in 39 patients were studied. The mean follow-up time was 24 months (6-47 months); 19 hips (38.8%) were good and 30 hips (61.2%) had failed (two hips were lost to follow-up). The good results as stated in the literature could not be obtained, but we believe core decompression can delay the need for total hip replacement in avascular necrosis of the femoral head.

Adolescent↗

Detection and partial characterization of a bacteriocin produced by Carnobacterium piscicola 213.

BLIS 213, is a bacteriocin-like inhibitory substance produced by Carnobacterium piscicola 213. It is active against Carnobacterium, Enterococcus and Listeria spp. No activity was observed against tested Lactobacillus, Lactococcus, Leuconostoc and Pediococcus strains, nor against Gram-negative bacteria. The BLIS 213 activity was inactivated by several proteolytic enzymes. It was heat resistant (121 degrees C for 20 min), and stable over a pH range of 2-8. Activity was determined by a dilution micromethod; it was increased after SDS treatment. A mutant strain which lacks bacteriocin production was isolated and designated as Carnobacterium piscicola 213a. It had the same phenotypic and biochemical properties as the parent strain, and was not sensitive to bacteriocin activity. The apparent molecular weight of the bacteriocin in the crude extract was greater than 10 kDa. It was about 6 kDa after SDS-PAGE of a partially purified bacteriocin by adsorption on producer cells. The isoelectric point of the BLIS 213 was around 9.3.

Bacteriocins↗

Wear of a titanium-alloy shoulder prosthetic head.

We present a case report of extensive wear that occurred on the surface of the titanium-alloy head of a shoulder prosthesis after only 2 years' service. Such wear warrants discontinuing the use of titanium-alloy articulating surfaces even in nonweight-bearing joints.

Alloys↗