PubMed Health⌕ Search

Biomedical subjects

A Hachem

Publications and source records attributed to A Hachem.

18 recordsLinked to original sources
PubMed2006

Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage.

We discovered a novel oncogene in a T-cell lymphoma cell line, multiple copies in T-cell lymphoma-1 (MCT-1), that has been shown to decrease cell-doubling time, shorten the duration of G(1) transit time and/or G(1)-S transition, and transform NIH3T3 fibroblasts. We subsequently demonstrated that there were significantly increased levels of MCT-1 protein in a subset of primary diffuse large B-cell lymphomas. Levels of MCT-1 protein were shown to be increased after exposure to DNA damaging agents. This increase did not require new protein synthesis, suggesting that post-translational mechanisms were involved. Phosphorylation is one potential mechanism by which the activity of molecules involved in cell cycle/survival is rapidly modulated. The RAS/mitogen-activated/extracellular-regulated kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway plays a prominent role in the regulation of cell growth and proliferation through phosphorylation-dependent regulation of several substrates. The MCT-1 protein is predicted to have numerous putative phosphorylation sites. Using a combination of genetic and pharmacological approaches, we established that phosphorylation of MCT-1 protein by p44/p42 mitogen-activated protein kinases is critical for stabilization of MCT-1 protein and for its ability to promote cell proliferation. Our data suggests that targeting the RAS/MEK/ERK signal transduction cascade may provide a potential therapeutic approach in lymphomas and related malignancies that exhibit high levels of MCT-1 protein.

3T3 Cells↗
PubMed2006

Monte Carlo simulation of a medical linear accelerator for radiotherapy use.

A Monte Carlo code MCNPX (Monte Carlo N-particle) was used to model a 25 MV photon beam from a PRIMUS (KD2-Siemens) medical linear electron accelerator at the Centre Antoine Lacassagne in Nice. The entire geometry including the accelerator head and the water phantom was simulated to calculate the dose profile and the relative depth-dose distribution. The measurements were done using an ionisation chamber in water for different square field ranges. The first results show that the mean electron beam energy is not 19 MeV as mentioned by Siemens. The adjustment between the Monte Carlo calculated and measured data is obtained when the mean electron beam energy is approximately 15 MeV. These encouraging results will permit to check calculation data given by the treatment planning system, especially for small fields in high gradient heterogeneous zones, typical for intensity modulated radiation therapy technique.

Body Burden↗
PubMed2006

[Screw fixation without bone graft of calcaneal joint fractures: 35 cases].

PURPOSE OF THE STUDY: The prognosis of calcaneal joint fractures is less favorable than fractures without joint involvement. Surgical treatment is frequently recommended. The type of fixation and the usefulness of a bone graft remain subjects of debate. The purpose of this work was to present the functional and anatomic results obtained with simple screw fixation without bone grafting in a retrospective series of 35 displaced joint fractures of the calcaneus. MATERIAL AND METHODS: The series included 31 patients (four bilateral fractures), 86% men. Mean age was 36 years (17-60 years). Using the Duparc classification, there were 12% type III fractures and 88% type IV fractures. Horizontal joint impaction was observed in 36% of patients, vertical impaction in 8%, and mixted impaction in 56%. The mean Bohler angle was 2 degrees (range -25 degrees to 15 degrees ). According to the Utheza classification, 70% of the fractures had two sagittal fracture lines, 16.5% one sagittal fracture line, and 13.5% comminutive fractures. Incongruency of the subtalar joint was noted in 70%, with a conflict with the lateral malleolus in 50%. Mean time to surgery was 12 days (7-30 days). The sub- and retromalleolar approach was used to achieve simple screw fixation. Bone grafts were not used. Mean follow-up was two years (range 12-38 months). RESULTS: There were no serious complications. Functional outcome was analyzed with the Kitaoka scale, mean score 74.3 +/- 1.1 (range 46-98), with 16% excellent outcome, 56% good outcome, 25.2% fair outcome, and 2.5% poor outcome. There was a correlation between functional outcome and age, etiology, and type of fracture. Anatomic results were assessed with the Babin scale and were very good in 24%, good in 8%, fair in 28%, and poor in 40%. Secondary loss of the initial heightening of the joint surface was noted in 48% of the cases, 3 degrees on average. DISCUSSION: This series confirms the value of surgical treatment compared with conservative treatment. Compared with plate fixation, screw fixation exposes the patient to less risk of skin and infectious problems. Simple screwing generally provides satisfactory results with acceptable stability. In light of the present results, adjunction of a bone graft would not be necessary since the loss of correction of the joint surface height was often minimal. CONCLUSION: Screw fixation of calcaneal joint fractures is a reliable technique. Adjunction of a bone graft does not appear to be necessary.

Adolescent↗
PubMed2004

[Distal radius anterior marginal fractures treated with anterior plating. Mid-term results].

PURPOSE OF THE STUDY: We report a retrospective series of anterior marginal fractures of the distal radius treated by anterior plating in order to analyze results and identify prognostic factors. MATERIAL AND METHODS: This continuous series included 22 patients with an anterior marginal fracture of the distal radius treated between 1993 and 1999. Three patients were lost to follow-up. This analysis thus concerned 19 fractures in 15 men and 4 women, mean age 39 years. Surgical reduction and T-plate anterior fixation was used in all cases. RESULTS: Mean follow-up was 26 months. Anatomic results were satisfactory in 15 patients and poor in one. Function was satisfactory in 17 patients and poor in one. We noted two types of complication: spontaneously regressive reflex dystrophy (n=2) and osteoarthritis which developed in two patients after incomplete reduction. DISCUSSION: Anterior plating can provide satisfactory results for anterior marginal fractures of the distal radius if anatomic reduction is achieved. This method remains our preferred therapeutic approach with special attention being required for anatomic reduction.

Adolescent↗
PubMed2003

[Pediatric vesical lithiasis. 70 case reports].

The study focuses on 70 vesicals lithiasis, with a sample consisting of 60 boys (86%) and ten girls (14%). The age varies from one year to 14 years. The revealing signs are dominated by mictional troubles in 47 cases (67%), macroscopic hematurie in 26 cases (37%), the pyurie in 12 cases (17%) and acute retention of urine in 7 cases (10%). The most frequent germs are the staphylococcus aureus with 28% of cases, the protéus mirabilis with 24% of cases and the Echerichia coli with 24% of the cases. Associated malformations were observed in 9% of the cases. The treatment was essentially surgical (99%). The evolution was simple in 97% of the cases.

Adolescent↗
PubMed2003

[Study of theoretical cases of intensity-modulated beams with step-and-shoot technique].

To initiate Intensity-Modulated Radiation Therapy (IMRT) in our department, theoretical cases were used as a training, to define methods of measurements and to verify the software by comparing results of calculation and measurement on a PMMA phantom. Irradiation was performed with 6 and 25 MV X-rays from a linear accelerator. For measurements, films and ionization chambers have been chosen. The comparison between calculations and measurements shows some discrepancies at the level of junctions and also in areas of low doses especially when many segments were used. These theoretical cases provide a first step on the way towards treatments with intensity modulation.

Bias↗
PubMed2003

Validation of intensity modulation on a commercial treatment planning system.

For two years now, a study on intensity modulated radiotherapy (IMRT) has been in progress at the Antoine Lacassagne Hospital Center for Cancer Therapy (in Nice) in collaboration with the University of Nice-Sophia Antipolis. The kind of intensity modulation that was used is the "step and shoot" technique in which the modulated beam is created both by adding andjoining elementary fields. Before carrying out clinical tests, several problems regarding the production of modulated beams has to be mastered. The current developments of our study enable us to dosimetrically produce (in water phantom and in the PMMA phantom) complexmodulated whose segmentation was calculated by one commercial treatment planning system (TPS). Nevertheless, we showed and studied some critical discrepancies between standard clinical calculations and the calculations using field segmentation. We showed that with nonoptimal conditions of segmentation the discrepancies, which are due to the type of algorithm used, could bring about significant errors inside the field of up to 10% of maximum dose. Another point of our study is the quantification and resolution of differences between measurements and calculations due to the internal segmentation of calculated modulated fields and their realization on Linac. Once again, in none optimal conditions of segmentation and inside the field we obtained discrepancies up to 20% of maximum dose between calculations using field segmentation and measurements. That was mainly due to the tongue and groove effect and penumbra phenomena. This study allows us to show that the discrepancies between segmentation calculations and standard clinical calculations should be solved by the use of penumbra models during segmentation calculations. We will introduce both the study and its near-future perspectives.

Algorithms↗
PubMed2001

Effect of S(-) perillic acid on protein prenylation and arterial smooth muscle cell proliferation.

A number of proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, protein farnesyltransferase (PFTase) and protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and protein prenylation in cancer cells. In the present study, we evaluated the effect of S(-) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to protein prenylation. S(-) PA (1-3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S(-) PA on SMC and confirmed a block of the cell cycle progression in G(0)/G(1) phase. The antiproliferative effect of S(-) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S(-) PA (1-3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular proteins. We provide evidence that S(-) PA affects protein prenylation, an effect that may contribute to its inhibition of SMC proliferation.

Animals↗
PubMed1998

Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations.

Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has been calculated. The thermal neutron flux has been compared with experimental results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD-700, respectively, doped with 6Li or 7Li). The theoretical results were in good agreement with the experimental results: the thermal neutron flux was calculated at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose deposition the calculated and experimental curves have the same slope but different shape: only the experimental curve shows a maximum at 2.27 cm depth corresponding to the build-up. The difference is due to the Monte Carlo simulation which does not follow the secondary particles. Finally, a dose enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues. It is anticipated that this calculation method may be used to improve BNCE of fast neutron irradiations through collimation modifications.

Biophysical Phenomena↗
PubMed1988

Origin of the 13C

Explore the source record for details and available documents.

Journal Article↗
PubMed1978

[Adipose tissue cellularity and skinfold thickness of the deltoid and retrotrochanteric areas in obese women (author's transl)].

301 women, 261 of them obese, were the subject of an anthropometric study of brachial and femoral adipomuscular ratio, adipocytometry in the deltoid and retro-trochanteric areas and oral glucose tolerance. Deltoid adipocyte volume was highly correlated (p less than 0,001) with total fat deposition in this area, while no such relationship was found in the retrotrochanteric area. In obese women with chemical or overt diabetes, deltoid adipose cells were significantly larger than those of non-diabetic obese women. This, however, was not the case for retro-trochanteric adipose cells.

Adipose Tissue↗