[Multiple myeloma in an elderly patient with history of breast cancer : the value of multidisciplinary oncogeriatric collaboration]. / Cas clinique. Prise en charge d'un myélome multiple chez une patiente âgée aux antécédents de néoplasie mammaire : intérêt d'une collaboration multidisciplinaire onco-gériatrique.

As the prevalence of cancers increases with age, some elderly patients are confronted with multiple tumoural pathologies. The clinical case of a 70-year-old patient with adenocarcinoma of the breast and multiple myeloma complicated by severe renal failure illustrates the complexity of oncogeriatric management. The geriatric assessment makes it possible to detect frailty and provides assistance in the development of a personalized care plan while respecting the quality of life.

Comme la prévalence des cancers augmente avec l'âge, certains patients âgés se trouvent confrontés à plusieurs pathologies tumorales. Ce cas clinique d'une patiente de 70 ans, avec un adénocarcinome du sein et un myélome multiple compliqué d'une insuffisance rénale sé-vère, illustre la complexité de la prise en charge oncogériatrique. En effet, l'évaluation gériatrique permet de dépister la fragilité et apporte une aide à l'élaboration d'un plan de soins personnalisé en respectant la qualité de vie.

Elementary mechanisms of shear-coupled grain boundary migration.

A detailed theoretical study of the elementary mechanisms occurring during the shear-coupled grain boundary (GB) migration at low temperature is performed focusing on both the energetic and structural characteristics. The migration of a Σ13(320) GB in a copper bicrystal in response to external shear displacements is simulated using a semiempirical potential. The minimum energy path of the shear-coupled GB migration is computed using the nudge elastic band method. The GB migration occurs through the nucleation and motion of GB steps identified as disconnections. Energy barriers for the GB and disconnection migrations are evaluated.

Fluorescence-detected X-ray magnetic circular dichroism of well-defined Mn(II) and Ni(II) doped in MgO crystals: credential evaluation for measurements on biological samples.

L(2,3)-edge X-ray magnetic circular dichroism (XMCD) spectra have been measured for the well-defined dilute Ni(II) and Mn(II) ions doped into a MgO crystal, with sub-Kelvin dilution refrigerator cooling and 2 T magnetic field magnetization. A 30-element Ge array X-ray detector has been used to measure the XMCD for these dilute ions, whose concentrations are 1400 ppm for Ni(II) and 10,000 ppm for Mn(II). Large XMCD effects have been observed for both Ni(II) and Mn(II), and multiplet simulation described the observed spectra. The fluorescence-detected L-edge absorption spectrum and XMCD of Ni(II) in MgO are comparable with both theoretical calculations and the total electron yield measured ions in similar chemical environments, at least qualitatively validating the use of the sensitive fluorescence detection technique for studying XMCD for dilute 3d metal ions, such as various metalloproteins. Sum rule analyses on the XMCD spectra are also performed. In addition, these XMCD measurements have also been used to obtain the sample's magnetization curve and the beamline's X-ray helicity curve. This study also illustrated that bend magnet beamlines are still useful in examining XMCD on dilute and paramagnetic metal sites.

Oxidative stress induces unfolding protein response and inflammation in nasal polyposis.

BACKGROUND: Nasal polyposis, a chronic inflammatory disease affecting the upper airways, is a valuable and accessible model to investigate the mechanisms underlying chronic inflammation. The main objective of this study was to investigate a potential involvement of the unfolded protein response (UPR) in the context of oxidative stress and inflammation in nasal epithelial cells from nasal polyps (NP). METHODS: Epithelial cells from NP (n = 20) and normal mucosa (Controls, n = 15) in primary culture were analyzed by global proteomic approach and cell biology techniques for the glucose-regulated protein 78 (GRP78), the spliced X-box-binding protein 1 (sXBP-1), the glucose-regulated protein 94 (GRP94), and the calreticulin (immunoblot, mass spectrometry, immunocytochemistry). RESULTS: Proteomics analysis of human nasal epithelial cells in culture revealed the activation of the unfolded protein response in NP. Systematic cell biology and biochemical analysis of two markers (GRP78, sXBP-1) in the presence and absence of oxidative stress in NP showed a susceptibility of the unfolded protein response to oxidative stress compared to controls at least partially linked to an abnormal redox state of the protein disulfide-isomerase 4. This unfolded protein response was correlated with mitochondrial depolarization and secretion of interleukin 8 (IL-8) and leukotriene B4 (LTB4) and was prevented by mitochondrial antioxidant. CONCLUSIONS: We show the existence of UPR in nasal epithelial cells that is linked to oxidative stress leading to IL-8 and LTB4 secretions. These mechanisms may participate in chronic inflammation in nasal polyposis.

Cold gelation of alginates induced by monovalent cations.

A new reversible gelation pathway is described for alginates in aqueous media. From various samples differing by their mannuronic/guluronic content (M/G), both enthalpic and viscoelastic experiments demonstrate that alginates having a high M content are able to form thermoreversible assemblies in the presence of potassium salts. The aggregation behavior is driven by the low solubility of M-blocks at low temperature and high ionic strength. In semidilute solutions, responsive assemblies induce a strong increase of the viscosity below a critical temperature. A true physical gel is obtained in the entangled regime, although the length scale of specific interactions between M-blocks decreases with increasing density of entanglements. Cold setting takes place at low temperatures, below 0 °C for potassium concentrations lower than 0.2 mol/kg, but the aggregation process can be easily shifted to higher temperatures by increasing the salt concentration. The self-assembling process of alginates in solution of potassium salts is characterized by a sharp gelation exotherm and a broad melting endotherm with a large hysteresis of 20-30 °C between the transition temperatures. The viscoelastic properties of alginate gels in potassium salts closely depend on thermal treatment (rate of cooling, time, and temperature of storage), polymer and salt concentrations, and monomer composition as well. In the case of alginates with a high G content, a similar aggregation behavior is also evidenced at higher salt concentrations, but the extent of the self-assembling process remains too weak to develop a true gelation behavior in solution.

[Lips reanimation with temporalis myoplasty technique]. / Réanimation labiale par myoplastie du muscle temporal.

PURPOSE OF THE STUDY: The authors report their experience in lips reanimation with lengthening temporalis myoplasty for treatment of facial paralysis. MATERIALS AND METHODS: We studied 8 patients with permanent facial paralysis. The surgical technique allowed to transfer temporalis tendinous of coronoid process onto lips muscular strap, without aponevrotic relay. RESULTS: Functional and aesthetic results are exposed and so complications. Specialized facial physiotherapy rehabilitation is necessary in order to improve.

[Ethmoid adenocarcinoma: a series of 17 cases]. / Adénocarcinomes de l'ethmoïde. Notre expérience à propos d'une série de 17 cas.

INTRODUCTION: Ethmoid adenocarcinoma are and represent rare, 2.5 to 3% of head and neck cancers. The 5-year survival is around 50% for all stages. We present a series of 17 patients treated in our institution. OBJECTIVES: Expose the treatment of these patients and evaluate the results. METHODS: A retrospective study of 17 consecutive patients, treated between 1992 and 1999 for an ethmoid adenocarcinoma (15 T4 and 2 T2) and evaluated in 2002, with a mean follow-up of 5.8 years. RESULTS: In May 2002, 4 (23.53%) patients were alive and disease-free, 3 (17.65%) were alive with recurrence and 10 (58.82%) was died. The 5-year survival with Kaplan Meyer method is 41%. CONCLUSION: This series demonstrates the contribution of a combined approach for T3 and T4 tumors. The bifrontal approach induced an important morbidity in our series and should be replaced by the nasofrontal approach. Most teams agree that postoperative radiotherapy is necessary but the appropriateness of chemotherapy is still discussed. Some authors are of the opinion that it has no action on adenocarcinoma and others that it improves survival. It seems to have been efficient in our T4 patients.

[Acute Mastoiditis in Children: a series of 38 Cases]. / Les mastoïdites aiguës de l'enfant.

OBJECTIVE: We reviewed retrospectively the clinical, radiological and therapeutic findings in 38 infants and children with acute mastoiditis. MATERIAL AND METHODS: From 1988 to 2001, 38 children (mean age 36 months) were treated for acute mastoiditis and periostitis or retroauricular abscess. RESULTS: Diagnosis was usually made on the basis of typical retroauricular signs (60% of the cases), but was sometimes delayed owing to inappropriate antibiotics in 16 cases (42%) or atypical presentation in 3 (8%). Twenty-four children (70%) had no otolaryngological history. Pneumococci were isolated in most of the cases (n=15, 57%) with 13% having penicillin-resistant pneumococci. Lateral sinus thrombophlebitis was the most frequent complication, observed in 3 children (8%). Mastoiditis revealed congenital or acquired cholesteatoma in 4 children, who were all four infected with Gram-negative bacteria. Intravenous antibiotic therapy was associated with antroatticotomy in 36 children. CONCLUSION: Despite emergence of new antibiotic resistance, the annual rate of mastoiditis has remained unchanged, remaining a serious complication of middle ear acute otitis. Cholesteatoma should be suspected in case of Gram-negative bacteria or in older children.

Basic instinct in a feline.

Reported cases in Europe of large felines attacking humans are rare. Recently, in France, a man was attacked in an animal park by a tigress he had raised. He received fatal cervical wounds. This case of death by bites and lacerations, together with others in the recent international literature, underline the hereditary ferocity of such felines and the way in which they prefer to inflict lesions to the neck.

In situ observations of unusual dislocation mechanisms in the intermetallic alloy Ti3Al.

In situ straining experiments in a transmission electron microscope have been carried out on a Ti3Al intermetallic alloy, with the aim of determining the microscopic mechanisms controlling glide in prism, basal and pyramidal planes. Five different antiphase boundary energies have been measured and compared with the corresponding densities of incorrect first nearest neighbour atoms. The determination of a tension-compression asymmetry in pyramidal slip, and the detailed analysis of the complex microscopic mechanisms involved illustrate the efficiency of in situ experiments to solve complex problems in plasticity. A comparison between the properties of the different slip systems shows that they are controlled by different microscopic mechanisms, none of them being of covalent origin.

High resolution protein localization using soft X-ray microscopy.

Soft X-ray microscopes can be used to examine whole, hydrated cells up to 10 microm thick and produce images approaching 30 nm resolution. Since cells are imaged in the X-ray transmissive "water window", where organic material absorbs approximately an order of magnitude more strongly than water, chemical contrast enhancement agents are not required to view the distribution of cellular structures. Although living specimens cannot be examined, cells can be rapidly frozen at a precise moment in time and examined in a cryostage, revealing information that most closely approximates that in live cells. In this study, we used a transmission X-ray microscope at photon energies just below the oxygen edge (lambda = 2.4 nm) to examine rapidly frozen mouse 3T3 cells and obtained excellent cellular morphology at better than 50 nm lateral resolution. These specimens are extremely stable, enabling multiple exposures with virtually no detectable damage to cell structures. We also show that silver-enhanced, immunogold labelling can be used to localize both cytoplasmic and nuclear proteins in whole, hydrated mammary epithelial cells at better than 50 nm resolution. The future use of X-ray tomography, along with improved zone plate lenses, will enable collection of better resolution (approaching 30 nm), three-dimensional information on the distribution of proteins in cells.

Drug resistance induced by ouabain via the stimulation of MDR1 gene expression in human carcinomatous pulmonary cells.

The inhibition of the Na+/K+-ATPase by cardiotonic drugs like ouabain deeply perturbs both the properties of the cell membrane and the ionic composition of the cytoplasm and hence alters fundamental cell reactions. These three types of reactions may be involved in the stimulation of multidrug resistance 1 (MDR-1) gene expression and the synthesis of permeability glycoprotein [P-glycoprotein (P-gp)]. We have determined whether ouabain, which binds to an extracellular motif of the Na+/K+-ATPase, stimulates MDR-1 gene expression by measuring both mRNA and protein and whether the resulting P-gp extrudes hydrophobic compounds and causes resistance to antimitotic agents. The experiments were performed on Calu-3 cells, a human cell line from a pulmonary carcinoma. Northern blotting showed that treating the cells with submicromolar concentrations of ouabain stimulated MDR-1 gene expression within 24 h. The ouabain-induced stimulation of MDR-1 expression was not restricted to Calu-3 cells but also occurred in human carcinomatous colon (T-84 and HT-29) and hepatic (H7V3) cells. However, it is not ubiquitous because it was not found in HeLa cells. The stimulation was reproduced by other Na+/K+-ATPase inhibitors and occurred via enhanced gene transcription, apparently due to the increased cytosolic calcium concentration. Ouabain also increased the membrane content of P-gp, as detected by immunoblotting and immunohistology. We have developed a microvideo assay based on the properties of acetoxymethyl ester calcein and calcein to show that this P-gp extruded the hydrophobic acetoxymethyl ester calcein. Ouabain also caused the Calu-3 cells to become resistant to doxorubicin and vinblastine. Thus, although ouabain acts extracellularly, it may stimulate MDR-1 gene expression and P-gp synthesis and make cells resistant to hydrophobic cytotoxic compounds.

NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta.

Inflammation of the airways is a major feature of the inherited disease cystic fibrosis. Previous studies have shown that the pro-inflammatory cytokines tumor necrosis factor alpha and interferon gamma reduce the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (CFTR) in HT-29 and T84 cells by acting post-transcriptionally. We have investigated the effect of the pro-inflammatory peptide interleukin 1beta (IL-1beta) on the expression of the CFTR in Calu-3 cells. IL-1beta increased the production of CFTR mRNA in a dose- and time-dependent manner. Its action was inhibited by inhibitors of the NF-kappaB pathway, including N-acetyl-l-cysteine, pyrrolidine dithiocarbamate, and a synthetic cell-permeable peptide containing the NF-kappaB nuclear localization signal sequence. Gel shift analysis showed that IL-1beta activated NF-kappaB in Calu-3 cells, and transfection experiments using p50 and RelA expressing vectors showed that exogenous transfected NF-kappaB subunits increased the concentration of CFTR mRNA. Gel shift analysis with antibody supershifting also showed that IL-1beta caused the binding of NF-kappaB to a kappaB-like response element at position -1103 to -1093 in the CFTR 5'-flanking region. Transfection experiments using -2150 to +52 CFTR reporter gene constructs showed that the activity of the CFTR promoter is enhanced by exogenous transfected NF-kappaB and IL-1beta and that this enhancement is due, at least in part, to the -1103 to -1093 kappaB site. We conclude that the intracellular signaling that leads to increased CFTR mRNA in response to IL-1beta in Calu-3 cells includes the binding of NF-kappaB to the -1103 kappaB element and a subsequent increase in CFTR promoter activity.

Comparative reactivity of different HLA-G monoclonal antibodies to soluble HLA-G molecules.

Different HLA-G monoclonal antibodies (mAbs) were first evaluated for their capability to identify soluble HLA-G (sHLA-G) in ELISA. Three of them, namely 87G, BFL.1 and MEM-G/9, when used as coating mAbs together with W6/32 capture mAb, identified beta2-microglobulin (beta2m)-associated-sHLA-G but not soluble HLA-B7 (sHLA-B7) in cell culture supernatants from transfected cells. By comparison, the anti-HLA class I mAb 90 did recognize both sHLA-G and sHLA-B7. By using these HLA-G mAbs, sHLA-G was identified in amniotic fluids as well as in culture supernatants of first trimester and term placental explants but not in cord blood. Intron 4-retaining sHLA-G isoforms were identified in some amniotic fluids by the use of an intron 4-specific mAb (16G1). Reactivity of these different HLA-G mAbs was then compared to determine their respective binding sites on soluble and membrane-bound HLA-G. Using both ELISA and flow cytometry analysis, we showed that they did not compete with each other, which suggested that they did not recognize the same determinants. Finally, we report that two mAbs directed against the alpha1 domain of HLA class I heavy chain (mAb 90 and YTH 862) did compete with 87G, therefore demonstrating that this latter mAb recognized an epitope localized on this external domain of HLA-G.

Modulation of CFTR gene expression in HT-29 cells by extracellular hyperosmolarity.

Hypertonicity has pleiotropic effects on cell function, including activation of transporters and regulation of gene expression. It is important to investigate the action of hypertonicity on cystic fibrosis gene expression because cystic fibrosis transmembrane conductance regulator (CFTR), the cAMP-regulated Cl(-) channel, regulates ion transport across the secretory epithelia, which are often in a hypertonic environment. We found that adding >150 mosmol/l NaCl, urea, or mannitol to the culture medium reduced the amount of CFTR mRNA in colon-derived HT-29 cells in a time-dependent manner. Studies with inhibitors of various kinases [H-89 (protein kinase A inhibitor), bisindolylmaleimide (protein kinase C inhibitor), staurosporine (serine/threonine kinase inhibitor) and herbimycin A (tyrosine kinase inhibitor), SB-203580 and PD-098059 (mitogen-activated protein kinase inhibitors)] showed that CFTR gene expression and its decrease by added NaCl required p38 kinase cascade activity. The CFTR gene activity is regulated at the transcriptional level, since adding NaCl diminished the luciferase activity of HeLa cells transiently transfected with the CFTR promoter. This regulation requires protein synthesis. The complexity of the reactions involved in blocking CFTR gene transcription by NaCl strongly suggests that the decrease in CFTR mRNA is part of a general cell response to hyperosmolar stress.

[Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques (CSH) dans le traitement des cancers du sein métastatiques: résultats du programme national Pegase 04.

UNLABELLED: We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients. PATIENTS AND METHODS: Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response. RESULTS: The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12). CONCLUSION: The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.