CD34+ selected haematopoietic stem cell (HSC) not preceded by any immunosuppressive therapy as effective treatment for graft failure.
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Biomedical subjects
Publications and source records attributed to S Mercurio.
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We performed a randomized study to compare 'G-CSF alone' (administered at dose of 10 mcg/kg/day) and 'cyclophosphamide plus G-CSF' (cyclophosphamide at dose of 4 g/m(2) and G-CSF at dose of 10 microg/kg/day), as PBPC mobilization schedules in 52 patients with NHL or HD. Randomization was stratified according to the amount of previous chemotherapy (< or =2 and >2 lines of previous chemotherapy). Mean CD34+ cell peak in P.B., mean 'Total CD34+ cells' harvested and percentage of patients successfully mobilized, in the group mobilized with 'G-CSF alone' vs the group mobilized with 'cyclophosphamide plus G-CSF', were: 35.3 x 10(6) vs 45.8 x 10(6)/l (P=0.3), 5.4 x 10(6) vs 6.8 x 10(6)/kg (P>0.9) and 50 vs 61% (P=0.4). No differences were observed in the stratum of less pretreated patients. However, in the stratum of patients who had previously received more than two lines of chemotherapy, CD34+cell peak (P=0.05) and percentage of successful mobilization (P=0.01) were higher when 'cyclophosphamide plus G-CSF' was used. Using logistic regression, both age and mobilization with 'G-CSF alone' were significantly associated with a low CD34+ cell peak in P.B. However, in the stratum of less pretreated patients, only age was significantly associated with this risk.
Cyr61 is a secreted, heparin-binding, extracellular matrix-associated protein whose activities include the promotion of adhesion and chemotaxis, and the stimulation of fibroblast and endothelial cell growth. Many, if not all, of these activities of Cyr61 are mediated through interactions with integrins. We explore the role of Cyr61 in the early development of Xenopus laevis. Gain- and loss-of-function experiments show that Xcyr61 is required for normal gastrulation movements. This role is mediated in part through the adhesive properties of Xcyr61 and its related ability to modulate assembly of the extracellular matrix. In addition, Xcyr61 can, in a context-dependent manner, stimulate or inhibit signalling through the Wnt pathway. These properties of Xcyr61 provide a mechanism for integrating cell signalling, cell adhesion and cell migration during gastrulation.
In order to identify factors involved in posteriorization of the central nervous system, we undertook a functional screen in Xenopus animal cap explants which involved coinjecting noggin RNA together with pools of RNA from a chick somite cDNA library. In the course of this screen, we isolated a clone encoding a truncated form of beta-catenin, which induced posterior neural and dorsal mesodermal markers when coinjected with noggin in animal caps. Similar results were obtained with Xwnt-8 and Xwnt-3a, suggesting that these effects are a consequence of activating the canonical Wnt signalling pathway. To investigate whether the activation of posterior neural markers requires mesoderm induction, we performed experiments using a chimeric inducible form of beta-catenin. Activation of this protein during blastula stages resulted in the induction of both posterior neural and mesodermal markers, while activation during gastrula stages induced only posterior neural markers. We show that this posteriorizing activity occurs by an indirect and noncell-autonomous mechanism requiring FGF signalling.
Neocorticogenesis in mice homozygous for an Emx2 null allele is the topic of this article. The development of both main components of neocortex, primordial plexiform layer derivatives and cortical plate, was analyzed, paying special attention to radial migration of neurons forming the cortical plate. The products of the Reelin gene, normally playing a key role in orchestrating radial migration of these neurons, display normal distribution at the beginning of the cortical neuronogenesis but are absent in the neocortical marginal zone of the mutant mice at the time when the cortical plate is laid down. As a consequence, the development of radial glia is impaired, and neurons making up the cortical plate display abnormal migration patterns. In addition, restricted defects along the rostrocaudal and the mediolateral axes are present in the subplate, suggesting an Emx2-specific role in priming the proper development of this layer.
The clinical course of acute otitis media is usually short, and the process terminates because of the host's immune system, the infection-resistant properties of the mucosal linings, and the susceptibility of the major organisms (beta-hemolytic streptococcus or pneumococcus) to penicillin. However, a small proportion (1% to 5%) of untreated or inadequately treated patients may experience complications. Prior to the development of an intracranial complication of otomastoiditis, warning symptoms or signs may be evident; these include severe earache, severe headache, vertigo, chills and fever, and meningeal symptoms and signs. Increasing headache, particularly temporoparietal headache near the affected ear, often indicates an impending intracranial complication. This symptom, often the only indication of an epidural abscess, demands prompt investigation and medical and surgical intervention. In our experience, computed tomography (CT) permits accurate diagnosis of acute coalescent or latent (masked) mastoiditis and its associated complications. However, magnetic resonance imaging (MRI) remains the study of choice to evaluate otogenic intracranial complications. This article demonstrates the important role of MRI in diagnosing various stages of acute otomastoiditis and its associated complications.
The distribution of EMX2, the protein product of the homeobox gene Emx2, was analyzed in the developing mouse CNS by means of a polyclonal antibody we raised against it. The protein is present in the rostral brain, the olfactory area and a set of scattered cells lying between the nasal pits and the telencephalon. In the cortical neuroepithelium EMX2 is expressed all along the rostro-caudal axis in a graded distribution with a caudal-medial maximum and a rostral-lateral minimum. Anti-EMX2 immunoreactivity is also detectable in Cajal-Retzius cells as well as in apical dendrites of marginal neurons of the cortical plate. We also observe that the EMX2 and EMX1 homeoproteins display complementary expression patterns in olfactory bulbs and amygdaloid complex. Here, they demarcate different neuronal populations, involved in processing olfactory information coming from the vomero-nasal organ and from the main olfactory epithelium, respectively. EMX2 is also detectable in mesencephalic structures, such as the optic tectum and tegmentum. The graded distribution of EMX2 along antero-posterior and medial-lateral axes of the primitive cortex prefigures a role of this protein in the subdivision of the cortex in cytoarchitectonic regions and possibly functional areas, whereas its presence in Cajal-Retzius cells suggests a role in the process of cortical lamination.
An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p < 0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.
Fibroblast mitogenic activity (MA) has been identified in scleroderma (SD) sera. Control and scleroderma skin fibroblasts in early passage were observed for replication (cell counts) after 72 h of serum exposure. SD sera at 15% concentration induced a significant increase in control fibroblast numbers when compared with control sera; this effect was not seen with SD cells while at higher serum concentrations (30%); SD cells were slightly responsive to the MA. MA was completely abrogated by the proteinase inhibitors STI and TLCK which did not affect mitogens in healthy sera. Circulating mitogenic proteinases selective for fibroblasts could play a role in the fibrosis of SD by modulating fibroblast replication.
To explore the mechanism of increased collagen synthesis by scleroderma skin fibroblasts in vitro, control and scleroderma fibroblasts were compared in confluent monolayer cultures growth-arrested by serum deprivation; responses to optimal mitogenic doses of platelet-derived growth factor, fibroblast growth factor, epidermal growth factor and nerve growth factor were compared. Platelet-derived growth factor had a selective mitogenic effect on control skin fibroblasts not observed with scleroderma skin fibroblasts. None of the factors studied had a selective effect on collagen synthesis independent of cell replication; scleroderma and control fibroblasts responded similarly. Therefore, the growth factors studied may not be involved in generating the activated scleroderma fibroblast directly; platelet-derived growth factor may play an indirect role in fibroblast replication in human fibrotic disorders.U
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