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1.
Arch Suicide Res ; : 1-15, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567726

ABSTRACT

INTRODUCTION: In 2021, in Argentina there were 3,639 deaths by suicide, equivalent to one death every three hours. Evidence indicates that brief suicide preventive interventions in emergency services, such as the Safety Planning Intervention (SPI), effectively reduce future suicidal ideation and attempts in both adults and adolescents. OBJECTIVE: To evaluate the perception of self-efficacy, and the feasibility and usefulness of a training in SPI in early career mental health professionals. METHOD: Sixty-nine early career mental health professionals from Buenos Aires participated in a 3-hour SPI training. Through an online survey, measurements were taken in three times: before and after the training and 8-10 weeks after the training. RESULTS: All participants completed the pre- and post-training measures, and 43 of them completed the follow-up survey. Post-training measures showed an increase in self-efficacy, maintaining the effect at 8-10 weeks. The SPI was found useful and feasible to be implemented in clinical care. More than half of the participants reported having used the SPI during follow-up. CONCLUSION: Results suggest that training in SPI is associated with an increased perception of self-efficacy of early career mental health professionals; this is maintained after 2 months post-training. In addition, the intervention is perceived as feasible, acceptable and useful for professionals in training.

2.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 79(Pt 1): 73-77, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36748900

ABSTRACT

Carbon doping is studied in MgB2 pellets during one-step synthesis by solid-state reaction, employing both undoped and carbon-doped boron with and without the addition of nano-SiC. The phase formation during the synthesis as a function of time was followed using powder X-ray diffraction and Rietveld refinement. The superconducting properties were characterized with a magnetometer to investigate doping-induced changes. Mg(B1-xCx)2 is obtained with nano-precipitates and different compositions depending on the synthesis temperature. It is found that the addition of nano-SiC prevents the phase formation at low temperature (700°C). Nevertheless, the best superconducting properties are obtained for the sample treated at 900°C using simultaneously C and SiC, with a critical current density of 105 A cm-2 at 3 T and 20 K, named the 900-20-C-nanoSiC sample.

3.
Surgeon ; 20(1): 61-65, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34961700

ABSTRACT

The American College of Surgeons (ACS), founded in 1913, is the one of the oldest surgical professional organizations in the United States. Originally founded to foster surgical professional excellence and collaboration among surgeons in North America, the ACS has now expanded to over 80,000 members worldwide with programs delivering a rich portfolio of professional services in the domains of surgical education, clinical surgery and global surgery, surgical quality and leadership, surgical research, member services. ACS international programs initially focused on international professional exchange and hosting of young surgeons from around the world in US based surgical centers to develop scholarly and clinical collaborations. Over the last 20 years, with the founding of the ACS-Operation Giving Back (OGB) Program, the ACS has broadened its international perspective to support surgical care in emerging nations and to develop collaborative programs with host institutions in emerging nations to support surgical care capacity growth through on site partnerships, and educational and policy initiatives. To that end, in recent years, OGB has developed global surgical programs in the COSECSA region of sub-Saharan Africa creating opportunities to participate in Global Surgical Training Hubs. After developing a pilot hub project in Hawassa, Ethiopia, OGB is now in the process of scaling up two additional sites. In this manuscript, we will describe ACS's rich history of activities promoting international surgical collaboration and scholarship and discuss the process of creating the global surgical training hub model in Hawassa.


Subject(s)
General Surgery , Surgeons , Humans , United States
4.
J Neurol Sci ; 390: 222-226, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29801894

ABSTRACT

OBJECTIVES: To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura. MATERIALS: 31 migraine patients, 28 females and 3 males, with MRI evidence of white matter lesions suggestive of demyelinating disease according to the Barkhof Criteria. All patients underwent further diagnostics including lumbar puncture, autoimmunity panel and cardiological evaluation to detect the presence of PFO. The mean duration of follow-up was 3.46 years and MIPAV software was used to analyze MRI imaging. RESULTS: 14 of the 31 patients (45%) had PFO. A significant association was found between PFO and migraine with visual aura (p < 0.001). No difference in lesion number, volume or area between patients with and without PFO was found, but the distribution was mainly occipital (p < 0.001) in patients with PFO. The follow-up showed a stationary lesion load in all PFO patients; no infratentorial or spinal cord lesion and no enhancement or corpus callosum lesion was ever detected. At the end of follow-up four patients developed multiple sclerosis: younger age at first MRI and oligoclonal bands were associated risk factors. CONCLUSIONS: Migraine is often one of the main symptoms leading to MRI, and in many cases white matter lesions of unspecific significance are discovered, thus placing demyelinating diseases in the differential diagnosis. Our study underlines the potential pathogenetic role of PFO in generating white matter lesions in migraine patients (45%), particularly those with visual aura and occipital lesions. For this reason, we affirm that PFO represents a cardinal point in the differential diagnosis of suspected demyelinating disease.


Subject(s)
Demyelinating Diseases/diagnosis , Foramen Ovale, Patent/diagnosis , Migraine with Aura/diagnosis , Adult , Brain/diagnostic imaging , Demyelinating Diseases/complications , Diagnosis, Differential , Female , Follow-Up Studies , Foramen Ovale, Patent/complications , Heart/diagnostic imaging , Humans , Male , Migraine with Aura/complications , Migraine without Aura/complications , Migraine without Aura/diagnosis , Oligoclonal Bands/cerebrospinal fluid , Retrospective Studies , Spinal Cord/diagnostic imaging
5.
Biochem Pharmacol ; 154: 303-317, 2018 08.
Article in English | MEDLINE | ID: mdl-29803506

ABSTRACT

Neurodegenerative diseases (NDs) and brain tumors are severe, disabling, and incurable disorders that represent a critical problem regarding human suffering and the economic burden on the healthcare system. Because of the lack of effective therapies to treat NDs and brain tumors, the challenge for physicians is to discover new drugs to improve their patients' quality of life. In addition to risk factors such as genetics and environmental influences, increased cellular oxidative stress has been reported as one of the potential common etiologies in both disorders. Given their antioxidant and anti-inflammatory potential, dietary polyphenols are considered to be one of the most bioactive natural agents in chronic disease prevention and treatment. Despite the protective activity of polyphenols, their inefficient delivery systems and poor bioavailability strongly limit their use in medicine and functional food. A potential solution lies in polymeric nanoparticle-based polyphenol delivery systems that are able to enhance their absorption across the gastrointestinal tract, improve their bioavailability, and transport them to target organs. In the present manuscript, we provide an overview of the primary polyphenols used for ND and brain tumor prevention and treatment by focusing on recent findings, the principal factors limiting their application in clinical practice, and a promising delivery strategy to improve their bioavailability.


Subject(s)
Brain Neoplasms/prevention & control , Drug Delivery Systems/methods , Nanoparticles/administration & dosage , Neurodegenerative Diseases/prevention & control , Phytochemicals/administration & dosage , Polyphenols/administration & dosage , Animals , Antioxidants/administration & dosage , Antioxidants/chemistry , Antioxidants/metabolism , Brain Neoplasms/metabolism , Clinical Trials as Topic/methods , Humans , Nanoparticles/chemistry , Nanoparticles/metabolism , Neurodegenerative Diseases/metabolism , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/chemistry , Neuroprotective Agents/metabolism , Phytochemicals/chemistry , Phytochemicals/metabolism , Polyphenols/chemistry , Polyphenols/metabolism
6.
Clin Genet ; 93(5): 982-991, 2018 05.
Article in English | MEDLINE | ID: mdl-29364500

ABSTRACT

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.


Subject(s)
Collagen/genetics , Hydroxylation/genetics , Myopia/genetics , Prolyl Hydroxylases/genetics , Adolescent , Adult , Child , China/epidemiology , Collagen/metabolism , Exome/genetics , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Mutation, Missense/genetics , Myopia/epidemiology , Myopia/pathology , Pedigree , Phenotype , Young Adult
7.
Clin Genet ; 93(1): 138-143, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28456002

ABSTRACT

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain.


Subject(s)
Mutation, Missense , Neurofibromatosis 1/genetics , Noonan Syndrome/genetics , SOS1 Protein/genetics , Spinal Nerves/metabolism , Adolescent , Adult , Family Health , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Mothers , Neurofibromatosis 1/pathology , Noonan Syndrome/pathology , Phenotype , Spinal Nerves/pathology
8.
Stem Cell Res ; 10(1): 85-94, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23142801

ABSTRACT

Neural stem cells (NSCs) raised the hope for cell-based therapies in human neurodevelopmental and neurodegenerative diseases. Current research strategies aim to isolate, enrich, and propagate homogeneous populations of neural stem cells. Unfortunately, several concerns with NSC cultures currently may limit their therapeutic promise. Exhaustion of growth factors and/or their uncontrolled release with burst and fall in their concentration may greatly affect the in vitro behavior of NSCs. In this context, we investigate whether a device containing heparan sulfate (HS), which is a co-factor in growth factor-mediated cell proliferation and differentiation, could potentiate and prolong the delivery of fibroblast growth factor-2 (FGF-2) and thus improve in vitro NSC cultivation. We demonstrated that NSCs cultivated in media with a controlled release of FGF-2 from a polyelectrolyte polymer showed a higher proliferation rate, and reduced apoptosis and senescence. In these experimental conditions NSCs preserve their stemness properties for a longer period of time compared with controls. Also of interest is that cell fate properties are conserved as well. The controlled release of FGF-2 reduced the level of oxidative stress and this is associated with a lower level of damaged DNA. This result may explain the reduced level of senescence and apoptosis in NSCs cultivated in the presence of hydrogel-releasing FGF-2.


Subject(s)
Cell Culture Techniques/methods , Fibroblast Growth Factor 2/pharmacology , Neural Stem Cells/drug effects , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Electrolytes/chemistry , Heparitin Sulfate/chemistry , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Kinetics , Mice , Neural Stem Cells/cytology , Polymers/chemistry
11.
Minerva Pediatr ; 59(1): 13-21, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17301720

ABSTRACT

AIM: Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the prevalence and the outcome of OPG in 200 NF1 patients (122 males and 78 females, aged 1-25 years) followed up to 16 years (mean of 6 years). METHODS: All children were evaluated by a detailed physical, neurological and ophthalmological examination. Fifteen out of 200 (7.5%) of these patients (7 males, 8 females) were identified with evidence of optic pathway tumours. RESULTS: Nine children had symptoms such as endocranial hypertension, seizures, headache; 4 patients only showed anomalies at ophthalmological examination; 2 patients had no symptoms or signs. All children had evidence of optic pathway tumour on magnetic resonance imaging. Three had a prechiasmal tumour, 2 had a chiasmal tumour, 1 had prechiasmal/chiasmal tumour, 2 had a prechiasmal/chiasmal and postchiasmal tumour, 2 had a chiasmal and postchiasmal tumour, 4 had a massive involvement of the optic system, 1 child exhibited a bilateral involvement of the optic nerves with additional impairment of the chiasm. Four patients had partial and/or subtotal spontaneous regression. CONCLUSIONS: Because optic pathway tumours arise in children younger than 6 years of age, all NF1 children should undergo yearly ophtalmologic examination and growth assessment to monitor signs of precocious puberty.


Subject(s)
Neurofibromatosis 1/epidemiology , Optic Nerve Glioma/epidemiology , Visual Pathways/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Intracranial Hypertension/epidemiology , Magnetic Resonance Imaging , Male , Neurofibromatosis 1/pathology , Optic Chiasm/pathology , Optic Nerve Glioma/pathology , Prevalence , Remission, Spontaneous , Retrospective Studies , Severity of Illness Index , Time Factors
12.
Neuroscience ; 140(1): 281-92, 2006 Jun 19.
Article in English | MEDLINE | ID: mdl-16616430

ABSTRACT

We studied the distribution and cellular localization of Na(+)-coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na(+)-coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na(+)-coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na(+)-coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na(+)-coupled neutral amino acid transporter 2. Na(+)-coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na(+)-coupled neutral amino acid transporter 1- and Na(+)-coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na(+)-coupled neutral amino acid transporter 1/synaptophysin and Na(+)-coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate-glutamine cycle. The strong expression of Na(+)-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier suggests that Na(+)-coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.


Subject(s)
Amino Acid Transport System A/metabolism , Cerebral Cortex/cytology , Neurons/metabolism , Animals , Blotting, Western/methods , Calcium-Binding Proteins/metabolism , Cerebral Cortex/metabolism , Female , Glial Fibrillary Acidic Protein/metabolism , Humans , Immunohistochemistry/methods , Male , Membrane Proteins/metabolism , Microscopy, Electron, Transmission/methods , Middle Aged , Muscle Proteins/metabolism , Neurons/ultrastructure , Phosphopyruvate Hydratase/metabolism , Rats , Rats, Sprague-Dawley , gamma-Aminobutyric Acid/metabolism
13.
Cell Death Differ ; 12(6): 603-13, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15846373

ABSTRACT

Recent studies suggest a close relationship between cell metabolism and apoptosis. We have evaluated changes in lipid metabolism on permeabilized hepatocytes treated with truncated Bid (tBid) in the presence of caspase inhibitors and exogenous cytochrome c. The measurement of beta-oxidation flux by labeled palmitate demonstrates that tBid inhibits beta-oxidation, thereby resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease. Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the effects exerted by tBid on beta-oxidation. The unexpected role of tBid in the regulation of lipid beta-oxidation suggests a model in which tBid-induced metabolic decline leads to the accumulation of toxic lipid metabolites such as palmitoyl-CoA, which might become participants in the apoptotic pathway.


Subject(s)
Carnitine O-Palmitoyltransferase/antagonists & inhibitors , Carrier Proteins/pharmacology , Fatty Acids/metabolism , Mitochondria, Liver/metabolism , BH3 Interacting Domain Death Agonist Protein , Cardiolipins/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Carrier Proteins/metabolism , Caspase Inhibitors , Caspases/metabolism , Cell Membrane Permeability/drug effects , Cells, Cultured , Cytochromes c/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Malonyl Coenzyme A/metabolism , Membrane Potentials/drug effects , Membrane Proteins/genetics , Mitochondria, Liver/genetics , Oxidation-Reduction/drug effects , Protein Binding , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2 Homologous Antagonist-Killer Protein
14.
Cell Death Differ ; 12(1): 65-77, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15459751

ABSTRACT

Marrow stromal stem cells (MSCs) are stem-like cells that are currently being tested for their potential use in cell therapy for a number of human diseases. MSCs can differentiate into both mesenchymal and nonmesenchymal lineages. In fact, in addition to bone, cartilage and fat, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes. RB and RB2/p130 genes are involved in the differentiation of several systems. For this reason, we evaluated the role of RB and RB2/p130 in the differentiation and apoptosis of MSCs under experimental conditions that allow for MSC differentiation toward the neuron-like phenotype. To this end, we ectopically expressed either RB or RB2/p130 and monitored proliferation, differentiation and apoptosis in rat primary MSC cultures induced to differentiate toward the neuron-like phenotype. Both RB and RB2/P130 decreased cell proliferation rate. In pRb-overexpressing cells, the arrest of cell growth was also observed in the presence of the HDAC-inhibitor TSA, suggesting that its antiproliferative activity does not rely upon the HDAC pathway, while the addition of TSA to pRb2/p130-overexpressing cells relieved growth inhibition. TUNEL reactions and studies on the expression of genes belonging to the Bcl-2 family showed that while RB protected differentiating MSCs from apoptosis, RB2/p130 induced an increase of apoptosis compared to controls. The effects of both RB and RB2/p130 on programmed cell death appeared to be HDAC- independent. Molecular analysis of neural differentiation markers and immunocytochemistry revealed that RB2/p130 contributes mainly to the induction of generic neural properties and RB triggers cholinergic differentiation. Moreover, the differentiation potentials of RB2/p130 and RB appear to rely, at least in part, on the activity of HDACs.


Subject(s)
Cell Differentiation/physiology , Mesenchymal Stem Cells/physiology , Neurons/cytology , Proteins/physiology , Retinoblastoma Protein/physiology , Acetylcholinesterase/genetics , Acetylcholinesterase/metabolism , Adenoviridae/genetics , Animals , Apoptosis/physiology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Death/physiology , Cell Differentiation/drug effects , Cell Proliferation , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p27 , DNA-Binding Proteins/genetics , E2F Transcription Factors , Enzyme Inhibitors/pharmacology , Gene Expression/drug effects , Gene Expression/genetics , Genetic Vectors/genetics , Histone Deacetylase Inhibitors , Histone Deacetylases/physiology , Hydroxamic Acids/pharmacology , Immunohistochemistry , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurofilament Proteins/metabolism , Neurons/metabolism , Proteins/genetics , Proteins/metabolism , Rats , Retinoblastoma Protein/genetics , Retinoblastoma Protein/metabolism , Retinoblastoma-Like Protein p130 , Transcription Factors/genetics , Transfection , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/metabolism
15.
Neuroscience ; 123(2): 547-56, 2004.
Article in English | MEDLINE | ID: mdl-14698761

ABSTRACT

The cellular localization of the vesicular glutamate transporter 1, VGLUT1, was studied in the rat cerebral cortex with immunocytochemical techniques. VGLUT1 immunoreactivity (ir) was localized to punctate structures dispersed in the neuropil of all cortical layers as well as around the profile of somata and proximal dendritic segments of virtually all pyramidal neurons. Using a correlative light and electron microscopic method, we found that VGLUT1 ir is expressed in axon terminals forming synapses exclusively with dendritic shafts and spines. Perisomatic VGLUT1-positive terminals never formed synapses with the pyramidal cell bodies to which they were in apposition, but formed asymmetric synapses with adjacent neuropilar dendritic elements. The high probability of a close spatial relationship between glutamatergic and GABAergic terminals in perisomatic regions suggests that spilled-out glutamate may act on inhibitory axon terminals innervating the soma of cortical pyramidal neurons.


Subject(s)
Carrier Proteins/metabolism , Glutamine/metabolism , Membrane Transport Proteins , Presynaptic Terminals/metabolism , Pyramidal Cells/metabolism , Vesicular Transport Proteins , Animals , Carrier Proteins/ultrastructure , Female , Immunoblotting , Immunohistochemistry , Male , Microscopy, Electron , Neocortex/metabolism , Neocortex/ultrastructure , Neuropil/metabolism , Neuropil/ultrastructure , Presynaptic Terminals/ultrastructure , Pyramidal Cells/ultrastructure , Rats , Rats, Sprague-Dawley , Vesicular Glutamate Transport Protein 1
16.
Neurology ; 61(7): 988-90, 2003 Oct 14.
Article in English | MEDLINE | ID: mdl-14557576

ABSTRACT

The authors report an Italian family with autosomal-dominant Charcot-Marie-Tooth disease (CMT) in which there were giant axons in the sural nerve biopsy. Linkage to the known CMT2 loci (CMT2A, CMT2B, CMT2D, CMT2F) and mutations in the known CMT2 genes (Cx32, MPZ, NEFL), GAN, NEFM, and CMT1A duplication/HNPP deletion were excluded. This family with CMT and giant axons has a pathologic and genetic entity distinct from classic CMT.


Subject(s)
Axons/pathology , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/pathology , Adult , Aged , Axons/ultrastructure , Biopsy , Charcot-Marie-Tooth Disease/physiopathology , Child , DNA Mutational Analysis , Electrodiagnosis , Female , Genes, Dominant , Humans , Italy , Male , Middle Aged , Pedigree , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Sural Nerve/pathology , Sural Nerve/ultrastructure
17.
J Cell Physiol ; 195(2): 220-33, 2003 May.
Article in English | MEDLINE | ID: mdl-12652649

ABSTRACT

Neural stem cells (NSCs) could be very useful for the "cell therapy" treatment of neurological disorders. For this reason basic studies aiming to well characterize the biology of NSCs are of great interest. We carried out a molecular and immunocytochemical analysis of EGF-responsive NSCs obtained from rat pups. After the initial growth of NSCs as floating neurospheres in EGF-containing medium, cells were plated on poly-L-ornithine-coated dishes either in the presence or absence of EGF. We followed cell differentiation and apoptosis for 21 days in vitro and analyzed the expression levels of some genes having a major role in these processes, such as pRB, pRB2/p130, p27, and p53. We observed that EGF impairs neuronal differentiation. Furthermore, in the absence of mitogens, apoptosis, which appeared to proceed through the "p53 network," was significantly lower than in the presence of EGF. The cyclin kinase inhibitor p27, while important for cell cycle exit, seemed dispensable for cell survival and differentiation.


Subject(s)
Cell Culture Techniques/methods , Cell Differentiation/drug effects , Cell Lineage/drug effects , Cell Separation/methods , Epidermal Growth Factor/pharmacology , Nerve Tissue Proteins , Proteins , Stem Cell Transplantation/methods , Stem Cells/metabolism , Animals , Animals, Newborn , Apoptosis/drug effects , Apoptosis/physiology , Astrocytes/cytology , Astrocytes/drug effects , Astrocytes/metabolism , Blood Proteins/drug effects , Blood Proteins/genetics , Blood Proteins/metabolism , Cell Cycle Proteins/drug effects , Cell Cycle Proteins/metabolism , Cell Differentiation/physiology , Cell Lineage/physiology , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p27 , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Glial Fibrillary Acidic Protein/drug effects , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Immunohistochemistry , Intermediate Filament Proteins/drug effects , Intermediate Filament Proteins/genetics , Intermediate Filament Proteins/metabolism , Nestin , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Proto-Oncogene Proteins c-bcl-2/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Retinoblastoma Protein/drug effects , Retinoblastoma Protein/genetics , Retinoblastoma Protein/metabolism , Retinoblastoma-Like Protein p130 , Stem Cells/cytology , Stem Cells/drug effects , Tumor Suppressor Protein p53/drug effects , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/drug effects , Tumor Suppressor Proteins/metabolism
19.
Biochem J ; 360(Pt 3): 569-77, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11736646

ABSTRACT

The activity of the RB2/p130 gene, which is a member of the retinoblastoma gene family, is cell-cycle-regulated and plays a key role in growth inhibition and differentiation. We used neuroblastoma cell lines as a model for studies on neural crest progenitor cell differentiation. We show that Rb2/p130 ectopic protein expression induces morphological and molecular modifications, promoting differentiation of intermediate (I) phenotype SK-N-BE(2)-C neuroblastoma cells towards a neuroblastic (N) rather than a Schwann/glial/melanocytic (S) phenotype. These modifications are stable as they persist even after treatment with an S-phenotype inducer. Rb2/p130 ectopic expression also induces a more differentiated phenotype in N-type SH-SY-5Y cells. Further, this function appears to be independent of cell-cycle withdrawal. The data reported suggest that the Rb2/p130 protein is able to induce neuronal lineage specification and differentiation in neural crest stem and committed neuroblastoma cells, respectively. Thus, the Rb2/p130 protein seems to be required throughout the full neural maturation process.


Subject(s)
Blood Proteins/genetics , Cell Differentiation/physiology , Multigene Family , Neuroblastoma/genetics , Proteins , Cell Cycle Proteins/genetics , Cell Division , Cell Line , Gene Expression Regulation, Neoplastic , Humans , Kidney , Neuroblastoma/pathology , RNA, Messenger/genetics , Recombinant Proteins/biosynthesis , Retinoblastoma-Like Protein p130 , Reverse Transcriptase Polymerase Chain Reaction , Stem Cells/metabolism , Transcription, Genetic , Transfection , Tumor Cells, Cultured
20.
Mol Psychiatry ; 6(4): 380-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11443521

ABSTRACT

We show here that clozapine, a beneficial antipsychotic, down-regulates the expression of the glutamate transporter GLT-1 in the rat cerebral cortex, thereby reducing glutamate transport and raising extracellular glutamate levels. Clozapine treatment (25--35 mg kg(-1) day(-1) orally) reduced GLT-1 immunoreactivity in several brain regions after 3 weeks; this effect was most prominent after 9 weeks and most evident in the frontal cortex. GLT-1 protein levels were reduced in the cerebral cortex of treated rats compared with controls and were more severely affected in the anterior (71.9 +/- 4.5%) than in the posterior (53.2 +/- 15.4%) cortex. L-[(3)H]-glutamate uptake in Xenopus laevis oocytes injected with mRNA extracted from the anterior cerebral cortex of rats treated for 9 weeks was remarkably reduced (to 30.6 +/- 8.6%) as compared to controls. In addition, electrophysiological recordings from oocytes following application of glutamate revealed a strong reduction in glutamate uptake currents (46.3 +/- 10.2%) as compared to controls. Finally, clozapine treatment led to increases in both the mean basal (8.1 +/- 0.7 microM) and the KCl-evoked (28.7 +/- 7.7 microM) output of glutamate that were 3.1 and 3.5, respectively, higher than in control rats. These findings indicate that clozapine may potentiate glutamatergic synaptic transmission by regulating glutamate transport.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Cerebral Cortex/metabolism , Clozapine/pharmacology , Frontal Lobe/metabolism , Gene Expression Regulation/drug effects , Glutamic Acid/metabolism , ATP-Binding Cassette Transporters/analysis , Amino Acid Transport System X-AG , Animals , Antipsychotic Agents/pharmacology , Cerebral Cortex/drug effects , Female , Frontal Lobe/drug effects , In Vitro Techniques , Microdialysis , Oocytes/drug effects , Oocytes/physiology , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Recombinant Proteins/metabolism , Xenopus laevis
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