M Pumarola

Autonomous University of Barcelona, Cerdanyola del Vallès, Catalonia, Spain

Are you M Pumarola?

Claim your profile

Publications (129)357.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-invasive monitoring of response to treatment of glioblastoma (GB) is nowadays carried out using MRI. MRS and MR spectroscopic imaging (MRSI) constitute promising tools for this undertaking. A temozolomide (TMZ) protocol was optimized for GL261 GB. Sixty-three mice were studied by MRI/MRS/MRSI. The spectroscopic information was used for the classification of control brain and untreated and responding GB, and validated against post-mortem immunostainings in selected animals. A classification system was developed, based on the MRSI-sampled metabolome of normal brain parenchyma, untreated and responding GB, with a 93% accuracy. Classification of an independent test set yielded a balanced error rate of 6% or less. Classifications correlated well both with tumor volume changes detected by MRI after two TMZ cycles and with the histopathological data: a significant decrease (p < 0.05) in the proliferation and mitotic rates and a 4.6-fold increase in the apoptotic rate. A surrogate response biomarker based on the linear combination of 12 spectral features has been found in the MRS/MRSI pattern of treated tumors, allowing the non-invasive classification of growing and responding GL261 GB. The methodology described can be applied to preclinical treatment efficacy studies to test new antitumoral drugs, and begets translational potential for early response detection in clinical studies. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 09/2014; · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans.
    Aging cell 07/2014; · 7.55 Impact Factor
  • Source
    Emerging Infectious Diseases 06/2014; 20(6):1062-4. · 6.79 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: A case of protothecosis causing non-ambulatory paraparesis in a dog without clinical evidence of disseminated infection is described. A five-year-old female Labrador retriever was referred with a 10-day history of progressive non-ambulatory paraparesis and lumbar pain as the only physical and neurological abnormalities. Lumbar myelography revealed severe extradural spinal cord compression extending from L4 to L7 vertebrae, and a right hemilaminectomy was performed. Surgical findings included an adherent whitish hard ill-defined mass. Cytology and biopsy results disclosed the presence of algae enclosed in a matrix of chronic inflammatory infiltrate. Culture confirmed the presence of Prototheca species. Neurological improvement occurred within a month, and the dog received antifungal treatment without evidence of clinical disseminated disease for 6 months, but died after a generalised tonic-clonic seizure. Post-mortem examination revealed multiple foci of inflammatory granulomatous infiltrate and algae-like structures in the brain, lumbar intumescence and cauda equina. Prototheca zopfii was identified using molecular biology methods.
    Journal of Small Animal Practice 02/2014; · 1.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Case Description-A 9-year-old male Miniature Poodle was evaluated because of progressive severe right hemiparesis, right forelimb lameness, and signs of cervical pain. Clinical Findings-A low body condition score (2/9) and popliteal lymphadenopathy were detected. Results of a CBC, serum biochemical analyses, urinalysis, cytologic examination of bone marrow and popliteal lymph node aspirates, and serum ELISA were consistent with systemic leishmaniasis. Magnetic resonance imaging of the cervical spinal cord revealed an intramedullary mass extending from the caudal aspect of the C5 vertebral body to the C5-6 intervertebral disk space with a contrast medium-enhanced pattern that had 3 zones (central contrast medium-enhanced core, intermediate isointense zone, and peripheral contrast medium-enhanced ring). Surgical biopsy of the mass was performed by means of a right C5-6 dorsal hemilaminectomy. Results of PCR assays for detection of Leishmania DNA in CSF and tissue biopsy samples were positive. Treatment and Outcome-Treatment for systemic leishmaniasis was initiated. Two months later, body condition, neurologic signs, and gait of the dog had substantially improved; the dog had mild right forelimb paresis at that time. Results of follow-up MRI indicated resolution of the cervical spinal cord lesion. Four months after diagnosis, the dog's neurologic condition was stable. Clinical Relevance-To the authors' knowledge, this report is the first in which clinical findings, clinicopathologic data, and MRI characteristics of an intramedullary inflammatory spinal cord lesion presumptively attributable to leishmaniasis in a dog have been reported, and the first report of CNS leishmaniasis in a dog with MRI resolution and a successful clinical response to treatment.
    Journal of the American Veterinary Medical Association 01/2014; 244(2):200-4. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In human gliomas tissue factor (TF) is overexpressed associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma samples, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. A second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. Immunohistochemical studies, using antibodies against TF, fibrin/fibrinogen and D-dimers were performed on 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III and IV) than in low-grade gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.
    The Veterinary Journal 01/2014; · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prion responsible for the Bovine Spongiform Encephalopathy (BSE) shows unique features when compared with other prions. One of these features is its ability to infect almost all experimentally tested animal models. In the paper published in The Journal of Neuroscience (1) we describe a series of experiments directed toward elucidating which would be the in vivo behavior of BSE if it would infect dogs and rabbits, two alleged prion resistant species. Protein misfolding cyclic amplification (PMCA) was used to generate canidae and leporidae in vitro adapted BSE prions. A characterization of their in vivo pathobiological properties showed that BSE prions were capable not only of adapting to new species but they maintained, in the case of rabbits, their ability to infect transgenic mice expressing human PrP. The remarkable adaptation ability of certain prions implies that any new host species could lead to the emergence of new infectious agents with unpredictable transmission potential. Our results suggest that caution must be taken when considering the use of any mammal derived protein in feedstuffs.
    Prion 11/2013; 7(6). · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis.
    The Canadian veterinary journal. La revue veterinaire canadienne 10/2013; 54(10):948-54. · 0.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An 8-year-old, male Boxer was examined for an acute onset of ambulatory paraparesis. Neurologic examination was consistent with a T3-L3 myelopathy. Myelography revealed an extradural spinal cord compression in the region of the T10-T13 vertebrae. On magnetic resonance (MR) imaging, a well-defined epidural mass lesion was detected. The mass was mildly hyperintense on T1-weighted, hyperintense on T2-weighted and STIR images compared to normal spinal cord and enhanced strongly and homogenously. Postmortem examination confirmed a primary epidural hemangiosarcoma. Findings indicated that the MRI characteristics of spinal epidural hemangiosarcoma may mimic other lesions including meningioma and epidural hemorrhages/hematomas of non-neoplastic etiology.
    Veterinary Radiology &amp Ultrasound 07/2013; · 1.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For most lysosomal storage diseases (LSDs) affecting the CNS, there is currently no cure. The BBB, which limits the bioavailability of drugs administered systemically, and the short half-life of lysosomal enzymes, hamper the development of effective therapies. Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomic recessive LSD caused by a deficiency in sulfamidase, a sulfatase involved in the stepwise degradation of glycosaminoglycan (GAG) heparan sulfate. Here, we demonstrate that intracerebrospinal fluid (intra-CSF) administration of serotype 9 adenoassociated viral vectors (AAV9s) encoding sulfamidase corrects both CNS and somatic pathology in MPS IIIA mice. Following vector administration, enzymatic activity increased throughout the brain and in serum, leading to whole body correction of GAG accumulation and lysosomal pathology, normalization of behavioral deficits, and prolonged survival. To test this strategy in a larger animal, we treated beagle dogs using intracisternal or intracerebroventricular delivery. Administration of sulfamidase-encoding AAV9 resulted in transgenic expression throughout the CNS and liver and increased sulfamidase activity in CSF. High-titer serum antibodies against AAV9 only partially blocked CSF-mediated gene transfer to the brains of dogs. Consistently, anti-AAV antibody titers were lower in CSF than in serum collected from healthy and MPS IIIA-affected children. These results support the clinical translation of this approach for the treatment of MPS IIIA and other LSDs with CNS involvement.
    The Journal of clinical investigation 07/2013; · 15.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An 8-year-old cat was presented with severe neurological deficits secondary to a traumatic cervical spinal cord injury caused by an airgun pellet. This report describes, for the first time, the myelographic findings of a dural rupture in a cat and also describes a bilateral Horner's syndrome in a cat.
    The Canadian veterinary journal. La revue veterinaire canadienne 07/2013; 54(7):679-82. · 0.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present publication is to describe a spontaneous outbreak of leukoencephalomyelopathy in an established European commercial Specific Pathogen Free (SPF) laboratory cat breeder, and to suggest a possible association with long-term feeding with a gamma-irradiated commercial diet.
    12th FELASA-SECAL congress; 06/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 3-year-old, intact female Golden Retriever was presented with acute tetraplegia. Neurologic examination was consistent with a C1-C5 myelopathy. On magnetic resonance (MR) imaging a well-defined, extradural mass was detected within the spinal canal at the level of C1-C2. The mass was isointense to normal spinal cord gray matter on T1-weighted (T1W) images, hyperintense on T2-weighted (T2W), and gradient-echo (GE) images, and enhanced homogeneously after intravenous contrast administration. MR imaging features were mainly consistent with a meningioma. Surgical treatment was refused by the owners, and the dog was euthanized. Postmortem examination demonstrated that the intraspinal mass was a schwannoma.
    Veterinary Radiology &amp Ultrasound 06/2013; · 1.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Feline cutaneous nerve sheath tumours (CNSTs) are uncommonly reported in the skin, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In this study, 26 nerve sheath tumours selected from 337 skin neoplasms of cats were examined. Histologically, they were classified into malignant (MPNSTs) and benign tumours (BPNSTs) based on degree of cellular atypia and polymorphism as well as mitotic rate and diffuse necrosis. CPNSTs were tipically characterised by Antoni A pattern, in some cases associated with Antoni B pattern. In the malignant peripheral nerve sheath tumours (MPNSTs) the polymorphism was marked, while it was mild to moderate in the benign forms (BPNSTs). In the MPNSTs the mitotic activity was generally higher than in the BPNSTs. In five cases, including three MPNSTs and two BPNSTs, there were multinucleated giant cells. Necrotic foci occurred in a BPNST and in two MPNSTs, while osseous/chondroid metaplasia was found in two cases. Immunohistochemically, all the tumours showed a marked diffuse vimentin expression. S-100 protein was expressed in 17 cases, including 81.8% of BPNSTs and 57.14% of MPNSTs. Twenty-five tumours expressed NSE and twenty-four cases showed immunoreaction for laminin. Thirteen tumours were positive for GFAP, while five tumours were positive for SMA. PGP 9.5 expression was detected in all cases, except for two MPNSTs. NGFR was expressed in eleven cases, including four MPNSTs and seven BPNSTs. Ki67 was expressed in twenty tumours without any relationship with morphologic malignancy of the neoplasm. In this case series we confirmed neoplastic spindloid cells with wavy cytoplasm arranged in compact areas, with occasional nuclear palisading or whirls, and interchanged with loosely arranged areas, as the morphological features supporting a diagnosis of CPNST. A constant concurrent expression of vimentin, NSE, and laminin might confirm the diagnosis of PNST in the absence of clear S-100 protein positivity, especially in the malignant forms. In this study, conclusive data were not obtained on the diagnostic relevance of NGFR- and PGP 9.5-expression in feline CPNSTs.
    Research in Veterinary Science 05/2013; · 1.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.
    Journal of Neuroscience 05/2013; 33(18):7778-7786. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The molecular pathogenic mechanisms of prion diseases are far from clear. Genomic analyses have revealed genetic biomarkers potentially involved in prion neuropathology in naturally scrapie-infected sheep, a good animal model of infectious prionopathies. However, these biomarkers must be validated in independent studies at different stages of the disease. The gene and protein expression profiles and protein distribution of six potential genetic biomarkers (i.e., CAPN6, COL1A2, COL3A1, GALA1, MT2A and MTNR1B) are presented here for both the early and terminal stages of scrapie in five different brain regions. Gene transcription changes were confirmed in the medulla oblongata, and the expression profiles were generally similar in other central nervous system regions. The changes were more substantial in clinical animals compared to preclinical animals. The expression of the CAPN6 protein increased in the spinal cord and cerebellum of the clinical and preclinical brains. The distribution of the GALA1 was identified in glial cells from the cerebellum of scrapie-infected animals, GALA1 protein expression was increased in clinical animals in the majority of regions, and the increase of MT2A was in agreement with previous reports. The downregulation of MTNR1B was especially marked in the Purkinje cells. Finally, although collagen genes were downregulated the protein immunostaining did not reveal significant changes between the scrapie-infected and control animals. In conclusion, this study of gene transcription and protein expression and distribution confirm CAPN6, GALA1, MTNR1B and MT2A as potential targets for further prion disease research.
    Veterinary Research 03/2013; 44(1):14. · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Finding a marker of neural stem cells remains a medical research priority. It was reported that the proteins doublecortin and nucleostemin were related with stem/progenitor cells in central nervous system. The aim of the present immunohistochemical study was to evaluate the expression of these proteins and their pattern of distribution in canine brain, including age-related changes, and in non-nervous tissues. We found that doublecortin had a more specific expression pattern, related with neurogenesis and neuronal migration, while nucleostemin was expressed in most cells of almost every tissue studied. The immunolabeling of both proteins decreased with age. We may conclude that nucleostemin is not a specific marker of stem/progenitor cells in the dog. Doublecortin, however, is not an exclusive marker of neural stem cells, but also of neuronal precursors.
    European journal of histochemistry: EJH 01/2013; 57(1):e9. · 2.41 Impact Factor
  • Journal of Comparative Pathology. 01/2013; 148(1):57.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 7-month-old Australian kelpie dog and a 14-month-old Labrador retriever dog were diagnosed with an uncommon form of cerebellar abiotrophy called cerebellar granuloprival degeneration. This was characterized by a loss of the granular neurons with relative sparing of the Purkinje neurons.
    The Canadian veterinary journal. La revue veterinaire canadienne 01/2013; 54(1):55-60. · 0.77 Impact Factor

Publication Stats

972 Citations
357.56 Total Impact Points

Institutions

  • 1994–2014
    • Autonomous University of Barcelona
      • • Centre for Animal Biotechnology and Gene Therapy (CBATEG)
      • • Faculty of Veterinary
      • • Department of Medicine and Animal Surgery
      Cerdanyola del Vallès, Catalonia, Spain
  • 2012
    • Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
      Caesaraugusta, Aragon, Spain
  • 2003–2012
    • CReSA Research Centre for Animal Health
      Cerdanyola del Vallès, Catalonia, Spain
  • 2011
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2005
    • Universidad de León
      • Facultad de Veterinaria
      León, Castile and Leon, Spain
  • 1998
    • University of Cordoba (Spain)
      Cordoue, Andalusia, Spain
  • 1991
    • Complutense University of Madrid
      • Facultad de Veterinaria
      Madrid, Madrid, Spain