Ectopic expression of the atypical HLH FaPRE1 gene determines changes in cell size and morphology.

PACLOBUTRAZOL RESISTANCE (PRE) genes code atypical HLH transcriptional regulators characterized by the absence of a DNA-binding domain but present an HLH dimerization domain. In vegetative tissues, the function of these HLH proteins has been related with cell elongation processes. In strawberry, three FaPRE genes are expressed, two of them (FaPRE2 and FaPRE3) in vegetative tissues while FaPRE1 is fruit receptacle-specific. Ubiquitous FaPRE1 accumulation produced elongated flower receptacles and plants due to the elongation of the main aerial vegetative organs, with the exception of leaves. Histological analysis clearly demonstrated that the observed phenotype was due to significant changes in the parenchymal cell's morphology. In addition, transcriptomic studies of the transgenic elongated flower receptacles allowed to identify a small group of differentially expressed genes that encode cell wall-modifying enzymes. Together, the data seem to indicate that, in the strawberry plant vegetative organs, FaPRE proteins could modulate the expression of genes related with the determination of the size and shape of the parenchymal cells.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso / Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case

Introducción: La falta de criterios homogéneos aceptados para la definición de algunas de las patologías desmielinizantes dificulta la caracterización diagnóstica limitando la reproducibilidad de los resultados y las recomendaciones terapéuticas. Especialmente controvertidas son las formas de encefalomielitis recurrentes (EAD-RR) y otras formas infrecuentes de neuromielitis óptica (NMO).Objetivo: Describimos la evolución clínico-radiológica de un caso de EAD-RR del adulto versus NMO, seguida durante 9 años. Paciente y métodos: La paciente debutó con síntomas severos de rombencefalomielitis y la resonancia magnética (RM) craneal y medular mostraron lesiones extensas, con captación de gadolinio en el tronco encefálico y de la médula, acorde con los síntomas clínicos de la paciente. Se excluyó etiología infecciosa, el índice IgG fue normal y fueron negativos los anticuerpos para NMO. Tras tratamiento con corticoides por vía intravenosa y plasmaféresis la recuperación del episodio fue excelente. Durante el seguimiento ha presentado 7 recurrencias, preferentemente medulares, con buena recuperación, que reproducen con severidad variable los mismos síntomas. Desde el inicio ha recibido tratamiento inmunosupresor. Conclusiones: Nuestro caso comparte características clínicas con EAD-RR y NMO e ilustra que, pese a los criterios vigentes, la caracterización diagnóstica de estas entidades no es fácil (AU)

Introduction: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. Objective:To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. Patient and methods: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning.Conclusions: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria (AU)

Long-lasting treatment effect of rituximab in MuSK myasthenia.

OBJECTIVE: Rituximab has emerged as an efficacious option for drug-resistant myasthenia gravis (MG). However, reports published only describe the short-term follow-up of patients treated and little is known about their long-term clinical and immunologic evolution. Our objective was to report the clinical and immunologic long-term follow-up of 17 patients (6 MuSK+MG and 11 AChR+MG) and compare the response between AChR+MG and MuSK+MG patients. METHODS: Myasthenia Gravis Foundation America postintervention status and changes in treatment and antibody titers were periodically determined. Lymphocyte subpopulations, total immunoglobulin, immunoglobulin G (IgG) anti-MuSK subclasses, and anti-tetanus toxoid IgG before and after treatment were also studied. RESULTS: After a mean post-treatment period of 31 months, 10 of the AChR+MG patients improved but 6 of them needed reinfusions. In contrast, all MuSK+MG patients achieved a remission (4/6) or minimal manifestations (2/6) status and no reinfusions were needed. Consequently, in the MuSK+MG group, prednisone doses were significantly reduced and concomitant immunosuppressants could be withdrawn. Clinical improvement was associated with a significant decrease in the antibody titers only in the 6 MuSK+MG patients. At last follow-up MuSK antibodies were negative in 3 of these patients and showed a decrease of over 80% in the other 3. CONCLUSION: In view of the long-lasting benefit observed in MuSK+MG patients, we recommend to use rituximab as an early therapeutic option in this group of patients with MG if they do not respond to prednisone. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IV rituximab improves the clinical and immunologic status of patients with MuSK+MG.

[Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case]. / ¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso.

INTRODUCTION: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. OBJECTIVE: To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. PATIENT AND METHODS: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning. CONCLUSIONS: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria.

[Catastrophic neuromuscular diseases]. / Enfermedades neuromusculares catastrófi cas.

Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies).

Enfermedades neuromusculares catastróficas / Catastrophic neuromuscular diseases

El neurólogo debe anticipar y reconocer el inicio de la insuficiencia respiratoria en los pacientes neuromusculares. La sintomatología varía en función de la velocidad de instauración de la debilidad de la musculatura respiratoria. Las situaciones de catástrofe sue- len acontecer en 3 supuestos clínicos: 1) manejo incorrecto de una insuficiencia respiratoria aguda de origen neuromuscular, disautonomía o durante una anestesia general a pacientes neuromusculares; 2) pronóstico y tratamiento erróneos por falta de un diagnóstico acertado; esta situación es más frecuente en pacientes críticos dependientes de un ventilador con debilidad muscular asociada, en el diferencial de neuropatías agudas o enfermedad de la neurona motora, y 3) inadecuada actuación médica en el paciente neuromuscular con diagnóstico definido, pero con larga evolución (esclerosis lateral amiotrófica, atrofia muscular espinal, distrofia miotónica y otras distrofias musculares) (AU)

Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies) (AU)

Desarrollo de una vía clínica para la atención a pacientes con esclerosis lateral amiotrófica en un ámbito regional. Red de Atención de ELA-Comunidad de Madrid / Development of a clinical pathway for the attention of patients with amyotrophic lateral sclerosis in a regional network. ALS Assistance Network-Comunidad de Madrid

Introducción. La esclerosis lateral amiotrófica (ELA) precisa una atención multidisciplinaria compleja. Las vías clínicas son planes asistenciales para determinadas enfermedades con curso predecible establecidas en centros aislados, no en regiones multicéntricas. El objetivo es desarrollar una vía clínica capaz de organizar y homogeneizar la atención en la Red de Atención de ELA-Comunidad de Madrid constituida por cinco hospitales, desde el inicio hasta el fin de la enfermedad.Métodos. Neurólogos de estos hospitales y miembros del Servicio Madrileño de Salud en sucesivas reuniones revisaron las guías terapéuticas publicadas y otros documentos utilizados en la atención de la ELA y desarrollaron una vía clínica adaptando la información a la realidad sociosanitaria de la Comunidad de Madrid siguiendo el modelo FOCUSPDCA para el desarrollo de la misma.Resultados. Se crea una vía clínica compuesta por una matriz cientificotécnica que ordena la atención a los pacientes en relación al diagnóstico y tratamiento según el grado de afectación y un cronograma. Se acompaña de unos documentos de información a los pacientes sobre la enfermedad y las pruebas a realizar y evaluación de la atención recibida. Se establecen los estándares a alcanzar en la atención para promover la mejora continua asistencial.Conclusiones. La vía clínica para la atención de la ELA en una red regional organiza la atención y cuidados que deben recibir los pacientes desde el inicio de los síntomas hasta el fin de la enfermedad. Esta ordenación y homogenización mejora la calidad asistencial, disminuye la variabilidad y racionaliza el uso de los recursos sanitarios

Introduction. Amyotrophic lateral sclerosis (ALS) requires complex multidisciplinary attention. Clinical pathways are assistance plans for certain diseases with a predictable course. These plans are established in isolated centers, not in multicenter regions. The aim is to develop a clinical pathway capable of organizing and homogenizing assistance given in ALS Assistance Network-Comunidad de Madrid which is made up of five hospitals, from the beginning until the end of the disease.Methods. In successive meetings, neurologists of these hospitals and members of the Madrid Health Service evaluated published therapeutic guidelines and other documents used in ALS assistance. A clinical pathway was developed adapting this information to social-health care conditions in the Comunidad de Madrid following the FOCUS-PDCA model.Results. A clinical pathway was created consisting of a scientist-technical framework which arranges the attention in relationship to the diagnosis and treatment, according to the degree of disease progression and a chronogram. This is accompanied by several patient information documents on the disease and the tests that are required, and a patient assistance evaluation form. The standards are established to reach and to promote 354 constant improvement in patient care.Conclusions. Clinical pathway for the ALS assistance in a regional network organizes the attention and cares that the patients must receive from the beginning to the end of the disease. This arrangement and homogenization of the attention improves the quality of patient care, diminishes variability and rationalizes the use of the health care resources

[Development of a clinical pathway for the attention of patients with amyotrophic lateral sclerosis in a regional network. ALS Assistance Network-Comunidad de Madrid]. / Desarrollo de una vía clínica para la atención a pacientes con esclerosis lateral amiotrófica en un ámbito regional. Red de Atención de ELA-Comunidad de Madrid.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) requires complex multidisciplinary attention. Clinical pathways are assistance plans for certain diseases with a predictable course. These plans are established in isolated centers, not in multicenter regions. The aim is to develop a clinical pathway capable of organizing and homogenizing assistance given in ALS Assistance Network-Comunidad de Madrid which is made up of five hospitals, from the beginning until the end of the disease. METHODS: In successive meetings, neurologists of these hospitals and members of the Madrid Health Service evaluated published therapeutic guidelines and other documents used in ALS assistance. A clinical pathway was developed adapting this information to social-health care conditions in the Comunidad de Madrid following the FOCUS-PDCA model. RESULTS: A clinical pathway was created consisting of a scientist-technical framework which arranges the attention in relationship to the diagnosis and treatment, according to the degree of disease progression and a chronogram. This is accompanied by several patient information documents on the disease and the tests that are required, and a patient assistance evaluation form. The standards are established to reach and to promote 354 constant improvement in patient care. CONCLUSIONS: Clinical pathway for the ALS assistance in a regional network organizes the attention and cares that the patients must receive from the beginning to the end of the disease. This arrangement and homogenization of the attention improves the quality of patient care, diminishes variability and rationalizes the use of the health care resources.

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.

Cloning, expression and immunolocalization pattern of a cinnamyl alcohol dehydrogenase gene from strawberry (Fragaria x ananassa cv. Chandler).

Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) catalyses the conversion of p-hydroxy-cinnamaldehydes to the corresponding alcohols and is considered a key enzyme in lignin biosynthesis. By a differential screening of a strawberry (Fragariax ananassa cv. Chandler) fruit specific subtractive cDNA library, a full-length clone corresponding to a cad gene was isolated (Fxacad1). Northern blot and quantitative real time PCR studies indicated that the strawberry Fxacad1 gene is expressed in fruits, runners, leaves, and flowers but not in roots. In addition, the gene presented a differential expression in fruits along the ripening process. Moreover, by screening of a strawberry genomic library a cad gene was isolated (Fxacad2). Similar to that found in other cad genes from higher plants, this strawberry cad gene is structured in five exons and four introns. Southern blot analyses suggest that, probably, a small cad gene family exists in strawberry. RT-PCR studies indicated that only the Fxacad1 gene was expressed in all the fruit ripening stages and vegetative tissues analysed. The Fxacad1 cDNA was expressed in E. coli cells and the corresponding protein was used to raise antibodies against the strawberry CAD polypeptide. The antibodies obtained were used for immunolocalization studies. The results showed that the CAD polypeptide was localized in lignifying cells of all the tissues examined (achenes, fruit receptacles, runners, leaves, pedicels, and flowers). Additionally, the cDNA was also expressed in yeast (Pichia pastoris) as an extracellular protein. The recombinant protein showed activity with the characteristic substrates of CAD enzymes from angiosperms, indicating that the gene cloned corresponds to a CAD protein.

A fruit-specific and developmentally regulated endopolygalacturonase gene from strawberry (Fragaria x ananassa cv. Chandler).

A fruit-specific and developmentally regulated polygalacturonase gene (spG gene) from strawberry (Fragaria x ananassa cv. Chandler) has been cloned and characterized at a molecular and physiological level. Comparison analysis of the corresponding deduced sPG protein have shown that this strawberry gene is similar to Clade A endopolygalacturonase genes. Moreover, the spatio-temporal and hormonal gene expression pattern suggests a close relationship between the expression of this gene and the onset of the strawberry fruit ripening process and agrees with that of the production of oligosaccharins which have already been described as active molecules involved in fruit ripening. The results are discussed in terms of a putative role of this enzyme in the release of oligosaccharins from the strawberry fruit cell wall.

[Thymectomy in myasthenia gravis]. / Timectomía en la miastenia gravis.

OBJECTIVE: To analyze outcome after thymectomy in patients with myasthenia gravis (MG). MATERIAL AND METHODS: Thirty-five patients with MG underwent surgery in our service between June 1987 and June 1998. Ten had associated thymomas. Preoperative Osserman classification showed 2 at level I, 20 at level IIA, 11 at level IIB and 2 at level III. Extended thymectomy through a medial sternotomy was performed in all. RESULTS: Postoperative complications developed in three patients (1 medullary aplasia, 1 postoperative reintubation, 1 myasthenic crisis). Mean follow-up was 89 months, with 22.8% achieving complete remission and 97.1% reporting improvements. The results were similar in the 10 patients with thymomas (20% full remission and 90% showing improvement). By DeFilippi classification, 22.8% were in class 1, 22.8% in class 2, 51.4% in class 3 and 2.8% in class 4. By Osserman classification, 9 were in the same category before and after surgery, 12 had improved one level, 10 had improved 2 levels, 3 had improved 3 levels and 1 patient had improved 4 levels. CONCLUSION: Thymectomy is an appropriate therapeutic procedure in the multidisciplinary treatment of patients with MG and it is the approach of choice for patients with associated thymomas. The intra- and post-operative complication rate is low and the rate of clinical improvement is high.

[Segmental motor paralysis caused by the varicella zoster virus. Clinical study and functional prognosis]. / Parálisis motora segmentaria por virus varicela-zoster. Estudio clínico y pronóstico funcional.

INTRODUCTION: Segmental motor paralysis of the limbs (SMP) complicates 2-3% of the cases of cutaneous herpes zoster. Viral invasion and inflammation of the motor neurons of the anterior horn cells by the varicella-zoster virus (VVZ) causes clinical weakness at the same time and site as the cutaneous eruption. OBJECTIVES: To analyze the clinical findings, complementary investigations and functional prognosis of patients with SMP at brachial plexus and lumbosacral levels. PATIENTS AND METHODS: We made a retrospective study of 10 patients with SMP admitted to the Hospital Universitario Gregorio Maranon de Madrid during 1989-1999, aged between 38 and 84 years (6 women, 4 men). Neurological examination was done, including muscle balance, complementary studies including microbiology (serum and CSF serology, viral PCR-ADN), neurophysiology using MNR of the spine and plexuses and functional prognosis on the NDS, NSS and RANKIN scales. RESULTS: There is a close relationship between dermatome and myotome involvement (90%). The brachial and lumbosacral plexuses were equally affected (50%). Plasma and CSF VVZ serology was positive in 50% of the cases, permitting diagnosis of a patient with no cutaneous lesions (zoster sine herpete). Denervation of the myotomes involved and the paraspinal muscles was shown on neurophysiological studies. In most cases there was functional improvement, with complete functional recovery in 80% of the cases after 12 months. CONCLUSIONS: VVZ should be considered amongst the aetiologies of SMP, even in the absence of cutaneous lesions (zoster sine herpete). The SMP coincides in time and place with the dermatome lesions. In most patients there is complete functional recovery within 12 months.

Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium.

Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMOR) system and induces apoptosis in transformed cells. Using a cytofluorimetric approach we have determined that capsaicin induces a rapid increase of reactive oxygen species (ROS) followed by a subsequent disruption of the transmembrane mitochondrial potential (DeltaPsim) and DNA nuclear loss in transformed cell lines and in mitogen activated human T cells. This apoptotic pathway is biochemically different from the typical one induced by either ceramide or edelfosine where, in our system, the DeltaPsim dissipation precedes the generation of reactive oxygen species. Neither production of ROS nor apoptosis was found in capsaicin-treated resting T cells where the activity of the PMOR system is minimal when compared with mitogen activated or transformed T cells. Capsaicin also induces Ca2+ mobilization in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS generation or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and that the apoptotic pathway may be separated from the one that mobilizes calcium. Moreover, we present data for the implication of a possible vanilloid receptor in calcium mobilization, but not in ROS generation. These results provide evidence that the PMOR system may be an interesting target to design antitumoral and anti-inflammatory drugs.

[Neurological complications of Mediterranean boutonneuse fever. Presentation of a case of acute encephalomeningomyelitis and review of the literature]. / Complicaciones neurológicas de la fiebre botonosa mediterránea. Presentación de un caso de encefalomeningomielitis aguda y revisión de la literatura.

Mediterranean spotted fever is an infectious disease due to Rickettsia conorii usually considered as benign; however, 10% of cases may have severe complications. We report a patient with celiac disease who developed encephalomeningomyelitis secondary to Mediterranean spotted fever. Meningoencephalitic involvement occurred during the acute phase, with myelitis appearing early during convalescence, as acute onset paraplegia involving the lumbosacral spinal cord. A magnetic resonance study showed multifocal white matter disturbances, with no lesions in the spinal cord. One month following onset, R. conorii antibodies serum level was 1/640. A cutaneous biopsy performed during the acute phase revealed endothelial hyperplasia, intraluminal thrombosis and lymphocytic perivascular infiltrate. Several immunological disturbances were found (circulating immune complexes, antinuclear antibodies, IgG paraproteinemia). The development of a systemic vasculitis is the major pathogenetic factor in the origin of systemic complications of Mediterranean spotted fever. We review the neurological syndromes reported in association with R. conorii infection. Our case is the second described as acute myelopathy complicating Mediterranean spotted fever.