Intraneural microcystic lymphatic malformation of the ulnar nerve at the Guyon canal: Unusual cause of ulnar pain in a child.

We present a case of an unusual cause of ulnar pain on a 9-year-old patient. The patient had pain on the ulnar side of the wrist after a fall. MRI showed a poorly defined lesion on the ulnar nerve at Guyon's canal. The initial diagnosis was traumatic neuropathy. Following conservative treatment of symptoms for one year, the pain started again. Therefore, a new MRI was performed where progression of the lesion was observed. Excision of the lesion was performed and the specimen sent for pathologic analysis. The diagnosis was of microcystic lymphatic malformation. The patient had a satisfactory evolution, with complete resolution. This is the first description of a microcystic lymphatic malformation in an intraneuronal location.

p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture.

The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B-cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell-type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73-deficient ependymal cells have noticeably impaired ciliogenesis and they fail to organize into pinwheels, disrupting SVZ niche structure and function. Therefore, p73 is essential for appropriate ependymal cell maturation and the establishment of the neurogenic niche architecture. Accordingly, lack of p73 results in impaired neurogenesis. Moreover, p73 is required for translational planar cell polarity establishment, since p73 deficiency results in profound defects in cilia organization in individual cells and in intercellular patch orientation. Thus, our data reveal a completely new function of p73, independent of p53, in the neurogenic architecture of the SVZ of rodent brain and in the establishment of ependymal planar cell polarity with important implications in neurogenesis. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 730-747, 2016.

Characterization and isolation of immature neurons of the adult mouse piriform cortex.

Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA-NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar-pyramidal transitional neurons. Most were also immunoreactive for DCX, confirming their immature nature. In agreement with this, detection of PSA-NCAM combined with that of different cell lineage-specific antigens revealed that most PSA-NCAM positive cells did not co-express markers of glial cells or mature neurons. Their time of origin was evaluated by birthdating experiments with halogenated nucleosides performed at different developmental stages and in adulthood. We found that virtually all cells in this paleocortical region, including PSA-NCAM-positive cells, are born during fetal development. In addition, proliferation analyses in adult mice revealed that very few cells were cycling in layer II of the piriform cortex and that none of them was PSA-NCAM-positive. Moreover, we have established conditions to isolate and culture these immature neurons in the adult piriform cortex layer II. We find that although they can survive under certain conditions, they do not proliferate in vitro either. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 748-763, 2016.

Prosurvival effect of human wild-type alpha-synuclein on MPTP-induced toxicity to central but not peripheral catecholaminergic neurons isolated from transgenic mice.

In the present work we report the generation of a new line of alpha-synuclein (alpha-SYN) transgenic mice in which the human wild-type alpha-SYN cDNA is expressed under the control of a tyrosine hydroxylase (TH) promoter. We provide evidence that the ectopic protein is found in TH expressing neurons of both central and peripheral nervous systems. The transgene is expressed very early in development coinciding with the activity of the TH promoter and in the adult brain the human protein distributes normally to the nerve endings and cell bodies of dopaminergic nigral neurons without any evidence of abnormal aggregation. Our results indicate that expression of human wild-type alpha-SYN does not affect normal development or maintenance of TH immunoreactive nigral neurons, striatal dopamine content, or locomotor activity. Systemic administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a loss of TH immunoreactive nigral neurons and terminals and of dopamine levels to the same degree in both transgenic and non-transgenic adult mice. Intoxication also results in a similar loss of cardiac noradrenaline in both genotypes. Surprisingly, cultured transgenic ventral mesencephalic fetal dopaminergic neurons exhibit complete resistance to cell death induced by 1-methyl-4-phenylpyridinium ion (MPP(+)) intoxication, without changes in dopamine transporter (DAT) surface levels. Interestingly, this protection is not observed in other populations of catecholaminergic neurons such as peripheral sympathetic neurons, despite their high sensitivity to MPP(+)in vitro.

Abnormal development of pacinian corpuscles in double trkB;trkC knockout mice.

Pacinian corpuscles depend on either Aalpha or Abeta nerve fibers of the large- and intermediate-sized sensory neurons for the development and maintenance of the structural integrity. These neurons express TrkB and TrkC, two members of the family of signal transducing neurotrophin receptors, and mice lacking TrkB and TrkC lost specific neurons and the sensory corpuscles connected to them. The impact of single or double targeted mutations in trkB and trkC genes in the development of Pacinian corpuscles was investigated in 25-day-old mice using immunohistochemistry and ultrastructural techniques. Single mutations on trkB or trkC genes were without effect on the structure and S100 protein expression, and caused a slight reduction in the number of corpuscles. In mice carrying a double mutation on trkB;trkC genes most of the corpuscles were normal with a reduction of 17% in trkB-/-;trkC+/- mice, and 8% in trkB +/-;trkC -/- mice. Furthermore, a subset of the remaining Pacinian corpuscles (23% in trkB-/-;trkC+/- mice; 3% in trkB+/-;trkC-/- mice) were hypoplasic or atrophic. Present results strongly suggest that the development of a subset of murine Pacinian corpuscles is regulated by the Trk-neurotrophin system, especially TrkB, acting both at neuronal and/or peripheral level. The precise function of each member of this complex in the corpuscular morphogenesis remains to be elucidated, though.

Dermatitis de contacto liquenoide por reveladores fotográficos / No disponible

Los agentes de revelado fotográfico son derivados de la parafenilendiamina, que pueden actuar como irritantes y/o sensibilizantes cutáneos en trabajadores de procesos fotográficos, manifestándose las lesiones no sólo en forma de eczema de contacto, sino también como lesiones liquenoides. La incidencia de dermatosis profesionales por reveladores de color ha disminuido en los últimos años debido a la automatización de los procesos de revelado y a la aparición de la fotografía digital. Presentamos un caso de dermatitis de contacto liquenoide secundaria al revelador CD2 en un trabajador de laboratorio fotográfico automatizado que ocasionalmente reparaba las averías que se presentaban en la maquinaria. Las lesiones eran clínica e histológicamente liquenoides y las pruebas epicutáneas resultaron positivas a CD2. Nuestro caso presenta además la particularidad de la diseminación de las lesiones hacia zonas donde no era evidente el contacto con el líquido revelador

Colour developing agents, derivatives of paraphenylendiamine, can be both irritants and sensitizers in photographic processing workers. They cause allergic contact dermatitis and also lichenoid reactions. The incidence of occupational dermatosis from colour developers has decreased in the last years because of the automation in the developer processing and the emergence of digital photography. We present a case of lichenoid contact dermatitis in a mechanized photographic laboratory worker, who occasionally repaired machinery's damages. Lesions were clinical and histhopatological lichenoid and patch test were positives to CD2. Our case presents the singularity of the dissemination of the lesions to areas of the skin where it was not evident the contact with the colour developers agents

[Splanchnic remodeling secondary to experimental prehepatic portal hypertension]. / Remodelación esplácnica secundaria a hipertensión portal prehepática experimental.

OBJECTIVE: Portal hypertension as an inducer of intestinal inflammatory response would cause epithelial and splanchnic vascular remodeling in the long-term. This experimental study was carried out to verify this hypothesis. METHOD: Structural alterations characteristic of intestinal epithelial and mesenteric vascular remodeling, the density of goblet cells and the diameter of mesenteric vein branches were studied, respectively, in rats with partial portal vein ligation in the short (1 month) and long-term (1 year). RESULTS: Hyperplasia of goblet cells in the small intestine (duodenum, jejunum, ileum) is maximum after 1 year of evolution of the portal hypertension and is associated with dilatation of the distal branches (3rd and 4th order) of the superior mesenteric vein. CONCLUSION: Long-term splanchnic remodeling in experimental portal hypertension suggests the existence of a chronic inflammatory process in this clinical condition.

Remodelación esplácnica secundaria e hipertensión portal prehepática experimental / Splanchnic remodeling secondary to experimental prehepatic portal hipertensión

Objetivo: La hipertensión portal, en tanto que inductora de una respuesta inflamatoria intestinal, causaría a largo plazo remodelación epitelial y vascular esplácnicas. Con el objeto de verificar esta hipótesis se ha realizado éste trabajo experimental. Método: Se han estudiado como alteraciones estructurales propias de remodelación epitelial intestinal y vascular mesentérica la densidad de células caliciformes y el diámetro de las ramas de la vena mesentérica, respectivamente, en ratas con ligadura parcial de la vena porta a corto (1 mes) y largo (1 año) plazo. Resultados: La hiperplasia de células caliciforrnes en intestino delgado es máxima al año de evolución de la hipertensión portal y se asocia con dilatación de las ramas distales (3er y 4° orden) de la vena mesentérica superior. Conclusión: La remodelación esplácnica que ocurre a largo plazo en la hipertensión portal experimental sugiere la existencia de un proceso inflamatorio crónico en ésta patología

Objective: Portal hypertension as an inducer of intestinal inflammatory response would cause epithelial and splanchnic vascular remodeling in the long-termo This experimental study was carried out to verify this hypothesis. Method: Structural alterations characteristic of intestinal epithelial and mesenteric vascular remodeling, the density of goblet cells and the diameter of mesenteric vein branches were studied, respectively, in rats with partial portal vein ligation in the short (1 month) and long-term (1 year ). Results: Hyperplasia of goblet cells in the small intestine (duodenum, jejunum, ileum) is maximum after I year of evolution ofthe portal hypertension and is associated with dilatation of the distal branches (3rd and 4th order) of the superior mesenteric vein. Conclusion: Long-term splanchnic remodeling in experimental portal hypertension suggests the existence of a chronic inflammatory process in this clinical condition

[Clinical importance of the CagA and VacA proteins and of the host factores in the development of peptic ulcer in patients infected by Helicobacter pylori]. / Relevancia clínica de las proteínas CagA y VacA y de los factores del huésped en el desarrollo de úlcera péptica en pacientes infectados por Helicobacter pylori.

OBJECTIVE: Demonstrate the role of the virulence factors of Helicobacter pylori, the sex, and tobacco and alcohol use in the development of peptic ulcer in patients infected by H. pylori. PATIENTS AND METHODS: One hundred and seventy-four patient with dyspepsia were studied after they went consecutively for gastroscopy. The diagnosis of infection by H. pylori was carried out by culture and/or histology. Through western-blot the presence of specific anti-H. pylori antibodies was determined. The tobacco and alcohol use data were collected. RESULTS: One hundred and twenty-five patients (32 with ulceration, 12 with duodenitis and 81 with functional dyspepsia) showed H. pylori infection with anti-bacterium IgG antibodies. The detection of the proteins CagA and VacA, male sex and heavy consumption of alcohol and tobacco were associated with the finding of peptic ulcer. In the multivariate analysis only anti-CagA antibodies (OR: 4.1; 95% CI: 1.1-15.3; p = 0.036), anti-VacA (OR: 3.9; 95% CI: 1.4-10.8; p = 0.009) and male sex (OR: 3.1; 95% CI: 1.2-8.3; p = 0.02) were associated with the ulcerative disease. CONCLUSIONS: The proteins CagA and VacA, and the male sex, contribute independent risk factors for peptic ulcer in patients infected by H. pylori.

Relevancia clínica de las proteínas CagA y VacAy de los factores del huésped en el desarrollo de úlcera péptica en pacientes infectadospor Helicobacter pylori / Clinical importance of the CagA and VacA proteins and of the host factores in the development of peptic ulcer in patients infected by Helicobacter pylori

Objetivo. Determinar el papel de los factores de virulencia de Helicobacter pylori, el sexo y el consumo de tabaco y alcohol en el desarrollo de úlcera péptica en pacientes infectados por H. pylori. Pacientes y métodos. Se estudiaron 174 pacientes dispépticos que acudieron consecutivamente a realizarse una gastroscopia. El diagnóstico de infección por H. pylori se realizó por cultivo y/o histología. La presencia de anticuerpos específicos anti-H. pylori se determinó mediante western-blot. Se recogió el consumo de tabaco y alcohol. Resultados. Ciento veinticinco pacientes (32 con úlcera, 12 con duodenitis y 81 con dispepsia funcional) fueron diagnosticados de infección por H. pylori con anticuerpos IgG frente a la bacteria. La detección de las proteínas CagA y VacA, el sexo masculino y el consumo elevado de alcohol y tabaco se asociaron con el hallazgo de úlcera péptica. En el análisis multivariante sólo los anticuerpos anti-CagA (odds ratio [OR]: 4,1; intervalo de confianza [IC] 95 por ciento: 1,1-15,3; p = 0,036), anti-VacA (OR: 3,9; IC 95 por ciento: 1,4-10,8; p = 0,009) y el sexo masculino (OR: 3,1; IC 95 por ciento: 1,2-8,3; p = 0,02) se asociaron con la enfermedad ulcerosa. Conclusiones. Las proteínas CagA y VacA y el sexo masculino contribuyen de manera independiente al riesgo de padecer úlcera péptica en pacientes infectados por H. pylori (AU)

p75NTR in the spleen: age-dependent changes, effect of NGF and 4-methylcatechol treatment, and structural changes in p75NTR-deficient mice.

In addition to their well-known actions within the nervous system, neurotrophins and their receptors are involved in immune system functioning, as demonstrated by their wide distribution in lymphoid tissues and their in vitro actions on immunocompetent cells. Nevertheless, the in vivo roles of neurotrophin-receptor systems in lymphoid tissues, as well as the scope of their influence throughout development and adulthood, are yet to be clarified. In the present study, we used combined morphological and immunohistochemical techniques to investigate the presence and cellular localization of p75NTR, the pan-neurotrophin receptor protein, in rat spleen from newborns to aging individuals, and the structural and innervation changes in the spleens of p75NTR-deficient mice. In rats, p75NTR was expressed by splenic nerve fibers and dendritic cells in an age-regulated fashion, with maximal expression detected at 2 weeks. Consistently, the spleens of newborn mice lacking this receptor protein showed no signs of ingrowing sympathetic fibers, along with an absence of defined white pulp areas. The present findings suggest a prolonged role of p75NTR in the physiology of the spleen; at least during the embryonic development period, the receptor may be critical for correct innervation and compartmentalization processes to occur.

Development and evolution of inner ear sensory epithelia and their innervation.

The development and evolution of the inner ear sensory patches and their innervation is reviewed. Recent molecular developmental data suggest that development of these sensory patches is a developmental recapitulation of the evolutionary history. These data suggest that the ear generates multiple, functionally diverse sensory epithelia by dividing a single sensory primordium. Those epithelia will establish distinct identities through the overlapping expression of genes of which only a few are currently known. One of these distinctions is the unique pattern of hair cell polarity. A hypothesis is presented on how the hair cell polarity may relate to the progressive segregation of the six sensory epithelia. Besides being markers for sensory epithelia development, neurotrophins are also expressed in delaminating cells that migrate toward the developing vestibular and cochlear ganglia. These delaminating cells originate from multiple sites at or near the developing sensory epithelia and some also express neuronal markers such as NeuroD. The differential origin of precursors raises the possibility that some sensory neurons acquire positional information before they delaminate the ear. Such an identity of these delaminating sensory neurons may be used both to navigate their dendrites to the area they delaminated from, as well as to help them navigate to their central target. The navigational properties of sensory neurons as well as the acquisition of discrete sensory patch phenotypes implies a much more sophisticated subdivision of the developing otocyst than the few available gene expression studies suggest.

Sensing life: regulation of sensory neuron survival by neurotrophins.

Neurotrophins are a family of structurally and functionally related neurotrophic factors which, in mammals, include: nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and NT-4/5. In addition to their canonical role in promoting neuronal survival, these molecules appear to regulate multiple aspects of the development of the nervous system in vertebrates, including neuronal differentiation, axon elongation and target innervation, among others. Actions of neurotrophins and of their receptors in vivo are being analyzed by loss-of-function or gain-of-function experiments in mice. Here, we review the phenotypes of the primary sensory system in these mutant mouse strains and the different strategies specifically involved in the regulation of neuronal survival by neurotrophins in this portion of the nervous system.

Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression.

Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) in cochlear innervation patterning in different null mutants. We now show that all NT-3 null mutants have a similar phenotype and lose all neurons in the basal turn of the cochlea. To understand these longitudinal deficits in neurotrophin mutants, we have compared the development of the deficit in the NT-3 mutant to the spatial-temporal expression patterns of brain-derived neurotrophic factor (BDNF) and NT-3, using lacZ reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In the NT-3 mutant, almost normal numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and E15.5. During the period preceding apoptosis, NT-3 is expressed in supporting cells, whereas BDNF is expressed mainly in hair cells, which become postmitotic in an apical to basal temporal gradient. During the period of neuronal loss, BDNF is absent from the basal cochlea, accounting for the complete loss of basal turn neurons in the NT-3 mutant. The spatial gradients of neuronal loss in these two mutants appear attributable to spatial-temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors, TrkB and TrkC, in spiral sensory neurons and thus do not relate to the basal turn loss. Mice in which NT-3 was replaced by BDNF show a qualitative normal pattern of innervation at E13.5. This suggests that the pattern of expression of neurotrophins rather than their receptors is essential for the spatial loss of spiral sensory neurons in NT-3 null mutants.

[Primary effusion lymphoma associated with type-8 human herpes virus infection]. / Linfoma primario de cavidades asociado a infección por herpes virus humano tipo 8.

Primary Effusion Lymphoma is an unusual entity and it has been described as a subset associated with human herpes virus 8 infection in homosexual males with AIDS. Its inclusion as a new entity in the Revised European-American Lymphoma Classification has been recommended. The case in which it is presented is a 47-year-old man, diagnosed with AIDS two years ago, who came with Kaposi's sarcoma. Nowadays, he has a right pleural effusion and a thoracentesis has been carried out. We obtain 10 ml of haemorrhagic fluid which is processed by standard methods. The morphologic study reveals a non-Hodgkin's lymphoma of high-grade. The immunophenotypic study shows a lymphoid neoplasm of indeterminate lineage and high proliferation index. It confirms the HHV-8 in the neoplastic cells by PCR. The diagnosis is a non-Hodgkin's lymphoma of high-grade compatible with Primary Effusion Lymphoma.

Linfoma primario de cavidades asociado a infección por herpes virus humano tipo 8 / Primary effusion lymphoma associated with human herpes virus 8 infection

El linfoma primario de cavidades es una rara entidad, habiéndose descrito un subgrupo asociado a infección por HHV-8 en varones homosexuales con Sida, recomendándose su inclusión como una nueva entidad en la Clasificación Revisada Europea-Americana de los Linfomas. El caso que se presenta es el de un varón de 47 años, diagnosticado de Sida hace dos, que debutó con sarcoma de Kaposi. En la actualidad, se presenta con un derrame pleural derecho y se realiza toracocentesis. Se obtienen 10ml de un líquido hemorrágico, que se procesa de forma rutinaria. El estudio morfológico revela un linfoma no Hodgkin de alto grado. El estudio inmunofenotípico pone de manifiesto una neoplasia de estirpe linfoide, de línea indeterminada y de alto índice proliferativo. Se confirma la infección por HHV-8 en las células neoplásicas, mediante PCR. El diagnóstico es linfoma no Hodgkin de alto grado compatible con linfoma primario de cavidades (AU)

Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.

alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.

NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors.

Superior cervical ganglia of postnatal mice with a targeted disruption of the gene for neurotrophin-3 have 50% fewer neurons than those of wild-type mice. In culture, neurotrophin-3 increases the survival of proliferating sympathetic precursors. Both precursor death (W. ElShamy et al., 1996, Development 122, 491-500) and, more recently, neuronal death (S. Wyatt et al., 1997, EMBO J. 16, 3115-3123) have been described in mice lacking NT-3. Consistent with the second report, we found that, in vivo, neurogenesis and precursor survival were unaffected by the absence of neurotrophin-3 but neuronal survival was compromised so that only 50% of the normal number of neurons survived to birth. At the time of neuron loss, neurotrophin-3 expression, assayed with a lacZ reporter, was detected in sympathetic target tissues and blood vessels, including those along which sympathetic axons grow, suggesting it may act as a retrograde neurotrophic factor, similar to nerve growth factor. To explore this possibility, we compared neuron loss in neurotrophin-3-deficient mice with that in nerve growth factor-deficient mice and found that neuronal losses occurred at approximately the same time in both mutants, but were less severe in mice lacking neurotrophin-3. Eliminating one or both neurotrophin-3 alleles in mice that lack nerve growth factor does not further reduce sympathetic neuron number in the superior cervical ganglion at E17.5 but does alter axon outgrowth and decrease salivary gland innervation. Taken together these results suggest that neurotrophin-3 is required for survival of some sympathetic neurons that also require nerve growth factor.

Neurotrophin actions during the development of the peripheral nervous system.

Neurotrophins are important regulators of the development and maintenance of the vertebrate nervous system. Besides their well-established role in promoting neuronal survival during development, in vitro data suggest that they can regulate proliferation, survival, and differentiation of precursor cells. Analysis of the developing peripheral nervous system in mouse strains carrying mutations in genes encoding the neurotrophins and their receptors indicate, however, that lack of neurotrophin signalling results in specific neuronal deficits that are primarily due to neuronal death. Many of these deficits occur before final target encounter.