Localized interstitial granuloma annulare induced by subcutaneous injections for desensitization.

We describe a patient with interstitial granuloma annulare associated with subcutaneous injection therapy (SIT) for desensitization to a type I allergy. Asymptomatic, erythematous, violaceous annular patches were located at the injection sites on both her arms. Medical history revealed perennial rhinoconjonctivitis treated with SIT (Phostal Stallergen® cat 100% and D. pteronyssinus/D.farinae 50%:50%).

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development.

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3-deficient mice show several hallmarks of ciliopathies including left-right asymmetry defects and hydrocephalus. Here we show that Rfx3-deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies.

Oral findings in Midline Syndrome: a case report and literature review

We describe a female patient with a midline syndrome. The patient presents agenesis of the corpus callosum, encephalocele, iris coloboma, hypertelorism, submucosal cleft palate and dental anomalies. Despite being very characteristic, her phenotypical traits do not coincide exactly with those reported to date in the literature. The karyotype and the molecular cytogenetic study do not show mutations. We identify the presence of dental anomalies in the mother and other family members, not being identified MSX1 and PAX9 mutations that could the related with their etiology. Despite the fact that dental agenesis has been related to a large number of other malformation syndromes and congenital conditions, dental anomalies have only rarely been mentioned when reporting midline syndromes. These dental phenotypical traits, present in the patient and her family, could be considered part of the midline syndrome in carriers as well as in the patients.

Granuloma periférico de células gigantes. A propósito de 5 casos y revisión de la literatura

El granuloma periférico de células gigantes (GPCG) es una lesión reactiva benigna relativamente frecuente de la cavidad bucal. Se origina a partir del periostio o de la membrana periodontal tras una irritación o un traumatismo crónico que actúa localmente. Se manifiesta en forma de nódulo de color rojo-púrpura, situado en la encía o en el reborde alveolar edéntulo, preferentemente en la mandíbula. Aparece a cualquier edad, con una mayor incidencia entre la quinta y sexta décadas de la vida, con una ligera predilección por el sexo femenino. Es una lesión de las partes blandas que muy rara vez implica el hueso subyacente, aunque puede causarle una erosión superficial. Se han revisado cinco casos de GPCG que afectaban a 3 hombres y a 2 mujeres de edades comprendidas entre los 19 y 66 años, presentándose tres de ellos en el maxilar superior. En dos casos se observaba radiográficamente una reabsorción ósea en forma de"aplanamiento". El tratamiento consistió en realizar la exéresis-biopsia, efectuándose dos casos mediante láser de CO2 y tres con bisturí frío. No se ha observado ninguna recidiva en el seguimiento postoperatorio (rango de 10 meses a 4 años). En el diagnóstico diferencial se deben descartar lesiones de características clínicas e histológicas muy similarescomo el granuloma central de células gigantes-, que asientan en el interior del propio maxilar y cuyo comportamiento es más agresivo; solamente el estudio radiológico permitirá esta distinción. El diagnóstico precoz y preciso de esta lesión permite efectuar un tratamiento conservador sin riesgo para los dientes vecinos ni para el hueso adyacente

Granuloma periférico de células gigantes. A propósito de 5 casos y revisión de la literatura

El granuloma periférico de células gigantes (GPCG) es una lesión reactiva benigna relativamente frecuente de la cavidad bucal. Se origina a partir del periostio o de la membrana periodontal tras una irritación o un traumatismo crónico que actúa localmente. Se manifiesta en forma de nódulo de color rojo-púrpura, situado en la encía o en el reborde alveolar edéntulo, preferentemente en la mandíbula. Aparece a cualquier edad, con una mayor incidencia entre la quinta y sexta décadas de la vida, con una ligera predilección por el sexo femenino. Es una lesión de las partes blandas que muy rara vez implica el hueso subyacente, aunque puede causarle una erosión superficial. Se han revisado cinco casos de GPCG que afectaban a 3 hombres y a 2 mujeres de edades comprendidas entre los 19 y 66 años, presentándose tres de ellos en el maxilar superior. En dos casos se observaba radiográficamente una reabsorción ósea en forma de"aplanamiento". El tratamiento consistió en realizar la exéresis-biopsia, efectuándose dos casos mediante láser de CO2 y tres con bisturí frío. No se ha observado ninguna recidiva en el seguimiento postoperatorio (rango de 10 meses a 4 años). En el diagnóstico diferencial se deben descartar lesiones de características clínicas e histológicas muy similares -como el granuloma central de células gigantes-, que asientan en el interior del propio maxilar y cuyo comportamiento es más agresivo; solamente el estudio radiológico permitirá esta distinción. El diagnóstico precoz y preciso de esta lesión permite efectuar un tratamiento conservador sin riesgo para los dientes vecinos ni para el hueso adyacente

Granuloma reparador de células gigantes: relato de cinco casos

O granuloma reparador de células gigantes é lesão óssea rara, correspondendo a cerca de 7% de todos os tumores ósseos benignos da mandíbula, com maior incidência no sexo feminino. Embora seja considerada resposta a um trauma, este antecedente nem sempre está presente. O aspecto radiológico característico é de lesão lítica, uni ou multiloculada, com afilamento da cortical, podendo apresentar calcificações no seu interior. Neste trabalho relatamos os aspectos clínicos e radiológicos de cinco casos de granuloma reparador de células gigantes envolvendo a mandíbula e o maxilar, e as principais características que permitem o diagnóstico diferencial com outras lesões fibro-ósseas que acometem a face.

Aspectos radiológicos e epidemiológicos do granuloma central de células gigantes

OBJETIVO: Este estudo teve como objetivo avaliar os principais aspectos radiográficos e epidemiológicos das lesões de células gigantes (granulomas centrais de células gigantes e tumores marrons do hiperparatireoidismo). MATERIAIS E MÉTODOS: A amostra consistiu de 26 lesões de células gigantes diagnosticadas em 22 pacientes divididos em dois grupos, um deles composto por 17 pacientes que não tinham hiperparatireoidismo (grupo A) e o outro formado por cinco pacientes portadores de tal distúrbio (grupo B). RESULTADOS: O sexo feminino (72,7%) foi o mais acometido. As lesões ocorreram mais freqüentemente na segunda década de vida, com média de idade de 27 anos. A mandíbula (61,5%) foi o arco mais envolvido. Radiograficamente, 57,7% das lesões eram multiloculares e 42,3% eram uniloculares com limites definidos. Todas as 26 lesões provocaram expansão óssea, 15,4% produziram reabsorção radicular, 50% causaram deslocamento dentário e 11,5% produziram dor. Na mandíbula, 18,7% das lesões cruzavam a linha média. O grupo A apresentou 66,7% das lesões na mandíbula e o grupo B mostrou igualdade na distribuição das lesões entre os arcos. O grupo A apresentou 66,7% das lesões multiloculares e 33,3%, uniloculares. O grupo B apresentou 62,5% das lesões uniloculares e 37,5%, multiloculares. CONCLUSÃO: As lesões de células gigantes podem manifestar-se, radiograficamente, com um amplo espectro, desde pequenas lesões uniloculares de crescimento lento até extensas lesões multiloculares. Elas apresentam características de benignidade, embora algumas lesões possam demonstrar um comportamento localmente agressivo.

Síndrome do granuloma letal da linha média: um dilema diagnóstico

A rara síndrome do granuloma letal da linha média apresenta difícil diagnóstico, em razão da grande variedade de doenças que podem causá-la e um desconhecimento pela maioria da classe médica. No presente artigo relatamos caso de paciente com esta doença, provocada por carcinoma epidermoide, chamando a atenção para os diagnósticos diferenciais e aspectos clínico-radiológicos que podem auxiliar no diagnóstico.

Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers

The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases) by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers), from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells.

Antigenic stimulation is more efficient than LPS in inducing nitric oxide production by human mononuclear cells on the in vitro granuloma reaction in schistosomiasis

Nitric oxide (NO) is an extremely important and versatile messenger in biological systems. It has been identified as a cytotoxic factor in the immune system, presenting anti- or pro-inflammatory properties under different circumstances. In murine monocytes and macrophages, stimuli by cytokines or lipopolysaccharide (LPS) are necessary for inducing the immunologic isoform of the enzyme responsible for the high-output production of NO, nitric oxide synthase (iNOS). With respect to human cells, however, LPS seems not to stimulate NO production in the same way. Addressing this issue, we demonstrate here that peripheral blood mononuclear cells (PBMC) obtained from schistosomiasis-infected patients and cultivated with parasite antigens in the in vitro granuloma (IVG) reaction produced more nitrite in the absence of LPS. Thus, LPS-induced nitrite levels are easily detectable, although lower than those detected only with antigenic stimulation. Concomitant addition of LPS and L-N-arginine methyl ester (L-NAME) restored the ability to produce detectable levels of nitrite, which had been lost with L-NAME treatment. In addition, LPS caused a mild decrease of the IVG reaction and its association with L-NAME was responsible for reversal of the L-NAME-exacerbating effect on the IVG reaction. These results show that LPS alone is not as good an NO inducer in human cells as it is in rodent cells or cell lines. Moreover, they provide evidence for interactions between LPS and NO inhibitors that require further investigation.

Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum

The corpus callosum is a large fiber tract that connects neurons in the right and left cerebral hemispheres. Agenesis of the corpus callosum (ACC) is associated with a large number of human syndromes but little is known about why ACC occurs. In most cases of ACC, callosal axons are able to grow toward the midline but are unable to cross it, continuing to grow into large swirls of axons known as Probst bundles. This phenotype suggests that in some cases ACC may be due to defects in axonal guidance at the midline. General guidance mechanisms that influence the development of axons include chemoattraction and chemorepulsion, presented by either membrane-bound or diffusible molecules. These molecules are not only expressed by the final target but by intermediate targets along the pathway, and by pioneering axons that act as guides for later arriving axons. Midline glial populations are important intermediate targets for commissural axons in the spinal cord and brain, including the corpus callosum. The role of midline glial populations and pioneering axons in the formation of the corpus callosum are discussed. Finally the differential guidance of the ipsilaterally projecting perforating pathway and the contralaterally projecting corpus callosum is addressed. Development of the corpus callosum involves the coordination of a number of different guidance mechanisms and the probable involvement of a large number of molecules.

Interhemispheric connections between primary visual areas: beyond the midline rule

In the last five years, a number of detailed anatomical, electrophysiological, optical imaging and simulation studies performed in a variety of non-human species have revealed that the functional organization of callosal connections between primary visual areas is more elaborate than previously thought. Callosal cell bodies and terminals are clustered in columns whose correspondence to features mapped in the visual cortex, such as orientation and ocularity, are starting to be understood. Callosal connections are not restricted to the vertical midline representation nor do they establish merely point-to-point retinotopic correspondences across the hemispheres, as traditionally believed. In addition, anatomical studies have revealed the existence of an ipsilateral component of callosal axons. The aim of this short review is to propose how these new data can be integrated into an updated scheme of the circuits responsible for assembling the primary visual field map.

Frontonasal Dysplasia, Severe Neuropsychological Delay, and Midline Central Nervous System Anomalies: Report of 10 Brazilian Male Patients

Here we report on 10 male patients with frontonasal dysplasia, cleft lip/palate, mental retardation, lack of language acquisition, and severe central nervous system involvement. Imaging studies disclosed absence of the corpus callosum, midline cysts, and an abnormally modeled cerebellum. Neuronal heterotopias were present in five patients and parieto-occipital encephalocele in three patients. We suggest that this pattern found exclusively in males, most likely represents a newly recognized syndrome distilled from the group of disorders subsumed under frontonasal dysplasia. (C) 2009 Wiley-Liss, Inc.

Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection

The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN(+) cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.

Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler

COSTA MIGUEL, M. C.; NONAKA, C. F. W.; GERMANO, A. R.; SOUZA, L. B.; SOUZA, L. B. Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler. International journal of oral and maxillofacial surgery, v. 38, p. 385-387, 2009.