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BACKGROUND: Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in GAN, the gene encoding gigaxonin. METHODS: We conducted an intrathecal dose-escalation study of scAAV9/JeT-GAN (a self-complementary adeno-associated virus-based gene therapy containing the GAN transgene) in children with giant axonal neuropathy. Safety was the primary end point. The key secondary clinical end point was at least a 95% posterior probability of slowing the rate of change (i.e., slope) in the 32-item Motor Function Measure total percent score at 1 year after treatment, as compared with the pretreatment slope. RESULTS: One of four intrathecal doses of scAAV9/JeT-GAN was administered to 14 participants - 3.5×1013 total vector genomes (vg) (in 2 participants), 1.2×1014 vg (in 4), 1.8×1014 vg (in 5), and 3.5×1014 vg (in 3). During a median observation period of 68.7 months (range, 8.6 to 90.5), of 48 serious adverse events that had occurred, 1 (fever) was possibly related to treatment; 129 of 682 adverse events were possibly related to treatment. The mean pretreatment slope in the total cohort was -7.17 percentage points per year (95% credible interval, -8.36 to -5.97). At 1 year after treatment, posterior mean changes in slope were -0.54 percentage points (95% credible interval, -7.48 to 6.28) with the 3.5×1013-vg dose, 3.23 percentage points (95% credible interval, -1.27 to 7.65) with the 1.2×1014-vg dose, 5.32 percentage points (95% credible interval, 1.07 to 9.57) with the 1.8×1014-vg dose, and 3.43 percentage points (95% credible interval, -1.89 to 8.82) with the 3.5×1014-vg dose. The corresponding posterior probabilities for slowing the slope were 44% (95% credible interval, 43 to 44); 92% (95% credible interval, 92 to 93); 99% (95% credible interval, 99 to 99), which was above the efficacy threshold; and 90% (95% credible interval, 89 to 90). Between 6 and 24 months after gene transfer, sensory-nerve action potential amplitudes increased, stopped declining, or became recordable after being absent in 6 participants but remained absent in 8. CONCLUSIONS: Intrathecal gene transfer with scAAV9/JeT-GAN for giant axonal neuropathy was associated with adverse events and resulted in a possible benefit in motor function scores and other measures at some vector doses over a year. Further studies are warranted to determine the safety and efficacy of intrathecal AAV-mediated gene therapy in this disorder. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, NCT02362438.).
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Técnicas de Transferência de Genes , Terapia Genética , Neuropatia Axonal Gigante , Criança , Humanos , Proteínas do Citoesqueleto/genética , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/terapia , Transgenes , Injeções EspinhaisRESUMO
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive malignancy of the central nervous system (CNS) usually diagnosed in infancy or childhood, most often characterized by loss of expression of the SMARCB1 gene product integrase interactor 1 (INI1) protein. We report a case of AT/RT in a 3 month old boy with retained expression of INI1 by immunohistochemistry. Additional testing demonstrated loss of expression of the SMARCA4 gene product Brahma-related gene 1 (BRG1) protein by immunohistochemistry, confirmed by next generation sequencing showing a nonsense mutation in SMARCA4. This case illustrates that positivity for INI1 does not rule out a diagnosis of AT/RT, and additional testing, including BRG1/SMARCA4 analysis, is warranted in cases where clinical suspicion is high.
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DNA Helicases/genética , Proteínas Nucleares/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Teratoma/genética , Fatores de Transcrição/genética , Códon sem Sentido , Humanos , Lactente , Masculino , Tumor Rabdoide/patologia , Teratoma/patologiaRESUMO
PURPOSE: Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood. METHODS: Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice. RESULTS: Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice. CONCLUSIONS: For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care.
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Sistema Nervoso Autônomo/fisiopatologia , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/fisiopatologia , Animais , Sistema Nervoso Autônomo/patologia , Peso Corporal , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Sistema Nervoso Entérico/patologia , Sistema Nervoso Entérico/fisiopatologia , Fezes/química , Feminino , Trato Gastrointestinal/patologia , Trato Gastrointestinal/fisiopatologia , Neuropatia Axonal Gigante/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Sistema Nervoso Parassimpático/patologia , Sistema Nervoso Parassimpático/fisiopatologia , Sistema Nervoso Simpático/patologia , Sistema Nervoso Simpático/fisiopatologia , Sistema Urinário/patologia , Sistema Urinário/fisiopatologiaRESUMO
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Doenças dos Nervos Cranianos , Humanos , Transtornos Relacionados ao Uso de Cocaína/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/induzido quimicamente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Cocaína/efeitos adversos , EncéfaloRESUMO
BACKGROUND: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. METHODS: We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. RESULTS: Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (nâ =â 10, 30%). Most tumors were in the cerebral hemispheres (nâ =â 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3%â ±â 8.3%; the 5-year overall survival (OS) rate was 96.4%â ±â 4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6%â ±â 15.2% (Pâ <â .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. CONCLUSIONS: pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.
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Neoplasias Encefálicas , Glioma , Proteínas Proto-Oncogênicas c-myb , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Seguimentos , Glioma/patologia , Glioma/genética , Gradação de Tumores , Prognóstico , Proteínas Proto-Oncogênicas , Proteínas Proto-Oncogênicas c-myb/genética , Estudos Retrospectivos , Taxa de Sobrevida , Transativadores/genéticaRESUMO
Xanthogranuloma (XG) of the sellar region is a non-neoplastic inflammatory lesion characterized histologically by recent and remote hemorrhage, necrotic debris, fibrosis, chronic inflammation, and cholesterol clefts with associated foreign-body giant cells. The inflammatory lesion was recognized by the World Health Organization in 2000. XG of the sellar region is rare. Cases of pituitary adenoma (PA) with an associated XG (PA/XG) are extremely rare, with a total of 16 cases in the literature. PA/XG lacks specific clinical and radiologic signs, making pre-operative diagnosis challenging. Herein, we report a case of PA/XG, describe the radiologic and pathologic findings, and discuss the role of so-called silent or "subclinical pituitary apoplexy" in the possible histogenesis of PA/XGs.
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Giant Axonal Neuropathy (GAN) is a pediatric neurodegenerative disease caused by KLHL16 mutations. KLHL16 encodes gigaxonin, which regulates intermediate filament (IF) turnover. Previous neuropathological studies and examination of postmortem brain tissue in the current study revealed involvement of astrocytes in GAN. To develop a clinically-relevant model, we reprogrammed skin fibroblasts from seven GAN patients to pluripotent stem cells (iPSCs), which were used to generate neural progenitor cells (NPCs), astrocytes, and brain organoids. Multiple isogenic control clones were derived via CRISPR/Cas9 gene editing of one patient line carrying the G332R gigaxonin mutation. All GAN iPSCs were deficient for gigaxonin and displayed patient-specific increased vimentin expression. GAN NPCs had lower nestin expression and fewer nestin-positive cells compared to isogenic controls, but nestin morphology was unaffected. GAN brain organoids were marked by the presence of neurofilament and GFAP aggregates. GAN iPSC-astrocytes displayed striking dense perinuclear vimentin and GFAP accumulations and abnormal nuclear morphology. In over-expression systems, GFAP oligomerization and perinuclear aggregation were augmented in the presence of vimentin. GAN patient cells with large perinuclear vimentin aggregates accumulated significantly more nuclear KLHL16 mRNA compared to cells without vimentin aggregates. As an early effector of KLHL16 mutations, vimentin may be a potential target in GAN.
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Giant Axonal Neuropathy (GAN) is a pediatric neurodegenerative disease caused by KLHL16 mutations. KLHL16 encodes gigaxonin, a regulator of intermediate filament (IF) protein turnover. Previous neuropathological studies and our own examination of postmortem GAN brain tissue in the current study revealed astrocyte involvement in GAN. To study the underlying mechanisms, we reprogrammed skin fibroblasts from seven GAN patients carrying different KLHL16 mutations to iPSCs. Isogenic controls with restored IF phenotypes were derived via CRISPR/Cas9 editing of one patient carrying a homozygous missense mutation (G332R). Neural progenitor cells (NPCs), astrocytes, and brain organoids were generated through directed differentiation. All GAN iPSC lines were deficient for gigaxonin, which was restored in the isogenic control. GAN iPSCs displayed patient-specific increased vimentin expression, while GAN NPCs had decreased nestin expression compared to isogenic control. The most striking phenotypes were observed in GAN iPSC-astrocytes and brain organoids, which exhibited dense perinuclear IF accumulations and abnormal nuclear morphology. GAN patient cells with large perinuclear vimentin aggregates accumulated nuclear KLHL16 mRNA. In over-expression studies, GFAP oligomerization and perinuclear aggregation were potentiated in the presence of vimentin. As an early effector of KLHL16 mutations, vimentin may serve as a potential therapeutic target in GAN.
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We describe a 72-year-old white man with erosive rheumatoid arthritis in whom subacute neurologic and psychiatric symptoms developed after 3 years of treatment with infliximab, prednisone, and methotrexate. White matter demyelination was seen on magnetic resonance imaging of the brain, and progressive multifocal leukoencephalopathy (PML) was ultimately confirmed by brain biopsy. The patient was treated with supportive therapy and discontinuation of disease-modifying antirheumatic drugs, resulting in stabilization of the disease process. The patient survived, but neurologic and cognitive deficits persisted. The distribution and pathology of this patient's disease are unique from almost all reported incidents of oral methotrexate-associated leukoencephalopathy. The pathogenesis of disease may be linked to a T cell-mediated process that is potentially impacted by infliximab. This case provides the first reported evidence that PML can be seen in association with infliximab therapy.
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Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/terapia , Leucoencefalopatia Multifocal Progressiva/patologia , Metotrexato/uso terapêutico , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Humanos , Infliximab , Leucoencefalopatia Multifocal Progressiva/complicações , Imageamento por Ressonância Magnética , Masculino , Fibras Nervosas Mielinizadas/patologia , Prednisona/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Background: Giant axonal neuropathy (GAN; ORPHA: 643; OMIM# 256850) is a rare, hereditary, pediatric neurodegenerative disorder associated with intracellular accumulations of intermediate filaments (IFs). Validation of therapeutic efficacy and viral vector delivery systems with GAN knockout (KO) mouse models has provided the springboard for the development of a viral vector being delivered intrathecally in an ongoing Phase I gene therapy clinical trial for the treatment of children with GAN (https://clinicaltrials.gov/ct2/show/NCT02362438).Purpose: To characterize the ocular pathologic phenotype of newly developed GAN rat models.Materials and Methods: Microscopic examination of eyes at various timepoints.Results: We noted the unexpected finding of progressive and extensive degeneration of rod and cone photoreceptor (PR) cells in the retinas of GAN rat models.Conclusion: This PR-cell loss in rat models of GAN raises the possibility that PR-cell loss may contribute to the visual impairment observed in human GAN. The intrathecal viral vector employed in the ongoing Phase I gene therapy clinical trial for the treatment of children with GAN was not specifically designed to address PR-cell degeneration. If GAN-associated PR-cell loss is present and clinically significant in humans, then future treatment protocols for GAN may need to include a gene transfer approach or combinatorial treatment strategy that also targets retinal PR cells.
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Distrofias de Cones e Bastonetes/patologia , Modelos Animais de Doenças , Terapia Genética , Neuropatia Axonal Gigante/patologia , Células Fotorreceptoras de Vertebrados/patologia , Animais , Animais Geneticamente Modificados , Feminino , Neuropatia Axonal Gigante/terapia , Humanos , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344 , Ratos Long-EvansRESUMO
A 4-year-old girl with PHACES syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies/coarctation of the aorta, eye abnormalities, and sternal clefting/supraumbilical raphe) developed a cerebellar pilocytic astrocytoma 18 months after resolution of her neck, ear, and thoracic hemangiomas. Because cutaneous hemangiomas may have involuted by the time a patient is diagnosed with a central nervous system neoplasm, it seems possible that in other such patients the association may have gone unrecognized. Cerebellar pilocytic astrocytoma may be a rare manifestation of the posterior fossa malformations of PHACES.
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Anormalidades Múltiplas , Astrocitoma/etiologia , Encéfalo/anormalidades , Hemangioma/complicações , Neoplasias Infratentoriais/etiologia , Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/fisiopatologia , Astrocitoma/patologia , Encéfalo/patologia , Pré-Escolar , Feminino , Comunicação Interventricular/complicações , Hemangioma/congênito , Humanos , Neoplasias Infratentoriais/patologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , SíndromeRESUMO
Giant axonal neuropathy (GAN; ORPHA: 643; OMIM# 256850) is a rare, hereditary, pediatric neurodegenerative disorder associated with intracellular accumulations of intermediate filaments (IFs). GAN knockout (KO) mouse models mirror the IF dysregulation and widespread nervous system pathology seen in human GAN. Validation of therapeutic efficacy and viral vector delivery systems with these GAN KO models has provided the springboard for the development of a viral vector being delivered intrathecally in an ongoing Phase I gene therapy clinical trial for the treatment of children with GAN ( https://clinicaltrials.gov/ct2/show/NCT02362438 ). During the course of a comprehensive pathologic characterization of the GAN KO mouse, we discovered the very early and unexpected involvement of the ocular lens. Light microscopy revealed the presence of intracytoplasmic inclusion bodies within lens epithelial cells. The inclusion bodies showed strong immunohistochemical positivity for glial fibrillary acidic protein (GFAP). We confirmed that intracytoplasmic inclusion bodies are also present within lens epithelial cells in human GAN. These IF inclusion bodies in lens epithelial cells are unique to GAN. Similar IF inclusion bodies in lens epithelial cells have not been reported previously in experimental animal models or human diseases. Since current paradigms in drug discovery and drug repurposing for IF-associated disorders are often hindered by lack of validated targets, our findings suggest that lens epithelial cells in the GAN KO mouse may provide a potential target, in vivo and in vitro, for evaluating drug efficacy and alternative therapeutic approaches in promoting the clearance of IF inclusions in GAN and other diseases characterized by intracellular IF accumulations.
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Neuropatia Axonal Gigante/patologia , Cristalino/patologia , Animais , Proteínas do Citoesqueleto/metabolismo , Neuropatia Axonal Gigante/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Filamentos Intermediários/metabolismo , Cristalino/metabolismo , Camundongos , Camundongos KnockoutRESUMO
BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. METHODS: We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. RESULTS: The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. CONCLUSIONS: Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Imageamento por Ressonância Magnética/métodos , Mutação , Neoplasias Neuroepiteliomatosas/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Criança , Metilação de DNA , Feminino , Humanos , Masculino , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/metabolismo , Prognóstico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Taxa de SobrevidaRESUMO
PURPOSE: We report a case of retrocorneal fibrous membrane (RCFM) formation following penetrating keratoplasty (PK) and intraoperative optical coherence tomography (OCT)-guided excision of this membrane. OBSERVATIONS: A 68-year-old woman with primary open angle glaucoma and corneal decompensation of the right eye secondary to tube shunt presented for 3-month follow-up of PK. On examination of the right eye, the patient was noted to have a glassy pupillary membrane with traction on the iris. Anterior segment OCT confirmed a membrane connecting the iris to host cornea. The patient underwent biopsy and excision of the membrane assisted by intraoperative OCT. Pathological examination was consistent with Descemet's membrane proliferation. We suspect that this membrane represents retained host's Descemet's membrane following corneal transplantation. CONCLUSIONS: This case highlights the existence of RCFM formation in the context of retained host cornea following PK and the role of intraoperative OCT in management.
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SWI/SNF is a chromatin-remodeling complex important in gene regulation, cytokine responses, tumorigenesis, differentiation, and development. As a multitude of signaling pathways require SWI/SNF, loss of SWI/SNF function is expected to have an impact on cellular phenotypes. The SWI/SNF ATPase subunits, BRG1 and BRM, have been shown to be lost in a subset of human cancer cell lines and human primary cancers and may represent tumor suppressor proteins. To better understand the biology of these proteins, the authors examined the expression pattern of BRG1 and BRM in a variety of normal tissues. BRG1 expression was predominantly seen in cell types that constantly undergo proliferation or self-renewal; in contrast, BRM was preferentially expressed in brain, liver, fibromuscular stroma, and endothelial cell types, cell types not constantly engaged in proliferation or self-renewal. This differential expression suggests that these proteins serve distinct functions in human tissues.
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Adenosina Trifosfatases/química , Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas Nucleares/metabolismo , Subunidades Proteicas/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Anticorpos Monoclonais/metabolismo , Linhagem Celular , DNA Helicases , Ectoderma/metabolismo , Células HeLa , Humanos , Imuno-Histoquímica , Mesoderma/metabolismo , Distribuição TecidualRESUMO
Abnormalities of the ependyma can serve as a marker of early brain insults. The presence of ependymal abnormalities was determined in sections containing ependyma of the temporal horn obtained from the Stanley Neuropathology Consortium: 15 subjects with schizophrenia, 15 with bipolar illness, 15 with major depression and 15 normal controls. There were no significant differences in numbers of subjects with ependymal discontinuities or subventricular rosettes. Subjects with schizophrenia had significantly less nodular gliosis than normal subjects (p=0.02); there was a trend for subjects with depression to have less nodular gliosis than normal subjects (p=0.06). Control subjects had unexpectedly high rates of ependymal abnormalities, indicating that ependymal abnormalities may not be a useful marker of pre- or perinatal events associated with schizophrenia and other psychiatric disorders in adult postmortem tissue.
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Transtorno Bipolar/patologia , Transtorno Depressivo/patologia , Epêndima/anormalidades , Esquizofrenia/patologia , Adulto , Estudos de Casos e Controles , Epêndima/patologia , Feminino , Gliose/patologia , Humanos , Ventrículos Laterais/anormalidades , Ventrículos Laterais/patologia , Masculino , Pessoa de Meia-Idade , North CarolinaRESUMO
Proton magnetic resonance spectroscopy (H1-MRS) has been increasingly receiving more attention from radiologists, neurosurgeons, radiation and medical oncologists in the "in situ" clinical evaluation of human tumors. The utilization of H1-MRS, especially in human brain tumors, coupled to both routine magnetic resonance imaging (MRI) and functional MRI techniques provides greater information concerning tumor grading and extension and characterization of the normal surrounding tissue than what is possible with any other imaging technique alone. In this paper, we will review the current status of proton MR spectroscopy with emphasis on its clinical utility to diagnose tumors, its utility in planning surgical and radiation therapy interventions, and in its use in monitoring tumor treatment.
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Espectroscopia de Ressonância Magnética , Neoplasias/diagnóstico , Prótons , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
PURPOSE: To describe the histopathology of familial, band-shaped, spheroidal keratopathy in ethnic Chinese siblings. New histopathologic findings are presented that may shed light on the etiology of this rare and unique condition. METHODS: Three ethnic Chinese siblings in Urumqi, People's Republic of China, were examined. One brother and sister had spheroidal, amber-colored droplets in the superficial, central corneal stroma. Each had a diffuse gray haze and thickening of the peripheral corneal stroma. A histopathologic study of penetrating keratoplasty specimens was performed. Another sister had only thickening and haze of the corneal stroma. RESULTS: Typical spheroidal deposits in the superficial stroma were demonstrated. One cornea had vascularization and amyloid deposition. One cornea had loss of endothelial cells and a thickened Descemet's membrane. CONCLUSION: Neovascularization and amyloid deposition are likely secondary phenomena in this familial disease. A new clinical finding is the hazy, thickened stroma. New pathologic findings are the loss of endothelial cells and the marked thickening of Descemet's membrane. An endothelial cell dystrophy may accompany familial, band-shaped, spheroidal keratopathy.
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Distrofias Hereditárias da Córnea/patologia , Adulto , Amiloidose/patologia , China/epidemiologia , Distrofias Hereditárias da Córnea/etnologia , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/cirurgia , Epitélio Corneano/patologia , Feminino , Humanos , Ceratoplastia Penetrante , MasculinoRESUMO
Standardised proton magnetic resonance spectroscopic imaging (MRSI) was initially developed for routine in-situ clinical assessment of human brain tumours, and its use was later extended for examination of prostate and breast cancers. MRSI coupled with both routine and functional MRI techniques provides more detailed information about a tumour's location and extent of its infiltration than any other modality alone. Information obtained by adding MRSI data to anatomical and functional MRI findings aid in clinical management decisions (such as watchful waiting vs immediate intervention). In this Review, we discuss the current status of proton MRSI, with emphasis on its clinical use to map the location and extent of tumour processes for spectroscopic image-guided biopsy procedures and to monitor treatment paradigms for brain, prostate, and breast cancer.