Sparing of the substantia nigra in sporadic Creutzfeldt-Jakob disease presenting as an acute corticobasal syndrome

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Histological alterations induced by electrode implantation and electrical stimulation in the human brain: A review

Objectives. Electrical brain stimulation is used as a treatment for patients with intractable chronic pain and movement disorders. However, the implantation of electrodes and electrical stimulation may induce histological changes around the electrode tip. We aimed to review the histological changes in humans that were electrically stimulated in the brain. Methods. We traced 26 autopsy studies of which 19 patients received cerebellar stimulation and 37 patients deep brain stimulation.Results. Electrode implantation and electrical stimulation induced in part of the cases formation of a fibrous sheath around the electrode, loss of fairly large neurons, and limited gliosis. Macroscopic lesions were present in only some cases, mostly due to pulling at the extension cable in the postoperative evaluation period preceding definite implantation of the electrode wire and stimulator. Conclusions. Electrical brain stimulation induces histological changes in some patients. According to electrical brain stimulation studies in animals, these changes can be related to the charge and charge density per phase (and their interaction).status: publishe

[Lipoma and atypical lipomatous tumor within the same neoplasia : Evidence for a continuous transition.]

The case of a lipomatous tumor with a predominant lipoma component and transition to an atypical lipomatous tumor is presented. A deep-seated soft tissue tumor of the right thigh with a maximum size of 14 cm was resected in a 70-year-old female patient. Corresponding to a comparable macroscopic aspect, the lesion revealed the histological features of an ordinary lipoma without atypia in about 80% of the specimen. In the remaining portion (approximately 20%) histopathology showed an atypical lipomatous tumor (ALT, lipoma-like subtype). Immunohistochemistry for MDM 2 and CDK4 revealed no immunoreactivity in the lipoma component, but within the ALT component. Interphase dual-color fluorescence in situ hybridization showed no amplification of the MDM 2 gene and rarely CDK4 gene amplification within the lipoma component, but high level amplification of MDM 2/CDK4 gene in the ALT area, further supporting the morphologically based diagnosis of a lipomatous tumor including areas of a true lipoma and ALT. This case underlines the concept of a continuous stepwise development of lipomatous soft tissue tumors from benign to malignant counterparts as a biological continuum.status: publishe

[Atypical lipomatous tumors of the stomach : Clinical, morphological and molecular findings.]

Two cases of primary gastric atypical lipomatous tumors (ALT) are presented. In case No.1, a 7x4x3 cm submucosal ALT (lipoma-like subtype) of the antrum/pyloric region in a 60-year-old woman was completely resected. Using interphase dual-color-FISH, MDM2- and CDK4 amplifications could be detected in distinguished amplicons. The patient was continuously free of disease after 56 months. In case No. 2, a 3.5 cm (in diameter) submucosal ALT (lipoma-like subtype) of the gastric body in a 56-year-old woman was completely resected. FISH revealed MDM2 amplification while the CDK4 gene remained in diploid copies. This patient was continuously free of disease after 36 months. The morphologic and molecular biological findings of this rare primary gastric mesenchymal tumor are discussed in comparison with the corresponding soft tissue lesions.status: publishe

Identification of a novel PHIP::BRAF gene fusion in infantile fibrosarcoma.

The ETV6::NTRK3 fusion is the most common gene alteration in infantile fibrosarcoma, a soft tissue tumor affecting patients under two years of age. Less frequently, these tumors harbor fusions of genes encoding other kinases, such as BRAF, which activates MEK in the mitogen-activated protein kinase pathway. The identification and characterization of these oncogenes is crucial to facilitate diagnosis, validate new treatments and better understand the pathophysiology of these neoplasms. Herein, we analyzed an ETV6::NTRK3-negative infantile fibrosarcoma from a 5-day-old patient by RNA-sequencing to identify new fusion transcripts. Functional exploration of the fusion of interest was performed by in vitro assays to study its activity, oncogenicity and sensitivity to the MEK inhibitor trametinib. We identified a novel fusion involving the PHIP and BRAF genes. The corresponding fusion protein constitutively activated the mitogen-activated protein kinase pathway, resulting in fibroblast transformation. Treatment of transfected cells with trametinib effectively inhibited signaling by PHIP::BRAF. PHIP::BRAF is a novel fusion oncogene that can be targeted by trametinib in infantile fibrosarcoma. This article is protected by copyright. All rights reserved

Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa

OBJECTIVE: The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. MATERIALS AND METHODS: The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). RESULTS: Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. CONCLUSIONS: Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.status: publishe

Toxicological investigations of the effects carboxymethylcellulose on ciliary beat frequency of human nasal epithelial cells in primary suspension culture and in vivo on rabbit nasal mucosa

The objective of this study was to investigate the safety of a mucoadhesive carboxymethylcellulose (CMC) formulation for intranasal administration of apomorphine. The effect of different concentrations of CMC on ciliary beat frequency (CBF) was studied using a human nasal epithelial suspension cell culture system. The CBF was determined by computerized microscope photometry. The in vivo rabbit nasal mucosal tolerance of the mucoadhesive polymer was investigated using light microscopy. Twice daily, six rabbits received CMC powder in one nostril and CMC/apomorphine powder in the alternate nostril for 4 weeks. Two control rabbits received air puffs in one nostril and nothing in the alternate nostril. The rabbits were subsequently sacrificed and the stained nasal sections examined microscopically. CMC showed both concentration- and time-dependent inhibitory effects on the CBF. Only mild-to-moderate cilio-inhibition was recorded with the different concentrations of the polymer. CMC (both with and without apomorphine) caused mild-to-moderate inflammation after 4 weeks. Necrosis, squamous metaplasia or ciliary degeneration was not observed. Based on: (1) the mild-to-moderate cilio-inhibition induced by different concentrations of CMC; and (2) the mild-to-moderate nasal mucosal inflammation caused by CMC with and without apomorphine, we conclude that this polymer can be considered as a safe carrier for short-term intranasal administration. However, further investigations are required for its use in the treatment of chronic diseases such as with apomorphine in Parkinson's disease.status: publishe

Accuracy of diffusion-weighted MR imaging in the diagnosis of sporadic Creutzfeldt-Jakob disease

The definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is based on brain autopsy. The 14-3-3 analysis in the CSF is considered a highly sensitive and specific procedure. Sensitivity, specificity and accuracy of EEG, the 14-3-3 assay and MR imaging in 12 patients referred for suspected sCJD were calculated. We suggest that diffusion-weighted MR imaging (DWI) should be included in the array of diagnostic tests because of the 100 % sensitivity and specificity.Demaerel P., Sciot R., Robberecht W., Dom R., Vandermeulen D., Maes F., Wilms G., ''Accuracy of diffusion-weighted MR imaging in the diagnosis of sporadic Creutzfeldt-Jakob disease'', Journal of neurology, vol. 250, pp. 222-225, 2003.status: publishe

The effects of electrical stimulation or an electrolytic lesion in the mediodorsal thalamus of the rat on survival, body weight, food intake, and running activity in the activity-based anorexia model

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The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4

Subungual exostosis is a benign bone- and cartilage-forming tumor known to harbour a pathognomonic t(X;6)(q22;q13-14). Using global gene expression analysis and quantitative real-time PCR we could show that this translocation results in increased expression of the IRS4 gene, presumably due to disruption and/or exchange of regulatory sequences with the translocation partner, the COL12A1 gene. A corresponding deregulation at the protein level could be demonstrated in primary cell cultures using a combination of fluorescence in situ hybridization and immunostaining. As the t(X;6) usually is the sole cytogenetic aberration in subungual exostosis, the deregulated expression of IRS4 is likely to be pathogenetically essential. The exact role of IRS4 is still poorly investigated, but IRS proteins are known to act as mediators of signalling from receptors, such as the insulin and insulin-like growth factor 1 receptors, and thus have an important effect on cell growth and survival. (c) 2010 UICC.status: publishe