1. The high-resolution 1H NMR (MRS) spectra of human brain tumor homogenates revealed a broad resonance at 5.3-5.4 ppm in glioblastoma multiforme (N = 16) and brain metastases (N = 3). The broad resonance was identified as ceramide, a sphingosine-fatty acid combination portion of ganglioside, indicating an elevated abundance of monounsaturated fatty acids. GLC analysis of gangliosides in the highly malignant glioblastoma multiforme revealed that the elevated monounsaturated fatty acid is oleic acid (C18:1). The resonance at 5.3-5.4 ppm region was not detectable in normal human brain (N = 2), in meningiomas (N = 2), or in low-grade astrocytomas (N = 12). In normal human brain the abundance of monounsaturated fatty acid is minimal. 2. This investigation was made possible because the method of producing homogenate resulted in (i) no loss of lipids during the process and (ii) a well-homogenised sample, with (iii) no loss in chemical integrity. 3. The properties of tumor gangliosides include antigenic specificity and immunosuppressive activity and the ceramide, a sphingosine-fatty acid combination, noticeably influences the ganglioside immunosuppressive activity. 4. The observation of 1H NMR ceramide resonance in high-malignant brain tumors emphasizes the dramatic role of aberant gangliosides and ceramide precursors on the grade of malignancy and invasiveness. 5. Further insight into the specific nature of the ceramide portion of gangliosides in grading the malignancy of brain tumors should be investigated further.
Background and aim: Spinal bulbar muscular atrophy (SBMA) is a progressive adult-onset X-linked neuromuscular disease. Although traditionally considered a motor neuron disorder, recent advances have highlighted a primary myopathic component. We evaluated levels of phosphorylated neurofilament heavy chain (pNfH), a known biomarker for neurodegeneration, in SBMA.
Materials and methods:We collected plasma and serum from 46 SBMA, 50 ALS and 50 healthy control cases, alongside with plasma from a mouse model of SBMA (AR100) and littermate controls. We measured pNfH plasma levels using Single molecule array (Simoa), we assessed functional scales and we gathered demographic data. We analysed data using Mann-Whitney U test, Kruskal-Wallis test and Cox regression analysis.Results: Plasma pNfH levels were significantly increased in ALS, but, intriguingly, there was no change in SBMA. These results were also confirmed in SBMA mice.The ROC curve highlighted that pNfH levels can effectively distinguish between ALS and SBMA (AUC 0.95).Conclusions: Unexpectedly, levels of pNfH are normal in SBMA, whilst they are increased in ALS, and suggest pNfH could serve as a biomarker to differentiate the two diseases. Further, this finding is in agreement with recent evidence showing that primary muscle damage is a crucial feature in SBMA.
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