Haematology
Kaji Sritharan, Jonathan Rohrer, Alexandra C Rankin, Sachi Sivananthan in Essential Notes for Medical and Surgical Finals, 2021
ALL is more common in children; AML and chronic leukaemias are more common in adults. Diagnosis is based on detecting serum paraprotein, serum free light chains, or urinary BJP and increased plasma cells in bone marrow, in association with evidence of end-organ damage, i.e. anaemia, hypercalcaemia, renal failure, peripheral neuropathy, lytic lesions on plain x-ray or MRI, amyloid. Diagnosis is made when tissue biopsy demonstrates apple green birefringence under polarised light following staining with Congo red, and using Serum Amyloid P (SAP) scanning in specialist centres. Treatment of AL amyloid is similar to that for symptomatic myeloma; treatment of AA amyloid requires management of the chronic inflammatory state. Reduced production of either alpha or beta globin chains leads to alpha and beta thalassaemia respectively. Usually taken from the posterior superior iliac spine, occasionally from the sternum (or tibia in children only); provides important information regarding haematopoiesis and infiltration of bone marrow with abnormal cells.
Neuroprotective Role of Resveratrol in Alzheimer’s Disease
Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu in Phytomedicine and Alzheimer’s Disease, 2020
Many polyphenols plays a pivotal role in the treatment of many diseases, including neurodegenerative disorders (NDs). Resveratrol has long been used in the treatment of NDs. It exerts its protective effect via multiple pathways, such as antioxidant, anti-inflammatory, and antiamyloidogenic cleavage. However, resveratrol also exhibits several disadvantages, such as low solubility and low bioavailability. To overcome these challenges associated with resveratrol, several drug delivery systems were evaluated, a few of which resulted in profound improvements in the therapeutic efficacy of resveratrol. This chapter throws light on some of the pathways by which resveratrol achieves neuroprotection, and the drug delivery systems used to overcome innate challenges, such as low bioavailability.
Other Common Peripheral Neuropathies
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
This chapter discusses the common conditions of rare peripheral nerve disorders seen in clinical practice. It describes the causes, clinical features, and pathological findings. Primary amyloidosis occurs in 50% of cases and is associated with paraprotein deposition and underlying plasma cell diseases such as multiple myeloma. Findings of monoclonal free-light chain or plasma cells in bone marrow biopsy and urinary test are suggestive for primary amyloidosis. Secondary amyloidosis is the rarest causative variant of amyloid neuropathy because it is always present with peripheral neuropathy. Secondary amyloidosis is commonly associated with systemic chronic inflammatory diseases. The main histological sign of toxic neuropathy is axonal degeneration. Generally, patients present with symmetrical distal sensorimotor neuropathy with muscle weakness, hammer toes, and pes cavus. The patient typically presents during childhood with kinky hair, peripheral neuropathy, white matter changes in the brain, and skeletal abnormalities.
Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis
Published in Amyloid, 2010
Jean D. Sipe, Merrill D. Benson, Joel N. Buxbaum, Shu-Ichi Ikeda, Giampaolo Merlini, Maria J.M. Saraiva, Per Westermark
A system of amyloid fibril nomenclature based on the chemical identity of the amyloid fibril forming protein is recommended. This system has been in use for approximately 40 years, but current literature remains confused with clinical and histochemical designations used when the amyloid disease processes were poorly understood. To be designated an amyloid fibril protein, the protein must occur in tissue deposits and exhibit affinity for Congo red and green birefringence when viewed by polarisation microscopy. Furthermore, the protein must have been unambiguously characterised by protein sequence analysis (DNA sequencing in the case of familial diseases). Current nomenclature lists of 27 human and nine animal fibril proteins are provided together with a list of eight inclusion bodies that exhibit some of the properties of amyloid fibrils.
Atypical AA amyloid deposits in bovine AA amyloidosis
Published in Amyloid, 2012
Tomoaki Murakami, Yasuo Inoshima, Yoshiyasu Kobayashi, Takane Matsui, Hisashi Inokuma, Naotaka Ishiguro
In bovine amyloid protein A (AA) amyloidosis, amyloid deposits are typically observed in the kidney and spleen at necropsy. To determine the distribution of amyloid deposits in cows affected with AA amyloidosis, we examined organs known to be sites of amyloid deposits that are also processed for human consumption in 14 cows: 11 with typical clinical symptoms (typical amyloidosis) and three with no typical clinical symptoms (atypical amyloidosis). We found unusually high amounts of amyloid deposits in the tongue and other organs in all 14 cows regardless of the presence or absence of clinical amyloidosis symptoms. Cows with typical amyloidosis had heavier amyloid deposits in the spleen and renal glomeruli than cows with atypical amyloidosis. From clinical symptoms and histological examinations, we found that cows with typical and atypical amyloidosis can be classified into two groups, class I and class II, according to the presence or absence of heavy amyloid deposits in the spleen and renal glomeruli. However, no significant differences were observed between the amyloid fibrils of class I and class II amyloidosis by electron microscopy and Western blot analysis.
Cell assay for the identification of amyloid inhibitors in systemic AA amyloidosis
Published in Amyloid, 2019
Ioana Puscalau-Girtu, Judith S. Scheller, Stephanie Claus, Marcus Fändrich
Systemic AA amyloidosis is still, up to this day, a life-threatening complication of chronic inflammatory diseases. Despite the success of anti-inflammatory treatment, the prognosis of some AA patients is still poor, which is why therapies directed at the amyloidogenic pathway in AA amyloidosis are being sought after. The cell culture model of amyloid formation from serum amyloid A1 (SAA1) protein remodels crucial features of AA amyloid deposit formation in vivo. We here demonstrate how the cell model can be utilized for the identification of compounds with amyloid inhibitory activity. Out of five compounds previously reported to inhibit self-assembly of various amyloidogenic proteins, we found that epigallocatechin gallate (EGCG) inhibited the formation of SAA1-derived fibrils in cell culture. From a series of compounds targeting the protein quality control machinery, the autophagy inhibitor wortmannin reduced amyloid formation, while the other tested compounds did not lead to a substantial reduction of the amyloid load. These data suggest that amyloid formation can be targeted not only via the protein self-assembly pathway directly, but also by treatment with compounds that impact the cellular protein machinery.
Related Knowledge Centers
- Polypeptides
- Protein Folding
- Proteins
- Ribosomes
- Saa
- Multiprotein Complexes
- Amino Acids