glycogen and Lipidoses

Topics: Animals; Cats; Cattle; Disease Models, Animal; Dogs; G(M2) Ganglioside; Gangliosidoses; Gaucher Disease; Glycogen; Glycogen Storage Disease Type II; Glycopeptides; Humans; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lipidoses; Lysosomes; Mannosidases; Metabolism, Inborn Errors; Mice; Niemann-Pick Diseases; Rabbits; Sphingolipids

Topics: Animals; Animals, Domestic; Breeding; Cats; Cattle; Dogs; Enzymes; Genes, Recessive; Glycogen; Glycoproteins; Humans; Hydrolases; Leukocytes; Lipidoses; Lysosomes; Metabolism, Inborn Errors; Mink; Sex Chromosomes; Sheep; Sphingolipids; Swine

Topics: Angiokeratoma; Arthritis; Autopsy; Biopsy; Carbohydrate Metabolism, Inborn Errors; Central Nervous System Diseases; Child; Diffuse Cerebral Sclerosis of Schilder; Encephalitis; Encephalomyelitis; Gangliosides; Gaucher Disease; Glycogen; Glycosaminoglycans; Humans; Lipid Metabolism; Lipidoses; Medical History Taking; Metabolic Diseases; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Multiple Sclerosis; Myelin Sheath; Nerve Degeneration; Neurons; Niemann-Pick Diseases; Retinal Degeneration; Slow Virus Diseases; Virus Diseases

Drug-induced phospholipidosis (PL) is a storage disorder caused by the formation of phospholipid-drug complexes in lysosomes. Because of the diversity of PL between species, human cell-based assays have been used to predict drug-induced PL in humans. We established three-dimensional (3D) human liver organoids as described previously and investigated their liver characteristics through multiple analyses. Drug-induced PL was initiated in these organoids and in monolayer HepG2 cultures, and cellular changes were systemically examined. Organoids that underwent differentiation showed characteristics of hepatocytes rather than HepG2 cells. The organoids also survived under PL-inducing drug conditions for 48 h and maintained a more stable albumin secretion level than the HepG2 cells. More cytoplasmic vacuoles were observed in organoids and HepG2 cells treated with more potent PL-induced drugs, but to a greater extent in organoids than in HepG2 cells. Lysosome-associated membrane protein 2, a marker of lysosome membranes, showed a stronger immunohistochemical signal in the organoids. PL-distinctive lamellar bodies were observed only in amiodarone-treated organoids by transmission electron microscopy. Human liver organoids are thus more sensitive to drug-induced PL and less affected by cytotoxicity than HepG2 cells. Since PL is a chronic condition, these results indicate that organoids better reflect metabolite-mediated hepatotoxicity in vivo and could be a valuable system for evaluating the phospholipidogenic effects of different compounds during drug development.

Topics: Albumins; Biomarkers; Cell Survival; Disease Susceptibility; Gene Expression; Glycogen; Hep G2 Cells; Humans; Immunohistochemistry; Lipidoses; Liver; Organoids; Phospholipids; Tissue Culture Techniques

Sacramento splittail (Pogonichthys macrolepidotus) is a species of special concern in California, due to multiple anthropogenic stressors. To better understand the potential impact of contaminant exposure, adult splittail were captured from the Sacramento-San Joaquin River Delta (California, USA) and analyzed for histopathology and contaminant exposure. Organochlorine contaminants (PCBs, DDTs, dieldrin, chlordanes, and PBDEs) and trace metals (Ag, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sn, V, and Zn) were detected in the tissues of all fish. In many samples, human health screening values were exceeded for PCBs (83 of 90 samples), DDTs (32 samples), and dieldrin (37 samples). In contrast, thresholds for fish effects were rarely exceeded. Histopathological analysis indicated the presence of macrophage aggregates in gonads, kidneys, and liver and a high incidence of liver abnormalities. In the liver, observed effects were often moderate to severe for glycogen depletion (55 of 95 fish), lipidosis (hepatocellular vacuolation; 51 fish), and cytoplasmic inclusion bodies (33 fish). Correlations between histopathology and tissue contaminant concentrations were weak and inconsistent. Significant correlations were observed between histopathology indicators and reductions in fish size, body condition, lipid content, and liver weight. These results suggest that splittail histopathology varies as a function of health and nutritional status, rather than exposure to legacy organic and metal pollutants.

Topics: Analysis of Variance; Animals; California; Cyprinidae; DDT; Dieldrin; Female; Glycogen; Gonads; Inclusion Bodies; Kidney; Lipidoses; Liver; Male; Metals, Heavy; Polychlorinated Biphenyls; Rivers; Water Pollutants, Chemical

A patient suffering from a progressive keratopathy which could not be identified clinically underwent penetrating keratoplasty. Light microscopy showed cholesterol deposits in deep stromal regions. Further ultrastructural investigations confirmed these findings and, in addition, fibrous long spacing collagen was found in that region; this represents a new factor in the possible pathogenesis of corneal lipid degenerations.

Topics: Cholesterol; Collagen; Cornea; Corneal Opacity; Corneal Transplantation; Endothelium; Epithelium; Glycogen; Humans; Lipid Metabolism; Lipidoses; Male; Microscopy, Electron; Middle Aged

Topics: Adult; Biological Transport; Brain; Cerebellum; Cerebral Cortex; Cerebral Palsy; Diffuse Cerebral Sclerosis of Schilder; Dysentery; Glycogen; Hepatolenticular Degeneration; Humans; Intellectual Disability; Kernicterus; Lipidoses; Medulla Oblongata; Neuroglia; Neurons; Pons; Synapses

Topics: Glycogen; Humans; Intermittent Claudication; Kinetics; Lipidoses; Muscles

Topics: Child; Glycogen; Glycogen Storage Disease; Humans; Infant; Lipidoses; Liver; Xanthomatosis

Topics: Brain; Brain Diseases; Glycogen; Glycogen Storage Disease; Lipid Metabolism; Lipidoses; Liver