Dissecting a neuron‐to‐liver crosstalk to modulate lipid metabolism in lisosomal storage diseases

This book begins with a general survey of the biochemistry and metabolism of fatty acids, glycerolipids, phospholipids, sphingolipids and cholesterol. A number of diseases involving "synthesis, transport or deposit" of these lipids are then reviewed, not including disorders of metabolism of steroids other than cholesterol, nor the carotenoids. The descriptions of clinical and pathologic aspects of the various diseases of lipid metabolism vary from good to excellent, and the author demonstrates both judgement and willingness to take a stand in some of the more controversial fields, such as the glycogen storage diseases.

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Cytoplasmic Granules in Lymphocytes from Rats Dosed with SK&F 14336-D

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066838 ◽

1971 ◽

Vol 29 ◽

pp. 556-557

Author(s):

T. G. Merrill ◽

B. J. Payne ◽

A. J. Tousimis

Keyword(s):

Lipid Storage ◽

Pokeweed Mitogen ◽

Electron Microscopic ◽

Cytoplasmic Granules ◽

Storage Diseases ◽

Tay Sachs Disease ◽

Large Numbers ◽

Microscopic Studies ◽

Neurovisceral Lipidosis

Rats given SK&F 14336-D (9-[3-Dimethylamino propyl]-2-chloroacridane), a tranquilizing drug, developed an increased number of vacuolated lymphocytes as observed by light microscopy. Vacuoles in peripheral blood of rats and humans apparently are rare and are not usually reported in differential counts. Transforming agents such as phytohemagglutinin and pokeweed mitogen induce similar vacuoles in in vitro cultures of lymphocytes. These vacuoles have also been reported in some of the lipid-storage diseases of humans such as amaurotic familial idiocy, familial neurovisceral lipidosis, lipomucopolysaccharidosis and sphingomyelinosis. Electron microscopic studies of Tay-Sachs' disease and of chloroquine treated swine have demonstrated large numbers of “membranous cytoplasmic granules” in the cytoplasm of neurons, in addition to lymphocytes. The present study was undertaken with the purpose of characterizing the membranous inclusions and developing an experimental animal model which may be used for the study of lipid storage diseases.

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A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115924 ◽

1975 ◽

Vol 33 ◽

pp. 460-461

Author(s):

Sidney D. Kobernick ◽

Edna A. Elfont ◽

Neddra L. Brooks

Keyword(s):

Lipid Metabolism ◽

New Zealand ◽

Aortic Wall ◽

Rabbit Aorta ◽

Plaque Formation ◽

Metabolic Changes ◽

Atherosclerotic Plaques ◽

Cytochemical Study ◽

Cellular Alteration ◽

New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

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Electron Microscopy in the diagnosis of lysosomal storage diseases

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156316 ◽

1989 ◽

Vol 47 ◽

pp. 866-867

Author(s):

Carole Vogler ◽

Harvey S. Rosenberg

Keyword(s):

Electron Microscopy ◽

Lysosomal Enzyme ◽

Rectal Mucosa ◽

Lysosomal Storage Diseases ◽

Cell Types ◽

Lysosomal Storage ◽

Storage Material ◽

Ultrastructural Examination ◽

Blood Leukocytes ◽

Storage Diseases

Diagnostic procedures for evaluation of patients with lysosomal storage diseases (LSD) seek to identify a deficiency of a responsible lysosomal enzyme or accumulation of a substance that requires the missing enzyme for degradation. Most patients with LSD have progressive neurological degeneration and may have a variety of musculoskeletal and visceral abnormalities. In the LSD, the abnormally diminished lysosomal enzyme results in accumulation of unmetabolized catabolites in distended lysosomes. Because of the subcellular morphology and size of lysosomes, electron microscopy is an ideal tool to study tissue from patients with suspected LSD. In patients with LSD all cells lack the specific lysosomal enzyme but the distribution of storage material is dependent on the extent of catabolism of the substrate in each cell type under normal circumstances. Lysosmal storages diseases affect many cell types and tissues. Storage material though does not accumulate in all tissues and cell types and may be different biochemically and morphologically in different tissues.Conjunctiva, skin, rectal mucosa and peripheral blood leukocytes may show ultrastructural evidence of lysosomal storage even in the absence of clinical findings and thus any of these tissues can be used for ultrastructural examination in the diagnostic evaluation of patients with suspected LSD. Biopsy of skin and conjunctiva are easily obtained and provide multiple cell types including endothelium, epithelium, fibroblasts and nerves for ultrastructural study. Fibroblasts from skin and conjunctiva can also be utilized for the initiation of tissue cultures for chemical assays. Brain biopsy has been largely replaced by biopsy of more readily obtained tissue and by biochemical assays. Such assays though may give equivical or nondiagnostic results and in some lysosomal storage diseases an enzyme defect has not yet been identified and diagnoses can be made only by ultrastructural examination.

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