Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha- granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor

Weiss, Harvey J.; Witte, Larry; Kaplan, Karen L.; Lages, Bruce; Chernoff, Arthur; Nossel, Hymie L.; Goodman, DeWitt S.; Baumgartner, Hans R.

doi:10.1182/blood.v54.6.1296.1296

Cited by 222 publications

(98 citation statements)

References 54 publications

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“…Gunmetal platelets have an unusual alteration in migration pattern upon sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of low molecular weight guanosine triphosphate (GTP)-binding proteins, implicated in the regulation of the biosynthesis and intracellular movement of organelles (Schimmoller et al, 1998;Chavrier & Goud, 1999). A related combined alpha and dense granule abnormality has been described in alpha/delta storage pool deficiency syndrome (Weiss et al, 1979). Alpha granule deficiencies, similar to those of the gunmetal mouse, occur in the rare grey platelet syndrome (Smith et al, 1997), and similar combined hypopigmentation and dense granule abnormalities occur in Hermansky-Pudlak syndrome (HPS) (Shotelersuk & Gahl, 1998;Swank et al, 1998;Spritz, 1999).…”

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confidence: 99%

Cell‐specific abnormal prenylation of Rab proteins in platelets and melanocytes of the gunmetal mouse

Zhang

Zhen

et al. 2002

Br J Haematol

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Summary. The mutant gunmetal mouse exhibits reduced rates of platelet synthesis, abnormalities of platelet alpha and dense granules and hypopigmentation. Several of these features resemble those of human alpha/delta platelet storage pool disease, grey platelet syndrome and HermanskyPudlak syndrome. Gunmetal mice have reduced levels of Rab geranylgeranyltransferase (RabGGTase), which adds lipophilic prenyl groups to the carboxyl terminus of Rab proteins. The degree of prenylation and the subcellular distribution of several Rab proteins were evaluated in mutant platelets, melanocytes and other tissues. Significant deficits in prenylation and membrane binding of most Rabs were observed in platelets and melanocytes. In contrast, minimal alterations in Rab prenylation were apparent in several other gunmetal tissues despite the fact that RabGGTase activity was equally diminished in these tissues. The mutant tissue-specific effects are probably due to increased concentrations of Rab proteins in platelets and melanocytes. These experiments show that Rab proteins are differentially sensitive to levels of RabGGTase activity and that normal platelet synthesis, platelet organelle function and normal pigmentation are highly sensitive to the degree of prenylation and membrane association of Rab proteins. Further, the tissue-specific effects of the gunmetal mutation suggest that RabGGTase is a potential target for therapy of thrombocytosis.

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confidence: 99%

Cell‐specific abnormal prenylation of Rab proteins in platelets and melanocytes of the gunmetal mouse

Zhang

Zhen

et al. 2002

Br J Haematol

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“…This thromboplastic activity was ascribed to the presence of numerous membranous blebs, vesicles and lamellar structures and bodies as seen in TEM (197). Similarly looking material originating from activated platelets in the form of multivesicular structures was discussed (1 10-1 14,116,135,136,181). It probably should be pointed out, that platelet multivesicular structures or bodies bear striking morphological resemblance also to multivesicular bodies isolated from fibroblasts (73) and share blebs appearance similar to secondary lysosomes of certain endothelia during their exocytosis (123).…”

Section: Platelet Multivesicular Bodies Versus Pneumocyte Type II Mumentioning

confidence: 94%

“…As is the case in lysosomes, platelet storage organelles accumulate mepacrine and acridine orangelysosomotropic drugs with a great affinity to an acidic interior of lysosomes, where they can be detected easily by their fluorescence (126,(224)(225)(226)(227). A claim that mepacrine accumulates only in platelet dense bodies (227) is contradicted by the fact, that many granules in a given platelet stain with mepacrine (126,(224)(225)(226)(227), whereas frequency of dense bodies in human platelets seems to be less then 1 per platelet (14,15). Recently Costa et al (228) suggested that 60% of quinacrine resides in dense granules and 14% in platelet lysosomes, but their morphometry technique includes alphagranules under the term of dense granules and is thus in agreement with important observation on mepacrine accumulation in platelet alphagranules (224).…”

Section: A Lysosomal Concept Of Platelet Secretionmentioning

confidence: 99%

“…Using electron microscope transmission (TEM) or scanning (SEM) morphological and cytochemical techniques with biochemical correlations, previously called granulomer of chromomer (12), has been now subdivided into platelet alphagranules and dense bodies (secretory granules), lysosomes and mitochondria (7,13). Alpha granules are most abundant and comprise cca 10% of a platelet volume, whereas dense granules only 0.1% and correspondingly are 100% less frequent then alphagranules (14,15). A possibility, that dense bodies may represent a fixation artefact was expressed (16).…”

Section: Introductionmentioning

confidence: 99%

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Lysosomal Consept of Platelet Secretion ‐ Revisited

Polasek

1989

European J of Haematology

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Certain morphological and biochemical aspects of platelet secretion are discussed. Based on own experiments and review of the literature a hypothesis is forwarded that platelet secretory granules or rather storage organelles can be viewed as secondary lysosomes participating in platelet endocytosis and exocytosis. Formation of the platelet thromboplastic activity, so called PF3, is linked to the platelet storage organelles disintegration and lypolysis during their exocytosis through the platelet plasma membrane.

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“…Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a mild bleeding diathesis caused by a storage pool platelet defect, and widespread deposition of ceroid pigment in cells of the reticuloendothelial system. 2294,2295 Complications include pulmonary fibrosis, renal failure, cardiomyopathy and a granulomatous colitis. 2294 The disease is autosomal recessive and genetically heterogeneous, 2296,2297 resulting from defects in genes affecting the function of multiple cytoplasmic organelles.…”

Section: Hermansky-pudlak Syndromementioning

confidence: 99%

Developmental and Inherited Liver Disease

Quaglia¹,

Roberts²,

Torbenson³

2018

Macsween's Pathology of the Liver

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Diagnostic approach to histology 113 Neonatal and early infantile liver disease 113 Postneonatal, childhood and adulthood presentation 118 Neonatal hepatitis 119 Histopathological features 120 Biliary atresia 121 Classification and aetiopathogenesis 121 Pathological features at surgical intervention 124 Pathology of intrahepatic changes 126 Paucity of intrahepatic bile ducts 129 Alagille syndrome (arteriohepatic dysplasia) 129 Nonsyndromic duct paucity disorders 131 Bile duct anomalies, congenital dilations and ductal plate malformation disorders 131 Choledochal cyst 132 Hereditary fibropolycystic disease (ductal plate malformation) 133 Cystic fibrosis 141 Hereditary disorders of bile acid synthesis and bilirubin metabolism 143 Primary disorders of bile acid synthesis 143 Disorders of bile canalicular transporters 146 Other diseases causing intrahepatic cholestasis 150 Hereditary defects of bilirubin metabolism 151 Disorders of porphyrin metabolism 153 Porphyria cutanea tarda 154 Erythropoietic protoporphyria 155 Disorders of carbohydrate metabolism and related conditions 156 Glycogen storage diseases (glycogenoses) 156 Myoclonus epilepsy, Lafora type (Lafora disease) 161 Galactosaemia Hereditary fructose intolerance Disorders of glycoprotein and glycolipid metabolism Mucopolysaccharidoses Aspartylglucosaminuria α-Mannosidosis Fucosidosis Mucolipidoses Congenital disorders of glycosylation (carbohydrate-deficient glycoprotein syndrome) Endoplasmic reticulum storage diseases α1-Antitrypsin deficiency α1-Antichymotrypsin deficiency Afibrinogenaemia and hypofibrinogenaemia Antithrombin III deficiency Disorders of amino acid metabolism Hereditary tyrosinaemia type 1 Congenital hyperammonaemia syndromes and urea cycle disorders Cystinosis Homocystinuria (cystathionine β-synthase deficiency) Disorders of lipoprotein and lipid metabolism Abetalipoproteinaemia Familial hypobetalipoproteinaemia Familial high-density lipoprotein deficiency (Tangier disease) Familial hypercholesterolaemia Wolman disease and cholesteryl ester storage disease Gangliosidoses α-Galactosidase A deficiency (Fabry disease) Sulphatide lipidosis (metachromatic leucodystrophy) Chapter 3 Developmental and Inherited Liver Disease

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Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha- granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor

Cited by 222 publications

References 54 publications

Cell‐specific abnormal prenylation of Rab proteins in platelets and melanocytes of the gunmetal mouse

Cell‐specific abnormal prenylation of Rab proteins in platelets and melanocytes of the gunmetal mouse

Lysosomal Consept of Platelet Secretion ‐ Revisited

Developmental and Inherited Liver Disease

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