Isolation and characterization of an abnormal high density lipoprotein in Tangier Diesase.
(17/102)
The nature of the high density lipoproteins has been investigated in five patients homozygous for Tangier disease (familial high density lipoprotein deficiency). It has been established that Tangier high density lipoproteins, as isolated by ultracentrifugation, are morphologically heterogenous and contain several proteins (Apo B, albumin, and Apo A-II). An abnormal lipoprotein has been isolated from the d = 1.063-1.21 g/ml ultracentrifugal fraction by agarose-column chromatography which contains apoprotein A-II as the sole protein constituent. In negative-stain electron microscopy, these lipoproteins appeared as spherical particles 55-75 A in diameter. By a variety of criteria (immunochemical, polyacrylamide electrophoresis, amino acid composition, and fluorescence measurements), apoprotein A-I the major apoprotein of normal high density lipoproteins and the C apoproteins were absent from this lipoprotein. As demonstrated by (125)I very low density lipoprotein incubation experiments with Tangier plasma, C apoproteins did not associate with lipoproteins of d = 1.063-1.21 g/ml. Tangier apoprotein A-II, isolated to homogeneity by delipidation of the apoprotein A-II-containing lipoprotein or Sephadex G-200 guanidine-HCl chromatography of the d = 1.063-1.21 g/ml fraction, was indistinguishable from control apoprotein A-II with respect to amino acid composition and migration of tryptic peptides in urea-polyacrylamide electrophoresis. The ability of Tangier apoprotein A-II to bind phospholipid was demonstrated by in vitro reconstitution experiments and morphological and chemical analysis of lipid-protein complexes. It is concluded that normal high density lipoproteins, as defined by polypeptide composition and morphological appearance, are absent from Tangier plasma and that as a consequence, the impairment of C apoprotein metabolism contributes to the hypertriglyceridemia and fasting chylomicronemia observed in these patients. (+info)
Hereditary C1q deficiency: a new family with C1qA deficiency.
(18/102)
Hereditary deficiency of complement component C1q is a rare genetic disorder with susceptibility to recurrent infections with polysaccharide-containing encapsulated microorganisms and a high prevalence of autoimmune diseases, most often systemic lupus erythematosus (SLE). Here, we report a 29-month-old boy who presented with facial rash and history of early death of a sibling with infections, who was found to have a selective deficiency of C1q. The facial rash was composed of patchy erythematous plaques and centrally hypopigmented macules and desquamation. Two siblings had died of severe bacterial infections and his uncle had died of meningitis. Molecular study disclosed a homozygous point mutation in the C1qA chain gene. Five members of the family, including the parents and three healthy siblings, were heterozygous for this mutation. (+info)
Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A.
(19/102)
Peripheral neuropathy in angioimmunoblastic lymphadenopathy with dysproteinaemia.
(20/102)
A case of angioimmunoblastic lymphadenopathy with dysproteinaemia complicated by a subacute peripheral neuropathy is described. Clinically the neuropathy was mainly motor, but pain and paraesthesiae in the legs were also present. Sural nerve biopsy indicated decreased numbers of myelinated fibres, mainly the largest, without actual signs of degeneration or regeneration. However, the occurrence of denervation bands indicated that degeneration had led to loss of myelinated fibres. (+info)
Subset of natural killer cells is induced by immune complexes to display Fc receptors for IgE and IgA and demonstrates isotype regulatory function.
(21/102)
Expression of Fc receptors for IgE (FcER) or IgA (FcAR) on purified natural killer (NK) cells was investigated. No FcER+ and a few FcAR+ NK cells were detectable on freshly separated NK (NKH-1+) cells from normal donors. Incubation of NK cells with IgE-anti-IgE immune complexes or IgA-anti-IgA immune complexes induced up to 10 and 20% FcER+ or FcAR+ cells, respectively. These FcR were induced on CD3- but not on CD3+ NKH-1+ cells. In contrast, NK cells from patients with various dysgammaglobulinemias could not be induced to express FcER or FcAR corresponding to their abnormal circulating IgE and/or IgA levels. Enriched FcER+ or FcAR+ induced NK cell supernatants from normals enhanced IgE or IgA synthesis from Ig secreting B cell lines in an isotype-specific fashion without increasing proliferation. Thus NK cells, after interaction with specific Ig isotypes in complexes, express FcR and produce differentiation factors for that isotype. (+info)
Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.
(22/102)
In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis. (+info)
Glycoprotein-180 deficiency: genetics and abnormal neutrophil activation.
(23/102)
Neutrophil function was studied in a patient with polymorphonuclear leukocyte (PMN) glycoprotein-180 deficiency and in her parents. PMNs of the patient had abnormal chemotaxis, phagocytosis, adherence, surface charge, and membrane-associated events of activation. Selective defects to C3b, immunoglobulin G (IgG), phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) are described, although C3b receptor density was normal. The parents were found to have abnormal adherence to nylon-wool fibers, abnormal transmembrane potential depolarization with PMA, and reduced amounts of glycoprotein-180 in their PMNs. These studies provide further evidence that the oxidative burst has several different pathways for activation. They demonstrate that the absence of a single PMN surface glycoprotein is associated with a broad spectrum of PMN functional abnormalities. Finally, the observations made in the parents support an autosomal recessive mode of inheritance. (+info)
Liver replacement for alpha1-antitrypsin deficiency.
(24/102)
A 16-year-old girl with advanced cirrhosis and severe alpha 1-antitrypsin deficiency of the homozygous Pi ZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal Pi MM phenotype, the alpha 1-antitrypsin concentration in the recipient's serum rose to normal; it had the Pi MM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous Pi MZ donor was followed by the identification of that phenotype in the recipient's serum. Neither liver graft developed the alpha 1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic-based inborn error of metabolism is metabolically cured by liver replacement. (+info)