György Pfliegler

The platelet insulin receptor: Detection, partial characterization, and search for a function

A direct demonstration and partial characterization of the insulin receptor on human platelets was obtained by immunoprecipitation with a monoclonal antibody against the human insulin receptor. Two subunits were detected, one with a MW of 95 KD, which dose-dependently was phosphorylated upon challenge of the platelets with insulin and another with a MW of 69 KD that does not become phosphorylated. Retention on wheat germ agglutinin indicates that at least part of the receptor protein is glycosylated. In a search for cellular effects provoked by insulin on platelets, no changes could be detected in cAMP formation or degradation, inositol phosphate formation or phosphorylation of proteins other than the receptor itself.

Platelet insulin receptor determination in non-insulin dependent diabetes mellitus

The platelet membrane insulin receptors of healthy and non-insulin dependent (type 2) diabetic patients were studied. Receptor number and affinity proved to be decreased in type 2 diabetes mellitus. The changes in platelet insulin receptor characteristics are in good correlation with the alterations reported in other tissues or cells. The possible role of these phenomena in the pathogenesis of disturbed platelet function in diabetics needs further investigation.

Trombophilic screening for nonarteritic anterior ischemic optic neuropathy

BackgroundNonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic infarction of the optic nerve head, frequently leading to sudden, mostly irreversible loss of vision. In this study blood thrombophilic factors, as well as cardiovascular risk factors were investigated for their relevance to this pathology. Trombophilic risk factors so far not evaluated were included in the study.Patients and methods37 NAION patients (4 with sequential second eye involvement) and 81 matched control subjects were examined. From blood, protein C, protein S, antithrombin, von Willebrand antigen levels (vWFAg), and factor V (Leiden) mutation, factor VIIIC level, plasminogen activity, lipoprotein (a) and fibrinogen levels, and presence of anticardiolipin antibodies were investigated. Possibly relevant pathologies [e.g. diabetes mellitus (DM), hypertension, and ischemic heart disease] were also registered.ResultsElevated Lp(a) and vWFAg levels, DM, F V (Leiden), hypercholesterolemia, and hyperfibinogenemia proved to be significant risk factors associated with NAION. Forward stepwise logistic regression analysis revealed that high Lp(a), DM, and FV (Leiden) were the main predictive components, with odds ratios 16.88 (p=0.012), 5.78 (p=0.022) and 4.44 (p=0.033), respectively.ConclusionsBased on our results it appears that thrombophilia is likely to contribute to the development of NAION besides vascular damage due to the presence of cardiovascular risk factors. Further data are needed, however, to justify the suggested use of secondary prophylaxis using anticoagulant/antiplatelet therapy.

Plasma levels of beta-thromboglobulin and factor viii-related antigen in diabetic children and adults

In order to investigate the relationship between the in vivo platelet activation in diabetes mellitus and the endothelial damage connected with the diabetic micro- and/or macroangiopathy, plasma levels of beta-thromboglobulin (B-TG) and of factor VIII-related antigen (VIII R:Ag) were studied (1) in juvenile-onset (Type I) diabetics without clinical signs of angiopathy (age under 12 years) and (2) in mostly maturity-onset (Type II) diabetics with and without overt angiopathy (age between 14 and 60 years). Normal controls and nondiabetics with atherosclerosis were also studied. Plasma levels of both proteins were found to be elevated in all the groups of diabetic and atherosclerotic patients in comparison with the controls. Highest levels were found in adult diabetics with angiopathy and in atherosclerotics even without diabetes, but values of the diabetic children were also elevated. The data suggest a causal relationship between the vascular damage and the enhanced platelet reactivity in which the former may play the primary role.

Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding

Summary.  Development of autoantibody against coagulation factor V (FV) is a rare clinical condition with hemorrhagic complications of varying severity. The aim of this study was to establish the pathomechanism of an acquired FV deficiency and characterize the FV inhibitor responsible for the clinical symptoms. A 78‐year‐old female was admitted to hospital with severe gastrointestinal bleeding. General clotting tests and determination of clotting factors were performed by standard methods. FV antigen and FV containing immune complexes were measured by ELISA. The FV molecule was investigated by Western blotting and by sequencing the f5 gene. The binding of patients IgG to FV and activated FV (FVa) was demonstrated in an ELISA system and its effect on the procoagulant activity of FVa was tested in clotting tests and in a chromogenic prothrombinase assay. Localization of the epitope for the antibody was performed by blocking ELISA. FV activity was severely suppressed both in plasma and platelets. FV antigen levels were normal by ELISA using polyclonal anti‐FV antibody or monoclonal antibody against the connecting region of FV, but depressed when HV1 monoclonal antibody against the C2 domain in the FV light‐chain was used as capture antibody. The FV molecule was found intact. An IgG reacting with both FV and FVa was present in the patients plasma and its binding to FV was inhibited by HV1 antibody. FV‐containing immune complexes were detected in the patients plasma and platelet lysate. The patients IgG inhibited the procoagulant function of FVa. An anti‐FV IgG was present in the patients plasma and platelets. The autoantibody reacted with an epitope in the C2 domain of FV light chain and neutralized the procoagulant function of FVa.

Variable response of Hermansky-Pudlak syndrome to prophylactic administration of 1-desamino 8D-arginine in subsequent pregnancies

Hermansky-Pudlak syndrome is characterised by oculocutaneous albinism and haemorrhagic diathesis. The bleeding tendency that is associated with this autosomal recessive disease is caused by storage-pool deficiency and has been reported to be controllable by prophylactic administration of 1-desamino 8D-arginine (desmopressin, DDAVP). The DDAVP prophylaxis at the first delivery of our patient did not prevent the severe haemorrhagic sequeal requiring transfusion of packed red cells and platelets, but the same preventive measure was successful at her second childbirth. Response to prophylactic DDAVP administration varies between as well as within patients with Hermansky-Pudlak syndrome.

The influence of catecholamines on Na, K transport in slow- and fast-twitch muscles of the rat

The effects of catecholamines on active sodium and potassium transport was compared in slow- (SOL) and fasttwitch (EDL) skeletal muscles of the rat. Stimulation of active Na+-extrusion and K+-uptake induced by adrenaline (6–30 μmol · 1−1) and isoprenaline (1–40 μmol · l−1) was markedly greater in slow- than in fast-twitch muscle. In sodiumpreloaded muscles the maximal stimulation of24Na-efflux induced by adrenaline was about 2-fold higher in SOL than in EDL. Isoprenaline caused a 2.4-fold increase in ouabainsensitive86Rb influx in SOL muscle, but failed to alter the ouabain-sensitive influx in EDL. The stimulating action of isoprenaline on86Rb influx in EDL was due to an increase in the ouabain-insensitive fraction of Rb uptake. The effects of catecholamines of fast- and slow-twitch muscles were probably due to the accumulation of cyclic AMP, however the fact that there were no significant differences between the nucleotides levels in fast- and slow-twitch muscle suggests the participation of other mechanism as well. The results presented suggest that cyclic AMP-induced stimulation of ouabain-insensitive transport of cation in the isolated EDL muscle of the rat is similar to that of barnacle muscle.

Hepatitis C virus presumably associated bilateral consecutive anterior ischemic optic neuropathy

Purpose To report a case of bilateral nonarteritic anterior ischemic optic neuropathy (NAION) in a hepatitis C (HCV) infected patient and demonstrate the relationship between HCV and the development of NAION. Methods Case report. Results A 43-year-old woman with chronic HCV infection and long-term euthyroid autoimmune thyroiditis suddenly lost vision in her right eye, and 6 months later in her left eye, due to NAION. Slightly elevated levels of aminotransferases suggested liver infection activity. Anti-HCV antibody was detected; the genotype of the virus was 1b and the viral RNA level was 1.8 × 106 IU/mL. Liver biopsy proved chronic active hepatitis (Ishak score grading: 7, staging: 2). Except for the elevated levels of antithyroid antibodies and a weak antinuclear factor, the detailed laboratory examinations (thrombophilia, cryoglobulin, anticardiolipin antibodies, co-infections) revealed no other abnormalities; a causative relationship between the underlying chronic hepatitis C and bilateral NAION therefore seems probable. The patient was treated with pegylated interferon and ribavirin for 1 year and a sustained viral remission could be achieved. Her vision has neither improved nor deteriorated further. Conclusions This appears to be the first reported case of bilateral NAION presumably caused by HCV infection.

Founder effect is responsible for the p.Leu131Phe heparin-binding-site antithrombin mutation common in Hungary: phenotype analysis in a large cohort

Essentials Antithrombin Budapest3 (ATBp3; p.Leu131Phe) causing heparin‐binding‐site defect is common. We studied the clinical and laboratory phenotype of a large Hungarian ATBp3 cohort (n = 102). Founder effect of ATBp3 was confirmed by 12 genetic markers; anti‐FXa AT assay was 100% sensitive. The spectrum of thrombotic symptoms was wide in ATBp3 patients including arterial thrombosis.

Bilateral Central Retinal Vein Occlusion Caused By Malignant Hypertension in a Young Patient

Central retinal vein occlusion (CRVO) occurring simultaneously in both eyes is a rare condition, in such cases usually associated with severe systemic disease. Overall, only 10% of all CRVO patients are younger than 40 years. A relatively young patient reported with simultaneous bilateral CRVO associated with chronic kidney disease and malignant hypertension. A case of a 35-year-old male patient presented with the complaint of decreased vision in both eyes. Ophthalmic examination revealed bilateral CRVO. Chronic kidney disease leading to malignant hypertension and hyperviscosity was diagnosed as the underlying cause. Clinical support and medical therapy effectively controlled the hypertension, leading to improvement of both the systemic and ocular changes. To the best of our knowledge, this is the first case report of simultaneous bilateral CRVO in a young patient associated with chronic renal failure and malignant hypertension. Primary care providers, either ophthalmologists or physicians, need to consider both common and atypical risk factors for retinal vein occlusion, in order to prevent further ocular morbidity and systemic complications.