OBJECTIVE: The etiology and pathogenesis of moyamoya disease remain unclear. Furthermore, the definitive diagnostic protein-biomarkers for moyamoya disease are still unknown. The present study analyzed serum proteomes from normal controls and moyamoya patients to identify novel serological biomarkers for diagnosing moyamoya disease. METHODS: We compared the two-dimensional electrophoresis patterns of sera from moyamoya disease patients and normal controls and identified the differentially-expressed spots by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry. RESULTS: We found and analyzed 22 differently-expressed proteomes. Two proteins were up-regulated. Twenty proteins were down-regulated. Complement C1 inhibitor protein and apolipoprotein C-III showed predominantly changed expressions (complement C1 inhibitor protein averaged a 7.23-fold expression in moyamoya patients as compared to controls, while apolipoprotein C-III averaged a 0.066-fold expression). CONCLUSION: Although our study had a small sample size, our proteomic data provide serologic clue proteins for understanding moyamoya disease.
Apolipoprotein C-III ; Biomarkers ; Complement C1 Inhibitor Protein ; Electrophoresis ; Humans ; Mass Spectrometry ; Moyamoya Disease ; Proteins ; Proteome ; Sample Size

PURPOSE: To determine the prevalence of hematologic abnormalities in patients with retinal vein occlusion (RVO) less than 55 years of age. METHODS: Medical records of twenty-three patients with RVO less than 55 years old were reviewed to evaluate the results of CBC, ESR, homocysteine, Protein C, Protein S, antithrombin III, anticardiolipin antibody, lupus anticoagulant and lipid profile. Patients were considered to have a positive test if the results were outside the laboratory's established range. RESULTS: Four patients had ischemic central retinal vein occlusion (CRVO), 8 non-ischemic CRVO, and 11 branch retinal vein occlusion (BRVO). The prevalence of AT III and protein S deficiency were 4.3% and 13.0% respectively. The prevalence of homocystinemia, lupus anticoagulant, hyperlipidemia were 8.7%, 4.3% and 26.1% respectively. There was no positive finding in anticardiolipin antibody or protein C deficiency. CONCLUSIONS: Hypercoagulability may play a role in the pathogenesis of RVO in patients less than 55 years old, especially in those who had no systemic risk factors. The authors recommend examining systemic risk factor evaluation and hematologic evaluation to rule out thrombophilia. Those who show positive findings should be given a consultation with a hematologist for the proper management.
Antibodies, Anticardiolipin ; Antithrombin III ; Homocysteine ; Humans ; Hyperlipidemias ; Lupus Coagulation Inhibitor ; Medical Records ; Middle Aged ; Prevalence ; Protein C ; Protein C Deficiency ; Protein S ; Protein S Deficiency ; Retinal Vein Occlusion* ; Retinal Vein* ; Retinaldehyde* ; Risk Factors* ; Thrombophilia

PURPOSE: To evaluate the significance of thrombophilic factors in retinal vein occlusive diseases. METHODS: Thirty-two patients with retinal vein occlusion (19 patients at the age of 55 or less, 13 patients at the age of 56 or more) underwent laboratory evaluation for CBC, lipid profile, VDRL/TPHA, homocysteine, protein C activity, protein S activity, lipoprotein (a), platelet aggregation test, Factor V Leiden, lupus anticoagulant, anticardiolipin antibody, fibrinogen, and antithrombin III. RESULTS: The abnormal laboratory findings (high homocysteine, hyperlipidemia, thrombocytosis, lipoprotein (a), high ESR, and decreased protein S activity) were found more often in patients of 55 years or less than those of 56 or more. CONCLUSIONS: The thrombophilic factors were more common positive findings at or less than 55 years. Thrombophilic factor tests are recommended in young patients with retinal vein occlusion.
Antibodies, Anticardiolipin ; Antithrombin III ; Factor V ; Fibrinogen ; Homocysteine ; Humans ; Hyperlipidemias ; Lipoprotein(a) ; Lupus Coagulation Inhibitor ; Platelet Aggregation ; Protein C ; Protein S ; Retinal Vein Occlusion ; Retinal Vein* ; Retinaldehyde* ; Thrombocytosis

BACKGROUND/AIMS: Idiopathic portal hypertension (IPH) is defined as portal hypertension with splenomegaly and hypersplenism in the absence of cirrhosis or obstruction of portal vein or hepatic vein. It has been recently suggested that hypercoagulable state and thromboembolic event of small portal veins have an important role in the pathogenesis of IPH. In this study, we evaluated the clinical and pathological characteristics of IPH. METHODS: We reviewed clinical, endoscopic, radiologic and liver biopsy findings of 10 cases of IPH retrospectively. RESULTS: The tests for antithrombin III deficiency, protein C deficiency, protein S deficiency, resistance to activated protein C, lupus anticoagulant, antiphospholipid antibodies, anticardiolipin antibodies were normal. Pathologic findings revealed portal vein dilatation (10/10), loss of portal vein (6/10), portal vein sclerosis (1/10), dilated megasinusoids (9/10), dilation of terminal hepatic vein (8/10), narrowing of terminal hepatic vein (2/10), hairline fibrous septa (1/10), and regenerative nodule (1/10). CONCLUSIONS: The pathologic finding of IPH showed various manifestations of obliterative portal venopathy although there was no hypercoagulable state.
Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Antithrombin III Deficiency ; Biopsy ; Dilatation ; Fibrosis ; Hepatic Veins ; Hypersplenism ; Hypertension, Portal* ; Liver ; Lupus Coagulation Inhibitor ; Portal Vein ; Protein C ; Protein C Deficiency ; Protein S Deficiency ; Retrospective Studies ; Sclerosis ; Splenomegaly

Thrombosis is a well known manifestation in patients with systemic lupus erythematosus, along with lupus anticoagulant, anticardiolipin antibody and anti beta2-glycoprotein I. We describe here a 44-year-old female with an abdominal aorta thrombosis of SLE and the patient had no antiphospholipid antibodies. She had this unusual site of thrombosis and this was associated with protein C and S deficiency. She had no other cause of thrombosis. After anticoagulant treatment, her thrombosis of the abdominal aorta resolved.
Adult ; Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Aorta ; Aorta, Abdominal ; beta 2-Glycoprotein I ; Female ; Humans ; Lupus Coagulation Inhibitor ; Lupus Erythematosus, Systemic ; Protein C ; Thrombosis

PURPOSE: We performed this study to evaluate the incidence and clinical significance of antiphospholipid antibodies (aPL Ab) in Korean children with Henoch-Schonlein purpura (HSP). METHODS: The medical records of 62 patients (31 boys and 31 girls) aged 6.0+/-3.1 (1-16) years with a clinical diagnosis of HSP based on the EULAR/PReS criteria were reviewed retrospectively. From the years 2007 to 2009, the sera from children with acute HSP were tested for aPL Ab such as LA, anti-cardiolipin antibody and anti-beta2 glycoprotein I antibody. RESULTS: LA was positive in 18 (29%) of the 62 patients with HSP and We divided the patients into the two groups LA positive group (N=18) and LA negative group (N=44). There were no significant differences between the two groups with regard to abdominal pain, arthralgia and renal involvement, but LA positive group had significantly higher C-reactive protein (4.3+/-7.2 mg/dL vs. 1.3+/-1.8 mg/dL, P=0.035), erythrocyte sedimentation rate (37.5+/-26.2 mm/hr vs. 25.1+/-22.6 mm/hr, P= 0.039), IgM (148.1+/-48.4 mg/dL vs. 114.9+/-41.5 mg/dL, P=0.024), C3 (143.1+/-21.9 mg/dL vs. 129.7+/-24.5 mg/dL, P=0.048) and C4 levels (30.9+/-6.3 mg/dL vs. 24.9+/-7.8 mg/dL, P=0.002) compared with LA negative group. CONCLUSION: We found that the incidence of positive aPL Ab tests was relatively higher in Korean children with HSP and the presence of aPL Ab was associated with acute inflammatory process of HSP. These results suggest that the aPL Ab are involved in the pathogenesis of HSP in children.
Abdominal Pain ; Aged ; Antibodies, Antiphospholipid ; Arthralgia ; Blood Sedimentation ; C-Reactive Protein ; Child ; Glycoproteins ; Humans ; Immunoglobulin M ; Incidence ; Lupus Coagulation Inhibitor ; Medical Records ; Purpura, Schoenlein-Henoch ; Retrospective Studies

BACKGROUND: After multiple trauma, blood coagulation activity is enhanced and fibrinolytic activity is suppressed. Due to high tissue thromboplastin concentration in cerebral tissue, more serious coagulation and fibrinolytic abnormalities may occur when concomitant head trauma is present. The aim of this study was to determine the changes in coagulation and fibrinolysis after trauma and the effects of head trauma on coagulation and fibrinolysis. METHODS: This study includes 35 trauma patients: 16 patients with head trauma (group A) and 19 patients without head trauma (group B). We measured the plasma levels of functional protein C, antithrombin III (AT III), thrombin antithrombin III complex (TAT), plasmin alpha 2 plasmin inhibitor complex (PIC), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 antigen (PAI-1) on admission and on days 1, 2, 4, and 6 after the trauma. RESULTS: The TAT and the TAT/PIC were significantly higher in group A than in group B on all days. PIC was significantly lower in group A than in group B on all days except the day of admission. Over the course of time, the TAT and the TAT/PIC decreased in both groups and PIC increased. On admission, the PAI-1 of both groups was increased, but it decreased over the course of time. The t-PA was increased on admission, was suppressed on the 1st day, and then increased again. The PAI-1 and the t-PA showed no significant difference between the two groups. CONCLUSIONS: After multiple trauma, coagulation was enhanced and fibrinolysis was suppressed. Enhanced coagulation and suppressed fibrinolysis were significantly greater in group A than in group B.
alpha-2-Antiplasmin ; Antithrombin III ; Blood Coagulation ; Craniocerebral Trauma ; Fibrinolysin ; Fibrinolysis* ; Humans ; Multiple Trauma* ; Plasma ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Protein C ; Thrombin ; Thromboplastin ; Tissue Plasminogen Activator

This study was purposed to investigate the mechanism of C-reactive protein (CRP) on proliferation of U266 cells. The human multiple myeloma cell line U266 was incubated with human CRP (0, 5, 10, 20 mg/L) for 24 hours, then the proliferation level of U266 cells was detected by using blood analyser. The mRNA expressions of survivin and HSP90alpha were examined by RT-PCR. The results showed that the proliferation ratio was increased, as compared with the control group (p<0.05); furthermore, the mRNA levels of survivin and HSP90alpha were up-regulated in proportion to the increased CRP concentrations. There was significant correlation between expression of survivin and HSP90alpha (r=0.737, p<0.0001) in incubated cells. It is concluded that CRP can stimulate the proliferation of MM cells directly by up-regulating the expression of survivin and HSP90alpha in MM cells. CRP can be regarded as a potential target for MM treatment.
Apoptosis ; C-Reactive Protein ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; RNA, Messenger ; genetics

Acute lung injury (ALI) is a common, life-threatening cause of acute respiratory failure, which is ultimately caused by a variety of local and systemic insults. Alterations in the coagulation and fibrinolysis profiles are present in almost all the patients suffering with ALI. The classic histologic findings in ALI patients include alveolar fibrin formation and microthrombi in the pulmonary vasculature. Decreased circulating levels of protein C and increased concentrations of thrombomodulin are present in patients with septic and nonseptic ALI. The circulating and pulmonary concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in the setting of ALI, and the degree of elevation in the PAI-1 level directly correlates with mortality. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI. This review summarizes the current understanding of coagulation and fibrinolysis in ALI with an emphasis on the pathways that could be potential therapeutic targets, including the tissue factor pathway, the protein C pathway and the modulation of fibrinolysis via plasminogen activator inhibitor-1.
Acute Lung Injury ; Fibrin ; Fibrinolysis ; Humans ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Protein C ; Research Personnel ; Respiratory Insufficiency ; Stress, Psychological ; Thrombomodulin ; Thromboplastin

Trauma-induced coagulopathy is classified into primary and secondary coagulopathy, with the former elicited by trauma and traumatic shock itself and the latter being acquired coagulopathy induced by anemia, hypothermia, acidosis, and dilution. Primary coagulopathy consists of disseminated intravascular coagulation and acute coagulopathy of trauma shock (ACOTS). The pathophysiology of ACOTS is the suppression of thrombin generation and neutralization of plasminogen activator inhibitor-1 mediated by activated protein C that leads to hypocoagulation and hyperfibrinolysis in the circulation. This review tried to clarify the validity of activated protein C hypothesis that constitutes the main pathophysiology of the ACOTS in experimental trauma models.
Acute Disease ; Animals ; Blood Coagulation Disorders ; etiology ; Disease Models, Animal ; Disseminated Intravascular Coagulation ; etiology ; Humans ; Mice ; Plasminogen Activator Inhibitor 1 ; Protein C ; physiology ; Thrombin ; Wounds and Injuries ; complications