Urinary Fibrinogen Degradation Products Research Articles

Analysis of the urinary peptidome associated withHelicobacter pyloriinfection

To investigate the relationship between urinary peptide changes and Helicobacter pylori (H. pylori) infection using urinary peptidome profiling. The study was performed in volunteers (n=137) who gave informed consent. Urinary peptides were enriched by magnetic beads based weak cation exchange chromatography and spectrums acquired by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). ClinProTools bioinformatics software was used for statistical analysis and the recognition of peptide patterns. The marker peptides were identified by LTQ Obitrap XL tandem MS. Approximately 50 proteins or peptides which loaded onto the magnetic beads were detected by MALDI-TOF MS. By optimizing the parameters of the model, the Genetic Algorithm model had good recognition capability (97%) and positive predictive value (94%). Based on the model, 2 markers with molecular masses of 6788 and 1912 Da were found that differentiated between H. pylori positive and negative volunteers. The m/z 1912 sequence was parsed as SKQFTSSTSYNRGDSTF. The peptide was identified as isoform 1 of the fibrinogen α chain precursor, whose concentration in urine was markedly higher in H. pylori infected volunteers than in H. pylori non-infected ones. The appearance of urinary fibrinogen degradation products is caused by an active H. pylori-induced process.

Proteomic analysis of urinary fibrinogen degradation products in patients with urothelial carcinomas

Despite many years of research efforts and continued progress in the identification of urine markers for detection of bladder cancer, none of the markers described to date has been able to replace cystoscopy and urine cytology, the current gold standards for diagnosis. Here, we present a comprehensive gel-based proteomic study in which we have analyzed the presence and origin of fibrinogen (FG) and its degradation products (FDPs) in the urine of patients with and without urothelial carcinoma (UCs), with the aim of evaluating the potential of two-dimensional (2D) gel FDP profiling for detecting bladder cancer. A total of 151 urine samples collected from patients with Ucs of varying degrees of atypia and stages of invasion were compared with a control group consisting of 34 healthy volunteers with no clinical history of bladder cancer. The level and degree of degradation of FG in the urine were determined by 2D gel Western blotting in combination with enhanced chemilumenscence detection. Elevated levels of urine FG/FDPs were found in 99% of patients bearing superficial tumors, in 97% of the cases with early invasive disease, and in 96% of patients with highly invasive tumors. 2D gel profiling of urine FG/FDPs showed that the FG chains exhibited differential susceptibility to in situ proteolysis, with the α-chain being the most susceptible and the γ-chain the most resistant. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identified peptide sequence regions in several of the most representative and common FDPs, which can be of value for producing novel specific antibodies to detect FG/FDPs in the urine. In addition, we present evidence indicating that FG is not produced by normal or malignant urothelium, although it is present both in the stroma of malignant tissue and tumor lesions. Taken together, the data indicate that increased levels of FG/FDPs amounts in the urine are a characteristic feature of bladder cancer, and emphasize the value of 2D gel profiling of urine FG/FDPs for detecting low-grade, noninvasive UCs.

Relationship between urinary fibrinogen degradation products and various types of chronic nephritis

The concentration of urinary fibrin(ogen) degradation products (FDP) was determined by using enzyme immunoassay and radio immunoassay, and their urinary levels were compared with histologically classified types of glomerulonephritis. Urinary FDP levels were higher in the severe type of proliferative glomerulonephritis and at the active phase of systemic lupus erythematosus (SLE). They were also high in the membranous glomerulonephritis. Molecular weight of urinary FDP of a patient with severe proliferative glomerulonephritis was determined to be 150,000 and 68,000, respectively after gel filtration. Urinary FDP levels were higher in patients with glomerular fibrin deposit than in patients without fibrin deposit or normal volunteers. The amounts of excreted protein in urine was not related to the amounts of FDP. Decrease in the reciprocal of serum creatinine levels resulted in high urinary FDP levels, indicating that high urinary FDP levels may represent deterioration of renal function.

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We have studied the effects of urokinase (UK) on concentration changes of α2-antiplasmin (α2-AP) and on fibrinogenolysis. Medium dose (480.000u) or large dose (960, 000u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total α2-AP, which includes free α2-AP and α2-AP-plasmin complex, decreased about 50 per cent of the original value with large dose of UK. α2-AP-plasmin complex appeared in the plasma one hour after UK infusion and increased up to 50 per cent of total α2-AP at the end of UK infusion. Bβ1-42, which liberated from fibrinogen at the very early stage of fibrinogenolysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary Bβ1-42 increased as well as plasma Bβ1-41. On the other hand, fibrinogen degradation products (FDP) measured with enzyme immunoassay (ETA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen level did not decrease and it changed within the normal range in both groups. We then gave 960, 000u of UK to three patients with deep vein thrombosis and blood analysis was carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of three patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP.In conclusion, we consider that infusion of 960, 000u of UK is enough to neutralyze α2-AP and enough to express thrombolytic activity. It causes only very early stage of fibrinogenolysis without advanced fibrinogenolysis which may result in bleeding tendency in normal volunteers. On the other hand, in thrombotic patients, advanced fibrinolysis was observed with UK infusion.

Prognostic value of urinary fibrinogen degradation products in bladder carcinoma.

In this study, the value of urinary fibrinogen degradation products as a biological marker of bladder carcinoma has been studied. An increase in fibrinogen degradation products was found in 86% of bladder cancer patients independent of the fact that they had active tumors or that they were disease free. A highly significant correlation between the amount of the increase, the grade, local invasiveness, and the risk of recurrence of the tumor has been established. One can conclude that urinary fibrinogen degradation products are of great prognostic value in patients with bladder carcinoma.

Unusual Immunologic Findings in Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an inherited disease of unknown etiology. We report a case in which, during an acute febrile attack, rheumatoid factor and immunoglobulin levels rose, and the levels of complement components fell. The level of urinary fibrinogen degradation products also increased, and all results of tests returned to normal at the end of the acute attack. This suggests that an immunologic phenomenon may play a substantial role in the etiology of FMF.

Urinary fibrinogen degradation products (FDP) in bladder cancer.

The value of urinary fibrinogen degradation products (EPD) as a biological marker of bladder cancer has been studied. An increase in FDP was found in 75% of bladder cancer patients, independent of the fact that they had active tumours or that they were disease free. A high correlation between the amount of the increase and the grade, local invasiveness, and risk of recurrence of the tumour has been established. The assessment of urinary FDP is considered as a valuable screening and follow-up test in patients with bladder neoplasms.

Evaluation of Biological Markers in Bladder Cancer

The value of biological markers of bladder cancer was studied in 66 patients. The markers included serum and urine carcinoembryonic antigens, serum and urine fibrinogen degradation products, total lymphocyte counts, urine lymphocytes and urine cytology. A high degree of accuracy (90 per cent) was found in correlating cytology and urinary fibrinogen degradation products with the activity of the disease. Serum and urine carcinoembryonic antigens, serum fibrinogen degradation products, total lymphocyte counts and urine lymphocytes were found to have no value in screening bladder cancer patients. Urinary fibrinogen degradation products and cytology in combination are recommended for screening and followup of patients at high risk.

ASSESSMENT OF HUMAN RENAL TRANSPLANTATION

A renal-transplant unit was established to work with an existing hæmodialysis unit; initially it was decided to adopt a policy of close HL-A matching. Most of the recipients had been on long-term hæmodialysis and had received multiple transfusions in the past. Those patients who had not developed antibodies on this regimen had the best prognosis. It is suggested that good matching and prior exposure to blood-transfusion without antibody production are both factors indicating a favourable outcome in renal transplantation. Rejection episodes were also infrequent, and although several tests were used to determine early rejection none was entirely satisfactory. Estimation of urinary fibrinogen-degradation products generally gave the most helpful results.

Fibrinogen degradation products in serum and urine of patients with systemic lupus erythematosus. Relation to renal disease and pathogenetic mechanism.

AbstractSerum and concentrated urine from blood donors, patients with rheumatoid arthritis and SLE patients with and without renal disease were tested for the presence of fibrinogen degradation products (FDP), using the tanned red cell hemagglutination inhibition immunoassay. The majority of blood donors had serum titers of 1:2 to 1:4, while the majority of patients with rheumatoid arthritis and systemic lupus erythematosus had titers of 1:8 to 1:32. FDP were detected in low titers in urine of nearly all blood donors, patients with rheumatoid arthritis and SLE patients without renal disease, whereas elevated titers were found in SLE patients with active renal disease. Several possible sources of the urinary FDP are discussed, and the role of fibrin deposition in glomerular injury is reviewed.