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1.
Proteomics Clin Appl ; 10(4): 358-70, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26703953

ABSTRACT

Urinary proteomics has become one of the most attractive topics in disease biomarker discovery. MS-based proteomic analysis has advanced continuously and emerged as a prominent tool in the field of clinical bioanalysis. However, only few protein biomarkers have made their way to validation and clinical practice. Biomarker discovery is challenged by many clinical and analytical factors including, but not limited to, the complexity of urine and the wide dynamic range of endogenous proteins in the sample. This article highlights promising technologies and strategies in the MS-based biomarker discovery process, including study design, sample preparation, protein quantification, instrumental platforms, and bioinformatics. Different proteomics approaches are discussed, and progresses in maximizing urinary proteome coverage and standardization are emphasized in this review. MS-based urinary proteomics has great potential in the development of noninvasive diagnostic assays in the future, which will require collaborative efforts between analytical scientists, systems biologists, and clinicians.


Subject(s)
Acute Kidney Injury/urine , Mass Spectrometry/methods , Proteome/analysis , Proteomics/methods , Urinary Bladder Neoplasms/urine , Acute Kidney Injury/diagnosis , Acute Kidney Injury/pathology , Antigens, Neoplasm/urine , Antigens, Nuclear/urine , Biomarkers/urine , Biomarkers, Tumor/urine , Cell Cycle Proteins , Fibrin/urine , Humans , Insulin-Like Growth Factor Binding Proteins/urine , Mass Spectrometry/instrumentation , Nuclear Matrix-Associated Proteins/urine , Tissue Inhibitor of Metalloproteinase-2/urine , Urinalysis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology
2.
Rinsho Byori ; 63(2): 252-8, 2015 Feb.
Article in Japanese | MEDLINE | ID: mdl-26529979

ABSTRACT

Urinary sediments may be associated with the pathogenesis of renal diseases. It is important to examine the presence of dysmorphic red blood cells, macrophages, tubular epithelial cells, fibrin casts, glomerular epithelial cells, and ammonium acid urate crystals in urine for evaluating the clinical status of glomerulonephritis. Collecting evidence regarding the relationship between urinary sediments and renal disease activity may provide cost-effective and prompt clinical information to improve clinical practice.


Subject(s)
Kidney Diseases/diagnosis , Kidney Diseases/urine , Urinalysis , Crystallization , Epithelial Cells/pathology , Erythrocytes/pathology , Fibrin/urine , Humans , Kidney Glomerulus/cytology , Kidney Tubules/cytology , Macrophages , Podocytes/pathology , Uric Acid/urine
3.
Rinsho Byori ; 57(4): 319-23, 2009 Apr.
Article in Japanese | MEDLINE | ID: mdl-19489432

ABSTRACT

Soluble fibrin (SF) is produced by activated blood coagulation reaction and is useful to diagnose thrombotic diseases. We measured plasma and urine SF levels in nephritic patients to assess the hypercoagulability state associated with the disease. Before they received anti-coagulation or anti-platelet therapies, 60 patients underwent measurement of plasma SF and D-dimer levels by Latex agglutination turbidimetric immnoassay (LA). Urinary SF levels were also measured by LA. Plasma and urinary thrombin antithrombin III complex (TAT) levels were measured by enzyme immunoassay (EIA). Plasma SF levels showed a good correlation with plasma TAT levels but only weak positive correlations were observed between plasma D-dimer and SF or TAT levels. Plasma SF and D-dimer levels were significantly higher in the Iatients with nephrotic-range hypoalbuminemia (< or =3 g/dL) than those without it. Contrarily there was no significant difference in plasma TAT levels between these two groups of patients. In almost all patients, urinary SF levels were under the detection limit. However, TAT was excreted into urine more frequently in patients showing the nephrotic range of hypoalbuminemia at 38.2% than in non-nephrotic patients at 8.0%. Thus, plasma SF levels more precisely indicate activated blood coagulation reaction than plasma TAT levels in nephrotic patients, probably because the plasma SF is not excreted into urine, while plasma TAT is.


Subject(s)
Biomarkers/blood , Fibrin/analysis , Nephrotic Syndrome/complications , Thrombophilia/diagnosis , Thrombophilia/etiology , Antithrombin III/urine , Biomarkers/urine , Fibrin/urine , Fibrin Fibrinogen Degradation Products/analysis , Humans , Latex Fixation Tests , Nephelometry and Turbidimetry , Peptide Hydrolases/blood , Peptide Hydrolases/urine
4.
Acta Paediatr Jpn ; 34(5): 525-9, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1442024

ABSTRACT

We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly-sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non-glomerular hematuria. If U-FDP concentrations less than 0.25 microgram/ml are accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 microgram/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria.


Subject(s)
Fibrin Fibrinogen Degradation Products/urine , Fibrin/urine , Hematuria/urine , Adolescent , Child , Child, Preschool , Evaluation Studies as Topic , Female , Hematuria/classification , Hematuria/epidemiology , Humans , Infant , Japan/epidemiology , Latex Fixation Tests , Male , Sensitivity and Specificity
5.
Acta Med Okayama ; 43(1): 29-38, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2470234

ABSTRACT

Renal tissues from 208 human necropsies were observed histologically for disseminated intravascular coagulation (DIC). The tissues were stained with hematoxylin-eosin, Mallory's phosphotungstic acid hematoxylin (PTAH) and cationic ferric hydroxide colloid stabilized with cacodylate (Fe-Cac), and tested by immunoenzyme histochemical (IEH) reaction for fibrin-related materials (FRMs). The use of the IEH method increased FRM recognition, and FRMs were detected in a total of 80 cases (38.5%). In 26 cases diagnosed clinically as DIC, FRMs were shown in 23 of the cases (88.5%). Thus, 57 patients with FRMs were clinically asymptomatic. In rats with DIC induced by endotoxin injection, glomerulus FRM was effluxed into the tubulus through the Bowman's capsule and was excreted into urine. The electric charge was reduced on the endothelial surface of the glomerular capillaries in both human and rat DIC. Under the scanning electron microscopy, the endothelial surface appeared coarse in the glomerular capillary and fibrin degradation was present. Our conclusions are: (a) PTAH is non-specific for FRMs, (b) IEH aids the pathohistological diagnosis of DIC, especially in asymptomatic forms including the compensated DIC state, (c) FRMs in tubuli suggest DIC, and (d) DIC is possibly initiated by a reduction in the capillary electric surface charge.


Subject(s)
Disseminated Intravascular Coagulation/diagnosis , Animals , Disseminated Intravascular Coagulation/pathology , Fibrin/urine , Humans , Immunohistochemistry , Male , Microscopy, Electron, Scanning , Platelet Count , Rats , Rats, Inbred Strains , Species Specificity , Staining and Labeling
6.
Biull Eksp Biol Med ; 106(10): 424-6, 1988 Oct.
Article in Russian | MEDLINE | ID: mdl-3142531

ABSTRACT

The plasminogen activator 960 IU/mg protein activity isolated from cultured fluid of the calf kidney cells was introduced to albino rats (180-200 g) with experimental Heynmann nephritis every day during 4 days. Nephritis caused activation of haemostasis and inhibition of fibrinolysis in the blood. There was increased excretion of the fibrin, fibrinogen degradation products in urine as a results of the local fibrin deposition in diseased kidneys. The fibrinolytic activity of the cortical zone of kidney was markedly decreased. The plasminogen activator, infused to experimental animals, resulted in normalization of the altered indexes.


Subject(s)
Fibrinolysis/drug effects , Hemostasis/drug effects , Nephritis/physiopathology , Tissue Plasminogen Activator/pharmacology , Animals , Cattle , Cells, Cultured , Fibrin/urine , Fibrin Fibrinogen Degradation Products/urine , Kidney/analysis , Male , Nephritis/blood , Nephritis/drug therapy , Rats , Tissue Plasminogen Activator/isolation & purification , Tissue Plasminogen Activator/therapeutic use
8.
Cancer Res ; 44(12 Pt 1): 5886-93, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6498846

ABSTRACT

An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody was developed to determine the clinical value of urinary fibrinogen/fibrin degradation product levels for the identification and management of patients with bladder cancer. Assays were performed on 286 serial urine specimens from 56 bladder carcinoma patients. Specimens were grouped according to whether the patient had an evident tumor at the time of specimen collection (134 specimens, 41 patients) or was clinically disease-free following treatment (152 specimens, 38 patients). Many patients contributed specimens to both groups as determined by their clinical status at the time of collection. In addition, 45 specimens from 33 patients with inflammation of the urogenital tract and 81 specimens from 19 patients with renal or prostatic cancer were assayed for urinary fibrin degradation products. The ELISA, using a high-sensitivity procedure, identified 83% of the specimens from bladder cancer-positive patients with an overall accuracy with all specimens of 78% and a false-negative rate of 5% for all specimens tested. The high-sensitivity ELISA appeared most appropriate for monitoring bladder cancer patients for recurrence of tumor after surgery. The ELISA using a high-specificity procedure appeared most appropriate for screening. The high-specificity ELISA accurately identified 96% of urine specimens from non-bladder cancer patients with a false-positive rate of only 5%. These results demonstrate that the ELISA is an efficient, reliable, quantitative, and noninvasive immunoassay that can be useful both for the identification of bladder cancer patients and for monitoring the course of the disease.


Subject(s)
Fibrin/urine , Fibrinogen/urine , Urinary Bladder Neoplasms/diagnosis , Aged , Antibodies, Monoclonal , Cell Line , Cell Membrane/analysis , Enzyme-Linked Immunosorbent Assay , Female , Fibrinogen/analysis , Humans , Male , Prognosis , Urinary Bladder Neoplasms/analysis
10.
Br Med J (Clin Res Ed) ; 287(6408): 1838-40, 1983 Dec 17.
Article in English | MEDLINE | ID: mdl-6423037

ABSTRACT

Urinary casts from 46 healthy volunteers and 60 patients with glomerulonephritis were examined for the presence of Tamm-Horsfall glycoprotein and other proteins. All samples gave immunofluorescence evidence of Tamm-Horsfall protein in casts. Casts from 59 of the patients but only three of the controls contained other proteins in addition (p less than 0.001). Immunoglobulins (IgG, IgM, IgA) were detected in casts from 53 of the patients but none of the healthy volunteers. Examination of urinary casts for immunoglobulins, complement, and fibrin provides a non-invasive method for distinguishing patients with active glomerular disease.


Subject(s)
Glomerulonephritis/urine , Mucoproteins/urine , Proteinuria/urine , Complement Activating Enzymes/metabolism , Complement C1q , Complement C3/metabolism , Fibrin/urine , Humans , Immunoglobulins/urine , Uromodulin
12.
Curr Probl Clin Biochem ; (9): 257-72, 1979.
Article in English | MEDLINE | ID: mdl-376226

ABSTRACT

This study compares the usefulness of serum and urine fibrin split products and the urinary enzyme, beta-glucuronidase, in the diagnosis and management of renal transplant rejection. Fibrin split products, determined by a tanned human red cell agglutination inhibition immunoassay, were measured as a reflection of the secondary fibrinolysis from fibrin deposited in the renal microvasculature as a result of rejection. Urinary beta-glucuronidase, expressed as the ratio of enzyme activity to creatinine concentration, was determined by a colorimetric technique following dialysis of urine to remove endogenous activators and inhibitors. Activity of this lysosomal enzyme is thought to reflect tubular injury. Twenty-nine renal transplant recipients (15 from living donors and 14 from cadaver donors) were evaluated. Both serum and urinary fibrin split products and urinary beta-glucuronidase were markedly elevated in the immediate postoperative period, probably reflecting ischemic trauma. Acute rejection occurring within the first three months was associated with elevations of fibrin split products (particularly urine) and beta-glucuronidase. Elevated values returned to normal following successful treatment with steroids and/or heparin, but remained high in the presence of continued rejection. After the first 48 hours post-transplant, in the absence of rejection, values for fibrin split products were within the normal range. Urinary beta-glucuronidase remained elevated if the transplanted kidney was recovering from acute tubular necrosis. Fibrin split products and urinary beta-glucuronidase were usually normal in chronic rejection.


Subject(s)
Fibrin/urine , Glucuronidase/urine , Graft Rejection , Kidney Transplantation , Clinical Laboratory Techniques , Female , Fibrin/metabolism , Humans , Male , Sex Factors , Transplantation, Homologous
13.
Biomedicine ; 27(2): 89-92, 1977 Mar.
Article in English | MEDLINE | ID: mdl-324533

ABSTRACT

Correlations between immunofluorescent protein deposits in the glomeruli, urinary sediment and proteinuria selectivity pattern have been attempted in different glomerulonephritis. The overall study showed following results: a) Glomerular and urinary casts deposits of immunoglobulins, C3 and fibrin/fibrinogen are related to moderately selective proteinuria; b) IgG and IgA are most often found in urinary sediment and c) Glomerular deposits of IgG and IgA are well correlated with the presence of these immunoglobulins in urinary casts. Analysis according to different histological types of nephritis: a) In "minimal changes" nephropathy, deposits are infrequent and well correlated with urinary sediment, when they are present; b) In lupus nephritis, constant and intense glomerular deposits of immunoglobulins, fibrin/fibrinogen are correlated with the same proteins found in urinary casts; c) Inconstant correlations are found in membranous nephritis and in IgA-IgG nephropathy.


Subject(s)
Glomerulonephritis/urine , Kidney Glomerulus/pathology , Complement C3/urine , Fibrin/urine , Fibrinogen/urine , Fluorescent Antibody Technique , Glomerulonephritis/pathology , Humans , Immunoelectrophoresis , Immunoglobulins/urine , Proteinuria/pathology , Proteinuria/urine
15.
Br J Obstet Gynaecol ; 82(9): 711-7, 1975 Sep.
Article in English | MEDLINE | ID: mdl-1182091

ABSTRACT

In view of the association between pre-eclampsia and disseminated intravascular coagulation, three patients presenting with severe pre-eclampsia before the 28th week of pregnancy were treated with heparin. In all three patients, there was deterioration of hypertension and proteinuria that necessitated the withdrawal of treatment after five to six days. During treatment, serum and urinary fibrinolytic degradation products (FDPs) continued to rise or remained unaltered, plasminogen levels showed a steady fall, and the platelet count remained at a reduced level. These data suggest that heparin was an ineffective form of treatment and did not prevent the intravascular fibrin deposition associated with severe pre-eclampsia.


Subject(s)
Heparin/therapeutic use , Pre-Eclampsia/drug therapy , Blood Cell Count , Blood Coagulation Tests , Blood Platelets , Dipyridamole/therapeutic use , Disseminated Intravascular Coagulation/complications , Female , Fibrin/urine , Humans , Hypertension/drug therapy , Pre-Eclampsia/complications , Pregnancy , Pregnancy Trimester, Second , Proteinuria/drug therapy
17.
Schweiz Med Wochenschr ; 105(33): 1040-7, 1975 Aug 16.
Article in German | MEDLINE | ID: mdl-1099647

ABSTRACT

The concentration of fibrin/fibrinogen degradation products in urine (FDPu) was measured in samples obtained from 114 patients and 63 clinically healthy volunteers, once or repeatedly. The FDP titers measured by the hemagglutination inhibition (HI) method corresponded to less than 2.6 mug/ml FDP in all samples from healthy controls. Slightly elevated FDP concentrations were found in urine obtained from a few patients with disorders not primarily involving the urinary tract. The clinical importance of these isolated findings remains unclear. Urinary tract infections were not frequently accompanied by elevated FDPu concentrations. In patients with glomerulonephritis FDP excretion correlated somewhat better with severity of the renal affection. A further group of patients showed an unequivocal correlation between FDP excretion in the urine and postoperative complications following renal transplantation. However, the clinical diagnosis of acute rejection crisis was usually established at the same time or even before an increase in FDPu was found. Our results suggest that among diagnostic procedures the measurement of FDPu contributes little specific information for the evaluation of urinary tract disease. FDPu measurements in the immediate postoperative phase following renal transplantation may however be important for prognostic evaluation and, in individual cases, predict transplant rejection. We also attempted to define the FDPu qualitatively by simultaneous measurements using HI and the staphylococcal clumping test (SCT). Immunoelectrophoresis confirmed the well-known fact that the SCT detects only high-molecular FDP; this limits its clinical usefulness, despite its high sensitivity.


Subject(s)
Fibrin/urine , Fibrinogen/urine , Urologic Diseases/urine , Female , Glomerulonephritis/urine , Graft Rejection/urine , Hemagglutination Inhibition Tests , Humans , Hydronephrosis/urine , Kidney Calculi/urine , Kidney Transplantation , Male , Pregnancy , Pregnancy Complications/urine , Proteinuria/urine , Pyelonephritis/urine , Time Factors , Transplantation, Homologous
18.
Br Med J ; 2(5961): 17-9, 1975 Apr 05.
Article in English | MEDLINE | ID: mdl-48398

ABSTRACT

To elucidate the origin of the fibrin/fibrinogen degradation products (F.D.P.) occurring in the urine in glomerulonephritis 28 patients with glomerulonephritis were examined for renal fibrinolytic activity, F.D.P. in urine and serum, and blood fibrinolytic activators and blood fibrinolytic activators and inhibitors. Unlike the glomerful of healthy kidneys, which were fibrinolyticly inactive, those of kidneys with glomerulonephritis constantly showed fibrinolytic activity. The presence or absence of fibrin in the glomeruli was almost always accompanied by, respectively, the presence or absence of urinary F.D.P., which suggested a renal origin of urinary F.D.P. in glomerulonephritis. The low fibrinolytic activity of the blood and the absence of F.D.P. in the serum of these patients make it unlikely that the urinary F.D.P. in glomerulonephritis result from glomerular filtration.


Subject(s)
Fibrin/urine , Fibrinogen/urine , Glomerulonephritis/physiopathology , Glomerulonephritis/urine , Alpha-Globulins/analysis , Fibrin/metabolism , Fibrinogen/metabolism , Fibrinolysis , Fluorescent Antibody Technique , Glomerulonephritis/pathology , Humans , Kidney Cortex/pathology , Kidney Glomerulus/metabolism , Macroglobulins/analysis , Urokinase-Type Plasminogen Activator/antagonists & inhibitors
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