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Cystatin C (cystatin + c)

Distribution by Scientific Domains

Medical Sciences	78%
Life Sciences	11%
Chemistry	9%

Distribution within Medical Sciences

Neurology	14%
Pathology	8%
13 Other Subdomains	64%

Kinds of Cystatin C

serum cystatin c

Terms modified by Cystatin C

cystatin c level

Selected Abstracts

Cystatin C as an index of cerebral small vessel disease: results of a cross-sectional study in community-based Japanese elderly

EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010
M. Wada
Background and purpose:, Recent studies have shown that kidney dysfunction is associated with cerebral small vessel disease (SVD). Although creatinine-based estimating equations have been used as the standard measure for the evaluation of kidney function, the accuracy of these is limited in the elderly because of muscle mass decrease with aging. Cystatin C is a more useful measurement than creatinine-based estimating equations for evaluating kidney function, however, the relationship amongst cystatin C, cognitive dysfunction, and cerebral SVD has not been fully examined in community-based elderly. Methods:, We performed a cross-sectional study using MRI to determine the relationship amongst cystatin C, cognitive function, and cerebral SVD in a total of 604 community-based Japanese elderly. Results:, In this study, subjects with higher cystatin C levels tended to have more lacunas and higher grades of white matter lesions. Although a decline of the Mini-Mental State Examination (MMSE) scores was associated with SVD-related lesions, the relationship between the tertiles of cystatin C and mean MMSE scores was not statistically significant. In the logistic regression analysis, the association between cystatin C and SVD-related lesions was statistically significant, even after adjustment for conventional risk factors and high-sensitivity C-reactive protein. Furthermore, subjects with higher cystatin C levels accompanied with albuminuria had a greater risk for the presence of subclinical cerebral SVD than those with lower cystatin C levels without albuminuria. Conclusions:, The present study suggests that there is a close relationship between cystatin C and subclinical cerebral SVD, independently of conventional risk factors, in community-based elderly. [source]

Serum cystatin C may predict the early prognostic stages of patients with type 2 diabetic nephropathy

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2003
Ayumi Shimizu
Abstract We determined the relationship between levels of serum cystatin C or serum creatinine (s-Cr) and prognostic stages of type 2 diabetic nephropathy. Serum samples from 174 patients with type 2 diabetes were obtained from Juntendo University Hospital, Tokyo and Juntendo Urayasu Hospital, Chiba, Japan. They were classified into four groups according to the Report of the Ministry of Health and Welfare of Japan as follows: Stage I (normoalbuminuric stage), Stage II (microalbuminuric stage), Stage IIIA (macroalbuminuric stage without renal dysfunction), Stage IIIB (macroalbuminuric stage with renal dysfunction), and Stage IV (renal failure stage). Among these patients, 68 were Stage I, 29 Stage II, 32 Stage IIIA, 17 Stage IIIB, and 28 Stage IV. The levels of serum cystatin C were measured using the Dade Behring Cystatin C assay with automated Dade Behring Nephelometer II (BNII) (Dade Behring Marburg GmbH, Germany). The mean levels of serum cystatin C in Stage IIIA were significantly higher than those in Stage I or II (P<0.00001, P<0.0005, respectively). The mean levels of serum cystatin C in Stage IIIB and Stage IV were also significantly higher than those in Stage I (P<0.00001). However, the mean levels of serum creatinine (s-Cr) in Stage IIIA were not significantly higher than those in Stage I or II. The levels of s-Cr in Stage IIIB and Stage IV were significantly higher than those in Stage I (P<0.00001). Receiver operating characteristic (ROC) plots demonstrated that the area under the curve (AUC) of cystatin C (0.76) was greater than that of s-Cr (0.66). As an early prognostic marker of type 2 diabetic nephropathy, serum cystatin C was better than s-Cr in terms of sensitivity and specificity. It appears that the levels of serum cystatin C may predict early prognostic stages of patients with type 2 diabetic nephropathy. J. Clin. Lab. Anal. 17:164,167, 2003. © 2003 Wiley-Liss, Inc. [source]

Salivary cystatin activity and cystatin C in natural and experimental gingivitis in smokers and non-smokers

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2001
M. A. Lie
Abstract Background: Recent studies show that subjects with natural gingivitis or periodontitis have elevated levels of salivary cystatins compared to periodontally healthy individuals. Increased glandular output of cystatins in inflammatory conditions suggests an active, most likely protective, rôle for these proteins in inflammatory processes. Furthermore, it has been shown that the development of gingival inflammation is suppressed in smokers during experimental gingivitis. Aims: The purpose of the present study was to investigate whether (i) the levels of salivary cystatins in natural gingivitis are related to smoking status, and (ii) to study whether experimentally induced gingivitis is associated with changes in salivary cystatin levels, in both smokers and non-smokers. Material and Methods: Whole saliva samples were taken in relation to natural gingivitis, gingival health and 14-day experimental gingivitis in 25 non-dental students (14 non-smokers and 11 smokers). The salivary flowrate was determined. Samples were analyzed for levels of protein, cystatin and cystatin-C. Results: Salivary flow and protein concentrations in cleared human whole saliva samples of non-smokers and smokers were not different from each other at any timepoint during the trial. With regard to cystatins, the results showed that in the state of natural gingivitis cystatin activity is lower in smokers as compared to non-smokers. In smokers, the resolution of natural gingivitis to the state of gingival health did not result in a change of cystatin activity and levels of cystatin C. At the end of the 14-day experimental gingivitis period, smokers showed a decrease in cystatin activity and cystatin C as well as lower outputs of cystatin activity and cystatin C. Conclusion: Smoking is associated with lower cystatin activity and output of cystatin C during gingival inflammation. Zusammenfassung Hintergrund: Neuere Untersuchungen haben bezeigt, dass bei Patienten mit natürlicher Gingivitis oder Parodontitis die Cystatinspiegel im Speichel im Vergleich zu parodontal gesunden Personen erhöht sind. Ein erhöhter Ausstoß von Cystatinen durch Speicheldrüsen bei entzündlichen Prozessen spricht für eine aktive, sehr wahrscheinlich protektive Rolle dieser Proteine bei Entzündungen. Darüber steht die Unterdrückung der Entwicklung der gingivalen Entzündung bei Rauchern während einer experimentellen Gingivitis möglicherweise mit der verstärkten Expression von Cystatin C in Verbindung. Zielsetzung: Untersuchung, (1) ob die Cystatinspiegel im Speichel bei natürtlicher Gingivitis mit dem Zigarettenkonsum in Verbindung stehen und (2) ob eine Assoziation zwischen experimentell induzierter Gingivitis und Veränderungen der Cystatinspiegel im Speichel bei Rauchern und Nichtrauchern besteht. Material und Methoden: Bei 25 Studenten (14 Nichtraucher, 11 Raucher), die keine Zahnmediziner waren, wurden Speichelproben in Relation zu natürlicher Gingivitis, gingivaler Gesundheit und während einer 14 Tage dauernden experimentellen Gingivitis entnommen. Die Speichelsekretioinsrate wurde gemessen und die Speichelkonzentrationen von Protein, Cystatin und Cystatin C bestimmt. Ergebnisse: Die Speichelsekretionsraten und Proteinkonzentrationen der Speichelproben zeigten zu keinem Zeitpunkt der Untersuchung Unterschiede zwischen Rauchern und Nichtrauchern. Die Cystatinaktivität bei natürlicher Gingivitis war bei Rauchern geringer als bei Nichtrauchern. Bei Rauchern veränderten sich die Cystatinaktivität und der Cystatin-C-Spiegel beim Übergang von natur,rlicher Gingivitis zu gingivaler Gesundheit nicht. Am Ende der experimentellen Gingivitis von 14 Tagen war bei Rauchern eine Abnahme der Cystatinaktivität und des Cystatin C sowie ein geringerer Ausstoss von Cystatinaktivität und Cystatin C zu beobachten. Schlußfolgerungen: Rauchen ist geringerer Cystatinaktivität und geringerer Cystatin-C-Ausschüttng während gingivaler Entzündung assoziiert. Résumé Origine: De récentes études montrent que des sujets présentant des gingivites ou des parodontites naturelles ont des niveaux élevés de cystatines salivaires par rapport aux individus au parodonte sain. La production glandulaire augmentée de cystatine dans des conditions inflammatoires suggère un rôle actif, voire vraissemblablement protecteur, de ces protéines lors des processus inflammatoires. De plus, il a été montré que le développement de l'inflammation gingivale est supprimé chez le fumeur lors des gingivites expérimentales. But: Le but de cette étude était de rechercher si (i) le niveau de cystatine salivaire lors des gingivites naturelles est en relation avec le tabagisme et (ii) d'étudier si une gingivite expérimentale est associée une modification des niveaux salivaire de cystatine, chez les fumeurs et chez les non-fumeurs. Matériaux et méthodes: Des échantillons de salive totale était prélevés lors de gingivite naturelle, sur des patients avec des gencives saines, et lors de gingivites expérimentales sur 14 jours chez 25 étudiants (n'étudiant pas la chirurgie dentaire) (14 non-fumeurs et 11 fumeurs). Le taux de flux salivaire a été déterminé. Les échantillons furent étudiés pour les niveaux en protéine, cystatine et cystatine C. Resultats: Le flux salivaire, et les concentrations en protéines dans les échantillons de salive totale clarifiée des fumeurs et des non-fumeurs, ne présentaient aucune différence à aucun moment de l'étude. Pour la cystatine, les résultats montraient que lors des gingivites naturelles, l'activité de cette cystatine était moindre chez les fumeurs, et chez ces derniers, la résolution de cette gingivite vers l'état de santé gingivale n'entrainait pas de modifications de l'activité de la cystatine, ni du niveau de cystatine C. À la fin des 14 jours de gingivite expérimentale, les fumeurs montraient une diminution de l'activité de la cystatine et de la cystatine C ainsi qu'une diminution de la production de l'acitivité de la cystatine et de la cystatine C. Conclusion: Le tabagisme est associé avec une diminution de l'activité de la cystatine et une diminution de la production de cystatine C pendant l'inflammation gingivale. [source]

Cystatin C: an emerging marker for pre-timely mortality

JOURNAL OF INTERNAL MEDICINE, Issue 2 2010
Lars-Olof Hansson
No abstract is available for this article. [source]

Regulation of glial development by cystatin C

JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
Akiko Hasegawa
Abstract Cystatin C (CysC) is an endogenous cysteine proteases inhibitor produced by mature astrocytes in the adult brain. Previously we isolated CysC as a factor activating the glial fibrillary acidic protein (GFAP) promoter, and showed that CysC is expressed in astrocyte progenitors during development. Here we show that protease inhibitor activity increased daily in conditioned medium, and that this activity was mainly a result of CysC released from primary cultured cells. Human CysC added to the culture medium of primary brain cells increased the number of GFAP-positive and nestin-positive cells. Human CysC also increased the number of neurospheres formed from embryonic brain, and thus it increases the number of neural stem/precursor cells in a manner similar to glycosylated rat CysC. The addition of a neutralizing antibody, on the other hand, greatly decreased the number of GFAP and glutamate aspartate transporter (GLAST)-positive astrocytes. This decrease was reversed by the addition of CysC but not by another cysteine protease inhibitor. Thus, the promotion of astrocyte development by CysC appears to be independent of its protease inhibitor activity. The antibody increased the number of oligodendrocytes and their precursors. Therefore, CysC modifies glial development in addition to its activity against neural stem/precursor cells. [source]

Cystatin C colocalizes with amyloid-, and coimmunoprecipitates with amyloid-, precursor protein in sporadic inclusion-body myositis muscles

JOURNAL OF NEUROCHEMISTRY, Issue 6 2003
Gaetano Vattemi
Abstract Cystatin C (CC), an endogenous cysteine protease inhibitor, is accumulated within amyloid-, (A,) amyloid deposits in Alzheimer's disease (AD) brain and was proposed to play a role in the AD pathogenesis. Because the chemo-morphologic muscle phenotype of sporadic inclusion-body myositis (s-IBM) has several similarities with the phenotype of AD brain, including abnormal accumulation of A, deposits, we studied expression and localization of CC in muscle biopsies of 10 s-IBM, and 16 disease- and five normal-control muscle biopsies. Physical interaction of CC with amyloid-, precursor protein (A,PP) was studied by a combined immunoprecipitation/immunoblotting technique in the s-IBM muscle biopsies and in A,PP-overexpressing cultured human muscle fibers. In all s-IBM muscle biopsies, CC-immunoreactivity either colocalized with, or was adjacent to, the A,-immunoreactive inclusions in 80,90% of the vacuolated muscle fibers, mostly in non-vacuolated regions of their cytoplasm. Ultrastructurally, CC immunoreactivity-colocalized with A, on 6,10 nm amyloid-like fibrils and floccular material. By immunoblotting, CC expression was strongly increased in IBM muscle as compared to the controls. By immunoprecipitation/immunoblotting experiments, CC coimmunoprecipitated with A,PP, both in s-IBM muscle and in A,PP-overexpressing cultured normal human muscle fibers. Our studies (i) demonstrate for the first time that CC physically associates with A,PP, and (ii) suggest that CC may play a novel role in the s-IBM pathogenesis, possibly by influencing A,PP processing and A, deposition. [source]

Cystatin C as a marker of renal function immediately after liver transplantation

LIVER TRANSPLANTATION, Issue 2 2006
Gianni Biancofiore
To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (SCyst), serum creatinine (Scr), and creatinine clearance (Ccr) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, SCyst and Scr was measured in simultaneously drawn blood samples, whereas Ccr was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/SCyst and I-GFR was stronger than that of 1/Scr or Ccr (P< 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m), Scr remained within the normal range, whereas the increase in Scyst was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m), Scr increased slightly, whereas Scyst was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were ,30% lower than that recorded on the first postoperative day, SCyst(P< 0.0001) and Scr (P< 0.01) levels were increased, whereas Ccr remained unchanged (P= 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of Scyst was better than that of Scr and Ccr. Scyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR. Liver Transpl 12:285,291, 2006. © 2006 AASLD. [source]

Cystatin C should be measured in pediatric renal transplant patients!

PEDIATRIC TRANSPLANTATION, Issue 5 2002
Guido Filler MD PhD
First page of article [source]

The Role of Cystatin C in Cerebral Amyloid Angiopathy and Stroke: Cell Biology and Animal Models

BRAIN PATHOLOGY, Issue 1 2006
Efrat Levy
A variant of the cysteine protease inhibitor, cystatin c, forms amyloid deposited in the cerebral vasculature of patients with hereditary cerebral hemorrhage with amyloidosis, icelandic type (hchwa-i), leading to cerebral hemorrhages early in life. however, cystatin c is also implicated in neuronal degenerative diseases in which it does not form the amyloid protein, such as alzheimer disease (ad). accumulating data suggest involvement of cystatin c in the pathogenic processes leading to amyloid deposition in cerebral vasculature and most significantly to cerebral hemorrhage in patients with cerebral amyloid angiopathy (caa). This review focuses on cell culture and animal models used to study the role of cystatin c in these processes. [source]

The accuracy of cystatin C and commonly used creatinine-based methods for detecting moderate and mild chronic kidney disease in diabetes

DIABETIC MEDICINE, Issue 4 2007
R. J. MacIsaac
Abstract Background, The accuracy of measuring serum cystatin C levels for detecting various stages of chronic kidney disease (CKD) in diabetes is still unclear. Methods In a cross-sectional study of 251 subjects, a reference glomerular filtration rate (GFR) was measured using 99cTc-DTPA plasma clearance (iGFR). Multivariate analysis was used to identify independent clinical and biochemical associations with serum cystatin C and iGFR levels. The diagnostic accuracy of cystatin C and commonly used creatinine-based methods of measuring renal function (serum creatinine, the MDRD four-variable and Cockcroft,Gault formulae) for detecting mild and moderate CKD was also compared. Results, In the entire study population the same five variables, age, urinary albumin excretion rates, haemoglobin, history of macrovascular disease and triglyceride levels were independently associated with both cystatin C and iGFR levels. A serum cystatin C level cut-off > 82.1 nmol/l (1.10 mg/l) had the best test characteristics as a screening tool for detecting moderate CKD (< 60 ml/min per 1.73 m2) when compared with creatinine-based methods. At the upper threshold for mild CKD (< 90 ml/min per 1.73 m2), cystatin C also had greater diagnostic accuracy than creatinine, but had similar diagnostic accuracy when compared with creatinine-based formulae for predicting renal function. Conclusions, This study suggests that the clinical and biochemical parameters associated with serum cystatin C levels are closely linked to those associated with GFR and highlights the potential usefulness of screening for moderate or mild CKD in subjects with diabetes by simply measuring serum cystatin C levels. [source]

Cystatin C as an index of cerebral small vessel disease: results of a cross-sectional study in community-based Japanese elderly

Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase

FEBS JOURNAL, Issue 17 2000
Ivica Klemen
Cathepsin X, purified to homogeneity from human liver, is a single chain glycoprotein with a molecular mass of ,,33 kDa and pI 5.1,5.3. Cathepsin X was inhibited by stefin A, cystatin C and chicken cystatin (Ki = 1.7,15.0 nm), but poorly or not at all by stefin B (Ki > 250 nm) and l -kininogen, respectively. The enzyme was also inhibited by two specific synthetic cathepsin B inhibitors, CA-074 and GFG-semicarbazone. Cathepsin X was similar to cathepsin B and found to be a carboxypeptidase with preference for a positively charged Arg in P1 position. Contrary to the preference of cathepsin B, cathepsin X normally acts as a carboxymonopeptidase. However, the preference for Arg in the P1 position is so strong that cathepsin X cleaves substrates with Arg in antepenultimate position, acting also as a carboxydipeptidase. A large hydrophobic residue such as Trp is preferred in the P1, position, although the enzyme cleaved all P1, residues investigated (Trp, Phe, Ala, Arg, Pro). Cathepsin X also cleaved substrates with amide-blocked C-terminal carboxyl group with rates similar to those of the unblocked substrates. In contrast, no endopeptidase activity of cathepsin X could be detected on a series of o -aminobenzoic acid-peptidyl- N -[2,-dinitrophenyl]ethylenediamine substrates. Furthermore, the standard cysteine protease methylcoumarine amide substrates (kcat/Km,,5.0 × 103 m,1·s,1) were degraded ,,25-fold less efficiently than the carboxypeptidase substrates (kcat/Km , 120.0 × 103 m,1·s,1). [source]

Serum cystatin C may predict the early prognostic stages of patients with type 2 diabetic nephropathy

Salivary cystatin activity and cystatin C in natural and experimental gingivitis in smokers and non-smokers

Delineating protein,protein interactions via biomolecular interaction analysis,mass spectrometry

JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2003
Dobrin Nedelkov
Abstract The utility of biomolecular interaction analysis,mass spectrometry (BIA/MS) in screening for protein,protein interactions was explored in this work. Experiments were performed in which proteins served as ligands for screening of possible interactions with other proteins from human plasma and urine. The proteins utilized were beta-2-microglobulin, cystatin C (cysC), retinol binding protein (RBP), transthyretin (TTR), alpha-1-microglobulin, C-reactive protein, transferrin and papain. The immobilization of functionally active proteins was confirmed via interactions with antibodies to the corresponding proteins. Various dilutions of human urine and plasma were injected over the protein-derivatized surfaces. It was observed that the urine injections generally yielded smaller SPR responses than those observed after the plasma injections. The BIA/MS experiments did not reveal novel protein,protein interactions, although several established interactions (such as those between RBP and TTR, and cysC and papain) were validated. Few protein ligand deficiencies (such as truncations) leading to false negative and false positive BIA/MS results were also discovered. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Design and use of multi-affinity surfaces in biomolecular interaction analysis,mass spectrometry (BIA/MS): a step toward the design of SPR/MS arrays

JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2003
Dobrin Nedelkov
Abstract The feasibility of multi-affinity ligand surfaces in biomolecular interaction analysis,mass spectrometry (BIA/MS) was explored in this work. Multi-protein affinity surfaces were constructed by utilizing antibodies to beta-2-microglobulin, cystatin C, retinol binding protein, transthyretin, serum amyloid P and C-reactive protein. In the initial experiments, all six antibodies were immobilized on a single site (flow cell) on the sensor chip surface, followed by verification of the surface activity via separate injections of purified proteins. After an injection of diluted human plasma aliquot over the antibodies-derivatized surfaces, and subsequent MALDI-TOF MS analysis, signals representing five out of the six targeted proteins were observed in the mass spectra. Further, to avoid the complexity of the spectra, the six proteins were divided into two groups (according to their molecular weight) and immobilized on two separate surfaces on a single sensor chip, followed by an injection of human plasma aliquot. The resulting mass spectra showed signals from all proteins. Also, the convolution resulting from the multiply charged ion species was eliminated. The ability to create such multi-affinity surfaces indicates that smaller-size ligand areas/spots can be employed in the BIA/MS protein interaction screening experiments, and opens up the possibilities for construction of novel multi-arrayed SPR-MS platforms and methods for high-throughput parallel protein interaction investigations. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Regulation of glial development by cystatin C

Review article: renal function assessment in cirrhosis , difficulties and alternative measurements

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2007
E. CHOLONGITAS
Summary Background, Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end-stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA. Aim, To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis. Method, We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis. Results, Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the ,gold standard', but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft-Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine. Conclusions, Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate. [source]

Cystatin C as a marker of renal function immediately after liver transplantation

Change of glomerular filtration rate in healthy adults with aging

NEPHROLOGY, Issue 5 2009
XUEFENG SUN
SUMMARY Aim: In order to determine the relationship between glomerular filtration rate (GFR) and age, the associated factors, and the accurate method of GFR in healthy adults, we conducted a cross-sectional study in community-dwelling adults in Beijing. Methods: Renal function of 201 clinically healthy subjects was determined using technetium-99 m-labelled diethylene triamine pentacetic acid (99mTc-DTPA). Estimated GFR was calculated with the Cockcroft,Gault (CG) equation, abbreviated Modification of Diet in Renal Disease (MDRD) equation, and plasma clearance of creatinine (Ccr). Serum cystatin C, biomarkers of inflammatory and endothelial cells were analyzed as well. Protein intake, carotid artery intima-media thickness and plaque formation were assayed as well. Results: Glomerular filtration rate was negatively associated with age and the correlation coefficient for 99mTc-GFR, CG-GFR, MDRD-GFR, Ccr were ,0.643, ,0.736, ,0.55 and ,0.619, respectively (P < 0.001), while the correlation coefficient between cystatin C and age was 0.681 (P < 0.001). Estimated GFR were associated with measured GFR, and the correlation coefficient for Ccr, CG-GFR and MDRD-GFR were 0.813, 0.582 and 0.418, respectively (P < 0.001). The area under the receiver,operator curve of Ccr was larger, CG was smaller while MDRD was the smallest, and the difference was significant (P < 0.001). So a predicted equation was presented by cystatin C and C-reactive protein for the elderly. Conclusion: In the clinically healthy adults, GFR declined with age. MDRD and CG equation are not suitable to estimate GFR in healthy adults. The predicted equation established by cystatin C and C-reactive protein may be more accurate. [source]

Evaluation of serum cystatin C levels and 99mTechnetium-mercaptoacetyltriglycine-3 renal scintigraphy for the early detection of cisplatin-induced renal toxicity in cancer patients

NEPHROLOGY, Issue 2 2002
Nazan GÜNEL
SUMMARY: Cisplatin has a broad-spectrum antineoplastic activity. Nephrotoxicity is a prominent component of the toxicity profile of cisplatin-based chemotherapy. In recent years, several reports have confirmed that cystatin C (cys-C) demonstrates a better correlation with the glomerular filtration rate than with serum creatinine. Scintigraphic techniques are also widely used in evaluating renal function. In the present study, serum cys-C, serum creatinine concentrations and 99mTechnetium-mercaptoacetyltriglycine-3 (99mTc-MAG-3) scintigraphy were studied in 22 cisplatin-naive cancer patients, 3 days before and 24 h after the first cycle of cisplatin-based chemotherapy. Serum cystatin C and creatinine levels increased in cancer patients after chemotherapy (creatinine: from 68 ± 12 to 72 ± 17 nmol/L; cystatin-C: from 0.064 ± 0.025 to 0.072 ± 0.033 jimol/L), but these differences were not statistically significant (P>0.05). Semiquantitative variables of 99mTc-MAG-S scintigraphy significantly elevated after chemotherapy (T½*: from 10.27 ± 5.00to 16.17 ± 9.40 min, R20/max*: from 0.40 ± 0.12 to 0.67+0.45, Tmax**: from 5.40 ± 4.01 to 7.59 ± 5.30 min; *P<0.001, **P<0.01, respectively). These results suggest that MAG-3 scintigraphy is a highly sensitive method in the early detection of cisplatin-induced nephrotoxicity. Serum cystatin C doesn't seem to play a role in the early detection of cisplatin-induced nephrotoxicity. As a result, MAG-3 scintigraphy may be used in selected patients who have a predisposition for renal toxicity. [source]

Bunina bodies in amyotrophic lateral sclerosis

NEUROPATHOLOGY, Issue 2 2008
Koichi Okamoto
Bunina bodies, which are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are generally considered to be a specific pathologic hallmark of amyotrophic lateral sclerosis (ALS). One year before a publication by Bunina, van Reeth et al. described similar intracytoplasmic inclusions in the anterior horn cells in a patient with Pick's dementia with atypical ALS. At present, only two proteins have been shown to be present in Bunina bodies, one is cystatin C and the other is transferrin. Bunina bodies consist of amorphous electron-dense material surrounded by tubular and vesicular structures on electron microscopy. Although the nature and significance of Bunina bodies in ALS are not yet clear, the bodies may be abnormal accumulations of unknown proteinous materials. [source]

Cerebral amyloid angiopathy: An overview

NEUROPATHOLOGY, Issue 1 2000
Masahito Yamada
Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition in cortical and leptomeningeal vessels. Several cerebrovascular amyloid proteins (amyloid ,-protein (A,), cystatin C (ACys), prion protein (AScr), transthyretin (ATTR), gelsolin (AGel), and ABri (or A-WD)) have been identified, leading to the classification of several types of CAA. Sporadic CAA of A, type is commonly found in elderly individuals and patients with Alzheimer's disease. Cerebral amyloid angiopathy is an important cause of cerebrovascular disorders including lobar cerebral hemorrhage, leukoencephalopathy, and small cortical hemorrhage and infarction. We review the clinicopathological and molecular aspects of CAA and discuss the pathogenesis of CAA with future perspectives. [source]

Short-term follow-up of patients with sickle cell disease and albuminuria

PEDIATRIC BLOOD & CANCER, Issue 6 2008
Ofelia Alvarez MD
Abstract Background Albuminuria with normal serum creatinine occurs frequently in patients with sickle cell disease (SCD), but the rate of progression to more advanced chronic renal disease is unknown. The purpose of this study was to investigate the rate of progression of children and young adults with SCD and albuminuria over time. Procedure Urine albumin/creatinine (A/C) ratios and serum creatinine were obtained serially. Serum cystatin C levels were determined in a subgroup of 20 patients. Results Of 38 patients with SCD who had albuminuria (30 with microalbuminuria and 8 with proteinuria), 10.5% had progressive disease during follow-up of 20,±,12 months. Progressive disease was observed in 2 of 30 patients with MA because MA worsened to either intermittent proteinuria (1 patient), or persistent proteinuria after 7 months follow-up (1 patient). Two of eight patients with proteinuria worsened to nephrotic-range after 8 and 17 months with elevations of serum creatinine. All eight patients with proteinuria were treated with angiotensin blockade and/or hydroxyurea. Of those, six patients responded to treatment with decreased albuminuria and no changes in serum creatinine. Serum cystatin C level trended to increase before serum creatinine in patients with proteinuria. Conclusions Patients with rapid progression to nephrotic-range proteinuria showed decreased kidney function. Therefore, patients with albuminuria should be monitored closely for progression, and therapy with hydroxyurea and/or angiotensin blockade should be considered for patients who develop proteinuria. Serum cystatin C appears more sensitive than serum creatinine to detect early decrease in kidney function. Pediatr Blood Cancer 2008;50:1236,1239. © 2008 Wiley-Liss, Inc. [source]

Renal dysfunction in cystic fibrosis: Is there cause for concern?,

PEDIATRIC PULMONOLOGY, Issue 10 2009
Natalie Soulsby
Abstract Most people associate cystic fibrosis (CF) with lung disease. Although this is the major cause of morbidity and mortality, CF is in fact a multi-organ disease. Patients with CF are living longer. Accompanying their increased life expectancy are complications not previously encountered. One of the less obvious concerns is that of renal dysfunction associated with long-term exposure to aminoglycosides as well as renally toxic immunosuppressants in lung transplant recipients. This article reviews what is known about the extent of the problem, summarizes what the current practices of measuring and monitoring renal function in patients with CF, and makes suggestions for alternative approaches. In particular, the potential role of cystatin C will be discussed. Pediatr Pulmonol. 2009; 44:947,953. ©2009 Wiley-Liss, Inc. [source]

Proteomic analysis of factors released from p21-overexpressing tumour cells

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 13 2006
Caroline A. Currid
Abstract The p21Waf1/Cip1/Sdi1 cyclin-dependent kinase inhibitor is a key regulator of cell cycle progression and has also been observed to influence the expression of genes associated with several age-related disorders. Previous work has shown that expression of p21 in tumour cells mediates an antiapoptotic and mitogenic paracrine effect, which is in contrast to the arrested state of p21-expressing cells. Here, we have employed SELDI-MS technology to characterise, at a proteomic level, factors released from HT-1080 human fibrosarcoma cells displaying inducible p21,expression. Conditioned media from induced and noninduced cells were profiled on a range of diverse ProteinChip arrays and subjected to SELDI-MS analysis. Evaluation of proteins binding onto IMAC, Q10 or CM10 surfaces led to the discovery of a number of putative p21-regulated factors. We further validated three p21-regulated proteins observed at 10.2, 11.7 and 13.4,kDa. Using Q,Ceramic HyperD fractionation columns, we were able to selectively enrich for each of these three proteins. Subsequent SDS-PAGE and MS analysis of tryptic digests identified the 13.4,kDa protein as cystatin C and the 10.2,kDa protein as pro-platelet basic protein (PPBP). Judging by the apparent MW and the pI of the 11.7,kDa protein, we reasoned that it may be ,-2-microglobulin, which was confirmed by subsequent identification. Increased levels of cystatin,C and ,-2-microglobulin in conditioned media from p21-expressing cells was confirmed by antibody capture experiments using anticystatin,C and anti-,-2-microglobulin antibodies on preactivated PS-20 arrays. Western blot analysis demonstrated increased expression of intracellular and extracellular cystatin,C and ,-2-microglobulin in p21-expressing cells, compared to noninduced controls. Increased levels of PPBP were validated in cell lysates from p21-expressing cells. The three secreted factors that we have identified in this study, have all been shown previously to have growth modulating effects and, as such, may contribute to the observed mitogenic and anti-apoptotic paracrine activity of p22-expressing cells. [source]

Identification of the human salivary cystatin complex by the coupling of high-performance liquid chromatography and ion-trap mass spectrometry

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2003
Alessandro Lupi
Abstract Human salivary cystatins, five major (S, S1, S2, SA, SN) and two minor (C and D), are multifunctional proteins playing a different role in the oral environment. Salivary cystatin SN is able to effectively inhibit lysosomal cathepsins B, C, H and L and cystatin SA inhibits cathepsins C and L in vitro. These activities suggest, particularly for cystatin SN, an important role in the control of proteolytic events in vivo. Differently, cystatins S are involved, together with statherin, in the mineral balance of the tooth. Due to their distinct role, a reliable method for identification and quantification of the different cystatins, as well as of possible truncated and derived forms, could be helpful for the assessment of the status of the oral cavity. To this purpose high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI MS) was applied to the analysis of human saliva obtained from healthy subjects. All known salivary cystatins, with the exception of cystatin C, were detected. Strong evidence was also obtained for the presence in saliva of post-translational modified isoforms of cystatins, which may be related to donor habits. Cystatin SN and cystatins S, S1 and S2 were well separated by HPLC-ESI MS coupling from other components and thus this approach can be successfully applied to their quantification. [source]

Identification of breast cancer biomarkers in transgenic mouse models: A proteomics approach

PROTEOMICS - CLINICAL APPLICATIONS, Issue 6-7 2010
Wendy Rodenburg
Abstract Purpose: Transgenic mouse models for cancer circumvent many challenges that hamper human studies aimed at biomarker discovery. Lower biological variances among mice combined with controllable factors such as food uptake and health status may enable the detection of more subtle protein expression differences. This is envisioned to result in the identification of biomarkers better discriminating cancer cases from controls. Experimental design: The current study used two innovative mouse models for breast-cancer to identify new serum biomarkers. Multi-analyte profiling technique was used to analyze 70 proteins in individual serum samples of non-tumor and mammary tumor-bearing Tg.NK (MMTV/c-neu) mice. Results: A small set of proteins fully differentiated tumor samples from controls. These comprised osteopontin, interleukin-18, cystatin C and CD40 antigen. Comparison of protein expression in another breast-cancer mouse model, the humanized p53.R270H mice, showed common discriminatory expression of osteopontin. However, other biomarkers showed distinct expression in the two different breast-cancer models, indicating that different mammary tumor sub-types with respect to molecular and estrogen receptor status reveal divergent serum biomarker sets. Conclusions and clinical relevance: The current study supports the concept that serum proteins can discriminate mammary tumor cases from controls, and yielded interesting biomarkers that need further testing and validation in human studies. [source]

Cleavage of cystatin C is not associated with multiple sclerosis

ANNALS OF NEUROLOGY, Issue 2 2007
Piero Del Boccio PhD
Recently, Irani and colleagues proposed a C-terminal cleaved isoform cystatin C (12.5kDa) in cerebrospinal fluid as a marker of multiple sclerosis. In this study, we demonstrate that the 12.5kDa product of cystatin C is formed by degradation of the first eight N-terminal residues. Moreover, such a degradation is not specific in the cerebrospinal fluid of multiple sclerosis, but rather is given by an inappropriate sample storage at ,20°C. We conclude that the use of the 12.5kDa product of cystatin C in cerebrospinal fluid might lead to a fallacious diagnosis of multiple sclerosis. Preanalytical validation procedure is mandatory for proteomics investigations. Ann Neurol 2007 [source]

Synthesis and antibacterial properties of peptidyl derivatives and cyclopeptides structurally based upon the inhibitory centre of human cystatin C: Dissociation of antiproteolytic and antibacterial effects

APMIS, Issue 7-8 2000
FRANCISZEK Kasprzykowski
Cysteine protease-inhibiting proteins of the cystatin superfamily can inhibit the replication of certain viruses and bacteria. The inhibitory centre of human cystatin C, the most widely distributed human cystatin, comprises three peptide segments. The present work describes the synthesis and antibacterial activity of 27 new peptidyl derivatives or cyclopeptides based upon the aminoterminal segment Arg8 -Leu9 -Val10 -Gly11. Fourteen of the new compounds displayed antibacterial activity against from 1 up to 9 of 17 clinically important bacterial species tested. Antiproteolytic activity of a compound was usually not required for its antibacterial capacity. Peptidyl diazomethanes generally had a very narrow antibacterial spectrum, inhibiting only Streptococcus pyogenes, whereas cyclopeptides and peptidyl derivatives of the general structure X-Arg-Leu-NH-CH(iPr)-CH2 -NH-Y had a much wider spectrum. The most potent of these substances displayed approximately equal minimal inhibitory and bactericidal concentrations of about 20 ,g/ml for both Staphylococcus aureus and S. pyogenes and were devoid of antiproteolytic activity. Several of the new substances could protect mice against lethal intraperitoneal challenge with S. pyogenes. Though their target remains to be disclosed, the group of substances here reported might be promising for the development of antibacterial drugs and the discovery of novel principles of action. [source]