Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A narrow therapeutic index is a characteristic feature of cytotoxic agents. Some of these agents are almost entirely eliminated renally in unchanged active form. As a consequence, assessment of the individual glomerular filtration rate (GFR) may help to predict the pharmacokinetic behaviour of cytotoxic agents in plasma more precisely. In addition, GFR-adapted individualization of cancer chemotherapy may have an enormous impact on the severity of side effects. Several methods are available to determine GFR or creatinine clearance (CrCl). GFR-measurement based on experimental methods with radiolabelled isotopes, contrast media or inulin helps to reflect the real situation very closely. In addition, 24-h urine collection is a convenient and feasible method to measure creatinine clearance. Finally, several mathematical equations exist to estimate GFR or CrCl based on serum creatinine and other parameters. Only a few of these equations have been developed in oncologic patients. However, some of these equations are routinely used in clinical practice, because they allow a rapid estimation of GFR. Based on the fact that clinically relevant differences have been assessed between calculated values and the real situation, mathematical calculation of GFR or CrCl does not seem to be appropriate to assess individual renal function precisely enough over a broad range of individual GFR or CrCl. Whether the measurement of low-molecular-weight proteins, such as cystatin C and ss-trace protein, may help to reflect the real situation more precisely is a matter of controversial debate.
J Cancer Res Clin Oncol 2005 Sep
PMID:Accurate measurement of individual glomerular filtration rate in cancer patients: an ongoing challenge. 1601 66

Topical application of dibenzo[a,l]pyrene (DB[a,l]P) to the dorsal skin of SENCAR mice induces codon 61 (CAA Gln to CTA Leu) mutations in the Harvey (H)-ras gene within 12 h after treatment. Between days 1 and 3, the frequency of these mutations increases rapidly, suggesting that skin cells carrying the codon 61 mutations proliferate in this period. We have investigated DB[a,l]P-treated mouse skin (12 h-7 d) for further evidence of H-ras expression and epidermal cell proliferation. Two waves of cell proliferation were observed: the first wave (1-2 d) correlated with the clonal proliferation of codon 61-mutated cells, and the second wave (3-7 d) correlated with DB[a,l]P-induced hyperplasia. DB[a,l]P-induced early preneoplastic cell proliferation correlated with H-ras and specific G1 cyclin expression. Total H-ras protein and cyclin D1 were found to increase during DB[a,l]P-induced hyperplasia, but the levels of guanosine triphosphate-bound (active) H-ras protein and cyclin E were increased during the putative clonal proliferation of codon 61-mutated cells. These results suggest that DB[a,l]P-induced oncogenically mutated cells proliferate in early preneoplastic skin. As this proliferation occurs in the absence of any promoting treatment, we propose that this phenomenon is a tumor initiation event.
J Invest Dermatol 2005 Sep
PMID:Harvey-ras gene expression and epidermal cell proliferation in dibenzo[a,l]pyrene-treated early preneoplastic SENCAR mouse skin. 1611

Cystatin C, an inhibitor of cysteine proteinases, is suggested to be involved in oxidative stress-induced apoptosis of cultured CNS neurons and various neuronal diseases in vivo; however, little is known about its mechanism of action. To address the role cystatin C plays in oxidative stress-induced neuronal cell death, we established PC12 cell lines that stably expressed rat cystatin C. These cystatin C-expressing PC12 cells showed remarkable resistance to high (50%) oxygen atmosphere. This resistance correlate with expression levels of cystatin C, demonstrating that cystatin C has a protective effect on high oxygen-induced cell death. In contrast, in a normal (20%) oxygen atmosphere neither control nor cystatin C-expressing PC12 cells showed a significant change in the number of living cells, indicating that cystatin C does not play an important role in the regulation of cellular proliferation. Furthermore, the cystatin C-expressing cell line also resisted other oxidative stresses, including glutamate- and 13-L-hydroperoxylinoleic acid (LOOH)-induced cell death. These results demonstrate that cystatin C has protective effects against various oxidative stresses that induce cell death.
Brain Res Bull 2005 Sep 30
PMID:Expression of cystatin C prevents oxidative stress-induced death in PC12 cells. 1614 Jan 67

Cathepsin B, one of the lysosomal cysteine proteases, has been related to tumor invasiveness. Cystatin C is the strongest inhibitor of cathepsin B. Knowledge of its participation in the progression of gliomas is limited. We investigated the expression of cystatin C and its association with the clinicopathologic features of 57 gliomas. Cystatin C and cathepsin B expressions were evaluated by immunohistochemical methods and by semiquantitative real-time polymerase chain reaction analysis for the corresponding messenger RNA. Disease-free survival was analyzed by the Kaplan-Meier method. Tumors with low cystatin C protein expression and high cathepsin B protein expression were significantly more likely to be of high grade, and this pattern was significantly correlated with high Ki-67 LI and tumor recurrence. Depressed expression of cystatin C messenger RNA in glioblastomas compared with low-grade astrocytomas was demonstrated. Multivariate analysis demonstrated high tumor grade, high Ki-67 labeling index, high cathepsin B expression, and low cystatin C expression correlated significantly with shorter disease-free survival. These results suggest that gliomas in patients with an unfavorable clinical outcome are characterized by depressed expression of cystatin C. Evaluation of cystatin C expression in gliomas provides useful clinical information, especially as a prognostic indicator.
Hum Pathol 2005 Sep
PMID:Clinicopathologic significance of cystatin C expression in gliomas. 1615 65

Nine major transfer RNA (tRNA) gene clusters were analysed in various Vibrio cholerae strains. Of these, only the tRNA operon I was found to differ significantly in V. cholerae classical (sixth pandemic) and El Tor (seventh pandemic) strains. Amongst the sixteen tRNA genes contained in this operon, genes for tRNA Gln3 (CAA) and tRNA Leu6 (CUA) were absent in classical strains as compared to El Tor strains. The observation strongly supported the view that the above two pandemic strains constitute two different clones.
J Biosci 2005 Sep
PMID:Structural organization of the transfer RNA operon I of Vibrio cholerae: differences between classical and El Tor strains. 1618 8

The use of marker-peptides, measured by LC-MS/MS, is investigated for the quantitative analysis of proteins. To that end, cystatin C is chosen as a model protein. It not only functions as a proof of concept protein but the growing interest in cystatin C as a new marker of kidney failure provides a practical application at the same time. The use of trypsin-based proteolysis, to obtain so-called marker-peptides, simplifies the quantification of a protein to the quantification of a single or a number of peptides. Reproducibility of the trypsin proteolysis procedure is vital and has been optimised. A number of the marker-peptides obtained are selected for LC-MS(/MS) analysis. They are completely separated by high-pressure LC allowing maximum selectivity and mass spectrometric multiple reaction monitoring sensitivity. By doing so, linear calibration curves can be obtained for cystatin C over two orders of magnitude. Experiments have been performed on a triple quadrupole mass spectrometer by single ion monitoring (maximum sensitivity) as well as by multiple reaction monitoring (maximum specificity).
J Sep Sci 2005 Sep
PMID:The use of tryptic marker-peptides for the quantitative analysis of cystatin C. 1622 71

Cystatin C is the major inhibitor of the cysteine cathepsins. Polymorphisms in the cystatin C gene have recently been associated with the risk of developing Age-related Macular Degeneration (AMD). Oxidative stress is also thought to play a key role in the pathogenesis of AMD. We surveyed the retinal pigment epithelium (RPE) and choroid of the C57BL/6J mouse for the expression of the cysteine cathepsins under normoxic and hyperoxic (75% O(2)) conditions. Microarray analysis of RPE/choroid mRNA revealed the expression of cathepsins B and L, as well as cystatin C under all experimental conditions. The microarray results were confirmed by real-time quantitative polymerase chain reaction (PCR). Localization of the mRNA species for cystatin C and cathepsin B, as well as, localization of protein species for cystatin C, cathepsins B and L were performed to evaluate the tissue distribution of these species. Our results indicate that cystatin C is largely synthesized in the RPE and secreted from the basal side. Cathepsin B is the major cysteine protease in the RPE and choroid. The expression of all mRNAs and proteins was elevated by exposure to oxidative stress.
Exp Eye Res 2006 Sep
PMID:Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse. 1668 24

Previous studies indicate that serum cystatin C predicts incident heart failure in older adults. Children with chronic kidney disease (CKD) develop left ventricular (LV) diastolic dysfunction, often the initial abnormality of cardiac function. We hypothesized that cystatin C might predict LV diastolic dysfunction in children with CKD. Fifty-seven subjects, aged 6-21 years, with stage 2-4 CKD underwent echocardiography. Diastole was assessed from transmitral Doppler [maximum early (E wave) and late (A wave) diastolic flow velocities (E/A ratio)] and from tissue Doppler [septal mitral annular peak velocities (E')]. LV filling pressures were determined, using a ratio of E/E'. Fourteen (25%) patients had low E' and 15 (26%) had high E/E'. Children with abnormal E' or E/E' had significantly higher cystatin C levels than children with normal indices (P<0.05). Neither serum creatinine nor measured glomerular filtration rate (GFR) significantly correlated with E' or E/E'. Stepwise multiple regression analysis showed that cystatin C (beta=-0.825, P=0.023) and left ventricular mass (LVM) index (beta=0.099, P=0.006) independently predicted E'; LVM index independently predicted E/E' (beta=0.0173, P=0.01). We conclude that, in contrast to measured GFR or serum creatinine level, elevated serum cystatin C might be associated with diastolic dysfunction in children with CKD.
Pediatr Nephrol 2006 Sep
PMID:Serum cystatin C and left ventricular diastolic dysfunction in children with chronic kidney disease. 1672 86

We report a novel fibrinogen variant (fibrinogen Seoul II), which has a heterozygous point mutation from CAA to CCA leading to AalphaGln328Pro. The mutation site is among several glutamine residues that serve as alpha-chain cross-linking acceptor sites. Fibrinogen Seoul II was found in a 51-year-old male patient and his family in Seoul, Korea. The patient was diagnosed with myocardial infarction at age 43. Eight years later he was admitted to the emergency room due to recurrence of the disease, where he expired under treatment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the patient's relatives, showed a decreased final turbidity, suggesting Seoul II fibrin clots are composed of thinner fibers. This supposition was verified using scanning electron microscopy. Alpha-polymer formation by the mutant fibrinogen upon thrombin treatment in the presence of factor XIII and calcium was distinctly impaired. This result confirms that the residue Aalpha328 plays a pivotal role in alpha-chain cross-linking.
Blood 2006 Sep 15
PMID:A novel fibrinogen variant (fibrinogen Seoul II; AalphaGln328Pro) characterized by impaired fibrin alpha-chain cross-linking. 1673 2

Serum cystatin C (cysC) is a potential marker of the glomerular filtration rate (GFR) that has generated conflicting reports in children. A prospective study was conducted to assess the benefit of considering cysC together with serum creatinine (SCr) and demographic and morphologic characteristics to better estimate the 51Cr-ethylenediaminetetraacetate (EDTA) clearance (CL), i.e., the GFR. Plasma 51Cr-EDTA data from 100 children or young adults (range: 1.4-22.8 years old) were analyzed according to the population pharmacokinetic approach by using the nonlinear mixed effects model (NONMEM) program. The actual CL was compared to the CL predicted according to different covariate equations. The best covariate equation (+/-95% confidence interval) was: GFR (ml/min)=63.2(+/-3.4) . [(SCr (microM)/96)(-0.35 (+/-0.20))] . [(cysC (mg/l)/1.2)(-0.56 (+/-0.19))] . [(body weight (kg)/45)(0.30 (+/-0.17))] . [age (years)/14)(0.40 (+/-0.16))]. This equation was associated with a less biased and more precise estimation than the Schwartz equation. CysC improves the estimation of the GFR in children if considered with other covariates within the mathematical formula.
Pediatr Nephrol 2006 Sep
PMID:GFR is better estimated by considering both serum cystatin C and creatinine levels. 1679 18


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