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)

Point mutations in codons 12, 13 or 61 of the oncogenes Ha-ras, Ki-ras or N-ras have been identified in human malignancies of many types. Using the PCR (polymerase chain reaction) technique for DNA amplification in vitro and stringent probing of the amplified DNA on dot blots with a library of specific oligonucleotides, we have screened for the presence of ras mutations in oral and para-oral malignancies and some associated lesions. The material, from UK patients, consisted of 22 oral squamous-cell carcinomas including 5 neck metastases, 1 oral mucosal dysplasia, 1 proliferative verrucous leukoplakia, 1 antral and 1 tonsillar carcinoma, 1 basal-cell carcinoma, 1 salivary adenocarcinoma, 1 salivary adenoid cystic carcinoma and 1 lung adenocarcinoma metastatic to the gingiva. Genomic DNA was extracted from tissues which were fresh or preserved in liquid nitrogen. Two DNA samples contained point mutations in codon 61 of Ki-ras. One of these mutations was in the lymphocytes infiltrating a retromolar SCC. The other mutation (CAA to CAU; substitution of glutamine by histidine) was in the lung adenocarcinoma metastasis. The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras. While ras activations arising from point mutations may occur in a high proportion of oral malignancies associated with chewing tobacco (quid), this was not the case in UK oral malignancies, even where tobacco was smoked.
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PMID:Ras mutations in United Kingdom examples of oral malignancies are infrequent. 204 May 36

We studied the metabolic response to acute aneurysm surgery and its modification by parenteral nutrition. Forty-eight patients receiving perioperative corticosteroid treatment were randomly assigned to receive glucose alone (7.2 kcal/day, D5W + C), glucose and a conventional amino acid solution (7.2 kcal/day and 0.15 gN/day, CAA + C) or glucose and branched chain amino acid enriched solution (7.2 kcal/day and 0.14 gN/day, BCAA + C). Twenty patients without corticosteroid treatment received either glucose alone (7.2 kcal/day, D5W) or glucose and a conventional amino acid solution (7.2 kcal/day and 0.14 gN/day, CAA). Poor nitrogen utilization was indicated by strongly negative nitrogen balance in all groups and a failure of the infused amino acids to improve nitrogen balance. (Day 0; D5W + C: -9.3 +/- 3.6 g/day and CAA + C: -8.2 +/- 9.7 g/day vs CAA: -2.6 +/- 4.9 g/day, p less than 0.05, Day 1; D5W + C: -14.9 +/- 9 g/day vs CAA: -7.7 +/- 6.5 g/day, p less than 0.05, MANOVA). We conclude that subarachnoid haemorrhage and its surgical treatment induce a catabolic response and impaired utilization of exogenous nitrogen, further amplified by perioperative corticosteroids, which is in sharp contrast to the response to surgery not involving the central nervous system.
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PMID:Impaired utilization of exogenous amino acids after surgery for subarachnoid haemorrhage. 212 2

Enhanced nitrogen utilization occurs when adults with gastrointestinal disease are fed partially hydrolyzed proteins instead of isonitrogenous, isocaloric crystalline amino acids. A controlled trial was conducted to determine if this difference was also seen in malnourished stressed cancer patients and to gain an understanding of the underlying mechanism. Sixteen malnourished patients with head and neck cancer were prospectively randomized to either crystalline amino acid-glucose (CAA-G) or partially hydrolyzed protein-glucose (PHP-G) diets. Patients were fed via an enteral tube for 10 days starting on the second postoperative day. Blood SMA-6 and amino acid levels were measured on Days 1 and 10. Daily calorie counts and fluid balance were obtained. Daily 24-hr urine and stools were analyzed for total N during the last 5 days of the study period. The daily positive N balance with both diets was the same (CAA-G = +7.8 +/- 0.8 vs PHP-G = +8.2 +/- 1.0 g; mean +/- SE) and 3-methylhistidine:creatinine ratio did not differ. Patients on PHP-G diet gained significantly more weight (+0.5 vs - 1.5 kg; P less than 0.01) and had significantly higher serum albumin (3.2 +/- 0.2 vs 2.8 +/- 0.1 g/dl; P = 0.5) by the end of the 10th study day. Weight changes were not due to fluid retention: serum Na+, K+, creatinine and mean fluid intake for the two groups remained the same during the study period. A significantly greater rise in BUN occurred on the CAA-G diet (from 9.2 +/- 1.7 to 15.4 +/- 1.4 mg/dl; P less than 0.05) while BUN remained unchanged on the PHP-G diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of elemental diet on albumin and urea synthesis: comparison with partially hydrolyzed protein diet. 637 51

This two phase study evaluates nitrogen utilization by the body as a function of fixed caloric intake but different nitrogen loads. Nitrogen use by the body was estimated from measures of nitrogen balance, net protein utilization, and urea accumulation rate. Phase 1 of this study included 411 measurements of nitrogen use in 120 patients assigned, according to clinical condition, to receive one of the four following therapies: dextrose (D) 25%, amino acids (CAA) 4.25% (Group 1); D 35%, CAA 4.25% (Group 2); D 25%, CAA 21.3% (Group 3); or D 35%, CAA 21.3% (Group 4). Forty patients in Phase 2 were assigned in a randomized, prospective, double blind manner, to receive one of the following regimens; D 35%, CAA 2.75% (Group 5); D 25%, CAA 2.75% (Group 6); D 35%, CAA 4.25% (Group 7); or D 25%, CAA 4.25% (Group 8). In Phase 1, positive nitrogen balance was achieved with the exception of Group 3 where neither the estimated caloric nor nitrogen needs of the patients were met. It appeared that protein utilization was maximal in patients receiving the therapy of highest calorie:nitrogen ratio (Group 4). Phase 2 patients achieved positive nitrogen balance to the same extent (p greater than 0.05) and although net protein utilization improved from 53 to 71%/d as the calorie:nitrogen ratio was increased, the differences were not significant (p greater than 0.05). There was a significant improvement in total iron binding capacity in Phase 2 patients (p less than 0.01) that was most prominent at the lower concentrations of amino acids (high cal:n ratio) (Groups 5 and 6). Smaller amounts of nitrogen appear adequate in producing a positive nitrogen balance and may be better utilized in hospitalized patients if the patients' caloric requirements are achieved.
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PMID:Evaluation of nitrogen utilization in patients receiving total parenteral nutrition. 640

The effects of total parenteral nutrition (TPN) in partially nephrectomized rats (n = 17) and sham-operated controls (n = 12) were evaluated and compared to the effect of low and high nitrogen oral diets (6% and 24% protein). TPN included fat (9 g/kg per day), high energy (1385 KJ/kg per day), and low nitrogen content (0.6 g N/kg per day, corresponding to 8% protein) either as essential amino acids (EAA) or as a mixture of essential and nonessential amino acids (CAA). The parenteral nutrition was administered intravenously via a permanent catheter continuously for 10 days. Most animals tolerated the treatment with no signs of overhydration or electrolyte imbalances. Uremic rats on TPN gained in weight similarly to control animals, whereas uremic rats given oral diets showed a lower weight increase. Both amino acid solutions promoted positive nitrogen balance and growth. Plasma urea dropped during TPN and low protein oral feeding in uremic and control rats, but not in the high protein-fed animals. Serum creatinine decreased with TPN but not with oral feeding in uremic rats. Albumin and hemoglobin levels were significantly reduced in all uremic rats irrespective of dietary treatment. The experimental model presented here could be useful for further studies on parenteral nutrition in uremia.
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PMID:Effects of total parenteral nutrition in rats with experimental chronic renal failure. 680 93

The literature does not contain reports regarding teicoplanin overdose in newborns. In a neonate with a history of recent postasphyctic acute renal failure which recovered within 7 days of life, antibiotic therapy with teicoplanin was started for sepsis due to Staphylococcus hominis. However, for 5 days the dosage was excessive (20 mg/kg twice daily instead of an initial dose of 16 mg/kg and then doses of 8 mg/kg once daily). Once this error had been noted, therapy was immediately suspended. Clinically the newborn had improved and blood culture at the end of the therapy was negative. Biohumoral tests revealed constantly normal levels of serum creatinine, serum cystatin C and blood nitrogen. Urinary parameters of tubulotoxicity were also within normal values. Urinary epidermal growth factor was increased. Teicoplanin was well tolerated at the renal level in the newborn even in this case of excessive dosage.
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PMID:Renal tolerability of teicoplanin in a case of neonatal overdose. 982 56

Human cystatin C is a cysteine proteinase inhibitor with potential applications as an anti-viral agent, cancer tumor growth inhibitor, and in prevention of proteolysis during food processing. A glycosylated cystatin C mutant with increased temperature stability was developed for the latter application [Nakamura et al. (1998) FEBS Lett 427:252-254]. A recombinant variant of cystatin C [Nakamura et al. (2000) International patent no. PLTCA99/00717] with two potential sites for N-linked glycosylation was expressed in Pichia pastoris Mut(s). Little of the cystatin C produced was in the glycosylated form under fermentation conditions of pH 6, temperature 28 degrees C, methanol only feed, and ammonium hydroxide as a nitrogen source. Thus, the effect of addition of complex nitrogen sources, peptone and amino acid supplements, on the yield and glycosylation of this mutant cystatin C were investigated. A full factorial design experiment using 2-l fermenters was performed with three factors: ammonium hydroxide, peptone, and an amino acid mix, at two levels, absent or present. Peptone addition was found to have a positive, and the most significant, effect on cell specific cystatin C yield. A maximum mutant cystatin C yield of 0.82 mumol (g-dry cell weight)(-1) min(-1) was obtained when all three nitrogen sources were used together. However, under these conditions only 16% of protein was in the glycosylated form since ammonia was found to have a significant negative effect on glycosylation extent. The maximum extent of glycosylation was 30% when peptone and amino acid mix were the only nitrogen sources added.
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PMID:The effect of nitrogen source on yield and glycosylation of a human cystatin C mutant expressed in Pichia pastoris. 1566 45

Drug-induced kidney injury is a serious and not uncommon adverse event which needs to be considered during drug development. The current standards used to monitor kidney function, such as blood urea nitrogen and serum creatinine, are late indicators of kidney injury and thus do not allow for timely intervention before loss of function. Improving the diagnosis and monitoring of kidney damage goes hand-in-hand with the identification of new biomarkers and the development of technologies that enable their sensitive and specific measurements. In order to move beyond restriction to internal company decisions, every entity that demonstrates the qualities of a biomarker must gain acceptance by health authorities if it is to be used for regulatory decision making in preclinical studies and clinical trials. This review focuses on the most promising achievements of new technologies applied to monitoring drug-induced nephrotoxicity (eg, gene expression, imaging, in vitro screening, protein assays) and on the use and implications of peripheral biomarkers such as the urinary protein biomarkers glutathione S-transferase-alpha, N-acetyl-beta-d-glucosaminidase, total protein, cystatin C, beta2-microglobulin, KIM-1, lipocalin-2 and serum cystatin C. Finally, the associated regulatory processes for use in clinics are also discussed.
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PMID:Monitoring kidney safety in drug development: emerging technologies and their implications. 1817 68

Acute renal failure (ARF) is an acute loss of kidney function that occurs over days to weeks and results in an inability to appropriately excrete nitrogenous wastes and creatinine (Cre). ARF is diagnosed by elevations of blood urea nitrogen and serum Cre level, which is classified as prerenal, intrinsic and postrenal according to their mechanisms. However, discriminate diagnosis of these types by blood biochemistry findings is difficult. Recently, cystatin C (Cys-C), a basic protein having isoelectric point 9.3 with a molecular weight of 13.3 kDa, is freely filtered at the level of the glomerulus and virtually all is reabsorbed and metabolized by the proximal tubular cells. Therefore, assuming constant cellular production, serum Cys-C level has the potential to be an excellent surrogate marker of glomerular filtration rate. Because Cre is electrically charged neutrally, there is a possibility that the permeation of Cys-C, which is positively charged, is diffluent from that of Cre through glomerular basement membrane due to the type of the renal failure. We determined blood concentrations of Cys-C and Cre in a patients with prerenal renal failure (17 patients), intrinsic renal failure (232 patients) and postrenal renal failure (13 patients) as compared with healthy subjects (n = 771). We found that patients with postrenal renal failure displayed significantly elevated Cre/Cys-C ratio (mean +/- standard deviation) (8.3 +/- 8.0, p < 0.001) as compared with healthy subjects (1.1 +/- 0.2), prerenal (0.6 +/- 0.2) and intrinsic (1.6 +/- 0.5). These findings suggest that measurement of Cys-C concentration and Cre/Cys-C ratio may be useful for the discriminate diagnosis of postrenal renal failure.
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PMID:[Plasma creatinine and cystatin C ratio is useful for discriminate diagnosis of postrenal renal failure]. 1840 24

The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
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PMID:New equations to estimate GFR in children with CKD. 1915 56


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