Muneo Aoyama

Cytochrome c and tumor necrosis factor-alpha values in serum and cerebrospinal fluid of patients with influenza-associated encephalopathy

Cytochrome c and tumor necrosis factor-α concentrations were measured in serum and cerebrospinal fluid samples from 10 patients with influenza-associated encephalopathy. In the acute exacerbation phase, serum tumor necrosis factor-α and cytochrome c values were high in patients with a poor prognosis. In the convalescent phase, cerebrospinal fluid cytochrome c values increased remarkably in patients with subsequent brain atrophy.

Prognostic predictive values of serum cytochrome c , cytokines, and other laboratory measurements in acute encephalopathy with multiple organ failure

Aims: To evaluate the prognostic predictive values of cytochrome c, cytokines, and other laboratory measurements in serum collected during neurological onset in acute encephalopathy with multiple organ failure. Methods: In addition to general laboratory examinations, the concentrations of cytochrome c (apoptosis marker) and cytokines (inflammatory markers) were measured in serum samples collected at the initial phase in 29 patients with acute encephalopathy. The obtained values were evaluated as predictors for the development of severe encephalopathy. Results: Cytochrome c, tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble TNF-receptor 1 (sTNF-R1), and aspartate aminotransferase (AST) concentrations at the initial phase were high and correlated well with patient outcome. High concentrations of serum cytochrome c (>45 ng/ml), sTNF-R1 (>2000 pg/ml), AST (>58 IU/dl), IL-6 (>60 pg/ml), and TNF-α (>15 pg/ml) predicted an unfavourable prognosis (sequelae and death) at 93%, 79%, 82%, 77%, and 60%, respectively. The specificity of those markers was 100%, 89%, 83%, 100%, and 100%, respectively. Conclusions: Serum cytochrome c is the most sensitive and specific predictor for the development of severe encephalopathy at the initial phase. Results suggest that this marker might be used to guide decisions regarding the start of the initial treatment and further intensive care.

Cytochrome c is a possible new marker for fulminant hepatitis in humans

BackgroundCytochrome c is known as a substance related to apoptosis. We investigated serum cytochrome c levels in patients with fulminant hepatitis (FH) compared with these levels in patients with acute or chronic liver diseases.MethodsSerum cytochrome c was measured by an electrochemiluminescence immunoassay (ECLIA) method. The numbers of patients were as follows: fulminant hepatitis (FH; n = 15), acute hepatitis (AH; n = 12), chronic hepatitis (CH; n = 30), chronic hepatitis with acute aggravation (CHA; n = 6), liver cirrhosis (LC; n = 30), hepatocellular carcinoma (HCC; n = 30), and healthy volunteers (controls; n = 9).ResultsThe serum cytochrome c level in FH was 10 686 ± 7787 pg/ml, with a significant difference (P < 0.01) compared to levels in the other groups. In the FH patients, the serum cytochrome c level was significantly correlated to serum mitochondria (m)-GOT, hepatocyte growth factor (HGF), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and alkaline phosphatase (ALP), and it was negatively correlated to serum alpha-fetoprotein (AFP), and total bilirubin (T.Bil.) The serum cytochrome c level seemed to parallel the severity of hepatic coma. Immunohistochemical study indicated TdT mediated dUTP nick end labeling (TUNEL)-positive cells in the livers of patients with FH.ConclusionsThese results suggest that serum cytochrome c may be a possible new marker for acute liver failure.

Serum cytochrome c to indicate the extent of ongoing tumor cell death

Despite the significant implication of apoptosis in tumorigenesis, there is no biomarker to assess the extent of ongoing apoptosis in vivo for hematological malignancies. We investigated the potential of serum cytochrome c (cyto‐c) as a biomarker for apoptosis. Cyto‐c and lactate dehydrogenase (LD) were released into the culture medium from apoptotic cells induced by tumor necrosis factor‐related apoptosis‐inducing ligand in a time‐dependent manner in vitro, with different kinetic patterns. Only one‐third of 153 patients with hematological malignancies showed high levels of serum cyto‐c (>20 ng/ml). Although serum cyto‐c level was roughly correlated to serum LD activity, their different kinetic patterns from serial measurements indicated that serum cyto‐c rather than LD is a more sensitive indicator for tracking changes of tumor status. Furthermore, serum cyto‐c level stratified patients with acute adult T‐cell leukemia into favorable and unfavorable subgroups with 5‐year survival rates of 67%vs. 11%. In conclusion, serum cyto‐c may provide a fast real‐time biomarker for tracking changes of tumor status involved in apoptotic cell death, but lacking disease or cell‐type specificity.