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Effective Marker (effective + marker)
Selected AbstractsClose association of CD8+/CD38bright with HIV-1 replication and complex relationship with CD4+ T-cell count,CYTOMETRY, Issue 4 2009Edouard Tuaillon Abstract Background: Measuring lymphocyte activation provides information in addition to CD4+ T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8+ T-cells. Focusing specifically on CD38 high expression (CD8+/CD38bright) may be an interesting surrogate gating strategy because CD38bright characterizes principally activated memory cells. Methods: CD8+/CD38bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4+ T-cell count. Results: The CD8+/CD38bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8+/CD38bright moderately correlated with CD4+ T-cell count independently of the VL (r = ,0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4+ T-cell depletion (median 39% for CD4+ T-cell counts <50/mm3). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals. Conclusions: CD8+/CD38bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society [source] Nitric Oxide Metabolites Are Associated with Survival in Older PatientsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2007Toshio Hayashi MD OBJECTIVES: To assess the efficacy of various vascular endocrinological substances, such as plasma nitric oxide metabolites (NOx), as surrogate markers of survival in older patients. DESIGN: Prospective cohort, observational. SETTING: Nagoya University Hospital and related hospitals, Japan. PARTICIPANTS: One hundred fifty patients aged 70 and older, recruited consecutively from the outpatient clinics of Nagoya University Hospital and related hospitals. MEASUREMENT: Serum biochemical analyses such as albumin and total cholesterol, various prognostic markers, such as tumor necrosis factor (TNF)-,, NOx, activities of daily living (ADLs), and instrumental ADLs (IADLs) were evaluated on enrollment. ADLs, IADLs, and comorbidities, especially depression and impaired cognition, were evaluated on enrollment. The main outcome was survival rate over 2.75 years. RESULTS: Forty-nine patients died during the follow-up period. Mann-Whitney U -test showed that hemoglobin, total protein, serum albumin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high sensitive c-reactive protein, NOx, B-type natriuretic peptide, interleukin-6, and TNF-, levels; ADLs; cognitive impairment; and depressive status were significantly different for subjects who survived and those who died. Of the dependent variables in the Cox proportional hazards regression analyses, only ADLs, NOx, and albumin were significantly different. In the Kaplan-Meier analyses of mortality, the prognosis of patients in the third and fourth quartiles of NOx was significantly worse than that of patients in the first or second quartile. The prognosis of patients with impaired ADLs was worse than that of other patients for the overall period. CONCLUSION: Lower levels of NOx may be associated with survival in older patients. It may be an effective marker, like ADLs, which is a well-known marker. [source] Study of Cytochrome P4502E1 mRNA Level of Mononuclear Cells in Patients With Alcoholic Liver DiseaseALCOHOLISM, Issue 2001Hirokazu Yano Background: Cytochrome P-4502E1 (CYP2E1) is an important enzyme because of its unique ability to convert many substrates to cytotoxins. The increased production of reactive intermediates by elevated enzyme concentrations leads to various pathological conditions. Therefore, it is important to detect induced CYP2E1 levels in alcoholic individuals to avoid xenobiotic-promoted liver injury. In the present investigation, we detected CYP2E1 mRNA levels of mononuclear cells obtained from 10 ml of blood by using competitive polymerase chain reaction (PCR) method. Methods: Mononuclear cells were obtained from healthy individuals who did and did not drink habitually and patients with alcoholic liver disease (ALD). Complementary DNA synthesis was performed with RNA obtained from mononuclear cells by reverse transcription-PCR. Competitive PCR of CYP2E1 was performed with the sense (5,-CTGCAACGTCATA-GCCGACA-3,) and antisense (5,-TCCATTTCCACGAGCAGGCA-3,) primer and competitor DNA. Competitive PCR of ,-actin also was performed. Electrophoresis was scanned, and each band was digitized. The concentration of CYP2E1 and ,-actin mRNA was calculated from the ratio of competitor DNA. Results: In healthy individuals who did and did not drink habitually, CYP2E1 mRNA levels were 103.3 copies/,l RNA and 101.7 copies/,l RNA, respectively. In actively drinking patients with ALD, CYP2E1 mRNA levels were 103.5 copies/,l RNA, but those levels decreased to 101.7 copies/,l RNA after 4 days of abstinence. No significant difference was observed in CYP2E1 mRNA levels between alcoholic fibrosis and cirrhosis. As control, we measured ,-actin mRNA levels in mononuclear cells in all samples. The mean value of ,-actin mRNA was 104.3 copies/,l RNA in all cases, which included patients with ALD. Conclusions: The results demonstrated that it is possible to measure the CYP2E1 mRNA levels of mononuclear cells in a 10 ml blood sample. The CYP2E1 mRNA level in mononuclear cells increases during drinking and decreases in abstinence for a short period of 3 to 4 days. It is concluded that CYP2E1 mRNA level may be used as an effective marker for alcoholic intake. [source] Off-line liquid chromatography-MALDI by with various matrices and tandem mass spectrometry for analysis of glycated human serum albumin tryptic peptidesMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4 2007Annunziata Lapolla Abstract Advanced glycation end-product (AGE)/peptides, arising from in vivo digestion of glycated proteins, are biologically important compounds, due to their reactivity against circulating and tissue proteins. For information on their possible structure, in vitro glycation of HSA and its further enzymatic digestion were performed. The resulting digestion product mixture was analysed directly by MALDI MS with various matrices [2,5-dihydroxy benzoic acid (DHB) and ,-cyano-4-hydroxy cinnamic acid (CHCA)]. Alternatively, offline microbore LC prior to MALDI analysis was used, and showed that 63% of the free amino groups prone to glycation are modified, indicating the contemporary presence of unglycated peptides. This result proves that, regardless of the high glucose concentration employed for HSA incubation, glycation does not go to completion. Further studies showed that the collisionally activated decomposition of singly charged glycated peptides leads to specific fragmentation pathways, all related to the condensed glucose molecule. These unique product ions can be used as effective markers to establish the presence of a glucose molecule within a peptide ion. [source] | |||||||||||||