Energy metabolism and lipid peroxidation of human erythrocytes as a function of increased oxidative stress.

To study the influence of oxidative stress on energy metabolism and lipid peroxidation in erythrocytes, cells were incubated with increasing concentrations (0.5-10 mM) of hydrogen peroxide for 1 h at 37 degrees C and the main substances of energy metabolism (ATP, AMP, GTP and IMP) and one index of lipid peroxidation (malondialdehyde) were determined by HPLC on cell extracts. Using the same incubation conditions, the activity of AMP-deaminase was also determined. Under nonhaemolysing conditions (at up to 4 mM H2O2), oxidative stress produced, starting from 1 mM H2O2, progressive ATP depletion and a net decrease in the intracellular sum of adenine nucleotides (ATP + ADP + AMP), which were not paralleled by AMP formation. Concomitantly, the IMP level increased by up to 20-fold with respect to the value determined in control erythrocytes, when cells were challenged with the highest nonhaemolysing H2O2 concentration (4 mM). Efflux of inosine, hypoxanthine, xanthine and uric acid towards the extracellular medium was observed. The metabolic imbalance of erythrocytes following oxidative stress was due to a dramatic and unexpected activation of AMP-deaminase (a twofold increase of activity with respect to controls) that was already evident at the lowest dose of H2O2 used; this enzymatic activity increased with increasing H2O2 in the medium, and reached its maximum at 4 mM H2O2-treated erythrocytes (10-fold higher activity than controls). Generation of malondialdehyde was strictly related to the dose of H2O2, being detectable at the lowest H2O2 concentration and increasing without appreciable haemolysis up to 4 mM H2O2. Besides demonstrating a close relationship between lipid peroxidation and haemolysis, these data suggest that glycolytic enzymes are moderately affected by oxygen radical action and strongly indicate, in the change of AMP-deaminase activity, a highly sensitive enzymatic site responsible for a profound modification of erythrocyte energy metabolism during oxidative stress.     

Spatial analysis of hepatocellular carcinoma and socioeconomic status in China from a Population-based Cancer Registry

Background: Little is known about geographic variations in liver cancer at high incident regions. We aimed to identify spatial variation of hepatocellular carcinoma (HCC) at a high-risk area in China and determine its association with socioeconomic status (SES). Methods: Based on 2299 liver cancer cases diagnosed in Haimen from 2003 to 2006, we calculated age–sex standardized incidence ratios (SIRs) and used two spatial scan statistics to determine the geographic variations in HCC. Bayesian hierarchical model was used to explore the association between HCC incidence and SES. Results: Age and sex SIRs for HCC varied from 0.54 to 1.97 for 24 townships. The eastern region of Haimen was identified to have a significantly increased risk of HCC. Fitting of a Bayesian hierarchical model linking per-capita fiscal revenue with SIRs of HCC indicated that the area with a lower revenue had a significantly higher incidence of HCC [β_log(revenue) = ?0.179, posterior 95% Bayesian credible interval (CI) = (?0.326, ?0.04)]. Conclusions: This study demonstrated substantial geographic variation in the incidence of HCC within a high-risk region, which was associated with SES. HCC control and intervention should focus on disadvantaged areas to reduce the HCC disparities.     

Endogenous CD8+ T cell expansion during regression of monoclonal EBV-associated posttransplant lymphoproliferative disorder.

There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vbeta repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vbeta pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vbeta-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells.     

Cell cycle dependent alterations of chromatin structure in situ as revealed by the accessibility of the nuclear protein AF-2 to monoclonal antibodies.

We have recently described a novel nuclear antigen, AF-2, which is related to cell cycle dependent alterations of chromatin structure. We show by two parameter flow cytometry on a cell by cell basis that the antigen is accessible to specific monoclonal antibodies only in mitotic and postmitotic early G1-phase cells. The evaluation of nuclease susceptibility and AF-2 antigen accessibility reveals different subcompartments of the G1-phase of the cell cycle with distinct chromatin conformations. Digestion with DNase I seems to alter the chromatin structure according to concentration and this is reflected by an increase of the antigen accessibility. Chromatin in the more condensed early G1-phase is specifically digested by lower concentrations of the enzyme than chromatin in later stages of interphase. Chromatin from cells in the late-G1, S-, and G2-phases shows a higher relative resistance to DNase I and a reduced accessibility of the AF-2 antigen to monoclonal antibodies. Nuclease S1 has a similar effect on chromatin topology, as revealed by the reaction with anti-AF-2 antibodies, without digestion of detectable amounts of DNA. The antigen becomes available to the antibodies in almost all cells by digestion with high concentrations of DNase I or Nuclease S1.     

中国吉丁虫新纪录种简记

近年来。笔在研究各地送鉴的大呈吉丁虫标本过程中。鉴定出一批中国新纪录种，今集中加以报道．并分别作简述如下。     

The evolution of food-producing glands in eusocial bees (Apoidea,Hymenoptera)1

A food-producing role for cephalic exocrine glands has arisen independently in both taxa of highly eusocial bees, Apis and Meliponini. With several exceptions, there is little evidence that food is produced by glands of solitary bees or by most bees at lower levels of sociality. We suggest that this association with sociality is due to four adaptive features of these glands: (1) food from the glands allows feces from queens and larvae to have a small volume, (2) the queen's fecundity can be increased, (3) nutrient recovery via cannibalism can be facilitated, and (4) rearing of emergency replacement queens is accelerated. Acceleration of the rearing of other castes and of queens in the normal process of colony fission is not clearly an advantage ascribed to these glands. Trophic eggs produced by meliponine colony workers are analogous to the secretions from food-producing glands in Meliponini and Apis workers.     

Entry of [(1,2-13C2)acetyl]-L-carnitine in liver tricarboxylic acid cycle and lipogenesis: a study by 13C NMR spectroscopy in conscious, freely moving rats.

The biochemical pathways involved in acetyl-L-carnitine utilization were investigated in conscious, freely moving rats by 13C NMR spectroscopy. Following 4-h [(1,2-13C2)acetyl]-L-carnitine infusion in fasted animals, the free carnitine levels in serum were increased, and an efflux of unlabelled acetyl-L-carnitine from tissues was observed. [(1,2-13C2)Acetyl]-L-carnitine was found to enter biosynthetic pathways in liver, and the acetyl moiety was incorporated into both cholesterol and 3-hydroxybutyrate carbon skeleton. In accord with the entry of [(1,2-13C2)acetyl]-L-carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the 13C label was also found in liver glutamate, glutamine, and glutathione. The analysis of the 13C-labelling pattern in 3-hydroxybutyrate and cholesterol carbon skeleton provided evidence that the acetyl-L-carnitine-derived acetylCoA pool used for ketone bodies synthesis in mitochondria was homogeneous, whereas cholesterol was synthesized from two different acetylCoA pools located in the extra- and intramitochondrial compartment, respectively. Furthermore, cholesterol molecules were shown to be preferentially synthesized by the metabolic route involving the direct channelling of CoA-activated mitochondria-derived ketone bodies into 3-hydroxy-3-methylglutarylCoA pathway, prior to equilibration of their acyl groups with extramitochondrial acetylCoA pool via acetoacetylCoA thiolase.     

Tissue and serum TPA in subjects at risk for bladder cancer

We tested the presence of tumour polypeptide antigen (TPA) in lower urinary tract cells from 59 workers exposed to known bladder carcinogens and from 30 control subjects. We then correlated immunocytological expression and serum TPA levels. Lower urinary tract cells from 31 subjects gave either moderately or strongly positive immunocytological stains. Five also had high serum TPA. The detection of TPA by cytology and in serum differed significantly in workers exposed to cancer agents and the control group.