The structure analysis of porcine hemoglobin alphabeta dimer and the calculation of solvent accessible surface of the amino acids showed the epsilon-amino groups of the lysine are suitable for modification by polyethylene glycol (PEG). The modification of the lysine residues will not affect the carring oxygen capacity of Hb. Three types of linker have been designed to connect PEG and porcine hemoglobin. The lysines between porcine and bovine hemoglobin (pHb and bHb) are highly conserved, but the solvent accessible surface of conserved lysines are different. These suggested that the properties of homologous proteins are similar in pHb and bHb, but the characteristic derived from the homology analysis will be deviated from the actual status. The results of molecular dynamics simulation suggested that the chemical modified porcine hemoglobin would be no immunogenicity.

OBJECTIVETo observe the liver oxidant damage for diabetic model in mice.

METHODSMale kunming mice were feed with high fat dietary for a week and then were randomly divided into two groups by weight, with 10 mice in each group. One group was induced by small dose streptozotocin (STZ) and obtained STZ-induced diabetic mice, and the other group was regarded as the control. Both of the two groups were feed with high fat dietary. After 6 weeks, the activities of enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and nitric oxide synthase (NOS) were measured. Glutathione (GSH), maleic dialdehyde (MDA), nitric oxide (NO) levels in the liver and the liver viscera quotient were also measured. Liver histological manifestations were observed.

RESULTSIn diabetes group, there was a significant decrease in body weight, and the activities of GSH, CAT, and NOS decreased significantly (t value were 5.370, 10.639, 5.235, 3.089, respectively, P < 0.01). While, the liver viscera quotient, the levels of MDA, GSH-PX and NO increased remarkably (t value were -6.246, -2.728, -2.660, -4.924, respectively, P < 0.01 or P < 0.05). The significant difference was not observed in SOD between the two groups (t value was -0.405, P > 0.05). The liver histological damages were observed in diabetes group, light microscope observation showed hepatocytes swelling, ballooned changing and fatty droplets clustering.

CONCLUSIONThe oxidant damage might exist in the liver diabetic model in mice.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Nitric Oxide ; metabolism ; Oxidative Stress ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the effects of prenatal exposure to Di-(2-ethylhexyl)-phthalate (DEHP) on genome-wide epigenetic alterations in ovary of adult offspring rat.

METHODSPregnant Wistar rats were randomly treated with DEHP (1000 mg/kg) or con oil at 12 - 17 days upon pregnance. DNA methylation changes in the ovary for the adult offsprings which were 70 days old were detected by Rat DNA methylation promoter plus CpG island arrays CpG island chip. Gene ontology (GO) method was performed to analyze the function of genes which were significantly different between exposed group and control group. Gene Igfbp1 (insulin-like growth factor binding protein 1) and Itga3 (integrin alpha 3) were randomly selected and the methylation status were verified by bisulfite genomic sequencing (BSP).

RESULTSThe methylation status were significantly different between exposed and control group in 406 genes (71 genes as hypermethylation and 335 genes as hypomethylation) (P < 0.05). GO analysis revealed that molecular transducer activity, cell part, cell, cellular process, multicellular organismal process, response to stimulus, biological regulation, regulation of biological process, reproduction, reproductive process, and rhythmic process were involved. The sequencing results were consistent with the data obtained by chips.

CONCLUSIONThis study provides evidence that prenatal exposure of DEHP may be associated with methylation changes on the genes in the rat ovary. Genes related to reproductive process have highly significant methylation changes, which may shed new light on mechanisms of reproductive and developmental toxicity after prenatal exposure to DEHP.

Animals ; CpG Islands ; genetics ; DNA Methylation ; Diethylhexyl Phthalate ; toxicity ; Female ; Genome ; Maternal Exposure ; Ovary ; pathology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar

This paper presents a new deformable model using both population-based and patient-specific shape statistics to segment lung fields from serial chest radiographs. First, a modified scale-invariant feature transform (SIFT) local descriptor is used to characterize the image features in the vicinity of each pixel, so that the deformable model deforms in a way that seeks for the region with similar SIFT local descriptors; second, the deformable model is constrained by both population-based and patient-specific shape statistics. At first, population-based shape statistics plays an leading role when the number of serial images is small, and gradually, patient-specific shape statistics plays a more and more important role after a sufficient number of segmentation results on the same patient have been obtained. The proposed deformable model can adapt to the shape variability of different patients, and obtain more robust and accurate segmentation results.
Algorithms ; Artificial Intelligence ; Computer Simulation ; Data Interpretation, Statistical ; Humans ; Lung ; diagnostic imaging ; Lung Diseases ; diagnosis ; Models, Statistical ; Pattern Recognition, Automated ; methods ; Radiographic Image Enhancement ; methods ; Radiographic Image Interpretation, Computer-Assisted ; methods ; Radiography, Thoracic ; methods ; Reproducibility of Results ; Sensitivity and Specificity

Objective: The effects of prenatal exposure to brominated diphenyl ethers-209 to the Influence of male offspring rats hippocampus BDNF potein expression and its mechanism of action. Methods: Pregnant Sprague-Dawley (SD) rats were randomly treated with BDE-209 (100, 300, and 900 mg/kg body weight) or corn oil by gavage on gestational days 6-20. Blood was obtained through heart puncture for thyroid hormone analysis in male rats offspring on PND 60. The hippocampus tissues were excised. The expression levels of BDNF protein were measured by Western blot. Results: 1) In hippocampal tissue, BDNF protein expression concentration ratio relative to the control group (control group concentration of 1) were 0.87 (300 mg/kg dose group) and 0.67 (900 mg/kg) (P<0.01) . 2) Compared to controls, total T4 levels and free T4 levels were significantly decreased in the BDE-209 treated-group (900 mg/kg, 300 mg/kg) (P<0.05) . Total T3 levels in 300 mg/kg group were also significantly decreased compared to the control (P<0.05) . However, no significant difference was observed in 100 mg/kg group (P>0.05) . Conclusion During 300 and 900 mg/kg dose group of BDE-209 exposure to male offspring BDNF protein expression in rat hippocampus decreased, may be related to its interference with thyroid hormone.

BACKGROUNDChronic heart failure (CHF) and diabetes mellitus portend high morbidity and mortality because of an interrelated pathophysiologic process. This large cohort study aimed to analyze the prevalence, clinical characteristics and long-term outcome of patients with CHF and diabetes.

METHODSA total of 1119 patients with NYHA functional class II - IV and left ventricular ejection fraction (LVEF) < 45% between January 1995 and May 2009 were recruited. Clinical variables, biochemical and echocardiographic measurements were retrospectively reviewed, and composite major cardiac events (MCE) including death, heart transplantation, and refractory heart failure requiring multiple hospitalizations were recorded.

RESULTSThe prevalence of CHF with diabetes was progressively increased with time (16.9% in 1995 - 1999; 20.4% in 2000 - 2004, and 29.1% in 2005 - 2009) and age (18.5% in < 60 years, 26.6% in 60 - 80 years, and 26.6% in > 80 years). Compared with CHF patients without diabetes, those with diabetes had worse cardiac function, more abnormal biochemical changes, and higher mortality. Treatment with glucose-lowering agents significantly improved LVEF and decreased MCE. An elevated serum HbA1c level was associated with large left ventricular end-systolic diameter (P < 0.05), decreased LVEF (P < 0.01) and reduced survival (P < 0.05). Multivariable Logistic regression analysis revealed that after adjustment for confounding factors, NYHA functional class (OR 2.65, 95%CI 1.14 - 6.16, P = 0.024) and HbA1c level >or= 7% (OR 2.78, 95%CI 1.00 - 7.68, P = 0.049) were independent risk factors for adverse outcomes in CHF patients with diabetes.

CONCLUSIONSPrevalence of CHF with diabetes was increasing during past decades, and patients with CHF and diabetes had worse clinical profiles and prognosis. Aggressive anti-CHF and diabetes therapies are needed to improve overall outcomes for these patients.

Adult ; Aged ; Aged, 80 and over ; Diabetes Complications ; epidemiology ; etiology ; Diabetes Mellitus ; drug therapy ; epidemiology ; Female ; Glycated Hemoglobin A ; analysis ; Heart Failure ; drug therapy ; epidemiology ; etiology ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Prevalence ; Ventricular Function, Left

OBJECTIVETrace and toxic elements have great influences on the fetus growth during the pregnancy. The status of Pb, As, Cd, Mn and Zn in maternal and umbilical cord blood and influence factors were analyzed.

METHODSFrom September 2006 to April 2007, 130 pairs of maternal blood and cord blood in total were collected at the time of spontaneous delivery or cesarean section. At the same time, the development of newborn was measured immediately. The concentrations of elements were determined by inductively coupled plasma mass spectrometry, the relationship of these elements between maternal and cord blood were also analyzed.

RESULTSThe median (microg/L) concentration of blood Pb, As, Cd, Mn and Zn in maternal blood were 64.32, 3.81, 0.84, 54.26 and 6312.50. And the median (microg/L) of those elements in cord blood were 35.72, 2.84, 0.32, 78.99 and 2250. The levels of Cd (r=0.341, P=0.000) and As (r=0.552, P=0.000) in maternal blood were positively correlated with the elements in the cord blood. From the questionnaire we conclude that the occupational hazardous factors and room decorated were the risk factors for the blood As and Zn levels. After multilinear regression analysis we also found mother weight, occupational hazardous factors and mother systolic pressure might affect the levels of blood Mn, Zn, As and Cd.

CONCLUSIONSThe levels of these elements were affected by environmental and maternal factors. In this study, although the levels of all heavy metals in pregnant women were below those considered hazardous, however, they were still higher than those in the developed countries. The effects of heavy metals of maternal exposure on developing fetuses should deserve attention further.

Adult ; Arsenic ; blood ; Cadmium ; blood ; Environmental Exposure ; Female ; Fetal Blood ; chemistry ; Humans ; Infant, Newborn ; Lead ; blood ; Male ; Manganese ; blood ; Maternal Exposure ; Pregnancy ; Zinc ; blood

Adult ; Aged ; Antiviral Agents ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; drug effects ; Female ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Middle Aged

Coexistence of chronic lymphocytic leukemia (CLL) and essential thrombocythemia (ET) in a patient is extremely rare, with only 10 cases reported thus far in literature. This paper describes a 94-year-old male having atypical B-CLL with CD5⁻ (CD5⁻) phenotype and ET. In this patient, we performed interphase fluorescence in situ hybridization (FISH) analysis which revealed 13q14.3 deletion in 31% of B-lymphocyte nuclei and RB1 deletion in 27% of B-lymphocyte nuclei, but not in neutrophils and T-lymphocytes. Furthermore, we identified JAK2 V617F mutation in the peripheral blood nucleated cells and neutrophils, but not in the B- and T-lymphocyte populations. Therefore, it was concluded that the occurrence of CD5− B-CLL and ET in this patient was pathogenically independent.
Aged, 80 and over ; CD5 Antigens ; metabolism ; Humans ; In Situ Hybridization ; Janus Kinase 2 ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; metabolism ; Male ; Mutation ; Thrombocythemia, Essential ; genetics ; metabolism

OBJECTIVETo evaluate the association between chemical exposure, DNA methylation status and gene-environment interactions in the development of childhood acute leukemia (AL).

METHODSFrom January 1st 2009 to December 31st 2010, an exploratory case-control study was conducted on childhood AL among children who were less than 15 years of age in Shanghai, China. A total of 131 patients with newly diagnosed AL were recruited from 3 Shanghai children hospitals. The controls selected from the same hospital were healthy children who attended the physical check-up held by the department of Children's Healthcare, or who visited the clinic of developmental pediatrics or orthopedics (excluding blood diseases and malignant tumors). 140 controls matched with cases in gender and age were included in this study. Chemical exposure were investigated by questionnaires, methylation specific polymerase chain reaction (MSP) was adopted to analyze the methylation or deletion status of 8 genes, and gene-environment interactions were analyzed by relative excess risk of interaction (RERI), attributable proportion of interaction (API) and synergy index (S).

RESULTSThere were 131 and 140 subjects in case and control group, who were aged (6.9 ± 3.8) and (6.9 ± 3.9) years old (t = 0.01, P = 0.911), respectively. After adjusting age and other potential confounding factors, chemical substances' exposure of children/mother/father were all significantly higher in cases than that in controls (Children: OR = 3.90, 95% CI: 1.69-9.02; Mother: OR = 2.71, 95% CI: 1.12-6.52; Father: OR = 1.91, 95% CI: 1.05-3.47). For the 8 genes analyzed, the methylation status of DAPK and PTEN and P73 in case group were significantly higher than that in control group (cases: 3.1% (4 cases), 16.0% (21 cases), 7.6% (10 cases); controls: 0.7% (1 case), 2.9% (4 cases), 0.7% (1 case); χ²: 7.11, 16.90, 11.38; P value: 0.029, 0.000, 0.003). The methylation status of P16 in case group was significantly lower than that in control group (cases: 3.8% (5 cases); controls: 8.6% (12 cases), χ² = 10.33, P = 0.007). The interactions of children chemical substances' exposure and 3 genes' (PTEN, P16 and P73) methylation status were probably existed after adjusted for confounding factors (PTEN: RERI = -7.01, API = -2.14, S = 0.24; P16: RERI = 4.08, API = 0.53, S = 2.59; P73: RERI = 4.32, API = 0.48, S = 2.19), we also found the potential interaction between maternal chemical substances' exposure and PTEN, P16 gene methylation status (PTEN: RERI = -1.30, API = -0.38, S = 0.65; P16: RERI = 1.70, API = 0.38, S = 1.97).

CONCLUSIONThe study suggested the strong combined effects of chemical substances exposure of children and abnormal methylation status were risk factors of childhood AL, and there existed different interaction between them, which may indicate the important role in the pathogenesis process of childhood AL.

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; China ; DNA Methylation ; Environmental Exposure ; Female ; Gene-Environment Interaction ; Humans ; Leukemia ; epidemiology ; Maternal Exposure ; Polymerase Chain Reaction ; Risk Factors