Search

The insulin-like growth factor (IGF) system is highly conserved across species and plays a central role in cellular differentiation, cellular proliferation, apoptosis, metabolism, wound repair, and somatic growth (1–6). IGF-I, the main effector peptide of the IGF system and the principal mediator of growth hormone (GH) effects, may influence the development of age-related cardiovascular diseases (7–11). A report from the Framingham Heart Study identified low IGF-I as a risk factor for incident congestive heart failure (CHF) in the elderly (7). IGF binding proteins (IGFBPs) modulate IGF-I activity and may also have IGF-I-independent effects. Circulating IGFBP-3, like IGF-I, is responsive to GH status (12) and in older adults IGFBP-3 and IGF-I decline in concert with decreased GH. Most IGF-I in circulation is bound to IGFBP-3, suggesting a role of IGFBP-3 in determining the circulating half-life of IGF-I and its delivery to target tissues. IGFBP-1 is less abundant than IGFBP-3, but appears particularly important in regulating IGF-I bioavailability, with strong inverse correlations between circulating IGFBP-1 and free IGF-I (13) (14). IGFBP-1 has a very different system of regulation than IGFBP-3, with hepatic IGFBP-1 production strongly (inversely) regulated by insulin. Aging, cachectic conditions, malnutrition, inflammatory cytokines, and oxidative stress all increase IGFBP-1 expression (15–21), which may in turn lead to inhibition of anabolic IGF-I effects by IGFBP-1 during catabolic states. High circulating IGFBP-1 levels predict cardiovascular events after myocardial infarction (22) and cardiovascular mortality among apparently healthy older men (23). Prior data also indicate increased IGFBP-1 levels in CHF patients (24) which suggests that high circulating IGFBP-1 levels may be a CHF risk factor, although no prior studies of IGFBP-1 and incident CHF are available. We assessed the association between fasting IGF-I, IGFBP-1, IGFBP-3, and insulin levels and incident CHF among older adults in the Cardiovascular Health Study (CHS).

OBJECTIVES: To assess the association between total in-sulinlike growth factor (IGF)-1, IGF binding protein-1(IGFBP-1), and IGFBP-3 levels and functioning and mor-tality in older adults.DESIGN: Cohort study.SETTING/PARTICIPANTS: One thousand one hundredtwenty-two individuals aged 65 and older without priorcardiovascular disease events participating in the Cardio-vascular Health Study.MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) wereexaminedinrelationshiptohandgripstrength,timetowalk15 feet, development of new difficulties with activities ofdaily living (ADLs), and mortality.RESULTS: Higher IGFBP-1 predicted worse handgripstrength (P-trend

Increasing evidence suggests that the insulin-like growth factor (IGF)-system may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women ≥65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95% CI: 0.26, 0.64; p-trend

Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HRq4-q1), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HRq4-q1, 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HRq4-q1, 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data. (Cancer Epidemiol Biomarkers Prev 2008;17(4):921–9)

Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P0.05) but not with risk of fatal MI or fatal coronary heart disease.Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

As targets for cancer therapy, endoplasmic reticulum (ER) stress and autophagy are closely linked. However, the signaling pathways responsible for induction of autophagy in response to ER stress and its cellular consequences appear to vary with cell type and stimulus. In the present study, we showed that dithiothreitol (DTT) induced ER stress in HeLa cells in a time- and dose-dependent fashion. With increased ER stress, reactive oxygen species (ROS) production increased and autophagy flux, assessed by intracellular accumulation of LC3B-II and p62, was inhibited. N-acetyl-L-cysteine (NAC), a classic antioxidant, exacerbated cell death induced by 3.2 mM of DTT, but attenuated that induced by 6.4 mM DTT. Low cytotoxic doses of DTT transiently activated c-JNU N-terminal kinase (JNK) and p38, whereas high dose of DTT persistently activated JNK and p38 and simultaneously reduced extracellular signal-regulated kinase (ERK) activity. Combined treatment with DTT and U0126, an inhibitor of ERK upstream activators mitogen-activated protein kinase (MAPK) kinase 1 and 2 (MEK1/2), blocked autophagy flux in HeLa cells. This effect was similar to that caused by a combination of DTT and chloroquine (CQ). These data suggested that insufficient autophagy was accompanied by increased ROS production during DTT-induced ER stress. ROS appeared to regulate MAPK signaling, switching from a pro-survival to a pro-apoptotic signal as ER stress increased. ERK inhibition by ROS during severe ER stress blocked autophagic flux. Impaired autophagic flux, in turn, aggravated ER stress, ultimately leading to cell death. Taken together, our data provide the first reported evidence that ROS may control cell fate through regulating the MAPK pathways and autophagic flux during DTT-induced ER/oxidative stress.

Due to concerns over health risk of disinfection byproducts (DBPs), removal of trihalomethanes (THMs) precursor from bio-treated wastewater by coagulation and adsorption was investigated in this study. Ultrafiltration (UF) membranes and nonionic resins were applied to fractionate THMs precursor into various molecular weight (MW) fractions and hydrophobic/hydrophilic fractions. Characteristics of coagulated water and adsorbed water were evaluated by the three-dimensional excitation and emission matrix (3DEEM) fluorescence spectroscopy. Results showed that coagulation and adsorption were suitable for removing different hydrophobic/hydrophilic and fluorescent fractions. Coagulation decreased THMs concentration in hydrophobic acids (HoA) fraction from 59 μg/L to 39 μg/L, while the lowest THMs concentration (9 μg/L) in hydrophilic substances (HiS) fraction was obtained in adsorbed water. However, both coagulation and adsorption were ineffective for removing fractions with MW5 kDa. Although coagulation and adsorption processes could reduce THMs formation, some specific THMs formation potential (STHMFP) in residual dissolved organic matter (DOM) fractions increased in this study. Hydrophobic acid and hydrophilic fractions increased after coagulation treatment, and low MW and hydrophobic fractions increased after adsorption treatment. In addition, active carbon adsorbed more organic matter than coagulant, but brominated disinfection byproducts (Br-DBPs) in adsorbed water turned to the major THMs species after chlorination.

This paper presents an intact scheme of timing synchronization for Multi-Band Orthogonal Frequency Division Multiplexing (MB-OFDM) Ultra Wide Band (UWB) systems. Frame detection and coarse timing are implemented with the Maximum Correlation (MC) method based on the first-band information of the preamble. Fine timing is achieved with the Minimum Energy Ratio (MER) method based on the information of all the three bands. Lag corrections are performed twice to avoid Inter-Symbol Interference (ISI). Simulations show that residual timing error can be kept at a small scale under multipath channels which can be compensated with channel in the frequency domain.

Particulate matter (PM) is a chemically non-specific pollutant, and may originate or be derived from different emission source types. Thus, its toxicity may well vary depending on its chemical composition. If the PM toxicity could be determined based on source types, the regulation of PM may be implemented more effectively. A large number of monitors began collecting PM less than 2.5 μm in diameter (PM2.5) mass samples for subsequent chemical speciation starting 2000–2001 in the US. The data from this chemical speciation network can be useful for source-oriented evaluations of PM health effects. However, there are several issues that need to be considered in the analysis and interpretation of these data. One major issue is a monitor's representation of regional, sub-regional, and local air pollution exposures to the population in a city or metropolitan area. Because health outcomes in time-series air pollution epidemiological studies are aggregated over a wide geographical area, regional PM pollution may have smaller errors in exposure estimates than more spatially varying local pollution. However, the relative strength of association between source-apportioned PM and health outcomes may not be interpretable as the relative causal role of the source types. To our knowledge, there has not yet been a systematic and quantitative evaluation of this issue. In this study, we attempt to evaluate this issue by analyzing newly available PM2.5 speciation data from three monitors (a few miles apart) in New York City during 2001–2002. The strongest temporal correlations across the three monitors were found for the individual PM components that are related to secondary aerosols (e.g., S, NH4). We also conducted source-apportionment of the data using absolute principal component analysis and positive matrix factorization. We identified four major source/pollution types: (1) secondary (largely regional) aerosols; (2) soil; (3) traffic-related; and (4) residual oil burning/incineration, in each of the three monitors. The estimated source-apportioned PM2.5 mass showed generally the highest monitor-to-monitor correlation for the secondary aerosol factor (r range: 0.72–0.93). The correlation for the more localized traffic-related factor was more variable (r range: 0.26–0.95). The estimated mean PM2.5 mass contributions by source/pollution type across the monitors varied least for the secondary aerosol factor. The extent of variability in the source-apportioned PM2.5 mass by the monitor was comparable to that from the difference due to the two source-apportionment techniques used. The implication of the results of our study is that a source-oriented evaluation of PM health effects needs to take into consideration the uncertainty associated with spatial representative of the species measured at a single monitor.

LAIR-1, the leukocyte-associated Ig-like receptor-1, is a trans-membrane molecule that functions as an inhibitory receptor on natural killer cells, T lymphocytes and monocytes. It has been well known that many trans-membrane receptors can shed from the cell surface and be released into the circulation in soluble form when lymphocytes, endothelials and other immune cells are activated. In many cases, the levels of soluble receptors in the circulation can be used as markers of lymphocyte activation in transplant patients and virus infection patients. To investigate whether LAIR-1 is able to be released into the sera, we developed a sandwich enzyme-linked immunosorbent assay (ELISA) system based on two anti-LAIR-1 monoclonal antibodies (MAb) with different epitope specificities. Using this ELISA, we found that sLAIR-1 existed in the supernatants collected from PMA, PHA or CD3 MAb-stimulated lymphocytes cultures in vitro for the first time. Moreover, we found that LAIR-1 level in serum samples from healthy individuals was 6.2 +/- 3.3 ng/ml, whereas the levels in sera of patients with hemorrhagic fever with renal syndrome (HFRS) and patients 3-7 days after kidney transplant increased to 47.2 +/- 35.9 and 24.4 +/- 16.0 ng/ml, respectively. Furthermore, HFRS patients in oliguric phase showed higher serum sLAIR-1 levels than those in other phases, and transplant patients with rejection showed higher serum sLAIR-1 level than those without rejection. These findings demonstrated that LAIR-1 can be released when lymphocytes are activated, suggesting sLAIR-1 may be used as a predictor for monitoring immune reaction in some virus infections and organ transplants which may be useful in clinical treatment of these diseases.

Low-fat diet may play a role in prevention of cardiovascular disease (CVD) by altering the levels of hemostatic factors. There are yet limited data on the effects of low-fat diet on the circulating levels of these factors and existing studies are limited by small sample size and short duration of follow-up. We conducted an analysis in a subset of women (active arm = 723; control arm = 1,036) within the Women's Health Initiative Dietary Modification Trial to investigate the long-term effect of a low-fat diet on circulating levels of fibrinogen, factor VII concentration and factor VII activity among postmenopausal women aged 50-79 years. Using linear mixed effects model with random intercept and data from three follow-up visits (years 1, 3 and 6) we evaluated the change in each factor over time. Overall, the changes in these factors were small (less than 5%) in both the arms of the trials at the end of intervention and there was no significant difference in mean change between the two arms. Our results indicate that the low-fat dietary intervention was not associated with significant changes in hemostatic factors among postmenopausal women.

The area of seasonally frozen soil in China accounts for about 54% of the national territorial area. The property of seasonally frozen soil has a great influence on highway, railway and architectural foundation. The effect of freeze-thaw cycle for saturated silty clay in Northeast Area on stress-strain behaviour was investigated by triaxial test in this paper, where three different freezing temperature and five different freeze-thaw cycle times were considered. The results showed that silty clay exhibited strain softening characteristics for small number of freeze-thaw cycles, while strain hardening characteristics will appear with the increase in freeze-thaw cycles. The deviatoric stress-axial strain relationship shows the transitional form from strain softening to strain hardening. It will be helpful to understand the strain behaviour of soil under freeze-thaw cycle.

The aim was to describe the clinicopathological features and prognosis of young patients with breast cancer.We reviewed the records of 1478 consecutive patients aged ≤50 years with first diagnosis of invasive breast cancer referred to surgery from January 1999 to March 2005. A total of 174 patients were aged35 years (group I) and 1304 were aged 35-50 years (group II).Compared with patients of group II, patients of group I had a higher percentage of tumors classified as estrogen receptors (ER) negative, progesterone receptors (PR) negative, with a Ki-67 labeling index ≥20% of the cells. The 5-year survival of group I was 78.3% as compared with 84.2% for group II (P = 0.006).Compared with patients aged between 35 and 50 years, patients aged35 years have a greater chance of having an endocrine-unresponsive tumor and a significantly poor prognosis.

The self-assembly of floating particles is a widely observed phenomenon. Ideally, rafts of identical floating spheres or cylinders should assemble in a closed-packed fashion. However, rafts are observed to exhibit large and various defects, and we show that the conjunction of lateral liquid bridges between particles and contact angle hysteresis freezes the rotation of particles around their neighbors, a mechanism that generates imperfect rafts. Conversely, we demonstrate how this capillary bond can be exploited to sculpt 2D aggregates far from equilibrium that are persistent.

This paper presents a method for SAR image segmentation by relying on active contour model with the non-local processing principle [1]. The idea is to partition a SAR image via computing the patch similarity in the SAR image non-locally, and formulize the segmentation problem with an active contour model. More precisely, after computing the statistical features of SAR images, non-local comparisons between feature patches are used to calculate the active contour energy, which is defined by integrating the interactions between pairs of patches inside and outside the segmented region. A level set method is finally used to minimize the non-local energy. Compared with existing approaches for SAR image segmentation, the only requirement of this method is a local similarity between patches, and it is less sensitive to initial segmentation. The experimental results show the effectiveness and feasibility of the proposed method.

This paper addresses the problem of denoising for complex tensor image. In particular, we extend the anisotropic diffusion, also known as PM model (Perona and Malik, 1990) for filtering images based on PDE, from scalar or vector images to complex tensor ones and apply the new method to remove speckle noises of PolSAR images.

Socialism, which began in a historical world situation, has its serious flaws. It has not fulfilled Marx's prediction that the world revolution would first take place in countries with the most advanced productive forces; nor has it proven Lenin's foresight that, once the weakest link was broken, the whole chain would be smashed and the world revolution would break out. Proletarian revolution with socialist characteristics takes place one by one, in some backward countries over a relatively long period of time. This distinguishing feature is mostly determined by the imbalance in the development of the world. It has also created obstacles to continuing the socialist revolution in these countries after the revolution is won in these countries. Marx and Lenin were unable to conduct in-depth investigations of the backward regions of Asia, Africa, and Latin America. Consequently, they were unable to predict to what extent such an imbalance would have an impact on socialist revolution around the world.

To establish the HPLC fingerprint of Gymnadenia conopsea from different regions of Qinghai-Tibet Plateau.12 batches of Gymnadenia conopsea were measured by the RP-HPLC, and their fingerprints were obtained. Chromatographic condition: The sample was separated on column of Kromasil C18 (4.6 mm x 250 mm,5 microm) and gradiently eluted with a mixture of methanol and water (containing 0.04% phosphoric acid). The flow rate was 0.7 mL/min. The detection wavelength was set at 222 nm and the column temperature was 30 degrees C.The HPLC fingerprint of Gymnadenia conopsea was set up and 13 common peaks were selected,the results of method validation met technical requirement of fingerprint,the similarity of 12 batches Gymnadenia conopsea was 0.904 - 0.989. Principal components analysis and clustering analysis were used in the identification of the samples.The method is simple, practicable and reliable, which can be used for the quality control of Gymnadenia conopsea.

A reduction-sensitive graft polymer PHEA-S-S-C16 with poly{α,β-[N-(2-hydroxyethyl)-L-aspartamide]} (PHEA) as a backbone and a disulfide-containing alkyl as a side chain (HOOC-S-S-C16 ) is synthesized and evaluated for intracellular DOX delivery. PHEA-S-S-C16 can self-assemble into micelles in aqueous media and load DOX at a total content of 7.3%. In vitro release studies reveal that the release rate of DOX from PHEA-S-S-C16 micelles is accelerated in the presence of DTT. The results of cell experiments indicate that DOX-loaded mPEG-S-S-C16 micelles can achieve rapid DOX release in HeLa cells, as compared with their reduction-insensitive counterparts. Endocytosis inhibition analysis indicates that PHEA-S-S-C16 micelles entered cells mainly via clathrin-mediated endocytosis.

Human leukocyte antigen (HLA) genotype has been associated with the probability of spontaneous clearance of hepatitis C virus (HCV). However, no prior studies have examined whether this relationship may be further characterized by grouping HLA alleles according to their supertypes, defined by their binding capacities. There is debate regarding the most appropriate method to define supertypes. Therefore, previously reported HLA supertypes (46 class I and 25 class II) were assessed for their relation with HCV clearance in a population of 758 HCV-seropositive women. Two HLA class II supertypes were significant in multivariable models that included: (i) supertypes with significant or borderline associations with HCV clearance after adjustment for multiple tests, and (ii) individual HLA alleles not part of these supertypes, but associated with HCV clearance in our prior study in this population. Specifically, supertype DRB3 (prevalence ratio (PR)=0.4; P=0.004) was associated with HCV persistence, whereas DR8 (PR=1.8; P=0.01) was associated with HCV clearance. Two individual alleles (B*57:01 and C*01:02) associated with HCV clearance in our prior study became nonsignificant in analysis that included supertypes, whereas B*57:03 (PR=1.9; P=0.008) and DRB1*07:01 (PR=1.7; P=0.005) retained their significance. These data provide epidemiologic support for the significance of HLA supertypes in relation to HCV clearance.

In this paper, a method is proposed to reduce the impact of delay time and packet loss, because they have serious effects on serviceability of the remote operation mechanical system. The stability of a nonlinear bilateral teleoperation system with force feedback which has the similar combination of structure is discussed, and the system stability conditions are studied. The self-adaptive algorithm is designed by the relations of sampling time, delay time and the variable procedure of the data transfer in the nonlinear discrete teleoperation system. Through the experiment, this method is confirmed to be able to reduce data error and increase accuracy effectively, while it also assures the stability of the system.

To evaluate the possibility of an alternative to the traditional orthodontic stainless steel implants, the antibacterial activity against Porphyromonas gingivalis (P. gingivalis) and the related cytotoxicity of a type 304 Cu bearing antibacterial stainless steel were studied. The results indicated that the antibacterial stainless steel showed excellent antibacterial property against P. gingivalis, compared with the control steel (a purchased medical grade 304 stainless steel). Compared to the control steel, there were fewer bacteria on the surface of the antibacterial stainless steel, with significant difference in morphology. The cytotoxicities of the antibacterial stainless steel to both MG-63 and KB cells were all grade 1, the same as those of the control steel. There were no significant differences in the apoptosis rates on MG-63 and KB cells between the antibacterial stainless steel and the control steel. This study demonstrates that the antibacterial stainless steel is possible to reduce the incidence of implant-related infections and can be a more suitable material for the micro-implant than the conventional stainless steel in orthodontic treatment.

This paper presented an optimization model for the generic multi-commodity logistics network design, in which the objective function was to minimize the total cost, including the location cost and inventory cost and supply and demand cost. The heuristic algorithm was developed for the model. Practical application denotes the optimization method operates rapidly and the result is rational, so it can provide a scientific decision-making support method for the design of the network, it is an effective method for solving large-scale problems, and the cost of total saving is feasibility.

To study the effects of dietary different ratios of n-3 to n-6 polyunsaturated fatty acids on food intake of SD rats and potential mechanisms.According to their serum total cholesterol level, male rats were randomly divided into 6 groups, and were fed common feed diet, high fat diet, high fat with n-3/n-6 1:1 PUFA diet, high fat with n-3/n-6 1:5 PUFA diet, common feed with n-3/n-6 1:1 PUFA diet, and common feed with n-3/n-6 1:5 PUFA diet, respectively. Weights were measured about every 6 days, and food intake were measured everyday. At 0, 15, 30 and 45 days, triglycerides (TG) and total cholesterol (TC) in the plasma were measured using kits. After 45 days, the rats were sacrificed. RT-PCR was used for measuring the expression of neuropepide Y (NPY) and AMP-activated protein kinase-alpha2 (AMPK-alpha2) mRNA in the hypothalamus.Four diets with any ratio of n-3/n-6 PUFA resulted in significant restraint of body weight gain, TC and TG level in the plasma, NPY and AMPK-alpha2 mRNA level in the hypothalamus compared to high fat diets (P0.05). These situations in two groups with common diet and one group with high diet added 1:1 PUFA are more significant than the high fat diet group.These results indicate that dietary PUFA improved lipid metabolism which may be related with appetite control through AMPK path.

To investigate the effects of dietary genistein on the development of young rats.SD rats aged three-week were randomly divided into three groups according to their weight (eight male and eight female). Each group was fed a diet containing genistein at levels of 0, 20 and 100 mg/kg. Several development indices were observed each week. At the age of 9 weeks, blood samples were collected and the plasma estradiol level of female rats and plasma testosterone level of male pups were measured. At the age of 13 weeks, organs( ovary and uterns in female, testes in male) were examined for histopathological changes and the expression of the estrogen receptor was measured by Western blotting.The plasma estradiol level of female rats increased and the plasma testosterone level of male rats decreased at the age of 9 weeks compared to the control group. At the age of 13 weeks, decreased body weight, food consumption, anogenital distance (AGD) and overy weight in female rats were observed. Also, the vaginal open time of female pups was earlier than control group. Histopathology showed that the cavity of uterus was larger than control group. Otherwise, treatment with genistein caused reduction in the plasma estradiol level of female rats and the expression of estrogen receptor-alpha in uterus. There were few changes of male rats' body weight, testicular descent, testes weight and histopathology except that the increased food consumption from 10-week-old and plasma testosterone level.Genistein exposure could effect on both sexes of young rats' development. The effects on female rats were much more than that on male rats and the effect of rats body weight and food consumption was mainly after their growing up. Although the mechanism of these effects are still obscure, it seems that the change of hormone level and expression of estrogen receptor have some relation with these effects.

To investigate the expression of LAIR-1 in patients with tumors and the function of LAIR-1 in anticancer immunity.A sandwich ELISA was employed to detect the serum sLAIR-1 from tumor patients and healthy individuals. The expression of LAIR-1 in CD4+ T cells, CD8+ T cells, NK cells and B cells isolated from the peripheral blood of cancer patients was examined by fluorescence staining and flow cytometry.The level of serum sLAIR-1 in tumor patients was higher than that in healthy individuals [4.6+/-3.2 microg/L vs 3.9+/-3.0 microg/L, P0.05]. NK cells, CD4+ T cells and CD8+ T cells expressed the up-regulated LAIR-1. The ratio of CD4/CD8 in lung cancer patients decreased significantly while the percentage of B cells in cancer patients increased greatly compared with healthy individuals.The expression of LAIR-1 is up-regulated in tumor patients, which may contribute to cancer immune escape.

The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy. (Cancer Res 2006; 66(23): 11238-46)

This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma.Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry.The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P0.01; r=0.70, P0.05). The IL-16 level correlated positively with the IgE level at acute attack stage of asthma (r=0.624, P0.01).IL-16, IL-18 and IgE may be involved in the pathogenesis of asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

To identify cell lines expressing the putative ligand(s) for LAIR-1 and LAIR-2.CHO cell lines secreting LAIR-1-Fc or LAIR-2-Fc fusion protein were prepared and the supernatants from the CHO cell lines were collected and purified by protein A affinity chromatography column. Several cell lines were stained with the purified LAIR-1-Fc and LAIR-2-Fc fusion proteins and then analyzed by flow cytometry for detecting the expression of their putative ligand(s). To exclude non-specific binding between the cells and the fusion proteins, the cell lines expressing their putative ligand(s) were pre-incubated with the mAbs against LAIR-1 or LAIR-2, stained with the fusion proteins, and analyzed by flow cytometry.Both LAIR-1 and LAIR-2 fusion proteins bound strongly with human amnion-derived epithelial cell line WISH, and moderately with human melanoma cell line C32, human embryo kidney epithelial cell line 293T, and human umbilical vein endothelial cell line ECV304. Furthermore, this binding could be blocked by the mAb FMU-LAIR-2.2 (recognizing both LAIR-1 and LAIR-2) or mAb FMU-LAIR-2.1(recognizing LAIR-2).The putative ligand(s) for LAIR-1 and LAIR-2 were expressed on WISH, C32, 293T and ECV304 cell lines. LAIR-1 and LAIR-2 may share the same ligand(s). These findings lay the foundation for the molecular cloning of the putative ligand(s) for LAIR-1 and LAIR-2.

Transforming growth factorbeta1 (TGFbeta1) is considered to be the principal contributor to liver fibrosis. So in this study the ribozymes against TGFbeta1 were designed. The in vitro cleavage activities of the ribozymes were assayed through incubation of (32)p-labeled target RNAs and (32)p-labeled ribozymes in different conditions. HSC-T6 cells were transfected with the eukaryotic constructs encoding ribozyme and disable ribozyme, then the stable cell clones were used to evaluate its antifibrotic characteristic through the effect of ribozyme on biological character of activated hepatic stellate cells (HSCs). The results demonstrated that two ribozymes (Rz803 and Rz1395) could cleave target RNAs into expected products effectively, Rz803 possessed better cleavage activity in vitro. Stable transfection of Rz803 into activated HSCs reduced TGFbeta1 expression in mRNA and protein level efficiently. The further studies demonstrated that Rz803 reduced deposition of collagen I, suppressed HSC proliferation, but had no effect on HSC activation in transfected HSC-T6 cells. Therefore, it indicated that Rz803 could reverse the character of activated HSCs by down-regulating TGFbeta1 expression efficiently and diminishing TGFbeta1 signaling underlying activation of hepatic stellate cells. As the consequence, it would provide a potential therapeutic approach for liver fibrosis.

Purpose: Neurogenic bladder is a major problem for children with spina bifida. Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic. We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying. We report our experience with this procedure in 20 children with spina bifida. Materials and Methods: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis. The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration. All patients underwent urodynamic evaluation before and after surgery. Results: Preoperative urodynamic studies revealed 2 types of bladder dysfunction— areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence. Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding. In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any improvement. Conclusions: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida.

To provide materials for the study of the function of ESC42 protein specifically expressed in the human epididymis.The ESC42 gene was amplified from the human epididymis cDNA library by PCR and then cloned into prokaryotic expression vector pGEX-4T-1, expressed and purified by recombinant DNA techniques. The specificity of ESC42 protein was identified by Western blot and MALDI-TOF-MS. The database was searched by Ms-Fit.The recombinant plasmid expressed a Mr 38 x 10(3) fusion protein in E. coli at a level of 30% of the total protein, and the purity was as high as 99%. The ESC42 protein was identified by ESC42 monoclonal antibody and its molecular weight was 11 978.12, tested by MALDI-TOF-MS. The peptide mass fingerprint analysis showed that the coverage rate of the sequence reached 48% with 100% matching. The motif scan in Prosite database reveal that ESC42 belonged to the beta-defensin family and had antibacterial activity.Obtaining high purity of rhESC42 protein may lay a foundation for the study of its functions.

To prepare and characterize mAb to Fc fragment of Ig fusion protein, and to establish sandwich ELISA for detecting Ig fusion proteins and affinity chromatography method for Ig fusion protein purification.hBCMA-Ig was used as antigen to immune BALB/c mice. The lymphocyte hybridoma technique was used to establish hybridoma cell lines stably secreting anti-Fc mAb. ELISA was employed to detect the isotype, epitopes, and species specificity of mAbs. Western blot was used to assess the reactivity between anti-Fc mAbs and denatured Ig fusion protein. LAIR1-Ig fusion protein was purified through affinity column anti-Fc mAb cross-linked to Sepharose 4B.Seven hybridoma cell lines(FMUFc1-FMUFc7) were acquired. A sandwich ELISA was successfully established using FMUFc4 as coating mAb and FMUFc5 as enzyme-labeled mAb. FMUFc6 could be used for Western blot. LAIR1-Ig fusion protein was effectively purified through FMUFc5-Sepharose affinity chromatography column.mAb against Fc fragment of Ig fusion protein has been prepared successfully, and methods to detect and purify Ig fusion protein are established. These mAbs provide useful tool for further application of Ig fusion protein.

To clone and express the leukocyte-associated immunoglobulin-like receptor (LAIR) and to identify the immune reactivity of LAIR-2 to anti-LAIR-1 specific monoclonal antibodies(mAb).Genes encoding LAIR-1 and LAIR-2 were cloned by RT-PCR from human peripheral blood mononuclear cells(PBMC) and two leukemia cell lines Jurkat and HL-60. The extracellular region gene of LAIR1 and LAIR-2 were inserted into vector pGEX-4T-3 expressing GST fusion protein, expressed on IPTG induction and purified through glutathione-sepharose 4B column. The immunological reactivity of expressed LAIR-2 to anti-LAIR-1 mAb was identified by indirect ELISA.LAIR-1 and LAIR-2 cDNAs had been cloned and expressed. Five new LAIR-1 cDNA isoforms were cloned. Among them, two isoforms from HL-60 included LAIR-1 open reading frames (ORF) and three isoforms from Jurkat were LAIR-1 cDNA segments. The LAIR-1 and LAIR-2 showed different immunological reactivities.The transcription, processing after transcription and expression of LAIRs may be related to disparities in individuals and disease status. The difference in immunological reactivity may be involved in their structure.

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and soluble interleukin 6 receptor (sIL-6R) have been studied as risk factors of cardiovascular disease in longitudinal studies. However, it is unknown about their long-term intra-individual variations and whether single measurements of these cytokines and receptor are reliable biomarkers in epidemiological studies. In this study, serum levels of TNF-alpha, IL-6, and sIL-6R were assayed by ELISAs in 36 young, healthy women from whom three blood samples were collected at 12-month intervals over 2 years, and the intraclass correlation coefficients (ICC) were estimated. The ICC of 0.73 (95% CI=0.49-0.79) for TNF-alpha was comparable to those of other commonly used biomarkers, justifying its use in epidemiological studies. The ICC of 0.48 (95% CI=0.25-0.58) for IL-6 was not optimal. However, IL-6 has been demonstrated as a consistent risk factor for cardiovascular disease, suggesting it could still be a useful biomarker if its disease association is substantial. The ICC of 0.36 (95% CI=0.10-0.47) for sIL-6R was relatively low, and multiple samples would need to be collected in prospective studies for this receptor.