Sensitivity of long-standing xenografts of rat hearts to humoral antibodies.

Long-standing rat skin xenografts on immunosuppressed mice are known to become insensitive to destruction by mouse anti-rat serum. Our present experiments demonstrate that long-standing primarily vascularized rat-to-mouse cardiac xenografts, unlike skin, remain fully sensitive to antiserum-mediated destruction, even in mice also bearing a long-standing skin graft that is resistant to antiserum. It appears that skin grafts become resistant to antiserum-mediated destruction because of extensive replacement of the endothelium by cells of host origin. The hearts remain sensitive to antiserum since such an extensive endothelial replacement would not occur as readily in these whole organ grafts.     

IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis.

Few studies have addressed the importance of vascular remodeling in the lung during the development of bleomycin-induced pulmonary fibrosis (BPF). For fibroplasia and deposition of extracellular matrix to occur, there must be a geometric increase in neovascularization. We hypothesized that net angiogenesis during the pathogenesis of fibroplasia and deposition of extracellular matrix during BPF are dependent in part on a relative deficiency of the angiostatic CXC chemokine, IFN-gamma-inducible protein-10 (IP-10). To test this hypothesis, we measured IP-10 by specific ELISA in whole lung homogenates in either bleomycin-treated or control mice and correlated these levels with lung hydroxyproline. We found that lung tissue from mice treated with bleomycin, compared with that from saline-treated controls, demonstrated a decrease in the presence of IP-10 that was correlated to a greater angiogenic response and total lung hydroxyproline content. Systemic administration of IP-10 significantly reduced BPF without any alteration in lung lymphocyte or NK cell populations. This was also paralleled by a reduction in angiogenesis. Furthermore, IP-10 had no direct effect on isolated pulmonary fibroblasts. These results demonstrate that the angiostatic CXC chemokine, IP-10, inhibits fibroplasia and deposition of extracellular matrix by regulating angiogenesis.     

Maps of the Sri Lanka malaria situation preceding the tsunami and key aspects to be considered in the emergency phase and beyond

In Vietnam, a large proportion of all malaria cases and deaths occurs in the central mountainous and forested part of the country. Indeed, forest malaria, despite intensive control activities, is still a major problem which raises several questions about its dynamics. A large-scale malaria morbidity survey to measure malaria endemicity and identify important risk factors was carried out in 43 villages situated in a forested area of Ninh Thuan province, south central Vietnam. Four thousand three hundred and six randomly selected individuals, aged 10–60 years, participated in the survey. Rag Lays (86%), traditionally living in the forest and practising "slash and burn" cultivation represented the most common ethnic group. The overall parasite rate was 13.3% (range [0–42.3] while Plasmodium falciparum seroprevalence was 25.5% (range [2.1–75.6]). Mapping of these two variables showed a patchy distribution, suggesting that risk factors other than remoteness and forest proximity modulated the human-vector interactions. This was confirmed by the results of the multivariate-adjusted analysis, showing that forest work was a significant risk factor for malaria infection, further increased by staying in the forest overnight (OR= 2.86; 95%CI [1.62; 5.07]). Rag Lays had a higher risk of malaria infection, which inversely related to education level and socio-economic status. Women were less at risk than men (OR = 0.71; 95%CI [0.59; 0.86]), a possible consequence of different behaviour. This study confirms that malaria endemicity is still relatively high in this area and that the dynamics of transmission is constantly modulated by the behaviour of both humans and vectors. A well-targeted intervention reducing the "vector/forest worker" interaction, based on long-lasting insecticidal material, could be appropriate in this environment.     

High frequencies of de novo CNVs in bipolar disorder and schizophrenia

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n?= 185), schizophrenia (n?= 177), and healthy controls (n?= 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR?= 4.8 [1.4,16.0], p?= 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR?= 6.3 [1.7,22.6], p?= 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR?= 5.0 [1.5,16.8], p?= 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.     

Influence of injectable hyaluronic acid hydrogel degradation behavior on infarction-induced ventricular remodeling

Increased myocardial wall stress after myocardial infarction (MI) initiates the process of adverse left ventricular (LV) remodeling that is manifest as progressive LV dilatation, loss of global contractile function, and symptomatic heart failure, and recent work has shown that reduction in wall stress through injectable bulking agents attenuates these outcomes. In this study, hyaluronic acid (HA) was functionalized to exhibit controlled and tunable mechanics and degradation once cross-linked, in an attempt to assess the temporal dependency of mechanical stabilization in LV remodeling. Specifically, two hydrolytically degrading (low and high HeMA-HA, degrading in ~3 and 10 weeks, respectively) and two stable (low and high MeHA, little mass loss even after 8 weeks) hydrogels with similar initial mechanics (low: ~7 kPa; high: ~35-40 kPa) were evaluated in an ovine model of MI. Generally, the more stable hydrogels maintained myocardial wall thickness in the apical and basilar regions more efficiently (low MeHA: apical: 6.5 mm, basilar: 7 mm, high MeHA: apical: 7.0 mm basilar: 7.2 mm) than the hydrolytically degrading hydrogels (low HeMA-HA: apical: 3.5 mm, basilar: 6.0 mm, high HeMA-HA: apical: 4.1 mm, basilar: 6.1 mm); however, all hydrogel groups were improved compared to infarct controls (IC) (apical: 2.2 mm, basilar: 4.6 mm). Histological analysis at 8 weeks demonstrated that although both degradable hydrogels resulted in increased inflammation, all treatments resulted in increased vessel formation compared to IC. Further evaluation revealed that while high HeMA-HA and high MeHA maintained reduced LV volumes at 2 weeks, high MeHA was more effective at 8 weeks, implying that longer wall stabilization is needed for volume maintenance. All hydrogel groups resulted in better cardiac output (CO) values than IC.     

The establishment of genetically engineered canola populations in the U.S

Concerns regarding the commercial release of genetically engineered (GE) crops include naturalization, introgression to sexually compatible relatives and the transfer of beneficial traits to native and weedy species through hybridization. To date there have been few documented reports of escape leading some researchers to question the environmental risks of biotech products. In this study we conducted a systematic roadside survey of canola (Brassica napus) populations growing outside of cultivation in North Dakota, USA, the dominant canola growing region in the U.S. We document the presence of two escaped, transgenic genotypes, as well as non-GE canola, and provide evidence of novel combinations of transgenic forms in the wild. Our results demonstrate that feral populations are large and widespread. Moreover, flowering times of escaped populations, as well as the fertile condition of the majority of collections suggest that these populations are established and persistent outside of cultivation.     

Gangliosides expressed on breast cancer cells are E-selectin ligands

Cancer cell adhesion to vascular endothelium is a critical process in hematogenous metastasis. We hypothesized that breast cancer cells express ligands that bind under blood flow conditions to E-selectin expressed by endothelial cells. At a hemodynamic wall shear rate, BT-20 and MDA-MB-468 breast cancer cells adhered to cytokine-activated human umbilical cord vein endothelial cells (HUVECs) but not to anti-E-selectin monoclonal antibody treated HUVECs, demonstrating that adhesion was specifically mediated by E-selectin. Characterization of glycans expressed on breast cancer cells by a panel of antibodies revealed that BT-20 cells expressed sialyl Lewis X (sLe^x) and sialyl Lewis A (sLe^a) but MDA-MB-468 cells did not, suggesting that the former possess classical glycans involved in E-selectin mediated adhesion while the latter have novel binding epitopes. Protease treatment of the breast cancer cells failed to significantly alter the carbohydrate expression profiles, binding to soluble E-selectin–Ig chimera, or the ability of the cells to tether and roll on E-selectin expressed by HUVECs, indicating that glycosphingolipids are functional E-selectin ligands on these cells. Furthermore, extracted breast cancer cell gangliosides supported binding of E-selectin–Ig chimera and adhesion of E-selectin transfected cells under physiological flow conditions. In summary, our results demonstrate that breast cancer cells express sialylated glycosphingolipids (gangliosides) as E-selectin ligands that may be targeted for prevention of metastasis.     

Enhancement of the acute phase response to a lipopolysaccharide challenge in steers supplemented with chromium

The study examined the effect of chromium supplementation on the response of steers to an LPS challenge. Steers received a premix that added 0 (control; n?=?10) or 0.2 mg/kg of chromium (n?=?10) to the total diet on a dry matter basis for 56 d. Steers were fitted with jugular catheters and rectal temperature (RT) recording devices on d 52. Blood samples were collected and sickness behavior scores assigned to each steer relative to an LPS challenge (0.5 μg/kg) on d 55. Pre-LPS RT were greater in chromium-supplemented than in control steers. Post-LPS RT increased in both treatments, with control steers producing a greater change in RT than chromium-supplemented steers. Sickness behavior scores were greater in control than in chromium-supplemented steers post-LPS (P?=?0.03). Cortisol concentrations did not differ between treatments pre-LPS. Post-LPS cortisol concentrations increased but did not differ due to treatment. Concentrations of IL-4 increased post-LPS but were not affected by treatment pre- or post-LPS. Treatment did not affect pre-LPS TNF-α or IFN-γ. Post-LPS TNF-α and IFN-γ increased in both treatments, with chromium-supplemented steers producing greater TNF-α (P?=?0.005) and IFN-γ (P?=?0.004) than control steers. Pre-LPS IL-6 was greater (P?=?0.027) in chromium-supplemented steers than in control steers. Post-LPS IL-6 increased in both treatments and was greater (P?相似文献