The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the ...role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor-1 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.
Expression of the T1 gene, also known as ST2, DER4, and Fit-1, has been shown to be associated with cell proliferation. It gives rise to two different mRNAs that encode a receptor-like protein and a ...soluble molecule representing the ectodomain of the receptor form. Although T1 is a member of the IL-1R family, its biologic function is currently unknown. In this study, we have analyzed the expression of the T1 surface Ag in murine hemopoietic organs. Mast cells (MCs) were shown to be the only identifiable cell lineage that expressed T1 at high levels. T1 expression was found on cultured bone marrow-derived immature MCs. Similarly, freshly isolated connective tissue-type MCs from the i.p. cavity were also shown to express high levels of T1. Interestingly, the earliest detectable committed MC precursor isolated from fetal blood (FB) at day 15.5 of gestation, but not circulating hemopoietic stem cells in FB, also expresses high level of T1. Since FB promastocytes lack expression of the high affinity IgE receptor (Fc epsilonRI), T1 expression precedes expression of Fc epsilonRI in MC ontogeny. The finding that the T1 Ag is selectively expressed at several stages during development of the MC lineage suggests that this cell surface molecule, in combination with the well-established markers c-Kit and Fc epsilonRI, should be valuable for studying the MC lineage.
Neovascularization is a prerequisite for tumor growth. Thus, selective destruction of the tumor vasculature should prevent tumor expansion. We have established a method to identify proteins that are ...specifically expressed on the surface of endothelial cells in tumors. CD31-positive endothelial cells were isolated from Lewis lung carcinoma lung metastases as well as from normal lung tissue. cDNAs derived from these cells were subjected to a subtractive hybridization procedure, and cDNAs overrepresented in tumor-derived endothelial cells were isolated; those encoding surface proteins were selected using a signal sequence trap assay. One isolated cDNA encoded H/T-cadherin. In this report, we show that mouse H/T-cadherin is overexpressed on endothelial cells of several tumors, whereas it is expressed only on a subset of endothelial cells in healthy organs. On the basis of the expression of H/T-cadherin in lung metastases of different tumors, we suggest that different tumors can have a differential influence on the expression of endothelial cell surface proteins.
Background Postoperative hemorrhage is one of the most severe complications after pancreatic surgery. Due to the lack of an internationally accepted, universal definition of postpancreatectomy ...hemorrhage (PPH), the incidences reported in the literature vary considerably, even in reports from randomized controlled trials. Because of these variations in the definition of what constitutes a PPH, the incidences of its occurrence are not comparable. Methods The International Study Group of Pancreatic Surgery (ISGPS) developed an objective, generally applicable definition of PPH based on a literature review and consensus clinical experience. Results Postpancreatectomy hemorrhage is defined by 3 parameters: onset, location, and severity. The onset is either early (≤24 hours after the end of the index operation) or late (>24 hours). The location is either intraluminal or extraluminal. The severity of bleeding may be either mild or severe. Three different grades of PPH (grades A, B, and C) are defined according to the time of onset, site of bleeding, severity, and clinical impact. Conclusions An objective, universally accepted definition and clinical grading of PPH is important for the appropriate management and use of interventions in PPH. Such a definition also would allow comparisons of results from future clinical trials. Such standardized definitions are necessary to compare, in a nonpartisan manner, the outcomes of studies and the evaluation of novel operative treatment modalities in pancreatic surgery.
Background Delayed gastric emptying (DGE) is one of the most common complications after pancreatic resection. In the literature, the reported incidence of DGE after pancreatic surgery varies ...considerably between different surgical centers, primarily because an internationally accepted consensus definition of DGE is not available. Several surgical centers use a different definition of DGE. Hence, a valid comparison of different study reports and operative techniques is not possible. Methods After a literature review on DGE after pancreatic resection, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition with grades of DGE based primarily on severity and clinical impact. Results DGE represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management. Conclusion The proposed definition, which includes a clinical grading of DGE, should allow objective and accurate comparison of the results of future clinical trials and will facilitate the objective evaluation of novel interventions and surgical modalities in the field of pancreatic surgery.
The long-term decline of managed honeybee hives in the world has drawn significant attention to the scientific community and bee-keeping industry. A high pathogen load is believed to play a crucial ...role in this phenomenon, with the bee viruses being key players. Most of the currently characterized honeybee viruses (around twenty) are positive stranded RNA viruses. Techniques based on RNA signatures are widely used to determine the viral load in honeybee colonies. High throughput screening for viral loads necessitates the development of a multiplex polymerase chain reaction approach in which different viruses can be targeted simultaneously. A new multiparameter assay, called "BeeDoctor", was developed based on multiplex-ligation probe dependent amplification (MLPA) technology. This assay detects 10 honeybee viruses in one reaction. "BeeDoctor" is also able to screen selectively for either the positive strand of the targeted RNA bee viruses or the negative strand, which is indicative for active viral replication. Due to its sensitivity and specificity, the MLPA assay is a useful tool for rapid diagnosis, pathogen characterization, and epidemiology of viruses in honeybee populations. "BeeDoctor" was used for screening 363 samples from apiaries located throughout Flanders; the northern half of Belgium. Using the "BeeDoctor", virus infections were detected in almost eighty percent of the colonies, with deformed wing virus by far the most frequently detected virus and multiple virus infections were found in 26 percent of the colonies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision ...oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
The Korea-United States Air Quality Study (KORUS-AQ) conducted during May-June 2016 offered the first opportunity to evaluate direct-sun observations of formaldehyde (HCHO) total column densities ...with improved Pandora spectrometer instruments. The measurements highlighted in this work were conducted both in the Seoul megacity area at the Olympic Park site (37.5232° N, 27.1260° E; 26 ma.s.l.) and at a nearby rural site downwind of the city at the Mount Taehwa research forest site (37.3123° N, 127.3106° E; 160ma.s.l.). Evaluation of these measurements was made possible by concurrent ground-based in situ observations of HCHO at both sites as well as overflight by the NASA DC-8 research aircraft. The flights provided in situ measurements of HCHO to characterize its vertical distribution in the lower troposphere (0-5km). Diurnal variation in HCHO total column densities followed the same pattern at both sites, with the minimum daily values typically observed between 6:00 and 7:00 local time, gradually increasing to a maximum between 13:00 and 17:00 before decreasing into the evening. Pandora vertical column densities were compared with those derived from the DC-8 HCHO in situ measured profiles augmented with in situ surface concentrations below the lowest altitude of the DC-8 in proximity to the ground sites. A comparison between 49 column densities measured by Pandora vs. aircraft-integrated in situ data showed that Pandora values were larger by 16% with a constant offset of 0.22DU (Dobson units;
= 0.68). Pandora HCHO columns were also compared with columns calculated from the surface in situ measurements over Olympic Park by assuming a well-mixed lower atmosphere up to a ceilometer-measured mixed-layer height (MLH) and various assumptions about the small residual HCHO amounts in the free troposphere up to the tropopause. The best comparison (slope = 1.03±0.03; intercept = 0.29±0.02DU; and
= 0.78±0.02) was achieved assuming equal mixing within ceilometer-measured MLH combined with an exponential profile shape. These results suggest that diurnal changes in HCHO surface concentrations can be reasonably estimated from the Pandora total column and information on the mixed-layer height. More work is needed to understand the bias in the intercept and the slope relative to columns derived from the in situ aircraft and surface measurements.