Pre-harvest soil acidification, liming or N fertilization did not significantly affect the survival and growth of young Norway spruce

Abstract

In situ RHAMM protein expression in acute myeloid leukemia blasts suggests poor overall survival.

Treatment options for patients with high-risk acute myeloid leukemia (AML) include high-dose chemotherapy regimens in combination with allogeneic hematopoietic stem cell transplantation, which takes advantage of the donor T-cell-mediated graft-versus-leukemia effect. Together with beneficial responses observed in assays targeted at leukemia-associated antigens (LAA), this encouraged research on cancer vaccines and adoptive cellular therapies in AML. The receptor for hyaluronic acid-mediated motility (RHAMM, CD168) was identified as one of the most promising LAA in AML. Thus far, little is known about in situ expression in leukemic bone marrow blasts or the prognostic role of RHAMM and its interaction partners in AML. We immunohistochemically analyzed the expression and prognostic significance of RHAMM on trephine bone marrow biopsies from 71 AML cases that had been evaluated for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. Fifty-five patients (77%) were treated with curative intent, while 16 (23%) received the most appropriate supportive care. Twenty of 71 (28%) AML cases were considered RHAMM+. Receiver operating characteristic curves showed significant discriminatory power considering overall survival (OS) in AML patients treated curatively for RHAMM (p = 0.015). Multivariable analysis revealed that expression of RHAMM in >5% of leukemic blasts identifies a subgroup of curatively treated cases with adverse OS independent of failures to achieve complete remission. RHAMM not only represents a promising LAA with specific T-cell responses in AML but, if assessed in situ on blasts, also a probable prognostic factor.

Fitness cost and impaired survival in penicillin-resistant Streptococcus gordonii isolates selected in the laboratory.

Cycling of Streptococcus gordonii (115 times) with penicillin resulted in a MIC increase of more than 100-fold, from 0.008 to 2 microg/ml. The 2-microg/ml MIC maximum was already reached after 36 passages but resulted in impaired fitness. Although the MIC did not increase further, fitness was partially recovered during the 79 additional cycles.

Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart.

BACKGROUND: Stem cell labeling with iron oxide (ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats. METHODS AND RESULTS: We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and beta-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology (at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no beta-galactosidase-positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively. CONCLUSIONS: The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart.

The Glucocorticoid-induced leucine zipper (GILZ) Is essential for spermatogonial survival and spermatogenesis.

Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of the glucocorticoid-induced leucine zipper protein (GILZ) encoded by the X-linked Tsc22d3 (Gilz) gene. We found that GILZ is specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes. While Gilz mutant female mice were fully fertile, constitutive or male germ cell-specific ablation of Gilz led to sterility due to a complete absence of post-meiotic germ cells and mature spermatozoa. Alterations were observed as early as postnatal day 5 during the first spermatogenic wave and included extensive apoptosis at the spermatogonial level and meiotic arrest in the mid-late zygotene stage. Overall, these data emphasize the essential role played by GILZ in mediating spermatogonial survival and spermatogenesis.

Cancer survival from the incident cases of the Registry of Vaud, Switzerland.

Survival statistics from the incident cases of the Vaud Cancer Registry over the period 1974-1980 were computed on the basis of an active follow-up based on verification of vital status as to December 31, 1984. Product-moment crude and relative 5 to 10 year rates are presented in separate strata of sex, age and area of residence (urban or rural). Most of the rates are comparable with those in other published series from North America or Europe, but survival from gastric cancer (24% 5-year relative rates) tended to be higher, and that from bladder cancer (about 30%) lower than in most other datasets. No significant difference in survival emerged according to residence in urban Lausanne vs surrounding (rural) areas. Interesting indications according to subsite (higher survival for the pyloric region vs the gastric fundus, but absence of substantial differences for various colon subsites), histology (higher rates for squamous carcinomas of the lung, seminomas of the testis or chronic lymphatic leukemias as compared with other histotypes), or site of origin (higher survival for lower limb melanomas), require further quantitative assessment from other population-based series. A Cox proportional hazard model applied to melanomatous skin cancers showed an independent favorable effect on long-term prognosis of female gender and adverse implications for advanced age, stage at diagnosis and tumor site other than lower limb.

Community structures of soil animals and survival of land snails on an island of the Ogasawara Archipelago

On Chichijima, one of the Ogasawara (Bonin) Islands located in the Western Pacific Ocean, land snails have declined, the suggested cause being predation pressure by an invasive flatworm (Platydemus manokwari). Soil fauna were investigated in areas where the snail survives, and where it has become extinct. Much of the fauna, dominated by introduced earthworms and ants, was undiminished, however, one undescribed but endemic carabid (Badister sp.), which selectively feeds on land snails, was absent in snail-extinct areas. The invasive flatworm P. manokwari has been reported to feed also on the carcasses of earthworms, as well as on live snails, and is therefore expected to occur in most parts of Chichijima Island. Among other groups, the density of isopods (also dominated by exotic species) was very low, in comparison with the reported ones 30 years ago. Community structure is currently reflected by dominance of earthworms and ants, decline of endemic isopods, and a high frequency of introduced or alien species.

Malignant gastroduodenal obstruction: palliation with self-expanding metallic stents.

PURPOSE: To evaluate the feasibility, efficacy, and tolerance of self-expanding metallic stent insertion under fluoroscopic guidance for palliation of symptoms related to malignant gastroduodenal obstruction. MATERIALS AND METHODS: Seventy-two patients (38 men, 34 women) aged 25-98 years (mean, 62 years) with duodenal (n = 43), antropyloric (n = 13), surgical gastrojejunostomy (n = 10), or pyloroduodenal (n = 6) malignant obstruction were referred for insertion of self-expanding metallic stents over a 6-year period. Stent insertion was performed with use of a peroral or transgastric approach when necessary (n = 11). RESULTS: Stents were successfully inserted in 70 of the 72 patients (97%) and provided symptom relief in 65 patients (90%). Inserted stents were mainly uncovered vascular (n = 55) or enteral (n = 10) Wallstents. One hundred eight stents were initially inserted: one, two, three, or four stents were indicated in 43, 17, nine, and one patient, respectively. Mean follow-up was 119 days (range, 4-513 days). Mean stent patency was 113 days (range, 4-513 days). Mean survival of patients was 120 days. During follow-up, stent obstruction occurred in seven patients as a result of tumoral overgrowth (n = 5) or ingrowth (n = 2). Complications occurred in 12 of the 72 patients (17%), including stent migration (n = 8), stent fracture (n = 1), duodenal perforation (n = 1), and death related to general anesthesia (n = 1). CONCLUSION: Despite a significant complication rate, self-expanding metallic stent insertion under fluoroscopic guidance appears to be a feasible and useful technique in the palliative management of malignant gastroduodenal obstruction.

Loss of insulin synthesis and beta cell survival induced by oxidized LDL require activation of reticulum endoplasmic stress: a mechanism countered by HDL

Elevated circulating concentrations in modified LDL-cholesterol particles (e.g. oxidised LDL) and low levels in HDL increase not only the risk for diabetic patients to develop cardiovascular diseases but also may contribute to development and progression of diabetes by directly having adverse effects on β-cells. Chronic exposure of β-cells to 2 mM human oxidised LDL-cholesterol (oxLDL) increases the rate of apoptosis, reduce insulin biosynthesis and the secretory capacity of the cells in response to nutrients. In line with the protective role, HDL efficiently antagonised the harmful effects of ox- LDL, suggesting that low levels of HDL would be inefficient to protect β-cells against oxLDL attack in patients. Activation of endoplasmic reticulum (ER) stress is pointed out to contribute to β-cell dysfunction elicited by environmental stressors. In this study we investigated whether activation of ER stress is required for oxLDL to mediate detrimental effects on β-cells and we tested the potential antagonist properties of HDL: The mouse MIN6 insulin-secreting cells were cultured with 2 mM of LDL-cholesterol preparation (native or in vitro oxidized) in the presence or absence of 1 mM of HDL-cholesterol or the ER stress inhibitor 4-phenylbutyrate (4-PBA): Prolonged exposure of MIN6 cells to 2 mM oxLDL-cholesterol for 48 hours led to an increase in expression of ER stress markers such as ATF4, CHOP and p58 and stimulated the splicing of XBP-1 whereas, induction of these markers was not observable in the cells cultured with native LDL. Treatment of the cells with the 4-PBA chemical chaperone molecule efficiently blocked activation of the ER stress markers induced by oxLDL. The latter mediates β-cell dysfunction and apoptosis by diminishing the expression of islet brain 1 (IB1) and Bcl2. The levels of these two proteins were preserved in the cells that were co-treated with oxLDL and the 4-PBA. Consistent with this result we found that blockade of ER stress activation alleviated the loss of insulin synthesis and abolished apoptosis evoked by oxLDL. However incubation of the cells with 4-PBA did not prevent impairment of insulin secretion elicited by oxLDL, indicating that ER stress is not responsible for the oxLDL-mediated defect of insulin secretion. Co-incubation of the cells with HDL mimicked the effects of 4-PBA on the expression of IB1 and Blc2 and thereby counteracted oxLDL attacks on insulin synthesis and cell survivals. We found that HDL efficiently inhibited activation of the ER stress mediated by oxLDL: These data highlight the contribution of the ER stress in the defects of insulin synthesis and cell survivals induced by oxLDL and emphasize the potent role of HDL to counter activation of the oxLDL-mediated ER-stress activation:

FY2015 Equipment and Vehicle Revolving Fund report

The Equipment and Vehicle Revolving Fund report covers all equipment and vehicle purchases through the highway materials and equipment revolving fund during FY 2015.

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-kappaB activation and endothelial cell survival.

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine exerting pleiotropic effects on endothelial cells. Depending on the vascular context it can induce endothelial cell activation and survival or death. The microenvironmental cues determining whether endothelial cells will survive or die, however, have remained elusive. Here we report that integrin ligation acts permissive for TNF-induced protein kinase B (PKB/Akt) but not nuclear factor (NF)-kappaB activation. Concomitant activation of PKB/Akt and NF-kappaB is essential for the survival of endothelial cells exposed to TNF. Active PKB/Akt strengthens integrin-dependent endothelial cell adhesion, whereas disruption of actin stress fibers abolishes the protective effect of PKB/Akt. Integrin-mediated adhesion also represses TNF-induced JNK activation, but JNK activity is not required for cell death. The alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 sensitizes endothelial cells to TNF-dependent cytotoxicity and active PKB/Akt attenuates this effect. Interferon gamma synergistically enhanced TNF-induced endothelial cell death in all conditions tested. Taken together, these observations reveal a novel permissive role for integrins in TNF-induced PKB/Akt activation and prevention of TNF-induced death distinct of NF-kappaB, and implicate the actin cytoskeleton in PKB/Akt-mediated cell survival. The sensitizing effect of EMD121974 on TNF cytotoxicity may open new perspectives to the therapeutic use of TNF as anticancer agent.

Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer.

BACKGROUND: At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. METHODS: Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). RESULTS: Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). CONCLUSIONS: p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.

Consolidation with Radioimmunotherapy May Prolong Survival in First Remission of Mantle Cell Lymphoma Patients Uneligible for Stem Cell Transplantation, An Analysis of the International RIT-Network

Background: Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of Non Hodgkin Lymphoma (NHL) with a relatively poor prognosis (5-year survival < 40%). Although consolidation of first remission with autologous stem cell transplantation (ASCT) is regarded as "golden standard", less than half of the patients may be subjected to this intensive treatment due to advanced age and co-morbidities. Standard-dose non-myeloablative radioimmunotherapy (RIT) seems to be a very efficient approach for treatment of certain NHL. However, there are almost no data available on the efficacy and safety of RIT in MCL. Methods and Patients: In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age - 63 (range 31-78); males - 70.4%, stage III/IV - 92%. RIT (i.e. application of ibritumomab tiuxetan) was a part of the first line therapy in 48 pts. (43%). Further 38 pts. (33%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 33 pts. (24%) after completing 3-8 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response; the rest of the patients received ibritumomab tiuxetan because of relapse/refractory disease. At the moment follow up data are available for 74 MCL patients. Results: After RIT the patients achieved high response rate: CR 60.8%, PR 25.7%, and SD 2.7%. Only 10.8% of the patients progressed. For survival analysis many data had to be censored since the documentation had not been completed yet. The projected 3-year overall survival (OAS, fig.1 - image 001.gif) after radioimmunotherapy was 72% for pts. subjected to RIT consolidation versus 29% for those treated in relapse/refractory disease (p=0.03). RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 45, 40 and 38 days respectively. Conclusion: Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may prolong survival of patients who achieved clinical response after chemotherapy. Therefore, this consolidation approach should be considered as a treatment strategy for those, who are not eligible for ASCT. RIT also has a potential role as a palliation therapy in relapsing/resistant cases.

mTORC2 is an important signaling intermediary in VEGF-mediated endothelial cell proliferation, survival and migration

Objective: The vascular endothelial growth factor (VEGF) is a prominent¦contributor of tumor angiogenesis. VEGF induces endothelial cell migration,¦proliferation and survival, which are critical steps for the development of new¦blood vessels, through the activation of the Mek/Erk and PI3K/Akt signaling¦pathways. Recent findings have demonstrated that mTORC2 regulates Akt and¦Erk in endothelial cells. The role of mTORC2 in VEGF-mediated endothelial¦cell responses has however not been characterized.¦Methods: We used human umbilical vein endothelial cells (HUVEC). The¦effects of VEGF on the Mek/Erk and PI3K/Akt pathway were analyzed by¦Western blot. Inhibition of mTORC2 was achieved using small interfering¦RNAs to rictor. Cell proliferation rate was assessed by BrdU incorporation and¦immunocytofluorescence. Apoptosis rate was determined by ELISA as well as¦propidium iodine staining and FACS analysis. Migration of endothelial cells¦was evaluated using a modified Boyden chamber assay.¦Results:Wefound thatVEGF activatesmTORC2 in endothelial cells. Indeed,¦treatment of endothelial cells with VEGF increases Akt phosphorylation, a¦downstream effector of mTORC2. We have further determined the role¦of mTORC2 in VEGF signaling by knocking down rictor, a component¦of mTORC2. We observed that VEGF failed to activate Akt and Erk in¦endothelial cells transfected with rictor siRNA. To next analyze the functional¦significance of mTORC2 inhibition on VEGF-mediated endothelial cell¦responses we performed proliferation, survival and migration assays. We found¦that VEGF failed to induce endothelial cell proliferation, survival and migration¦in endothelial cell lacking mTORC2 activity.¦Conclusion: These results show that mTORC2 is an important signaling¦intermediary in VEGF-induced endothelial cell responses and thus represents¦an interesting target to block VEGF-induced angiogenesis.

Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells.

Development of Peyer's patches and lymph nodes requires the interaction between CD4+ CD3- IL-7Ralpha+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells. Here we showed that by promoting their survival, enhanced expression of interleukin-7 (IL-7) in transgenic mice resulted in accumulation of LTi cells. With increased IL-7 availability, de novo formation of VCAM-1+ Peyer's patch anlagen occurred along the entire fetal gut resulting in a 5-fold increase in Peyer's patch numbers. IL-7 overexpression also led to formation of multiple organized ectopic lymph nodes and cecal patches. After immunization, ectopic lymph nodes developed normal T cell-dependent B cell responses and germinal centers. Mice overexpressing IL-7 but lacking either RORgamma, a factor required for LTi cell generation, or lymphotoxin alpha1beta2 had neither Peyer's patches nor ectopic lymph nodes. Therefore, by controlling LTi cell numbers, IL-7 can regulate the formation of both normal and ectopic lymphoid organs.