Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions

In-vitro and in-vivo studies have shown that autocrine growth factors and receptors are frequently expressed in human malignancies. Few of these studies, however, provide evidence that the identified autocrine pathway is functional. In this study, a functional autocrine growth pathway in pancreatic cancer has been identified using an in-vitro cell culture system. When pancreatic cancer cells were grown without change of medium, proliferation was greater than when either medium was replaced frequently (HPAF, CAPAN-2, PANC-1 or SW1990) or cells were grown in the presence of the EGF receptor tyrosine kinase inhibitor AG1478 or the MEK inhibitor PD098059 (HPAF or CAPAN-2). Activity of extracellular-regulated kinases (ERK) 1 and 2 and c- jun and c- fos mRNA levels were significantly elevated in CAPAN-2 cells cultured continuously in serum-free medium. Collectively, the observations indicate that the EGF receptor and the ERK MAP kinase pathway mediate autocrine signals. In contrast to previous reports, the GRP and IGF-I receptors were shown not to be required for autocrine effects on pancreatic cancer cell proliferation. Autocrine stimulation of the EGF receptor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells. © 2001 Cancer Research Campaign http://www.bjcancer.co

Use of traditional knowledge by the United States Bureau of Ocean Energy Management to support resource management

Professionals who collect and use traditional knowledge to support resource management decisions often are preoccupied with concerns over how and if traditional knowledge should be integrated with science. To move beyond the integration dilemma, we treat traditional knowledge and science as distinct and complementary knowledge systems. We focus on applying traditional knowledge within the decision-making process. We present succinct examples of how the Bureau of Ocean Energy Management has used traditional knowledge in decision making in the North Slope Borough, Alaska: 1) using traditional knowledge in designing, planning, and conducting scientific research; 2) applying information from both knowledge systems at the earliest opportunity in the process; 3) using traditional knowledge in environmental impacts assessment; 4) consulting with indigenous leaders at key decision points; and 5) applying traditional knowledge at a programmatic decision level. Clearly articulating, early in the process, how best to use traditional knowledge and science can allow for more complete and inclusive use of available and pertinent information

Patterns of woodboring beetle activity following fires and bark beetle outbreaks in montane forests of California, USA

Increasingly frequent and severe drought in the western United States has contributed to more frequent and severe wildfires, longer fire seasons, and more frequent bark beetle outbreaks that kill large numbers of trees. Climate change is expected to perpetuate these trends, especially in montane ecosystems, calling for improved strategies for managing Western forests and conserving the wildlife that they support. Woodboring beetles (e.g., Buprestidae and Cerambycidae) colonize dead and weakened trees and speed succession of habitats altered by fire or bark beetles, while serving as prey for some early-seral habitat specialists, including several woodpecker species. To understand how these ecologically important beetles respond to different sources of tree mortality, we sampled woodborers in 16 sites affected by wildfire or bark beetle outbreak in the previous one to eight years. Study sites were located in the Sierra Nevada, Modoc Plateau, Warner Mountains, and southern Cascades of California, USA. We used generalized linear mixed models to evaluate hypotheses concerning the response of woodboring beetles to disturbance type, severity, and timing; forest stand composition and structure; and tree characteristics.</p

Treatment Strategies for Persistent Methicillin-Resistant Staphylococcus aureus Bacteraemia

What is known and objective: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a long-standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia. Methods: A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin-resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English-language, peer-reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data. Results and discussion: Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high-dose daptomycin in combination with an antistaphylococcal β-lactam, ceftaroline, trimethoprim-sulfamethoxazole (TMP-SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP-SMX; linezolid alone or in combination with a carbapenem, or telavancin. What is new and conclusion: Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm

Failure of Ceftolozane-Tazobactam Salvage Therapy in Complicated Pneumonia With Lung Abscess

Treatment of Pseudomonas aeruginosa remains challenging, despite the availability ceftolozane-tazobactam. We report a treatment failure with ceftolozane-tazobactam salvage therapy for pneumonia complicated by lung abscess. Drug resistance, dose selection, and source control are possible contributing factors. Ceftolozane-tazobactam susceptibility testing should precede therapy and consideration should be given to dosing selection

Patterns of woodboring beetle activity following fires and bark beetle outbreaks in montane forests of California, USA

Increasingly frequent and severe drought in the western United States has contributed to more frequent and severe wildfires, longer fire seasons, and more frequent bark beetle outbreaks that kill large numbers of trees. Climate change is expected to perpetuate these trends, especially in montane ecosystems, calling for improved strategies for managing Western forests and conserving the wildlife that they support. Woodboring beetles (e.g., Buprestidae and Cerambycidae) colonize dead and weakened trees and speed succession of habitats altered by fire or bark beetles, while serving as prey for some early-seral habitat specialists, including several woodpecker species. To understand how these ecologically important beetles respond to different sources of tree mortality, we sampled woodborers in 16 sites affected by wildfire or bark beetle outbreak in the previous one to eight years. Study sites were located in the Sierra Nevada, Modoc Plateau, Warner Mountains, and southern Cascades of California, USA. We used generalized linear mixed models to evaluate hypotheses concerning the response of woodboring beetles to disturbance type, severity, and timing; forest stand composition and structure; and tree characteristics

Detection and quantification of Leptographium wageneri, the cause of black-stain root disease, from bark beetles (Coleoptera: Scolytidae) in Northern California using regular and Real-time PCR

Black-stain root disease is a threat to conifer forests in western North America. The disease is caused by the ophiostomatoid fungus Leptographium wageneri (W.B. Kendr.) M.J. Wingf., which is associated with a number of bark beetle (Coleoptera: Scolytidae) and weevil species (Coleoptera: Curculionidae). We developed a polymerase chain reaction test to identify and quantify fungal DNA directly from insects. Leptographium wageneri DNA was detected on 142 of 384 bark beetle samples (37%) collected in Lassen National Forest, in northeastern California, during the years 2001 and 2002. Hylastes macer (LeConte) was the bark beetle species from which Leptographium DNA was amplified most regularly (2001: 63.4%, 2002: 75.0% of samples) . Lower insect?fungus association rates were found for Hylurgops porosus (LeConte), Hylurgops subcostulatus (Mannerheim), Hylastes gracilis (LeConte), Hylastes longicollis (Swaine), Dendroctonus valens (LeConte), and Ips pini (Say). The spore load per beetle ranged from 0 to over 1 × 105 spores, with only a few beetles carrying more than 1 × 103 spores. The technique permits the processing of a large number of samples synchronously, as required for epidemiological studies, to study infection rates in bark beetle populations and to identify potential insect vectors