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Burgener A.,Public Health Agency of Canada | Burgener A.,University of Manitoba | Burgener A.,Karolinska Institutet | McGowan I.,University of Pittsburgh | And 3 more authors.
Current Opinion in Immunology | Year: 2015

The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios. © 2015.


Schiller D.,Mount Sinai School of Medicine | Eichenbaum H.,Boston University | Buffalo E.A.,Washington National Primate Research Center | Davachi L.,New York University | And 3 more authors.
Journal of Neuroscience | Year: 2015

More than 50 years of research have led to the general agreement that the hippocampus contributes to memory, but there has been a major schism among theories of hippocampal function over this time. Some researchers argue that the hippocampus plays a broad role in episodic and declarative memory, whereas others argue for a specific role in the creation of spatial cognitive maps and navigation. Although both views have merit, neither provides a complete account of hippocampal function. Guided by recent reviews that attempt to bridge between these views, here we suggest that reconciliation can be accomplished by exploring hippocampal function from the perspective of Tolman’s (1948) original conception of a cognitive map as organizing experience and guiding behavior across all domains of cognition.Weemphasize recent studies in animals and humans showing that hippocampal networks support a broad range of domains of cognitive maps, that these networks organize specific experiences within the contextually relevant map, and that network activity patterns reflect behavior guided through cognitive maps. These results are consistent with a framework that bridges theories of hippocampal function by conceptualizing the hippocampus as organizing incoming information within the context of a multidimensional cognitive map of spatial, temporal, and associational context. © 2015 the authors.


News Article | November 12, 2016
Site: www.latimes.com

Kathy Bentson keeps the brass ID tags in a small table inside her front door. They belonged to research subjects at the University of Washington, two monkeys that died and one that survived. The tags are a reminder that her work is not done, that she has not published data showing the monkeys endured more pain and distress than they should have as subjects in medical studies. As the University of Washington builds a controversial, $124-million animal research and care facility, this former UW researcher says school officials have suppressed her data showing that some categories of monkeys used in its studies exhibited dramatically high levels of disturbing behavior not seen in the wild. The mild-mannered 62-year-old with a doctorate in neurobiology and behavior is no fiery animal rights activist. But Bentson has found the last decade to be a struggle between emotion and intellect. Animal welfare and animal research. Conscience and career. Such debates, both internal and public, are taking place throughout the scientific community. In 2011, the National Institutes of Health concluded that most research conducted with chimpanzees was unnecessary — that chimps, as humans’ closest relatives, merited “special consideration and respect.” Last year, the NIH said its remaining 50 research chimps would live out their days at a sanctuary. Bentson says using animals as research subjects is sometimes necessary. “I would likely be dead, and you might too without it,” she said. “It prolongs and improves the quality of life for humans and animals.” There were two main conclusions in Bentson’s original manuscript: If a monkey exhibited “floating limb suite,” which causes its legs to contort, it was more likely to bite itself. And such behavior occurred in levels that vary by species, sex and whether the monkey was raised in a nursery or by its mother. Taken together, the data showed that it was possible to know which monkeys would be more resilient during medical research, and therefore, it was largely possible to avoid using monkeys that would suffer more. Bentson and her colleagues at the Washington National Primate Research Center published half of the results in the American Journal of Primatology, in a 2010 article that showed a relationship between floating limb behavior and self-biting. The UW has quashed the second part of the study’s conclusions, Bentson said. University officials describe the data in question as sloppily gathered and out of date. They say Bentson’s colleagues found her manner unprofessional. Tina Mankowski, UW Medicine’s associate vice president for medical affairs, said Bentson “was insistent on her point of view that others did not share.” Bentson is a scientist who believes in the limits of data. She is loath to use the word “suffering” when describing the animals she has studied so closely. It is subjective, a layman’s term, an unsupportable leap into monkeys’ minds. “Distress,” she said, over and over, is the better word. Only after years of fighting with the university and hours of interviews did the word spring unbidden — in an email to a reporter in which she described the impact of non-human primates on her very human heart. “Imagine being tasked with spending 5 years looking for ways to predict and reduce the incidence of severe abnormal behaviors in laboratory monkeys,” she wrote. She thought it would be tough work, and it was. “I compartmentalized, as most people who deal with suffering do.” But she was quick to continue: “Any ways they affected me did not in any way influence my careful recording of behaviors based on definitions.” Bentson’s journey to the primate research center began while growing up in rural Gunnison, Colo., where she would ride her bike to a hidden place she called paradise, a pond choked with low-lying foliage. She would get down on her knees and watch a changing world up close. Frogs. Bugs. Dragonflies. “It was the first time,” Bentson said, that “I learned how much joy you can derive and how much you can learn just by being an observer.” Twenty-five years later, Bentson was accepted into the University of Washington’s doctoral program in neurobiology and behavior and met her first monkey. Working with the UW bioengineering department, she helped develop a means of collecting blood samples by remote control from a group of freely moving baboons at the primate center. The samples let Bentson measure stress hormones, and the result was a dissertation on how physiological changes varied by a baboon’s rank in its group. Two years of post-doctoral work at UC Davis followed, and then Bentson returned to Seattle. That’s where Carolyn Crockett, head of the psychological well-being program at UW’s primate research center, invited her to create a research project. Together they received an NIH grant, $750,000 over five years for a study called “Predicting and reducing severe behavior disorders in laboratory monkeys.” The primary goal, Bentson said, was “to improve the well-being of monkeys that are used in medical research.” The investigators defined behaviors that were abnormal and collected data showing which monkeys exhibited them. Their ensuing manuscript was based on three years of data collected from 1,117 macaques involved in medical research. For another part of the study, Bentson observed a group of monkeys for eight minutes at a time. Many of the monkeys were used in infectious disease research. Bentson was required to wear protective gear from head to toe. “I couldn’t talk to them or touch them or give them food,” she said. “The ones I knew about and cared about very much had a lot of problems. That was my job — to deal with the ones that had problems.” As she watched the monkeys bite themselves or pace or contort their legs, Bentson would remind herself that she could not help the animals in front of her. But “the way I could help more monkeys, is to write up our results in peer-reviewed journals.” She remained objective, she said, but she was especially touched by a female macaque she figured out later had been taken from its mother and partially reared in a nursery. When Bentson began observing that monkey, the macaque was “full of life” and would acknowledge her with a greeting unique to pigtail macaques — lips forward, ears back, neck extended. “I could never return that greeting,” Bentson said. “The only part of my face she could see was my eyes, and I was the neutral observer.” Over time, Bentson began to worry about the monkey. The macaque’s coat looked greasy, and she appeared quite weak. All in addition to biting herself and contorting her limbs. “After I observed her one day, I went down to my desk,” Bentson recalled, the macaque’s ID tag in her hand, her eyes welling with tears. “I put my head down, and I cried.”


Hass C.A.,University of Washington | Horwitz G.D.,University of Washington | Horwitz G.D.,Washington National Primate Research Center
Journal of Vision | Year: 2011

Microsaccades can elevate contrast detection thresholds of human observers and modulate the activity of neurons in monkey visual cortex. Whether microsaccades elevate contrast detection thresholds in monkey observers is not known and bears on the interpretation of neurophysiological experiments. To answer this question, we trained two monkeys to perform a 2AFC contrast detection task. Performance was worse on trials in which a microsaccade occurred during the stimulus presentation. The magnitude of the effect was modest (threshold changes of <0.2 log unit) and color specific: achromatic sensitivity was impaired, but red-green sensitivity was not. To explore the neural basis of this effect, we recorded the responses of individual V1 neurons to a white noise stimulus. Microsaccades produced a suppression of spiking activity followed by an excitatory rebound that was similar for L - M cone-opponent and L + M nonopponent V1 neurons. We conclude that microsaccades in the monkey increase luminance contrast detection thresholds and modulate the spiking activity of V1 neurons, but the luminance specificity of the behavioral suppression is likely implemented downstream of V1. © ARVO.


Palermo R.E.,University of Washington | Palermo R.E.,Washington National Primate Research Center | Fuller D.H.,University of Washington | Fuller D.H.,Washington National Primate Research Center
Current Topics in Microbiology and Immunology | Year: 2012

In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics investigations as applied to understanding of HIV pathogenesis and innate immunity, drawing from our own research as well as the literature examples that utilized in vitro cell-based models or studies in nonhuman primates. We will also discuss the potential for systems biology to help guide strategies for HIV vaccines that offer significant protection by either preventing acquisition or strongly suppressing viral replication levels post-infection. © 2013 Springer-Verlag Berlin Heidelberg.


Adams Waldorf K.M.,University of Washington | Adams Waldorf K.M.,Washington National Primate Research Center | Rubens C.E.,Seattle Childrens Hospital | Rubens C.E.,University of Washington | And 2 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2011

Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits or sheep demonstrate the key link between infection and premature birth, but differ in the mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed, emphasising the role of infections and the potential development of preventative and therapeutic strategies. © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.


Mustari M.J.,Washington National Primate Research Center | Mustari M.J.,University of Washington | Ono S.,Washington National Primate Research Center
Annals of the New York Academy of Sciences | Year: 2011

The visual and oculomotor systems of primates are immature at birth and sensitive to injury. If synergistic interactions between visual and oculomotor systems are compromised during the first months of life, disorders in eye alignment, gaze holding, and smooth pursuit (SP) follow. Here we consider some potential neural mechanisms supporting SP and associated vestibular ocular reflex (VOR) behavior in normal and strabismic monkeys. Experimental strabismus was created by prism goggle wearing or eye muscle surgery in rhesus monkeys (Macaca mulatta). SP and cancellation of the VOR were highly asymmetric in strabismic monkeys during monocular viewing conditions. Similar asymmetric SP and VOR cancellation could be produced in normal monkeys by delivering unilateral muscimol injections to the dorsolateral pontine nucleus (DLPN). We suggest that failure to develop balanced cortical-brainstem circuits in strabismus accounts for many of the components of infantile strabismus syndrome. © 2011 New York Academy of Sciences.


News Article | November 10, 2016
Site: www.sciencedaily.com

A new paper published in FEMS Microbiology Letters, resulting from an investigation of a laundry facility that services several Seattle-area hospitals, suggests that soiled clinical linens may be a source of surface Clostridium difficile contamination. C. difficile is a hospital and community acquired pathogen. C. difficile are spore-forming anaerobic bacteria that have been identified in 2-3% of healthy, non-hospitalized adults and in 10-25% of hospitalized adults. Toxin-producing C. difficile is the most common cause of hospital-acquired diarrhea. It is estimated that 25% of all C. difficile infections occur from exposures in the community that may stem from potential sources including water, soil, livestock, meats, vegetables and pets. There is evidence that C. difficile infections are seasonal and are correlated with 151 respiratory illnesses in the winter, due to antibiotic use. The study determined if C. difficile could be cultured from clinical laundry facility surfaces. A total of 240 surface samples were collected from dirty areas, which handle soiled clinical linens, and from clean areas, which process and fold the clean linens, within the University of Washington Consolidated Laundry facility in 2015. All samples were collected at a laundry facility in Seattle, WA. This facility processes linens from six Seattle area hospitals, 30 local outpatient clinics and the Washington National Primate Research Center. Each week about 300,000 lbs. of laundry are processed. The facility is separated into two floors with the majority of the soiled linen handled on the 2nd floor and the clean linen handled exclusively on the 1st floor. The dirty area surface sample sites included the receiving area, the primary sort area, the secondary sort area, and the customer owned goods area for a total of 30 samples at each visit. The clean area sampling sites included washers, the folding area, the processing area and the break area. Thirty samples per sampling time with 120 samples total were collected each from the dirty and clean areas. All of the samples that tested positive were in areas where dirty linens are handled; no C. difficile contamination was found in areas where only clean laundry was handled. Of the samples taken from surfaces in the dirty side of the laundry facility, 23% (25/120 samples) tested positive for C. difficile. Only 2% (2/120 samples) of sampled surfaces from the clean side were positive for C. difficile. The two surfaces that were positive for C. difficile both came from a small area where soiled linen is handled in small batches. While the area is distinct from where clean linen is dried, ironed, and folded, it is on the same floor as the clean side. This indicates that the dirty linens were the likely source of the environmental contamination in the laundry. According to researchers, their data may be an underestimation of true prevalence and diversity of C. difficile on surfaces. The study is limited by the inherently poor recovery of microbes from environmental surfaces, difficulty in culturing C. difficile spores, differences in recommended incubation times and media used. "This research supports the idea that its possible for the soiled hospital linens to contaminate the environment with C. difficile, which is the number one cause of hospital associated diarrhea," said study author Marilyn Roberts, PhD. "It's also extremely hard to remove from the environment. Due to this contamination, laundry facilities should be considered an extension of the healthcare environment when considering infection prevention and occupational health."


News Article | November 7, 2016
Site: www.eurekalert.org

A new paper published in FEMS Microbiology Letters, resulting from an investigation of a laundry facility that services several Seattle-area hospitals, suggests that soiled clinical linens may be a source of surface Clostridium difficile contamination. C. difficile is a hospital and community acquired pathogen. C. difficile are spore-forming anaerobic bacteria that have been identified in 2-3% of healthy, non-hospitalized adults and in 10-25% of hospitalized adults. Toxin-producing C. difficile is the most common cause of hospital-acquired diarrhea. It is estimated that 25% of all C. difficile infections occur from exposures in the community that may stem from potential sources including water, soil, livestock, meats, vegetables and pets. There is evidence that C. difficile infections are seasonal and are correlated with 151 respiratory illnesses in the winter, due to antibiotic use. The study determined if C. difficile could be cultured from clinical laundry facility surfaces. A total of 240 surface samples were collected from dirty areas, which handle soiled clinical linens, and from clean areas, which process and fold the clean linens, within the University of Washington Consolidated Laundry facility in 2015. All samples were collected at a laundry facility in Seattle, WA. This facility processes linens from six Seattle area hospitals, 30 local outpatient clinics and the Washington National Primate Research Center. Each week about 300,000 lbs. of laundry are processed. The facility is separated into two floors with the majority of the soiled linen handled on the 2nd floor and the clean linen handled exclusively on the 1st floor. The dirty area surface sample sites included the receiving area, the primary sort area, the secondary sort area, and the customer owned goods area for a total of 30 samples at each visit. The clean area sampling sites included washers, the folding area, the processing area and the break area. Thirty samples per sampling time with 120 samples total were collected each from the dirty and clean areas. All of the samples that tested positive were in areas where dirty linens are handled; no C. difficile contamination was found in areas where only clean laundry was handled. Of the samples taken from surfaces in the dirty side of the laundry facility, 23% (25/120 samples) tested positive for C. difficile. Only 2% (2/120 samples) of sampled surfaces from the clean side were positive for C. difficile. The two surfaces that were positive for C. difficile both came from a small area where soiled linen is handled in small batches. While the area is distinct from where clean linen is dried, ironed, and folded, it is on the same floor as the clean side. This indicates that the dirty linens were the likely source of the environmental contamination in the laundry. According to researchers, their data may be an underestimation of true prevalence and diversity of C. difficile on surfaces. The study is limited by the inherently poor recovery of microbes from environmental surfaces, difficulty in culturing C. difficile spores, differences in recommended incubation times and media used. "This research supports the idea that its possible for the soiled hospital linens to contaminate the environment with C. difficile, which is the number one cause of hospital associated diarrhea," said study author Marilyn Roberts, PhD. "It's also extremely hard to remove from the environment. Due to this contamination, laundry facilities should be considered an extension of the healthcare environment when considering infection prevention and occupational health." The paper "Clostridium difficile Environmental Contamination within a Clinical Laundry Facility in the USA" is available at: http://femsle. Direct correspondence to: Marilyn C. Roberts, PhD Department of Environmental and Occupational Health Sciences University of Washington Elizabeth Sharpe- esharpe@uw.edu or 206-685-6737 To request a copy of the study, please contact: Daniel Luzer- daniel.luzer@oup.com or 212-726-6113


News Article | November 7, 2016
Site: www.rdmag.com

Seattle-based researchers are airing out the dirty laundry that is leading to many getting sick while in the hospital. A study has determined that dirty laundry and linens are significant sources of surface Clostridium difficile contamination, which is the most common cause of hospital-acquired diarrhea. “This research supports the idea that its possible for the soiled hospital linens to contaminate the environment with C. difficile, which is the number one cause of hospital associated diarrhea,” study author and professor in the University of Washington’s School of Public Health Marilyn Roberts, Ph.D., said in a statement. “It's also extremely hard to remove from the environment. Due to this contamination, laundry facilities should be considered an extension of the healthcare environment when considering infection prevention and occupational health.” Clostridium difficile is a hospital and community-acquired pathogen where spore-forming anaerobic bacteria form. It is estimated that the toxin-producing bacteria is identified in 2-to-3 percent of healthy, non-hospitalized adults and in 10-to-25 percent of hospitalized adults. It is also estimated that 25 percent of all C. difficile infections occur from exposures in the community that stem from potential sources including water, soil, livestock, meats, vegetables and pets. There is also evidence that the infections are seasonal and are correlated with 151 respiratory illnesses in the winter, due to antibiotic use. The study took samples at a laundry facility in Seattle that processes linens from six local hospitals, 30 outpatient clinics and the Washington National Primate Research Center. Researchers took 240 surface samples from dirty areas including the receiving area, the primary sort area, the secondary sort area and the customer-owned goods area. About 23 percent of samples in areas where dirty linens were handled tested positive, while 2 percent of the samples from areas where only clean laundry was handled tested positive. The study was published in FEMS Microbiology Letters.

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