Biomedical subjects

James Allen

Publications and source records attributed to James Allen.

At least 19 recordsLinked to original sources

PubMed2006

Foamy-virus-mediated gene transfer to canine repopulating cells.

Foamy virus (FV) vectors are particularly attractive gene-transfer vectors for stem-cell gene therapy because they form a stable transduction intermediate in quiescent cells and can efficiently transduce hematopoietic stem cells. Here, we studied the use of FV vectors to transduce long-term hematopoietic repopulating cells in the dog, a clinically relevant large animal model. Mobilized canine peripheral blood (PB) CD34+ cells were transduced with an enhanced green fluorescent protein (EGFP)-expressing FV vector in an 18-hour transduction protocol. All 3 dogs studied had rapid neutrophil engraftment to greater than 500/microL with a median of 10 days. Transgene expression was detected in all cell lineages (B cells, T cells, granulocytes, red blood cells, and platelets), indicating multilineage engraftment of transduced cells. Up to 19% of blood cells were EGFP+, and this was confirmed at the DNA level by real-time polymerase chain reaction (PCR) and Southern blot analysis. These transduction rates were higher than the best results we obtained previously with lentiviral vectors in a similar transduction protocol. Integration site analysis also demonstrated polyclonal repopulation and the transduction of multipotential hematopoietic repopulating cells. These data suggest that FV vectors should be useful for stem-cell gene therapy, particularly for applications in which short transduction protocols are critical.

Animals↗

PubMed2006

Promising pharmacologic innovations in treating pulmonary fibrosis.

Idiopathic pulmonary fibrosis is the most common form of the interstitial lung diseases and is characterized by chronic progressive pulmonary parenchymal fibrosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there remains no effective therapy for this disease. Therapies initially aimed at inflammation have proven ineffective, and newer strategies targeting aspects of aberrant wound repair involving alveolar epithelial cells or septal endothelial cells are now being investigated. Therapeutic strategies include the anti-fibrotic agents pirfenidone and interferon-gamma. Agents targeting specific cytokines, including connective tissue growth factor, transforming growth factor-beta and chemokines, are being evaluated. The restoration of oxidant balance and inhibition of leukotrienes represent other strategies. Additionally, the role of the coagulation/fibrinolytic systems and angiogenesis has also been examined.

Angiogenesis Inhibitors↗

PubMed2006

Chester: towards a personal medication advisor.

Dialogue systems for health communication hold out the promise of providing intelligent assistance to patients through natural interfaces that require no training to use. But in order to make the development of such systems cost effective, we must be able to use generic techniques and components which are then specialized as needed to the specific health problem and patient population. In this paper, we describe Chester, a prototype intelligent assistant that interacts with its user via conversational natural spoken language to provide them with information and advice regarding their prescribed medications. Chester builds on our prior experience constructing conversational assistants in other domains. The emphasis of this paper is on the portability of our generic spoken dialogue technology, and presents a case study of the application of these techniques to the development of a dialogue system for health communication.

Artificial Intelligence↗

PubMed2006

Molecular biomarkers of oxidative stress associated with bromate carcinogenicity.

Potassium bromate (KBrO3) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO3-induced cancer, male F344 rats were administered KBrO3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 (18O) labeled KBrO3 was administered to male rats by oral gavage and tissues were analyzed for 18O deposition. Tissue enrichment of 18O was observed at 5 and 24 h post-KBr18O3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18O deposition between 0.25 and 50 mg/L (equivalent dose) KBr18O3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis.

Animals↗

PubMed2006

Acute eosinophilic pneumonia.

Acute eosinophilic pneumonia is a sudden and severe febrile illness that can result in life-threatening respiratory failure. Because this disease can mimic other diseases causing acute respiratory failure, the diagnosis may be missed or delayed. It is clinically distinguishable from other pulmonary eosinophilic diseases and can be diagnosed with bronchoalveolar lavage. Treatment with corticosteroids results in rapid reversal of respiratory failure and complete recovery, generally without relapse. In some patients, acute eosinophilic pneumonia may be caused by drugs, tobacco smoke, or other inhaled substances; however, in the majority of patients, the condition is idiopathic.

Acute Disease↗

PubMed2006

The tools to understand: community as co-researcher on culture-specific protective factors for Alaska Natives.

A collaborative research process engaging Alaska Native communities in the study of protective factors in Alaska Native sobriety and the design of a preventative intervention using its findings is described. Study 1 was discovery oriented qualitative research whose objectives were identification of protective factors and development of a heuristic model. Study 2 involved quantitative survey methods to develop and test ameasure of protective factors identified by the qualitative study. Empirical data from these studies is presented, and the role of Alaska Native co-researchers who did not possess specialist research training is described in the design and implementation of the study, interpretation of findings, and design of the intervention model and tools. Benefits that emerged from co-researcher involvement in this process, to the community and to the co-researchers themselves, are described.

Adult↗

PubMed2005

Efficacy of DB289 in Thai patients with Plasmodium vivax or acute, uncomplicated Plasmodium falciparum infections.

BACKGROUND: DB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis. METHODS: We tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23. RESULTS: All patients cleared parasites by day 7, with a mean+/-SD clearance time of 43+/-41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate. CONCLUSIONS: DB289 is a promising new antimalarial compound that could become an important component of new antimalarial combinations.

Antiprotozoal Agents↗

PubMed2005

A nurse-led ambulatory care pathway for patients with deep venous thrombosis in an acute teaching hospital.

This article describes the management of deep vein thrombosis (DVT) using an ambulatory nurse-led pathway and the compression technique using duplex ultrasound. This pathway permits the management of the "walking wounded" as well as other patients at varying risks of having DVT and in so doing has changed the approach toward the management of this common clinical event. The success of the described pathway is attributed to the development of low molecular weight heparin and the reliability of diagnostics.

Ambulatory Care↗

PubMed2004

"Tied together like a woven hat:" Protective pathways to Alaska native sobriety.

BACKGROUND: The People Awakening Project (1RO1 AA 11446-03) had two purposes, completed in Phase I and Phase II of the project. The purpose of Phase I was to complete a qualitative study; the research objective was discovery oriented with the specific aim of identification of protective and recovery factors in Alaska Native sobriety. Results were used to develop a heuristic model of protective and recovery factors, and measures based on these factors. The research objective of Phase II was to pilot these measures and provide initial validity data. METHODS: Phase I utilized a life history methodology. People Awakening interviewed a convenience sample of 101 Alaska Natives who had either recovered from alcoholism (n = 58) or never had a drinking problem (n = 43). This later group included both lifetime abstainers (LAs) and non-problem drinkers (NPs). Life histories were transcribed and analyzed using grounded theory and consensual data analytic procedures within a participatory action research framework. Analyses were utilized to generate heuristic models of protection and recovery from alcohol abuse among Alaska Natives. RESULTS: Analyses generated a heuristic model of protective factors from alcohol abuse. The resulting multilevel and multi-factorial model describes interactive and reciprocal influences of (a) individual, family, and community characteristics; (b) trauma and the individual and contextual response to trauma, (c) experimental substance use and the person's social environment; and (d) reflective processes associated with a turning point, or a life decision regarding sobriety. The importance of cultural factors mediating all these protective processes is emphasized. For NPs, the resilience process drew from personal stores of self-confidence, self-efficacy, and self-mastery that derived from ability to successfully maneuver within stressful or potentially traumatizing environments. In contrast, for many LAs, efficacy was instead described in more socially embedded terms better understood as communal mastery. One style of mastery is more associated with individualistic orientations, the other with more collectivistic. Future research is needed regarding the generalizeability of this group difference. CONCLUSIONS: Results suggest that preventative interventions should focus on intervening simultaneously at the community, family, and individual levels to build resilience and protective factors at each level. Of particular importance is the building of reflexivity along with other cognitive processes that allow the individual to think through problems and to reach a life decision to not abuse alcohol.

Journal Article↗

PubMed2004

The Circles of Care evaluation: doing participatory evaluation with American Indian and Alaska Native communities.

Little information exists regarding mental health and special needs related to American Indian and Alaska Native (AI-AN) families. In this paper we emphasize the use of oral tradition during the Circles of Care initiative, which was essential in understanding cultural history and historical trauma of AI-ANs while giving a greater understanding of an AI-AN-based definition of severe emotional disturbance (SED). The success of these methods serves as a template for improving systems of care and may be useful in evaluation among a wide range of ethnic communities.

Adolescent↗

PubMed2004

The evaluation life cycle: a retrospective assessment of stages and phases of the circles of care initiative.

A life cycle metaphor characterizes the evolving relationship between the evaluator and program staff. This framework suggests that common developmental dynamics occur in roughly the same order across groups and settings. There are stage-specific dynamics that begin with Pre-History, which characterize the relationship between the grantees and evaluator. The stages are: (a) Pre-History, (b) Process, (c) Development, (d) Action, (e) Findings-Compilation, and (f) Transition. The common dynamics, expectations, and activities for each stage are discussed.

Child↗

PubMed2004

Words have power: (re)-defining serious emotional disturbance for American Indian and Alaska Native children and their families.

Circles of Care grantees were provided the opportunity to develop a locally relevant definition of serious emotional disturbance that would be used to define what type of emotional, behavioral, and mental disability would be required to receive services. After conducting detailed assessments of the definition in the guidance for applicants GFA and the definitions used by others in their respective states, seven of the nine grantees developed their own local, project-specific definitions through the participation of community focus groups and Advisory Councils. The six definitions for SED developed by rural grantees all included American Indian and Alaska Native concepts specific to each tribal community's culture; the urban grantee's definition was purposely focused for reaching out to non-professional members of the community. This opportunity for the communities to redefine SED not only provided each community with a definition which would be more culturally specific, but also proved to be an extraordinarily exercise in empowerment and self-determination.

Adolescent↗

PubMed2004

Mapping pathways to services: description of local service systems for American Indian and Alaska Native children by Circles of Care.

The process of describing existing services for American Indian and Alaska Native children with serious emotional disturbance by the Circles of Care strategic planning initiative is overviewed. We explain why service system description is important and how it helped define the role of evaluation within the initiative. Primary goals and methodologies of the service system description are described. Key findings, challenges and opportunities presented by the findings, and impact on the planning process are described.

Adolescent↗

PubMed2004

Efficacy of distinct energy delivery protocols comparing two biphasic defibrillators for cardiac arrest.

Limited data have been published on the use of external defibrillators that deliver impedance compensated biphasic (ICB) waveforms in patients. We compared 2 ICB defibrillators, the Heartstream XL (150-150-150 J protocol) and Heartsine Samaritan (100-150-200 J protocol) in 78 consecutive patients in cardiac arrest. The performance of the 2 devices over the first 2 shocks was statistically equivalent. By the third shock, the Heartsine Samaritan had significantly better performance in removing ventricular fibrillation (p = 0.029). Energy selection for ICB waveforms requires further validation.

Aged↗

PubMed2004

Unheard Alaska: culturally anchored participatory action research on sobriety with Alaska Natives.

Alcohol research in Alaska Native communities has a contentious history. This project has attempted to address a critical need for research to guide alcohol abuse prevention and treatment with Alaska Natives using culturally anchored participatory action research. The process of grounding the research methodology in the culture and community is described, along with its contribution to community psychology's understanding of the importance of cultural factors. Tensions between indigenous values and ways of knowing, and Western research methodologies are delineated, along with how these tensions were resolved. Important issues that arose in doing culturally anchored participatory action research are described. These included the development of a community of inquiry, key methodological decisions, the empowerment of participants as coresearchers, and flexibility in research implementation.

Alaska↗

PubMed2004

Methodological issues in cross-cultural and multicultural rorschach research.

Hermann Rorschach researched the utility of his inkblot experiment to understand psychopathology and cultural differences. Contemporary research with the Rorschach has evaluated its utility as a test, although it may more properly represent a clinical method with somewhat different evaluation criteria. Recent controversy regarding the adequacy of the Rorschach as a test and the adequacy of its normative data has at times distorted and oversimplified important methodological issues inherent in the study of cultural difference. Cultural processes remain a central and inadequately examined variable in Rorschach research; an important emergent area of inquiry is the Rorschach's clinical utility as a cross-cultural assessment instrument. We review multicultural and cross-cultural methodological issues intrinsic to contemporary Rorschach research here. Consideration of cultural issues enlarges and enriches the Rorschach clinical utility debate and suggests underexplored research strategies that can contribute to its resolution.

Cross-Cultural Comparison↗

PubMed2003

Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy.

We report the generation and use of pseudotyped adeno-associated viral (AAV) vectors for the liver-specific expression of human blood coagulation factor IX (hFIX). Therefore, an AAV-2 genome encoding the hfIX gene was cross-packaged into capsids of AAV types 1 to 6 using efficient, large-scale technology for particle production and purification. In immunocompetent mice, the resultant vector particles expressed high hFIX levels ranging from 36% (AAV-4) to more than 2000% of normal (AAV-1, -2, and -6), which would exceed curative levels in patients with hemophilia. Expression was dose- and time-dependent, with AAV-6 directing the fastest and strongest onset of hFIX expression at all doses. Interestingly, systemic administration of 2 x 1012 vector particles of AAV-1, -4, or -6 resulted in hFIX levels similar to those achieved by portal vein delivery. For all other serotypes and particle doses, hepatic vector administration yielded up to 84-fold more hFIX protein than tail vein delivery, corroborated by similarly increased vector DNA copy numbers in the liver, and elicited a reduced immune response against the viral capsids. Finally, neutralization assays showed variable immunologic cross-reactions between most of the AAV serotypes. Our technology and findings should facilitate the development of AAV pseudotype-based gene therapies for hemophilia B and other liver-related diseases.

Adenoviridae↗

PubMed2003

Racial identity and the MMPI in African American male college students.

The relation of the Minnesota Multiphasic Personality Inventory (MMPI) to the Racial Identity Attitude Scale--Black, Short Form (RIAS-B) was examined among 50 African American male college students in a reanalysis of unpublished MMPI data described in R. H. Dana (1993). This permitted study of relationships between MMPI scores and specific psychological variables hypothesized to produce cultural differences among African Americans. Results indicated RIAS-B scale scores functioned as predictors of MMPI scale scores. Similar research with the MMPI-2 incorporating larger samples that more adequately represent African American heterogeneity is needed. Methodological implications of these findings for MMPI-2 research with ethnic and racial groups are discussed, emphasizing the importance of research to depathologize African American racial and cultural identity.

Adaptation, Psychological↗