In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient

AbstractThe influenza A(H1N1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. Reports have identified an increased prevalence of the hemagglutinin receptor binding domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. Virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the D222, but isolates collected later in his course from a bronchoalveolar lavage contained primarily the G222 mutation and was mixed with a minor population of D222. These clinical isolates were compared to a G222 plaque purified virus in the ferret model. The G222 predominant clinical isolate was the most pathogenic in ferrets and developed the most diversity at the 222 amino acid position during infection, suggesting that increased diversity and not a specific polymorphism at HA 222 may be important in predicting pathogenic potential

The epistemological model of disability, and its role in understanding passive exclusion in eighteenth and nineteenth century protestant educational asylums

This article examines how the process of constructing knowledge on impairment has affected the institutional construction of an ethic of disability. Its primary finding is that the process of creating knowledge in a number of historical contexts was influenced more by traditions and the biases of philosophers and educators in order to signify moral and intellectual superiority, than by a desire to improve the lives of disabled people through education. The article illustrates this epistemological process in a case study of the development of Protestant asylums in the latter years of the nineteenth century

Ornamental plants: annual reports and research summaries

The Ohio State University Extension Nursery, Landscape, and Turf Team (ENLTT) -- Extension Nursery, Landscape, and Turf Team (ENLTT) directory -- An evaluation of composts for landscape soil amendments / Mary Ann Rose and Hao Wang -- Aesthetic evaluation of crabapples at Secrest Arboretum in Wooster, Ohio: 1994-1995 / James A. Chatfield, Erik A. Draper, Kenneth C. Cochran, Peter W. Bristol and Charles E. Tubesing -- Evaluation of crabapples for apple scab at Secrest Arboretum in Wooster, Ohio: 1995 / Erik A. Draper, James A. Chatfield, Kenneth C. Cochran, Peter W. Bristol and Charles E. Tubesing -- Emergence, longevity, and aesthetic evaluations of flowers in ornamental crabapples at Secrest Arboretum in Wooster, Ohio: 1995 / Erik A. Draper, James A. Chatfield and Kenneth C. Cochran -- Environmental and cultural ornamental plant problems in Ohio: 1995 / Pamela J. Bennett and Jane A. Martin -- 1995 -A Challenging Year for Ohio golf courses / Joseph W. Rimelspach, John R. Street, Karl Danneberger, William E. Pound, Barbara Bloetscher -- Plant insect pest problems in Ohio: 1995 / Joseph F. Boggs, David J. Shetlar, Gary Yu Gao, Daniel Balser, Douglas C. Caldwell, Randall H. Zondag and James A. Chatfield -- Gypsy moth in Ohio: 1995 / Allan Baumgard, David F. James and Randall H. Zondag -- Landscape ornamental disease problems in Ohio: 1995 / James A. Chatfield, Nancy Taylor, Randall H. Zondag, Mary Ann Rose, Gary Yu Gao, Daniel R. Balser and David J. Shetlar -- The Response of native and naturalized trees to construction activity / T. Davis Sydnor, Joseph F. Boggs and Mary Ann Ros

Macrophage Tropism of Human Immunodeficiency Virus Type 1 Isolates from Brain and Lymphoid Tissues Predicts Neurotropism Independent of Coreceptor Specificity

The viral determinants that underlie human immunodeficiency virus type 1 (HIV-1) neurotropism are unknown, due in part to limited studies on viruses isolated from brain. Previous studies suggest that brain-derived viruses are macrophage tropic (M-tropic) and principally use CCR5 for virus entry. To better understand HIV-1 neurotropism, we isolated primary viruses from autopsy brain, cerebral spinal fluid, blood, spleen, and lymph node samples from AIDS patients with dementia and HIV-1 encephalitis. Isolates were characterized to determine coreceptor usage and replication capacity in peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages (MDM), and microglia. Env V1/V2 and V3 heteroduplex tracking assay and sequence analyses were performed to characterize distinct variants in viral quasispecies. Viruses isolated from brain, which consisted of variants that were distinct from those in lymphoid tissues, used CCR5 (R5), CXCR4 (X4), or both coreceptors (R5X4). Minor usage of CCR2b, CCR3, CCR8, and Apj was also observed. Primary brain and lymphoid isolates that replicated to high levels in MDM showed a similar capacity to replicate in microglia. Six of 11 R5 isolates that replicated efficiently in PBMC could not replicate in MDM or microglia due to a block in virus entry. CD4 overexpression in microglia transduced with retroviral vectors had no effect on the restricted replication of these virus strains. Furthermore, infection of transfected cells expressing different amounts of CD4 or CCR5 with M-tropic and non-M-tropic R5 isolates revealed a similar dependence on CD4 and CCR5 levels for entry, suggesting that the entry block was not due to low levels of either receptor. Studies using TAK-779 and AMD3100 showed that two highly M-tropic isolates entered microglia primarily via CXCR4. These results suggest that HIV-1 tropism for macrophages and microglia is restricted at the entry level by a mechanism independent of coreceptor specificity. These findings provide evidence that M-tropism rather than CCR5 usage predicts HIV-1 neurotropism

Ornamental plants: annual reports and research reviews

Ohio State University Extension Nursery, Landscape, and Turf Team Directory: 1998 / Jack Kerrigan -- Floriculture Industry Roundtable of Ohio: 1998 / Charles Behnke -- Ohio State University Extension Buckeye Yard and Garden Line / James A. Chatfield, Pamela J. Bennett, Joseph F. Boggs, Gary Y. Gao, Jane C. Martin, David J. Shetlar and Randall H. Zondag -- Environmental and cultural problems of ornamental plants in Ohio: 1997 / Pamela J. Bennett and Jane C. Martin -- Insect and mite activity noted in Ohio nurseries and landscapes: 1997 / Joseph F. Boggs, David J. Shetlar, Jane C. Martin, Pamela J. Bennett, James A. Chatfield, Gary Y. Gao and Chris Carlson -- Summary of ornamental diseases in Ohio: 1997 / James A. Chatfield, Nancy J. Taylor, Stephen N. Nameth, Chris Carlson, Joseph F. Boggs, Jane C. Martin, Dan Balser and David Madison -- Weed problems in Ohio landscapes and nurseries: 1997 / Gary Y. Gao, Joseph F. Boggs, Pamela J. Bennett, Jane C. Martin, Mary Ann Rose, Joseph W. Rimelspach, Randall H. Zondag and William E. Pound -- Wildlife problems in Ohio landscapes: 1997 / Gary Y. Gao, Joseph F. Boggs, Jane C. Martin, Charles T. Behnke and James A. Chatfield -- Summary of turf cultural and disease problems in 1997 / Gary Y. Gao, Joseph F. Boggs, Pamela J. Bennett, Jane C. Martin, Joseph W. Rimelspach and James A. Chatfield -- Master Gardeners serve Ohio / Marianne Riofrio -- The greening of Poland's nurseries / Kenneth D. Cochran and Wojtek Grabczewski -- The marketing potential of Ginkgo biloba in the United States / Kenneth D. Cochran -- Composts in the Landscape: Effects on Soil pH and plant growth / Mary Ann Rose and Hao Wang -- How to optimize disease control using composts / Harry A. J. Hoitink, Wei-Zheng Zhang, David Y. Han, Alexandra G. Stone, Matthew S. Krause and Warren A. Dick -- The flowering sequence of ornamental plants as a tool for predicting the phenology of insect pests / Daniel A. Herms -- Reducing maintenance costs may mean selecting plants with the fewest flaws / T. Davis Sydnor-- Comprehensive aesthetic evaluations of crabapples at Secrest Arboretum in Wooster: 1993-1997 / Erik A. Draper, James A. Chatfield, Kenneth D. Cochran, Peter W. Bristol and David E. Allen -- Precision control of microirrigation for container-grown mini-roses / Robert C. Hansen, Ted H. Short, C. C. Pasian and R. Peter Fynn -- Red thread (Laetisaria fuciformis) control study on perennial ryegrass / Joseph W. Rimelspach, Kerry Kline, Karl Danneberger and Michael Boehm-- Red thread (Laetisaria fuciformis) control study on Kentucky bluegrass / Joseph W. Rimelspach, Kerry Kline, Karl Danneberger and Michael Boehm -- Red thread - from novelty to nuisance / Joseph W. Rimelspach -- Chrysanthemum cultivars differ in response to photoperiod when grown under far-red absorbing filters / M. J. McMahon -- Improving fuchsia cutting performance by grafting / D. M. Napier and M. J. McMahon -- Paint/paclobutrazol mix on the inside surface of rooting wedge cells to control poinsettia cutting height / Claudio C. Pasian -- Response of poinsettias to paclobutrazol in paint applications / Claudio C. Pasian and Daniel K. Struve -- Dynamic transpiration of highly stressed container-grown Acer rubrum / Ted H. Short, Ahmet Irvem and Robert C. Hansen -- Effects of temperature on the development of Asiatic Lilies / J. Steininger and C. C. Pasian-- New publications for 1997-199

E-cadherin expression and bromodeoxyuridine incorporation during development of ovarian inclusion cysts in age-matched breeder and incessantly ovulated CD-1 mice

BACKGROUND: Female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12-month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas. The majority of cysts appeared to be dilated rete ovarii tubules, but high ovulation number resulted in more cortical inclusion cysts. We hypothesized that comparison of inclusion cyst pathology in animals of the same age, but with differences in total lifetime ovulation number, might allow us to determine distinguishing characteristics of the two types of cyst. METHODS: Ovaries from breeder mice (BR) or females subjected to incessant ovulation (IO) were compared at 6-, 9- and 12-months of age. Ovaries were serially sectioned and cysts characterized with regard to location and histology, E-cadherin immunoreactivity and rates of BrdU incorporation. RESULTS: Inclusion cysts developed with age in BR and IO ovaries. The majority of cysts were connected to the ovarian hilus. Two cortical inclusion cysts were observed in ten IO ovaries and one in ten BR ovaries. Low or no E-cadherin immuno-staining was seen in the OSE of all mice studied. Conversely, strong membrane immuno-staining was observed in rete ovarii epithelial cells. Variable E-cadherin immunoreactivity was seen in cells of hilar inclusion cysts, with strong staining observed in cuboidal ciliated cells and little or no staining in flat epithelial cells. Two of the three cortical cysts contained papillae, which showed E-cadherin immuno-staining at the edge of cells. However hilar and cortical cysts were not distinguishable by morphology, cell type or E-cadherin immunoreactivity. BrdU incorporation in cyst cells (1.4% [95% CI: 1.0 to 2.1]) was greater than in OSE (0.7% [95% CI: 0.4 to 1.2]) and very few BrdU-labeled cells were observed in rete ovarii at any age. Incessant ovulation significantly increased BrdU incorporation in OSE of older animals. CONCLUSION: These experiments confirm ovarian inclusion cysts develop with age in the CD-1 mouse strain, irrespective of total ovulation burden. We conclude longer periods of incessant ovulation do not lead to significant changes in inclusion cyst formation or steroidogenesis in CD-1 mice and inclusion cyst type can not be distinguished by morphology, cell proliferation rate or E-cadherin immunoreactivity

Pre-Clinical Evaluation of a 213Bi-Labeled 2556 Antibody to HIV-1 gp41 Glycoprotein in HIV-1 Mouse Models as a Reagent for HIV Eradication

Any strategy for curing HIV infection must include a method to eliminate viral-infected cells. Based on our earlier proof-of-principle results targeting HIV-1 infected cells with radiolabeled antibody (mAb) to gp41 viral antigen, we embarked on identifying a suitable candidate mAb for preclinical development.Among the several human mAbs to gp41 tested, mAb 2556 was found to have high affinity, reactivity with multimeric forms of gp41 present on both the surface of virus particles and cells expressing HIV-1 Env, and recognition of a highly conserved epitope of gp41 shared by all HIV-1 subtypes. Also, mAb 2556 was the best in competition with HIV-1+ serum antibodies, which is an extremely important consideration for efficacy in the treatment of HIV patients. When radiolabeled with alpha-emitting radionuclide 213-Bismuth ((213)Bi) - (213)Bi-2556 efficiently and specifically killed ACH-2 human lymphocytes chronically infected with HIV-1, and HIV-1 infected human peripheral blood mononuclear cells (hPBMCs). The number of binding sites for (213)Bi-2556 on the surface of the infected cells was >10(6). The in vivo experiments were performed in two HIV-1 mouse models--splenic and intraperitoneal. In both models, the decrease in HIV-1 infected hPBMCs from the spleens and peritoneum, respectively, was dose-dependent with the most pronounced killing of hPBMCs observed in the 100 µCi (213)Bi-2556 group (P = 0.01). Measurement of the blood platelet counts and gross pathology of the treated mice demonstrated the lack of toxicity for (213)Bi-2556.We describe the preclinical development of a novel radiolabeled mAb reagent that could potentially be part of an HIV eradication strategy that is ready for translation into the clinic as the next step in its development. As viral antigens are very different from "self" human antigens - this approach promises high selectivity, increased efficacy and low toxicity, especially in comparison to immunotoxins