Modulation of immunity by macrophages

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22754/1/0000309.pd

Inhibition of rat mixed lymphocyte cultures by suppressor macrophages

Normal rat spleens contain suppressor cells which can inhibit proliferative and cytotoxic responses of lymphocytes to alloantigens in vitro. The suppressor cells are adherent, phagocytic, resistant to treatment with ATS and C, radioresistant, resistant to treatment with mitomycin C, apparently absent from the thymus, and found in very high concentrations in peritoneal exudates. These characteristics indicate that the suppressor cell is a macrophages and not a T cell. When suppressor cells were removed from spleen cell suspensions, strong in vitro proliferative and cytotoxic responses to alloantigens could consistently be observed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22959/1/0000526.pd

Endoscopic identification and removal of an unusual symptomatic colonic foreign body

The discovery and removal of a life-threatening colonic wire suture using the flexible fiberoptic colonoscope has been described. Such reports demonstrate the versatility and usefulness of diagnostic and therapeutic endoscopic procedures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44387/1/10620_2005_Article_BF01308437.pd

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

In vitro inhibition of lymphoproliferative responses to tumor associated antigens and of lymphoma cell proliferation by rat splenic macrophages

Spleens from W/Fu rats bearing a syngeneic progressively growing (C58NT)D tumor contain cells which can inhibit lymphoproliferative responses in a mixed lymphocyte-tumor interaction designed to demonstrate suppressor activity. Spleens from rats having rejected (C58NT)D tumors also contained suppressor cells but to a lesser degree. The growth inhibition assay, which measures inhibition of proliferation of tumor cells, was evaluated as a simple assay system to screen for suppressor cell activity. The effector cells in both assays had the same characteristics, indicating a predominant role of macrophages. Normal rat spleens were found to contain growth inhibition activity which led to the demonstration of suppressor cell activity in spleens of normal animals. Removal of suppressor cells from the spleens of immunne rats results in consistently higher lymphoproliferative responses to tumor associated antigens on the tumor cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22991/1/0000559.pd

Origin and significance of decameter-scale polygons in the lower Peace Vallis fan of Gale crater, Mars

Decameter-scale polygons are extensively developed in the Bedded Fractured (BF) Unit of the lower Peace Vallis fan. The polygons occur in a likely extension of the Gillespie Lake Member, north of Yellowknife Bay, the section first drilled by the Mars Science Laboratory (MSL) mission. We examine hypotheses for the origin of these polygons to provide insight into the history of Gale crater. The polygons are ∼4–30 m across, square to rectangular, and defined by ∼0.5–4 m wide, generally straight troughs with orthogonal intersections. Polygon networks are typically oriented-orthogonal systems, with occasional nearly circular patterns, hundreds of meters across. Potential origins include cooling of lava, and for sedimentary units, syneresis, unloading, weathering, desiccation, impact processes, and cold-climate thermal contraction. Cold-climate thermal contraction is the hypothesis most consistent with the sedimentary nature of the BF Unit and the polygon morphology, geometry, networks, and apparent restriction to the coarse-grained Gillespie Lake Member. A periglacial setting further provides the best analogs for the circular networks and is consistent with geologic context and MSL data. Most of the decametric polygons appear to be ancient. They are confined to the Hesperian BF Unit, and only a few of their bounding fractures extend into younger or recently exposed units. In this regard, they differ from the majority of proposed thermal-contraction polygons on Mars, as those are generally thought to be young features, and, accordingly, the history of formation, preservation and reactivation of the decametric polygons is likely to be more complex than that of any proposed young polygons on Mars. The decametric polygons in the BF Unit may represent landforms developed in a cold but still comparatively wet interlude between a clement early Mars and the much drier and colder planet of today.DZO was supported by the Astromaterials Research and Exploration Science (ARES) Division at Johnson Space Center and the NASA Mars Science Laboratory (MSL) Participating Scientist Grant No. 10-MSLPSP10-0094. French authors (NM and LL) were supported by grants from the French National Agency for Space Studies, Centre National d'Etudes Spatiales (CNES). BH and RSS were supported by NASA Mars Science Laboratory via Malin Space Science Systems. AGF was supported by the Project “icyMARS”, funded by the European Research Council Starting Grant No. 307,496.Peer reviewe

Different 2-Aminothiazole Therapeutics Produce Distinct Patterns of Scrapie Prion Neuropathology in Mouse Brains.

Because no drug exists that halts or even slows any neurodegenerative disease, developing effective therapeutics for any prion disorder is urgent. We recently reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT) chemical scaffold that almost doubled the incubation times in scrapie prion-infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion inoculation extended survival from ∼120 days to over 450 days. In addition to IND24, we evaluated the pharmacokinetics and efficacy of five additional 2-AMTs; one was not followed further because its brain penetration was poor. Of the remaining four new 2-AMTs, IND114338 doubled and IND125 tripled the incubation times of RML-inoculated wt and Tg4053 mice overexpressing wt mouse prion protein (PrP), respectively. Neuropathological examination of the brains from untreated controls showed a widespread deposition of self-propagating, β-sheet-rich "scrapie" isoform (PrP(Sc)) prions accompanied by a profound astrocytic gliosis. In contrast, mice treated with 2-AMTs had lower levels of PrP(Sc) and associated astrocytic gliosis, with each compound resulting in a distinct pattern of deposition. Notably, IND125 prevented both PrP(Sc) accumulation and astrocytic gliosis in the cerebrum. Progressive central nervous system dysfunction in the IND125-treated mice was presumably due to the PrP(Sc) that accumulated in their brainstems. Disappointingly, none of the four new 2-AMTs prolonged the lives of mice expressing a chimeric human/mouse PrP transgene inoculated with Creutzfeldt-Jakob disease prions

Different 2-Aminothiazole Therapeutics Produce Distinct Patterns of Scrapie Prion Neuropathology in Mouse Brains.

Because no drug exists that halts or even slows any neurodegenerative disease, developing effective therapeutics for any prion disorder is urgent. We recently reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT) chemical scaffold that almost doubled the incubation times in scrapie prion-infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion inoculation extended survival from ∼120 days to over 450 days. In addition to IND24, we evaluated the pharmacokinetics and efficacy of five additional 2-AMTs; one was not followed further because its brain penetration was poor. Of the remaining four new 2-AMTs, IND114338 doubled and IND125 tripled the incubation times of RML-inoculated wt and Tg4053 mice overexpressing wt mouse prion protein (PrP), respectively. Neuropathological examination of the brains from untreated controls showed a widespread deposition of self-propagating, β-sheet-rich "scrapie" isoform (PrP(Sc)) prions accompanied by a profound astrocytic gliosis. In contrast, mice treated with 2-AMTs had lower levels of PrP(Sc) and associated astrocytic gliosis, with each compound resulting in a distinct pattern of deposition. Notably, IND125 prevented both PrP(Sc) accumulation and astrocytic gliosis in the cerebrum. Progressive central nervous system dysfunction in the IND125-treated mice was presumably due to the PrP(Sc) that accumulated in their brainstems. Disappointingly, none of the four new 2-AMTs prolonged the lives of mice expressing a chimeric human/mouse PrP transgene inoculated with Creutzfeldt-Jakob disease prions

Different 2-Aminothiazole Therapeutics Produce Distinct Patterns of Scrapie Prion Neuropathology in Mouse Brains

Because no drug exists that halts or even slows any neurodegenerative disease, developing effective therapeutics for any prion disorder is urgent. We recently reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT) chemical scaffold that almost doubled the incubation times in scrapie prion-infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion inoculation extended survival from ∼120 days to over 450 days. In addition to IND24, we evaluated the pharmacokinetics and efficacy of five additional 2-AMTs; one was not followed further because its brain penetration was poor. Of the remaining four new 2-AMTs, IND114338 doubled and IND125 tripled the incubation times of RML-inoculated wt and Tg4053 mice overexpressing wt mouse prion protein (PrP), respectively. Neuropathological examination of the brains from untreated controls showed a widespread deposition of self-propagating, β-sheet-rich “scrapie” isoform (PrP(Sc)) prions accompanied by a profound astrocytic gliosis. In contrast, mice treated with 2-AMTs had lower levels of PrP(Sc) and associated astrocytic gliosis, with each compound resulting in a distinct pattern of deposition. Notably, IND125 prevented both PrP(Sc) accumulation and astrocytic gliosis in the cerebrum. Progressive central nervous system dysfunction in the IND125-treated mice was presumably due to the PrP(Sc) that accumulated in their brainstems. Disappointingly, none of the four new 2-AMTs prolonged the lives of mice expressing a chimeric human/mouse PrP transgene inoculated with Creutzfeldt-Jakob disease prions