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  • 90
    Durect Corporation osmotic minipump implantation osmotic minipumps
    Development of mean arterial blood pressure ( MAP ) during follow‐up. MAP increases in animals after implantation of ANG II ‐containing osmotic <t>minipumps</t> ( n = 9), whereas no changes were detected in vehicle control ( n = 7). Data are expressed as mean ± SD .
    Osmotic Minipump Implantation Osmotic Minipumps, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 90/100, based on 432 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    90
    ALZA osmotic minipump
    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS <t>minipumps</t> were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P
    Osmotic Minipump, supplied by ALZA, used in various techniques. Bioz Stars score: 90/100, based on 17 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Charles River Laboratories osmotic minipumps
    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS <t>minipumps</t> were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P
    Osmotic Minipumps, supplied by Charles River Laboratories, used in various techniques. Bioz Stars score: 92/100, based on 7 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Durect Corporation 2ml2 osmotic minipumps
    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS <t>minipumps</t> were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P
    2ml2 Osmotic Minipumps, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 88/100, based on 7 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    ALZA 1002 osmotic minipump
    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS <t>minipumps</t> were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P
    1002 Osmotic Minipump, supplied by ALZA, used in various techniques. Bioz Stars score: 93/100, based on 5 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Durect Corporation 2001 osmotic minipump
    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS <t>minipumps</t> were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P
    2001 Osmotic Minipump, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 85/100, based on 9 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    85
    Durect Corporation osmotic minipump infusion
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    Osmotic Minipump Infusion, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 85/100, based on 18 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ALZA 2004 osmotic minipump
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    2004 Osmotic Minipump, supplied by ALZA, used in various techniques. Bioz Stars score: 85/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Durect Corporation 2002 osmotic minipump
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    2002 Osmotic Minipump, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 85/100, based on 8 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ALZA 2001 osmotic minipumps
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    2001 Osmotic Minipumps, supplied by ALZA, used in various techniques. Bioz Stars score: 88/100, based on 7 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Durect Corporation 1004 osmotic minipumps
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    1004 Osmotic Minipumps, supplied by Durect Corporation, used in various techniques. Bioz Stars score: 90/100, based on 12 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ALZA 2002 osmotic minipump
    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous <t>minipump</t> infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P
    2002 Osmotic Minipump, supplied by ALZA, used in various techniques. Bioz Stars score: 85/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    Development of mean arterial blood pressure ( MAP ) during follow‐up. MAP increases in animals after implantation of ANG II ‐containing osmotic minipumps ( n = 9), whereas no changes were detected in vehicle control ( n = 7). Data are expressed as mean ± SD .

    Journal: Physiological Reports

    Article Title: Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model. Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model

    doi: 10.14814/phy2.12897

    Figure Lengend Snippet: Development of mean arterial blood pressure ( MAP ) during follow‐up. MAP increases in animals after implantation of ANG II ‐containing osmotic minipumps ( n = 9), whereas no changes were detected in vehicle control ( n = 7). Data are expressed as mean ± SD .

    Article Snippet: Implantation of osmotic minipumps Osmotic minipumps (2ML4, ALZET, Cupertino, CA) were loaded with ANG II acetate (Sigma‐Aldrich, St. Louis, MO) dissolved in 0.9% NaCl according to body weight to achieve a dose of 500 ng/kg per hour (ANG II group) or 0.9% NaCl (control group), respectively (McMahon et al. ; Odenbach et al. ; Brand et al. ; Lemley et al. ).

    Techniques:

    Study protocol. Mean arterial blood pressure ( MAP ) was measured weekly throughout the experiment, starting 2 weeks before the implantation of osmotic minipumps (baseline). Cardiovascular magnetic resonance was performed in the same procedure as pump implantation and after 7 weeks of treatment (follow‐up). Two animals were implanted with cardiac rhythm monitoring devices. After 8 weeks, all animals were electrophysiologically characterized using epicardial multielectrode mapping.

    Journal: Physiological Reports

    Article Title: Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model. Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model

    doi: 10.14814/phy2.12897

    Figure Lengend Snippet: Study protocol. Mean arterial blood pressure ( MAP ) was measured weekly throughout the experiment, starting 2 weeks before the implantation of osmotic minipumps (baseline). Cardiovascular magnetic resonance was performed in the same procedure as pump implantation and after 7 weeks of treatment (follow‐up). Two animals were implanted with cardiac rhythm monitoring devices. After 8 weeks, all animals were electrophysiologically characterized using epicardial multielectrode mapping.

    Article Snippet: Implantation of osmotic minipumps Osmotic minipumps (2ML4, ALZET, Cupertino, CA) were loaded with ANG II acetate (Sigma‐Aldrich, St. Louis, MO) dissolved in 0.9% NaCl according to body weight to achieve a dose of 500 ng/kg per hour (ANG II group) or 0.9% NaCl (control group), respectively (McMahon et al. ; Odenbach et al. ; Brand et al. ; Lemley et al. ).

    Techniques:

    T cell survival is mediated by DC-secreted factors and IL-6. (A) Expression of GM-CSFR-α, GM-CSFR-β (AIC2B), and IL-2Rβ was determined by quantitative RT-PCR using cDNA of cells indicated. Naive CD62L + CD4 + T cells (lane 1) and splenic CD11c + DC (lane 5) were purified by flow cytometry (purity > 98%). Th1 (lane 2), Th2 (lane 3), and Th17 (lane 4) polarized CD4 + T cells. (B and C) DC of GM-CSF −/− or GM-CSF +/+ mice were cultured with purified CD4 + T cells from DO11.10/GM-CSF −/− or DO11.10/GM-CSF +/+ mice, respectively, in the presence of titrating amounts of OVA 323-339. (B) IL-6 levels in the culture supernatant at day 3 were determined by ELISA. (C) Proliferation measured by 3 H-Thymidine incorporation in the absence and in the presence of 20 ng/ml rIL-6. (D) Splenocytes of DO11.10/GM-CSF +/+ or GM-CSF −/− mice were cultured with 1 μM OVA 323-339 in the absence and presence of 20ng/ml rIL-6 for 3 d before staining of cells with KJ1-26 + mAb, Annexin V (AV), and PI and analysis by flow cytometry. Dot plot gated on KJ1-26 + cells shows early apoptotic cells (PI − AV + ), late apoptotic (PI + AV + ), and dead cells (PI + AV − ). (E) GM-CSF–deficient cultures were supplemented with rIL-1, rIL-2, or rIL-6. Proliferation was measured by 3 H-Thymidine incorporation after 3 d of culture. Proliferation index was calculated as described in Materials and methods. (F) CD4 + T cells purified from DO11.10/GM-CSF +/+ or DO11.10/GM-CSF −/− mice were injected i.v. into GM-CSF +/+ or GM-CSF −/− mice, respectively. 2 d later, groups of KO and WT mice were implanted with osmotic minipumps containing hIL-6 or were sham operated. Subsequently, mice were immunized with 200 μg OVA 323-339 peptide emulsified in CFA. After 7 d, draining LN and spleen cells were analyzed by flow cytometry. Symbols indicate total number of splenic KJ1-26 + cells of individual mice. Horizontal lines indicate averages of groups. Shown is one representative experiment of three performed. *,

    Journal: The Journal of Experimental Medicine

    Article Title: GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival

    doi: 10.1084/jem.20071119

    Figure Lengend Snippet: T cell survival is mediated by DC-secreted factors and IL-6. (A) Expression of GM-CSFR-α, GM-CSFR-β (AIC2B), and IL-2Rβ was determined by quantitative RT-PCR using cDNA of cells indicated. Naive CD62L + CD4 + T cells (lane 1) and splenic CD11c + DC (lane 5) were purified by flow cytometry (purity > 98%). Th1 (lane 2), Th2 (lane 3), and Th17 (lane 4) polarized CD4 + T cells. (B and C) DC of GM-CSF −/− or GM-CSF +/+ mice were cultured with purified CD4 + T cells from DO11.10/GM-CSF −/− or DO11.10/GM-CSF +/+ mice, respectively, in the presence of titrating amounts of OVA 323-339. (B) IL-6 levels in the culture supernatant at day 3 were determined by ELISA. (C) Proliferation measured by 3 H-Thymidine incorporation in the absence and in the presence of 20 ng/ml rIL-6. (D) Splenocytes of DO11.10/GM-CSF +/+ or GM-CSF −/− mice were cultured with 1 μM OVA 323-339 in the absence and presence of 20ng/ml rIL-6 for 3 d before staining of cells with KJ1-26 + mAb, Annexin V (AV), and PI and analysis by flow cytometry. Dot plot gated on KJ1-26 + cells shows early apoptotic cells (PI − AV + ), late apoptotic (PI + AV + ), and dead cells (PI + AV − ). (E) GM-CSF–deficient cultures were supplemented with rIL-1, rIL-2, or rIL-6. Proliferation was measured by 3 H-Thymidine incorporation after 3 d of culture. Proliferation index was calculated as described in Materials and methods. (F) CD4 + T cells purified from DO11.10/GM-CSF +/+ or DO11.10/GM-CSF −/− mice were injected i.v. into GM-CSF +/+ or GM-CSF −/− mice, respectively. 2 d later, groups of KO and WT mice were implanted with osmotic minipumps containing hIL-6 or were sham operated. Subsequently, mice were immunized with 200 μg OVA 323-339 peptide emulsified in CFA. After 7 d, draining LN and spleen cells were analyzed by flow cytometry. Symbols indicate total number of splenic KJ1-26 + cells of individual mice. Horizontal lines indicate averages of groups. Shown is one representative experiment of three performed. *,

    Article Snippet: After 1–2 d, osmotic minipumps (Alzet 2001; DURECT Corporation) were filled with 26 μg (3 μg/d delivery) rec hIL-6 and s.c. implanted in mice.

    Techniques: Expressing, Quantitative RT-PCR, Purification, Flow Cytometry, Cytometry, Mouse Assay, Cell Culture, Enzyme-linked Immunosorbent Assay, Staining, Injection

    EC-SOD KO mice are sensitized to angiotensin II–induced proteinuric renal injury. Mice undergo unilateral nephrectomy and are then treated with 1.5 mg/kg per day of angiotensin II via an osmotic minipump and euthanized after 4 weeks. (A–G)

    Journal: Journal of the American Society of Nephrology : JASN

    Article Title: Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease

    doi: 10.1681/ASN.2014060613

    Figure Lengend Snippet: EC-SOD KO mice are sensitized to angiotensin II–induced proteinuric renal injury. Mice undergo unilateral nephrectomy and are then treated with 1.5 mg/kg per day of angiotensin II via an osmotic minipump and euthanized after 4 weeks. (A–G)

    Article Snippet: On day 0, a subcutaneous osmotic minipump (model 2004; Alzet, Cupertino, CA) was implanted to deliver a constant infusion of angiotensin II (1.5 mg/kg per day; Sigma-Aldrich).

    Techniques: Mouse Assay

    Blockade of αv integrins by a novel small molecule (CWHM 12) attenuates liver and lung fibrosis ( a ) Dosing regime in the prophylactic liver fibrosis model (left panel). Alzet minipumps containing CWHM 12 or vehicle were inserted, followed by CCl 4 I.P. twice weekly for 6 weeks. Picrosirius red (upper) and αSMA immunohistochemistry (lower) of liver tissue from control and CWHM 12 treated mice ( n = 6 female mice per group) after chronic CCl 4 treatment. Scale bar, 200μm. ( b ) Digital image analysis of picrosirius red staining. ( c ) Hydroxyproline analysis. ( d ) Digital image analysis of αSMA staining. ( e ) Dosing regime in the therapeutic liver fibrosis model (left panel). Mice were given CCl 4 I.P. twice weekly for 3 weeks, then Alzet minipumps containing either CWHM 12 or vehicle were inserted, followed by a further 3 weeks of CCl 4 I.P. twice weekly. Picrosirius red (upper) and αSMA immunohistochemistry (lower) of liver tissue from control and CWHM 12 treated mice ( n =14 female mice per group) after chronic CCl 4 treatment. Scale bar, 200μm. ( f ) Digital image analysis of picrosirius red staining. ( g ) Hydroxyproline analysis. ( h ) Digital image analysis of αSMA staining. ( i ) Dosing regime in the therapeutic lung fibrosis model. Alzet minipumps containing either CWHM 12 or vehicle were inserted 14 days after treatment with bleomycin or saline, and lungs were harvested at 28 days. ( j ) Picrosirius red staining of lung tissue from control and CWHM 12 treated mice 28 days after bleomycin instillation ( n = 15 female mice per group). Scale bar, 100μm (left panel). Hydroxyproline analysis (right panel). Data are mean ± s.e.m. * P

    Journal: Nature medicine

    Article Title: Selective ?v integrin depletion identifies a core, targetable molecular pathway that regulates fibrosis across solid organs

    doi: 10.1038/nm.3282

    Figure Lengend Snippet: Blockade of αv integrins by a novel small molecule (CWHM 12) attenuates liver and lung fibrosis ( a ) Dosing regime in the prophylactic liver fibrosis model (left panel). Alzet minipumps containing CWHM 12 or vehicle were inserted, followed by CCl 4 I.P. twice weekly for 6 weeks. Picrosirius red (upper) and αSMA immunohistochemistry (lower) of liver tissue from control and CWHM 12 treated mice ( n = 6 female mice per group) after chronic CCl 4 treatment. Scale bar, 200μm. ( b ) Digital image analysis of picrosirius red staining. ( c ) Hydroxyproline analysis. ( d ) Digital image analysis of αSMA staining. ( e ) Dosing regime in the therapeutic liver fibrosis model (left panel). Mice were given CCl 4 I.P. twice weekly for 3 weeks, then Alzet minipumps containing either CWHM 12 or vehicle were inserted, followed by a further 3 weeks of CCl 4 I.P. twice weekly. Picrosirius red (upper) and αSMA immunohistochemistry (lower) of liver tissue from control and CWHM 12 treated mice ( n =14 female mice per group) after chronic CCl 4 treatment. Scale bar, 200μm. ( f ) Digital image analysis of picrosirius red staining. ( g ) Hydroxyproline analysis. ( h ) Digital image analysis of αSMA staining. ( i ) Dosing regime in the therapeutic lung fibrosis model. Alzet minipumps containing either CWHM 12 or vehicle were inserted 14 days after treatment with bleomycin or saline, and lungs were harvested at 28 days. ( j ) Picrosirius red staining of lung tissue from control and CWHM 12 treated mice 28 days after bleomycin instillation ( n = 15 female mice per group). Scale bar, 100μm (left panel). Hydroxyproline analysis (right panel). Data are mean ± s.e.m. * P

    Article Snippet: We initially examined the potential of CWHM 12 to prevent liver fibrosis by inserting Alzet osmotic minipumps containing either CWHM 12 or vehicle control into mice, followed by CCl4 injections twice weekly for 6 weeks ( ).

    Techniques: Immunohistochemistry, Mouse Assay, Staining

    HSVLatEnk-infected polyarthritic rats exhibited reduced thermal hyperalgesia and improved spontaneous locomotor activity. Response (paw withdrawal) latencies ( A ) of controls ( n = 9) and HSVLatEnk-infected ( n = 15) polyarthritic rats to radiant heating (intensity 7; Ugo Basile) were measured 3 weeks after infection. Rearings ( B ) and horizontal locomotor activity ( C ) of control (sham- or HSVLatβ-gal-infected) ( n = 12) and HSVLatEnk-infected ( n = 15) polyarthritic rats in a red-lighted open field were video monitored and assessed every minute during a 7 min period. Animals were then implanted subcutaneously for 3 d with an Alzet osmotic minipump delivering 3 mg · kg −1 · d −1 of either naloxone (○) or naloxone methiodide (▵) ( antago ), and thermal hyperalgesia and locomotor activity were assessed. Performances of normal healthy rats are indicated by the horizontal dashed line and gray band in the three behavioral tests (mean ± SEM; n = 6–7). * p

    Journal: The Journal of Neuroscience

    Article Title: Therapeutic Efficacy in Experimental Polyarthritis of Viral-Driven Enkephalin Overproduction in Sensory Neurons

    doi: 10.1523/JNEUROSCI.21-20-07881.2001

    Figure Lengend Snippet: HSVLatEnk-infected polyarthritic rats exhibited reduced thermal hyperalgesia and improved spontaneous locomotor activity. Response (paw withdrawal) latencies ( A ) of controls ( n = 9) and HSVLatEnk-infected ( n = 15) polyarthritic rats to radiant heating (intensity 7; Ugo Basile) were measured 3 weeks after infection. Rearings ( B ) and horizontal locomotor activity ( C ) of control (sham- or HSVLatβ-gal-infected) ( n = 12) and HSVLatEnk-infected ( n = 15) polyarthritic rats in a red-lighted open field were video monitored and assessed every minute during a 7 min period. Animals were then implanted subcutaneously for 3 d with an Alzet osmotic minipump delivering 3 mg · kg −1 · d −1 of either naloxone (○) or naloxone methiodide (▵) ( antago ), and thermal hyperalgesia and locomotor activity were assessed. Performances of normal healthy rats are indicated by the horizontal dashed line and gray band in the three behavioral tests (mean ± SEM; n = 6–7). * p

    Article Snippet: The skin was incised at the level of the scapula, an Alzet osmotic minipump (delivery rate of 1 μl/hr; 2001 model; AlzaScientific Products, Palo Alto, CA) was implanted subcutaneously, and the incision was then sutured.

    Techniques: Infection, Activity Assay

    Angiotensin II-induced hypertension is attenuated in Pkd 2 smKO mice. ( A ) Telemetric blood pressure time course showing the development of angiotensin II-induced hypertension in Pkd2 fl/fl (n = 6) and Pkd 2 smKO mice (n = 9). Osmotic minipumps containing either saline or angiotensin II were implanted one day prior to day 0. * indicates p

    Journal: eLife

    Article Title: Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

    doi: 10.7554/eLife.42628

    Figure Lengend Snippet: Angiotensin II-induced hypertension is attenuated in Pkd 2 smKO mice. ( A ) Telemetric blood pressure time course showing the development of angiotensin II-induced hypertension in Pkd2 fl/fl (n = 6) and Pkd 2 smKO mice (n = 9). Osmotic minipumps containing either saline or angiotensin II were implanted one day prior to day 0. * indicates p

    Article Snippet: Angiotensin II (1.5 ng/g/min) and saline (0.9 NaCl) were infused in mice using subcutaneous osmotic minipumps (Alzet).

    Techniques: Mouse Assay

    Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS minipumps were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P

    Journal: Annals of neurology

    Article Title: Recovery from Chronic Spinal Cord Contusion after Nogo Receptor Intervention

    doi: 10.1002/ana.22527

    Figure Lengend Snippet: Recovery of weight bearing after NgR1 treatment of chronically spinal cord contused rats A , Spontaneous improvement of open field locomotion (BBB score) as a function of time after thoracic spinal cord contusion injury for all rats prior to randomization to IgG or NgR1 treatment. Mean ± sem, n = 64. B , Schematic of experiment. Two weeks after the i.c.v. cannula implantation (12 weeks post-contusion injury), rats were assigned to one of two treatment groups. The PBS minipumps were replaced with new osmotic minipumps filled with 2.25 mg AA-NgR(310)ecto-Fc (0.29 mg/kg/day) or 2.25 mg rat IgG in 2 ml PBS. The duration of treatment was 12 weeks. A new osmotic mimipump filled with same amount of AA-NgR(310)ecto-Fc or rat IgG replaced each depleted pump every 4 weeks. C , Examples of a control rat without weight support at the end of the treatment period and two of the seven AA-NgR(310)ecto-Fc treated rats that regained weight support. D , The increase in the percentage of rats showing body weight support with at least one hindlimb as a function of time during therapy is reported. P =0.022 by repeated measures ANOVA for the effect of NgR1 versus IgG treatment, and *, P

    Article Snippet: Two weeks after cannula implantation (12 weeks post-contusion injury), the rats were reanesthetized and the minipumps were replaced with new osmotic minipumps (Alza Scientific Products) connected to the same cannula.

    Techniques:

    Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous minipump infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: Rcan1 mediates AngII-induced neointima formation. The left femoral artery was wire injured and AngII was administrated by subcutaneous minipump infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative Rcan1 immunostaining of left femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice ( n = 5/group). Bar, 50 µm. (B) Images of femoral artery cross sections from AngII-treated Rcan1 +/+ and Rcan1 −/− mice stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome stains. Bar, 50 µm. Representative experiments are shown of 8–11 performed. (C) Quantification of the I/M ratio between groups. Data are means ± SEM. Mice per group were 8 Rcan1 +/+ AngII and 11 Rcan1 −/− AngII. *, P

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: Immunostaining, Mouse Assay, Staining

    Rcan1 mediates AngII-induced AAA. Apoe −/− Rcan1 +/+ or Apoe −/− Rcan1 −/− mice were minipump infused with 1 µg/kg/min AngII for 28 d. (A) Rcan1 immunostaining (top) of abdominal aortic cross sections from saline- and AngII-treated Apoe −/− Rcan1 +/+ mice. IgG-staining serves as negative control. Rcan1-4 immunoblot of thoracic aorta (t) and the AAA segment of Apoe −/− Rcan1 +/+ mice are shown. Bar, 50 µm. (B) CD3, Mac3, SMA, and vimentin immunostaining of abdominal aortic cross sections from AngII-treated Apoe −/− Rcan1 +/+ mice. Bar, 50 µm. (A and B) Representative experiments are shown of four performed. (C) Abdominal aortas from AngII-treated mice. (D) Ultrasound images of abdominal aortas from AngII-infused animals. Transverse (top) and longitudinal (bottom) images were taken at the level of the suprarenal aorta. Yellow lines mark lumen boundary. (E) Suprarenal abdominal aorta cross sections stained with Masson’s trichrome. Bar, 100 µm. (C–E) Representative experiments are shown of 15–16 performed. (F and G) Maximum suprarenal abdominal aortic diameter (in millimeters) in AngII-treated mice measured at treatment start and treatment finish. (F) Triangles and squares represent individual mice and means ± SEM from Apoe −/− Rcan1 +/+ mice ( n = 16) and Apoe −/− Rcan1 −/− mice ( n = 15), respectively. *, P

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: Rcan1 mediates AngII-induced AAA. Apoe −/− Rcan1 +/+ or Apoe −/− Rcan1 −/− mice were minipump infused with 1 µg/kg/min AngII for 28 d. (A) Rcan1 immunostaining (top) of abdominal aortic cross sections from saline- and AngII-treated Apoe −/− Rcan1 +/+ mice. IgG-staining serves as negative control. Rcan1-4 immunoblot of thoracic aorta (t) and the AAA segment of Apoe −/− Rcan1 +/+ mice are shown. Bar, 50 µm. (B) CD3, Mac3, SMA, and vimentin immunostaining of abdominal aortic cross sections from AngII-treated Apoe −/− Rcan1 +/+ mice. Bar, 50 µm. (A and B) Representative experiments are shown of four performed. (C) Abdominal aortas from AngII-treated mice. (D) Ultrasound images of abdominal aortas from AngII-infused animals. Transverse (top) and longitudinal (bottom) images were taken at the level of the suprarenal aorta. Yellow lines mark lumen boundary. (E) Suprarenal abdominal aorta cross sections stained with Masson’s trichrome. Bar, 100 µm. (C–E) Representative experiments are shown of 15–16 performed. (F and G) Maximum suprarenal abdominal aortic diameter (in millimeters) in AngII-treated mice measured at treatment start and treatment finish. (F) Triangles and squares represent individual mice and means ± SEM from Apoe −/− Rcan1 +/+ mice ( n = 16) and Apoe −/− Rcan1 −/− mice ( n = 15), respectively. *, P

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: Mouse Assay, Immunostaining, Staining, Negative Control

    Systemic delivery of LxVP lentivirus inhibits development of AngII-induced AAA. (A) Mice were inoculated with lentivirus expressing GFP-tagged LxVP or LxVPmutant 100 µl virus solution (10 11 particles in 100 µl) injected directly into the right jugular vein 1 mo before staining of aortic sections. (A) GFP immunostaining in aortic sections. IgG staining serves as a negative control. Bars: 100 µm (left); 50 µm (middle and right). A representative experiment is shown of six performed in independent mice. (B) Apoe −/− mice were inoculated with lentivirus expressing GFP-tagged LxVP or LxVPmutant 1 mo before minipump-infusion of 1 µg/kg/min AngII for 28 d. Maximum suprarenal abdominal aortic diameter (in millimeters) is shown. Triangles and squares represent individual mice and means ± SEM from six mice per condition, respectively. *, P

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: Systemic delivery of LxVP lentivirus inhibits development of AngII-induced AAA. (A) Mice were inoculated with lentivirus expressing GFP-tagged LxVP or LxVPmutant 100 µl virus solution (10 11 particles in 100 µl) injected directly into the right jugular vein 1 mo before staining of aortic sections. (A) GFP immunostaining in aortic sections. IgG staining serves as a negative control. Bars: 100 µm (left); 50 µm (middle and right). A representative experiment is shown of six performed in independent mice. (B) Apoe −/− mice were inoculated with lentivirus expressing GFP-tagged LxVP or LxVPmutant 1 mo before minipump-infusion of 1 µg/kg/min AngII for 28 d. Maximum suprarenal abdominal aortic diameter (in millimeters) is shown. Triangles and squares represent individual mice and means ± SEM from six mice per condition, respectively. *, P

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: Mouse Assay, Expressing, Injection, Staining, Immunostaining, Negative Control

    CsA inhibits AngII-induced neointimal formation in a model of femoral artery injury. The left femoral artery was wire injured and AngII was administrated by subcutaneous minipump infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative images of left femoral artery cross sections stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome (Masson). Bar, 50 µm. (B) Summary of morphometric data of the different treatment groups. Area data are shown in micrometers squared. Because the endothelial monolayer appeared as a line in the noninjured arteries, its area was considered to be 0, and the mean I/M ratio and percentage of stenosis were also 0. (C) Quantification of the ratio of the thickness of intima and media (I/M ratio) in the injured conditions shown in A. Data are means ± SEM. Numbers of mice per group were 7 saline, 13 AngII, 7 CsA+AngII, 5 CsA, and 10 noninjured. *, P

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: CsA inhibits AngII-induced neointimal formation in a model of femoral artery injury. The left femoral artery was wire injured and AngII was administrated by subcutaneous minipump infusion during 14 d. CsA administration commenced 24 h before treatment with AngII and continued throughout the AngII infusion period. (A) Representative images of left femoral artery cross sections stained with hematoxylin-eosin (HE), Van Gieson (VG), and Masson’s trichrome (Masson). Bar, 50 µm. (B) Summary of morphometric data of the different treatment groups. Area data are shown in micrometers squared. Because the endothelial monolayer appeared as a line in the noninjured arteries, its area was considered to be 0, and the mean I/M ratio and percentage of stenosis were also 0. (C) Quantification of the ratio of the thickness of intima and media (I/M ratio) in the injured conditions shown in A. Data are means ± SEM. Numbers of mice per group were 7 saline, 13 AngII, 7 CsA+AngII, 5 CsA, and 10 noninjured. *, P

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: Staining, Mouse Assay

    CsA inhibits development of AngII-induced AAA. Apoe −/− mice were minipump infused with 5 mg/kg/d CsA, 1 d before commencing similar administration with saline or 1 µg/kg/min AngII for 28 d. (A) Representative abdominal aortas of Apoe −/− mice treated as indicated. (B) Representative high-frequency ultrasound (US) images of abdominal aortas. Transverse (top) and longitudinal (bottom) images were taken at the level of the suprarenal aorta. Yellow lines mark the lumen boundary. (C) Maximum suprarenal abdominal aortic diameter (in millimeters) measured from transverse US images. Triangles and squares represent individual mice and means ± SEM, respectively. Numbers of mice per group were 9 saline, 24 AngII, 9 CsA+AngII, and 7 CsA. *, P

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: CsA inhibits development of AngII-induced AAA. Apoe −/− mice were minipump infused with 5 mg/kg/d CsA, 1 d before commencing similar administration with saline or 1 µg/kg/min AngII for 28 d. (A) Representative abdominal aortas of Apoe −/− mice treated as indicated. (B) Representative high-frequency ultrasound (US) images of abdominal aortas. Transverse (top) and longitudinal (bottom) images were taken at the level of the suprarenal aorta. Yellow lines mark the lumen boundary. (C) Maximum suprarenal abdominal aortic diameter (in millimeters) measured from transverse US images. Triangles and squares represent individual mice and means ± SEM, respectively. Numbers of mice per group were 9 saline, 24 AngII, 9 CsA+AngII, and 7 CsA. *, P

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: Mouse Assay

    AngII activates the CN–NFAT pathway in VSMCs in vivo. (A–C) Mice were inoculated with 5 mg/kg/d CsA, 10 mg/kg/d of the AngII type 1 receptor (AT 1 ) blocker losartan, or 30 mg/kg/d of the AngII type 2 receptor (AT 2 ) blocker PD123319 by subcutaneous osmotic minipump infusion for 24 h before similar administration of 1 µg/kg/min AngII for 1 h. Aortic sections from these mice were analyzed by Southwestern histochemistry with NFAT probe (A), hematoxylin-eosin (HE) staining (B), and Sp1 immunohistochemistry (C). Bars, 50 µm. (D) NFAT immunoblot in extracts from VSMCs stimulated with 1 µM AngII for 1 h after pretreatment as indicated (1 h) with 200 ng/ml CsA. Arrowheads indicate NFAT proteins with different degrees of phosphorylation. NFATc2 was tested in parallel protein extracts of Jurkat cells (JK). Representative experiments are shown of four to six performed.

    Journal: The Journal of Experimental Medicine

    Article Title: Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    doi: 10.1084/jem.20110503

    Figure Lengend Snippet: AngII activates the CN–NFAT pathway in VSMCs in vivo. (A–C) Mice were inoculated with 5 mg/kg/d CsA, 10 mg/kg/d of the AngII type 1 receptor (AT 1 ) blocker losartan, or 30 mg/kg/d of the AngII type 2 receptor (AT 2 ) blocker PD123319 by subcutaneous osmotic minipump infusion for 24 h before similar administration of 1 µg/kg/min AngII for 1 h. Aortic sections from these mice were analyzed by Southwestern histochemistry with NFAT probe (A), hematoxylin-eosin (HE) staining (B), and Sp1 immunohistochemistry (C). Bars, 50 µm. (D) NFAT immunoblot in extracts from VSMCs stimulated with 1 µM AngII for 1 h after pretreatment as indicated (1 h) with 200 ng/ml CsA. Arrowheads indicate NFAT proteins with different degrees of phosphorylation. NFATc2 was tested in parallel protein extracts of Jurkat cells (JK). Representative experiments are shown of four to six performed.

    Article Snippet: 2-mo-old mice were administered with various compounds by subcutaneous osmotic minipump infusion (Alzet Corp) as described previously ( ).

    Techniques: In Vivo, Mouse Assay, Staining, Immunohistochemistry