Characterization of aortic root atherosclerosis in ApoE knockout mice: High-resolution in vivo and ex vivo MRM with histological correlation

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.

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Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

Bioconjugate Chemistry ◽

10.1021/acs.bioconjchem.1c00271 ◽

2021 ◽

Author(s):

Massis Krekorian ◽

Gerwin G. W. Sandker ◽

Kimberley R. G. Cortenbach ◽

Oya Tagit ◽

N. Koen van Riessen ◽

...

Keyword(s):

Glycolic Acid ◽

Ex Vivo ◽

Cell Labeling ◽

Autologous Cell

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In VivoVisualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1αActivity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/262741 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Hirofumi Fujii ◽

Masayuki Yamaguchi ◽

Kazumasa Inoue ◽

Yasuko Mutou ◽

Masashi Ueda ◽

...

Keyword(s):

High Resolution ◽

Ex Vivo ◽

Hypoxia Inducible Factor ◽

Chimeric Protein ◽

Small Animal ◽

Ct Scanner ◽

Heterogeneous Distribution ◽

Fusion Images ◽

Intratumoral Distribution

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α(HIF) activity in tumor tissuesin vivo.Methods. We synthesized of125I-IPOS, a125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtainedin vivoSPECT-CT fusion images were compared withex vivoimages of excised tumors. Fusion imaging with MRI was also examined.Results.125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of125I-IPOS.Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activityin vivo.

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About Puncture Testing Applied for Mechanical Characterization of Fetal Membranes

Journal of Biomechanical Engineering ◽

10.1115/1.4028446 ◽

2014 ◽

Vol 136 (11) ◽

Cited By ~ 6

Author(s):

Wilfried Bürzle ◽

Edoardo Mazza ◽

John J. Moore

Keyword(s):

Deformation Behavior ◽

Mechanical Characterization ◽

Ex Vivo ◽

Fetal Membrane ◽

Membrane Rupture ◽

Resistance To Deformation ◽

Ex Vivo Testing ◽

Insight Into

Puncture testing has been applied in several studies for the mechanical characterization of human fetal membrane (FM) tissue, and significant knowledge has been gained from these investigations. When comparing results of mechanical testing (puncture, inflation, and uniaxial tension), we have observed discrepancies in the rupture sequence of FM tissue and significant differences in the deformation behavior. This study was undertaken to clarify these discrepancies. Puncture experiments on FM samples were performed to reproduce previous findings, and numerical simulations were carried out to rationalize particular aspects of membrane failure. The results demonstrate that both rupture sequence and resistance to deformation depend on the samples' fixation. Soft fixation leads to slippage in the clamping, which reduces mechanical loading of the amnion layer and results in chorion rupturing first. Conversely, the stiffer, stronger, and less extensible amnion layer fails first if tight fixation is used. The results provide a novel insight into the interpretation of ex vivo testing as well as in vivo membrane rupture.

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In vivo characterization of the transitional bronchioles by aerosol-derived airway morphometry

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.3.920 ◽

1999 ◽

Vol 87 (3) ◽

pp. 920-927 ◽

Cited By ~ 4

Author(s):

Kirby L. Zeman ◽

Gerhard Scheuch ◽

Knut Sommerer ◽

James S. Brown ◽

William D. Bennett

Keyword(s):

Ex Vivo ◽

Normal Subjects ◽

Characteristic Line ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Lung Capacity ◽

Single Breath ◽

In Vivo Characterization

Effective airway dimensions (EADs) were determined in vivo by aerosol-derived airway morphometry as a function of volumetric lung depth (VLD) to identify and characterize, noninvasively, the caliber of the transitional bronchiole region of the human lung and to compare the EADs by age, gender, and disease. By logarithmically plotting EAD vs. VLD, two distinct regions of the lung emerged that were identified by characteristic line slopes. The intersection of proximal and distal segments was defined as VLDtransand associated EADtrans. In our normal subjects ( n = 20), VLDtrans [345 ± 83 (SD) ml] correlated significantly with anatomic dead space (224 ± 34 ml) and end of phase II of single-breath nitrogen washout (360 ± 53 ml). The corresponding EADtranswas 0.42 ± 0.07 mm, in agreement with other ex vivo measurements of the transitional bronchioles. VLDtrans was smaller (216 ± 64 ml) and EADtrans was larger (0.83 ± 0.04 mm) in our patients with chronic obstructive pulmonary disease ( n = 13). VLDtrans increased with age for children (age 8–18 yr; P = 0.006, n = 26) and with total lung capacity for age 8–81 yr ( P < 0.001, n = 61). This study extends the usefulness of aerosol-derived airway morphometry to in vivo measurements of the transitional bronchioles.

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Ex Vivo Isolation and Characterization of Cd4+Cd25+ T Cells with Regulatory Properties from Human Blood

Journal of Experimental Medicine ◽

10.1084/jem.193.11.1303 ◽

2001 ◽

Vol 193 (11) ◽

pp. 1303-1310 ◽

Cited By ~ 797

Author(s):

Detlef Dieckmann ◽

Heidi Plottner ◽

Susanne Berchtold ◽

Thomas Berger ◽

Gerold Schuler

Keyword(s):

T Cells ◽

Cytotoxic T Lymphocyte ◽

Ex Vivo ◽

Cell Receptor ◽

Regulatory Cells ◽

Suppressor T Cells ◽

Isolation And Characterization ◽

Regulatory Properties

It has been known for years that rodents harbor a unique population of CD4+CD25+ “professional” regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4+CD25+CD45RO+ T cells (mean 6% of CD4+ T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4+CD25+ T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte–associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4+CD25+ T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4+CD25+ T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4+ and CD8+ T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4+CD25+ T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.

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