Parametric approaches to micro-scale characterization of tissue volumes in vivo and ex vivo: Imaging microvasculature, attenuation, birefringence, and stiffness (Conference Presentation)

Author(s):  
David D. Sampson ◽  
Lixin Chin ◽  
Peijun Gong ◽  
Philip Wijesinghe ◽  
Shaghayegh Es’haghian ◽  
...  
Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1791
Author(s):  
Rosa Scala ◽  
Fatima Maqoud ◽  
Nicola Zizzo ◽  
Giuseppe Passantino ◽  
Antonietta Mele ◽  
...  

(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.


Author(s):  
Massis Krekorian ◽  
Gerwin G. W. Sandker ◽  
Kimberley R. G. Cortenbach ◽  
Oya Tagit ◽  
N. Koen van Riessen ◽  
...  

2014 ◽  
Vol 136 (11) ◽  
Author(s):  
Wilfried Bürzle ◽  
Edoardo Mazza ◽  
John J. Moore

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.


1999 ◽  
Vol 87 (3) ◽  
pp. 920-927 ◽  
Author(s):  
Kirby L. Zeman ◽  
Gerhard Scheuch ◽  
Knut Sommerer ◽  
James S. Brown ◽  
William D. Bennett

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.


2001 ◽  
Vol 193 (11) ◽  
pp. 1303-1310 ◽  
Author(s):  
Detlef Dieckmann ◽  
Heidi Plottner ◽  
Susanne Berchtold ◽  
Thomas Berger ◽  
Gerold Schuler

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.


Blood ◽  
2020 ◽  
Author(s):  
Neeta Bala Tannan ◽  
Mandana T Manzari ◽  
Laurie Herviou ◽  
Mariana da Silva Ferreira ◽  
Connor J Hagen ◽  
...  

Cancer and normal cells utilize multiple anti-apoptotic BCL2 proteins to prevent cell death. Therapeutic targeting of multiple BCL2 family proteins enhances tumor killing, but is also associated with increased systemic toxicity. Here, we demonstrate that the dual targeting of MCL1 and BCL2 proteins, using the small molecules S63845 and venetoclax, induces durable remissions in mice harboring human DLBCL tumors but is accompanied by hematological toxicity and weight loss. To mitigate these toxicities, we encapsulated S63845 or venetoclax into nanoparticles targeting P-selectin that is enriched in tumor endothelial cells. In vivo and ex vivo imaging demonstrated preferential targeting of the nanoparticles to lymphoma tumors over vital organs. Mass-spectrometry analyses after nanoparticle drug administration confirmed tumor enrichment of the drug while reducing plasma levels. Furthermore, nanoparticle encapsulation allowed 3.5 to 6.5-fold reduction in drug dose, induced sustained remissions and minimized toxicity. Our results support the development of nanoparticles to deliver BH3 mimetic combinations in lymphoma and in general for toxic drugs in cancer therapy.


2016 ◽  
Vol 17 (4) ◽  
pp. 721-734 ◽  
Author(s):  
Wichaya Sriuttha ◽  
Nantawat Uttamo ◽  
Apisek Kongkaew ◽  
Jongkolnee Settakorn ◽  
Suchanan Rattanasalee ◽  
...  

2012 ◽  
Vol 18 (S2) ◽  
pp. 1420-1421 ◽  
Author(s):  
D. Frazer ◽  
P. Hosemann ◽  
C.A. Back ◽  
C. Deck ◽  
H. Khalifa

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.


2011 ◽  
Vol 52 (9) ◽  
pp. 978-988 ◽  
Author(s):  
Hitoshi Nakayama ◽  
Tomoyuki Kawase ◽  
Kazuhiro Okuda ◽  
Larry F Wolff ◽  
Hiromasa Yoshie

Background In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using 99mTc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner. Purpose To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model. Material and Methods The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (μCT) analysis, and histopathological examination. Results Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data ( r > 0.8, P < 0.02). Other good to excellent correlations ( r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume. Conclusion This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.


2018 ◽  
Author(s):  
Ksenia V. Shatilova ◽  
Georgii A. Aloian ◽  
Ilya V. Yaroslavsky ◽  
Gregory B. Altshuler ◽  
Maria Karabut ◽  
...  
Keyword(s):  
Ex Vivo ◽  

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