Focal nodular hyperplasia and hepatocellular adenoma: The value of shear wave elastography for differential diagnosis

[DOI:\hrefhttps://dx.doi.org/10.1016/j.ejrad.2015.07.02910.1016/j.ejrad.2015.07.029] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2629932326299323]This study assessed the clinical usefulness of shear wave elastography (SWE) during ultrasound for differentiating between focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HAs).\ SWE was performed on 56 patients presenting with 76 liver lesions (57 FNHs and 19HAs) that were confirmed by MRI and contrast-enhanced ultrasound (CEUS) (n=55) or by histology (n=21). A mean elasticity value was obtained for each lesion. The ratios of the elasticity of the lesions to the elasticity of the surrounding liver were determined. The optimal elasticity cut-off value for distinguishing between the two lesion types was determined using ROC analysis. All lesions that were classified as "undetermined" after CEUS were reclassified using the elasticity values.\ The mean elasticity value was 46.99 ± 31.15 kPa for FNHs and 12.08 ± 10.68 kPa for HAs (p<0.0001). The mean relative elasticity ratio values were 7.94 ± 6.43 and 1.91 ± 1.70, respectively (p<0.0001). The ROC analysis showed a maximal accuracy of 95% for identification with a cut-off of 18.8 kPa for lesion elasticity (accuracy of 96% with a cut-off of 1.98 for the relative elasticity ratio). A total of 68 CEUS were performed, and 17 lesions (25%) were classified as "undetermined" after CEUS. With these cut-off values 16 lesions (94.1%) were correctly reclassified as FNHs.\ SWE is a useful adjunctive tool for differentiation between FNH and HA during ultrasound examination

Evaluation of shearwave elastography for the characterisation of focal liver lesions on ultrasound

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Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro

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Neutrophil Recruitment to Lymph Nodes Limits Local Humoral Response to <i>Staphylococcus aureus</i>

<div><p>Neutrophils form the first line of host defense against bacterial pathogens. They are rapidly mobilized to sites of infection where they help marshal host defenses and remove bacteria by phagocytosis. While splenic neutrophils promote marginal zone B cell antibody production in response to administered T cell independent antigens, whether neutrophils shape humoral immunity in other lymphoid organs is controversial. Here we investigate the neutrophil influx following the local injection of <i>Staphylococcus aureus</i> adjacent to the inguinal lymph node and determine neutrophil impact on the lymph node humoral response. Using intravital microscopy we show that local immunization or infection recruits neutrophils from the blood to lymph nodes in waves. The second wave occurs temporally with neutrophils mobilized from the bone marrow. Within lymph nodes neutrophils infiltrate the medulla and interfollicular areas, but avoid crossing follicle borders. <i>In vivo</i> neutrophils form transient and long-lived interactions with B cells and plasma cells, and their depletion augments production of antigen-specific IgG and IgM in the lymph node. <i>In vitro</i> activated neutrophils establish synapse- and nanotube-like interactions with B cells and reduce B cell IgM production in a TGF- β1 dependent manner. Our data reveal that neutrophils mobilized from the bone marrow in response to a local bacterial challenge dampen the early humoral response in the lymph node.</p></div

Local LAC-GFP infection recruits neutrophils to the iLN.

<p>C57BL/6 or dsRed BM chimeric mice were injected subcutaneously near the iLN with LAC-GFP in amount of 1 x 10⁵ CFU per iLN or given PBS as a control. Neutrophil recruitment to the iLN was analyzed by flow cytometry between 0 and 48 h. PBS injected control is shown as a time point 0 of infection. DsRed chimeric mice were imaged using TP-LSM between 2 and 12 h after infection. (<b>A</b>) Kinetics of neutrophil mobilization to the iLN between 0 and 48 h after infection is shown. (<b>B</b>) Kinetics of neutrophil mobilization to the iLN between days 0 and 7 after infection is shown. (A, B) Percentages of Ly6G^hi/CD11b^hi population (left) and total Ly6G^hi/CD11b^hi cell numbers per iLN (right) in live cell gate are shown. N = 4 mice/8 iLNs. Means ± SD. (<b>C</b>) TP-LSM images of neutrophil accumulation (dsRed^hi, bright red) in iLN at 0 h (left), 2 h (middle), and 12 h (right) after LAC-GFP (green) injection are shown (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004827#ppat.1004827.s013" target="_blank">S7 Movie</a>). Blood vessels (EB, gray); collagen (second harmonic, blue). IFZ (IF), LN follicle (B, dotted line), and LN borders (dashed line) are labeled. Scale bars: 50 μm. (<b>D</b>) At indicated time points, representative flow cytometry plots show Ly6G^hi/CD11b^hi cell population in the iLN of infected dsRed mice. Data is representative of 4 iLNs. (<b>E</b>) 2 min migration route of a single neutrophil (red) loaded with LAC-GFP bacteria (green) is shown. IFZ, 6 h after infection (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004827#ppat.1004827.s014" target="_blank">S8 Movie</a>). Enlarged images of the same cell at time points 1 and 100 sec are shown to the right. Neutrophil cell border is outlined with dotted line; cell track is shown with solid line. Scale bars: 20 μm (left), 5 μm (right). Data is representative of 4 imaging sessions. (<b>F</b>, <b>G</b>) Infected and control mice were injected with isotype control or 1A8 antibody at 100 μg/mouse on day -1 and 0 of infection and LN cells were analyzed for GFP signal using flow cytometry. Analysis of LAC-GFP uptake by (F) Ly6G^hi/CD11b^hi and (G) CD169⁺ populations in the iLN of isotype control or 1A8 injected mice between 0 and 48 h after infection is shown. N = 4 mice/8 iLNs. Means ± SD.</p

Neutrophil depletion results in increased population of BLIMP1-YFP+ and GC B cells in immunized iLN.

<p>BLIMP1-YFP BM reconstituted mice were immunized with <i>S</i>. <i>aureus</i> subcutaneously, and injected with isotype control antibody or depleted of neutrophils using 1A8 antibody at days -1, 0 and 1 of immunization. ILNs were examined using epifluorescent microscopy, TP-LSM or flow cytometry. (<b>A, B</b>) Immunized mice were injected intravenously with Evans blue, and the iLNs of euthanized mice were exposed on a skin flip for imaging using stereomicroscope. Epifluorescent images of intact iLNs in immunized mice injected with (A) isotype control or (B) 1A8 antibody are shown. BLIMP1-YFP⁺ cells (green); blood vessels (red). Fluorescent images (top); corresponding bright field images (bottom left); scale bars, 400 μm. Lymph node borders and single blood vessels in IFZ are shown with dashed lines. Representative perivascular areas occupied with BLIMP1-YFP⁺ cells within the IFZ are outlined with white squares and their enlarged images are shown (bottom right); scale bars: 100 μm. (<b>C</b>) DsRed B cells or BM derived neutrophils were adoptively transferred at day 1–2 after immunization. TP-LSM images show LN follicles (red) from an immunized iLN of an isotype control-injected (left) or neutrophil-depleted (right) mouse. Scale bars, 20 μm. (<b>D-F</b>) Results from flow cytometry analysis of GC B cell (D) number and (E) percentage within the B220⁺ gate; and (F) BLIMP1-YFP⁺ GC B cell number within the B220⁺ gate. (<b>G</b>) Representative flow cytometry patterns of GC B cells from isotype control or 1A8 treated mice. (D-G) N = 4 iLNs; 3 independent experiments. Means ± SEM (<b>H</b>) BLIMP1-YFP B cells were isolated from the iLN and activated with LPS <i>in vitro</i> for 72 h. DsRed neutrophils were isolated from the BM and activated with LPS <i>in vitro</i> for 24 h. The cells were co-cultured for 2 h on ICAM-1/VCAM-1 coated surface. A confocal image of neutrophils (dsRed, red) interacting with a B cell (YFP, green) is shown. Scale bar: 5 μm. (<b>I</b>) DsRed BM derived neutrophils were adoptively transferred at day 7 after immunization, and recipient mice imaged 24 h later. A TP-LSM image of neutrophils (dsRed, red) interacting with B cells (YFP, green) is shown. Blood vessels (EB, gray). Scale bar: 10 μm. (<b>J</b>) Representative TP-LSM image of BLIMP1-YFP⁺ cells (green) localized in perivascular niches (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004827#ppat.1004827.s007" target="_blank">S1 Movie</a>) with neutrophils (red) migrating through the niches (left panel). Neutrophil tracks localized within the inside perimeter (outline, gray) of the niches (right panel). Scale bar: 20 μm. (H-J) Representative of 3 experiments.</p