Figure 1. 1A: Computerized tomography scan of the chest (sagittal view) showing a soft tissue mass at the junction of the cervical and thoracic esophagus (arrow).Figure 1B-C:Esophagogastroduodenoscopy showing an esophageal mass located at 16 cm from incisors causing near complete obstruction of the esophagus. Figure 1D: A high power (400x, H&E) view shows a highly cellular tumor comprised of basophilic cells, with scant cytoplasm, high nuclear/cytoplasmic ratio, salt-and pepper chromatin, and nuclear molding with crush artifact. There are abundant
Figure 1. A-B: Biopsy of both polyps showed polypoid colonic mucosa with a lamina propria expanded by atypical clusters of spindled mast cells and prominent background eosinophilia. C: Immunohistochemistry for C-kit/CD117 confirmed a marked increase in clustered and spindled mast cells. D: CD25 was also positive in the mast cells, a marker typically positive in systemic mastocytosis. E: Cecal picture with very subtle nodularity change. F: NBI picture of nodularity change in cecum.
Background and Purpose:
Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This effect is lost in NOS3-KO mice. We wanted to determine if the beneficial effect of C-RIC can be restored by bone marrow cell-derived NOS3.
Methods:
We prepared BM chimera from adult WT (B6.SJL-Ptprc
a
; CD45.1) to adult NOS3-KO (B6.129; CD45.2) & vice versa in male mice (5-6 months) following confirmation for BM engrafting with flow cytometry at 2 weeks. Microcoil (0.18 mm) induced BCAS model was used to induce chronic hypoperfusion. Mice were randomly assigned to 3-groups: (1) Sham (2) BCAS and (3) BCAS+RIC. RIC was started 7d post-surgery daily for 3-4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. We measured whole blood P-NOS3, P-AMPK and VEGFR2/CD31 by flow cytometry.
Results:
C-RIC-therapy for 3-4 weeks improves CBF in engrafted BM of WT into NOS3-KO in the BCAS+RIC groups at both 2 weeks and 4 weeks compared to BCAS (Sham RIC groups).No effect of C-RIC was shown in engrafted BM of NOS3 into WT. There was significant change between the BCAS and BCAS+RIC groups in the functional outcomes and histopathological evidences also reflects major changing in the groups in the BM of WT into NOS3-KO mice. Whole blood P-NOS3, P-AMPK and VEGFR2/CD31 was increased by C-RIC. However, no effect was shown in the NOS3-KO into WT chimera.
Conclusions:
The Beneficial effect of C-RIC is dependent upon bone marrow derived NOS3.Further studies are needed to determine if the red blood cell is the key cell carrying NOS3
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