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Ca2+ Modulation System of Myometrial Contraction During Gestation
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Phorbol ester increases sensitization of the contractile apparatus without change of [Ca2+]i in rabbit mesenteric artery, porcine coronary artery, or pregnant rat myometrium.34,35,72 Activation of protein kinase C by stimulation with phorbol ester has been reported to result in MLC phosphorylation at sites other than serine-19.4,6 It has been also reported that contractions elicited by agonists that trigger phosphoinositide turnover do not involve PKC-catalyzed phosphorylation of either myosin or MLCK.4 Recently, it has been demonstrated that the putative thin-filament regulatory proteins, calponin and caldesmon, may be involved in the agonist-induced increase in myofilament Ca2+ sensitivity. Unphosphorylated calponin and caldesmon bind to actin and depress actin-activated myosin ATPase activity.62,81 In rabbit myometrium caldesmon inhibits myosin ATPase activity.55 Translocation of PKC to the sarcolemma activated by agonist is considered to result in phosphorylation of caldesmon and calponin to produce slow sustained contractions.4,62,81 Thus, increased protein kinase C activity may therefore relieve the inhibitory effects of calponin or caldesmon and account for phorbol ester-induced increase in force shown in our study.
Stimulus-Secretion Coupling: Intracellular Proteins and Nucleotides
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
Burgoyne, Cheek and Norman (1986) demonstrated that one of the cytosolic vesicle-binding proteins, molecular mass 70 kDa, is a form of caldesmon, the calmodulin-regulated actin-binding protein. Cytoplasmic gels assembled from an adrenal medullary extract in the absence of calcium contained actin and the 70 kDa protein. The association of both of these proteins with the cytoplasmic gel was inhibited by low concentrations of calcium. Also, they demonstrated that the 70 kDa protein is localized at the periphery of chromaffin cells. These results are consistent with the concept that caldesmon has a role in regulating the organization of actin filaments at the cell periphery during secretion.
Endometrial malignant lesions
Published in T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng, Richard Wing-Cheuk Wong, Hao Chen, Diagnostic Endometrial Pathology, 2019
T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng
The main differential diagnoses for undifferentiated carcinoma include poorly differentiated or FIGO grade 3 endometrioid carcinoma, neuroendocrine carcinoma and mesenchymal malignancy. As described above, undifferentiated carcinoma shows a patternless feature without any clue of histologic differentiation. In contrast, poorly differentiated or FIGO grade 3 endometrioid carcinoma often shows focal areas of glandular differentiation, which is haphazardly admixed with the solid components. Immunohistochemically, partial maintenance of ER expression is common in FIGO grade 3 cancers, while it is commonly absent in undifferentiated carcinoma. Cytokeratin (CK7) is likely diffusely positive in FIGO grade 3 cancers but only patchy or focally positive in undifferentiated carcinoma. Regarding neuroendocrine carcinoma and poorly differentiated carcinoma with neuroendocrine differentiation, we arbitrarily use 10% neuroendocrine differentiation as a dividing line. The diagnosis of undifferentiated carcinoma is made when neuroendocrine differentiation is less than 10% of the tumor volume. In contrast, if neuroendocrine markers, typically more than 2, are positive in more than 10% of the tumor volume, the diagnosis of neuroendocrine carcinoma is appropriate. Mesenchymal malignancies such as undifferentiated endometrial sarcoma or leiomyosarcoma are other entities in the differential diagnosis list. At close examination at both low and high magnitudes, we should find at least focally spindled pleomorphic cells, which are suggestive of sarcomas. In addition to CK7, multiple cytokeratin markers are negative, which will be important clues separating undifferentiated carcinoma from other mesenchymal malignancy. Other markers such as smooth muscle markers and cyclin D1 may also help to confirm sarcoma. Leiomyosarcomas are positive for smooth-muscle markers such as desmin and H-caldesmon. It is known that approximately 50% of undifferentiated endometrial sarcomas show overexpression of cyclin D1 but featured uniform nuclei.87 Therefore, positive cyclin D1 expression is supportive for an undifferentiated endometrial sarcoma. Although leiomyosarcoma or undifferentiated endometrial sarcoma can be focally positive for cytokeratin, positive expression of the smooth-muscle markers or cyclin D1 is sufficient for leimyosarcoma or undifferentiated endometrial sarcoma. When all the markers including cytokeratins are negative and the tumor is morphologically ambiguous, a diagnosis of undifferentiated neoplasm should be considered.
More to what meets the eyes: Myopericytoma of the preauricular sinus
Published in Acta Oto-Laryngologica Case Reports, 2021
Azlina Ab Rani, Goh Bee See, Nordashima Abdul Shukur, Noor’Ain Mohd Nasir
Aung et al. further depict cutaneous myopericytomas to be benign in nature with a rare rate of recurrence [4]. These lesions may be identified microscopically when having hemangioperycytoma-like areas which are seen as numerous thin-walled, dilated with branching vessels, it may be angioleiomyoma-like when having perivascular bundles of elongated spindle-shaped cells and also may have occasional prominent atypia and mitotic activity and immunohistochemical staining revealed the lesion to be actin-positive and caldesmon-positive, as well as negative for other smooth muscle markers namely S100 protein, Mart-1/Melan A, EMA, CD31 and CD34 [4]. This corresponds well to the finding of our histopathological examination where the neoplastic cells are positive to actin immunohistochemistry, but negative to CD31 immunohistochemistry.
Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks
Published in Stress, 2021
Damien Huzard, Virginie Rappeneau, Onno C. Meijer, Chadi Touma, Margarita Arango-Lievano, Michael J. Garabedian, Freddy Jeanneteau
Mechanisms of adaptive plasticity utilize immediate early genes as first-line responders to glucocorticoid stimulation to prepare cells for a changing environment based on prior experience. For example, the MAPK specific phosphatases (Mitogen-Activated Protein Kinase Phosphatase 1/6 [MKP1/6]) are induced to terminate coincident growth factor signaling pathways converging on the GR phosphorylation code and the epigenome (Deinhardt & Jeanneteau, 2012; Jeanneteau & Deinhardt, 2011). Another example is the stress-induced transcription factors NR4A1/2/3, which shuttle in and out of the nucleus and mitochondria to coordinate metabolism and synapses number (Jeanneteau et al., 2018). Finally, actin binding proteins such as the Ca2+ sensor caldesmon and the cofilin kinase LIM-kinase 1 (LIMK1) are induced to reorganize the cytoskeleton supporting neuronal migration, differentiation, and connectivity (Fukumoto et al., 2009; Mayanagi et al., 2008; Morsink et al., 2006). Altogether, these responses set in motion the adaptive machinery that updates many attributes of neuronal function to its environment based on prior experience.
A rare case of orbital angioleiomyoma
Published in Orbit, 2021
Shiao Wei Wong, James Laybourne, Luciane Irion, Anne Cook
Histopathology is key for diagnosis. Henderson and Harrison4 and Wolter2 reported the earliest cases of angioleiomyoma which predates the Morimoto1 classifications. However more recent reports have described the morphological features of the orbital angioleiomyomas excised. The cavernous type was the most commonly reported (which includes our case), followed by the venous type and then the solid type (Table 1). On immunohistochemistry the lesion shows positivity for alpha smooth muscle actin (Figure 5), vimentin, desmin, calponin and h-caldesmon. CD31 and CD34 highlight the endothelial component (Figure 4a,4b). Angioleiomyoma lacks expression for HMB45 and oestrogen receptors. Histopathology and immunohistochemistry therefore help to differentiate angioleiomyoma from closely related lesions such as leiomyoma, angiomyoma, angiomyofibroma and angiomyolipoma.9,13,13