Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
David W. Hobson in Dermal and Ocular Toxicology, 2020
One of the best methods available for distinguishing Langerhans’ cells from other epidermal cells is TEM. These cells have been classified as nonkeratinocytes because they lack the characteristic features, namely tonofilaments and desmosomes. They possess slender processes which penetrate the intercellular spaces among the prickle cells. These processes contain all the organelles which are normally found in the perikaryon.149 Their nucleus (Figure 9) is indented and the cytoplasm contains Golgi complexes, smooth and rough endoplasmic reticulum, and lysosomes. The characteristic feature which distinguishes Langerhans’ cells from other cells is the presence of a rod- or racket-shaped structure in the cytoplasm (Figures 10 and 11)38,89,142,143,150,151 his structure, first described by Birbeck, is commonly known as the Birbeck or Langerhans’ cell granule.152 This specific granule (Figure 11) is shaped like a racket, having a “handle” portion and an expanded end. The “handle” consists of an outer limiting membrane with a central lamella which appears as a row of particles exhibiting a 50 to 70 Å periodicity. The expanded end of the limiting membrane is usually clear, and on occasion may have a cross-striated pattern within.38,89,142,152
Phagocytosis By Human Neutrophils
Hans H. Gadebusch in Phagocytes and Cellular Immunity, 2020
Finally, Iverson et al.25< have some evidence that a very heavy granule (peak IV) contains the putative oxidase and sediments farthest into the gradient. This might correspond to a very large granule visualized in the intact cell by Breton-Gorius et al.274 utilizing the electron microscope. These results are not conclusive, and more work must be done before the identity of this granule can be accepted; most workers feel that the oxidase is localized on the plasma membrane of the cell, and not in a granule at all.231,233,275 However, Patriarca et al.247 have demonstrated a granule localization for NADPH oxidase in rabbit neutrophils where the enzyme appears to cosediment with the azurophil granule.
Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
During embryonic growth, neural precursor cells generated in the rhombic lip of the dorsal hindbrain migrate along the surface of the cerebellum to form the external granule layer (EGL). The secretion of bone morphogenic proteins (BMPs), such as BMP6, BMP7, and GDF7, encourages further proliferation generating a rich pool of granule cell precursors (GCPs) in the developing EGL [20, 36]. As older cells exit the EGL and migrate through a layer of Purkinje cells, they encounter the Hedgehog pathway ligand, Sonic hedgehog (SHH), a highly conserved embryonic signaling system which binds to its receptor, Patched 1 (PTCH1), expressed on GCPs in the EGL [37, 38]. Downstream effectors include the GLI family of transcription factors (GLI1, GLI2, and GLI3), which activate transcription of genes, such as cyclinD1 (CCND1) and MYC, thereby facilitating GCP proliferation and migration [7, 20, 36, 39]. After post-natal cerebellar development, this pathway goes dormant with the 12-pass transmembrane receptor, PTCH1, keeping the 7-pass transmembrane protein, Smoothened (SMO), in an inactivated state [40]. This, in turn, leads to the sequestration of downstream effectors of the SHH pathway by Suppressor-of-Fused (SUFU), effectively silencing gene expression [7]. Deregulated binding of SHH to PTCH1 releases and constitutively activates SMO which, in turn, inhibits SUFU, leading to release and nuclear translocation of GLI1-3; as a result, aberrant gene transcription is activated, facilitating phenotypic transformation into medulloblastoma [7].
Effects of pyrethroids on the cerebellum and related mechanisms: a narrative review
Published in Critical Reviews in Toxicology, 2023
Fei Hao, Ye Bu, Shasha Huang, Wanqi Li, Huiwen Feng, Yuan Wang
Recently, it has been suggested that DM may exert its neurotoxic effects through intracellular accumulation and low release of the reelin protein (Kumar et al. 2013). Reelin is an extracellular matrix molecule that supports the normal development of the CNS, including hippocampus, cerebellum and cortex. In the cerebellum, reelin participates in arranging Purkinje cell monolayers, Bergman glial fibers and facilitating granule cell migration. Reelin protein deficiency in DM-treated animals may lead to certain structural abnormalities that could directly impact the functional performance of the cerebellum. It included impaired migration of granule cells and Purkinje cells, inhibition of neuronal outgrowth, reduced density of dendritic spines and decreased rotational movements (Zhao et al. 1995). Reelin signaling involves several factors, including the lipoprotein receptor lipoprotein E receptor 2 (ApoER2), the very low-density lipoprotein receptor (VLDLR) and adaptor protein Dab1 (Dab1). Reelin can bind to the ApoER2 and VLDLR, leading to phosphorylation of Dab1. Therefore, it is hypothesized that DM may cause cerebellar dysfunction through the reelin signaling pathway.
Young steady-state rabbit platelets do not have an enhanced capacity to expose procoagulant phosphatidylserine
Published in Platelets, 2018
Emily C. Reddy, Hong Wang, K.W. Annie Bang, Marian A. Packham, Margaret L. Rand
In the report that young platelets are more reactive than old platelets in forming a procoagulant subpopulation [7], young and old platelets were identified on the basis of positive and negative thiazole orange (TO) fluorescence, respectively. TO is a cell permeable dye that increases several thousandfold in fluorescence emission upon binding to RNA and DNA; it has been used to identify reticulated platelets, considered to be the youngest circulating platelets based on the presence of residual megakaryocyte-derived messenger RNA [12]. While the assessment of reticulated platelets by TO fluorescence can be useful in detecting young platelets in the circulation of ITP patients [12–17], the identification of young platelets by positive TO fluorescence, particularly in the steady-state, is somewhat imprecise and lacking standardization. A primary concern is the wide variability in published reference ranges, which range from less than 1% to approximately 16% TO-positive platelets [16, 18]. TO binds not only to cytoplasmic RNA but also to mitochondrial DNA, and, moreover, almost half of platelet TO fluorescence is derived from dense granule nucleotides, ADP and ATP [17–19]. Thus, large platelets would be expected to have higher TO fluorescence due to larger volume and higher granule content [20].
Leptin receptor defect with diabetes causes skeletal muscle atrophy in female obese Zucker rats where peculiar depots networked with mitochondrial damages
Published in Ultrastructural Pathology, 2021
Jacques Gilloteaux, Charles Nicaise, Lindsay Sprimont, John Bissler, Judith A Finkelstein, Warren R Payne
Throughout all the muscles of the obese adult female Zucker rat, many of the mitochondria profiles showed either compacted matrices or with blurry aspects of matrices under high TEM magnifications in SO and FOG fibers (Figures 4(a-c), 7, 8(a,b), 9(a,b), 11(a-c)). Some others also showed scattered damage, and remnants of them. The damaged organelles were either swollen (Figure 4(a)) or both in part swollen and degraded (Figures 4(a), 5(a,b), 7, 8(a), 9(a), 10(a), 11(a-c)) as well as entirely obliterated from the muscle fibers (Figures 11(a-c), 12(a-e)). Even with the small number of fibers illustrated throughout the illustrations collected of this report, we evaluated the ratios of mitochondria profiles degraded were most numerous in the FG fibers compared with both oxidative SO and FOG ones (Figures 12(a-d), 13(a-e); Table 1). In damaged organelles, inner membranes and cristae were still recognized within but in peculiar aspects, as illustrated by the pane of Figure 10(a-d), the mitochondrial remnants appeared as irregular morsels associated with electron dense droplets with a somewhat concentrically-aligned deposits as tiny electron dense deposits or granule-like with an accumulated centripetal-like pattern in the spaces made by the swollen or partially deteriorated mitochondria Internum or matrix (Figures 10(a-d), 11(a) and 14).