It is widely accepted that development of autoimmunity in the central nervous system (CNS) is triggered by autoreactive T cells, that are activated in the periphery and gain the capacity to migrate through endothelial cells at the blood–brain barrier (BBB) into the CNS. Upon local reactivation, an inflammatory cascade is initiated, that subsequently leads to a recruitment of additional immune cells ultimately causing demyelination and axonal damage. Even though the interaction of immune cells with the BBB has been in the focus of research for many years, the exact mechanisms of how immune cells enter and exit the CNS remains poorly understood. In this line, the factors deciding immune cell entry routes, lesion formation, cellular composition as well as distribution within the CNS have also not been elucidated. The following factors have been proposed to represent key determinants for lesion evaluation and distribution: (i) presence and density of (auto) antigens in the CNS, (ii) local immune milieu at sites of lesion development and resolution, (iii) trafficking routes and specific trafficking requirements, especially at the BBB and (iv) characteristics and phenotypes of CNS infiltrating cells and cell subsets (e.g. features of T helper subtypes or CD8 cells). The heterogeneity of lesion development within inflammatory demyelinating diseases remains poorly understood until today, but here especially orphan inflammatory CNS disorders such as neuromyelitis optica spectrum disorder (NMOSD), Rasmussen encephalitis or SUSAC syndrome might give important insights in critical determinants of lesion topography. Finally, investigating the interaction of T cells with the BBB using in vitro approaches or tracking of T cells in vivo in animals or even human patients, as well as the discovery of lymphatic vasculature in the CNS are teaching us new aspects during the development of CNS autoimmunity. In this review, we discuss recent findings which help to unravel mechanisms underlying lesion topography and might lead to new diagnostic or therapeutic approaches in neuroinflammatory disorders including multiple sclerosis (MS).
The aim of this study was to assess the significance of bizarre cells (cells of squamous origin with a superficial squamous cell‐type cytoplasm and characterised by multinucleation that produces bizarre nuclear shapes) in liquid‐based cytology (LBC) Papanicoaou (pap) smears with clinical and histological follow‐up correlation.
Methods
Fifteen patients, all with LBC samples containing bizarre cells, were identified in routine ThinPrep® LBC workload. HPV testing was performed in each case using residual LBC material. Cytological‐histological correlations were reviewed.
Results
All 15 LBC samples contained bizarre cells and tested positive for high‐risk HPV types. Ten of the 15 cases were identified as atypical squamous cells ‐ cannot exclude an HSIL (ASC‐H) with secondary diagnosis of low‐grade squamous intraepithelial lesion (LSIL), while five cases were identified as high‐grade squamous intraepithelial lesion (HSIL), and a subsequent biopsy was recommended. Additionally, 13/15 cases underwent cone biopsy or hysterectomy within 1‐11 months, of which 10 showed histologically confirmed HSIL end‐points. LSIL was present in three cases. Bizarre cells were identified in the HSIL epithelium of five cone biopsies.
Conclusions
Identification of bizarre cells in LBC is straightforward and may facilitate diagnosis. The cytology of bizarre cells is associated with HSIL in cone biopsies. We recommend assigning LBC samples containing bizarre cells as ASC‐H with secondary diagnosis of LSIL. 相似文献
The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery. 相似文献
Specific binding sites for [3H]nitrendipine, an organic Ca2+ channel antagonist, were abolished in crude synaptosomal membranes of kainic acid-lesioned caudate nuclei. In contrast, specific lesions of dopaminergic or serotonergic axon terminals in caudate nuclei failed to alter the density or the affinity of [3H]nitrendipine binding sites. In addition, the basal and veratridine-stimulated 45Ca2+ accumulations were greatly impaired in slices prepared from kainic acid-lesioned caudate nuclei. The veratridine-elicited accumulation of 45Ca2+ in control slices was attenuated by addition of tetrodotoxin in the incubation medium. The present data provide evidence that most of the [3H]nitrendipine binding sites and the voltage-dependent Ca2+ channels are located in intrinsic neurons or interneurons in caudate nucleus. In contrast, destruction of dopaminergic or serotonergic nerve terminals emanating from other brain areas and innervating the caudate nucleus failed to change the apparent Bmax value for [3H]nitrendipine binding. 相似文献
Of eight corn inbreds tested in the greenhouse and field, three (H60, H95, and H84) supported lower populations of Pratylenchus hexincisus than other inbreds included in this study. No apparent differences existed among inbreds in nematode invasion or development in the roots, or in population structure. Differences in population were therefore attributed to differential reproduction. 相似文献
Population increase of Pratylenchus hexincisus on corn was tested over 3 months at 15, 20, 25, and 30 C in Marshall silt loam, Clarion silt loam, Buckner coarse sand, and Haig silty clay loam soils. The optimum temperature for increase was 30 C in all soils. The nematode population was significantly larger in Buckner coarse sand than in other soil types at 50 C. The recovered P. hexincisus populations equaled or exceeded initial inoculum levels at the two higher temperatures in Marshall silt loam and Haig silty clay loam and at 30 C in Clarion silt loam and Buckner coarse sand. P. hexincisus required 32,400 heat units in Haig silty clay loam and more than 40,000 heat units in the three other soil types to reach a level that is known to cause significant height and biomass reduction in corn under controlled condition. 相似文献
Size of lesions caused by Pratylenchus scribneri on roots of ''Clark 63'' soybean was correlated with nematode colony size within roots. A single nematode was capable of causing a detectable lesion. When a root became highly necrotic and shrunken, few nematodes but numerous eggs remained in the tissue. In histological sections made 5, 11, 18, and 45 d after planting, P. scribneri was located entirely within the cortex and generally was oriented longitudinally to the vascular cylinder, either outstretched in the same plane or coiled through several cells. Nematodes moved intracellularly, causing extensive rupturing of cell walls, retraction and disappearance of cytoplasm, and thickening of cell walls and necrosis of cells around feeding sites. Depth of penetration within the cortex and necrosis of cells increased with time after infection, eventually resulting in formation of cavities in the cortex and occasional secondary injury to the endodermis. Stele tissue was unaffected by feeding, and damage to the epidermis was limited to nematode entry points. Orientation of P. alleni and histopathology of its infection at 45 days were identical to those of P. scribneri, except that there was no injury to the endodermis. 相似文献