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Charles Feldman Ronald Anderson Annette J. Theron Grace Ramafi Peter J. Cole Robert Wilson 《Inflammation》1997,21(6):655-665
The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations 1 g/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes. 相似文献
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Johanna L. Schmidt MPH MGC CGC Amy Pizzino MS CGC Jessica Nicholl MS CGC Allison Foley MMSc CGC Yue Wang PhD FACMG Jill A. Rosenfeld MS CGC Lindsey Mighion MS CGC Lora Bean PhD Cristina da Silva MS Megan T. Cho MS CGC Rebecca Truty PhD John Garcia PhD Virginia Speare PhD Kirsten Blanco BS Zoe Powis MS CGC Grace M. Hobson PhD Susan Kirwin BS Bryan Krock PhD FACMG Hane Lee PhD Joshua L. Deignan PhD Maggie A. Westemeyer MS CGC Ryan L. Subaran PhD Isabelle Thiffault PhD FABMGG Ellen A. Tsai PhD Terry Fang PhD Guy Helman BS Adeline Vanderver MD 《American journal of medical genetics. Part A》2020,182(8):1906-1912
Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening. 相似文献
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IL-15 is a potent T cell chemoattractant, and this cytokine and its unique α subunits, IL-15Rα, can modify immune cell expression of several T cell chemokines and their receptors. Facial nerve axotomy in mice leads to T cell migration across an intact blood–brain-barrier (BBB), and under certain conditions T cells can provide neuroprotection to injured neurons in the facial motor nucleus (FMN). Although chemokines and chemoattractant cytokines are thought to be responsible for T cell migration to the injured cell bodies, data addressing this question are lacking. This study tested the hypothesis that T cell homing to the axotomized FMN would be impaired in knockout (KO) mice with the IL-15 and IL-15Rα genes deleted, and sought to determine if microglial responsiveness and motoneuron death are affected. Both IL-15KO and IL-15RαKO mice exhibited a marked reduction in CD3+ T cells and had fewer MHC2+ activated microglia in the injured FMN than their respective WT controls at day 14 post-axotomy. Although there was a relative absence of T cell recruitment into the axotomized FMN in both knockout strains, IL-15RαKO mice had five times more motoneuron death (characterized by perineuronal microglial clusters engulfing dead motoneurons) than their WT controls, whereas dead neurons in IL-15KO did not differ from their WT controls. Further studies are needed to dissect the mechanisms that underlie these observations (e.g., central vs. peripheral immune contributions). 相似文献
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Pancreatoblastoma is a rare tumor and has been reported only four times in the cytologic literature, three times in fine-needle aspiration (FNA) biopsy and once in an imprint of resected tumor. We are reporting the fourth case of FNA cytology with immunohistochemical and electron microscopic studies. The patient is a 24-yr-old African American woman, who presented with a pancreatic mass, hepatic masses, and abdominal lymphadenopathy. The aspiration smears of the liver mass showed a biphasic tumor composed of bland-appearing primitive spindled stromal fragments with "spider-web"-like long fibrils interconnecting with sharply angulated islands of cohesive epithelium. At high power, the epithelium is composed of medium-sized cells with round-to-oval vesicular nuclei with fine chromatin and one-to-two small nucleoli. The neuroendocrine component was demonstrated immunohistochemically with synaptophysin and chromogranin expressions. The acinar component and squamoid component were demonstrated ultrastructurally by the presence of 400-600 nm zymogen granules and tonofilaments. The literature was reviewed and the cytological features of all the four cases of pancreatoblastoma are summarized. 相似文献
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The fine-needle aspiration cytologic findings of Wilms' tumor occurring in a 20-yr-old female patient and a 35-yr-old male patient showing blastemal, spindled sarcomatous and rare epithelial components are reported. The male patient had the typical presentation of renal mass with metastasis to lung and pleura, whereas the female patient had an unusual presentation with the tumor originated from the subcapsular nephrogenic zone of the kidney, extending into the liver without invasion into the renal cortex. Cytogenetic analysis of this case identified: 90, XXXX, +2x3-4, -5, -15, -16, -17, -17, i (17)(q10) x2. This finding may represent a genetic change associated with Wilms' tumor of older pediatric and young adult patients. To the best of our knowledge, this case is the sixth case with cytogenetic study and the first case revealing isochromosome 17q of an adult Wilms' tumor. 相似文献
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