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1.
Cureus ; 16(5): e60703, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38899253

RESUMO

Sickle cell disease (SCD) is marked by episodic vaso-occlusive crisis (VOC). Recurrent VOC creates a pro-inflammatory state that induces phenotypic alterations in innate immune cells. Monocytes are of particular interest to VOC pathophysiology because they are especially malleable to inflammatory signaling. Indeed, inflammatory disease states such as chronic obstructive pulmonary disease (COPD), obesity and atherosclerosis are known to influence monocyte development and alter monocyte subpopulations. In this study, we describe SCD monocyte subsets by performing immunophenotypic flow cytometric, enzymatic, and morphologic analysis on peripheral blood. Herein, we add to the growing body of evidence suggesting aberrant monocyte populations underpin VOC pathophysiology. We found that SCD monocytes possess an immature phenotype as demonstrated by 1) decreased CD4 positivity (p < .01), 2) low α-naphthyl butyrate esterase (ANBE) expression, and 3) naïve morphologic features. We additionally found an increase in CD14+CD16-CD4- monocytes (p < .01), a subset associated with the impaired immune response of post-trauma patients. Interestingly, we also found a large proportion of CD14+CD4-HLA-DR- monocytes which, under normal circumstances, are exclusively found in neonates (p < .01). Finally, we report an increase in nonclassical monocytes (CD14dimCD16+), a subset recently shown to have a critical role in prevention and recovery from VOC.

2.
Cureus ; 15(9): e46183, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37905287

RESUMO

Recurrent respiratory papillomatosis (RRP), which is usually benign, is an intractable disease characterized by recurrent papillomas (wart-like lesions). Although it most commonly involves the mucosal epithelial lining of the upper respiratory tract, on rare occasions, it can also involve lung parenchyma. RRP carries the risk of malignant transformation, most often to non-small-cell squamous lung cancer. Here, we present the case of a 32-year-old pregnant female with a past medical history of RRP who developed mild respiratory distress during her immediate postpartum period. This prompted imaging of the chest which revealed right lower lobe hypodensities with extensive hilar and perihilar lymphadenopathy. Histopathology of the bronchial specimen showed squamous cell carcinoma with 100% programmed death-ligand 1 (PD-L1) expression. Gross examination of the patient's placenta showed multiple tan-colored nodules which was confirmed on histopathological examination as multifocal regions of squamous cell carcinoma metastatic from the lung. The patient underwent a staging positron emission tomography (PET) scan which showed hypermetabolic regions in the right middle and lower lobes of the lung, with avidity in the right paratracheal region and an enhancing lesion in the left breast. Biopsy from the breast lesion was also positive for squamous cell carcinoma and PD-L1. She was diagnosed with Stage IVB (T1c, N3, M1c) non-small-cell squamous lung cancer and was started on pembrolizumab. Carboplatin and paclitaxel were added after an initial mixed response to therapy. The patient was non-compliant with her updated treatment regimen as well as with outpatient follow-up visits. A restaging PET scan demonstrated an inadequate response to the amended immunotherapy/chemotherapy regimen. Ultimately, she passed away within one and a half years of her initial diagnosis. Malignant transformation of papillomatous lesions into squamous cell cancer is infrequent, and the occurrence of metastasis to the breast and/or placenta is exceptionally rare. To our knowledge, this is the first reported case of placental and breast metastasis of squamous cell lung cancer in a patient with RRP.

3.
G3 (Bethesda) ; 10(6): 2111-2115, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32321837

RESUMO

Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD+ males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsps locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD+ males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previously, we have shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. Herein, we show that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Ativadoras de GTPase/genética , Masculino , Meiose , Protaminas/genética
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