Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is a provisional entity in the 2017 Revision of the World Health Organization Classification. This indolent entity, which is frequently discovered incidentally, is currently classified under the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), an aggressive lymphoma with poor survival. Several authors have proposed that it be classified separately since, in contrast to DLBCL-CI, transformation to aggressive lymphoma has rarely been reported and this entity has distinct clinical and histological features.
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April 2020
Thrombotic thrombocytopenic purpura may be seen with several autoimmune disorders such as immune thrombocytopenia purpura, immune hemolytic anemia, and systemic lupus erythematosus, but it is rarely associated with Graves' disease. We report a patient with thrombotic thrombocytopenic purpura associated with Graves' disease.
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January 2020
Extramedullary hematopoiesis (EMH) is a well-known phenomenon occurring during fetal development. In the postfetal condition, EMH is commonly associated with hematologic conditions including chronic myeloproliferative or lymphoproliferative disorders, leukemias, and chronic and inherited anemias. We report an unusual location for EMH that masqueraded as a cranial tumor.
View Article and Find Full Text PDFMagnetic resonance imaging (MRI) has specific limitations in theater and has unique requirements for its safe use with patients which require additional technician training and strict adherence to MRI-specific safety protocols. Neuroimaging is recommended for the evaluation of service members with clinical red flags new onset or persistent or worsening symptoms, and individuals whose recovery is not progressing as anticipated. This article is a brief discussion of when MRI is appropriate.
View Article and Find Full Text PDFBackground: Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Our previous study revealed that in osteosarcoma, human apurinic/apyrimidinic endonuclease 1 (APE1) regulates transforming growth factor-β (TGF-β), an important player in EMT. We therefore hypothesized a link between APE1 and EGFR-TKI responsiveness in NSCLC.
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January 2018
Lymphangioleiomyomatosis (LAM) is a rare cystic pulmonary disease that may occur in association with mutations in the tuberous sclerosis genes or arise sporadically. The histologic hallmark of the disease is the "LAM" cell, a spindled to epithelioid smooth muscle-like cell that bears morphologic and immunohistochemical resemblance to the perivascular epithelioid cell tumors (PEComas). The origin of the "LAM" cell is unknown; emerging theories suggest that a member of the PEComa family, the renal angiomyolipoma, may be the primary source and that both LAM and angiomyolipomas are associated with the genetic syndrome tuberous sclerosis.
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October 2017
A 56-year-old Texas rancher with a prior diagnosis of acquired erythropoietic protoporphyria secondary to an underlying myelodysplastic disorder developed an uncommon tumor, blastic plasmacytoid dendritic cell neoplasm (BPDCN). During his initial disease, analysis revealed a mutation, which is the most common mutation associated with BPDCN. This article discusses this unusual hematopoietic neoplasm, the possible evolution from erythropoietic protoporphyria, and the underlying myelodysplastic process.
View Article and Find Full Text PDFTraumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue.
View Article and Find Full Text PDFPurpose: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy.
Results: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.
Objective: Determine changes in cognition and post-traumatic stress disorder (PTSD) symptoms in subjects with traumatic brain injury (TBI) exposed to 2.4 atmospheres absolute (atm abs) breathing 100% oxygen vs. sham (1.
View Article and Find Full Text PDFIn this single-center, double-blind, randomized, sham-controlled, prospective trial at the U.S. Air Force School of Aerospace Medicine, the effects of 2.
View Article and Find Full Text PDFTraumatic brain injury (TBI) has been not only a major focus of concern during the recent conflicts in Afghanistan and Iraq, but also among our garrison service members. The prevalence of these injuries has compelled the nation and Congress to invest in the development of policies and programs that support evidence-based care for the full continuum of TBI, from mild (otherwise known as concussion) to severe and penetrating brain injuries. Although, the Department of Defense has made great strides in the areas of TBI clinical care, education, and research, there remains a great need to leverage scientific, policy, and clinical advancement to maximize care of the service member.
View Article and Find Full Text PDFBackground: HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78) which contains the helical SH3 domain binding protein motif, PXXPXR.
View Article and Find Full Text PDFObjective: Evaluation of the elbow in Ironman triathletes for ulnar compression neuropathy caused by aerobar use.
Design: Descriptive laboratory study.
Setting: Ironman California 70.
Dually targeted mitochondrial proteins usually possess an unconventional mitochondrial targeting sequence (MTS), which makes them difficult to predict by current bioinformatics approaches. Human apurinic/apyrimidinic endonuclease (APE1) plays a central role in the cellular response to oxidative stress. It is a dually targeted protein preferentially residing in the nucleus with conditional distribution in the mitochondria.
View Article and Find Full Text PDFThe human immunodeficiency virus type 1 (HIV-1) accessory protein Nef downregulates major histocompatibility complex class I (MHC-I) from the cell surface. It has been proposed that the direct interaction of the acidic cluster (AC) of Nef, (62)EEEE(65), with the furin binding region (fbr) of PACS-1 is crucial for this Nef function. Contrary to this proposal, evidence is presented here that the four glutamates in Nef do not functionally engage the PACS-1 fbr.
View Article and Find Full Text PDFNeurocardiogenic syncope is not an uncommon occurrence in the general population and affects people across a wide range of age groups. Several sub-specialties are involved in the management of this phenomenon and quite often a multidisciplinary approach is needed for arriving at the final diagnosis and deciding on the optimal treatment for this condition. Often, a thorough history and physical examination will aid in narrowing the differential of syncope and, in the right setting, both passive and provocative testing can be complementary.
View Article and Find Full Text PDFThe design of antiviral strategies against human immunodeficiency virus type 1 (HIV-1) has been largely derived from studies of subtype B viruses, although they constitute only 12% of infections worldwide. At 50% of all HIV-1 infections worldwide, subtype C viruses are the most predominant. Here, we present evidence that subtype C Nefs display functional Pak2-activating motifs that differ from those found in subtype B and E Nefs.
View Article and Find Full Text PDFHuman immunodeficiency virus type 1 (HIV-1) Nef activation of p21-activated kinase 2 (PAK-2) was recapitulated in a cell-free system consisting of in vitro-transcribed RNA, rabbit reticulocyte lysate, and microsomal membranes on the basis of the following observations: (i) Nef associated with a kinase endogenous to the rabbit reticulocyte lysate that was identified as PAK-2, (ii) Nef-associated kinase activity was detected with Nefs from HIV-1(SF2), HIV-1(YU2), and SIV(mac239), (iii) kinase activation was not detected with a myristoylation-defective Nef (HIV-1(SF2)NefG2A) or with a Nef defective in PAK-2 activation but fully competent in other Nef functions (HIV-1(SF2)NefF195I), and (iv) Nef-associated kinase activation required activated endogenous p21 GTPases (Rac1 or Cdc42). The cell-free system was used to analyze the mechanism of Nef activation of PAK-2. First, studies suggest that the p21 GTPases may act transiently to enhance Nef activation of PAK-2 in vitro.
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