Publications by authors named "John S Van Arnam"

Article Synopsis
  • Solitary fibrous tumors (SFTs) have malignant potential and are rare in the breast and axilla; this study examined clinical and pathologic data from two institutions, focusing on five patients identified with these tumors.
  • The research involved a review of existing literature on breast and axillary SFTs, finding a total of 58 additional patients, with a significant number showing no evidence of disease after varying follow-up durations.
  • The study evaluated various risk models for predicting tumor behavior, revealing that the modified Demicco model had the best performance in assessing recurrence-free probability, indicating that while most SFTs are relatively indolent, some can recur or metastasize.
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Aims: To report a series of acute lymphoblastic leukemia (ALL) cases with spontaneous remission and provide presenting clinical and pathologic information and details of clinical course to raise awareness among oncologists and patients.

Methods: We identified and analyzed nine patients with ALL and spontaneous remission. Review of literature reveals an additional nine previously reported cases with similar clinical course.

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Elevated serum lactate dehydrogenase (sLDH) is associated with poor clinical outcomes in patients with stage IV metastatic melanoma (MM). It is currently unknown if sLDH elevation correlates with distinct molecular, metabolic, or immune features of melanoma metastases. The identification of such features may identify rational therapeutic strategies for patients with elevated sLDH.

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The distribution and appearance of nuclei are essential markers for the diagnosis and study of cancer. Despite the importance of nuclear morphology, there is a lack of large scale, accurate, publicly accessible nucleus segmentation data. To address this, we developed an analysis pipeline that segments nuclei in whole slide tissue images from multiple cancer types with a quality control process.

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Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (F-FDG and F-1-(2'-deoxy-2'-fluoro-arabinofuranosyl)cytosine [F-FAC]) and hepatocyte biology (F-2-deoxy-2-fluoroarabinose [F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis.

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T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic, and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing, and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that although genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes.

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Mutational inactivation of the SWI/SNF chromatin regulator ATRX occurs frequently in gliomas, the most common primary brain tumors. Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear, despite its recent implication in both genomic instability and telomere dysfunction. Here we report that Atrx loss recapitulates characteristic disease phenotypes and molecular features in putative glioma cells of origin, inducing cellular motility although also shifting differentiation state and potential toward an astrocytic rather than neuronal histiogenic profile.

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Article Synopsis
  • * A targeted next generation sequencing study analyzed 90 primary pNETs and 32 liver metastasis samples, revealing that many tumors had multiple genetic variants, with MEN1 being the most frequently mutated gene.
  • * The findings suggest that mutations in genes like TSC2, KRAS, and TP53 are linked to worse disease outcomes, while identifying potential predictive biomarkers for mTOR inhibitors, which could help in treatment decisions.
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Liver biopsies obtained for abnormal liver enzymes or unexplained ascites occasionally appear histologically almost normal. The differential diagnosis for these cases is challenging because literature addressing this topic is lacking. We aimed to establish a differential diagnosis and determine clinical associations and outcomes for almost-normal liver biopsies.

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A 41-year-old woman who had been fitted with a pacemaker 18 years prior presented for lead extraction because of device infection. First, we tried laser sheath. However, it cannot cross the binding in the innominate vein.

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Purpose: Prior research in animal models has suggested that retinal macrophages play an important role in age-related macular degeneration (AMD), but studies have insufficiently characterized the distribution of retinal macrophages in various stages of human AMD.

Methods: In this case series, we analyzed H&E, periodic acid-Schiff, and CD163 and CD68 immunostained slides from 56 formaldehyde-fixed, paraffin-embedded autopsy eyes of patients over age 75: 11 age-matched, normal eyes, and 45 AMD eyes.

Results: Qualitative analysis of the macula and retinal periphery revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells.

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The long-held concept that transplanted bone marrow (BM)-derived cells contribute only to cells of the hematopoietic system was challenged by data from our laboratory showing that a single male BM-derived cell could not only reconstitute the hematopoietic system of an irradiated female recipient, but could also lead to the generation of mature BM-derived epithelial cells in the liver, lung, skin, and gastrointestinal tract. Careful costaining and single-cell analyses have been used to rule out false positive cells due to inadequate detection techniques in microscopy or cell overlay. Since this initial discovery, we have sought to understand the mechanisms underlying the formation of BM-derived epithelial cells, and to evaluate their therapeutic use for gene therapy and/or tissue regeneration.

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Most flagellar proteins are exported via a type III export apparatus which, in part, consists of the membrane proteins FlhA, FlhB, FliO, FliP, FliQ, and FliR and is housed within the membrane-supramembrane ring formed by FliF subunits. Salmonella FlhA is a 692-residue integral membrane protein with eight predicted transmembrane spans. Its function is not understood, but it is necessary for flagellar export.

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Analysis of developmental plasticity of bone marrow-derived cells (BMDCs) is complicated by the possibility of cell-cell fusion. Here we demonstrate that epithelial cells can develop from BMDCs without cell-cell fusion. We use the Cre/lox system together with beta-galactosidase and enhanced green fluorescent protein expression in transgenic mice to identify epithelial cells in the lung, liver, and skin that develop from BMDCs without cell fusion.

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Salmonella FliR and FlhB are membrane proteins necessary for flagellar export. In Clostridium a fliR-flhB fusion gene exists. We constructed a similar Salmonella fusion gene which is able to complement fliR, flhB, and fliR flhB null strains.

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