Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC.
View Article and Find Full Text PDFT cell-mediated rejection (TCMR) remains a significant cause of long-term kidney allograft loss, either indirectly through induction of donor-specific anti-HLA alloantibodies or directly through chronic active TCMR. Whether found by indication or protocol biopsy, Banff defined acute TCMR should be treated with antirejection therapy and maximized maintenance immunosuppression. Neither isolated interstitial inflammation in the absence of tubulitis nor isolated tubulitis in the absence of interstitial inflammation results in adverse outcomes, and neither requires antirejection treatment.
View Article and Find Full Text PDFAdv Chronic Kidney Dis
November 2021
Transplantation remains the optimal mode of kidney replacement therapy, but unfortunately long-term graft survival after 1 year remains suboptimal. The main mechanism of chronic allograft injury is alloimmune, and current clinical monitoring of kidney transplants includes measuring serum creatinine, proteinuria, and immunosuppressive drug levels. The most important biomarker routinely monitored is human leukocyte antigen (HLA) donor-specific antibodies (DSAs) with the frequency based on underlying immunologic risk.
View Article and Find Full Text PDFActa Neuropathol Commun
March 2022
Entrapment peripheral neuropathies are clinically characterized by sensory impairment and motor deficits. They are usually caused by mechanical injuries, but they are also a frequent manifestation of metabolic diseases, toxic agent exposure, or systemic fibrotic disorders. Here we describe the clinical, radiological, and histopathological features of a novel progressive fibrotic disorder characterized by progressive multifocal fibrosing neuropathy.
View Article and Find Full Text PDFMonoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS.
View Article and Find Full Text PDFHistologic antibody-mediated rejection (hAMR) is defined as a kidney allograft biopsy satisfying the first 2 Banff criteria for diagnosing AMR: tissue injury and evidence of current/recent antibody interaction with the endothelium. In approximately one-half of such cases, circulating human leukocyte antigen (HLA) donor-specific antibodies (DSA) are not detectable by current methodology at the time of biopsy. Some studies indicated a better prognosis for HLA-DSA-negative cases of hAMR compared to those with detectable HLA-DSA, whereas others found equally poor survival compared to hAMR-negative cases.
View Article and Find Full Text PDFDefined as histologic evidence of rejection on a protocol biopsy in the absence of kidney dysfunction, subclinical rejection has garnered attention since the 1990s. The major focus of much of this research, however, has been subclinical T cell-mediated rejection (TCMR). Herein, we review the literature on subclinical antibody-mediated rejection (AMR), which may occur with either preexisting donor-specific antibodies (DSA) or upon the development of de novo DSA (dnDSA).
View Article and Find Full Text PDFCell-free DNA (cfDNA) exists in plasma and can be measured by several techniques. It is now possible to differentiate donor-derived cfDNA (ddcfDNA) from recipient cfDNA in the plasma or urine of solid organ transplant recipients in the absence of donor and recipient genotyping. The assessment of ddcfDNA is being increasingly studied as a noninvasive means of identifying acute rejection (AR) in solid organ transplants, including subclinical AR.
View Article and Find Full Text PDFMicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following -nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% ( = 0.038) and miR-31 gene knockout abrogated development of ESCC ( = 1 × 10).
View Article and Find Full Text PDFThe majority of cells comprising the inflammatory infiltrates in kidney allografts undergoing acute and/or chronic rejection are typically T cells and monocyte/macrophages with B cells, plasma cells, and eosinophils accounting for <5%. In a significant minority of biopsies, B lineage cells (B cells and/or plasma cells) may be found more abundantly. Although plasma cell infiltrates tend to be more diffuse, B cells tend to aggregate into nodules that may mature into tertiary lymphoid organs.
View Article and Find Full Text PDFObjective: The objective was to use two ultrasound image and signal processing techniques (MicroPure and superb microvascular imaging [SMI]; Toshiba Medical, Tokyo, Japan) to investigate carotid plaque calcification and intraplaque neovascularity flow as biomarkers for plaque vulnerability in patients before endarterectomy.
Methods: Thirty patients, with preoperative computed tomography angiography and scheduled for carotid endarterectomy, were enrolled in an institutional review board-approved study. Bilateral grayscale, power Doppler, SMI and MicroPure imaging of the carotids were performed using an Aplio 500 Platinum scanner (Toshiba).
Proc Natl Acad Sci U S A
November 2018
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry ( = 8/group).
View Article and Find Full Text PDFIn the renal allograft, transplant glomerulopathy represents a morphologic lesion and not a specific diagnosis. The hallmark pathologic feature is glomerular basement membrane reduplication by light microscopy or electron microscopy in the absence of immune complex deposits. Transplant glomerulopathy results from chronic, recurring endothelial cell injury that can be mediated by HLA alloantibodies (donor-specific antibodies), various autoantibodies, cell-mediated immune injury, thrombotic microangiopathy, or chronic hepatitis C.
View Article and Find Full Text PDFCentral to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use.
View Article and Find Full Text PDFMembranous nephropathy (MN) may occur in a kidney transplant as recurrence of the original disease (rMN) or as a de novo MN (dnMN). rMN often occurs early, within the first year, and often in a mild or subclinical fashion. Recurrence cannot be predicted by clinical features at the time of transplantation.
View Article and Find Full Text PDFAcute tubular injury (ATI) is common at reperfusion, but its relationship to graft outcomes is unclear. Prior studies lack standardization of morphological assessments and included elements of acute and chronic tubular injury. This study aimed to evaluate the impact of ATI on graft outcomes.
View Article and Find Full Text PDFHemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by defective lytic capability of cytotoxic T lymphocytes and NK cells, which results in proliferation of benign hemophagocytic histiocytes. A cytokine storm ensues, and a severe systemic inflammatory response syndrome, multiorgan dysfunction syndrome, and death frequently follow. It may occur as a primary (inherited) form, or be acquired secondary to malignancy, infection, rheumatologic disease, or immunosuppression.
View Article and Find Full Text PDFAmpullary adenocarcinomas are a rare subset of periampullary tumors with an overall poor prognosis. Treatment decisions are generally extrapolated from pancreatic chemotherapy protocols and consist mainly of traditional chemotherapy drugs. There are no known targets for therapeutic intervention in ampullary adenocarcinoma at this time.
View Article and Find Full Text PDFObjective: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).
Methods: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers.
Background: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined.
Methods: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks.