Genomics Proteomics Bioinformatics
December 2021
Recent findings indicate the presence of T cell receptor (TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages. In this study, using a semiquantitative trilineage immune repertoire sequencing approach as well as under rigorous bioinformatic conditions, we identify highly complex TCRβ transcriptomes in human circulating monocytes and neutrophils that separately encode repertoire diversities one and two orders of magnitude smaller than that of T cells. Intraindividual transcriptomic analyses reveal that neutrophils, monocytes, and T cells express distinct TCRβ repertoires with less than 0.
View Article and Find Full Text PDFBacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαβ-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological, and mass spectrometric techniques.
View Article and Find Full Text PDFPurpose: To assess the diagnostic potential of dynamic real-time MRI for fundoplication failure in patients with persistent or recurrent GERD-like (gastroesophageal reflux disease) complaints.
Material And Methods: Twenty-two consecutive patients (male n = 11; female n = 11; median age 59 years) with recurrent or persistent GERD-like symptom after fundoplication were enrolled between 2015 and 2017. Median duration of GERD-like symptoms was 21 months.
Recent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in chronic inflammatory diseases such as tuberculosis and atherosclerosis and in the tumor microenvironment. Here, we demonstrate that a second subpopulation of macrophages expresses rearranged heavy and light chain immunoglobulins. We identify immunoglobulin expression in human and murine monocytes, in ex vivo differentiated macrophages and macrophages from the tumor microenvironment of five randomly selected distinct human tumor entities.
View Article and Find Full Text PDFThe purpose of this study was to assess the reproducibility of functional and anatomical parameters of swallowing events as determined by real-time MRI at 40 ms temporal resolution (25 frames per second). Twenty-three consecutive patients with gastroesophageal reflux disease (GERD) underwent real-time MRI of the gastroesophageal junction at 3.0 T.
View Article and Find Full Text PDFBackground: Robot-assisted minimally invasive surgery (RVATS) is a relatively new technique applied for thymectomies. Only few studies directly compare RVATS to the mainstay therapy, open surgery (sternotomy).
Methods: A systematic search of the literature was performed in October 2016.
The origin of gastrointestinal stromal tumors (GIST) from interstitial cells of Cajal or their precursor cells has been understood since the early 1990s. The first mutations within the KIT-gene have been described in the late 1990s. Even though these mutations were the breakthrough of small molecular therapy, we still do not know the factors responsible for their malignant transformation.
View Article and Find Full Text PDFWhile the oncological outcome of patients with rectal cancer has been considerably improved within the last decades, anorectal, urinary and sexual functions remained impaired at high levels, regardless of whether radical surgery was performed open or laparoscopically. Consequently, intraoperative monitoring of the autonomic pelvic nerves with simultaneous electromyography of the internal anal sphincter and manometry of the urinary bladder has been introduced to advance nerve-sparing surgery and to improve functional outcome. Initial results suggested that pelvic neuromonitoring may result in better functional outcomes.
View Article and Find Full Text PDFRecent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in two major inflammatory diseases, tuberculosis and atherosclerosis. Inflammation is also a well-established attribute of cancer progression and macrophages are one of the major immune cells that infiltrate tumors. Here, we demonstrate that the macrophage-TCRαβ is expressed in the tumor microenvironment of human and murine malignancies.
View Article and Find Full Text PDFA small angle (His angle) between the oesophagus and the fundus of the stomach is considered to act as flap valve and anti-reflux barrier. A wide angle results in dysfunction of the oesophagogastric junction and subsequently in gastroesophageal reflux disease (GERD). Here, we used real-time magnetic resonance imaging (MRI) at 50 ms resolution (20 frames per second) in 12 volunteers and 12 patients with GERD to assess transport of pineapple juice through the oesophagogastric junction and reflux during Valsalva.
View Article and Find Full Text PDFRecent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ(+) macrophages within the atherosclerotic lesions.
View Article and Find Full Text PDFAims: Rhabdoid morphology resembling that of the aggressive paediatric rhabdoid tumours occurs in various malignancies usually lacking characteristic SMARCB1 (INI1) loss. Little is known about the clinicopathological and molecular characteristics of the rhabdoid phenotype in gastrointestinal stromal tumours (GISTs).
Methods And Results: Six gastric rhabdoid GISTs were examined by immunohistochemistry, KIT and platelet-derived growth factor receptor-α gene (PDGFRA) mutation analysis, and comparative genomic hybridization (CGH).
Recent evidence indicates that monocytes and macrophages express T cell receptor (TCR)αβ-like combinatorial immune receptors. Here, we demonstrate the presence of a second recombinatorial immunoreceptor, which is structurally based on the TCR γ- and δ-chains, in human and murine monocytes and differentially activated macrophages (referred to here as TCRL(m)γδ). In vitro, infection of macrophages with mycobacteria and gram positive or gram negative bacteria induced expression of donor-specific and differential TCRL(m)Vδ repertoires indicating that the novel immunoreceptor represents a dynamic flexible host defense system that responds to bacterial challenge.
View Article and Find Full Text PDFLongstanding immunological dogma holds that flexible immune recognition, which forms the mechanistic basis of adaptive immunity, is strictly confined to the lymphocyte lineage. In higher vertebrates, flexible immune recognition is represented by recombinatorial antigen receptors of enormous diversity known as immunoglobulins, expressed by B lymphocytes, and the T cell receptor (TCR), expressed by T lymphocytes. The recent discovery of recombinatorial immune receptors that are structurally based on the TCR (referred to as TCR-like immunoreceptors, "TCRL") in myeloid phagocytes such as neutrophils and monocytes/macrophages now challenges the lymphocentric paradigm of flexible immunity.
View Article and Find Full Text PDFSince decades there is consensus among immunologists that in jawless and jawed vertebrates flexible immune recognition is strictly confined to the lymphoid lineage. In jawed vertebrates the adaptive immune system is represented by two lineages of lymphocytes, B cells and T cells that express recombinatorial antigen receptors of enormous diversity known as immunoglobulins and the T cell receptor (TCR). The recent identification of recombined immune receptors that are structurally based on the TCR in subpopulations of neutrophils and eosinophils (referred to here as TCR-like immunoreceptors, "TCRL") provides unexpected evidence for the existence of flexible host defense mechanisms beyond the realm of lymphocytes.
View Article and Find Full Text PDFPurpose: The duodenum as primary site for gastrointestinal stromal tumors (GISTs) is rare and mitotic rate, tumor size, type of mutation and number of chromosomal aberrations have prognostic implications.
Methods: We analyzed the outcome of 13 patients with duodenal GISTs who underwent surgical tumor resection. Either segmental duodenectomy or pylorus-preserving duodenopancreatectomy was performed.
Recent evidence has revealed the existence of T cell receptor (TCR) αβ-based recombinatorial immune receptors in phagocytes. Here, we performed a systematic survey of the variable β-chain repertoires of the neutrophil TCR-like αβ immunoreceptor (referred to as TCRL(n)αβ) in defined cohorts of young and old individuals. Peripheral blood CD15(+) neutrophils from young adults (age 30 ± 7 years, n=12) expressed an average number of 13 ± 6 distinct TCRL(n) Vβ-chains from the total pool of 25 human Vβ-chains.
View Article and Find Full Text PDFIntroduction: The gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the intestinal tract, known to be refractory to conventional chemotherapy or radiation. Its pathogenesis is defined by mutations within the KIT and PDGFRA gene, which constitutively activate KIT and PDGFRA oncoproteins, and serve as crucial diagnostic and therapeutic targets.
Discussion: Besides surgery, therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST.
Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis.
View Article and Find Full Text PDFBasaloid squamous cell carcinoma (BSCC) and carcinosarcoma of the esophagus are rare entities, making up fewer than 2% of esophageal malignancies. Comparative genomic hybridization (CGH) in 1 case of BSCC and 2 cases of carcinosarcoma and subsequent array CGH in 1 case each of BSCC and carcinosarcoma revealed common chromosomal gains at 2p25.3-2p12, 7q21.
View Article and Find Full Text PDFPurpose: A common and serious problem after living donor liver transplantation (LDLT) of small grafts is small-for-size syndrome (SFSS). Although hyperdynamic portal inflow and portal hypertension are cornerstones in the development of SFSS, inadequate outflow may aggravate SFSS. Therefore, enlargement of the portal outflow tract by incision of the anterior rim of the orifice of the right hepatic vein (RHV) has been advocated for right lobe LDLT.
View Article and Find Full Text PDFAim: To assess the outcome of patients, who underwent transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and subsequently liver transplantation (OLT) irrespective of tumor size when no tumor progression was observed.
Methods: Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT.