a-two-step-method-for-percutaneous-transhepatic-choledochoscopic

A Two-Step Method for Percutaneous Transhepatic Choledochoscopic Lithotomy

Intrahepatic and extrahepatic choledocholithiasis is a challenge in the field of biliary surgery. We present our experience using a two-step percutaneous ...

Shantou University Medical College

The liver has the extraordinary properties of regeneration and immune tolerance; however, the mechanisms governing these abilities are poorly understood. To address these questions, we examined the possible expression of immunoglobulins in the human and rat liver and the relationship of IgG expression to hepatocyte proliferation, metastasis, apoptosis and immune tolerance. Immunohistochemistry, in situ hybridization, laser-guided microdissection and reverse transcription-PCR were performed to examine the expression of IgG in normal human and rat liver, severe combined immunodeficient mouse (SCID) liver and human liver cancers and corresponding cell lines. Small interfering RNA (siRNA) was transfected into cultured hepatocarcinoma cells to downregulate the expression of IgG heavy chain genes. Cell proliferation and apoptosis were assayed with flow cytometry. Cell metastasis was assayed with a Transwell cell assay. Partial hepatectomy (70%) was performed in rats to examine the relationship between hepatocyte IgG and hepatocyte proliferation. IgG, together with essential enzymes for its synthesis, were expressed in the cytoplasm of hepatocytes of normal adult human and hepatoma patients and rat livers, SCID mouse liver and BRL-3A, L-02 and HepG-2 cell lines. Downregulation of IgG inhibited cell proliferation and metastasis and promoted apoptosis. Postsurgery livers expressed significantly more IgG than the livers before surgery and decreased to the original levels when hepatocytes stopped regeneration. IgA and IgM but not IgD and IgE were also positive in hepatocytes. Our findings demonstrate that normal and malignant hepatocytes are capable of synthesizing immunoglobulin, which has important roles in hepatocyte proliferation, apoptosis and cancer growth with profound clinical implications.

Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver.

Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications.

Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils.

Sleeve anastomosis is the most common technique used to rearterialize orthotopic liver transplants (OLT). However, this technique has a number of disadvantages, including difficulty of performance of the technique visually unaided. We herein describe a novel rearterialized OLT model in the rat.

Development of a New Technique for Reconstruction of Hepatic Artery during Liver Transplantation in Sprague-Dawley Rat.

Influenza viruses possess a great threat to human health, but there is still no effective drug to deal with the outbreak of possible new influenza subtypes. In this study, we first fractionated sialylated immunoglobulin G (IgG), mainly Fab sialylated fraction, with sambucus nigra agglutinin affinity chromatography. We then demonstrated that sialylated IgG possessed more effective neutralizing activity against 2009 A (H1N1) subtype than that of IgG mixture, and sialosides on the Fab is crucial in this neutralization reaction as when such residues were removed with neuraminidase A digestion the blocking effect was significantly reduced. It appears that sialic acid residues attached to Fab could serve as binding moieties to receptor binding site of influenza virus. These findings indicate that sialylated IgG probably is an effective anti-influenza broad-spectrum drug utilizing its receptor mimicry to competitively inhibit the attachment of influenza viruses with sialic acid receptors on target cells. This property would be particularly useful if it can be applied to prevent newly emerged influenza virus strain infections in future epidemics. 

Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry.

Concanavalin A (ConA) chromatography has been extensively used to separate asymmetric Immunoglobulin G (IgG), which possesses oligosaccharide attached to one of the two F(ab')2 arms, from symmetric IgG with no glycan attached to Fab fragments. In this study, applying affinity chromatography, silver stain, Western blot and lectin stain techniques, N- linked oligosaccharide attached to Fab fragment was demonstrated to be exposed on the surface of the protein and be accessible by ConA. In contrast, N- linked oligosaccharide attached to asparagine (Asn) 297 of IgG Fc was located in the inside of the natural protein and was inaccessible by ConA. In addition to asymmetric IgG, there are also detectable level of IgG with both F(ab')2 arms glycosylated that has not been reported previously. The discoveries of new basic molecular structure of IgG would have implications in understanding the function and properties of this important immune molecule with clinical applications. 

Fractionation of Fab glycosylated immunoglobulin G with concanavalin A chromatography unveils new structural properties of the molecule.

Immunoglobulin G (IgG) has been shown to protect graft rejection after transplantation, whereas the molecular mechanism of IgG in promoting graft acceptance has not been well established. In this study, we tested the effectiveness of IgG in preventing rejection of transplanted skin graft in an immunologically potent rat model, and studied the mechanism of this protection. We found that systemic or local administration of IgG significantly prolonged the survival of skin grafts with the immune tolerance induced by IgG and subcutaneous local injection of 1mg IgG to adult SD rat yielded the longest survival of skin grafts from 5.8 to 17.3 days. We also found that IgG reduced the number of pro-inflammatory cells especially lymphocytes, neutrophils and basophils, increased the seral levels of anti-inflammatory factors including IL-10 and IL-4, and activated CD4+CD25+Foxp3+ regulatory T cells, unveiling the mechanisms of this protective effect. These findings provide new insight to support clinical application of IgG in treating transplantation.

Immunoglobulin G promotes skin graft acceptance in an immunologically potent rat model.

Better early detection methods are needed to improve the outcomes of patients with colorectal cancer (CRC). Proton nuclear magnetic resonance spectroscopy (H-NMR), a potential non-invasive early tumor detection method, was used to profile urine metabolites from 55 CRC patients and 40 healthy controls (HCs). Pattern recognition through orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to H-NMR processed data. Model specificity was confirmed by comparison with esophageal cancers (EC, n=18). Unique metabolomic profiles distinguished all CRC stages from HC urine samples. A total of 16 potential biomarker metabolites were identified in stage I/II CRC, indicating amino acid metabolism, glycolysis, tricarboxylic acid (TCA) cycle, urea cycle, choline metabolism, and gut microflora metabolism pathway disruptions. Metabolite profiles from early stage CRC and EC patients were also clearly distinguishable, suggesting that upper and lower gastrointestinal cancers have different metabolomic profiles. Our study assessed important metabolomic variations in CRC patient urine samples, provided information complementary to that collected from other biofluid-based metabolomics analyses, and elucidated potential underlying metabolic mechanisms driving CRC. Our results support the utility of NMR-based urinary metabolomics fingerprinting in early diagnosis of CRC.

NMR-based metabolomic techniques identify potential urinary biomarkers for early colorectal cancer detection.

To explore percutaneous transhepatic choledochoscopic lithotomy (PTCSL) as a treatment for intrahepatic and extrahepatic choledocholithiasis.

Percutaneous Transhepatic Choledochoscopic Lithotomy (PTCSL) is Effective for the Treatment of Intrahepatic and Extrahepatic Choledocholithiasis.

Hepatic ischemia-reperfusion injury (I/R) is an important factor affecting the prognosis of patients undergoing liver surgery. This study aimed to explore the value of intravenous immunoglobulin (IVIG) in hepatic I/R and its mechanism in a rat model.

Intravenous immunoglobulin is effective in alleviating hepatic ischemia-reperfusion injury: a rat model study.

The aim of this study is to explore the effect of intravenous immunoglobulin (IVIG) on the development of rat hepatocellular carcinoma and its possible molecular mechanism.

Article	Year
Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver. Laboratory investigation; a journal of technical methods and pathology\| PubMed ID: 25264708	2014
Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils. Scientific reports\| PubMed ID: 26639836	2015
Development of a New Technique for Reconstruction of Hepatic Artery during Liver Transplantation in Sprague-Dawley Rat. PloS one\| PubMed ID: 26716457	2015
Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry. Oncotarget\| PubMed ID: 26870994	2016
Fractionation of Fab glycosylated immunoglobulin G with concanavalin A chromatography unveils new structural properties of the molecule. Oncotarget\| PubMed ID: 27145274	2016
Immunoglobulin G promotes skin graft acceptance in an immunologically potent rat model. Oncotarget\| PubMed ID: 27276685	2016
NMR-based metabolomic techniques identify potential urinary biomarkers for early colorectal cancer detection. Oncotarget\| PubMed ID: 29285295	2017
Percutaneous Transhepatic Choledochoscopic Lithotomy (PTCSL) is Effective for the Treatment of Intrahepatic and Extrahepatic Choledocholithiasis. Surgical laparoscopy, endoscopy & percutaneous techniques\| PubMed ID: 33234849	2020
Intravenous immunoglobulin is effective in alleviating hepatic ischemia-reperfusion injury: a rat model study. Molecular biology reports\| PubMed ID: 34727292	2022
Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis. Journal of oncology\| PubMed ID: 35874633	2022

Xingmu Liu

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