Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells.

Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is considered a major cause of RIF. Although long non-coding RNAs (lncRNAs) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms of lncRNAs in the progression of RIF are poorly understood. In this study, we investigated the function of lncRNAs in RIF. Microarray assays showed that expression of the lncRNA lnc-CHAF1B-3 (also called claudin 14 antisense RNA 1) was significantly upregulated in human renal proximal tubular cells by both transforming growth factor-ß1 (TGF-ß1) and hypoxic stimulation, accompanied with increased expression of EMT-related genes. Knockdown of lnc-CHAF1B-3 significantly suppressed TGF-ß1-induced upregulated expression of collagen type I alpha 1, cadherin-2, plasminogen activator inhibitor-1, snail family transcriptional repressor I (SNAI1) and SNAI2. Quantitative reverse transcriptase PCR analyses of paraffin-embedded kidney biopsy samples from IgA nephropathy patients revealed lnc-CHAF1B-3 expression was correlated positively with urinary protein levels and correlated negatively with estimated glomerular filtration rate. In situ hybridization demonstrated that lnc-CHAF1B-3 is expressed only in proximal tubules. These findings suggest lnc-CHAF1B-3 affects the progression of RIF by regulating EMT-related signaling. Thus, lnc-CHAF1B-3 is a potential target in the treatment of RIF.

Two cases of ceftriaxone-induced encephalopathy treated by hemoperfusion in hemodialysis patients.

Ceftriaxone is a third-generation cephalosporin commonly used to treat infection. However, encephalopathy is an emerging adverse effect of ceftriaxone infusion. These patients present with various symptoms, including those of neurotoxicity, that typically resolve 1 week after discontinuation of ceftriaxone. We experienced two cases of ceftriaxone-induced encephalopathy that were successfully treated by rapid removal of ceftriaxone by hemoperfusion.

Usefulness of Percutaneous Transesophageal Gastro-Tubing in Patients Receiving Chemoradiotherapy for Advanced Esophageal Cancer: A Case Report.

Percutaneous endoscopic gastrostomy (PEG) is often performed for nutritional management in advanced esophageal cancer. We here report a patient who initially received enteral nutrition via a nasogastric tube and in whom the subsequent use of percutaneous transesophageal gastro-tubing (PTEG) circumvented the need for a gastrostomy. It is believed that PEG is less painful than a nasogastric tube. However, we selected PTEG because a PEG would have been within the planned irradiation field and there was concern about radiation dermatitis. We were able to administer chemoradiotherapy with sufficient nutrition via an enteral feeding tube via esophagostomy. PTEG is a very useful tool in patients at risk of radiation dermatitis of the abdomen.

A simple and effective technique for identification of intersegmental planes by infrared thoracoscopy after transbronchial injection of indocyanine green.

OBJECTIVE: Pulmonary segmentectomy has been recognized as an operative option for complete resection of early-stage lung cancer in patients with poor pulmonary function. However, identification of anatomic pulmonary segments is sometimes difficult in patients with emphysema. We developed an intraoperative method for identifying intersegmental planes of the lung with high-sensitivity infrared fluorescence imaging after transbronchial injection of indocyanine green. METHODS: The study included 10 patients with early-stage lung cancer who underwent thoracoscopic segmentectomy. Under general anesthesia, indocyanine green was injected into the bronchus of target pulmonary segments. The target segments of the lung were identified using the indocyanine green fluorescence endoscope (Hamamatsu Photonics, Hamamatsu, Japan). The intersegmental lines and planes were identified and allowed removal of the segments. To evaluate operative outcomes, we compared the indocyanine green injection group with a retrospective control group with 10 matched-pair patients who underwent traditional thoracoscopic segmentectomy. RESULTS: Accurate, real-time intraoperative detection of indocyanine green with an infrared thoracoscope was confirmed. Sparing of intersegments was safely performed using both staples and electric cautery. Furthermore, infrared thoracoscopy allowed visualization of any residual portion of resected segments after segmentectomy. There was no difference between the experimental indocyanine green and control groups in terms of operative time, duration of postoperative chest drainage, or postoperative complications. Length of stay was shorter in the indocyanine green group than in the control group (P = .055). CONCLUSIONS: Transbronchial indocyanine green injection into the relevant bronchus with the use of an infrared thoracoscope allows identification of intersegmental lines and planes during thoracoscopic segmentectomy.

Intraoperative exploration of biliary anatomy using fluorescence imaging of indocyanine green in experimental and clinical cholecystectomies.

BACKGROUND/PURPOSE: We evaluated the usefulness of intraoperative exploration of the biliary anatomy using fluorescence imaging with indocyanine green (ICG) in experimental and clinical cholecystectomies. METHODS: The experimental study was done using two 40-kg pigs and the clinical study was done in 12 patients for whom cholecystectomy was planned from January 2009 to June 2009. Initially we used a laparoscopic approach for the evaluation of fluorescence imaging of the biliary system in the two pigs. Then the clinical study was started on the basis of these experimental results. ICG (1.0 ml/body of 2.5 mg/ml ICG) was infused 1-2 h before surgery. With the subjects under general anesthesia we observed in real time the condition of the biliary tract under the guidance of fluorescence imaging employing an infrared camera or a prototype laparoscope. ICG was added intravenously to observe the location or flow condition of the cystic artery. RESULTS: We obtained a clear view of the biliary tract and the location of the cystic duct in the two pigs. Local compression with a transparent hemispherical plastic device was effective for offering a clearer view. The biliary tract, except for the gallbladder, was clearly recognized in all clinical subjects. Local compression with a transparent hemispherical plastic device for open cholecystectomy and a flat plastic device for laparoscopy provided clearer visualization of the confluence between the cystic duct and common bile duct or common hepatic duct. The location of the cystic artery was revealed after division of the connective tissues, and the flow condition of the cystic artery was confirmed 7-10 s after intravenous re-infusion of ICG. There were no adverse events related to the intraoperative procedure or the ICG itself. CONCLUSIONS: This method is safe and easy for the identification of the biliary anatomy, without requiring cannulation into the cystic duct, X-ray equipment, or the use of radioactive materials. Although fluorescence imaging is still at an early stage of application in comparison with ordinary intraoperative cholangiography, we expect that this method will become routine, offering a lower degree of invasiveness that will help avoid bile duct injury.

Neuropeptide Y functions as a facilitator of GDNF-induced budding of the Wolffian duct.

Ureteric bud (UB) emergence from the Wolffian duct (WD), the initiating step in metanephric kidney morphogenesis, is dependent on GDNF; however, GDNF by itself is generally insufficient to induce robust budding of the isolated WD in culture. Thus, additional factors, presumably peptides or polypeptide growth factors, might be involved. Microarray data from in vivo budding and non-budding conditions were analyzed using non-negative matrix factorization followed by gene ontology filtering and network analysis to identify sets of genes that are highly regulated during budding. These included the GDNF co-receptors GFRalpha1 and RET, as well as neuropeptide Y (NPY). By using ANOVA with pattern matching, NPY was also found to correlate most significantly to the budded condition with a high degree of connectedness to genes with developmental roles. Exogenous NPY [as well as its homolog, peptide YY (PYY)] augmented GDNF-dependent budding in the isolated WD culture; conversely, inhibition of NPY signaling or perturbation of NPY expression inhibited budding, confirming that NPY facilitates this process. NPY was also found to reverse the decreased budding, the downregulation of RET expression, the mislocalization of GFRalpha1, and the inhibition of AKT phosphorylation that resulted from the addition of BMP4 to the isolated WD cultures, suggesting that NPY acts through the budding pathway and is reciprocally regulated by GDNF and BMP4. Thus, the outgrowth of the UB from the WD might result from a combination of the upregulation of the GDNF receptors together with genes that support GDNF signaling in a feed-forward loop and/or counteraction of the inhibitory pathway regulated by BMP4.

Percutaneous transesophageal gastrostomy tube for decompression of malignant obstruction: report of the first case and our series in the US.

BACKGROUND: Historically, surgical gastrostomies, gastrojejunostomy, and percutaneous endoscopic gastrostomy have been used palliatively. Recently, enteral stenting has also provided a means of reestablishing gastrointestinal flow in proximal and colonic obstructions. STUDY DESIGN: Seven patients with known intraabdominal malignancy leading to gastrointestinal obstruction were evaluated for PTEG. Ultrasonography, fluoroscopy, and a rupture-free balloon were used in placement. An endoscope was not used. Consent was obtained from all patients. The procedure was performed by a single surgical endoscopist in an endoscopy suite. Patients had appropriate hemodynamic monitoring with pulse oximetry, and they were given preprocedure antibiotics and sedation. RESULTS: PTEG was successfully placed and alleviated symptoms in all seven patients. One complication occurred; in the fourth patient subcutaneous emphysema developed on postoperative day 1, and was managed nonoperatively. All patients were discharged from the hospital. CONCLUSIONS: PTEG is a safe and effective technique for decompression in malignant gastrointestinal obstruction.

b-series Ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve.

The polymorphic carbohydrate structures of gangliosides play regulatory roles. In particular, b-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to be critical in various biological events such as adhesion, toxin binding, neurite extension, cell growth, and apoptosis. To clarify the physiological functions of b-series gangliosides in vivo, we have established a gene knockout mouse of GD3 synthase. Although all b-series structures were deleted in the mutant mice, they showed an almost complete nervous tissue morphology with no apparent abnormal behavior. Moreover, no differences in Fas-mediated apoptotic reaction of lymphocytes between wild type and the mutant mice were detected. However, the mutant mice exhibited clearly reduced regeneration of axotomized hypoglossal nerves compared with the wild type, suggesting that b-series gangliosides are more important in the repair rather than in the differentiation of the nervous system and apoptotic process induced via Fas.