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Morris Hoffman posted an update 6 months ago
Then, mouse embryonic stem cells (mESCs) were transplanted into the scala tympani and survival and distribution of transplanted cells were compared between the acute and chronic auditory neural hearing loss models induced by ouabain or kanamycin (KM), respectively. The mESC survival was similar to the acute model, and perilymphatic distribution of cell aggregates was more predominant in the chronic model. Lastly, the effects of mESC transplantation on neural signal transduction observed in the cochlear nucleus (CN) were compared and a statistical increase was observed in the chronic model compared with other models. These results indicated that after transplantation, mESCs survived in the cochlea and increased the neural signaling toward the central auditory pathway, even in the chronic (secondary) hearing loss mouse model.Pseudomonas aeruginosa is a gram-negative opportunistic pathogen capable of causing both acute and chronic infections, particularly in individuals with compromised host defenses. The quorum sensing transcriptional activator LasR is widely recognized for its role in regulating the expression of acute virulence factors, notably several secreted proteases which cause direct host damage and subvert host immunity in acute infections. Paradoxically, lung infections caused by LasR-deficient variants, which are found in at least a third of cystic fibrosis (CF) patients with chronic P. aeruginosa infections, are associated with accelerated lung disease and increased markers of inflammation compared to infections caused by strains with a functional LasR system. While the loss of LasR function often (although not always) results in impaired production of LasR-controlled acute virulence factors, the implication of this pathoadaptation on host-pathogen interactions and chronic disease pathology is less well recognized. We recently observed that loss of LasR function in lasR variants, which results in impaired secreted protease production, led to increased expression of the membrane-bound surface adhesion molecule mICAM-1 in the airway epithelium, and increased neutrophilic inflammation. Specifically, human airway epithelial cells stimulated with lasR variants had higher mICAM-1 expression and greater neutrophil binding in vitro compared to stimulation with wild-type P. aeruginosa. In a subacute non-lethal P. aeruginosa lung infection model, lasR variant infection also induced higher mICAM-1 expression in the murine airway epithelium and was associated with increased neutrophilic pulmonary inflammation in vivo. Here, we discuss how (loss of) LasR function and LasR-regulated proteases affect host immunity, inflammation and tissue pathology in acute vs. chronic P. aeruginosa lung infection.Ageing-related processes are largely conserved, with simple organisms remaining the main platform to discover and dissect new ageing-associated genes. Yeasts provide potent model systems to study cellular ageing owing their amenability to systematic functional assays under controlled conditions. Even with yeast cells, however, ageing assays can be laborious and resource-intensive. Here we present improved experimental and computational methods to study chronological lifespan in Schizosaccharomyces pombe. We decoded the barcodes for 3206 mutants of the latest gene-deletion library, enabling the parallel profiling of ~700 additional mutants compared to previous screens. We then applied a refined method of barcode sequencing (Bar-seq), addressing technical and statistical issues raised by persisting DNA in dead cells and sampling bottlenecks in aged cultures, to screen for mutants showing altered lifespan during stationary phase. This screen identified 341 long-lived mutants and 1246 short-lived mutants which point to many previously unknown ageing-associated genes, including 46 conserved but entirely uncharacterized genes. The ageing-associated genes showed coherent enrichments in processes also associated with human ageing, particularly with respect to ageing in non-proliferative brain cells. We also developed an automated colony-forming unit assay to facilitate medium- to high-throughput chronological-lifespan studies by saving time and resources compared to the traditional assay. Results from the Bar-seq screen showed good agreement with this new assay. This study provides an effective methodological platform and identifies many new ageing-associated genes as a framework for analysing cellular ageing in yeast and beyond.
Neuroma of the biliary tree is extremely rare with no more than 100 cases reported so far. They mostly present with obstructive jaundice and have been commonly described after surgery or abdominal trauma. Although involvement of the extrahepatic bile duct is far more common, occurrence in the intrahepatic ducts has not so far been reported.
We describe 3 cases of diffuse biliary tree neuroma affecting 3 females aged 53-68 years. None had a history of neurofibromatosis type1. BI-2493 purchase All presented with progressive obstructive jaundice with no evidence of gallstones. A history of previous surgery was noted in 2 patients. Initial impression on clinical and imaging examination was highly suspicious for bile duct carcinoma in 2 patients. Histology showed diffuse neuromatous proliferation replacing and thickening the bile duct walls. The third patient had concurrent neuroma and recurrent cholangiocarcinoma causing great clinical confusion as initial biopsy showed only benign neuroma, but CA 19-9 was steadily increasing, necessitating a second biopsy which then confirmed recurrent carcinoma.
This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.
This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.Pseudomyxoma peritonei (PMP) refers to accumulation of mucinous ascites with or without neoplastic cells in the peritoneal cavity. It most commonly originates from a low or a high grade primary appendiceal mucinous neoplasm. Though adenocarcinoma of gall bladder has been reported to give rise to PMP, to the best of our knowledge, this is the first report of a PMP arising from a low grade mucinous tumour of the gall bladder. A 72-year-old patient was diagnosed with PMP 1.5 years after a cholecystectomy. After initial oral TS1 (combination of tegafur, gimeracil and oteracil) and later intraperitoneal (IP) chemotherapy with docetaxel and cisplatin, the patient was operated with the goal of tumour debulking, including removal of 5.5 L of mucinous ascites, an appendectomy, and ovariectomy. The histopathologic report showed a normal appendix and metastasis of PMP to the right ovary. After the exclusion of the 2 most common sites of origin (appendix and ovary), the specimen of the cholecystectomy was reviewed. It showed low grade mucinous tumour in the gall bladder, with immuno-histochemical markers (IHCs) suggestive of CK7, CDX2, MUC 2 positive and CK20, MUC5AC negative.
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