Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

AbstractAutosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration

Central Venous Stenosis Caused by Traction of the Innominate Vein due to a Tuberculosis-Destroyed Lung

We report a case of central venous stenosis due to a structural deformity caused by a tuberculosis-destroyed lung in a 65-year-old woman. The patient presented with left facial edema. She had a history of pulmonary tuberculosis, and the chest X-ray revealed a collapsed left lung. Angiography showed leftward deviation of the innominate vein leading to kinking and stenosis of the internal jugular vein. Stent insertion improved her facial edema

An Infrarenal Aortic Hypoplasia Presented with Claudication

We describe a case of infrarenal aortic hypoplasia in a 52-yr-old woman who presented with claudication. Computed tomographic angiography revealed an abrupt absence of the infrarenal aorta, with collateral flow reconstituting the iliofemoral systems. After a polytetrafluoroethylene graft was interposed between the aortic stump and the iliac bifurcation, the patient's claudication resolved

Peritoneal carcinomatosis with desmoplasia and osseous metaplasia mimicking encapsulating peritoneal sclerosis in a cat: case report

A 13-year-old neutered male Korean short-hair cat presented with anorexia, lethargy, and a severely distended abdomen, suggestive of ascites. Abdominocentesis yielded serosanguineous fluid. A subsequent diagnostic workup, including blood tests, ascitic fluid analysis, imaging studies [radiography, ultrasound, and computed tomography (CT)], and histopathological examination, was performed to identify the underlying cause. Imaging studies revealed characteristics of encapsulating peritoneal sclerosis (EPS) such as peritoneal thickening, fat stranding, and calcification. During laparotomy, fibrous membranes encapsulating the abdominal organs and ascites were observed, and multiple calcified regions were detected on the abdominal wall. Histopathological analysis confirmed the diagnosis of poorly differentiated invasive malignant neoplasms, which were further classified as carcinomatosis based on positive cytokeratin and negative vimentin immunohistochemistry results. To our knowledge, this is the first report of sclerosing peritoneal carcinomatosis with osseous metaplasia in a cat

Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons (MNs) and subsequent muscle weakness. These pathological features are associated with numerous cellular changes, including alteration in mitochondrial morphology and function. However, the molecular mechanisms associating mitochondrial structure with ALS pathology are poorly understood. In this study, we found that Dynamin-related protein 1 (Drp1) was dephosphorylated in several ALS models, including those with SOD1 and TDP-43 mutations, and the dephosphorylation was mediated by the pathological induction of protein phosphatase 1 (PP1) activity in these models. Suppression of the PP1-Drp1 cascade effectively prevented ALS-related symptoms, including mitochondrial fragmentation, mitochondrial complex I impairment, axonal degeneration, and cell death, in primary neuronal culture models, iPSC-derived human MNs, and zebrafish models in vivo. These results suggest that modulation of PP1-Drp1 activity may be a therapeutic target for multiple pathological features of ALS

Gender differences in characteristics of adolescents with suicide attempt at the emergency department

Purpose This study was performed to investigate the gender differences in suicide attempts in adolescents. Methods We reviewed the medical records of adolescents (≤ 18 years) who had visited a university hospital emergency department (ED) for suicide attempts from January 2018 through December 2019. General characteristics of the adolescents, details of the attempt, and outcomes were analyzed. The characteristics were age, gender, the Korean Triage and Acuity Scale, previous attempts, and psychiatric history. The details were initial Glasgow Coma Scale, attempt-arrival time, living alone, method, place, and motivation of the attempt, and concurrent use of alcohol. The outcomes included psychiatric consultation, ED length of stay, and ED outcomes. Results A total of 86 adolescents were included. Their age ranged from 13 to 18 years, and girls accounted for 65.1%. The girls had more frequent psychiatric history than boys (66.1% vs. 30.0%; P = 0.001) without a significant difference in previous attempts (55.4% vs. 46.7%; P = 0.442). The most common methods of the attempt in the girls and boys were poisoning and sharp objects (53.3% [16 of the 30 boys] vs. 60.7% [34 of the 56 girls]; P = 0.002), respectively. No differences were found in the other details of the attempt and in the rate of psychiatric consultation. The girls had a longer ED length of stay (247.0 minutes vs. 186.5; P = 0.033), a lower rate of discharge against medical advice, and higher rates of hospitalization (discharge against medical advice, 53.6% vs. 76.7%; non-psychiatric, 23.2% vs. 3.3%; psychiatric, 12.5% vs. 0%; P = 0.003). Conclusion Girls may make suicide attempts, usually by poisoning, and undergo relevant hospitalization, more often than boys. In contrast, boys usually use sharp objects, with a higher rate of discharge against medical advice and lower rates of the attempt and hospitalization

Waldenstrom Macroglobulinemia with CD5+ Expression Presented as Cryoglobulinemic Glomerulonephropathy: A Case Report

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders