Involvement of selective autophagy mediated by p62/SQSTM1 in KLHL3-dependent WNK4 degradation.

We reported that kelch-like protein 3 (KLHL3)-Cullin3 E3 ligase ubiquitinates with-no-lysine kinase 4 (WNK4) and that impaired WNK4 ubiquitination causes pseudohypoaldosteronism type II, a hereditary hypertensive disease. However, we also found that KLHL3-induced WNK4 degradation could not be inhibited completely by a proteasome inhibitor. Rather, on exposure, for 24 h, of HEK293T cells expressing WNK4 and KLHL3 to a proteasome inhibitor, epoxomicin, the WNK4 protein level was further decreased.

Unusual bleeding from hepaticojejunostomy controlled by adult variable stiffness colonoscopy: report of a case and literature review.

We herein present a case of a 59-year-old man who had undergone pylorus preserving pancreaticoduodenectomy with regional lymph node dissection prior to episodes of melena. Series of conventional endoscopic investigations failed to identify the bleeding source. Enhanced computed tomography scan revealed complete obstruction of the main portal vein with numerous collateral veins running towards the hepatic hilus.

Primary papillary hyperplasia of the gallbladder mimicking gallbladder cancer.

Primary papillary hyperplasia of the gallbladder (PPHG) is a rare entity. PPHG is a benign diffuse mucosal projection without any background chronic inflammation-related disease of the gallbladder or bile ducts. Reported cases of PPHG are limited in that its characteristics are not well defined.

Copper-deficiency anemia after esophagectomy: A pitfall of postoperative enteral nutrition through jejunostomy.

Introduction: Copper deficiency leads to functional disorders of hematopoiesis and neurological system. There have been some reports of copper deficiency occurring to the patients on enteral nutrition through a jejunostomy in long-term-care hospitals. However, it is extremely rare to find patients with copper deficiency several months after esophagectomy, regardless of enteral nutrition through the jejunostomy.

Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms.

Recently, we demonstrated that WNK4 is a substrate for KLHL3-Cullin3 (CUL3) E3 ubiquitin ligase complexes and that impaired WNK4 ubiquitination is a common mechanism for pseudohypoaldosteronism type II (PHAII) caused by WNK4, KLHL3, and CUL3 mutations. Among the various KLHL3 mutations that cause PHAII, we demonstrated that the R528H mutation in the Kelch domain decreased the binding to WNK4, thereby causing less ubiquitination and increased intracellular levels of WNK4. However, the pathogenic mechanisms of PHAII caused by other KLHL3 mutants remain to be determined.

KLHL2 interacts with and ubiquitinates WNK kinases.

Mutations in the WNK1 and WNK4 genes result in an inherited hypertensive disease, pseudohypoaldosteronism type II (PHAII). Recently, the KLHL3 and Cullin3 genes were also identified as responsible genes for PHAII. Although we have reported that WNK4 is a substrate for the KLHL3-Cullin3 E3 ligase complex, it is not clear whether all of the WNK isoforms are regulated only by KLHL3.

Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension.

Mutations in WNK kinases cause the human hypertensive disease pseudohypoaldosteronism type II (PHAII), but the regulatory mechanisms of the WNK kinases are not well understood. Mutations in kelch-like 3 (KLHL3) and Cullin3 were also recently identified as causing PHAII. Therefore, new insights into the mechanisms of human hypertension can be gained by determining how these components interact and how they are involved in the pathogenesis of PHAII.

[A case of vaginal metastasis of rectal cancer post -operation].

Vaginal metastasis is extremely rare, as is metastatic colorectal cancer. A 78-year-old woman was diagnosed with rectal cancer and uterine fibroid. Low anterior resection and simple hysterectomy was performed and the final diagnosis was fStage IIIa.

Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination.

Na-Cl cotransporter (NCC) is phosphorylated in its amino terminus based on salt intake under the regulation of the WNK-OSR1/SPAK kinase cascade. We have observed that total protein abundance of NCC and its apical membrane expression varies in the kidney based on the phosphorylation status. To clarify the mechanism, we examined NCC ubiquitination status in mice fed low, normal and high salt diets, as well as in a model mouse of pseudohypoaldosteronism type II (PHAII) where NCC phosphorylation is constitutively elevated.

[Curative resection of gallbladder cancer with simultaneous liver metastasis].

A 67-year-old man visited our hospital for further check-up of biliary tract disease since his two brothers suffered from biliary tract cancer. Abdominal CT scan revealed a wall thickning at the fundus of gallbladder and its vascularity was rich. Chronic cholecystitis was diagnosed, however, cancer was highly suspected.

[A case report of chemoradiotherapy combined with S-1 responding to squamous cell carcinoma of the anal canal].

A 79-year-old woman was reffered to our hospital with the chief complaint of hematochezia. Type-2 tumor was found on anal canal by colonoscopy, and pathologic examination revealed a poorly differentiated squamous cell carcinoma. Computed tomography of the abdomen demonstrated obturatory node metastasis.

[mFOLFOX6 and FOLFIRI/bevacizumab treatment in a patient on hemodialysis with metastatic colon cancer].

A 58-year-old woman, who was undergoing peritoneal dialysis( PD) for chronic kidney disease (CKD) and had been operated by sigmoidectomy for early colonic cancer, was diagnosed as peritoneal recurrence of the colonic cancer. Her treatment for CKD was switched from PD to hemodialysis. She was administered mFOLFOX6 therapy(reducing the dose to 70%).

[Gallbladder carcinoma, progressed along cholecystoduodenal fistula--a case report].

A 75-year-old woman had an operation for gallstone ileus without cholecystectomy in other hospital and she was admitted to our hospital because of duodenal adenoma with severe atypia and small carcinoid in proximal duodenal wall. Distal gastrectomy and cholecystectomy were performed. Histological studies revealed the existence of cholecystoduodenal fistula and suggested the existence of gallbladder carcinoma progressed to the duodenal wall through the fistula.

[A case of ruptured hepatocellular carcinoma originated from nonalcoholic steatohepatitis (NASH)].

A 69-year-old woman visited our emergency room because of sudden right lower quadrant abdominal pain. Abdominal CT revealed a ruptured tumor in the anterior segment of the liver. Emergency laparotomy was selected due to interventional radiology was not available.

[Two cases of pancreatic cancer with fairly good prognosis].

We report two cases of advanced pancreatic cancer whose prognoses are fairly good with surgery and chemotherapy. Case 1: A 71-year-old male patient was diagnosed as pancreatic head cancer by abdominal ultrasound. The tumor size was about 2 cm in diameter.

Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide.

A 73-year-old man was admitted with complaints of a 2-month history of generalized weakness and numbness. Laboratory examination revealed hypercalcemia, metabolic alkalosis, and kidney injury, similar to the traditional milk-alkali syndrome. The clinical history and the response to therapy indicated that alphacalcidol and thiazide taken daily were the cause.

Assessment and significance of abdominal aortic calcification in chronic kidney disease.

Background: Abdominal aortic calcification is a common complication and a predictor of cardiovascular mortality in dialysis patients. However, abdominal aortic calcification in pre-dialysis chronic kidney disease (CKD) is poorly understood.

Methods: A cohort study of 101 adult Japanese patients (mean age 66.

[Case of Henoch-Schönlein purpura nephritis successfully treated with tonsillectomy and steroid pulse therapy].

A 30-year-old Japanese man was admitted to our hospital because of fever, sore throat, abdominal pain, purpura skin lesion of the lower legs, and macrohematuria. On admission, his urine was positive (++) for protein; the sediment contained 100 red blood cells per high-power field, and the daily proteinuria level was 1.7 g.