[Autoimmune acquired coagulation factor XIII/13 deficiency caused by type Ab anti-FXIII-A autoantibody].

An 88-year-old man became unconscious and was admitted to our hospital due to severe anemia. Extensive subcutaneous hemorrhage around the chest and back and pectoralis major muscle hematoma were observed. Coagulation screening tests showed moderately reduced factor XIII/13 (FXIII) activity. During hospitalization, the patient had repeated bleeding events in the gastrointestinal tract and muscles, leading to hemorrhagic shock. We suspected the presence of FXIII inhibitors from FXIII infusion test results. The cross-mixing test for cross-linking of fibrin revealed inhibition of polymerization of α-chain and α2-plasmin inhibitor incorporation into fibrin. In addition, by detecting IgG autoantibody to thrombin-activated FXIII, we confirmed the presence of type Ab anti-FXIII-A subunit autoantibody, which represses the catalytic subunit activity of activated FXIII. Autoimmune FXIII deficiency should be considered when a patient presents with severe hemorrhagic diathesis with no other cause than moderately reduced of FXIII activity, as reported in this case.

High-dose dexamethasone therapy as the initial treatment for idiopathic thrombocytopenic purpura.

There is a controversy which short term high dose dexamethasone therapy (HDD) or standard dose prednisolone therapy as the initial treatment leads to long term efficacy in idiopathic thrombocytopenic purpura (ITP) patients. We conducted a multicenter, prospective trial to determine the efficacy and safety of short-term HDD in ITP patients aged 18-80 years with platelet counts of < 20 × 109/l, or < 50 × 109/l and bleeding symptoms. The primary endpoints are the proportion of complete response (CR) plus partial response (R) on day 180 after the completion of the 46-day HDD. Twenty-three patients were enrolled. Test for Helicobacter pylori (H. pylori) was positive for 6 patients and negative for 17 patients. In positive patients, 5 were received successful H. pylori eradication therapy. The proportion of CR + R was 60.9% (14/23) with 90% confidence interval of 41.7-77.8%. For patients with positive H. pylori and successful eradication, the proportion of CR + R was 80.0% (4/5). There was one grade 4 adverse event. Although we have enrolled relatively old, severe ITP patients with a median age of 63 years in this study, the efficacy was comparable to the reported clinical trials with HDD therapy.

Biological implications of somatic DDX41 p.R525H mutation in acute myeloid leukemia.

The DDX41 gene, encoding a DEAD-box type ATP-dependent RNA helicase, is rarely but reproducibly mutated in myeloid diseases. The acquired mutation in DDX41 is highly concentrated at c.G1574A (p.R525H) in the conserved motif VI located at the C-terminus of the helicase core domain where ATP interacts and is hydrolyzed. Therefore, it is likely that the p.R525H mutation perturbs ATPase activity in a dominant-negative manner. In this study, we screened for the DDX41 mutation of CD34-positive tumor cells based on mRNA sequencing and identified the p.R525H mutation in three cases among 23 patients. Intriguingly, these patients commonly exhibited acute myeloid leukemia (AML) with peripheral blood cytopenias and low blast counts, suggesting that the mutation inhibits the growth and differentiation of hematopoietic cells. Data from cord blood cells and leukemia cell lines suggest a role for DDX41 in preribosomal RNA processing, in which the expression of the p.R525H mutant causes a certain ribosomopathy phenotype in hematopoietic cells by suppressing MDM2-mediated RB degradation, thus triggering the inhibition of E2F activity. This study uncovered a pathogenic role of p.R525H DDX41 in the slow growth rate of tumor cells. Age-dependent epigenetic alterations or other somatic changes might collaborate with the mutation to cause AML.

A case of a large cholangiolocellular carcinoma.

Cholangiolocellular carcinoma (CoCC) is a rare malignant primary liver tumor that is considered to originate from the canals of Hering, where hepatic progenitor cells are located. CoCC has various clinicopathological findings, therefore it is difficult to describe a clear diagnostic criteria for CoCC. Reported is a case of a large CoCC in a 45-year-old Japanese woman, which could not be preoperatively diagnosed as CoCC. The final diagnosis of CoCC was determined by pathological observation. Since both the biological behavior and diagnostic criteria of CoCC remain unclear, it is necessary to accumulate more information on CoCCs in order to elucidate these characteristic findings.

[An effective treatment by chemotherapy with S-1 and CDDP intraperitoneal administration for the peritoneal dissemination of gastric cancer--a case report].

The most common treatment for patients of peritoneal dissemination of gastric cancer is a systemic chemotherapy, but the prognosis of these patients is very poor. For these diseases, some have reported the usefulness of intraperitoneal chemotherapy with cisplatin (CDDP), because of the direct cytotoxicity. Here, we report an effective treatment by chemotherapy with S-1 plus CDDP, intraperitoneal administration for the patients of peritoneal dissemination of gastric cancer. The patient was a 41-year-old male with upper abdominal pain. Upper gastrointestinal endoscopy showed a large type 3 gastric cancer from the cardia to antrum. Intraoperative peritoneal lavage cytology and dissemination was positive, thus we performed the total gastrectomy and implanted the intraperitoneal (IP) port in the Douglas's pouch. S-1 was given orally twice daily for the first 3 weeks of a 5-week cycle. CDDP was given as an intraperitoneal infusion on day 8 of each cycle. After 10 courses, he was treated with S-1 alone because he had an allergic reaction of CDDP. In 35 courses, he had survived for 5 years as disease free. Intraperitoneal chemotherapy may be a promising treatment for the patients who have peritoneal dissemination from gastric cancer.

Axin localizes to the centrosome and is involved in microtubule nucleation.

Axin is known to have an important role in the degradation of beta-catenin in the Wnt pathway. Here, we reveal a new function of Axin at the centrosome. Axin was localized to the centrosome in various cell lines and formed a complex with gamma-tubulin. Knockdown of Axin reduced the localization of gamma-tubulin and gamma-tubulin complex protein 2-components of the gamma-tubulin ring complex-to the centrosome and the centrosomal microtubule nucleation activity after treatment with nocodazole. These phenotypes could not be rescued by the reduction in the levels of beta-catenin. Although the expression of Axin rescued these phenotypes in Axin-knockdown cells, overexpression of Axin2, which is highly homologous to Axin, could not. Axin2 was also localized to the centrosome, but it did not form a complex with gamma-tubulin. These results suggest that Axin, but not Axin2, is involved in microtubule nucleation by forming a complex with gamma-tubulin at the centrosome.