Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis

Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms.     

Evaluation of aggressive surgical treatment for advanced carcinoma of the gallbladder

Background/Purpose. An aggressive approach is required to resect advanced carcinoma of the gallbladder. Therefore, an extended surgical procedure often brings about a poor surgical outcome. To test whether an aggressive surgical treatment can improve the survival rate for primary advanced carcinoma of the gallbladder, 59 patients with stage IV primary gallbladder carcinoma were studied. Methods. Patients were divided into three treatment groups for the survival analysis: group A (resectional surgery, n = 29), group B (low-dose cis-diamminedichloroplatinum-II and 5-fluorouracil therapy, n = 10), and group C (exploratory laparotomy, other treatment modalities, or no treatment, n = 20). Results. The prognosis of group A patients was significantly better than that of group B (P = 0.018) or group C (P = 0.0009). Furthermore, group A patients were divided into subgroups. The prognosis of patients resected with no distant metastasis (group A1) was significantly better than that of patients resected with distant metastases of the distant lymph nodes and the liver (group A2) (P = 0.0004). Also, there was no significant difference in the survival rate between the patients resected with distant metastasis (group A2) and chemotherapy cases (group B). Conclusions. These results indicated that radical surgery should be performed for patients with no distant metastasis, and that chemotherapy might be a useful alternative treatment for patients with distant metastasis in advanced carcinoma of the gallbladder.     

Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients.

STUDY OBJECTIVE: To characterize clinical, radiographic, and CT findings of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with pneumoconiosis. METHODS: We studied 10 patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of CNPA during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. RESULTS: All patients were men, ranging in age from 48 to 77 years (mean, 60.1 years). Their occupational histories included pottery making (n = 9) and coal mining (n = 1). Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, hemoptysis, and dyspnea. Serum findings were positive for the Aspergillus antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. CONCLUSIONS: Chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.     

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg¹⁶⁸⁹. The method used a coating alloantibody which recognized amino acid residues 2248–2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675–1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC₅₀) was approximately 1·0 U/ml. The plasma of four haemophilia A positive (A⁺) and two haemophilia A reduced (A^R) patients were analysed. The IC₅₀ of all patients was more than 1·0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A⁺ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0·04 U/ml and FVIII:Ag of 1·78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646–1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg¹⁶⁸⁹.     

Prescription of potentially inappropriate medications in elderly outpatients: a survey using 2015 Japanese Guidelines

International Journal of Clinical Pharmacy - Background In recent years, rapid increase of elderly population has become a major social problem in developed countries. They tend to...     

Molecular and immunological developments in placentas

Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune cells in placentas, and EVTs, which invade the decidua and uterine myometrium, face the cells in the uterus. This situation, in which trophoblasts come into contact with maternal immune cells, is known as the maternal-fetal interface. Despite fetuses and fetus-derived trophoblast cells being of the semi-allogeneic conceptus, fetuses and placentas are not rejected by the maternal immune system because of maternal-fetal tolerance. The acquired tolerance develops during normal placentation, resulting in normal fetal development in humans. In this review, we introduce placental development from the viewpoint of molecular biology. In addition, we discuss how the disruption of placental development could lead to complications in pregnancy, such as hypertensive disorder of pregnancy, fetal growth restriction, or miscarriage.     

Mantle cell lymphoma with EBV-positive Hodgkin and Reed–Sternberg-like cells in a patient after autologous PBSCT: Phenotypically distinct but genetically related tumors

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed–Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5⁻, CD15⁺, CD20⁻, CD30⁺, PAX5⁺, Bob.1⁻, Oct2⁻ and EBER⁺. The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein–Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.     

Rhythmic adenosine triphosphate release from the cyanobacterial circadian clock protein KaiC revealed by real-time monitoring of bioluminescence using firefly luciferase

The cyanobacterial circadian clock is composed of three clock proteins, KaiA, KaiB and KaiC. This KaiABC clock system can be reconstituted in vitro in the presence of adenosine triphosphate (ATP) and Mg²⁺, and shows circadian rhythms in the phosphorylation level and ATPase activity of KaiC. Previously, we found that ATP regulates a complex formation between KaiB and KaiC, and KaiC releases ATP from KaiC itself (PLoS One, 8, 2013, e80200). In this study, we examined whether the ATP release from KaiC shows any rhythms in vitro. We monitored the release of ATP from wild-type and ATPase motif mutants of KaiC as a bioluminescence in real time using a firefly luciferase assay in vitro and obtained the following results: (a) ATP release from KaiC oscillated even without KaiA and KaiB although period of the oscillation was not 24 hr; (b) ATP was mainly released from the N-terminal domain of KaiC; and (c) the ATP release was enhanced and suppressed by KaiB and KaiA, respectively. These results suggest that KaiC can generate basal oscillation as a core clock without KaiA and KaiB, whereas these two proteins contribute to adjusting and stabilizing the oscillation.