L-carbocisteine can cause cholestasis with vanishing bile duct syndrome in children: A case report.

RATIONALE: Vanishing bile duct syndrome (VBDS) is the acquired progressive destruction and disappearance of intrahepatic interlobular bile ducts in the absence of underlying liver or biliary tract disease, causing chronic cholestasis. Infections, drugs, toxins, malignant diseases, and certain immunological processes are associated with the development of this syndrome. There have been no reports of children developing VBDS as a consequence of the administration of L-carbocisteine. PATIENT CONCERNS: A 9-year-old Japanese girl presented with fever, jaundice, and skin rash. Laboratory investigations revealed elevated levels of serum transaminases, γ-glutamyltransferase, and bilirubin. Histopathological features were consistent with a diagnosis of VBDS. Drug-induced lymphocyte stimulation tests (DLST) were positive for L-carbocisteine. DIAGNOSIS: VBDS caused by L-carbocisteine. INTERVENTIONS: Ursodeoxycholic acid and discontinuation of L-carbocisteine. OUTCOMES: The patient responded to treatment based upon discontinuation of L-carbocisteine and administration of ursodeoxycholic acid. Her transaminase and bilirubin levels were normalized gradually. LESSONS: Physicians should be aware of the fact that L-carbocisteine can cause cholestasis with VBDS in children.

Child requiring tracheostomy for removal of an airway foreign body at the tracheal bifurcation.

Airway foreign bodies are typically removed orally using a rigid bronchoscope. We present a rare case of a foreign body at the tracheal bifurcation that required removal via tracheostomy. A child turned pale while eating nuts and was suspected to have choked on a foreign body. CT revealed a foreign body at the tracheal bifurcation. As his respiratory condition was unstable, tracheal intubation and removal were attempted using a rigid bronchoscope. Tracheal obstruction during oral removal resulted in respiratory failure and bradycardia. Following emergency tracheostomy, the foreign body was removed via the tracheal stoma after his respiratory condition stabilised. The patient was discharged 21 days later without neurological sequelae. To avoid hypoxaemia during airway foreign body removal, as in this case, assessing the size of the upper airway and foreign body is necessary. Tracheostomy and foreign body removal through the tracheal opening should be considered proactively.

Fracture of a Temporary Inferior Vena Cava Filter.

Anticoagulation is recommended for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT). In some cases, an inferior vena cava (IVC) filter is used to prevent PE. We report the case of a 70-year-old woman who developed non-massive PE and proximal DVT, which were treated using an IVC filter; two filters were placed owing to the fracture of the filters. Few previous reports have discussed IVC fractures and the difficulty in detecting such fractures on computed tomography before retrieval. Based on our experience, we suggest that a temporary IVC filter for DVT treatment should be considered carefully.

Percutaneous Catheter Thrombus Aspiration of Right Renal Infarction Caused by Left Ventricular Thrombi due to Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TC) is a temporal dysfunction of the left ventricle (LV) due to psychological or physiological stress; however, it rarely causes LV thrombus. We report a case of a 49-year-old woman who developed LV thrombi due to TC despite anticoagulation therapy. The thrombi caused acute systemic infarction, with the most severe occlusion being in the right renal artery. The patient underwent percutaneous catheter aspiration thrombectomy of the right renal artery and her renal function recovered shortly after. The results of this case suggest that catheter aspiration thrombectomy is effective in the treatment of thromboembolism in TC.

Incidence, Clinical Course, and Risk Factors of Amiodarone-Induced Thyroid Dysfunction in Japanese Adults With Congenital Heart Disease.

BACKGROUND: Although amiodarone (AMD)-induced thyroid dysfunction (AITD) is an important complication of AMD therapy, little is known about AITD in adult Japanese patients with congenital heart disease (CHD). METHODS AND RESULTS: We retrospectively studied 131 adult patients with CHD who were on low-dose AMD (median, 150 mg/day). The median patient age was 28 years, and the median follow-up was 44 months. The incidence, clinical course, and risk factors of AITD, including AMD-induced thyrotoxicosis (AIT) and AMD-induced hypothyroidism (AIH), were evaluated. The total incidence of AITD was 30% (AIT: 18%, n=24; AIH: 12%, n=16). Approximately 67% of patients with AIT displayed deterioration of tachyarrhythmia, and 38% patients underwent steroid therapy. Although thyroid function and symptoms associated with AIT improved within 6 months after diagnosis in most patients with AIT (92%), 1 patient died suddenly during an acute phase of AIT. No patient with AIH exhibited deterioration of tachyarrhythmia, and 9 patients underwent thyroid hormone replacement therapy. Cox multivariate analysis identified no independent risk factor for AIT, whereas liver dysfunction (hazard ratio 2.573; 95% confidence interval 1.102-5.795) was an independent risk factor for AIH. CONCLUSIONS: AITD commonly occurred in adult Japanese patients with CHD even though they were on a low-dose AMD regimen. Risk factors for AITD may vary according to ethnicity and diet.

Function of the head-tail junction in the activity of myosin II.

All class II myosins have the conserved amino acid sequence Pro-Leu-Leu at their head-tail junctions. We systematically altered this sequence in smooth muscle heavy meromyosin (HMM) by site-directed mutagenesis and examined the effects of these mutations on actin-myosin interactions. Deletion of the proline and second leucine did not cause any noticeable change in either actin-activated ATPase activity or actin-sliding velocity. In contrast, deletion of the two leucine residues and substitution of the first leucine with alanine resulted in a 14-fold and 5-fold decrease, respectively, in actin-activated ATPase activity. However, both these mutations did not appreciably affect actin-sliding velocity, which was consistent with a result that there was no considerable change in the ADP release rate from acto-HMM in the deletion mutant. In contrast to double-headed HMM, a single-headed subfragment-1 (S1) with a Leu-Leu deletion mutation exhibited actin activated ATPase activity similar to that by wild type S1. Our results suggest that the first leucine of the conserved Leu-Leu sequence at the head-tail junction profoundly affects the cooperativity between the two heads involved in the actin activated ATPase activity of myosin II.

Ruptured mucinous cystic neoplasm with an associated invasive carcinoma of pancreatic head in a pregnant woman: report of a case and review of literature.

Mucinous cystic neoplasm (MCN) of the pancreas is characterized by mucin-producing columnar epithelium and an ovarian-type stroma. It occurs almost exclusively in women and is almost always located in the pancreatic body or tail. Here, we report a case of large MCN located in the pancreatic head but not in the body nor tail in a 32-year-old pregnant woman, which was thought to have grown rapidly during pregnancy. It was ruptured at 34 weeks of gestation and the patient was admitted to the emergency department of the University of Fukui Hospital with an acute abdomen. Emergency cesarean section followed by pancreaticoduodenectomy was performed. The tumor consisted of many small cysts lined by a single-layer of mucinous epithelium with papillary growth and partial solid parts showing invasive growth and sarcomatoid changes, indicating mucinous cystic neoplasm with an associated invasive carcinoma (previously referred as mucinous cystadenocarcinoma). Thickened septa revealed ovarian-type stroma strongly positive for α-inhibin and partly positive for progesterone receptor immunohistochemically. We also review and discuss previous reports of MCNs including those with an associated invasive carcinoma in pregnant patients.

The effectiveness of transverse coloplasty in patients with ultra-lower rectal cancer.

Rectal cancer accounts for 40% of colon cancer, and postoperative defecatory function is considered to markedly affect the patients' quality of life. We performed transverse coloplasty in 33 patients with rectal cancer who had undergone an anal function preservation operation in which the anastomotic site was within 1 cm of the dentate line (ultra-low anterior resection) and evaluated its effectiveness in controlling the patients' defecatory function. The average daily defecation frequency 1, 6, and 12 months postoperatively was 7.8, 5, and 3.6 times daily following straight colorectal reconstruction (the anastomotic site was more than 5 cm from the dentate line) and 7.5, 3.5, and 2.4 times daily following transverse coloplasty, respectively. Concerning postoperative complications, anastomotic leakage, soiling, and constipation were observed in 1, 1, and 1 cases, respectively. Transverse coloplasty can be performed in a short time, and it is considered a safe and useful method to manage defecatory

Binuclear Ni(II)-DpaTyr complex as a high affinity probe for an oligo-aspartate Tag tethered to proteins.

A complementary recognition pair of a short-peptide tag and a small molecular probe is a versatile molecular tool for protein detection, handling, and purification, and so forth. In this manuscript, we report that the binuclear Ni(II)-DpaTyr (DpaTyr=bis((dipicolylamino)methyl)tyrosine) complex serves as a strong binding probe for an oligo-aspartate tag tethered to a protein. Among various binuclear metal complexes of M-DpaTyr (M=Zn(II), Ni(II), Mn(II), Cu(II), Cd(II), Co(III), and Fe(III)), we have found that Ni(II)-DpaTyr (1-2Ni(II)) displays a strong-binding affinity (apparent binding constant: K(app) approximately 10(5) M(-1)) for an oligo-aspartate peptide under neutral aqueous conditions (50 mM HEPES, 100 mM NaCl, pH 7.2). Detailed isothermal-titration calorimetry (ITC) studies reveal that the tri-aspartate D3-tag (DDD) is an optimal sequence recognized by 1-2Ni(II) in a 1:1 binding stoichiometry. On the other hand, other metal complexes of DpaTyr, except for Ni(II)- and Zn(II)-DpaTyr, show a negligible binding affinity for the oligo-aspartate peptide. The binding affinity was greatly enhanced in the pair between the dimer of Ni(II)-DpaTyr and the repeated D3 tag peptide (D3x2), such as DDDXXDDD, on the basis of the multivalent coordination interaction between them. Most notably, a remarkably high-binding affinity (K(app)=2x10(9) M(-1)) was achieved between the Ni(II)-DpaTyr dimer 4-4Ni(II) and the D3x2 tag peptide (DDDNGDDD). This affinity is approximately 100-fold stronger than that observed in the binding pair of the Zn(II)-DpaTyr (4-4Zn(II)) and the D4x2 tag (DDDDGDDDD), a useful tag-probe pair previously reported by us. The recognition pair of the Ni(II)-DpaTyr probe and the D3x2 tag can also work effectively on a protein surface, that is, 4-4Ni(II) is strongly bound to the FKBP12 protein tethered with the D3x2 tag (DDDNGDDD) with a large K(app) value of 5x10(8) M(-1). Taking advantage of the strong-binding affinity, this pair was successfully applied to the selective inactivation of the tag-fused beta-galactosidase by using the chromophore-assisted light inactivation (CALI) technique under crude conditions, such as cell lysate.

Biliopancreatic fistula and abscess formation in the bursa omentalis associated with intraductal papillary mucinous cancer of the pancreas.

We describe an unusual case of biliopancreatic fistula, free perforation, and subsequent abscess formation within the lesser peritoneal sac associated with intraductal papillary mucinous carcinoma (IPMC). A 71-year-old man presented with general fatigue and loss of appetite that had persisted for 1 month. Abdominal computed tomography (CT) revealed findings consistent with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas, accompanied by abscess formation in the bursa omentalis. Gastrointestinal fiberscopy revealed a swollen papilla of Vater expanded by sticky mucus, and a communication between the pancreatic duct and bile duct was demonstrated by the injection of indigo carmine solution into the pancreatic duct. Percutaneous transhepatic abscess drainage (PTAD) was performed on the day of admission. After this procedure, the patient was managed for 1 month and supported nutritionally with glycemic control for diabetes mellitus. After admission, the patient had an episode of obstructive jaundice that was treated by retrograde biliary drainage. Pancreaticoduodenectomy with lymph node dissection was then performed. Pathological examination revealed IPMN with patchy, scattered carcinoma of the pancreatic head and uncinate process with the formation of a biliopancreatic fistula. Bile duct epithelium in the area of the biliopancreatic fistula demonstrated atypical papillary epithelium suggestive of tumor invasion.

Chemo-hyperthermic peritoneal perfusion (CHPP) for appendiceal pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei is derived mostly from the rupture of an appendiceal cystic tumor and produces a large quantity of mucinous substance. Though its malignancy level is low, radical resection is difficult and its prognosis is poor. In some institutes in European countries and the United States, multidisciplinary treatment with chemo-hyperthermia at a relatively low temperature is performed following subtotal peritonectomy. We carried out high-temperature chemo-hyperthermic peritoneal perfusion following incomplete resections of mucinous tumors in six patients. METHODS: After resection of the main tumor and macroscopic gross tumor resection of dissemination, heated perfusate containing anticancer agents was poured into the peritoneal cavity and stirred and pumped into a circulation between the abdomen and a reservoir. The temperature of the surface of the peritoneum was maintained at around 43 degrees C. RESULTS: The intraperitoneal space was sufficiently heated without severe complications. The pathological diagnosis in four of the patients was peritoneal mucinous carcinomatosis, and in the other two patients, it was intermediate type between peritoneal mucinous carcinomatosis and disseminated peritoneal adenomucinosis. Two patients died, 15 and 26 months after the treatment. The other four patients have survived for 4, 24, 26, and 80 months now, and two of them, who have survived for 26 and 80 months, received a second treatment 18 and 32 months, respectively, after the initial treatment. These results seemed not to be inferior to those in the reports from institutes in Europe and the United States which performed subtotal peritonectomy and then used mild hyperthermia in chemo-hyperthermia. CONCLUSION: For treating pseudomyxoma peritonei, high-temperature chemo-hyperthermic peritoneal perfusion following incomplete tumor resection is effective even without peritonectomy.

Ratiometric fluorescence detection of a tag fused protein using the dual-emission artificial molecular probe.

We have successfully developed a ratiometric detection system for protein of interest using the complementary recognition pair of the tetra-aspartate peptide tag and the SNARF-appended Zn(ii)-DpaTyr probe.

Oligo-Asp tag/Zn(II) complex probe as a new pair for labeling and fluorescence imaging of proteins.

To accomplish the selective labeling of a specific protein in complicated biological systems, a peptide tag incorporated into the protein and a complementary small molecular probe are required. Although a variety of peptide tag/probe pairs have been developed as molecular tools for protein analyses, the availability of pairs suitable for real-time imaging of proteins is still limited. We now report a new peptide tag/artificial probe pair composed of a genetically encodable oligo-aspartate sequence (D4 tag, (D4)n, n = 1-3) and the corresponding multinuclear Zn(II) complexes (Zn(II)-DpaTyrs). The strong binding affinity of the Zn(II)-DpaTyr probes with the D4 tag was a result of the multiple coordination bonds and the multivalent effect. It was measured quantitatively by isothermal titration calorimetry. The high affinity between the tag and the probe, indispensable for the selective protein labeling, enabled the pair to be used for the labeling and fluorescence imaging of a membrane-bound receptor protein tethering a triply repeated D4 tag ((D4)3) in an intact cell configuration without significantly affecting the receptor signal transduction.

Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study.

OBJECTIVE: Some human studies and animal models of experimental osteoporosis have shown that soy isoflavones may be effective on bone health. In this study, we carried out an intervention study to explore the effects of dietary isoflavone on bone metabolism. METHODS: Forty healthy female postmenopausal Japanese immigrants living in Brazil were divided into two groups: isoflavone-administered (n = 20) or placebo (n = 20). Subjects in the isoflavone-administered group ingested 37.3 mg per day for 10 weeks. The collection of 24-hour urine and the measurement of bone stiffness were performed at 0 and 10 weeks. Urinary excretion of isoflavones and bone resorption markers were analyzed. RESULTS: Urinary isoflavone excretion in the isoflavone-administered group was significantly increased at weeks 3 and 10. Urinary excretion of bone resorption markers was reduced in the isoflavone-administered group, while the placebo group did not show any significant reduction. Differences in levels of urinary isoflavones and bone resorption markers between the two groups were significant. CONCLUSION: This study demonstrated that the bone resorption was associated with the intake of soy isoflavones in postmenopausal women, and continuous dietary intake of isoflavone may inhibit postmenopausal osteoporosis.

Aurora-B associated protein phosphatases as negative regulators of kinase activation.

The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ipl1p from S cerevisiae and aurora from Drosophila melanogaster, which are key regulators of mitosis. The present study shows that human Aurora-B is activated by okadaic acid and forms complexes with the protein serine/threonine phosphatase type 1 (PP1) or PP2A, but not with PP5. These data identified Aurora-B associated protein phosphatases as negative regulators of kinase activation. We then used a series of substrates based on a histone H3 phosphorylation site (residues 5-15) to determine the substrate specificity of human Aurora-B. We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase.

Degradation of human Aurora-A protein kinase is mediated by hCdh1.

Human Aurora-A is related to a protein kinase originally identified by its close homology to Ipl1p from Saccharomyces cerevisiae and aurora from Drosophila melanogaster, which are key regulators of the structure and function of the mitotic spindle. We previously showed that human Aurora-A is turned over through the anaphase promoting complex/cyclosome (APC/C)-ubiquitin-proteasome pathway. The association of two distinct WD40 repeat proteins known as Cdc20 and Cdh1, respectively, sequentially activates the APC/C. The present study shows that Aurora-A degradation is dependent on hCdh1 in vivo, not on hCdc20, and that Aurora-A is targeted for proteolysis through distinct structural features of the destruction box, the KEN box motifs and its kinase activity.

Intraductal mucinous tumors occurring simultaneously in the liver and pancreas.

A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a 67-year-old man is described. Abdominal ultrasonography and computed tomography (CT) revealed the presence of cystic lesions with intraluminal septae both in the caudate lobe of the liver and in the uncinate process of the pancreas; these cystic lesions communicated with the hepatic duct and pancreatic duct, respectively. Mucin retention was observed in the cysts, and cholestasis was induced by mucin secretion into the common bile duct. The lesions were resected by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy. Both lesions were multilocular cystic tumors with no papillary projections or focal mass effect in their walls. Histologically, both cystic lesions were a mixture of hyperplasia and adenoma lined by low papillary columnar epithelium. There were no cellular or histological features to suggest malignant change. The fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma. The hepatic lesion was considered to be of a similar nature to intraductal papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions occurred simultaneously in the liver and pancreas. This case is of interest in regard to the diagnosis and management of mucinous hepatopancreatobiliary lesions.