Site-specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer.

Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 only in cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core-type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers.

Spontaneous Bilateral Cervical Internal Carotid and Vertebral Artery Dissection in a Japanese Patient without Collagen Vascular Disease with Special Reference to Single-Nucleotide Polymorphisms.

Spontaneous cervical artery dissection (sCAD) is a major cause of ischemic stroke in young adults. Frequently, sCAD involves multiple neck arteries, accounting for 13%-28% of the total sCAD cases. However, little is known about factors related to multiple sCAD. In this case, a 52-year-old man was admitted due to headache without aura. There was a personal history of migraine with aura and a family history of similar symptoms. The patient's younger brother had a left vertebral artery (VA) dissecting aneurysm and underwent endovascular occlusion of his parent artery at the age of 48. Magnetic resonance imaging of our admitted patient showed hyperintensities in the right internal carotid artery (ICA) without acute infarction, and magnetic resonance angiography revealed a narrowing of the right ICA. Angiography was then performed, which showed a trace of dissection of the left ICA and both VAs as well as the right ICA. The patient did not fulfill any major criteria of collagen vascular disease such as Ehlers-Danlos syndrome type IV or Loeys-Dietz syndrome. The data in our patient are quite similar to those reported in patients with single-nucleotide polymorphism (SNP) of PHACTR1. Obtaining the patient's informed consent, we analyzed a common SNP variation in the rs9349379[G] allele (PHACTR1), which has been reported to be associated with a lower risk of sCAD.

iPSC-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by inhibiting inflammatory signaling and oxidative stress.

Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.

"Computed Tomography Perihematomal Rims": A Perihematomal Low-Density Area Is a Part of an Acute Brain Hemorrhage.

Objective Computed tomography (CT) can be used for visualizing acute intracerebral hemorrhages (ICHs) as distinct hyperdense areas and cerebral edema as perihematomal low-density areas (LDAs). We observed a perihematomal LDA on CT, which appeared to be part of a hemorrhage on magnetic resonance imaging (MRI) in acute ICH. We named this "CT perihematomal rim" and evaluated its characteristics and clinical significance. Methods We stratified patients with acute ICH according to the presence or absence of a CT perihematomal rim and then compared their radiologic findings. Logistic regression analyses were performed to assess whether the CT findings can predict the presence of a CT perihematomal rim. Patients Patients within 24 hours of ICH onset who were admitted between September 1, 2014, and October 31, 2018, were registered. Results Overall, 139 patients (91 men; mean age, 66 years) were investigated. CT perihematomal rims were observed in 40 patients (29%). ICH volumes on CT were 30% smaller than those on MRI in patients with CT perihematomal rims. On a multivariate analysis, the presence of a CT perihematomal rim was independently associated with the maximum diameter of the perihematomal LDA. According to a receiver operating characteristic analysis, the maximum LDA diameter threshold was 7.5 mm (sensitivity, 85%; specificity, 83%). Conclusion CT perihematomal rims were observed in 29% of the patients with acute ICH. A perihematomal LDA (>7.5 mm) in acute ICH cases should be considered a CT perihematomal rim. Clinicians should be aware that the ICH volume on CT may be underestimated by 30%.

[Visualization of stenosis in vascular access by bubble method under carbon dioxide (CO2) angiographic procedures].

A percutaneous transvascular angioplasty (PTA) is performed to relieve failed vascular access for hemodialysis. Angiography using non-ionic iodinated contrast media is the imaging modality of choice for performing PTA. However, the use of iodinated contrast media is contraindicated for patients with a history of iodine allergy. Since 1920, carbon dioxide (CO(2)) has been used as a safe contrast medium in various studies. In CO(2) shunt angiography for hemodialysis, visualization of the vascular structures was often suboptimal due to shunt-specific conditions, such as rapid flow and narrow diameter of the vessels. In the present report, we attempted an improvement of the visualization by injection of CO(2) bubbles in view of the properties of CO(2) (floating and low viscosity). The results indicated that the CO(2) bubbles angiography clearly demonstrated the narrow vessels and stenotic portions that were not visualized by conventional CO(2) angiography. In addition, the required volume of CO(2) could be reduced in comparison with previous studies in the literature. Therefore, the method seemed to be effective in reducing exposure and preventing complication by CO(2). Thus, CO(2) bubbles angiography may be useful for shunt angiography and sequential angioplasty when experiencing shunt problems.

Radioanatomical study of the bronchovascular anomalies of the middle and lower lobes of the right lung using multidetector computed tomography.

OBJECTIVE: Preoperative evaluation of bronchovascular structures is useful for prevention of accidents in pulmonary lobectomy. The purpose of this study was to examine the frequency and multidetector computed tomographic (CT) appearances of bronchovascular anomalies between the right middle and lower lobes. METHODS: A total of 1116 consecutive chest CT examinations were analyzed in the present study. On display, the bronchovascular anomalies between the right middle and lower lobes were searched. When anomalous structures were observed, 3-dimensional images were reconstructed. RESULTS: Sixty-seven cases (6.0%) with anomalous findings were observed. In 20 cases (1.79%), the right middle lobe bronchus and artery supplied the lower lobe, whereas the lower lobe artery supplied the right middle lobe in 46 cases (4.12%). In 1 case (0.09%), the 2 patterns previously mentioned were observed concomitantly. CONCLUSIONS: Anomalous bronchovascular structures between the right middle and lower lobes were identified by a multidetector CT with an incidence of 6.0%. Knowledge of the frequency and CT features is useful for preoperative CT evaluation.

[Basic and clinical studies of visualizing right inferior phrenic artery by multi detector row-CT].

To perform transcatheter arterial embolization (TAE) successfully, it is important to obtain information about parasitic arterial supply to the hepatocellular carcinoma (HCC). Among these extrahepatic collateral vessels, the right inferior phrenic artery (RIPA) is the most frequent and important extrahepatic collateral artery supplying the HCC. In the present study, we obtained multi-planar reformation (MPR) images of RIPA using multi detector row computed tomography (MDCT), assessed the ability of MDCT to demonstrate the origin of RIPA, and then analyzed the morphology of the origin. In a basic study using an original phantom simulating vessel origin, the origin was poorly visualized depending on the phantom diameter and angle of the origin to the scanned section. A clinical study was performed in 28 patients with HCC who underwent both MDCT and angiography within a short period. In 19 of 28 patients, RIPA originated at the celiac artery. In 3 patients, RIPA originated at the right renal artery, and in 6, directly at the abdominal aorta. The origin of RIPA was categorized into four patterns according to the inclination of the origin on transverse sections of MDCT. RIPA that originated at the right renal artery and showed an upward course perpendicular to the scan section of MDCT were most clearly visualized at the origin. In addition, RIPA could be observed in an optional direction on the workstation. Pre-angiographic visualization of the origin of RIPA may save angiographic time, curtail contrast medium, and reduce radiation exposure.

Efficacy of multi-slice computed tomography cholangiography before laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury is one of the serious surgical complications of laparoscopic cholecystectomy (LC). Clear biliary tract imaging to detect the anomaly of the bile ducts before operation is thought to be useful to prevent this complication. The objective of this study was to investigate the preoperative feasibility of using multi-slice computed tomography scanning after drip infusion cholangiography-computed tomography (DIC-CT) for LC. METHODS: Laparoscopic cholecystectomies were carried out in 33 patients and DIC-CT and magnetic resonance cholangiography (MRC) were also carried out in all of these patients. We evaluated the recognition of the junction of the cystic duct and detection of anomalies of the extrahepatic bile ducts using the latter two methods. RESULTS: In 33 patients, DIC-CT showed the junction of the cystic duct in 31 (94%) and MRC in 25 (76%) patients, respectively. Anomalies of the extrahepatic bile ducts or the cystic duct were detected in four (12%) patients by DIC-CT, but MRC could show only one of these lesions. There were no major adverse reactions in either examination. CONCLUSION: DIC-CT is an efficacious preoperative technique as compared with MRC for the biliary tract imaging. DIC-CT may be of benefit for both patients scheduled to undergo LC and their surgeons.

Postoperative bronchial stump fistula responding well to occlusion with metallic coils and fibrin glue via a tracheostomy: a case report.

An 80-year-old man underwent middle and lower lobectomy of the right lung to treat squamous cell carcinoma (SCC) (4 cm in diameter) originating from the right B4 bronchus. On the 4th postoperative day, a massive air leak from the thoracic drain was noted. At that time, a diagnosis of bronchial stump fistula was made on the basis of the bronchoscopic findings. Continuous thoracic drainage, aspiration of sputum via a tracheostomy and intravenous administration of antibiotics were performed immediately after the diagnosis. However, the patient's condition was complicated by aspiration pneumonia. On the 11th postoperative day, bronchoscopic procedure to close the bronchial fistula was performed via the tracheostomy. During this procedure, metallic coils were first inserted into the fistula to serve as the core for occlusion. Then, instead of directly infusing fibrin glue, several small beans-sized pieces of Surgicell cotton (Johnson & Johnson Co., Cincinnati, OH) soaked in fluid A (concentrated fibrinogen) and the same number of Surgicell cotton pieces soaked in fluid B (thrombin) were alternately inserted into the fistula, to allow closure of the bronchial fistula. After this procedure, the embolus created remained in place without being expectorated, and the aspiration pneumonia entered remission, allowing the patient to be discharged from the hospital on the 24th postoperative day. At preset, 14 months after surgery, the patient is in good condition. This technique allows simple and reliable closure of a fistula if a tracheostomy is available. It should be selected as a therapy of first choice when dealing with patients with a postoperative bronchial stump fistula in poor general condition. Patients undergoing right pneumonectomy or middle and lower lobectomy of the right lung should be considered as belonging to a high risk group for bronchial fistula and as requiring preventable measures (e.g., covering the stump with an intercostal muscle flap).

Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin.

BACKGROUND: Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that increases in various pathological conditions. We previously established a Fuc-Hpt lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to diagnose several diseases, including various cancers. AAL recognizes both α1-3/1-4 and α1-6 fucosylation on N/O-linked glycans. These fucosylation types differ in biological function, and in regulation by different fucosyltransferases. Recently, we identified a novel lectin, Pholiota squarrosa lectin (PhoSL), which specifically recognizes α1-6 fucosylation (core-fucosylation). METHODS: We developed a lectin-antibody ELISA kit using PhoSL to determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer patients. RESULTS: Serum levels of AAL-reactive Hpt are higher in pancreatic cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal cancer patients. Mass spectrometry analyses of Hpt fucosylation levels were consistent with lectin-antibody ELISA results. Hpt-transfected colorectal cancer cell lines produced significant amounts of core-Fuc-Hpt, suggesting that colorectal cancer tissues produce core-Fuc-Hpt. CONCLUSIONS: These differences in Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which produce Hpt.

Gastric cancer occurred after coronary artery bypass grafting using the right gastroepiploic artery.

We recently encountered a rare case where gastric cancer developed in the long-term postoperative stage after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) and distal partial gastrectomy was performed to treat the cancer. The patient was a 64-year-old man. In November 2001, he underwent three-vessel CABG, involving bypassing between the right coronary artery (RCA) and the RGEA, to treat an old myocardial infarction. In May 2003, he was admitted to our hospital because of exacerbation of diabetes mellitus and anemia. Gastric endoscopy revealed gastric cancer affecting the pylorus. Preoperative abdominal angiography showed the RGEA graft remained well patent. In June 2003, he underwent distal partial gastrectomy and regional lymph node dissection. Because the RGEA had been freed adequately to the point of bifurcation of the gastroduodenal artery during the previous CABG, the RGEA graft was preserved during distal partial gastrectomy. When the RGEA is used for CABG, it seems advisable to free the RGEA adequately to a point of bifurcation of the gastroduodenal artery. If done so, regional lymph node dissection around the RGEA is easier to perform when gastric cancer has occurred in these cases, eventually reducing the risk for injury of the graft. Following CABG with the RGEA, it seems essential to perform periodical checks for gastric cancer to facilitate early detection of gastric cancer. The necessity of close follow-up of these cases is endorsed by the fact that healing of gastric cancer by endoscopic mucosal resection (EMR) is highly probable if the cancer is detected at early stages.

Advanced lung cancer invading the left atrium wall treated with pneumonectomy and combined resection of the left atrium using stapling devices: report of two cases.

In chest surgery, stapling devices are primarily used to close bronchi. However, they are also used for dissection and suturing between lung lobes, resection and plication of lung tissue (including bullae), combined resection of the superior vena cava, closure of the pulmonary great vessels, closure of the left atrium following combined resection of the left atrium, and so on. We recently treated two cases of advanced lung cancer, which had invaded the left atrial wall, with pneumonectomy and combined resection of the left atrium using stapling devices, and obtained favorable results. For combined resection of the left atrium, it is safer to use stapling devices than vascular clamps, since the latter involve the risk of dislocation during use. Furthermore, since stapling devices require no margin for suturing, the left atrium can be resected at a point sufficiently distant from the cancer, thus allowing for highly radical resection. Stapling devices are also useful because they can be manipulated even within narrow operative fields. When dealing with lung cancer requiring combined resection of the left atrium, pneumonectomy is needed in most cases. When performing surgery for these cases, it is essential to first close and divide the bronchi and pulmonary arteries and veins as far as possible so that adequate adherence around the left atrium can be developed and the entire lung can be lifted up, followed by resection of the left atrium with a stapling device applied to the left atrium without any tension.

Athermal silica-based interferometer-type planar light-wave circuits realized by a multicore fabrication method.

Athermal silica-based interferometer-type planar light-wave circuits were realized by a newly developed multicore fabrication method. In this method, inductively coupled chemical-vapor deposition and polishing technologies are adopted on a silica substrate with a trench-type waveguide pattern prepared by reactive ion etching. Two kinds of deposited core material, 10GeO2-90SiO2 (mol. %) and 8GeO2-5B2O3-87SiO2 (mol. %), which show wavelength temperature dependence of 9.7 and 8.1 pm/degree C, respectively, were used to prepare the waveguide sections in a device. By adjustment of the lengths of waveguide sections with these two different core materials, athermal characteristics of less than 0.5 pm/degree C were achieved for Mach-Zehnder interferometer filter devices at the 1.55-microm wavelength range while the temperature varied from -20 to 80 degrees C. The new method is also applicable for the preparation of many other kinds of functional devices.