Intrahepatic cholangiocarcinoma and portal hypertension developing in a patient with multicystic biliary microhamartomas.

INTRODUCTION: We report a case of intrahepatic cholangiocarcinoma and portal hypertension developing in a liver with biliary microhamartomas (von Meyenburg's complex). CASE REPORT: The patient was a 55-year-old man who had a past medical history of diffuse multiple liver abscesses. During follow-up examination, a hypovascular nodule measuring 2.1 cm in diameter was incidentally found in segment 8 of the liver. Surgical resection was performed based on a suspected diagnosis of hepatocellular carcinoma. A gastrofiberscopy examination detected characteristic findings of portal hypertensive gastropathy. During the laparotomy, multiple tiny cystic lesions were observed in a diffuse pattern across the liver surface. The liver parenchyma was slightly fibrotic and haemorrhagic. A histopathological examination revealed intrahepatic cholangiocarcinoma with vascular invasions in von Meyenburg's complex. Multiple biliary adenomas were also observed among the biliary microhamartomas adjacent to the main tumour, suggesting that the malignant transformation of the biliary adenomas might have been responsible for the development of the intrahepatic cholangiocarcinoma. The histopathologic examination also revealed sinusoidal dilation and abnormal spacing of the portal tracts and central veins as evidence of portal hypertension.

A diffusion model for the coordination of DNA replication in Schizosaccharomyces pombe.

The locations of proteins and epigenetic marks on the chromosomal DNA sequence are believed to demarcate the eukaryotic genome into distinct structural and functional domains that contribute to gene regulation and genome organization. However, how these proteins and epigenetic marks are organized in three dimensions remains unknown. Recent advances in proximity-ligation methodologies and high resolution microscopy have begun to expand our understanding of these spatial relationships. Here we use polymer models to examine the spatial organization of epigenetic marks, euchromatin and heterochromatin, and origins of replication within the Schizosaccharomyces pombe genome. These models incorporate data from microscopy and proximity-ligation experiments that inform on the positions of certain elements and contacts within and between chromosomes. Our results show a striking degree of compartmentalization of epigenetic and genomic features and lead to the proposal of a diffusion based mechanism, centred on the spindle pole body, for the coordination of DNA replication in S. pombe.

Bacterial loads of Ureaplasma urealyticum contribute to development of urethritis in men.

Ureaplasma urealyticum could be a pathogen of non-gonococcal urethritis (NGU) in men. However, ureaplasma is often detected in men without NGU, and the proportion of cases possibly attributable to this pathogen is still undefined. We attempted to determine the bacterial loads of U. urealyticum significantly associated with NGU. The 16S rRNA genes of U. urealyticum were quantified by a real-time polymerase chain reaction-based assay in first-void urine (FVU) from 26 asymptomatic and 25 symptomatic men positive for U. urealyticum. The leucocyte counts in first-void urine (FVU) were determined as an objective measure of inflammatory response to ureaplasma in the hosts by automated quantitative urine particle analysis. Positive correlations were observed between copies of the 16S rRNA genes of U. urealyticum per ml and the leucocyte counts per µl in FVU (r = 0.49, p = 0.0003). Loads of ≥10(4) copies of the 16S rRNA gene of U. urealyticum/ml, corresponding to ≥5 × 10(3) cells of U. urealyticum/ml in FVU, were significantly associated with the presence of urethritis symptoms (p < 0.0001) and with higher leukocyte counts in FVU (p < 0.0001). The bacterial load of U. urealyticum, possibly of ≥5 × 10(3) cells of U. urealyticum/ml in FVU, could be significantly associated with the development of symptomatic NGU.

Room temperature ferromagnetism with large magnetic moment at low field in rare-earth-doped BiFeO3 thin films.

Thin films of rare earth (RE)-doped BiFeO3 (where RE=Sm, Ho, Pr and Nd) were grown on LaAlO3 substrates by using the pulsed laser deposition technique. All the films show a single phase of rhombohedral structure with space group R3c. The saturated magnetization in the Ho- and Sm-doped films is much larger than the values reported in the literature, and is observed at quite a low field of 0.2 T. For Ho and Sm doping, the magnetization increases as the film becomes thinner, suggesting that the observed magnetism is mostly due to a surface effect. In the case of Nd doping, even though the thin film has a large magnetic moment, the mechanism seems to be different.

A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

Results of chemoradiotherapy for stage I esophageal cancer in medically inoperable patients compared with results in operable patients.

The purpose of the present study was to evaluate long-term results of chemoradiotherapy for clinical T1b-2N0M0 esophageal cancer and to compare outcomes for operable and inoperable patients. Patients with stage I esophageal cancer (Union for International Cancer Control [UICC] 2009), excluding patients with cT1a esophageal cancer, were studied. All patients had histologically proven squamous cell carcinoma. Operable patients received cisplatin and 5-fluorouracil with concurrent radiotherapy of 60 Gy including a 2-week break. Inoperable patients received nedaplatin and 5-fluorouracil with concurrent radiotherapy of 60-70 Gy without a pause. End-points were overall survival rate (OS), cause-specific survival rate (CSS), progression-free survival rate (PFS), and locoregional control rate (LC). Thirty-seven operable patients and 30 medically inoperable patients were enrolled. There was a significant difference in only age between the operable group and inoperable group (P = 0.04). The median observation period was 67.9 months. In all patients, 5-year OS, CSS, PFS, and LC were 77.9%, 91.5%, 66.9%, and 80.8%, respectively. Comparison of the operable group and inoperable group showed that there was a significant difference in OS (5-year, 85.5% vs. 68.7%, P = 0.04), but there was no difference in CSS, PFS, or LC. Grade 3 or more late toxicity according to Common Terminology Criteria for Adverse Events v 3.0 was found in seven patients. Even in medically inoperable patients with stage I esophageal cancer, LC of more than 80% can be achieved with chemoradiotherapy. However, OS in medically inoperable patients is significantly worse than that in operable patients.

A pilot study to assess mediastinal emphysema after esophageal endoscopic submucosal dissection with carbon dioxide insufflation.

BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO2 insufflation vs. standard air insufflation during esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were enrolled in this study (CO2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. RESULTS: Mediastinal emphysema detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS: Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO2 can be considered as insufflating gas for esophageal ESD.

The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage.

The CNS inflammatory reaction occurring after aneurysmal subarachnoid hemorrhage (SAH) involves the upregulation of numerous cytokines and prostaglandins. Cyclooxygenase (COX) inhibition is a well-established pharmacological anti-inflammatory agent. Previous studies have shown marked increases in COX-2 expression in neurons, astrocytes, microglia, and endothelial cells following brain injury. COX-2 inhibition has been shown to be beneficial following various types of brain injury. This experiment investigates the role of COX-2 activity in early brain injury following SAH. CD-1 mice were subjected to an endovascular perforation model of SAH or SHAM surgery. Following experimental SAH animals were treated with the specific COX-2 inhibitor, NS398, in dosages of either 10 or 30 mg/kg. Neurological performance and brain edema were evaluated 24 and 72 h after SAH. NS398 at 30 mg/kg significantly reduced SAH-induced neurological deterioration. NS 398 at 30 mg/kg resulted in a trend toward the reduction of SAH-induced cerebral edema. Treatment had no effect on mortality. This experiment provides preliminary evidence that COX-2 inhibition is an effective pharmacological intervention for the prevention of brain edema and the preservation of neurological function following SAH.

Relationship between peripheral visual field loss and vision-related quality of life in patients with retinitis pigmentosa.

PURPOSE: To determine the vision-related quality of life (VRQOL) with the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with retinitis pigmentosa (RP), and to examine the relationship between VRQOL and peripheral visual field defects. DESIGN: Prospective study. METHODS: The Japanese version of the NEI VFQ-25 was used to study 40 patients with typical RP whose visual acuity was >/=0.7 (better than 0.15 in log MAR). For control, 40 volunteers with normal vision were studied in the same way. The peripheral visual field was evaluated by Goldmann's perimetry, and the degree of field loss was classified into seven grades. The correlation between the mean of the total composite score of the NEI VFQ-25 and the degree of the visual field loss was determined. RESULTS: The mean NEI VFQ-25 score was 68.4 in RP patients and 90.1 in normal controls. This difference was highly significant (P=0.00004). Among RP patients, there was a significant negative correlation between the mean NEI VFQ-25 score and the degree of visual field loss (r=-0.519, P=0.0006). CONCLUSION: The significant correlation between the peripheral visual field loss and VRQOL score obtained with the NEI VFQ-25, indicates that a good estimate of the QOL can be determined by the degree of visual field loss in RP patients.

[Clinical analysis of bronchoplastic surgery for lung cancer after 2000].

We investigated surgical complications and prognosis of bronchoplasty and bronchoplasty with pulmonary angioplasty (broncho-angioplasty) for lung cancer. Between October 2000 and October 2007, 37 bronchoplastic procedures were done in 572 patients who underwent lung resections for lung cancer. Eleven (29.7%) bronchoplasties were done with pulmonary angioplasty. There was no operative mortality and 1 hospital mortality (2.7%) causing by myocardial infarction. Six of 11 postoperative complications were bronchial complications and 2 additional lung resections were needed. The 5-year survival for all patients was 55.2% and for bronchoplasty was 57.8%. Though the 5-year survival of broncho-angioplasty was not able to calculate at present, the 3-year survival of which was 72.9%. There was no death of patients with adenocarcinoma after introduction of pre-operative assessment by FDG-PET for lymph node metastasis. These data suggest that bronchoplasty and broncho-angioplasty are safe operative procedures and could provide acceptable intermediate survivals with modern multimodality diagnostic and therapeutic tools.

Magnetic resonance imaging in the canine double-haemorrhage subarachnoid haemorrhage model.

In this study, we investigated T2 weighted imaging (T2WI) and T2 values of the cortex, thalamus and cerebrospinal fluid (CSF) of the ventricles in the canine double-haemorrhage subarachnoid haemorrhage (DHSAH) model. T2 values in the cortex increased compared to prescan values from 123.07 +/- 18.72 msec on day 2 to 89.43 +/- 1.98 msec on day 7 (p < 0.05). A trend toward a temporal increase in T2 values was observed in the thalamus, but did not reach significance. The T2 values of the ventricular CSF increased by 102.2% on day 2 and 159.6% on day 7 compared to prescan values. These changes reached significance (p < 0.05) on day 7. Additionally, the ventricular size increased over the study period. Our data suggest that we can use this model to investigate acute brain injury and normal pressure hydrocephalus (NPH) after SAH.

Role of statins in cerebral vasospasm.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, commonly known as statins, are widely used clinically for their lipid lowering properties. Recent evidence shows that statins are also effective in ameliorating cerebral vasospasm, which occurs as sequelae of subarachnoid haemorrhage. This review focuses on the pleiotropic effects of statins, and the putative mechanisms involved in statin mediated attenuation of cerebral vasospasm.

The use of patient-controlled epidural fentanyl in elderly patients.

We studied whether delivering postoperative analgesia, using a patient-controlled epidural analgesia (PCEA) device was effective and safe in elderly patients. We enrolled 40 patients aged > 65 years (elderly group) and 40 patients aged 20-64 years (young group) scheduled for elective major abdominal surgery. PCEA infusion was started following completion of surgery. Mean (SD) fentanyl consumption (10.7 (3.7) compared with 10.5 (2.7) microg.kg(-1), p = 0.76) and number of times patients pressed the bolus switch (32 (36) compared with 44 (38), p = 0.16) during the first 24 h postoperatively were similar in the two groups. Pain scores, which were similar in both groups at rest, were significantly lower in the elderly on coughing (at 24 h, p < 0.05). In addition, average pain scores were similar at the time of PCEA bolus demands in the two groups. Elderly and young adult patients therefore required similar amounts of patient-controlled epidural fentanyl to produce satisfactory pain relief.

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity.

Aspirin prevents the production of thromboxane A2 (TXA2) by irreversibly inhibiting platelet cyclooxygenase, exhibiting antiplatelet actions. This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infarction via this action mechanism. However, there are individual differences in this action, and aspirin is not effective in some patients, which is referred to as 'aspirin resistance'. In this study, we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms (SNPs) of nine genes involved in platelet aggregation/hemorrhage. Among SNPs involved in platelet aggregation, aspirin was less effective for 924T homozygote of a TXA2 receptor, 924T>C, and 1018C homozygote of a platelet membrane glycoprotein GPIbalpha, 1018C>T, suggesting that 924T and 1018C alleles are involved in aspirin resistance.

Phenotypes and genotypes in epilepsy with febrile seizures plus.

In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.

Both N-terminal and C-terminal regions of steroid sulfatase are important for enzyme activity.

Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes desulfation of 3beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an inherited skin disorder caused by deficiency of STS enzyme activity. We previously reported a case in which XLI with a one-base change in the STS gene and variation in amino acid Q560P developed. In this study, we performed molecular analysis to determine the importance of terminal regions of STS and the effect of mutant STS on STS enzyme activity. To examine the effect of terminal truncated STS on the enzyme activity, N- and C-terminal truncated STS expression vectors were transfected into COS-1 cells. The activity of truncated STS lacking the N-terminal regions declined, and the activity of C-terminal-truncated STS declined with extension of the truncated C-terminal region. Although the results of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C-terminal-truncated STS (deltaC2 (1-559)) had no effects on protein synthesis and degradation, the mutant STS and C-terminal-truncated STS have dominant negative effect on STS enzyme activity when the STS mutant or truncated STS protein and a wild-type STS protein coexist in cells. Results of coprecipitation of the truncated STS with an STS-FLAG fusion protein showed that STS formed a dimer conformation in cells. In this study, we have shown that both the N-terminal region and C-terminal region are important for STS enzyme activity. The C-terminal mutant has a dominant negative effect on wild-type STS.

Development of a recombinant yeast assay to detect ah-receptor ligands.

Endocrine systems of humans and animals are disturbed by dioxin-like compounds, which are ligands of the aryl hydrocarbon receptor (AhR). It is important to determine the accumulation of dioxin-like compounds in the environment for maintenance of human health. In this study, we developed a new method for screening ligands of the AhR using a yeast hybrid system. Reporter genes constructed by the insertion of dioxin response elements were integrated into HIS and lacZ yeast genomes. Then yeast was transformed with GAL4-activated domain-fused AhR and aryl hydrocarbon receptor nuclear translocator expression constructs. At 10(-4) M of beta-naphthoflavone, which is an AhR ligand, the absorbance of optical density at 600 nm (OD 600) and beta-galactosidase activity was significantly increased. beta-galactosidase activity was increased when the concentration of 3-methylcholanthrene (MC) was increased. ATP concentration increased as concentration of MC increased up to 10(-10) M but decreased at higher concentrations. The concentration of ATP in the cell suspensions increased linearly with OD 600, used as an index of cell density (r(2) = 0.8366, F = 209.9, p < 0.0001, n = 44). The established yeast assay could possibly be used in the future to detect dioxin-like compounds in environmental samples.

Multiple spinal dural arteriovenous fistulas.

Multiple spinal dural arteriovenous fistulas (DAVFs) have been rarely reported and only two such cases are found in the literature. A 71-year-old man complained of muscle weakness and hypesthesia in both legs and angiographically diagnosed as thoracic DAVF. The fistula was surgically treated, however, the symptoms recurred 14 months after the first treatment. Angiography revealed a new fistula in the lumbar region and this was also treated surgically. In the previously reported cases of multiple spinal DAVFs, the second fistulas were also diagnosed after the initial treatment. Symptomatic patients after the initial treatment of DAVF should be re-examined angiographically.

Early pathophysiologic feature of arthropathy in juvenile dogs induced by ofloxacin, a quinolone antimicrobial agent.

Arthropathy in dogs induced by ofloxacin, a quinolone antimicrobial agent, was pathophysiologically investigated. In the in vivo studies, ofloxacin was administered orally once or twice at 20 mg/kg/day to male juvenile (3-month-old, n=3) or adult (36-month-old, n=2) dogs, and the humeral and femoral heads were examined pathologically. Unlike adult dogs, fluid-filled vesicles were macroscopically observed on the articular surfaces of one juvenile dog 24 hours after a single treatment with ofloxacin. These lesions were seen in all juvenile dogs by twice dosing. Microscopically, fissures or cavity formations in the middle zone of the articular cartilage were noted only in juvenile dogs. Furthermore, the cartilage matrix from the abnormal area to the articular surface showed a decreased safranin-O staining intensity, suggesting proteoglycan depletion. Ultrastructurally, chondrocytes in the middle zone of juvenile dogs displayed dilatation of the cisternae in the rough endoplasmic reticulum as an initial hallmark. In the in vitro studies, chondrocytes isolated from the articular cartilage of naive juvenile dogs were exposed to ofloxacin at 6.3-100 microg/ml for 24 hours. Although no changes were noted in the deoxyribonucleic acid synthesis, protein synthesis, or proteoglycan release at concentrations of up to 100 microg/ml, the proteoglycan synthesis was evidently decreased in a dose-dependent manner from 12.5 microg/ml. The results obtained suggest that the inhibitory action of ofloxacin on proteoglycan syntheses in the chondrocytes may largely contribute to the early morphologic features in the articular cartilage of the juvenile dog.

Characterization of binding between SF-1 and Sp1: predominant interaction of SF-1 with the N-terminal region of Sp1.

The transcription factor specificity protein 1 (Sp1) binds to GC boxes and interacts with many transcription factors to regulate gene expression. Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor and plays a major role in regulation of the human steroidogenic acute regulatory (StAR) gene. We demonstrated that there is interaction between SF-1 and Sp1 on the human StAR promoter. In the present study, we examined the mechanism of the interaction between Sp1 and SF-1 on the human StAR gene promoter. Results of glutathione S-transferase (GST) pull-down assays and a mammalian two-hybrid assay showed that SF-1 interacted with Sp1 through the N-terminal domains of Sp1. Results of electrophoretic mobility shift assays using nuclear extracts showed that Sp1 is associated with SF-1-DNA complex formation. The density of SF-1-DNA complex was much greater when recombinant Sp1 was added to the incubation mixture. These results suggest that Sp1 interacts with SF-1 and that Sp1 enhances SF-1-DNA complex formation to regulate human StAR transcription.