Detection of Fecal DNA Methylation for Colorectal Neoplasia : Does It Lead to an Optimal Screening Test?

Aberrant promoter methylation, an 'epigenetic' form of genomic instability that leads to transcriptional silencing of tumor suppressor genes, is increasingly being recognized as a crucial component in the evolution of human cancers. With our limited knowledge of the molecular basis and timing of the initiation of altered methylation events in the stepwise progression of cancers, the biggest challenge we currently face is to identify novel biomarkers and technologies for the timely screening of patients carrying such alterations. One such strategy would be to develop tests for the detection of fecal DNA methylation patterns that will improve the sensitivity of noninvasive screening tests for colorectal neoplasia, and moreover, will decrease both mortality and the incremental costs of treating colorectal cancers

Methylation profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients

Aberrant methylation of DNA has been shown to play an important role in a variety of human cancers, developmental disorders and aging. Hence, aberrant methylation patterns in genes can be a molecular marker for such conditions. Therefore, a reliable but uncomplicated method to detect DNA methylation is preferred, not merely for research purposes but for daily clinical practice. To achieve these aims, we have established a precise system to identify DNA methylation patterns based on an oligonucleotide microarray technology. Our microarray method has an advantage over conventional methods and is unique because it allows the precise measurement of the methylation patterns within a target region. Our simple signal detection system depends on using an avidin–biotinylated peroxidase complex and does not require an expensive laser scanner or hazardous radioisotope. In this study, we applied our technique to detect promoter methylation status of O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Our easy-handling technology provided reproducible and precise measurement of methylated CpGs in MGMT promoter and, thus, our method may bring about a potential evolution in the handling of a variety of high-throughput DNA methylation analyses for clinical purposes

Acute Vertebral Artery Origin Occlusion Leading to Basilar Artery Thrombosis Successfully Treated by Angioplasty with Stenting and Intracranial Fibrinolysis

There are few reports describing stroke due to the acute occlusion of the vertebral artery (VA) origin successfully treated by endovascularily. The authors report a case of 78-year-old man suffering from stroke owing to acute VA origin occlusion associated with contralateral hypoplastic VA leading to basilar artery (BA) thrombosis. Cerebral angiography demonstrated that the right VA was occluded at its origin, the left VA was hypoplastic, and BA was filled with thrombus. The occlusion of VA origin was initially passed through with a microcatheter and microwire. Hereafter, angioplasty was performed followed by stenting with a coronary stent. The VA origin was successfully recanalized. Next, a microcatheter was navigated intracranially through the stent and fibrinolysis was performed for BA thrombus. The patient's symptoms gradually improved postoperatively. Stroke due to acute VA origin occlusion leading to BA thrombosis was successfully treated by angioplasty and stenting followed by intracranial fibrinolysis

Pharmacist-physician collaborative care for outpatients with left ventricular assist devices using a cloud-based home medical management information-sharing system: a case report

[Background] The standard anticoagulation therapy for patients implanted with left ventricular assist devices (LVADs) includes warfarin therapy. We developed a cloud-based home medical management information-sharing system named as LVAD@home. The LVAD@home system is an application designed to be used on iPad tablet computers. This system enables the sharing of daily information between a patient and care providers in real time. In this study, we reported cases of outpatients with LVADs using this system to manage anticoagulation therapy. [Case presentation] The patient, a man in his 40s with end-stage heart failure owing to non-ischemic dilated cardiomyopathy, underwent LVAD implantation and warfarin was started on postoperative day 1. He started to use LVAD@home to manage warfarin therapy after discharge (postoperative day 47). He sent his data to care providers daily. By using this system, the pharmacist observed his signs of reduced dietary intake 179 days after discharge, and after consulting the physician, told the patient to change the timing of the next measurement earlier than usual. On the next day, the prothrombin time-international normalized ratio increased from 2.0 to 3.0, and thus the dose was decreased by 0.5 mg. Four patients used this system to monitor warfarin therapy from October 2015 to March 2018. In these patients, the time in therapeutic range was 90.1 ± 1.3, which was higher than that observed in previous studies. Additionally, there were no thromboembolic events or bleeding events. [Conclusions] The cloud-based home management system can be applied to share real-time patient information of factors, including dietary intake that interact with warfarin. It can help to improve long-term anticoagulation outcomes in patients implanted with LVAD

An Association Analysis between Mitochondrial DNA A10398G Polymorphism and Temperament in Japanese Young Adults

The mitochondrial (mt) DNA C5178A and A10398G polymorphisms have been reported to be associated with mental disorders such as bipolar disorder. However, the effects of these polymorphisms on temperament in healthy people are poorly understood. Evaluating healthy subjects can have the advantage of providing new strategies for maintaining psychological health and preventing mental illness. We examined the association between mtDNA polymorphisms and temperament in Japanese students. There was no significant difference in examined temperament when analysed by genotypes, 5178–10398 haplotypes, or sex. The subgroup analysis based on sex indicated that there was an interactive effect of the mtDNA A10398G polymorphism and sex on anxiety and obsession. This finding is preliminary and cannot exclude the possibility of false-positive due to small sample size (144 subjects) and multiple statistical testing. Further studies involving a larger sample size or other ethnic groups are necessary to confirm that mtDNA A10398G polymorphism can be a genetic factor for temperament

Effects of demethylating agent 5-aza-2 '-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines

Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2'-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell tines. The expression levels of maspin mRNA were divided into two groups, which was the maspin tow-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell tines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.</p

A dialysis patient with multiple intestinal diverticula in whom partial penetration was recognized.

　小腸憩室は比較的稀な疾患で，多くが無症状で経過するが，穿孔した場合は腸間膜内に穿通し膿瘍形成をきたす．高齢者に多く，その診断および治療の遅れから重篤な経過をたどることも少なくない．その診断にはコンピュータ断層撮影（CT）が有用とされているが，穿孔部位や憩室の特定は困難とされ，術前に指摘できるものは決して多くない．透析患者では高リン血症に対し陰イオン交換樹脂剤などが一般的に使用されるが，消化管穿孔の注意が記載されている．今回我々は，透析患者の腸管穿孔の原因検索に体外式超音波（US）が有用であった１例を経験したので，文献的考察を含めて報告する．症例は70歳台男性，18年前から血液透析を行っている．10日前に発熱で近医を受診し，保存的に経過を見ていたが炎症反応の上昇を認め当院紹介受診した．身体所見は心窩部付近に軽度の圧痛を認めたが腹膜刺激兆候は明らかでなかった．単純 CT で消化管外の free air が疑われ，精査目的に US が行われた．US では空腸に多発している憩室と，憩室周囲の膿瘍形成およびその内部の free air と思われる点状高エコーが認められ，小腸憩室穿通と診断した．同日小腸切除術が行われ，病理組織学的検索の結果，US と同様の所見であった．また穿通した憩室にセベラマー結節が認められ，憩室穿通に関与した可能性が示唆された．US は透析患者における憩室穿通の診断に有用である．　Jejunal diverticula (JD) are considered to be rare and are asymptomatic in most cases. However, they are potentially associated with serious complications, such as diverticulitis and perforation/penetration, especially in the elderly. In the event of perforation/ penetration, JD usually penetrates the mesentery, resulting in the formation of an abscess in the mesentery, which is difficult to diagnose, because there are no specific signs. Anion exchange resin agents, such as sevelamer hydrochloride (SH), are often used for hyperphosphatemia in dialysis patients, but the package insert cautions against the development of the adverse effect of gastrointestinal perforation. Herein, we report a case in which abdominal ultrasonography (US) was useful for the diagnosis of jejunal diverticular penetration in a hemodialysis patient. The patient was a male in his 70s who had been on hemodialysis for 18 years and was receiving SH 2.25g/day. He presented to a neighborhood hospital with a 10-days’history of fever. The fever did not improve with conservative therapy, and the patient was referred to our hospital. Physical examination revealed mild epigastric tenderness, but there were no signs of peritoneal irritation. Computed tomography (CT) was performed, and the presence of free air was suspected. Abdominal US performed subsequently showed multiple jejunal diverticula and abscess formation around the diverticulum. Furthermore, free air was recognized in the abscess, which was finally diagnosed as a mesenteric abscess complicating JD penetration. On the same day, jejunal resection was performed and histopathological examination of the surgical specimen revealed findings consistent with the US findings. Histopathology revealed sevelamer crystals in the penetrated diverticulum. US is useful for the diagnosis of penetration of JD in dialysis patients

Role of O-6-methylguanine-DNA methyltransferase and effect of O-6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines

The DNA repair enzyme, O-6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell tines. CDDP depleted MGMT protein and mRNA levels in all four cell tines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell tines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O-6-benzylguanine (O-6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O-6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy. (c) 2005 Elsevier Ltd. All rights reserved. </p

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C