Characteristics of shifting ability in children with mild intellectual disabilities: an experimental study with a task-switching paradigm.

BACKGROUND: Shifting enables flexible switch between tasks or mental sets. It is a component of the executive function that plays critical roles in human behaviour control. However, shifting ability in individuals with intellectual disability (ID) has not been well clarified because of the use of intellectually demanding tasks in previous studies. The present study invented a novel shifting task with minimal intellectual demands and aimed to clarify the characteristics of shifting in adolescents with ID. METHODS: Adolescents with ID (n = 21) and chronological-age-matched (n = 10) and mental-age-matched controls (n = 33) performed a novel shifting task with simple rule switching (i.e. change in direction). Analyses focused on the switch cost or the increase in the reaction time associated with rule switching. RESULTS: Two subtypes of adolescents with ID were found with respect to the switch cost: one that lacks it and another with an increased switch cost. The lack of a switch cost was unique to the subgroup adolescents with ID and was not indicated in the control group. CONCLUSIONS: The present study indicated that shifting in adolescents with ID does not depend solely on their intellectual function and is highly heterogeneous. This finding further implies that executive functions, including shifting, must be evaluated separately from their intellectual functions.

Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients.

Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.

Multicentred surgical site infection surveillance using partitioning analysis.

BACKGROUND: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan. AIM: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI. METHODS: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period. FINDINGS: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012). CONCLUSION: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.

Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) often arises from preceding dysplastic lesions in the oesophageal epithelium. However, the molecular changes occurring in premalignant lesions are not well understood. An epigenetic change is an example of OSCC that may occur within the epithelium. AIM: To investigate the methylation status of multiple promoters in cancer-derived DNA, as well as in the background epithelium of OSCC, including dysplastic lesions and non-neoplastic mucosa. The normal epithelium from patients without cancer was also examined. The findings were correlated with the mutational status of p53. PATIENTS AND METHODS: 56 patients with advanced OSCC, 21 patients with intraepithelial neoplasia (IEN), 56 patients with a background of non-neoplastic epithelium, adjacent to the OSCC, and 42 normal control epithelia from healthy volunteers were studied. The promoter methylation status of SFRP1, SFRP2, DCC, APC, p16(INK4a), p14(ARF), MINT1, MINT2, MINT31, CACNA1G, COX2, DAPK, hMLH1 and MGMT was examined by methylation-specific single polymerase chain reaction or combined bisulphite restriction analysis. The mutation of p53 by direct sequencing was assessed. RESULTS: DNA methylation was observed in OSCC and in its background epithelium. The frequency of CpG island methylation increased from a baseline level in the background non-neoplastic epithelium, through IEN, to advanced OSCC. However, mutations in p53 were almost exclusively observed in IEN and OSCC. More extensive DNA methylation was seen in the neoplastic lesions (OSCC or IEN) having a p53 mutation than in those with wild-type p53. CONCLUSION: DNA methylation is present at low levels in the non-neoplastic oesophageal epithelium and appears to contribute to the progression of the dysplasia-carcinoma sequence in OSCC carcinogenesis.

Intra-aortic stent graft in oesophageal carcinoma invading the aorta. Prophylaxis for fatal haemorrhage.

In patients with advanced oesophageal carcinoma with aortic invasion, any therapy potentially causes fatal haemorrhage. We describe here the successful application of intra-aortic stent graft to prevent haemorrhage before radical oesophagectomy for advanced oesophageal cancer. Four patients with advanced oesophageal cancer complicated by invasion of the aorta. Under general anaesthesia, aortic invasion is evaluated by an intravascular sonography. The stent graft is passed through the right femoral artery into the descending aorta. Subsequently, the stent graft is released to expand in the thoracic aorta during an artificial cardiac arrest. Aortography is performed to check for any stent migration or endoleakage. This procedure was successful in all four patients without any complications. All patients underwent radical oesophagectomy following aortic stent-grafting. One patient survived more than 2 years after stent grafting and operation. This procedure is safe and applicable for the patient with aortic invasion before radiochemotherapy or operation.

Heparanase expression correlates with malignant potential in human colon cancer.

PURPOSE: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. METHODS: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. RESULTS: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003). CONCLUSIONS: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.

Impedance pharyngography to assess swallowing function.

We evaluated impedance pharyngography (IPG), a new method to assess swallowing function based on changes in the electrical impedance of the neck during swallowing. The electrical impedance of the neck, recorded by the 4-electrode method, changed with the equivalent cross-sectional area of the route of the electric current due to reflex activities of related organs during swallowing. IPG waveforms accurately recorded the swallowing process, therefore. We recommend IPG for assessing swallowing function because we expect IPG to provide the following advantages over conventional diagnostic techniques: it is a quantitative method that allows for the objective assessment of swallowing function; it is a simple procedure that is convenient for the patient and could be used for screening; it is inexpensive and non-invasive, so could be performed repeatedly in situations such as rehabilitation; and it uses highly portable equipment suitable for community use.

Two cases of superficial basaloid squamous carcinoma of the esophagus.

. Basaloid squamous carcinoma of the esophagus is very rare. We report two cases of basaloid squamous carcinoma of the esophagus. Both tumors histologically consisted of solid cell nests with intervening fibromyxoid stroma. In some tumor nests were comprised of pseudoglandular structures containing myxoid matrix, and displayed focal immunoreactivity for laminin. Thoracic esophagectomy with lymph node dissection was followed by intrathoracic esophagogastrostomy in both patients. The patients had uneventful postoperative courses. Regular periodic follow-up showed no evidence of recurrence or metastasis in the 22-month postoperative period.

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells.

E2F is a family of transcription factors implicated in the regulation of gene expression required for progression through the G(1)-S transition. We have previously detected tumor-specific mutations at a trinucleotide repeat coding sequence of E2F-4 gene in a subset of human sporadic colorectal cancers. The purpose of this study was to investigate the potential functional consequences of these E2F-4 mutations. We transfected NIH3T3 fibroblasts with expression constructs containing wild-type as well as mutant E2F-4 cDNA, and the effect of the E2F-4 mutations on proliferation was examined. Alteration in transactivation of the E2F consensus promoter sequence was also examined by transient cotransfection of a E2F-4 with a DP-2 construct into cultured human cells. Transfected cell clones overexpressing mutant E2F-4 grew more rapidly and showed higher proliferative activity by increased immunohistochemical staining for proliferating cell nuclear antigen (PCNA). All three mutant forms of E2F-4 showed elevated transactivation of the E2F consensus promoter sequence. Thus, expression of mutant E2F-4s confers a growth advantage in vivo, and this effect may be related to the acquisition of a neoplastic phenotype.

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

A build-up treatment for thickness gauging of steel plates based on gamma-ray transmission

A thickness gauging model of steel plates with build-up treatment, which is based on a gamma-ray transmission technique, has been proposed. Its performance has been evaluated by experiments using the real 137Cs thickness gauge equipped at the heavy plate mill in the steel industry. It is shown that the calculated values with the new model are in good agreement with experimental data obtained by the gamma-ray thickness gauge in the thickness range from 0 to 10 cm.

Wall correction factors for calibration of plane-parallel ionization chambers with high-energy photon beams.

Most dosimetry protocols recommend that calibration of plane-parallel ionization chambers be performed in an electron beam of sufficiently high energy by comparison with cylindrical chambers. For various plane-parallel chambers, the 1997 IAEA TRS-381 protocol includes an overall perturbation factor pQ for electron beams, a wall correction factor p(wall) for a 60Co beam and the product of two wall corrections k(att)k(m) for 60Co in-air calibration. The recommended values of p(wall) for plane-parallel chambers, however, are limited to certain phantom materials and a 60Co beam, and are not given for other phantom materials and x-ray beams. In this work, the p(wall) values of the commercially available NACP, PTW/Markus and PTW/Roos plane-parallel chambers in a solid water phantom have been determined with 60Co and 4 and 10 MV photon beams. The k(att)k(m) values for the NACP and PTW/Markus chambers have also been obtained. The wall correction factors p(wall) and k(att)k(m) have been determined by intercomparison with a calibrated Farmer chamber. The average value of p(wall) for these plane-parallel chambers was 1.005 +/- 0.1% (1 SD) for 60Co beams and 1.007 +/- 0.2% (1 SD) for both 4 MV and 10 MV photons. The k(att)k(m) values for the NACP and PTW/Markus chambers were about 1.5% lower than other published data.

First example of memory of chirality in carbenium ion chemistry

The non-Kolbe reaction of N-benzoyloxazolidine derivatives 6 derived from L-serine gave optically active N,O-acetals 7 when graphite was used as an anode material. This reaction represents the first example of "memory of chirality" in carbenium ion chemistry. The material used for the anode was critical for the memory of chirality. The substitution of carboxyl group with methoxyl group was found to proceed with an inversion mechanism.

Differences in reactivity to vitamin K administration of the vitamin K-dependent procoagulant factors, protein C and S, and osteocalcin.

Vitamin K is a trace nutrient necessary not only for the synthesis of four plasma clotting factors but also the production of two important anticlotting factors, protein C and protein S, and the synthesis of two bone proteins. If protein C and protein S are produced more quickly and/or in higher quantities than four plasma coagulation factors after vitamin K administration, then the result is unfavorable for stopping of hemorrhage. We therefore studied the difference of time dependence of prothrombin procoagulant factors, protein C and S and bone Gla protein after the administration of vitamin K in normal and vitamin K-deficient neonates. Results of our study showed that, on the whole, coagulation factors increased markedly more than anticlotting factors after vitamin K administration. Furthermore, the increase in bone Gla protein was also higher compared with protein C activity, although the detailed mechanism of the difference in reactivity of prothrombin procoagulant factors, protein C and S and bone Gla protein to vitamin K administration is not clear.

Dose calculation for asymmetric photon fields with independent jaws and multileaf collimators.

We have developed a simple method for dose calculation in dual asymmetric open and irregular fields with four independent jaws and multileaf collimators. Our calculation method extends the scatter correction method of Kwa et al. [Med. Phys. 21, 1599-1604 (1994)] based on the principle of Day's equivalent-field calculation. The scatter correction factor was determined by the ratio of the derived doses of a smaller asymmetric open field or irregular field to a larger symmetric field. The algorithm with the scatter correction method can be calculated from output factors, tissue maximum ratios, and off-axis ratios for conventional symmetric fields. The doses calculated by this method were compared with the measured doses for various asymmetric open and irregular fields. The agreement between the calculated and measured doses for 4 and 10 MV photon beams was within 0.5% at the geometric center of the asymmetric open fields. For the asymmetric irregular fields with the same geometrical center, agreement within 1% was found in most cases.

Topological analysis of p21WAF1/CIP1 expression in esophageal squamous dysplasia.

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.

[Surgical treatment for distal aortic arch aneurysm using stent grafting].

To alleviate the invasiveness of surgical treatment for distal aortic aneurysm or dissection, we have been using a stented graft to replace the distal anastomotic suture of the descending aorta. We also developed a new stent graft implanting method for distal aortic aneurysm or dissection which uses cervical branch bypasses from the ascending aorta and requires no extracorporeal circulation. These new surgical treatments for distal arch aneurysm result in low surgical mortality (3.8%) and low surgical morbidity rates (stroke, 7.7%; respiratory complications, 7.7%; no renal complications). These results indicate that these new graft implanting methods using stent graft should be considered as a less-invasive surgical treatment for distal aortic aneurysm or dissection.