Observational study on the identification of left atrial tachycardia circuits using Local Activation Time Histogram.

BACKGROUND: Mapping of atypical atrial arrythmias arising in the left atrium is often challenging. The Local Activation Time (LAT) Histogram, a new function of the 3D color mapping system CARTO version 7, may help improve identification of atrial tachycardia circuits. We aimed to assess the effectiveness of the LAT Histogram for identification of left atrial tachycardia circuits. METHODS: This retrospective study compared 25 consecutive cases of left atrial tachycardia that were treated before use of LAT Histogram (unused group) and 25 consecutive cases that were treated after introduction of LAT Histogram (used group) at Nagano Chuo Hospital. We evaluated whether we could identify the circuit of left atrial tachycardia from the electrophysiology lab data during ablation and the CARTO system data and whether we could perform effective ablation. RESULTS: Door-to-door time, skin-to-skin time, and fluoroscopy time (p ≤ .011) were all shorter in the LAT Histogram used group versus unused group, while mapping analysis times were longer in the used group (p ≤ .019). A significantly greater number of cases in the LAT Histogram used compared with the unused group had ablation for entrance or exit points (19 vs. 10 cases; p = .001 for first map). Ablation resulted in a return to sinus rhythm and changed cycle length at the first mapping in 20 cases (80%) in the LAT Histogram unused group and in 24 cases (96%) in the used group. CONCLUSIONS: LAT Histogram may provide a simple and effective method to identify entrance and exit locations in left atrial tachycardia.

Establishment of a New Model Sea Anemone for Comparative Studies on Cnidarian-Algal Symbiosis.

Frequent coral bleaching has drawn attention to the mechanisms of coral dinoflagellate endosymbiosis. Owing to the difficulty of rearing corals in the laboratory, model symbiosis systems are desired. The sea anemone Exaiptasia diaphana, hosting clade B1 of the genus Breviolum, has long been studied as a model system; however, a single species is insufficient for comparative studies and thus provides only limited resources for symbiosis research, especially regarding the specificity of host-symbiont associations. We established a clonal strain of the sea anemone Anthopleura atodai, whose symbiont was identified as a novel subclade of Symbiodinium (clade A) using a novel feeding method. We also developed a method to efficiently bleach various sea anemone species using a quinoclamine-based herbicide. Bleached A. atodai polyps were vital and able to reproduce asexually, exhibiting no signs of harmful effects of the drug treatment. Pilot studies have suggested that host-symbiont specificity is influenced by multiple steps differently in A. atodai and E. diaphana. RNAseq analyses of A. atodai showed that multiple NPC2 genes were expressed in the symbiotic state, which have been suggested to function in the transport of sterols from symbionts to host cells. These results reveal the usefulness of A. atodai in comparative studies of cnidarian-algal symbiosis.

Metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer.

BACKGROUND: Colorectal metastasis of lobular carcinoma of the breast is a diagnostic challenge. It may macroscopically simulate primary colon cancer or inflammatory bowel disease. In some cases, the interval between the primary breast cancer and metastatic colorectal lesions is so long that the critical records for diagnosis including history might be lost or missed. CASE PRESENTATION: Reported herein is a case of metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer developed in a 62-year-old Japanese woman. The case initially presented as a circumferential rectal lesion, and information on the patient's history of breast cancer was not noted. As the result of endoscopic biopsy, diagnosis of poorly differentiated rectal adenocarcinoma was made. The lesion was surgically resected after chemo-radiotherapy. Histopathological examination of the resected specimen with hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical analysis revealed an immunophenotype consistent with lobular carcinoma of the breast. Because further review of the patient's history revealed an occurrence of 'poorly differentiated adenocarcinoma of the breast', which she had experienced 24 years earlier, the final diagnosis of the lesion was made as rectal metastasis from lobular breast carcinoma. CONCLUSIONS: Poorly differentiated adenocarcinoma of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer of the colorectum is also rarer than that of the stomach. A lesson from the present case is that before we conclude a linitis plastica-type cancer of poorly differentiated type as a primary colorectal cancer, it is critical to exclude a possibility of metastatic colorectal cancer.

Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection.

The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.

Alterations of the base excision repair gene MUTYH in sporadic colorectal cancer.

The base excision repair gene MUTYH encodes glycosylase which removes adenine residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic germline mutations of the MUTYH gene are known to cause multiple colorectal adenomas including polyposis and cancer, mostly due to G:C➝T:A transversions in proto-oncogenes or tumor suppressor genes. The risk of colorectal cancer (CRC) in monoallelic mutation carriers of MUTYH is estimated to be higher in comparison with non-carriers. To investigate the possible role in sporadic CRC, we examined alterations of the MUTYH gene including somatic mutations and allelic loss in 101 cases of sporadic CRC, together with the KRAS mutation in some cases. MUTYH mutations in cancer DNA were detected in 3 cases, while mutations were also found in DNA samples from normal tissues, indicating that all were germline mutations. Allelic loss at the MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS mutations were found in 33 of the 101 (32.7%) samples. There was no significant difference in the rate of G:C➝T:A transversion in KRAS between cases with allelic loss (1 of 10, 10.0%) and without allelic loss (9 of 41, 22.0%). Investigation of quantitative allelic imbalance at SNP rs3219489 of MUTYH showed that CRC cases with C allele dominance (minor type corresponding to His) were more frequently detected with G:C➝T:A transversions than in those with G allele dominance (major type corresponding to Gln). In conclusion, somatic alterations of MUTYH in sporadic CRC were rare, similar to other DNA repair genes. However, it is possible that unknown mutations of regions not analyzed in this study and epigenetic changes of the promoter region of MUTYH may contribute to the disease.

[A case report of pathologically complete response of rectal cancer after preoperative treatment of CPT-11, S-1, and radiation therapy].

A 52-year-old woman diagnosed with lower rectal cancer was referred to our hospital for the operation of anal sphincter preservation. Rectal examination and colonoscopy showed a type 2 semicircular tumor on the posterior wall at 4 .5-7 cm from anal verge with incomplete mobility (cT3). She was diagnosed as the moderately differentiated tubular adenocarcinoma by biopsy. Computed tomography and magnetic resonance imaging showed no sign of invasion to the surrounding organs and metastasis to lymph nodes or the other organs (cN0, cM0). We performed a preoperative chemoradiotherapy (CRT) combined with S-1 and CPT-11. Radiation (1.8 Gy) was administered a total of 45 Gy( day 1-5, 8-12, 15-19, 22-26, 29-33). S-1 was taken orally( 100 mg/day: day 1-5, 8-12, 22-26, 29-33), and CPT-11 was administered intravenously (60 mg/m²: day 1, 8, 22, 29). Endoscopy after CRT showed a reduction of the tumor size (from semicircular to quarter-circular) and lowering of marginal wall. Rectal examination revealed an improvement of tumor mobility. Eight weeks after CRT, the patient underwent ISR with partial ESR and covering ileostomy pathological examination demonstrated no residual cancer cell in the primary lesion and lymph node (Grade 3, pCR). Preoperative CRT can be a promising tool for locally advanced rectal cancer.

G protein signaling mediates developmental processes and pathogenesis of Alternaria alternata.

A G protein alpha subunit gene (AGA1) has been cloned and characterized from a toxigenic and necrotrophic Alternaria alternata pathogen. Targeted disruption of AGA1 in the apple pathotype of A. alternata gave rise to mutants that differed in colony and conidial morphology as well as sporulation. The conidia of wild type and deltaAGA1 mutants showed equal germination on cellulose membranes. However, wild-type germ tubes formed readily from different points around the conidia, grew randomly, and were often branched, whereas those of the mutants formed only at one or both ends of the conidia and tended to grow in straight paths. Targeted disruption of AGA1 also resulted in reduction of pathogenicity on apple leaves, although the mutant produced host-specific AM-toxin, a fungal secondary metabolite associated with pathogenicity of the pathogen, at levels similar to the wild-type strain. Measurement of the intracellular cAMP levels of the mutant revealed that it was consistently higher than that of the wild type, indicating that AGA1 negatively regulates cAMP levels similar to mammalian Galphai systems. These results indicate that the signal transduction pathway represented by AGA1 appears to be involved in developmental pathways leading to sporulation and pathogenesis of A. alternata.

[A case of non-curatively resected gastric cancer successfully treated over 17 months with TS-1 and irinotecan combination therapy].

We report a case of non-curatively resected gastric cancer successfully treated with TS-1 and irinotecan (CPT-11) combination therapy, resulting in long-term survival of 17 months. A 56-year-old woman underwent noncurative resection with total gastrectomy for advanced gastric cancer with severe lymph node metastasis on June 3, 2004. Postoperatively, She received TS-1 and CPT-11 combination therapy (TS-1 80 mg/m(2) day 1-21, CPT-11 80 mg/m(2) day 1, 15, every 5 weeks). However, due to grade 4 neutropenia, and grade 3 nausea and anorexia in the first course, both doses were reduced. Since then, no grade 3 or severer adverse reactions have been observed. After 5 courses, partial response to lymph node metastasis was obtained, and her quality of life was improved. Thus, TS-1 and CPT-11 combination therapy has been effective for 17 months, suggesting that it is promising for long-term administration and survival to continue it perseveringly.

[A case of non-curatively resected gastric cancer successfully treated over 3 years with biweekly paclitaxel therapy].

We report a case of non-curatively resected gastric cancer successfully treated over 3 years with biweekly administration of paclitaxel. A 69-year-old man underwent non-curative resection with distal gastrectomy for advanced gastric cancer with remarkable lymph node metastasis on June 10, 2002. The metastatic lymph node (No. 8 a, 8 p and 12 a) linked up with the retroperitoneal node, making resection impossible. Postoperatively, he was initially treated with weekly administration of paclitaxel 100 mg/body (68 mg/m(2)) per week. However, due to grade 3 neutropenia in the first course, weekly administration was changed to biweekly administration with dose reduction to 60 mg/body (41 mg/m(2)), resulting in the continuation of paclitaxel therapy. Since then, no grade 3 or more severe adverse reactions have been observed. He has maintained NC for 3 years, and is still being treated on an outpatient basis at present. We believe that, in paclitaxel therapy for advanced gastric cancer, it is important for long-term survival to continue it perseveringly by dose reduction or change of schedule, when major adverse reactions are seen.

Functional analysis of the CXXC motif using phage antibodies that cross-react with protein disulphide-isomerase family proteins.

Polyclonal antibodies that had been raised against particular PDI (protein disulphide-isomerase) family proteins did not cross-react with other PDI family proteins. To evade immune tolerance to the important self-motif Cys-Xaa-Xaa-Cys, which is present in PDI family proteins, we used the phage display library [established by Griffiths, Williams, Hartley, Tomlinson, Waterhouse, Crosby, Kontermann, Jones, Low, Allison et al. (1994) EMBO J. 13, 3245-3260] to isolate successfully the phage antibodies that can cross-react with human and bovine PDIs, human P5, human PDI-related protein and yeast PDI. By measuring the binding of scFv (single-chain antibody fragment of variable region) to synthetic peptides and to mutants of PDI family proteins in a surface plasmon resonance apparatus, we identified clones that recognized sequences containing the CGHC motif or the CGHCK sequence. By using the isolated phage antibodies, we demonstrated for the first time that a lysine residue following the CXXC motif significantly increases the isomerase activities of PDI family proteins. Moreover, we demonstrated that the affinity of isolated scFvs for mutant PDI family proteins is proportional to the isomerase activities of their active sites.