[Carcinoma in situ arising in adenomyomatous hyperplasia of the ampulla of Vater: the first case report].

A man in his 70s was admitted to our hospital due to jaundice and upper abdominal pain. Laboratory findings indicated elevated serum hepatobiliary enzyme and amylase levels. Contrast-enhanced computed tomography revealed smooth wall thickening of the terminal bile duct (tBD) with a faintly enhanced inner line. ERCP revealed stenosis from the tBD to the ampulla of Vater (AV) with upstream dilatation. Intraductal ultrasound (IDUS) circumferentially revealed a thickened wall preserving a three-layered structure throughout the same region. Furthermore, a thick innermost hyperechoic layer was identified in the bile duct portion of the AV (Ab). Findings suggestive of adenocarcinoma were obtained from the tissue samples from the biliary stricture using biopsy forceps. Thus, pancreatoduodenectomy was performed. A pathological examination revealed a thickened AV wall spreading over the tBD with hyperplasia of the glands and smooth muscle fibers. In addition, low-grade biliary intraepithelial neoplasia (BilIN) was scattered throughout the lesion, and high-grade BilIN was partly observed in the peribiliary glands of the Ab. Based on these results, a diagnosis of carcinoma in situ arising in adenomyomatous hyperplasia (ADMH) of the AV was made. To date, there are no reports on ADMH-associated carcinoma of the BD or AV. We here report this original case with the IDUS findings, which are presumed to reflect the histologic features of ADMH showing ductal proliferation surrounded by smooth muscle fibers. Also, we discuss the process through which carcinoma arises from ADMH in AV.

Characterization of arylalkylamine N-acetyltransferase from silkmoth (Antheraea pernyi) and pesticidal drug design based on the baculovirus-expressed enzyme.

Arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) catalyzes the N-acetylation of arylalkylamines. A cDNA encoding AANAT (ApAANAT) was cloned from Antheraea pernyi by PCR. The cDNA of 1966 bp encodes a 261 amino acid protein. The amino acid sequence was found to have a high homology with Bombyx mori AANAT (BmNAT) but had very low homology with vertebrate AANATs. Amino acid sequence analysis revealed that four insect AANATs cloned from three species including ApAANAT formed a distinct cluster from the vertebrate group. A recombinant ApAANAT protein was expressed in Sf9 cells using a baculovirus expression system, having AANAT activity. The transformed cell extract acetylated tryptamine, serotonin, dopamine, tyramine, octopamine and norepinephrine. The AANAT activity was inhibited at over 0.03 mM tryptamine. Although insect AANATs have been considered as a target of insecticide, this type of insecticide has never been developed. Screening a chemical library of Otsuka Chemical Co., Ltd., we found a novel compound and its derivatives that inhibited the AANAT activity of ApAANAT. This may facilitate investigation of the monoamine metabolic pathway in insects and the development of new types of insecticides and inhibitors of AANATs.

A secreted placental alkaline phosphatase-based reporter assay system for screening of compounds acting at an octopamine receptor stably expressed in a mammalian cell line.

Octopamine receptors are attractive insecticide targets. To screen compounds acting at octopamine receptors simply and rapidly, we constructed a chemiluminescent reporter gene assay system that detects secreted placental alkaline phosphatase transcriptionally regulated by the cAMP response element for a silkworm octopamine receptor. This system proved useful in high-throughput screening to develop octopamine receptor-specific insecticides.

Combined large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder.

Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant neuroendocrine tumor that was first defined in the lungs. There are six previous reports on LCNEC in the gallbladder, comprising three cases combined with another tumor and three pure LCNECs. We describe a tumor combined with LCNEC and adenocarcinoma elements arising in the gallbladder and give a review of the literature. A 68-year-old woman was diagnosed as having gallbladder wall thickening and a hepatic mass. The surgically resected tumor had a dumbbell shape with gallbladder and liver elements. Histological examination revealed LCNEC in the liver and a deep infiltrative portion of the gallbladder, as well as a well-differentiated tubular adenocarcinoma in the mucosa of the gallbladder. The pseudoglandular structures of LCNEC were marked in the transitional area. Immunoreactivities for carcinoembryonic antigen and CA19-9 as well as for chromogranin A and synaptophysin were detected in the LCNEC element. High p53-protein expression and high proliferative activity estimated by Ki-67 positivity were observed in both elements. The results suggest a close relationship between LCNEC and adenocarcinoma, and support the theory that these elements originate from common cancer stem cells.

Synthesis of quinolactacide via an acyl migration reaction and dehydrogenation with manganese dioxide, and its insecticidal activities.

Quinolactacide isolated from Penicillium citrinum F 1539 was synthesized and evaluated for its insecticidal activities. The key steps of the total synthesis were an acyl migration reaction of the enol ester intermediate and dehydrogenation of tetrahydroquinolactacide with manganese dioxide. The synthesized quinolactacide showed 100% and 42% mortality against the green peach aphid (Myzus persicae) and diamondback moth (Plutella xylostella) at 500 ppm, respectively.

[A case of transverse colon cancer with left supraclavicular lymph node metastasis and paraaortic lymph node metastases responding to TS-1].

A 61-year-old man was seen at our hospital because he noticed a mass on the left side of his neck. After examinations, he was diagnosed as transverse colon cancer with the left supraclavicular lymph node metastasis and paraaortic lymph node metastases. Rt. hemicolectomy was performed for the transverse colon cancer. At 15 days after operation, TS-1 chemotherapy was started (each treatment course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the left supraclavicular lymph node had shrunk markedly in physical findings. After the second course, both the left supraclavicular lymph node metastasis and paraaortic lymph node metastases had disappeared in CT findings. A complete remission was observed after the second course, and was maintained thereafter. The serum level of CA 19-9 decreased from 62 U/ml under the normal value after the second course, and was kept under this normal value. Leukopenia and eruption (grade 2) were the only observed adverse effects. This patient continues to undergo outpatient treatment with good QOL.

Quinolactacide, a new quinolone insecticide from Penicillium citrinum Thom F 1539.

By a screening program searching for new pesticides from fungal sources, an insecticidal compound was isolated from Penicillium citrinum F 1539. The compound, named quinolactacide, was novel and showed 88% mortality against green peach aphids (Myzus persicae) at 250 ppm. Its structure was determined by spectroscopic techniques.