Kumiko Yoshida

Anti-human placental antigen complex X-P2 (hPAX-P2) anti-serum recognizes C-terminus of huntingtin-associated protein 1A common to 1B as a determinant marker for the stigmoid body

The anti-serum against an unknown human placental antigen complex X-P2 (hPAX-P2) immunohistochemically recognizes three putative molecules (hPAX-P2S, hPAX-P2N, and hPAX-P2R), each of which is associated with the stigmoid bodies (STBs), necklace olfactory glomeruli (NOGs), or reticulo-filamentous structures (RFs) in the rat brain. The STBs also contain huntingtin-associated protein 1 (HAP1), and the HAP1-cDNA transfection induces STB-like inclusions in cultured cells. In order to clarify the relationship between hPAX-P2S and HAP1 isoforms (A/B), we performed Western blotting, immuno-histo/cytochemistry for light- and electron-microscopy and pre-adsorption tests with HAP1 deletion fragments. The results showed that the anti-hPAX-P2 anti-serum recognizes HAP1474–577 of HAP1A/B in Western blotting and strongly immunostains HAP1A-induced STB-like inclusions but far weakly detects HAP1B-induced diffuse structures in HAP1-transfected HEK 293 cells. In the rat brain, immunoreactivity of the anti-hPAX-P2 anti-serum for the STBs was eliminated by pre-adsorption with HAP1474–577, whereas no pre-adsorption with any different HAP1 fragments can suppress immunoreactivity for the NOGs and RFs, which were not immunoreactive to anti-HAP1 anti-serum. These findings indicate that hPAX-P2S, which is distinct from hPAX-P2N and hPAX-P2R, is identical with STB-constituted HAP1 and that the HAP1-induced/immunoreactive inclusions correspond to the hPAX-P2-immunoreactive STBs previously identified in the brain.

Influence of stapling the intersegmental planes on lung volume and function after segmentectomy

OBJECTIVES Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy. METHODS Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function. RESULTS The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips. CONCLUSIONS Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes.

Abstract 1072: Synergistic effect of gemcitabine and a Dclk1 inhibitor on pancreatic cancer cell survival

Pancreatic cancer has the highest mortality rate of all major cancers and is one of the most lethal malignancies. There is a constant upward trend in the number of patients diagnosed with pancreatic cancer and the number of deaths due to pancreatic cancer. Gemcitabine (GEM) is often used in the treatment of pancreatic cancer (PDAC), but has limited effects. Doublecortin-like kinase 1 (Dclk1) is important in the progression of early pancreatic neoplastic lesions and PDAC. However, the functional role of Dclk1 in PDAC is unknown. To identify the substrate protein phosphorylated by Dclk1, we performed a protein microarray analysis on Dclk1 knockdown cells. The results of this analysis directed our studies toward Chk1, which is known to be a potential regulator of the cell cycle and experiences upregulation of phosphorylation after GEM treatment. In general, GEM treatment results in DNA damage to pancreatic cancer cells, an increase in phosphorylated Chk1 (p-Chk1), and arrests the cell cycle progression to repair the damaged DNA. On the basis of the preliminary data, we hypothesized that the decrease in Chk1 phosphorylation by Dclk1 inhibition circumvents cell cycle arrest and impairs the subsequent DNA repair. The aim of this study was to evaluate the synergistic effect of Dclk1 inhibition and GEM treatment on pancreatic cancer cell survival. We used the human pancreatic cancer cell line MIA PaCa-2 and LRRK2-IN-1 (LRRK) as the Dclk1 inhibitor for this study. First, we examined the effects of GEM or the Dclk1 inhibitor or both on cancer cell proliferation and the expression of p-Chk1. Significantly decreased cell proliferation was observed on co-treatment of GEM and LRRK compared to GEM treatment alone. In addition, the expression of p-Chk1 significantly decreased on co-treatment compared to GEM treatment alone. Second, we used flow cytometry to analyze the cell cycle after treatment with GEM and/or LRRK. Almost all cancer cells treated with GEM alone were arrested in the S phase of the cell cycle. The addition of LRRK allows the cell cycle to proceed in the same manner as untreated control cancer cells do. We also evaluated DNA damage by measuring the intensity of gamma-H2AX. Cancer cells that were co-treated experienced more DNA damage than with GEM treatment alone. The co-treatment induced apoptosis without the repair of DNA damage in the cancer cells. In conclusion, the combined treatment with GEM and a Dclk1 inhibitor decreased the cell survival rate compared to treatment with GEM alone through the suppression of p-Chk1. Targeting Dclk1 in combination with GEM might offer an excellent opportunity for future pancreatic cancer treatments. Citation Format: Daichi Kawamura, Yoshihiro Takemoto, Arata Nishimoto, Toshiki Tanaka, Yukari Hironaka, Kumiko Yoshida, Junichi Murakami, Naruji Kugimiya, Eijiro Harada, Koji Ueno, Tohru Hosoyama, Kimikazu Hamano. Synergistic effect of gemcitabine and a Dclk1 inhibitor on pancreatic cancer cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1072. doi:10.1158/1538-7445.AM2017-1072

Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation.

A case of multiple pleural cryptococcosis without pleural effusion.

Pulmonary cryptococcosis is most likely to occur in immunocompromised patients. The radiological manifestations generally include pulmonary parenchymal lesions, namely, pulmonary nodules, cavitary lesions, and consolidation; thus, multiple pleural nodules are unusual presentation. Here, we report a woman who presented with multiple pleural cryptococcosis without pleural effusion. The patient had previously undergone surgery for stage II rectal cancer. In addition, she received 6 cycles of chemotherapy for follicular lymphoma. Computed tomography (CT) revealed multiple small nodules involving the pleura without pleural effusion, which suggested possible recurrence of rectal cancer or malignant lymphoma as pleural dissemination. Thoracoscopic examination was performed, and pleural cryptococcosis was diagnosed. Although pleural cryptococcosis without pleural effusion is extremely rare presentation, clinicians should consider it when an immunocompromised patient presents with multiple pleural nodules. Thoracoscopic exploration should be the best procedure for the definitive diagnosis of multiple pleural nodules.

Bleeding from a diverticulum of the appendix (with video)

volume of oxygen gas that they generatedhelpful information in understanding the rationale for their use to dislodge impacted stool. Thus, when 1 volume of 10-volume H2O2 is decomposed, it produces 10 volumes of oxygen; a 3% solution is equivalent to 10-volume concentration. For laboratory use, 30% solutions are most common, and commercial grades from 70% to 98% are also available, but potentially quite hazardous. H2O2 can cause mucosal damage when it contacts the surface of the GI tract, and the so-called snow-white sign is produced when the H2O2 penetrates the epithelium, contacts catalase, and the resultant microbubbles of oxygen force blood out of the intramural vasculature with ischemic and free radical–induced injury. In larger volume, H2O2 has caused colonic gangrene and rupture, gas embolization, and fulminant colitis. I do not know the effect on Helicobacter pylori of ingested H2O2, but because there are so many available and relatively safer anti–H pylori agents, I would keep H2O2 out of arm’s reach except perhaps to rinse wounds and maybe take advantage of its oxidative properties to render colorless any blood that we might have gotten on garments at work or elsewhere. Lawrence J. Brandt, MD Associate Editor for Focal Points