Angular spectrum matching for digital holographic microscopy under extremely low light conditions.

Digital holographic microscopy (DHM) is a future three-dimensional (3D) microscopy due to its high-resolution and high-precision 3D images. Thus, it is getting attention in bioinformatics, semiconductor defect detection, etc. However, some limitations still exist. Especially, high-speed holographic imaging requires high-power lasers, which are difficult to image on highly absorbent or light-sensitive samples. To overcome these issues, we propose a new, to the best of our knowledge, digital hologram recovery algorithm called angular spectrum matching (ASM), which achieves hologram imitation to recover holograms in digital holography at low light intensities. The hologram used for the background phase comparison is recorded without objects; thus, no power limitation is required. The ASM utilizes this background hologram to recover dark holograms. We present experimental results showing improved DHM numerical reconstructions and recovered holograms under extremely low light conditions.

Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review.

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

A Catalog of GAL4 Drivers for Labeling and Manipulating Circadian Clock Neurons in Drosophila melanogaster.

Daily rhythms of physiology, metabolism, and behavior are orchestrated by a central circadian clock. In mice, this clock is coordinated by the suprachiasmatic nucleus, which consists of 20,000 neurons, making it challenging to characterize individual neurons. In Drosophila, the clock is controlled by only 150 clock neurons that distribute across the fly's brain. Here, we describe a comprehensive set of genetic drivers to facilitate individual characterization of Drosophila clock neurons. We screened GAL4 lines that were obtained from Drosophila stock centers and identified 63 lines that exhibit expression in subsets of central clock neurons. Furthermore, we generated split-GAL4 lines that exhibit specific expression in subsets of clock neurons such as the 2 DN2 neurons and the 6 LPN neurons. Together with existing driver lines, these newly identified ones are versatile tools that will facilitate a better understanding of the Drosophila central circadian clock.

[A patient with advanced gastric cancer who responded to neoadjuvant S-1 plus cisplatin chemotherapy].

The patient was a 49-year-old man who was diagnosed as having gastric cancer and was suspected of having lymph node metastasis on computed tomography( CT) scans. He received neoadjuvant chemotherapy with S-1 and cisplatin (CDDP). He underwent total gastrectomy after 2 courses of neoadjuvant chemotherapy. The pathological effect was Grade 1b. The patient was treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 3 years and 10 months after surgery.

Radiolabeled cyclosaligenyl monophosphates of 5-iodo-2'-deoxyuridine, 5-iodo-3'-fluoro-2',3'-dideoxyuridine, and 3'-fluorothymidine for molecular radiotherapy of cancer: synthesis and biological evaluation.

Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC(50) values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

Resectable gallbladder cancer presenting with acute pancreatitis caused by hemobilia.

A 79-year-old female was transferred to our hospital because of suspicion that her acute pancreatitis was caused by stone impaction in the common bile duct (CBD). Laboratory examination showed aspartate aminotransferase, 1645 U/l; alanine aminotransferase, 476 U/l; amylase, 1365 U/l; and white blood cells, 10700/µl. Computed tomography (CT) showed an enhanced tumor in the neck of the gallbladder, an abnormal CBD filled with a high-density area, and localized swelling in the head of the pancreas. Magnetic resonance cholangiopancreatography also showed a low-intensity area in the CBD. Endoscopic retrograde cholangiopancreatography showed coagulated blood discharged from the papilla of Vater. The diagnosis was acute pancreatitis caused by impaction of coagulated blood from a gallbladder tumor. A curative operation was performed 10 days after endoscopic bile duct drainage. Gallbladder cancer (GBCa) has no special symptoms and is usually diagnosed at an advanced stage; however, hemobilia and acute pancreatitis are unusual as an initial presentation of GBCa.

PDGFRbeta and HIF-1alpha inhibition with imatinib and radioimmunotherapy of experimental prostate cancer.

The clinical application of radioimmunotherapy (RIT) as a single modality in the treatment of prostate cancer is held back because of poor tumor responses to RIT and unacceptable normal tissue toxicities. The purpose of reported here studies was to develop a multimodality approach to RIT of prostate cancer that includes imatinib, a potent PDGFRbeta inhibitor, and in the course of these studies to define the mechanism of imatinib effects on RIT. Hypothesized interactions between these two modalities depend on the reduction of tumor interstitial fluid pressure with the subsequent increase of (131)ICC49 uptake into the tumor, and the inhibition of HIF-1alpha resulting in the improved tumor radiosensitivity. Levels of HIF-1alpha, IGF-1, PDGF-BB, phospho-PDGFRbeta and VEGF in response to imatinib were examined in PC-3 human prostate adenocarcinoma cells in vitro and in xenografts. RIT was based on (131)ICC49 and it was augmented with imatinib. Although PDGFRbeta appears to be functional in PC-3 tumors, the effect of imatinib on the tumor interstitial fluid pressure was insignificant. PC-3 cells and PC-3 xenografts express constitutive HIF-1alpha, which was significantly inhibited by imatinib. Reduced levels of HIF-1alpha were accompanied by the notable suppression of IGF-1. Simultaneously the increase in tumor levels of mouse and human PDGF-BB was observed. Improved PC-3 responses to RIT+imatinib treatment were significant and lasted approximately two weeks. Tumor doubling times in mice treated with (131)ICC49+imatinib were 21.6 +/- 0.7 days compared to 17.2 +/- 0.5 days in (131)ICC49+PBS-treated control mice. Imatinib alone had no effect on the tumor growth. In conclusion, imatinib inhibits HIF-1alpha expression in PC-3 tumors and improves RIT, but it has no effect on VEGF indicating absence of anti-angiogenic effects. There is a significant time- and dose-dependent reduction in the expression of IGF-1 suggesting an alternative pathway of imatinib-regulated HIF-1alpha expression leading to the improved PC-3 responses to RIT.

Angiographic features in acute pancreatitis: the severity of abdominal vessel ischemic change reflects the severity of acute pancreatitis.

CONTEXT: Assessment of tissue microcirculation is one of the important aspects of pathological evaluation in acute pancreatitis. Severe ischemic change sometimes leads to the development of organ dysfunction and/or infectious complications. OBJECTIVE: To evaluate the angiographic features of acute pancreatitis and correlate them with the severity of the disease. DESIGN: Retrospective study. PATIENTS: Twenty-seven consecutive patients with acute pancreatitis who had undergone angiography were retrospectively investigated. MAIN OUTCOME MEASURES: Vascular findings and Ranson score. RESULTS: Ischemic changes were found in 18 patients (66.7%); 11 (40.7%) were severe changes. Pseudoaneurysm, bleeding, and staining were seen in 4 (14.8%), 2 (7.4%) and 5 (18.5%) patients, respectively. The rate of severe ischemic changes was significantly correlated with the Ranson score (P=0.012). Conclusions Angiographic findings are useful for the evaluation of severe acute pancreatitis.

Non-occlusive mesenteric ischemia and its associated intestinal gangrene in acute pancreatitis.

BACKGROUND/AIMS: Non-occlusive mesenteric ischemia (NOMI) has been defined as diffuse intestinal ischemia that often results in intestinal gangrene in the presence of a patent arterial trunk. The prevalence and nature of NOMI in acute pancreatitis was investigated. METHODS: A total of 120 consecutive patients with acute pancreatitis managed in the Department of Surgery II, Kumamoto University Medical School, from April 1992 through December 2002, were investigated retrospectively. Among them, 60 patients had the severe form. RESULTS: The overall mortality of acute pancreatitis patients was 8.3% (10/120). The prevalence and mortality of acute pancreatitis associated with NOMI were 6.7% (8/120) and 63% (5/8), respectively, while those of patients with NOMI-associated intestinal gangrene were 4.2% (5/120) and 100% (5/5), respectively. The mortality of patients with severe acute pancreatitis who did not develop NOMI was 10% (5/52). All patients with NOMI-associated intestinal gangrene quickly progressed and subsequently died of multiple organ failure. Plasma creatine phosphokinase (CPK) and lactate levels were elevated significantly in patients with NOMI. CONCLUSION: Acute pancreatitis associated with NOMI was extremely severe. If the plasma CPK and lactate levels are extremely high, NOMI should be suspected.

Dynamic aspects of granulocyte activation in rat severe acute pancreatitis.

We demonstrated dynamic aspects of granulocyte activation in rat severe acute pancreatitis, which was induced by cerulein and aggravated following lipopolysaccharide (LPS) injection. Pancreatitis induced by cerulein increased intracellular elastase activity of granulocytes in the blood. However, significant systemic cytokinemia was not provoked under such conditions. After induction of severe pancreatitis by LPS, intracellular elastase activity of circulating granulocytes decreased markedly and immediately. This decrease occurred simultaneous to induction of systemic hypercytokinemia and granulocyte migration into the lung. Overall results imply that: (1) circulating granulocytes are activated by induction of mild pancreatitis; (2) activation of granulocytes is mediated by factors other than systemic cytokinemia, such as locally produced cytokines; (3) those priming granulocytes immediately and significantly migrate from the circulation into the extravascular space by induction of endotoxemia; and (4) migration of granulocytes, in turn, may be mediated by systemic cytokinemia.

Further evidence for endothelin as an important mediator of pancreatic and intestinal ischemia in severe acute pancreatitis.

INTRODUCTION: Severe acute pancreatitis is occasionally associated with pancreatic and intestinal necrosis. Mesenteric vasoconstriction is one of the most probable types of pathogenesis of these complications. AIM: To investigate the involvement of endothelin-1 (ET-1), a potent vasoconstrictor. METHODOLOGY AND RESULTS: Plasma ET-1 concentrations were extremely high in patients with pancreatic and/or diffuse intestinal necrosis. ET-1 mRNA was demonstrated in the rat pancreas, and the production of ET-1 protein by human umbilical vein endothelial cells was enhanced by tumor necrosis factor-alpha, thrombin, and protease-activated receptor-2-activating peptide. Administration of ET-1 in vivo induced mesenteric arterial spasm and decreased pancreatic and intestinal blood flow. CONCLUSION: These results suggest the following: ET-1 is produced in and around the pancreas, mainly by endothelial cells, in severe acute pancreatitis; in the inflammatory setting, cytokines, activated thrombin and trypsin, may stimulate ET-1 production in a paracrine fashion; produced ET-1 may exaggerate the splanchnic microcirculation; and progressive ischemia may lead to necrosis of the pancreas and intestine.