Studies on metal-ion complex formation of crown ether derivatives incorporating a photoionizable spirobenzopyran moiety by electrospray ionization mass spectrometry

Metal-ion complexation of crown ether derivatives incorporating one and two spirobenzopyran units was investigated by electrospray ionization mass spectrometry.The crowned spirobenzopyran derivatives exhibited very different metal ion-complexing behavior from their corresponding parent crown ether rings,preferring multivalent to monovalent metal ions owing to the additional ionic interaction with the nitrophenolate anion of the merocyanine moiety.The on-line photochemical reaction for mass spectrometry indicated that the metal ion-complexing ability and ion selectivities of the crowned spirobenzopyrans can be switched photochemically,taking advantage of the difference between the spiropyran and merocyanine isomers

Infrared Spectroscopy of 15 Radio Galaxies at 2<z<2.6

Near-infrared spectra of 15 high-redshift radio galaxies (HzRGs) located at $2<z<2.6$ were obtained by the OH Airglow Suppressor spectrograph mounted on the Subaru telescope. The UV-optical line ratio diagnostic diagrams indicate that half of the observed HzRGs have extended emission-line regions with low metal abundance, photoionized by a flat-continuum active galactic nucleus such as a quasar. We also found two probable correlations between radio and rest-optical parameters: (1) HzRGs with massive hosts tend to have a redder rest-optical continuum, and (2) HzRGs with smaller radio sizes also show a redder optical continuum. On the basis of the correlations, the nature of HzRGs at $2<z<2.6$ is discussed.Comment: 23 pages, 7 figures, Corrected typos and style. Accepted for publication in ApJ (November 20, 2003

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial.

PURPOSE:To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).METHODS:Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.RESULTS:Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.CONCLUSIONS:IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02305238

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion in Immunodeficient Rats With Liver Xenografts of Patient-Derived Pancreatic Ductal Adenocarcinoma

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis

Cyclic AMP Responsive Element Binding Proteins Are Involved in ‘Emergency’ Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β

In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)–induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation

インターフェロンαが著効した腎癌骨格筋・小腸転移の1例

Skeletal muscle and small intestine are rare sites of metastasis in renal cell carcinoma. Therefore very few reports of interferon-alpha (IFN-alpha) therapy exist for these types of metastasis. Here, a case of metastatic renal cell carcinoma to muscle and jejunum is reported. After IFN-alpha therapy for 9 weeks, muscle metastasis completely disappeared and intestinal lesions were markedly reduced. However, subsequent patient compliance for this therapy was poor, resulting in death after relapse of the RCC.腎癌では骨格筋転移や小腸転移は稀であり, これらの転移に対するインターフェロンαによる療法の報告は非常に少ない。われわれは腎癌骨格筋・空腸転移の1例を経験した。9週間のインターフェロンα療法により筋肉転移は完全に消失し, 空腸転移も著明に縮小した。しかしながら治療の自己中断により病変の再燃を認め, 癌死の転帰をとった。(著者抄録