Two new alkaloids from Crinum asiaticum var. japonicum

Journal of Natural Medicines - A new crinine-type alkaloid crijaponine A (1), a new galanthamine-type alkaloid crijaponine B (2), and 11 known alkaloids—ungeremine (3), lycorine (4),...     

Anti-melanin deposition activity and active constituents of Jatropha multifida stems

Journal of Natural Medicines - Jatropha multifida is a medicinal plant that belongs to the Euphorbiaceae family. Our investigation revealed that the chloroform extract of J. multifida stems showed...     

Carbon dioxide insufflation during colorectal endoscopic submucosal dissection for patients with obstructive ventilatory disturbance

Purpose

Carbon dioxide (CO₂) insufflation reduces abdominal pain and discomfort after endoscopic procedures; however, there is no previous study focusing the safety of CO₂ insufflation for patients with obstructive ventilatory disturbance. Here, we investigated the safety of CO₂ insufflation during colorectal endoscopic submucosal dissection (ESD) for patients with obstructive disturbance.

Methods

Between January 2010 and January 2013, colorectal ESD was performed using CO₂ insufflation for 385 consecutive patients. End-tidal CO₂ (EtCO₂) and transcutaneous oxygen saturation (SpO₂) were consecutively measured from the time before insertion of the colonoscope to the end of ESD. Patients were monitored by two nurses during the procedure and controlled for clinical symptoms of hypercapnia such as apnea or a depressed level of consciousness. According to their respiratory function, patients were stratified into a normal group and an obstructive disturbance group. We retrospectively compared EtCO₂ and SpO₂ during the procedures and the incidence of symptoms related to CO₂ retention between the two groups.

Results

The obstructive disturbance group consisted of 77 patients. There were similar changes of EtCO₂ in the obstructive disturbance group and normal group and no significant rise in EtCO_2. The maximum EtCO₂ level in any patient was <60 mmHg. In the obstructive disturbance group, there were no symptoms associated with CO₂ retention. There were no significant differences in the median SpO₂ between both groups and no prolonged drop of SpO₂.

Conclusions

CO₂ insufflation during colorectal ESD is safe for patients with obstructive ventilatory disturbance.     

Solid-state structures of peapod bearings composed of finite single-wall carbon nanotube and fullerene molecules

A supramolecular combination of carbon nanotube and fullerene, so-called a peapod, has attracted much interest, not solely because of its physical properties but also for its unique assembled structures of carbonaceous entities. However, the detailed structural information available was not sufficient for in-depth understanding of its structural chemistry or for exploratory research inspired by novel physical phenomena, mainly because of the severely inhomogeneous nature of currently available carbon nanotubes. We herein report solid-state structures of a molecular peapod. This structure, solved with a belt-persistent finite carbon nanotube molecule at the atomic level by synchrotron X-ray diffraction, revealed the presence of a smooth, inflection-free Hirshfeld surface inside the tube, and the smoothness permitted dynamic motion of the C₆₀ guest molecule even in the solid state. This precise structural information may inspire the molecular design of carbonaceous machines assembled purely through van der Waals contacts between two neutral molecules.A carbonaceous supramolecular system called a peapod, i.e., a host–guest composite of a single-wall carbon nanotube (SWNT) and fullerene, is attracting considerable interest in various fields due to its unique electronic and molecular structures (1). Although interesting physical phenomena of peapods are being discovered, especially in solid-state physics (2–5), little fundamental and in-depth understanding of peapods has been accumulated at the molecular or atomic levels until quite recently. The first reports of structural chemistry related to peapods appeared through the studies of [10]cycloparaphenylene ([10]CPP) (6): Yamago and coworkers (7) first reported a moderate level of association (association constant K_a ∼ 10³ M in o-dichlorobenzene) with C₆₀ in the solution phase, and solid-state crystal structures were reported with C₆₀ and C₇₀ by Jasti and coworkers (8) and Yamago and coworkers (9). Although this moderate level of association in [10]CPP raised a question regarding the stability of peapods in general (5, 10), we recently showed that the association of belt-persistent tubular molecules, [4]cyclo-2,8-chrysenylenes ([4]CC_2,8) (11–13), with C₆₀ was much higher and recorded a 10⁶- and 10⁹-fold higher association constant in the same medium (K_a ∼ 10⁹ M) and in benzene (K_a ∼ 10¹² M), respectively (Fig. 1A) (14, 15). The level of association in this molecular peapod was comparable to the one expected from theoretical studies with infinite SWNT peapods (10) and, to the best of our knowledge, was highest among host–guest complexes in organic media to date. The uniqueness of molecular recognition in the curved π-systems was further accentuated by the fact that this tight association does not hamper dynamic rolling motions of the guest, providing an intriguing possibility as a molecular bearing (16). To deepen the understanding of tightest host–guest complex composed of two apolar and neutral components and also to accelerate the development of carbonaceous molecular machines (17), the structural information of this molecular peapod, especially at the atomic level, is indispensable. We herein report the solid-state structures of the peapod bearing. We show that, even in the solid state, the belt-persistent tubular molecule allows the dynamic motion of the encapsulated C₆₀ molecule. An inflection-free, smooth surface inside the tube was revealed by a combination of diffraction analysis using a high-flux X-ray beam (18) and graphical inspection using the Hirshfeld surface of the encapsulated C₆₀ probe (19). The atomic-level structural information at the tube–sphere interface should be valuable and useful for the in-depth understanding of curved π-systems, for the discussion of peapods in the solid state, and for the design of peapod molecular machines in the future.Open in a separate windowFig. 1.Solid-state NMR analysis of peapod bearing. (A) Chemical structure of (M)-(12,8)-[4]CC_2,8⊃C₆₀. (B) Spectra of C₆₀, (M)-(12,8)-[4]CC_2,8⊃C₆₀ and a mixture of C₆₀ and (M)-(12,8)-[4]CC_2,8⊃C₆₀ at 25 °C under MAS conditions. See SI Appendix, Fig. S1, for the whole region. (C) VT NMR spectra of (M)-(12,8)-[4]CC_2,8⊃C₆₀ under static conditions without MAS. See SI Appendix, Fig. S3, for all of the data.     

Suppression of ventricular fibrillation by electrical modification of the Purkinje system in hypertrophic cardiomyopathy

A 56-year-old man in hypertrophic cardiomyopathy had an electrical storm caused by ventricular fibrillation (VF). Mapping during the initiation of the VF triggered by a premature ventricular contraction (PVC1), with right bundle branch block (RBBB)-like morphology and superior axis, demonstrated a prominent Purkinje–muscle junction (PMJ) delay at the distal portion of the left posterior fascicle. Delivery of radiofrequency (RF) energy to this area abolished the VF triggered by the PVC1. However, VF emerged by triggering another PVC (PVC2) with RBBB-like morphology and inferior axis. Similarly, the initiation of VF was associated with the PMJ delay at the peripheral left anterior fascicle, where RF delivery completely suppressed the VF. The PMJ delay and subsequent Purkinje–muscle reentry-like activity could be essential for the initiation of the Purkinje-related VF.     

Weekend versus weekday hospital admission and outcomes during hospitalization for patients due to worsening heart failure: a report from Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)

The day of the week of admission may influence the length of stay and in-hospital death. However, the association between the admission day of the week and in-hospital outcomes has been inconsistent in heart failure (HF) patients among studies reported from Western countries. We thus analyzed this association in HF patients encountered in routine clinical practice in Japan. We studied the characteristics and in-hospital treatment in 1620 patients hospitalized with worsening HF by using the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). Patients were divided into two groups according to weekday (n = 1355; 83.6 %) or weekend admission (n = 265; 16.4 %). The mean age was 70.7 years and 59.4 % were male. Etiology was ischemic in 34.0 %, and mean left ventricular ejection fraction was 42.5 %. Patients admitted on the weekend were significantly older and had more comorbidities, and more severe symptoms and signs of HF on admission. Length of stay was comparable between weekend and weekday admission (35.2 ± 47.0 days vs 33.6 ± 32.0 days, P = 0.591). Crude in-hospital mortality did not differ between patients admitted on the weekend and weekdays (7.5 % vs 5.2 %, P = 0.136). Even after adjustment for covariates in multivariable modeling with patients admitted on weekday as the reference, in-hospital death was comparable between patients admitted on the weekend and weekdays (adjusted odds ratio 1.125, 95 % confidence interval 0.631–2.004, P = 0.691). Among patients hospitalized for worsening HF, admission day of the week did not affect in-hospital death and length of stay.     

Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ–TIF2 fusion

Chromosomal translocations that involve the monocytic leukemia zinc finger (MOZ) gene are typically associated with human acute myeloid leukemia (AML) and often predict a poor prognosis. Overexpression of HOXA9, HOXA10, and MEIS1 was observed in AML patients with MOZ fusions. To assess the functional role of HOX upregulation in leukemogenesis by MOZ–TIF2, we focused on bromodomain-PHD finger protein 1 (BRPF1), a component of the MOZ complex that carries out histone acetylation for generating and maintaining proper epigenetic programs in hematopoietic cells. Immunoprecipitation analysis showed that MOZ–TIF2 forms a stable complex with BRPF1, and chromatin immunoprecipitation analysis showed that MOZ–TIF2 and BRPF1 interact with HOX genes in MOZ–TIF2-induced AML cells. Depletion of BRPF1 decreased the MOZ localization on HOX genes, resulting in loss of transformation ability induced by MOZ–TIF2. Furthermore, mutant MOZ–TIF2 engineered to lack histone acetyltransferase activity was incapable of deregulating HOX genes as well as initiating leukemia. These data indicate that MOZ–TIF2/BRPF1 complex upregulates HOX genes mediated by MOZ-dependent histone acetylation, leading to the development of leukemia. We suggest that activation of BRPF1/HOX pathway through MOZ HAT activity is critical for MOZ–TIF2 to induce AML.     

Dysregulation of microRNAs and their association in the pathogenesis of T-cell lymphoma/leukemias

MicroRNAs (miRNAs) are non-coding regulatory RNAs consisting of 20–24 nucleotides. Over 4,500 miRNAs have been identified in humans, and it is known that nearly all human protein-encoding genes can be controlled by miRNAs in both healthy and malignant cells. Abnormal miRNA expression is known to occur in many cancers, including in malignant lymphomas (MLs). Detailed genome-wide miRNA expression analysis has been performed in various ML subtypes, and these analyses have led to the discovery of subtype-specific miRNA alterations. Actually, in B-cell lymphomas, several miRNAs have been used as prognostic markers, and their targets are for new agents for ML therapy. Successful studies for delineating miRNA functions in B-cell lymphomas lead us to hypothesize that miRNA dysregulation may also be deeply associated with the pathogenesis of T-cell lymphomas. Indeed, studies for delineating essential miRNAs have been conduced against comparatively well-defined T-cell lymphoma entities. In this review, we describe several key miRNAs and their targets in distinct T-cell lymphoma subsets and their roles in their pathogenesis, studies of which will lead to new therapeutic strategies against T-cell lymphomas.     

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu–Yamaguchi Children’s Cancer Study Group

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.