Copolymerization of 1,6-anhydro-sugar derivatives with cyclic monomers, 1. Tri-O-benzyl ether and tri-O-methyl ether of 1,6-anhydro-ß-D-glucopyranose as sugar monomers

The cationic, ring-opening copolymerization of 1,6-anhydro-2,3,4-tri-O-benzyl-ß-D -glucopyranose with epichlorohydrin, 3,3-bis(chloromethyl)oxetane and 1,3-dioxolane was investigated with phosphorus pentafluoride as catalyst at low temperatures. Besides, copolymerization of 1,6-anhydro-2,3,4-tri-O-methyl-ß-D -glucopyranose with epichlorohydrin was studied. Structure and composition of the copolymers were determined by ¹H and ¹³C NMR spectroscopy, indicating that copolymerization occurred in each combination of monomers. Number-average molecular weights of copolymers were in the range of 1 400 to 22 800. From the specific rotation and ¹³C NMR spectrum of copolymers, it was revealed that the ring-opening copolymerization of the benzylated 1,6-anhydro-glucopyranose with the cyclic monomers occurred in a stereoregular manner to give the C-1 carbon of glucose unit with α-configuration. Debenzylation of a copolymer prepared from 1,6-anhydro-2,3,4-tri-Obenzyl-ß-D -glucopyranose and 1,3-dioxolane gave a copolymer composed of free sugar units in the polymer main chain. Assignment of ¹³C NMR spectra of 2,3,4-tri-O-benzyl-ß-D -glucopyranan and of a copolymer of 1,6-anhydro-2,3,4-tri-O-benzyl-ß-ß-glucopyranose with 1,3-dioxolane was attempted.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

31P and 19F NMR spectroscopic studies on ring-opening polymerization of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose by PF5 catalyst

In order to elucidate the catalytic behavior of phosphorus pentafluoride in the polymerization of anhydro sugars, ¹³P and ¹⁹F NMR spectra were measured on a reaction mixture of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D -glucopyranose (LGTBE) and PF₅ with different mole ratios in a temperature range of ?40 to ?80°C. In the ³¹P NMR spectrum measured at low temperatures, there was a total of 16 peaks, which consisted of a broad quintet, a septet, and a sharp quartet, being assigned to the PF₄O-group, to PF, and to POF₃, respectively. These fluoro compounds were also determined by the ¹⁹F NMR spectrum of the reaction mixture. The concentration of PF ions was found to correspond to that of oxonium ions, which are assumed to be actual propagating species, by determining both the concentration of PF from ¹⁹F NMR spectrum and the degree of polymerization of 2,3,4-tri-O-benzyl-α-D -glucopyranan obtained. Formation of the PF₅: LGTBE complex was observed from the ³¹P NMR spectrum of the polymerization system at ?80°C, which exhibits a broad sextet as well as absorptions due to POF₃, PF₄O–, and PF. To confirm the PF₅:LGTBE complex, the NMR measurement of the PF₅: tetrahydropyran complex was carried out. A polymerization mechanism of LGTBE by PF₅ catalyst is discussed on the basis of the NMR measurement of the polymerization system.     

Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor induce adhesion and chemotaxis of human eosinophils via p38 mitogen-activated protein kinase and nuclear factor kappaB

Hematopoietic cytokines such as interleukin (IL)-3, IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF) play a fundamental role in eosinophil functions in allergic asthma. The intracellular signal transduction mechanisms of these cytokines regulating the activation of eosinophils have been potential therapeutic targets. We investigated the roles of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-kappaB) in IL-3, IL-5, and GM-CSF-induced adhesion, morphological changes, and subsequence transmigration of human eosinophils. IL-3, IL-5, and GM-CSF could augment the phosphorylation of p38 MAPK and nucleus translocation of NF-kappaB in eosinophils. cDNA expression arrays demonstrated that the gene expression levels of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), alpha6, beta2 integrin (CD18), and CD44 were upregulated by these cytokines. Results from functional assays showed that adhesion of eosinophils onto airway epithelial cells was enhanced after IL-3 and IL-5 but not GM-CSF stimulation. These cytokines could markedly induce shape change and augment the transmigration of eosinophils. Moreover, administration of either p38 MAPK inhibitor, SB 203580, or proteasome inhibitor, N-cbz-Leu-Leu-leucinal (MG-132), could inhibit the cytokine-induced adhesion, shape change, and transmigration of eosinophils. Together, our findings suggest that IL-3, IL-5, and GM-CSF regulated the adhesion and chemotaxis of human eosinophils through shared signaling pathways involving both p38 MAPK and NF-kappaB. Our results therefore shed light on the further development of more effective agents for allergic and inflammatory diseases.     

Factors influencing the length of emergency room stay and hospital stay in nonfatal bicycle accidents: A retrospective analysis

Purpose: Lengthy hospitalization places a burden on patients and healthcare resources. However, the factors affecting the length of hospital stay (LHoS) and length of emergency room stay (LERS) in non-fatal bicycle accidents are currently unclear. We investigated these factors to inform efforts to minimize hospitalization. Methods: We performed a retrospective analysis of data from non-fatal injured bicyclists admitted to the Emergency and Critical Care Center at Kyoto Medical Center between January 2012 and December 2016. We measured LHoS, LERS, mechanism of injury, head injury prevalence, polytrauma, operations performed, injury severity score (ISS), abbreviated injury scale (AIS) score, maximum AIS score, and trauma and injury severity score probability of survival. We conducted multiple regression analysis to determine predictors of LHoS and LERS. Results: Within the study period, 82 victims met the inclusion and exclusion criteria and were included. Mean age was (46.0 ± 24.7) years. Overall mean LHoS was (16.8 ± 25.2) days, mean LERS was (10.6 ± 14.7) days, median ISS was 9 (interquartile range (IQR): 3-16), median maximum AIS was 3 (IQR: 1-4), and median trauma and injury severity score probability of survival was 98.0% (IQR: 95.5%-99.6%). Age, maximum AIS, ISS, and prevalence of surgery were significantly greater in long LHoS and LERS group compared with short LHoS and LERS group (p < 0.05). Performance of surgery independently explained LHoS (p = 0.0003) and ISS independently explained LERS (p = 0.0009). Conclusion: Surgery was associated with long hospital stays and ISS was associated with long emergency room stays. To improve the quality life of the bicyclists, preventive measures for reducing injury severity or avoiding injuries needing operation are required.     

ASO Visual Abstract: Influence of Damaged Stomach on Anastomotic Leakage After Cervical Esophagogastrostomy for Patients with Esophageal Cancer

Annals of Surgical Oncology -     

Analysis of Cdc2 and Cyclin D1 expression in breast cancer by immunoblotting

Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3% and 75.0% of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-double negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.