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1.
BMC Ophthalmol ; 24(1): 170, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627750

ABSTRACT

BACKGROUND: This study aimed to compare the results of the Chronos binocular/monocular refraction system, that measures objective and subjective ocular refraction in one unit, to objective findings obtained from a conventional autorefractometer and a conventional subjective ocular refraction using a trial-frame in real space. METHODS: Twenty-eight healthy volunteers (21.2 ± 1.5 years old) were included in this study. Objective ocular refraction was measured using two tests: the Chronos binocular/monocular refraction system under binocular conditions and a conventional autorefractometer under monocular conditions. Subjective ocular refraction was measured using three tests: Chronos binocular/monocular refraction system under binocular, monocular conditions, and trial-frame in the real space under monocular conditions. The measurement distance was set to 5.0 m for each test. All ocular refractions were converted into spherical equivalents (SEs). RESULTS: The objective SE was significantly more negative with Chronos binocular/monocular refraction system under binocular condition (- 4.08 ± 2.76 D) than with the conventional autorefractometer under monocular condition (- 3.85 ± 2.66 D) (P = 0.002). Although, the subjective SE was significantly more negative with Chronos binocular/monocular refraction system under binocular condition (- 3.55 ± 2.67 D) than with the trial-frame in the real space under monocular condition (- 3.33 ± 2.75 D) (P = 0.002), Chronos binocular/monocular refraction system under monocular condition (- 3.17 ± 2.57 D) was not significantly different from that in trial-frame in real space under monocular condition (P = 0.33). CONCLUSION: These findings suggest that the Chronos binocular/monocular refraction system, which can complete both objective and subjective ocular refraction tests in a single unit, is suitable for screening ocular refraction, although it produces slightly more myopic results. Furthermore, subjective ocular refraction testing accuracy in Chronos binocular/monocular refraction system can be equivalent to trial-frame in real-space testing by switching from binocular to monocular condition.


Subject(s)
Refraction, Ocular , Vision, Binocular , Humans , Young Adult , Adult , Visual Acuity , Vision Tests , Eye
2.
Kyobu Geka ; 76(9): 737-740, 2023 Sep.
Article in Japanese | MEDLINE | ID: mdl-37735736

ABSTRACT

A 33-year-old man with atopic dermatitis underwent thoracic drainage was initiated for the right spontaneous pneumothorax. On the third hospital day, he developed acute empyema with pleural fluid opacity and elevated inflammatory reaction on blood test. For prolonged air leakage and acute empyema, thoracoscopic bullectomy and thoracic lavage and curettage were performed on the 6th hospital day. Because the preoperative cultural test of pleural effusion showed meticillin-resistant Staphylococcus aureus( MRSA), he was treated with vancomycin and ampicillin/sulbactam, and discharged on the 11th hospital day( the 5th postoperative day). Although spontaneous pneumothorax is rarely associated with empyema, patients with atopic dermatitis are prone to infections caused by Staphylococcus aureus, and the relation between atopic dermatitis and empyema was suspected in this case. As percutaneous medical procedures pose a risk of deep bacterial infection, when medical procedures including thoracic drainage is performed for patients with dermatosis, it is important to keep the possibility of bacterial infection in mind, and to quickly shift to treatment by detecting early signs of infection.


Subject(s)
Dermatitis, Atopic , Empyema , Methicillin-Resistant Staphylococcus aureus , Pneumothorax , Male , Humans , Adult , Dermatitis, Atopic/complications , Pneumothorax/etiology , Pneumothorax/surgery , Drainage , Empyema/etiology , Empyema/surgery
3.
J Biol Chem ; 299(7): 104890, 2023 07.
Article in English | MEDLINE | ID: mdl-37286039

ABSTRACT

Maintenance of metabolic homeostasis is secured by metabolite-sensing systems, which can be overwhelmed by constant macronutrient surplus in obesity. Not only the uptake processes but also the consumption of energy substrates determine the cellular metabolic burden. We herein describe a novel transcriptional system in this context comprised of peroxisome proliferator-activated receptor alpha (PPARα), a master regulator for fatty acid oxidation, and C-terminal binding protein 2 (CtBP2), a metabolite-sensing transcriptional corepressor. CtBP2 interacts with PPARα to repress its activity, and the interaction is enhanced upon binding to malonyl-CoA, a metabolic intermediate increased in tissues in obesity and reported to suppress fatty acid oxidation through inhibition of carnitine palmitoyltransferase 1. In line with our preceding observations that CtBP2 adopts a monomeric configuration upon binding to acyl-CoAs, we determined that mutations in CtBP2 that shift the conformational equilibrium toward monomers increase the interaction between CtBP2 and PPARα. In contrast, metabolic manipulations that reduce malonyl-CoA decreased the formation of the CtBP2-PPARα complex. Consistent with these in vitro findings, we found that the CtBP2-PPARα interaction is accelerated in obese livers while genetic deletion of CtBP2 in the liver causes derepression of PPARα target genes. These findings support our model where CtBP2 exists primarily as a monomer in the metabolic milieu of obesity to repress PPARα, representing a liability in metabolic diseases that can be exploited to develop therapeutic approaches.


Subject(s)
Alcohol Oxidoreductases , Co-Repressor Proteins , Obesity , PPAR alpha , Humans , Fatty Acids/metabolism , Liver/metabolism , Obesity/genetics , Obesity/metabolism , PPAR alpha/genetics , PPAR alpha/metabolism , Alcohol Oxidoreductases/metabolism , Co-Repressor Proteins/metabolism , Allosteric Regulation
4.
J Allergy Clin Immunol ; 151(4): 1067-1080.e9, 2023 04.
Article in English | MEDLINE | ID: mdl-36592705

ABSTRACT

BACKGROUND: Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear. OBJECTIVES: This study sought to evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma. METHODS: Expressions of ELOVL6 and other isoforms were examined in the airways of patients who are severely asthmatic and in mouse models of asthma. Wild-type and ELOVL6-deficient (Elovl6-/-) mice were analyzed for ovalbumin-induced, and also for house dust mite-induced, allergic airway inflammation by cell biological and biochemical approaches. RESULTS: ELOVL6 expression was downregulated in the bronchial epithelium of patients who are severely asthmatic compared with controls. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides, and sphingosine-1-phosphate were higher in the lungs of ovalbumin-immunized Elovl6-/- mice compared with those of wild-type mice, while the aggravated airway inflammation was ameliorated by treatment with fumonisin B1 or DL-threo-dihydrosphingosine, inhibitors of ceramide synthase and sphingosine kinase, respectively. CONCLUSIONS: This study illustrates a crucial role for ELOVL6 in controlling allergic airway inflammation via regulation of fatty acid composition and ceramide-sphingosine-1-phosphate biosynthesis and indicates that ELOVL6 may be a novel therapeutic target for asthma.


Subject(s)
Asthma , Ceramides , Animals , Mice , Disease Models, Animal , Inflammation/drug therapy , Ovalbumin/adverse effects
5.
J Exp Med ; 219(7)2022 07 04.
Article in English | MEDLINE | ID: mdl-35608941

ABSTRACT

Microbiota alteration and IFN-γ-producing CD4+ T cell overactivation are implicated in Crohn's disease (CD) pathogenesis. However, it remains unclear how dysbiosis enhances Th1 responses, leading to intestinal inflammation. Here, we identified key metabolites derived from dysbiotic microbiota that induce enhanced Th1 responses and exaggerate colitis in mouse models. Patients with CD showed elevated lysophosphatidylserine (LysoPS) concentration in their feces, accompanied by a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A. LysoPS induced metabolic reprogramming, thereby eliciting aberrant effector responses in both human and mouse IFN-γ-producing CD4+ T cells. Administration of LysoPS into two mouse colitis models promoted large intestinal inflammation. LysoPS-induced aggravation of colitis was impaired in mice lacking P2ry10 and P2ry10b, and their CD4+ T cells were hyporesponsive to LysoPS. Thus, our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota promote Th1-mediated intestinal pathology.


Subject(s)
Colitis , Crohn Disease , Microbiota , Animals , Colitis/pathology , Crohn Disease/etiology , Dysbiosis/complications , Humans , Inflammation/pathology , Intestinal Mucosa/metabolism , Lysophospholipids , Mice , Th1 Cells/metabolism
6.
Nucl Med Biol ; 108-109: 33-43, 2022.
Article in English | MEDLINE | ID: mdl-35276446

ABSTRACT

INTRODUCTION: Theranostic applications are currently difficult to achieve owing to the limited evaluation of suitable chelators for therapeutic nuclides, such as 225Ac and 227Th. With a focus on targeted α therapy and theranostics using human IgG as a drug-delivery system (i.e., combining highly cytotoxic α-particle emitter radiation with efficient tumor targeting), we developed a recombinant humanized Nd2 (hNd2) as an anti-MUC5AC antibody since MUC5AC is highly expressed in patients with pancreatic cancer. Therefore, we aimed to evaluate the performance of 89Zr- (for diagnosis) and 225Ac- (for therapy) labeling of these antibodies using well-controlled radioisotope (RI)-labeling technology in pancreatic cancer mouse models. METHODS: 89Zr-labeled hNd2 (NMK89) and 225Ac-labeled hNd2 (NMT25) were manufactured by chemical conjugation using affinity peptides. A binding assay and the evaluation of plasma stability were performed in vitro to confirm the properties of NMK89 and NMT25. In vivo, we evaluated biodistribution, positron emission tomography (PET)/computed tomography (CT) imaging, antitumor effects, and toxicity. Moreover, the exposure dose in humans was estimated based on the biodistribution evaluation in normal mice. RESULTS: NMK89 and NMT25 showed binding specificity to MUC5AC and stability with radiochemical purity ≥90% in mice and human plasma following incubation for 168 h. NMK89 showed high accumulation in tumors and low non-specific accumulation in normal tissues. The antitumor effect of NMT25 was dose-dependent and significantly suppressed tumor growth in the NMT25 treatment groups compared with the control group (p < 0.05). NMK89 and NMT25 showed similar pharmacokinetics and biodistribution characteristics. Additionally, the human estimated exposure dose of NMK89 and NMT25 was confirmed, and the effective dose of NMK89 and NMT25 was 0.33 mSv/MBq and 177.5 mSv/MBq, respectively. CONCLUSION: NMK89 showed specific accumulation in the MUC5AC-expressing tumors, while NMT25 showed strong antitumor effects. These results suggest NMK89 and NMT25 as promising theranostic agents for pancreatic cancer.


Subject(s)
Pancreatic Neoplasms , Positron-Emission Tomography , Animals , Cell Line, Tumor , Humans , Mice , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/radiotherapy , Positron-Emission Tomography/methods , Radiometry , Tissue Distribution , Zirconium/chemistry , Pancreatic Neoplasms
7.
Respir Res ; 21(1): 153, 2020 Jun 16.
Article in English | MEDLINE | ID: mdl-32546152

ABSTRACT

BACKGROUND: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection. METHODS: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease. RESULTS: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence. CONCLUSIONS: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/surgery , Aged , Combined Modality Therapy/methods , Combined Modality Therapy/trends , Female , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/diagnosis , Prognosis , Retrospective Studies , Treatment Outcome
8.
J Gastroenterol Hepatol ; 35(8): 1355-1364, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32285970

ABSTRACT

BACKGROUND AND AIM: Lipids play important roles in inflammation and may be involved in the pathophysiology of inflammatory bowel disease (IBD). Here, we evaluated the characteristics of the plasma lipid profile in patients with IBD. METHODS: Plasma samples were collected from 20 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC), and 10 healthy volunteers (HVs) after overnight fasting. The subjects were men between 20 and 49 years of age with no history of hyperlipidemia. A total of 698 molecular species in 22 lipid classes were analyzed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Lipid classes of lysophosphatidic acid, lysophosphatidylserine (LPS), phosphatidylserine (PS), and shingosine-1-phosphate (S1P) were significantly increased in UC patients compared with the HV. The LPS, PS, and S1P levels were significantly increased, while those of lysophosphatidylinositol and phosphatidylcholine were significantly decreased in CD patients compared with HV. Among PS species, the levels of PSacyl (PSa) 40:3, PSa 38:3, and PSa 42:4 were significantly higher in CD patients, both active and remissive stage, than in HV. The LPS 18:0 level was significantly higher in CD and UC patients compared with HV. PSa 40:3 and PSa 38:3 levels positively correlated with the Crohn's Disease Activity Index, erythrocyte sedimentation rate, and platelet count and negatively correlated with hemoglobin, hematocrit, and albumin levels in CD patients. CONCLUSION: The lipid profile in IBD patients exhibits significant alterations, and PS levels are associated with clinical disease activity in CD patients.


Subject(s)
Chromatography, High Pressure Liquid/methods , Inflammatory Bowel Diseases/diagnosis , Lipidomics/methods , Phosphatidylserines/blood , Spectrometry, Mass, Electrospray Ionization/methods , Adult , Biomarkers/blood , Colitis, Ulcerative/blood , Colitis, Ulcerative/diagnosis , Crohn Disease/blood , Crohn Disease/diagnosis , Female , Humans , Inflammatory Bowel Diseases/blood , Lysophospholipids/blood , Male , Middle Aged , Young Adult
9.
Int J Mol Sci ; 21(3)2020 Jan 30.
Article in English | MEDLINE | ID: mdl-32019132

ABSTRACT

Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by abnormal accumulation of free cholesterol and sphingolipids in lysosomes. The iminosugar miglustat, which inhibits hexosylceramide synthesis, is used for NPC treatment, and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), a cyclic oligosaccharide derivative, is being developed to treat NPC. Moreover, therapeutic potential of 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) was shown in NPC models, although its mechanism of action remains unclear. Here, we investigated the effects of HP-ß-CD, HP-γ-CD, and their homolog 2-hydroxypropyl-α-cyclodextrin (HP-α-CD) on lipid accumulation in Npc1-null Chinese hamster ovary (CHO) cells compared with those of miglustat. HP-ß-CD and HP-γ-CD, unlike HP-α-CD, reduced intracellular free cholesterol levels and normalized the lysosome changes in Npc1-null cells but not in wild-type CHO cells. In contrast, miglustat did not normalize intracellular free cholesterol accumulation or lysosome changes in Npc1-null cells. However, miglustat decreased the levels of hexosylceramide and tended to increase those of sphingomyelins in line with its action as a glucosylceramide synthase inhibitor in both Npc1-null and wild-type CHO cells. Interestingly, HP-ß-CD and HP-γ-CD, unlike HP-α-CD, reduced sphingomyelins in Npc1-null, but not wild-type, cells. In conclusion, HP-ß-CD and HP-γ-CD reduce the accumulation of sphingolipids, mainly sphingomyelins, and free cholesterol as well as lysosome changes in Npc1-null, but not in wild-type, CHO cells.


Subject(s)
1-Deoxynojirimycin/analogs & derivatives , 2-Hydroxypropyl-beta-cyclodextrin/pharmacology , Cyclodextrins/pharmacology , Niemann-Pick C1 Protein/genetics , Niemann-Pick Disease, Type C/drug therapy , 1-Deoxynojirimycin/therapeutic use , Animals , CHO Cells , Cholesterol/metabolism , Cricetulus , Lysosomes/metabolism , Niemann-Pick Disease, Type C/metabolism , Sphingolipids/metabolism
10.
J Pineal Res ; 67(3): e12594, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31286565

ABSTRACT

Astronauts experience osteoporosis-like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O-methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast-inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.


Subject(s)
Bone Resorption/prevention & control , Melatonin/therapeutic use , Space Flight , Animals , Bone Density/drug effects , Calcitonin/metabolism , Cell Differentiation/drug effects , Goldfish , Immunohistochemistry , NF-kappa B/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , RNA, Messenger/metabolism , Rats , Real-Time Polymerase Chain Reaction , Weightlessness/adverse effects
11.
Nature ; 566(7742): 110-114, 2019 02.
Article in English | MEDLINE | ID: mdl-30675063

ABSTRACT

Small intestinal mononuclear cells that express CX3CR1 (CX3CR1+ cells) regulate immune responses1-5. CX3CR1+ cells take up luminal antigens by protruding their dendrites into the lumen1-4,6. However, it remains unclear how dendrite protrusion by CX3CR1+ cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1+ cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1+ cells, showed defective dendrite protrusions of CX3CR1+ cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1+ cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1+ cells of wild-type mice, but not of Gpr31b-/- mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the small intestine of wild-type mice, but not in that of Gpr31b-/- mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1+ cells.


Subject(s)
Bacteria/metabolism , CX3C Chemokine Receptor 1/metabolism , Cell Surface Extensions/metabolism , Intestine, Small/cytology , Intestine, Small/microbiology , Lactic Acid/metabolism , Pyruvic Acid/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Bacteria/immunology , CX3C Chemokine Receptor 1/deficiency , CX3C Chemokine Receptor 1/genetics , Cell Surface Extensions/drug effects , Cell Surface Extensions/immunology , Female , HEK293 Cells , Humans , Intestine, Small/drug effects , Intestine, Small/immunology , Lactic Acid/pharmacology , Lactobacillus helveticus/metabolism , Male , Methanol , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Pyruvic Acid/pharmacology , Receptors, G-Protein-Coupled/deficiency , Receptors, G-Protein-Coupled/genetics , Salmonella/immunology , Salmonella/metabolism
12.
Surg Case Rep ; 4(1): 51, 2018 Jun 07.
Article in English | MEDLINE | ID: mdl-29882097

ABSTRACT

BACKGROUND: Surgical resection is the first choice for intralobar sequestration (ILS). A lobectomy is often performed, though we consider that a segmentectomy may be sufficient for benign cases if the sequestration is completely included within a segment. CASE PRESENTATION: We treated a 36-year-old female diagnosed with ILS. Chest computed tomography (CT) revealed several cystic lesions with niveau formation and consolidation in left segment (S)10 without communication of the bronchus and abnormal artery branching from the descending aorta. We performed a sublobar resection of left S10 including sequestration through a thoracoscopic minimally sized incision. The sequestration had dark red appearance and was completely included in the S10. The boundary line of S10 was clear with inflation of the lung after cutting bronchus 10. The postoperative course was uneventful. Chest CT findings at 2 years after surgery showed good expansion of the residual left lower lobe with no consolidation and respiratory function were nearly the same as the preoperative condition. CONCLUSIONS: A thoracoscopic segmentectomy for ILS is a feasible and useful procedure for qualified cases, even in adult patients who had repeated inflammation.

13.
ACS Omega ; 3(2): 2363-2373, 2018 Feb 28.
Article in English | MEDLINE | ID: mdl-31458534

ABSTRACT

A mono-potassium cation-encapsulated Preyssler-type phosphotungstate, [P5W30O110K]14- (1), was prepared as a potassium salt, K14[P5W30O110K] (1a), by heating mono-bismuth- or mono-calcium-encapsulated Preyssler-type phosphotungstates (K12[P5W30O110Bi(H2O)] or K13[P5W30O110Ca(H2O)]) in acetate buffer. Characterization of the potassium salt 1a by single-crystal X-ray structure analysis, 31P and 183W nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy, high-resolution electrospray ionization mass spectroscopy, and elemental analysis revealed that one potassium cation is encapsulated in the central cavity of the Preyssler-type phosphotungstate molecule with a formal D 5h symmetry. Density functional theory calculations have confirmed that the potassium cation prefers the central position of the cavity over a side position, in which no water molecules are coordinated to the encapsulated potassium cation. 31P NMR and cyclic voltammetry analyses revealed the rapid protonation-deprotonation of the oxygens in the cavity compared to that of other Preyssler-type compounds. Heating of 1a in the solid state afforded a di-K+-encapsulated compound, K13[P5W30O110K2] (2a), indicating that a potassium counter-cation is introduced in one of the side cavities, concomitantly displacing the internal potassium ion from the center to a second side cavity, thus providing a new method to encapsulate an additional cation in Preyssler compounds.

14.
Int J Hematol ; 106(4): 562-572, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28527129

ABSTRACT

To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 µg/m2/day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 µg/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ≥6 × 106 CD34+ cells/kg were collected. A total of 7 patients were randomized in each treatment group. Five patients in PG group and no patients in G group achieved a collection of ≥6 × 106 CD34+ cells/kg in ≤2 days of apheresis [difference of 71.4% (90%CI 29-100%)]. These results were supported by the shorter median time to collect ≥6 × 106 CD34+ cells/kg (2 days in PG group; no patient in G group). The incidence of treatment emergent adverse events (TEAEs) was higher in PG group than in G group. Plerixafor was well tolerated, and effective for the mobilization/collection of peripheral HSCs for autologous transplantation in Japanese patients with MM.


Subject(s)
Hematopoietic Stem Cell Mobilization , Heterocyclic Compounds/administration & dosage , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation , Adult , Aged , Asian People , Autografts , Benzylamines , Cyclams , Filgrastim/administration & dosage , Filgrastim/adverse effects , Heterocyclic Compounds/adverse effects , Humans , Japan , Male , Middle Aged
15.
J Clin Pathol ; 70(8): 712-714, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28264878

ABSTRACT

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Receptor Protein-Tyrosine Kinases/genetics , Adult , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase , Female , Gene Rearrangement/genetics , Humans , In Situ Hybridization, Fluorescence/methods , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction/methods
16.
Sci Rep ; 7: 40008, 2017 01 10.
Article in English | MEDLINE | ID: mdl-28071674

ABSTRACT

Presence of exercise-induced pulmonary hypertension (EIPH) in asymptomatic degenerative mitral regurgitation (DMR) determines prognosis. This study aimed to elucidate the mechanism and predictors of EIPH in asymptomatic DMR. Ninety-one consecutive asymptomatic patients with DMR who underwent exercise stress echocardiography were prospectively included. We obtained various conventional echocardiographic parameters at rest and during peak exercise, as well as left atrial (LA) function at rest using 2-dimensional speckle-tracking analysis. The 25 patients (33.3%) with EIPH were significantly older and had a greater ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity during peak exercise than those without EIPH. LA strain (LAS)-s and LAS-e, indices of LA reservoir and conduit function, respectively, were significantly lower in those with EIPH than in those without EIPH. Multivariate analysis indicated that LAS-s was the only resting echocardiographic parameter that independently predicted EIPH, with a cut-off value of 26.9%. Furthermore, Kaplan-Meier curve analysis showed that symptom-free survival was markedly lower among those with reduced LAS-s. In conclusion, decreased LA reservoir function contributes to EIPH, and LAS-s at rest is a useful indicator for predicting EIPH in asymptomatic patients with DMR.


Subject(s)
Exercise , Hypertension, Pulmonary/diagnosis , Mitral Valve Insufficiency/physiopathology , Adult , Aged , Area Under Curve , Atrial Function, Left/physiology , Blood Pressure , Disease-Free Survival , Echocardiography , Female , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Humans , Hypertension, Pulmonary/complications , Kaplan-Meier Estimate , Male , Middle Aged , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/mortality , Predictive Value of Tests , Prognosis , ROC Curve , Risk Factors
17.
J Echocardiogr ; 15(2): 70-78, 2017 06.
Article in English | MEDLINE | ID: mdl-27873174

ABSTRACT

BACKGROUND: Surgical timing of chronic aortic regurgitation (AR) remains a matter of debate because of limited data. This study assessed the prognostic value of exercise echocardiography in asymptomatic AR. METHODS: This prospective study included 60 consecutive asymptomatic patients with isolated moderate or severe AR (mean regurgitant volume 56.7 ± 11.8 ml) and preserved ejection fraction who underwent exercise echocardiography. The clinical outcomes were defined by the presence of major adverse cardiovascular events (MACE) and the indication for aortic valve replacement (AVR) with class I or IIa classification in the current guidelines. RESULTS: During the average follow-up of 731 days, 12 patients suffered from the clinical events, including two patients developing MACE (3%) and ten patients indicating for AVR (17%). No difference in left ventricular (LV) ejection fraction at rest was found between the patients with and without the clinical events. The indexed LV diameters and LV volumes were significantly dilated in the patients with the clinical events. The Cox proportional hazards regression analysis resulted that the exercise LV end-systolic volume index (LVESVi) was significantly associated with the clinical outcomes [hazard ratio, 1.116; 95% CI (1.032-1.205); p = 0.006]. The Kaplan-Meier analysis showed that exercise LVESVi was clearly stratified the event-free survival. CONCLUSIONS: Exercise LVESVi might be an independent predictor of prognosis in patients with asymptomatic moderate or severe AR.


Subject(s)
Aortic Valve Insufficiency/diagnosis , Aortic Valve Insufficiency/surgery , Echocardiography , Exercise , Heart Valve Prosthesis Implantation , Heart Ventricles/diagnostic imaging , Adult , Aged , Aged, 80 and over , Aortic Valve Insufficiency/diagnostic imaging , Echocardiography/methods , Female , Follow-Up Studies , Heart Valve Prosthesis Implantation/methods , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Sensitivity and Specificity
18.
Inorg Chem ; 55(21): 11583-11592, 2016 Nov 07.
Article in English | MEDLINE | ID: mdl-27775333

ABSTRACT

Dipotassium cation (K+)-encapsulated Preyssler-type phosphotungstate, [P5W30O110K2]13-, was prepared by heating monobismuth (Bi3+)-encapsulated Preyssler-type phosphotungstate, [P5W30O110Bi(H2O)]12-, in acetate buffer in the presence of an excess amount of potassium cations. Characterization of the isolated potassium salt, K13[P5W30O110K2] (1a), and its acid form, H13[P5W30O110K2] (1b), by single crystal X-ray structure analysis, 31P and 183W nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, cyclic voltammetry (CV), high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and elemental analysis revealed that two potassium cations are encapsulated in the Preyssler-type phosphotungstate molecule with formal D5h symmetry, which is the first example of a Preyssler-type compound with two encapsulated cations. Incorporation of two potassium cations enhances the thermal stability of the potassium salt, and the acid form shows catalytic activity for hydration of ethyl acetate. Packing of the Preyssler-type molecules was observed by high-resolution high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM).

19.
Surg Case Rep ; 2(1): 40, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27108124

ABSTRACT

A colopleural fistula is a rare condition reported to be caused by Crohn's disease, a malignant tumor of the gastrointestinal tract, and other clinical conditions. Some studies have noted that a sub-diaphragmatic abscess, usually organized following abdominal surgery, may play some role in the formation of this type of fistula. Therefore, a colopleural fistula is a complication very rarely encountered by thoracic surgeons after lung resection.We experienced an extremely rare case of colopleural fistula following a left lower lobectomy for lung aspergillosis. Here, we report a 71-year-old man with a surgical history of proximal gastrectomy for gastric cancer. He underwent left lower lobectomy of the lung for aspergillosis, and a colopleural fistula occurred on the second operative day as a complication. Aspergillus might be responsible for forming a fistula between the colon and lung via the diaphragm, and lung surgery manifested this rare condition. Although some reports suggest that surgical treatment is mandatory to cure this fistula, an immediate colostomy in our case reduced the internal pressure of the colon, thus enabling spontaneous closure of the fistula with appropriate drainage and antibiotics. The patient was discharged in a good condition.

20.
J Cardiol ; 65(2): 128-33, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24953246

ABSTRACT

BACKGROUND: Insulin resistance (IR) is characterized as a metabolic disorder syndrome that is upstream of hypertension, dyslipidemia, and diabetes mellitus (DM). This study investigated exercise training effects on the exercise tolerance and heart rate dynamics in patients with IR or pancreatic ß-cell dysfunction. METHODS: Seventy patients (mean age, 60.1 years) with myocardial infarction (MI) participating in a phase II cardiac rehabilitation program were studied. Patients diagnosed with DM were excluded. Homeostasis model-assessment indices were used to divide patients into three groups - A: IR; B: normal; and C: ß-cell dysfunction. A cardiopulmonary exercise test (CPX) was performed and peak oxygen uptake (V˙O2) was measured. After baseline testing, subjects participated in a supervised, combined aerobic and resistance exercise program. RESULTS: Peak V˙O2 at baseline was comparable among the three groups, and it improved after training in all groups (p<0.05). However, both the increase and percentage increase in peak V˙O2 were smaller in Group C than in Group A (p<0.05). Heart rate (HR) reserve (peak HR-rest HR), and HR recovery immediately 1min after exercise during CPX were calculated in 45 patients who were not taking negative chronotropic agents. Group C alone did not show any significant increase in HR reserve. HR reserve at both baseline and after training had significant positive correlations with peak V˙O2. HR recovery was 1.9 beats/min lower in group C than group A, but this was not significant. HR recovery in group C did not increase after cardiac rehabilitation. CONCLUSION: Impaired HR reserve increase after training in patients with pancreatic ß-cell dysfunction attenuates exercise training effects on functional capacity. Comprehensive treatment including vigorous exercise training will be needed in such prediabetic patients.


Subject(s)
Exercise Tolerance/physiology , Heart Rate/physiology , Insulin Resistance/physiology , Insulin-Secreting Cells/physiology , Myocardial Infarction/physiopathology , Aged , Diabetes Mellitus , Exercise Test , Female , Humans , Male , Middle Aged , Oxygen Consumption , Physical Conditioning, Human
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