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1.
Nature ; 613(7944): 479-484, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36653570

RESUMEN

Chiral molecules can exhibit spin-selective charge emission, which is known as chirality-induced spin selectivity1,2. Despite the constituent light elements of the molecules, their spin polarization can approach or even exceed that of typical ferromagnets. This powerful capability may lead to applications in the chiral spintronics2 field. Although the origin of spin selectivity is elusive, two microscopic phenomena have been suggested based on experimental results: effective enhancement of spin-orbit interactions3 and chirality represented by a pair of oppositely polarized spins4,5. However, the hypotheses remain to be verified. Here we report the simultaneous observation of these two phenomena in an organic chiral superconductor by magnetoresistance measurements in the vicinity of the superconducting transition temperature. A pair of oppositely polarized spins is demonstrated by spatially mapping the spin polarity in an electric alternating current excitation. The obtained spin polarization exceeds that of the Edelstein effect6-10 by several orders of magnitude, which indicates an effective enhancement of the spin-orbit interaction. Our results demonstrate a solid-state analogue of spin accumulations assumed for chiral molecules, and may provide clues to the origin of their molecular counterparts. In addition, the innovative capability of spin-current sourcing will invigorate superconducting spintronics research11.

2.
Arch Toxicol ; 97(12): 3095-3111, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37792044

RESUMEN

1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid pathway. Therefore, the overall objective of this study was to evaluate species-differences in glutathione (GSH) dependent in vitro metabolism of HFO-1123 in susceptible versus less susceptible species and humans as a basis for human risk assessment. Biotransformation of HFO-1123 to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH) and subsequent cysteine S-conjugate ß-lyase-mediated cleavage of the corresponding cysteine conjugate (1123-CYS) was monitored in hepatic and renal subcellular fractions of mice, rats, minipigs, rabbits, and humans. While 1123-GSH formation occurred at higher rates in rat and rabbit liver S9 compared to minipig and human S9, increased ß-lyase cleavage of 1123-CYS was observed in minipig kidney cytosol as compared to cytosolic fractions of other species. Increased ß-lyase activity in minipig cytosol was accompanied by time-dependent formation of monofluoroacetic acid (MFA), a highly toxic compound that interferes with cellular energy production via inhibition of aconitase. Consistent with the significantly lower ß-lyase activity in human cytosols, the intensity of the MFA signal in human cytosols was only a fraction of the signal obtained in minipig subcellular fractions. Even though the inconsistencies between GSH and ß-lyase-dependent metabolism do not allow to draw a firm conclusion on the overall contribution of the mercapturic acid pathway to HFO-1123 biotransformation and toxicity in vivo, the ß-lyase data suggest that humans may be less susceptible to HFO-1123 toxicity compared to minipigs.


Asunto(s)
Acetilcisteína , Liasas , Ratas , Ratones , Animales , Humanos , Conejos , Porcinos , Porcinos Enanos/metabolismo , Liasas/metabolismo , Biotransformación , Glutatión/metabolismo , Riñón/metabolismo
3.
Lupus ; 29(1): 79-82, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31789124

RESUMEN

Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.


Asunto(s)
Alopecia/tratamiento farmacológico , Antirreumáticos/administración & dosificación , Hidroxicloroquina/administración & dosificación , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Adulto , Alopecia/etiología , Alopecia/patología , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Femenino , Humanos , Lupus Eritematoso Cutáneo/complicaciones , Receptores de Superficie Celular , Piel/patología
4.
Br J Dermatol ; 180(4): 881-887, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30120913

RESUMEN

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.


Asunto(s)
Autoanticuerpos/inmunología , Dermatomiositis/inmunología , Proteína 28 que Contiene Motivos Tripartito/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Autoanticuerpos/aislamiento & purificación , Dermatomiositis/sangre , Dermatomiositis/diagnóstico , Femenino , Humanos , Inmunoprecipitación , Masculino , Persona de Mediana Edad , Adulto Joven
5.
Inorg Chem ; 58(1): 114-120, 2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30556698

RESUMEN

A multiple-hydrogen-bond approach was applied to shorten Pt-X-Pt distances in Cl- and Br-bridged Pt chain complexes. [Pt(dabdOH)2Cl]Cl2 (5) and [Pt(dabdOH)2Br]Br2 (6) (dabdOH = (2 S,3 S)-2,3-diaminobutane-1,4-diol) contain hydroxy groups, which form additional hydrogen bonds with counteranions. 5 has the shortest Pt-Cl-Pt distance (5.0747(8) Å) of all Cl-bridged Pt chain complexes reported to date. Furthermore, the smallest optical gap (1.45 eV for 5 and 1.19 eV for 6) in any Cl- or Br-bridged Pt chain complex was achieved. 6 has the highest electrical conductivity (1.9 × 10-5 S cm-1 at room temperature) of all Br-bridged Pt chain complexes. This study shows that the introduction of additional hydrogen bonds between the ligands and halides is effective to enhance the electronic properties of halogen-bridged metal complexes.

7.
Nat Mater ; 16(11): 1100-1105, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28825731

RESUMEN

The transition of a Mott insulator to metal, the Mott transition, can occur via carrier doping by elemental substitution, and by photoirradiation, as observed in transition-metal compounds and in organic materials. Here, we show that the application of a strong electric field can induce a Mott transition by a new pathway, namely through impulsive dielectric breakdown. Irradiation of a terahertz electric-field pulse on an ET-based compound, κ-(ET) 2Cu[N(CN) 2]Br (ET:bis(ethylenedithio)tetrathiafulvalene), collapses the original Mott gap of ∼30 meV with a ∼0.1 ps time constant after doublon-holon pair productions by quantum tunnelling processes, as indicated by the nonlinear increase of Drude-like low-energy spectral weights. Additionally, we demonstrate metallization using this method is faster than that by a femtosecond laser-pulse irradiation and that the transition dynamics are more electronic and coherent. Thus, strong terahertz-pulse irradiation is an effective approach to achieve a purely electronic Mott transition, enhancing the understanding of its quantum nature.

8.
Lupus ; 27(14): 2220-2227, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30376790

RESUMEN

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.


Asunto(s)
Dermatitis/etiología , Granuloma/etiología , Lupus Eritematoso Sistémico/complicaciones , Piel/patología , Adulto , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Dermatitis/patología , Femenino , Granuloma/patología , Humanos , Macrófagos/patología , Neutrófilos/patología , Receptores de Superficie Celular/inmunología , Factores Sexuales
9.
Dis Esophagus ; 31(7)2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29346536

RESUMEN

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.


Asunto(s)
Carcinoma de Células Escamosas/patología , Quimioradioterapia Adyuvante/métodos , Neoplasias Esofágicas/patología , Anciano , Biopsia , Carcinoma de Células Escamosas/terapia , Resección Endoscópica de la Mucosa , Mucosa Esofágica/patología , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Esófago/patología , Esófago/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasia Residual , Periodo Posoperatorio , Resultado del Tratamiento
10.
J Fish Biol ; 92(5): 1590-1603, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29624686

RESUMEN

Migration of wild and cultivated juvenile honmoroko Gnathopogon caerulescens of from the spawning and nursery areas in Lake Biwa were investigated, both in the Ibanaiko Lagoon and its outlet to Daido River, using beam-trawl surveys in 2013 and 2014. The study demonstrated migration of G. caerulescens from a nursery lagoon toward Lake Biwa after the juvenile stage. These findings appear to be the first direct evidence for migration of an exclusively pelagic cyprinid species from a littoral nursery to a pelagic adult habitat in a large deep lake.


Asunto(s)
Migración Animal , Cyprinidae/fisiología , Animales , Cyprinidae/crecimiento & desarrollo , Ecosistema , Japón , Lagos , Ríos
11.
J Gen Virol ; 98(11): 2645-2646, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29022866

RESUMEN

The family Hepeviridae includes enterically transmitted small non-enveloped positive-sense RNA viruses. It includes the genera Piscihepevirus, whose members infect fish, and Orthohepevirus, whose members infect mammals and birds. Members of the genus Orthohepevirus include hepatitis E virus, which is responsible for self-limiting acute hepatitis in humans and several mammalian species; the infection may become chronic in immunocompromised individuals. Extrahepatic manifestations of Guillain-Barré syndrome, neuralgic amyotrophy, glomerulonephritis and pancreatitis have been described in humans. Avian hepatitis E virus causes hepatitis-splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Hepeviridae, which is available at www.ictv.global/report/hepeviridae.


Asunto(s)
Hepatitis Viral Animal/virología , Hepatitis Viral Humana/virología , Hepevirus/clasificación , Animales , Humanos
12.
Ann Oncol ; 28(2): 285-291, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28426104

RESUMEN

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).


Asunto(s)
Antraciclinas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Antraciclinas/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Docetaxel , Resistencia a Antineoplásicos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Taxoides/efectos adversos , Resultado del Tratamiento
13.
Phys Rev Lett ; 118(10): 107602, 2017 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-28339244

RESUMEN

A rapid polarization control in paraelectric materials is important for an ultrafast optical switching useful in the future optical communication. In this study, we applied terahertz-pump second-harmonic-generation-probe and optical-reflectivity-probe spectroscopies to the paraelectric neutral phase of an organic molecular dielectric, tetrathiafulvalene-p-chloranil and revealed that a terahertz pulse with the electric-field amplitude of ∼400 kV/cm produces in the subpicosecond time scale a large macroscopic polarization whose magnitude reaches ∼20% of that in the ferroelectric ionic phase. Such a large polarization generation is attributed to the intermolecular charge transfers and breathing motions of domain walls between microscopic neutral and ionic domains induced by the terahertz electric field.

14.
Phys Rev Lett ; 118(10): 107404, 2017 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-28339275

RESUMEN

Croconic acid crystals show proton displacive-type ferroelectricity with a large spontaneous polarization reaching 20 µC/cm^{2}, which originates from the strong coupling of proton and π-electron degrees of freedom. Such a coupling makes us expect a large polarization change by photoirradiations. Optical-pump second-harmonic-generation-probe experiments reveal that a photoexcited croconic-acid crystal loses the ferroelectricity substantially with a maximum quantum efficiency of more than 30 molecules per one absorbed photon. Based on density functional calculations, we theoretically discuss possible pathways toward the formation of a one-dimensional domain with polarization inversion and its recovery process to the ground state by referring to the dynamics of experimentally obtained polarization changes.

15.
Proc Biol Sci ; 283(1832)2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27252021

RESUMEN

Highly migratory marine species can travel long distances and across entire ocean basins to reach foraging and breeding grounds, yet gaps persist in our knowledge of oceanic dispersal and habitat use. This is especially true for sea turtles, whose complex life history and lengthy pelagic stage present unique conservation challenges. Few studies have explored how these young at-sea turtles navigate their environment, but advancements in satellite technology and numerical models have shown that active and passive movements are used in relation to open ocean features. Here, we provide the first study, to the best of our knowledge, to simultaneously combine a high-resolution physical forcing ocean circulation model with long-term multi-year tracking data of young, trans-oceanic North Pacific loggerhead sea turtles during their 'lost years' at sea. From 2010 to 2014, we compare simulated trajectories of passive transport with empirical data of 1-3 year old turtles released off Japan (29.7-37.5 straight carapace length cm). After several years, the at-sea distribution of simulated current-driven trajectories significantly differed from that of the observed turtle tracks. These results underscore current theories on active dispersal by young oceanic-stage sea turtles and give further weight to hypotheses of juvenile foraging strategies for this species. Such information can also provide critical geographical information for spatially explicit conservation approaches to this endangered population.


Asunto(s)
Distribución Animal , Tortugas/fisiología , Exoesqueleto , Animales , Ecología/métodos , Ecosistema , Japón , Océanos y Mares
16.
Phys Rev Lett ; 116(7): 076402, 2016 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-26943548

RESUMEN

To control the efficiency of photoinduced charge-order melting in perovskite manganites, we performed femtosecond pump-probe spectroscopy using double-pulse excitation on Pr_{0.6}Ca_{0.4}MnO_{3}. The results revealed that the transfer of the spectral weight from the near-infrared to infrared region by the second pump pulse is considerably enhanced by the first pump pulse and that the suppression of crystal anisotropy, that is, the decrease of long-range lattice deformations due to the charge order by the first pump pulse is a key factor to enhance the charge-order melting. This double-pulse excitation method can be applied to various photoinduced transitions in complex materials with electronic and structural instabilities.

17.
Lupus ; 25(9): 997-1003, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26846690

RESUMEN

OBJECTIVE: To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE. METHODS: 52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-α in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-α concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA. RESULTS: The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-α, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL-8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 × 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 × 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients. CONCLUSION: In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE.


Asunto(s)
Quimiocinas/sangre , Quimiocinas/líquido cefalorraquídeo , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos/líquido cefalorraquídeo , Vasculitis por Lupus del Sistema Nervioso Central/sangre , Vasculitis por Lupus del Sistema Nervioso Central/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Quimiocina CCL2/sangre , Quimiocina CCL2/líquido cefalorraquídeo , Quimiocina CXCL10/sangre , Quimiocina CXCL10/líquido cefalorraquídeo , Femenino , Humanos , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/sangre , Interleucina-8/líquido cefalorraquídeo , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Masculino , Persona de Mediana Edad , Regulación hacia Arriba , Adulto Joven
18.
Vox Sang ; 111(3): 242-246, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27280485

RESUMEN

BACKGROUND AND OBJECTIVES: Human hepatitis E virus (HEV) is prevalent worldwide. Iatrogenic HEV has recently been identified based on the reports of transfusion-transmitted cases. The detection rate of HEV-RNA and seroprevalence of HEV-IgG/IgM have been regionally evaluated in Japan, and donor plasma collected in Hokkaido is currently screened by nucleic acid amplification testing. However, the detection rate of HEV-RNA in blood donors in Japan outside of Hokkaido has not been reported. MATERIALS AND METHODS: A total of 620 140 qualified donor plasma samples from Japanese regions excluding Hokkaido were tested for HEV-RNA (pools of 50 or 500) between 2004 and 2014. HEV-RNA-positive plasma bags were identified, and the HEV viral load, genotype and anti-HEV immunoglobulin (Ig)G/IgM were evaluated. RESULTS: The detection rate of HEV-RNA (pools of 50) was 1/15 075 and higher in eastern than in western Japan. All 36 HEV-RNA-positive samples were genotype 3 with viral load ranging from <1·69 to 7·22 log10 copies/ml. CONCLUSIONS: Our detection rate of HEV-RNA in donor populations in Japan outside Hokkaido (1/15 075 donations) is generally lower than reported in Europe and lower than previously reported for Hokkaido (1/8173 donations). As methods varied, we cannot exclude that these differences are reflective of differing RNA detection limits. In contrast to Hokkaido where genotype 4 has been reported among blood donations, all our positive donations were genotype 3, which is less pathogenic.


Asunto(s)
Virus de la Hepatitis E/genética , Hepatitis E/epidemiología , Donantes de Sangre , Genotipo , Anticuerpos Antihepatitis/sangre , Hepatitis E/prevención & control , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Japón/epidemiología , Límite de Detección , Prevalencia , ARN Viral/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas Serológicas , Carga Viral
19.
Phys Chem Chem Phys ; 18(40): 27885-27896, 2016 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-27711481

RESUMEN

We have investigated the crystal, electronic, and magnetic structures of Mn5O8 by means of state-of-the-art density functional theory calculations and neutron powder diffraction (NPD) measurements. This compound stabilizes in the monoclinic structure with space group C2/m where the Mn ions are in the distorted octahedral and trigonal prismatic coordinations with oxygen atoms. The calculated structural parameters based on total energy calculations are found to be in excellent agreement with low temperature NPD measurements when we accounted for the correct magnetic structure and Coulomb correlation effect in the computation. Using fully relativistic generalized-gradient approximation with Hubbard U (GGA+U) we found that the magnetic ordering in Mn5O8 is A-type antiferromagnetic and the direction of the easy axis is [1 0 0] in agreement with susceptibility and NPD measurements. However, the calculation without the inclusion of Hubbard U leads to ferrimagnetic half metal as a ground state contradictory to experimental findings, indicating the presence of a strong Coulomb correlation effect in this material. The GGA calculation without the Coulomb correction effect itself is sufficient to reproduce the experimentally observed magnetic moments in various Mn sites. We found that Mn in this material exhibits mixed valence behavior with 2+ and 4+ oxidation states reflecting different magnetic moments in the Mn sites. We explored the electronic band characteristics using total, site-, and orbital-projected density of states which emphasized the mixed-valent nature of Mn. A dominant Mn 3d character of the density of states at Fermi energy is the origin for the metallic behavior of Mn5O8. The bond strength analysis based on the crystal orbital Hamiltonian population between constituents indicates strong anisotropy in the bonding behavior which results from the layered nature of its crystal structure. Our bonding analysis shows that there is a noticeable covalent bond between Mn 3d-O 2p states which stabilizes the observed low symmetric structure. Our experimental findings and theoretical predictions suggest that Mn5O8 can be classified as a strongly correlated mixed valent antiferromagnetic metal.

20.
Ann Oncol ; 26(7): 1401-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25908605

RESUMEN

BACKGROUND: Platinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL). PATIENTS AND METHODS: Patients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0-1 and adequate organ function were randomized to receive either oral S-1 80 mg/m(2)/day on days 1-21 plus cisplatin 60 mg/m(2) on day 8 every 4-5 weeks, or docetaxel 60 mg/m(2) on day 1 plus cisplatin 80 mg/m(2) on day 1 every 3-4 weeks, both up to six cycles. RESULTS: A total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837-1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin. CONCLUSION: Oral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC. CLINICAL TRIAL NUMBER: UMIN000000608.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Administración Oral , Adulto , Anciano , Carcinoma de Células Grandes/mortalidad , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Docetaxel , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Pronóstico , Tasa de Supervivencia , Taxoides/administración & dosificación , Tegafur/administración & dosificación
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