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Eperisone Hydrochloride was launched in Japan in 1983 and has been used to improve muscle tone and treat spastic paralysis (Originator: Eisai Co., Ltd.). However, its biochemical mechanism of action is unknown. SB Drug Discovery was used to evaluate purinergic P2X (P2X) receptor antagonism using fluorescence. In this study, we discovered that its target protein is the P2X7 receptor. Also, P2X receptor subtype selectivity was high. This finding demonstrates the (Eperisone-P2X7-pain linkage), the validity of P2X7 as a drug target, and the possibility of drug repositioning of Eperisone Hydrochloride.
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Relajantes Musculares Centrales , Propiofenonas , Relajantes Musculares Centrales/farmacología , Relajantes Musculares Centrales/uso terapéutico , Antagonistas del Receptor Purinérgico P2X/farmacología , Propiofenonas/farmacología , Propiofenonas/uso terapéutico , MúsculosRESUMEN
Liquid marbles were prepared using a water droplet and nonprotonated hydrophobic poly(2-N,N-diisopropylaminoethyl methacrylate) (PDiPAEMA) powder. Although the nonprotonated PDiPAEMA was hydrophobic, PDiPAEMA became hydrophilic because of the protonation of the pendant tertiary amino groups under acidic conditions. Therefore, liquid marbles stabilized with PDiPAEMA powder could float on a neutral to basic water surface, but they immediately disintegrated on an acidic water surface. Furthermore, the liquid marbles floating on the water surface disintegrated in response to CO2 gas because the water became acidic as a result of carbonic acid formation.
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BACKGROUND: There have been reports of isolated trace elements or vitamin deficiencies due to imbalanced diets, but no cases of selenium deficiency combined with scurvy have been reported. CASE PRESENTATION: A 7 year-old boy diagnosed with autistic spectrum disorder and mild psychomotor retardation, started an imbalanced diet including specific snacks and lacto-fermenting drinks from 5 years of age. Gingival hemorrhage and perioral erosions occurred at 6 years and 8 months of age, and he was referred to our hospital at 7 years of age. Slight tachycardia was found. Serum vitamin C level was 1.1 µg/dL (reference range (rr): 5-17.5 µg/dL), and selenium level was 2.8 µg/dL (rr: 7.7-14.8 µg/dL). He was diagnosed with both selenium deficiency and scurvy. Multivitamins and sodium selenate were administered for 12 days during admission, and symptoms of selenium deficiency and scurvy improved. After discharge, symptoms abated following the administration of multivitamins and regular administration of sodium selenate every 3 months. CONCLUSIONS: We report a complicated case of both selenium deficiency and scurvy due to an imbalanced diet of snacks and lacto-fermenting drinks in a 7-year-old boy with autism spectrum disorder. In patients with imbalanced diet, regular blood tests including trace elements and vitamins are necessary.
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AIM: To evaluate the feasibility of biweekly paclitaxel treatment as maintenance chemotherapy for patients with advanced müllerian carcinoma. METHODS: Thirty patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who underwent primary optimal surgery and standard 6 cycles of carboplatin/taxane-based chemotherapy and exhibited a complete clinical response were entered in this study. Paclitaxel 80 mg/m(2) was administered biweekly for 12 cycles. Patients were evaluated monthly for treatment-related toxicity. RESULTS: Four patients, including 3 disease progressions and 1 bone marrow suppression, came off the protocol therapy. Twenty-six (86.7%) patients received complete treatment. Although the major toxicity was neutropenia, most of those patients (27/30, 90.0%) did not experience grade 3 or 4 neutropenia. Twenty-four (80.0%) patients showed persistent grade 1 neuropathy and the remaining 6 (20.0%) did not as a result of prior therapy. However, none experienced neuropathy progression during or after the protocol therapy. Most (17/22, 77.3%) of the completely treated patients experienced a regression of symptoms during and after therapy. CONCLUSION: Biweekly paclitaxel therapy is well tolerated by patients with advanced müllerian carcinoma and is therefore acceptable as a candidate for maintenance chemotherapy in these patients.
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Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Quimioterapia de Mantención , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma Mucinoso/tratamiento farmacológico , Adulto , Anciano , Carcinoma Endometrioide/tratamiento farmacológico , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/efectos adversos , Resultado del TratamientoRESUMEN
A dinoflagellate cyst record from the highly resolved Chiba composite section in Japan has been used to reconstruct sea-surface paleoceanographic changes across the Lower-Middle Pleistocene Subseries (Calabrian-Chibanian Stage) boundary at the global stratotype, constituting the first detailed study of this microfossil group from the Pleistocene of the Japanese Pacific margin. Cold, subarctic water masses from 794.2 ka gave way to warming and rapid retreat of the Subpolar Front at 789.3 ka, ~ 2000 years before the end of Marine Isotope Stage (MIS) 20. Throughout the fully interglacial conditions of MIS 19c, assemblages are consistent with warm sea surface temperatures but also reveal instability and latitudinal shifts in the Kuroshio Extension system. The abrupt dominance of Protoceratium reticulatum cysts between 772.9 and 770.4 ka (MIS 19b) registers the influence of cooler, mixed, nutrient-rich waters of the Kuroshio-Oyashio Interfrontal Zone resulting from a southward shift of the Kuroshio Extension. Its onset at 772.9 ka serves as a local ecostratigraphic marker for the Chibanian Stage Global Boundary Stratotype Section and Point (GSSP) which occurs just 1.15 m (= 1300 years) below it. An interval from 770.1 ka to the top of the examined succession at 765.8 ka (MIS 19a) represents warm, presumably stratified but still nutrient-elevated surface waters, indicating a northward shift of the Kuroshio Extension ~ 5 kyrs after the termination of full interglacial conditions on land. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40645-021-00438-3.
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The fluctuating position of the boundary between the Kuroshio (warm) and Oyashio (cold) currents in the mid-latitude western North Pacific affects both heat transport and air-ocean interactions and has significant consequences for the East Asian climate. We reconstruct the paleoceanography of Marine Isotope Stages (MIS) 20-18, MIS 19 being one of the closest astronomical analogues to the present interglacial, through multiple proxies including microfossil assemblage data, planktonic foraminiferal isotopes (δ18O and δ13C), and foraminiferal Mg/Ca-based temperature records, from the Chiba composite section (CbCS) exposed on the Boso Peninsula, east-central Japan. Principal component analysis (PCA) is used to capture dominant patterns of the temporal variation in these marine records, and shows that the relative abundances of calcareous nannofossil and radiolarian taxa are consistent with the water mass types inferred from geochemical proxies. The leading mode (36.3% of total variance) mirrors variation in the terrestrial East Asian winter monsoon (EAWM), reflecting seasonal trends dominated by the winter monsoon system. In the CbCS, this mode is interpreted as reflecting the interplay between the warm Kuroshio and cold Oyashio waters, which is likely related to the latitudinal shift of the subtropical-subarctic gyre boundary in the North Pacific. The second mode (15.4% of total variance) is closely related to subsurface conditions. The leading mode indicates that MIS 19b and 19a are represented by millennial-scale stadial/interstadial oscillations. Northerly positions for the gyre boundary during late MIS 19c, the interstadials of MIS 19a, and early MIS 18 are inferred from the leading mode, which is consistent with a weak EAWM and consequent mild winter climate in East Asia. Nonetheless, the northerly positions for the gyre boundary during late MIS 19c and early MIS 19a were not associated with subsurface warming presumably due to the suppressed gyre circulation itself caused by the weak Aleutian Low. Intermittent southerly positions for the gyre boundary are inferred for the stadials of MIS 19b and 19a. Regional sea surface temperature (SST) comparisons in the western North Pacific reveal that the moderate SSTs during MIS 19a through early MIS 18 were restricted to the mid- to high latitudes, influenced by the weak EAWM. Comparison between MIS 20-18 and MIS 2-1 suggests that glacial MIS 20 and 18 had significantly milder winters than MIS 2, likely related to the relatively weak EAWM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40645-020-00395-3.
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We theoretically investigate optical birefringence originating from subwavelength structures in intrinsic birefringent media. Assuming alternating layers of isotropic and anisotropic materials, the propagation of optical waves is simulated on the basis of the finite difference time domain method. Optical polarization changes throughout the structure reveal the birefringence of the layered structure as a whole. In addition, the birefringence is also analyzed on the basis of effective medium theory. The results indicate that the optical birefringence of the structure as a whole can be modified by the magnitude and direction of the intrinsic birefringence of the anisotropic layers. This theoretical prediction will be useful for micro- and nanofabrication in optical devices.
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This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD.
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Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Castleman/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Enfermedad de Castleman/diagnóstico por imagen , Enfermedad de Castleman/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/patología , Ganglios Linfáticos/patología , Receptores de Interleucina-6/antagonistas & inhibidores , Tacrolimus/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
Inter-event times of various human behaviour are apparently non-Poissonian and obey long-tailed distributions as opposed to exponential distributions, which correspond to Poisson processes. It has been suggested that human individuals may switch between different states, in each of which they are regarded to generate events obeying a Poisson process. If this is the case, inter-event times should approximately obey a mixture of exponential distributions with different parameter values. In the present study, we introduce the minimum description length principle to compare mixtures of exponential distributions with different numbers of components (i.e. constituent exponential distributions). Because these distributions violate the identifiability property, one is mathematically not allowed to apply the Akaike or Bayes information criteria to their maximum-likelihood estimator to carry out model selection. We overcome this theoretical barrier by applying a minimum description principle to joint likelihoods of the data and latent variables. We show that mixtures of exponential distributions with a few components are selected, as opposed to more complex mixtures in various datasets, and that the fitting accuracy is comparable to that of state-of-the-art algorithms to fit power-law distributions to data. Our results lend support to Poissonian explanations of apparently non-Poissonian human behaviour.
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The monocyte chemotactic protein 3 (MCP-3) belongs to the MCP subgroup of the CC chemokines and promotes chemotaxis of immune cells. MCP-1 is believed to play an important role in monocyte infiltration into tumor tissues; however, the relationship between tumor-infiltrating macrophage/microglia (TIM/M) and the expression of chemokines has not been investigated in detail in human glioma samples; therefore, we first examined the expression of several chemokines and chemokine receptors in human tumor cell lines, which included glioma lines, using real-time PCR. We found that several glioma lines expressed MCP-3 predominantly, and not MCP-1. In order to assess the significance of MCP-3 expression in human glioma tissues, we then examined the number of CD68+ TIM/M, the percentage of TIM/M in the total cell population, and the expression of MCP-1 and MCP-3 in glioma tissues. There was a correlation between the percentage of TIM/M and MCP-3 expression levels; however, there was no correlation between the percentage of TIM/M and MCP-1 expression. There was no correlation between the number of TIM/M and prognosis of patients. These data indicate that tumor cell-derived MCP-3, but not MCP-1, facilitates the infiltration of macrophage/microglia into tumor tissues. This is the first study that clearly compared the significance of MCP-3 with that of MCP-1 in the tumor infiltration rates of TIM/M.
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Quimiocina CCL2/metabolismo , Quimiocina CCL7/metabolismo , Glioma/metabolismo , Glioma/patología , Macrófagos/patología , Microglía/patología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Quimiocina CCL2/genética , Quimiocina CCL7/genética , Niño , Preescolar , Femenino , Humanos , Técnicas para Inmunoenzimas , Lactante , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Adulto JovenRESUMEN
PURPOSE: To assess the antitumor efficacy and safety of 2 treatment modalities: intraperitoneal carboplatin combined with intravenous (IV) paclitaxel. PATIENTS AND METHODS: Eligible patients were those with epithelial ovarian carcinoma or primary peritoneal carcinoma stages II to IV who underwent initial surgery and had a residual tumor size of 2 cm or larger. Patients received IV paclitaxel 175 mg/m followed by intraperitoneal carboplatin AUC6. The primary end point was a response. Secondary end points were toxicity, progression-free survival, and overall survival. RESULTS: Twenty-six patients were enrolled, and 24 patients were eligible for assessment. The response rate was 83.3% (95% CI, 62.6%-95.3%; ). The median progression-free survival was 25 months. The median overall survival had not been reached. Incidences of grade (G) 3/4 hematological toxicities were absolute neutrophil count, 96%; hemoglobin, 29%; and thrombocytopenia, 16%. Nonhematological toxicities included G2 liver function, 4%; G3 sensory neuropathy, 8%; and G3 myalgia and arthralgia, 4%. CONCLUSIONS: Intraperitoneal administration of carboplatin combined with IV paclitaxel was well tolerated and showed satisfactory response in the patients with bulky residual tumor. Large-scale phase III trial comparing with IV carboplatin is warranted in this patient population.
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Adenocarcinoma Mucinoso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Carboplatino/administración & dosificación , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Dosis Máxima Tolerada , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Pronóstico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Here, tumor-infiltrating CD11b(+) myelomonocytoid cells in murine colon adenocarcinoma-38 and GL261 murine glioma were phenotypically characterized. Over 90% were of the CD11b(+)F4/80(+) monocyte/macrophage lineage. They also had a myeloid-derived suppressor cell (MDSC) phenotype, as they suppressed the proliferation of activated splenic CD8(+) T cells and had a CD11b(+)CD11c(+)Gr-1(low)IL-4Ralpha(+) phenotype. In addition, the cells expressed CX(3)CR1 and CCR2 simultaneously, which are the markers of an inflammatory monocyte. The MDSCs expressed CD206, CXCL10, IL-1beta, and TNF-alpha mRNAs. They also simultaneously expressed CXCL10 and CD206 proteins, which are typical, classical (M1) and alternative (M2) macrophage activation markers, respectively. Peritoneal exudate cells (PECs) strongly expressed CD36, CD206, and TGF-beta mRNA, which is characteristic of deactivated monocytes. The MDSCs also secreted TGF-beta, and in vitro culture of MDSCs and PECs with anti-TGF-beta antibody recovered their ability to secrete NO. However, as a result of secretion of proinflammatory cytokines, MDSCs could not be categorized into deactivated monocyte/macrophages. Thus, tumor-infiltrating MDSCs bear pleiotropic characteristics of M1 and M2 monocytes/macrophages. Furthermore, CD206 expression by tumor-infiltrating MDSCs appears to be regulated by an autocrine mechanism that involves TGF-beta.
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Linfocitos T CD8-positivos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Macrófagos/citología , Monocitos/citología , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Animales , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Citometría de Flujo , Glioma/inmunología , Glioma/patología , Proteínas Fluorescentes Verdes/genética , Linfocitos Infiltrantes de Tumor/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
BACKGROUND AND OBJECTIVES: Angiotensin (Ang) II plays an important role in fibrogenesis in various organs, including the lung. The aim of this study is to elucidate (i) the effects of Ang II on the expression of cytokines, growth factors or matrix proteins in normal human lung fibroblasts, and (ii) the inhibitory effects of an Ang II type 1 (AT1) receptor blocker, candesartan. METHODS: Normal human adult lung fibroblasts were cultured. Candesartan was added and the cells were incubated. All the cells in culture dishes were collected at day 0 and 2, and the cell numbers were counted using a Neubauer haemocytometer (Clay-Adams, Parsippany, NJ, USA). The cell proliferation rates at day 2 were calculated in comparison to those at day 0. Total cellular RNA was extracted for real-time quantitative PCR, or the culture supernatant was collected for either a Sircol assay or enzyme-linked immunosorbent assay (ELISA). Laser scanning confocal microscopy was used for analyzing the cells with and without prior exposure to candesartan. Comparisons between the means of multiple groups were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's test or Games-Howell's test. Values of P < 0*05 were considered to be statistically significant. RESULTS: Among the 12 fibrosis-associated cytokines and growth factors, mRNA expressions of interleukin (IL)-4, IL-7, and platelet-derived growth factor-D were significantly modulated by Ang II, and suppressed by candesartan. Soluble collagen and elastin levels were significantly elevated by Ang II, and suppressed by candesartan. Under confocal microscopy, the intracellular distribution of elastin was significantly increased by Ang II, and suppressed by candesartan. CONCLUSION: These data indicate that Ang II promotes lung fibrosis by increasing the matrix formation, which was suppressed by AT1 receptor blocker.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Angiotensina II/metabolismo , Bencimidazoles/farmacología , Fibroblastos/metabolismo , Tetrazoles/farmacología , Adulto , Angiotensina II/farmacología , Compuestos de Bifenilo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Elastina/efectos de los fármacos , Elastina/metabolismo , Proteínas de la Matriz Extracelular/efectos de los fármacos , Proteínas de la Matriz Extracelular/metabolismo , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Pulmón/citología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Microscopía Confocal , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: Positron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification. METHODS: In total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers. RESULTS: There were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG. CONCLUSIONS: PET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.
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Polyarteritis nodosa (PN) occasionally develops in association with malignant disorders. A 71-year-old man suddenly suffered from bleeding due to the rupture of a hepatic artery aneurysm. The ruptured lesion was embolized endovascularly by coiling, and the bleeding was stopped. A biopsy of the right inguinal lymph node demonstrated angioimmunoblastic T cell lymphoma (AITL). He received immunosuppressive treatment with transient response, although he relapsed 4 months later. To our knowledge, this is the first case of which PN was associated with AITL.
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Aneurisma Roto/terapia , Embolización Terapéutica , Arteria Hepática/patología , Linfadenopatía Inmunoblástica/complicaciones , Poliarteritis Nudosa/complicaciones , Anciano , Aneurisma Roto/complicaciones , Humanos , Linfadenopatía Inmunoblástica/patología , Linfoma de Células T/complicaciones , Linfoma de Células T/patología , MasculinoRESUMEN
Suborbital-scale climate variations, possibly caused by solar activity, are observed in the Holocene and last-glacial climates. Recently published bicentennial-resolution paleoceanic environmental records reveal millennial-scale high-amplitude oscillations postdating the last geomagnetic reversal in the Marine Isotope Stage (MIS) 19 interglacial. These oscillations, together with decoupling of post-reversal warming from maximum sea-level highstand in mid-latitudes, are key features for understanding the climate system of MIS 19 and the following Middle Pleistocene. It is unclear whether the oscillations are synchronous, or have the same driver as Holocene cycles. Here we present a high resolution record of western North Pacific submarine anoxia and sea surface bioproductivity from the Chiba Section, central Japan. The record reveals many oxic events in MIS 19, coincident with cold intervals, or with combined cold and sea-level fall events. This allows detailed correlations with paleoceanic records from the mid-latitude North Atlantic and Osaka Bay, southwest Japan. We find that the millennial-scale oscillations are synchronous between East and West hemispheres. In addition, during the two warmest intervals, bioproductivity follows the same pattern of change modulated by bicentennial cycles that are possibly related to solar activity.
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Inosine is absorbed via a N1 transporter that is selective for purine nucleosides. It is conceivable that inosine and inosinic acid might affect the intestinal absorption of mizoribine, an imidazole nucleoside that inhibits the de novo production pathway of guanine ribonucleotide. An in situ loop experiment was performed using four intestinal loop segments prepared by ligation: segment 1, about 6 to 9 cm from the end of the pylorus; segment 2, about 10 to 13 cm; segment 3, about 14 to 17 cm; and segment 4, about 18 to 21 cm. Mizoribine (0.1 mg/ml) or mizoribine+inosine (1 or 10 mg/ml) were infused into each loop. The absorption rate in the most proximal segment of intestinal loop was the highest. In the presence of inosine, this rate decreased significantly. Urinary recovery rates of mizoribine were significantly decreased by pretreatment with inosine or inosinic acid. The Cmax in the group given mizoribine+inosinic acid was significantly lower than that in the group given mizoribine alone. These results strongly indicate that (I) the N1 transporter in the intestine might act to absorb mizoribine; and (II) inosine and inosinic acid might competitively inhibit the absorption of mizoribine via the N1 transporter.
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Inosina Monofosfato/farmacología , Inosina/farmacología , Absorción Intestinal/efectos de los fármacos , Ribonucleósidos/farmacocinética , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Inmunosupresores/farmacocinética , Masculino , Tasa de Depuración Metabólica , Ratas , Ratas Sprague-Dawley , Ribonucleósidos/sangre , Ribonucleósidos/orinaRESUMEN
INTRODUCTION: Thrombin, a serine protease, plays an important role in such actions as coagulation, cell proliferation and inflammation. It has been sporadically reported that endothelial cells, when stimulated by thrombin via protease-activated receptors (PAR), express various mediators and proteins including cytokines, chemokines, growth factors, and adhesion molecules. However, the pleiotropic effect of thrombin on endothelial cells has not yet been fully elucidated. MATERIALS AND METHODS: We newly searched for the up-regulated genes in the thrombin-stimulated endothelial cells by thorough screening using a microarray chip, printed with 22,575 human genes, followed by verification using real-time PCR (n=3). RESULTS AND CONCLUSIONS: Twelve genes, which were 4.8 times or more up-regulated in a microarray analysis, were selected and further analyzed. In real-time PCR, ICAM-1, IL-8, BIRC3, COL3A1, CXCL3, and CXCL1 were significantly up-regulated in the thrombin-stimulated cells: 16.0-, 8.81-, 5.92-, 3.74-, 1.74-, and 1.66-fold, respectively. VCAM-1, CXCL2, CCL20, CSF2, CD69, and CCL2 were up-regulated in the thrombin-stimulated cells: 12.2-, 2.44-, 1.90-, 1.82-, 1.62-, and 1.06-fold, respectively, without attaining statistical significance. We demonstrated, for the first time, that BIRC3 (anti-apoptotic protein), COL3A1 (matrix protein synthesis), and CXCL3 (chemokine) were up-regulated in the thrombin-stimulated HUVECs.
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Quimiocinas CXC/metabolismo , Colágeno Tipo III/metabolismo , Proteínas Inhibidoras de la Apoptosis/metabolismo , Trombina/fisiología , Regulación hacia Arriba , Proteína 3 que Contiene Repeticiones IAP de Baculovirus , Técnicas de Cultivo de Célula , Células Endoteliales/metabolismo , Perfilación de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Ubiquitina-Proteína Ligasas , Venas Umbilicales/metabolismoRESUMEN
Adjusting the free-surface condition facilely controls the in-plane and out-of-plane orientations in liquid crystalline polymer (LCP) films. Top coating with aromatic molecules onto LC polymethacrylate films with N-benzylideneaniline (NBA) or 4-methoxybiphenyl (MB) side groups (PNBAM or PMBM) and subsequent annealing generate a random planar orientation while simultaneously removing the coated aromatic molecules, whereas annealing noncoated films induces a homeotropic orientation of the mesogenic side groups. Additionally, irradiating a top-coated PNBAM film with linearly polarized (LP) 365 nm light induces an in-plane molecular reorientation of the NBA side groups without changing the orientation in the homeotropically oriented region. Changes in the surface topology of the LCP films due to the reorientation processes are investigated in detail. Inkjet coating with aromatic molecules and LP 365 nm light exposure precisely controls the in-plane and out-of-plane alignment pattern in a PNBAM film.
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OBJECTIVE: We aimed to establish an enzyme-linked immunosorbent assay for measuring soluble elastin fragments (sELAF) in serum and to reveal its usefulness in diagnosing acute aortic dissection (AAD). METHODS AND RESULTS: An enzyme-linked immunosorbent assay to measure sELAF in serum was developed by using the newly created double monoclonal antibodies, which recognize the different epitopes of human aortic elastin. Twenty-five AAD patients, 50 patients with acute myocardial infarction (AMI), and 474 healthy individuals were enrolled in the study. The sELAF levels from healthy subjects gradually increased with aging. When the cutoff point for positivity was set at the mean+3 SD (ie, 3 SD above the mean in healthy subjects at each age), 16 AAD patients (64.0%) were found be positive, whereas only 1 AMI patient was found to be positive (2.0%). AAD patients with either an open or a partially open pseudolumen were found be 88.9% positive for sELAF, whereas those with its early closure were 0% positive. The difference in the sELAF levels between AAD patients with and without a thrombotic closure of false lumen was significant (60.3+/-15.6 versus 135.4+/-53.2 ng/mL, respectively; P<0.005). CONCLUSIONS: The sELAF level in serum may be a useful marker for helping in the diagnosis and screening of AAD and may also help to distinguish AAD from AMI.