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1.
Phys Rev Lett ; 125(19): 191801, 2020 Nov 06.
Article in English | MEDLINE | ID: mdl-33216576

ABSTRACT

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

2.
Phys Rev Lett ; 122(23): 232501, 2019 Jun 14.
Article in English | MEDLINE | ID: mdl-31298906

ABSTRACT

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

3.
Phys Chem Chem Phys ; 21(5): 2325-2336, 2019 Jan 30.
Article in English | MEDLINE | ID: mdl-30656304

ABSTRACT

The production of gas-phase hydroperoxyl radicals, HO2, is observed directly from sub-micron airborne TiO2 nanoparticles irradiated by 300-400 nm radiation. The rate of HO2 production as a function of O2 pressure follows Langmuir isotherm behaviour suggesting O2 is involved in the production of HO2 following its adsorption onto the surface of the TiO2 aerosol. Reduction of adsorbed O2 by photogenerated electrons is likely to be the initial step followed by reaction with a proton produced via oxidation of adsorbed water with a photogenerated hole. The rate of HO2 production decreased significantly over the range of relative humidities between 8.7 and 36.9%, suggesting competitive adsorption of water vapour inhibits HO2 production. From the data, the adsorption equilibrium constants were calculated to be: KO2 = 0.27 ± 0.02 Pa-1 and KH2O = 2.16 ± 0.12 Pa-1 for RH = 8.7%, decreasing to KO2 = 0.18 ± 0.01 Pa-1 and KH2O = 1.33 ± 0.04 Pa-1 at RH = 22.1%. The increased coverage of H2O onto the TiO2 aerosol surface may inhibit HO2 production by decreasing the effective surface area of the TiO2 particle and lowering the binding energy of O2 on the aerosol surface, hence shortening its desorption lifetime. The maximum yield (i.e. when [O2] is projected to atmospherically relevant levels) for production of gas-phase HO2, normalised for surface area and light intensity, was found to be at a RH of 8.7% for the 80% anatase and 20% rutile formulation of TiO2 used here. This yield decreased to as the RH was increased to 22.1%. Using this value, the rate of production of HO2 from TiO2 surfaces under atmospheric conditions was estimated to be in the range 5 × 104-1 × 106 molecule cm-3 s-1 using observed surface areas of mineral dust at Cape Verde, and assuming a TiO2 fraction of 4.5%. For the largest loadings of dust in the troposphere, the rate of this novel heterogeneous production mechanism begins to approach that of HO2 production from the gas-phase reaction of OH with CO in unpolluted regions. The production of gas-phase OH radicals could only be observed conclusively at high aerosol surface areas, and was attributed to the decomposition of H2O2 at the surface by photogenerated electrons.

4.
Am J Transplant ; 18(2): 424-433, 2018 02.
Article in English | MEDLINE | ID: mdl-28758336

ABSTRACT

ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease score was 12.2 ± 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3-, and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.


Subject(s)
ABO Blood-Group System/adverse effects , Biliary Tract Diseases/mortality , Blood Group Incompatibility/complications , Graft Rejection/mortality , Liver Transplantation/adverse effects , Living Donors , Adult , Aged , Biliary Tract Diseases/etiology , Biliary Tract Diseases/pathology , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , Humans , Liver Function Tests , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome
5.
Phys Rev Lett ; 121(20): 201801, 2018 Nov 16.
Article in English | MEDLINE | ID: mdl-30500262

ABSTRACT

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

6.
Am J Transplant ; 17(11): 2890-2900, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28510341

ABSTRACT

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70-78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in-hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1- and 5-year patient survival rates were 84.0% and 69.8%, and the 1- and 5-year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.


Subject(s)
Graft Rejection/mortality , Liver Failure/mortality , Liver Transplantation/mortality , Living Donors , Postoperative Complications , Adult , Aged , Female , Follow-Up Studies , Graft Survival , Humans , Liver Failure/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate
7.
Am J Transplant ; 17(7): 1833-1842, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28097804

ABSTRACT

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute-on-chronic liver failure (ACLF) among high-Model for End-Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high-MELD score recipients were categorized into ACLF and non-ACLF groups, and their outcomes were compared. The 5-year graft and patient survival in the high-MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30-34 points. The 5-year graft survivals in the ACLF group was 70.5% and in the non-ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high-MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.


Subject(s)
Acute-On-Chronic Liver Failure/surgery , End Stage Liver Disease , Liver Transplantation/methods , Living Donors , Severity of Illness Index , Acute-On-Chronic Liver Failure/physiopathology , Adolescent , Adult , Animals , Child , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Liver Transplantation/adverse effects , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Young Adult
8.
Am J Transplant ; 16(1): 157-70, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26372830

ABSTRACT

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Desensitization, Immunologic , Graft Rejection/immunology , Liver Transplantation , Living Donors , Rituximab/pharmacology , Adolescent , Adult , Aged , Female , Humans , Immunosuppressive Agents/pharmacology , Liver Diseases/immunology , Liver Diseases/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young Adult
10.
Nature ; 465(7296): 322-5, 2010 May 20.
Article in English | MEDLINE | ID: mdl-20485429

ABSTRACT

Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae. Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The 'old' environment near the supernova location, and the very low derived ejected mass ( approximately 0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous or a regular type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive (44)Ti.

11.
Clin Endocrinol (Oxf) ; 83(1): 85-90, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25523467

ABSTRACT

OBJECTIVE: Treatment of growth hormone (GH)-deficient adults with GH has been shown to improve a range of metabolic abnormalities and enhance quality of life. However, the results of access to nationally funded treatment have not been reported. DESIGN: Retrospective case series auditing nationally funded treatment of defined GH-deficient adults in New Zealand, with carefully designed entry and exit criteria overseen by a panel of endocrinologists. PATIENTS: Applications for 201 patients were assessed and 191 approved for funded treatment over the initial 3 years since inception. The majority had GH deficiency following treatment of pituitary adenomas or tumours adjacent to the pituitary. RESULTS: After an initial 9-month treatment period using serum IGF-I measurements to adjust GH dosing, all patients reported a significant improvement in quality of life (QoL) score on the QoL-AGHDA(®) instrument (baseline (95%CI) 19 (18-21), 9 months 6 (5-7.5)), and mean serum IGF-I SD scores rose from -3 to zero. Mean waist circumference decreased significantly by 2.8 ± 0.6 cm. The mean maintenance GH dose after 9 months of treatment was 0.39 mg/day. After 3 years, 17% of patients had stopped treatment, and all of the remaining patients maintained the improvements seen at 9 months of treatment. CONCLUSION: Carefully designed access to nationally funded GH replacement in GH-deficient adults was associated with a significant improvement in quality of life over a 3-year period with mean daily GH doses lower than in the majority of previously reported studies.


Subject(s)
Drug Costs , Financing, Government , Hormone Replacement Therapy/methods , Human Growth Hormone/therapeutic use , Hypopituitarism/drug therapy , Adolescent , Adult , Aged , Cohort Studies , Eligibility Determination , Female , Hormone Replacement Therapy/economics , Human Growth Hormone/deficiency , Human Growth Hormone/economics , Humans , Hypopituitarism/metabolism , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , New Zealand , Quality of Life , Retrospective Studies , Treatment Outcome , Young Adult
12.
Clin Exp Dermatol ; 39(1): 25-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24341477

ABSTRACT

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.


Subject(s)
Alopecia/epidemiology , Adult , Age Distribution , Age of Onset , Alcohol Drinking/adverse effects , Alopecia/etiology , Alopecia/physiopathology , Female , Humans , Life Style , Male , Prevalence , Republic of Korea/epidemiology , Risk Factors , Sex Distribution , Sleep/physiology , Smoking/adverse effects
13.
Am J Med Genet C Semin Med Genet ; 163C(4): 259-70, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24127277

ABSTRACT

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.


Subject(s)
Acrocephalosyndactylia/genetics , Craniofacial Dysostosis/genetics , Craniosynostoses/genetics , Acrocephalosyndactylia/diagnosis , Acrocephalosyndactylia/pathology , Australia , Craniofacial Dysostosis/diagnosis , Craniofacial Dysostosis/pathology , Craniosynostoses/classification , Craniosynostoses/diagnosis , Craniosynostoses/pathology , Humans , Mutation , New Zealand , Nuclear Proteins/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Twist-Related Protein 1/genetics
14.
Br J Cancer ; 109(4): 1072-8, 2013 Aug 20.
Article in English | MEDLINE | ID: mdl-23867999

ABSTRACT

BACKGROUND: We tested the hypothesis that BRCA1/2 mutation carriers with ovarian cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs). METHODS: Medical records of women enrolled in two carboplatin+olaparib clinical trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles containing carboplatin were administered. RESULTS: All women (N=87) had good performance status and end-organ function. Incidences of carboplatin HSR before enrolment and on study were 17% and 21%, respectively. Most patients who developed carboplatin HSR had a deleterious BRCA1/2 mutation (93%) vs 50% in patients without HSR (P<0.0001). Multivariable analysis accounting for potential confounding variables including age, history of allergies, and cumulative prior carboplatin cycles confirmed deleterious BRCA1/2 mutation as an independent risk factor for carboplatin HSR (odds ratio 13.1 (95% confidence interval 2.6-65.4), P=0.0017). Mutation carriers had onset of carboplatin HSR at lower cumulative exposure (P=0.003). No significant difference in outcome was observed on our study between patients with and without a history of HSR. CONCLUSION: Deleterious BRCA1/2 mutation increased susceptibility and shortened time to carboplatin HSR, independently of other reported factors. These data suggest that at-risk women should be counselled regarding likelihood, symptoms, and potential earlier onset of carboplatin HSRs.


Subject(s)
Antineoplastic Agents/adverse effects , Carboplatin/adverse effects , Drug Hypersensitivity/genetics , Genes, BRCA1 , Genes, BRCA2 , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma/drug therapy , Carcinoma/genetics , Drug Hypersensitivity/etiology , Female , Humans , Middle Aged , Multivariate Analysis , Mutation , Odds Ratio , Ovarian Neoplasms/genetics , Phthalazines/administration & dosage , Piperazines/administration & dosage , Retrospective Studies , Risk Factors
15.
Nature ; 447(7143): 458-60, 2007 May 24.
Article in English | MEDLINE | ID: mdl-17522679

ABSTRACT

Historically, variable and transient sources have both surprised astronomers and provided new views of the heavens. Here we report the discovery of an optical transient in the outskirts of the lenticular galaxy Messier 85 in the Virgo cluster. With a peak absolute R magnitude of -12, this event is distinctly brighter than novae, but fainter than type Ia supernovae (which are expected in a population of old stars in lenticular galaxies). Archival images of the field do not show a luminous star at that position with an upper limit in the g filter of about -4.1 mag, so it is unlikely to be a giant eruption from a luminous blue variable star. Over a two-month period, the transient source emitted radiation energy of almost 10(47) erg and subsequently faded in the optical sky. It is similar to, but six times more luminous at peak than, an enigmatic transient in the galaxy M31 (ref. 1). A possible origin of M85 OT2006-1 is a stellar merger. If so, searches for similar events in nearby galaxies will not only allow study of the physics of hyper-Eddington sources, but also probe an important phase in the evolution of stellar binary systems.

16.
Anaesthesia ; 68(11): 1120-3, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23937540

ABSTRACT

We investigated the rate of injections interpreted as intravascular during imaging of lumbosacral transforaminal epidural injections, using fluoroscopy alone or with digital subtraction. We evaluated 732 injections performed on 348 patients: 8.1% (59/732) and 10.5% (77/732) of injections were interpreted as intravascular during fluoroscopy and digital subtraction, respectively, p = 0.13. The odds ratio (95% CI) for interpreting injections as intravascular increased for both fluoroscopy and digital subtraction fluoroscopy, with: each year of age, 1.04 (1.01-1.07) and 1.03 (1.00-1.06), p = 0.011 and 0.024, respectively; sacral compared with lumbar injections, 10 (5-19) and 8 (5-15), p < 0.001 for both. The odds ratio for intravascular injection increased with three other variables during digital subtraction fluoroscopy: spinal stenosis, 5.1 (1.5-17.1), p = 0.009; failed back surgery syndrome, 4.3 (1.2-15.8), p = 0.025; compression fracture, 8.0 (1.6-39.4), p = 0.011.


Subject(s)
Angiography, Digital Subtraction/methods , Contrast Media/administration & dosage , Medical Errors/statistics & numerical data , Age Distribution , Failed Back Surgery Syndrome/complications , Female , Fluoroscopy , Fractures, Compression/complications , Humans , Injections, Epidural , Injections, Intravenous , Lumbosacral Region , Male , Middle Aged , Odds Ratio , Prospective Studies , Spinal Stenosis/complications
17.
Clin Exp Immunol ; 167(1): 73-83, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22132887

ABSTRACT

Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma (RCC), serves as a potential target for RCC-specific immunotherapy using dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient for generation of a therapeutic anti-tumour immune response against RCC. In this study, in order to generate a potent anti-tumour immune response against RCC, we produced recombinant CA9-Acinetobacter baumannii outer membrane protein A (AbOmpA) fusion proteins, designated CA9-AbOmpA, and investigated the ability of DCs pulsed with CA9-AbOmpA fusion proteins in a murine renal cell carcinoma (RENCA) model. A recombinant CA9-AbOmpA fusion protein was composed of a unique proteoglycan-related region of CA9 (1-120 amino acids) fused at the C-terminus with transmembrane domain of AbOmpA (1-200 amino acids). This fusion protein was capable of inducing DC maturation and interleukin (IL)-12 production in DCs. Interaction of DCs pulsed with CA9-AbOmpA fusion proteins with naive T cells stimulated secretion of IL-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in T cells. Lymphocytes harvested from mice immunized with DCs pulsed with CA9-AbOmpA fusion proteins secreted IFN-γ and showed a specific cytotoxic activity against CA9-expressing RENCA (RENCA-CA9) cells. Administration of CA9-AbOmpA-pulsed DC vaccine suppressed growth of RENCA-CA9 cells in mice with an established tumour burden. These results suggest that DCs pulsed with CA9-AbOmpA fusion proteins generate a specific anti-tumour immune response against RCC, which can be utilized in immunotherapy of RCC.


Subject(s)
Acinetobacter baumannii/immunology , Antigens, Neoplasm/immunology , Bacterial Outer Membrane Proteins/immunology , Cancer Vaccines/therapeutic use , Carbonic Anhydrases/immunology , Carcinoma, Renal Cell/therapy , Dendritic Cells/transplantation , Kidney Neoplasms/therapy , Acinetobacter baumannii/genetics , Animals , Antigens, Neoplasm/genetics , Bacterial Outer Membrane Proteins/genetics , Carbonic Anhydrase IX , Carbonic Anhydrases/genetics , Cell Line, Tumor/immunology , Cell Line, Tumor/transplantation , Cytotoxicity, Immunologic , Dendritic Cells/drug effects , Dendritic Cells/immunology , Drug Screening Assays, Antitumor , Humans , Interferon-gamma/metabolism , Interleukin-2/metabolism , Male , Mice , Mice, Inbred BALB C , Protein Structure, Tertiary , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/pharmacology , Specific Pathogen-Free Organisms , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism , Tumor Necrosis Factor-alpha/metabolism
18.
Nature ; 444(7122): 1053-5, 2006 Dec 21.
Article in English | MEDLINE | ID: mdl-17183318

ABSTRACT

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

19.
Nature ; 442(7106): 1014-7, 2006 Aug 31.
Article in English | MEDLINE | ID: mdl-16943832

ABSTRACT

Over the past decade, long-duration gamma-ray bursts (GRBs)--including the subclass of X-ray flashes (XRFs)--have been revealed to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 10(48) erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

20.
Nature ; 440(7081): 181-3, 2006 Mar 09.
Article in English | MEDLINE | ID: mdl-16525465

ABSTRACT

Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.

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