NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its target antigen is aquaporin-4 (AQP4) water channel. Recently, we established a sensitive anti-AQP4 antibody assay ...using human AQP4-transfected cells, which appeared more sensitive than the original NMO-IgG assay. So far, there has been no large-scale study on anti-AQP4 antibody titre in NMO and related disorders. We tested 148 sera of patients with NMO, high-risk syndrome of NMO, multiple sclerosis (MS), clinically isolated syndrome suggestive of MS and miscellaneous diseases. We analysed the relation of anti-AQP4 antibody titres and clinical and laboratory parameters. The sensitivity of anti-AQP4 antibody assay was 91% (95% CI 79-100) for NMO and 85% (65-100) for high-risk syndrome, and the specificity was 100% (91-100) for NMO and high-risk syndrome, that is, none with the other disorders was positive. Among 21 anti-AQP4 antibody-positive cases whose NMO-IgG were tested, 15 were NMO-IgG-positive and 6 were NMO-IgG-negative. Higher anti-AQP4 antibody titres were associated with complete blindness and extensive or large cerebral lesions on MRI. The lengths of spinal cord lesions on MRI were positively correlated with the titres of anti-AQP4 antibody at the nadir of exacerbations. A few patients who had short (approx. one to two vertebral segments) spinal cord lesions on MRI were also seropositive with low anti-AQP4 antibody titres, but did have other clinical and MRI features of NMO. Anti-AQP4 antibody titres became lower after high-dose methylprednisolone, and a follow-up showed anti-AQP4 antibody titres remained low in relapse-free periods under immunosuppression. Cerebrospinal fluid (CSF)-anti-AQP4 antibody was detected when the serum-antibody titres exceeded 512×, at the ratio of 1 (CSF) to 500 (serum). Using a sensitive assay, the results of the present study suggest that NMO and high-risk syndrome may be essentially anti-AQP4 antibody-associated disorders, and that the anti-AQP4 antibody titres have significant clinical and immunological implications in NMO.
To evaluate the usefulness of diffusion-weighted MRI (DWI) for the early diagnosis of Creutzfeldt-Jakob disease (CJD).
Thirty-six consecutive patients (age 56 to 82 years) were enrolled, and 26 were ...examined by DWI. Nine were definite based on the World Health Organization criteria, and 27 were probable. The percentages of DWI abnormalities, periodic sharp wave complexes (PSWCs) on the EEG, detection of CSF 14-3-3 protein, and increase of CSF neuron-specific enolase (>25 ng/mL) on the first examination were compared. For DWI, 32 patients (age 31 to 84 years) who showed progressive dementia or impaired consciousness served as disease controls.
The percentage of DWI abnormalities was 92.3%, of PSWCs 50.0%, of 14-3-3 protein detection 84.0%, and of NSE increase 73.3%. Two of the 32 control subjects were falsely positive on DWI. The sensitivity of DWI was 92.3% (95% CI 74.8 to 99.5%) and specificity 93.8% (95% CI 79.2 to 99.2%). In 17 patients who did not show PSWCs on the first EEG, abnormal DWI findings were still clearly detected. Four patients who were negative for 14-3-3 protein also showed DWI abnormalities. DWI abnormalities were detected as early as at 3 weeks of symptom duration in four patients in whom PSWCs were not yet evident.
DWI can detect characteristic lesions in the majority of patients with CJD regardless of the presence of PSWCs. DWI was the most sensitive test for the early clinical diagnosis of CJD; consideration should be given to its inclusion in the clinical diagnostic criteria of CJD.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody ...(NMO-IgG) binding to the blood–brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21–67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2–3 L each). Three of the patients(one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.
Neuromyelitis optica (NMO) is a relapsing neurologic disease characterized by severe optic neuritis and transverse myelitis. A disease-modifying therapy for NMO has not been established. We ...retrospectively analysed the effect of low-dose corticosteroid (CS) monotherapy on the annual relapse rate in nine patients with NMO. We divided the clinical course in each patient into two periods; the CS Period in which CS was administered, and the No CS Period in which CS was not administered. Periods related to other immunological therapies, such as high-dose methylprednisolone, immunosuppressants, interferon-beta, and plasma exchange, were excluded. As a result, the annual relapse rate during the CS Periods median, 0.49 (range, 0—1.31) was found to be significantly lower than that during the No CS Periods 1.48 (0.65—5.54). As for the dose of CS, relapses occurred significantly more frequently with `10 mg/day or less' than with `over 10 mg/day' (odds ratio: 8.75). The results of the present study suggest a beneficial effect of low-dose CS monotherapy in reducing relapses in NMO. Multiple Sclerosis 2007; 13: 968—974. http://msj.sagepub.com
This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was ...tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic–spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (>3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic–spinal disease.
Terrestrial biospheric models (TBMs) are used to extrapolate local observations and process-level understanding of land-atmosphere carbon exchange to larger regions, and serve as predictive tools for ...examining carbon-climate interactions. Understanding the performance of TBMs is thus crucial to the carbon cycle and climate science communities. In this study, we present and assess an approach to evaluating the spatiotemporal patterns, rather than aggregated magnitudes, of net ecosystem exchange (NEE) simulated by TBMs using atmospheric CO2 measurements. The approach is based on statistical model selection implemented within a high-resolution atmospheric inverse model. Using synthetic data experiments, we find that current atmospheric observations are sensitive to the underlying spatiotemporal flux variability at sub-biome scales for a large portion of North America, and that atmospheric observations can therefore be used to evaluate simulated spatiotemporal flux patterns as well as to differentiate between multiple competing TBMs. Experiments using real atmospheric observations and four prototypical TBMs further confirm the applicability of the method, and demonstrate that the performance of TBMs in simulating the spatiotemporal patterns of NEE varies substantially across seasons, with best performance during the growing season and more limited skill during transition seasons. This result is consistent with previous work showing that the ability of TBMs to model flux magnitudes is also seasonally-dependent. Overall, the proposed approach provides a new avenue for evaluating TBM performance based on sub-biome-scale flux patterns, presenting an opportunity for assessing and informing model development using atmospheric observations.
Summary
Stroke can be a cause of death, while in non‐fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen ...is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2–6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18–1·31, P < 0·001 and C‐reactive protein (OR = 1·29, 95% CI = 1·10–1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55–6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.
We examined risk factors for unfavorable outcome following stroke occurrence including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset. Logistic regression analysis showed that detection of the antibody for F. nucleatum ATCC10953 in serum were independently associated with unfavorable outcome after stroke.
Excited states in the nucleus 133Sn, with one neutron outside the doubly-magic 132Sn core, were populated following one-neutron knockout from a 134Sn beam on a carbon target at relativistic energies ...at the Radioactive Isotope Beam Factory at RIKEN. Besides the γ rays emitted in the decay of the known neutron single-particle states in 133Sn additional γ strength in the energy range 3.5-5.5 MeV was observed for the first time. Since the neutron-separation energy of 133Sn is low, Sn=2.402(4) MeV, this observation provides direct evidence for the radiative decay of neutronunbound states in this nucleus. The ability of electromagnetic decay to compete successfully with neutron emission at energies as high as 3 MeV above threshold is attributed to a mismatch between the wave functions of the initial and final states in the latter case. These findings suggest that in the region south-east of 132Sn nuclear structure effects may play a significant role in the neutron vs. γ competition in the decay of unbound states. As a consequence, the common neglect of such effects in the evaluation of the neutron-emission probabilities in calculations of global β-decay properties for astrophysical simulations may have to be reconsidered.
Inclusive one- and multi-nucleon removal cross sections have been measured for several Sn, Sb and Te isotopes just beyond the N=82 neutron shell closure. The beams were produced in the projectile ...fission of a 238U beam at the Radioactive Isotope Beam Factory at RIKEN. The experimental cross sections are compared to predictions from the most recent version of the Liege intranuclear cascade model. Although the overall agreement is good, severe discrepancies are observed for the cases of one- and two-neutron removal from 134Sn and 135Sb projectiles and one-proton knockout from all measured N=84 isotones. These discrepancies, as well as the relevance of quasi-elastic reaction channels to the one-neutron removal cross sections, are discussed. In addition, the measured inclusive one-proton knockout cross section for the semi-magic 134Sn projectile is compared to eikonal direct reaction theory calculations to assess if the suppression factors to these calculated cross sections, deduced from data on reactions of lighter projectile nuclei, are also applicable to heavy nuclei.
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