34 results on '"Saji E"'
Search Results
2. Structure of Λ13C hypernucleus studied by the (K −, π −γ) reaction
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Sakaguchi, A., Ajimura, S., Hayakawa, H., Kishimoto, T., Kohri, H., Matsuoka, K., Minami, S., Miyake, Y.S., Morikubo, K., Saji, E., Shimizu, Y., Sumihama, M., Chrien, R.E., May, M., Pile, P., Rusek, A., Sutter, R., Eugenio, P.M., Franklin, G., Khaustov, P., Paschke, K., Quinn, B., Schumacher, R.A., Franz, J., Fukuda, T., Gan, L., Tang, L., Yuan, L., Nakano, J., Noumi, H., Outa, H., Tamagawa, T., Tanida, K., Sawafta, R., Tamura, H., and Akikawa, H.
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- 2003
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3. Recent data from E929 experiment at BNL
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Sakaguchi, A., Ajimura, S., Hayakawa, H., Kishimoto, T., Kohri, H., Matsuoka, K., Minami, S., Mori, T., Morikubo, K., Saji, E., Shimizu, Y., Sumihama, M., Chrien, R.E., May, M., Pile, P., Rusek, A., Sutter, R., Eugenio, P.M., Franklin, G., Khaustov, P., Paschke, K., Quinn, B., Franz, J., Fukuda, T., Noumi, H., Outa, H., Gan, L., Tang, L., Yuan, L., Tamura, H., Nakano, J., Tamagawa, T., Tanida, K., and Sawafta, R.
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- 2001
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4. DLC films formed by hybrid pulse plasma coating (HPPC) system
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Awazu, K, Sakudo, N, Yasui, H, Saji, E, Okazaki, K, Hasegawa, Y, Ikenaga, N, Kanda, K, Nambo, Y, and Saitoh, K
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- 2001
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5. Development of hybrid pulse plasma coating system
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Sakudo, N, Awazu, K, Yasui, H, Saji, E, Okazaki, K, Hasegawa, Y, Ikenaga, N, Kanda, K, Nambo, Y, and Saitoh, K
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- 2001
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6. The Extracellular Vesicles Proteome of Endometrial Cells Simulating the Receptive Menstrual Phase Differs from That of Endometrial Cells Simulating the Non-Receptive Menstrual Phase
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Amber Rose Hart, Norhayati Liaqat Ali Khan, Keerthie Dissanayake, Kasun Godakumara, Aneta Andronowska, Saji Eapen, Paul R Heath, and Alireza Fazeli
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extracellular vesicles ,endometrium ,receptivity ,fertility ,proteomics ,Microbiology ,QR1-502 - Abstract
Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial-derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by the menstrual cycle hormones estrogen (E2; proliferative phase), progesterone (P4; secretory phase), and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentrations and sizes of particles and EV proteomic analysis was performed using shotgun label-free mass spectrometry. Our results showed that although endometrial derived EVs were secreted in numbers independent of hormonal stimulation, EV sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EV’s proteome, with proteins enhanced within the EV E2P4 group shown to be involved in different processes, such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs.
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- 2023
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7. Clinical, radiological and immunological features of ependymitis in neuromyelitis optica
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Kawachi, I., Yanagimura, F., Saji, E., Wakasugi, T., Hokari, M., Toyoshima, Y., Kakita, A., Takahashi, H., Nishizawa, M., and Onodera, O.
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- 2017
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8. Dynamics of melanoma cell adhesion molecule on the blood vessels in neuromyelitis optica
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Yanagimura, F., Saji, E., Wakasugi, T., Hokari, M., Toyoshima, Y., Kakita, A., Takahashi, H., Nishizawa, M., Onodera, O., and Kawachi, I.
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- 2017
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9. A follow-up study of cognitive assessments in a Japanese cohort of multiple sclerosis
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Saji, E., Wakasugi, T., Hokari, M., Yanagimura, F., Yanagawa, K., Nishizawa, M., Onodera, O., and Kawachi, I.
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- 2017
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10. Evaluation of the 2016 diagnostic approach for autoimmune encephalitis
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Wakasugi, T., Saji, E., Yanagimura, F., Hokari, M., Nishizawa, M., Onodera, O., and Kawachi, I.
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- 2017
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11. Structure of <f>13Λ</f>C hypernucleus studied by the (<f>K−,π−γ</f>) reaction
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Sakaguchi, A., Ajimura, S., Hayakawa, H., Kishimoto, T., Kohri, H., Matsuoka, K., Minami, S., Miyake, Y.S., Morikubo, K., Saji, E., Shimizu, Y., Sumihama, M., Chrien, R.E., May, M., Pile, P., Rusek, A., Sutter, R., Eugenio, P.M., Franklin, G., and Khaustov, P.
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- 2003
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12. Cerebellar compensation: a case of aphasia due to cerebellar hemorrhage.
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Kinoshita Y, Hatakeyama M, Otsuki M, Ishiguro T, Saji E, Kanazawa M, and Onodera O
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- Humans, Cerebellar Diseases complications, Cerebellar Diseases diagnostic imaging, Male, Intracranial Hemorrhages complications, Intracranial Hemorrhages diagnostic imaging, Middle Aged, Female, Aphasia etiology, Cerebellum diagnostic imaging
- Published
- 2024
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13. Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ.
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Nakajima A, Yanagimura F, Saji E, Shimizu H, Toyoshima Y, Yanagawa K, Arakawa M, Hokari M, Yokoseki A, Wakasugi T, Okamoto K, Takebayashi H, Fujii C, Itoh K, Takei YI, Ohara S, Yamada M, Takahashi H, Nishizawa M, Igarashi H, Kakita A, Onodera O, and Kawachi I
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- Humans, Female, Male, Middle Aged, Immunologic Memory, Adult, Aged, Th17 Cells immunology, Th17 Cells pathology, Neuromyelitis Optica immunology, Neuromyelitis Optica pathology, Aquaporin 4 immunology, Neutrophils immunology, Neutrophils pathology, Autoantibodies immunology
- Abstract
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies. To address these knowledge gaps, we conducted a comprehensive 'stage-dependent' investigation of immune cell elements in situ in human NMOSD lesions, based on neuropathological techniques for autopsied/biopsied CNS materials. The present study provided three major findings. First, activated or netting neutrophils and melanoma cell adhesion molecule-positive (MCAM
+ ) helper T (TH ) 17/cytotoxic T (TC ) 17 cells are prominent, and the numbers of these correlate with the size of NMOSD lesions in the initial or early-active stages. Second, forkhead box P3-positive (FOXP3+ ) regulatory T (Treg ) cells are recruited to NMOSD lesions during the initial, early-active or late-active stages, suggesting rapid suppression of proinflammatory autoimmune events in the active stages of NMOSD. Third, compartmentalized resident memory immune cells, including CD103+ tissue-resident memory T (TRM ) cells with long-lasting inflammatory potential, are detected under "standby" conditions in all stages. Furthermore, CD103+ TRM cells express high levels of granzyme B/perforin-1 in the initial or early-active stages of NMOSD in situ. We infer that stage-dependent compartmentalized immune traits orchestrate the pathology of anti-AQP4 antibody-guided NMOSD in situ. Our work further suggests that targeting activated/netting neutrophils, MCAM+ TH 17/TC 17 cells, and CD103+ TRM cells, as well as promoting the expansion of FOXP3+ Treg cells, may be effective in treating and preventing relapses of NMOSD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
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14. Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder.
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Hongo S, Shimizu H, Saji E, Nakajima A, Okamoto K, Kawachi I, Onodera O, and Kakita A
- Abstract
An 84-year-old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high-intensity signal lesions on fluid-attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well-defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8-positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti-AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing-remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS., (© 2024 Japanese Society of Neuropathology.)
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- 2024
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15. Legislation on cancer notification in India: current status.
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Saji E and Mathew A
- Abstract
Competing Interests: Authors declare no conflicts of interest.
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- 2024
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16. A case report of reversible cerebral vasoconstriction syndrome with thunderclap headache significantly exacerbated in the supine position and alleviated in the standing position.
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Toyama G, Tsuboguchi S, Igarashi K, Saji E, Konno T, and Onodera O
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- Female, Humans, Adult, Vasoconstriction physiology, Standing Position, Supine Position, Headache complications, Cerebrovascular Disorders complications, Vasospasm, Intracranial, Headache Disorders, Primary complications
- Abstract
Background: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden onset thunderclap headache and multiple segmental reversible cerebral vasoconstrictions that improve within 3 months. The postpartum period is a well-known precipitating factor for the onset of RCVS. Cerebral venous thrombosis (CVT) causes thunderclap headaches in the postpartum period. While headache in CVT is sometimes exacerbated in the supine position, the severity of the headache in RCVS is usually independent of body position. In this study, we report a case of RCVS with thunderclap headache exacerbated in the supine position, and headache attacks that resolved quickly in the standing position during the postpartum period., Case Presentation: A 33-year-old woman presented with a sudden increase in blood pressure and thunderclap headache on the fifth postpartum day (day 1: the first sick day). The headache was severe and pulsatile, with onset in the supine position in bed, and peaked at approximately 10 s. It was accompanied by nausea and chills but there were no scintillating scotomas or ophthalmic symptoms. The headache resolved in the standing or sitting position but was exacerbated and became unbearable within a few seconds when the patient was in the supine position. Therefore, she was unable to lie supine at night. Computed tomography angiography (CTA) of the head on day 2 and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) on day 3 showed no abnormalities. However, considering the possibility of RCVS, verapamil was initiated on day 3. The headache resolved the following day. MRA of the head on day 10 revealed diffuse and segmental stenoses in the bilateral middle and posterior cerebral arteries and basilar artery. Therefore, the patient was diagnosed with RCVS. The headache gradually resolved and disappeared completely on day 42. Cerebral vasoconstriction was also improved on MRA on day 43., Conclusions: This postpartum RCVS case was notable for the exacerbation of headaches in the supine position. For the diagnosis of thunderclap headache in the postpartum period, RCVS should be considered in addition to CVT when the patient presents with a headache that is exacerbated in the supine position., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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17. Proportion of papillary thyroid microcarcinoma in Kerala, India, over a decade: a retrospective cohort study.
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Benny SJ, Boby JM, Chirukandath R, Thomas T, Vazhuthakat A, Saji E, Raju AR, and Mathew A
- Abstract
Background: Overdiagnosis is a phenomenon where an indolent cancer is diagnosed that otherwise would not have caused harm to the patient during their lifetime. The rising incidence of papillary thyroid cancer (PTC) in various regions of the world is attributed to overdiagnosis. In such regions, the rates of papillary thyroid microcarcinoma (PTMC) are also rising. We aimed to study whether a similar pattern of rising PTMC is found in Kerala, a state in India, where there has been a doubling of thyroid cancer incidence over a decade., Methods: We conducted a retrospective cohort study in two large government medical colleges, which are tertiary referral facilities in the state of Kerala. We collected data on the PTC diagnosis in Kozhikode and Thrissur Government Medical colleges from 2010 to 2020. We analysed our data by age, gender and tumor size., Results: The incidence of PTC at Kozhikode and Thrissur Government Medical colleges nearly doubled from 2010 to 2020. The overall proportion of PTMC in these specimens was 18.9%. The proportion of PTMC only marginally increased from 14.7 to 17.9 during the period. Of the total incidence of microcarcinomas, 64% were reported in individuals less than 45 years of age., Conclusion: The rise in the number of PTCs diagnosed in the government-run public healthcare centres in Kerala state in India is unlikely to be due to overdiagnosis since there was no disproportionate rise in rates of PTMCs. The patients that these hospitals cater to may be less likely to show healthcare-seeking behavior or ease of healthcare access which is closely associated with the problem of overdiagnosis., Competing Interests: The authors declare no conflict of interest., (© the authors; licensee ecancermedicalscience.)
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- 2023
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18. Visual outcome of aquaporin-4 antibody-positive optic neuritis with maintenance therapy.
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Ueki S, Hatase T, Kiyokawa M, Kawachi I, Saji E, Onodera O, Fukuchi T, and Igarashi H
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- Autoantibodies, Female, Humans, Male, Retrospective Studies, Visual Acuity, Aquaporin 4, Optic Neuritis diagnosis, Optic Neuritis drug therapy
- Abstract
Purpose: To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis., Study Design: Retrospective study., Methods: The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative., Results: The mean ages were 49.3 and 45.2 years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01)., Conclusion: This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis., (© 2021. Japanese Ophthalmological Society.)
- Published
- 2021
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19. HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.
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Watanabe M, Nakamura Y, Sato S, Niino M, Fukaura H, Tanaka M, Ochi H, Kanda T, Takeshita Y, Yokota T, Nishida Y, Matsui M, Nagayama S, Kusunoki S, Miyamoto K, Mizuno M, Kawachi I, Saji E, Ohashi T, Shimohama S, Hisahara S, Nishiyama K, Iizuka T, Nakatsuji Y, Okuno T, Ochi K, Suzumura A, Yamamoto K, Kawano Y, Tsuji S, Hirata M, Sakate R, Kimura T, Shimizu Y, Nagaishi A, Okada K, Hayashi F, Sakoda A, Masaki K, Shinoda K, Isobe N, Matsushita T, and Kira JI
- Subjects
- Adult, Case-Control Studies, Female, Genotype, Humans, Japan epidemiology, Male, Middle Aged, Multiple Sclerosis epidemiology, Multiple Sclerosis genetics, Multiple Sclerosis immunology, Neuromyelitis Optica epidemiology, Neuromyelitis Optica genetics, Neuromyelitis Optica immunology, Phenotype, Biological Specimen Banks, Genetic Association Studies, HLA-DP beta-Chains genetics, HLA-DRB1 Chains genetics, Multiple Sclerosis pathology, Neuromyelitis Optica pathology
- Abstract
HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.
- Published
- 2021
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20. Refractory Myositis Affecting the Intrinsic Muscles of the Hand.
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Nakamura K, Sugai A, Saji E, Kasuga K, and Onodera O
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- Autoantibodies blood, Diagnosis, Differential, Female, Hand, Humans, Immunoglobulins, Intravenous administration & dosage, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors administration & dosage, Immunologic Factors therapeutic use, Magnetic Resonance Imaging, Middle Aged, Muscle, Skeletal immunology, Myositis blood, Myositis diagnostic imaging, Myositis drug therapy, Signal Recognition Particle immunology, Myositis diagnosis
- Abstract
Myositis generally affects the proximal muscles. However, we herein report a case of a 48-year-old woman with intractable myositis affecting the intrinsic muscles of the hands. Her myositis, which developed in childhood, was refractory to treatment with steroids and several immunosuppressants, causing walking disability. After experiencing pain and swelling in the hands for six months, she was diagnosed with myositis of the intrinsic muscles of the hands and tested positive for the anti-signal recognition particle antibody. Intravenous immunoglobulin therapy improved the myositis of the hands. This case suggests that inflammation caused by intractable myositis can extend to the hands.
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- 2020
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21. The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.
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Machado-Santos J, Saji E, Tröscher AR, Paunovic M, Liblau R, Gabriely G, Bien CG, Bauer J, and Lassmann H
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- Adult, Aged, B-Lymphocytes immunology, B-Lymphocytes physiology, Brain pathology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes physiology, Demyelinating Diseases pathology, Encephalitis metabolism, Encephalitis pathology, Female, Humans, Inflammation immunology, Inflammation metabolism, Inflammation pathology, Lymphocytes physiology, Male, Middle Aged, Phenotype, Lymphocytes immunology, Multiple Sclerosis immunology, Multiple Sclerosis pathology
- Abstract
Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.
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- 2018
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22. Differences in T cell cytotoxicity and cell death mechanisms between progressive multifocal leukoencephalopathy, herpes simplex virus encephalitis and cytomegalovirus encephalitis.
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Laukoter S, Rauschka H, Tröscher AR, Köck U, Saji E, Jellinger K, Lassmann H, and Bauer J
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- AIDS-Related Opportunistic Infections pathology, Adult, Aged, Apoptosis Inducing Factor metabolism, Brain immunology, Brain pathology, Brain virology, Caspase 3 metabolism, Child, Cytomegalovirus Infections pathology, Encephalitis, Herpes Simplex pathology, Female, Humans, Immunohistochemistry, Leukoencephalopathy, Progressive Multifocal pathology, Male, Microscopy, Confocal, Microscopy, Fluorescence, Middle Aged, Neurons immunology, Neurons pathology, Oligodendroglia physiology, T-Lymphocytes pathology, T-Lymphocytes virology, AIDS-Related Opportunistic Infections immunology, Cell Death physiology, Cytomegalovirus Infections immunology, Encephalitis, Herpes Simplex immunology, Leukoencephalopathy, Progressive Multifocal immunology, T-Lymphocytes immunology
- Abstract
During the appearance of human immunodeficiency virus infection in the 1980 and the 1990s, progressive multifocal leukoencephalopathy (PML), a viral encephalitis induced by the JC virus, was the leading opportunistic brain infection. As a result of the use of modern immunomodulatory compounds such as Natalizumab and Rituximab, the number of patients with PML is once again increasing. Despite the presence of PML over decades, little is known regarding the mechanisms leading to death of infected cells and the role the immune system plays in this process. Here we compared the presence of inflammatory T cells and the targeting of infected cells by cytotoxic T cells in PML, herpes simplex virus encephalitis (HSVE) and cytomegalovirus encephalitis (CMVE). In addition, we analyzed cell death mechanisms in infected cells in these encephalitides. Our results show that large numbers of inflammatory cytotoxic T cells are present in PML lesions. Whereas in HSVE and CMVE, single or multiple appositions of CD8
+ or granzyme-B+ T cells to infected cells are found, in PML such appositions are significantly less apparent. Analysis of apoptotic pathways by markers such as activated caspase-3, caspase-6, poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) showed upregulation of caspase-3 and loss of caspase-6 from mitochondria in CMVE and HSVE infected cells. Infected oligodendrocytes in PML did not upregulate activated caspase-3 but instead showed translocation of PARP-1 from nucleus to cytoplasm and AIF from mitochondria to nucleus. These findings suggest that in HSVE and CMVE, cells die by caspase-mediated apoptosis induced by cytotoxic T cells. In PML, on the other hand, infected cells are not eliminated by the immune system but seem to die by virus-induced PARP and AIF translocation in a type of cell death defined as parthanatos.- Published
- 2017
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23. Clinicopathological features in anterior visual pathway in neuromyelitis optica.
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Hokari M, Yokoseki A, Arakawa M, Saji E, Yanagawa K, Yanagimura F, Toyoshima Y, Okamoto K, Ueki S, Hatase T, Ohashi R, Fukuchi T, Akazawa K, Yamada M, Kakita A, Takahashi H, Nishizawa M, and Kawachi I
- Subjects
- Adult, Astrocytes immunology, Astrocytes pathology, Axons immunology, Axons pathology, Female, Humans, Male, Multiple Sclerosis immunology, Multiple Sclerosis physiopathology, Neuromyelitis Optica immunology, Neuromyelitis Optica physiopathology, Optic Neuritis immunology, Optic Neuritis physiopathology, Vision Disorders immunology, Vision Disorders physiopathology, Visual Pathways immunology, Visual Pathways physiopathology, Aquaporin 4 immunology, Multiple Sclerosis pathology, Neuromyelitis Optica pathology, Optic Neuritis pathology, Vision Disorders pathology, Visual Pathways pathology
- Abstract
Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd., Methods: Thirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP., Results: The AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON., Interpretation: Severe and widespread neuroaxonal damage and unique dynamics of astrocytes/Müller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd., (© 2016 American Neurological Association.)
- Published
- 2016
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24. Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody.
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Yokoseki A, Saji E, Arakawa M, Kosaka T, Hokari M, Toyoshima Y, Okamoto K, Takeda S, Sanpei K, Kikuchi H, Hirohata S, Akazawa K, Kakita A, Takahashi H, Nishizawa M, and Kawachi I
- Subjects
- Adult, Aged, Biomarkers blood, Biomarkers cerebrospinal fluid, Female, Humans, Hypertrophy enzymology, Male, Meningitis enzymology, Middle Aged, Retrospective Studies, Vasculitis blood, Vasculitis cerebrospinal fluid, Antibodies, Antineutrophil Cytoplasmic blood, Antibodies, Antineutrophil Cytoplasmic cerebrospinal fluid, Hypertrophy blood, Hypertrophy cerebrospinal fluid, Meningitis blood, Meningitis cerebrospinal fluid, Peroxidase blood, Peroxidase cerebrospinal fluid, Vasculitis enzymology
- Abstract
The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.
- Published
- 2014
- Full Text
- View/download PDF
25. [Gray matter lesions and cognitive impairment in multiple sclerosis].
- Author
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Kawachi I, Saji E, and Nishizawa M
- Subjects
- Cognition Disorders etiology, Humans, Multiple Sclerosis etiology, Neuromyelitis Optica etiology, Neuromyelitis Optica pathology, White Matter pathology, Cognition Disorders pathology, Gray Matter pathology, Multiple Sclerosis pathology
- Abstract
Multiple sclerosis (MS) has long been considered to be the autoimmune disease that primarily affects oligodendrocyte and myelin in the white matter (WM) of the CNS. However, renewed interest in the gray matter (GM) pathology including cortical and deep GM of MS is emerging. Radiological and pathological assessments demonstrate that substantial cortical demyelination is prominent in all stages or courses of MS, and cortical neurodegeneration is also present in even normal-appearing GM in MS. Patients with MS have cognitive impairment as represented by the latent start of impairment from the very early stage of the disease course, and not only WM lesions but also GM lesions might be good predictors for cognitive impairment in MS. Although the cause of the GM lesions in MS has not been fully determined, an increase in knowledge of the structure of GM lesions in MS brains will result in more targeted therapeutic approaches to the disease.
- Published
- 2014
- Full Text
- View/download PDF
26. Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy.
- Author
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Yokoseki A, Saji E, Arakawa M, Hokari M, Ishiguro T, Yanagimura F, Ishihara T, Okamoto K, Nishizawa M, and Kawachi I
- Subjects
- Brain pathology, Fingolimod Hydrochloride, Flow Cytometry, Humans, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting immunology, Receptors, CCR7 immunology, Sphingosine therapeutic use, Young Adult, CD4-Positive T-Lymphocytes immunology, Immunosuppressive Agents therapeutic use, Multiple Sclerosis, Relapsing-Remitting cerebrospinal fluid, Propylene Glycols therapeutic use, Sphingosine analogs & derivatives
- Abstract
Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis (MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4(+) T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4(+) T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.
- Published
- 2013
- Full Text
- View/download PDF
27. Cognitive impairment and cortical degeneration in neuromyelitis optica.
- Author
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Saji E, Arakawa M, Yanagawa K, Toyoshima Y, Yokoseki A, Okamoto K, Otsuki M, Akazawa K, Kakita A, Takahashi H, Nishizawa M, and Kawachi I
- Subjects
- Asian People genetics, Asian People psychology, Astrocytes pathology, Cognition Disorders diagnosis, Cognition Disorders psychology, Humans, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases psychology, Neuromyelitis Optica diagnosis, Neuromyelitis Optica psychology, Aquaporin 4 genetics, Cerebral Cortex pathology, Cognition Disorders genetics, Neurodegenerative Diseases genetics, Neuromyelitis Optica genetics
- Abstract
Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains., Methods: Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd., Results: In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessments showed neuronal loss in cortical layers II, III, and IV, with nonlytic reaction of aquaporin-4 (AQP4)-negative astrocytes in layer I, massive activated microglia in layer II, and meningeal inflammation in NMOsd brains. All NMO cases showed no evidence of cortical demyelination., Interpretation: We demonstrate cognitive impairment and substantial cortical neuronal loss with unique AQP4 dynamics in astrocytes in NMOsd. These data indicate pathological processes consisting not only of inflammatory demyelinating events characterized by pattern-specific loss of AQP4 immunoreactivity but also cortical neurodegeneration in NMOsd brains., (Copyright © 2012 American Neurological Association.)
- Published
- 2013
- Full Text
- View/download PDF
28. Reduced bowel sounds in Parkinson's disease and multiple system atrophy patients.
- Author
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Ozawa T, Saji E, Yajima R, Onodera O, and Nishizawa M
- Subjects
- Aged, Auscultation methods, Case-Control Studies, Female, Gastrointestinal Motility physiology, Humans, Male, Middle Aged, Supranuclear Palsy, Progressive physiopathology, Gastrointestinal Tract physiopathology, Multiple System Atrophy physiopathology, Parkinson Disease physiopathology, Sound
- Abstract
Digital auscultation of bowel sounds was performed in newly diagnosed, drug-naïve patients with Parkinson's disease (PD) (n = 10), multiple system atrophy (MSA) (n = 12), progressive supranuclear palsy/corticobasal degeneration (PSP/CBD) (n = 7), and control subjects (n = 18). The number of bowel sounds per minute and the integrated time of bowel sounds were significantly lower in PD and MSA patients than in control subjects. Reduced bowel sounds may herald compromised gastrointestinal motility in patients with PD and MSA.
- Published
- 2011
- Full Text
- View/download PDF
29. [Diagnosis and management of paraneoplastic neurological syndromes].
- Author
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Saji E, Kawachi I, and Nishizawa M
- Subjects
- Humans, Neoplasms diagnosis, Neoplasms immunology, Neoplasms therapy, Nervous System immunology, Autoantibodies, Biomarkers, Tumor, Paraneoplastic Syndromes, Nervous System diagnosis, Paraneoplastic Syndromes, Nervous System therapy
- Abstract
Paraneoplastic neurological syndromes (PNS) are infrequent tumor-related disorders that are not caused by direct tumor invasion or metastases, metabolic and nutritional deficits, infections, coagulopathy, or the side effects of cancer treatment. PNS can affect any part of the central and peripheral nervous systems, the neuromuscular junction, or muscles. Because the onset of PNS often antedates the diagnosis of an underlying cancer, it is difficult to establish a definitive early diagnosis. Therefore, it is important for neurologists to consider the possibility of PNS when rapidly progressive neurological syndromes cannot be explained by other causes. Detection of onconeural antibodies is useful for diagnosing PNS, and detection of specific antibodies can aid the identification of the underlying tumor. However, not all patients with PNS have onconeural antibodies, and not all patients with onconeural antibodies have PNS. Although PNS are considered to be mediated by the immune system, various forms of immunotherapy have yielded disappointing results, with some exceptions (i.e., PNS cases with antibodies against neuronal cell-surface antigens such as N-methyl-D-aspartate receptors). The lack of clinical trials due to the rarity of patients with PNS makes it difficult to test the efficacy of immunomodulatory treatment. Rapid detection and immediate treatment of the underlying tumor is an important approach that offers the highest chances of improvilng or stabilizing the syndrome before irreversible neuronal damage occurs. In this review, we discuss the diagnostic criteria and management of PNS based on the PNS Euronetwork and other reports.
- Published
- 2010
30. Aortocoronary dissection complicated with percutaneous coronary intervention: a case report.
- Author
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Ozaki K, Kubo T, Saji E, Ohtaki K, Fukaya H, and Aizawa Y
- Subjects
- Aged, Aortic Aneurysm etiology, Female, Humans, Sinus of Valsalva, Aortic Dissection etiology, Angioplasty, Balloon, Coronary adverse effects, Aorta injuries, Coronary Disease etiology, Coronary Vessels injuries
- Abstract
A 74-year-old female developed aortocoronary dissection during percutaneous coronary intervention. The forceful manipulation of the guide catheter and contrast medium injection seemed to be the cause of the aortocoronary dissection involving the coronary sinus of Valsalva. The entry of the dissection was closed with subsequent obliteration of the false lumen by coronary stenting under the guidance of intracoronary ultrasonography and angiography.
- Published
- 2006
31. Observation of spin-orbit splitting in lambda single-particle states.
- Author
-
Ajimura S, Hayakawa H, Kishimoto T, Kohri H, Matsuoka K, Minami S, Mori T, Morikubo K, Saji E, Sakaguchi A, Shimizu Y, Sumihama M, Chrien RE, May M, Pile P, Rusek A, Sutter R, Eugenio P, Franklin G, Khaustov P, Paschke K, Quinn BP, Schumacher RA, Franz J, Fukuda T, Noumi H, Outa H, Gan L, Tang L, Yuan L, Tamura H, Nakano J, Tamagawa T, Tanida K, and Sawafta R
- Abstract
The spin-orbit splitting of Lambda single-particle states in (13)(Lambda)C was measured. The 13C(K-,pi(-))(13)(Lambda)C reaction was used to excite both the 1/2(-) and 3/2(-) states simultaneously, which have predominantly 12C(0(+)) x p(Lambda) configuration. gamma rays from the states to the ground state were measured in coincidence with the pi(-)'s, by which ls splitting was found to be 152+/-54(stat)+/-36(syst) keV. The value is 20-30 times smaller than exhibited by the ls splitting in the nuclear shell model. This value gives us new insight into the YN interaction.
- Published
- 2001
- Full Text
- View/download PDF
32. [The pharmacokinetics of cisplatin and its influence on renal functions based on different infusion methods].
- Author
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Takahashi A, Takagi M, Hishida H, Saji E, Takagi N, Amano H, and Ogura Y
- Subjects
- Acetylglucosaminidase urine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin administration & dosage, Cisplatin pharmacology, Doxorubicin administration & dosage, Drug Administration Schedule, Female, Humans, Infusions, Intravenous, Kidney physiopathology, Kidney Function Tests, Lung Neoplasms drug therapy, Lung Neoplasms physiopathology, Male, Middle Aged, Mitomycin, Mitomycins administration & dosage, beta 2-Microglobulin urine, Cisplatin pharmacokinetics, Kidney drug effects, Lung Neoplasms metabolism
- Abstract
The pharmacokinetics of cisplatin, together with its renal toxicity in relation to different infusion methods were examined. The subjects were 21 in-patients suffering from pulmonary carcinoma treated by anti-neoplastic agents including cisplatin. The patients included 12 given a 5-division dosage, 5 cases given 24-hour continuous infusion, 6 given 12-hour continuous infusion, and 7 given 6-hour continuous infusion. Cisplatin was determined as the concentrations of Pt in plasma and non-protein-bound Pt. Also, as indices of renal function, NAG in urine together with beta 2-microglobulin were examined. No substantial difference could be found in Pt concentration in plasma upon completion of the respective infusion methods. A dual-phase attenuation curve was obtained after the completion of infusion and the half-life period of the beta-phase was around 200 hours. With respect to non-protein-bound Pt concentrations, the 5-division dosage showed the highest value, which was considered to be a temporary phenomenon, while with continuous infusion, the shorter the infusion period, the higher the value became. With respect to the amount of NAG excreted in urine, 12-and 6-hour continuous infusion showed the higher value in comparison with the others in terms of the maximum value and the total amount. With regard to beta 2-microglobulin, 6-hour continuous infusion showed the highest value. The above results therefore suggest that in continuous infusion, the shorter the infusion period the greater the degree of renal tubule injury, and that particularly, 6-hour continuous infusion will possibly cause dysfunction of the renal tubules.
- Published
- 1987
33. Effects of monoamine oxidase inhibitors on the vasopressor actions of several sympathomimetic agents.
- Author
-
KONO C, KANDA Z, SEKIYA A, and SAJI E
- Subjects
- Humans, Monoamine Oxidase Inhibitors pharmacology, Sympathomimetics pharmacology, Vasomotor System pharmacology
- Published
- 1962
34. [Comparison of toxicity of some digitalis preparations by amounts lethal for pigeons].
- Author
-
SAJI E
- Subjects
- Animals, Columbidae, Digitalis toxicity, Digitalis Glycosides, Plant Extracts
- Published
- 1961
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