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41.
42.
Kimura T Nakamori M Lueck JD Pouliquin P Aoike F Fujimura H Dirksen RT Takahashi MP Dulhunty AF Sakoda S 《Human molecular genetics》2005,14(15):2189-2200
Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle. 相似文献
43.
Michio Yoneyama Shohei Inoue Teiji Tsuruta 《Macromolecular chemistry and physics.》1967,107(1):241-245
During thermal degradation of poly(vinyl chloride) in a nitrogen atmosphere polyene sequences of different lengths are formed by dehydrochlorination. The distribution of the sequence lengths in the polymer is approximated by analysis of the electron spectra, and the spectroscopically determined polyene content is compared with the amount of hydrogen chloride split off. With increasing temperature, as well as with increasing time of degradation, the distribution of the polyene sequence lengths shifts towards shorter sequences. In contrast to degraded poly(vinyl chloride) powder, degraded poly(vinyl chloride) foils exhibit a marked shift towards longer sequences. Vinylisobutyl ether as comonomer unit in the polymer chains effects a considerable shift of the sequence lengths distribution towards shorter polyene sequences. The spectroscopically determined polyene content agrees with the amount of liberated hydrogen chloride only a t very low conversions while with increasing dehydrochlorination a growing polyene deficit is found. Therefore, it is to be concluded that polyene sequences are consumed by consecutive reactions in which primarily the longer polyene sequences are involved. A further conclusion that may be drawn from these experiments is that the formation of long polyene sequences takes place very rapidly once the initial step of dehydrochlorination has occurred at a labile site. Apart from the above mentioned consecutive reactions, only the number, not the average length, of the polyene sequences changes substantially with increasing time of degradation. 相似文献
44.
Structure of the functional interleukin-2 receptor: Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line 总被引:2,自引:0,他引:2
Yamaguchi Akira; Ide Takashi; Hatakeyama Masanori; Doi Takeshi; Kono Takeshi; Uchiyama Takashi; Kikuchi Kokichi; Taniguchi Tadatsugu; Uede Toshimitsu 《International immunology》1989,1(2):160-168
The structural basis of the high affinity interleukin-2 receptorwhich was previously reconstituted in a cultured murine T cellline, EL4 by expressing either wild-type Tac antigen complementaryDNA (cDNA) or a chimeric cDNA was characterized. The chimericcDNA encodes a membrane portion whose extracellular portionconsists of that of Tac antigen whereas transmembrane and cytoplasmicportions consists of those the human insulin beta chain. TheTac antigen/anti-Tac antibody complex was treated by chemicalcrosslinking reagents, purified by goat anti-mouse immunoglobulin(lg), and was analysed by SDS–PAGE. We here demonstrated the presence in mouse EL4 transfectantsof a novel membrane protein which is closely associated withthe products of transfected cDNAs in the absence of interleukln-2.The protein is 75 kDa in size and is detected in cells whichexpress high affinity interieukln-2 receptor but not in cellswhich only express low affinity interleukin-2 receptor. Thetransmembrane region and the cytoplasmic region of Tac antigenis not necessary for the formation of the complex consistingof Tac antigen and 75 kDa molecule, indicating that a murine75 kDa molecule associates with Tac antigen extra-cellularly. 相似文献
45.
Ndembi N Takehisa J Zekeng L Kobayashi E Ngansop C Songok EM Kageyama S Takemura T Ido E Hayami M Kaptue L Ichimura H 《Journal of acquired immune deficiency syndromes (1999)》2004,37(5):1641-1650
To monitor the presence of genotypic HIV-1 variants circulating in eastern Cameroon, blood samples from 57 HIV-1-infected individuals attending 3 local health centers in the bordering rural villages with Central African Republic (CAR) were collected and analyzed phylogenetically. Out of the 40 HIV-1 strains with positive polymerase chain reaction (PCR) profile for both gag and env-C2V3,12 (30.0%) had discordant subtype or CRF designation: 2 subtype B/A (gag/env), 1 B/CRF01, 2 B/CRF02, 1 CRF01/CRF01.A, 2 CRF11/CRF01, 1 CRF13/A, 1 CRF13/CRF01, 1 CRF13/CRF11, and 1 G/U (unclassified). Twenty-eight strains (70.0%) had concordant subtypes or CRF designation between gag and env: 27 subtype A and 1 F2. Out of the remaining 17HIV-1 strains negative for PCR with the env-C2V3 primers used, 10 (58.8%) had discordant subtype or CRF, and 7 (41.2%) had concordant one based on gag/pol/env-gp41 analysis. Altogether, a high proportion (22/57, 38.6%) of the isolates were found to be recombinant strains. In addition, an emergence of new forms of HIV-1 strains, such as subtype B/A (gag/env), B/CRF01 and B/CRF02, was identified. The epidemiologic pattern of HIV-1 in eastern Cameroon, relatively low and high prevalence of CRF02 and CRF11, respectively, was more closely related to those of CAR and Chad than that of other regions of Cameroon, where CRF02 is the most predominant HIV-1 strain. These findings strongly suggest that this part of Cameroon is a potential hotspot of HIV-1 recombination, with a likelihood of an active generation of new forms of HIV-1 variants, though epidemiologic significance of new HIV-1 forms is unknown. 相似文献
46.
The occurrence of a post-traumatic epidural hematoma in two patients with long-standing arrested hydrocephalus is reported. There was a relatively long interval between the head injury and the onset of symptoms. The large hematoma was accommodated by the decrease in size of the markedly dilated ventricles. This report stresses the possibility of the presence of an epidural hematoma in the management of head injury in patients with long-standing arrested hydrocephalus. 相似文献
47.
Kiyoji Kimura Ryuzo Ohno Ichita Amaki Kenichi Hattori Yutaka Hirota Akira Hoshino Michito Ichimaru Munemoto Ito Ikuo Kimura Tadashi Maekawa Toru Masaoka Toru Nakamura Makoto Ogawa Masao Oguro Kazuo Ohta Shigeyuki Osamura Masanori Shimoyama Fumimaro Takaku Yoshiro Uzuka Kazumasa Yamada 《Medical oncology (Northwood, London, England)》1986,3(1):15-24
A phase I study ofN 4-behenoyl-1-β-d-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg?1 which was escalated up to 7 mg kg?1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg?1. In Schedule 2, the daily dose was started with 1.5 mg kg?1 which was escalated up to 8 mg kg?1 and given for 2–16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg?1 daily × 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg?1 of BHAC were administered the half-lives of the initial phase (t 1/2α) and the second phase (t 1/2β) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin’s disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma. 相似文献
48.
Carnitine is a naturally occurring amino acid derivative that is involved in the transport of long-chain fatty acids to the mitochondrial matrix. There, these substrates undergo β-oxidation, producing energy. The major sources of carnitine are dietary intake, although carnitine is also endogenously synthesized in the liver and kidney. However, in patients on dialysis, serum carnitine levels progressively fall due to restricted dietary intake and deprivation of endogenous synthesis in the kidney. Furthermore, serum-free carnitine is removed by hemodialysis treatment because the molecular weight of carnitine is small (161 Da) and its protein binding rates are very low. Therefore, the dialysis procedure is a major cause of carnitine deficiency in patients undergoing hemodialysis. This deficiency may contribute to several clinical disorders in such patients. Symptoms of dialysis-related carnitine deficiency include erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension. However, levocarnitine administration might replenish the free carnitine and help to increase carnitine levels in muscle. This article reviews the previous research into levocarnitine therapy in patients on maintenance dialysis for the treatment of renal anemia, cardiac dysfunction, dyslipidemia, and muscle and dialytic symptoms, and it examines the efficacy of the therapeutic approach and related issues. 相似文献
49.
Kyo Togashi Shingo Hatakeyama Yuta Kojima Masaki Momota Takuma Narita Hiromichi Iwamura Itsuto Hamano Tomoko Hamaya Naoki Fujita Teppei Okamoto Tohru Yoneyama Hayato Yamamoto Takahiro Yoneyama Yasuhiro Hashimoto Chikara Ohyama 《Urologic oncology》2021,39(3):192.e7-192.e14
ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP. 相似文献
50.
Hirotaka Horiguchi Shingo Hatakeyama Tohru Yoneyama Mihoko Sutoh Yoneyama Toshikazu Tanaka Naoki Fujita Teppei Okamoto Hayato Yamamoto Takahiro Yoneyama Tadashi Yoshizawa Yasuhiro Hashimoto Toshiaki Kawaguchi Chikara Ohyama 《Urologic oncology》2021,39(4):238.e9-238.e17
ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC. 相似文献