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991.
Doo‐Yi Oh Yoshihiro Matsumoto Shin‐ichiro Kitajiri Nayoung K.D. Kim Min Young Kim Ah Reum Kim Mingyu Lee Chung Lee Alan E. Tomkinson Tatsuya Katsuno So Young Kim Hyun‐Woo Shin Jin Hee Han Seungmin Lee Woong‐Yang Park Byung Yoon Choi 《Human mutation》2020,41(5):913-920
DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for synthesizing the lagging strand of DNA. Single heterozygous POLD1 mutations in domains with polymerase and exonuclease activities have been reported to cause syndromic deafness as a part of multisystem metabolic disorder or predisposition to cancer. However, the phenotypes of diverse combinations of POLD1 genotypes have not been elucidated in humans. We found that five members of a multiplex family segregating autosomal recessive nonsyndromic sensorineural hearing loss (NS‐SNHL) have revealed novel compound heterozygous POLD1 variants (p.Gly1100Arg and a presumptive null function variant, p.Ser197Hisfs*54). The recombinant p.Gly1100Arg polymerase δ showed a reduced polymerase activity by 30–40%, but exhibited normal exonuclease activity. The polymerase activity in cell extracts from the affected subject carrying the two POLD1 mutant alleles was about 33% of normal controls. We suggest that significantly decreased polymerase δ activity, but not a complete absence, with normal exonuclease activity could lead to NS‐SNHL. 相似文献
992.
Obara Hiromichi Morito Noriyuki Matsuno Naoto Yoshikawa Ryo Nakajo Tetsuya Gochi Mikako Otani Masahide Shonaka Tatsuya Furukawa Hiroyuki Hirano Toshihiko Enosawa Shin 《Journal of artificial organs》2020,23(1):62-69
Journal of Artificial Organs - Improvement of machine perfusion (MP) technologies is required to enhance organ quality for donor after cardiac death (DCD) grafts. Installing a dialyzer or a filter... 相似文献
993.
Hiroki Tanaka Ayana Kanatome Shin Takagi 《Genes to cells : devoted to molecular & cellular mechanisms》2020,25(6):391-401
Vesicular transport serves as an important mechanism for cell shape regulation during development. Although the semaphorin signaling molecule, a well‐known regulator of axon guidance, induces endocytosis in the growth cone and the axonal transport of vertebrate neurons, the underlying molecular mechanisms remain largely unclear. Here, we show that the Caenorhabditis elegans SNT‐1/synaptotagmin‐UNC‐41/stonin2 system, whose role in synaptic vesicle recycling in neurons has been studied extensively, is involved in semaphorin‐regulated vesicular transport in larval epidermal cells. Mutations in the snt‐1/unc‐41 genes strongly suppressed the cell shape defects of semaphorin mutants. The null mutation in the semaphorin receptor gene, plx‐1, altered the expression and localization pattern of endocytic and exocytic markers in the epidermal cells while repressing the transport of SNT‐1‐containing vesicles toward late endosome/lysosome pathways. Our findings suggest that the nematode semaphorins regulate the vesicular transport in epidermal cells in a manner distinct from that of vertebrate semaphorins in neurons. 相似文献
994.
Donghoon Han Jae Hyuk Choi Sehun Kim Sang Min Park Dong Geum Shin Min-Kyung Kang Seonghoon Choi Namho Lee Jung Rae Cho 《The Journal of international medical research》2020,48(12)
ObjectiveActivated platelets release serotonin, causing platelet aggregation and vasoconstriction. Serotonin levels were investigated in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA) treated with percutaneous coronary intervention (PCI).MethodsConsecutive patients undergoing PCI for either ACS or CSA were enrolled between July 2009 and April 2010. Patients were pre-treated with dual antiplatelet agents (aspirin and clopidogrel) before PCI. Serum serotonin levels, measured at baseline, pre- and post-PCI, and at 90 min, and 6, 12, 24 and 48 h following PCI, were compared between ACS and CSA groups.ResultsSixty-three patients with ACS and 60 with CSA were included. Overall baseline characteristics were similar between the two groups. Serotonin levels at post-PCI (55.2 ± 120.0 versus 20.1 ± 24.0) and at peak (regardless of timepoint; 94.0 ± 170.9 versus 38.8 ± 72.3) were significantly higher in the ACS versus CSA group. At 90 min and 6, 24 and 48 h post-PCI, serum serotonin was numerically, but not significantly, higher in patients with ACS. Serotonin levels fluctuated in both groups, showing an initial rise and fall, rebound at 24 h and drop at 48 h post-PCI.ConclusionsIn patients undergoing PCI, serum serotonin was more elevated in patients with ACS than those with CSA, suggesting the need for more potent and sustained platelet inhibition, particularly in patients with ACS. 相似文献
995.
996.
Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28–30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1–10) with papain were also intranasally administered 15 min before each OVA challenge. The results showed that treatment with O1–10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1–10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen. 相似文献
997.
The etiology of benign paroxysmal positional vertigo (BPPV) is still elusive even though detached otolith particles from the utricular macula are generally thought to be responsible for the pathogenesis of BPPV. Sudden sensorineural hearing loss (SSNHL), of which the etiology is also idiopathic in most cases, may accompany concurrent BPPV. This uncommon condition of concurrent BPPV with SSNHL has been assumptively explained as selective damage of the cochlea and the utricle due to viral neurolabyrinthitis. Recently, radiological evidences that inner ear hemorrhage is observed in patients with SSNHL accompanied by severe vertigo have been reported. The basic hypothesis for this study is that blood debris in the endolymphatic fluid due to inner ear hemorrhage is one of the causes of concurrent posterior semicircular canal (PSCC) BPPV in patient with ipsilateral SSNHL. In this report, we will outline the clinical findings of 4 patients with PSCC BPPV with SSNHL, and present an experimental results using whole blood in artificial endolymph to evaluate the hypothesis. 相似文献
998.
Sung Hee Oh Eun Hwa Choi Seon Hee Shin Yun-Kyung Kim Jin Keun Chang Kyong Min Choi Jae Kyun Hur Kyung-Hyo Kim Jae Youn Kim Eun Hee Chung Soo Young Lee Su Eun Park Sungho Cha Kwang-Nam Kim Sang Hyuk Ma Byung Wook Eun Nam Hee Kim Dae Sun Jo Bo Youl Choi Shin Ah Kim 《Clinical and Vaccine Immunology : CVI》2014,21(5):762-768
With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea. 相似文献
999.
Dong-Yeop Chang Sang Hoon Song Sooseong You Jino Lee Jihye Kim Vito Racanelli Hwancheol Son Eui-Cheol Shin 《Clinical and experimental medicine》2014,14(3):305-313
Genital papilloma is caused by human papilloma virus (HPV) infection and recurs frequently. Although T cells are known to play a critical role in the control of HPV infection and papilloma development, the function and phenotype of these cells in the lesion remain to be elucidated. In the present study, we examined the function and phenotype of CD4+ T cells isolated from the lesions of primary (n = 9) and recurrent (n = 11) genital papillomas. In recurrent papillomas, the frequency of proliferating (Ki-67+) CD4+ T cells was significantly reduced compared with primary papillomas. Cytokine production was evaluated by intracellular cytokine staining in anti-CD3/anti-CD28-stimulated CD4+ T cells. CD4+ T cells from recurrent lesions showed impaired production of IL-2, IFN-γ, and TNF-α. Of interest, the frequency of cytokine-producing CD4+ T cells significantly correlated with the frequency of Ki-67+CD4+ T cells. We also studied expression of programmed death-1 (PD-1), a T-cell exhaustion marker. The frequency of PD-1+CD4+ T cells was significantly increased in recurrent lesions and inversely correlated with the frequency of cytokine-producing CD4+ T cells. The functional significance of PD-1 expression was determined in blocking assays with anti-PD-L1, which restored cytokine production of CD4+ T cells from recurrent lesions. Taken together, in recurrent genital papilloma lesions, proliferation, and cytokine production by CD4+ T cells are impaired and the PD-1/PD-L1 interaction is responsible for the functional impairment of CD4+ T cells. 相似文献
1000.