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121.
Johanna L. Schmidt MPH MGC CGC Amy Pizzino MS CGC Jessica Nicholl MS CGC Allison Foley MMSc CGC Yue Wang PhD FACMG Jill A. Rosenfeld MS CGC Lindsey Mighion MS CGC Lora Bean PhD Cristina da Silva MS Megan T. Cho MS CGC Rebecca Truty PhD John Garcia PhD Virginia Speare PhD Kirsten Blanco BS Zoe Powis MS CGC Grace M. Hobson PhD Susan Kirwin BS Bryan Krock PhD FACMG Hane Lee PhD Joshua L. Deignan PhD Maggie A. Westemeyer MS CGC Ryan L. Subaran PhD Isabelle Thiffault PhD FABMGG Ellen A. Tsai PhD Terry Fang PhD Guy Helman BS Adeline Vanderver MD 《American journal of medical genetics. Part A》2020,182(8):1906-1912
Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening. 相似文献
122.
Genome-wide profiling of oral squamous cell carcinoma 总被引:7,自引:0,他引:7
Chen YJ Lin SC Kao T Chang CS Hong PS Shieh TM Chang KW 《The Journal of pathology》2004,204(3):326-332
Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c-Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21-tel; 20q; 11q13; 3q27-29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC. 相似文献
123.
Hong Chou Ching-Yun Chang Jaw-Ji Tsai Ren-Bin Tang Shinn-Shing Lee Soo-Ray Wang Ho-Jen Peng Horng-Der Shen 《Annals of allergy, asthma & immunology》2003,90(2):248-253
BACKGROUND: Penicillium species are prevalent airborne fungi. However, the prevalence of allergic sensitization to Penicillium antigens and the true impact of these ubiquitous fungi on atopic respiratory disorders remain to be determined. OBJECTIVE: The purpose of this study was to analyze the prevalence of immunoglobulin (Ig)E and IgG antibodies against Penicillium chrysogenum (Pen ch 13), the alkaline serine protease major allergen of P. chrysogenum, in asthmatic patients of different age groups. METHODS: Pen ch 13 was purified from a culture medium of P. chrysogenum. The reactivity of IgE and IgG antibodies to Pen ch 13 in the serum samples of 212 asthmatic patients was analyzed by immunoblotting methods. RESULTS: Sixty-nine (33%) of the 212 sera analyzed showed IgE and/or IgG immunoblot reactivity to Pen ch 13. Significant differences in the prevalence of IgE and/or IgG antibody reactivity to Pen ch 13 were found among eight different age groups of 212 asthmatic patients. The frequency of IgE-binding reactivity to Pen ch 13 increased significantly with the age of the patients. It was 7% for the group less than 10 years old and 42% for the group older than 70 years old. In addition, a significant difference between the prevalence of IgE (7%) and IgG (33%) antibodies against Pen ch 13 in the group aged 10 or less was also found. CONCLUSIONS: Our study demonstrates that IgE and IgG antibodies specific for Pen ch 13 were detected in approximately one-third of the 212 asthmatic patients analyzed. Our results suggest that allergic sensitization to Pen ch 13, and possibly to other airborne Penicillium species, is more common in older asthmatic patients. 相似文献
124.
Comparison of different PCR approaches for characterization of Burkholderia (Pseudomonas) cepacia isolates. 总被引:1,自引:2,他引:1 下载免费PDF全文
P Y Liu Z Y Shi Y J Lau B S Hu J M Shyr W S Tsai Y H Lin C Y Tseng 《Journal of clinical microbiology》1995,33(12):3304-3307
In this study, we evaluated three PCR methods for epidemiological typing of Burkholderia (Pseudomonas) cepacia--PCR-ribotyping, arbitrarily primed PCR (AP-PCR) and enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR)--and compared them with pulsed-field gel electrophoresis. The analysis was performed with 31 isolates of B. cepacia, comprising 23 epidemiologically unrelated isolates and 8 isolates collected from the same patient during two episodes of bacteremia. Pulsed-field gel electrophoresis, ERIC-PCR, and AP-PCR identified 23 distinct types among the 23 unrelated isolates, while PCR-ribotyping only identified 12 strain types, even after AluI digestion of the amplification products. Among the eight isolates collected from the same patient, all typing techniques revealed two clones of strains. The day-to-day reproducibilities of PCR-ribotyping and ERIC-PCR were good, while greater day-to-day variations were noted in the fingerprints obtained by AP-PCR. We conclude that all three PCR techniques are useful for rapid epidemiological typing of B. cepacia, but ERIC-PCR seems to be more reproducible and discriminative. 相似文献
125.
Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components. 相似文献
126.
Site-directed cytotoxic antibody against the C-terminal segment of the surface glycoprotein gp90 of avian reticuloendotheliosis virus 总被引:4,自引:0,他引:4
The major mature env-gene products of avian reticuloendotheliosis-associated virus (REV-A) are the surface glycoprotein (gp90) and the transmembrane protein (gp20). We have previously reported that gp90 was detected in the REV-A virus by Western blot analysis as well as in the REV-A-infected cells by radioimmunoprecipitation with antibodies raised in rabbits against the gp90 C-terminal tridecapeptide which was predicted from the nucleotide sequence (Wilhemsen et al., J. Virol., 52, 172, 1984). We have now shown that this antibody detected antigens on the REV-A-infected cells by fluorescence-activated cell sorter (FACS) analysis, and conferred specific cytotoxic effects on the infected cells in the presence of rabbit complement using the chromium release assay. These results clearly indicate that the C-terminal epitope of gp90 is situated on the surface of the REV-A-infected cells and accessible to site-directed antibodies which cause cytotoxicity by activating the complement system. The possible in vivo roles of this antibody are discussed. 相似文献
127.
Yi-Giien Tsai Jenn-Haung Lai San-Yuan Kuo Hsiang-Cheng Chen Deh-Ming Chang 《Journal of microbiology, immunology, and infection》2005,38(3):218-220
Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. We report a 51-year-old female thymoma patient who presented with recurrent herpes zoster, pneumonia, diarrhea and opportunistic infections. She was found to have acquired hypogammaglobulinemia with absent B cells. Despite repeat intravenous immunoglobulin replacement and antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory distress syndrome. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with recurrent infections. 相似文献
128.
A J Cohen F P Li S Berg D J Marchetto S Tsai S C Jacobs R S Brown 《The New England journal of medicine》1979,301(11):592-595
129.
Effect of Group A Streptococcal Cysteine Protease on Invasion of Epithelial Cells 总被引:3,自引:6,他引:3 下载免费PDF全文
Pei-Jane Tsai Chih-Feng Kuo Kuei-Yuan Lin Yee-Shin Lin Huan-Yao Lei Fen-Fen Chen Jen-Ren Wang Jiunn-Jong Wu 《Infection and immunity》1998,66(4):1460-1466
Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had the ability to invade A-549 human respiratory epithelial cells. Isogenic protease mutants were constructed by using integrational plasmids to disrupt the speB gene and confirmed by Southern hybridization and Western immunoblot analyses. No extracellular protease activity was produced by the mutants. The mutants had growth rates similar to those of the wild-type strains and produced normal levels of other extracellular proteins. When invading A-549 cells, the mutants had a two- to threefold decrease in activity compared to that of the wild-type strains. The invasion activity increased when the A-549 cells were incubated with purified cysteine protease and the mutant. However, blockage of the cysteine protease with a specific cysteine protease inhibitor, E-64, decreased the invasion activity of GAS. Intracellular growth of GAS was not found in A-549 cells. The presence or absence of protease activity did not affect the adhesive ability of GAS. These results suggested that streptococcal cysteine protease can enhance the invasion ability of GAS in human respiratory epithelial cells. 相似文献
130.
Huang CC Tsai WC Hseu RS Wang HH 《Zhonghua Minguo wei sheng wu ji mian yi xue za zhi = Chinese journal of microbiology and immunology》1997,30(1):18-31
Candida albicans is a pathogenic yeast. Two sets of universal primers were used for specific identification of Candida albicans with PCR-amplified ribosomal DNA internal transcribed spacers (ITS). Among the species of Candida, the amplified ITSI and ITSII of DNA fragments were similar in size. The PCR product was purified and labeled with digoxigenin and used as DNA probe in the detection with target DNA of Candida albicans by hybridization. Two sets of specific primers (CA1 and CA2 to amplify ITSI, CA3 and CA4 to amplify ITSII) were designed by alignment of ribosomal ITS sequence of pathogenic Candida albicans with other species to detect C. albicans by PCR. The sensitivity of PCR using the specific primers to detect pure culture of C. albicans was 0.1 ng (about 10(3)-10(4) cells). If the yeast cells were mixed with two other strains, there was a 10-fold decrease in sensitivity (1 ng or 10(4)-10(5) cells) under the same PCR conditions. 相似文献