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1.
As we have seen, natural antibodies first emerged as an experimental phenomenon without a plausible theoretical explanation. They were originally denied the status of antibody; then, adjustments to the side-chain theory transformed them from a curiosity into a foundation of the theory. However, in accommodating natural antibodies, Ehrlich had opened several holes in his mechanism of antibody formation.Thus, by 1905, natural antibodies were clearly established as problematic. From the practical standpoint, it seemed unwise to maintain an identity between normal and immune antibodies, given the therapeutic differences in their avidity. With the decline of Ehrlich's theory of antibody formation and the spread of Landsteiner's hapten technique for the production of antibodies against artificial antigens after World War I, the theoretical possibility of their existence as other than anomaly seemed more remote than ever. However, outside the theory and despite clinical considerations, natural antibodies remained a perplexing experimental phenomenon.49 相似文献
2.
Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America 总被引:10,自引:0,他引:10 下载免费PDF全文
Toro JR Nickerson ML Wei MH Warren MB Glenn GM Turner ML Stewart L Duray P Tourre O Sharma N Choyke P Stratton P Merino M Walther MM Linehan WM Schmidt LS Zbar B 《American journal of human genetics》2003,73(1):95-106
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder characterized by smooth-muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in North America has not been studied. We screened for germline mutations in FH in 35 families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (89%). Twenty different mutations in FH were identified, of which 18 were novel. Of these 20 mutations, 2 were insertions, 5 were small deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine leiomyomas. Eighty-nine percent (41/46) of women with cutaneous and uterine leiomyomas had a total hysterectomy, 44% at age < or =30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Seven individuals from four families had papillary type II renal cell carcinoma, and another individual from one of these families had collecting duct carcinoma of the kidney. The present study shows that mutations in FH are associated with HLRCC in North America. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. The present study also expands the histologic spectrum of renal tumors and FH mutations associated with HLRCC. 相似文献
3.
Xingxing Yuan Yurong Tan Ousman Bajinka Modou L. Jammeh Abubakarr Dukureh Chidera N. Obiegbusi Khalid A. Abdelhalim Mahmoud Mohanad 《Cell biochemistry and function》2024,42(2):e3941
Both the epigenetic changes and gut microbiota (GM) have attracted a growing interest in establishing effective diagnostics and potential therapeutic strategies for a number of diseases. These disorders include metabolic, central nervous system-related diseases, autoimmune, and gastrointestinal infections (GI). Despite the number of studies, there is no extensive review that connects the epigenetics modifications and GM as biomarkers that could confer effective diagnostics and confer treatment options. To this end, this review hopes to give detailed information on connecting the modifications in epigenetic and GM. An updated and detailed information on the connection between the epigenetics factors and GM that influence diseases are given. In addition, the review showed some associations between the epigenetics to the maternal GM and offspring health. Finally, the limitations of the concept and prospects into this new emerging discipline were also looked into. Although this review elucidated on the maternal diet and response to offspring health with respect to GM and epigenetic modifications, there still exist various limitations to this newly emerging discipline. In addition to integrating complementary multi-omics data, longitudinal sampling will aid with the identification of functional mechanisms that may serve as therapeutic targets. To this end, this review gave a detailed perspective into harnessing disease diagnostics, prevention and treatment options through epigenetics and GM. 相似文献
4.
Fei Zhao Weiwei Huang Tamgue Ousman Bin Zhang Yangyang Han Daguia Zambe John Clotaire Chen Wang Huanhuan Chang Huanan Luo Xiaoyong Ren Ming Lei 《PloS one》2013,8(11)
Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug. 相似文献
5.
Yan BS Pichugin AV Jobe O Helming L Eruslanov EB Gutiérrez-Pabello JA Rojas M Shebzukhov YV Kobzik L Kramnik I 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):6919-6932
Using a mouse model for genetic analysis of host resistance to virulent Mycobacterium tuberculosis, we have identified a genetic locus sst1 on mouse chromosome 1, which controls progression of pulmonary tuberculosis. In vitro, this locus had an effect on macrophage-mediated control of two intracellular bacterial pathogens, M. tuberculosis and Listeria monocytogenes. In this report, we investigated a specific function of the sst1 locus in antituberculosis immunity in vivo, especially its role in control of pulmonary tuberculosis. We found that the sst1 locus affected neither activation of Th1 cytokine-producing T lymphocytes, nor their migration to the lungs, but rather controlled an inducible NO synthase-independent mechanism of innate immunity. Although the sst1(S) macrophages responded to stimulation with IFN-gamma in vitro, their responsiveness to activation by T cells was impaired. Boosting T cell-mediated immunity by live attenuated vaccine Mycobacterium bovis bacillus Calmette-Guérin or the adoptive transfer of mycobacteria-activated CD4(+) T lymphocytes had positive systemic effect, but failed to improve control of tuberculosis infection specifically in the lungs of the sst1(S) animals. Thus, in the mouse model of tuberculosis, a common genetic mechanism of innate immunity mediated control of tuberculosis progression in the lungs and the efficiency of antituberculosis vaccine. Our data suggest that in immunocompetent humans the development of pulmonary tuberculosis and the failure of the existing vaccine to protect against it, in some cases, may be explained by a similar defect in a conserved inducible NO synthase-independent mechanism of innate immunity, either inherited or acquired. 相似文献
6.
Marieke Klaasen Hendrik-Jan Roest Wim van der Hoek Bart Goossens Arss Secka Arjan Stegeman 《PloS one》2014,9(1)
Background
Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia.Methodology/Principal Findings
This survey was carried out from March to May 2012 at two areas in The Gambia. The first area comprised a cluster of seven rural villages situated 5–15 km west of Farafenni as well as the local abattoir. A second sampling was done at the central abattoir in Abuko (30 km from the capital, Banjul) in the Western Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67 milk samples were obtained from lactating dams. Sera were tested with a Q fever ELISA kit. C. burnetii DNA was extracted from milk samples and then detected using a specific quantitative multiplex PCR assay, targeting the IS1111a element. A multivariable mixed logistic regression model was used to examine the relationship between seropositivity and explanatory variables. An overall seroprevalence of 21.6% was found. Goats had a significantly higher seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals were significantly older than seronegative animals. Animals from the villages had a significantly lower seroprevalence than animals from the central abattoir (15.1% versus 29.1%). C. burnetii DNA was detected in 2 out of 67 milk samples, whereas 8 samples gave a doubtful result.Conclusion/Significance
A substantial C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated. People living in close proximity to small ruminants are exposed to C. burnetii. Q fever should be considered as a possible cause of acute febrile illness in humans in The Gambia. Future studies should include a simultaneous assessment of veterinary and human serology, and include aetiology of febrile illness in local clinics. 相似文献7.
8.
Sugata Roy Sebastian Schmeier Erik Arner Tanvir Alam Suraj P. Parihar Mumin Ozturk Ousman Tamgue Hideya Kawaji Michiel?J.?L. de?Hoon Masayoshi Itoh Timo Lassmann Piero Carninci Yoshihide Hayashizaki Alistair?R. R. Forrest Vladimir B. Bajic Reto Guler FANTOM Consortium Frank Brombacher Harukazu Suzuki 《Nucleic acids research》2015,43(14):6969-6982
9.
Michael P. Kurnellas Sara E. Brownell Leon Su Andrey V. Malkovskiy Jayakumar Rajadas Gregory Dolganov Sidharth Chopra Gary K. Schoolnik Raymond A. Sobel Jonathan Webster Shalina S. Ousman Rachel A. Becker Lawrence Steinman Jonathan B. Rothbard 《The Journal of biological chemistry》2012,287(43):36423-36434
To determine whether the therapeutic activity of αB crystallin, small heat shock protein B5 (HspB5), was shared with other human sHsps, a set of seven human family members, a mutant of HspB5 G120 known to exhibit reduced chaperone activity, and a mycobacterial sHsp were expressed and purified from bacteria. Each of the recombinant proteins was shown to be a functional chaperone, capable of inhibiting aggregation of denatured insulin with varying efficiency. When injected into mice at the peak of disease, they were all effective in reducing the paralysis in experimental autoimmune encephalomyelitis. Additional structure activity correlations between chaperone activity and therapeutic function were established when linear regions within HspB5 were examined. A single region, corresponding to residues 73–92 of HspB5, forms amyloid fibrils, exhibited chaperone activity, and was an effective therapeutic for encephalomyelitis. The linkage of the three activities was further established by demonstrating individual substitutions of critical hydrophobic amino acids in the peptide resulted in the loss of all of the functions. 相似文献
10.