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41.
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Tone Ikdahl Andersen Hans Geir Eiken Fergus Couch Grete Kaada Martina Skrede Hilde Johnsen Thomas A. Aloysius Kjell M. Tveit Lisbeth Tranebjrg Anne Drum Pl Mller Barbara L. Weber Anne-Lise Brresen-Dale 《Human mutation》1998,11(2):166-174
Screening for mutations in the breast and ovarian cancer susceptibility gene, BRCA1, is complicated by the wide spectrum of mutations found in this large gene. In the present study a constant denaturant gel electrophoresis (CDGE) mutation screening strategy was established for ˜80% of the genomic coding sequence (exons 2, 11, 13–16, 20, 24). This strategy was applied to screen genomic DNA from 50 familial breast and/or ovarian cancer patients who had previously been examined for BRCA1 mutations by SSCP. A total of 14 carriers of 12 distinct disease-associated mutations and 7 carriers of 6 distinct rare substitutions leading to amino acid substitutions were identified. The SSCP failed to detect 40% of the different deletions/insertions (4/10) and 75% (6/8) of the different base substitutions leading to terminating codons or rare amino acid changes. SSCP did, however, identify one rare base substitution that could not be detected in the CDGE screening. To evaluate the CDGE mutation screening strategy further, 25 unrelated patients from Norwegian breast and/or ovarian cancer families were examined for BRCA1 mutations using a combined genomic DNA/cDNA approach covering the entire coding sequence of the gene. A total of six mutation carriers were detected, all of whom had cases of ovarian cancer in their families. Three patients from independent families carried an 1135insA mutation in exon 11, two others had a Gly484ter and an 1675delA mutation, respectively, and the sixth carried a splice mutation (5194-2 a→c) causing deletion of exon 18. CDGE may become an efficient tool in diagnostic and population based screening for BRCA1 mutations. Hum Mutat 11:166–174, 1998. © 1998 Wiley-Liss, Inc. 相似文献
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Mohammed Lamorde John R.S. Tabuti Celestino Obua Collins Kukunda-Byobona Hindam Lanyero Pauline Byakika-Kibwika Godfrey S. Bbosa Aloysius Lubega Jasper Ogwal-Okeng Mairin Ryan Paul J. Waako Concepta Merry 《Journal of ethnopharmacology》2010
Introduction and objectives
In Uganda, there are over one million people with HIV/AIDS. When advanced, this disease is characterized by life-threatening opportunistic infections. As the formal health sector struggles to confront this epidemic, new medicines from traditional sources are needed to complement control efforts. This study was conducted to document herbal medicines used in the treatment of HIV/AIDS and related opportunistic infections, and to document the existing knowledge, attitudes and practices related to HIV/AIDS recognition, control and treatment in Sembabule, Kamuli, Kabale and Gulu districts in Uganda.Methods
In this study, 25 traditional medicine practitioners (TMPs) were interviewed using structured questionnaires.Results
The TMPs could recognize important signs and symptoms of HIV/AIDS and its associated opportunistic infections. The majority of practitioners treated patients who were already receiving allopathic medicines including antiretroviral drugs (ARVs) prescribed by allopathic practitioners.There were 103 species of medicinal plants identified in this survey. Priority plants identified include Aloe spp., Erythrina abyssinica, Sarcocephalus latifolius, Psorospermum febrifugum, Mangifera indica and Warburgia salutaris. There was low consensus among TMPs on the plants used. Decoctions of multiple plant species were commonly used except in Gulu where mono-preparations were common. Plant parts frequently used were leaves (33%), stem bark (23%) and root bark (18%). About 80% of preparations were administered orally in variable doses over varied time periods. The TMP had insufficient knowledge about packaging and preservation techniques.Conclusions
Numerous medicinal plants for treatment of HIV/AIDS patients were identified in the four districts surveyed and the role of these plants in the management of opportunistic infections warrants further investigation as these plants may have a role in Uganda's public health approach to HIV/AIDS control. 相似文献45.
Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin,PINK1, DJ1: MDSGene Systematic Review 下载免费PDF全文
Ana Westenberger PhD Eva‐Juliane Vollstedt MD Alexander Balck MD Aloysius Domingo MD PhD Franca Vulinovic PhD Marija Dulovic MD PhD Ingo Zorn Harutyun Madoev Hanna Zehnle Christina M. Lembeck BSc Leopold Schawe BSc Jennifer Reginold BSc Jana Huang BHS Inke R. König PhD Lars Bertram MD Connie Marras MD PhD Katja Lohmann PhD Christine Klein MD 《Movement disorders》2018,33(5):730-741
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González Cabrera D Douelle F Feng TS Nchinda AT Younis Y White KL Wu Q Ryan E Burrows JN Waterson D Witty MJ Wittlin S Charman SA Chibale K 《Journal of medicinal chemistry》2011,54(21):7713-7719
An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC(50): 0.08 μM (K1, chloroquine and multidrug resistant strain) and 0.07 μM (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Compound 3 also exhibited in vivo activity in the P. berghei mouse model at 4 × 50 mg/kg administration via the oral route, showing 99.5% activity and 9 days survival and showed low in vitro cytotoxicity. Pharmacokinetic studies in rats revealed good oral bioavailability (51% at 22 mg/kg) with a moderate rate of absorption, reasonable half-life (t(1/2) 3 h), and high volume of distribution with moderately high plasma and blood clearance after IV administration. Toward toxicity profiling, 3 exhibited moderate potential to inhibit CYP1A2 (IC(50) = 1.5 μM) and 2D6 (IC(50) = 0.4 μM) as well as having a potential hERG liability (IC(50) = 3.7 μM). 相似文献
48.
Westin ER Aykin-Burns N Buckingham EM Spitz DR Goldman FD Klingelhutz AJ 《Antioxidants & redox signaling》2011,14(6):985-997
Telomere attrition is a natural process that occurs due to inadequate telomere maintenance. Once at a critically short threshold, telomeres signal growth arrest, leading to senescence. Telomeres can be elongated by the enzyme telomerase, which adds de novo telomere repeats to the ends of chromosomes. Mutations in genes for telomere binding proteins or components of telomerase give rise to the premature aging disorder dyskeratosis congenita (DC), which is characterized by extremely short telomeres and an aging phenotype. The current study demonstrates that DC cells signal a DNA damage response through p53 and its downstream mediator, p21(WAF/CIP), which is accompanied by an elevation in steady-state levels of superoxide and percent glutathione disulfide, both indicators of oxidative stress. Poor proliferation of DC cells can be partially overcome by reducing O(2) tension from 21% to 4%. Further, restoring telomerase activity or inhibiting p53 or p21(WAF/CIP) significantly mitigated growth inhibition as well as caused a significant decrease in steady-state levels of superoxide. Our results support a model in which telomerase insufficiency in DC leads to p21(WAF/CIP) signaling, via p53, to cause increased steady-state levels of superoxide, metabolic oxidative stress, and senescence. 相似文献
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Ceesay MM Matutes E Taylor GP Fields P Cavenagh J Simpson S Ho A Devereux S Mufti GJ Pagliuca A 《Leukemia research》2012,36(7):857-861
Adult T-cell leukaemia lymphoma (ATLL) is an aggressive T-cell malignancy caused by the human T-lymphotropic virus type-1 (HTLV-1) and is associated with a very poor prognosis. Combination chemotherapy has had little impact on the long term survival of these patients. ATLL cells are characterised by the expression of CD25 (IL-2Rα), which is not expressed in normal resting T-cells. Daclizumab (Zenapax(?)) is a humanised murine anti-CD25 monoclonal antibody, which contains 10% murine CDR sequences. In this prospective trial 15 patients with aggressive ATLL were treated with CHOP-Zenapax (CHOP-Z) to determine the tolerability and feasibility of this novel regimen as well as evaluate its efficacy. Eleven patients had acute ATLL and four had the lymphoma subtype. The main presenting features were elevated LDH (100%), lymphocytosis (73%), lymphadenopathy (67%), skin lesions (40%), hypercalcaemia (53%), and hepato-splenomegaly (27%). Ten (67%) patients received the six scheduled cycles. Complete response (CR) lasting for two months or more was seen in 5 (33%), partial response in 3 (20%), minor response in 1 (7%), and no response in 6 (40%) patients. The median overall survival was 10 months (95% CI: 0.05-20.88) but this was significantly longer among responders (18 months) compared to non responders (3 months) (P = 0.019). For patients who achieved CR the disease free survival (DFS) was 15 months while the event-free survival (EFS) was 5 months. In conclusion CHOP-Z is safe and in those who achieve a complete response it was associated with prolonged overall survival. 相似文献