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1.
Regnier V; Meddeb M; Lecointre G; Richard F; Duverger A; Nguyen VC; Dutrillaux B; Bernheim A; Danglot G 《Human molecular genetics》1997,6(1):9-16
Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase
activating protein family and is considered to be a tumor suppressor gene.
Its very high rate of de novo mutation in humans led us to study a specific
feature of this gene: the presence of numerous NF1-related sequences.
According to our results, the human genome contains at least 11 NF1-related
sequences, nine of which are scattered near centromeric sequences of seven
different chromosomes. These NF1-related sequences, whose extent is quite
varied according to loci, are unprocessed copies of the NF1 gene, and bear
numerous mutations. A phylogenetic analysis of the six largest sequences
indicates that they are all derived from a common ancestor, which would
have appeared 22-33 million years ago, and was subsequently duplicated
several times during hominoid evolution. The most recent duplication and
interchromosomal transposition occurred in the last million years
suggesting that the process could still be ongoing. Intriguing similarities
between the evolution of alpha- satellite DNA and NF1-related sequences
suggest the involvement of a common genetic mechanism for the generation
and pericentric spreading of these NF1 partial copies.
相似文献
2.
Kristin K Zorn Tomas Bonome Lisa Gangi Gadisetti V R Chandramouli Christopher S Awtrey Ginger J Gardner J Carl Barrett Jeff Boyd Michael J Birrer 《Clinical cancer research》2005,11(18):6422-6430
PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished. 相似文献
3.
Arbour NC; Zlotogora J; Knowlton RG; Merin S; Rosenmann A; Kanis AB; Rokhlina T; Stone EM; Sheffield VC 《Human molecular genetics》1997,6(5):689-694
Achromatopsia is an autosomal recessive disease of the retina,
characterized clinically by an inability to distinguish colors, impaired
visual acuity, nystagmus and photophobia. A genome-wide search for linkage
was performed using an inbred Jewish kindred from Iran. To facilitate the
genome-wide search, we utilized a DNA pooling strategy which takes
advantage of the likelihood that the disease in this inbred kindred is
inherited by all affected individuals from a common founder. Equal molar
amounts of DNA from all affected individuals were pooled and used as the
PCR template for short tandem repeat polymorphic markers (STRPs). Pooled
DNA from unaffected members of the kindred was used as a control. A
reduction in the number of alleles in the affected versus control pool was
observed at several loci. Upon genotyping of individual family members,
significant linkage was established between the disease phenotype and
markers localized on chromosome 2. The highest LOD score observed was 5.4
(theta = 0). When four additional small unrelated families were genotyped,
the combined peak LOD score was 8.2. Analysis of recombinant chromosomes
revealed that the disease gene lies within a 30 cM interval which spans the
centromere. Additional fine-mapping studies identified a region of
homozygosity in all affected individuals, narrowing the region to 14 cM. A
candidate gene for achromatopsia was excluded from this disease interval by
radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an
essential first step in the identification of the disease-causing gene.
相似文献
4.
Two-hundred and eighty bacterial isolates from wound and soft tissue infections were studied for species identification and antibiotic resistance pattern. Amongst them 122 isolates were from community acquired infection and 158 were from nosocomial infections. The common community acquired pathogens were Staphylococcus aureus (67.8%) and Streptococcus pyogenes (10.7%), whereas Staphylococcus aureus (60.1%) and E. Coli (8.9%) were common in nosocomial infection. Only two anaerobes (Cl perfringens) were isolated. Penicillin resistance was found to be 87% and 92% for Staphylococccus aureus in community acquired and noscomial infections respectively. 85% of Proteus isolates were resistant to ampicillin. There was relatively lower level of resistance by all isolates to cefotaxime. Gentamicin showed higher rate of resistance than netilmicin and amikacin. Resistance of E. coli isolates to fluoroquinolones being 79% for norfloxacin, 81% for ciprofloxacin and 60% for ofloxacin. The study showed a higher resistance of methicillin resistant Staphylococcus aureus (MRSA) to other antibiotics. Amikacin and ofloxacin were the best recommended drugs for empirical therapy for all organisms, the susceptibility rate being 80.7% and 80.4%.KEY WORDS: Antibiotic resistance, Soft tissue infections, Wound infections 相似文献
5.
目的观察再发性低血糖后脑内葡萄糖转运蛋白1(glucose transporter 1,GLUT1)及葡萄糖转运蛋白3(GLUT3)表达的变化,从而探讨无症状低血糖的发生机制。方法将80只15日龄野生型小鼠随机分为正常对照组及低血糖组,每组40只。低血糖组给予正规胰岛素腹腔注射3次,每次剂量为5U/kg,对照组注射等体积生理盐水。两组分别在最后1次注射后12、24、48及72 h处死小鼠取脑组织(每组每时间点10只),应用免疫组化方法观察小鼠脑内GLUT1及GLUT3表达的变化。结果低血糖后脑内微血管上GLUT1表达有增加趋势,皮质增加高于海马,72 h皮质GLUT1表达显著高于对照组;低血糖后48、72 h皮质及海马GLUT3表达均显著高于相应对照组。结论再发性低血糖后脑内GLUT1及GLUT3适应性增高,这种适应既能节省神经元的能量代谢,但也能削减神经元对低血糖的反应。 相似文献
6.
7.
Wajngot A Chandramouli V Schumann WC Ekberg K Jones PK Efendic S Landau BR 《Metabolism: clinical and experimental》2001,50(1):47-52
Contributions of gluconeogenesis to glucose production were determined between 14 to 22 hours into a fast in type 2 diabetics (n = 9) and age-weight-matched controls (n = 7); ages, 60.4 +/- 2.3 versus 55.6 +/- 1.2 years and body mass indices (BMI) 28.6 +/- 2.3 versus 26.6 +/- 0.8 kg/m2. Production was measured using a primed-continuous [6,6-2H2]glucose infusion and gluconeogenesis from 2H enrichment at carbons 2 and 5 of blood glucose on 2H2O ingestion. Plasma glucose concentration declined from 9.6 +/- 0.6 at 14 hours to 7.3 +/- 0.6 at 22 hours in the diabetics (P = .001) and from 5.4 +/- 0.1 to 5.0 +/- 0.1 in the controls (P < .05). Production from the 17th to 22nd hour declined 27.1% +/- 0.6% in the diabetics versus 18.5% +/- 0.8% in the controls (P = .001); from 10.4 +/- 0.3 to 7.6 +/- 0.2 versus 10.0 +/- 0.4 to 8.2 +/- 0.4 micromol/kg/min. Percent contributions of gluconeogenesis to production measured at 1 1/2 to 2-hour intervals beginning the 15th hour were 6.8% +/- 1.0% more in the diabetics than controls. The quantity of glucose contributed by gluconeogenesis declined 19.8% +/- 3.8% (P < .001) in the diabetics and 6.9% +/- 2.3% in the controls (P = .05); 7.21 +/- 0.32 to 5.74 +/- 0.26 versus 6.20 +/- 0.28 to 5.75 +/- 0.24 micromol/kg/min. The contribution of glycogenolysis to production, estimated from the difference between production and gluconeogenesis, declined to the same extent in diabetic and control subjects, 40.7% +/- 6.6% and 37.7% +/- 4.1%; from 3.23 +/- 0.35 to 1.86 +/- 0.26 versus 3.81 +/- 0.22 to 2.42 +/- 0.28 micromol/kg/min. Thus, gluconeogenesis contributed more to glucose production in the diabetic than control subjects. Production and the contribution of gluconeogenesis declined more in the diabetic subjects during the fast. The factors regulating these changes remain uncertain. 相似文献
8.
Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL- 3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines. 相似文献
9.
Patient perspectives on de‐simplifying their single‐tablet co‐formulated antiretroviral therapy for societal cost savings
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Objectives
The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV‐infected patients are substantial, so cost‐saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de‐simplifying (i.e. switching) more expensive single‐tablet formulations (STFs) to less expensive generic‐based multi‐tablet components. We determined physician and patient perceptions and acceptance of STF de‐simplification within the context of a publicly funded ARV budget.Methods
Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de‐simplified to eligible generic co‐formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de‐simplification would be acceptable.Results
Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de‐simplifying could be safely achieved. Forty‐eight per cent of 221 patients surveyed were agreeable to de‐simplifying for altruistic reasons, 27% said no, and 25% said maybe.Conclusions
De‐simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de‐simplifying other STFs. Both physicians and patients agreed that selective de‐simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de‐simplification strategies seems warranted.10.