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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.
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
3.
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
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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.7.
8.
The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells 总被引:15,自引:16,他引:15
Sitnicka E; Lin N; Priestley GV; Fox N; Broudy VC; Wolf NS; Kaushansky K 《Blood》1996,87(12):4998-5005
In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated. 相似文献
9.