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11.
p16INK4A and p15INK4B gene deletions in primary leukemias 总被引:4,自引:0,他引:4
Haidar MA; Cao XB; Manshouri T; Chan LL; Glassman A; Kantarjian HM; Keating MJ; Beran MS; Albitar M 《Blood》1995,86(1):311-315
The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene. 相似文献
12.
Janneke AL van Kempen Henk J Schers Anne Jacobs Sytse U Zuidema Franca Ruikes Sarah HM Robben René JF Melis Marcel GM Olde Rikkert 《The British journal of general practice》2013,63(608):e225-e231
Background
Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.Aim
This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.Design and setting
Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.Method
The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.Results
The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.Conclusion
The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care. 相似文献13.
TRA Lane HM Moore IJ Franklin AH Davies 《Annals of the Royal College of Surgeons of England》2015,97(2):e18-e20
The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein® device, without adverse sequelae. 相似文献
14.
Raimund HM Preidl Tobias Ebker Martin Raithel Falk Wehrhan Friedrich W Neukam Philipp Stockmann 《BMC gastroenterology》2014,14(1):1-6
Background
Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.Methods
Normal colorectal mucosa and paired cancerous tissue from 60 patients with colorectal cancer was investigated for the levels of COX-2 mRNA by real-time quantitative Polymerase Chain Reaction (qPCR). COX-2 levels were expressed relative to either: tissue weight or levels of the housekeeping genes beta-2 microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).Results
COX-2 mRNA levels, normalized with respect to tissue weight or mRNA levels of the housekeeping genes B2M or GAPDH, were over-expressed in 80%, 70% and 40% of the colorectal tumor tissues, as compared to the paired adjacent normal colorectal mucosa samples, respectively. Highest mRNA COX-2 ratios tumor/normal were measured when expressed per mg tissue (mean ratio 21.6). When normalized with respect to the housekeeping genes B2M or GAPDH, mean tumor/normal ratios were 16.1 and 7.5, respectively.Conclusion
Expression of COX-2 mRNA levels per mg tissue is most simple in comparison to normalization with respect to the housekeeping genes B2M or GAPDH. Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer. 相似文献15.
BackgroundPeripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed. We performed a systematic review of guidelines to evaluate the value of PAD screening in asymptomatic adults.MethodsGuidelines in English published between January 1, 2003 and January 20, 2011 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on PAD screening, were included. Two reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was validated by a second reviewer.ResultsOf 2779 titles identified, 8 guidelines were included. AGREE scores varied from 33% to 81%. Five guidelines advocated PAD screening, others found insufficient evidence for PAD screening or were against it. Measurement of the ankle-brachial index (ABI) was generally recommended for middle-aged populations with elevated cardiovascular risk levels. Those identified as having PAD are reclassified as high risk, warranting intensive preventive interventions to reduce their risk of a cardiovascular event. The underlying evidence mainly consisted of studies performed in patients with established PAD. A meta-analysis that evaluated ABI testing in the context of traditional cardiovascular risk assessment was interpreted differently.ConclusionsRecommendations on PAD screening vary across current guidelines, making the value of PAD screening uncertain. The variation seems to reflect lack of studies that show added value of detection of early PAD beyond expectant management and traditional risk assessment. 相似文献
16.
D.B. Spronk C.P.M. Veth M. Arns P.R. Schofield C. Dobson-Stone J.G. Ramaekers B. Franke E.R.A. de Bruijn R.J. Verkes 《Clinical neurophysiology》2013,124(5):909-915
ObjectiveThe amplitude and latency of the P300 may be associated by variations in dopaminergic genes. The current study was conducted to determine whether functional variants of the catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) gene were associated with P300 amplitude and latency in an auditory oddball task.MethodsThe P300 ERP was assessed by a two-tone auditory oddball paradigm in a large sample of 320 healthy volunteers. The Val108/158Met polymorphism (rs4680) of the COMT gene and the ?1021C>T polymorphism (rs1611115) of the DBH gene were genotyped. P300 amplitude and latency were compared across genotype groups using analysis of variance.ResultsThere were no differences in demographic characteristics in subjects for genotypic subgroups. No genotype associations were observed for the P300 amplitude and latency on frontal, central and parietal electrode positions.ConclusionsCOMT Val108/158Met and DBH ?1021C>T polymorphisms do not show evidence of association with characteristics of the P300 ERP in an auditory oddball paradigm in healthy volunteers.SignificanceWe failed to find evidence for the association between dopaminergic enzymatic polymorphisms and the P300 ERP in healthy volunteers, in the largest study undertaken to date. 相似文献
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Bone Mass and Strength in School‐Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study 下载免费PDF全文
Carolina Medina‐Gomez Denise HM Heppe Jia‐Lian Yin Katerina Trajanoska André G Uitterlinden Thomas J Beck Vincent WV Jaddoe Fernando Rivadeneira 《Journal of bone and mineral research》2016,31(5):1099-1106
Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school‐age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole‐body and hip scans were measured using the same densitometer (GE‐Lunar iDXA) at a mean age of 6.2 years. Hip dual‐energy X‐ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole‐body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre‐ and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research. 相似文献
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