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1.
Germline mutations of the CDKN2 gene in UK melanoma families 总被引:4,自引:1,他引:4
Harland M; Meloni R; Gruis N; Pinney E; Brookes S; Spurr NK; Frischauf AM; Bataille V; Peters G; Cuzick J; Selby P; Bishop DT; Bishop JN 《Human molecular genetics》1997,6(12):2061-2067
Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin
D kinase inhibitor p16, and more rarely, mutations in the gene coding for
CDK4, the protein to which p16 binds, underlie susceptibility in some
melanoma families. We have sequenced all exons of CDKN2 and analysed the
CDK4 gene for mutations in 27 UK families showing evidence of
predisposition to melanoma. Five different germline mutations in CDKN2 were
found in six families. Three of the mutations (Met53Ile, Arg24Pro and
23ins24) have been reported previously. We have identified two novel CDKN2
mutations (88delG and Ala118Thr) which are likely to be associated with the
development of melanoma, because of their co-segregation with the disease
and their likely functional effect on the CDKN2 protein. In binding assays
the protein expressed from the previously described mutation, Met53Ile, did
not bind to CDK4/CDK6, confirming its role as a causal mutation in the
development of melanoma. Ala118Thr appeared to be functional in this assay.
Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were
detected in exon 2 of CDK4, suggesting that causal mutations in this gene
are uncommon. The penetrance of these mutant CDKN2 genes is not yet
established, nor is the risk of non-melanoma cancer to gene carriers.
相似文献
2.
Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient''s state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.KEY WORDS: Histocompatibility (HLA) matching, Cross match, Sensitization 相似文献
3.
Abstract: This female Asian (Malay) baby had clinical features of Proteus syndrome. She had a large right facial lipolymphangioma with hyperpigmentation of the overlying skin. There was a smaller lymphangioma over the left side of her neck with excess nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the extensive hemifacial swelling, there was no evidence of upper respiratory tract obstruction. Generalized seizures developed on the sixth day of life which were controlled with phenobarbital. The lymphangiomas were excised without recurrence. 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.
Vikram Kilambi F. Reed Johnson Juan Marcos González Ateesha F. Mohamed 《Value in health》2014,17(8):838-845
BackgroundThe value of the information that genetic testing services provide can be questioned for insurance-based health systems. The results of genetic tests oftentimes may not lead to well-defined clinical interventions; however, Lynch syndrome, a genetic mutation for which carriers are at an increased risk for colorectal cancer, can be identified through genetic testing, and meaningful health interventions are available via increased colonoscopic surveillance. Valuations of test information for such conditions ought to account for the full impact of interventions and contingent outcomes.ObjectivesTo conduct a discrete-choice experiment to elicit individuals’ preferences for genetic test information.MethodsA Web-enabled discrete-choice experiment survey was administered to a representative sample of US residents aged 50 years and older. In addition to specifying expenditures on colonoscopies, respondents were asked to make a series of nine selections between two hypothetical genetic tests or a no-test option under the premise that a relative had Lynch syndrome. The hypothetical genetic tests were defined by the probability of developing colorectal cancer, the probability of a false-negative test result, privacy of the result, and out-of-pocket cost. A model specification identifying necessary interactions was derived from assumptions of risk behavior and the decision context and was estimated using random-parameters logit.ResultsA total of 650 respondents were contacted, and 385 completed the survey. The monetary equivalent of test information was approximately $1800. Expenditures on colonoscopies to reduce mortality risks affected valuations. Respondents with lower income or who reported being employed significantly valued genetic tests more.ConclusionGenetic testing may confer benefits through the impact of subsequent interventions on private individuals. 相似文献
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8.
Hasegawa DK; Bennett AJ; Coccia PF; Ramsay NK; Nesbit ME; Krivit W; Edson JR 《Blood》1980,56(4):585-595
Factor V deficiency has been identified in 8 of 8 patients 7--20 yr of age, with Philadelphia-positive (Ph1+) chronic myelogenous leukemia (CML). In these 8 patients, factor V deficiency was not due to hepatic dysfunction, factor V inhibitors, or disseminated intravascular coagulation. In 3 patients, factor V activity rose 10%--12% (0.10--0.12 U/ml) after the infusion of 28--31 ml/kg body weight of fresh frozen plasma (FFP). The rise persisted less than 14 hr. The mean measured postinfusion rise in factor V was 18% of the expected rise calculated from the volume of FFP infused in the patients' plasma volume. In 4 patients, a small transient rise in factor V activity occurred after splenectomy or plateletpheresis. Factor V deficiency was completely corrected after a marked reduction in bone marrow cellularity in 2 patients with Ph1+ CML treated with extensive chemotherapy, total body irradiation, and bone marrow transplantation. Factor V deficiency was retrospectively observed in 6 of 20 patients, ages 20--80 yr, with Ph1+ CML and 3 of 6 patients with other myeloproliferative disorders. The factor V deficiency appears to be associated with the large myeloid- megakaryocytic cell mass characteristic of CML and other myeloproliferative disorders. 相似文献
9.
Ashley E. Davis Sanjay Mehrotra Vikram Kilambi Joseph Kang Lisa McElroy Brittany Lapin Jane Holl Michael Abecassis John J. Friedewald Daniela P. Ladner 《Clinical journal of the American Society of Nephrology》2014,9(8):1449-1460
Background and objectives
The Statewide Sharing variance to the national kidney allocation policy allocates kidneys not used within the procuring donor service area (DSA), first within the state, before the kidneys are offered regionally and nationally. Tennessee and Florida implemented this variance. Known geographic differences exist between the 58 DSAs, in direct violation of the Final Rule stipulated by the US Department of Health and Human Services. This study examined the effect of Statewide Sharing on geographic allocation disparity over time between DSAs within Tennessee and Florida and compared them with geographic disparity between the DSAs within a state for all states with more than one DSA (California, New York, North Carolina, Ohio, Pennsylvania, Texas, and Wisconsin).Design, setting, participants, & measurements
A retrospective analysis from 1987 to 2009 was conducted using Organ Procurement and Transplant Network data. Five previously used indicators for geographic allocation disparity were applied: deceased-donor kidney transplant rates, waiting time to transplantation, cumulative dialysis time at transplantation, 5-year graft survival, and cold ischemic time.Results
Transplant rates, waiting time, dialysis time, and graft survival varied greatly between deceased-donor kidney recipients in DSAs in all states in 1987. After implementation of Statewide Sharing in 1992, disparity indicators decreased by 41%, 36%, 31%, and 9%, respectively, in Tennessee and by 28%, 62%, 34%, and 19%, respectively in Florida, such that the geographic allocation disparity in Tennessee and Florida almost completely disappeared. Statewide kidney allocations incurred 7.5 and 5 fewer hours of cold ischemic time in Tennessee and Florida, respectively. Geographic disparity between DSAs in all the other states worsened or improved to a lesser degree.Conclusions
As sweeping changes to the kidney allocation system are being discussed to alleviate geographic disparity—changes that are untested run the risk of unintended consequences—more limited changes, such as Statewide Sharing, should be further studied and considered. 相似文献10.
Sushma Bhatnagar Saraswathi Devi NK Vinod PN Jain G Durgaprasad Sanjaykumar H Maroo Ketan R Patel 《Indian Journal of Palliative Care》2014,20(3):182-187