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51.
Bedilu R Nummy KA Cooper A Wevers R Smeitink J Kleijer WJ Friderici KH 《Molecular genetics and metabolism》2002,77(4):282-290
Beta-mannosidosis is an autosomal recessive lysosomal storage disease resulting from a deficiency of the lysosomal enzyme beta-mannosidase. The clinical manifestations of this disease in reported human cases are very heterogeneous ranging from relatively mild to moderately severe. This is in contrast with the severe prenatal onset seen in ruminant beta-mannosidosis. In humans, mental retardation, hearing loss, frequent infections, and behavioral problems are relatively common. Dysmorphology and skeletal involvement such as those seen in ruminants are unusual. The purpose of this study is to determine the range of clinical expression in human beta-mannosidosis resulting from null mutations. We determined that the beta-mannosidase gene consists of 17 exons. Intron-based PCR primers were designed and used to amplify each of the exons in genomic DNA isolated from patient fibroblasts. We identified two patients with null mutations. Results of the analysis showed that one patient was heterozygous for nonsense mutations G334T (E83X) in exon 2 and C1363T (Q426X) in exon 10, resulting in truncation of the deduced peptide sequence from 879 to 82 and 425 amino acids, respectively. The second patient was homozygous for a deletion mutation in exon 11 (1541delAT). This deletion causes a reading frame shift and 26 out of frame amino acids before a stop codon occurs in exon 12, resulting in truncation of the deduced peptide sequence from 879 to 510 amino acids. Because disease presentation in these patients with null mutations is very variable, ranging from mild to severe, we conclude that beta-mannosidosis in humans may indeed be milder than typical of other lysosomal storage disorders. 相似文献
52.
Metes D Logar A Rudert WA Zeevi A Woodward J Demetris AJ Abu-Elmagd K Eghtesad B Shapiro R Fung JJ Trucco M Starzl TE Murase N 《Human immunology》2003,64(8):787-795
Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples. Detection of small numbers of major histocompatibility complex (MHC) mismatched cells was first studied using four-color flow cytometry in artificially created cell mixtures. By selecting the CD45(+) population and simultaneous staining with several leukocyte lineage markers (CD3, CD4, CD8, CD56, and CD19), MHC-mismatched leukocytes were consistently detected in cell suspensions prepared from directly stained whole blood samples with a threshold sensitivity as low as 0.1%-0.2%. When the fresh peripheral blood mononuclear cells were separated by conventional Ficoll gradient purification, similar, but slightly lower levels of donor cells were detected. Blood samples obtained 1-5 months after liver, kidney, and intestine transplants revealed that the kind of organ allograft influenced levels and lineage pattern of the circulating donor cells. This procedure provided a simple and reliable method in determining early chimerism in transplant recipients. However, the detection of MHC-mismatched leukocytes of all lineages was much lower when frozen peripheral blood mononuclear cells were used. 相似文献
53.
Identification of a novel coronavirus in patients with severe acute respiratory syndrome 总被引:1,自引:0,他引:1
Drosten C Günther S Preiser W van der Werf S Brodt HR Becker S Rabenau H Panning M Kolesnikova L Fouchier RA Berger A Burguière AM Cinatl J Eickmann M Escriou N Grywna K Kramme S Manuguerra JC Müller S Rickerts V Stürmer M Vieth S Klenk HD Osterhaus AD Schmitz H Doerr HW 《The New England journal of medicine》2003,348(20):1967-1976
54.
Simon Sanderson Ron Zimmern Mark Kroese Julian Higgins Christine Patch Jon Emery 《Genetics in medicine》2005,7(7):495-500
Advances in genetic technology are increasing the availability of genetic tests, not only for rare single gene disorders, but also for common diseases such as breast and colo-rectal cancer. Before there can be widespread uptake of these tests, they must be evaluated to confirm the benefits of their use. But how should genetic tests be evaluated, given the speed at which new tests are emerging? One highly influential approach is the analytic validity, clinical validity, clinical utility and ethical, legal and social issues (ACCE) framework, which has provided a benchmark for the evaluation of genetic tests. The approach has been adopted and adapted by the United Kingdom Genetic Testing Network, with the help of the Public Health Genetics Unit in Cambridge, to evaluate new genetic tests for use in the National Health Service. We discuss a number of conceptual, methodological, and practical issues concerning the evaluation of genetic tests, based on lessons learned from applying the ACCE framework and from the UK experience, and make a number of recommendations to further strengthen the evaluation of genetic tests. 相似文献
55.
56.
Joanne Young Barbara Leggett Corinne Gustafson Michael Ward Jeffrey Searle Lesley Thomas Ron Buttenshaw Georgia Chenevix-Trench 《Human mutation》1993,2(5):351-354
Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc. 相似文献
57.
58.
Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately. 相似文献
59.
Sarkar S Flores I Ron Y Derosa C Ozzello L Pestka S 《International journal of oncology》1995,7(1):17-24
Highly aggressive murine B16 melanoma was engineered to secrete IFN-alpha constitutively. Cells expressing IFN-alpha were injected into syngeneic C57BL/6 mice and the mice were monitored for tumor development. Secretion of IFN-alpha by B16 melanoma cells completely abrogated their tumorigenicity in syngeneic mice. LFN-alpha-secreting cells also abrogated the tumorigenicity of IFN-gamma-secreting and TNF-alpha-secreting cells when injected in combination whereas cells secreting either IFN-gamma or TNF-alpha grow progressively in mice when injected alone. Moreover, protected animals developed significant immunity against subsequent challenge with parental cells. Injection of parental cells and IFN-alpha-secreting cells together in a mixed tumor transplantation assay resulted in a significant reduction of tumorigenicity of the parental cells. Histopathological studies of the tissues from the injection site of the mice inoculated with a combination of parental and B16.IFN-alpha cells revealed the existence of a massive cellular infiltrate composed of lymphocytes and granulocytes at an early stage (7-11 days). In the later stages (22 days), no recognizable tumor tissue was detected. Injection of irradiated IFN-alpha-secreting cells in the mice carrying an established tumor completely prevented tumor development in 80% of the treated mice when injection was performed on the same side as the tumors. Injection of irradiated IFN-alpha-secreting cells in the contralateral site showed much less effect on the established tumor. Systemic antitumor effects on the established tumor can be enhanced by using a combination of irradiated IFN-alpha and IFN-gamma secreting cells as a vaccinating inoculum. 相似文献
60.
NGOs in community health insurance schemes: examples from Guatemala and the Philippines 总被引:3,自引:0,他引:3
Ron A 《Social science & medicine (1982)》1999,48(7):939-950
In poor rural communities, access to basic health care is often severely limited by inadequate supply as well as financial barriers to seeking care. National policies may introduce social health insurance, but these are likely to begin with the salaried public and private sector workers while the informal sector population may be the last to be covered. Community initiatives to generate health care financing require a complex development process. This paper covers attempts to develop such schemes in rural populations in Guatemala and the Philippines through non-government organizations and notes the major factors which have contributed to unequal progress in the two schemes. The scheme of the Association por Salud de Barillas (ASSABA) in Guatemala was not sufficiently established as an administrative body at the conceptual stage and there was no clear national policy on health care financing. By the time the necessary action was taken, local conflicts hindered progress. In the Philippines, the ORT Health Plus Scheme (OHPS) was implemented during the period of legislation of a national health insurance act. The appraisal after three years of operation shows that OPHS has made health care affordable and accessible to the target population, composed mainly of low and often unstable income families in rural areas. The major success factors are probably the administrative structure provided by a cooperative and controls in the delivery system and in expenditures, through the salaried primary health care team, referral process and the capitation agreement for hospital-based services. The proliferation of such schemes could benefit from national guidelines, a formal accreditation process and an umbrella organization to provide assistance in design, training and information services, involving government, non-government and academic institutions as an integral part of the development process. 相似文献