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991.
Mouse mutagenesis-systematic studies of mammalian gene function 总被引:5,自引:0,他引:5
The mouse will play a pivotal role in mammalian gene function studies as we
enter the post-genomics era. The challenge is to develop systematic,
genome-wide mutagenesis approaches to the study of gene function. The
current mouse mutant resource has been an important source of human genetic
disease models. However, despite an apparently large catalogue of mouse
mutations, we have access to mutations at only a small fraction of the
likely total number of mammalian genes-there is a phenotype gap that needs
to be filled by the establishment of new mutagenesis programmes. Two
routes, genotype- and phenotype-driven, can be used for the recovery of
novel mouse mutations. For the former, gene trap embryonic stem cell
libraries appear set to deliver a large number of mutations around the
mouse genome. The advantage of genotype-driven approaches is the ease of
identification of the mutated locus; the disadvantage that a priori
assumptions have to be made concerning the function and likely phenotype of
the mutated gene. In contrast, phenotype-driven mutagenesis emphasizes the
recovery of novel phenotypes. One phenotype-driven approach that will play
an important role in expanding the mouse mutant resource employs the
mutagen N-ethyl- N-nitrosourea (ENU). The phenotype-driven route makes no
assumptions about the underlying genes involved, and ENU mutagenesis
programmes can be expected to play a significant role in uncovering novel
pathways and genes; the disadvantage is that the identification of the
mutant gene is still not trivial. Together, the complementary routes of
genotype- and phenotype-driven mutagenesis will provide a much enlarged
catalogue of mouse mutations and phenotypes for future gene function
studies.
相似文献
992.
Weksberg R.; Teshima I.; Williams B.R.G.; Greenberg C.R.; Pueschel S.M.; Chernos J.E.; Fowlow S.B.; Hoyme E.; Anderson I.J.; Whiteman D.A.H.; Fisher N.; Squire J. 《Human molecular genetics》1993,2(5):549-556
To define the region of 11p15 involved in BeckwlthWiedemannsyndrome (BWS), we have carried out a molecular genetic analysisof six patients with features of BWS and constitutional cytogeneticabnormalities involving chromosome band 11pl5. Molecular analysisconfirmed the 11p origin of the duplicated material and definedthe smallest region of overlap for such duplications, withinwhich a gene involved in BWS must be located. This region encompassesthe ß-globin gene complex (HBB) to 11pter. In bothof our informative cases, the 11p duplication was found to beof paternal origin. Two BWS associated balanced traitslocatioasof 11p15 were studied to localize the breakpoints on 11p15.Somatic cell hybrids, Southern blotting and fluorescent in situhybridization (FISH) showed that both breakpoints were betweenD11S12 and the insulin-like growth factor 2 (IGF2) gene. A non-BWStranslocation breakpoint was more proximal, between HBB andcalcitonin-A (CALCA). Pedigree analysis showed that both BWSassociated 11p15 translocations were transmitted by phenotypicallynormal mothers. The data are compatible with the hypothesisthat the BWS gene is imprinted and that the maternally inheritedBWS gene is normally suppressed whereas the paternally inheritedallele is active. Thus, duplications of paternal origin wouldlead to increased dosage of the BWS gene. Similarly increaseddosage of the BWS gene could account for the findings in maternallyinherited 11p15 translocations by altering normal imprinting,so that the translocated maternal allele remains active. Thisstudy defines one or more gene loci for BWS on 11p15.5 in thegenomic region from D11512
[GenBank] to IGF2. 相似文献
993.
Chondromyxoid fibroma is a rare benign bone tumor most commonly arising in the metaphysis of long bones in young adults. Histopathologically, chondromyxoid fibroma may be difficult to distinguish from other cartilaginous neoplasms. Recently, a pericentric inversion of chromosome 6 [inv(6)(p25q13)] has been proposed as a specific genetic marker for chondromyxoid fibroma. In this study, cytogenetic and spectral karyotypic analyses of 2 chondromyxoid fibroma cases showed clonal abnormalities of chromosome 6 but at a breakpoint on the long arm (q25) distal to that described in the pericentric inversion. These findings suggest that several distinct breakpoints on chromosome 6 are nonrandomly involved in chondromyxoid fibroma. 相似文献
994.
Male rats treated with either budesonide, prednisolone, or triamcinolone acetonide in drinking water for up to 104 weeks developed slightly increased incidences of basophilic foci, and significantly increased incidences of combined hepatocellular adenomas/carcinomas as compared to controls. Based upon reduced body weight gains and survivals, the doses administered were considered to be toxic. It was concluded that the positive findings represented a class effect, and probably involved glucocorticoid receptors. 相似文献
995.
Cemented rotating-platform total knee replacement. A nine to twelve-year follow-up study 总被引:9,自引:0,他引:9
Callaghan JJ Squire MW Goetz DD Sullivan PM Johnston RC 《The Journal of bone and joint surgery. American volume》2000,82(5):705-711
BACKGROUND: Although the LCS (low contact stress) rotating-platform mobile-bearing knee replacement has been used extensively, there have been few intermediate or long-term clinical and radiographic follow-up studies evaluating the device. The purpose of this study was to report the nine to twelve-year results of a consecutive series of patients who had a primary total knee replacement performed with this device. METHODS: Between November 1985 and November 1988, the senior author (R. C. J.) performed 119 consecutive total knee arthroplasties in eighty-six patients with LCS rotating-platform femoral and tibial components and a Townley all-polyethylene dome patellar component. All components were fixed with cement. The average age of the patients at the time of the operation was seventy years (range, thirty-seven to eighty-eight years). Fifty-two patients (seventy-six knees) were female, and thirty-four patients (forty-three knees) were male. The patients were evaluated with clinical knee ratings and radiographic analysis nine to twelve years following the knee replacement. RESULTS: At the time of the nine to twelve-year follow-up, sixty-four patients (eighty-six knees) were alive, eighteen patients (twenty-eight knees) had died, and four patients (five knees) had been lost to follow-up. Of the 114 knees in the eighty-two patients for whom the final outcome was known, none required a reoperation and none had a dislocation of the mobile-bearing prosthesis. For the forty-five patients (sixty-six knees) who returned for final clinical and radiographic follow-up examinations at nine to twelve years, the average clinical and functional Knee Society ratings were 30 points (range, 2 to 70 points) and 44 points (range, 0 to 80 points) preoperatively and 90 points (range, 63 to 102 points) and 75 points (range, 30 to 100 points) at the final follow-up evaluation. The average Hospital for Special Surgery knee rating was 57 points (range, 28 to 80 points) preoperatively and 84 points (range, 59 to 97 points) at the final follow-up evaluation. The average active range of knee flexion was from 0 degrees (range, 0 to 10 degrees) to 102 degrees (range, 15 to 120 degrees) at the final follow-up evaluation. Seven of the sixty-six knees were painful anteriorly. There was no periprosthetic osteolysis and no evidence of loosening on follow-up radiographs. CONCLUSIONS: After nine to twelve years of follow-up, the cemented LCS rotating-platform knee replacement was found to be performing well, with durable clinical and radiographic results. 相似文献
996.
Assessment of Mycn Amplification in Neuroblastoma Biopsies by Differential Polymerase Chain Reaction
Scott Boerner Jeremy Squire Paul Thorner Gregory McKenna Maria Zielenska 《Fetal and pediatric pathology》1994,14(5):823-832
Amplification of the oncogene MYCN is a genetic change frequently observed in neuroblastoma and is an indicator of poor prognosis. MYCN copy number is currently determined by Southern blot hybridization. This technique takes 2 to 3 weeks, is labor-intensive, is sensitive to DNA degradation, and requires large quantities of DNA. We have evaluated a new, semiquantitative method of estimating gene copy number that uses differential polymerase chain reaction (PCR). The procedure can be performed in 1 day, is highly reproducible, and requires only nanogram quantities of DNA. It employs a semiquantitative, nonisotopic PCR technique based on differential competition for PCR substrates. MYCN gene primers are amplified together with primers from a single-copy internal control gene. Following electrophoretic separation, the ratio of the two PCR products is determined visually and by densitometric analysis of ethidium bromide-stained agarose gels. This differential ratio is then compared to a series of ratios generated from standards of known MYCN gene copy number. We compared the results obtained by this differential PCR method with those obtained by conventional Southern blotting in 16 cases of primary neuroblastoma. All amplified tumors were detected by differential PCR and no false positives were observed. We confirmed that differential PCR is a rapid and reliable alternative to Southern blotting for MYCN copy number assessment and is highly suited to the analysis of DNA derived from needle biopsies. 相似文献
997.
Validity of a Self-reported Periodontal Disease Measure 总被引:3,自引:0,他引:3
Kaumudi J. Joshipura BDS SD ; Chester W. Douglass DMD PhD ; Raul I. Garcia DMD MMedSc ; Richard Valachovic DMD MPH ; Walter C. Willett MD DrPH 《Journal of public health dentistry》1996,56(4):205-212
Objectives : The purpose of this study was to determine the validity of a self-reported periodontal disease measure for use in the Health Professionals Follow-up Study. Methods : Participating dentists responded to the question “Have you had periodontal disease with bone loss?” Radiographs obtained from 140 participants were evaluated for bone loss at 32 posterior sites and used as the standard. A site was positive if it had bone loss >2 mm and/or complete loss of crestal lamina dura. To avoid falsely classifying participants as positive, three blinded examiners independently evaluated each participant's radiographs. An a priori decision rule was used to classify a participant positive if all examiners independently assessed the same two or more sites positive. Results : The validity of the self-reported measure was good among dentists, with positive and negative predictive values of 0.76 and 0.74, respectively. Among nondentists, the self-reported measure showed discriminatory power by confirming associations with known risk factors such as age and smoking. Conclusion : Dentists have a good perception of their periodontal status, and there is reasonable consensus among dentists regarding the threshold for defining periodontal disease. Self-reported measures might have potential for use in studies of other populations with substantial cost reduction, and deserve further evaluation. 相似文献
998.
High rates of TB amongst new arrivals to the UK require flexible, innovative responses that go beyond traditional biomedical models and take into account the needs of these heterogeneous groups. This article explores the merging of public health and human rights based approaches to TB control in response to the challenge of increasing rates of TB amongst new arrivals in the UK. 相似文献
999.
1000.
Memory for relations in the short term and the long term after medial temporal lobe damage 下载免费PDF全文
Larry R. Squire 《Hippocampus》2017,27(5):608-612
A central idea about the organization of declarative memory and the function of the hippocampus is that the hippocampus provides for the coding of relationships between items. A question arises whether this idea refers to the process of forming long‐term memory or whether, as some studies have suggested, memory for relations might depend on the hippocampus even at short retention intervals and even when the task falls within the province of short‐term (working) memory. The latter formulation appears to place the operation of relational memory into conflict with the idea that working memory is independent of medial temporal lobe (MTL) structures. In this report, the concepts of relational memory and working memory are discussed in the light of a simple demonstration experiment. Patients with MTL lesions successfully learned and recalled two word pairs when tested directly after learning but failed altogether when tested after a delay. The results do not contradict the idea that the hippocampus has a fundamental role in relational memory. However, there is a need for further elaboration and specification of the idea in order to explain why patients with MTL lesions can establish relational memory in the short term but not in long‐term memory. © 2017 Wiley Periodicals, Inc. 相似文献