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61.
Kerr PJ Perkins HD Inglis B Stagg R McLaughlin E Collins SV Van Leeuwen BH 《Virology》2004,324(1):117-128
Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization. 相似文献
62.
63.
Somatic mutation processes at a human minisatellite 总被引:6,自引:3,他引:6
Germline instability at human minisatellites frequently involves complex
inter-allelic transfers of repeat units usually restricted to one end of
the repeat array and apparently regulated by flanking DNA. In contrast,
nothing is known about the structural basis of somatic instability at
minisatellites. An electrophoretic size-enrichment strategy was therefore
developed at minisatellite MS32 (D1S8) to enable rare abnormal-length
mutants to be detected, validated and quantitated in blood DNA by single
molecule PCR. Structural analysis of rare mutant alleles in blood revealed
simple deletions/duplications of repeat unit blocks located at random along
the tandem repeat array, a mode of mutation completely different from that
seen in sperm. Furthermore, allele-specific suppression of sperm
instability at MS32 did not affect somatic instability. These data suggest
that conversion-based minisatellite mutation in sperm is completely
germline-specific and most likely meiotic in origin. Somatic instability
appears to occur by a separate pathway involving replication slippage or,
more likely, intra-allelic unequal crossing over.
相似文献
64.
Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT) 总被引:4,自引:0,他引:4
Mutations in the TSC2 gene on chromosome 16p13.3 are responsible for
approximately 50% of familial tuberous sclerosis (TSC). The gene has 41
small exons spanning 45 kb of genomic DNA and encoding a 5.5 kb mRNA. Large
germline deletions of TSC2 occur in <5% of cases, and a number of small
intragenic mutations have been described. We analysed mRNA from 18
unrelated cases of TSC for TSC2 mutations using the protein truncation test
(PTT). Three cases were predicted to be TSC2 mutations on the basis of
linkage analysis or because a hamartoma from the patient showed loss of
heterozygosity for 16p13.3 markers. Three overlapping PCR products,
covering the complete coding sequence of mRNA, were generated from
lymphoblastoid cell lines, translated into 35S-methionine labelled protein,
and analysed by SDS-PAGE. PCR products showing PTT shifts were directly
sequenced, and mutations confirmed by restriction enzyme digestion where
possible. Six PTT shifts were identified. Five of these were caused by
mutations predicted to produce a truncated protein: (i) a sporadic case
showed a 32 bp deletion in exon 11, and a mutant mRNA without exon 11 was
produced; the normal exon 10 was also spliced out; (ii) a sporadic case had
a 1 bp deletion in exon 12 (1634delT); (iii) a TSC2-linked mother and
daughter pair had a G-->T transversion in exon 23 (G2715T) introducing a
cryptic splice site causing a 29 bp truncation of mRNA from exon 23; (iv) a
sporadic case showed a 2 bp deletion in exon 36; (v) a sporadic case showed
a 1 bp insertion disrupting the donor splice site of exon 37 (5007+2insA),
resulting in the use of an upstream exonic cryptic splice site to cause a
29 bp truncation of mRNA from exon 37. In one case, the PTT shift was
explained by in-frame splicing out of exon 10, in the presence of a normal
exon 10 genomic sequence. Alternative splicing of exon 10 of the TSC2 gene
may be a normal variant. Three 3rd base substitution polymorphisms were
also detected during direct sequencing of PCR products. Confirmed mutations
were identified in 28% of the families studied and on the assumption that
half of the sporadic cases should have TSC2 mutations, a crude estimate of
the detection rate would be 60%. This compares favourably with other
screening methods used for TSC2, notably SSCP, and since PTT involves much
less work it may be the method of choice.
相似文献
65.
A critical evaluation of current views regarding eye movement desensitization and reprocessing (EMDR): clarifying points of confusion. 总被引:1,自引:0,他引:1
EMDR is an active psychological treatment for PTSD that has received widely divergent reactions from the scientific and professional community. This article examines points of confusion in the published literature on EMDR, including the theoretical, empirical, and historical issues around EMDR and placebo effects, exposure procedures, the eye movement component, treatment fidelity issues, and outcome studies. It also examines historical information relevant to the scientific process and charges of "pseudoscience" regarding EMDR. We conclude that the confusion in the literature is due to (a) the lack of an empirically validated model capable of convincingly explaining the effects of the EMDR method, (b) inaccurate and selective reporting of research, (c) some poorly designed empirical studies, (d) inadequate treatment fidelity in some outcome research, and (e) multiple biased or inaccurate reviews by a relatively small group of authors. Reading the original research articles frequently helps to reduce the confusion arising from the research review literature. 相似文献
66.
Primary respiratory syncytial virus infection in mice 总被引:22,自引:0,他引:22
A mouse model of respiratory syncytial virus (RSV) infection is described. A high-titered, large-volume inoculum results in replication of RSV to a high titer in lungs of BALB/c mice. Mice older than 15 weeks of age are more susceptible to RSV infection. Titers up to 10(6.9) plaque-forming units (pfu)/gram lung can be attained in 32-week-old mice. Older mice experience a clinical illness manifested by ruffled fur, reduced activity, and weight loss. Lung histology of older mice infected with RSV shows bronchiolitis and increased number of lymphocytes and macrophages in alveolar spaces compared with that of mice less than 8 weeks old. This model will serve as the basis for investigating immunodeterminants of recovery and protection from RSV infection. 相似文献
67.
Detecting pre-ovulatory luteinizing hormone surges in urine 总被引:2,自引:1,他引:2
Kesner JS; Knecht EA; Krieg EF Jr; Wilcox AJ; O'Connor JF 《Human reproduction (Oxford, England)》1998,13(1):15-21
The study objectives were to determine (i) if pre-ovulatory luteinizing
hormone (LH) surges, undetected in urine by two immunoradiometric assays
(IRMA), were detectable by an ultrasensitive immunofluorometric assay
(IFMA) and (ii) the influence of creatinine adjustment on the detection and
timing of the urinary LH surges. Daily urine specimens were contributed by
healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for
an epidemiological study conducted in 1983-1985. Specimens were selected as
having been previously assayed by two IRMA without consistently detecting
LH surges. These urine specimens were remeasured using an IFMA and adjusted
for creatinine concentration. IFMA measurements revealed unambiguous LH
surges in all cycles. Adjusting IRMA urinary LH values for creatinine
concentrations revealed previously undetected LH surges in four of eight
cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH
surges by 1-5 days. These results demonstrate an IFMA that detects pre-
ovulatory LH surges in unpreserved, frozen urine from cycles where such
surges were previously undetectable. Further, creatinine adjustment can
markedly affect detection and timing of the onset and peak of the urinary
LH surge. While our analysis suggests that this adjustment improves the
validity of the LH measure, this requires further investigation.
相似文献
68.
69.
The cannabinoid system and immune modulation 总被引:13,自引:0,他引:13
Klein TW Newton C Larsen K Lu L Perkins I Nong L Friedman H 《Journal of leukocyte biology》2003,74(4):486-496
70.