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101.
102.
JUAN C. DE LA TORRE MARGARET MALLORY MICHELLE BROT LISA GOLD GEORGE KOOB MICHAEL B. A. OLDSTONE ELIEZER MASLIAH 《Virology》1996,220(2):508
Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury. 相似文献
103.
104.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
105.
106.
Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts 总被引:4,自引:1,他引:4
Kilpatrick MW; Phylactou LA; Godfrey M; Wu CH; Wu GY; Tsipouras P 《Human molecular genetics》1996,5(12):1939-1944
The hammerhead ribozyme is a small catalytic RNA molecule. Potential
hammerhead ribozymes that possess a catalytic domain and flanking sequence
complementary to a target mRNA can cleave in trans at a putative cleavage
site within the target molecule. We have investigated the potential of
hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene
(FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of
the elastin-associated microfibrils. Mutations in the FBN1 gene are
responsible for Marfan syndrome (MFS), a common systemic disorder of the
connective tissue. Many FBN1 mutations responsible for MFS appear to act in
a dominant-negative fashion, raising the possibility that reduction of the
amount of product from the mutant FBN1 allele might be a valid therapeutic
approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to
the 5' end of the human FBN1 mRNA has been designed and synthesized, and
shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is
magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of
the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor-
mediated endocytosis of a ribozyme-transferrin-polylysine complex,
specifically reduces both cellular FBN1 mRNA and the deposition of
fibrillin in the extracellular matrix. These results suggest that the use
of hammerhead ribozymes is a valid approach to the study of fibrillin gene
expression and possibly to the development of a therapeutic approach to
MFS.
相似文献
107.
J. Richard Jennings Maurits W. VAN DER Molen Riek J.M. Somsen Cynthia Terezis 《Psychophysiology》1990,27(4):385-395
The influence of inducing motor responses of low and high force at different times in the cardiac cycle was examined. A handgrip response was used which allowed the separation of response initiation from response completion. Based on earlier work, we expected initiation, rather than completion, to initiate poststimulus cardiac acceleration. We also thought that preparation for a high force response might alter preparatory changes of interbeat interval differently from preparation for a low force response. Fifteen college-aged male subjects performed a warned reaction time task in which a visual stimulus signalled a handgrip requiring either a high or a low force to close. NoGo trials in which an inhibit signal was presented occurred on 12% of the trials. Stimuli occurred either on the R-wave of the electrocardiogram or 300 ms later. Reaction speed was varied in different trial blocks by rewarding response times of 200 ms (+/- 50 ms), 300 ms, or 400 ms. Results based on the timing of response initiation were essentially identical to those based on the timing of response completion. High force relative to low force was associated with both earlier response initiation and earlier cardiac acceleration. Force did not alter preparatory cardiac deceleration. Force and response speed did, however, alter the level of heart rate after response occurrence. Thus, response initiation (or an earlier response process) appears to induce a cardiac acceleration whose level is influenced by the speed and force of the motor response. 相似文献
108.
C. DE GRAAF-IN'T VELD I. M. GARRELDS A. P. H. JANSEN A. W. VAN TOORENENBERGEN P. G. H. MULDER J. MEEUWIS R. GERTH VAN WIJK 《Clinical and experimental allergy》1995,25(10):966-973
Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa. 相似文献
109.
Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1) 总被引:2,自引:0,他引:2
Banfi S; Servadio A; Chung M; Capozzoli F; Duvick LA; Elde R; Zoghbi HY; Orr HT 《Human molecular genetics》1996,5(1):33-40
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant
neurodegenerative disorder caused by the expansion of a CAG trinucleotide
repeat which encodes glutamine in the novel protein ataxin-1. In order to
characterize the developmental expression pattern of SCA1 and to identify
putative functional domains in ataxin-1, the murine homolog (Sca1) was
isolated. Cloning and characterization of the murine Sca1 gene revealed
that the gene organization is similar to that of the human gene. The murine
and human ataxin-1 are highly homologous but the CAG repeat is virtually
absent in the mouse sequence suggesting that the polyglutamine stretch is
not essential for the normal function of ataxin-1 in mice. Cellular and
developmental expression of the murine homolog was examined using RNA in
situ hybridization. During cerebellar development, there is a transient
burst of Sca1 expression at postnatal day 14 when the murine cerebellar
cortex becomes physiologically functional. There is also marked expression
of Sca1 in mesenchymal cells of the intervertebral discs during development
of the spinal column. These results suggest that the normal Sca1 gene, has
a role at specific stages of both cerebellar and vertebral column
development.
相似文献
110.
JE Robb LA Rymaszewski HB Bentley PT Donnan 《Surgical and radiologic anatomy : SRA》1991,13(3):181-185
Summary This study investigated the effect of tilt and observer reliability on radiographic measurements of the position of a prosthetic acetabular cup in seven dry bone pelves using the teardrop as a landmark. Coronal or sagittal tilt of more than five degrees was easily recognisable and there was effectively no observer variation in the measurements up to this limit. In addition, 90 out of 100 randomly selected antero-posterior pelvic radiographs from an outpatient department were not significantly rotated and 93 demonstrated a clearly defined teardrop. Measurements about the teardrop on routine radiographs are therefore sufficiently accurate to allow assessment of prosthetic position.
La valeur du sourcil cotyloidien comme repère d'analyse radiologique
Résumé Cette étude, conduite sur 7 bassins secs, apprécie l'effet de l'inclinaison du bassin sur la qualité de l'analyse radiographique de la position d'une cupule prothétique de hanche en utilisant le sourcil cotyloïdien comme repère. Une inclinaison du bassin dans les plans coronal et sagittal est aisément détectable et il n'existe pas de variation d'analyse entre les différents observateurs en dessous de 5° d'inclinaison. De plus, sur 100 radiographies antéro-postérieures de bassin choisies au hasard dans les dossiers de consultation, 90 avaient été réalisées sans incidence particulièrement adaptée et l'on pouvait repérer facilement le sourcil sur 93% d'entre elles. Les mesures faites sur des radios de routine sont donc suffisamment précises pour permettre l'évaluation de la position d'une prothèse à partir du sourcil cotyloïdien.相似文献