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Jessica Lasky-Su Tobias Banaschewski Jan Buitelaar Barbara Franke Keeley Brookes Edmund Sonuga-Barke Richard Ebstein Jacques Eisenberg Michael Gill Iris Manor Ana Miranda Fernando Mulas Robert D Oades Herbert Roeyers Aribert Rothenberger Joseph Sergeant Hans-Christoph Steinhausen Eric Taylor Kaixin Zhou Margaret Thompson Philip Asherson Stephen V Faraone 《Neuropsychopharmacology》2007,62(9):985-990
BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association. 相似文献
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Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel 总被引:13,自引:0,他引:13
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Shulman LM Manor Y Handsher R Delpeyroux F McDonough MJ Halmut T Silberstein I Alfandari J Quay J Fisher T Robinov J Kew OM Crainic R Mendelson E 《Journal of clinical microbiology》2000,38(10):3729-3734
An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40 degrees C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A(481) to G in the 5' untranslated region and the VP1 amino acid I(143) to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for approximately 6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication. 相似文献
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Integration of viral into chromosomal deoxyribonucleic acid in an inducible line of polyoma-transformed cells 总被引:10,自引:0,他引:10
RNA-DNA hybridization has shown that in poiyoma-transformed rat cells which can be induced to synthesize infectious virus (LPT cells), polyoma DNA sequences are associated with chromosomal DNARNA complementary to the viral DNA (cRNA) was synthesized in vitro, using purified viral DNA as a template and Escherichia coli RNA polymerase. High-molecular-weight chromosomal DNA was fractionated from linear and supercoiled viral DNA molecules by centrifugation of whole cells through alkaline glycerol gradients. Hybridization carried out between the cRNA and fractionated chromosomal DNA showed that the amount of RNA hybridized to the LPT DNA was two to three times larger than the amount hybridized to DNA from normal rat cells. cRNA was also hybridized, under the same conditions, with mixtures containing a constant amount of normal cell DNA and varying quantities of purified viral DNA. These assays have established that a linear relationship exists between the amount of cRNA specifically hybridized with a given sample of DNA and the quantity of viral DNA in the sample. Using this relationship, it is estimated that LPT chromosomal DNA contains 6–9 genome-equivalents of polyoma DNA per cell. This quantity represents 18–29% of the amount of polyoma DNA found in the cells, as determined by hybridization of cRNA with unfractionated LPT DNA.To exclude the possibility that the chromosomally associated viral DNA is an artifact due to incomplete removal of the extrachromosomal viral DNA, control experiments were performed in which the cells were superinfected with polyoma virus (m.o.i.-500; 3 hr infection). In these experiments, less than 1% of the viral DNA introduced into the cells by the superinfecting virus were found by the same techniques to be associated with chromosomal DNA. Other experiments show that LPT cells do not contain significant amounts of complex viral DNA molecules which sediment in the vicinity of chromosomal DNA. It is therefore suggested that viral and chromosomal DNA are bound to each other by bonds which cannot be disrupted by alkali treatment. 相似文献
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Hagit Daum Hagar Mor‐Shaked Asaf Ta‐Shma Avraham Shaag Shira Silverstein Mordechai Shohat Orly Elpeleg Vardiella Meiner Tamar Harel 《American journal of medical genetics. Part A》2020,182(4):689-696
Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms. 相似文献
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Sigal Teitz M.D. Ahuva Guidetti-Sharon M.D. Hana Manor M.D. Prof. Ariel Halevy M.D. 《Diseases of the colon and rectum》1995,38(11):1220-1223
PURPOSE: Carcinoma of the colon, manifested clinically as an enterococcal hepatic abscess, in the absence of liver metastases, is very uncommon. However, having treated a patient with such a condition, we would like to draw the attention of surgeons to this possibility. Most reports describe secondary infections of hepatic metastases only in patients with a known malignancy. However, increased awareness of colonic cancer as an underlying cause of pyogenic liver abscesses will afford earlier diagnosis and treatment. METHODS: The case was analyzed for history, presentation, laboratory data, radiologic studies, and bacteriology. RESULTS: A 66-year-old woman presented with abdominal pain, fever, and chills. Imaging scans revealed a solitary liver abscess, which was successfully treated with percutaneous drainage and broad-spectrum intravenous antibiotics. Pus cultures grew
Streptococcus faecalis.A search for the underlying cause led to the discovery of an adenocarcinoma of the sigmoid colon. CONCLUSIONS: An aggressive search for the underlying cause of pyogenic liver abscesses should be an integral part of the definitive treatment of this disease. After prevailing etiologies have been excluded, silent colonic cancer should be considered. 相似文献
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I. Blickstein M. Manor R. Levi R. Goldchmit A. Weissman 《International journal of gynaecology and obstetrics》1995,50(3):253-255
Objective: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. Method: The fetal ponderal index (estimated fetal weight ÷ femur length3) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. Results: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (<15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15–25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (>25%) pairs. Conclusion: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations. 相似文献
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Vishlitzky V Nessabramof R Zemer R Ellis M Lishner M Manor Y Yuklea M Klein A 《Oncology reports》1995,2(3):461-463
Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. One group of apoptosis inducers are glucocorticosteroids which are also found in the battery of cytotoxic drugs used to treat CLL. In the present study we have examined the potency of the glucocorticosteroid-dexamethasone to induce apoptosis in lymphocytes of patients with B-CLL. Lymphocytes of 15 nontreated patients and 5 controls were isolated and incubated for 24 h in the presence or absence of dexamethasone (2 mu M) Following incubation the cells were harvested and their DNA extracted. The extracted DNA samples were analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. Five patients showed neither spontaneous nor dexamethasone induced apoptosis. Whereas, 10 patients, showed a dexamethasone-non-dependent spontaneous apoptosis which appeared 24 h after the start of incubation. The cells of these patients were the only ones to respond to dexamethasone showing an enhanced apoptosis effect. This study shows that apoptosis monitoring in CLL may provide important information regarding susceptibility of the cells to steroid induced apoptosis. 相似文献
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