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111.
Jennifer A. Ruskey Lior Greenbaum Léanne Roncière Armaghan Alam Dan Spiegelman Christopher Liong Oren A. Levy Cheryl Waters Stanley Fahn Karen S. Marder Wendy Chung Gilad Yahalom Simon Israeli-Korn Vered Livneh Tsvia Fay-Karmon Roy N. Alcalay Sharon Hassin-Baer Ziv Gan-Or 《European journal of medical genetics》2019,62(1):65-69
Background
Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.Methods
GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (n?=?3044) from the Inflammatory Bowel Disease Exome Portal was used.Results
Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA-associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (OR?=?2.7, 95%CI?=?1.9–3.8, p?<?0.0001).Conclusion
Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials. 相似文献112.
R B Levisky A M Vianna-Morgante O Frota-Pessoa M Scaff A M Tsanaclis J A Levy 《Journal of medical genetics》1977,14(1):51-53
The present report describes a sibship with 2 individuals affected by myotonic dystrophy and a third with syringomyelia. The mother was affected by myotonic dystrophy. A balanced 2/13 translocation was detected in the individual with syringomyelia, in one affected by myotonic dystrophy and in their clinically normal father. The association between the phenotypic anomalies and the chromosome alteration is coincidental. 相似文献
113.
Catherine Neauport-Sautes Daniele Silvestre Marie-Gabrielle Niccolai F. M. Kourilsky J. P. Levy 《Immunology》1972,22(5):833-845
The localization of HL-A histocompatibility antigens at the surface of human lymphocytes in electron microscopy has been studied using hybrid antibodies to bind electron-dense particles (ferritin and plant viruses) to anti-HL-A antibody. A discontinuous distribution of the markers is observed at the cell surface, which is identical with that described for H-2 antigens on mouse lymphocytes with the same technique. Double labelling experiments suggest that the areas of the cell surface where HL-A antigens are detected contain also the heterologous lymphocyte antigens detected by an anti-thymocyte serum and that HL-A antigens are not renewed at a detectable level during the period of the labelling procedure in the areas of the cell surface which are not labelled primarily with ferritin-anti-IgG-anti-HL-A complexes. The interpretation of the discontinuous labelling of HL-A antigens with direct immunoferritin techniques is discussed. 相似文献
114.
1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
115.
Subcellular Localization of Salmonella enteritidis Endotoxin in Liver and Spleen of Mice and Rats 下载免费PDF全文
Salmonella enteritidis14C-endotoxin was recovered predominantly from the nuclear and mitochondrial subcellular fractions of livers and spleens of mice and rats, 3.5 hr and 3 days after intravenous administration. Of the recovered radioactivity, 10 to 20% was present in the liver mitochondrial fraction as high-molecular-weight, biologically active material, suggesting the presence of intact endotoxin. Autoradiographic studies demonstrated nuclear and cytoplasmic labeling in the liver and at least nuclear label in spleen cells. The resistance of rats, as compared to mice, to the induction of amyloidosis does not appear to be based on a difference in subcellular localization of endotoxin within the reticuloendothelial system. 相似文献
116.
Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant. 总被引:1,自引:2,他引:1 下载免费PDF全文
Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity. The primary antibody response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine was significantly potentiated if the vaccine was combined with PICLC prior to vaccination. The antibody response was maintained at a significantly higher level than controls for 2.5 months postvaccination and paralleled immunological responses reported for live, attenuated (TC-83) vaccine. 相似文献
117.
Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. 总被引:8,自引:4,他引:8 下载免费PDF全文
Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model. 相似文献
118.
L M Dunkle A M Arvin R J Whitley H A Rotbart H M Feder S Feldman A A Gershon M L Levy G F Hayden P V McGuirt 《The New England journal of medicine》1991,325(22):1539-1544
BACKGROUND. Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS. To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS. The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS. Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain. 相似文献
119.
One contributing factor to the loss of T cells in AIDS may be the impaired ability of T cell precursors to expand, as reflected in a decreased ability of patient cells to form T cell colonies in agar. We and others have noted such a defect in people with AIDS and ARC, and have found that suppressor cells and suppressive plasma contribute to decreased T-CFC formation. We report here that the reducing agents 2-mercaptoethanol (2-ME) and n-acetyl cysteine (NAC) can enhance colony formation in vitro. In part, 2-ME can reverse the defect in T cell colony-forming cells (T-CFC) formation by overcoming the effect of suppressor cells. In a group of 46 AIDS patients, T-CFC formation was initially 42 +/- 8% (mean +/- s.e.) that of control levels. 2-ME caused an increase of 401 +/- 76% in T-CFC formation which was significantly greater than the increase in control T-CFC formation; it also significantly enhanced T-CFC formation by cells from ARC patients. Suppressor cell activity from ten AIDS patients decreased from 58 +/- 21% to 12 +/- 10% when 2-ME was added. Similar data were obtained from 14 ARC patients. NAC, a related antioxidant with low toxicity, also enhanced T-CFC in cells of AIDS and ARC patients. Vitamin C generally did not increase T-CFC formation. The data suggest that certain antioxidants such as 2-ME and NAC may be useful in treatment protocols to enhance T cell numbers in patients with AIDS or ARC. 相似文献
120.
Susceptibility of thymectomized and irradiated mice to challenge with several organisms and the effect of dapsone on infection with Mycobacterium leprae. 总被引:1,自引:4,他引:1 下载免费PDF全文
B6C3F1 mice that had been thymectomized at 8 to 12 weeks of age, subjected to 950 R of whole-body X irradiation, and transfused with syngeneic bone marrow were challenged in a footpad with Mycobacterium leprae or M. marinum, or intravenously or intraperitioneally with Listeria monocytogenes. Also, mice inoculated with M. leprae in a hind footpad were administered dapsone in the mouse chow. The thymectomized-irradiated (T + R) mice did not survive as well as non-thymectomized mice when housed in the vivarium with no special precautions, but survived sufficiently well to permit the completion of some long-term experiments. M. leprae multiplied to a higher "ceiling" and survived longer in the T + R mice than in the non-thymectomized controls. But a ceiling to multiplication of M. leprae was imposed, and finally the organisms were killed. The histopathological appearance of the footpad tissues, studied by electron microscopy, was consistent with the measurements of bacterial numbers and viability. Swelling of the footpad after local inoculation with M. marinum was greater in T + R mice than in non-thymectomized controls. Similarly, the number of L. monocytogenes following intravenous challenge was greater in the spleens of T + R than of non-thymectomized mice, and the survival of the T + R mice was impaired after intraperitoneal challenge with L.monocytogenes, compared to the survival of non-thymectomized mice. None of these differences was striking, suggesting that these T + R mice had retained or regained some immune competence. The effects of dapsone treatment of T + R mice inoculated with M. leprae were much the same as those of treatment of non-thymectomized mice. Because these T + R mice were not greatly immunosuppressed, they would not have provided a model of human lepromatous leprosy suitable for chemotherapeutic studies. 相似文献