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101.
102.
Liu QR Drgon T Walther D Johnson C Poleskaya O Hess J Uhl GR 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(33):11864-11869
Association genome scanning is of increasing interest for identifying the chromosomal regions that contain gene variants that contribute to vulnerability to complex disorders, including addictions. To improve the power and feasibility of this approach, we have validated "10k" microarray-based allelic frequency assessments in pooled DNA samples and have used this approach to seek allelic frequency differences between heavy poly-substance abusers and well characterized control individuals. Thirty-eight loci contain SNPs that display robust allele frequency differences between abusers and controls in both European- and African-American samples. These loci identify an alcohol/acetaldehyde dehydrogenase gene cluster and genes implicated in cellular signaling, gene regulation, development, "cell adhesion," and Mendelian disorders. The results converge with previous linkage and association results for addictions. Pooled association genome scanning provides a useful tool for elucidating molecular genetic underpinnings of complex disorders and identifies both previously understood and previously unanticipated mechanisms for addiction vulnerability. 相似文献
103.
Structure of the gene 2.5 protein, a single-stranded DNA binding protein encoded by bacteriophage T7
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Hollis T Stattel JM Walther DS Richardson CC Ellenberger T 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(17):9557-9562
The gene 2.5 protein (gp2.5) of bacteriophage T7 is a single-stranded DNA (ssDNA) binding protein that has essential roles in DNA replication and recombination. In addition to binding DNA, gp2.5 physically interacts with T7 DNA polymerase and T7 primase-helicase during replication to coordinate events at the replication fork. We have determined a 1.9-A crystal structure of gp2.5 and show that it has a conserved OB-fold (oligosaccharide/oligonucleotide binding fold) that is well adapted for interactions with ssDNA. Superposition of the OB-folds of gp2.5 and other ssDNA binding proteins reveals a conserved patch of aromatic residues that stack against the bases of ssDNA in the other crystal structures, suggesting that gp2.5 binds to ssDNA in a similar manner. An acidic C-terminal extension of the gp2.5 protein, which is required for dimer formation and for interactions with the T7 DNA polymerase and the primase-helicase, appears to be flexible and may act as a switch that modulates the DNA binding affinity of gp2.5. 相似文献
104.
Monteiro CA Bachmann LH Desmond RA Squires KE Vermund SH Hook EW Schwebke JR Hoesley CJ 《AIDS research and human retroviruses》2004,20(6):577-583
The objectives of this study were to assess the prevalence and incidence of curable sexually transmitted infections (STI), i.e., gonorrhea, chlamydial infection, or trichomoniasis, in a cohort of HIV-infected women. The study population was derived from women seeking primary care at an outpatient university HIV clinic who were participants in a women's natural history study. Enrollees (n = 225) were predominantly African-American, heterosexually infected, with mean age 35 years. Mean entry CD4+ T cell count was 405 cells/mm3. Over 6% were STI positive at initial screening. Subsequently, the combined curable STI incidence was 4.82/1000 woman-months over a median of 33 months of observation. Of 36 incident STIs, trichomoniasis was most common (n = 32). Predictors for acquisition of a curable STI included absenteeism at scheduled clinic appointments, RR = 1.99 (1.28, 3.08), and a higher CD4+ T cell count, RR = 1.15 (1.0028, 1.3115) for 100 cells. Interventions to prevent curable STI in HIV-infected women are warranted in primary care settings. 相似文献
105.
Noedl H Attlmayr B Wernsdorfer WH Kollaritsch H Miller RS 《The American journal of tropical medicine and hygiene》2004,71(6):711-714
With the spread of antimalarial drug resistance, simple and reliable tools for the assessment of antimalarial drug resistance, particularly in endemic regions and under field conditions, have become more important than ever before. We therefore developed a histidine-rich protein 2 (HRP2)-based drug sensitivity assay for testing of fresh isolates of Plasmodium falciparum in the field. In contrast to the HRP2 laboratory assay, the field assay uses a procedure that further simplifies the handling and culturing of malaria parasites by omitting centrifugation, washing, the use of serum, and dilution with uninfected red blood cells. A total of 40 fresh Plasmodium falciparum isolates were successfully tested for their susceptibility to dihydroartemisinin, mefloquine, quinine, and chloroquine (50% inhibitory concentration [IC50] = 3.43, 61.89, 326.75, and 185.31 nM, respectively). Results very closely matched those obtained with a modified World Health Organization schizont maturation assay (R2 = 0.96, P < 0.001; mean log difference at IC50 = 0.054). 相似文献
106.
Ahmed A. Harhash Teresa L. May Chiu-Hsieh Hsu Sachin Agarwal David B. Seder Michael R. Mooney Nainesh Patel John McPherson Paul McMullan Richard Riker Eldar Soreide Karen G. Hirsch Pascal Stammet Alison Dupont Sten Rubertsson Hans Friberg Niklas Nielsen Tanveer Rab Karl B. Kern 《Journal of the American College of Cardiology》2021,77(4):360-371
BackgroundThe American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.ObjectivesThis study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.MethodsUsing the INTCAR (International Cardiac Arrest Registry), the impact of each proposed “unfavorable feature” on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.ResultsSeven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.ConclusionsPatients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable. 相似文献
107.
Modjarrad K Zulu I Redden DT Njobvu L Freedman DO Vermund SH 《The American journal of tropical medicine and hygiene》2005,73(4):777-782
Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1-infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1-infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care. 相似文献
108.
Abdul-Nasser Elzouki Stefan Lindgren Stefan Nilsson Béla Veress Sten Ericksson 《Journal of hepatology》1997,26(6):1403-1407
Background/Aims: Nephropathy associated with α1-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe α1-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life.Methods/Results: A renal biopsy was consistent with membranosproliferative glomerulophritis. An immunofluorescence study revealed the presence of α1-anti-trypsin (PiZ) in the subendothelial region of the glomerular basement membrane. The renal disease was reversible after orthotopic liver transplantation.Conclusions: The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane may suggest a possible role for this protein in the pathogenesis of glomerulonephritis. The case should add impetus to the search for α1-antitrypsin deficiency in any patient presenting with combined liver and renal disease, in the absence of evidence of hepato-renal syndrome, and illustrates that liver transplantation alone may reverse the neophropathy associated with α1-antitrypsin deficiency. 相似文献
109.