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Prp40 Homolog A Is a Novel Centrin Target.
Díaz Casas A, Chazin WJ, Pastrana-Ríos B
(2017) Biophys J 112: 2529-2539
MeSH Terms: Binding Sites, Calorimetry, Carrier Proteins, Chlamydomonas reinhardtii, Circular Dichroism, Humans, Hydrophobic and Hydrophilic Interactions, Protein Unfolding, Recombinant Proteins, Sequence Homology, Amino Acid, Spectroscopy, Fourier Transform Infrared, Thermodynamics, Trimethoprim, Sulfamethoxazole Drug Combination, Two-Hybrid System Techniques
Show Abstract · Added March 24, 2018
Pre-mRNA processing protein 40 (Prp40) is a nuclear protein that has a role in pre-mRNA splicing. Prp40 possesses two leucine-rich nuclear export signals, but little is known about the function of Prp40 in the export process. Another protein that has a role in protein export is centrin, a member of the EF-hand superfamily of Ca-binding proteins. Prp40 was found to be a centrin target by yeast-two-hybrid screening using both Homo sapiens centrin 2 (Hscen2) and Chlamydomonas reinhardtii centrin (Crcen). We identified a centrin-binding site within H. sapiens Prp40 homolog A (HsPrp40A), which contains a hydrophobic triad WLL that is known to be important in the interaction with centrin. This centrin-binding site is highly conserved within the first nuclear export signal consensus sequence identified in Saccharomyces cerevisiae Prp40. Here, we examine the interaction of HsPrp40A peptide (HsPrp40Ap) with both Hscen2 and Crcen by isothermal titration calorimetry. We employed the thermodynamic parameterization to estimate the polar and apolar surface area of the interface. In addition, we have defined the molecular mechanism of thermally induced unfolding and dissociation of the Crcen-HsPrp40Ap complex using two-dimensional infrared correlation spectroscopy. These complementary techniques showed for the first time, to our knowledge, that HsPrp40Ap interacts with centrin in vitro, supporting a coupled functional role for these proteins in pre-mRNA splicing.
Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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14 MeSH Terms
Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.
Williams DJ, Cooper WO, Kaltenbach LA, Dudley JA, Kirschke DL, Jones TF, Arbogast PG, Griffin MR, Creech CB
(2011) Pediatrics 128: e479-87
MeSH Terms: Adolescent, Anti-Infective Agents, Child, Child, Preschool, Clindamycin, Female, Humans, Infant, Male, Methicillin-Resistant Staphylococcus aureus, Retrospective Studies, Skin Diseases, Bacterial, Soft Tissue Infections, Staphylococcal Skin Infections, Trimethoprim, Sulfamethoxazole Drug Combination
Show Abstract · Added February 3, 2014
OBJECTIVE - To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and β-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs).
METHODS - A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a β-lactam was created. Outcomes included treatment failure and recurrence, defined as an SSTI within 14 days and between 15 and 365 days after the incident SSTI, respectively. Adjusted models stratified according to drainage status were used to estimate the risk of treatment failure and time to recurrence.
RESULTS - Among the 6407 children who underwent drainage, there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49-2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71-2.90) for β-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI: 1.06-1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19-1.69) for β-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44-1.95) for trimethoprim-sulfamethoxazole and 1.22 (95% CI: 1.06-1.41) for β-lactams; the adjusted hazard ratios for recurrence were 1.30 (95% CI: 1.18-1.44) for trimethoprim-sulfamethoxazole and 1.08 (95% CI: 0.99-1.18) for β-lactams.
CONCLUSIONS - Compared with clindamycin, use of trimethoprim-sulfamethoxazole or β-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.
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15 MeSH Terms
Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimen.
Giullian JA, Cavanaugh K, Schaefer H
(2010) Clin Transplant 24: 636-42
MeSH Terms: Adult, Anti-Infective Agents, Urinary, Antibiotic Prophylaxis, Cohort Studies, Dapsone, Female, Graft Survival, Humans, Immunosuppressive Agents, Kidney Transplantation, Male, Middle Aged, Pneumocystis Infections, Pneumocystis carinii, Retrospective Studies, Risk Factors, Survival Rate, Trimethoprim, Sulfamethoxazole Drug Combination, Urinary Tract Infections
Show Abstract · Added March 7, 2014
BACKGROUND - Urinary tract infections (UTI) are common in renal transplant recipients. Trimethoprim/sulfamethoxazole (TMP/SMZ) in moderate to high daily doses prevents Pneumocystis jiroveci (PCP) and reduces the risk of UTI in renal transplant patients. Low-dose TMP/SMZ also reduces the risk of PCP, although its ability to reduce the risk of UTI is uncertain.
DESIGN - Retrospective review of 158 patients who received a renal transplant without corticosteroids for maintenance immunosuppression.
RESULTS - Forty percent of patients initially prescribed TMP/SMZ ultimately stopped this medication early because of an adverse reaction. Urinary infection occurred in 16% without a significant difference in the risk of UTI between those treated with dapsone vs. those treated with TMP/SMZ (HR [95%CI]: 1.7 [0.75, 3.9], p = 0.2). In the subset of patients who were older than age 47 yr (mean age for this cohort, SD ± 6.2 yr), those treated with dapsone originally or who switched from TMP/SMZ to dapsone had a greater risk of UTI compared to patients who remained on TMP/SMZ (HR [95%CI]: 4.3 [1.2, 15.5], p = 0.024).
CONCLUSIONS - For renal transplant recipients over the age of 47 yr, treated without long-term glucocorticoids, our retrospective data suggest that low-dose TMP/SMZ is associated with a lower risk of UTI compared to dapsone prophylaxis.
© 2009 John Wiley & Sons A/S.
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19 MeSH Terms
Effect of zidovudine and Pneumocystis carinii pneumonia prophylaxis on progression of HIV-1 infection to AIDS. The Multicenter AIDS Cohort Study.
Graham NM, Zeger SL, Park LP, Phair JP, Detels R, Vermund SH, Ho M, Saah AJ
(1991) Lancet 338: 265-9
MeSH Terms: Acquired Immunodeficiency Syndrome, Aerosols, CD4-Positive T-Lymphocytes, Evaluation Studies as Topic, Follow-Up Studies, HIV Seropositivity, HIV-1, Humans, Leukocyte Count, Male, Pentamidine, Pneumonia, Pneumocystis, Prospective Studies, Regression Analysis, Risk Factors, Time Factors, Trimethoprim, Sulfamethoxazole Drug Combination, Zidovudine
Show Abstract · Added March 5, 2014
Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.
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18 MeSH Terms