Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Preservation in Renal Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72258/1/j.1600-6143.2007.02065.x.pd

Fiber-Optic Imaging Probe Developed for Space Used to Detect Diabetes Through the Eye

Approximately 16 million Americans have diabetes mellitus, which can severely impair eyesight by causing cataracts, diabetic retinopathy, and glaucoma. Cataracts are 1.6 times more common in people with diabetes than in those without diabetes, and cataract extraction is the only surgical treatment. In many cases, diabetes-related ocular pathologies go undiagnosed until visual function is compromised. This ongoing pilot project seeks to study the progression of diabetes in a unique animal model by monitoring changes in the lens with a safe, sensitive, dynamic light-scattering probe. Dynamic light scattering (DLS), has the potential to diagnose cataracts at the molecular level. Recently, a new DLS fiber-optic probe was developed at the NASA Glenn Research Center at Lewis Field for noncontact, accurate, and extremely sensitive particle-sizing measurements in fluid dispersions and suspensions (ref. 1). This compact, portable, and rugged probe is free of optical alignment, offers point-and-shoot operation for various online field applications and challenging environments, and yet is extremely flexible in regards to sample container sizes, materials, and shapes. No external vibration isolation and no index matching are required. It can measure particles as small as 1 nm and as large as few micrometers in a wide concentration range from very dilute (waterlike) dispersions to very turbid (milklike) suspensions. It is safe and fast to use, since it only requires very low laser power (10 nW to 3 mW) with very short data acquisition times (2 to 10 sec)

Melengestrol Acetate at Greater Doses Than Typically Used for Estrous Synchrony in Bovine Females Does Not Mimic Endogenous Progesterone in Regulation of Secretion of Luteinizing Hormone and 17β-Estradiol

Our working hypothesis was that doses of melengestrol acetate (MGA) greater than those typically administered in estrous synchrony regimens would regulate secretion of LH and 17β-estradiol (E2) as endogenous progesterone (P4) does during the midluteal phase of the estrous cycle. We also hypothesized that endogenous P4 from the CL would interact with MGA to further decrease the frequency of LH pulses and E2. Cows on Day 5 of their estrous cycle (Day 0 = estrus) were randomly assigned to an untreated control group (CONT, n = 5) or to one of six MGA treatment groups (n = 5 per group): 1) MGA administered orally each day via a gelatin capsule at a dose of 0.5 mg MGA/cow with the CL present (0.5CL); 2) 0.5 mg MGA/cow daily in the absence of CL (0.5NO); 3) 1.0 mg MGA with CL present (1.OCL); 4) 1.0 mg MGA without CL (1.ONO); 5) 1.5 mg MGA with CL present (1.5CL); 6) 1.5 mg without CL (1.5NO). MGA was administered for 10 days (Day 5 = initiation of treatment). To regress CL, cows assigned to groups without CL received injections of prostaglandin F2α (PGF, 0; 25 mg) on Days 6 and 7 of their estrous cycle. All cows were administered PGF2α. at the end of the 10-day treatment period. During the treatment period, daily blood samples were collected to determine concentrations of E2. Serial blood samples were collected at 15-min intervals for 24 h on Days 8, 11, and 14 to determine pattern of LH secretion. Frequency of LH pulses on Days 8, 11, and 14 was greater (p \u3c 0.05) in cows without CL (0.5NO, 1.ONO, and 1.5NO) than in cows with CL (0.5CL, 1.OCL, 1.5CL, and CONT). Mean concentrations of LH were greater (p \u3c 0.05) in cows from the 0.5NO group on Days 8 and 11 and were greater (p \u3c 0.05) in cows from the 0.5NO, 1.ONO, and 1.5NO groups on Day 14 as compared to cows with CL. Overall mean concentrations of LH across Days 8, 11, and 14 were greatest (p \u3c 0.05) in cows from the 0.5NO group and were also greater (p \u3c 0.05) in cows from the 0.5NO, 1.ONO, and 1.5NO groups as compared to cows in the 0.5CL, 1.OCL, 1.5CL, and CONT groups. Mean concentrations of E2 during the treatment period were greater (p \u3c 0.05) in cows from the 0.5NO group than in cows from either the 1.ONO or the 1.5NO group; these values were also greater (p \u3c 0.05) in cows of the 0.5NO, 1.ONO, and 1.5NO groups as compared to cows of the 1.OCL and CONT groups. Therefore, we reject our working hypothesis because doses of MGA greater than those typically used in estrous synchrony protocols did not suppress LH and E2 to the same extent that endogenous P4 does. In addition, MGA treatment when CL were present did not result in a further suppression of LH pulse frequency or of E2 as compared to the values in control cows with functional CL

CYP2D6 Genotype is Not Associated with Survival in Breast Cancer Patients Treated with Tamoxifen: Results from a Population-based Study

Purpose: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Methods: Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). Results: CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). Conclusions: This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice

A putative antiviral role of plant cytidine deaminases

[EN] Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions. Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes. This and control plants were then infected with CaMV. Virus accumulation and mutational spectra where characterized in both types of plants. Results: We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated. Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.This work was supported by the former Spanish Ministerio de Ciencia e Innovación-FEDER grant BFU2009-06993 to SFE. JMC was supported by the CSIC JAE-doc program/Fondo Social Europeo. AG-P was supported by a grant for Scientific and Technical Activities and by grant P10-CVI-65651, both from Junta de Andalucía.Martín, S.; Cuevas, J.; Grande-Perez, A.; Elena Fito, SF. (2017). A putative antiviral role of plant cytidine deaminases. F1000Research. 1-14. https://doi.org/10.12688/f1000research.11111.2S11

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE