Preliminary development of a physiological model for perchlorate in the adult male rat: a framework for further studies.
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Animals↗
Biomedical subjects
K Yu
Publications and source records attributed to K Yu.
Tris(2,6-di-tert-butyl-4-methylphenolato-O)(triphenylphosphine oxide-O)samarium(III).
In the title complex, [Sm(C(15)H(23)O)(3)(C(18)H(15)OP)], the central metal atom is coordinated by three O atoms of the aryloxo ligands and by one O atom of the triphenylphosphine oxide molecule resulting in a distorted tetrahedral geometry. The Sm-O(Ar) distances (Ar is aryl) range from 2.122 (2) to 2.190 (2) A and the Sm-O(PPh(3)) bond length is 2.306 (2) A.
Journal Article↗
A commercial preparation of catalase inhibits nitric oxide production by activated murine macrophages: role of arginase.
Catalase is widely used as a pharmacological probe to evaluate the role of hydrogen peroxide in antimicrobial activities of phagocytic cells. This report demonstrates that the ability of a commercial preparation of catalase to inhibit concomitantly macrophage antimycobacterial activity and production of reactive nitrogen intermediates can be attributed, at least in part, to the depletion of L-arginine by contaminating arginase. In experimental systems that employ pharmacological probes, the existence of nonspecific effects should be considered in data interpretation.
Animals↗
The nicking step in V(D)J recombination is independent of synapsis: implications for the immune repertoire.
In all of the transposition reactions that have been characterized thus far, synapsis of two transposon ends is required before any catalytic steps (strand nicking or strand transfer) occur. In V(D)J recombination, there have been inconclusive data concerning the role of synapsis in nicking. Synapsis between two 12-substrates or between two 23-substrates has not been ruled out in any studies thus far. Here we provide the first direct tests of this issue. We find that immobilization of signals does not affect their nicking, even though hairpinning is affected in a manner reflecting its known synaptic requirement. We also find that nicking is kinetically a unireactant enzyme-catalyzed reaction. Time courses are no different between nicking seen for a 12-substrate alone and a reaction involving both a 12- and a 23-substrate. Hence, synapsis is neither a requirement nor an effector of the rate of nicking. These results establish V(D)J recombination as the first example of a DNA transposition-type reaction in which catalytic steps begin prior to synapsis, and the results have direct implications for the order of the steps in V(D)J recombination, for the contribution of V(D)J recombination nicks to genomic instability, and for the diversification of the immune repertoire.
Animals↗
Processing of the Drosophila Sog protein creates a novel BMP inhibitory activity.
Structurally unrelated neural inducers in vertebrate and invertebrate embryos have been proposed to function by binding to BMP4 or Dpp, respectively, and preventing these homologous signals from activating their receptor(s). In this study, we investigate the functions of various forms of the Drosophila Sog protein using the discriminating assay of Drosophila wing development. We find that misexpression of Drosophila Sog, or its vertebrate counterpart Chordin, generates a very limited vein-loss phenotype. This sog misexpression phenotype is very similar to that of viable mutants of glass-bottom boat (gbb), which encodes a BMP family member. Consistent with Sog selectively interfering with Gbb signaling, Sog can block the effect of misexpressing Gbb, but not Dpp in the wing. In contrast to the limited BMP inhibitory activity of Sog, we have identified carboxy-truncated forms of Sog, referred to as Supersog, which when misexpressed cause a broad range of dpp(-) mutant phenotypes. In line with its phenotypic effects, Supersog can block the effects of both misexpressing Dpp and Gbb in the wing. Vertebrate Noggin, on the other hand, acts as a general inhibitor of Dpp signaling, which can interfere with the effect of overexpressing Dpp, but not Gbb. We present evidence that Sog processing occurs in vivo and is biologically relevant. Overexpression of intact Sog in embryos and adult wing primordia leads to the developmentally regulated processing of Sog. This in vivo processing of Sog can be duplicated in vitro by treating Sog with a combination of the metalloprotease Tolloid (Tld) plus Twisted Gastrulation (Tsg), another extracellular factor involved in Dpp signaling. In accord with this result, coexpression of intact Sog and Tsg in developing wings generates a phenotype very similar to that of Supersog. Finally, we provide evidence that tsg functions in the embryo to generate a Supersog-like activity, since Supersog can partially rescue tsg(-) mutants. Consistent with this finding, sog(- )and tsg(-) mutants exhibit similar dorsal patterning defects during early gastrulation. These results indicate that differential processing of Sog generates a novel BMP inhibitory activity during development and, more generally, that BMP antagonists play distinct roles in regulating the quality as well as the magnitude of BMP signaling.
Animals↗
Dual protease inhibitor therapy in the management of the HIV-1.
Throughout the first 20 years of the HIV-1 epidemic, there have been tremendous advances in the development of antiretroviral therapy (ART). In 1995, the availability of protease inhibitors (PI) as part of triple drug regimens resulted in durable viral suppression with an associated decline in HIV-1-related morbidity and mortality. Despite this early success, limitations of therapy have become apparent. In particular, the need for highly potent antiviral regimens, the importance of outstanding adherence to therapy, drug-related toxicity and the increasing problem of drug-drug and drug-food interactions. Dual PI therapy has been investigated with the hope of overcoming these problems. Select PI combinations may result in synergistic antiviral activity with enhanced viral suppression. Moreover, the ability of select agents to inhibit the cytochrome P450 (CYP450) system results in pharmacologic enhancement that allows for dosing with fewer pills on a less frequent basis, both of which can enhance drug adherence. Furthermore, these pharmacologic interactions can overcome drug-drug and drug-food interactions. Finally, the ability to increase drug levels using certain PI combinations may allow for drug concentrations to exceed those needed to inhibit resistant strains of HIV-1. The rationale for using dual PI therapy, along with the results of clinical trials using various PI combinations in treatment-naïve and experienced patients, is reviewed in this article.
Drug Combinations↗
Primary HIV infection. Current trends in transmission, testing, and treatment.
In the changing kaleidoscope of HIV disease, early detection of primary infection has become increasingly important. Primary care physicians who recognize the signs and symptoms are in an ideal position to diagnose the disease at an early stage and to help stem the tide of new infections in the community. In this article, Drs Yu and Daar discuss current strategies for early diagnosis, including recommended testing and steps to prevent transmission of the virus, and present the latest thinking about antiretroviral therapy during primary HIV infection.
HIV Infections↗
Production and reduction of nitrous oxide in agricultural and forest soils.
A soil-water slurry experiment was conducted to study the potentials of N2O production and reduction in denitrification of agricultural and beech forest soils in Denmark. The effects of nitrate and ammonium additions on denitrification were also investigated. The forest soil showed a higher denitrification potential than the agricultural soil. However, N2O reduction potential of the agricultural soil was higher than the beech forest soil, shown by the ratio of N2O/N2 approximately 0.11 and 3.65 in the agricultural and the beech forest soils, respectively. Both nitrate and ammonium additions stimulated the N2O production in the two soils, but reduced the N2O reduction rates in the agricultural soil slurries. In contrast to the effect on the agricultural soil, nitrate reduced the N2O reduction rate in the beech forest soil, while ammonium showed a stimulating effect on the N2O reduction activity. After one week incubation, all of the N2O produced was reduced to N2 in the agricultural soil when nitrate was still present. Nitrous oxide reduction in the beech forest soil occurred only when nitrate almost disappeared. The different nitrate inhibitory effect on the N2O reduction activity in the two soils was due to the difference in soil pH. Inhibition of nitrate on N2O reduction was significant under acidic condition. Consequently, soil could serve as a sink of atmospheric N2O under the conditions of anaerobic, pH near neutral and low nitrate content.
Crops, Agricultural↗
[A comparison between latanoprost and timolol in treatment of patients with primary open-angle glaucoma and ocular hypertension].
OBJECTIVE: To evaluate the therapeutic value of latanoprost on glaucoma. METHODS: In an open-label fashion, multicenter, randomized control clinical trial, the efficacy and adverse drug reactions of topical application of 0.005% latanoprost once daily were compared with that of 0.5% timolol twice daily for 12 weeks in patients with open-angle glaucoma or ocular hypertension. RESULTS: The study included 128 patients (63 patients in latanoprost group and 65 patients in timolol group) and 117 patients remained at the end of the study (60 cases in latanoprost group and 57 cases in timolol group). Comparing 12 weeks with baseline diurnal intraocular pressure (IOP), the IOP reduction (mean +/- standard deviation) in latanoprost group was (7.5 +/- 0.3) mm Hg (1 mm Hg = 0.133 kPa) (32%, t = 22.73, P < 0.0001) greater than the reduction in timolol group (6.1 +/- 0.3) mm Hg (26%, t = 17.94, P < 0.0001), the difference between the two groups being significant (F = 9.54, P = 0.0026). Two patients treated with timolol and none treated with latanoprost were withdrawn from the study because of inadequate IOP control; 3 patients with latanoprost had foreign body sensation. In latanoprost group, there was one patient whose eyelashes became darker and longer at the last visit (the 12th week). No ocular and systemic adverse events related to the two drugs were found. CONCLUSION: It is demonstrated that 0.005% latanoprost topically applied once daily is well tolerated and more effective in reducing IOP than 0.5% timolol topically applied twice daily. Thus, latanoprost has the potential to be a new first-line antiglaucoma drug.
Adrenergic beta-Antagonists↗
[Clinical observation on treatment of pediatric intractable nephropathy with modified taohong siwu decoction].
OBJECTIVE: To observe the clinical effect of Modified Taohong Siwu Decoction (MTSD) in treating pediatric intractable nephropathy (PIN). METHODS: Ninety-five cases of PIN were divided into 2 groups at random. The 60 cases in the treated group were administered with MTSD and the 35 patients in the control group were treated with heparin. The clinical therapeutic effect and levels of thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha before and after treatment were observed. RESULTS: The total effective rate of the treated group was 81.7%, which was similar to that in the control group (80.0%, P > 0.05). The levels of TXB2 and TXB2/6-ketoprostaglandin F1 alpha ratio were higher in both groups of patients as compared with those of the healthy control (P < 0.01), After treatment, the two criteria were significantly improved in the two groups, as compared with those before treatment, the difference was significant (P < 0.01), while in comparson between the treated and the control group, no significant difference was found (P > 0.05). CONCLUSION: MTSD has good effect in treating PIN, it could improve the metabolic unbalance of thromboxane and prostacyclin.
6-Ketoprostaglandin F1 alpha↗
[Principle of evidence-based medicine and its application in clinical trial practice for glutamine and gut permeability].
Evidence-based medicine (EBM) was developed from the progress of traditional clinical model trial patterns. EBM was based on well-designed, randomized, double blind, controlled, multiple center trails in order to assess end pont parameters, prognosis parameters (as: mortality, morbidity of complications and hospital stay etc.), quality of life and cost/effect ratio. It has been accepted in developed countries and could be the guidelines for Chinese clinical trials in the future. This article summarized the principle of EBM and attached with a clinical trial sample about effects of glutamine dipeptide on gut barrier function, post-operative complications and the hospital stay.
Aged↗
Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis.
The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.
Culture Media↗
RGS proteins determine signaling specificity of Gq-coupled receptors.
Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits, thereby attenuating signaling. RGS4 is a GTPase-activating protein for Gi and Gq class alpha subunits. In the present study, we used knockouts of Gq class genes in mice to evaluate the potency and selectivity of RGS4 in modulating Ca2+ signaling transduced by different Gq-coupled receptors. RGS4 inhibited phospholipase C activity and Ca2+ signaling in a receptor-selective manner in both permeabilized cells and cells dialyzed with RGS4 through a patch pipette. Receptor-dependent inhibition of Ca2+ signaling by RGS4 was observed in acini prepared from the rat and mouse pancreas. The response of mouse pancreatic acini to carbachol was about 4- and 33-fold more sensitive to RGS4 than that of bombesin and cholecystokinin (CCK), respectively. RGS1 and RGS16 were also potent inhibitors of Gq-dependent Ca2+ signaling and acted in a receptor-selective manner. RGS1 showed approximately 1000-fold higher potency in inhibiting carbachol than CCK-dependent signaling. RGS16 was as effective as RGS1 in inhibiting carbachol-dependent signaling but only partially inhibited the response to CCK. By contrast, RGS2 inhibited the response to carbachol and CCK with equal potency. The same pattern of receptor-selective inhibition by RGS4 was observed in acinar cells from wild type and several single and double Gq class knockout mice. Thus, these receptors appear to couple Gq class alpha subunit isotypes equally. Difference in receptor selectivity of RGS proteins action indicates that regulatory specificity is conferred by interaction of RGS proteins with receptor complexes.
Animals↗
Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic stress.
In the cellular response to genotoxic stress, cell cycle checkpoint and apoptosis are considered to be two of the major biological events in maintaining genomic stability. The tumor suppressor p53 has been shown to play critical roles in these stress-induced cellular responses at least in part through the activation of its down-stream genes, such as p21CIP1/WAF1, GADD45 and BAX. In addition, p53 has been found to down-regulate the expression of BCL-2, which is able to block apoptosis induced by both p53-dependent and independent signaling events. In this report, we have found that increased expression of Bcl-2 protein in the human Burkitt's lymphoma WMN cell line suppressed apoptosis induced by different DNA-damaging agents. The induction of p53-regulated genes including GADD45, p21CIP1/WAF1 and BAX by genotoxic stress was substantially reduced in cells expressing high levels of Bcl-2 protein. Furthermore, Bcl-2 protein was shown to specifically suppress the p53-mediated transactivation of p21CIP1/WAF1 and PG13-CAT, which is a typical p53-binding-site reporter construct. Similarly, the inhibitory effect of Bcl-2 protein was seen in a GADD45 promoter reporter construct after treatment with methylmethane sulfonate or UV-radiation. These results indicate that in addition to its apoptosis-suppressing activity, Bcl-2 protein is able to inhibit transactivation of p53-regulated genes, which function in multiple important cellular responses to genotoxic stress, including the control of cell cycle checkpoints, cell growth suppression and DNA repair.
Apoptosis↗
Psychosocial, school, and parent factors associated with recent smoking among early-adolescent boys and girls.
BACKGROUND: Experimentation with smoking often begins during adolescence, but an adequate understanding of the factors associated with early initiation remains elusive. METHODS: Sixth- to eighth-grade students (n = 4,263, 67.1% white, 23.5% black, 7.2% other) from seven middle schools were surveyed. RESULTS: The overall prevalence of recent smoking (past 30 days) of 10.4% was similar for boys and girls and by race, but increased from 3.7% in sixth to 17.8% in eighth grade. In multiple logistic regression analyses positive outcome expectations, high perceived prevalence, deviance acceptance, and trouble at school were independently associated with smoking for both boys and girls. Among boys, problem-behaving friends, peer pressure, authoritative parenting, and mother's education and among girls, self-control problems, knowledgeable parents, and grade were independently associated with smoking. CONCLUSIONS: This is one of the few studies to report an independent association between smoking and outcome expectations, the first study to report an independent effect for peer influences among boys only, and one of several to find a negative association between smoking and positive parenting behavior. These findings suggest that the effectiveness of preventive interventions might be improved by targeting parent, school, and student outcomes, including outcome expectations, deviance acceptance, and social norms for both boys and girls, peer influences among boys, and self-control among girls.
Adolescent↗
Toxicity of nitrogen oxides and related oxidants on mycobacteria: M. tuberculosis is resistant to peroxynitrite anion.
OBJECTIVE: To test the toxicity of reactive nitrogen intermediates (RNI), including authentic nitric oxide (NO), nitrogen dioxide (NO2), and peroxynitrite anion (ONOO-), a potent oxidant derived from NO and superoxide anion, on various mycobacterial strains including M. tuberculosis. DESIGN: Relatively avirulent mycobacteria including M. smegmatis and BCG, as well as the pathogenic M. Bovis Ravenel and M. tuberculosis Erdman and the clinical isolate M160 (also known as the C strain) were tested for their susceptibility to the toxic effects of NO, NO2, and ONOO-, Deaerated, NO-saturated solutions as well as an anaerobic in vitro system in which mycobacteria can be exposed to desired concentrations of authentic NO or NO2, were employed in these studies. An in vitro ONOO- killing assay was used to examine the adverse effects of this NO-derived oxidant on the various strains of mycobacteria. RESULTS: Both NO and NO2 exhibit antimycobacterial activity, with the former being more potent. Results obtained using ONOO- killing assay revealed that while avirulent mycobacteria including BCG and M. smegmatis are susceptible to this NO-derived oxidant, the virulent Erdman strain of M. tuberculosis and M. bovis, as well as the clinical tuberculous isolate M160, are remarkably resistant. CONCLUSION: These results suggest that the interactions between RNI and various species of mycobacteria could be highly specific. And since activated macrophages produce peroxynitrite, the significance of the ONOO- resistance of M. tuberculosis strains in relation to intracellular survival deserves further investigation.
Adult↗
Diltiazem reduces retinal neovascularization in a mouse model of oxygen induced retinopathy.
PURPOSE: To assess the effect of diltiazem, a calcium channel blocking agent, on oxygen induced retinopathy (OIR) in a mouse model using neovascular nuclei quantitation and a quantitative scoring system based on examining fluorescein perfused retinal whole mount preparations. METHODS: The mouse model of oxygen induced retinopathy consisting of a 5 day exposure to 75% oxygen from postnatal day 7 to 12 was used to produce retinal neovascularization. Fluorescein conjugated dextran angiography of retinal vasculature was performed and retinal whole mounts were prepared to score features of retinopathy. The parameters that were scored in a masked fashion included blood vessel growth, blood vessel tuft formation, extra retinal neovascularization, degree of central vasoconstriction, retinal hemorrhage, and tortuosity of vessels. Diltiazem (0.05-0.5 mg/kg/day subcutaneously for five days) was administered to mice pups during exposure to oxygen to determine if calcium channel blockade altered retinopathy. In addition, quantification of retinal neovascular nuclei was performed in a masked fashion with periodic acid Schiff (PAS) staining of frozen eye sections. RESULTS: Animals that were exposed to hyperoxia for five days had a median (25th, 75th quartile) retinopathy score of 9 (8,11) versus control animals that had a retinopathy score of 1 (0,1) with p<0.001. Subscores for blood vessel growth, blood vessel tufts, extra-retinal neovascularization, central vasoconstriction, hemorrhage, and blood vessel tortuosity were all significantly different between control and treated animals. In addition, quantification of neovascular nuclei showed a significant increase in the number of nuclei extending beyond the inner limiting membrane into the vitreous in hyperoxic treated animals. Diltiazem at doses of 0.2 and 0.5 mg/kg/day improved the retinopathy as measured by the total retinopathy score [5 (4,6) and 4 (3.75,5.25), respectively]. The average number of extraretinal neovascular nuclei per retinal section (mean +/-standard deviation) was significantly decreased by diltiazem at doses of 0.2 and 0.5 mg/kg/day (31.4+/-18.8 and 20.9+/-6.9, respectively) when compared to hyperoxic treated animals (56.1+/-21.5). CONCLUSIONS: Diltiazem reduces oxygen induced retinopathy in the mouse as measured by a scoring system based on a retinal whole mount method of retinal neovascularization and by quantification of extra retinal neovascular nuclei.
Animals↗
Alcohol and drug use in victims of life-threatening trauma.
OBJECTIVE: Alcohol and drug use has been implicated as a contributing factor to all types of trauma. This investigation seeks to determine the prevalence of alcohol and drug use in patients who are victims of life-threatening injuries and the association of alcohol and drug use with intentional trauma. METHODS: The Medical Center of Louisiana at New Orleans (Charity Campus) trauma registry was used to identify patients sustaining life-threatening injuries that presented to our American College of Surgeons Level 1 trauma center over a 6-month period. Serum ethanol levels and urine toxicology were assessed at initial presentation for all patients. RESULTS: A total of 557 patients were evaluated. Seventy percent (n = 319) of tested patients (n = 450) had positive serum ethanol and/or urine toxicology results. Male gender (75% vs. 55%; p < 0.001) was associated with positive screens; ethnicity was not. No difference in hospital days or mortality was seen between positive and negative screens. Victims of intentional trauma showed a higher percent of positive screens (80% vs. 63%; p < 0.005). CONCLUSION: These data suggest that alcohol and drug use is associated with life-threatening injury, especially intentional injury. Prevention of substance abuse is essential for the prevention of trauma.
Adolescent↗