Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control.

Hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER pre secretory proteolysis (PERPP), that is increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). We now report the molecular processes by which PUFA-derived ROS regulate PERPP of apoB.

Design and synthesis of bisubstrate inhibitors of type 1 17beta-hydroxysteroid dehydrogenase: overview and perspectives.

Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) is a key steroidogenic enzyme that catalyses the reduction of steroid estrone into the most potent endogenous estrogen estradiol using the cofactor NAD(P)H. Bisubstrate inhibition is a good way to enhance the potency of inhibitors of cofactor-assisted enzymes. The design of a bisubstrate inhibitor of 17beta-HSD1, the estradiol/adenosine hybrid EM-1745, is reviewed and strategies for future designs of inhibitors are proposed.

Dissemination of the CDC's Hand Hygiene Guideline and impact on infection rates.

Background: The diffusion of national evidence-based practice guidelines and their impact on patient outcomes often go unmeasured.

Methods: Our objectives were to (1) evaluate implementation and compliance with clinical practices recommended in the new Centers for Disease Control and Prevention (CDC) Hand Hygiene Guideline, (2) compare rates of health care-associated infections (HAI) before and after implementation of the Guideline recommendations, and (3) examine the patterns and correlates of changes in rates of HAI. We used pre- and post-Guideline implementation site visits and surveys in the setting of 40 US hospitals--members of the National Nosocomial Infections Surveillance System--and measured HAI rates 1 year before and after publication of the CDC Guideline and used direct observation of hand hygiene compliance and Guideline implementation scores.

Structure function analysis of west nile virus RNA dependent RNA polymerase: molecular model and implications for drug design.

West Nile virus (WNV) is a mosquito-borne disease that emerged in North America. In 2002 it caused the largest arboviral meningoencephalitis outbreak ever recorded in the US and Canada. The key enzyme responsible for the replication of the virus is the RNA-dependent RNA polymerase (RdRp) enzyme represented by nonstructural protein NS5 in WNV.

Effects of arachidonic acid metabolites on airway sensors.

Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by different enzymatic pathways. These lipid metabolites, along with other mediators, play an important role in the inflammatory processes. Many of them can bind directly to the receptors on the sensory endings and initiate electrical impulses to be transmitted to the central nervous system, causing reflex responses.

Cinnamomin: separation, crystallization and preliminary X-ray diffraction study.

Cinnamomin from Cinnamonum camphora seeds, a type II ribosome-inactivating protein that interferes with protein biosynthesis in mammalian cells, can induce the apoptosis of carcinoma cells and be used as an insecticide. A rapid and improved method has been developed for the extraction and purification of cinnamomin from camphora seed. Purification of cinnamomin is achieved with two successive steps of hydrophobic interaction chromatography carried out on a fast protein liquid chromatography (FPLC) system.

[Effects of arsenic trioxide on the autoimmunity and survival time in BXSB lupus mice].

Objective: To investigate the effect of arsenic trioxide (ATO) on the autoimmunity and survival time in BXSB lupus mice.

Methods: The model BXSB lupus mice were randomly divided into two groups equally, the ATO treated group and the control group, 17 in each group. Mice in the ATO group were given intraperitoneal injection of ATO at the daily dose of 0.

Prevalence of the metabolic syndrome among US middle-aged and older adults with and without diabetes--a preliminary analysis of the NHANES 1999-2002 data.

Objective: This study examined the racial differences in the distribution of the individual and clustered metabolic syndrome components among diabetics and nondiabetics and the presence of inflammatory markers.

Study Design And Method: This is a secondary data analysis of the National Health and Nutrition Examination Survey (NHANES) from 1999-2002. The analysis only included adults aged > or = 40 years who were White, Black, and Mexican American.

Structure-based inhibitor design for an enzyme that binds different steroids: a potent inhibitor for human type 5 17beta-hydroxysteroid dehydrogenase.

Human type 5 17beta-hydroxysteroid dehydrogenase plays a crucial role in local androgen formation in prostate tissue. Several chemicals were synthesized and tested for their ability to inhibit this enzyme, and a series of estradiol derivatives bearing a lactone on the D-ring were found to inhibit its activity efficiently. The crystal structure of the type 5 enzyme in complex with NADP and such a novel inhibitor, EM1404, was determined to a resolution of 1.

Crystallization and preliminary X-ray diffraction analysis of E. coli arginyl-tRNA synthetase in complex form with a tRNAArg.

Amino acids are building blocks of proteins, while aminoacyl-tRNA synthetases (aaRSs) catalyze the first reaction in such building: the biosynthesis of proteins. The E. coli arginyl-tRNA synthetase (ArgRS) has been crystallized in complex form with tRNA(Arg) (B.

Determination of trace selenium by solid substrate-room temperature phosphorescence enhancing method based on potassium chlorate oxidizing phenyl hydrazine-1,2-dihydroxynaphthalene-3,6-disulfonic acid system.

A new method for the determination of trace selenium based on solid substrate-room temperature phosphorimetry (SS-RTP) has been established. This method was based on the fact that in HCl-KCl buffer solution, potassium chlorate could oxidize phenyl hydrazine to form chloridize diazo-ion after being heated at 100 degrees C for 20 min, and then the diazo-ion reacted with 1,2-dihydroxynaphthalene-3,6-disulfonic acid to form red azo-compound which could emit strong room temperature phosphorescence (RTP) signal on filter paper. Selenium could catalyze potassium chlorate oxidizing the reaction between phenyl hydrazine and 1,2-dihydroxynaphthalene-3,6-disulfonic acid, which caused the sharp enhancement of SS-RTP.

Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells.

Epidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal-epidermal junction. Regulatory T cells (T(reg)) suppress self antigen-mediated autoimmune responses. To investigate the role of T(reg) in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T(reg).

[Inhibitory effect of angiogenesis inhibitor YH-16 on liver metastases from colorectal cancer].

Background & Objective: YH-16, a new recombinant angiogenesis inhibitor, has demonstrated synergetic effects with chemotherapy in non-small-cell lung cancer treatment in stage II clinical trial. This study was to investigate the effect of YH-16 on liver metastases from colon cancer.

Methods: Inhibitory concentration 50% (IC(50)) of YH-16 on vascular endothelial cells and colon cancer cell line CT26 was determined by MTT assay.

CCL27 is a critical factor for the development of atopic dermatitis in the keratin-14 IL-4 transgenic mouse model.

The keratin-14 IL-4 transgenic (Tg) mouse model of atopic dermatitis (AD) is characterized by skin infiltration of T cells, early up-regulation of T(h)2 cytokines and late surge of T(h)1 cytokines. In the present study, we investigated the role of CCL27, a T cell skin-homing chemokine known to be elevated in sera of human AD patients, in disease development in our animal model of AD. The results showed that the mRNA and protein levels of CCL27 in the skin and serum were significantly increased in IL-4 Tg mice.

Three-dimensional modeling of cytomegalovirus DNA polymerase and preliminary analysis of drug resistance.

Cytomegalovirus (CMV) is the leading cause of congenital infection and a frequent opportunistic agent in immunocompromised hosts such as transplant recipients and AIDS patients. CMV DNA polymerase, a member of the polymerase B family, is the primary target of all available antivirals (ganciclovir, cidofovir, and foscarnet) and certain variations of this enzyme could lead to drug resistance. However, understanding the drug resistance mechanisms at the atomic level is hampered by the lack of its three-dimensional (3D) structure.

Attempts to rationalize protein crystallization using relative crystallizability.

Protein crystal growth (PCG) remains the bottleneck of crystallography despite many decades of study. The nucleation zone in the two-dimensional-phase diagram has been used to evaluate the relative crystallizability of proteins, which is expressed as a percentage over the phase area delineated by experimental protein and precipitating agent concentration ranges. For protein-salts which are subject to a direct temperature effect on solubility, as represented by Egg Lysozyme, a decrease in temperature augments the nucleation zone percentage whereas for those with retrograde solubility as a function of temperature, for example fructose-1,6-bisphosphatase in the presence and absence of AMP, an increase in temperature can significantly enhance the relative crystallizability.

Organizational climate and intensive care unit nurses' intention to leave.

Objective: The purposes of this study were to a) estimate the incidence of intensive care units nurses' intention to leave due to working conditions; and b) identify factors predicting this phenomenon.

Design: Cross-sectional design.

Setting: Hospitals and critical care units.

[Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer].

Objective: To study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.

Methods: In vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group.

[Study of sequence variations of Epstein-Barr virus LMP1 gene in nasopharyngeal carcinoma].

Objective: To detect the sequence variations frequently found within the N- and C-terminal regions of Epstein-Barr virus (EBV) LMP1 gene in nasopharyngeal carcinoma (NPC) and to study the underlying mechanisms.

Methods: Fresh tumor tissues were sampled from 63 patients with untreated NPC encountered in Affiliated Tumor Hospital of Sun Yat-sen University, Guangzhou. The N-terminal region of EBV LMP1 gene was amplified with nested polymerase chain reaction (PCR), followed by XhoI enzyme digestion.

Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues.

N-myc downstream-regulated gene 2 (NDRG2) is believed to be involved in cell growth events. However, its exact function is still unknown. To elucidate the role of this gene, we used an anti-Ndrg2 monoclonal antibody in immunohistochemistry and immunofluorescence assays to analyze the expression pattern of Ndrg2 protein in mouse embryos at various gestational ages and in a variety of adult mouse tissues.

A U.S. population-based survey of Staphylococcus aureus colonization.

Background: The epidemiology of staphylococcal colonization and community-associated methicillin-resistant Staphylococcus aureus (MRSA) is changing, and little is known from the national perspective.

Objective: To describe the U.S.

Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5.

17Beta-hydroxysteroid dehydrogenases/ketosteroid reductases (17beta-HSDs/KSRs) catalyze the last step of sex steroid synthesis or the first step of their degradation, and are thus critical for many physiological processes. The multispecificity demonstrated by 17beta-HSDs is important for steroid metabolism in gonadal and peripheral tissues, and is a consequence of the architecture of their binding and catalytic sites. Structurally, most of the family members are short chain dehydrogenase-reductases (SDRs) except the type 5 enzyme, which is an aldo-keto reductase (AKR).

Epstein-Barr virus infection in precursor lesions of nasopharyngeal carcinoma.

Background & Objective: The infiltrating neoplastic cells within early-stage nasopharyngeal carcinoma (NPC) are consistently infected with Epstein-Barr virus (EBV). The precursor lesions could often be found in paracancerous epithelium of early-stage NPC. This study was to investigate the role of EBV infection and the intrahost evolution of EBV genotype developed in nasopharyngeal carcinogenesis through detection of EBV harboring in precursor lesions.

Estradiol-adenosine hybrid compounds designed to inhibit type 1 17beta-hydroxysteroid dehydrogenase.

The steroidogenic enzyme type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is involved in the synthesis of estradiol (E(2)), a hormone well-known to stimulate the growth of estrogen-sensitive tumors. To obtain compounds able to control E(2) formation, two moieties were linked with a methylene side chain: an adenosine moiety for interacting with the cofactor-binding site and an E(2) moiety for interacting with the substrate-binding site. When tested as inhibitors of type 1 17beta-HSD, the hybrid compounds inhibited the reductive activity (E(1) into E(2)) with IC(50) values ranging from 52 to 1,000 nM.