Azidophosphazenes as Functionalized Intermediates.

The synthesis of phosphazene cyclic trimers with azido side groups and aryloxy, alkoxy, or dialkylamino cosubstituent groups was accomplished. The compounds have the basic structure N(3)P(3)(R)(x)()(N(3))(6)(-)(x)(), where R represents phenoxy, trifluoroethoxy, dimethylamino, or diethylamino groups and x = 3-5. Experiments were also conducted to determine the ability of these materials to undergo a reaction unique to azido compounds known as nitrene insertion.

Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue.

We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs.

Mutations in the Escherichia coli receptor FepA reveal residues involved in ligand binding and transport.

FepA is the Escherichia coli outer membrane receptor for ferric enterobactin, colicin D and colicin B. The transport processes through FepA are energy-dependent, relying on the periplasmic protein TonB to interact with FepA. Through this interaction, TonB tranduces energy derived from the cytoplasmic membrane across the periplasmic space to FepA.

Linoleic acid partially restores the triglyceride content of conjugated linoleic acid-treated cultures of 3T3-L1 preadipocytes.

We have previously demonstrated that a crude mixture of commercially available conjugated linoleic acid (CLA) isomers suppressed triglyceride (TG) content and induced apoptosis in post-confluent cultures of murine 3T3-L1 preadipocytes. Furthermore, we found that 100 &mgr;M of trans-10, cis-12 isomer of CLA had a greater TG-lowering and apoptotic effect than the crude mixture of CLA isomers. Therefore, the purpose of this study was to: 1) compare the potencies of the two main isomers found in the crude mixture of CLA isomers, e.

Relationship between underlying renal disease and renal transplantation outcome.

The purpose of this study is to better characterize graft and patient survival posttransplantation by examining survival according to underlying renal disease for all first-time renal allograft recipients in the United Network for Organ Sharing (UNOS) registry. From 1987 through 1996, the UNOS registry collected data on 23,838 living and 67,183 cadaveric renal transplantations. This investigation included all patients undergoing their first renal transplantation for whom the underlying cause of renal failure could be identified and categorized.

Two classes of plant-like vacuolar-type H(+)-pyrophosphatases in malaria parasites.

In plants, cytosolic inorganic pyrophosphate (PP(i)) is hydrolyzed by energy-conserving vacuolar-type H(+)-pyrophosphatases (V-PPases) that harness the free energy of PP(i) hydrolysis to establish transmembrane H(+) gradients. Here we describe the identification and cloning of two genes, PfVP1 and PfVP2, from the malaria parasite Plasmodium falciparum. Inferred to encode type I (K(+)-dependent) and type II (K(+)-independent) V-PPases, respectively, PfVP1 and PfVP2 appeared more sequence divergent from each other than from their type I and type II counterparts in plants.

Factors influencing serum CA125II levels in healthy postmenopausal women.

Our objective was to identify factors that correlate with CA125 concentrations in healthy postmenopausal women and to introduce recommendations for reporting and interpreting individual CA125 assay results. We analyzed repeated serum CA125 levels, as measured by the CA125II assay, in 18,748 postmenopausal women who participated in the ST: Bartholomew's/Royal London Hospital Ovarian Cancer screening trial from 1986 to 1994 and were not diagnosed with ovarian cancer during the 12-year follow-up period. We found that race is a substantial predictor of normal levels of CA125, with average CA125II concentration from African (median, 9.

A diet containing food rich in soluble and insoluble fiber improves glycemic control and reduces hyperlipidemia among patients with type 2 diabetes mellitus.

The clinical significance of fiber on metabolic control among people with type 2 diabetes is debatable. Patients with type 2 diabetes who consumed a diet containing food naturally rich in fiber (e.g.

Design issues for conducting cost-effectiveness analyses alongside clinical trials.

In response to rising demands for timely economic data on new medical technologies, cost-effectiveness studies are increasingly being conducted alongside clinical trials. Because of the historical differences in perspective and methods between cost-effectiveness studies and clinical trials, the design phase of these hybrid trials requires special consideration. Cost-effectiveness studies require more comprehensive evaluations of outcomes than the endpoints typically measured in clinical trials.

A simple and efficient high-performance liquid chromatographic assay for etomidate in plasma.

The development and validation of an effective and simplified LC assay for the quantitation of etomidate in beagle plasma is described. The methodology employs a rapid and simple protein precipitation procedure in combination with previously reported chromatographic conditions. Using a 0.

Regulatory architecture of the iron-regulated fepD-ybdA bidirectional promoter region in Escherichia coli.

The overlapping and opposing promoter elements for the Escherichia coli fepDGC operon and the ybdA gene (encoding a 43-kDa cytoplasmic membrane protein) within the enterobactin gene cluster were investigated by measuring the effects of site-specific mutations on transcript levels and on expression of reporter genes in a bidirectional transcriptional fusion vector. Primary promoter structures for the opposing transcripts overlapped extensively such that their -10 sequences were almost directly opposed on the two strands of the DNA helix and their +1 transcription start sites were only 23 bp apart. Relative to the E.

Parameter solicitation for planning cost effectiveness studies with dichotomous outcomes.

When economic endpoints are included alongside clinical effectiveness measures in randomized clinical trials (RCT), they are summarized together by the incremental cost effectiveness ratio (ICER). Adding economic endpoints to an RCT complicates the planning of experiments because investigators must now solicit their beliefs about costs, but even more challenging, they must also specify their association with effectiveness. Solicitation of correlations between costs and effects can be unintuitive, and so potentially highly inaccurate.

Race, ethnicity, and the health care system: public perceptions and experiences.

To assess the public's perceptions and attitudes about racial and ethnic differences in health care, the Kaiser Family Foundation surveyed a nationally representative sample of 3,884 whites, African Americans, and Latinos in 1999. The survey found that the majority of Americans are uninformed about health care disparities--many were unaware that blacks fare worse than whites on measures such as infant mortality and life expectancy, and that Latinos are less likely than whites to have health insurance. Views on whether the health system treats people equally were strikingly different by race.

Ovarian cancer tumor marker behavior in asymptomatic healthy women: implications for screening.

Ovarian cancer screening protocols generally have been limited by inadequate recognition of the normal behavior of tumor markers in women at risk of ovarian cancer. We have characterized the behavior of five serum tumor markers in a large cohort of healthy women and examined the implications for screening. Serial measurements of CA125, HER-2/neu, urinary gonadotropin peptide, lipid-associated sialic acid, and Dianon marker 70/K were obtained during 6 years of follow-up of 1257 healthy women at high risk of ovarian cancer.

Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes.

Four sets of experiments were conducted to examine the influence of conjugated linoleic acid (CLA) isomers during proliferation and differentiation of cultures of 3T3-L1 preadipocytes using physiological culturing conditions. Cultures treated with either albumin [bovine serum albumin (BSA) vehicle] or linoleic acid (LA) served as controls. For the proliferation study (Expt.

Simulation modeling of outcomes and cost effectiveness.

Modeling will continue to be used to address important issues in clinical practice and health policy issues that have not been adequately studied with high-quality clinical trials. The apparent ad hoc nature of models belies the methodologic rigor that is applied to create the best models in cancer prevention and care. Models have progressed from simple decision trees to extremely complex microsimulation analyses, yet all are built using a logical process based on objective evaluation of the path between intervention and outcome.

beta3 subunit is present in different nicotinic receptor subtypes in chick retina.

Although the neuronal nicotinic beta3 subunit was cloned several years ago, it has only recently been shown to form heteromeric channels when associated with other nicotinic subunits, and very little information is available concerning its assembly in the native nicotinic receptors of the nervous system. Using subunit-specific antibodies and immunoprecipitation experiments, we have identified the retina as being the chick central nervous system (CNS) area that expresses the highest level of the beta3 subunit. Sequential immunopurification experiments showed that there are at least two populations of beta3-containing receptors in chick retina: in one, the beta3 subunit is associated with the alpha6 and beta4 subunits; in the other more heterogeneous population, the beta3 subunit is associated with the alpha2, alpha3, alpha4, beta2 and beta4 subunits.

Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure.

Objective: Myocardial cellular electrophysiology and intracellular Ca2+ regulation are altered in heart failure. The extent of these changes may vary within the layers of the ventricular wall. To examine this, cell size, action potential and intracellular Ca2+ transient characteristics (Fura-2) were measured in single cardiac myocytes from sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of rabbits with heart failure.

Improved graft survival after renal transplantation in the United States, 1988 to 1996.

Background: The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known.

Methods: We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation.

Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. Steroid Withdrawal Study Group.

Background: Prospective randomized trials have shown a reduced rate of acute rejection (AR) in mycophenolate mofetil-treated kidney transplant recipients. We hypothesized that this increased protection from AR could allow successful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-treated recipients.

Methods: A multicenter, prospective, randomized, double-blind trial of P withdrawal at 3 months post-transplant was initiated.

Pharmacokinetics and tolerability of a novel 5-HT1D agonist, PNU-142633F.

Objectives: The objectives of this study were to characterize the safety, tolerability and pharmacokinetics of a single, oral dose of PNU-142633F escalating over the range of 1.0 mg to 100 mg (free base equivalents).

Methods: This was a randomized, double-blind, single-dose, placebo-controlled, dose-escalation trial, with each dose group (1.

Instrumental variables when evaluating screening trials: estimating the benefit of detecting cancer by screening.

When evaluating the benefit of detecting cancer by screening we try to answer the question, 'what would a screen detected subject's outcome have been if his/her cancer had progressed to clinical detection'. By 'outcome' we mean survival time, cancer size and stage, lead time effects and more. Because only an unethical study can answer it directly, researchers have attempted to answer the question indirectly using data from randomized cancer screening studies (subjects randomized to study (screened) or control (not screened)).

A meta-analysis of fibromyalgia treatment interventions.

Objective: To evaluate and compare the efficacy of pharmacological and nonpharmacological treatments of fibromyalgia syndrome (FMS).

Methods: This meta-analysis of 49 fibromyalgia treatment outcome studies assessed the efficacy of pharmacological and nonpharmacological treatment across four types of outcome measures-physical status, self-report of FMS symptoms, psychological status, and daily functioning.

Results: After controlling for study design, antidepressants resulted in improvements on physical status and self-report of FMS symptoms.

Prostate-specific antigen for prostate cancer screening. Do physician characteristics affect its use?

Purpose: Screening for prostate cancer with the prostate-specific antigen (PSA) test remains controversial. This controversy is reflected in a lack of consensus in the medical literature and among professional and policy organizations regarding routine screening by PSA. It is not known how physicians respond when recommendations from experts are inconsistent.