Therapeutic LMP1 polyepitope vaccine for EBV-associated Hodgkin disease and nasopharyngeal carcinoma.

Development of an epitope-based vaccination strategy designed to enhance Epstein-Barr virus (EBV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) is increasingly being considered as a preferred approach for the treatment of EBV-associated relapsed Hodgkin disease (HD) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane proteins, LMP1 and LMP2, are the only target antigens available for therapeutic augmentation of CTL responses in patients with HD and NPC. Here, we describe preclinical studies using a recombinant poxvirus vaccine that encodes a polyepitope protein comprising 6 HLA A2-restricted epitopes derived from LMP1.

The case for fire safe cigarettes made through industry documents.

Objectives: To examine the extensive research undertaken by the tobacco industry over the past 25 years toward development of a fire safe cigarette.

Methods: Research was conducted through a web based search of internal tobacco industry documents made publicly available through the 1998 Master Settlement Agreement.

Results: The documents reveal that the tobacco industry produced a fire safe cigarette years ago, but failed to put it on the market.

Development of fluorescent adjacent hybridization probes and their application in real-time PCR for the simultaneous detection and identification of Fervidobacterium and Caloramator.

A stretch of nucleotides consisting of a conserved region and an adjacent upstream variable region in the 16S rDNA of members of domain Bacteria was identified as a suitable target site for developing a real-time PCR adjacent hybridization assay. A single universal fluorogenic cyanin 5-labelled probe, CY5 1046+, targeting the conserved region, and two FITC-labelled probes, Calo and Fervi, targeting the variable region were designed and synthesized for the identification and differentiation of the thermophilic anaerobes Caloramator and Fervidobacterium. The simultaneous hybridization of probes CY5 1046+ and Fervi to the 16S rDNA target sites of Fervidobacterium species during PCR amplification resulted in an increase in fluorescence emission that was monitored continuously in a LightCycler.

Eclipse: does it live up to its health claims?

Objective: To examine the plausibility of health claims for Eclipse, a novel smoking article being marketed by the RJ Reynolds Tobacco Company (RJR) as potentially reducing the risk of cancer and other diseases compared to conventional cigarettes.

Data Sources: A company product website (www.eclipse.

Cigarette advertising in magazines: the tobacco industry response to the Master Settlement Agreement and to public pressure.

Objective: The Master Settlement Agreement (MSA) of November 1998 prohibited participating tobacco companies from directly or indirectly targeting youth in marketing. Widely publicised information in May 2000 showed increased cigarette advertising in magazines with substantial youth readership and companies were pressed to change their practices. The responses of the tobacco industry to the MSA and to the public pressure are examined.

How cigarette design can affect youth initiation into smoking: Camel cigarettes 1983-93.

Context: Internal industry documents may shed light on how cigarettes are designed to promote youth smoking.

Objective: To determine changes in the design of Camel cigarettes in the period surrounding the "Smooth Character" advertising campaign and to assess the impact of these changes on youth smoking.

Data Sources: Internal documents made available through the document website maintained by RJ Reynolds, manufacturer of Camel cigarettes.

Methodologic issues in the conduct and interpretation of pediatric effectiveness research.

Effectiveness research represents a number of methodologic challenges not shared with randomized, controlled clinical trials. This practice-based research attempts to translate clinical practices to a wide variety of different practice settings and situations and to diverse patient subgroups. However, because study designs most often used in the conduct of effectiveness research limit the ability to establish firm causal links between medical care and outcomes, it is important to address key methodologic features to generate sound, useable findings.

Inhibition of Mrp2- and Ycf1p-mediated transport by reducing agents: evidence for GSH transport on rat Mrp2.

Mammalian Mrp2 and its yeast orthologue, Ycf1p, mediate the ATP-dependent cellular export of a variety of organic anions. Ycf1p also appears to transport the endogenous tripeptide glutathione (GSH), whereas no ATP-dependent GSH transport has been detected in Mrp2-containing mammalian plasma membrane vesicles. Because GSH uptake measurements in isolated membrane vesicles are normally carried out in the presence of 5-10 mM dithiothreitol (DTT) to maintain the tripeptide in the reduced form, the present study examined the effects of DTT and other sulfhydryl-reducing agents on Ycf1p- and Mrp2-mediated transport activity.

The HELLP syndrome, a prospective study.

Objective: We undertook this study to evaluate the incidence and outcome of HELLP in Irish patients. In addition, duration and trends of the abnormal laboratory results were studied.

Study Design: This prospective observational study screened 12068 pregnant women between January 1995 and March 1997.

Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women.

Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in preeclamptic females was objectively assessed and compared with normal pregnant and nonpregnant females. Fifteen females with pre-eclampsia were compared to 15 females from each of the three trimesters of pregnancy, as well as to 15 matched nonpregnant control females (total study population, 75 subjects).

Hypoxanthine-guanine phosphoribosyltransferase-deficiency produces aberrant neurite outgrowth of rodent neuroblastoma used to model the neurological disorder Lesch Nyhan syndrome.

Lesch Nyhan syndrome (LNS) manifests in bizarre and horrific neurological symptoms, the primary cause being a deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). How and why this enzyme deficiency leads to abnormal brain development is unknown. To investigate this phenomenon the present study was designed to examine if the growth of two HGPRT-deficient neuroblastomas, mouse N2aTG and rat B103-4C was different with respect to their corresponding control cell lines, N2a and B103.

Abnormal development of hypoxanthine-guanine phosphoribosyltransferase-deficient CNS neuroblastoma.

Lesch-Nyhan syndrome encompasses a host of neurological symptoms, caused by a deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). How the absence of this enzymes activity affects development of the nervous system is unknown. In this study, we examined the ability of N2aTG, a HGPRT-deficient neuroblastoma and its HGPRT-positive counterpart to proliferate and differentiate at various densities.

Cell imaging and morphology: application to studies of inherited purine metabolic disorders.

A number of inherited or drug-induced metabolic disorders involving dysfunctions in purines and pyrimidines are strongly associated with neurological dysfunction, e.g., Lesch Nyhan syndrome.

The prognostic significance of CD44s and CD44v6 expression in stage two breast carcinoma: an immunohistochemical study.

Aims: Expression of the v6 variant isoform of CD44 has been causally associated with the development of metastases. This study, using immunohistochemical techniques, examined the prognostic significance of CD44s and CD44v6 expression.

Methods: A cohort of 109 women presenting with stage 2 breast cancer, with a minimum follow-up of 5 years, were assessed.

A five year review of scar dehiscence in the Rotunda Hospital, Dublin.

The aims of this study were to identify risk factors for scar dehiscence in labour, to illustrate the clinical presentations of patients with scar dehiscence and to quantify the risk posed by the use of oxytocin in labour. This was a case controlled, 5 year retrospective study. Patients with scar dehiscence were identified from labour ward records with matched controls and chart review of case and control patients were performed.

Methyl orange antagonizes uridine 5' triphosphate and not alpha,beta-methylene-adenosine 5' triphosphate-evoked depolarization of rat superior cervical ganglia.

1. Compared with the effects of adenosine 5' triphosphate (ATP) on the nervous system, the actions of pyrimidine nucleosides and their 5'-nucleotides, such as uridine 5' triphosphate (UTP), have received less attention. In part, this is because there is a need for a selective antagonist for responses mediated by UTP-activated receptors.

Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma model of Lesch Nyhan syndrome.

Extracellular purines have essential roles in neuronal development; hence, disruptions in their metabolism as reported in Lesch Nyhan syndrome (LNS) could result in developmental abnormalities. The deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in LNS leads to increased hypoxanthine and uric acid production. We have reported that HGPRT-deficient B103-4C neuroblastoma, a neuronal model of LNS, proliferated less and differentiated more than their HGPRT-positive B103 counterparts.

Attitude to home birth in an antenatal population at the Rotunda Hospital.

195 Women attending the antenatal clinics at the hospital were interviewed, about their attitudes to home birth using a standardised questionnaire. One hundred and seventy one women (88%) said that they would not favour a home birth in a subsequent delivery, 19 (9.5%) said that they would consider a home birth in a subsequent pregnancy and the remaining 5 (2.

The effect of strength training on the apparent inhibition of eccentric force production in voluntarily activated human quadriceps.

Ten male and ten female young adults trained the knee extensors of one leg eccentrically and those of the other concentrically for 6 weeks, using a gymnasium leg-extension machine. Before and after training, both legs of each subject were tested isometrically for maximum voluntary knee-extensor force, and in both eccentric and concentric isokinetic modes at 30-250 degrees x s(-1) All limbs showed improvements in mean eccentric force (ranging from 18% in the concentrically trained legs of the females to 31% in the eccentrically trained legs of the males, P < 0.01-0.

How cigarette additives are used to mask environmental tobacco smoke.

Objective: To understand the tobacco industry's research on and use of cigarette additives that alter the perception of exposure to environmental tobacco smoke (ETS).

Data Sources: Internal documents from four websites maintained by the major US tobacco manufacturers and company patents pertaining to the use of ETS altering additives obtained from the US Patent and Trademark Office online database.

Study Selection: Electronic searches of the four industry websites and the US patent database were conducted using keywords to identify relevant data.

Health risks associated with cigar smoking.

This article summarizes principal findings from a conference convened by the American Cancer Society in June 1998 to examine the health risks of cigar smoking. State-of-the-science reports were presented and 120 attendees (representing government and private agencies, academia, health educators, and tobacco control experts) participated in panels and summary development discussions. The following conclusions were reached by consensus: (1) rates of cigar smoking are rising among both adults and adolescents; (2) smoking cigars instead of cigarettes does not reduce the risk of nicotine addiction; (3) as the number of cigars smoked and the amount of smoke inhaled increases, the risk of death related to cigar smoking approaches that of cigarette smoking; (4) cigar smoke contains higher concentrations of toxic and carcinogenic compounds than cigarettes and is a major source of fine-particle and carbon monoxide indoor air pollution; and (5) cigar smoking is known to cause cancers of the lung and upper aerodigestive tract.