Boronate-based fluorescent probes for imaging cellular hydrogen peroxide.

The syntheses, properties, and biological applications of the Peroxysensor family, a new class of fluorescent probes for hydrogen peroxide, are presented. These reagents utilize a boronate deprotection mechanism to provide high selectivity and optical dynamic range for detecting H2O2 in aqueous solution over similar reactive oxygen species (ROS) including superoxide, nitric oxide, tert-butyl hydroperoxide, hypochlorite, singlet oxygen, ozone, and hydroxyl radical. Peroxyresorufin-1 (PR1), Peroxyfluor-1 (PF1), and Peroxyxanthone-1 (PX1) are first-generation probes that respond to H2O2 by an increase in red, green, and blue fluorescence, respectively.

Screening mercury levels in fish with a selective fluorescent chemosensor.

Societal concerns over toxic mercury accumulation in humans from fish and other dietary and environmental sources provide motivation to develop new tools and tactics for mercury detection in a wide range of laboratory and field settings. Here we report the synthesis, properties, and application of a selective and sensitive small-molecule chemosensor for fluorescence screening of mercury levels in fish. Mercuryfluor-1 (MF1) is a water-soluble, fluorescein-based reagent that features excellent selectivity for Hg2+ over competing analytes and the largest turn-on fluorescence response to date (>170-fold increase) for reporting this heavy metal ion in aqueous solution.

Plasma, serum, and platelet expression of CD40 ligand in adults with cardiovascular disease.

The application of soluble CD40 ligand (sCD40L) as a biomarker has garnered great scientific and clinical interest. However, there are many uncertainties with regard to the biology of sCD40L. Although presumed to be a marker of platelet activation, relative levels in plasma, serum, and platelet expression are unknown, as is the optimal method for its measurement.

Effect of local restaurant smoking regulations on progression to established smoking among youths.

Background: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis.

Objective: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents.

Immune responses to p53 in patients with cancer: enrichment in tetramer+ p53 peptide-specific T cells and regulatory T cells at tumor sites.

Objective: A majority of human cancers, including head and neck cancer (HNC), "overexpress" p53. Although T cells specific for wild-type (wt) sequence p53 peptides are detectable in the peripheral blood of patients with HNC, it is unknown whether such T cells accumulate in tumor-involved tissues. Also, the localization of "regulatory" T cells (Treg) to tumor sites in HNC has not been investigated to date.

[Ki-67 antisense therapy in murine renal cell carcinoma models].

Purpose: The Ki-67 antigen is only expressed in proliferating cells. Previously, it was shown that Ki-67 derived antisense oligonucleotides (asONs) specifically inhibit the proliferation of tumor cells and tumour growth in vitro and in subcutaneous bladder and prostate tumor models. We intended to evaluate the effects of this therapeutic concept in two renal cell carcinoma (RCC) models.

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.

Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4+CD25+ (Treg) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of Treg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry.

Preferences for different methods of communicating information regarding adjuvant chemotherapy for breast cancer.

Many patients play an active role in determining their cancer treatments, and the communication of medical information influences patient decision-making. This study examined participants' preferences between various methods of communicating quantitative risks and benefits of adjuvant chemotherapy. Using clinical vignettes, participants were first asked to decide whether or not to endorse chemotherapy and were subsequently asked about their preferences for the methods used to communicate the risks and benefits.

Adults only: the prevalence of tobacco promotions in bars and clubs in the Boston area.

Objective: To document the nature and prevalence of tobacco promotions in bars and clubs in a major US city.

Design: We conducted systematic observations in a representative sample of 38 establishments in the Boston area, half of which had been advertised in a tobacco company ad. We also observed seven events in six additional clubs hosting Camel Casbah promotions.

Relation between local restaurant smoking regulations and attitudes towards the prevalence and social acceptability of smoking: a study of youths and adults who eat out predominantly at restaurants in their town.

Objective: To examine the relation between strength of local restaurant smoking regulations and smoking related social norms among youths and adults.

Design: We used generalised estimating equations logistic regression analysis to examine the relation between regulation strength and youths' and adults' perceptions of adult smoking prevalence and the social acceptability of smoking in their town, while controlling for baseline anti-smoking sentiment in the town.

Setting: Each of the 351 Massachusetts towns were classified as having strong (complete smoking ban), medium (restriction of smoking to enclosed, separately ventilated areas), or weak (all others) restaurant smoking regulations.

Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis.

HeLaHF cells are transformation revertants of cervical cancer HeLa cells and have lost anchorage-independent growth potential and tumorigenicity. Activation of tumor suppressor(s) was implicated previously in this transformation reversion. In this study, expression profiling analysis was carried out to identify potential oncogenes that are down-regulated in HeLaHF cells.

Impact of p53-based immunization on primary chemically-induced tumors.

In mice as well as humans, cytotoxic T lymphocytes (CTL) specific for wild-type-sequence (wt) p53 peptides have been shown to react against a wide range of tumors, but not normal cells. As such, they are attractive candidates for developing broadly applicable cancer vaccines. Of particular interest is the potential of using p53-based vaccines in high-risk individuals to prevent cancer.

Effects of restaurant and bar smoking regulations on exposure to environmental tobacco smoke among Massachusetts adults.

Objectives: We examined the association of local restaurant and bar regulations with self-reported exposure to environmental tobacco smoke among adults.

Methods: Data were derived from a telephone survey involving a random sample of Massachusetts households.

Results: Compared with adults from towns with no restaurant smoking restrictions, those from towns with strong regulations had more than twice the odds of reporting nonexposure to environmental tobacco smoke (odds ratio [OR]=2.

Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone.

Postheparin plasma hepatic lipase (HL) activity has been shown to correlate with features of the metabolic syndrome and type 2 diabetes in humans. We examined HL postheparin plasma enzyme activity, hepatocyte mRNA, and protein mass in the insulin-resistant, fructose-fed Syrian golden hamster, and the response of the insulin-sensitizing peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Male Syrian golden hamsters were treated for 5 weeks with 1) normal diet (DIET group), 2) 60% fructose diet (FRUC group), or 3) 60% fructose and rosiglitazone (20 mmol .

The impact of emotional tone, message, and broadcast parameters in youth anti-smoking advertisements.

Objectives: In the context of controversy regarding the optimal characteristics of anti-smoking advertisements for youth, this study examines the impact on recall and perceived effectiveness of variations in the message, emotional tone, reach and frequency of broadcast, remoteness of broadcast, and characteristics of the adolescent audience such as changes in smoking behavior, ownership of cigarette promotional items, and demographic variables.

Method: A two-wave longitudinal survey of a population-based sample of 618 Massachusetts youth 12 to 15 years old was carried out in 1993 and 1997. A Generalized Estimating Equation (GEE) approach was used to model the recall and perceived effectiveness of eight advertisements as a function of viewer and ad characteristics.

One-week 96-well soft agar growth assay for cancer target validation.

Soft agar growth, used to measure cell anchorage-independent proliferation potential, is one of the most important and most commonly used assays to detect cell transformation. However, the traditional soft agar assay is time-consuming, labor-intensive, and plagued with inconsistencies due to individual subjectivity. It does not, therefore, meet the increasing demands of today's oncology drug target screening or validation processes.

Additive effects of TRAIL and paclitaxel on cancer cells: implications for advances in cancer therapy.

In cancer therapy outgrowth of chemoresistant tumor cells is the most important factor that ultimately determines-apart from immediate adverse effects during treatment-the life span and prognosis of cancer patients. Despite many advances in cancer treatment and the integration of supportive medications, including new and better drugs for pain management, antiemesis, infection, and reconstitution of the hematopoietic system, both toxic effects and the development of resistance in response to the treatment remain a major problem. New treatment regimens have to be developed to target cancer more specifically using multiple cellular pathways.

Young adults: vulnerable new targets of tobacco marketing.

Objectives: We examined young adult smoking patterns and receptivity to cigarette advertising to assess vulnerability to tobacco marketing strategies.

Methods: We obtained data from a telephone survey of 12,072 Massachusetts adults.

Results: Smokers aged 18 to 30 years were more likely than older adults to smoke only occasionally and to consume fewer than 10 cigarettes per day.

Effect of local restaurant smoking regulations on environmental tobacco smoke exposure among youths.

Objectives: We examined the effect of local restaurant smoking regulations on restaurant environmental tobacco smoke exposure among youths.

Methods: We interviewed 3863 Massachusetts youths aged 12-17 years and ascertained how often they saw smokers in restaurants in their town. We assessed the effect of local restaurant smoking regulation strength on nonexposure to environmental tobacco smoke (seeing smokers never or only rarely).

P53(110-124)-specific human CD4+ T-helper cells enhance in vitro generation and antitumor function of tumor-reactive CD8+ T cells.

Current evidence suggests that the optimal vaccines for cancer should incorporate tumor-specific cytotoxic as well as helper epitopes. Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, which could combine multiple tumor epitopes defined by CD8(+) CTLs, as well as CD4(+) T-helper cells. To test this possibility, we generated anti-p53 CD4(+) T cells from peripheral blood obtained from an HLA-DRB1*0401(+) donor by in vitro stimulation with dendritic cells and recombinant human p53 protein.

Adolescent participation in tobacco promotions: the role of psychosocial factors.

Objectives: To identify psychosocial factors that place adolescents at risk for participation in tobacco promotions, and to further investigate the hypothesis that psychosocial vulnerabilities have an indirect effect on smoking initiation among youth by way of involvement with tobacco promotions.

Methods: Data were from a follow-up telephone survey of youth in Massachusetts. A subset of adolescents who were not established smokers, had not smoked cigarettes in the past 30 days, and did not own a promotional item at baseline in 1993 was used for the analyses (n = 468).

Suppression of tumorigenicity in neuroblastoma cells by upregulation of human vasoactive intestinal peptide receptor type 1.

We hypothesize that vasoactive intestinal peptide (VIP) promotes neural crest differentiation through VIP receptor type I (VPAC1). In order to test this hypothesis, SKNSH neuroblastoma cells were stably transfected with VPAC1 and receptor expression was verified by real-time RT-PCR. Overexpression of VPAC1 in SKNSH cells resulted in upregulation of endogenous retinoic acid receptor expression for both RARalpha and RXRalpha with no change in expression of RARbeta.

Influence of rBAT-mediated amino acid transport on cytosolic pH.

rBAT, together with its subunit b(0,+) AT mediates the hetero- and homoexchange of neutral and dibasic amino acids. Since the heteroexchange of dibasic amino acids against neutral amino acids is coupled to net transport of positive charge, this transport is electrogenic. Extracellular addition of histidine could create an inward or an outward current depending on extracellular pH (pH(e)) and cell membrane potential.

Human tumor-derived genomic DNA transduced into a recipient cell induces tumor-specific immune responses ex vivo.

This article describes a DNA-based vaccination strategy evaluated ex vivo with human cells. The vaccine was prepared by transferring tumor-derived genomic DNA to PCI-13 cells, a highly immunogenic tumor cell line ("recipient cell"), which had been genetically modified to secrete IL-2 (PCI-13/IL-2). PCI-13 cells expressed class I MHC determinants (HLA-A2) shared with the tumor from which the DNA was obtained as well as allogeneic determinants.