Improved fluorescent probes for the measurement of rapid changes in membrane potential

To improve the quality of fluorescent voltage-sensitive probes twenty new styryl dyes were synthesized. Some of the new probes are significantly better than any used in the past. A signal-to-noise ratio of 90 root mean square (rms) noise was obtained for an optical recording of action potentials from neuroblastoma cells maintained in monolayer culture. The fluorescence fractional change of the optical signal is as large as 14%/100 mV. Photodynamic damage and bleaching are much less significant with the new probes. These fluorescent probes can be used to measure small and rapid changes in membrane potential from single cells maintained in monolayer cultures, from single cells in invertebrate ganglia, from their arborization, and from other preparations. The optical measurement can be made with a standard fluorescent microscope equipped with DC mercury illumination. Guidelines for the design of even better fluorescent probes and more efficient instruments are suggested

Relative and Attributable Risk for Cervical Cancer: A Comparative Study in the United States and Italy

Parazzini F {Istituto di Ricerche Farmacologiche ‘Mario Negri' via Eritrea 62,20157 Milan, Italy), Hildesheim A, Ferraroni M, La Vecchia C and Brinton LA. Relative and attributable risk for cervical cancer: A comparative study in Italy and the United States. International Journal of Epidemiology 1990, 19: 539-545. The attributable risk for invasive cervical cancer in the US and Italian populations has been estimated in relation to main ‘aetiological' factors (number of sexual partners, age at first intercourse, parity, oral contraceptive use and smoking) and history of Pap smear using data from two case-control studies conducted in the US (466 cases and 788 controls) and Italy (528 cases and 456 controls). The risk of cervical cancer increased in both studies with multiple sexual partners, decreasing age at first intercourse, higher parity, oral contraceptive use and smoking. Levels of exposure to various risk factors were markedly different in the two countries (ie number of sexual partners, frequency of oral contraceptive use and smoking were greater in the US). Multiple Pap smears and a short interval since last Pap smear strongly reduced risk of cervical cancer in both populations, although screening was much more widespread in the US study population, with only 9% of controls reporting no previous smear versus 38% of the Italian control series. The combined population attributable risk for the five ‘aetiological' risk factors was slightly greater in the US study (76%) than in the Italian one (69%), chiefly because of a higher prevalence of exposure to sexual factors in US study women. A substantially larger proportion of Italian cases were due in part to deficiency in screening (46% in US and 84% in Italy). Thus, further inclusion of the effect of screening programmes (number of Pap smears and time since last Pap) led to an overall proportion of cases attributable to the examined risk factors of 87% in the US and 95% in Ital

Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare tumor in most parts of the world but occurs at relatively high frequency among people of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is responsible for the metabolic activation of nitrosamines, and has been shown to be a susceptibility gene for NPC development in Taiwan [RR = 2.6; 95%CI = 1.2-5.7]. Since there has been only one report of this link, it was decided to investigate the susceptibility of CYP2E1 to NPC development in other populations. Therefore, the correlation between the RsaI polymorphism of this gene and NPC was studied in-patients including Thai and Chinese in Thailand. The present study comprised 217 cases diagnosed with NPC and 297 healthy controls. RESULTS: Similar to the result found in Taiwanese, a homozygous uncut genotype demonstrated a higher relative risk both when all cases were analyzed [RR = 2.19; 95%CI = 0.62-8.68] or individual racial groups, Thai [RR = 1.51; 95%CI = 0.08-90.06] or Chinese [RR = 1.99; 95%CI = 0.39-10.87]. The ethnicity-adjusted odds ratio is 2.39 with 95%CI, 0.72-7.89. CONCLUSIONS: Though our finding was not statistically significant due to the moderate sample size of the study, similarity to the study in Taiwan with only a slight loss in precision was demonstrated. The higher RR found for the same genotype in distinct populations confirmed that CYP2E1 is one of several NPC susceptibility genes and that the RsaI minus variant is one mutation that affects phenotype

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

Determinants of Acceptance of Cervical Cancer Screening in Dar es Salaam, Tanzania.

To describe how demographic characteristics and knowledge of cervical cancer influence screening acceptance among women living in Dar es Salaam, Tanzania. Multistage cluster sampling was carried out in 45 randomly selected streets in Dar es Salaam. Women between the ages of 25-59 who lived in the sampled streets were invited to a cervical cancer screening; 804 women accepted and 313 rejected the invitation. Information on demographic characteristics and knowledge of cervical cancer were obtained through structured questionnaire interviews. Women aged 35-44 and women aged 45-59 had increased ORs of 3.52 and 7.09, respectively, for accepting screening. Increased accepting rates were also found among single women (OR 2.43) and among women who had attended primary or secondary school (ORs of 1.81 and 1.94). Women who had 0-2 children were also more prone to accept screening in comparison with women who had five or more children (OR 3.21). Finally, knowledge of cervical cancer and awareness of the existing screening program were also associated with increased acceptance rates (ORs of 5.90 and 4.20). There are identifiable subgroups where cervical cancer screening can be increased in Dar es Salaam. Special attention should be paid to women of low education and women of high parity. In addition, knowledge and awareness raising campaigns that goes hand in hand with culturally acceptable screening services will likely lead to an increased uptake of cervical cancer screening