The "epidemic" of breast cancer in the U.S.--determining the factors

Breast cancer incidence rates in the United States rose by 24% between 1973 and 1991. Mortality during this period, however, remained stable. Both the 5-year relative survival rate and the rates of in situ and stage I breast cancers have been increasing, while the incidence of later-stage cancers has been decreasing. Increased mammography screening may explain the documented jump in breast cancer incidence rates during the mid-1980s. Differences in the distribution of breast cancer risk factors may account, in part, for the temporal trends in breast cancer incidence. In particular, breast cancer risk factors may vary by birth cohort, including age at menarche, age at first birth, physical activity, obesity, diet, alcohol intake, estrogen therapy, and exposure to environmental organochlorines. After decades of epidemiologic research, a preventive approach to breast cancer that focuses on the physiologic effects of the sex steroid hormones, and their potential interactions with family history, is being carefully formulated.     

Characteristic Anthocyanin Pattern from Onions and other Allium spp

Three red onion (Allium cepa) cultivars, top onion (A. cepa var. vivi-parum), A. altaicum and chive (A. schoenoprasum) contained several or all of the following anthocyanins: 3-(6′-malonyl-3′-glucosylglucoside), 3-(3′,6′-dimalonylglucoside), 3-(6′-malonylglucoside), 3-(3′-malonyl-glucoside), 3-(3′-glucosylglucoside) and 3-glucoside of cyanidin. Trace amounts of two pelargonidin derivatives and the 3,5-diglucosides of cyanidin and peonidin were for the first time reported in red onion. Carbon NMR data showed that the sugars of the 3-(6′-malonyl-3′-glu-cosylglucoside), 3-(6′-malonylglucoside) and 3-glucoside of cyanidin were pyranoses. Substitution either by sugar or acid in the sugar 3-position of an anthocyanin has never been reported outside the genus Allium.     

Finite element stress analysis of a new design of synthetic leaflet heart valve

This paper presents a parametric finite element analysis of the stresses in the leaflets of a new design of polyurethane heart valve in the closed position. The alpharabola geometry of the valve has previously been reported by Leat and Fisher (1) and has been shown to demonstrate good opening characteristics. The effects of variations in leaflet offset parameter, g, length, h, and local thickening have been determined for a valve where the frame is assumed rigid. A spherical leaflet geometry has also been analysed for comparative purposes. Results have shown that the alpharabola leaflet geometry can reduce the maximum principal tensile stress to 60 per cent of that for a spherical valve of the same mesh density.     

Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoprotein or MRP overexpression

MCF-7 human breast cancer cells selected in Adriamycin in the presence of verapamil developed a multidrug resistant phenotype, which was characterized by as much as 100,000-fold resistance to mitoxantrone, 667-fold resistance to daunorubicin, and 600-fold resistance to doxorubicin. Immunoblot and PCR analyses demonstrated no increase in MDR-1 or MRP expression in resistant cells, relative to parental cells. This phenotype is similar to one previously described in mitoxantrone-selected cells. The cells, designated MCF-7 AdVp, displayed a slower growth rate without alteration in topoisomerase II alpha level or activity. Increased efflux and reduced accumulation of daunomycin and rhodamine were observed when compared to parental cells. Depletion of ATP resulted in complete abrogation of efflux of both daunomycin and rhodamine. No apparent alterations in subcellular daunorubicin distribution were observed by confocal microscopy. No differences were noted in intracellular pH. Molecular cloning studies using DNA differential display identified increased expression of the alpha subunit of the amiloride-sensitive sodium channel in resistant cells. Quantitative PCR studies demonstrated an eightfold overexpression of the alpha subunit of the Na+ channel in the resistant subline. This channel may be linked to the mechanism of drug resistance in the AdVp cells. The results presented here support the hypothesis that a novel energy-dependent protein is responsible for the efflux in the AdVp cells. Further identification awaits molecular cloning studies.     

Predictive modeling of mercury speciation in combustion flue gases using GMDH-based abductive networks

Modeling mercury speciation is an important requirement for estimating harmful emissions from coal-fired power plants and developing strategies to reduce them. First-principle models based on chemical, kinetic, and thermodynamic aspects exist, but these are complex and difficult to develop. The use of modern data-based machine learning techniques has been recently introduced, including neural networks. Here we propose an alternative approach using abductive networks based on the group method of data handling (GMDH) algorithm, with the advantages of simplified and more automated model synthesis, automatic selection of significant inputs, and more transparent input–output model relationships. Models were developed for predicting three types of mercury speciation (elemental, oxidized, and particulate) using a small dataset containing six inputs parameters on the composition of the coal used and boiler operating conditions. Prediction performance compares favourably with neural network models developed using the same dataset, with correlation coefficients as high as 0.97 for training data. Network committees (ensembles) are proposed as a means of improving prediction accuracy, and suggestions are made for future work to further improve performance.     

A novel zinc finger cDNA with a polymorphic pentanucleotide repeat (ATTTT)n maps on human chromosome 19p

PURPOSE: To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS: Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS: Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION: These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).     

Polymerase chain reaction amplification analyses of clonality in T-cell malignancy including peripheral T-cell lymphoma

Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V beta 1-20 family primers and polymerase chain reaction amplification (PCR) of cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR amplification of the VDJ joints of primary PCR products was performed to distinguish clonal from polyclonal products, and clonal V beta gene products were confirmed by direct PCR sequencing in the majority of cases. In eight T-cell malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot analysis, one or two primary PCR products were identified and shown to be clonal. In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were identified after primary PCR amplification, and clonal products were identified in two cases after secondary amplification; TcR V beta clonal families could not be demonstrated in the remaining three cases. These data were in agreement with previous Southern blot analysis of these cases, and confirmed the presence of reactive T cells in PTCL as well as providing further evidence for the genotypic heterogeneity of this entity. In the remaining case, a blood lymphocytosis, primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family products, of which the V beta 6 family proved clonal after secondary PCR amplification. There was no evidence for overrepresentation of TCR V beta families by the tumour populations in this study, furthermore the data confirm the involvement of reactive cells in T-cell malignancy and the genetic heterogeneity of PTCL.