Phase II trial of irinotecan, cisplatin and mitomycin for relapsed small cell lung cancer.

There is no standard therapy for relapsed small cell lung cancer (rSCLC). We evaluated the efficacy and toxicity of a new triplet consisting of irinotecan (100 mg/m(2) Days 1 and 15 q28), cisplatin (40 mg/m(2) Days 1 and 15 q28) and mitomycin (6 mg/m(2) d1 q28) administered to a maximum of 6 cycles in individuals with rSCLC that had relapsed following first line treatment. Partial remissions were observed in 35% and progression in 30% of patients.

SigmaB and SarA independently regulate polysaccharide intercellular adhesin production in Staphylococcus epidermidis.

The production of polysaccharide intercellular adhesin (PIA) is an essential process in foreign body infections mediated by Staphylococcus epidermidis. Transcriptional regulation of the icaADBC operon, the genes responsible for production of enzymes that synthesize PIA, is multi-factorial and involves at least SarA and sigmaB. Transcriptional and promoter fusion studies revealed that the decreased transcription of the icaADBC operon observed in a S.

The impact of retail cigarette marketing practices on youth smoking uptake.

Objective: To examine the differential associations of cigarette retail marketing practices on youth smoking uptake.

Design: Analyses from annual, nationally representative, cross-sectional surveys of 8th, 10th, and 12th graders in the United States.

Setting: The February 1999 through June 2003 Monitoring the Future surveys involved 109,308 students and data on retail cigarette marketing collected from 966 communities in which the students reside, as part of the Bridging the Gap Initiative: Research Informing Practice and Policy for Healthy Youth Behavior.

1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism.

1,25-Dihydroxyvitamin D(3) (1,25D) is known primarily as a regulator of calcium, but 1,25D also promotes phosphate absorption from intestine, reabsorption from kidney, and bone mineral resorption. FGF23 is a newly discovered phosphaturic hormone that, like PTH, lowers serum phosphate by inhibiting renal reabsorption via Npt2a. We show that 1,25D strongly upregulates FGF23 in bone.

Breast cancer (metastatic).

Introduction: Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered unusual.

Methods And Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line hormonal treatment? What are the effects of second-line hormonal treatment in women who have not responded to tamoxifen? What are the effects of first-line chemotherapy? What are the effects of first-line chemotherapy in combination with a monoclonal antibody? What are the effects of second-line chemotherapy? What are the effects of treatments for bone metastases? What are the effects of treatments for spinal cord metastases? What are the effects of treatments for cerebral or choroidal metastases? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: implications for polysaccharide intercellular adhesin synthesis and autolysis.

The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S.

Competitive binding of protein kinase Calpha to membranes and Rho GTPases.

Previously, we have shown that protein kinase C (PKC) forms a direct high-affinity, isozyme-specific and membrane lipid-independent interaction with Rho GTPases [Slater, S. J., Seiz, J.

Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression.

We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of beta-catenin. In this study we demonstrate directly that growth factors stimulate beta-catenin/T-cell factor (TCF) signaling in primary VSMCs. To determine whether beta-catenin/TCF signaling regulates VSMC proliferation via modulation of the beta-catenin/TCF responsive cell cycle genes, cyclin D1 and p21, we inhibited beta-catenin/TCF signaling by adenoviral-mediated over-expression of N-Cadherin, ICAT (an endogenous inhibitor of beta-catenin/TCF signaling), or a dominant negative (dn) mutant of TCF-4.

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals.

Food store availability and neighborhood characteristics in the United States.

Objective: This study provides a multivariate analysis of the availability of food store outlets in the US and associations with neighborhood characteristics on race, ethnicity and socioeconomic status (SES).

Method: Commercial food store outlet data are linked across 28,050 zip codes to Census 2000 data. Multivariate regression analyses are used to examine associations between the availability of chain supermarkets, non-chain supermarkets, grocery stores and convenience stores and neighborhood characteristics on race, ethnicity and SES including additional controls for population size, urbanization and region.

Availability of physical activity-related facilities and neighborhood demographic and socioeconomic characteristics: a national study.

Objectives: We examined associations between neighborhood demographic characteristics and the availability of commercial physical activity-related outlets by zip code across the United States.

Methods: Multivariate analyses were conducted to assess the availability of 4 types of outlets: (1) physical fitness facilities, (2) membership sports and recreation clubs, (3) dance facilities, and (4) public golf courses. Commercial outlet data were linked by zip code to US Census Bureau population and socioeconomic data.

Biochemical limitations to high-level expression of humanized monoclonal antibodies in transgenic maize seed endosperm.

Transgenic plants are potentially valuable systems for the large scale manufacture of therapeutic proteins. To improve this technology, determining the importance of transgene transcript levels on protein accumulation in sink tissues during their development is crucial. In transgenic maize (Zea mays L.

Increase in schizophrenia incidence rates: findings in a Canadian cohort born 1975-1985.

Background: Results from previous studies on the incidence rates for schizophrenia are inconsistent, with some showing a declining rate [e.g., Suvisaari et al.

Application of the Synechococcus nirA promoter to establish an inducible expression system for engineering the Synechocystis tocopherol pathway.

Tocopherols are important antioxidants in lipophilic environments. They are synthesized by plants and some photosynthetic bacteria. Recent efforts to analyze and engineer tocopherol biosynthesis led to the identification of Synechocystis sp.

Patent ductus arteriosus in a 9-day-old Grant's zebra.

A 9-day old Grant's zebra with a 3-day history of lethargy, weight loss, inappetance, and diarrhea was treated with ampicillin, vitamin E and selenium, and tetanus antitoxin without effect in 24 h. On transfer to the local veterinary clinic, a grade IV/VI continuous heart murmur was detected and a patent ductus arteriosus found at necropsy.

Bacterial contaminants and antibiotic prophylaxis in total hip arthroplasty.

We have investigated the contaminating bacteria in primary hip arthroplasty and their sensitivity to the prophylactic antibiotics currently in use. Impressions (627) of the gloved hands of the surgical team in 50 total hip arthroplasties were obtained on blood agar. The gloves were changed after draping, at intervals of 20 minutes thereafter, and before using cement.

Complementary role of adjunctive breast magnetic resonance imaging and scintimammography in patients of all ages undergoing breast cancer surgery.

The aims of this study were to assess breast MRI and scintimammography (SMM) for the detection of breast cancer, and to determine any complementary role of these tests to each other and conventional imaging. Seventy-two patients (age 35-81 years) with a suspicious breast mass were investigated by mammography, breast ultrasound, breast MRI and SMM before undergoing surgical excision of the breast mass. Sensitivity, specificity and area under receiver operator characteristic curves were calculated for each test.

The social realities of adherence to protease inhibitor regimens: substance use, health care and psychological states.

Adherence to HIV antiretroviral treatments is impacted by a variety of factors nested within the realities of people's lives. To understand this phenomenon, we undertook an investigation to assess HIV medication adherence in a community-based sample of 300 HIV seropositive men-who-have-sex-with-men (MSM). Using multiple measurement strategies (self-report, electronic monitoring, calendar-based assessments) we assessed factors related to medication adherence.

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study.

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30-49 years, who probably mainly had type II.

The use of time-resolved fluorescence imaging in the study of protein kinase C localisation in cells.

Background: Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was used to investigate the association of protein kinase C alpha (PKCalpha) with caveolin in CHO cells. PKCalpha is found widely in the cytoplasm and nucleus in most cells. Upon activation, as a result of increased intracellular Ca2+ and production of DAG, through G-protein coupled-phospholipase C signalling, PKC translocates to a variety of regions in the cell where it phosphorylates and interacts with many signalling pathways.

Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95.

Aims: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus.

Methods: Data about diabetes from the Diabetes UK cohort were linked to data on births from the Scottish Hospital In-Patient Record System. This identified 1112 eligible singleton deliveries during 1979-95 to 706 insulin-treated women.

N-cadherin-dependent cell-cell contacts promote human saphenous vein smooth muscle cell survival.

Objective: Vascular smooth muscle cell (VSMC) apoptosis is thought to contribute to atherosclerotic plaque instability. Cadherin mediates calcium-dependent homophilic cell-cell contact. We studied the role of N-cadherin in VSMC apoptosis.

Social marketing improved the use of multivitamin and mineral supplements among resource-poor women in Bolivia.

Objective: To test the hypothesis that social marketing improves women's awareness and consumption of multivitamin and mineral supplements.

Design: Formative research and baseline and final surveys using a multistaged stratified cluster sample.

Setting: Department of Santa Cruz, Bolivia.