tbuckley/cabot-search huggingface dataset:
p66 Shc Tumor Levels Show a Strong Prognostic Correlation with Disease Outcome in Stage IIA Colon Cancer
Authors: Steven R. Grossman, Stephen Lyle, Murray B. Resnick, Edmond Sabo, Rosina T. Lis, Elizabeth Rosinha, Qin Liu, Chung-Cheng Hsieh, Gajanan Bhat, A. Raymond Frackelton, Laurie J. Hafer
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Most stage IIA colon cancer patients receive no adjuvant therapy despite an estimated 15% risk of disease-related death within 5 years of resection. Prognostication of disease outcome would benefit the clinician by categorizing patients with stage IIA disease by risk. The abundance of the signal transduction proteins p66 Shc and tyrosine-phosphorylated (PY)-Shc in tumor cells is a prognostic indicator of disease outcome in breast cancer, suggesting that Shc analysis may provide prognostic information in stage IIA colon cancer. Experimental Design: Immunohistochemical staining of p66 Shc and PY-Shc was examined in resection specimens from 240 chemotherapy-naïve patients with stage IIA (T3N0M0) colon cancer from two independent (130 and 110 cases, respectively) retrospective cohorts. Staining was scored on a 0 to 5 scale and correlated with relapse-free survival and disease-specific survival in a multivariate analysis to obtain hazard ratios (HR) for both outcomes. Results: In a pooled analysis of both cohorts, p66 Shc score was a significant prognostic indicator of relapse-free survival (full-range HR, 13.0; P = 0.012) and disease-specific survival (full-range HR, 36.6; P = 0.004) when analyzed as a continuous variable in a multivariate Cox proportional hazards model stratified by study site and adjusted for age, sex, grade, and lymphovascular involvement. PY-Shc in this multivariate Cox model, however, did not achieve statistical significance for either outcome. Conclusions: Measuring p66 Shc tumor levels provides a unique and simple tool for stratifying stage IIA colon cancer patients by risk of recurrence and disease-specific death and may assist in determining treatment strategies for these patients.
The sensitivity of the child to sex steroids: possible impact of exogenous estrogens
Authors: Lise Aksglaede, Anders Juul, Henrik Leffers, Niels E Skakkebaek, Anna-Maria Andersson
Journal: Human Reproduction Update (2006)

The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.
CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo
Authors: Roberto Maldonado-López, Thibaut De Smedt, Patrick Michel, Jacques Godfroid, Bernard Pajak, Carlo Heirman, Kris Thielemans, Oberdan Leo, Jacques Urbain, Muriel Moser
Journal: The Journal of Experimental Medicine (1999)

Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that differ by their CD8α expression and their localization in lymphoid organs. The physiologic function of both cell populations remains obscure. Studies conducted in vitro have suggested that CD8α+ DCs could play a role in the regulation of immune responses, whereas conventional CD8α− DCs would be more stimulatory. We report here that both subclasses of DCs efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper (Th) populations. Antigen-pulsed CD8α+ and CD8α− DCs are separated after overnight culture in recombinant granulocyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8α− DCs induces a Th2-type response, whereas injection of CD8α+ DCs leads to Th1 differentiation. We further show that interleukin 12 plays a critical role in Th1 development by CD8α+ DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptative immune response.
Phase I Study of the Intravenous Administration of Attenuated Salmonella typhimurium to Patients With Metastatic Melanoma
Authors: J. F. Toso
Journal: Journal of Clinical Oncology (2002)

PURPOSE: A strain of Salmonella typhimurium (VNP20009), attenuated by chromosomal deletion of the purI and msbB genes, was found to target to tumor and inhibit tumor growth in mice. These findings led to the present phase I study of the intravenous infusion of VNP20009 to patients with metastatic cancer. PATIENTS AND METHODS: In cohorts consisting of three to six patients, 24 patients with metastatic melanoma and one patient with metastatic renal cell carcinoma received 30-minute intravenous bolus infusions containing 106 to 109 cfu/m2 of VNP20009. Patients were evaluated for dose-related toxicities, selective replication within tumors, and antitumor effects. RESULTS: The maximum-tolerated dose was 3 × 108 cfu/m2. Dose-limiting toxicity was observed in patients receiving 1 × 109 cfu/m2, which included thrombocytopenia, anemia, persistent bacteremia, hyperbilirubinemia, diarrhea, vomiting, nausea, elevated alkaline phosphatase, and hypophosphatemia. VNP20009 induced a dose-related increase in the circulation of proinflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor alpha, IL-6, and IL-12. Focal tumor colonization was observed in two patients receiving 1 × 109 cfu/m2 and in one patient receiving 3 × 108 cfu/m2. None of the patients experienced objective tumor regression, including those patients with colonized tumors. CONCLUSION: The VNP20009 strain of Salmonella typhimurium can be safely administered to patients, and at the highest tolerated dose, some tumor colonization was observed. No antitumor effects were seen, and additional studies are required to reduce dose-related toxicity and improve tumor localization.
Presence of somatostatin in normal human epidermis
Authors: A. GAUDILLÈRE, L. MISERY, C. BERNARD, C. SOUCHIER, A. CLAUDY, D. SCHMITT
Journal: British Journal of Dermatology (1997)

Somatostatin (SOM) is a ubiquitous peptide which is responsible for the inhibition of numerous biological functions. SOM is described as an antiproliferative molecule and an inhibitor of exocrine or endocrine secretion from a variety of tissues, including pancreas, gastrointestinal tract, central and peripheral nervous system. Mediation of SOM effects can be indirect or direct, respectively, through other molecules or receptors on target cells. We have searched for the presence of SOM in the epidermis using immunofluorescence, confocal laser scanning microscopy, radioimmunoassay, and chromatography. Immunofluorescence and confocal laser scanning microscopy studies were performed using rabbit antiserum anti-SOM and mouse monoclonal antibody directed to CD1a Langerhans cell (LC) marker disclosed with fluorescein or tetramethylrhodamine isothiocyanate conjugates. SOM was extracted from whole skin or epidermal cell suspension or LC-enriched suspensions and analysed by radioimmunoassay. We used an antiserum which was reactive for the 6-11 portion of native SOM. Chromatographic columns were performed on extracts from whole skin. The epidermis was SOM immunoreactive. LC were immunoreactive for SOM and the staining was membranous. SOM was extracted from the whole skin at about 0.13 +/- 0.02 fmol/mg of tissue (mean +/- SEM). The SOM concentration in epidermal cell suspensions was 1.5 +/- 0.9 fmol/10(6) cells. Data obtained with LC-enriched suspensions showed large variations between donors. Extracts from skin showed one peak with an elution profile like that of 14 amino acid SOM. This study demonstrates that 14 amino acid SOM is expressed in normal human epidermis.
Rhinovirus and risk of childhood asthma
Authors: Chris Course
Journal: Thorax (2013)

Rhinovirus and risk of childhood asthmaCaliskan et al 1 report a significant interaction between genotype variants at the 17q21 locus and human rhinovirus (HRV) wheezing illness in early life leading to the development of childhood onset asthma.The authors studied the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts, as well as 100 adults.Genotype-specific effects of HRV stimulation on peripheral blood mononuclear cells (PBMCs) were examined.Five asthma-associated 17q21 single nucleotide polymorphisms (SNPs) were genotyped in the COAST and COPSAC cohorts.Each was tested for an association with asthma and phenotypes of viral wheezing illness using either a linear or binary regression model.PBMCs were analysed in vitro from each of the adult participants using PCR to assess the expression of 17q21 polymorphisms in HRV-stimulated and HRV-unstimulated cells.All SNPs examined in the COAST cohort showed significant associations with HRV wheezing illness and the number of illnesses experienced in the first 3 years of life.This association was not found with respiratory syncytial virus (RSV) wheezing illness.Children with the 17q21 genotype and HRV wheezing illness were at increased risk of developing childhood asthma (OR 5.2).This finding was replicated in the COPSAC cohort (OR 3.9).The authors found significant upregulation of ORMDL3, hypothesised to prevent apoptosis in virally infected cells, in HRV-exposed PBMCs with the 17q21 genotype.They postulated that overexpression of this protein may increase the efficiency of viral infection and prevent HRV clearance.This study does not provide any evidence of causality and the importance of the aetiological influence of the lung's bacterial microbiome is not examined.It was also underpowered to effectively assess the interaction with RSV-induced wheezing illness.Further research is needed in this area; however, this study highlights the importance of understanding the interaction between genetics and environmental risk factors in the development of airways disease.
Bronchial lavage in the treatment of asthma.
Authors: E S Jones
Journal: Thorax (1969)

<h3>Background and objectives</h3> Patients without Medicare who develop ESKD in the United States become Medicare eligible by their fourth dialysis month. Patients without insurance may experience delays in obtaining arteriovenous fistulas or grafts before obtaining Medicare coverage. <h3>Design, setting, participants, &amp; measurements</h3> In this retrospective cohort study, we used a national registry to compare uninsured patients starting in-center hemodialysis with a central venous catheter between 2010 and 2013 with similar patients with Medicare or Medicaid. We evaluated whether insurance status at dialysis start influenced the likelihoods of switching to dialysis through an arteriovenous fistula or graft and hospitalizations involving a vascular access infection. We used multivariable logistic and Cox regression models and transformed odds ratios to relative risks using marginal effects. <h3>Results</h3> Patients with Medicare or Medicaid were more likely to switch to an arteriovenous fistula or graft by their fourth dialysis month versus uninsured patients (Medicare hazard ratio, 1.63; 95% confidence interval, 1.14 to 2.43; Medicaid hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.38). There were no differences in rates of switching to arteriovenous fistulas or grafts after all patients obtained Medicare in their fourth dialysis month (Medicare hazard ratio, 1.17; 95% confidence interval, 0.97 to 1.42; Medicaid hazard ratio, 1.01; 95% confidence interval, 0.96 to 1.06). Patients with Medicare at dialysis start had fewer hospitalizations involving vascular access infection in dialysis months 4–12 (hazard ratio, 0.60; 95% confidence interval, 0.37 to 0.97). <h3>Conclusions</h3> Insurance-related disparities in the use of arteriovenous fistulas and grafts persist through the fourth month of dialysis, may not fully correct after all patients obtain Medicare coverage, and may lead to more frequent vascular access infections.
Albumin-to-Creatinine Ratio in Random Urine Samples Might Replace 24-h Urine Collections in Screening For Micro- and Macroalbuminuria in Pregnant Woman With Type 1 Diabetes
Authors: Thomas I. Justesen, Jens L.A. Petersen, Pia Ekbom, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2006)

Pre-eclampsia, a clinical syndrome of unknown etiology, is among the most common reasons for perinatal and maternal mortality (1). The incidence of pre-eclampsia in women with type 1 diabetes is considerably higher (10–20%) than in the background population (4–5%) (2). Microalbuminuria, defined as a urinary albumin excretion from 30 to 300 mg/24 h before or in early pregnancy has proven to be a good risk marker for pre-eclampsia in women with type 1 diabetes (3). However, the urinary albumin status is often not known at booking for pregnancy. The traditional method for diagnosing microalbuminuria, collection of 24-h urine samples, is cumbersome and time consuming and may be associated with collection errors and poor compliance.

The aim of this study was to determine whether measurement of the albumin-to-creatinine ratio in random urine samples can replace 24-h urine collection in screening for micro- and macroalbuminuria in pregnant women with type 1 diabetes.

The study was conducted at Copenhagen University Hospital from 2000 to 2003. All women with type 1 diabetes who were admitted to our obstetric department before 14 weeks of gestation were asked to participate, and 119 women were enrolled.

The women were asked to make two 24-h urine collections and two random urine samples. The samples were collected between gestational weeks 7 and 22, since we previously have found the urinary albumin excretion …
Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial
Authors: Ajay K Kakkar, Benjamin Brenner, Ola E Dahl, Bengt I Eriksson, Patrick Mouret, Jim Muntz, Andrea G Soglian, Ákos F Pap, Frank Misselwitz, Sylvia Haas
Journal: The Lancet (2008)
Teaching as therapy: cross sectional and qualitative evaluation of patients' experiences of undergraduate psychiatry teaching in the community
Authors: K. Walters
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> To explore the impact of participating in undergraduate teaching in general practice for patients with common mental disorders. <b>Design:</b> Questionnaire survey and qualitative in-depth interviews. <b>Setting:</b> Community based undergraduate teaching programme for fourth year students at a London medical school doing a psychiatry attachment. <b>Participants:</b> Questionnaire survey: all patients involved in the teaching programme over one academic year. In-depth interviews: 20 patients, 14 students, and 12 general practitioner tutors participating in the programme. <b>Results:</b> The questionnaire showed high levels of satisfaction with teaching encounters for participating patients, which were corroborated in the interviews. Many patients and general practitioners reported specific therapeutic benefits for patients from contact with students, including raised self esteem and empowerment; the development of a coherent “illness narrative”; new insights into their problems; and a deeper, more balanced, and understanding doctor-patient relationship. For a few patients the teaching caused some distress, which may relate to a lack of insight into their condition or deficits in students9 interviewing skills. <b>Conclusions:</b> Participation in teaching can have additional positive therapeutic outcomes for selected patients with common mental disorders, although a small minority report negative effects. Testing in a larger sample is needed to determine the characteristics of patients in these two subgroups and establish whether these effects persist. <h3>What is already known on this topic</h3> Patients show high levels of general satisfaction with their participation in teaching Little is known in detail about outcomes for patients who participate in teaching—in particular, patients with common mental disorders in community settings <h3>What this study adds</h3> Patients with common mental disorders respond well to participation in undergraduate teaching in primary care Most patients value time to talk and reflect, and some gained a stronger, more balanced doctor-patient relationship In some patients the process results in higher self esteem and empowerment, a more coherent “illness narrative,” and new insights A few patients find the teaching encounter distressing
Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin
Authors: Pierre Savi, Beng H. Chong, Andreas Greinacher, Yves Gruel, John G. Kelton, Theodore E. Warkentin, Petra Eichler, Dick Meuleman, Maurice Petitou, Jean-Pascal Herault, Roger Cariou, Jean-Marc Herbert
Journal: Blood (2004)
Quantitative In Vitro Transformation of Syrian Golden Hamster Embryo Cells With the Use of Frozen Stored Cells2
Authors: Joseph A. DiPaolo
Journal: JNCI Journal of the National Cancer Institute (1980)

Quantitative transformation by carcinogens of Syrian golden hamster embryo cells from primary, secondary, or tertiary cultures could be obtained from cell pools frozen prior to any culturing with the same efficiency as with fresh cells. Cells retained the ability to activate a wide range of chemical carcinogens when the noncultured hamster cells were cooled at a controlled rate and when the established procedures for culturing cells were followed. The number of experiments that could be done with cells derived from frozen hamster pools could be increased by substitution of a hamster cell line for the feeder layer. The response to chemical carcinogens of different classes including carcinogenic hydrocarbons, aromatic amine derivatives, metal complexes, aflatoxin B1, N-methyl-N'-nitro-N-nitrosoguanidine, and UV irradiation was similar to that reported with fresh cells. Transformation rate increased with increasing carcinogen concentration. The factors important for the breeding of healthy animals and for selection of those appropriate for obtaining reproducible transformation experiments were enumerated.
Quantifying the Number of Pregnancies at Risk of Malaria in 2007: A Demographic Study
Authors: Stephanie Dellicour, Andrew J. Tatem, Carlos A. Guerra, Robert W. Snow, Feiko O. ter Kuile
Journal: PLoS Medicine (2010)

By combining data from the Malaria Atlas Project with country-specific data, Feiko ter Kuile and colleagues provide the first contemporary global estimates of the annual number of pregnancies at risk of malaria.
Design of Phase II Cancer Trials Using a Continuous Endpoint of Change in Tumor Size: Application to a Study of Sorafenib and Erlotinib in Non Small-Cell Lung Cancer
Authors: T. G. Karrison, M. L. Maitland, W. M. Stadler, M. J. Ratain
Journal: JNCI Journal of the National Cancer Institute (2007)

The primary objective of phase II cancer clinical trials is to determine whether a new regimen has sufficient activity to warrant further study, with activity generally defined as tumor shrinkage. However, oncology drug development has been limited by high rates of failure (lack of efficacy) in subsequent phase III testing. This high failure rate may reflect the process by which antineoplastic agents are usually evaluated in phase II trials, i.e., via single-arm studies in which the primary efficacy measure is the proportion of patients who achieve a complete or partial response to the treatment. This design may efficiently eliminate truly ineffective therapy but may not reliably indicate whether subsequent phase III testing is warranted. We describe the design of a randomized phase II clinical trial of sorafenib in combination with erlotinib for the treatment of patients with non–small-cell lung cancer using change in tumor size, measured on a continuous scale, as the primary outcome variable. For the purpose of determining the sample size of the trial, we made assumptions as to the likely magnitude of treatment effect and the variability in tumor size changes based on data from four previous trials using these agents. The study design includes two different dosage arms and a placebo group with a total sample size of 150 patients and is powered to detect a modest reduction in the mean tumor size burden in the high-dose sorafenib arm compared with a slight increase in the placebo group. Clinical trial designs that treat change in tumor size as a continuous variable rather than categorizing the changes are feasible, and by inclusion of a prospective control group they offer advantages over conventional single-arm trials.
Expression of RhCG, a New Putative NH3/NH4 + Transporter, along the Rat Nephron
Authors: Dominique Eladari, Lydie Cheval, Fabienne Quentin, Olivier Bertrand, Isabelle Mouro, Baya Cherif-Zahar, Jean-Pierre Cartron, Michel Paillard, Alain Doucet, Régine Chambrey
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Two non-erythroid members of the erythrocyte Rhesus (Rh) protein family, RhBG and RhCG, have been recently cloned in the kidney. These proteins share homologies with specific NH3/NH4+ transporters (Mep/Amt) in primitive organisms and plants. When expressed in a Mep-deficient yeast, RhCG can function as a bidirectional NH3/NH4+ transporter. The aim of this study was to determine the intrarenal and intracellular location of RhCG in rat kidney. RT-PCR on microdissected rat nephron segments demonstrated expression of mRNAs encoding RhCG in distal convoluted tubules, connecting ducts, and cortical and outer medullary collecting ducts but not in proximal tubules and thick ascending limbs of Henle's loop. Immunolocalization studies performed on rat kidney sections with rabbit anti-human RhCG 31 to 48 antibody showed labeling of the apical pole of tubular cells within the cortex, the outer medulla, and the upper portion of the inner medulla. All cells within connecting tubules had identical apical staining. In cortical collecting ducts, a subpopulation of cells that has either apical staining (α-intercalated cells) or diffuse staining (β-intercalated cells) for the β1 subunit of the H+-ATPase, was heavily stained at their apical pole with the RhCG antibody while principal cells identified as H+-ATPase negative cells showed a faint apical staining for RhCG that was much less intense than in adjacent intercalated cells. In the outer medulla and the upper portion of the inner medulla, RhCG labeling was restricted to a subpopulation of cells within the collecting duct that apically express the β1 subunit of the H+-ATPase, indicating that RhCG expression in medullary collecting ducts is restricted to intercalated cells. No labeling was seen in glomeruli, proximal tubules, and limbs of Henle's loop. Immunoblotting of apical membrane fractions from rat kidney cortex with the rabbit anti-human RhCG 31 to 48 antibody revealed a doublet band at approximatively 65 kD.