tbuckley/cabot-search huggingface dataset:
Mutations of the <b> <i>Epidermal Growth Factor Receptor</i> </b> Gene in Lung Cancer
Authors: Takayuki Kosaka, Yasushi Yatabe, Hideki Endoh, Hiroyuki Kuwano, Takashi Takahashi, Tetsuya Mitsudomi
Journal: Cancer Research (2004)

Abstract Recently it has been reported that mutations in the tyrosine kinase domain of the epidermal growth factor receptor(EGFR) gene occur in a subset of patients with lung cancer showing a dramatic response to EGFR tyrosine kinase inhibitors. To gain further insights in the role of EGFR in lung carcinogenesis, we sequenced exons 18–21 of the tyrosine kinase domain using total RNA extracted from unselected 277 patients with lung cancer who underwent surgical resection and correlated the results with clinical and pathologic features. EGFR mutations were present in 111 patients (40%). Fifty-two were in-frame deletions around codons 746–750 in exon 19, 54 were point mutations including 49 at codon 858 in exon 21 and 4 at codon 719 in exon 18, and 5 were duplications/insertions mainly in exon 20. They were significantly more frequent in female (P &amp;lt; 0.001), adenocarcinomas (P = 0.0013), and in never-smokers (P &amp;lt; 0.001). Multivariate analysis suggested EGFR mutations were independently associated with adenocarcinoma histology (P = 0.0012) and smoking status (P &amp;lt; 0.001), but not with female gender (P = 0.9917). In adenocarcinomas, EGFR mutations were more frequent in well to moderately differentiated tumors (P &amp;lt; 0.001) but were independent of patient age, disease stages, or patient survival. KRAS and TP53 mutations were present in 13 and 41%, respectively. EGFR mutations never occurred in tumors with KRAS mutations, whereas EGFR mutations were independent of TP53 mutations. EGFR mutations define a distinct subset of pulmonary adenocarcinoma without KRAS mutations, which is not caused by tobacco carcinogens.
Acceptability and Satisfaction With a Telecarer Approach to the Management of Type 2 Diabetes
Authors: Andrew F. Long, Tina Gambling, Robert J. Young, Jean Taylor, James M. Mason
Journal: Diabetes Care (2005)

To examine patients' views of the acceptability of and satisfaction with telephone care center support provided to improve blood glucose control in type 2 diabetes.The Pro-Active Call-Center Treatment Support (PACCTS) Trial randomized patients from 47 general practices in a deprived urban area in northwest England to usual care or to proactive call center support in addition to usual care. Satisfaction with care was assessed in all 591 patients at baseline and the end of the study using the Diabetes Satisfaction and Treatment Questionnaire (DTSQ). Acceptability was assessed in 394 intervention patients after at least three proactive calls from the call center and at the end of the trial. A purposive sample of 25 patients took part in in-depth semistructured interviews.The response rates to the questionnaires were 79% (DTSQ) and 65% (acceptability). Persons receiving the intervention continued to report high levels of satisfaction with their treatment (95% CI 32.3-33.2 at 1 year), and >90% strongly agreed or agreed that the telecarer approach was acceptable. Qualitative comments pointed to the importance of a personalized service; increased feelings of well-being, including confidence and self-control; help with problem-solving; and patients developing rapport and a strong bond with the telecarers.A personalized PACCTS approach is acceptable to patients. A service giving priority to the interpersonal dimension leads to increased commitment from patients to improve long-term glycemic control.
Integrin receptors on aortic smooth muscle cells mediate adhesion to fibronectin, laminin, and collagen.
Authors: R I Clyman, K A McDonald, R H Kramer
Journal: Circulation Research (1990)

Extracellular matrix receptors on vascular smooth muscle cells help in anchoring the cells during contraction and in promoting cellular migration after vessel injury. We found that rat aortic smooth muscle cells attach to surfaces coated with fibronectin, laminin, and collagen types I and IV. Cell attachment to these substrates appears to be mediated by members of the beta 1 integrin family of extracellular matrix receptors. Antibodies to the beta 1 subunit not only demonstrated the presence of integrin complexes in focal adhesion plaques but also blocked cell adhesion to the different substrates. Ligand-affinity chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis isolated a series of receptor complexes that were recognized by antisera to beta 1 integrin receptors. Each of the receptors appeared to be a heterodimer in which one of several alpha subunits shared a common 120-kDa (nonreduced) beta 1 subunit protein. The rat aortic smooth muscle cells had one alpha subunit (150 kDa nonreduced, 140 kDa reduced) that bound exclusively to fibronectin. There was a second alpha subunit (150 kDa nonreduced, 160 kDa reduced) that bound exclusively to collagen type I. In addition, there was a third alpha subunit (185 kDa nonreduced, 200 kDa reduced) that was promiscuous and bound to collagen types I and IV as well as to laminin; the 185-kDa alpha subunit appeared to bind to collagen more efficiently than it did to laminin. Thus, smooth muscle cells express multiple integrin receptors with different ligand specificities that appear to mediate cell interactions with the extracellular matrix.
Transcriptional regulation of Munc13-4 expression in cytotoxic lymphocytes is disrupted by an intronic mutation associated with a primary immunodeficiency
Authors: Frank Cichocki, Heinrich Schlums, Hongchuan Li, Vanessa Stache, Timothy Holmes, Todd R. Lenvik, Samuel C.C. Chiang, Jeffrey S. Miller, Marie Meeths, Stephen K. Anderson, Yenan T. Bryceson
Journal: The Journal of Experimental Medicine (2014)

Autosomal recessive mutations in UNC13D, the gene that encodes Munc13-4, are associated with familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Munc13-4 expression is obligatory for exocytosis of lytic granules, facilitating cytotoxicity by T cells and natural killer (NK) cells. The mechanisms regulating Munc13-4 expression are unknown. Here, we report that Munc13-4 is highly expressed in differentiated human NK cells and effector CD8+ T lymphocytes. A UNC13D c.118-308C&amp;gt;T mutation, causative of FHL3, disrupted binding of the ETS family member ELF1 to a conserved intronic sequence. This mutation impairs UNC13D intron 1 recruitment of STAT4 and the chromatin remodeling complex component BRG1, diminishing active histone modifications at the locus. The intronic sequence acted as an overall enhancer of Munc13-4 expression in cytotoxic lymphocytes in addition to representing an alternative promoter encoding a novel Munc13-4 isoform. Mechanistically, T cell receptor engagement facilitated STAT4-dependent Munc13-4 expression in naive CD8+ T lymphocytes. Collectively, our data demonstrates how chromatin remodeling within an evolutionarily conserved regulatory element in intron 1 of UNC13D regulates the induction of Munc13-4 expression in cytotoxic lymphocytes and suggests that an alternative Munc13-4 isoform is required for lymphocyte cytotoxicity. Thus, mutations associated with primary immunodeficiencies may cause disease by disrupting transcription factor binding.
Professional development session for early career scientists at SITC 2012
Authors: Christian M Capitini, William L Redmond, Kimberly A Shafer-Weaver
Journal: Journal for ImmunoTherapy of Cancer (2013)

The Society for Immunotherapy of Cancer (SITC) 2012 Professional Development Session was held as part of the SITC 27th Annual Meeting, Washington, DC, on October 24, 2012. The session was designed as a new opportunity for early career investigators to learn about relevant career development topics in a didactic setting.
Sex, Age, and Regional Differences in L-Type Calcium Current Are Important Determinants of Arrhythmia Phenotype in Rabbit Hearts With Drug-Induced Long QT Type 2
Authors: Carl Sims, Steven Reisenweber, Prakash C. Viswanathan, Bum-Rak Choi, William H. Walker, Guy Salama
Journal: Circulation Research (2008)

In congenital and acquired long QT type 2, women are more vulnerable than men to Torsade de Pointes. In prepubertal rabbits (and children), the arrhythmia phenotype is reversed; however, females still have longer action potential durations than males. Thus, sex differences in K + channels and action potential durations alone cannot account for sex-dependent arrhythmia phenotypes. The L-type calcium current ( I Ca,L ) is another determinant of action potential duration, Ca 2+ overload, early afterdepolarizations (EADs), and Torsade de Pointes. Therefore, sex, age, and regional differences in I Ca,L density and in EAD susceptibility were analyzed in epicardial left ventricular myocytes isolated from the apex and base of prepubertal and adult rabbit hearts. In prepubertal rabbits, peak I Ca,L at the base was 22% higher in males than females (6.4±0.5 versus 5.0±0.2 pA/pF; P &lt;0.03) and higher than at the apex (6.4±0.5 versus 5.0±0.3 pA/pF; P &lt;0.02). Sex differences were reversed in adults: I Ca,L at the base was 32% higher in females than males (9.5±0.7 versus 6.4±0.6 pA/pF; P &lt;0.002) and 28% higher than the apex (9.5±0.7 versus 6.9±0.5 pA/pF; P &lt;0.01). Apex–base differences in I Ca,L were not significant in adult male and prepubertal female hearts. Western blot analysis showed that Ca v 1.2α levels varied with sex, maturity, and apex–base, with differences similar to variations in I Ca,L ; optical mapping revealed that the earliest EADs fired at the base. Single myocyte experiments and Luo–Rudy simulations concur that I Ca,L elevation promotes EADs and is an important determinant of long QT type 2 arrhythmia phenotype, most likely by reducing repolarization reserve and by enhancing Ca 2+ overload and the propensity for I Ca,L reactivation.
The Epidemiology of Schizophrenia in Papua New Guinea
Authors: E. FULLER TORREY, BARBARA B. TORREY, BURTON G. BURTON-BRADLEY
Journal: American Journal of Psychiatry (1974)

The epidemiology of 478 cases of schizophrenia, acute psychosis, and manic-depressive psychosis was examined in Papua New Guinea for the years 1970 through 1973. Factors such as bias, referral habits of doctors, community tolerance, disease, accessibility to medical care, and migration are discussed as possible explanations for the sharply different patterns of prevalence of schizophrenia in certain areas of the country. The authors conclude, however, that these factors are not sufficient to explain the differences and that concomitants of Western civilization such as certain viruses must also be considered as possible etiological agents.
Newer Techniques of Transseptal Left-Heart Catheterization
Authors: CONSTANTIN COPE
Journal: Circulation (1963)

1. Teflon tubing is ideally suited for transseptal catheterization because of its low coefficient of friction. 2. Catheterization of the left ventricle can be easily performed with a maneuverable spring guide. 3. A Teflon-tipped cannula and a tough, flexible, Teflon guide are used for percutaneous catheter insertions. 4. Safety measures used in transseptal puncture are described. 5. Simultaneous percutaneous insertion of a retrograde Teflon aortic catheter and the transseptal catheter permit transvalvular gradients to be obtained even when a diseased mitral or aortic valve cannot be crossed.
<b><i>Ex Vivo</i></b>Expansion of CD8+CD56+ and CD8+CD56− Natural Killer T Cells Specific for MUC1 Mucin
Authors: Howard J. Wajchman, Carl W. Pierce, Vijay A. Varma, Muta M. Issa, John Petros, Kenneth E. Dombrowski
Journal: Cancer Research (2004)

Abstract Prostate cancers express MUC1, but nearly all metastatic cells lack HLA class I molecules. Thus, a lymphocyte population that can sense its antigenic environment, while also able to react to stimuli of natural killer (NK) cells, may be a more versatile effector cell population for antitumor immune responses. Herein, we report that tumor-specific MUC1 peptide, interleukin 2, and interleukin 12 act synergistically to stimulate the ex vivo expansion of CD8+CD56− T cells and CD8+CD56+ natural killer T (NKT) cells from the peripheral blood mononuclear cells of prostate cancer patients, as well as healthy male and female donors. Both the CD56+ NKT cells and CD56− T cells lysed allogeneic mucin-bearing target cells, as well as NK target cells, but not lymphokine-activated killer target cells. However, the CD56+ NKT cells displayed a 2-fold greater cytolytic activity than the CD56− T cells. The mucin-specific cytolytic activity and NK cytolytic activities for both lymphocyte populations were independent of HLA class I and CD1 molecules. The CD56− T cells up-regulated CD56 with continued antigenic stimulation in the presence of interleukin 12, suggesting that CD8+CD56− T cells are NKT cells. However, CD56+ NKT cells expand poorly to continued stimulation. All mucin-stimulated NKT cells exhibited the activated/memory CD45RO phenotype. The NKT cell lines express the α/β T-cell receptor (TCR). The TCR repertoire was limited and varied with cell line, but was not the Vα24Vβ11 TCR typically associated with NKT cells. Whereas CD161 is generally considered a marker of NKT cells, the mucin-stimulated NKT cells did not express this marker. Thus, we have described two phenotypically distinct NKT types that do not display a biased TCR repertoire, but do display specificity for a tumor-specific peptide antigen (CTL-like activity), as well as HLA class I-deficient target cells (NK-like activity).
The Big Blue Test: Effects of 14 Minutes of Physical Activity on Blood Glucose Levels
Authors: Sheri R. Colberg, Manuel J. Hernandez
Journal: Diabetes Care (2013)

For most with diabetes, physical activity has a blood glucose lowering effect (1). Hypoglycemia (i.e., blood glucose <65 mg/dL) resulting from exercise is a concern, particularly for insulin users (2). This study was undertaken to document the glycemic effects of engaging in 14 min of any physical activity done for the Big Blue Test (BBT; conducted by the Diabetes Hands Foundation), along with the incidence of hypoglycemia, in both insulin (78.9%) and noninsulin (21.1%) users. In 2011, all 3,916 BBT participants self-reported their diabetes status, physical activity performed, self-monitored …
Validity and reliability evidence of the nijmegen questionnaire in astma
Authors: Eirini Grammatopoulou, Emmanouil Scordilis, Afrodite Evangelodimou, Aikaterini Haniotou, Arietta Spinou, Nikolaos Tsamis, Konstantinos Grigoriadis, Dafni Antoniadou, Maria Xyki, Vlassia Belibassaki
Journal: European Respiratory Journal (2013)

Introduction  The Nijmegen Questionnaire (NQ) is the most commonly used screening tool for hyperventilation. The validity of the NQ has not been reported for Greek asthma out-patients.  Aim  Report the validity evidence of the Nijmegen Questionnaire in asthma.  Methods  162 Greek asthma out-patients (86 with mild and 76 moderate asthma) participated in the study. Hyperventilation was assessed using NQ and clinical measures such as breath holding time (BHT), respiratory rate (RR) and end-tidal CO2 (ETCO2). Construct validity was tested through factor analysis and cross-sectional validity through correlations of the NQ score with BHT, ETCO2 and RR (Pearson’s r correlation coefficient).  Results  Exploratory factor analysis for the three pre-hypothesized factors of the 16 item NQ showed low factor loadings which led to a principal component analysis (PCA) for NQ. The PCA revealed a one-factor solution with 11 items (Q1, Q2, Q4, Q5, Q6, Q7, Q8, Q9, Q11, Q13, and Q16). The one-factor solution revealed a total of 58.86% of explained variability and a high Cronbach alpha (a = .92). These findings were supported by confirmatory factor analysis for the 11 items NQ model [χ2 = 149.90, df 44, p  Conclusion  The NQ was valid and reliable in the present sample with asthma.
Feasibility and Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the Philippines
Authors: Thelma E Tupasi, Rajesh Gupta, Ma Imelda D Quelapio, Ruth B Orillaza, Nona Rachel Mira, Nellie V Mangubat, Virgil Belen, Nida Arnisto, Lualhati Macalintal, Michael Arabit, Jaime Y Lagahid, Marcos Espinal, Katherine Floyd
Journal: PLoS Medicine (2006)

Background Multidrug-resistant tuberculosis (MDR-TB) is an important global health problem, and a control strategy known as DOTS-Plus has existed since 1999. However, evidence regarding the feasibility, effectiveness, cost, and cost-effectiveness of DOTS-Plus is still limited. Methodology/Principal Findings We evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS-Plus pilot project established at Makati Medical Center in Manila, the Philippines, in 1999. Patients with MDR-TB are treated with regimens, including first- and second-line drugs, tailored to their drug susceptibility pattern (i.e., individualised treatment). We considered the cohort enrolled between April 1999 and March 2002. During this three-year period, 118 patients were enrolled in the project; 117 were considered in the analysis. Seventy-one patients (61%) were cured, 12 (10%) failed treatment, 18 (15%) died, and 16 (14%) defaulted. The average cost per patient treated was US$3,355 from the perspective of the health system, of which US$1,557 was for drugs, and US$837 from the perspective of patients. The mean cost per disability-adjusted life year (DALY) gained by the DOTS-Plus project was US$242 (range US$85 to US$426). Conclusions Treatment of patients with MDR-TB using the DOTS-Plus strategy and individualised drug regimens can be feasible, comparatively effective, and cost-effective in low- and middle-income countries.
Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients
Authors: Keith L. Knutson, Kathy Schiffman, Mary L. Disis
Journal: Journal of Clinical Investigation (2001)

CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell–mediated immunity. The goal of this study was to determine whether HER-2/neu–specific CD8 T-cell immunity could be elicited using HER-2/neu–derived MHC class II “helper” peptides, which contain encompassed HLA-A2–binding motifs. Nineteen HLA-A2 patients with HER-2/neu–overexpressing cancers received a vaccine preparation consisting of putative HER-2/neu helper peptides p369–384, p688–703, and p971–984. Contained within these sequences are the HLA-A2–binding motifs p369–377, p689–697, and p971–979. After vaccination, the mean peptide-specific T-cell precursor frequency to the HLA-A2 peptides increased in the majority of patients. In addition, the peptide-specific T cells were able to lyse tumors. The responses were long-lived and detectable for more than 1 year after the final vaccination in select patients. These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2–specific IFN-γ–producing CD8 T cells.
The Epidemiology of Blood Pressure and Its Worldwide Management
Authors: Kazem Rahimi, Connor A. Emdin, Stephen MacMahon
Journal: Circulation Research (2015)

Despite the vast amount of evidence on the benefits of blood pressure lowering accumulated to date, elevated blood pressure is still the leading risk factor for disease and disability worldwide. The purpose of this review is to summarize the epidemiological evidence underpinning the association between blood pressure and a range of conditions. This review focuses on the association between systolic and diastolic blood pressures and the risk of cardiovascular and renal disease. Evidence for and against the existence of a J-shaped curve association between blood pressure and cardiovascular risk, and differences in the predictive power of systolic, diastolic, and pulse pressure, are described. In addition, global and regional trends in blood pressure levels and management of hypertension are reviewed.
A cognitive behavioural intervention to reduce sexually transmitted infections among gay men: randomised trial
Authors: J. Imrie
Journal: BMJ (2001)

To determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men.Randomised controlled trial with 12 months' follow up.Sexual health clinic in London.343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year.Number of new sexually transmitted infections diagnosed during follow up and self reported incidence of unprotected anal intercourse.72% (361/499) of men invited to enter the study did so. 90% (308/343) of participants returned at least one follow up questionnaire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up. At baseline, 37% (63/172) of the intervention group and 30% (50/166) of the control group reported having had unprotected anal intercourse in the past month. At 12 months, the proportions were 27% (31/114) and 32% ( 39/124) respectively (P=0.56). However, 31% (38/123) of the intervention group and 21% (35/168) of controls had had at least one new infection diagnosed at the clinic (adjusted odds ratio 1.66, 95% confidence interval 1.00 to 2.74). Considering only men who requested a check up for sexually transmitted infections, the proportion diagnosed with a new infection was 58% (53/91) for men in the intervention group and 43% (35/81) for men in the control group (adjusted odds ratio 1.84, 0.99 to 3.40). Using a regional database that includes information from 23 sexual health clinics in London, we determined that few participants had attended other sexual health clinics.This behavioural intervention was acceptable and feasible to deliver, but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk. Even carefully designed interventions should not be assumed to bring benefit. It is important to evaluate their effects in randomised trials with objective clinical end points.
Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
Authors: Jennifer Lund, Ayuko Sato, Shizuo Akira, Ruslan Medzhitov, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2003)

Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG as well as several viruses. In this study, we examined the molecular mechanism of virus recognition by pDCs. First, we demonstrated that the CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels of IFN-α in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-α secretion by pDCs required the expression of the adaptor molecule MyD88, suggesting the involvement of a Toll-like receptor (TLR) in HSV-2 recognition. To test whether a TLR mediates HSV-2–induced IFN-α secretion from pDCs, various knockout mice were examined. These experiments revealed a clear requirement for TLR9 in this process. Further, we demonstrated that purified HSV-2 DNA can trigger IFN-α secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-α secretion by pDCs in a dose-dependent manner. The recognition of HSV-2 by TLR9 was mediated through an endocytic pathway that was inhibited by chloroquine or bafilomycin A1. The strict requirement for TLR9 in IFN-α secretion was further confirmed by the inoculation of HSV-2 in vivo. Therefore, these results demonstrate a novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs.
(7) Klippel-Trenaunay-Parkes-Weber syndrome
Authors: W.F.G. Tucker, C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (7) Klippel‐Trenaunay‐Parkes‐Weber syndrome Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar C.I. Harrington C.I. Harrington Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 49–50, https://doi.org/10.1111/j.1365-2133.1986.tb07702.x Published: 01 July 1986