tbuckley/cabot-search huggingface dataset:
Impact of Introducing Stereotactic Lung Radiotherapy for Elderly Patients With Stage I Non–Small-Cell Lung Cancer: A Population-Based Time-Trend Analysis
Authors: David Palma, Otto Visser, Frank J. Lagerwaard, Jose Belderbos, Ben J. Slotman, Suresh Senan
Journal: Journal of Clinical Oncology (2010)

Stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) is associated with high local control rates. The impact of introducing SBRT in patients 75 years of age or older was studied using a population-based cancer registry.The Amsterdam Cancer Registry was assessed in three eras: 1999 to 2001 (period A, pre-SBRT); 2002 to 2004 (period B, some availability of SBRT), and 2005 to 2007 (period C, full access to SBRT). χ(2), Kaplan-Meier, and Cox regression were used to compare treatment patterns and overall survival (OS) in three treatment groups: surgery, radiotherapy (RT), or neither.A total of 875 elderly patients were diagnosed with stage I NSCLC in the study period. Median follow-up was 54 months. Primary treatment was surgery in 299 patients (34%), RT in 299 patients (34%), and neither in 277 patients (32%). RT use increased between periods A and C (26% v 42%, P < .01), corresponding to a decrease in untreated patients. The percentage of RT patients undergoing SBRT in periods B and C was 23% and 55%, respectively. Median survival for all patients increased from 16 months in period A to 21 months in period C (log-rank P < .01; hazard ratio [HR] = 0.65; 95% CI, 0.54 to 0.80). The improvement in OS was confined to RT patients (HR = 0.70; 95% CI, 0.49 to 0.99), whereas no significant survival improvements were seen in the other groups.SBRT introduction was associated with a 16% absolute increase in RT use, a decline in the proportion of untreated elderly patients, and an improvement in OS.
Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells
Authors: TJ Braciale
Journal: The Journal of Experimental Medicine (1977)

Two distinct subpopulations of cytotoxic T cells are generated in the primary or secondary response of mice to type A influenza viruses. One subpopulation is specific for the immunizing virus strain. The other subpopulation shows a high degree of cross-reactivity for heterologous type A virus of a different subtype. This report examines the possibility that distinct influenza virus antigens, expressed on the surface of the infected cell, are recognized by the different subpopulations of influenza-specific cytotoxic T cells. Data are presented which demonstrate that influenza A matrix protein, an internal virion antigen, is detectable on the surface of target cells infected with influenza A viruses of different subtypes. Since this viral antigen is type specific, i.e., serologically cross-reactive among all type A influenza viruses, it could serve as the target for cross-reactive cytotoxic T cells. To further examine the specificity of the two cytotoxic T-cell subpopulations, experiments were carried out by using the inhibitor of glycoprotein synthesis - 2-Deoxy-D-Glucose 2-DG. These experiments examine first the effect of 2-DG on the expression of influenza matrix protein and viral glycoprotein on the infected cell surface and second, the susceptibility of 2-DG-treated target cells to lysis by cytotoxic T cells. 2-DG inhibits the expression of the viral hemagglutinin glycoprotein on the cell surface but does not inhibit the expression of the nonglycosylated matrix protein. Furthermore, inhibition of glycoprotein synthesis in infected target cells abrogates the reactivity of infected target cells to lysis by virus strain-specific but not cross- reactive cytotoxic T cells. These findings suggest that the influenza glycoproteins (hemagglutinin and/or neuraminidase) and the nonglycosylated matrix protein are the targets for the virus strain- specific and cross-reactive cytotoxic T cells, respectively. These results are discussed in the light of available information on influenza virus structure and the biology of influenza infection and in terms of current models for cytotoxic T-cell recognition of virus-infected cells.
Presence of a Failed Kidney Transplant in Patients Who Are on Hemodialysis Is Associated with Chronic Inflammatory State and Erythropoietin Resistance
Authors: Juan M. Lo[Combining Acute Accent]pez-Go[Combining Acute Accent]mez, Isabel Pe[Combining Acute Accent]rez-Flores, Rosa Jofre[Combining Acute Accent], Diana Carretero, Patrocinio Rodri[Combining Acute Accent]guez-Benitez, Maite Villaverde, Rafael Pe[Combining Acute Accent]rez-Garci[Combining Acute Accent]a, George M. Nassar, Enrique Niembro, Juan Carlos Ayus
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Patients returning to hemodialysis (HD) after failure of their kidney transplant suffer from high morbidity and mortality rates. It is common practice to keep failed kidney transplants in place. It is not known if these failed kidney transplants induce an inflammatory state that contributes to morbidity and mortality. In a single facility, patients starting on HD with failed kidney transplant were identified (Group A) and screened for the presence of chronic inflammatory state. Those with clinical symptoms attributed to the failed allograft (Group A1) were not offered transplant nephrectomy unless deemed necessary during follow-up. Their clinical and laboratory data were followed up for 6 months. Similar data were obtained from a group of incident HD patients (Group B). Forty-three patients had a failed Kidney transplant (Group A). Of these, 29 comprised Group A1 and 14 Group A2. Group B comprised 121 patients. In comparison with Group B, Group A exhibited worse anemia and erythropoietin resistance index (ERI), had lower serum albumin and prealbumin, and higher CRP. Group A1 had lower Hb and higher ferritin, CRP, and ESR in comparison with Group A2. Following transplant nephrectomy, Group A1 had improvement in ERI, serum albumin, prealbumin, ferritin, fibrnogen, CRP, and ESR. At 6 months, Group A1 had higher Hb and serum albumin levels, and lower CRP and ERI in comparison with Group A2. Group B parameters showed no change during follow-up. Patients returning to HD following failure of their kidney transplant suffer from a chronic inflammatory state. Resection of failed transplants in symptomatic patients is associated with amelioration of markers of chronic inflammation. Transplant nephrectomy should be considered a treatment option for patients with failed kidney transplants, especially if they exhibit signs and symptoms of chronic inflammatory state.
Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state.
Authors: W R Hiatt, J G Regensteiner, E E Wolfel, L Ruff, E P Brass
Journal: Journal of Clinical Investigation (1989)

Carnitine metabolism has been previously shown to change with exercise in normal subjects, and in patients with ischemic muscle diseases. To characterize carnitine metabolism further during exercise, six normal male subjects performed constant-load exercise on a bicycle ergometer on two separate occasions. Low-intensity exercise was performed for 60 min at a work load equal to 50% of the lactate threshold, and high-intensity exercise was performed for 30 min at a work load between the lactate threshold and maximal work capacity for the individual. Low-intensity exercise was not associated with a change in muscle (vastus lateralis) carnitine metabolism. In contrast, from rest to 10 min of high-intensity exercise, muscle short-chain acylcarnitine content increased 5.5-fold while free carnitine content decreased 66%, and muscle total carnitine content decreased by 19% (all P less than 0.01). These changes in skeletal muscle carnitine metabolism were present at the completion of 30 min of high-intensity exercise, and persisted through a 60-min recovery period. With 30 min of high-intensity exercise, plasma short-chain and long-chain acylcarnitine concentrations increased by 46% and 23%, respectively. Neither exercise state was associated with a change in the urine excretion rates of free carnitine or acylcarnitines. Thus, alterations in skeletal muscle carnitine metabolism, characterized by an increase in acylcarnitines and a decrease in free and total carnitine, are dependent on the work load and, therefore, the metabolic state associated with the exercise, and are poorly reflected in the plasma and urine carnitine pools.
Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure
Authors: B.P. Madden, H. Kariyawasam, A.J. Siddiqi, A. Machin, J.A. Pryor, M.E. Hodson
Journal: European Respiratory Journal (2002)

The experience of using noninvasive ventilation (NIV) in 113 adult cystic fibrosis (CF) patients with chronic respiratory failure, during episodes of acute deterioration in respiratory function is reported. The patients aged 15–44 yrs were divided into three groups. Group A consisted of 65 patients (median forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) 0.7/1.4 L) who were on a lung transplant waiting list. Group B consisted of 25 patients (median FEV 1 /FVC 0.7/1.4 L) who were being evaluated for lung transplantation. Group C consisted of 23 patients (median FEV 1 /FVC 0.6/1.2 L) who were not being considered for lung transplantation. The mean duration of NIV support for groups A, B and C was 61 (range: 1–600) days, 53 (1–279) days and 45 (0.5–379) days respectively. Twenty-three patients in group A subsequently received lung transplantation and 12 of these patients had a median survival of 39 months postsurgery. Thirty-nine patients died and three awaited transplantation. Five patients in group B received a transplant four of whom survived; thirteen patients died and seven awaited transplantation. Twenty patients in group C died. Noninvasive ventilation improved hypoxia but failed to correct hypercapnia in these cystic fibrosis patients. Noninvasive ventilation is useful in the treatment of acute episodes of respiratory failure in cystic fibrosis patients with end-stage lung disease who have been accepted, or are being evaluated, for lung transplantation. For these patients, there is a possibility of prolonging life if they are successfully treated for their acute episode of respiratory failure until transplantation. In this group, treatment is not merely prolonging the process of dying.
1051 THE ADENOVIRAL GENE DELIVERY OF RELAXIN SHOWS ANTIFIBROTIC EFFECT IN THIOACETAMIDE-INDUCED LIVER CIRRHOSIS IN RATS
Authors: Y.H. Paik, J.K. Kim, S.H. Kang, C.O. Yun, S.O. Yoon, K.S. Lee
Journal: Journal of Hepatology (2011)
<i>FOXO3</i> Encodes a Carcinogen-Activated Transcription Factor Frequently Deleted in Early-Stage Lung Adenocarcinoma
Authors: Oliver R. Mikse, Daniel C. Blake, Nathan R. Jones, Yuan-Wan Sun, Shantu Amin, Carla J. Gallagher, Philip Lazarus, Judith Weisz, Christopher R. Herzog
Journal: Cancer Research (2010)

The FOXO family of transcription factors elicits cell cycle arrest, apoptosis, and resistance to various physiologic and pathologic stresses relevant to sporadic cancer, such as DNA damage and oxidative stress. Although implicated as tumor suppressors, FOXO genetic inactivation has not been observed in human cancer. In an investigation of the two major types of non-small cell lung cancer, here, we identify the FOXO3 gene as a novel target of deletion in human lung adenocarcinoma (LAC). Biallelic or homozygous deletion (HD) of FOXO3 was detected in 8 of 33 (24.2%) mostly early-stage LAC of smokers. Another 60.6% of these tumors had losses of FOXO3 not reaching the level of HD (hereafter referred to as sub-HD). In contrast, no HD of FOXO3 was observed in 19 lung squamous cell carcinoma. Consistent with the deletion of FOXO3 were corresponding decreases in its mRNA and protein levels in LAC. The potential role of FOXO3 loss in LAC was also investigated. The carcinogen (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) is strongly implicated as a cause of human lung cancer. Here, we show that FOXO3a is functionally activated and augments the level of caspase-dependent apoptosis in cells exposed to this DNA-damaging carcinogen. These results implicate FOXO3 as a suppressor of LAC carcinogenesis, a role frequently lost through gene deletion.
The problem of content in embodied memory
Authors: Martin Kurthen, Thomas Grunwald, Christoph Helmstaedter, Christian E. Elger
Journal: Behavioral and Brain Sciences (2003)

An action-oriented theory of embodied memory is favorable for many reasons, but it will not provide a quick yet clean solution to the grounding problem in the way Glenberg (1997t) envisages. Although structural mapping via analogical representations may be an adequate mechanism of cognitive representation, it will not suffice to explain representation as such.
Surfactant Synthesis and Kinetics in Infants with Congenital Diaphragmatic Hernia
Authors: Paola E. Cogo, Luc J. I. Zimmermann, Federica Rosso, Francesca Tormena, Piergiorgio Gamba, Giovanna Verlato, Aldo Baritussio, Virgilio P. Carnielli
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

In animal models of congenital diaphragmatic hernia (CDH), surfactant deficiency contributes to the pathophysiology of the disease; however, information on CDH in humans is limited. We compared surfactant disaturated phosphatidylcholine (DSPC) synthesis and metabolism, by stable isotope technology, in newborn infants with CDH and in control subjects. DSPC amount, total proteins, and surfactant protein–A (SP-A) from tracheal aspirates were also measured. DSPC and SP-A were significantly lower in 14 infants with CDH than in the eight control subjects. Mean DSPC was 2.3 ± 1.3 mg/ml of epithelial lining fluid (ELF) in infants with CDH and 4.6 ± 1.5 mg/ml of ELF in control subjects (p = 0.001). Mean SP-A in infants with CDH and in control subjects was 16.2 ± 9.3 and 61.2 ± 30.6 μg/ml of ELF, respectively (p = 0.03). DSPC kinetics was measured in 12 of 14 infants with CDH and in 5 of 8 control subjects. Secretion time was 8.3 ± 5.5 and 8.5 ± 2.5 hours and peak time 51.9 ± 15.2 and 51 ± 13 hours in infants with CDH and in control subjects, respectively. Fractional synthesis rate was not different for infants with CDH and control subjects (p = 0.4). In conclusion, surfactant DSPC synthesis and kinetics were not significantly deranged in infants with CDH compared with control subjects. Other factors, such as lower surface area or increased DSPC catabolism, may contribute to surfactant pool alteration in CDH.
Farnesylation of Retinal Transducin Underlies Its Translocation during Light Adaptation
Authors: Hidetoshi Kassai, Atsu Aiba, Kazuki Nakao, Kenji Nakamura, Motoya Katsuki, Wei-Hong Xiong, King-Wai Yau, Hiroo Imai, Yoshinori Shichida, Yoshinori Satomi, Toshifumi Takao, Toshiyuki Okano, Yoshitaka Fukada
Journal: Neuron (2005)
Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: A double-blind, randomized study
Authors: Carin Gribetz, Mark Ling, Mark Lebwohl, David Pariser, Zoe Draelos, Alice B. Gottlieb, Nardo Zaias, Diana M. Chen, Anne Parneix-Spake, Thomas Hultsch, Alan Menter
Journal: Journal of the American Academy of Dermatology (2004)
Cardiac RKIP induces a beneficial β-adrenoceptor–dependent positive inotropy
Authors: Evelyn Schmid, Stefan Neef, Christopher Berlin, Angela Tomasovic, Katrin Kahlert, Peter Nordbeck, Katharina Deiss, Sabrina Denzinger, Sebastian Herrmann, Erich Wettwer, Markus Weidendorfer, Daniel Becker, Florian Schäfer, Nicole Wagner, Süleyman Ergün, Joachim P Schmitt, Hugo A Katus, Frank Weidemann, Ursula Ravens, Christoph Maack, Lutz Hein, Georg Ertl, Oliver J Müller, Lars S Maier, Martin J Lohse, Kristina Lorenz
Journal: Nature Medicine (2015)
THE LANGUAGE OF HEALTH CARE: The language of health care
Authors: K. Sikora
Journal: Journal of the Royal Society of Medicine (2006)

We can't lose our sense of humour just because Harry Cayton (JRSM October 2006) doesn't like it. All professions have amusing codes for their customers. He takes exception to the term ‘frequent flyer’ applied to those who use hospitals a lot. Many of my cancer patients are delighted to be gold members and refer to it with pride. But he's quite right about patronization and lack of customer focus. We could do well to take lessons from the travel industry. People don't get admitted and discharged from hotels—they check in and check out. They book services rather than get referred for them.

The NHS uses the language of passivity, not empowerment. The Choose and Book scheme is a poor man's version of buying a budget airline ticket. Most people haven't a clue what the options are. Real choice occurs when consumers have real cheque books. Competing outlets vie for their trade by providing user-friendly interfaces. Mobile phones are used equally well by all in society—rich or poor, black or white, young or old.

Harry wants patient-centred health care. So let's open the doors to a dynamic, competing marketplace and not a state monopoly. But his designation will have to go. Vodafone doesn't have a Director for Customers with the implication of line management over the people that are paying his salary. And the word patient goes back to the Greek pathos, meaning suffering. The cancer charities encourage us to talk about ‘people living with cancer’ or, even more PC ‘those whose lives have been touched by cancer’—but certainly not ‘cancer victims’, so loved by the media. This Journal should sponsor a competition to find Harry a more suitable designation.
Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis
Authors: Kim Papp, Alan Menter, Bruce Strober, Greg Kricorian, Elizabeth H.Z. Thompson, Cassandra E. Milmont, Ajay Nirula, Paul Klekotka
Journal: Journal of the American Academy of Dermatology (2014)
Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes
Authors: Katherine J. Baines, Jodie L. Simpson, Lisa G. Wood, Rodney J. Scott, Naomi L. Fibbens, Heather Powell, Douglas C. Cowan, D. Robin Taylor, Jan O. Cowan, Peter G. Gibson
Journal: Journal of Allergy and Clinical Immunology (2014)
A1, Cw7, B8, DR3 HLA antigen combination associated with rapid decline of T-helper lymphocytes in HIV-1 infection
Authors: R.A Kaslow, M vanRaden, H Friedman, R Duquesnoy, M Marrari, L Kingsley, C.R Rinaldo, S Su, A Saah, R Detels, J Phair
Journal: The Lancet (1990)
Unipolar Mania Over the Course of a 20-Year Follow-Up Study
Authors: David A. Solomon, Andrew C. Leon, Jean Endicott, William H. Coryell, Timothy I. Mueller, Michael A. Posternak, Martin B. Keller
Journal: American Journal of Psychiatry (2003)

Using data from a longitudinal study of the mood disorders, the investigators address the phenomenon of unipolar mania.Subjects diagnosed as having Research Diagnostic Criteria mania at intake into the study were prospectively followed for up to 20 years.Twenty-seven subjects had the diagnosis of unipolar mania at the time they entered the study and had no history of major depression before enrolling in the study. Seven of these subjects did not suffer any episodes of major depression during the 15- to 20-year follow-up.These data support the diagnostic validity of unipolar mania.
The dual inhibitor of lipoxygenase and cyclooxygenase ML3000 decreases the expression of CXCR3 ligands
Authors: C Ospelt, M Kurowska-Stolarska, M Neidhart, B A Michel, R E Gay, S Laufer, S Gay
Journal: Annals of the Rheumatic Diseases (2007)

Objective: To find previously unknown properties of ML3000, a competitive inhibitor of the cyclooxygenase and the lipoxygenase (LO) pathway. Methods: Gene expression of ML3000 treated and untreated rheumatoid arthritis synovial fibroblasts were measured with Affymetrix gene arrays. Downregulation of chemokine (C-X-C motif) ligands CXCL9, CXCL10 and CXCL11 was verified with Real-time polymerase chain reaction, CXCL10 protein levels were determined with ELISA. Rheumatoid arthritis synovial fibroblasts were treated with the cyclooxygenase inhibitor naproxen, the 5-LO inhibitor BWA4C and the 5-lipoxygenase-activating protein (FLAP) inhibitor MK886, and consecutive changes in CXCL10 protein levels measured. 5-LO expression was determined by polymerase chain reaction and Western blot. Results: In synovial fibroblasts and monocyte-derived macrophages ML3000 inhibited the tumour necrosis factor induced expression of CXCL9, CXCL10 and CXCL11, which are all ligands of the chemokine receptor CXCR3. No effect was observed in monocytes. Whereas inhibition of the cyclooxygenase pathway or the FLAP protein showed no effect, blockade of 5-LO significantly downregulated CXCL10 protein levels. 5-LO mRNA was detected in monocytes and in monocyte-derived macrophages. All tested cell types expressed 5-LO protein. Conclusions: ML3000 effectively downregulates CXCR3 ligands. This study confirms that a thorough analysis of the impact of a drug on its target cells cannot only reveal unexpected properties of a substance, but also helps to understand the underlying molecular mechanisms. Accordingly, our data provide the basis for further clinical studies testing the application of ML3000 in diseases such as rheumatoid arthritis or multiple sclerosis.
Immunological unresponsiveness to thymus-independent antigens: two fundamentally different genetic mechanisms of B-cell unresponsiveness to dextran
Authors: C Fernandez, G Moller
Journal: The Journal of Experimental Medicine (1977)

The immune response of mice to the α-l-6 epitope of dextran (Dx) B512 was found to be under genetic control. The congenic mouse strains A, A.CA, A.SW, A.TH, and A.TL exhibited a specific defect in their response to α-l-6. Also strain CBA/N was unresponsive to α-1-6, but the mechanism of unresponsiveness was found to be different. Unresponsiveness to α-l-6 in congenic A strains was not due to suppressor cells. Although these strains failed to respond to the α-l-6 epitope, they responded strongly to the hapten Fluorescein isothiocyanate (FITC) conjugated to Dx, indicating that the Dx can function as an efficient carrier in these strains. Dx was a potent polyclonal B-cell activator in congenic A strains as well as in high responder strains. Polyclonally-activating concentrations of lipopolysaccharide (LPS) failed to induce the synthesis of anti-α- l-6 antibodies in congenic A strains, although antibodies of all other specificities studied were produced. However, in high responder strains, LPS induced the synthesis of anti-α-l-6 antibodies. It was concluded that congenic A strains do not express V genes coding for antibodies against α-l-6. In contrast, strain CBA/N failed to respond to both the α-l-6 and FITC epitope on Dx, whereas they could respond to FITC conjugated to horse erythrocytes. Dx induced a very small, if any, polyclonal antibody response in B cells from CBA/N mice or male CBA/N x DBA hybrids, whereas Dx was a very potent polyclonal B-cell activator in female hybrids. It is concluded that CBA/N mice are nonresponders to Dx or haptenated Dx, because the cell population that can respond to the polyclonal B-cell activating properties of Dx is severely depleted.
Observational Research Databases in Renal Disease
Authors: Michael Shlipak, Catherine Stehman-Breen
Journal: Journal of the American Society of Nephrology (2005)

Observational, patient-oriented research is a term that describes clinical or community-based studies in that they do not involve an experiment or intervention. Observational research studies can be designed and implemented by a primary data collection or using previously collected patient data. The latter is less expensive, although it has some distinct limitations. Many research databases are readily available and can be used to answer important questions that are relevant to kidney disease. This review summarizes the types of research analyses that can be conducted using existing databases, the types of research databases available, and a general approach for addressing a proposed research question using existing data.