tbuckley/cabot-search huggingface dataset:
Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals.
Authors: H Secrist, C J Chelen, Y Wen, J D Marshall, D T Umetsu
Journal: The Journal of Experimental Medicine (1993)

Allergen specific CD4+ T cell clones generated from allergic individuals have been shown to produce increased levels of the cytokine interleukin 4 (IL-4), compared to allergen specific clones generated from nonallergic individuals. This difference between CD4+ T cells from allergic and nonallergic individuals with regard to cytokine production in response to allergen is thought to be responsible for the development of allergic disease with increased IgE synthesis in atopic individuals. We examined the production of IL-4 in subjects with allergic rhinitis and in allergic individuals treated with allergen immunotherapy, a treatment which involves the subcutaneous administration of increasing doses of allergen and which is highly effective and beneficial for individuals with severe allergic rhinitis. We demonstrated that the quantity of IL-4 produced by allergen specific memory CD4+ T cells from allergic individuals could be considerably reduced by in vivo treatment with allergen (allergen immunotherapy). Immunotherapy reduced IL-4 production by allergen specific CD4+ T cells to levels observed with T cells from nonallergic subjects, or to levels induced with nonallergic antigens such as tetanus toxoid. In most cases the levels of IL-4 produced were inversely related to the length of time on immunotherapy. These observations indicate that immunotherapy accomplishes its clinical effects by reducing IL-4 synthesis in allergen specific CD4+ T cells. In addition, these observations indicate that the cytokine profiles of memory CD4+ T cells can indeed be altered by in vivo therapies. Thus, the cytokine profiles of memory CD4+ T cells are mutable, and are not fixed as had been suggested by studies of murine CD4+ memory T cells. Finally, treatment of allergic diseases with allergen immunotherapy may be a model for other diseases which may require therapies that alter inappropriate cytokine profiles of memory CD4+ T cells.
Dysfunctional breathing in patients with asthma
Authors: C O Prys-Picard, R Niven
Journal: Thorax (2008)

Accuracy in suspicious lung infiltrationsWe read with interest the paper by Targowski et al. 1 Suspicious lung infiltra- tions such as malignant tumours are always difficult to diagnose in clinical practice.Transthoracic fine needle biopsy (TFNB) may be a useful procedure despite a high risk of false negative results.To improve the accuracy of the technique, telomerase activity in combination with TFNB was investigated in the study by Targowski et al.We suggest that alternative options such as positron tomography scanning (CT-PET) should be evaluated, which may provide better imaging quality and accurate guidance for performing TFNB, increasing the accuracy of lung cancer diagnosis.In the Continuing Observation of Smoking Subjects (COSMOS) study recently published by Veronesi et al 2 invol- ving 5200 current or former smokers, CT-PET had a sensitivity of 100% in the diagnosis of solid pulmonary nodules of 10 mm of more.In this study, TFNB was not part of the clinical routine.In contrast, the sensitivity of the combination of TFNB with telomerase activity used by Targowski et al was lower at 89.3% and the mean size of suspected lesions was not described.
Phosphodiesterase Type 5 Inhibitors in the Management of Non-neurogenic Male Lower Urinary Tract Symptoms: Critical Analysis of Current Evidence
Authors: Juan I. Martínez-Salamanca, Joaquin Carballido, Ian Eardley, Francois Giuliano, Christian Gratzke, Raymond Rosen, Andrea Salonia, Christian Stief
Journal: European Urology (2011)
2,3,7,8-Tetrachlorodibenzo-p-dioxin Levels in Adipose Tissue of Exposed and Control Persons in Missouri
Authors: Donald G. Patterson
Journal: JAMA (1986)

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin, was measured in the adipose tissue of 39 persons with a history of residential, recreational, or occupational exposure in Missouri and in 57 persons in a control group. All participants had detectable levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in their adipose tissue, but the exposed group had significantly higher levels. Levels of six of the exposed persons were more than five times greater than the level of the highest control. Measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in adipose tissue provides a much improved index of exposure, an important advance for research studies evaluating the possible health effects of this compound.
Emodin Inhibits Tumor Cell Adhesion through Disruption of the Membrane Lipid Raft-Associated Integrin Signaling Pathway
Authors: Qing Huang, Han-Ming Shen, Guanghou Shui, Markus R. Wenk, Choon-Nam Ong
Journal: Cancer Research (2006)

Abstract Cell adhesion and spreading is a crucial step in the metastatic cascade of cancer cells, and interruption of this step is considered to be a logical strategy for prevention and treatment of tumor metastasis. Emodin is the major active component of the rhizome of Rheum palmatum L., with known anticancer activities. Here, we first found that emodin significantly inhibited cell adhesion of various human cancer cells. This inhibition was achieved through suppressing the recruitment of focal adhesion kinase (FAK) to integrin β1 as well as the phosphorylation of FAK followed by the decreased formation of focal adhesion complex (FAC). In understanding the underlying mechanisms, we found that emodin inhibited the lipid raft clustering and subsequent colocalization of integrin β1 and FAC proteins within lipid rafts. Lipid profile analysis revealed significant decrease of cholesterol and sphingolipids in raft fraction after emodin treatment. Cholesterol replenishment abolished the adverse effect of emodin on the translocation of integrin β1 and FAC proteins into the lipid raft fraction and cell adhesion. Therefore, data from this study provide novel evidence that emodin inhibits cell adhesion and spreading through disruption of the membrane lipid raft-associated integrin signaling pathway. (Cancer Res 2006; 66(11): 5807-15)
Prognostic value of residual pulmonary congestion at discharge assessed by lung ultrasound imaging in heart failure
Authors: Stefano Coiro, Patrick Rossignol, Giuseppe Ambrosio, Erberto Carluccio, Gianfranco Alunni, Adriano Murrone, Isabella Tritto, Faiez Zannad, Nicolas Girerd
Journal: European Journal of Heart Failure (2015)
Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension
Authors: Tomás Pulido, Igor Adzerikho, Richard N. Channick, Marion Delcroix, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Pavel Jansa, Zhi-Cheng Jing, Franck-Olivier Le Brun, Sanjay Mehta, Camilla M. Mittelholzer, Loïc Perchenet, B.K.S. Sastry, Olivier Sitbon, Rogério Souza, Adam Torbicki, Xiaofeng Zeng, Lewis J. Rubin, Gérald Simonneau
Journal: New England Journal of Medicine (2013)

Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension.A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P=0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia.Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study. (Funded by Actelion Pharmaceuticals; SERAPHIN ClinicalTrials.gov number, NCT00660179.).
LIFE SITUATION TESTS AS AIDS IN PSYCHIATRIC PROGNOSIS
Authors: ABRAHAM A. LOW, H. DOUGLAS SINGER, CATHERINE L. MCCORRY
Journal: American Journal of Psychiatry (1939)

1. The scores obtained with a set of three "life situation tests" in an unselected group of 233 patients correlate closely with the average length of residence in the community. No correlation was found in the manic-depressive group of patients. 2. The high degree of correlation suggests that validity may be claimed for the tests. 3. The tests may be said to be reliable and to yield similar or parallel scores if repeated from three to six months after the original application. 4. The test scores seem to afford a fairly valid basis for predicting the probability of continuous residence in the community after discharge from the hospital.
Bronchial brushing and bronchial biopsy: comparison of diagnostic accuracy and cell typing reliability in lung cancer.
Authors: M Matsuda, T Horai, S Nakamura, H Nishio, T Sakuma, H Ikegami, R Tateishi
Journal: Thorax (1986)

A total of 443 patients with lung cancer underwent brush and forceps biopsy through a fibreoptic bronchoscope. The biopsy was taken from the area of suspected malignancy which had been brushed. Of 443 patients, 400 (90.3%) showed positive results on brushing and 287 (64.8%) on biopsy. A combination of both techniques yielded the highest percentage of positive diagnosis (93.7%). Histologically, there was a high incidence of positive diagnosis for squamous and small cell carcinoma. One hundred and three (83.7%) of 123 specimens obtained by brushing and 75 (81.5%) of 92 specimens obtained by biopsy agreed with the cell type found in the surgical or necropsy specimen. Cell typing accuracy was higher in squamous and in small cell carcinoma in both techniques. As the cell typing accuracy of the two methods is similar, the results obtained by both techniques should be taken into consideration in the management of individual cases of lung cancer.
The expression signature of in vitro senescence resembles mouse but not human aging.
Authors: Kristian Wennmalm, Claes Wahlestedt, Ola Larsson
Journal: Genome biology (2005)

Abstract Background The biological mechanisms that underlie aging have not yet been fully identified. Senescence, a phenomenon occurring in vitro , limits the number of cell divisions in mammalian cell cultures and has been suggested to contribute to aging. Results We investigated whether the changes in gene expression that occur during mammalian aging and induction of cellular senescence are similar. We compared changes of gene expression in seven microarray datasets from aging human, mouse and rat, as well as four microarray datasets from senescent cells of man and mouse. The datasets were publicly available or obtained from other laboratories. Correlation measures were used to establish similarities of the expression profiles and gene ontology analyses to identify functional groups of genes that are co-regulated. Robust similarities were established between aging in different species and tissues, indicating that there is an aging transcriptome. Although some cross-species comparisons displayed high correlation, intra-species similarities were more reliable. Similarly, a senescence transcriptome was demonstrated that is conserved across cell types. A similarity between the expression signatures of cellular senescence and aging could be established in mouse, but not in human. Conclusion Our study is the first to use microarray data from several studies and laboratories for dissection of a complex biological phenotype. We demonstrate the presence of a mammalian aging transcriptome, and discuss why similarity between cellular senescence and aging is apparent in aging mice only.
Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors That Do Not Express the Epidermal Growth Factor Receptor by Immunohistochemistry
Authors: Ki Young Chung, Jinru Shia, Nancy E. Kemeny, Manish Shah, Gary K. Schwartz, Archie Tse, Audrey Hamilton, Dorothy Pan, Deborah Schrag, Lawrence Schwartz, David S. Klimstra, Daniel Fridman, David P. Kelsen, Leonard B. Saltz
Journal: Journal of Clinical Oncology (2005)

Purpose To establish evidence of activity, or lack thereof, of cetuximab-based therapy in patients with refractory colorectal cancer with tumors that do not demonstrate epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC). Patients and Methods Pharmacy computer records were reviewed to identify all patients who received cetuximab at Memorial Sloan-Kettering Cancer Center in a nonstudy setting during the first 3 months of cetuximab's commercial availability. Medical records of these patients were then reviewed to identify colorectal cancer patients who had experienced failure with a prior irinotecan-based regimen and who had a pathology report indicating an EGFR-negative tumor by IHC. Pathology slides from these patients were reviewed by a reference pathologist to confirm EGFR negativity, and computed tomography scans during cetuximab-based therapy were reviewed by a reference radiologist. Response rates were reported using WHO criteria. Results Sixteen chemotherapy-refractory, EGFR-negative colorectal cancer patients who received cetuximab in a nonstudy setting were identified. Fourteen of these patients received cetuximab plus irinotecan, and two received cetuximab monotherapy. In the 16 patients, four major objective responses were seen (response rate, 25%; 95% CI, 4% to 46%). Conclusion Colorectal cancer patients with EGFR-negative tumors have the potential to respond to cetuximab-based therapies. EGFR analysis by current IHC techniques does not seem to have predictive value, and selection or exclusion of patients for cetuximab therapy on the basis of currently available EGFR IHC does not seem warranted.
Associations between Stroke Mortality and Weekend Working by Stroke Specialist Physicians and Registered Nurses: Prospective Multicentre Cohort Study
Authors: Benjamin D. Bray, Salma Ayis, James Campbell, Geoffrey C. Cloud, Martin James, Alex Hoffman, Pippa J. Tyrrell, Charles D. A. Wolfe, Anthony G. Rudd
Journal: PLoS Medicine (2014)

Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this "weekend effect" is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke.We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91-1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose-response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07-1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77-0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services.Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care. Please see later in the article for the Editors' Summary.
Plasma leucine enkephalin is increased in liver disease.
Authors: J R Thornton, M S Losowsky
Journal: Gut (1989)

Plasma methionine enkephalin is increased in liver disease and may contribute to some of the clinical manifestations of hepatic failure. To determine if another 9small9 opioid peptide is increased in the plasma of patients with liver disease, leucine enkephalin was measured by radioimmunoassay. Its plasma concentration was raised approximately five-fold in patients with acute liver disease (median 1490 pmol/l, range 830-2420) and three-fold in patients with cirrhosis with ascites (960 pmol/l, 470-2900), compared with disease controls (325 pmol/l, 180-740) and healthy controls (305 pmol/l, 180-560). The increase in plasma leucine enkephalin was proportional to the degree of liver damage, as judged in the patients with acute liver disease by its correlation with the prothrombin time (r = 0.691, p less than 0.01) and alanine aminotransferase (r = 0.502, p less than 0.05), and in the patients with cirrhosis by its negative correlation with the plasma albumin (r = -0.743, p less than 0.001). It is unclear whether the raised plasma leucine enkephalin in liver disease is a consequence of diminished hepatic inactivation, increased secretion from sympathetic nerves and adrenal glands, or both.
Multiple Actions of Steroid Hormones—A Focus on Rapid, Nongenomic Effects
Authors: Elisabeth Falkenstein, Hanns-Christian Tillmann, Michael Christ, Martin Feuring, Martin Wehling
Journal: Pharmacological Reviews (2000)

According to the traditional model, steroid hormones bind to intracellular receptors and subsequently modulate transcription and protein synthesis, thus triggering genomic events finally responsible for delayed effects. Based upon similarities in molecular structure, specific receptors for steroids, vitamin D(3) derivatives, thyroid hormone, retinoids, and a variety of orphan receptors are considered to represent a superfamily of steroid receptors. In addition, very rapid effects of steroids mainly affecting intracellular signaling have been widely recognized that are clearly incompatible with the genomic model. These rapid, nongenomic steroid actions are likely to be transmitted via specific membrane receptors. Evidence for nongenomic steroid effects and distinct receptors involved is presented for all steroid groups including related compounds like vitamin D(3) and thyroid hormones. The physiological and clinical relevance of these rapid effects is still largely unclear, but their existence in vivo has been clearly shown in various settings including human studies. Drugs that specifically affect nongenomic steroid action may find applications in various clinical areas such as cardiovascular and central nervous disorders, electrolyte homeostasis, and infertility. In addition to a short description of genomic steroid action, this review pays particular attention to the current knowledge and important results on the mechanisms of nongenomic steroid action. The modes of action are discussed in relation to their potential physiological or pathophysiological relevance and with regard to a cross-talk between genomic and nongenomic responses.
Conduction of Cardiovascular Sound Along Arteries
Authors: J. JOB FARBER, JAMES H. PURVIS
Journal: Circulation Research (1963)

The velocity of the transmission of the second heart sound in the thoracic aorta of dogs was measured. The average velocity was found to be 5.7 meters per second. The figure agrees well with the published figures for the pulse wave velocity in the thoracic aorta of dogs. It was shown in humans that the velocity with which the second heart sound is conducted along the carotid artery does not change appreciably with frequency between 25 and 100 cycles per second. The average increase in velocity of 2.7% per half octave increase in frequency is, with 30% probability, due to random errors. The fraction of the energy of a murmur transmitted in the form of a transverse vibration along the abdominal aorta of dogs was estimated from recordings made before and after the transverse motion of the arterial wall was impeded with a clamp. Most of the energy of the murmur was found to be transmitted in the form of a transverse vibration in the aortic wall. It was concluded that most of the energy of cardiovascular sound in arteries is transmitted in a mode which is exactly analogous to the transmission of the pulse wave. Some puzzling features of intravascular sound conduction, such as the apparent transmission of murmurs mainly in the direction of flow, could be explained on this basis.
Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle
Authors: H Sokol, L Beaugerie
Journal: Gut (2009)

The risk of lymphoproliferative disorders (LDs) has become a major concern for clinicians managing patients with inflammatory bowel disease (IBD). Yet it is difficult to distinguish the possible responsibility of immunosuppressive therapy from the background risk due to the inflammatory disorder itself. LDs are clonal B or T cell proliferation showing considerable heterogeneity and the incidence has increased since the 1970s. The strongest and best-established risk factors for LDs are primary and acquired immunodeficiency (HIV, immunosuppressant), notably via defective immune surveillance of Epstein–Barr virus. In many auto-immune diseases (eg, Sjögren's syndrome), inflammatory diseases (eg, rheumatoid arthritis) or chronic suppuration (chronic pyothorax), the risk of LD is increased. In IBD patients, in general, the risk of LD seems to be similar to or very slightly higher than in the general population. The role of immunosuppressants in lymphomagenesis is difficult to individualise because other factors potentially involved are inter-linked. Concordant data suggest that thiopurine therapy is associated with a moderately increased risk of LD. Data regarding methotrexate are scarce and come from diseases other than IBD but the risk seems low. Data regarding risk of LD in IBD patients receiving anti-tumour necrosis factor α (TNFα) agents are insufficient at this time, mainly because most of the patients are co-treated with thiopurines. The recently individualised risks of hepatosplenic T cell lymphoma and fatal post-mononucleosis LD, in young male patients with IBD who are co-treated with anti-TNFα and thiopurines, and EBV-seronegative IBD males, respectively, are probably low but remain to be better quantified.