tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.
Authors: F Mackay, H Loetscher, D Stueber, G Gehr, W Lesslauer
Journal: The Journal of Experimental Medicine (1993)

Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine triggering cell responses through two distinct membrane receptors. Stimulation of leukocyte adhesion to the endothelium is one of the many TNF-alpha activities and is explained by the upregulation of adhesion molecules on the endothelial cell surface. Human umbilical vein endothelial cells (HUVEC) were isolated, cultured, and demonstrated to express both TNF receptor types, TNF-R55 and TNF-R75. Cell adhesion to HUVEC was studied using the HL60, U937, and MOLT-4 cell lines. HUVEC were activated by either TNF-alpha, binding to both TNF-R55 and TNF-R75, and by receptor type-specific agonists, binding exclusively to TNF-R55 or to TNF-R75. The TNF-alpha-induced cell adhesion to HUVEC was found to be controlled almost exclusively by TNF-R55. This finding correlated with the exclusive activity of TNF-R55 in the TNF-alpha-dependent regulation of the expression of the intercellular adhesion molecule type 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule type 1 (VCAM-1). The CD44 adhesion molecule in HUVEC was also found to be upregulated through TNF-R55. However, both TNF-R55 and TNF-R75 upregulate alpha 2 integrin expression in HUVEC. The predominant role of TNF-R55 in TNF-alpha-induced adhesion in HUVEC may correlate with its specific control of NF-kappa B activation, since kappa B elements are known to be present in ICAM-1, E-selectin, and VCAM-1 gene regulatory sequences.
Metronomic Chemotherapy Enhances the Efficacy of Antivascular Therapy in Ovarian Cancer
Authors: Aparna A. Kamat, Tae Jin Kim, Charles N. Landen, Chunhua Lu, Liz Y. Han, Yvonne G. Lin, William M. Merritt, Premal H. Thaker, David M. Gershenson, Farideh Z. Bischoff, John V. Heymach, Robert B. Jaffe, Robert L. Coleman, Anil K. Sood
Journal: Cancer Research (2007)

Abstract Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic taxanes alone and in combination with AEE788—a dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) inhibitor—in an orthotopic mouse model of ovarian cancer. Growth-modulating effects of metronomic and maximum tolerated dose (MTD) regimens on overall survival were tested in vivo using both chemotherapy-sensitive (HeyA8 and SKOV3ip1) and chemotherapy-resistant (HeyA8-MDR) models. Treated tumors were stained for microvessel density (CD31), proliferation index (proliferating cell nuclear antigen), and apoptosis (terminal deoxyribonucleotide transferase–mediated nick-end labeling). The cytotoxic effects of MTD and metronomic dosing were tested with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of metronomic regimens on circulating endothelial precursors (CEP) and tumor-specific cell-free DNA levels were assessed. In vivo, metronomic docetaxel resulted in significant reduction of tumor growth in the taxane-sensitive cell lines, whereas metronomic docetaxel plus AEE788 had an additive effect resulting in significant prolongation in survival. Combination therapy was effective even in the taxane-resistant model. Metronomic chemotherapy alone and combined with AEE788 resulted in a decrease in the proliferative index and microvessel density of treated tumors, whereas combination therapy increased the apoptotic index (P &amp;lt; 0.001). In vitro, metronomic taxanes caused endothelial cell toxicity at 10- to 100-fold lower concentrations compared with MTD dosing. Metronomic regimens inhibited mobilization of CEPs (P &amp;lt; 0.05) and led to a decrease in cell-free DNA levels (P &amp;lt; 0.05). Our results suggest that metronomic taxane chemotherapy with dual EGFR and VEGFR inhibition is highly efficacious and should be considered for future clinical trials. [Cancer Res 2007;67(1):281–8]
CELLULAR REQUIREMENTS FOR THE REJECTION OF SKIN ALLOGRAFTS IN RATS
Authors: David M. Lubaroff
Journal: The Journal of Experimental Medicine (1973)

The role of bone marrow-derived cells in the rejection of skin allografts in rats was investigated. Lewis rats, rendered tolerant of BN antigens and bearing healthy grafts, were thymectomized, irradiated with 900 rad, and injected with varying doses of either normal isologous bone marrow, normal lymph node cells, and/or lymph node cells presensitized to BN antigens. In some experiments rats were also adoptively sensitized to tuberculin. Results showed that, although necessary for the elicitation of tuberculin skin reactions, bone marrow cells are not needed for the rejection of previously tolerated skin allografts. Rats receiving lymph node cells alone rejected their grafts in about 6–7 days. In addition, rats injected with bone marrow alone also rejected their grafts, although significantly later than did lymph node cell recipients, indicating that rat marrow contains a population of cells capable of reacting to transplantation antigens. These cells were found capable of reacting to major transplantation antigens but not minor as they were ineffective in causing the rejection of Ag-B compatible Fischer skin grafts. From experiments utilizing bone marrow from neonatally thymectomized donors and cells treated with an antiserum to rat T cells, these competent cells in the marrow were shown to be thymus derived.
Autophagy and the Immune System
Authors: Petric Kuballa, Whitney M. Nolte, Adam B. Castoreno, Ramnik J. Xavier
Journal: Annual Review of Immunology (2012)

Stressors ranging from nutrient deprivation to immune signaling can induce the degradation of cytoplasmic material by a process known as autophagy. Increasingly, research on autophagy has begun to focus on its role in inflammation and the immune response. Autophagy acts as an immune effector that mediates pathogen clearance. The roles of autophagy bridge both the innate and adaptive immune systems and include functions in thymic selection, antigen presentation, promotion of lymphocyte homeostasis and survival, and regulation of cytokine production. In this review, we discuss the mechanisms by which autophagy is regulated, as well as the functions of autophagy and autophagy proteins in immunity and inflammation.
Autonomic Cardiac Regulation During Spontaneous Nocturnal Hypoglycemia in Patients With Type 1 Diabetes
Authors: Minna L. Koivikko, Mikko P. Tulppo, Antti M. Kiviniemi, Mika A. Kallio, Juha S. Perkiömäki, Pasi I. Salmela, K.E. Juhani Airaksinen, Heikki V. Huikuri
Journal: Diabetes Care (2012)

Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation.Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night.The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms(2); P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms(2), respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation.Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.
Skin reaction and recovery: a repeated sodium lauryl sulphate patch test vs. a 24-h patch test and tape stripping
Authors: D.G. Koopman, S. Kezic, M.M. Verberk
Journal: British Journal of Dermatology (2004)

Background Little is known of the predictive value of methods to test an individual's susceptibility to acquiring occupational contact dermatitis. Recently, the recovery rate after induced irritation was suggested for this purpose. Although it is likely that repeated exposure to sodium lauryl sulphate (SLS) is preferable to a single application, there is little evidence to support this idea. Similarly, little is known about whether the outcome of a repeated SLS test can be predicted by a brief test. Objectives We studied the relationship between the skin reaction after a repeated SLS test and two brief tests, devoting special attention to the recovery rate. Methods In 29 healthy volunteers, we measured transepidermal water loss (TEWL) and erythema after applying 0·03, 0·1 and 0·3% SLS for 6 h, 3 days per week, over a course of 3 weeks. The data were compared with the effects after applying 0·1, 0·3 and 1·0% SLS for 24 h and with 10 and 15 repetitions of tape stripping. Results A poor correlation was found between the repeated test and the brief SLS test, or tape stripping, when using an increase in TEWL (r = 0·04 and 0·26, respectively) or its recovery rate (r = − 0·01 and 0·42, respectively). Conclusions We presume that in a repeated test of sufficient duration, additional mechanisms come into play that are absent in a brief test, e.g. an alteration in the thickness of the epidermis, with a resulting change in the permeability of SLS. When such an effect differs between subjects it could explain the lack of agreement between the acute and the repeated tests. At present, a brief irritation test will, in all likelihood, be unable to assess an individual's susceptibility to occupational contact dermatitis.
Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction
Authors: Shlomi Matetzky, Boris Shenkman, Victor Guetta, Michael Shechter, Roy Beinart, Ilan Goldenberg, Ilya Novikov, Hanna Pres, Naphtali Savion, David Varon, Hanoch Hod
Journal: Circulation (2004)

Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur.The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment-elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103+/-8% of baseline), ADP-induced aggregation was reduced to 69+/-3%, 58+/-7%, and 33+/-12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (P=0.007).Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.
Intestinal perfusion of dietary levels of aluminium: association with the mucosa.
Authors: J J Powell, C C Ainley, R Evans, R P Thompson
Journal: Gut (1994)

An aluminium (93 microM) sulphate solution freshly adjusted to pH 7.0 was perfused through the rat small bowel to mimic the reported physiological conditions that follow dietary aluminium ingestion. One third of this aluminium was taken up from the perfusate, but &gt; 90% of this was then recovered from the intestinal mucus/mucosa and most (&gt; 70%) from the distal third of the small bowel. The fresh perfusate was shown by ultrafiltration to contain largely particulate/colloidal aluminium-hydroxide, and this probably adhered to intestinal mucus which may be an important barrier to the gastrointestinal absorption of aluminium.
Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma
Authors: Zipei Feng, Sachin Puri, Tarsem Moudgil, William Wood, Clifford C. Hoyt, Chichung Wang, Walter J. Urba, Brendan D. Curti, Carlo B. Bifulco, Bernard A. Fox
Journal: Journal for ImmunoTherapy of Cancer (2015)

Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25-45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately.Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL.Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of CD8(+) T cells alone was insufficient to predict successful TIL generation, the CD8(+) to FoxP3(+) ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of CD8(+):PD-L1(+) expressing cells.This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates.
Post-necrotic cirrhosis with chronic cholestasis
Authors: D. V. Datta, S. Sherlock, P. J. Scheuer
Journal: Gut (1963)

Features of biliary obstruction were seen in 57 of 300 cases of post-necrotic cirrhosis but gave rise to real diagnostic difficulty in only 11 cases. The paper deals with the recognition and possible pathogenesis of this syndrome.
Utility of a Provocation Test for Diagnosis of Chronic Pigeon Breeder's Disease
Authors: ALEJANDRA RAMÍREZ-VENEGAS, RAÚL H. SANSORES, ROGELIO PÉREZ-PADILLA, GUILLERMO CARRILLO, MOISÉS SELMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Chronic hypersensitivity pneumonitis (CHP) can be difficult to differentiate from other interstitial lung diseases (ILD). To determine the diagnostic usefulness of a provocation test (PT), 17 patients with CHP induced by avian antigens, 17 with other ILD, and five healthy control subjects were challenged with pigeon serum. After PT, an increase in body temperature (BT) and a decrease in FVC, PaO2 and SaO2 % were observed in all patients with CHP and in three with ILD. No reaction was noticed in healthy subjects. ROC curves showed that for FVC the best cut point was a drop of 16% displaying sensitivity (S): 76%, specificity (SP): 81%, positive predictive value (PPV): 81%, and negative predictive value (NPV): 83%. For a drop of 3 mm Hg in PaO2 or 3% SaO2 , S was 88% for both, SP was 82 and 86%, PPV was 81 and 82%, and NPV was 82 and 86%, respectively. An increase of BT > 0.5o C showed S, 100%; SP, 82%; PPV, 100%; NPV, 86%. A univariate regression analysis confirmed that changes in BT and FVC are predicting values of CHP: RR, 82.5 (CI, 10.43 to 651.76) and 1.21 (CI, 1.06 to 1.36). There were no challenge test complications. These findings suggest that PT is a useful tool for diagnosis of CHP.
Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects
Authors: G. W. Chalmers, L. Thomson, K. J. Macleod, K. D. Dagg, B. J. McGinn, C. McSharry, K. R. Patel, N. C. Thomson
Journal: Thorax (1997)

BACKGROUND: Endothelin-1 (ET-1) is a potent bronchoconstrictor which may have a role in the pathogenesis of asthma. The levels of ET-1 in saliva, induced sputum, and plasma from asthmatic and non-asthmatic subjects were compared. METHODS: Sputum induction was performed on 28 asthmatic subjects and nine normal volunteers. ET-1 levels were measured in plasma, saliva, and sputum samples and reversed phase high performance liquid chromatography (RP-HPLC) was performed on saliva and sputum samples. RESULTS: ET-1 was present in the following order of concentration in both normal and asthmatic subjects: saliva &gt; sputum &gt; plasma (saliva, median 30.1 and 23.9 pg/ ml, respectively; sputum, median 15.5 and 11.2 pg/ml; plasma, median 3.1 and 3.6 pg/ ml). There were no differences between asthmatic and normal subjects in the levels of ET-1 in each fluid. The levels of ET-1 in asthmatic subjects were not influenced by whether or not they were taking inhaled steroids. RP-HPLC of sputum and saliva confirmed the presence of ET-1 in these fluids. CONCLUSIONS: Levels of ET-1 can be measured in saliva and sputum obtained by sputum induction in asthmatic and healthy subjects and, although no difference was found in basal levels of ET-1 in sputum, saliva and plasma between normal subjects and asthmatics without bronchoconstriction, it is apparent that ET-1 is produced or released locally within the respiratory tract in concentrations higher than those in plasma.
Intensive Care for Extreme Prematurity — Moving beyond Gestational Age
Authors: Jon E. Tyson, Nehal A. Parikh, John Langer, Charles Green, Rosemary D. Higgins
Journal: New England Journal of Medicine (2008)

Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients.
Cost and cost-effectiveness of multidrug-resistant tuberculosis treatment in Estonia and Russia
Authors: Katherine Floyd, Raymond Hutubessy, Kai Kliiman, Rosella Centis, Nina Khurieva, Wieslaw Jakobowiak, Manfred Danilovits, Genadi Peremitin, Salmaan Keshavjee, Giovanni Battista Migliori
Journal: European Respiratory Journal (2012)

Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant tuberculosis (MDR-TB) is limited, and no published data are available from former Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk Oblast), comparing cohorts enrolled on treatment according to World Health Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous years. Costs were assessed from a health system perspective in 2003 US$; effects were measured as cures, deaths averted and disability-adjusted life-years (DALYs) averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed, cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation accounted for 69–90% of total costs. The cost per DALY averted by treatment following WHO guidelines was US$579 (range US$297–US$902) in Estonia and US$429 (range US$302–US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be cost-effective, but requires substantial additional investment in tuberculosis control in priority countries.
Evolutionary Conservation of Expression Profiles Between Human and Mouse Orthologous Genes
Authors: Ben-Yang Liao, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2005)

Mouse models are often used to study human genes because it is believed that the expression and function are similar for the majority of orthologous genes between the two species. However, recent comparisons of microarray data from thousands of orthologous human and mouse genes suggested rapid evolution of gene expression profiles under minimal or no selective constraint. These findings appear to contradict non–array-based observations from many individual genes and imply the uselessness of mouse models for studying human genes. Because absolute levels of gene expression are not comparable between species when the data are generated by species-specific microarrays, use of relative mRNA abundance among tissues (RA) is preferred to that of absolute expression signals. We thus reanalyze human and mouse genome-wide gene expression data generated by oligonucleotide microarrays. We show that the mean correlation coefficient among expression profiles detected by different probe sets of the same gene is only 0.38 for humans and 0.28 for mice, indicating that current measures of expression divergence are flawed because the large estimation error (discrepancy in expression signal detected by different probe sets of the same gene) is mistakenly included in the between-species divergence. When this error is subtracted, 84% of human-mouse orthologous gene pairs show significantly lower expression divergence than that of random gene pairs. In contrast to a previous finding, but consistent with the common sense, expression profiles of orthologous tissues between species are more similar to each other than to those of nonorthologous tissues. Furthermore, the evolutionary rate of expression divergence and that of coding sequence divergence are found to be weakly, but significantly positively correlated, when RA and the Euclidean distance are used to measure expression-profile divergence. These results highlight the importance of proper consideration of various estimation errors in comparing the microarray data between species.