tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor-? promotes atherosclerotic lesion progression in APOE*3-leiden transgenic mice
Authors: L BOESTEN, A ZADELAAR, A VANNIEUWKOOP, M GIJBELS, M DEWINTHER, L HAVEKES, B VANVLIJMEN
Journal: Cardiovascular Research (2005)

Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine exerting both inflammatory and cell death modulatory activity, and is thought to play a role in the pathogenesis of atherosclerosis. Studies in mice indicated that TNFalpha affects atherosclerosis minimally or not under conditions that allow fatty streak formation. Here, we examined the possible role of TNFalpha in advanced and complex atherosclerotic lesions.To induce atherosclerosis, TNFalpha-deficient (Tnf-/-) APOE*3-Leiden and control APOE*3-Leiden only mice were fed a cholesterol-rich diet. Comparable levels of plasma cholesterol and triglycerides and the systemic inflammatory parameters, serum amyloid A and soluble intercellular adhesion molecule-1 were found in APOE*3-LeidenTnf-/- and control mice. Although absence of TNFalpha did not affect the quantitative area of atherosclerosis, APOE*3-LeidenTnf-/- mice had a higher relative number of early lesions (46.1% vs. 21.4%) and a lower relative number of advanced lesions (53.9% vs. 78.6%, P=0.04). In addition, the advanced lesions in APOE*3-LeidenTnf-/- mice showed less necrosis (9.9+/-12.1% vs. 23.4+/-19.3% of total lesion area, P=0.04) and an increase in apoptosis (1.5+/-1.5% vs. 0.4+/-0.6% of total nuclei, P=0.03).Our data indicate that TNFalpha stimulates the formation of lesions towards an advanced phenotype, with more lesion necrosis and a lower incidence of apoptosis.
CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease
Authors: Peter W.F. Wilson
Journal: Circulation (2004)

There is great interest in moving beyond established risk factors to consider markers of inflammation for the prediction of initial cardiovascular disease events. Inflammatory markers such as leukocyte count, serum amyloid A, C-reactive protein, and vascular outcomes in individuals free of cardiovascular disease at baseline are the key markers that have been investigated in the population setting. A meta-analysis of 11 prospective studies in asymptomatic individuals compared people in the bottom third of the C-reactive protein distribution with those in the top tertile. The authors reported an odds ratio of 2.0 (95% CI 1.6 to 2.5) for coronary heart disease among people in the top tertile. These results are among the strongest assembled thus far to recommend incorporating newer biomarkers into coronary heart disease risk estimation algorithms. A variety of issues should be considered and conditions satisfied before vascular disease risk factors are adopted into regular use. The type of vascular event and the follow-up interval are important features because results for short-, intermediate-, and long-term intervals may yield different results. The factors under consideration should have been standardized, and characteristics such as the variability of the measurements, correlations with established factors, evidence from observational studies and clinical trials, type of effect (linear, nonlinear, dichotomous), improvement in overall prediction (discrimination), generalization of results (calibration), and cost can affect the utility. Each of these issues needs to be considered and the effects on relative, absolute, and population-attributable risks described. In particular, we need to (1) develop sound strategies for implementing new testing and (2) demonstrate the benefit of testing by using the current foundation of prior probabilities developed from already-published risk factor assessments based on large population studies.
The C3b/C4b receptor is recognized by the Knops, McCoy, Swain-langley, and York blood group antisera.
Authors: J M Moulds, M W Nickells, J J Moulds, M C Brown, J P Atkinson
Journal: The Journal of Experimental Medicine (1991)

Erythrocytes (E) lacking high incidence blood group antigens were screened by an antiglobulin test with a monoclonal antibody to human complement receptor type 1 (CR1; C3b/C4b receptor; CD35). Some examples of E lacking Knops, McCoy, Swain-Langley, and York antigens, a serologically related group, were not agglutinated. Moreover, E of the null phenotype for these same antigens were nonreactive. To further explore this relationship, E expressing these antigens were surface labeled, solubilized, and incubated with the corresponding blood group-specific antisera. CR1 was immunoprecipitated, indicating that the epitopes recognized by each of these antisera are expressed on CR1. E of two individuals, putative null phenotypes for the Knops, McCoy, and Swain-Langley blood group antigens, expressed a very low number of CR1 (less than 30/E; approximately 10% of the normal mean). This observation accounts for their lack of reactivity in the antiglobulin test and their prior designation as null phenotypes. Also, the previously reported low as well as variable expression of CR1 on E explains prior difficulties in the serologic analyses of these blood group antigens.
Estrogen Inhibits Vascular Smooth Muscle Cell–Dependent Adventitial Fibroblast Migration In Vitro
Authors: Guohong Li, Yiu-Fai Chen, Geoffrey L. Greene, Suzanne Oparil, John A. Thompson
Journal: Circulation (1999)

Background —Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo. Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was designed to establish a mechanism whereby estrogen attenuates migration of adventitial fibroblasts. Methods and Results —Primary cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase–polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restricted to early-passage VSMCs. Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experimental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast migration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration. In contrast, treatment of VSMCs with 17β-estradiol (10 −9 to 10 −7 mol/L) before preconditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17β-estradiol and the ER antagonist ICI-182780 (10 −7 mol/L) blocked the inhibitory effect of estrogen on fibroblast migration. Conclusions —These observations suggest a novel mechanism of hormonal vasoprotection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechanism.
Regional edema formation in isolated perfused dog lungs.
Authors: C A Hales, D J Kanarek, B Ahluwalia, A Latty, J Erdmann, S Javaheri, H Kazemi
Journal: Circulation Research (1981)

Studies using gravimetric analysis of lungs of frozen animals have suggested that the differences in pulmonary microvascular pressure between non-dependent and dependent lung do not influence the formation of regional pulmonary edema. We wondered if the inability to detect variation in regional extravascular lung water (EVLW) was due to the slow freezing process and, therefore, reassessed the distribution of EVLW in vertically suspended isolated perfused dog lungs with a radioisotopic technique that does not require freezing. Total lung water (TLW), blood or intravascular lung water (IVLW), and EVLW were measured in absolute quantities using a positron camera and the positron-emitting isotopes C15O as a blood label and H2(15)O as a total lung water label. Mean isotopic TLW in 17 lungs that were normal or moderately edematous (wet:dry ratio &lt; 7) was 142 +/- 9 (SE) ml compared to the gravimetric estimate of 148 +/- 7 ml (r = 0.92) and isotopic EVLW was 64 +/- 6 ml compared to the gravimetric estimate of 70 +/- 6 ml (r = 0.8). Analysis of the distribution of regional isotopically measured EVLW in the 17 lungs in various states of spontaneous edema formation revealed a small non-dependent to dependent, gravity-related increase in percent regional EVLW compared to percent regional TLW, which did not vary with the degree of edema in the lung. Serial measurements of absolute regional EVLW in four lungs during spontaneously developing edema also failed to show a disproportionate increase in accumulation of EVLW in any lung zone. Thus, despite the wide variation in microvascular hydrostatic pressure between top and bottom of the vertical isolated lung, edema formation seems to be uniform.
Pectin and complications after gastric surgery: normalisation of postprandial glucose and endocrine responses.
Authors: D J Jenkins, S R Bloom, R H Albuquerque, A R Leeds, D L Sarson, G L Metz, K G Alberti
Journal: Gut (1980)

Pectin has been shown to minimise the fall in blood glucose seen in patients who are troubled by hypoglycaemia attacks after gastric surgery. We therefore performed 50 g glucose tolerance tests with and without 14.5 g pectin on 11 post-gastric surgery patients. After pectin, the high postprandial levels of glucose, insulin, and enteroglucagon were significantly reduced as was the fall in blood glucose between 90 and 120 minutes. These effects of pectin may reflect slower uptake of glucose from the gastrointestinal tract and provide evidence to support the use of unabsorbable carbohydrate gelling agents in treating hypoglycaemia after gastric surgery.
Red Cell Sodium in Hyperthyroidism
Authors: A. W. G. Goolden, D. Bateman, S. Torr
Journal: BMJ (1971)

A simple method of measuring red cell sodium has shown that about 90% of thyrotoxic patients have values above the upper limit of the normal range. Patients taking 0.3 mg of L-thyroxine daily were found to have a significantly higher mean value for red cell sodium than that of the normal controls. It is suggested that patients taking this amount of thyroxine may be hypermetabolic. The determination of red cell sodium may prove useful as a measure of the peripheral action of thyroid hormone.
Apoptotic and Cytostatic Farnesyltransferase Inhibitors Have Distinct Pharmacology and Efficacy Profiles in Tumor Models
Authors: Veeraswamy Manne, Francis Y. F. Lee, David K. Bol, Johnni Gullo-Brown, Craig R. Fairchild, Louis J. Lombardo, Richard A. Smykla, Gregory D. Vite, Mei-Li D. Wen, Chiang Yu, Tai Wai Wong, John T. Hunt
Journal: Cancer Research (2004)

BMS-214662 and BMS-225975 are tetrahydrobenzodiazepine-based farnesyltransferase inhibitors (FTIs) that have nearly identical structures and very similar pharmacological profiles associated with farnesyltransferase (FT) inhibition. Despite their similar activity against FT in vitro and in cells, these compounds differ dramatically in their apoptotic potency and tumor-regressing activity in vivo. BMS-214662 is the most potent apoptotic FTI known and exhibits curative responses in mice bearing a variety of staged human tumor xenografts such as HCT-116 human colon tumor. By contrast, BMS-225975 does not cause tumor regression and at best causes partial tumor growth inhibition in staged HCT-116 human colon tumor xenografts. Lack of tumor regression activity in BMS-225975 was attributable to its relatively weak apoptotic potency, not to poor cell permeability or pharmacokinetics. Both compounds were equally effective in inhibiting Ras processing and causing accumulation of a variety of nonfarnesylated substrates of FT in HCT-116 cells. Because BMS-225975 has poor apoptotic activity compared with BMS-214662 but inhibits FT to the same extent as BMS-214662, it is very unlikely that FT inhibition alone can account for the apoptotic potency of BMS-214662. Clearly distinct patterns of sensitivities in a cell line panel were obtained for the apoptotic FTI BMS-214662 and the cytostatic FTI BMS-225975. Activation of the c-Jun-NH(2)-terminal kinase pathway was readily observed with BMS-214662 but not with BMS-225975. We developed a highly sensitive San-1 murine xenograft tumor model that is particularly useful for evaluating the in vivo activity of cytostatic FTIs such as BMS-225975.
Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry
Authors: Erik Hulegårdh, Christer Nilsson, Vladimir Lazarevic, Hege Garelius, Petar Antunovic, Åsa Rangert Derolf, Lars Möllgård, Bertil Uggla, Lovisa Wennström, Anders Wahlin, Martin Höglund, Gunnar Juliusson, Dick Stockelberg, Sören Lehmann
Journal: American Journal of Hematology (2014)

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population‐based studies are crucial for its accurate characterization. In this first large population‐based study on secondary AML, we studied AML with an antecedent hematological disease (AHD‐AML) or therapy‐related AML (t‐AML) in the population‐based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD‐AML, and 259 (7.7%) t‐AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD‐AML (HR 1.51; 95% CI 1.26–1.79) and t‐AML (1.72; 1.38–2.15) were independent risk factors for poor survival. The negative impact of AHD‐AML and t‐AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population‐based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients. Am. J. Hematol. 90:208–214, 2015. © 2014 Wiley Periodicals, Inc.
Serum Levels and Metabolic Clearance of the Isoflavones Genistein and Daidzein in Hemodialysis Patients
Authors: Paolo Fanti, B. Peter Sawaya, Laurie J. Custer, Adrian A. Franke
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Genistein and daidzein are biologically active isoflavones that are especially abundant in soybeans. After intestinal absorption, circulating genistein and daidzein are eliminated primarily by the kidneys. This study was undertaken to assess the metabolism of genistein and daidzein in patients with end-stage renal disease (ESRD) on hemodialysis therapy, and to test whether this treatment modality can replace the lack of kidney function, with respect to the elimination of the isoflavones. Twenty-three hemodialysis patients and 10 healthy subjects were studied. While consuming a self-selected low isoflavone diet, baseline blood levels were undetectable in eight of 10 healthy subjects and in 14 of 23 dialysis patients. The remaining participants had detectable levels, with the nine dialysis patients displaying much higher blood concentrations than the two healthy control subjects. After the evening intake of one dose of an isoflavone-rich soy protein isolate drink, the early morning blood levels of genistein and daidzein were higher in seven dialysis patients than in eight healthy subjects (genistein 1271 ± 321 versus 425 ± 104, P &lt; 0.05; daidzein 1304 ± 352 versus 292 ± 78, P &lt; 0.05). The blood clearance of the isoflavones was studied in two healthy subjects and in three dialysis patients. Genistein and daidzein were eliminated within 2 d in the healthy subjects, but had not returned to baseline in two of three ESRD patients, 7 d after intake. The half-life of both compounds was estimated to be 10-fold longer in the ESRD patients than in the healthy subjects. Finally, genistein and daidzein levels were measured before and after dialysis in five patients, both while on their regular diet and after one dose of a soy protein isolate drink. In both instances, the dialysis treatment did not affect the blood isoflavone levels. In conclusion, approximately one-third of hemodialysis patients eating the standard American renal diet experience high blood levels of the isoflavones genistein and daidzein, while the remaining two-thirds have undetectable levels. After ingestion of isoflavone-rich food such as soy products, all patients have detectable levels that remain very high for several days due to lack of renal excretion.
Treatment of the Common Cold with Unrefined Echinacea
Authors: Bruce P. Barrett
Journal: Annals of Internal Medicine (2002)

Background: Echinacea preparations are widely used to treat the common cold. Objective: To assess the efficacy of dried, encapsulated, whole-plant echinacea as early treatment for the common cold. Design: Randomized, double-blind, placebo-controlled community-based trial. Setting: University of Wisconsin—Madison, Madison, Wisconsin. Participants: 148 registered students with common colds of recent onset. Intervention: An encapsulated mixture of unrefined Echinacea purpurea herb (25%) and root (25%) and E. angustifolia root (50%) taken in 1-g doses six times on the first day of illness and three times on each subsequent day of illness for a maximum of 10 days. Measurements: Severity and duration of self-reported symptoms of upper respiratory tract infection. Results: No statistically significant differences were detected between the echinacea and placebo groups for any of the measured outcomes. Trajectories of severity over time were nearly identical in the two groups. Mean cold duration was 6.01 days in both groups as a whole, 5.75 days in the placebo group, and 6.27 days in the echinacea group (between-group difference, −0.52 day [95% CI, −1.09 to 0.22 days]). After controlling for severity and duration of symptoms before study entry, sex, date of enrollment, and use of nonprotocol medications, researchers found no statistically significant treatment effect (adjusted hazard ratio, 1.24 [CI, 0.86 to 1.78]). Multivariable regression models assessing severity scores over time failed to detect statistically significant differences between the echinacea and placebo groups. Conclusion: Compared with placebo, unrefined echinacea provided no detectable benefit or harm in these college students who had the common cold.
Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer.
Authors: C M Bate, S P Wilkinson, G V Bradby, M C Bateson, W S Hislop, J P Crowe, C P Willoughby, E M Peers, P D Richardson
Journal: Gut (1990)

In a randomised, double blind, parallel group study in patients with symptomatic gastric ulcer (94% greater than or equal to 5 mm diameter), 102 received omeprazole 20 mg om and 87 cimetidine 400 mg bd. After four weeks 73% and 58% (p less than 0.05) respectively had healed (eight weeks: 84% and 75%, ns). After four weeks, a greater proportion (81%) of omeprazole treated patients was symptom free than of those receiving cimetidine (60%; p less than 0.01). Over the first two weeks, patients receiving omeprazole had less day pain, less night pain and took fewer antacids than those receiving cimetidine (all p less than 0.05). The difference between omeprazole and cimetidine was not appreciably affected by age, smoking, size of the ulcer and trial centre. Tolerability was similar in the two treatment groups. In the treatment of symptomatic gastric ulcer, omeprazole relieves the symptoms more quickly than cimetidine and heals a greater proportion of ulcers within four weeks.
Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)
Authors: K. Spieth, R. Kaufmann, R. Dummer, C. Garbe, J.C. Becker, A. Hauschild, W. Tilgen, S. Ugurel, M. Beyeler, E.B. Bröcker, K.C. Kaehler, C. Pföhler, J. Gille, U. Leiter, D. Schadendorf
Journal: Annals of Oncology (2008)
Relationships Between Changes in Sustained Fronto-Striatal Connectivity and Positive Affect in Major Depression Resulting From Antidepressant Treatment
Authors: Aaron S. Heller, Tom Johnstone, Sharee N. Light, Michael J. Peterson, Gregory G. Kolden, Ned H. Kalin, Richard J. Davidson
Journal: American Journal of Psychiatry (2012)

OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.