tbuckley/cabot-search huggingface dataset:
Predictors of Systolic Augmentation From Left Ventricular Preexcitation in Patients With Dilated Cardiomyopathy and Intraventricular Conduction Delay
Authors: Gregory S. Nelson, Cecilia W. Curry, Bradley T. Wyman, Andrew Kramer, Jerome Declerck, Maurice Talbot, Margaret R. Douglas, Ronald D. Berger, Elliot R. McVeigh, David A. Kass
Journal: Circulation (2000)

Background —VDD pacing can enhance systolic function in patients with dilated cardiomyopathy and discoordinate contraction; however, identification of patients likely to benefit is unclear. We tested predictors of systolic responsiveness on the basis of global parameters as well as directly assessed mechanical dyssynchrony. Methods and Results —Twenty-two DCM patients with conduction delay were studied by cardiac catheterization with a dual-sensor micromanometer to measure LV and aortic pressures during sinus rhythm and LV free-wall pacing. Pacing enhanced isovolumetric (dP/dt max ) and ejection-phase (pulse pressure, PP) systolic function by 35±21% and 16.4±11%, respectively, and these changes correlated directly ( r =0.7, P =0.001). %ΔdP/dt max was weakly predicted by baseline QRS ( r =0.6, P &lt;0.02), more strongly by baseline dP/dt max ( r =0.7, P =0.001), and best by bidiscriminate analysis combining baseline dP/dt max ≤700 mm Hg/s and QRS ≥155 ms to predict %ΔdP/dt max ≥25% and %ΔPP ≥10% ( P &lt;0.0005, χ 2 ), with no false-positives. Benefit could not be predicted by %ΔQRS. To test whether basal mechanical dyssynchrony predicted responsiveness to LV pacing, circumferential strains were determined at ≈80 sites throughout the LV by tagged MRI in 8 DCM patients and 7 additional control subjects. Strain variance at time of maximal shortening indexed dyssynchrony, averaging 28.0±7.1% in normal subjects versus 201.4±84.3% in DCM patients ( P =0.001). Mechanical dyssynchrony also correlated directly with %ΔdP/dt max ( r =0.85, P =0.008). Conclusions —These results show that although mechanical dyssynchrony is a key predictor for pacing efficacy in DCM patients with conduction delay, combining information about QRS and basal dP/dt max provides an excellent tool to identify maximal responders.
Urine Chemokines as Biomarkers of Human Systemic Lupus Erythematosus Activity
Authors: Brad H. Rovin, Huijuan Song, Dan J. Birmingham, Lee A. Hebert, Chack Yung Yu, Haikady N. Nagaraja
Journal: Journal of the American Society of Nephrology (2004)

The purpose of this study was to evaluate urine monocyte chemoattractant protein-1 (MCP-1) and IL-8 as biomarkers of SLE flare. Urine was collected every 2 mo from patients who were followed prospectively in the Ohio SLE Study. Renal and nonrenal flares were identified and MCP-1 and IL-8 were measured by specific ELISA in samples that were collected at flare. When available, MCP-1 and IL-8 were also measured in urine samples before and after flare. For comparison, MCP-1 and IL-8 were measured in the urine of healthy individuals and in renal and nonrenal SLE patients with stable disease activity (disease controls). Most patients were receiving maintenance immunosuppressive therapy before flare. At renal flare, mean urine MCP-1 (uMCP-1) was significantly greater than uMCP-1 at nonrenal flare and from healthy volunteers and renal disease controls. The level of uMCP-1 correlated with the increase in proteinuria at flare and was higher in patients with proliferative glomerulonephritis and in patients with impaired renal function. Urine MCP-1 was increased beginning 2 to 4 mo before flare. Patients who responded to therapy showed a slow decline in uMCP-1 over several months, whereas nonresponders had persistently high uMCP-1. In contrast, uIL-8 did not change with disease activity and was not elevated at renal or nonrenal flare compared with disease controls. In conclusion, uMCP-1 but not uIL-8 is a sensitive and specific biomarker of renal SLE flare and its severity, even in patients who receive significant immunosuppressive therapy. Persistently elevated uMCP-1 after treatment may indicate ongoing kidney injury that may adversely affect renal prognosis.
Differential downregulation of beta 2-adrenergic receptors in tissue compartments of rat heart is not altered by sympathetic denervation.
Authors: M Zhao, K H Muntz
Journal: Circulation Research (1993)

With agonist stimulation, cardiac beta 2-adrenergic receptors (beta 2ARs) are downregulated to a much greater extent than are beta 1ARs. It has been hypothesized that this effect is due to sympathetic innervation inhibiting the downregulation of beta 1ARs. To test this hypothesis, the technique of coverslip autoradiography was used to localize and quantify beta 1AR and beta 2AR subtypes in tissue compartments of the heart in rats subjected to sympathetic denervation by two intravenous injections of 6-hydroxydopamine (50 mg/kg per dose). After denervation, the rats were infused with L-isoproterenol (400 micrograms.kg-1 x h-1 for 7 days) or vehicle (0.001N HCI) by implantation of osmotic minipumps. Sections were incubated with 70 pmol/L of the beta AR antagonist [125I]iodocyanopindolol (ICYP) alone or in the presence of 5 mumol/L DL-propranolol or 5 x 10(-7) mol/L CGP 20712A (a beta 1AR antagonist). Binding of ICYP to sections of rat hearts was saturable and stereoselective and was displaced by beta AR agonists with the rank order of potency expected for beta ARs. There was an 89% reduction in catecholamine concentration in rat ventricles after 1 week of 6-hydroxydopamine treatment, before implantation of the minipumps. Chronic infusion of isoproterenol induced significant downregulation (63% to 74%) of beta 2ARs in atrial and ventricular myocytes, coronary arterioles, and connective tissue but no change in beta 1ARs in these regions in rats with intact sympathetic innervation. Similar changes were seen in denervated animals. There was a marked reduction in beta 2ARs but small insignificant decreases in beta 1ARs, despite the fact that in the denervated animals there was upregulation of beta 1ARs in atrial and ventricular myocytes (approximately 25%). Our study suggests that beta 1ARs in the heart are not significantly downregulated by chronic agonist exposure and that this is unrelated to sympathetic innervation. The underlying mechanism of preferential regulation of beta AR subtypes remains to be elucidated but may be related to differences in the molecular structure between beta 1ARs and beta 2ARs.
Preferential expression of IgG2b in nose draining cervical lymph nodes and its putative role in mucosal tolerance induction
Authors: J. M. L. M. Van Helvoort, J. N. Samsom, D. Chantry, W. Jansen, I. Schadee‐Eestermans, T. Thepen, R. E. Mebius, G. Kraal
Journal: Allergy (2004)

Induction of intranasal tolerance prevents the body from eliciting unwanted immune responses against harmless antigens that enter the body through the nasal mucosa. To study the intrinsic capacities of the cervical, nose draining lymph nodes (CLN), which are essential for tolerance induction, genes that are differentially expressed in CLN and not in peripheral lymph nodes (PLN) were characterized. The gene that is predominantly overexpressed in CLN codes for IgG2b. This is confirmed by a higher percentage of IgG2b + B220 + cells in CLN compared with any PLN. However, this predominance of IgG2b‐positive B cells in the CLN is not specific for the lymph node itself but rather determined by the region drained by lymph nodes at the cervical site, as transplanted PLN at these locations show a comparable predominance. It was demonstrated that IgG2b, when compared with IgG1, led to differential activation of dendritic cells (DC) through Fc receptor signalling. The results point to a unique local combination of cells and factors in the nose draining CLN leading to highly specialized immune reactivity. The results point out that predominance of a distinct IgG isotype in a lymphoid environment may lead to highly specialized immune reactivity.
Troponin T in pulmonary embolism
Authors: A J Bastin
Journal: Thorax (2003)

▴ Janata K, Holzer M, Laggner A, et al . Cardiac troponin T in the severity assessment of patients with pulmonary embolism: cohort study. BMJ2003;326:312–3 [OpenUrl][1][FREE Full Text][2] One hundred and thirty six consecutive patients with PE (diagnosed by CT or scintigraphy) presenting to an emergency department in Austria were assessed. Troponin T concentrations were measured in 106 patients and 93 … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DJanata%26rft.auinit1%253DK.%26rft.volume%253D326%26rft.issue%253D7384%26rft.spage%253D312%26rft.epage%253D313%26rft.atitle%253DCardiac%2Btroponin%2BT%2Bin%2Bthe%2Bseverity%2Bassessment%2Bof%2Bpatients%2Bwith%2Bpulmonary%2Bembolism%253A%2Bcohort%2Bstudy%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.326.7384.312%26rft_id%253Dinfo%253Apmid%252F12574045%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=326/7384/312&atom=%2Fthoraxjnl%2F58%2F5%2F416.atom
The regulation of adipose tissue and muscle lipoprotein lipase in runners by detraining.
Authors: R B Simsolo, J M Ong, P A Kern
Journal: Journal of Clinical Investigation (1993)

To study the mechanism of lipoprotein lipase (LPL) regulation by exercise, we recruited 16 healthy athletes to undergo a 2-wk period of detraining. Fasting fat and muscle biopsies were performed both before and after the detraining period. In muscle, detraining resulted in a decrease in LPL activity in both the heparin-releasable (HR) (-45%, P < 0.05) and cellular (extractable [EXT]) (-75%, P < 0.005) fractions, with no significant changes in LPL immunoreactive mass and mRNA levels. However, several subjects demonstrated parallel decreases in LPL mass and mRNA levels with detraining, suggesting that there is some degree of heterogeneity in response. In adipose tissue, detraining had the opposite effects on LPL activity. In the HR fraction, detraining resulted in an 86% increase (P < 0.005) in LPL activity, which was paralleled by a 100% (P = 0.02) increase in HR mass. However, there was no significant change in EXT LPL activity or EXT LPL mass. There were no changes in adipose LPL synthetic rate or LPL mRNA levels with detraining. The ratio of adipose tissue/muscle LPL, which may be an important indicator of the tendency for storage of circulating lipids in adipose tissue, increased significantly after detraining. The adipose/muscle LPL ratio was 0.51 +/- 0.17 in the exercising runners, and 4.45 +/- 2.46 in the same runners after detraining (P < 0.05). Thus, detraining of athletes resulted in a decrease in muscle LPL that occurred through post-translational mechanisms, whereas adipose tissue LPL increased, also due to posttranslational changes. This decrease in muscle LPL, coupled with an increase in adipose LPL, yielded a condition favoring adipose tissue storage.
Non-exhaustive DNA methylation-mediated transposon silencing in the black truffle genome, a complex fungal genome with massive repeat element content
Authors: Barbara Montanini, Pao-Yang Chen, Marco Morselli, Artur Jaroszewicz, David Lopez, Francis Martin, Simone Ottonello, Matteo Pellegrini
Journal: Genome biology (2014)

We investigated how an extremely transposon element (TE)-rich organism such as the plant-symbiotic ascomycete truffle Tuber melanosporum exploits DNA methylation to cope with the more than 45,000 repeated elements that populate its genome.
Effect of Sodium Balance on Arterial Blood Pressure and Renal Responses to Prostaglandin A <sub>1</sub> in Man
Authors: LAWRENCE R. KRAKOFF, DAISY DE GUIA, NICHOLAS VLACHAKIS, JENNIE STRICKER, MARVIN GOLDSTEIN
Journal: Circulation Research (1973)

The effect of sodium balance on systemic arterial blood pressure and the renal response to intravenous infusion of prostaglandin A 1 (PGA 1 ) was studied in hypertensive subjects. PGA 1 (0.4 µg/kg min -1 ) was infused for 1 hour in ten hypertensive subjects who were receiving a constant diet containing 40 mEq of sodium and 80 mEq of potassium. During PGA 1 infusion a significant fall in both systolic and diastolic arterial blood pressure occurred. There was a significant rise in urine flow rate, renal plasma flow, and urine sodium excretion; plasma renin activity (PRA) rose slightly but not significantly. Eight of the ten subjects and one additional subject were then placed on furosemide (80 mg/day) for 1 week. In all subjects, a significant weight loss and a rise in midday PRA occurred with the administration of the diuretic. Systolic blood pressure fell, but diastolic pressure was unchanged. Following salt depletion with furosemide, PGA 1 infusion studies were repeated. PGA 1 then produced no significant change in systolic or diastolic blood pressure. Urine flow, renal plasma flow, and urine sodium excretion rose, but the degree of increase was markedly less than that observed prior to furosemide administration. In the salt-depleted subjects, a significant rise in PRA occurred during PGA 1 infusion. The results indicate that volume depletion diminishes the systemic and renal hemodynamic response to infused PGA 1 but enhances the PRA response. The increased PRA response during PGA 1 infusion observed in saltdepleted subjects might in part account for the blunted hemodynamic changes. Alternatively, recent evidence indicates that the enhanced production of endogenous vasodilating prostaglandins which occurs in the salt-depleted state might account for the diminished hemodynamic responses to exogenous PGA 1 .
The tumor-rejection antigens of the 1591 ultraviolet fibrosarcoma. Potential origin and evolutionary implications.
Authors: R Linsk, S Watts, A Fischer, R S Goodenow
Journal: The Journal of Experimental Medicine (1989)

Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fibrosarcoma, 1591. We have extended the analysis of the polymorphic nature of these genes relative to the C3H strain. Scattered nucleotide differences among the tumor genes as compared with the C3H H-2 and Qa sequences make it highly unlikely that the novel tumor genes were generated by recombination between endogenous C3H sequences. Given that two of the tumor clones, A149 and A166, are remarkably similar in amino acid and DNA sequence to H-2Lq and H-2Dq, respectively, we also examined the 1591 RP2 and GUS loci for evidence of polymorphism. Compared with C3H and B10.AKM, 1591 appears to be heterozygous at each of these loci, consistent with an H-2q origin for the two novel 1591 class I genes. Interestingly, the third tumor gene, designated A216, shares certain characteristics with the H-2Ks antigen, reminiscent of the naturally occurring combination of H-2Ks, H-2Dq, and H-2Lq antigens found in some Swiss mouse strains. As a result, we propose that the non-C3H/HeN characteristics displayed by the 1591 tumor point to a non-C3H origin for the novel tumor class I genes of 1591.
To whom it concerns
Authors: J B. Walsh
Journal: BMJ (2000)

Smoking kills they say.

Maybe they are right.

But life kills also.

But how come in the cancer hospice, the smoking room is full.

Of life.

Of laughter. Of craic.

At one level the smoking is of no consequence.

The non-smoking room is always empty.

And dark.

And lonely.

No one there.

I don't …
Acantholytic Dyskeratotic Epidermal Nevus
Authors: Olushola Akinshemoyin Vaughn, Molly A. Hinshaw, Joyce M. Teng
Journal: JAMA Dermatology (2015)

This case report describes a possible solution to the challenge of clinically distinguishing acantholytic dyskeratotic epidermal nevus, often a congenital condition, from Darier disease, which is acquired.
Intratumoral Estrogen Disposition in Breast Cancer
Authors: Ben P. Haynes, Anne Hege Straume, Jürgen Geisler, Roger A'Hern, Hildegunn Helle, Ian E. Smith, Per E. Lønning, Mitch Dowsett
Journal: Clinical Cancer Research (2010)

The concentration of estradiol (E(2)) in breast tumors is significantly higher than that in plasma, particularly in postmenopausal women. The contribution of local E(2) synthesis versus uptake of E(2) from the circulation is controversial. Our aim was to identify possible determinants of intratumoral E(2) levels in breast cancer patients.The expression of genes involved in estrogen synthesis, metabolism, and signaling was measured in 34 matched samples of breast tumor and normal breast tissue, and their correlation with estrogen concentrations assessed.ESR1 (9.1-fold; P < 0.001) and HSD17B7 (3.5-fold; P < 0.001) were upregulated in ER(+) tumors compared with normal tissues, whereas STS (0.34-fold; P < 0.001) and HSD17B5 (0.23-fold; P < 0.001) were downregulated. Intratumoral E(2) levels showed a strong positive correlation with ESR1 expression in all patients (Spearman r = 0.55, P < 0.001) and among the subgroups of postmenopausal (r = 0.76, P < 0.001; n = 23) and postmenopausal ER(+) patients (r = 0.59, P = 0.013; n = 17). HSD17B7 expression showed a significant positive correlation (r = 0.59, P < 0.001) whereas HSD17B2 (r = -0.46, P = 0.0057) and HSD17B12 (r = -0.45, P = 0.0076) showed significant negative correlations with intratumoral E(2) in all patients. Intratumoral E(2) revealed no correlation to CYP19, STS, and HSD17B1 expression. Multivariate models comprising ESR1 and plasma E(2) predicted between 50% and 70% of intratumoral E(2) variability.Uptake due to binding to the ER, rather than intratumoral estrogen synthesis by aromatase or sulfatase, is the single most important correlate and a probable determinant of intratumoral E(2). An increased expression of HSD17B7 may explain the increased ratio of E(2) to estrone (E(1)) in breast tumors compared with normal tissue.
Runting Syndrome in Mice Inoculated With Polyoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. Vandeputte, P. de Somer
Journal: JNCI Journal of the National Cancer Institute (1965)

Wasting disease was observed in (C3H × AKR)F1 hybrids and in C3H mice inoculated at birth with high doses of polyoma virus. Evidence is presented that the induction of runting depends on the dose of virus inoculated as well as on the age at which the animal is infected. The age dependency could be correlated with a difference in virus multiplication in mice inoculated at different ages and might indicate that the virus growth must attain a certain threshold in the organs to induce runting. The autopsy and histological examination of the runted mice revealed visible lesions in the lymphoid tissues. These lesions consisted mostly of atrophy of the Peyer's patches and depletion of lymphocytes in the cortex of the lymph nodes and in the spleen. Thymic lesions were observed in severe cases of runting. A decrease of circulating lymphocytes was observed in the peripheral blood. The experiments support the concept that depletion of lymphocytes is a basic phenomenon in all runting syndromes. They also indicate that a virus may be the primum movens in the induction of runting.
Degradation of Fibrillar Collagen in a Human Melanoma Xenograft Improves the Efficacy of an Oncolytic Herpes Simplex Virus Vector
Authors: Trevor D. McKee, Paola Grandi, Wilson Mok, George Alexandrakis, Numpon Insin, John P. Zimmer, Moungi G. Bawendi, Yves Boucher, Xandra O. Breakefield, Rakesh K. Jain
Journal: Cancer Research (2006)

Abstract Oncolytic viral therapy provides a promising approach to treat certain human malignancies. These vectors improve on replication-deficient vectors by increasing the viral load within tumors through preferential viral replication within tumor cells. However, the inability to efficiently propagate throughout the entire tumor and infect cells distant from the injection site has limited the capacity of oncolytic viruses to achieve consistent therapeutic responses. Here we show that the spread of the oncolytic herpes simplex virus (HSV) vector MGH2 within the human melanoma Mu89 is limited by the fibrillar collagen in the extracellular matrix. This limitation seems to be size specific as nanoparticles of equivalent size to the virus distribute within tumors to the same extent whereas smaller particles distribute more widely. Due to limited viral penetration, tumor cells in inaccessible regions continue to grow, remaining out of the range of viral infection, and tumor eradication cannot be achieved. Matrix modification with bacterial collagenase coinjection results in a significant improvement in the initial range of viral distribution within the tumor. This results in an extended range of infected tumor cells and improved virus propagation, ultimately leading to enhanced therapeutic outcome. Thus, fibrillar collagen can be a formidable barrier to viral distribution and matrix-modifying treatments can significantly enhance the therapeutic response. (Cancer Res 2006; 66(5): 2509–13)
Do the ethnic differences in presentation and treatment strategy influence outcomes of contemporary percutaneous coronary intervention? A report from the national heart, lung, and blood institute dynamic registry
Authors: James Slater, Faith Selzer, Sharmila Dorbala, Deborah Tormey, Helen A. Vlachos, Robert L. Wilensky, Alice K. Jacobs, John S. Douglas, Sheryl F. Kelsey
Journal: Journal of the American College of Cardiology (2003)
The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring
Authors: K.K.L. Chan, T.J. Yao, B. Jones, J.F. Zhao, F.K. Ma, C.Y. Leung, S.K. Lau, M.W. Yip, H.Y.S. Ngan
Journal: Annals of Oncology (2011)
Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease associated pulmonary hypertension
Authors: Eduard J. van Beers, Erfan Nur, Cornelia M. Schaefer‐Prokop, Melvin R. Mac Gillavry, Joost W.J. van Esser, Dees P.M. Brandjes, Maria C. Kappers‐Klunne, Ashley J. Duits, Frits A.J. Muskiet, John‐John B. Schnog, Bart J. Biemond
Journal: American Journal of Hematology (2008)

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.5 m/sec). All patients were systematically evaluated by the aforementioned diagnostic tests comparing patients with and without PHT. The prevalence of PHT was 41% in HbSS/HbSbeta(0)-thalassemia patients and 13% in HbSC/HbSbeta(+)-thalassemia patients. No statistically significant differences were detected in ECG, chest radiography, HRCT, and pulmonary function testing between patients with and without PHT. The degree of anemia and renal dysfunction, but not the presence of PHT, were the most important determinants of plasma (NT-pro)BNP levels. The performed imaging and functional studies do not seem to be of value in identifying etiological conditions (such as airflow obstruction or parenchymal lung disease) nor do they offer clues to the presence of mild PHT in SCD.