tbuckley/cabot-search huggingface dataset:
Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study
Authors: T. M. L. Eagan, T. Ueland, P. D. Wagner, J. A. Hardie, T. E. Mollnes, J. K. Damas, P. Aukrust, P. S. Bakke
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40–75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of &gt;10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p&lt;0.05), and higher levels of CRP (p&lt;0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p&lt;0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p&lt;0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p&lt;0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.
Motivating grandparental investment
Authors: Debra Friedman, Michael Hechter
Journal: Behavioral and Brain Sciences (2010)

Abstract What makes the question of grandparental investment so very interesting is trying to tease out the underlying motivations. Grandparental investment is variable and grandparental altruism, if it exists at all, is also variable. Neither evolutionary theory nor rational choice theory has an easy time explaining this variation, and insight is further impeded by the absence of any compelling empirical studies designed for the purpose of testing alternative explanations of variations in grandparental investment.
Quantitative studies of microcirculatory structure and function. III. Microvascular hemodynamics of cat mesentery and rabbit omentum.
Authors: B W Zweifach, H H Lipowsky
Journal: Circulation Research (1977)

We made simultaneous measurements of intravascular pressure and red blood cell velocity for vessels which make up the modular configuration of microvascular networks in mesentery and omentum. An analysis of these variables and the computed volumetric flow rates is presented for arterioles which had a maximum diameter of 56 micrometer through the "true capillaries" (typically 7 micrometer for mesentery and 8 micrometer for omentum) to 56-micrometer venules. The spatial variance of pressure and flow is related to topographical features of each network. Vascularization statistics for each network are presented and demonstrate a unique ratio of potential microvascular exchange area to module planar area, with values of 0.71 +/- 0.22 (SD) for omentum and 0.19 "/- 0.03 (SD) for mesentery. Analysis of the volumetric flow rate for each module demonstrates a linear relationship to the planar area of tissue serviced by each modular network. In situ perfusion rates of 1180 ml/min per 100 g and 105 ml/min per 100 g were determined for omentum and mesentery, respectively. The hemodynamic resistance of the omental and mesenteric circuitry was evaluated, and in the case of the omentum, found to be inversely proportional to the planar area of the module. The arterial to venous distribution of pressure and flow for the mosaic of contiguous modules in omentum and mesentery is described and related to the deployment of parallel and serial microvessels of each network.
IPC: Professional Type 1 Interferon-Producing Cells and Plasmacytoid Dendritic Cell Precursors
Authors: Yong-Jun Liu
Journal: Annual Review of Immunology (2004)

▪ Abstract Type 1 interferon-(α, β, ω)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%–0.8% of peripheral blood mononuclear cells in both humans and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.
Oncogene Amplification in Urothelial Cancers With p53 Gene Mutation or MDM2 Amplification
Authors: T. Habuchi, H. Kinoshita, H. Yamada, Y. Kakehi, O. Ogawa, W.-J. Wu, R. Takahashi, T. Sugiyama, O. Yoshida
Journal: JNCI Journal of the National Cancer Institute (1994)

Previously, p53 (also known as TP53) gene mutations have been shown to be frequently detected in highly malignant urothelial cancers. Evidence has been accumulating that the disruption of the normal function of p53 may lead to genomic instability, including predisposition to gene amplification. Furthermore, the normal function of p53 may be abrogated by MDM2 (murine double minute-2) gene amplification in some human tumors. Our purpose was to investigate the relationship between proto-oncogene amplification and p53 alteration in urothelial cancers by examining the existence of amplification of MDM2 and 14 other proto-oncogenes in 50 urothelial tumors in which p53 gene status was known. We analyzed gene amplification by Southern-blot analysis in 50 urothelial cancer specimens. These tumors were previously examined for p53 mutations by polymerase chain reaction-single-strand conformation analysis, and 17 tumors contained p53 mutations. Two high-grade advanced tumors (4%) without p53 mutation harbored MDM2 amplification with concurrent int-2 gene amplification. As for other genes, amplification was detected for int-2 (also known as WNT2) (seven [14%] of 50), erbB-2 (also known as ERBB2) (three [6%] of 50), N-ras (also known as NRAS) (one [2%] of 50), L-myc (also known as MYCL1) (one [2%] of 50), and raf-1 (also known as RAF1) (one [2%] of 50). The amplification of at least one gene examined was observed in 11 (22%) of 50 tumors. The presence of p53 mutations was not significantly associated with the occurrence of gene amplification, since the amplification was detected in six (35%) of 17 tumors with p53 mutations and in five (15%) of 33 tumors without p53 mutations. However, eight (73%) of 11 tumors with proto-oncogene amplification harbored p53 mutations or MDM2 amplification. A subset of advanced urothelial cancers without p53 mutations may harbor MDM2 amplification. This finding should be taken into account when adopting p53 alteration as a marker of aggressiveness in urothelial cancers. Although the abrogation of normal p53 function may be one of the key steps to proto-oncogene amplification, the data further indicate that the predisposition to gene amplification in urothelial cancers was not determined by the presence of p53 alteration alone. [J Natl Cancer Inst 86: 1331–1335, 1994]
Effect of weather conditions on rheumatic patients.
Authors: D Guedj, A Weinberger
Journal: Annals of the Rheumatic Diseases (1990)

In a one month prospective study of 62 rheumatic patients--16 with rheumatoid arthritis (RA), 24 with osteoarthritis (OA), 11 with inflammatory arthritis, 11 with fibromyalgia joint pain--swelling and everyday activity was compared with changes in daily weather conditions. In most patients weather changes increased arthritic symptoms. Women were more sensitive to weather than men (62% v 37%). Pain was affected positively by barometric pressure and temperature in RA, by temperature, rain, and barometric pressure in OA, and by barometric pressure in fibromyalgia. These results support the belief of most rheumatic patients that weather conditions significantly influence their day to day symptoms.
Use of Hospital-Based Services Among Young Adults With Behavioral Health Diagnoses Before and After Health Insurance Expansions
Authors: Ellen Meara, Ezra Golberstein, Rebecca Zaha, Shelly F. Greenfield, William R. Beardslee, Susan H. Busch
Journal: JAMA Psychiatry (2014)

Young adults have high levels of behavioral health needs but often lack health insurance. Recent health reforms have increased coverage, but it is unclear how use of hospital-based care changed after expanding insurance. OBJECTIVE To evaluate the association between health insurance coverage expansions and use of hospital-based care among young adults with behavioral health diagnoses.Quasi-experimental analyses of community hospital inpatient and emergency department use from 2003-2009 based on hospital discharge data, comparing differential changes in service use among young adults with behavioral health diagnoses in Massachusetts vs other states before and after Massachusetts' 2006 health reform. This population-based sample included inpatient admissions (n = 2,533,307, representing 12,821,746 weighted admissions across 7 years) nationwide and emergency department visits (n = 6,817,855 across 7 years) from Maryland and Massachusetts for 12- to 25-year-old patients.Inpatient admission rates per 1000 population for primary diagnosis of any behavioral health disorder by diagnosis; emergency department visit rates per 1000 population by behavioral health diagnosis; and insurance coverage for hospital discharges.After 2006, uninsurance among 19- to 25-year-old individuals in Massachusetts decreased from 26% to 10% (16 percentage points; 95% CI, 13-20). Young adults experienced relative declines in inpatient admission rates of 2.0 per 1000 for primary diagnoses of any behavioral health disorder (95% CI, 0.95-3.2), 0.38 for depression (95% CI, 0.18-0.58), and 1.3 for substance use disorder (95% CI, 0.68-1.8). The increase in emergency department visits with any behavioral health diagnosis after 2006 was lower among young adults in Massachusetts compared with Maryland (16.5 per 1000; 95% CI, 11.4-21.6). Among young adults in Massachusetts, the percentage of behavioral health discharges that were uninsured decreased by 5.0 (95% CI, 3.0-7.2) percentage points in inpatient settings and 5.0 (95% CI, 1.7-7.8) percentage points in emergency departments relative to other states.Expanded health insurance coverage for young adults was not associated with large increases in hospital-based care for behavioral health, but it increased financial protection for young adults with behavioral health diagnoses and for the hospitals that care for them.
Cancer of the Breast
Authors: Juan A. del Regato
Journal: JAMA (1977)

IN THE Third National Cancer Survey (1969 to 1971), cancer of the breast was found to make up 27.5% of all cancer in white women and 23% of all cancer in black women.<sup>1</sup>In 1975 an estimated 88,700 new cases of cancer of the breast occurred in the United States; the risk, low for women younger than 25 years of age, rises thereafter and never declines, so that the older the patient, the greater her chance of having cancer of the breast. Progress made in this century in the diagnosis and treatment of malignant tumors has brought about a reduction in the mortality from some major forms of cancer: carcinoma of the cervix stands as a notable example. However, despite earlier diagnosis, reduced operative mortality, and the development of surgical adjuvants, there has been no reduction in the mortality from cancer of the breast. In the United States, the
Physiological concentrations of epinephrine potentiate thromboxane A2 release from platelets in the isolated rat heart.
Authors: M Purchase, G J Dusting, D M Li, M A Read
Journal: Circulation Research (1986)

The isolated rat heart perfused with washed platelets was used as a model to examine platelet-vessel wall interactions. Release of prostacyclin and thromboxane A2 was measured, using a cascade of smooth muscle bioassay tissues or radioimmunoassays of the stable hydration products. In hearts perfused with rabbit or human platelets, injection of sodium arachidonate caused release of both prostacyclin and thromboxane A2. In hearts perfused with aspirin-pretreated platelets, arachidonate released only prostacyclin indicating that thromboxane A2 originates largely in the platelets. Infusion of epinephrine (0.6-6 nmol/liter) through the heart potentiated arachidonate-induced release of thromboxane A2. Similar potentiation of thromboxane A2 release was observed in rat hearts perfused with either rabbit or human platelets, and in rabbit hearts perfused with rabbit platelets. In contrast, when rabbit platelets were infused through an incubation coil of tubing in place of the heart, epinephrine did not alter thromboxane A2 release. There was no significant loss of rabbit platelets on perfusion through rat hearts, and no aggregates were observed in the effluent either before or immediately after arachidonate injections, even in the presence of epinephrine. Thus, potentiation of thromboxane A2 production could not be explained by aggregation. However, it is clear from these studies that physiological concentrations of epinephrine can potentiate thromboxane A2 release from platelets when they are stimulated by arachidonic acid within the heart. This could result from a redirection of arachidonate metabolism to a local potentiating factor in the vessel wall. Potentiation of thromboxane A2 release might contribute to myocardial ischemia associated with platelet activation.
The ligands/activators for peroxisome proliferator-activated receptor α (PPARα) and PPARγ increase Cu2+, Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells
Authors: Ikuo Inoue, Sei-ichi Goto, Toshiyuki Matsunaga, Takanori Nakajima, Takuya Awata, Shigeru Hokari, Tsugikazu Komoda, Shigehiro Katayama
Journal: Metabolism (2001)
Electrical Coupling Between Endothelial Cells and Smooth Muscle Cells in Hamster Feed Arteries
Authors: Geoffrey G. Emerson, Steven S. Segal
Journal: Circulation Research (2000)

Endothelial cells (ECs) govern smooth muscle cell (SMC) tone via the release of paracrine factors (eg, NO and metabolites of arachidonic acid). We tested the hypothesis that ECs can promote SMC relaxation or contraction via direct electrical coupling. Vessels (resting diameter, 57+/-3 microm; length, 4 mm) were isolated, cannulated, and pressurized (75 mm Hg; 37 degrees C). Two microelectrodes were used to simultaneously impale 2 cells (ECs or SMCs) in the vessel wall separated by 500 microm. Impalements of one EC and one SMC (n=26) displayed equivalent membrane potentials at rest, during spontaneous oscillations, and during hyperpolarization and vasodilation to acetylcholine. Injection of -0.8 nA into an EC caused hyperpolarization ( approximately 5 mV) and relaxation of SMCs (dilation, approximately 5 microm) along the vessel segment. In a reciprocal manner, +0.8 nA caused depolarization ( approximately 2 mV) of SMCs with constriction ( approximately 2 microm). Current injection into SMCs while recording from ECs produced similar results. We conclude that ECs and SMCs are electrically coupled to each other in these vessels, such that electrical signals conducted along the endothelium can be directly transmitted to the surrounding smooth muscle to evoke vasomotor responses.
The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses
Authors: Amedeo Amedei, Andrea Cappon, Gaia Codolo, Anna Cabrelle, Alessandra Polenghi, Marisa Benagiano, Elisabetta Tasca, Annalisa Azzurri, Mario Milco D’Elios, Gianfranco Del Prete, Marina de Bernard
Journal: Journal of Clinical Investigation (2006)

The Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor of H. pylori that stimulates in neutrophils high production of oxygen radicals and adhesion to endothelial cells. We report here that HP-NAP is a TLR2 agonist able to induce the expression of IL-12 and IL-23 by neutrophils and monocytes. Addition in culture of HP-NAP, as an immune modulator, to antigen-induced T cell lines resulted in a remarkable increase in the number of IFN-γ–producing T cells and decrease of IL-4–secreting cells, thus shifting the cytokine profile of antigen-activated human T cells from Th2 to a Th1 cytotoxic phenotype. We also found that in vivo HP-NAP elicited an antigen-specific Th1-polarized T cell response in the gastric mucosa of H. pylori–infected patients. These data indicate HP-NAP as an important factor of H. pylori able to elicit cells of the innate immune system to produce IL-12 and IL-23, and they suggest it as a new tool for promoting Th1 immune responses.
Survival After Recurrence of Ewing’s Sarcoma Family of Tumors
Authors: Lisa M. Barker, Thomas W. Pendergrass, Jean E. Sanders, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2005)

The overall survival (OS) of patients with relapsed Ewing's sarcoma family of tumors (ESFT) is poor, and the relative benefit of high-dose therapy (HDT) is controversial.We retrospectively identified 55 consecutive ESFT patients with adequate medical records for review, who were treated at Children's Hospital and Regional Medical Center and who developed disease recurrence between January 1, 1985 and December 31, 2002.The median relapse-free interval (RFI) from diagnosis to first recurrence was 17 months (range, 5 to 90 months). Most recurrences were metastatic only (39 patients) or local and metastatic (10 patients). Twenty-seven patients (49%) achieved a partial or complete response to second-line treatment, with a median duration of response of 27 months (range, 5 to 119+ months). The 5-year OS rate for all relapsed patients was 23% (95% CI, 11% to 35%). By univariate analysis, improved OS was associated with response to second-line treatment versus no response (46% v 0%, respectively; P < .0001), RFI > or = 24 months versus less than 24 months (48% v 12%, respectively; P = .0001), and no metastases at initial diagnosis versus presence of metastases (31% v 12%, respectively; P = .05). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (relative risk, 0.14; 95% CI, 0.05 to 0.40), RFI > or = 24 months (relative risk, 0.29; 95% CI, 0.13 to 0.66), and receiving HDT (relative risk, 0.26; 95% CI, 0.08 to 0.85).HDT as consolidation therapy for relapsed ESFT seems to be associated with improved OS, even after adjusting for RFI and response to second-line treatment.
Analysis of R-R Intervals in Patients with Atrial Fibrillation at Rest and During Exercise
Authors: BERT K. BOOTSMA, ADRIAAN J. HOELEN, JAN STRACKEE, FRITS L. MEIJLER
Journal: Circulation (1970)

Serial autocorrelation functions and histograms of R-R intervals in patients with atrial fibrillation, with and without digitalis, at rest and during exercise, were produced by a computer. At rest with and without digitalis the first and higher order coefficients did not differ from zero. During exercise (also with and without digitalis) only the first autocorrelation coefficient became slightly positive (in the order of 0.07) whereas the form of the histograms was profoundly altered by both exercise and digitalis. The change in form of the histograms reveals the change in electrophysiologic properties of the A-V conduction system. Since the serial autocorrelation functions were not influenced by digitalis and only slightly by exercise, the conclusion seems justified that the refractory period of, and the concealed conduction in, the A-V system cannot be (solely) responsible for the random nature of the ventricular rhythm in patients with atrial fibrillation. The effect of randomly spaced atrial impulses of random strength reaching the A-V node from random directions can explain these results.
A suppressor lymphokine produced by human T leukemia cell lines. Partial characterization and spectrum of activity against normal and malignant hemopoietic cells.
Authors: D Santoli, D J Tweardy, D Ferrero, B L Kreider, G Rovera
Journal: The Journal of Experimental Medicine (1986)

Human T leukemia cell lines spontaneously release into their medium a suppressor lymphokine, T leukemia-derived suppressor lymphokine (TLSL), able to inhibit proliferation, DNA synthesis, and colony formation in a variety of malignant hemopoietic cell lines, as well as in normal myelomonocytic progenitor cells from bone marrow and peripheral blood. Titration curves indicated that the inhibitory activity in the crude supernatant preparations ranged from 10(-3)-10(-9): the supernatants from CCRF/CEM, HUT-78, and MOLT-4 cell lines were the most active, those from HPB-ALL, JM, and CCRF/HSB2 displayed an intermediate activity, and the Jurkat supernatant was the least active. Target cell lines of B cell origin (Burkitt lymphomas) were more sensitive than granulocytic, monocytic, erythroid, and T cell lines. Partial purification by ammonium sulfate precipitation and column chromatography demonstrated that TLSL is a protein with an Mr of 88,000, as determined by gel filtration. A high Mr form (greater than 300,000) was produced in serum-free medium by one of the most active producer cell lines (CCRF/CEM), and appeared to be an aggregate of the 88,000 Mr form. Neither the partially purified fractions obtained nor the crude supernatant preparations displayed antiviral activity or contained interleukin 2. Unlike lymphotoxin and tumor necrosis factor, TLSL is cytostatic: maximal inhibition of proliferation was observed 4-5 d after addition of crude supernatant to the target cells, and was not accompanied by a significant loss in cell viability. The antiproliferative capacity of TLSL was manifested both in suspension and methylcellulose cultures. Treated target cells accumulated either in the G1 or in the S phase of the cell cycle. The effect of TLSL on the target cells is irreversible: even brief (1 h) incubation of sensitive cells with TLSL resulted in inhibition of proliferation measured 5 d later. Although TLSL is produced by leukemic T cell lines, this lymphokine inhibits proliferation of normal peripheral blood T cells in response to mitogens or alloantigens: T lymphocyte activation was inhibited by all of the T cell supernatants tested. In contrast, when T cell lines were used as targets, no inhibition of proliferation was detected with two exceptions: the low producer Jurkat cell line was sensitive to all the T cell-derived supernatants, and the intermediate producer CCRF/HSB2 cell line was sensitive only to the three most active supernatants, CCRF/CEM, MOLT-4, and HUT-78. The possible significance of TLSL and its relationship with other suppressor lymphokines previously described in other systems is discussed.
Nasal carriage of Staphylococcus aureus, including community-associated methicillin-resistant strains, in Queensland adults
Authors: W.J. Munckhof, G.R. Nimmo, J.M. Schooneveldt, S. Schlebusch, A.J. Stephens, G. Williams, F. Huygens, P. Giffard
Journal: Clinical Microbiology and Infection (2009)