tbuckley/cabot-search huggingface dataset:
Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes.
Authors: P Poussier, P Edouard, C Lee, M Binnie, M Julius
Journal: The Journal of Experimental Medicine (1992)

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.
Neuronal Nitric Oxide Synthase
Authors: Gergely Kovács, Péter Komlósi, Amanda Fuson, János Peti-Peterdi, László Rosivall, P. Darwin Bell
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Macula densa (MD) cells detect changes in distal tubular sodium chloride concentration ([NaCl]L), at least in part, through an apical Na:2Cl:K co-transporter. This co-transporter may be a site for regulation of tubuloglomerular feedback (TGF), and recently angiotensin II (Ang II) was shown to regulate the MD Na:2Cl:K co-transporter. In addition, nitric oxide (NO) produced via neuronal NO synthase (nNOS) in MD cells attenuates MD-TGF signaling. This study investigated [NaCl]L-dependent MD-NO production, the regulation of co-transporter activity by NO, and the possible interaction of NO with Ang II. MD cell Na+ concentration ([Na+]i) and NO production were measured using sodium-binding benzofuran isophthalate and 4-amino-5-methylamino-2′,7′-difluorescein diacetate, respectively, using fluorescence microscopy. Na:2Cl:K co-transport activity was assessed as the initial rate of increase in [Na+]i when [NaCl]L was elevated from 25 to 150 mM. 10−4 M 7-nitroindazole, a specific nNOS blocker, significantly increased by twofold the initial rate of rise in [Na+]i when [NaCl]L was increased from 25 to 150 mM, indicating co-transporter stimulation. There was no evidence for an interaction between the stimulatory effect of Ang II and the inhibitory effect of NO on co-transport activity, and, furthermore, Ang II failed to alter MD-NO production. NO production was sensitive to [NaCl]L but increased only when [NaCl]L was elevated from 60 to 150 mM. These studies indicate that MD-NO directly inhibits Na:2Cl:K co-transport and that NO and Ang II independently alter co-transporter activity. In addition, generation of MD-NO seems to occur only at markedly elevated [NaCl]L, suggesting that NO may serve as a buffer against high rates of MD cell transport and excessive TGF-mediated vasoconstriction. E-mail: [email protected]
Prepregnancy Care and Pregnancy Outcomes in Women With Type 1 Diabetes
Authors: Rosemary C. Temple, Vivien J. Aldridge, Helen R. Murphy
Journal: Diabetes Care (2006)

OBJECTIVE—The objective of this study was to examine the relationship between prepregnancy care, glycemic control, maternal hypoglycemia, and pregnancy outcomes in women with type 1 diabetes. RESEARCH DESIGN AND METHODS—This was a prospective observational cohort study of women with type 1 diabetes who delivered from 1991 to 2002. Outcome measures were attendance at a clinic for prepregnancy care, maternal HbA1c (A1C) throughout pregnancy, maternal severe hypoglycemic episodes, macrosomia, preeclampsia, premature delivery (delivery before 37 weeks), very premature delivery (delivery before 34 weeks), spontaneous abortion, and adverse pregnancy outcome (defined as major malformation, stillbirth, and neonatal death). RESULTS—There were 290 pregnancies, in which 110 (38%) women had prepregnancy care. The prepregnancy care group contained more primiparous women (54.7 vs. 40.6%; P = 0.021) and fewer smokers (9.4 vs. 28.7%; P &amp;lt; 0.0001). They registered earlier (6.6 vs. 8.3 weeks, P &amp;lt; 0.0001) and had a lower A1C at the initial visit (6.5% vs. 7.6%; P &amp;lt; 0.0001). Adverse pregnancy outcomes and very premature deliveries were significantly lower in women who received prepregnancy care (2.9 vs. 10.2%; P = 0.03 and 5.0 vs. 14.2%; P = 0.02, respectively). In contrast, between groups, there was no difference in A1C after 24 weeks or in the rates of macrosomia, preeclampsia, or maternal severe hypoglycemic episodes. CONCLUSIONS—Prepregnancy care was associated with improved glycemic control in early pregnancy and significant reductions in adverse pregnancy outcome (malformation, stillbirth, and neonatal death) and very premature delivery. However, prepregnancy care failed to have an impact on glycemic control in later pregnancy or to reduce the risk of macrosomia and preeclampsia.
Matrix Metalloproteinases/Tissue Inhibitors of Metalloproteinases
Authors: S. Hinan Ahmed, Leslie L. Clark, Weems R. Pennington, Carson S. Webb, D. Dirk Bonnema, Amy H. Leonardi, Catherine D. McClure, Francis G. Spinale, Michael R. Zile
Journal: Circulation (2006)

Background— Chronic hypertension may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of chronic heart failure (CHF). Changes in the composition of the extracellular matrix (ECM) known to occur in hypertension are believed to be causally related to these structural, functional, and clinical outcomes. However, whether the determinants of ECM composition, such as the balance between ECM proteases (matrix metalloproteinases [MMPs]) and their tissue inhibitors [TIMPs]), are altered in hypertensive heart disease is unknown. Methods and Results— Plasma MMP-2, -9, and -13 values, TIMP-1 and -2 values, and Doppler echocardiography images were obtained for 103 subjects divided into 4 groups: (1) reference subjects (CTL) with no evidence of cardiovascular disease, (2) hypertensive (HTN) subjects with controlled blood pressure and no LV hypertrophy, (3) hypertensive subjects with controlled blood pressure and with LV hypertrophy (HTN+LVH) but no CHF, and (4) hypertensive subjects with controlled blood pressure, LVH, and CHF (HTN+LVH+CHF). Compared with CTL, patients with HTN had no significant changes in any MMP or TIMP. Patients with HTN+LVH had decreased MMP-2 and MMP-13 values and increased MMP-9 values. Only patients with HTN+LVH+CHF had increased TIMP-1 values. A TIMP-1 level &gt;1200 ng/mL was predictive of CHF. Conclusions— Patients with hypertension but normal LV structure and function had normal MMP/TIMP profiles. Changes in MMP profiles that favor decreased ECM degradation were associated with LVH and diastolic dysfunction. An increased TIMP-1 level predicted the presence of CHF. Although these findings should be confirmed in a larger prospective study, these data do suggest that changes in the MMP/TIMP balance may play an important role in the structural, functional, and clinical manifestations of hypertensive heart disease.
Treatment of Breast Cancer with Gonadotropin-Releasing Hormone
Authors: ANDREA MANNI, RICHARD SANTEN, HAROLD HARVEY, ALLAN LIPTON, DEVORAH MAX
Journal: Endocrine Reviews (1986)

Analogs of GnRH, given chronically in a continuous fashion, produce a paradoxic inhibition of pituitary gonadotropin secretion and, consequently, gonadal steroidogenesis. Thus, GnRH analogs are an attractive class of compounds for achieving a medical castration in the treatment of hormone-dependent neoplasms. In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months. All women treated for at least 10 weeks developed amenorrhea. Profound suppression of gonadotropins, estradiol, and progesterone secretion occurred in all patients on chronic therapy and persisted for the whole treatment period. These effects on tumor growth and ovarian hormone levels are similar to those observed after surgical ovariectomy. Other GnRH analogs such as Buserelin and Zoladex have been found to have similar antitumor and hormonal effects which are also comparable to those produced by surgical ovariectomy. The mode of drug administration is important. Consistent suppression of ovarian function has only been observed with sc injections of the analogs. Chronic intranasal therapy has been found to induce an incomplete suppression of ovarian function in most patients, probably as a result of the poor absorption of these compounds through this route (approximately 2%). Treatment of metastatic breast cancer with GnRH analogs has been associated with remarkable absence of significant toxicity. Despite some evidence in favor of a direct antitumor effect independent of suppression of ovarian function, the use of GnRH analogs in the therapy of advanced breast cancer should be restricted to premenopausal women.
Prospective Relationships of Physical Activity With Quality of Life Among Colorectal Cancer Survivors
Authors: Brigid M. Lynch, Ester Cerin, Neville Owen, Anna L. Hawkes, Joanne F. Aitken
Journal: Journal of Clinical Oncology (2008)

Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life over 2 years after a colorectal cancer diagnosis.Data were collected within the Colorectal Cancer and Quality of Life Study, in which 1,966 people diagnosed with colorectal cancer were recruited through the Queensland Cancer Registry. Participants completed telephone interviews at approximately 6, 12, and 24 months after diagnosis. Generalized linear mixed models were used to estimate the overall, interindividual, and intraindividual level independent effects of participation in physical activity on quality of life.There was an overall independent association between physical activity and quality of life. At a given time point, participants achieving at least 150 minutes of physical activity per week had an 18% higher quality of life score than those who reported no physical activity. Significant associations were also present at the interindividual level (differences between participants) and intraindividual level (within participant changes).These findings suggest that the positive association between physical activity and quality of life is consistent over time. Encouraging colorectal cancer survivors to be physically active may be a helpful strategy for enhancing quality of life.
Unique promotion of erythrophagocytosis by malondialdehyde
Authors: Robert P. Hebbel, Wesley J. Miller
Journal: American Journal of Hematology (1988)

Abstract Modification of the normal erythrocyte membrane by reagent malondialdehyde (MDA) promotes phagocytosis of red blood cells by human macrophages, a phenomenon previously shown to involve both IgG‐dependent and IgG‐independent mechanisms and to be demonstrable even at micromolar MDA concentrations. In the present studies, we demonstrate this effect using 1mM MDA prepared both by acid hydrolysis of malonaldehyde bis‐(dimethyl acetal) and by enzymatic synthesis from 1,3‐propanediol. Remarkably, we find that equimolar amounts of other mono‐ and dialdehydes fail to promote erythrophagocytosis despite similarity to MDA in size and structure and ability to cross link. Authentic MDA seems to be unique among small aldehydes in ability to promote erythrophagocytosis at low aldehyde concentration and, therefore, has a special biologic relevance among the great variety of peroxidation byproducts.
Allelic Loss of Chromosome 1p as a Predictor of Unfavorable Outcome in Patients with Neuroblastoma
Authors: Huib Caron, Peter van Sluis, Jan de Kraker, Jos Bökkerink, Maarten Egeler, Geneviève Laureys, Rosalyn Slater, Andries Westerveld, P.A. Voûte, Rogier Versteeg
Journal: New England Journal of Medicine (1996)

Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value.
Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa®: effects on cerebral oxygenation, circulation, and pressure
Authors: Julian Bösel, Jan C. Purrucker, Frank Nowak, Julian Renzland, Petra Schiller, Eva Benveniste Pérez, Sven Poli, Benjamin Brunn, Werner Hacke, Thorsten Steiner
Journal: Intensive Care Medicine (2012)
Association of Vitamin D With Insulin Resistance and β-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes
Authors: Sheena Kayaniyil, Reinhold Vieth, Ravi Retnakaran, Julia A. Knight, Ying Qi, Hertzel C. Gerstein, Bruce A. Perkins, Stewart B. Harris, Bernard Zinman, Anthony J. Hanley
Journal: Diabetes Care (2010)

OBJECTIVE To examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and β-cell dysfunction in 712 subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS Serum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and homeostasis model assessment of insulin resistance HOMA-IR. β-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). RESULTS Linear regression analyses indicated independent associations of 25(OH)D with ISOGTT and HOMA-IR (β = 0.004, P = 0.0003, and β = −0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (β = 0.004, P = 0.0286, and β = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI. CONCLUSIONS Vitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and β-cell function among individuals at risk of type 2 diabetes.
Ambient temperature and lung function in children with asthma in Australia
Authors: Shanshan Li, Peter J. Baker, Bin B. Jalaludin, Guy B. Marks, Lyn S. Denison, Gail M. Williams
Journal: European Respiratory Journal (2013)

The association between ambient temperature and lung function in children with asthma is still uncertain. A panel of 270 children (aged 7–12 years) with asthma was recruited from six Australian cities. They performed three successive forced expiratory manoeuvres twice daily for 4 weeks. The highest peak expiratory flow rate (PEF) and forced expiratory volume in 1 s (FEV 1 ) were stored for each session. During the same period, data were obtained daily on ambient temperature, relative humidity and air pollution. Mixed models were used to examine the effects of temperature on lung function, controlling for individual characteristics and environmental factors. Ambient temperature was negatively related to both morning and evening PEF and FEV 1 for 0–3 days lag. In general, the effects of temperature were stronger in males than in females for evening PEF, while the effects were stronger in females for evening FEV 1 . Children with asthma living in southern cities were more sensitive to high temperature than those in the northernmost city. Higher ambient temperature is associated with lower lung function in children with asthma. Preventive health policies will be required to protect children with asthma from increasingly frequent high temperatures.
Effect of Ischemia on Capillary Pressure and Equivalent Pore Radius in Capillaries of the Isolated Dog Hind Limb
Authors: JOHN N. DIANA, M. HAROLD LAUGHLIN
Journal: Circulation Research (1974)

Measurements were made of filtration coefficients ( L p ), area per unit path length ( A /Δ x ), and equivalent pore radius ( r p ) in the control state and following severe ischemia (arrested blood flow) for periods of 30 minutes, 1 hour, and 3 hours. The value of A s /Δ x for diffusion of all lipid-insoluble substances was not changed after 30 minutes of ischemia, but it was increased after 1 and 3 hours of ischemia. The value of r p calculated from the theory of restricted diffusion yielded values of 34-35 Å for both the control period and after all three periods of ischemia. Combination of hydrodynamic data ( L p ) and diffusion data ( A ω /Δ x ) yielded values for r p of 23 Å for control and ischemic periods. Measurements of plasma-protein osmotic pressure, tissue-protein osmotic pressure, tissue hydrostatic pressure, and capillary hydrostatic pressure supported the conclusion that extended periods of arrested blood flow did not affect muscle capillary membrane porosity. In 5 of 16 hind limbs, there appeared to be a porosity change following 3 hours of arrested blood flow. This change was demonstrated by a net decrease in plasma-protein osmotic pressure and an increase in r p from 34 Å to 54 Å. L p was not changed after 30 minutes but was increased after 1 hour of ischemia; the increase was associated solely with an increase in capillary surface area. After 3 hours of ischemia, the primary change in 11 of 16 hind limbs was an increase in capillary surface area, although an increase in the size of the pores per unit membrane area could not be rigorously excluded. In 5 hind limbs after 3 hours of ischemia, an increase in r p was the primary change and an increase in capillary surface area was of secondary importance. The data indicate that the edema which occurs subsequent to reperfusion of the vasculature after moderately long periods of severe ischemia results from an increase in capillary hydrostatic pressure augmented by an increase in capillary surface area not associated with an increase in membrane porosity. The rise in capillary pressure for any given arterial or venous pressure involves a decrease in precapillary resistance, but postcapillary resistance does not change for any given flow.
EVEC, a Novel Epidermal Growth Factor–Like Repeat-Containing Protein Upregulated in Embryonic and Diseased Adult Vasculature
Authors: Robert C. Kowal, James A. Richardson, Joseph M. Miano, Eric N. Olson
Journal: Circulation Research (1999)

Abstract —A hallmark of vascular lesions is the phenotypic modulation of vascular smooth muscle cells (VSMCs) from a quiescent, contractile state to a more primitive, proliferative phenotype with a more fetal pattern of gene expression. Using subtraction hybridization to identify genes that may regulate this transition, we cloned a novel gene named EVEC, an acronym for its expression in the e mbryonic v asculature and the presence of Ca 2+ binding e pidermal growth factor–like repeats c ontained in the predicted protein structure. Although these repeats are characteristic of the extracellular matrix proteins, fibrillin, fibulin, and the latent transforming growth factor-β binding proteins, EVEC most closely resembles the H411 and T16/S1-5 gene products, the latter of which are believed to regulate DNA synthesis in quiescent fibroblasts. Using in situ hybridization, we demonstrated that EVEC is expressed predominantly in the VSMCs of developing arteries in E11.5 through E16.5 mouse embryos. Lower levels of expression are also observed in endothelial cells, perichondrium, intestine, and mesenchyme of the face and kidney. EVEC mRNA expression is dramatically downregulated in adult arteries, except in the uterus, where cyclic angiogenesis continues; however, EVEC expression is reactivated in 2 independent rodent models of vascular injury. EVEC mRNA is observed in cellular elements of atherosclerotic plaques of LDL receptor–deficient, human apolipoprotein B transgenic mice and in VSMCs of the media and neointima of balloon-injured rat carotid arteries. These data suggest that EVEC may play an important role in the regulation of vascular growth and maturation during development and in lesions of injured vessels.
Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner
Authors: Maria Braoudaki, George I Lambrou, Konstantinos Vougas, Kalliopi Karamolegou, George T Tsangaris, Fotini Tzortzatou-Stathopoulou
Journal: Journal of Hematology & Oncology (2013)

Abstract The current study evaluated the differential expression detected in the proteomic profiles of low risk- and high risk- ALL pediatric patients to characterize candidate biomarkers related to diagnosis, prognosis and patient targeted therapy. Bone marrow and peripheral blood plasma and cell lysates samples were obtained from pediatric patients with low- (LR) and high-risk (HR) ALL at diagnosis. As controls, non-leukemic pediatric patients were studied. Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization. Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The differential expression of certain proteins was confirmed by Western blot analysis. The obtained data revealed that CLUS, CERU, APOE, APOA4, APOA1, GELS, S10A9, AMBP, ACTB, CATA and AFAM proteins play a significant role in leukemia prognosis, potentially serving as distinctive biomarkers for leukemia aggressiveness, or as suppressor proteins in HR-ALL cases. In addition, vitronectin and plasminogen probably contributed to leukemogenesis, whilst bicaudal D-related protein 1 could afford a significant biomarker for pediatric ALL therapeutics.
TCT-76 Does Age Affect Fractional Flow Reserve-Guided Percutaneous Coronary Intervention? A FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Trial Substudy
Authors: Hong-Seok Lim, Bernard De Bruyne, William F. Fearon, Bong-Ki Lee, Nico Pijls, Pim A. Tonino, Andy S. Yong
Journal: Journal of the American College of Cardiology (2013)