tbuckley/cabot-search huggingface dataset:
Decreased Expression and Activity of cAMP Phosphodiesterases in Cardiac Hypertrophy and Its Impact on β-Adrenergic cAMP Signals
Authors: Aniella Abi-Gerges, Wito Richter, Florence Lefebvre, Philippe Mateo, Audrey Varin, Christophe Heymes, Jane-Lise Samuel, Claire Lugnier, Marco Conti, Rodolphe Fischmeister, Grégoire Vandecasteele
Journal: Circulation Research (2009)

Multiple cyclic nucleotide phosphodiesterases (PDEs) degrade cAMP in cardiomyocytes but the role of PDEs in controlling cAMP signaling during pathological cardiac hypertrophy is poorly defined.Evaluate the beta-adrenergic regulation of cardiac contractility and characterize the changes in cardiomyocyte cAMP signals and cAMP-PDE expression and activity following cardiac hypertrophy.Cardiac hypertrophy was induced in rats by thoracic aortic banding over a time period of 5 weeks and was confirmed by anatomic measurements and echocardiography. Ex vivo myocardial function was evaluated in Langendorff-perfused hearts. Engineered cyclic nucleotide-gated (CNG) channels were expressed in single cardiomyocytes to monitor subsarcolemmal cAMP using whole-cell patch-clamp recordings of the associated CNG current (I(CNG)). PDE variant activity and protein level were determined in purified cardiomyocytes. Aortic stenosis rats exhibited a 67% increase in heart weight compared to sham-operated animals. The inotropic response to maximal beta-adrenergic stimulation was reduced by approximately 54% in isolated hypertrophied hearts, along with a approximately 32% decrease in subsarcolemmal cAMP levels in hypertrophied myocytes. Total cAMP hydrolytic activity as well as PDE3 and PDE4 activities were reduced in hypertrophied myocytes, because of a reduction of PDE3A, PDE4A, and PDE4B, whereas PDE4D was unchanged. Regulation of beta-adrenergic cAMP signals by PDEs was blunted in hypertrophied myocytes, as demonstrated by the diminished effects of IBMX (100 micromol/L) and of both the PDE3 inhibitor cilostamide (1 micromol/L) and the PDE4 inhibitor Ro 201724 (10 micromol/L).Beta-adrenergic desensitization is accompanied by a reduction in cAMP-PDE and an altered modulation of beta-adrenergic cAMP signals in cardiac hypertrophy.
Complex formation of platelet membrane glycoproteins IIb and IIIa with fibrinogen.
Authors: R L Nachman, L L Leung
Journal: Journal of Clinical Investigation (1982)

We have recently reported the isolation of purified platelet membrane glycoproteins IIb and IIIa and the generation of monospecific antisera to these membrane proteins. Using these monospecific antisera in an enzyme-linked immunosorbent assay system, it is no demonstrated that glycoprotein IIb (GPIIb) and glycoprotein IIIa (GPIIIa) form a complex with purified human fibrinogen. The formation of this GPIIb-GPIIIa fibrinogen complex is calcium dependent, fibrinogen specific, saturable, and inhibited by specific amino sugars and amino acids. These observations suggest that the GPIIb-GPIIIa macromolecular complex on the platelet surface acts under the proper physiologic circumstances as the fibrinogen binding site required for normal platelet aggregation.
Intensive Diabetes Management May Improve Pregnancy
Authors: Xilin Yang, Bridget Hsu-Hage, Ling Dong, Ping Shao, Hua Wang, Huiguang Tian, Yue Chen, Hong Zhang
Journal: Diabetes Care (2003)

In a study of diabetes in pregnancy in Tianjin, China (1,2), gravidas with impaired glucose tolerance (IGT) were found to have poor pregnancy outcomes (3). We studied the effect of an intensive diabetes management plan (IDMP) on pregnancy outcomes in 150 gravidas who developed IGT during pregnancy.

Women were randomized to receive either intensive care (IC; n = 95) or usual obstetric care (UC; n = 55). Of the 95 women randomized to the IC group, 48 (50%) completed the IDMP. All 55 women of the UC group completed the study. Comparisons of pregnancy outcomes were performed by intention to treat. The IDMP …
Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF
Authors: Martin Guilliams, Ismé De Kleer, Sandrine Henri, Sijranke Post, Leen Vanhoutte, Sofie De Prijck, Kim Deswarte, Bernard Malissen, Hamida Hammad, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2013)

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life.
Primary Testicular Diffuse Large B-Cell Lymphoma: A Population-Based Study on the Incidence, Natural History, and Survival Comparison With Primary Nodal Counterpart Before and After the Introduction of Rituximab
Authors: Jacob D. Gundrum, Michelle A. Mathiason, Derek B. Moore, Ronald S. Go
Journal: Journal of Clinical Oncology (2009)

Purpose We performed a population-based study of primary testicular diffuse large B-cell lymphoma (DLBCL) in the United States to determine its incidence and survival trends, prognostic factors, and clinical outcome compared with males with nodal DLBCL. Patients and Methods The Surveillance, Epidemiology, and End Results database was reviewed to identify patients diagnosed between 1980 and 2005. To study the potential impact of the introduction of rituximab on survival, we used the year 2000 as cutoff point. Results We identified 769 patients with testicular DLBCL. The median age at diagnosis was 68.0 years. The incidence of DLBCL increased over time, with the highest rate among whites (twice that of blacks). The median overall survival (OS) for the whole group was 4.6 years, whereas the disease-specific survival (DSS) rates at 3, 5, and 15 years were 71.5%, 62.4%, and 43.0%, respectively. Independent predictors of worse DSS were older age, diagnosis before 1986, advanced stage, left testicular involvement, and not having surgery and radiation. The use of radiation did not change significantly over time. When testicular and nodal DLBCL patients were analyzed together, testicular primary was an independent predictor of better OS and DSS. Unlike nodal DLBCL, DSS did not improve in the patients with testicular DLBCL diagnosed after the year 2000. Conclusion The incidence of testicular DLBCL is increasing. Compared with nodal DLBCL, testicular DLBCL patients have a better overall prognosis but are at higher risk of late disease-related deaths. The introduction of rituximab in clinical practice does not seem to improve their early outcome.
Assessment and Management of Hypertension in Patients on Dialysis
Authors: Rajiv Agarwal, Joseph Flynn, Velvie Pogue, Mahboob Rahman, Efrain Reisin, Matthew R. Weir
Journal: Journal of the American Society of Nephrology (2014)

Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD.
Gender Differences in Temporal Lobe Structures of Patients With Schizophrenia: A Volumetric MRI Study
Authors: Nancy L. Bryant, Robert W. Buchanan, Katalin Vladar, Alan Breier, Michael Rothman
Journal: American Journal of Psychiatry (1999)

The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects.Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects.There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions.These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.
Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells
Authors: Jeremy S. Duffield, Kwon Moo Park, Li-Li Hsiao, Vicki R. Kelley, David T. Scadden, Takaharu Ichimura, Joseph V. Bonventre
Journal: Journal of Clinical Investigation (2005)

Ischemia causes kidney tubular cell damage and abnormal renal function. The kidney is capable of morphological restoration of tubules and recovery of function. Recently, it has been suggested that cells repopulating the ischemically injured tubule derive from bone marrow stem cells. We studied kidney repair in chimeric mice expressing GFP or bacterial β-gal or harboring the male Y chromosome exclusively in bone marrow-derived cells. In GFP chimeras, some interstitial cells but not tubular cells expressed GFP after ischemic injury. More than 99% of those GFP interstitial cells were leukocytes. In female mice with male bone marrow, occasional tubular cells (0.06%) appeared to be positive for the Y chromosome, but deconvolution microscopy revealed these to be artifactual. In β-gal chimeras, some tubular cells also appeared to express β-gal as assessed by X-gal staining, but following suppression of endogenous (mammalian) β-gal, no tubular cells could be found that stained with X-gal after ischemic injury. Whereas there was an absence of bone marrow–derived tubular cells, many tubular cells expressed proliferating cell nuclear antigen, which is reflective of a high proliferative rate of endogenous surviving tubular cells. Upon i.v. injection of bone marrow mesenchymal stromal cells, postischemic functional renal impairment was reduced, but there was no evidence of differentiation of these cells into tubular cells of the kidney. Thus, our data indicate that bone marrow–derived cells do not make a significant contribution to the restoration of epithelial integrity after an ischemic insult. It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia.
Chromosome 20q13.2 Gain May Predict Intravesical Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Tumors
Authors: Jumpei Akao, Hideyasu Matsuyama, Yoshiaki Yamamoto, Kohsuke Sasaki, Katsusuke Naito
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Amplification or gain of copy number of chromosome 20q13.2 has been implicated as a causal factor for chromosome instability. We investigated the impact of chromosomal instability and its causative molecular markers, 20q13.2 gain and centrosome amplification, on patient outcome in upper urinary tract transitional cell carcinoma (UUT-TCC). Experimental Design: The number of centrosomes was assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9, and 17 that allowed the estimation of chromosomal instability and 20q13.2 gain were evaluated by fluorescence in situ hybridization in 96 frozen specimens from UUT-TCC and compared with clinicopathologic background and patient outcome. Results: Chromosomal instability, 20q13.2 gain, and centrosome amplification were detected in 62 of 96 (64.6%), 61 of 96 (63.5%), and 45 of 90 (50.0%) tumors, respectively. 20q13.2 Gain was significantly associated with tumor stage (P = 0.042), chromosomal instability (P &amp;lt; 0.0001), and centrosome amplification (P &amp;lt; 0.0001). Kaplan-Meier analysis showed that 20q13.2 gain was strongly associated with intravesical recurrence-free survival in all patients (P = 0.0050), as well as in patients with grade 2 tumors (P = 0.0011, log-rank test). On multivariate analysis, 20q13.2 gain was found to be the sole independent prognostic factor predicting subsequent intravesical recurrence (hazard ratio, 1.65; 95% confidence interval, 1.03–2.90; P = 0.036). Conclusions: 20q13.2 gain was strongly associated with a reduced time to intravesical recurrence in all patients. Our data suggest that 20q13.2 gain may be a predictive marker of intravesical recurrence in patients with UUT-TCC.
Application of Framingham risk estimates to ethnic minorities in United Kingdom and implications for primary prevention of heart disease in general practice: cross sectional population based study
Authors: F. P Cappuccio
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To compare the 10 year risk of coronary heart disease (CHD), stroke, and combined cardiovascular disease (CVD) estimated from the Framingham equations. <b>Design:</b>Population based cross sectional survey. <b>Setting:</b> Nine general practices in south London. <b>Population:</b> 1386 men and women, age 40-59 years, with no history of CVD (475 white people, 447 south Asian people, and 464 people of African origin), and a subgroup of 1069 without known diabetes, left ventricular hypertrophy, peripheral vascular disease, renal impairment, or target organ damage. <b>Main outcome measures:</b> 10 year risk estimates. <b>Results:</b> People of African origin had the lowest 10 year risk estimate of CHD adjusted for age and sex (7.0%, 95% confidence interval 6.5 to 7.5) compared with white people (8.8%, 8.2 to 9.5) and south Asians (9.2%, 8.6 to 9.9) and the highest estimated risk of stroke (1.7% (1.5 to 1.9), 1.4% (1.3 to 1.6), 1.6% (1.5 to 1.8), respectively). The estimate risk of combined CVD, however, was highest in south Asians (12.5%, 11.6 to 13.4) compared with white people (11.9%, 11.0 to 12.7) and people of African origin (10.5%, 9.7 to 11.2). In the subgroup of 1069, the probability that a risk of CHD 15% would identify risk of combined CVD 20% was 91% in white people and 81% in both south Asians and people of African origin. The use of thresholds for risk of CHD of 12% in south Asians and 10% in people of African origin would increase the probability of identifying those at risk to 100% and 97%, respectively. <b>Conclusion:</b> Primary care doctors should use a lower threshold of CHD risk when treating mild uncomplicated hypertension in people of African or south Asian origin.
The Circulatory Effects of Isoproterenol, Acetylstrophanthidin, and Volume Loading in Acute Pericardial Tamponade
Authors: B. Treister, R. E. Gianelly, K. E. Cohn, D. C. Harrison
Journal: Cardiovascular Research (1969)

Journal Article The Circulatory Effects of Isoproterenol, Acetylstrophanthidin, and Volume Loading in Acute Pericardial Tamponade Get access Bernard Treister, Bernard Treister From the Cardiology Division, Stanford University School of Medicine, Palo Alto, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph E. Gianelly, Ralph E. Gianelly From the Cardiology Division, Stanford University School of Medicine, Palo Alto, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Keith E. Cohn, Keith E. Cohn From the Cardiology Division, Stanford University School of Medicine, Palo Alto, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald C. Harrison Donald C. Harrison From the Cardiology Division, Stanford University School of Medicine, Palo Alto, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 3, July 1969, Pages 299–305, https://doi.org/10.1093/cvr/3.3.299 Published: 01 July 1969 Article history Received: 20 August 1968 Published: 01 July 1969
Effects of intracellular acidification on membrane currents in ventricular cells of the guinea pig.
Authors: R Sato, A Noma, Y Kurachi, H Irisawa
Journal: Circulation Research (1985)

The membrane currents of single ventricular cells were measured under whole cell voltage clamp using a giga-sealed patch electrode, and the effects of intracellular acidification were examined by perfusing the electrode pipette with different pH solutions. The plateau of the action potential was shortened when the pH of the pipette solution was lowered from the control of 7.2 to 6, and finally to 5. The pH 6 pipette solution evoked a time-independent outward current at positive potentials and increased the slope conductance near the resting potential. These changes were suppressed by removal of both intra- and extracellular potassium ion, indicating that these currents were carried by potassium ions, but not by protons. Increasing the calcium concentration in the pipette from pCa 8 to pCa 6 induced a time-dependent outward current which had a reversal potential of about -13 mV. This result clearly differed from the changes induced by the acidic pipette solution, suggesting that the calcium-mediated conductance was not involved in the genesis of the acidic effects. The calcium current was not significantly affected by perfusion at pH 6, but was decreased by the more acidic (pH 5) solution. When the calcium current was recorded in sodium- and potassium-free external solution but with a cesium-rich internal solution, however, the calcium current was suppressed even with a weak acidic (pH 6.8) pipette solution. This effect was attributed not to an increased sensitivity of the calcium channel to protons, but to a more extensive intracellular acidification, which might have been caused by a depressed extrusion of proton via a sodium-hydrogen exchange mechanism on the surface membrane.
Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis
Authors: D Franchimont
Journal: Gut (2004)

Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease (CD) and/or ulcerative colitis (UC).Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients (cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios.The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD (cohort 1: 11% v 5%, odds ratio (OR) 2.31 (95% confidence interval (CI) 1.28-4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 (95% CI 1.24-4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 (95% CI 1.07-3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p = 0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately.We have reported on a novel association of the TLR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD.
Binding and ingestion of human lactoferrin by mouse alveolar macrophages.
Authors: B Markowetz, J L Van Snick, P L Masson
Journal: Thorax (1979)

59Fe-labelled human lactoferrin was found to be preferentially ingested by mouse alveolar macrophages (MAM) when compared to 59Fe-labelled human transferrin. The cells bound and ingested 125I-labelled iron-saturated and iron-free lactoferrin. The latter was digested faster (t1/2 = 5.8 hours), however, than the iron-saturated compound (t1/2 = 10.5 hours). The constant elimination of the Fe-lactoferrin complex by alveolar macrophages could enhance the bacteriostatic effect of lactoferrin in the pulmonary secretions.
Inducible nitric oxide and pulmonary infection
Authors: S. SINGH, S J. WORT, T. W EVANS
Journal: Thorax (1999)

Nitric oxide (NO) is an endogenously produced vasodilator which modulates systemic and pulmonary blood flow through the actions of cyclic guanylate monophosphate (cGMP) on vascular smooth muscle.1-4 Non-haemodynamic properties of NO include the modulation of platelet inhibition, neurotransmission, hormone release, and cell growth. Under physiological circumstances the basal production of NO is regulated by constitutive forms of the enzyme NO synthase (cNOS). Under conditions of chemical and mechanical stress increased NO production is detectable, produced primarily via an inducible NOS isoform (iNOS).5 6 

Evidence has accumulated that NO is implicated in the pathogenesis of sepsis and septic shock and may contribute to the development of multiple organ dysfunction. Firstly, iNOS has been isolated from human neutrophils in urinary sepsis7 and from alveolar macrophages in sepsis induced acute lung injury (ALI).8Secondly, NO is known to influence the inflammatory response through actions on both innate and adaptive immune systems.9Thirdly, non-specific cNOS and iNOS inhibition using novel pharmacological …