tbuckley/cabot-search huggingface dataset:
Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.
Authors: P Ping, R Gelzer-Bell, D A Roth, D Kiel, P A Insel, H K Hammond
Journal: Journal of Clinical Investigation (1995)

To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling associated with chronic reduction in beta-adrenergic receptor agonist activation were found. First, there was coordinate downregulation of Gi alpha 2 and Gs alpha mRNA and protein expression in the left ventricle; reduced G-protein content was also found in the right atrium. Second, in the left ventricle, there was a twofold increase in beta-adrenergic receptor-dependent stimulation of adenylyl cyclase and a persistent high affinity state of the beta-adrenergic receptor. Finally, there was a reduction in left ventricular beta-adrenergic receptor kinase activity, suggesting a previously unrecognized association between the degree of adrenergic activation and myocardial beta-adrenergic receptor kinase expression. The heart appears to adapt in response to chronic beta-adrenergic receptor antagonist administration in a manner that would be expected to offset reduced agonist stimulation. The mechanisms for achieving this extend beyond beta-adrenergic receptor upregulation and include alterations in G-protein expression, beta-adrenergic receptor-Gs interaction, and myocardial beta-adrenergic receptor kinase activity.
Systemic Lupus Erythematosus: A Report on Twelve Cases Treated with Quinacrine (Atabrine(R))
Authors: S. K. Conner
Journal: Annals of the Rheumatic Diseases (1957)

and it has in fact been condemned by some authors because it is thought to aggravate the systemic manifestations.Whether this impression is true or false remains to be proved by a larger number of these cases adequately treated with Atabrine.The present series would indicate that its value is as great and possibly even greater in systemic lupus erythematosus than in the chronic form.Systemic lupus erythematosus is well known to be equal to syphilis as the great imitator; its varied symptoms may wax and wane, or progress rapidly,
Inhibition of airway proteases in cystic fibrosis lung disease
Authors: M. Griese, M. Kappler, A. Gaggar, D. Hartl
Journal: European Respiratory Journal (2008)

Progressive lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients. CF lung disease is characterised by endobronchial inflammation sustained by bacterial infections and an ongoing accumulation of airway neutrophils. Activated or necrotic neutrophils liberate proteases that cause damage to structural, cellular and soluble components of the pulmonary microenvironment. Among various proteases released by airway cells, elastase is considered to play the major role in CF lung disease. Based on this concept, several therapeutic approaches have been developed to inhibit free elastolytic activity, including small synthetic chemical compounds, semi-synthetic inhibitors and natural inhibitors of free elastase. The present review summarises and discusses the pathophysiological rationales, methodological requirements and clinical implications of inhibition of airway proteases in cystic fibrosis lung disease.
SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis
Authors: Ehud Ohana, Nikolay Shcheynikov, Orson W. Moe, Shmuel Muallem
Journal: Journal of the American Society of Nephrology (2013)

The combination of hyperoxaluria and hypocitraturia can trigger Ca2+-oxalate stone formation, even in the absence of hypercalciuria, but the molecular mechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wild-type mice, Slc26a6-null mice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. These findings reveal a molecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca2+-oxalate stone formation.
Neuropeptide Y as a putative modulator of the vagal effects on heart rate.
Authors: M R Warner, M N Levy
Journal: Circulation Research (1989)

Neuropeptide Y is stored in sympathetic nerve terminals throughout the heart and has direct and indirect effects on cardiac function. Although neuropeptide Y has been shown to be released upon intense (16-30 Hz) cardiac sympathetic stimulation, we sought to determine whether effective quantities of neuropeptide Y were released from cardiac sympathetic neurons under more natural conditions. We recorded arterial pressure and cardiac cycle length in 29 anesthetized dogs. We assessed neuropeptide Y release by measuring the attenuation of vagally induced increases in cardiac cycle length (10 seconds every 2 minutes) after trains of sympathetic stimulation. We examined the effect of constant-frequency sympathetic stimulation (frequencies of 2, 5, 10, and 15 Hz, applied for train durations of 1, 3, and 5 minutes) on vagally induced chronotropic responses. We also determined the effect of varying the pattern of sympathetic stimulation. Both the magnitude and duration of the inhibition of the vagal effects on cardiac cycle length were augmented significantly by increases in the frequency or duration of sympathetic stimulation. In contrast, the inhibition of the vagally induced chronotropic responses was not significantly affected by changes in the pattern of sympathetic stimulation. We also characterized the role of adrenergic receptors. Phentolamine significantly increased the sympathetically mediated inhibition of the vagal effects on cardiac cycle length, but propranolol had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Overexpression of <i>Cytochrome P450 1A1</i> and Its Novel Spliced Variant in Ovarian Cancer Cells: Alternative Subcellular Enzyme Compartmentation May Contribute to Carcinogenesis
Authors: Yuet-Kin Leung, Kin-Mang Lau, James Mobley, Zhong Jiang, Shuk-Mei Ho
Journal: Cancer Research (2005)

Abstract Epithelial ovarian cancer derived from the human ovarian surface epithelium (HOSE) is the leading cause of death from gynecologic malignancies among American women. Metabolic activation of endogenous and exogenous chemicals by cytochrome P450 (CYP) class I enzymes has been implicated in its etiology. In this study, we showed overexpression of CYP1A1 mRNA, but not CYP1B1 transcripts, in ovarian cancer cell lines when compared with primary cultures or immortalized HOSE cell lines. Importantly, we identified a novel, enzymatically active, spliced variant of CYP1A1 (CYP1A1v) formed by excision of an 84-bp cryptic intron in exon 2. CYP1A1v is overexpressed in ovarian cancer cell lines and exhibits a unique subcellular distribution restricted to the nucleus and mitochondria, contrary to the endoplasmic reticulum localization of the wild-type enzyme. In concordance, total CYP1A1 activity, as measured by the ethoxyresorufin O-deethylase assay, was detected in mitochondrial, nuclear, and microsomal fractions of ovarian cancer cells but was notably absent in all subcellular fractions of HOSE cells. Immunocytochemistry studies in 30 clinical specimens revealed overexpression of CYP1A1 in various types of ovarian cancers compared with benign epithelia and frequent localization of the enzyme to cancer cell nuclei. Forced expression of CYP1A1wt or CYP1A1v in HOSE cells resulted in nuclear localization of the enzyme and acquisition of anchorage-independent growth, which was further exacerbated following exposure to benzo(a)pyrene or 17β-estradiol. Collectively, these data provided the first evidence that CYP1A1 overexpression and alternative splicing could contribute to ovarian cancer initiation and progression.
Mechanism of suppression of renin secretion by clonidine in the dog.
Authors: P L Nolan, I A Reid
Journal: Circulation Research (1978)

The mechanism by which clonidine suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which renal perfusion pressure was controlled by means of an aortic clamp. Clonidine (30 microgram/kg, iv) lowered mean arterial pressure (MAP) from 124 +/- 8 to 104 +/- 4 mm Hg (P less than 0.01) and reduced plasma renin activity (PRA) to 32 +/- 4 percent of the control value (P less than 0.01) after 60 minutes. Ganglion blockade with pentolinium (3 mg/kg, im) decreased MAP from 148+/- 7 to 117 +/- 3 mm Hg (P less than 0.01) and reduced PRA to 55 +/- 13 percent of the control value (P less than 0.05) after 45 minutes. Pentolinium converted the hypotension produced by clonidine to hypertension (108 +/- 9 to 146 +/- 10 mm Hg at 60 minutes, P less than 0.05) and abolished the suppression of PRA (105 +/- 14 percent of control at 60 minutes, P less than 0.05). In a further series of experiments, the effects of oxymetazoline, an alpha-adrenergic receptor agonist which is closely related to clonidine but which does not cross the blood brain barrier, were studied. Oxymetazoline (10 microgram/kg, iv) increased MAP from 127 +/- 3 to 154 +/- 2 mm Hg (P less than 0.01) and elevated PRA TO 176 +/- 22 percent of the control value (P less than 0.02) after 30 minutes. A higher dose of oxymetazoline (30 microgram/kg) increased MAP from 129 +/- 10 to 161 +/- 9 mm Hg (P less than 0.05) and increased PRA to 256+/- 37 percent of control (P less than 0.05) after 30 minutes. Taken together, these data support the hypothesis that the inhibition of renin secretion by clonidine results from a centrally mediated decrease in sympathetic neural activity.
Airway responses to hypertonic saline, exercise and histamine challenges in bronchial asthma
Authors: NG Belcher, TH Lee, PJ Rees
Journal: European Respiratory Journal (1989)

The airway responses to histamine, exercise and ultrasonically nebulized hypertonic saline have been compared in ten asthmatic patients. The responses to hypertonic saline were not significantly different when the same volume of aerosol was given in a single dose or in 10 l aliquots, suggesting that the challenge is cumulative. The variability of the response to hypertonic saline challenge was not significantly different from that of exercise challenge. Response to hypertonic saline correlated significantly with exercise (r = 0.68, p less than 0.05) and with histamine response (r = 0.74, p less than 0.02), but the correlation between exercise and histamine was not statistically significant (r = 0.15, p greater than 0.1). These findings suggest that exercise-induced asthma has a closer relationship to bronchial responsiveness to hypertonic saline aerosol than it does to non-specific reactivity demonstrated by histamine challenge.
Classification of Choroidal Neovascularization by Digital Indocyanine Green Videoangiography
Authors: David R. Guyer, Lawrence A. Yannuzzi, Jason S. Slakter, John A. Sorenson, Prut Hanutsaha, Richard F. Spaide, Stephen G. Schwartz, James M. Hirschfeld, Dennis A. Orlock
Journal: Ophthalmology (1996)
Androgen-Induced Wnt Signaling in Preosteoblasts Promotes the Growth of MDA-PCa-2b Human Prostate Cancer Cells
Authors: Xin-Hua Liu, Alexander Kirschenbaum, Shen Yao, Guizhong Liu, Stuart A. Aaronson, Alice C. Levine
Journal: Cancer Research (2007)

Abstract The high morbidity and mortality associated with prostate cancer (PCa) result from its tendency to metastasize to bone where it produces predominantly osteoblastic lesions. The Wnt signaling pathway plays an important role in embryogenesis, tumorigenesis, osteoblast development, and bone formation. Androgen signaling via the androgen receptor (AR) is critical in both PCa and bone cell growth. We examined the effects of androgens on cell growth and Wnt signaling in the AR-positive MDA-PCa-2b cell line and MC3T3 preosteoblasts, grown alone and in coculture. We show that the potent androgen dihydrotestosterone increases AR expression and transcriptional activity only in the preosteoblasts. Although dihydrotestosterone induced an 80% increase in PCa cell growth when the cells were grown alone, dihydrotestosterone had a more significant effect on MDA-PCa-2b cell proliferation (3.2-fold increase) when the PCa cells were cocultured with preosteoblasts. Dihydrotestosterone addition to preosteoblasts promoted Wnt-dependent transcriptional reporter activity associated with GSK3βS-9 phosphorylation and accumulation of nuclear β-catenin as well as elevated Runx2 expression. In addition, the increased proliferation of PCa cells in coculture with MC3T3 cells in response to dihydrotestosterone was abrogated by the addition of either exogenous DKK-1 or sFRP-1 protein, two naturally occurring Wnt antagonists. Finally, we show that the paracrine growth-promoting effect of androgens is limited to MDA-PCa-2b cells. These data imply that Wnt signaling is involved in the androgen-regulated crosstalk between preosteoblasts and PCa cells and suggest that androgens may stimulate growth of some prostate tumor cells indirectly, via up-regulation of Wnt signaling in bone cells. [Cancer Res 2007;67(12):5747–53]
Multifaceted functional specialization of somatosensory information processing
Authors: K. Sathian, Simon Lacey, Gregory Gibson, Randall Stilla
Journal: Behavioral and Brain Sciences (2007)

Abstract We review evidence for multifaceted functional specialization of somatosensory information processing, both within and outside classical somatosensory cortex. We argue that the nature of such specialization has not yet been clarified adequately to regard the proposed action/perception dichotomy as being established. However, we believe this is a good working hypothesis that can motivate further work.
Disease‐specific health status as a predictor of mortality in patients with heart failure: a systematic literature review and meta‐analysis of prospective cohort studies
Authors: Mirjam H. Mastenbroek, Henneke Versteeg, Wobbe P. Zijlstra, Mathias Meine, John A. Spertus, Susanne S. Pedersen
Journal: European Journal of Heart Failure (2014)
Long-term <i>XPC</i> Silencing Reduces DNA Double-Strand Break Repair
Authors: Emmanuelle Despras, Petra Pfeiffer, Bernard Salles, Patrick Calsou, Steffi Kuhfittig-Kulle, Jaime F. Angulo, Denis S.F. Biard
Journal: Cancer Research (2007)

Abstract To study the relationships between different DNA repair pathways, we established a set of clones in which one specific DNA repair gene was silenced using long-term RNA interference in HeLa cell line. We focus here on genes involved in either nucleotide excision repair (XPA and XPC) or nonhomologous end joining (NHEJ; DNA-PKcs and XRCC4). As expected, XPAKD (knock down) and XPCKD cells were highly sensitive to UVC. DNA-PKcsKD and XRCC4KD cells presented an increased sensitivity to various inducers of double-strand breaks (DSBs) and a 70% to 80% reduction of in vitro NHEJ activity. Long-term silencing of XPC gene expression led to an increased sensitivity to etoposide, a topoisomerase II inhibitor that creates DSBs through the progression of DNA replication forks. XPCKD cells also showed intolerance toward acute γ-ray irradiation. We showed that XPCKD cells exhibited an altered spectrum of NHEJ products with decreased levels of intramolecular joined products. Moreover, in both XPCKD and DNA-PKcsKD cells, XRCC4 and ligase IV proteins were mobilized on damaged nuclear structures at lower doses of DSB inducer. In XPC-proficient cells, XPC protein was released from nuclear structures after induction of DSBs. By contrast, silencing of XPA gene expression did not have any effect on sensitivity to DSB or NHEJ. Our results suggest that XPC deficiency, certainly in combination with other genetic defects, may contribute to impair DSB repair. [Cancer Res 2007;67(6):2526–34]
Psychiatric Study of Homicide
Authors: EMANUEL TANAY
Journal: American Journal of Psychiatry (1969)

In evaluating 53 perpetrators of homicide, the author noted that a history of violent child-rearing, a severe superego, and an altered state of consciousness just prior to the act of homicide were marked characteristics of a majority of these individuals. He postulates three categories of homicide, based upon the immediate psychological state of the perpetrator: dissociative, psychotic, and ego-syntonic.
The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory
Authors: Keisuke Yoshida, Toshio Maekawa, Yujuan Zhu, Claire Renard-Guillet, Bruno Chatton, Kentaro Inoue, Takeru Uchiyama, Ken-ichi Ishibashi, Takuji Yamada, Naohito Ohno, Katsuhiko Shirahige, Mariko Okada-Hatakeyama, Shunsuke Ishii
Journal: Nature Immunology (2015)
The Regulation and Expression of <i>c-myc</i> in Normal and Malignant Cells
Authors: K Kelly, U Siebenlist
Journal: Annual Review of Immunology (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
A Phosphorus-Based Dendrimer Targets Inflammation and Osteoclastogenesis in Experimental Arthritis
Authors: Myriam Hayder, Mary Poupot, Michel Baron, Delphine Nigon, Cédric-Olivier Turrin, Anne-Marie Caminade, Jean-Pierre Majoral, Robert A. Eisenberg, Jean-Jacques Fournié, Alain Cantagrel, Rémy Poupot, Jean-Luc Davignon
Journal: Science Translational Medicine (2011)

Dendrimers are highly branched "tree-like" polymers that have demonstrated therapeutic potential in drug delivery, medical imaging, and tissue engineering in recent years. In addition, we have shown that an azabisphosphonate (ABP)-capped dendrimer selectively targets monocytes and directs them toward anti-inflammatory activation. We explored this property to assess the therapeutic potential of dendrimer ABP in the treatment of an inflammatory disease, rheumatoid arthritis. Intravenous injections of dendrimer ABP inhibited the development of inflammatory arthritis in two animal models: IL-1ra(-/-) mice and mice undergoing K/BxN serum transfer. Suppression of disease was characterized by normal synovial membranes, reduced levels of inflammatory cytokines, and the absence of cartilage destruction and bone erosion. Dendrimer ABP also exhibited anti-osteoclastic activity on mouse and human cells, mediated by c-FMS (cellular-feline McDonough strain sarcoma virus oncogene homolog) inhibition. These preclinical demonstrations suggest the potential use of dendrimer ABP as a nanotherapeutic for rheumatoid arthritis.
Hypoxia and estrogen are functionally equivalent in breast cancer-endothelial cell interdependence
Authors: Andrea L George, Shilpi Rajoria, Robert Suriano, Abraham Mittleman, Raj K Tiwari
Journal: Molecular Cancer (2012)

Abstract Background Rapid breast tumor development relies on formation of new vasculature to supply the growing malignancy with oxygenated blood. Previously we found that estrogen aided in this neovasculogenesis via recruitment of bone marrow derived endothelial progenitor cells (BM-EPCs), leading to increased vessel formation and vascular endothelial growth factor (VEGF) production in vivo . However, the cellular mechanism of this induction and the signaling pathways involved need elucidation. Results Using the murine mammary cell line TG1-1 we observed estrogen (E 2 ) lead to an up regulation of hypoxia inducible factor-1 (HIF-1), an effect abrogated by the anti-estrogen Fulvestrant and the HIF-1 inhibitor YC-1 (3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole) suggesting the interchangeability of hypoxia and estrogen mediated effects. Estrogen modulation of HIF-1 and subsequent effects on endothelial cells is dependent on the Akt/PI3K pathway and protein synthesis as validated by the use of the inhibitors wortmannin and cycloheximide which abrogated estrogen’s effects respectively. Estrogen treated TG1-1 cells secreted higher levels of VEGF which were comparable to secreted levels from cells grown under hypoxic conditions. Soluble factors in conditioned media from E 2 treated breast cancer cells also lead to migration and tube formation of human umbilical vein endothelial cells (HUVEC) in vitro . Conclusions Our data provide evidence that estrogen signaling mediates the tumor vasculogenic process required for breast cancer progression and involves a key regulator of the hypoxia signaling pathway. Further, hypoxia and estrogen are interchangeable as both similarly modulate epithelial-endothelial cell interaction.
HOW THE BRAIN PROCESSES SOCIAL INFORMATION: Searching for the Social Brain
Authors: Thomas R. Insel, Russell D. Fernald
Journal: Annual Review of Neuroscience (2004)

▪ Abstract Because information about gender, kin, and social status are essential for reproduction and survival, it seems likely that specialized neural mechanisms have evolved to process social information. This review describes recent studies of four aspects of social information processing: (a) perception of social signals via the vomeronasal system, (b) formation of social memory via long-term filial imprinting and short-term recognition, (c) motivation for parental behavior and pair bonding, and (d) the neural consequences of social experience. Results from these studies and some recent functional imaging studies in human subjects begin to define the circuitry of a “social brain.” Such neurodevelopmental disorders as autism and schizophrenia are characterized by abnormal social cognition and corresponding deficits in social behavior; thus social neuroscience offers an important opportunity for translational research with an impact on public health.
Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks
Authors: Deepali Malhotra, Anne L Fletcher, Jillian Astarita, Veronika Lukacs-Kornek, Prakriti Tayalia, Santiago F Gonzalez, Kutlu G Elpek, Sook Kyung Chang, Konstantin Knoblich, Martin E Hemler, Michael B Brenner, Michael C Carroll, David J Mooney, Shannon J Turley
Journal: Nature Immunology (2012)