tbuckley/cabot-search huggingface dataset:
Role of Ca <sup>2+</sup> -Independent Phospholipase A <sub>2</sub> and Store-Operated Pathway in Urocortin-Induced Vasodilatation of Rat Coronary Artery
Authors: Tarik Smani, Alejandro Domínguez-Rodríguez, Abdelkrim Hmadcha, Eva Calderón-Sánchez, Angélica Horrillo-Ledesma, Antonio Ordóñez
Journal: Circulation Research (2007)

Urocortin has been shown to produce vasodilatation in several arteries, but the precise mechanism of its action is still poorly understood. Here we demonstrate the role of store operated Ca2+ entry (SOCE) regulated by Ca2+-independent phospholipase A2 (iPLA2) in phenylephrine hydrochloride (PE)-induced vasoconstriction, and we present the first evidence that urocortin induces relaxation by the modulation of SOCE and iPLA2 in rat coronary artery. Urocortin produces an endothelium independent relaxation, and its effect is concentration-dependent (IC50 approximately = 4.5 nmol/L). We show in coronary smooth muscle cells (SMCs) that urocortin inhibits iPLA2 activation, a crucial step for SOC channel activation, and prevents Ca2+ influx evoked by the emptying of the stores via a cAMP and protein kinase A (PKA)-dependent mechanism. Lysophophatidylcholine and lysophosphatidylinositol, products of iPLA2, exactly mimic the effect of the depletion of the stores in presence of urocortin. Furthermore, we report that long treatment with urocortin downregulates iPLA2 mRNA and proteins expression in rat coronary smooth muscle cells. In summary, we propose a new mechanism of vasodilatation by urocortin which involves the regulation of iPLA2 and SOCE via the stimulation of a cAMP/PKA-dependent signal transduction cascade in rat coronary artery.
LINKAGE OF SUSCEPTIBILITY TO EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS TO THE MAJOR HISTOCOMPATIBILITY LOCUS IN THE RAT
Authors: R. Michael Williams, Michael J. Moore
Journal: The Journal of Experimental Medicine (1973)

Experimental allergic encephalomyelitis (EAE) was induced in rats of various genotypes by injection of 10 microg guinea pig basic protein in complete Freund's adjuvant containing 100 microg H(37) RV M. tuberculosis. Histologically verified EAE was present in 20/20 Lewis, 17/17 (Lewis x BN)F(1), 9/9 Lewis backcross, and 21/42 BN backcross rats. Among the BN backcross animals, 25/42 were determined to carry the major histocompatibility type characteristic of the Lewis strain and 21 of these had EAE. Separate groups of Lewis, BN, and (Lewis x BN)F(1) rats were immunized as described and skin tested on day 13 with 10 microg guinea pig basic protein and rat S basic protein. Animals of each genotype had Arthus and delayed skin reactivity to both antigens. These data are compatible with the hypothesis that susceptibility to EAE in rats is controlled by an autosomal dominant gene linked to the major histocompatibility locus. It is proposed that this is an immune response gene, designated Ir-EAE, which controls T cell reactivity directed against a highly encephalitogenic portion of the basic protein molecule.
A naturally occurring bone marrow-chimeric primate. II. Environment dictates restriction on cytolytic T lymphocyte-target cell interactions.
Authors: J Picus, K Holley, W R Aldrich, J D Griffin, N L Letvin
Journal: The Journal of Experimental Medicine (1985)

Restriction on cytolytic T lymphocyte (CTL)-target cell-interactions are studied in the primate S. oedipus, a naturally occurring A + B----A bone marrow-chimeric species. We show that the T cell, B cell, and myelomonocytic progenitor cell populations are chimeric in this species. We selected animals for study that are populated by fully major histocompatibility complex (MHC)-disparate hematopoietic cell populations, using a functional assay system. We then developed an in vitro system for analyzing at the clonal level the genetic restrictions on the trinitrophenyl-specific CTL-target cell interactions of this species. In this system, we have shown that tolerance to foreign MHC determinants was not, of itself, sufficient to facilitate the generation of CTL specific for target cells expressing those foreign MHC determinants. Rather, a marked preference for the expansion of CTL clones with a restriction for target cells bearing the host animals' MHC determinants was seen. Hematopoietically derived cells did not affect the repertoire of these T lymphocytes. These studies represent the first demonstration of the phenomenon of an environment dictating interactional restrictions on CTL in a naturally occurring bone marrow-chimeric animal. This is also the first demonstration of the profound influence of the environment on the repertoire of the T lymphocyte in a primate species.
Gamete competence assessment by polarizing optics in assisted reproduction
Authors: Markus Montag, Maria Köster, Katrin van der Ven, Hans van der Ven
Journal: Human Reproduction Update (2011)

The purpose of this study was first to give an overview of the historical development of polarization microscopy, second to describe the various applications of this technique in assisted reproduction techniques (ART) and third to discuss the potential benefit of polarization microscopy as a predictor for IVF success. The history of polarization microscopy was undertaken by performing a backward search in the scientific literature using Google and internet sites of several Societies for Microscopy and Cell Biology. Studies of polarization microscopy in ART were identified by using a systematic literature search in PubMed and Scopus. A total of 62 articles were identified by the direct search and further relevant articles were found by screening the cited literature in these articles. The topics relevant for assisted reproduction were spindle and zona imaging in combination with IVF success, meiotic cell cycle progression, pharmaceutical studies and cryopreservation. A separate topic was the use of sperm birefringence in ART. The majority of studies are observational studies and were not performed in a randomized manner and there is no direct comparison of techniques using other gamete selection markers. Despite this, most studies show that polarization microscopy may help us to further increase our knowledge on gametes and meiosis. Whether certain applications such as spindle or zona imaging may lead to an increase in IVF success is unclear at present. Publications on the use of polarization microscopy on sperm are still very limited.
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation
Authors: Saïd Bendahhou, Theodore R. Cummins, Angelika F. Hahn, Sylvie Langlois, Stephen G. Waxman, Louis J. Ptácek
Journal: Journal of Clinical Investigation (2000)

Hyperkalemic periodic paralysis (HyperKPP) is an autosomal dominant skeletal muscle disorder caused by single mutations in the SCN4A gene, encoding the human skeletal muscle voltage-gated Na+ channel. We have now identified one allele with two novel mutations occurring simultaneously in the SCN4A gene. These mutations are found in two distinct families that had symptoms of periodic paralysis and malignant hyperthermia susceptibility. The two nucleotide transitions predict phenylalanine 1490→leucine and methionine 1493→isoleucine changes located in the transmembrane segment S5 in the fourth repeat of the α-subunit Na+ channel. Surprisingly, this mutation did not affect fast inactivation parameters. The only defect produced by the double mutant (F1490L-M1493I, expressed in human embryonic kidney 293 cells) is an enhancement of slow inactivation, a unique behavior not seen in the 24 other disease-causing mutations. The behavior observed in these mutant channels demonstrates that manifestation of HyperKPP does not necessarily require disruption of slow inactivation. Our findings may also shed light on the molecular determinants and mechanism of Na+ channel slow inactivation and help clarify the relationship between Na+ channel defects and the long-term paralytic attacks experienced by patients with HyperKPP.
Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants
Authors: Erik A. Jensen, Sara B. DeMauro, Michael Kornhauser, Zubair H. Aghai, Jay S. Greenspan, Kevin C. Dysart
Journal: JAMA Pediatrics (2015)

Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population.To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation.We performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who were receiving mechanical ventilation. Analysis was conducted between November 2014 and February 2015. Data were obtained from the Alere Neonatal Database.The primary study exposures were the cumulative duration of mechanical ventilation and the number of ventilation courses.The primary outcome was bronchopulmonary dysplasia (BPD) among survivors. Secondary outcomes were death, use of supplemental oxygen at discharge, and tracheostomy.We identified 3343 ELBW infants, of whom 2867 (85.8%) survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%) underwent tracheostomy. Exposure to a greater number of mechanical ventilation courses was associated with a progressive increase in the risk of BPD and use of supplemental oxygen at discharge. Compared with a single ventilation course, the adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more courses. After adjustment for the cumulative duration of mechanical ventilation, the odds of BPD were only increased among infants exposed to 4 or more ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of ventilation courses was not associated with increased risk of supplemental oxygen use at discharge after adjustment for the length of ventilation. A greater number of ventilation courses did not increase the risk of tracheostomy.Among ELBW infants, a longer cumulative duration of mechanical ventilation largely accounts for the increased risk of chronic respiratory morbidity associated with reinitiation of mechanical ventilation. These results support attempts of extubation in ELBW infants receiving mechanical ventilation on low ventilator settings, even when success is not guaranteed.
Prognostic significance of precordial ST segment depression on admission electrocardiogram in patients with inferior wall myocardial infarction
Authors: Yochai Birnbaum, Izhak Herz, Samuel Sclarovsky, Bruria Zlotikamien, Angela Chetrit, Liraz Olmer, Gabriel I. Barbash
Journal: Journal of the American College of Cardiology (1996)
Hospital Infections: Gynecologic, Obstetric, and Perinatal Infections
Authors: WILLIAM J. LEDGER
Journal: Annals of Internal Medicine (1978)

Increased perinatal use of invasive monitoring techniques and a higher rate of cesarean section have led to an increase in the rate of maternal infection and to new types of infections in newborns. Control measures for maternal infections include antibiotic prophylaxis, direct administration of antibiotics to the amniotic fluid, extraperitoneal cesarean section, and cesarean hysterectomy. New types of infections in newborns include abscess resulting from use of electrodes to monitor fetal heart rate and the development of group B beta hemolytic streptococci infection, particularly in association with prolonged rupture of maternal membranes. Prospective studies are needed of preventive measures and proper management of maternal and perinatal infections. Obstetric and gynecologic problems that need further investigation include pelvic infection after vaginal hysterectomy, salpingo-oophoritis, and antibiotic dosages for pregnant women.
The pathogenesis of lung injury following pulmonary resection
Authors: S. Jordan, J.A. Mitchell, G.J. Quinlan, P. Goldstraw, T.W. Evans
Journal: European Respiratory Journal (2000)

Postpneumonectomy pulmonary oedema (PPO) develops in approximately 5% of patients undergoing pneumonectomy or lobectomy, and has a high associated mortality (&gt;50%). In its extreme form, PPO follows a clinical and histopathological course indistinguishable from acute respiratory distress syndrome. Perioperative fluid overload, impaired lymphatic drainage following node dissection and trauma caused by surgical manipulation have been implicated in the pathogenesis of PPO. However, PPO more probably represents the pulmonary manifestation of a panendothelial injury consequent upon inflammatory processes induced by the surgical procedure, which involves collapse and re-expansion of the operative lung to permit hilar dissection and pulmonary resection. High inspired oxygen concentrations are required to overcome the effects of shunt. Animal studies have shown that pulmonary ischaemia/reperfusion can result in oedema formation, possibly due to the generation of pro-oxidant forces. Moreover, plasma taken from patients undergoing lobectomy or pneumonectomy (but not lesser resections) shows evidence of oxidative damage. Such evidence suggests either that the high inspired oxygen concentrations associated with one-lung ventilation, or ischaemia/reperfusion injury, may modulate post-pneumonectomy pulmonary oedema. Mechanisms by which redox imbalance may result in tissue damage and postpneumonectomy pulmonary oedema are discussed.
Dermatomyositis with Carcinoma relieved by Hypophysectomy.
Authors: Roderick Howell
Journal: British Journal of Dermatology (1965)

Journal Article Dermatomyositis with Carcinoma relieved by Hypophysectomy. Get access Roderick Howell Roderick Howell Swansea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 3, 1 March 1965, Page 163, https://doi.org/10.1111/j.1365-2133.1965.tb14623.x Published: 01 March 1965
Identification and Biological Evaluation of a Novel and Potent Small Molecule Radiation Sensitizer via an Unbiased Screen of a Chemical Library
Authors: Brian E. Lally, Geoffrey A. Geiger, Steven Kridel, Alice E. Arcury-Quandt, Michael E. Robbins, Nancy D. Kock, Kenneth Wheeler, Prakash Peddi, Alexandros Georgakilas, Gary D. Kao, Constantinos Koumenis
Journal: Cancer Research (2007)

Abstract For patients with solid tumors, the tolerance of surrounding tissues often limits the dose of radiation that can be delivered. Thus, agents that preferentially increase the cytotoxic effects of radiation toward tumor cells would significantly alter the therapeutic ratio and improve patient survival. Using a high-throughput, unbiased screening approach, we have identified 4′-bromo-3′-nitropropiophenone (NS-123) as a radiosensitizer of human glioma cells in vitro and in vivo. NS-123 radiosensitized U251 glioma cells in a dose-dependent and time-dependent manner, with dose enhancement ratios ranging from 1.3 to 2.0. HT-29 colorectal carcinoma and A549 lung adenocarcinoma cells were also radiosensitized by NS-123 in vitro, whereas NS-123 did not increase the radiation sensitivity of normal human astrocytes or developmental abnormalities or lethality of irradiated Zebrafish embryos. In a novel xenograft model of U251 cells implanted into Zebrafish embryos, NS-123 enhanced the tumor growth-inhibitory effects of ionizing radiation (IR) with no apparent effect on embryo development. Similar results were obtained using a mouse tumor xenograft model in which NS-123 sensitized U251 tumors to IR while exhibiting no overt toxicity. In vitro pretreatment with NS-123 resulted in accumulation of unrepaired IR-induced DNA strand breaks and prolonged phosphorylation of the surrogate markers of DNA damage H2AX, ataxia telangiectasia mutated protein, DNA-dependent protein kinase, and CHK2 after IR, suggesting that NS-123 inhibits a critical step in the DNA repair pathway. These results show the potential of this cell-based, high-throughput screening method to identify novel radiosensitizers and suggest that NS-123 and similar nitrophenol compounds may be effective in antiglioma modalities. [Cancer Res 2007;67(18):8791–9]
PDZ-Binding and Di-Hydrophobic Motifs Regulate Distribution of Kir4.1 Channels in Renal Cells
Authors: Masayuki Tanemoto, Takaaki Abe, Sadayoshi Ito
Journal: Journal of the American Society of Nephrology (2005)

It was shown previously that the carboxyl-terminal cytoplasmic portion of Kir4.1 determines the localization of basolateral K<sup>+</sup> channel in renal distal tubules, which is composed from the assembly of Kir4.1 and Kir5.1. For clarifying the signals for this localization, specific sequence motifs of Kir4.1 were sought. In HEK293T cells, where Kir4.1 showed linear expression on the cell surface, disruption of the carboxyl-terminal PDZ-binding motif induced mostly clustered distribution but did not reduce whole-cell channel activity. Point mutation analysis revealed that serine<sup>377</sup> in this motif was responsible for the surface vicinity expression. Disruption of the di-hydrophobic array of valine<sup>333</sup>/valine<sup>334</sup> induced diffuse cytoplasmic distribution and diminished channel activity. Both valine<sup>333</sup> and valine<sup>334</sup> contributed to this effect. In contrast to the di-hydrophobic motifs of other membrane proteins that facilitate the sorting, valine<sup>333</sup>/valine<sup>334</sup> supported the cell-surface retention. Because both the PDZ-binding and di-hydrophobic motifs participated in the basolateral expression of both Kir4.1 homomer and Kir5.1/Kir4.1 heteromer in MDCK cells, they are thought to be responsible for the localization of basolateral K<sup>+</sup> channel in renal distal tubules.
RETRACTED: Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial
Authors: Halük Demiroglu, Osman I Özcebe, Ibrahim Barista, Semra Dündar, Bora Eldem
Journal: The Lancet (2000)
Effects of Salt Supplementation on the Albuminuric Response to Telmisartan With or Without Hydrochlorothiazide Therapy in Hypertensive Patients With Type 2 Diabetes Are Modulated by Habitual Dietary Salt Intake
Authors: Elif I. Ekinci, Georgina Thomas, David Thomas, Cameron Johnson, Richard J. MacIsaac, Christine A. Houlihan, Sue Finch, Sianna Panagiotopoulos, Chris O'Callaghan, George Jerums
Journal: Diabetes Care (2009)

OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; &amp;lt;100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; &amp;gt;200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response.
Blunted Counterregulatory Hormone Responses to Hypoglycemia in Young Children and Adolescents With Well-Controlled Type 1 Diabetes
Authors: Alex J. Graveling, Roderick E. Warren, Brian M. Frier
Journal: Diabetes Care (2010)

In adults with insulin-treated diabetes, hypoglycemia-associated autonomic failure (HAAF) is described as a syndrome that includes counterregulatory hormonal deficiencies and impaired symptomatic awareness in response to severe hypoglycemia (1). It is thought to result from failure of the central autonomic response to acute neuroglycopenia and is associated with recurrent exposure to hypoglycemia and increasing duration of diabetes. It is not known whether this syndrome occurs in children with type 1 diabetes, but the Diabetes Research in Children Network (DirecNet) Study Group has claimed that HAAF was present in at least a third of their participants with type 1 diabetes (2). Examination of the study design and methodology raises …
c-Jun NH2-Terminal Kinase-Mediated Up-regulation of Death Receptor 5 Contributes to Induction of Apoptosis by the Novel Synthetic Triterpenoid Methyl-2-Cyano-3,12-Dioxooleana-1, 9-Dien-28-Oate in Human Lung Cancer Cells
Authors: Wei Zou, Xiangguo Liu, Ping Yue, Zhongmei Zhou, Michael B. Sporn, Reuben Lotan, Fadlo R. Khuri, Shi-Yong Sun
Journal: Cancer Research (2004)

Abstract Death receptor (DR) 4 or 5, on binding to its ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), triggers apoptosis via activating the caspase-8–mediated caspase cascade. Certain anticancer drugs up-regulate the expression of these receptors and thereby induce apoptosis or enhance TRAIL-induced apoptosis. In this study, we explored the ability of methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) to activate the extrinsic DR-mediated apoptotic pathway in human lung cancer cells. We found that CDDO-Me not only activated caspase-8 but also induced expression of DRs, particularly DR5, in a p53-independent mechanism. Correspondingly, CDDO-Me augmented TRAIL-induced apoptosis in these cells regardless of p53 status as evidenced by enhanced DNA fragmentation and activation of caspase cascades, suggesting that CDDO-Me–induced DRs are functionally active. Moreover, silencing of DR5 expression using small interfering RNA suppressed apoptosis induced by CDDO-Me alone or by combination of CDDO-Me and TRAIL, indicating that DR5 up-regulation is required for induction of apoptosis by CDDO-Me and for enhancement of TRAIL-induced apoptosis by CDDO-Me. CDDO-Me rapidly activated c-Jun NH2-terminal kinase (JNK) before DR up-regulation and caspase-8 activation. Moreover, application of the JNK-specific inhibitor SP600125 blocked CDDO-Me–induced increases in JNK activation, DR up-regulation, caspase-8 activation, and DNA fragmentation. These results show that activation of JNK pathway results in CDDO-Me–induced DR up-regulation, caspase-8 activation, and apoptosis. Collectively, we conclude that CDDO-Me induces apoptosis via the JNK-mediated DR up-regulation in human lung cancer cells.