tbuckley/cabot-search huggingface dataset:
Fears aroused in patients by migraine.
Authors: J N Blau
Journal: BMJ (1984)

Griseofulvin modifies hepatic enzyme activity in mice,' so that enzyme induction and a consequent lowering of oestrogen concentra- tions may explain the intermenstrual bleeding on the basis of a withdrawal effect.Amenorrhoea is not so readily explained.Interestingly, however, rifampicin, a potent inducer of hepatic microsomal enzymes, causes the same range of cycle anomalies with intermenstrual bleeding, amenorrhoea, and unintended pregnancies in women using oral contraceptives.2The contributory role of griseofulvin in the two reported pregnan- cies is not established, as both women were also taking sulphonamides.These drugs may affect the enzymes concerned in steroid metabolism, at least in vitro,3 but are not a well established cause of pill failure.Pharmacokinetic studies may help in assessing the possible inter- action between griseofulvin and oral contraceptives.In the mean time prescribers of these drugs should be alert to the problem, which may lead to pill failure.We thank
CARDIAC I-123 METAIODOBENZYLGUANIDINE IMAGING COULD PREDICT CARDIAC EVENT IN CHRONIC HEART FAILURE PATIENTS IRRESPECTIVE OF OBESITY: A LONG TERM FOLLOW UP STUDY
Authors: Takumi Kondo, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Kaoruko Sengoku, Kentaro Ozu, Hironori Yamamoto, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2014)
SSRIs in early pregnancy were associated with increased risk for septal heart defects but not major congenital malformations overall
Authors: Gideon Koren
Journal: Annals of Internal Medicine (2009)

Source Citation Pedersen LH, Henriksen TB, Vestergaard M, et al. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. BMJ. 2009;339:b3569. 19776103
Stretch-activated ion channels
Authors: Henry Sackin
Journal: Kidney International (1995)

Mechanosensitive or stretch-activated (SA) channels respond to membrane stress by changes in open probability. These channels exist in auditory cells, stretch receptors, muscle spindles, vascular endothelium, and other neurosensory tissues where their physiological function seems readily apparent. It is less obvious why non-excitable cells, such as those of blood and epithelial tissues, need channels that respond to mechanical stimuli. Clearly, all cells must cope with the dual problems of volume regulation and electrolyte homeostasis. Since the primary function of epithelia is salt and water transport, these cells face both extracellular and intracellular osmotic challenges. For example, Na transporting epithelia in the intestine and kidney must accommodate significant variations in net solute uptake without suffering destructive changes in cell volume, caused by slight discrepancies between influx and efflux [1].  Since volume is a physical property of the cell, it can only be sensed physically, or mechanically. Although cell swelling may dilute the concentration of certain impermeants that could conceivably function as intracellular volume sensors, a volume-controller that relies on chemical sensors is inherently unstable because chemical concentration is affected by multiple factors within the cell. A reliable feedback system for short-term volume regulation ultimately requires some type of mechanical sensor to convey information about cell size. Similarly, regulation of cell growth may also require specific mechanotransducers that detect physical changes in cell size and shape. Conversely, the abnormal growth of cancer cells could involve a breakdown of such a mechano-transduction system.
Efficacy of pegylated interferon alpha-2B in combination with ribavirin in patients with chronic hepatitis C non-responders to a previous treatment
Authors: M. Chousterman, V. Auray-Cartier, H. Hagege, J.P. Arpurt, P. Cassan, J. Denis, D. Gargot, B. Nalet, O. Nouel, A. Pariente, C. Wartelle-Bladou
Journal: Journal of Hepatology (2003)
Allergic bronchial eosinophilia: a therapeutic approach for the selection of potential bronchial anti‐inflammatory drugs
Authors: N. Chand, J. E. Harrison, S. M. Rooney, K. W. Nolan, C. L. De Vine, R. G. Jakubicki, J. Pillar, W. Diamantis, R. D. Sofia
Journal: Allergy (1993)

Aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) in guinea pigs was used as a marker of bronchial inflammation. Drugs were administered orally 4 h after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was inhibited by orally administered dexamethasone and methylprednisolone. Terfenadine (a newer H1-receptor antagonist), theophylline (a nonspecific phosphodiesterase inhibitor), and salbutamol (a beta 2-agonist) did not influence allergic eosinophilic infiltration. Many of these agents, administered prophylactically, have been reported to suppress allergic eosinophilic infiltration in the BALF of guinea pigs. Methylprednisolone, a steroid, inhibits allergic bronchial eosinophilia regardless of the time of administration; that is, 2 h before or 4 h after aeroallergen challenge. The therapeutic approach used in this study may facilitate drug discovery for bronchial inflammation/asthma.
Furthering our understanding of pathogen transmission in cystic fibrosis
Authors: L. Saiman
Journal: Thorax (2009)

<h3>Background</h3> Appropriate timing of activity of the vastus medialis obliqus (VMO) and vastus lateralis (VL) muscles is a key factor for proper tracking of the patella in the trochlear groove during knee extension. This study investigates the relative timing of activation of the VMO and VL muscles during unexpected perturbations performed before and after eccentric exercise. <h3>Methods</h3> Surface electromyography signals were recorded from the VMO and VL muscles of the right leg in 11 healthy men during rapid postural perturbations performed at baseline, immediately after eccentric exercise of the quadriceps, and at 24 and 48 h after exercise. Participants stood on a moveable platform during which eight randomised postural perturbations were performed (4 repetitions of 2 perturbation types: 8 cm forward slides, 8 cm backward slides). <h3>Results</h3> Before the eccentric exercise, the onset of VMO activity was significantly earlier than the VL muscle (average for both forward and backward perturbations: VMO 39.0±7.1 ms; VL 43.7±7.9 ms). However, the onset of VMO activity was significantly later compared with VL muscle immediately after eccentric exercise and this remained 24 and 48 h after eccentric exercise (average across all postexercise sessions and perturbation directions: VMO 72.3±11.1 ms; VL 56.0±8.2 ms; p&lt;0.05). <h3>Conclusions</h3> The onset of VMO–VL activity in response to rapid destabilising perturbations is altered immediately after eccentric exercise and during eccentric exercise-induced muscle soreness up to 48 h later. These observations may help explain the high prevalence of knee disorders after high intensity eccentric exercise.
Postoperative Delirium
Authors: Edward R. Marcantonio
Journal: JAMA (2012)

Delirium (acute confusion) complicates 15% to 50% of major operations in older adults and is associated with other major postoperative complications, prolonged length of stay, poor functional recovery, institutionalization, dementia, and death. Importantly, delirium may be predictable and preventable through proactive intervention. Yet clinicians fail to recognize and address postoperative delirium in up to 80% of cases. Using the case of Ms R, a 76-year-old woman who developed delirium first after colectomy with complications and again after routine surgery, the diagnosis, prevention, and treatment of delirium in the postoperative setting is reviewed. The risk of postoperative delirium can be quantified by the sum of predisposing and precipitating factors. Successful strategies for prevention and treatment of delirium include proactive multifactorial intervention targeted to reversible risk factors, limiting use of sedating medications (especially benzodiazepines), effective management of postoperative pain, and, perhaps, judicious use of antipsychotics.
Clinical Characteristics, Tumor, Node, Metastasis Status, and Mutation Rate in Domain of Epidermal Growth Factor Receptor Gene in Serbian Patients with Lung Adenocarcinoma
Authors: Bojan Zaric, Vladimir Stojsic, Tomi Kovacevic, Tatjana Sarcev, Aleksandar Tepavac, Radmila Jankovic, Jelena Spasic, Davorin Radosavljevic, Paul Zarogoulidis, Nevena Vukobradovic-Djoric, Branislav Perin
Journal: Journal of Thoracic Oncology (2014)
Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495
Authors: H Lenasi
Journal: Cardiovascular Research (2003)

The Ca2+ antagonist amlodipine increases the generation of nitric oxide (NO) from native and cultured endothelial cells. The aim of this investigation was to determine whether or not the activation of the endothelial NO synthase (eNOS) by this Ca2+ antagonist is related to alterations in eNOS phosphorylation.In isolated, pre-contracted, endothelium-intact porcine coronary arteries, amlodipine elicited an NO-mediated relaxation and a leftward shift in the concentration-relaxation curve to bradykinin. Moreover, the Ca2+ antagonist increased the generation of NO from native endothelial cells, as detected by electron spin resonance spectroscopy and stimulated an 8-fold increase in cyclic GMP levels in cultured endothelial cells. In unstimulated endothelial cells, eNOS was not phosphorylated on Ser1177 but was phosphorylated on Thr495. Amlodipine elicited the phosphorylation of Ser1177 and attenuated Thr495 phosphorylation, with a time course similar to that of eNOS activation. The amlodipine-induced relaxation of porcine coronary arteries was attenuated by the B2 kinin receptor antagonist, icatibant, but this antagonist did not affect amlodipine-induced changes in eNOS phosphorylation in cultured endothelial cells. Moreover, amlodipine elicited the NO-mediated relaxation of rat aortic rings which do not express the B2 receptor. Amlodipine time-dependently attenuated the phosphorylation of protein kinase C (PKC) in endothelial cells, with a time course similar to the changes in eNOS phosphorylation, and prevented the phorbol-12-myristate-13-acetate-induced activation of PKC. The PKC inhibitor, Ro 31-8220, also elicited the phosphorylation of Ser1177 and the dephosphorylation of Thr495 in cultured cells and induced a leftward shift in the concentration-relaxation curve to bradykinin in rings of porcine coronary artery.The Ca2+ antagonist, amlodipine, enhances endothelial NO generation by inducing changes in the phosphorylation of eNOS. Although the activation of eNOS was related to the activation of the B2 kinin receptor in the porcine coronary artery, a B2 receptor-independent mechanism involving the inhibition of PKC appears to account for the effects observed in the rat aorta as well as in cultured endothelial cells.
Side effects of the pill.
Authors: M L Cox
Journal: BMJ (1973)

Recent studies indicate that the urge to reproduce is not an important source of the female libido. The Herzberg et al. studies showed that 19.8% of the women who stopped taking the pill gave loss of libido as the reason; 29.1% gave headache and 27.9% gave depression as their reasons for discontinuing. Women with a predisposition to depression tend to suffer loss of libido with pills and should not have them prescribed. The Herzberg studies showed women with IUDs to have a substantial increase in libido. The Simon Population Trust report of 1969 reported a very high percentage of increased sexual enjoyment after vasectomization and female sterilization.
How should health be defined?
Authors: A. R Jadad, L. O'Grady
Journal: BMJ (2008)

<h3>Abstract</h3> In the avian auditory brain stem, acoustic timing and intensity cues are processed in separate, parallel pathways via the two division of the cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Differences in excitatory and inhibitory synaptic properties, such as release probability and short-term plasticity, contribute to differential processing of the auditory nerve inputs. We investigated the distribution of synaptotagmin, a putative calcium sensor for exocytosis, via immunohistochemistry and double immunofluorescence in the embryonic and hatchling chick brain stem (<i>Gallus gallus</i>). We found that the two major isoforms, synaptotagmin 1 (Syt1) and synaptotagmin 2 (Syt2), showed differential expression. In the NM, anti-Syt2 label was strong and resembled the endbulb terminals of the auditory nerve inputs, while anti-Syt1 label was weaker and more punctate. In NA, both isoforms were intensely expressed throughout the neuropil. A third isoform, synaptotagmin 7 (Syt7), was largely absent from the cochlear nuclei. In nucleus laminaris (NL, the target nucleus of NM), anti-Syt2 and anti-Syt7 strongly labeled the dendritic lamina. These patterns were established by embryonic day 18 and persisted to postnatal day 7. Double labeling immunofluorescence showed Syt1 and Syt2 were associated with Vesicular Glutamate Transporter 2 (VGluT2), but not Vesicular GABA Transporter (VGAT), suggesting these Syt isoforms were localized to excitatory, but not inhibitory, terminals. These results suggest that Syt2 is the major calcium binding protein underlying excitatory neurotransmission in the timing pathway comprising NM and NL, while Syt2 and Syt1 regulate excitatory transmission in the parallel intensity pathway via cochlear nucleus NA.
Research, the Lifeline of Medicine
Authors: Arthur Kornberg
Journal: New England Journal of Medicine (1976)

Advances in medicine spring from discoveries in physics, chemistry and biology. Among key contributions to the diagnosis, treatment and prevention of cardiovascular and pulmonary diseases, a recent Comroe-Dripps analysis shows two thirds to have been basic rather than applied research. Without a firm foundation in basic knowledge innovations perceived as advances prove hollow and collapse. Strong social, economic and political pressures now threaten acquisition of basic knowledge. Scientists feel driven to undertake excessively complex problems and gamble against the historical record that science generally progresses by tackling discrete and well defined questions. Regardless of circumstances, professional standards require the physician and scientist to be creative and enlarge the fund of knowledge.
Malaysia Aborigine Medical Program
Authors: J. D. Kinzie
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The Gombak Aborigine Hospital in Malaysia is part of a most unusual overseas medical program. Through modern technology, 20th-century medicine is brought to the primitive aborigines in the jungle of Malaya. There are about 45,000 aborigines of diverse racial and linguistic origins scattered throughout the deep jungle and jungle fringe areas. These people were generally ignored until the time of the communist emergency when it became politically important for the government to maintain good relationships with them. Attempts were made to resettle them in other locations and to offer them medical care in general hospitals. However, they became very frightened and felt inferior once they were out of their own environment. In 1955 Dr. Malcolm Bolton, a British physician, began a program of medical service to the aborigines. First he gained their confidence by working with and through the local medicine men. Later he trained aborigines as
THE INTERACTION OF IgE WITH RAT BASOPHILIC LEUKEMIA CELLS
Authors: Anthony Kulczycki, Chaviva Isersky, Henry Metzger
Journal: The Journal of Experimental Medicine (1974)

A rat basophilic leukemia cell line originally described by Eccleston et al. (3) has been successfully transplanted into eight Wistar strains and adapted to suspension cell culture without noticeable morphological changes. The cells deplete the reaginic activity of mouse and rat immune sera to an extent roughly equivalent to that reported for normal rat mast cells. Studies utilizing radioiodinated antilight-chain antibodies and radioiodinated partially purified rat IgE indicate that the cells bind IgE to their surface membrane with high specificity. Heating or mildly reducing the rat IgE destroyed its binding activity. The binding is unaffected by the presence or absence of Ca++ and Mg++, and is markedly inhibited by reaginic but not by normal rat or mouse serums. The affinity of these cells for human IgE, if present at all, is substantially lower than for rat IgE.
Ventral Striatum Response During Reward and Punishment Reversal Learning in Unmedicated Major Depressive Disorder
Authors: Oliver J. Robinson, Roshan Cools, Christina O. Carlisi, Barbara J. Sahakian, Wayne C. Drevets
Journal: American Journal of Psychiatry (2011)

Objective: Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. Method: The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Results: Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Conclusions: Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.
Effects of elevating [Na] on membrane currents of canine ventricular myocytes: role of intracellular Ca ions
Authors: N SAXENA, J FAN, G TSENG
Journal: Cardiovascular Research (1997)

Objectives: Our first objective was to study how elevating [Na] i can modify the background membrane conductance in canine ventricular myocytes (CVM). In particular, we wanted to find evidence for a Na i -activated K current ( IK,Na ) in these cells. The second objective was to compare the effects of elevating [Na] i on membrane currents without and with intracellular Ca buffering. Methods: Whole-cell currents were recorded and [Na] i was elevated either by using a pipette perfusion device that allowed [Na] in the pipette solution to be varied (from 0 to 50 mM), or by 50 μM ouabain. Results: Although an outward current attributable to IK,Na was confirmed in guinea-pig ventricular myocytes (GPVM) under our recording conditions, no such current was seen in 29 CVM examined. With Ca i buffering, the main effect of elevating [Na] i on CVM was an increase in inward current around and negative to the resting membrane potential. Based on the dependence of this Na i -induced inward current on K ions and its pharmacological properties, especially the effects of low concentrations of external Ba ions (≤5 μM) at strongly hyperpolarized voltages, we hypothesize that this current was carried by extracellular K ions through the inward rectifier ( IKl ) channels that had been modified by the high level of [Na] i . With Ca i buffering, elevating [Na] i by ouabain had few or no effects on the L-type Ca channel current ( ICa ) or the slow delayed rectifier current ( IKS ). Without Ca i buffering, ouabain induced a rapid reduction of both currents along with an increase in a time-independent outward current at voltages positive to −60 mV. Conclusion: Our data suggest that there are species variations in K channel expression and/or K channel modulation by intracellular Na ions. Furthermore, intracellular Ca ions play a crucial role in mediating the effects of Na i loading on membrane currents in canine ventricular myocytes.
545 MTOR-INHIBITORS REDUCE THE INCIDENCE OF CYTOMEGALOVIRUS INFECTION AFTER LIVER TRANSPLANTATION
Authors: J. Hartl, M.N. Scherer, M. Loss, S. Farkas, A. Schnitzbauer, L. Baier, H.-J. Schlitt, B. Salzberger, G.I. Kirchner
Journal: Journal of Hepatology (2011)
Abstract 2234: Catechol suppresses EGF-induced cell transformation by inhibiting ERK2 activity as confirmed by a crystallographic study.
Authors: Do Young Lim, Margarita Malakhova, Igor Kurinov, Seung Ho Shin, Mee-Hyun Lee, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2013)

Abstract Catechol (pyrocathechol, 1,2-dihydroxybenzene) is a chemical that is used by industry in the manufacture of certain products. It also occurs naturally in many fruits such as apple, apricot, grape, bananas, pear, plum, mango, avocado, potato, and mushrooms. Browning of fruit occurs because of a chemical reaction between catechol and oxygen. Even though, catechol has toxicity at a high dose as shown by an in vivo study, the Environmental Protection Agency has not classified catechol with respect to potential carcinogenicity. Whether a lower concentration (&amp;lt; 40 μM) of catechol treatment has effects on carcinogenesis is not known. We found that catechol binds to ERK2 and inhibits its activity. The extracellular signal-regulated kinases (ERKs) belong to the mitogen-activated protein (MAP) kinase family, and regulate important biological processes such as cell growth, proliferation, differentiation, and transcription regulation. ERK2 is activated in response of UV, cytokines and growth factors, such as epidermal growth factor (EGF) and insulin-like growth factor. Constitutive activation of ERK2 is observed in many human cancers such as colon, breast, lung and skin cancers. In this study we present the co-crystal structure of ERK2 bound with catechol in the ATP-active site. The conserved amino acid residues within the hinge region that are involved in the interaction of ERK and its inhibitors make the contacts with catechol. Contacts include side chain of Q105, and the main chains of the D106 and M108 residues. We found that catechol inhibits ERK2 in vitro kinase activity more than two-fold at a 20 μM concentration. This was confirmed by the observed decrease of the phosphorylation of Elk1, a specific downstream target of ERK2. In addition, 20 μM catechol inhibited EGF-induced JB6 cell transformation. Interestingly, JB6 cell proliferation was not affected at 20 μM concentration. Taken together, the results showed that catechol inhibits EGF-induced cell transformation without any toxicity through the inhibition of ERK2 activity. Citation Format: Do Young Lim, Margarita Malakhova, Igor Kurinov, Seung Ho Shin, Mee-Hyun Lee, Ann M. Bode, Zigang Dong. Catechol suppresses EGF-induced cell transformation by inhibiting ERK2 activity as confirmed by a crystallographic study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2234. doi:10.1158/1538-7445.AM2013-2234