tbuckley/cabot-search huggingface dataset:
Differential Response to Na <sup>+</sup> Channel Blockade, β-Adrenergic Stimulation, and Rapid Pacing in a Cellular Model Mimicking the SCN5A and HERG Defects Present in the Long-QT Syndrome
Authors: Silvia G. Priori, Carlo Napolitano, Francesco Cantù, Arthur M. Brown, Peter J. Schwartz
Journal: Circulation Research (1996)

The long-QT syndrome (LQTS) is a hereditary disorder characterized by an abnormally prolonged QT interval and by life-threatening arrhythmias. Recently, two of the genes responsible for LQTS have been identified: SCN5A, a voltage-dependent Na+ channel on chromosome 3 (LQT3), and HERG, responsible for the rapid component of the delayed rectifier current (IKr), on chromosome 7 (LQT2). We developed an in vitro model to attempt reproduction of the expected alterations in LQT3 and LQT2 patients. Guinea pig ventricular myocytes were exposed to anthopleura toxin A (anthopleurin), an inhibitor of the inactivation of the Na+ current, and to dofetilide, a selective blocker of IKr. Both interventions significantly prolonged action potential duration (APD), by 54 +/- 13 and 62 +/- 16 ms, respectively. Cells pretreated with anthopleurin significantly shortened APD in response to mexiletine, isoproterenol, and rapid pacing (from 264 +/- 38 to 226 +/- 32 ms after mexiletine, P < .001). On the contrary, cells exposed to dofetilide did not shorten the APD after mexiletine and even prolonged it after initial exposure to isoproterenol (from 280 +/- 25 to 313 +/- 20 ms, P < .001); during rapid pacing, APD was shortened but less (38 +/- 9 versus 60 +/- 11 ms, P < .05) than in anthopleurin-treated cells. This study shows that a cellular model for LQTS, based on the recent advances in molecular genetics, can provide adequate "phenotypes" of prolonged repolarization amenable to the testing of interventions of potential clinical relevance. We found differential responses to Na+ channel blockade, to beta-adrenergic stimulation, and to rapid pacing according to specific pretreatment with either anthopleurin (to mimic LQT3) or dofetilide (to mimic LQT2). These different responses in myocytes bear striking similarities with the differential response to analogous interventions in LQTS patients with mutations on the SCN5A and HERG genes.
"TRANSPLANTING THE EYE"
Authors: Theodor Koppányi
Journal: JAMA (1924)

<h3>To the Editor:</h3> —In the communication of Dr. Joseph Imre inThe Journal, October 4, the following statements are made: Dr. Koppányi declares in the newspaper interview that transplantation of the human eye with the return of vision is possible. A year ago Dr. Koppányi filled the newspapers of Europe with these fantastic ideas. Dr. Koppányi admitted that the optic nerve was not severed in his eye transplantation experiments. These statements are not true.
Some Uncertainties in the Diagnosis of Cerebral Tumour
Authors: E. S. Reynolds
Journal: BMJ (1899)

these that I refer; I am dealing with those cases in which the tension is persistently raised.Now, Mahomed's view was that these were the early initial staces of granular kidney, and this I take to be also Goodhart's view.I do not think Mahomed's work has been estimated at its 'true value.The term he introduced may have had something ito do with this, for the expression, the pre-albuminuric stage, of which he considered high tension to be the chief indication, seemed to assume entirely what he lhad to prove.-His work was based on careful clinical observation, and I believe that he was in the main correct, though possibly lie attributed too much to high tension and too little to the thickening of the arteries to whiclh I have referred.Even his ~own descriptions show that high tension was not the only factor in the pulse, but that the arteries were also thickened.Sir William Broadbent, differing as he does from Mahomed in theory, yet attaches quite as great significance to the in- crease of pulse tension.He describes as the ultimate results -of this increased tension a variety of symptoms-for example, .cardiacfailure, general disturbance of health, a sort of eachexia, and even hiemorrhage, which, as he stated, could be truly predicted long before it occurred.
Exposures and health effects from inorganic agricultural dusts.
Authors: M Schenker
Journal: Environmental Health Perspectives (2000)

Most studies of respiratory disease from dust exposure in the agricultural workplace have focused on allergic diseases caused by inorganic dusts, specifically occupational asthma and hypersensitivity pneumonitis. Exposures to inorganic (mineral) dusts among farmers and farm workers may be substantial. Such exposures are most frequent in dry-climate farming regions. In such locations farming activities that perturb the soil (e.g., plowing, tilling) commonly result in exposures to farm operators of 1-5 mg/m(3) respirable dust and >= 20 mg/m(3) total dust. The composition of inorganic dust in agriculture generally reflects the soil composition. Crystalline silica may represent up to 20% of particles, and silicates represent up to 80%. These very high concentrations of inorganic dust are likely to explain some of the increase in chronic bronchitis reported in many studies of farmers. Pulmonary fibrosis (mixed dust pneumoconiosis) has been reported in agricultural workers, and dust samples from the lungs in these cases reflect the composition of agricultural soils, strongly suggesting an etiologic role for inorganic agricultural dusts. However, the prevalence and clinical severity of these cases are unknown, and many exposures are to mixed organic and inorganic dusts. Epidemiologic studies of farmers in diverse geographic settings also have observed an increase in chronic obstructive pulmonary disease morbidity and mortality. It is plausible that agricultural exposure to inorganic dusts is causally associated with chronic bronchitis, interstitial fibrosis, and chronic obstructive pulmonary disease, but the independent contribution of mineral dusts beyond the effects of organic dusts remains to be determined.
Risk of thrombosis in women with malignancies undergoing ovarian stimulation for fertility preservation
Authors: Edgardo Somigliana, Fedro Alessandro Peccatori, Francesca Filippi, Fabio Martinelli, Francesco Raspagliesi, Ida Martinelli
Journal: Human Reproduction Update (2014)

Compared with the general population, cancer patients have a higher risk of venous thromboembolism as well as arterial thrombotic events such as stroke, myocardial infarction and peripheral arterial embolism. Therefore a possible concern for women with malignancies undergoing ovarian stimulation for fertility preservation is the increased risk of venous or arterial thrombosis.In this article, we revised current available literature on the risk of thrombosis in patients with cancer and in women undergoing ovarian stimulation, with the ultimate aim of drawing some indications for preventive measures.Unfortunately, there are no specific data on the risk of thrombosis in women with cancer undergoing ovarian stimulation for fertility preservation. However, the literature suggests that the cancer type and stage, surgery, and chemotherapy all influence the risk of venous and, possibly, arterial thrombosis. Reports of cases of ovarian stimulation in women without malignancies have shown that venous thrombosis rarely occurs unless a pregnancy is achieved, while arterial thrombosis can occur in the absence of pregnancy but is usually only associated with ovarian hyperstimulation syndrome (OHSS). OHSS increases the risk of thrombotic events, but only the early form of the syndrome is relevant for women undergoing fertility preservation.The available evidence on the risks of thrombosis for women undergoing ovarian stimulation for fertility preservation due to a malignancy is reassuring. However the avoidance of the early form of OHSS in women preserving oocytes/embryos due to malignancy is crucial. For these cycles, we advocate the use of a regimen of ovarian stimulation with gonadotrophin releasing hormone (GnRH) antagonists using GnRH agonists to trigger ovulation, an approach that has been shown to markedly reduce the risk of OHSS. Antithrombotic prophylaxis should be administered only to selected subgroups of women such as those with other risk factors or those who do develop early OHSS.
Increase in platelet aggregation following a rise in plasma free fatty acids
Authors: Yoav Burstein, Lawrence Berns, Dov Heldenberg, Yael Kahn, Ben Zion Werbin, Israel Tamir
Journal: American Journal of Hematology (1978)

Abstract Platelet aggregation was studied following intravenous injection of heparin to nine healthy adults. Heparin is known to produce an increase in the concentration of free fatty acids (FFA) within 10 minutes of intravenous injection. A significant correlation was found between the intensity of primary platelet aggregation and changes in plasma FFA levels. No correlation was found between plasma FFA levels and the intensity of secondary platelet aggregation.
Patients and Therapies: Getting the Two Together
Authors: David L. Sackett
Journal: New England Journal of Medicine (1978)

"Compliance" is in the news these days. Its prominence in hypertension symposia now rivals that of the renin-angiotensin system; it has received independent billing in the Index Medicus, and of 15 drug advertisements in a recent issue of the Journal (November 10), 11 stress properties thought to enhance compliance and, thereby, efficacy.Yet is there any substance in all this hubub about compliance? The outbreak of publications since Blackwell's1 1973 review has spread in several directions, and three of them warrant discussion here.First of all, investigation has begun to show that more than intuition is needed to devise . . .
Oral Sildenafil Is an Effective and Specific Pulmonary Vasodilator in Patients With Pulmonary Arterial Hypertension
Authors: Evangelos Michelakis, Wayne Tymchak, Dale Lien, Linda Webster, Kyoko Hashimoto, Stephen Archer
Journal: Circulation (2002)

Background — The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO. Methods and Results — We studied 13 consecutive patients (mean±SEM, 44±2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (−19±5%) and sildenafil (−27±3%), whereas sildenafil+iNO was more effective than iNO alone (−32±5%, P &lt;0.003). Sildenafil and sildenafil+iNO increased cardiac index (17±5% and 17±4%, respectively), whereas iNO did not (−0.2±2.0%, P &lt;0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15±6 versus −9±7%, P &lt;0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP ( P &lt;0.0001). Conclusions — A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.
Developmental neurotoxicity elicited by gestational exposure to chlorpyrifos: when is adenylyl cyclase a target?
Authors: Armando Meyer, Frederic J Seidler, Mandy M Cousins, Theodore A Slotkin
Journal: Environmental Health Perspectives (2003)

The developmental neurotoxicity of chlorpyrifos (CPF) involves mechanisms over and above cholinesterase inhibition. In the present study, we evaluated the effects of gestational CPF exposure on the adenylyl cyclase (AC) signaling cascade, which regulates the production of cyclic AMP, a major controller of cell replication and differentiation. In addition to basal AC activity, we assessed the AC response to direct enzymatic stimulants [forskolin, manganese (Mn(2+))]; the response to isoproterenol, which activates signaling through beta-adrenoceptors (betaARs); and the concentration of betaAR binding sites. CPF administered to pregnant rats on gestational days (GD) 9-12 elicited little or no change in any components of AC activity or betaARs. However, shifting the treatment window to GD17-20 produced regionally selective augmentation of AC activity. In the brainstem, the response to forskolin or Mn(2+) was markedly stimulated by doses at or below the threshold for observable toxicity of CPF or for inhibition of fetal brain cholinesterase, whereas comparable effects were seen in the forebrain only at higher doses. In addition, low doses of CPF reduced betaAR binding without impairing receptor-mediated stimulation of AC. These results indicate that signal transduction through the AC cascade is a target for CPF during a discrete developmental period in late gestation, an effect that is likely to contribute to the noncholinergic component of CPF's developmental neurotoxicity.
Increased Tc-99m-Annexin uptake in doxorubicin induced myocardial apoptosis
Authors: Gurusher S. Panjrath, Dagmar Hartung, Artiom Petrov, Navneet Narula, Virendra Patel, Zheng Liu, Mani A. Vannan, Jagat Narula, Diwakar Jain
Journal: Journal of the American College of Cardiology (2003)
Review of Custer Atlas
Authors: R. PHILIP CUSTER
Journal: Annals of Internal Medicine (1976)

Comments and Correction1 January 1976Review of Custer AtlasR. PHILIP CUSTER, M.D.R. PHILIP CUSTER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-1-102_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: My attention has recently been called to the review of my book, An Atlas of the Blood and Bone Marrow, 2nd edition, (Ann Intern Med 82:440-441, 1975) by Dr. Anthony V. Pisciotta. He mentions its 562 pages as compared with the 321 pages in the first edition. He attributes this to a smaller page size and the addition of four new chapters by contributing authorities, not noticing the altered margins and typography and the popular "bleeding" of illustrations, which virtually compensate for the reduction to a more convenient shelf-size.Most damning is Dr. Pisciotta's statement, "Despite the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1976Volume 84, Issue 1Page: 102-102KeywordsBloodBone marrowHemorrhage Issue Published: 1 January 1976 PDF DownloadLoading ...
979-35 Factors of Acute Ischemia Increase Ca 2+ -Activated K + Currents in Cultured Human Endothelial Cells
Authors: Jelin Pu, Johannes Wiecha, Johannes Waltenberger, Ulrike Mayr, Peter Weisüller, Matthias Kochs, Vinzenz Hombach
Journal: Journal of the American College of Cardiology (1995)
<i>Ex vivo</i> pharmacologic modulation of basophil histamine release in asthmatic patients
Authors: B. Lebel, B. Arnoux, P. Chanez, Y.‐H. Bougeard, J. P. Daures, J. Bousquet, A. M. Campbell
Journal: Allergy (1996)

Histamine is one of a range of mediators which play an important role in asthma, and the “releasability” of basophils has been shown to be upregulated in this disease. In vitro , β 2 ‐agonists and to a lesser extent corticosteroids have been shown to reduce histamine release. The ex vivo effects of salmeterol and inhaled corticosteroids on histamine release were studied in 78 asthmatic patients with variable disease severity and 20 control subjects. Spontaneous and anti‐IgE‐induced histamine release was measured in all subjects. Fifteen patients were not receiving any form of treatment, 42 were treated with inhaled corticosteroids, and 21 received inhaled corticosteroids and salmeterol. Seven patients treated with inhaled corticosteroids and seven patients treated with inhaled corticosteroids and salmeterol were tested twice to assess the effect of salmeterol on histamine release. Nine patients treated with inhaled corticosteroids were tested before and after 1 month of salmeterol treatment to determine the possible inhibition by salmeterol. Patients who were treated with inhaled corticosteroids and salmeterol showed significantly lower levels of spontaneous histamine release (median: 2.5%) than untreated (5.2%) and inhaled corticosteroids‐treated asthmatics (3.4%). No tachyphylaxis to salmeterol was observed when patients were tested twice at a 3‐month interval. This study suggests that salmeterol may have an additive anti‐inflammatory effect with inhaled corticosteroids, although this hypothesis must be tested by further studies involving cells obtained by bronchoalveolar lavage and studies with bronchial biopsies.
Studies on the plasma membrane of normal and psoriatic keratinocytes.
Authors: J.M. GOMMANS, MIEKE BERGERS, P.E.J. ERP, JOSE J.M.A. HURK, P. KERKHOF, P.D. MIER, H. ROELFZEMA
Journal: British Journal of Dermatology (1979)

Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation.
Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines
Authors: Qian Xiong, Yadong Yang, Hai Wang, Jie Li, Shaobin Wang, Yanming Li, Yaran Yang, Kan Cai, Xiuyan Ruan, Jiangwei Yan, Songnian Hu, Xiangdong Fang
Journal: Genomics Proteomics & Bioinformatics (2014)

Abstract Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.
Tobacco, the Food and Drug Administration, and Congress
Authors: L H Glantz, G J Annas
Journal: New England Journal of Medicine (2000)

Smoking has been the number-one target of public health professionals in the United States for more than a decade because it is the leading cause of premature death. Nonetheless, no unified public health strategy has been developed. In 1995, with the strong endorsement of President Bill Clinton and Vice President Al Gore, the commissioner of the Food and Drug Administration (FDA), Dr. David Kessler, announced that the agency had jurisdiction over tobacco and would regulate cigarettes as “drug-delivery devices.”1 The tobacco companies objected and sued the FDA, arguing that Congress had not given the FDA jurisdiction over their product. The . . .
THE SYNDROME OF HYPERTONIC AND ATONIC COLOPATHY
Authors: FRED H. KRUSE
Journal: JAMA (1934)

Colitis is a much used and abused term, and most certainly the medical profession should limit its application to include only inflammatory states of the large bowel. These inflammations, from simple catarrhal to chronic ulcerative colitis, as well as related conditions producing definite pathologic lesions, have been well demonstrated, and their causative agents have been determined, ranging from chemical poisons, certain deficiency states, as noted in pellagra and sprue, protozoan infestations and, above all, bacterial infections. A diagnosis establishing a case of acute or chronic bowel disorder, in the foregoing category, as an actual colitis affords some satisfaction in classifying the disorder and some comfort in the knowledge that one may proceed with therapy more or less promising and universally recognized. There still remain chronic constipation and intermittent diarrhea to plague, confound and divide the profession. These complaints represent by far the greater proportion of chronic bowel disorders that occur
Deep Venous Thrombosis Shown on In-111 Labeled White Blood Cell Imaging
Authors: CYNTHIA L. BLOUNT, HELENA R. BALON
Journal: Clinical Nuclear Medicine (1997)

Thrombophlebitis was shown as an incidental finding on an In-111 WBC study performed for the evaluation of osteomyelities. A review of the literature yielded only two case reports of lower extremity deep venous thrombosis detected by In-111 WBC imaging. The use of other radiotracers such as In-111 platelets, Tc-99m HMPAO labeled platelets, and In-111 labeled monoclonal antifibrin antibodies for the diagnosis of deep venous thrombosis has been reported.
Delayed Restoration of Lung Perfusion After Removal of Aspirated Foreign Body
Authors: KAZUYOSHI SUGA, KAZUYA NISHIGAUCHI, NORIHIKO KUME, HIROMICHI UCHISAKO, TAZUKO YOSHIMIZU, TAKASHI NAKANISHI
Journal: Clinical Nuclear Medicine (1995)

Tc-99m MAA lung scan contributed to the diagnosis of an aspirated endobronchial foreign body in a 2-year-old boy, although there was no radiographic evidence of obstruction. Despite the complete removal of the foreign- body, a follow-up scan performed 8 days after removal demonstrated incomplete restoration of perfusion to the ipsilateral lung. It is not easy to explain this delayed improvement of hypoperfusion, but it may reflect a slow recovery of reflex vasoconstriction with a partial bronchial obstruction, or it may reflect reduced perfusion caused by persistent, subclinical inflammatory changes in the peripheral lung.
Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy: a stable isotope study
Authors: Rajagopal V. Sekhar, Sanjeet G. Patel, Susana D'Amico, Jianjian Shi, Ashok Balasubramanyam, Khaleel Rehman, Farook Jahoor, Fehmida Visnegarwala
Journal: Metabolism (2010)