tbuckley/cabot-search huggingface dataset:
Nitrofurantoin and Dantrolene; Liver and Lung
Authors: L. JACK FALING
Journal: Annals of Internal Medicine (1980)

Letters1 July 1980Nitrofurantoin and Dantrolene; Liver and LungL. JACK FALING, M.D., MITCHELL L. PETUSEVSKY, M.D., GORDON L. SNIDER, M.D.L. JACK FALING, M.D.Search for more papers by this author, MITCHELL L. PETUSEVSKY, M.D.Search for more papers by this author, GORDON L. SNIDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-1-151_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo The editor: In response to the recent article by Dr. Sharp and his colleagues (1), we wish to draw attention to the similar structures and toxicities of the antimicrobial agent, nitrofurantoin (1[(5-nitrofurfurylidene) amino] hydantoin) and the long-acting skeletal-muscle relaxant dantrolene sodium (1 - { [5 - (p - nitrophenyl) furfurylidene] amino} hydantoin sodium hydrate). Both compounds contain a hydantoin and furan ring with their major difference being a nitro substitution on the furan ring in nitrofurantoin and a nitrophenyl substitution on the furan ring in dantrolene sodium.In contrast to the more recently recognized hepatotoxicity of nitrofurantoin (1), hepatic...References1. SHARPISHAKZIMMERMAN JKH. Chronic active hepatitis and severe hepatic necrosis associated with nitrofurantoin. Ann Intern Med. 1980;92:14-9. LinkGoogle Scholar2. UTILIBOITNOTTZIMMERMAN RJH. Dantrolene-associated hepatic injury: incidence and character. Gastroenterology. 1977;72:610-6. CrossrefMedlineGoogle Scholar3. PETUSEVSKYFALINGROCKLIN MLR. Pleuropericardial reaction to treatment with dantrolene. JAMA. 1979;242:2772-4. CrossrefMedlineGoogle Scholar4. ELLISWESSELS KF. Muscle relaxant properties of the identified metabolites of dantrolene. Naunyn Schmiedebergs Arch Pharmacol. 1978;301:237-40. CrossrefMedlineGoogle Scholar5. CONKLIN J. The pharmacokinetics of nitrofurantoin and its related bioavailability. Antibiot Chemother. 1978;25:233-52. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Boston, MA 02130 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Cytoprotective Effects of DantroleneDantrolene: Mechanisms of Neuroprotection and Possible Clinical Applications in the Neurointensive Care UnitAdvances in measuring cellular bioenergetics using extracellular fluxDantrolene and pleural effusion: case report and review of literaturePleural Effusion Associated with Chronic Dantrolene AdministrationCombined nitrofurantoin toxicity to liver and lungWhole-Body Autoradiography of 14 C-Dantrolene in the Marmoset MonkeySpasticity and drug therapyAcute cholangitis and pancreatitis associated with sulindac (clinoril)Dantrolene—An Update 1 July 1980Volume 93, Issue 1_Part_1Page: 151-151KeywordsAntimicrobialsHydratesLiverLungsSodiumToxicity Issue Published: 1 July 1980 PDF downloadLoading ...
Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women
Authors: Marc J. Gunter, Donald R. Hoover, Herbert Yu, Sylvia Wassertheil-Smoller, Thomas E. Rohan, JoAnn E. Manson, Barbara V. Howard, Judith Wylie-Rosett, Garnet L. Anderson, Gloria Y.F. Ho, Robert C. Kaplan, Jixin Li, Xiaonan Xue, Tiffany G. Harris, Robert D. Burk, Howard D. Strickler
Journal: Cancer Research (2008)

Abstract Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has promitotic and antiapoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a case-cohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum specimens from all incident colorectal cancer cases (n = 438) and a random subcohort (n = 816) of Women's Health Initiative Observational Study subjects were tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [hazard ratio (HR)q4–q1, 1.73; 95% confidence interval (CI), 1.16–2.57; Ptrend = 0.005], waist circumference (HRq4–q1, 1.82; 95% CI, 1.22–2.70; Ptrend = 0.001), and free IGF-I (HRq4–q1, 1.35; 95% CI, 0.92–1.98; Ptrend = 0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became nonsignificant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels, 1.53; 95% CI, 1.05–2.22), even after control for insulin, free IGF-I, and waist circumference. These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I. [Cancer Res 2008;68(1):329–37]
Left ventricular mechanics related to the local distribution of oxygen demand throughout the wall.
Authors: R Beyar, S Sideman
Journal: Circulation Research (1986)

The complex interactions between left ventricular mechanics and the oxygen demand is studied by relating the left ventricular transmural oxygen demand to the myocardial structural and dynamic characteristics. The study utilizes a recent model of left ventricular contraction, which is based on a nested shell spheroidal geometry, a fan-like fibrous structure, the twisting motion of the left ventricle over its long axis, a transmural electrical activation propagation and the basic laws of sarcomere dynamics. The local "axial" stress (in the direction of the fibers) and the instantaneous sarcomere length are used to calculate the spatial distribution of the intramural oxygen demand per beat Vo2(y), where y is the distance from the endocardium. The normalized local sarcomere stress-length area SLAn(y) is related linearly to Vo2(y) by: Vo2(y) = K1 X SLAn(y) + K2, where K1 and K2 are constants. The calculations show a transmural metabolic gradient which is characterized by higher values of Vo2(y) in the endocardial layers than in the epicardial layers. Shorter endocardial sarcomeres and the twisting motion of the left ventricle around the long axis decrease the metabolic gradient across the wall, while a slow transmural electrical propagation wave as well as a wider angle of distribution of the fan-like fiber architecture increases the transmural metabolic gradient. Integration of the local oxygen demand across the left ventricular wall yields global values in agreement with those based on Suga's pressure-volume area approach. The model thus provides a qualitative and quantitative tool to assess the relation of the local and global oxygen demand to the complex left ventricular structure, fiber mechanics, and the dynamics of contraction.
Interleukin (IL)-1 Receptor–associated Kinase (IRAK) Requirement for Optimal Induction of Multiple IL-1 Signaling Pathways and IL-6 Production
Authors: Palanisamy Kanakaraj, Peter H. Schafer, Druie E. Cavender, Ying Wu, Karen Ngo, Patrick F. Grealish, Scott A. Wadsworth, Per A. Peterson, John J. Siekierka, Crafford A. Harris, Wai-Ping Fung-Leung
Journal: The Journal of Experimental Medicine (1998)

Interleukin (IL)-1 is a proinflammatory cytokine with pleiotropic effects in inflammation. IL-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (MAP) kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, as well as transcription factor nuclear factor kappaB (NF-kappaB). IL-1 signaling results in cellular responses through induction of inflammatory gene products such as IL-6. One of the earliest events in IL-1 signaling is the rapid interaction of IL-1 receptor-associated kinases, IRAK and IRAK-2, with the receptor complex. The relative roles of IRAK and IRAK-2 in IL-1 signaling pathways and subsequent cellular responses have not been previously determined. To evaluate the importance of IRAK in IL-1 signaling, IRAK-deficient mouse fibroblast cells were prepared and studied. Here we report that IL-1-mediated activation of JNK, p38, and NF-kappaB were all reduced in embryonic fibroblasts deficient in IRAK expression. In addition, IL-6 production in response to IL-1 was also dramatically reduced in IRAK-deficient embryonic fibroblasts and in skin fibroblasts prepared from IRAK-deficient mice. Our results demonstrate that IRAK plays an essential proximal role in coordinating multiple IL-1 signaling pathways for optimal induction of cellular responses.
Hyperactivated JNK Is a Therapeutic Target in pVHL-Deficient Renal Cell Carcinoma
Authors: Jiabin An, Huiren Liu, Clara E. Magyar, Yanchuan Guo, Mysore S. Veena, Eri S. Srivatsan, Jiaoti Huang, Matthew B. Rettig
Journal: Cancer Research (2013)

Clear cell renal cell carcinomas (RCC), the major histologic subtype of RCC accounting for more than 80% of cases, are typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Although accumulation of hypoxia-inducible factor alpha (HIF-α) is the most well-studied effect of VHL inactivation, direct inhibition of HIFα or restoration of wild-type pVHL protein expression has not proved readily feasible, given the limitations associated with pharmacologic targeting of transcription factors (i.e., HIF-α) and gene replacement therapy of tumor suppressor genes (i.e., VHL). Here, we have established that phosphorylated c-Jun, a substrate of the c-Jun-NH(2)-kinase (JNK), is selectively activated in clear cell RCC patient specimens. Using multiple isogenic cell lines, we show that HIF-α-independent JNK hyperactivation is unique to the pVHL-deficient state. Importantly, pVHL-deficient RCCs are dependent upon JNK activity for in vitro and in vivo growth. A multistep signaling pathway that links pVHL loss to JNK activation involves the formation of a CARD9/BCL10/TRAF6 complex as a proximal signal to sequentially stimulate TAK1 (MAPKKK), MKK4 (MAPKK), and JNK (MAPK). JNK stimulates c-Jun phosphorylation, activation, and dimerization with c-Fos to form a transcriptionally competent AP1 complex that drives transcription of the Twist gene and induces epithelial-mesenchymal transition. Thus, JNK represents a novel molecular target that is selectively activated in and drives the growth of pVHL-deficient clear cell RCCs. These findings can serve as the preclinical foundation for directed efforts to characterize potent pharmacologic inhibitors of the JNK pathway for clinical translation.
Evaluation of D-Dimer in the Diagnosis of Suspected Deep-Vein Thrombosis
Authors: Philip S. Wells, David R. Anderson, Marc Rodger, Melissa Forgie, Clive Kearon, Jonathan Dreyer, George Kovacs, Michael Mitchell, Bernard Lewandowski, Michael J. Kovacs
Journal: New England Journal of Medicine (2003)

Several diagnostic strategies using ultrasound imaging, measurement of D-dimer, and assessment of clinical probability of disease have proved safe in patients with suspected deep-vein thrombosis, but they have not been compared in randomized trials.Outpatients presenting with suspected lower-extremity deep-vein thrombosis were potentially eligible. Using a clinical model, physicians evaluated the patients and categorized them as likely or unlikely to have deep-vein thrombosis. The patients were then randomly assigned to undergo ultrasound imaging alone (control group) or to undergo D-dimer testing (D-dimer group) followed by ultrasound imaging unless the D-dimer test was negative and the patient was considered clinically unlikely to have deep-vein thrombosis, in which case ultrasound imaging was not performed.Five hundred thirty patients were randomly assigned to the control group, and 566 to the D-dimer group. The overall prevalence of deep-vein thrombosis or pulmonary embolism was 15.7 percent. Among patients for whom deep-vein thrombosis had been ruled out by the initial diagnostic strategy, there were two confirmed venous thromboembolic events in the D-dimer group (0.4 percent; 95 percent confidence interval, 0.05 to 1.5 percent) and six events in the control group (1.4 percent; 95 percent confidence interval, 0.5 to 2.9 percent; P=0.16) during three months of follow-up. The use of D-dimer testing resulted in a significant reduction in the use of ultrasonography, from a mean of 1.34 tests per patient in the control group to 0.78 in the D-dimer group (P=0.008). Two hundred eighteen patients (39 percent) in the D-dimer group did not require ultrasound imaging.Deep-vein thrombosis can be ruled out in a patient who is judged clinically unlikely to have deep-vein thrombosis and who has a negative D-dimer test. Ultrasound testing can be safely omitted in such patients.
TRUE TOTAL ENUCLEATION OF TWO HYDATID CYSTS FROM THE SAME LIVER
Authors: J. P. Buckley
Journal: BMJ (1913)

N TiR 725 equipped hospitals, where such a complicatiion as perfora- tion is likely to be recognized at the earliest possible moment, and immediate arrangements made for operation is eminently favourable to surgical success.2. It is very desirable to operate as rapidly as possible, and to avoid all unnecessary handling and exposure of intestine.These patients are totally unable to bear much manipulation.3. The quickest way to find the perforation is to go straighbt for the ileo-caecal valve and trace the ileum upwards.It will rarely be necessary to lhandle more than 2 to 3 ft. of bowel.4. All sutures should be of catgut, as silk or linen is almost certain to become infected and give rise to a troublesonme sinus.The catgut I use is prepared by boiling in absolute alcohol for thirty minutes, and stored in tincture of iodine one p)art, proof spirit ten parts.5. These patients bear the Fowler position and continuous rectal saline quite well.6. Coliuria being a very likely complication, it appears wise to put these patients at once on alkaline treatment.Whether as a result of this procedure or not, my last two cases showed no sign of this troublesome ailment.Success in the cases lhere recorded was chiefly due to the promptness with which Dr. Gardner Robb recognized the complication and made arrangements for operation; and in a very large measure also to the care and attention bestowed on tho patients by the resident officers, Drs.Kevin, Glass, and Millar.
Squatting Amplifies Pulse Pressure Increase With Disease Duration in Patients With Type 1 Diabetes
Authors: Jean-Christophe Philips, Monique Marchand, André J. Scheen
Journal: Diabetes Care (2008)

To evaluate pulse pressure changes according to duration of type 1 diabetes and to assess the influence of posture.We performed continuous measurement of blood pressure with a Finapres device during a 3 x 1 min posture test (standing, squatting, standing) in 159 type 1 diabetic patients divided into four groups according to diabetes duration (<or=10, 11-20, 21-30, and >30 years, groups 1-4, respectively) and compared the results with those of age-matched nondiabetic subjects.Pulse pressure progressively increased according to type 1 diabetes duration (P < 0.0001), especially in women, but not in age-matched nondiabetic subjects (NS). Pulse-pressure increase from group 1 to group 4 was amplified in the squatting position (from 50 +/- 17 to 69 +/- 14 mmHg) compared with standing (from 44 +/- 15 to 55 +/- 12 mmHg).Pulse pressure increases according to type 1 diabetes duration more in women than in men, and the squatting position sensitizes such pulse-pressure increase in both sexes.
RAS/PI3K Crosstalk and Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma
Authors: T. Rampias, A. Giagini, S. Siolos, H. Matsuzaki, C. Sasaki, A. Scorilas, A. Psyrri
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Cetuximab, an antibody directed against the EGF receptor, is an effective clinical therapy for patients with head and neck squamous cell cancer (HNSCC). Despite great clinical promise, intrinsic or acquired cetuximab resistance hinders successful treatment outcomes but little is known about the underlying mechanism. Experimental Design: To study the role of oncogenic HRAS in cetuximab resistance in HNSCC, the frequency of oncogenic HRAS mutations was determined in a cohort of 180 genomic DNAs from head and neck cancer specimens. We also used a combination of cetuximab-resistant cell lines and a transgenic mouse model of RAS-driven oral cancer to identify an oncogenic RAS-specific gene expression signature that promotes cetuximab resistance. Results: Here, we show that activation of RAS signaling leads to persistent extracellular signal–regulated kinase 1/2 signaling and consequently to cetuximab resistance. HRAS depletion in cells containing oncogenic HRAS or PIK3CA restored cetuximab sensitivity. In our study, the gene expression signature of c-MYC, BCL-2, BCL-XL, and cyclin D1 upon activation of MAPK signaling was not altered by cetuximab treatment, suggesting that this signature may have a pivotal role in cetuximab resistance of RAS-activated HNSCC. Finally, a subset of patients with head and neck cancer with oncogenic HRAS mutations was found to exhibit de novo resistance to cetuximab-based therapy. Conclusions: Collectively, these findings identify a distinct cetuximab resistance mechanism. Oncogenic HRAS in HNSCC promotes activation of ERK signaling, which in turn mediates cetuximab resistance through a specific gene expression signature. Clin Cancer Res; 20(11); 2933–46. ©2014 AACR.
N-myc Oncogene RNA Expression in Neuroblastoma
Authors: P. D. Nisen, P. G.Waber, M. A. Rich, S. Pierce, J. R. Garvin, F. Gilbert, P. Lanzkowsky
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article N-myc Oncogene RNA Expression in Neuroblastoma Get access Perry D. Nisen, Perry D. Nisen * Division of Hematology-Oncology, and M. A. Rich, Division of Urology, Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, and School of Medicine, State Universityof New York at Stony BrookStony Brook, NY *Correspondence to: Perry Nisen, M.D., Division of Hematology-Oncology, Department of Pediatrics, The University of Texas Southwestern Medical School, Dallas, TX 95235-9063. Search for other works by this author on: Oxford Academic PubMed Google Scholar Pamela G.Waber, Pamela G.Waber Division of Hematology-Oncology, and M. A. Rich, Division of Urology, Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, and School of Medicine, State Universityof New York at Stony BrookStony Brook, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark A. Rich, Mark A. Rich Department of Pediatrics, Division of Genetics, Mount Sinai School of MedicineNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Sean Pierce, Sean Pierce Division of Hematology-Oncology, and M. A. Rich, Division of Urology, Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, and School of Medicine, State Universityof New York at Stony BrookStony Brook, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar James R. Garvin, Jr., James R. Garvin, Jr. Division of Pediatric Hematology-Oncology, Babies Hospital, Columbia Presbyterian Medical Center, and Department of Pediatrics, College of Physicians and Surgeons, Columbia UniversityNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Fred Gilbert, Fred Gilbert Department of Pediatrics, Division of Genetics, Mount Sinai School of MedicineNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip Lanzkowsky Philip Lanzkowsky Division of Hematology-Oncology, and M. A. Rich, Division of Urology, Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, and School of Medicine, State Universityof New York at Stony BrookStony Brook, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 20, 21 December 1988, Pages 1633–1637, https://doi.org/10.1093/jnci/80.20.1633 Published: 21 December 1988 Article history Received: 15 August 1988 Revision received: 31 October 1988 Accepted: 31 October 1988 Published: 21 December 1988
Therapeutic Potentials of Ecto‐Nucleoside Triphosphate Diphosphohydrolase, Ecto‐Nucleotide Pyrophosphatase/Phosphodiesterase, Ecto‐5′‐Nucleotidase, and Alkaline Phosphatase Inhibitors
Authors: Mariya al‐Rashida, Jamshed Iqbal
Journal: Medicinal Research Reviews (2013)

Abstract The modulatory role of extracellular nucleotides and adenosine in relevance to purinergic cell signaling mechanisms has long been known and is an object of much research worldwide. These extracellular nucleotides are released by a variety of cell types either innately or as a response to patho‐physiological stress or injury. A variety of surface‐located ecto‐nucleotidases (of four major types; nucleoside triphosphate diphosphohydrolases or NTPDases, nucleotide pyrophosphatase/phosphodiesterases or NPPs, alkaline phosphatases APs or ALPs, and ecto‐5′‐nucleotidase or e5NT) are responsible for meticulously controlling the availability of these important signaling molecules (at their respective receptors) in extracellular environment and are therefore crucial for maintaining the integrity of normal cell functioning. Overexpression of many of these ubiquitous ecto‐enzymes has been implicated in a variety of disorders including cell adhesion, activation, proliferation, apoptosis, and degenerative neurological and immunological responses. Selective inhibition of these ecto‐enzymes is an area that is currently being explored with great interest and hopes remain high that development of selective ecto‐nucleotidase inhibitors will prove to have many beneficial therapeutic implications. The aim of this review is to emphasize and focus on recent developments made in the field of inhibitors of ecto‐nucleotidases and to highlight their structure activity relationships wherever possible. Most recent and significant advances in field of NTPDase, NPP, AP, and e5NT inhibitors is being discussed in detail in anticipation of providing prolific leads and relevant background for research groups interested in synthesis of selective ecto‐nucleotidase inhibitors.
Demonstration of Differential Effects on Pulmonary and Systemic Arterial Pressure by Variation in Oxygen Content of Inspired Air in Patients with Patent Ductus Arteriosus and Pulmonary Hypertension
Authors: HOWARD B. BURCHELL, H. J. C. SWAN, EARL H. WOOD
Journal: Circulation (1953)

Seven cases of patent ductus arteriosus with pulmonary hypertension and reversal of the usual direction of flow are described. Breathing of a low oxygen mixture either initiated or increased the reversed shunt, and breathing 100 per cent oxygen produced the reverse effect. Differences in oxygen saturation and dye-dilution curves recorded simultaneously from the radial and femoral arteries have allowed calculation of differences in the proportion of shunted blood flowing in these arteries and demonstrate that retrograde movement of blood in the aortic arch may occur.