tbuckley/cabot-search huggingface dataset:
Role of the cyclic AMP response element in rat fibronectin gene expression
Authors: Sun Miao, Parmjeet K. Suri, Liu Shu-Ling, Ann Abraham, Nanette Cook, Patrice Milos, Mark A. Zern
Journal: Hepatology (1993)

Fibronectin expression is of considerable importance in normal and fibrotic liver. Plasma fibronectin levels are correlated with good prognosis in liver failure, and cellular fibronectin plays a crucial role in fibrogenesis. In this study, we observed that the H4II rat hepatoma cell line does not express fibronectin. Furthermore, a recombinant vector (pFGH) containing the promoter elements of the fibronectin gene showed no promoter function when transfected into this cell line. However, pFGH was actively expressed in L-cells and rat skin fibroblasts, cell types that express large amounts of endogenous fibronectin. To study the mechanisms regulating fibronectin expression, we evaluated the transcriptional regulatory elements of the rat fibronectin gene by mutational analysis and DNA-protein binding studies. Deletional mutation analysis showed that the sequences between positions - 164 and -90 are essential for promoter activity. This region contains the consensus binding sites for CCAAT and the cyclic AMP-responsive element. Gel retardation assays demonstrated that although the binding activity to the CCAAT site at - 140 was essentially the same as that in extracts from L-cells, hepatoma cells and rat livers, substantially greater amounts and different patterns of binding to the adjacent cyclic AMP-responsive element were observed in the extracts from the expressing L-cells and rat livers compared with those in the nonexpressing hepatoma cell nuclear extracts. Furthermore, mutagenesis of the cyclic AMP-responsive element site dramatically reduced promoter activity in transient transfection assays. The cyclic AMP-responsive element at position -160 appears to play an important role in the constitutive expression of the rat fibronectin gene. (Hepatology 1993;17:882-890.)
JAMA's Contributing Writers
Authors: Catherine D. DeAngelis, Phil B. Fontanarosa
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity reactions to iodinated contrast media
Authors: M. J. Torres, F. Gomez, I. Doña, A. Rosado, C. Mayorga, I. Garcia, N. Blanca‐Lopez, G. Canto, M. Blanca
Journal: Allergy (2012)

Abstract Background Nonimmediate hypersensitivity reactions to iodinated contrast media ( CM ) are common. Allergological evaluation is necessary to confirm the diagnosis and to find a tolerated alternative. The aim of this study was to establish the role of skin testing and the drug provocation test ( DPT ) in the diagnosis of nonimmediate reactions to CM . Methods Skin intradermal testing and patch testing with delayed readings were carried out with different CM (iobitridol, iomeprol, iodixanol, iohexol, ioversol, iopramide and ioxaglate). Single‐blind placebo‐controlled DPT was carried out in those cases with a negative skin test. In seven cases, a skin biopsy was obtained from positive skin tests and positive DPT . Results Of the 161 subjects evaluated, 34 (21.1%) were skin‐test positive, 21 (50%) to I omeprol, 7 (16.7%) to I odixanol, 5 (11.9%) to Iobitridol, 4 (9.5%) to I oxaglate, 3 (7.1%) to I ohexol and 1 (2.4%) to I opramide. DPT was positive in 44 cases (34.6%) that were skin‐test negative, 38 (76%) to I odixanol, 8 (16%) to I omeprol and 4 (8%) to I ohexol. Of 78 cases (48.4%) with confirmed hypersensitivity, 34 (43.6%) were identified by skin testing and 44 (56.4%) by DPT . Skin biopsies showed a perivascular mononuclear cell infiltrate, mainly in the dermis, with higher levels of CD 4 than CD 8 T lymphocytes, with expression of activation markers and skin homing receptors. Conclusion Patients with nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT in 56.4%. The method to confirm the diagnosis differed depending on the CM involved.
Treatment of Rheumatoid Arthritis with Gammalinolenic Acid
Authors: Lawrence J. Leventhal
Journal: Annals of Internal Medicine (1993)

Objective: To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models. Design: A randomized, double-blind, placebo-controlled, 24-week trial. Setting: Rheumatology clinic of a university hospital. Patients: Thirty-seven patients with rheumatoid arthritis and active synovitis. Intervention: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo). Measurements: Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities. Results: Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions. Conclusion: Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than used in this trial. It is not approved in the United States for the treatment of any condition and should not be viewed as therapy for any disease. Further controlled studies of its use in rheumatoid arthritis are warranted.
Imported Plasmodium falciparum Malaria in American Travelers to Africa
Authors: Eve M. Lackritz
Journal: JAMA (1991)

Data from the US National Malaria Surveillance System were analyzed to assess characteristics of travelers who acquired<i>Plasmodium falciparum</i>infections in Africa and evaluate the impact of chloroquine resistance on the incidence of imported malaria. Although the number of cases acquired in East Africa has stabilized, the number of imported<i>P falciparum</i>infections acquired in West Africa increased threefold from 1985 to 1988, and the proportion of travelers who reported failure of chloroquine prophylaxis increased from 10% to 48%. Fifty-eight percent of patients who acquired malaria in West Africa had not used chemoprophylaxis. To curb the rising incidence of<i>P falciparum</i>infections in American travelers, the Centers for Disease Control revised malaria prophylaxis recommendations to include the use of mefloquine in areas of chloroquine resistance. Use of malaria protection measures by travelers to West Africa must also be improved. (<i>JAMA</i>. 1991;265:383-385)
Effects of topical treatment with H<sub>1</sub> and H<sub>2</sub> antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis
Authors: K. Holmberg, U. Pipkorn, B. Bake, L.‐O. Blychert
Journal: Allergy (1989)

Fifteen asymptomatic subjects with allergic rhinitis participated in a double‐blind, randomized, crossover, placebo‐controlled study. The subjects were pretreated intra‐nasally with a single dose of a selective H 1 receptor antagonist, levocabastine, and/or selective H 2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133 Xe wash‐out technique. After pretreatment with the H 1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H 2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H 1 and the H 2 antagonists. Pretreatment with the H 1 and/or the H 2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen‐induced reflex‐mediated symptoms. H 1 and H 2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H 1 and H 2 receptors on the capacitance vessels of the nasal mucosa alone. Both H 1 and H 2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.
Abstract 1587: Targeted deletion of Fra-1 blocks oncogenic K-ras induced lung tumor development and progression in mice
Authors: Michelle Vaz, Narsa M. Reddy, Erwin F. Wagner, Sekhar P. Reddy
Journal: Cancer Research (2010)

Abstract Background: Fra-1 (Fosl1) is a dimeric partner of AP-1 transcription factor and regulates gene expression in a context-dependent (cell-type and stimulus-specific) manner through the TPA response element (AP-1 site). We have previously shown that Fra-1 is strongly activated in lung epithelial cells by cigarette smoke, a major determinant of lung cancer, as well as tumor promoting mitogenic and pro-inflammatory stimuli. Ectopic expression of Fra-1 promotes human lung cancer cell progression in vitro, and tumor development in nude mice. We hypothesized that Fra-1, an effector of ERK signaling, is required for oncogenic K-ras promoted lung tumor development in vivo. Methods: To test our hypothesis and to better understand the role of Fra-1 in lung tumor development and progression in vivo, we have generated transgenic mice bearing floxed allele Fra-1 (Fra-1FF) and LSL K-rasG12D by cross-breeding Fra1F/F and LSL K-rasG12D mice (NCI), which carry a latent point-mutant allele of K-ras (K-rasG12D). Fra1wt/wt +LSL-K-rasG12D mice (abbreviated as Kras+/−) and Fra1F/F+ LSL-K-rasG12D mice (Fra1FF- K-rasG12D) were instilled intratracheally with adenovirus Cre (2.5 ×107 pfu) and then were allowed to recover for an additional 13 weeks. Mice were sacrificed, lungs were fixed, and lung tumor induction was analyzed by histopathology. Results: As anticipated, activation of K-ras oncogene by Ade-Cre instillation induced lung tumor development in Kras+/− mice bearing Fra-1 wild type alleles. Hyperplastic lesions with papillary structures and adenomas were clearly visible in these mice. Strikingly, the lung tumor formation in Fra-1 floxed mice bearing LSL-K-rasG12D allele (Fra1F/F+ LSL-K-rasG12D mice) infected with Adeno-cre virus was markedly reduced. In all animals, with exception of few hyperplastic lesions, no adenomas were detected in mice lacking Fra-1. Conclusions: The present data suggest that Fra-1 is critical for oncogenic K-ras promoted lung tumor development in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1587.
Reduced vasoactive responses in port wine stains
Authors: S.W. LANIGAN, J.A. COTTERILL
Journal: British Journal of Dermatology (1990)

Changes in skin blood flow and haemoglobin content of port wine stains and clinically normal contralateral skin were determined by laser-Doppler flowmetry and reflectance spectrophotometry in 14 patients after application of a vasodilating cream containing methyl nicotinate 1.0%, glycol salicylate 10.0% and capsaicin BPC 0.1% (Algipan cream) and in 16 patients after application of a corticosteroid tape containing flurandrenolone (Haelan tape). Changes in blood flow measured after application of vasodilator cream were significantly reduced in port wine stains compared with contralateral skin (P less than 0.01). After application of the vasoconstrictor steroid tape changes in blood flow were significantly reduced in the port wine stains (P less than 0.05) and changes in haemoglobin content were also significantly reduced in the port wine stains compared with normal skin (P less than 0.05). These results support the concept of reduced autonomic innervation of cutaneous vasculature in port wine stains.
Early Morphologic and Enzymatic Changes in Livers of Rats Treated with Chenodeoxycholic and Ursodeoxycholic Acids
Authors: Sarah Shefer, George F. Zaki, Gerald Salen
Journal: Hepatology (1983)

The effect of high doses of chenodeoxycholic and ursodeoxycholic acids on hepatic morphology and on cholesterol and hile acid metabolism was examined in the rat. After 2 weeks of either cheno or ursodeoxycholic acid feeding, the livers of the treated rats revealed marked proliferation of the smooth endoplasmic reticulum which appeared as an adaptation phenomenon of the microsomal enzyme system in response to bile acid intake. However, the livers of the chenodeoxycholic acid–treated rats showed early alteration that included mild triaditis, swelling of the bile canalicular microvilli, distended Golgi vesicles, whorling of the mitochondria, and presence of large vacuoles bound by single membranes. During cheno– or ursodeoxycholic acid treatment, the administered bile acid predominated in the bile and amounted to 79 or 67% of the biliary bile acids, respectively. At the same time, the concentration of the muricholic acids was also increased. Biliary cholic acid content dropped significantly, but no change in lithocholic acid concentration was observed. In addition, the activity of HMG–CoA reductase as well as that of cholesterol–7a–hydroxylase was reduced by either of the administered bile acids, while no change in hepatic cholesterol content was detected, and intestinal cholesterol absorption was not significantly different from that of controls. These results show that cheno– and ursodeoxycholic acids inhibited hepatic cholesterol and bile acid synthesis but did not increase either intestinal cholesterol absorption or hepatic microsomal cholesterol content. Since the amounts of biliary lithocholic acid were similar in the bile acid–treated animals, the morphologic abnormalities detected in the chenodeoxycholic acid–fed rats are probably due to an increased pool of chenodeoxycholic acid. However, lithocholic acid–induced liver injury cannot be excluded.
Abstract 686: Potentiation of the cytocidal effect of streptozotocin on carcinoid neuroendocrine cells by a pharmacological inhibitor of poly(ADP-ribose) polymerase
Authors: Véronique Richard, Girish M. Shah
Journal: Cancer Research (2010)

Abstract Carcinoid neuroendocrine tumors (CNETs) are resistant to chemotherapy and the higher level doses of single or combination chemotherapy that are effective against these cancers also cause significant side-effects to the surrounding healthy tissues; therefore it is necessary to potentiate chemotherapy of these cancers. In the advanced clinical trials for different cancers, the pharmacological inhibitors of the DNA damage-responsive nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1 or PARP) have shown a significant promise either as monotherapy or as potentiators of other chemotherapeutic agents. Here, we examined whether PARP-inhibitor PJ-34 can potentiate the therapy of CNETs by streptozotocin (STZ), because STZ causes DNA damage that is repaired by base excision repair pathway in which PARP-1 is known to play a significant role. We used the CNDT2.5 as model NET cells to show that treatment of cells with 1 μM PJ-34 could effectively block the activation of PARP in response to 0.5 and 1 mg/ml STZ. We also show that lower dose of STZ (0.5 mg/ml), which had no impact on the viability or the clonogenicity of cells becomes cytocidal by co-treatment with PJ-34. The potentiation effect by PJ-34 was also seen at higher (1 mg/ml) doses of STZ. We are currently examining the mechanism of potentiation of STZ in NETs by PARP-inhibitors. In conclusion, our results demonstrate that PARP-inhibitor can significantly potentiate therapeutic efficacy of STZ against NETs, and thus add back the chemotherapy option against these cancers. Acknowledgment: We are thankful to the Canadian Institutes of Health Research for the Banting &amp; Best Graduate Scholarship to VR and the research grant support (Grant # MOP-89964) to GMS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 686.
Hypoglycemic Symptoms and Decreased β-Adrenergic Sensitivity in Insulin-Dependent Diabetic Patients
Authors: Ivan Berlin, André Grimaldi, Christine Payan, Claude Sachon, Frédérique Bosquet, Francis Thervet, Alain J Puech
Journal: Diabetes Care (1987)

Thirty-seven insulin-dependent diabetic patients were tested for symptoms of hypoglycemia, cardiac autonomic neuropathy (i.e., heart rate variation during deep breathing, Valsalva maneuver, immediate heart rate response to standing), and isoproterenol sensitivity (defined as the dose of isoproterenol required to increase heart rate by 25 beats/min: I25). Tests of cardiac autonomic neuropathy showed no relation to hypoglycemic symptoms. On the contrary, a clear relationship could be established between isoproterenol sensitivity and adrenergic symptoms of hypoglycemia. Diabetic patients with decreased response to isoproterenol had fewer adrenergic symptoms, perceived hypoglycemia at a lower blood glucose level, and had more hypoglycemic accidents. Symptoms most related to isoproterenol sensitivity were tremor, sweaty palms, and hunger. With the isoproterenol-sensitivity test a distinction could be made between the groups at high (I25 greater than 3 micrograms) and low (I25 less than 3 micrograms) risk for hypoglycemic accidents. We suggest that the isoproterenol-sensitivity test could be used to identify diabetic patients at increased risk for hypoglycemia.
Adding aspirin to clopidogrel worsened outcomes in PCI patients receiving oral anticoagulants
Authors: Brigitta C. Brott
Journal: Annals of Internal Medicine (2013)

Source Citation Dewilde WJ, Oirbans T, Verheugt FW, et al; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013; 381:1107-15. 23415013
The mapping from acoustic structure to the phonetic categories of speech: The invariance problem
Authors: Sheila E. Blumstein
Journal: Behavioral and Brain Sciences (1998)

This commentary focuses on the nature of combinatorial properties for speech and the locus equation. The presence of some overlap in locus equation space suggests that this higher order property may not be strictly invariant and may require other cues or properties for the perception of place of articulation. Moreover, combinatorial analysis in two-dimensional space and the resultant linearity appear to have a “special” status in the development of this theoretical framework. However, place of articulation is only one of many phonetic dimensions in language. It is suggested that a multidimensional space including patterns derived in the frequency, amplitude, and time domains will be needed to characterize the phonetic categories of speech, and that although the derived properties ultimately may not meet the conditions of linearity, they will reflect a higher order acoustic invariance.
Joint Guideline Focuses on COPD Care
Authors: B. M. Kuehn
Journal: JAMA (2011)

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The Story of Medicine
Authors: Lester S. King
Journal: JAMA (1969)

Here is a popular history of medicine, lavishly illustrated, that we can heartily recommend. The author is not writing for the historian but for the layman, or for physicians whose knowledge of medical history is slender, and he has kept his audience clearly in mind at all times. Consequently the text is pitched at a popular level and does not bog down in minutiae, nor in interminable lists of names. Margotta has covered the entire field of medicine from primitive man to the modern period, and has done so in a brief compass. Nevertheless, the story is a connected one, distinguished by careful selection and an adequate presentation of major concepts. Then, the author has related the medical achievements to the culture of the different periods, and thereby has given substance and vitality to what otherwise might have been a rather bare chronicle. The great glory of the book is