tbuckley/cabot-search huggingface dataset:
Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice
Authors: Heping Yang, Kwangsuk Ko, Meng Xia, Tony W.H. Li, Pilsoo Oh, Jiaping Li, Shelly C. Lu
Journal: Hepatology (2009)

We previously showed that hepatic expression of glutathione (GSH) synthetic enzymes and GSH levels fell 2 weeks after bile duct ligation (BDL) in mice. This correlated with a switch in nuclear anti-oxidant response element (ARE) binding activity from nuclear factor erythroid 2–related factor 2 (Nrf2) to c–avian musculoaponeurotic fibrosarcoma (c-Maf)/V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (MafG). Our current aims were to examine whether the switch in ARE binding activity from Nrf2 to Mafs is responsible for decreased expression of GSH synthetic enzymes and the outcome of blocking this switch. Huh7 cells treated with lithocholic acid (LCA) exhibited a similar pattern of change in GSH synthetic enzyme expression as BDL mice. Nuclear protein levels of Nrf2 fell at 20 hours after LCA treatment, whereas c-Maf and MafG remained persistently induced. These changes translated to ARE nuclear binding activity. Knockdown of c-Maf or MafG individually blunted the LCA-induced decrease in Nrf2 ARE binding and increased ARE-dependent promoter activity, whereas combined knockdown was more effective. Knockdown of c-Maf or MafG individually increased the expression of GSH synthetic enzymes and raised GSH levels, and combined knockdown exerted an additive effect. Ursodeoxycholic acid (UDCA) or S-adenosylmethionine (SAMe) prevented the LCA-induced decrease in expression of GSH synthetic enzymes and promoter activity and prevented the increase in MafG and c-Maf levels. In vivo knockdown of the Maf genes protected against the decrease in GSH enzyme expression, GSH level, and liver injury after BDL. Conclusion: Toxic bile acid induces a switch from Nrf2 to c-Maf/MafG ARE nuclear binding, which leads to decreased expression of GSH synthetic enzymes and GSH levels and contributes to liver injury during BDL. UDCA and SAMe treatment targets this switch. (HEPATOLOGY 2010.)
Abstract 5262: Activating transcription factor 4 regulates RET autophosphorylation and ubiquitin-dependent degradation
Authors: Rozita Bagheri-Yarmand, Gilbert J. Cote, Robert F. Gagel
Journal: Cancer Research (2014)

Abstract RET proto-oncogene, a receptor tyrosine kinase (RTK), activates a complex network of signal transduction pathways that when unregulated contributes to cell transformation. Germ line missense mutations, which give rise to constitutively active oncogenic RET, were found to cause multiple endocrine neoplasia type 2 (MEN2), a dominant inherited cancer syndrome that affects multiple neuroendocrine organs. Recent findings also suggest that impairment of RTK down-regulation or deactivation may be involved in tumorigenesis. The molecular mechanism that functions to attenuate RET signaling remain elusive. ATF4 is a central mediator of integrated stress response pathway. Activation of ATF4 results in tumor cell death under stress conditions thereby suggesting that ATF4 agonists constitute a potential therapeutic strategy for inhibiting tumor growth. Here, we report that ATF4 overexpression in medullary thyroid cancer cells harboring RET C634W mutation decreases RET protein expression but not the mRNA levels. In addition, ATF4 accelerates RET turnover and promotes its ubiquitination. Moreover, a RET kinase dead mutant is more stable than wild type or M918T RET suggesting that kinase activity is required for ATF4-mediated degradation. Finally, ATF4 depletion upregulates RET protein levels and RET autophosphorylation. Our findings unravel ATF4 as a feedback negative attenuator of RET signaling that could be used as a potential therapeutic target for medullary thyroid cancer or other malignancy with RET abnormalities. Citation Format: Rozita Bagheri-Yarmand, Gilbert J. Cote, Robert F. Gagel. Activating transcription factor 4 regulates RET autophosphorylation and ubiquitin-dependent degradation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5262. doi:10.1158/1538-7445.AM2014-5262
Electrocardiographic characteristics and catheter ablation of parahissian accessory pathways.
Authors: M Haissaguerre, F Marcus, F Poquet, L Gencel, P Le Métayer, J Clémenty
Journal: Circulation (1994)

Accessory pathways may be located in close proximity to the His bundle, resulting in a high risk of heart block during attempted surgical or electrical interruption of these pathways. This study reports the prevalence, ECG characteristics, and results of catheter ablation of parahissian accessory pathways. They were defined on the basis of both the presence of a high amplitude (> 0.1 mV) of His bundle potential at the ablation site and an exclusion of anteroseptal or midseptal location of the accessory pathway.Eight patients with a parahissian accessory pathway were identified among 582 consecutive patients who underwent radiofrequency ablation of an accessory pathway. They were six males and two females with a mean age of 21 +/- 9 years. During maximal preexcitation, the ECG showed a positive delta wave in leads I, II, and a VF in all patients: six had a negative delta wave in leads V1 and V2 instead of the positivity usually observed in anteroseptal accessory pathways. This pattern had a sensitivity of 75%, a specificity of 96%, a positive predictive value of 86%, and a negative predictive value of 93% for a parahissian location in comparison with a group of 28 patients with anteroseptal accessory pathways. At the successful ablation site, the mean amplitude of the His bundle potential was 0.2 +/- 0.1 (0.12 to 0.4 mV). All accessory pathways were successfully ablated without causing heart block using 5 to 20 W of radiofrequency energy.Parahissian accessory pathways have a preexcitation pattern that is distinctive from that of anteroseptal accessory pathways. Catheter ablation of these pathways is feasible using low energy with preservation of normal atrioventricular conduction.
Practical Economic Considerations of Clinical Nuclear Magnetic Resonance
Authors: William G. Bradley
Journal: JAMA (1984)

Nuclear magnetic resonance (NMR) has generated more excitement and more confusion in the medical community than any other new technology in recent memory. Nuclear magnetic resonance has been applied to certain areas of clinical imaging where it competes favorably with computed tomography (CT) and ultrasound. It has been applied in research laboratories as a spectroscopic technique where it provides in vivo information about tissue metabolism. Where each of these applications of NMR fits into the general framework of medical diagnosis is yet to be determined. Even after such a medical determination has been made, various economic factors will ultimately determine if NMR will gain widespread use. Currently, NMR can image the body in thin tomographic slices in either the axial, sagittal, or coronal planes. The intensity of the NMR signal is determined by tissue hydrogen density and by the two magnetic relaxation times T1 and T2. Submillimeter spatial resolution has
Student electives overseas
Authors: T. White
Journal: BMJ (1980)

had low toxicity and gave an overall response rate of 73%0.In the multicentre study in 153 patients there were no drug-related deaths.We conclude that intracavitary bleomycin is well tolerated and is effective as palliative treatment for malignant effusions, preventing the need for frequent aspiration of accumulated fluid.Because of its lack of haematological toxicity it may be used safely in the already leucopenic patient.
SALVARSAN TREATMENT OF SYPHILIS: AN ANALYSIS OF TWO HUNDRED CASES
Authors: L. Jones, A. J. Gibson
Journal: BMJ (1917)

whather soft or fibrLous.(A) If fibirous aud almost pinpoint, start dilatatioin "w-ithi gini-elastic boui-gies.Tlhe first tinic youL will probably get in 1, 2, 3, 4 CharriMre, the neXt titile 4, 5, 6, 7, the next time 7, 8, 9, 10, the next timeC 10,11, 12, 13, 14, the next time 14, 15, 16, the next timc 16, 17, 18 Cliarii~re.Wlheln uip to 18 Clharri'rc procced withl your nickel bougies alid work up oni tllese till tlhe meatus (24 to 28 Chlarri6re) wvill not let youL use themii any more.Tlein start with tlho Kollniann's dilators.If tllh stricture is in the builb, work up with tlhese to 45 Charrii're; if in the penile, work up to 30 or 35 Clarr'i'ere.Tlen tell tho patient to come back for urethroseopic 'inspectio'n in six month0llls', time.In the largc mnajority of cases cure will b- found to be permanent if dilatationl has been carried out to these hiigl delgrees.(B) If you findcl a tunnel stricture thiat you can feel frolil the ouLtside, or if you liind that the stricturo will not -dilate up any more than to 8 or 9 Clharririe, theln take' tlhe patient into the hospital for internal unretljrotoiny.Ili actual practice only a few cases will require tlii; operation.Tlieie i-s no moitality-froom clilatatiion, but tlle mortality of interrnal urethrotomy may be as high as 4 to 5 per cent.When the patielit comes out after ani internal uretilrotony, go0 Onl dilatingt witlh nickel bougies and_1 tllen with the KoCullinann's dilators1 as above.The R lottiwe jou Paxssiiqj Dongycs.: Thle paticut passes water.Fill up the bladder withi oxycyanide of mwlercury solution 1 in 4,000 or silver nitrate solution 1 in 5,000 by Janet's mlethod fr'om a height; lubricate and pass tlue bougies.The patient then rises and passes ntit h4is irriaating filid.After the passage of bougics andl Kolliann's dilators wvarn the patient- 1.That he may bleed a little for twenty-fotir lhours.2. That he mnay havo utrethral discharge for twenty-four ]1 OL11 S. _ ,3. That it will hurt himi to pass water for twienty-four hours.110t1L'.S.~V r U~S Never forg-et thlat thio object of dilatations of all kinds is ilot to tear thle stricture or tear tlhe uirethira, but to tire out the stricture as rubber is tiredl.Yotu will find that absorp- tion of the stricttire goes oni between the treatments by plagocyLosis on the part of the tissues.If you tear, this process does not go on, but thle stricture becomes more resistant.Never (lilato more than twice a week, and sually once a week or Once, in ten days is sufficient.S0tAINARSAN-'TREATIENT F SY-PHILIS:.INANAL YSIS OF I[-0) IHUNDRED CASES.
Prenatal diagnosis of thalassemia in the Chinese
Authors: Ta-Chih Liu, Sheng-Fung Lin, Tzu-Yao Yang, Jing-Ping Lee, Tyen-Po Chen, Jan-Gowth Chang
Journal: American Journal of Hematology (1997)

There is a high prevalence of thalassemia in the Taiwan area. Prenatal diagnosis of severe forms of thalassemia is important for the prevention of this disease. We performed prenatal diagnosis in 167 cases, of which 59 cases were diagnosed by chorionic villi biopsy, 91 cases by amniotic fluid analysis, and 17 cases by cord blood analysis. Hb Bart's hydrops was detected by amplifying the break junction area of the α-thalassemia-1 Southeast Asia (SEA)-type gene, and β-thalassemia major was detected by using naturally occurring restriction sites and the amplified created restriction sites (ACRS) method. Screening for hemoglobin (Hg) Bart's hydrops revealed 26 cases of Hb Bart's hydrops, 67 cases of α-thalassemia-1 (including 6 Hb Bart's hydrops falsely diagnosed as α-thalassemia-1 from chorionic villi samples), and 38 normal cases. Screening for β-thalassemia major revealed 8 cases of β-thalassemia major, 17 cases of β-thalassemia minor, and 11 normal cases. In cases of α-thalassemia, maternal tissue contamination in the chorionic villi samples occurred in the diagnosis of the carrier state and further amniotic fluid analysis will be necessary. There were no any false-positive or false-negative results in β-thalassemia major screening. We conclude that prenatal diagnosis is a reliable and accurate screening method for thalassemia and may be valuable in other areas of high prevalence for thalassemia in Southeast Asia and in Southern China. Am. J. Hemat. 55:65-68, 1997. © 1997 Wiley-Liss, Inc.
Psychodynamic Aspects of Psychopharmacology in Functional Somatic Complaints
Authors: U. Rosin, G.-K. Köhler
Journal: Psychotherapy and Psychosomatics (1991)

Psychiatrists as well as general practitioners frequently prescribe psychotropic drugs (tranquilizers such as benzodiazepines and increasingly low-dose long-acting neuroleptics) to treat functional organic complaints. We are interested in finding out the psychodynamics in the doctor-patient relationship that determine whether the doctor puts more emphasis on eliminating symptoms by prescribing psychotropic drugs or on solving the underlying conflicts by psychotherapy. Furthermore we describe some interactions which are of importance for illustrating whether drugs are effective or lead to side effects.
Abstract 3392: Heat shock protein 27 increases metastasis of human head and neck squamous cancer cells <i>in vitro</i>
Authors: Zhenkun Zhu, Xin Xu, Yanke Yu, Martin Graham, Gangli Liu, Mark Prince, Thomas Carey, Duxin Sun
Journal: Cancer Research (2010)

Abstract The small heat shock protein 27 (Hsp27) is a molecular chaperone that is involved in a variety of cellular functions in cancer cells. The purpose of this research is to study the function of Hsp27 in metastasis of head and neck squamous cancer cells. The expression of Hsp27 in primary and metastatic head and neck cancer cells was determined using real-time PCR and western blotting. The siRNA knockdown of Hsp27 was performed in metastatic head and neck cancer cells using in vitro transfection. The proliferation of the primary and metastatic head and neck cancer cells were evaluated using MTS proliferation assay. The metastatic potential was determined using both migration assay and invasion assay in metastatic head and neck cancer cells after siRNA silencing of Hsp27. MTS proliferation showed that both primary (UM-SCC-22A) and metastatic (UM-SCC-22B) head and neck cancer cells have similar proliferation rate from 24-48 hrs. However, the metastatic head and neck cancer cells (UM-SCC-22B) showed more than 2-fold migration ability and more than 3-fold invasion ability than primary head and neck cancer cells (UM-SCC-22A). Real-time PCR demonstrated that Hsp27 mRNA is 22-fold higher in metastatic UM-SCC-22B than primary UM-SCC-22A. Similarly, Western blotting exhibited that primary UM-SCC-22A did not show any detectable levels of Hsp27, while metastatic UM-SCC-22B showed significant high levels (&amp;gt; 40-fold) of Hsp27. siRNA of Hsp27 knocked down expression of Hsp27 by more than 5-fold in mRNA level and 23-fold in protein levels in metastatic head and neck cancer cells UM-SCC-22B. Furthermore, siRNA knockdown of Hsp27 decreased metastasis of UM-SCC-22B by more than 50% in cell invasion assay. These data suggest that Hsp27 may regulate metastatic potential of head and neck squamous cancer cells. Silencing Hsp27 may decrease metastatic potential of head and neck squamous cancer cells. 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 3392.
Pigmentation and confusion
Authors: W.-h. Cheung, J. Dua, J. Reed, S. Russell
Journal: BMJ (2011)

A previously well 51 year old Cypriot woman presented to the emergency department with a five day history of vomiting. She reported no diarrhoea, fever, or abdominal pain. She had no unwell contacts or recent foreign travel. Her medical history included recently diagnosed depression and a review by dermatologists two years previously for generalised darkening of her skin. Her dentist had biopsied an area of discoloration on her gums. 

On examination, her pulse was 100 beats/min, temperature 37.9°C, and blood pressure 107/63 mm Hg. She was dehydrated and had mild epigastric tenderness. Initial blood tests showed a haemoglobin concentration of 118 g/L (normal range 120-152 g/L), white cell count of 2.8×109/L (4.1-10×109/L), neutrophil count of 1.2 mm3(2.5-7.5 mm3), sodium concentration of 131 mmol/L (135-145 mmol/L), potassium concentration of 4.4 mmol/L (3.5-4.5 mmol/L), corrected calcium concentration of 1.98 mmol/L (2.15-2.61 mmol/L), alanine transaminase concentration of 92 U/L (64-83 U/L), alkaline phosphatase concentration of 56 U/L (<55 U/L), bilirubin concentration of 7 µmol/L (0.2-1.3 µmol/L), and C reactive protein concentration of 45 mg/l (<1 mg/l).

The patient was admitted to a general medical ward and overnight became confused, disorientated, and agitated. Observations showed that her heart rate had changed to 110 beats/min, her blood pressure was 98/55 mm Hg, and her temperature had increased to 38°C. Her Glasgow coma scale score was 12, and she had developed brisk reflexes and bilateral extensor plantar responses. Her arterial blood gas showed a pH of 7.29, pO2 of 12.7 kPa, pCO2 of 2.8 kPa, base excess of −15 mmol/L, chloride concentration of −109 mmol/L, and bicarbonate concentration of −10 mmol/L. Her plasma glucose concentration was 1.1 mmol/L.

Figure 1⇓ shows the patient during admission, and figure 2⇓ is a photograph of the patient that was taken …
Rx for the Rural Doctor Shortage
Authors: HAROLD J. HARRIS
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 February 1971Rx for the Rural Doctor ShortageHAROLD J. HARRIS, M.D., F.A.C.P.HAROLD J. HARRIS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-2-296_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: May I comment on the doctor shortage, supplementing the letter of Dr. Thomas Findley (Ann Intern Med 73:490, 1970)?In 1967 I proposed to two medical centers (Albany, N.Y., and Burlington, Vt.) a plan that still seems feasible but that was rejected as impracticable. The essence of the proposal was to require that a resident physician be assigned to any rural practitioner requesting it, for a period of 4 to 6 weeks once or twice yearly. This would serve a severalfold purpose: (1) The rural physician would be free for vacation or postgraduate study during part of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Westport, N.Y. 12993 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1971Volume 74, Issue 2Page: 296-296 Issue Published: 1 February 1971 PDF DownloadLoading ...
Histopathological and electron microscopic studies of lymphangiectasia of the small intestine in Behcet's disease
Authors: H. Asakura, A. Morita, T. Morishita, M. Tsuchiya, Y. Watanabe, Y. Enomoto
Journal: Gut (1973)

The gastrointestinal involvement and immunological findings in 16 patients with Behçet's disease are described. Four of 15 biopsy specimens of jejunal mucosa showed marked lymphangiectasia in the lamina propria similar to the appearance which was thought to be a characteristic finding in protein-losing enteropathy. None of the patients had hypoproteinaemia. Increases in serum immunoglobulin IgA were proved in six of 15 cases; in IgM, five of 15; and in IgG, one of 15. Electron microscopic studies showed that there were thousands of precipitated lymph protein bodies in the extracellular spaces of the lamina propria. Ulcers and healed ulcers of the large intestine were studied by light microscopy.
Endothelial Cells Inhibit Flow-Induced Smooth Muscle Cell Migration
Authors: Eileen M. Redmond, John P. Cullen, Paul A. Cahill, James V. Sitzmann, Steingrimur Stefansson, Daniel A. Lawrence, S. Steve Okada
Journal: Circulation (2001)

Background —The endothelium may play a pivotal role in hemodynamic force–induced vascular remodeling. We investigated the role of endothelial cell (EC) plasminogen activator inhibitor-1 (PAI-1) in modulating flow-induced smooth muscle cell (SMC) migration. Methods and Results —Human SMCs cocultured with or without human ECs were exposed to static (0 mL/min) or flow (26 mL/min; shear stress 23 dyne/cm 2 ) conditions for 24 hours in a perfused capillary culture system. SMC migration was then assessed with a Transwell migration assay. In the absence but not in the presence of ECs, pulsatile flow significantly increased the migration of SMCs (264±26%) compared with SMCs under static conditions, concomitant with a 3- and 4-fold increase in PAI-1 mRNA and protein, respectively, in cocultured ECs. In the presence of PAI-1−/− ECs, flow increased wild-type SMC migration (226±25%), an effect that was reversed by exogenous PAI-1. To determine whether the antimigratory activity of PAI-1 was dependent primarily on inhibition of PAs or its association with vitronectin, experiments were conducted with PAI-1R (a mutant PAI-1 that binds to vitronectin but does not inhibit PA) and PAI-1K (a mutant that inhibits PA but has reduced affinity for vitronectin). PAI-1R inhibited both basal and flow-induced migration, whereas PAI-1K inhibited flow-induced migration in the absence of any effect on baseline migration. Conclusions —Flow-induced EC PAI-1 inhibits flow-induced SMC migration in vitro. EC PAI-1 expression may be one of the predominant mechanisms responsible for controlling the process of vascular remodeling.
Avoiding Papillary Muscle Infarction With Myocardial Contrast Echocardiographic Guidance of Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy
Authors: Sherif F. Nagueh, Nasser M. Lakkis, Katherine J. Middleton, Jennifer Franklin, William H. Spencer
Journal: Circulation (2004)
Objective Assessment in Asthma
Authors: I. Gregg
Journal: BMJ (1962)

Summary: When squamous cell carcinoma (SCC) involves the palatine tonsils, they are generally enlarged and demonstrate intermediate to high signal intensity on T2-weighted MR images and enhance after gadolinium administration. We have identified two patients with SCC of the tonsil where the affected tonsil has low signal intensity on T2-weighted MR images and is smaller than the contralateral normal tonsil. We present the “small, dark tonsil” as an alternative imaging presentation of SCC and a new sign to look for when evaluating the patient with metastatic lymphadenopathy from an unknown primary tumor.