tbuckley/cabot-search huggingface dataset:
S-adenosylhomocysteine sensitizes to TNF-? hepatotoxicity in mice and liver cells: A possible etiological factor in alcoholic liver disease
Authors: Zhenyuan Song, Zhanxiang Zhou, Silvia Uriarte, Lipeng Wang, Y. James Kang, Theresa Chen, Shirish Barve, Craig J. McClain
Journal: Hepatology (2004)

In alcoholic liver disease, tumor necrosis factor-α (TNFα) is a critical effector molecule, and abnormal methionine metabolism is a fundamental acquired metabolic abnormality. Although hepatocytes are resistant to TNFα-induced killing under normal circumstances, previous studies have shown that primary hepatocytes from rats chronically fed alcohol have increased TNFα cytotoxicity. Therefore, there must be mechanisms by which chronic alcohol exposure "sensitizes" to TNFα hepatotoxicity. S-adenosylhomocysteine (SAH) is product of methionine in transsulfuration pathway and a potent competitive inhibitor of most methyltransferases. In this study, we investigated the effects of increased SAH levels on TNFα hepatotoxicity. Our results demonstrated that chronic alcohol consumption in mice not only decreased hepatic S-adenosylmethionine levels but also increased hepatic SAH levels, which resulted in a significantly decreased S-adenosylmethionine-to-SAH ratio. This was associated with significant increases in hepatic TNFα levels, caspase-8 activity, and cell death. In vitro studies demonstrated that SAH-enhancing agents sensitized hepatocytes to TNFα killing, and the death was associated with increased caspase-8 activity, which was blocked by a caspase-8 inhibitor. In addition, increased intracellular SAH levels had no effect on nuclear factor κB activity induced by TNFα. In conclusion, these results provide a new link between abnormal methionine metabolism and abnormal TNFα metabolism in alcoholic liver disease. Increased SAH is a potent and clinically relevant sensitizer to TNFα hepatotoxicity. These data further support improving the S-adenosylmethionine-to-SAH ratio and removal of intracellular SAH as potential therapeutic options in alcoholic liver disease. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;40:989–997.)
Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible.
Authors: J C Drapier, J B Hibbs
Journal: Journal of Clinical Investigation (1986)

Previous studies show that cytotoxic activated macrophages cause inhibition of DNA synthesis, inhibition of mitochondrial respiration, and loss of intracellular iron from tumor cells. Here we examine aconitase, a citric acid cycle enzyme with a catalytically active iron-sulfur cluster, to determine if iron-sulfur clusters are targets for activated macrophage-induced iron removal. Results show that aconitase activity declines dramatically in target cells after 4 h of co-cultivation with activated macrophages. Aconitase inhibition occurs simultaneously with arrest of DNA synthesis, another early activated macrophage-induced metabolic change in target cells. Dithionite partially prevents activated macrophage induced aconitase inhibition. Furthermore, incubation of injured target cells in medium supplemented with ferrous ion plus a reducing agent causes near-complete reconstitution of aconitase activity. The results show that removal of a labile iron atom from the [4Fe-4S] cluster, by a cytotoxic activated macrophage-mediated mechanism, is causally related to aconitase inhibition.
Immediate surgery reduced long-term risk for nonperioperative stroke in severe asymptomatic carotid artery stenosis
Authors: Tamer Ammar, Ken Uchino
Journal: Annals of Internal Medicine (2011)

Source Citation Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376:1074-84. 20870099
361 EFFICACY OF SEQUENTIAL TRANSARTERIAL CHEMOEMBOLIZATION PLUS PERCUTANEOUS ETHANOL INJECTION FOR THE TREATMENT OF INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA: RESULTS OF A PILOT STUDY
Authors: J.F. Castroagudin, E. Molina, M. Garcia-Vazquez, C. Seoane, S. Seijo, A.M. Alvarez
Journal: Journal of Hepatology (2008)
Xanthomatous Pseudospectacles in Familial Hypercholesterolemia
Authors: M P Girish, Mohit Dayal Gupta
Journal: New England Journal of Medicine (2005)

A 40-year-old woman presented with exertional chest pain and was found to have familial hypercholesterolemia (type IIa) and severe three-vessel coronary artery disease. Xanthoma palpebrarum was noted on physical examination, manifested as pseudospectacles (Panel A). The patient also had associated tuberous xanthomas of tumorous proportion on the buttocks, hands, and feet (Panels B and C). Her lipid profile revealed the following levels: total cholesterol, 550 mg per deciliter (14.22 mmol per liter); triglycerides, 180 mg per deciliter (2.03 mmol per liter); high-density lipoprotein cholesterol, 34 mg per deciliter (0.88 mmol per liter); and low-density lipoprotein cholesterol, 480 mg per deciliter . . .
Only One Man Died: The Medical Aspects of the Lewis and Clark Expedition
Authors: William R. Barclay
Journal: JAMA (1980)

Eldon Chuinard, MD, clinical professor of orthopedics at the University of Oregon School of Medicine and past president of the Oregon Medical Society, has done a distinct service to the history of medicine by describing the Lewis and Clark expedition from a medical rather than a geographic point of view. The time between the Lewis and Clark expedition and the present is relatively short, while the change in medical practice in that time is enormous. When this band of hardy explorers began their journey in 1803, the principal treatment for all illnesses was blood-letting, a practice enthusiastically employed by Benjamin Rush, MD, who provided Lewis with instruction in the art of venesection. The expedition did not include a physician in its ranks, which is perhaps just as well in view of the treatments used at that time. <i>Continued on p 2529</i>.<i>Continued from p 2528</i>. The explorers suffered from physical
Angioedema after Substituting Lisinopril for Captopril
Authors: Sean McElligott, Mark Perlroth, Linda Raish
Journal: Annals of Internal Medicine (1992)

Letters1 March 1992Angioedema after Substituting Lisinopril for CaptoprilSean McElligott, PharmD, Mark Perlroth, MD, Linda Raish, PharmDSean McElligott, PharmDSearch for more papers by this author, Mark Perlroth, MDSearch for more papers by this author, Linda Raish, PharmDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-116-5-426_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Angiotensin-converting enzyme inhibitors are now among the ten most frequently prescribed drugs in the United States (1). Increased prescription of these inhibitors has exposed more persons to the possibly life-threatening side effect of angioedema (2). The risk for angioedema is estimated to be between 0.1% and 0.2% in patients receiving an angiotensin-converting enzyme inhibitor (3). Angioedema commonly involves the face and oropharyngeal tissues and can result in acute airway obstruction that necessitates emergency intervention. Such obstruction has been reported with the three most commonly prescribed of these inhibitors: captopril, enalapril, and lisinopril (2, 3). Other investigators have...References1. Simonsen L. What are pharmacists dispensing most often? Pharmacy Times. 1991;57-71. Google Scholar2. BarnaFrable JM. Life-threatening angioedema. Otolaryngol Head Neck Surg. 1990;103:795-8. CrossrefMedlineGoogle Scholar3. OrfanPattersonDykewicz NRM. Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema. JAMA. 1990;264:1287-9. CrossrefMedlineGoogle Scholar4. GannonEby TT. Angioedema from angiotensin converting enzyme inhibitors: a cause of upper airway obstruction. Laryngoscope. 1990;100:1156-60. CrossrefMedlineGoogle Scholar5. ChinBuchan HD. Severe angioedema after long-term use of an angiotensin-converting enzyme inhibitor [Letter]. Ann Intern Med. 1990;112:312-3. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Sean McElligott, PharmD; Mark Perlroth, MD; Linda Raish, PharmDAffiliations: Stanford University Hospital Stanford, CA 94305 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug ReactionsAdverse Dermatologic Effects of Cardiovascular Drug Therapy: Part IIAngiotensin converting enzyme inhibitor-induced angioedema more prevalent in transplant patientsAtypical Presentation of Angioedema Associated with an Angiotensin-Converting Enzyme InhibitorETIOLOGY OF URTICARIA AND ANGIOEDEMA IN THE ELDERLYAntihypertensive drugsFatal Angioedema Associated with LisinoprilLisinopril 1 March 1992Volume 116, Issue 5Page: 426-427KeywordsAngiotensin converting enzyme inhibitorDrugs ePublished: 1 December 2008 Issue Published: 1 March 1992 PDF downloadLoading ...
The Hazard of Transfusion Malaria after the War
Authors: A. Daniel Rubenstein, Maurice H. Shulman, Dudley Merrill
Journal: New England Journal of Medicine (1945)

ACCIDENTAL malaria subsequent to blood transfusion has not been a frequent occurrence in nonendemic areas. Since 1929 only 12 such cases have been reported to the Massachusetts Department of Public Health. In some other parts of the globe this route of transmission is more frequent. In Peiping, China, for example, Wang and Lee1 reported 54 cases of malaria complicating 3700 transfusions over a period of ten years. Thoroughman,2 working in Kiangsu, China, where malaria is encountered throughout the year, reported 45 cases of malaria after the administration of whole blood to 104 patients. In such endemic areas it is practically . . .
Production of and in vitro response to interleukin 2 in the acquired immunodeficiency syndrome.
Authors: H W Murray, K Welte, J L Jacobs, B Y Rubin, R Mertelsmann, R B Roberts
Journal: Journal of Clinical Investigation (1985)

To test the hypothesis that deficient interleukin 2 (IL-2) secretion may underlie the impaired capacity of T cells from patients with Acquired Immunodeficiency Syndrome (AIDS) and the AIDS-related complex (ARC) to generate the macrophage-activating lymphokine, gamma interferon (IFN-gamma), we used five specific microbial antigens to examine IL-2 production. Mononuclear cells from only one of 32 (3%) AIDS patients secreted normal levels of IL-2, and 21 (66%) failed to produce any detectable IL-2. For 36 ARC patients, IL-2 generation was normal in nine (25%) and absent in 11 (31%). Given these results, recombinant (r) IL-2 was tested for its capacity to stimulate or enhance IFN-gamma production. rIL-2 (10 U/ml) alone stimulated cells from controls, ARC, and AIDS patients to secrete 93 +/- 25, 99 +/- 33, and 7 +/- 3 U/ml of IFN-gamma, respectively. rIL 2 (10 U/ml) plus antigen induced no change in mean IFN-gamma levels for controls, a 4.4-fold increase for 17 AIDS patients (16 +/- 16 vs. 71 +/- 21 U/ml), and a 7.2-fold increase (18 +/- 5 vs. 130 +/- 27 U/ml) for 19 ARC patients with abnormal IFN-gamma generation to antigen alone. Individual responses indicated that six of the 17 (35%) AIDS patients with opportunistic infections and 12 of the 19 (63%) with ARC were apparent responders to 10-100 U/ml of rIL-2. These results (a) document profound impairment in antigen-induced IL-2 secretion by AIDS and ARC T cells, (b) indicate that, in vitro, mononuclear cells from certain patients can respond to rIL-2 with enhanced IFN-gamma production, and thus (c) suggest that in selected patients rIL-2 might have a potentially beneficial therapeutic (AIDS) or prophylactic (ARC) effect against opportunistic infections.
GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases
Authors: Hari Hendarto, Toyoshi Inoguchi, Yasutaka Maeda, Noriko Ikeda, Jing Zheng, Ryoko Takei, Hisashi Yokomizo, Eiichi Hirata, Noriyuki Sonoda, Ryoichi Takayanagi
Journal: Metabolism (2012)
Comparison of endoscopic closure modalities for standardized colonic perforations in a porcine colon model
Authors: R. Voermans, F. Vergouwe, P. Breedveld, P. Fockens, M. van Berge Henegouwen
Journal: Endoscopy (2011)

See also: Commentaire de travail de R. P. Voermans et al., pp. 217Endoscopy 2011; 43(03): 250-250DOI: 10.1055/s-0031-1291809
Positive Results on Tests for Steatorrhea in Persons Consuming Olestra Potato Chips
Authors: Ranga Balasekaran, Jack L. Porter, Carol A. Santa Ana, John S. Fordtran
Journal: Annals of Internal Medicine (2000)

Background: Olestra is a nonabsorbable fat substitute that consists of fatty acids esterified to a sucrose molecule. Objective: To determine the effect of olestra consumption on measurements of fecal fat excretion. Design: Controlled cross-over trial. Setting: Clinical research center and outpatient research laboratory. Participants: 10 healthy volunteers. Intervention: On days 1 to 6 of the study, participants consumed 5 oz of conventional potato chips per day; on days 7 to 12, they consumed 5 oz of potato chips containing 40 g of olestra per day. Measurements: Quantitative measurement of fecal fat by the van de Kamer titration, van de Kamer gravimetric, and Jeejeebhoy gravimetric methods and qualitative assessment of fecal fat by Sudan III staining. Results: Excellent correlation was seen among the three quantitative assays, but the van de Kamer titration method yielded lower measurements than the two gravimetric methods. When participants consumed 40 g of olestra per day, the excretion of fecal fat increased to levels observed in patients with steatorrhea caused by the malabsorption syndrome. Conclusion: Consumption of olestra can cause false-positive results on tests for steatorrhea and may therefore lead to an erroneous diagnosis of the malabsorption syndrome.
High Risk of Active Tuberculosis in HIV-Infected Drug Users With Cutaneous Anergy
Authors: Peter A. Selwyn
Journal: JAMA (1992)

To determine the incidence of active tuberculosis in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative drug injectors with cutaneous anergy and to examine the effectiveness of isoniazid chemoprophylaxis in preventing tuberculosis among drug injectors with positive tuberculin test results.Prospective observational study linked to an ongoing study of HIV infection within a New York City (NY) methadone program; subjects also underwent routine intradermal tuberculin testing and multiple-antigen delayed-type hypersensitivity skin testing. The 31-month study period ended December 31, 1990.Anergic subjects and tuberculin reactors who were HIV seropositive were compared by HIV disease status and CD4+ T-lymphocyte levels. Tuberculosis incidence was calculated for anergics (none treated with isoniazid) and for treated and untreated tuberculin reactors, by HIV serological status.Among those seropositive for HIV, anergic subjects had more advanced HIV disease and fewer CD4+ cells (median 0.33 vs 0.56 x 10(9)/L, P less than .01) compared with tuberculin reactors, although neither clinical status nor CD4+ cell counts consistently predicted anergy. Five (7.6%) of 68 anergic subjects who were HIV seropositive and none of 52 anergic subjects who were HIV seronegative (n = 18) or of unknown (n = 34) HIV serological status developed active tuberculosis during the study period (P less than .05). The tuberculosis incidence rate among anergic subjects who were HIV seropositive was 6.6 cases per 100 person-years (95% confidence interval [Cl], 2.1 to 15.3). Of 25 HIV-seropositive tuberculin reactors who did not receive or complete 12 months of isoniazid prophylaxis, tuberculosis incidence was 9.7 cases per 100 person-years (95% Cl, 2.6 to 24.7; P = 0.56, compared with the rate among anergic HIV seropositives); there were no cases of tuberculosis in 53.4 person-years of follow-up for 27 HIV-seropositive tuberculin reactors who received 12 months of prophylaxis (rate difference between treated and untreated groups, 9.7 cases per 100 person-years, 95% Cl, 1.3 to 18.0).Drug injectors with cutaneous anergy who are seropositive for HIV are at high risk of active tuberculosis, similar to that among untreated HIV-seropositive tuberculin reactors. A decreased incidence of active tuberculosis was seen in HIV-seropositive tuberculin reactors receiving 12 months of isoniazid chemoprophylaxis, compared with untreated or partially treated subjects. These results support the routine use of delayed-type hypersensitivity testing to accompany tuberculin testing for drug injectors with known or suspected HIV infection, and consideration of isoniazid prophylaxis for anergic as well as tuberculin-reactive subjects who are HIV seropositive, in populations with a high prevalence of coexisting HIV and Mycobacterium tuberculosis infection.
Respiratory muscle dysfunction associated with human immunodeficiency virus infection.
Authors: L Schulz, H N Nagaraja, N Rague, J Drake, P T Diaz
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Although skeletal muscle abnormalities have been described in association with human immunodeficiency virus (HIV), the effects of HIV infection on respiratory muscle function have not been well characterized. We hypothesized that HIV+ individuals may develop respiratory muscle weakness and that respiratory muscle dysfunction may contribute to the unexplained dyspnea that occurs in the setting of HIV. To test this hypothesis we studied maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), inspiratory muscle endurance, and respiratory symptoms in 23 HIV+ male outpatients who had no history of acquired immune deficiency syndrome (AIDS)-related pulmonary complications, with a CD4+ T-lymphocyte count of 331.6 +/- 62.1 (mean +/- SEM). Respiratory muscle endurance was measured with an incremental threshold loading (ITL) protocol. We compared these results to those for 14 HIV- males matched for age and weight. Compared with the controls, HIV+ subjects had a significantly lower mean MIP (98.7 +/- 7.4 versus 121.4 +/- 9.3 cm H2O, p < 0.05) and MEP (115.0 +/- 9.3 versus 152.1 +/- 14.8 cm H2O, p < 0.05). Furthermore, during ITL, the mean load at task failure in the HIV+ group was 295.7 +/- 36.2 g, versus 405.8 +/- 52.2 g in the control group (p < 0.05). In the HIV+ subjects there was no relationship between muscle performance and CD4+ count or azidothymidine (AZT) use. There was, however, a highly significant relationship between respiratory muscle dysfunction and symptoms of dyspnea. We conclude that HIV seropositivity is associated with a decline in respiratory muscle performance. This impairment in respiratory muscle function may contribute to the feeling of breathlessness that has been well described in this patient population.
Evolution of the Tbx6/16 Subfamily Genes in Vertebrates: Insights from Zebrafish
Authors: Daegwon Ahn, Kwan-Hee You, Cheol-Hee Kim
Journal: Molecular Biology and Evolution (2012)

In any comparative studies striving to understand the similarities and differences of the living organisms at the molecular genetic level, the crucial first step is to establish the homology (orthology and paralogy) of genes between different organisms. Determination of the homology of genes becomes complicated when the genes have undergone a rapid divergence in sequence or when the involved genes are members of a gene family that has experienced a differential gain or loss of its constituents in different taxonomic groups. Organisms with duplicated genomes such as teleost fishes might have been especially prone to these problems because the functional redundancies provided by the duplicate copies of genes would have allowed a rapid divergence or loss of genes during evolution. In this study, we will demonstrate that much of the ambiguities in the determination of the homology between fish and tetrapod genes resulting from the problems like these can be eliminated by complementing the sequence-based phylogenies with nonsequence information, such as the exon–intron structure of a gene or the composition of a gene's genomic neighbors. We will use the Tbx6/16 subfamily genes of zebrafish (tbx6, tbx16, tbx24, and mga genes), which have been well known for the ambiguity of their evolutionary relationships to the Tbx6/16 subfamily genes of tetrapods, as an illustrative example. We will show that, despite the similarity of sequence and expression to the tetrapod Tbx6 genes, zebrafish tbx6 gene is actually a novel T-box gene more closely related to the tetrapod Tbx16 genes, whereas the zebrafish tbx24 gene, hitherto considered to be a novel gene due to the high level of sequence divergence, is actually an ortholog of tetrapod Tbx6 genes. We will also show that, after their initial appearance by the multiplication of a common ancestral gene at the beginning of vertebrate evolution, the Tbx6/16 subfamily of vertebrate T-box genes might have experienced differential losses of member genes in different vertebrate groups and gradual pooling of member gene's functions in surviving members, which might have prevented the revelation of the true identity of member genes by way of the comparison of sequence and function.