tbuckley/cabot-search huggingface dataset:
Noninvasive<i>in vivo</i>magnetic resonance measures of glutathione synthesis in human and rat liver as an oxidative stress biomarker
Authors: John T. Skamarauskas, Fiona Oakley, Fiona E. Smith, Carlo Bawn, Michael Dunn, Daniel S. Vidler, Matthew Clemence, Peter G. Blain, Roy Taylor, Michael P. Gamcsik, Peter E. Thelwall
Journal: Hepatology (2013)

Oxidative stress (OS) plays a central role in the progression of liver disease and in damage to liver by toxic xenobiotics. We have developed methods for noninvasive assessment of hepatic OS defenses by measuring flux through the glutathione (GSH) synthesis pathway. 13 C-labeled GSH is endogenously produced and detected by in vivo magnetic resonance after administration of [2- 13 C]-glycine. We report on a successful first-ever human demonstration of this approach as well as preclinical studies demonstrating perturbed GSH metabolism in models of acute and chronic OS. Human studies employed oral administration of [2- 13 C]-glycine and 13 C spectroscopy on a 3T clinical magnetic resonance (MR) imaging scanner and demonstrated detection and quantification of endogenously produced 13 C-GSH after labeled glycine ingestion. Plasma analysis demonstrated that glycine 13 C fractional enrichment achieved steady state during the 6-hour ingestion period. Mean rate of synthesis of hepatic 13 C-labeled GSH was 0.32 ± 0.18 mmole/kg/hour. Preclinical models of acute OS and nonalcoholic steatohepatitis (NASH) comprised CCl 4 -treated and high-fat, high-carbohydrate diet-fed Sprague-Dawley rats, respectively, using intravenous administration of [2- 13 C]-glycine and observation of 13 C-label metabolism on a 7T preclinical MR system. Preclinical studies demonstrated a 54% elevation of GSH content and a 31% increase in flux through the GSH synthesis pathway at 12 hours after acute insult caused by CCl 4 administration, as well as a 23% decrease in GSH content and evidence of early steatohepatitis in the model of NASH. Conclusion : Our data demonstrate in vivo 13 C-labeling and detection of GSH as a biomarker of tissue OS defenses, detecting chronic and acute OS insults. The methods are applicable to clinical research studies of hepatic OS in disease states over time as well as monitoring effects of therapeutic interventions. (Hepatology 2014;59:2321–2330)
Catabolic Response to Lovastatin Therapy
Authors: Bennett P. Lustgarten
Journal: Annals of Internal Medicine (1988)

Letters and Corrections15 July 1988Catabolic Response to Lovastatin TherapyBennett P. Lustgarten, MDBennett P. Lustgarten, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-2-171_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which has been available in the United States for only 5 months, has already gained wide acceptance as an effective cholesterol-lowering agent with high patient acceptability (1-4). Major side effects include toxic hepatitis, cataracts, and myositis, the latter rarely associated with rhabdomyolysis and possibly due to concomitant use of gemfibrozil (4). The incidence of these side effects is less than 2%. We report a case that shows a previously undescribed reaction between lovastatin and levothyroxine in a patient on a complex therapeutic regimen.A 54-year-old white man had been...References1. Gordon D and Rifkind B. 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: a new class of cholesterol lowering agents. Ann Intern Med. 1987;107:759-61. LinkGoogle Scholar2. Malloy M, Kane J, Kunitake S, and Tun P. Complementarity of cholestipol niacin and lovastatin in treatment of severe familial hypercholesteremia. Ann Intern Med. 1987;107:616-23. LinkGoogle Scholar3. Havel R, Hunninghake D, and Illingwoth D. Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesteremia. Ann Intern Med. 1987;107:609-15. LinkGoogle Scholar4. Lovastatin for hypercholesteremia. Med Lett Drugs Ther. 1987;29:99-101. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Bennett P. Lustgarten, MDAffiliations: Hastings-on-Hudson, NY 10706 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypothyroidism as a risk factor for statin intoleranceDrug Interactions with Agents Used in the Treatment of Cardiovascular DiseaseLong Term Clinical Tolerance of Lovastatin (Mevinolin) and Simvastatin (Epistatin)Drug Interaction between Thyroxine and Lovastatin 15 July 1988Volume 109, Issue 2Page: 171-172KeywordsCataractsHepatitisMyositisRhabdomyolysisThyroxine ePublished: 1 December 2008 Issue Published: 15 July 1988 PDF downloadLoading ...
401 LIVER STIFFNESS DYNAMICS IN HCV-INFECTED PATIENTS WITH AND WITHOUT AN SVR TO PEGINTERFERON ALPHA-RIBAVIRIN TREATMENT. FINAL RESULTS OF A PROSPECTIVE STUDY
Authors: C. Hezode, L. Castéra, F. Roudot-Thoraval, I. Rosa, D. Roulot, V. Leroy, M. Bouvier-Alias, A. Mallat, J.-M. Pawlotsky
Journal: Journal of Hepatology (2010)
Diabetes and Dyslipidemia
Authors: Khanh Hoang, Y.-D. Ida Chen, Gerald Reaven, Lunan Zhang, Heather Ross, Margaret Billingham, Hannah Valantine
Journal: Circulation (1998)

Background —Clinical observations suggest that transplant coronary artery disease (TxCAD) is immunologically mediated but may be accelerated by metabolic derangements. We developed a rat model of heterotopic heart transplantation in the presence of diabetes and dyslipidemia to further study their role in TxCAD development. Methods and Results —Major histocompatibility complex–mismatched strains of inbred rats underwent heterotopic heart transplantation (ACI-to-Lewis allografts). Diabetes (DM) was induced by streptozotocin injection (80 mg/kg) after transplantation; dyslipidemia was worsened by feeding of a 60% high-fructose diet (+F). Allograft transplants were divided into four groups: (1) +DM/+F; (2) +DM/−F; (3) −DM/+F; and (4) −DM/−F. Isograft transplants (Lewis to Lewis, +DM/±F) were controls. All animals received daily cyclosporine (5 mg/kg). Grafts surviving &gt;30 days were evaluated for TxCAD on histological sections and graded 0 to 5 for intimal thickness. All streptozotocin-treated animals were diabetic within 2 weeks, with fourfold increases in plasma glucose concentrations versus nondiabetics. Severe TxCAD was observed in diabetic allografts only. The mean grade of TxCAD in diabetic allografts was 3.2±0.5 versus 1.1±0.4 in diabetic isografts ( P &lt;0.03) and zero TxCAD in nondiabetic allografts ( P ≤0.0001). Fructose feeding resulted in a 1.5-fold higher triglyceride and a 1.3-fold higher cholesterol level versus the regular diet (−F) but showed no independent contribution to the development of TxCAD. Conclusions —These findings suggest that metabolic derangements associated with diabetes play an important role in TxCAD development in heterotopic ACI-to-Lewis rat heart transplantation. In this model of TxCAD in major histocompatibility complex–mismatched, diabetic, and dyslipidemic rats, immunologic and metabolic mechanisms that contribute to TxCAD can be further delineated and approaches to its prevention assessed.
Bayesian Estimation of Sequence Damage in Ancient DNA
Authors: Simon Y. W. Ho, Tim H. Heupink, Andrew Rambaut, Beth Shapiro
Journal: Molecular Biology and Evolution (2007)

DNA extracted from archaeological and paleontological remains is usually damaged by biochemical processes postmortem. Some of these processes lead to changes in the structure of the DNA molecule, which can result in the incorporation of incorrect nucleotides during polymerase chain reaction. These base misincorporations, or miscoding lesions, can lead to the inclusion of spurious additional mutations in ancient DNA (aDNA) data sets. This has the potential to affect the outcome of phylogenetic and population genetic analyses, including estimates of mutation rates and genetic diversity. We present a novel model, termed the delta model, which estimates the amount of damage in DNA data and accounts for its effects in a Bayesian phylogenetic framework. The ability of the delta model to estimate damage is first investigated using a simulation study. The model is then applied to 13 aDNA data sets. The amount of damage in these data sets is shown to be significant but low (about 1 damaged base per 750 nt), suggesting that precautions for limiting the influence of damaged sites, such as cloning and enzymatic treatment, are worthwhile. The results also suggest that relatively high rates of mutation previously estimated from aDNA data are not entirely an artifact of sequence damage and are likely to be due to other factors such as the persistence of transient polymorphisms. The delta model appears to be particularly useful for placing upper credibility limits on the amount of sequence damage in an alignment, and this capacity might be beneficial for future aDNA studies or for the estimation of sequencing errors in modern DNA.
Histologic Diagnosis of Primary Hyperparathyroidism: A Concordance Analysis Between Three Pathologists
Authors: Leticia Bornstein-Quevedo, Armando Gamboa-Domínguez, Arturo Angeles-Angeles, Edgardo Reyes-Gutiérrez, Florencia Vargas-Voráckova, Rosa Gamino, Miguel F Herrera
Journal: Endocrine Pathology (2001)
The merck index. An encyclopedia of chemicals, drugs, and biologicals. Tenth Edition. Martha Windholz, Editor; Susan Budavari, Co-Editor; Rosemary F. Blumetti, Associate Editor, Elizabeth S. Otterbein, Assistant Editor. 2, 067 pp. (including tables and index). Rahway, New Jersey: Merck &amp; Co., Inc., 1983. $28.50
Authors: Michael A. Marletta
Journal: Hepatology (1985)
References on Penicillamine-Induced Renal Disease
Authors: ISRAELI A. JAFFE
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 March 1983References on Penicillamine-Induced Renal DiseaseISRAELI A. JAFFE, M.D.ISRAELI A. JAFFE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-3-417_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their article, Chalmers and associates (1) state that renal involvement is unusual in penicillamine-induced lupus erythematosus but that it has been described and give three literature citations (references 4, 8, 9). In their reference 4, Kirby and associates do describe renal disease in one of their four patients with penicillamine-induced lupus erythematosus; however, they also describe 17 additional patients with penicillamine-induced nephropathy, none of whom had lupus erythematosus. In reference 8, there is no mention of drug-induced lupus erythematosus among the various examples of penicillamine toxicity reported. Reference 9 refers only to penicillamine-induced Goodpasture's syndrome, not...References1. CHALMERSTHOMPSONSTEINREIDPATTERSON ADHGA. Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis. Ann Intern Med. 1982;97:659-63. LinkGoogle Scholar2. JAFFE I. Penicillamine treatment of rheumatoid arthritis—rationale, pattern of clinical response, and clinical pharmacology and toxicology. In: MUNTHE E, ed. Penicillamine Research in Rheumatic Disease. Oslo Fabritius and Sonner; 1976:11-24. Google Scholar3. JAFFE I. Penicillamine treatment in rheumatoid arthritis. In: MCCARTY D, ed. Arthritis And Allied Conditions. 9th ed. Philadelphia: Lea & Febiger; 1979:368-74. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: College of Physicians and Surgeons of the Columbia University New York, NY 10032 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byProgressive proliferative glomerulonephritis in a patient with rheumatoid arthritis treated with D-penicillamine. 1 March 1983Volume 98, Issue 3Page: 417-417KeywordsAdverse reactionsLupus erythematosusRenal diseasesToxicity ePublished: 1 December 2008 Issue Published: 1 March 1983 PDF downloadLoading ...
Lenalidomide in combination with an activin A-neutralizing antibody: preclinical rationale for a novel anti-myeloma strategy
Authors: T Scullen, L Santo, S Vallet, M Fulciniti, H Eda, D Cirstea, K Patel, N Nemani, A Yee, A Mahindra, N Raje
Journal: Leukemia (2013)
Analysis of exhaled leukotrienes in nonasthmatic adult patients with seasonal allergic rhinitis
Authors: P. Čáp, F. Pehal, J. Chládek, M. Malý
Journal: Allergy (2005)

Background: Leukotrienes (LTs) are increased in exhaled breath condensate (EBC) in patients with asthma. So far no data have been reported about LT levels in nonasthmatic patients with seasonal allergic rhinitis (SAR). The aim of the study was to find out whether the LT levels in EBC were increased in the nonasthmatic adult patients with SAR both during and after the pollen season in comparison with healthy controls and to assess the changes of the LT levels after the pollen season. Methods: Twenty‐nine nonasthmatic adult patients with SAR underwent measurement of exhaled LTs in the EBC during and after the pollen season. Leukotrienes B 4 , C 4 , D 4 and E 4 were analysed by a specific and sensitive gas chromatography/mass spectrometry (GC/MS) assay and compared with 50 healthy nonsmoking controls. Spirometry, skin prick tests and nonspecific IgE were evaluated. Results: Leukotrienes concentrations (B 4 , E 4 but not D 4 ) were significantly increased in and after the pollen season in patients with SAR in comparison with healthy controls. In most of the samples, LT C 4 was undetectable. The values of all exhaled LTs were significantly decreased after the pollen season compared with the seasonal baseline: LTB 4 ( P = 0.023), LTD 4 ( P = 0.020), LTE 4 ( P = 0.047). Conclusions: Levels of exhaled LTB 4 and LTE 4 were higher in SAR patients than in healthy controls and decreased after the pollen season as compared with levels in season. The SAR patients with the highest in season LT levels had also the post‐season levels elevated and this may be an early marker of inflammatory process in the lower airways despite the absence of clinical symptoms of asthma.
Results of biological standardization with standardized allergen preparations
Authors: S. Dreborg, L. Belin, N. E. Eriksson, Ø. Grimmer, G. Kunkel, H. J. Malling, G. Nilsson, I. Sjögren, O. Zetterström
Journal: Allergy (1987)

The aim of biological standardization (BS) is to equilibrate the activity (potency) of allergen extracts from different source materials. This was done by performing skin prick tests (SPT) on patients who were sensitive to one of the following 10 allergens: Birch, alder, hazel, timothy, rye grass, velvet grass, cultivated rye, mugwort, D. farinae and Cladosporium herbarum. Patient sensitivity varied within a range of diree to four powers of ten for each allergen investigated. The weal size in each patient corresponding to that elicited by histamine 1 mg/ml was calculated using the model log (mean weal diameter) = a + b log (concentration). The correlation coefficients of the regression lines of die allergen dose response relationship were found to be &gt; 0.85 in most cases. The median slope for all extracts was 0.24. The slope for Cladosporium was significantly steeper than that for pollens. The amount of material in ng dry weight (d.w./ml) equal to 1000 biological units/ml (BU/ml) varied within a factor of three between species for all tested purified allergen preparations but Cladosporium. For Cladosporium , about 30 times more material was needed than for D. farinae. When using crude radier than purified material, it was necessary to use five to ten times more to elicit a reaction corresponding to 1000 BU/ml, but the difference was significant only for Cladosporium. The narrow range of allergen concentrations used by us as well as other investigators does not assure positive skin prick test results in all patients with clinical symptoms due to the allergen in question. Skin prick testing should therefore be done over a wide range of concentrations to improve the methods for BS.
EXTERNAL DRAINAGE OF LUNG CAVITIES.
Authors: LE MOYNE WILLS
Journal: JAMA (1901)

The subject to which I wish to call your attention is one much neglected, though very near to us all, especially to those of us who live in the regions to which tuberculous patients are most frequently sent in all stages of the disease. Just why abscesses and cavities in the lungs should be allowed to run their course of breakdown and produce infection of the other lung and a pyemic condition of the system is hard to explain in these days of exploitation in all parts of the human body. It is partly due to the timidity of the physician in recommending, and in operating for, the relief of the suppurative process as elsewhere, but chiefly to the reluctance of the patient to submit to operation when there is yet time to do good by such interference. Of course it would not be good surgery to subject a patient
Statin use is associated with lower risk of liver cancer, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Taking a statin is associated with a near halving of the risk of liver cancer, show the results of a new study reported in the Journal of the National Cancer Institute .1

Previous research has linked statins to a reduced risk of liver cancer, but much of the evidence has been from areas of the world with high rates of this type of cancer. So, researchers analysed data from …
STUDIES ON CARBOHYDRATE METABOLISM IN PATIENTS WITH NEOPLASTIC DISEASE. II. REPONSE TO INSULIN ADMINISTRATION*†
Authors: Jonathan S. Bishop, Paul A. Marks
Journal: Journal of Clinical Investigation (1959)

A decrease in glucose tolerance, as indicated by a slower rate of disappearance of blood glucose following intravenous glucose administration, has been observed in patients with neoplastic disease (2). The group studied included subjects with chronic diffuse lymphomas and leukemias as well as clinically localized carcinomas who were carefully selected to exclude various other factors known to influence carbohydrate utilization. In view of the fact that the altered glucose metabolism was associated with localized carcinoma, it appeared likely that it reflected a defect in the metabolism of the host. The mechanism of this defect is unknown.
Perception of Neighborhood Problems, Health Behaviors, and Diabetes Outcomes Among Adults With Diabetes in Managed Care
Authors: Tiffany L. Gary, Monika M. Safford, Robert B. Gerzoff, Susan L. Ettner, Andrew J. Karter, Gloria L. Beckles, Arleen F. Brown
Journal: Diabetes Care (2008)

OBJECTIVE—Recent data suggest that residential environment may influence health behaviors and outcomes. We assessed whether perception of neighborhood problems was associated with diabetes behaviors and outcomes. RESEARCH DESIGN AND METHODS—This cross-sectional analysis included 7,830 diabetic adults enrolled in Translating Research Into Action for Diabetes, a study of diabetes care and outcomes in managed care settings. Perception of neighborhood problems was measured using a summary score of participants’ ratings of crime, trash, litter, lighting at night, and access to exercise facilities, transportation, and supermarkets. Outcomes included health behaviors and clinical outcomes. Hierarchical regression models were used to account for clustering of patients within neighborhoods and to adjust for objective neighborhood socioeconomic status (percentage living in poverty) and potential individual-level confounders (age, sex, race/ethnicity, education, income, comorbidity index, and duration of diabetes). RESULTS—After adjustment, residents of neighborhoods in the lowest tertile (most perceived problems) reported higher rates of current smoking (15 vs. 11%) than those in the highest tertile and had slightly lower participation in any weekly physical activity (95 vs. 96%). In addition, their blood pressure control was worse (25 vs. 31% &amp;lt;130/80 mmHg), and their Short Form 12 scores were slightly lower (44 vs. 46 units for emotional well-being and 43 vs. 44 units for physical well-being); all P &amp;lt; 0.01. CONCLUSIONS—Neighborhood problems were most strongly associated with more smoking and higher blood pressure, both of which have significant implications for cardiovascular risk. Potential mechanisms that explain these associations should be further explored in longitudinal studies.
The Anticoagulant Malingerer
Authors: DAVID P. AGLE
Journal: Annals of Internal Medicine (1970)

Psychiatric studies of three patients who had surreptitiously ingested anticoagulant drugs are contrasted with those of a patient who had taken bishydroxycoumarin (Dicumarol®) in error. The three patients had a variety of neurotic symptoms and displayed hysterical and masochistic character traits. Their backgrounds were strikingly similar, replete with physical beatings and sexual traumas. The data suggest that the attempt to induce bleeding by the ingestion of drugs was determined by a variety of life experiences and internal conflicts and that appropriate psychiatric therapy may be helpful in the management of this disorder.
Relation of aplastic anaemia to use of chloramphenicol eye drops in two international case-control studies
Authors: B.-E. Wiholm, J. P. Kelly, D. Kaufman, S. Issaragrisil, M. Levy, T. Anderson, S. Shapiro
Journal: BMJ (1998)

Although the use of chloramphenicol eye drops is thought to cause aplastic anaemia, 1 this side effect has not been studied critically.We examined the use of ocular chloramphenicol in two population based case-control studies conducted with the same methods. 2 3
Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions.
Authors: P Sarobe, C D Pendleton, T Akatsuka, D Lau, V H Engelhard, S M Feinstone, J A Berzofsky
Journal: Journal of Clinical Investigation (1998)

Since the natural immune response to hepatitis C virus (HCV) is often unable to clear the infection, to enhance immunogenicity we studied substituted peptides from an HCV cytotoxic T lymphocyte (CTL) epitope (C7A2) from a conserved region of the HCV core protein (DLMGYIPLV) recognized by CTL lines from HLA-A2.1(+) HCV-infected patients and HLA-A2.1 transgenic mice. HLA-A2.1 binding, human and murine CTL recognition, and in vivo immunogenicity (using mice transgenic for human HLA-A2 in lieu of immunizing humans) were analyzed to define peptides with enhanced immunogenicity. Peptides substituted at position 1 showed enhanced HLA-A2 binding affinity, but paradoxically poorer immunogenicity. A peptide with Ala substituted at position 8 (8A) showed higher HLA-A2 binding affinity and CTL recognition and was a more potent in vivo immunogen in HLA-A2-transgenic mice, inducing higher CTL responses with higher avidity against native C7A2 than induced by C7A2 itself. These results suggest that peptide 8A is a more potent in vitro antigen and in vivo immunogen than C7A2 and may be useful as a vaccine component. They provide proof of principle that the strategy of epitope enhancement can enhance immunogenicity of a CTL epitope recognized by human CTL.