tbuckley/cabot-search huggingface dataset:
Acyl-CoA:Cholesterol Acyltransferase Inhibitor Avasimibe Reduces Atherosclerosis in Addition to Its Cholesterol-Lowering Effect in ApoE*3-Leiden Mice
Authors: Dianne J. M. Delsing, Erik H. Offerman, Wim van Duyvenvoorde, Hans van der Boom, Elly C. M. de Wit, Marion J. J. Gijbels, Arnoud van der Laarse, J. Wouter Jukema, Louis M. Havekes, Hans M. G. Princen
Journal: Circulation (2001)

The present study investigated whether the ACAT inhibitor avasimibe can reduce atherogenesis independently of its cholesterol-lowering effect in ApoE*3-Leiden mice.Two groups of 15 female ApoE*3-Leiden mice were put on a high-cholesterol (HC) diet; 1 group received 0.01% (wt/wt) avasimibe mixed into the diet. The HC diet resulted in a plasma cholesterol concentration of 18.7+/-2.6 mmol/L. Addition of avasimibe lowered plasma cholesterol by 56% to 8.1+/-1.2 mmol/L, caused mainly by a reduction of and composition change in VLDL and LDL. In a separate low-cholesterol (LC) control group, plasma cholesterol was titrated to a level comparable to that of the avasimibe group (10.3+/-1.4 mmol/L) by lowering the amount of dietary cholesterol. After 22 weeks of intervention, atherosclerosis in the aortic root area was quantified. Treatment with avasimibe resulted in a 92% reduction of lesion area compared with the HC control group. Compared with the LC control, avasimibe reduced lesion area by 78%. After correction for the slight difference in cholesterol exposure between the LC control and avasimibe groups, the effect of avasimibe on lesion area (73% reduction) remained highly significant. In addition, monocyte adherence to the endothelium, free cholesterol accumulation, and lesion severity were reduced by avasimibe treatment.Treatment with avasimibe potently lowered plasma cholesterol levels in ApoE*3-Leiden mice and considerably reduced atherosclerotic lesion area in addition to its cholesterol-lowering effect. Because monocyte adherence to the endothelium and lesion severity were also reduced by avasimibe, treatment with avasimibe may result in higher plaque stability and therefore a reduced risk of plaque rupture.
Abstract PD06-07: Evaluation of an optimal cut-off point for the Ki-67 index as a prognostic factor in primary breast cancer.
Authors: R Tashima, R Nishimur
Journal: Cancer Research (2012)

Abstract Background: The proliferation biomarker Ki-67 is considered to be a prognostic factor for breast cancer and has been investigated in several studies. However, there is no standard cut-off point for the Ki-67 index. Therefore, we retrospectively investigated an optimal cut-off point in terms of the prognostic factor in primary breast cancer. Patients&amp;Methods: Immunohistochemical (IHC) analysis of the proliferation marker Ki-67 index was performed on 4338 patients with primary breast cancer until March 2012 at Kumamoto City Hospital. Out of these patients, there were 2375 consecutive cases with ER and/or PgR positive and HER2 negative tumors since 1997. Items examined were ER, PgR, HER2, tumor size, nodal status, nuclear grade, and p53 overexpression. The Kaplan-Meier test was used to calculate prognosis (cumulative disease-free survival (DFS) and overall survival (OS)) and tested with the log-rank procedure. Cox's proportional hazard model was used to perform a univariate and multivariate analyses of the factors related to DFS. In addition, an analysis was conducted to determine various cut-off values for the Ki-67 index. Results: The median Ki-67 value was 21%, with a mean of 26.2%. Univariate and multivariate analysis revealed that the Ki-67 index was an independent prognostic factor for DFS and OS. A multivariate analysis revealed the following hazard ratio (HR) and cut-off values for the Ki-67 index; HR was 1.92 in cases with a cut-off value of 20%, 1.91 in 35%, 1.87 in 40%, 1.89 in 45% and 1.79 in 50%, respectively. These findings suggested that the optimal cut-off point was 20%. In the cases with luminal type (ER and/or PgR positive and HER2 negative) breast cancer, a higher Ki-67 value (20% ≤) correlated with larger tumor size, positive nodes, higher grade, and overexpression of p53. Moreover, patients with a higher Ki-67 value showed significantly lower DFS/OS rates. A multivariate analysis also revealed that the Ki-67 index is a significant prognostic factor in luminal type breast cancer. Conclusion: The optimal cut-off value for the Ki-67 index is 20%. Moreover, this proliferation marker is a significant prognostic factor in evaluating primary breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD06-07.
Neonatal Screening for Inherited Disease
Authors: William L. Nyhan
Journal: New England Journal of Medicine (1985)

The latest addition to an enlarging list of inherited metabolic diseases that can be detected and effectively treated by means of programs of neonatal screening is described by Wolf and his colleagues in this issue of the Journal.1 The authors have developed a simple colorimetric test for biotinidase deficiency that can be employed with spots of blood dried on filter paper, and they have demonstrated that the test is suitable for incorporation into a statewide program of neonatal screening. In fact, 2 infants with the disease were identified among 81,243 infants screened.Biotinidase deficiency causes multiple carboxylase deficiency.2 It . . .
Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women
Authors: Charles S. Fuchs, Edward L. Giovannucci, Graham A. Colditz, David J. Hunter, Meir J. Stampfer, Bernard Rosner, Frank E. Speizer, Walter C. Willett
Journal: New England Journal of Medicine (1999)

We conducted a prospective study of 88,757 women, who were 34 to 59 years old and had no history of cancer, inflammatory bowel disease, or familial polyposis, who completed a dietary questionnaire in 1980. During a 16-year follow-up period, 787 cases of colorectal cancer were documented. In addition, 1012 patients with adenomas of the distal colon and rectum were found among 27,530 participants who underwent endoscopy during the follow-up period.
The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology
Authors: Daniel Glinoer
Journal: Endocrine Reviews (1997)

I. Introduction II. The Regulation of Thyroid Function in Normal Pregnancy A. The thyroid hormone transport proteins B. The thyroid hormones 1. Total thyroid hormones 2. Free thyroid hormones 3. Peripheral metabolism of thyroid hormones C. The serum levels of thyroglobulin (TG) D. The metabolism of iodine E. The hypothalamic-pituitary control of thyroid function and the role of hCG 1. Hypothalamic-pituitary-thyroid axis (HPTA) 2. Regulation of serum TSH 3. Thyrotropic action of hCG F. A global view of thyroidal economy in pregnancy III. Pathological Alterations of Thyroidal Regulation Associated with Pregnancy A. IDD 1. Consequences of iodine deficiency during pregnancy 2. Assessment of increased thyroidal stimulation 3. Gestational goitrogenesis and its prevention by iodine supplementation 4. Consequences of iodine deficiency for the offspring B. Hypothyroidism and pregnancy 1. Fertility and pregnancy outcome in hypothyroid women 2. Thyroid hormone replacement in the hypothyroid pregnant woman 3. Subclin...
Repair in Arterial Tissue
Authors: P. Helin, I. Lorenzen, C. Garbarich, M. E. Matthienen
Journal: Circulation Research (1971)

Male albino rabbits were subjected to a single mechanical dilatation of the descending thoracic aorta with a balloon catheter. The animals were killed 3, 6, 14, 30, and 60 days later. Between the sixth and the fourteenth days after injury, all the aortas which had been dilated developed severe, gross arteriosclerosis. Microscopic examination showed destruction and degeneration in the form of necrosis and calcification as well as regeneration and repair including new formation of cells, intercellular substance, and fibers. Biochemical and histochemical analyses revealed an early increase in hyaluronic acid and water followed by an increase in chondroitin-4, 6-sulfate and a later increase in heparan sulfate, dermatan sulfate, and collagen. These alterations were related to the focal lesions in the aortic wall. The permeability of the aorta to 125 I-albumin increased to a maximum 3 days after the dilatation, whereupon it decreased rapidly. The alterations were interpreted as nonspecific processes of repair in the vascular connective tissue. The pronounced dependence of the alterations on the time elapsed after injury must be considered in the study of vascular diseases where injury and repair may be involved.
Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis: An open-label pilot study
Authors: Yasuo Kubota, Kozo Yoneda, Kozo Nakai, Junko Katsuura, Tetsuya Moriue, Yoshie Matsuoka, Izumi Miyamoto, Yukihiro Ohya
Journal: Journal of the American Academy of Dermatology (2008)
Comparison of carbohydrate-containing and carbohydrate-restricted hypocaloric diets in the treatment of obesity. Endurance and metabolic fuel homeostasis during strenuous exercise.
Authors: C Bogardus, B M LaGrange, E S Horton, E A Sims
Journal: Journal of Clinical Investigation (1981)

Eight untrained, obese females (greater than 30% body fat), ages 25-33 yr, were studied before, at 1 wk, and after 6 wk while taking either of two 830-kcal/d diets: carbohydrate-containing (CC) group (n = 4): 35% protein, 29% fat, 36% carbohydrate-restricted (CR) group (n = 4): 35% protein, 64% fat, 1% carbohydrate. Endurance, at approximately 75% of VO2max (maximum oxygen uptake) on a cycle decreased from base line by 50% at 1 and 6 wk in the CR group, but there was no change in the CC group. Preexercise muscle glycogen (vastus lateralis) did not change significantly in the CC group, but was decreased by 49% in the CR group after 1 wk, and by 51% after 6 wk. There was a close correlation between percent decrease in resting muscle glycogen and percent decrease in endurance (r = 0.79, P less than 0.01). The mean fasting and exercise plasma glucose concentration was lower in the CR group than in the CC group after 6 wk, but no subject became hypoglycemic during exercise. Serum FFA, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon changed similarly in the two groups during exercise at base line, 1 and 6 wk. Glycerol concentration was higher in the CR group during exercise only after 6 wk. Increases in serum lactate concentrations, and a mean exercise respiratory quotient of 0.93 suggested that cycle exercise at approximately 75% VO2max used predominantly glucose as a fuel. Conclusions: Resting muscle glycogen and endurance, during cycle exercise at approximately 75% VO2max, were maintained during a 36% carbohydrate, 830-kcal/d diet. In contrast, significant decreases, occurred in resting muscle glycogen and endurance, during similar exercise, after 6 wk of a 1% carbohydrate, 830-kcal/d diet.
Tetracycline and Rises in Urea Nitrogen
Authors: A. M. Tannenberg
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I must take exception to several points made in the article entitled "Tetracycline and Drug Attributed Rises in Blood Urea Nitrogen" reported by the Boston Collaborative Drug Surveillance Program in the April 17th issue ofThe Journal(220:377, 1972). In the initial statement, the authors fail to clearly define what is meant by "clinically significant rises in BUN level." This point is crucial since, as Dosseter<sup>1</sup>has clearly shown, one may have wide variations in blood urea nitrogen (BUN) levels just on the basis of variation in protein metabolism without any variation in overall renal function or any clinical symptoms. Furthermore, there is no evidence that urea per se is toxic. It has been used and still is used on occasion as an osmotic diuretic. Secondly, it would have been helpful to mention the types of diuretics involved since some are known to adversely affect the
Drugs Five Years Later: Cimetidine: II. Adverse Reactions and Patterns of Use
Authors: James W. Freston
Journal: Annals of Internal Medicine (1982)

Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).
Blood-group Antibodies and Red-cell Destruction--II
Authors: P. L. Mollison
Journal: BMJ (1959)

In devising compatibility tests to precede transfusion, and in interpreting them, we need to know the precise relationships between the interactions of red cells and serum in vitro and the survival or destruction of the same red cells in vivo.An inquiry into this problem can be divided into the following questions:1. Does any interaction between red cells and serum at 370 C. in vitro, however trivial, imply some interference with survival in vivo ?If so, is the same true for 300 C. in vitro, and if not, what is the highest temperature of interaction in vitro associated with no effect in vivo ? 2. Are the characteristics of blood-group antibodies in vitro exactly related to their effects in vivo ?For example, if an antibody binds complement in vitro does it bring about the removal of red cells in a different way from that of an antibody which does not bind complement ?3. Is there a close relationsh;p between the potency of an antibody, judged by tests in vitro, anid the speed and extent of the red-cell destruction which it causes in vivo ? 4. Do antibodies display precisely the same specificity in vitro and in vivo ?This problem arises particularly in the selection of blood for transfusion to patients with acquired haemolytic anaemia.5. Is it possible for red cells to be compatible with the recipient's serum in vitro and yet to be treated as incompatible after transfusion ?An attempt will be made to answer these questions in turn.
Monocrotaline induced pulmonary vascular lesions in non-human primates
Authors: C. F. CHESNEY, J. R. ALLEN
Journal: Cardiovascular Research (1973)

Journal Article Monocrotaline induced pulmonary vascular lesions in non-human primates Get access CHARLES F. CHESNEY, CHARLES F. CHESNEY 2 From the Department of Pathology, University of Wisconsin Medical School, and the Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin, U.S.A. 2Recipient of Postdoctoral Research Fellowship 5 F02 ES46357 from the National Institute of Environmental Health Sciences. Search for other works by this author on: Oxford Academic PubMed Google Scholar JAMES R. ALLEN JAMES R. ALLEN From the Department of Pathology, University of Wisconsin Medical School, and the Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 4, July 1973, Pages 508–518, https://doi.org/10.1093/cvr/7.4.508 Published: 01 July 1973
BASELINE EXERCISE CAPACITY AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE: A POST HOC ANALYSIS OF THE COURAGE TRIAL
Authors: Santosh Padala, Mandeep Sidhu, Pamela Hartigan, Koon Teo, John Spertus, David Maron, G. B. John Mancini, Steven Sedlis, Bernard Chaitman, Gary Heller, William Weintraub, William Boden
Journal: Journal of the American College of Cardiology (2014)
Intention to treat analysis is related to methodological quality
Authors: M. Ruiz-Canela
Journal: BMJ (2000)

Analgesic effects of sweet solutions and pacifiers in term neonates Suckling at the breast is better than sweet solutions and pacifiersEditor-A breastfeeding mother spontaneously comforts her distressed infant by putting him or her to the breast.It is a pity that Carbajal et al, when assessing the analgesic effects of orally administered glucose and sucrose in healthy term neonates, did not include a comparison group of infants given breast milk, which is rich in lactose and naturally sweet. 1 It would also have been appropriate to compare the analgesic effect of using a pacifier with that of suckling at the breast before and immediately after the painful procedure.Pacifiers and sugar solutions given unnecessarily to healthy neonates are not proved to be "simple and safe interventions," as Carbajal et al state.Exclusive breast feeding (for about the first six months) is the World Health Organization's recommendation. 2Two of the evidence based "ten steps to successful breastfeeding," developed by the WHO/Unicef Baby Friendly Hospital Initiative, are step 6 ("Give newborn infants no food or drink other than breast milk, unless medically indicated") and step 9 ("Give no artificial teats or pacifiers, also called dummies or soothers, to breastfeeding infants"). 3nything that may interfere with the establishment of lactation or undermine the mother's confidence in breast feeding is to be avoided.I hope that this flawed piece of research will not result in either pacifiers or sugar solutions being "widely used for minor procedures in neonates."
Expression of the thrombin receptor in human liver: Up-regulation during acute and chronic injury
Authors: Fabio Marra, Raffaella DeFranco, Cecilia Grappone, Stefano Milani, Massimo Pinzani, Giulia Pellegrini, Giacomo Laffi, Paolo Gentilini
Journal: Hepatology (1998)

Thrombin is generated during tissue damage in several organs, including the liver, and participates in the process of tissue repair through proteolytic activation of a specific thrombin receptor(TR).The aim of this study was to investigate TR expression in human liver by immunohistochemistry and in situ hybridization. In normal liver, immunostaining for TR was present in the endothelial lining of the hepatic sinusoids. During chronic hepatitis, several cells expressing the TR were detected in the inflammatory infiltrate of portal tracts. In cirrhosis with chronic active hepatitis, expression of the TR was also present in mesenchymal cells of fibrous septa. TR expression was markedly up-regulated during fulminant hepatitis, with the highest expression in mesenchymal cells in areas of regeneration. Up-regulation of TR expression was associated with increased levels of TR messenger RNA (mRNA), as assessed by in situ hybridization and RNAse protection assay of liver RNA. Immunostaining of serial sections using specific cellular markers showed that different nonparenchymal cells contribute to TR expression during liver injury. TR expression was also shown in cultured human hepatic stellate cells, with increasing signal comparing activated versus quiescent cells. Because thrombin is rapidly generated after tissue damage, regulated TR expression may be involved in tissue remodeling and/or scarring during liver damage.
The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis
Authors: Diane van der Woude, Silje W Syversen, Ellen I H van der Voort, Kirsten N Verpoort, Guro L Goll, Michael P M van der Linden, Annette H M van der Helm-van Mil, Désirée M F M van der Heijde, Tom W J Huizinga, Tore K Kvien, René E M Toes
Journal: Annals of the Rheumatic Diseases (2010)

Background The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated. Objective To investigate the relationship between ACPA isotypes, disease progression and radiological outcome. Methods ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts. Results The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p&lt;0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors. Conclusions The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.
Severe cutaneous human papillomavirus infection associated with natural killer cell deficiency following stem cell transplantation for severe combined immunodeficiency
Authors: Qurat ul Ain Kamili, Filiz O. Seeborg, Kapil Saxena, Sarah K. Nicholas, Pinaki P. Banerjee, Laura S. Angelo, Emily M. Mace, Lisa R. Forbes, Caridad Martinez, Teresa S. Wright, Jordan S. Orange, Imelda Celine Hanson
Journal: Journal of Allergy and Clinical Immunology (2014)
Menopause: Biology and Pathobiology
Authors: Lori A. Bastian
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes17 July 2001Menopause: Biology and PathobiologyLori A. Bastian, MD, MPHLori A. Bastian, MD, MPHVeterans Affairs Medical Center, Durham, North Carolina. (Bastian)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-2-200107170-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Lobo RA, Kelsey J, Marcus R, eds. 672 pages. San Diego, CA: Academic Pr; 2000. $159.95. ISBN 0124537901. Order phone 800-321-5068.Field of medicine: Women's health.Format: Hardcover book.Audience: Basic scientists, clinical researchers, fellows, residents, and students.Purpose: To provide a multidisciplinary review of the biology and clinical manifestations of menopause.Content: The 46 chapters are organized into four parts. The first section covers menopause from the basic science perspective and describes the effects of estrogen at the cellular and organ system levels. The next two sections describe symptoms, diagnostic tests, and medical conditions related to menopause. The final ... Author, Article, and Disclosure InformationAffiliations: Veterans Affairs Medical Center, Durham, North Carolina. (Bastian) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 July 2001Volume 135, Issue 2Page: 144KeywordsAndrogensEstrogen replacement therapyEstrogensMedical conditionsMenopauseObstetrics and gynecologyPerimenopauseReproductive endocrinologyScientistsSoftware tools ePublished: 17 July 2001 Issue Published: 17 July 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...