tbuckley/cabot-search huggingface dataset:
A Prospective Clinical Trial of D–Penicillamine in the Treatment of Primary Biliary Cirrhosis
Authors: Henry C. Bodenheimer, Fenton Schaffner, Irmin Sternlieb, Franklin M. Klion, Salvatore Vernace, John Pezzullo
Journal: Hepatology (1985)

We conducted a prospective clinical trial to assess the relative efficacy and safety of high- vs. low-dose D-penicillamine in patients with primary biliary cirrhosis. Following clinical tests and liver biopsy diagnostic of primary biliary cirrhosis, 56 patients were randomized to receive either 250 or 750 mg D-penicillamine daily. Patients were monitored with clinical tests and annual liver biopsy. Randomization produced two groups without differences in demographic, clinical or histologic characteristics. During the trial, no differences were seen between the mean change in liver test results in patients in either treatment group. The 11% per year rise of bilirubin in the 750 mg dose group during the first 3 years was not significantly different from the 18% per year rise in the 250 mg dose group. No patient showed improvement on liver biopsy although patients on 750 mg D-penicillamine deteriorated more slowly. Side effects, particularly rash and dysgeusia, were more common in the 750 mg dose group. The frequency and severity of side effects were responsible for the early conclusion of our trial. Twenty-six patients experienced side effects necessitating discontinuation of D-penicillamine. No evidence of increased efficacy was demonstrated by high-dose D-penicillamine therapy, and side effects were observed in patients on 250 mg D-penicillamine daily. With the severity of adverse effects and continued progression of disease, D-penicillamine is not a clinically useful therapy in primary biliary cirrhosis.
Abnormal Glucagon Secretion in Diabetes Mellitus.
Authors: R. H. Unger
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Abnormal Glucagon Secretion in Diabetes Mellitus.R. H. Unger, M.D., F.A.C.P., E. Aguilar-Parada, M.D., W. A. Muller, M.D., A. M. EisentrautR. H. Unger, M.D., F.A.C.P.Search for more papers by this author, E. Aguilar-Parada, M.D.Search for more papers by this author, W. A. Muller, M.D.Search for more papers by this author, A. M. EisentrautSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-786_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDevelopment of a specific radioimmunoassay for pancreatic glucagon made possible the study of alpha cell function in normal and diabetic subjects. In 28 normals fasting plasma glucagon averaged 108 μμg/ml (SEM±10); during hyperglycemia averaging 210 mg (±15) induced by intravenous glucose, glucagon fell to 62 μμg/ml/100ml (±8). Yet in 33 fasting adult- and 12 juvenile-type diabetics with fasting hyperglycemia of 177 (±10) and 198 mg/100 ml (±25), respectively, glucagon averaged 114 (±8) and 118 (±9) μμg/ml, suggesting hyposuppressibility of the diabetic alpha cell to glucose. The most striking hyposuppressibility was observed in eight patients with severe diabetic ketoacidosis, in whom... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Dallas, Tex. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 786-786KeywordsBlood plasmaDiabetes mellitusGlucagonGlucoseHyperglycemiaRadioimmunoassays ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Abstract 5479: Glycogen synthase kinase-3 (GSK3) differently targets in MLL leukemia cells
Authors: Eun-Hye Hur, Dae-Young Kim, Mun-Jung Kang, Je-Whan Lee
Journal: Cancer Research (2010)

Abstract Propose: We evaluated the anti-leukemic effect of GSK3 inhibitor for specific type of MLL-tranlocated cell line. Materials and methods: l GSK3 inhibitor: LiCl, SB216763, GSK3-IX l Cell line: MV4-11 [human lymphoblast, t(4:11)] MOLM-13 [human acute myeloid leukemia, ins(9:11)(q23;p22p23)] l Cell proliferation assay: XTT assay, Clonogenic assay l GSK3i activity &amp; detection of histone acetylation and H3K4 methylation: Immunoblotting Summary: MLL gene encodes an enzyme which methylates histone H3 DNA-binding protein and positively regulates the expression of target genes in normal tissue. MLL rearrangement which is found in acute myeloid leukemia (AML), especially therapy-related AML, encodes fusion proteins that have lost H3 lys4-specific (H3K4) methyltransferase activity, and causes a transformation of hematopoietic cells into leukemia stem cells. GSK3, a serine/threonine kinase, plays a key role in glycogen metabolism and is constitutively expressed in resting cell. Although it has been thought that the inhibition of GSK3 causes apoptosis in neurons and other tissues, a paradoxical and unexpected cell death effect of GSK3 inhibition were reported recently in leukemic cell line with MLL translocation, especially t(4;11). Regarding the mechanism of the cytotoxic effect of GSK3 inhibitor, various molecules associated with the signaling pathway around MLL gene have been investigated. Acetylation of H3 peptides stimulates the activity of SET domain in MLL. MLL gene is cleaved at 2 conserved sites by taspase-1; N-terminal 320 kD fragment (N320) and a C-terminal 180 kD fragment (C180). RNA interference-mediated knockdown of taspase-1 resulted in an unprocessed MLL, and finally a loss of proper HOX gene expression. However, the exact mechanism has been still unknown and it remains to be uncertain whether GSK3 inhibitor shows cell death effect on various leukemic cell lines of MLL translocation with other partner gene. We intended to determine whether the inhibition of GSK3 induced cell death in different types of leukemia cell lines with MLL translocation. We examined the apoptotic effects of GSK3 inhibitors on MV4-11 and MOLM-13 cell line. LiCl and GSK3-IX induced cell death, H3K4 methylation and histone acetylation in dose-dependent manners on MV4-11 but did not induce on MOLM-13. However, SB216763 did not induced cell death both cell lines. Conclusion: Cell death effects with the inhibition of GSK3 may be different among leukemic cell line with MLL translocation according to the partner gene of MLL translocation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5479.
Positive End-Expiratory Pressure Increases the Right-to-Left Shunt in Mechanically Ventilated Patients with Patent Foramen Ovale
Authors: B Cujec, P Polasek, I Mayers, D Johnson
Journal: Annals of Internal Medicine (1993)

Objective: To determine the effect of the presence of a patent foramen ovale on the right-to-left shunt in patients with respiratory failure who receive positive end-expiratory pressure (PEEP). Design: Convenience sample with randomized application of PEEP. Setting: General intensive care unit of a university teaching hospital. Patients: A total of 46 mechanically ventilated patients with respiratory failure requiring an inspired oxygen concentration of at least 50% and a PEEP of at least 5 cm of H2O. Intervention: Randomized application of PEEP (0 and 10 cm of H2O). Measurements: A patent foramen ovale was detected by saline contrast transesophageal echocardiography. The alveolar-to-arterial oxygen difference and the right-to-left shunt were calculated from arterial and venous blood gas sampling. Results: In patients without a patent foramen ovale (n = 39), the alveolar-to-arterial oxygen difference and the shunt fraction decreased (50 mm Hg [95% CI, 21 to 67]and 0.05[CI, 0.03 to 0.07],respectively) after adding PEEP (10 cm of H2O). In patients with a patent foramen ovale (n = 7), minimal changes were noted in the alveolar-to-arterial oxygen difference (4 mm Hg, P > 0.2), but the shunt fraction increased (0.05, CI, 0 to 0.09). Adding PEEP (10 cm of H2O) increased the shunt fraction in 6 of 7 (86%) patients with a patent foramen ovale, whereas the shunt increased in only 7 of 39 (18%) patients without a patent foramen ovale (P < 0.007). Conclusions: A patent foramen ovale was found in 7 of 46 patients (15%; CI, 6% to 29%) with acute respiratory failure. This condition is a common cause of lack of improvement in oxygenation with the addition of PEEP in the mechanically ventilated patient. In patients with a patent foramen ovale, the right-to-left shunt is usually increased by using PEEP.
The Environmental Protection Agency: Asking the Wrong Questions. From Nixon to Clinton
Authors: M. Mccally
Journal: BMJ (1995)

Marc K Landy, Marc J Roberts, Stephen R Thomas Oxford University Press, pp 341 ISBN 0 19 508673 2

In the United States conservation initiatives for protecting species and open spaces were superseded in the 1960s by environmentalism, a fusion of scientific rationalism and political activism that has relied on legislation and legal challenge in the courts to promote environmental protection. The environmental movement's first focus was industrial pollution, and its founding document was Silent Spring by Rachel Carson, an examination of the threats to the environment and human health posed by unregulated industry.

In the 1970s the US Congress responded with surprising speed to concern over deterioration of the environment and produced far reaching environmental legislation. The National Environmental Policy Act of 1970 requires the federal government to disclose the environmental consequences of its activities as “environmental …
Clinical Evaluation in Healthy Adults of a Hepatitis B Vaccine Made by Recombinant DNA
Authors: Edward M. Scolnick
Journal: JAMA (1984)

A vaccine formulated from hepatitis B surface antigen (HBsAg) produced by a recombinant strain of the yeast Saccharomyces cerevisiae was administered to two groups of human volunteers composed of 37 healthy, low-risk adults. Each subject received a 10-micrograms dose of HBsAg at 0, 1, and 6 months. By one month, 27% to 40% of the vaccinees had antibody to HBsAg, and by three months 80% to 100% were antibody positive. Large boosts in titer followed the third dose at six months. The antibody formed is predominantly specific for the a determinant of HBsAg. There have been no serious reactions attributable to the vaccine. The most frequent complaint has been transient soreness at the injection site. As far as we know, this is the first reported use in man of a vaccine prepared by recombinant DNA technology.
Regulation of Helper T Cell Differentiation and Recruitment in Airway Inflammation
Authors: FRANCESCO SINIGAGLIA, DANIELE D'AMBROSIO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Section:ChooseTop of pageAbstract <<ROLE OF CYTOKINES AND APC...MOLECULAR BASIS OF Th CEL...MECHANISMS FOR RECRUITMEN...CHEMOKINE RECEPTORS ON EF...CHEMOKINE EXPRESSION IN T...ReferencesCITING ARTICLES
Respiratory contamination of polymerase chain reactions by human herpesvirus 6
Authors: Patrick K. Kelley, Kenneth L. McClain
Journal: American Journal of Hematology (1994)

Abstract Human herpesvirus type 6 DNA derived from human breath was discovered to contaminate PCR reactions during routine reaction preparation. Parallel PCR experiments were conducted in which expiratory secretions were blocked by a surgical mask, while others were performed without any attempt to circumvent respiratory contamination. The experimenter was previously determined to harbor HHV‐6 DNA in the saliva. All reactions in which expiration was obstructed were negative for HHV‐6 DNA via PCR. Reactions in which there was no attempt to obstruct respiratory secretions were positive for HHV‐6 DNA. These data suggest that PCR assays investigating the presence of HHV‐6 may be highly susceptible to contamination from the experimenter leading to false positive results. © 1994 Wiley‐Liss, Inc.
Endogenous prostaglandin endoperoxides may alter infarct size in the presence of thromboxane synthase inhibition: Studies in a rabbit model of coronary artery occlusion-reperfusion
Authors: Paolo Golino, Giuseppe Ambrosio, Bruno Villari, Massimo Ragni, Amelia Focaccio, Leonardo Pace, Fred De Clerk, Mario Condorelli, Massimo Chiariello
Journal: Journal of the American College of Cardiology (1993)
Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na<sup>+</sup> Current
Authors: Mark L. Dallas, Zhaokang Yang, John P. Boyle, Hannah E. Boycott, Jason L. Scragg, Carol J. Milligan, Jacobo Elies, Adrian Duke, Jérôme Thireau, Cyril Reboul, Sylvain Richard, Olivier Bernus, Derek S. Steele, Chris Peers
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Clinical reports describe life-threatening cardiac arrhythmias after environmental exposure to carbon monoxide (CO) or accidental CO poisoning. Numerous case studies describe disruption of repolarization and prolongation of the QT interval, yet the mechanisms underlying CO-induced arrhythmias are unknown.
Model of Complications of NIDDM: I. Model construction and assumptions
Authors: Richard C Eastman, Jonathan C Javitt, William H Herman, Erik J Dasbach, Arthur S Zbrozek, Fred Dong, Diane Manninen, Sanford A Garfield, Catherine Copley-Merriman, William Maier, Jeffery F Eastman, James Kotsanos, Catherine C Cowie, Maureen Harris
Journal: Diabetes Care (1997)

OBJECTIVE To develop a model of NIDDM for analyzing prevention strategies for NIDDM. RESEARCH DESIGN AND METHODS A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies. RESULTS Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1−3.0×) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis. CONCLUSIONS A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM.
Effect of monocyte migration on low density lipoprotein transport across aortic endothelial cell monolayers.
Authors: M Territo, J A Berliner, A M Fogelman
Journal: Journal of Clinical Investigation (1984)

Endothelial cell monolayers on polycarbonate filters present a barrier to low density lipoprotein (LDL) and albumin transport. These cells form a relatively tight monolayer as shown by measurements of electrical resistance across the monolayer (15 omega-cm2). Monocytes are able to migrate freely across the monolayers in response to chemotactic stimuli. Monocyte chemotaxis across the monolayer caused a marked increase in LDL and albumin transport across the monolayer in the direction of monocyte migration. However, transport in the opposite direction was not significantly increased. These results suggest that monocyte migration across the endothelium could lead to an increased LDL content of the intima.
Serum osteocalcin and carboxyterminal propeptide of type I procollagen in rheumatoid arthritis.
Authors: H Kroger, J Risteli, L Risteli, I Penttila, E Alhava
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--Previous reports indicate that serum osteocalcin (serum bone GLA protein (S-BGP)) and carboxyterminal propeptide of type I procollagen (PICP) can be used as indicators of bone formation and turnover. The purpose of this study was to assess the activity of bone formation in patients with rheumatoid arthritis (RA) using S-BGP and S-PICP. The biochemical data were compared with data obtained from bone histomorphometry. METHODS--Concentrations of S-BGP and S-PICP were measured in 119 women with RA aged 30-66 years and 47 healthy female controls matched for age. Bone histomorphometry of iliac crest samples was performed in 107 patients with RA. RESULTS--Weak to moderate correlations between the serum markers and histological bone formation parameters were found. Concentrations of S-BGP and S-PICP were significantly decreased in patients with RA compared with the controls (S-BGP 7.2 (2.3) v 8.7 (2.1) micrograms/l; S-PICP 105 (32) v 117 (38) micrograms/l. The lowest values were found in patients with recent onset RA. CONCLUSIONS--These findings suggest that bone formation and bone remodelling are generally reduced in patients with RA.
Association of 20-Year Changes in Cardiorespiratory Fitness With Incident Type 2 Diabetes
Authors: Mercedes R. Carnethon, Barbara Sternfeld, Pamela J. Schreiner, David R. Jacobs, Cora E. Lewis, Kiang Liu, Stephen Sidney
Journal: Diabetes Care (2009)

OBJECTIVE To test the association of fitness changes over 7 and 20 years on the development of diabetes in middle age. RESEARCH DESIGN AND METHODS Fitness was determined based on the duration of a maximal graded exercise treadmill test (Balke protocol) at up to three examinations over 20 years from 3,989 black and white men and women from the Coronary Artery Risk Development in Young Adults study. Relative fitness change (percent) was calculated as the difference between baseline and follow-up treadmill duration/baseline treadmill duration. Diabetes was identified as fasting glucose ≥126 mg/dl, postload glucose ≥200 mg/dl, or use of diabetes medications. RESULTS Diabetes developed at a rate of 4 per 1,000 person-years in women (n = 149) and men (n = 122), and lower baseline fitness was associated with a higher incidence of diabetes in all race-sex groups (hazard ratios [HRs] from 1.8 to 2.3). On average, fitness declined 7.6% in women and 9.2% in men over 7 years. The likelihood of developing diabetes increased per SD decrease (19%) from the 7-year population mean change (−8.3%) in women (HR 1.22 [95% CI 1.09–1.39]) and men (1.45 [1.20–1.75]) after adjustment for age, race, smoking, family history of diabetes, baseline fitness, BMI, and fasting glucose. Participants who developed diabetes over 20 years experienced significantly larger declines in relative fitness over 20 years versus those who did not. CONCLUSIONS Low fitness is significantly associated with diabetes incidence and explained in large part by the relationship between fitness and BMI.
Assisted Reproduction for HIV Serodiscordant Couples: The Ethical Issues in Perspective
Authors: Julian Savulescu
Journal: The American Journal of Bioethics (2003)

�� But it is hard to justify refusing seropositive women the cheaper, less burdensome, and less hazardous treatment option of IUI that does not involve having possibly infected fertilized eggs in the laboratory. When he is aware of an alternative that would minimize the possibility of vertical transmission, withholding the option of the less costly and less invasive procedure seems to violate the principle of beneacence. The section on “justice” begins and ends with a foray into the right to healthcare, an issue about which Sauer and Columbia’s ethics committee have no particular authority. Yet, they do not seem to appreciate the justice issues involved in their own policy. Justice requires policies to reoect important and common human concerns and to deal with similar considerations similarly. In this case Sauer acknowledges the common and profound importance of disease avoidance and procreation. These issues make the provision of sperm-washing services into a matter of justice. For policies relating to disease avoidance and reproductive assistance to be just, however, they must treat similar risks, of harming the woman or producing a child with a serious disease, similarly. Assisted reproduction programs could justly refuse services when HIV-1 was at issue only if they also systematically refused services to women with a similar chance of harm from a pregnancy (e.g., women with diabetes or heart disease) and to couples with a similar chance of producing seriously affected offspring (e.g., children with a serious genetic disease or multiple premature infants for couples who would refuse pregnancy reduction of multiple fetuses). Singling out the harms associated with HIV transmission to justify a refusal of services would be unjust. Conclusion
Effects of catecholamines and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man
Authors: John H. Ball, Neil I. Kaminsky, Joel G. Hardman, Arthur E. Broadus, Earl W. Sutherland, Grant W. Liddle
Journal: Journal of Clinical Investigation (1972)

Studies were performed in healthy volunteers to determine the effects of catecholamines and adrenergic-blocking agents on plasma and urinary levels of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP). Plasma cyclic AMP rose in response to infusions of the beta-adrenergic agent, isoproterenol, or in response to infusions of either epinephrine or norepinephrine alone or in combination with the alpha-adrenergic-blocking agent, phentolamine. Although urinary cyclic AMP also rose, the percentage increase was less than that observed in the plasma. These treatments caused no increase in plasma cyclic GMP. Plasma cyclic GMP rose in response to infusions of alpha-adrenergic agents, viz., epinephrine or norepinephrine infused together with the beta-blocking agent, propranolol. These treatments caused no increase in plasma cyclic AMP. These observations are consistent with the current concept that the actions of beta-adrenergic agents are mediated by increases in cyclic AMP formation in target tissues. Such a mediating role has not been established for cyclic GMP, but the data suggest the possibility that cyclic GMP metabolism is responsive either to alpha-adrenergic stimulation or to parasympathetic stimulation which occurs as a reflexive consequence of the pressor effect of alpha-adrenergic agents.
Identification of an Acceptor System for γ-Aminobutyric Acid on Isolated Rat Hepatocytes
Authors: Gerald Y. Minuk, John Vergalla, Peter Ferenci, E. Anthony Jones
Journal: Hepatology (1984)

gamma-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter which is synthesized by the enteric bacterial flora and delivered into portal venous blood. To determine whether the liver is likely to play an important role in regulating serum GABA levels, the uptake and metabolism of [3H]GABA by three populations of cells isolated from rat liver were studied. GABA was specifically taken up by hepatocytes but not by endothelial or Kupffer cells. Uptake by hepatocytes was saturable, as well as time and sodium dependent. At 0.5 degrees C, a temperature at which binding of GABA to the cell surface is considered to be the predominant component of the uptake process, the apparent affinity constant (Km) was 0.82 microM and a minimum value for binding velocity (Vmax) was 0.13 microM per min per 5 X 10(5) cells. Uptake of [3H]GABA by hepatocytes was markedly inhibited by excess unlabeled GABA (95%), alpha-aminoisobutyric acid (66%) and bicuculline (58%), but was inhibited much less by alanine (16%) and leucine (29%). These findings suggest that GABA binds specifically to the high affinity acceptor of the A amino acid transport system of rat hepatocytes. Impaired function of this transport system in liver failure could contribute to increased circulating levels of GABA.