tbuckley/cabot-search huggingface dataset:
Differential Induction of Carcinogen Metabolizing Enzymes in A Transgenic Mouse Model of Fulminant Hepatitis
Authors: I Chemin, S Takahashi, C Belloc, M A Lang, K Ando, L G Guidotti, F V Chisari, C P Wild
Journal: Hepatology (1996)

The objective of this work is to examine the possible modulation of carcinogen metabolism (activation by cytochrome P450s and detoxification by conjugation via glutathione S–transferases [GST]) in relation to hepatitis B virus (HBV)–associated liver injury. In HBV transgenic mouse lineage 107.5, the hepatitis B surface antigen (HBsAg) is expressed at noncytopathic concentrations but after injection of an HBsAg–specific, major histocompatibility complex (MHC) class I restricted cytotoxic T–lymphocyte (CTL) clone, the mice develop a severe acute necroinflammatory liver disease that reaches maximum severity within 3 days and gradually subsides during the next 2 to 3 weeks. In this model, using immunohistochemical analysis, we observed an increase of P450s (CYP1A and 2A5), both involved in aflatoxin B1, metabolism, but minor changes or no changes for others (2B, 2C, 2E, 3A). There was a fivefold decrease in the total liver P450 microsomal content 3 days' post–CTL injection with the result that the relative proportion of CYP2A5 and 1A compared with other P450s is increased. Individual microsomal P450 enzyme contents estimated by Western blotting; Northern blot analysis of liver CYP messenger RNA (mRNA) levels as well as in vitro metabolism of specific substrates for different P450 isoenzymes were consistent with the immunohistochemical data. Immunohistochemical staining with antibodies to cytosolic pi class GST was increased 1 and 3 days postinjection followed by a progressive decrease at later time points (the same phenomenon was observed to a lesser extent for GST α). The activity of hepatic cytosols toward substrates specific for different subclasses of GST (mu, pi, α) showed that while GST mu was not changed in the CTL–injected HBV transgenic mice, GST pi and, to a lesser extent, α were increased as compared with controls. These results suggest that liver cell injury induced by a process of acute fulminant–like hepatitis can lead to the induction of some carcinogen metabolizing enzymes notably, Cyp 1A, 2A5 and GST pi in the mouse.
Pituitary Tumors: Diagnosis and Therapy
Authors: D. M. Cook
Journal: CA A Cancer Journal for Clinicians (1983)

The newer diagnostic methods for identifying pituitary tumors have been presented, along with a discussion of therapy. Not all the issues are clear, particularly those for prolactin-secreting tumors. Drug therapy may play an increasing role, especially dopamine agonists, which control either hGH or prolactin secretion and can cause shrinkage of tumor tissue.
Overcoming immune-cell unresponsiveness in cancer
Authors: Guenther Lametschwandtner, Monika Ermann, Ina Sternberger, Thomas Hesterkamp, Isabella Haslinger, Hannes Mühleisen, Manfred Schuster, Hans Loibner
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Despite significant recent progress, cancer immunotherapy efficacies are still limited, since tumors can down-modulate and escape the immune system by various mechanisms. To overcome these limitations, we aimed to identify low molecular weight molecules that can enhance T cell
Intracellular acidification and ADP enhance nicorandil induction of ATP sensitive potassium channel current in cardiomyocytes
Authors: A. Jahangir, A. Terzic, Y. Kurachi
Journal: Cardiovascular Research (1994)

Objective: Potassium channel openers target ATP sensitive potassium (KATP) channels, and might be beneficial in the treatment of ischaemic cardiac conditions. Ischaemia is associated with an increase in the concentrations of intracellular nucleoside diphosphates and protons, two regulators of KATP channels. Since it is largely unknown whether these factors modulate the action of potassium channel openers, the aim of this study was to define the effects of ADP and intracellular acidification on KATP channel activation by nicorandil, a potassium channel opener currently in clinical use. Methods: To measure ionic currents, the whole cell patch clamp technique was employed in guinea pig single ventricular myocytes. Induction of KATP channel current by pinacidil, a potassium channel opener chemically unrelated to nicorandil, was used for comparison. Results: Nicorandil (300 (μM) and pinacidil (100 μM) induced a time independent K+ current, which was inhibited by glibenclamide (6 μM), a selective blocker of KATP channels. ADP in the pipette solution was required for the nicorandil induced activation of KATP channels when the pH of the pipette solution was 7.2. In the absence of ADP, lowering the pH of the pipette solution to 6.5 was necessary for nicorandil to induce KATP channel current. For pinacidil to induce KATPchannel current neither the addition of intracellular ADP nor acidification was required. Conclusions: Nicorandil may activate KATP channel current more effectively in conditions associated with a change in intracellular proton and ADP concentrations such as cardiac ischaemia. Cardiovascular Research 1994;28:831-835
Chromosomal abnormalities define clonal proliferation in CD3‐ large granular lymphocyte leukemia
Authors: Masafumi Taniwaki, Shinichi Tagawa, Hikari Nishigaki, Shigeo Horiike, Shinichi Misawa, Chihiro Shimazaki, Taira Maekawa, Hiroshi Fujii, Teruo Kitani, Tatsuo Abe
Journal: American Journal of Hematology (1990)

Abstract Six patients with lymphoproliferative disorder of large granular lymphocytes (LDGL) were studied for chromosomal abnormalities. When the patients were divided into two groups depending on the expression of a mature antigen of T cell lineage, CD3, two with CD3 + phenotype had a stable disease, whereas three of the four patients with CD3‐ phenotype had marked hepatosplenomegaly and a highly aggressive disease. Chromosomal abnormalities were detected in four of six patients, indicating a clonal proliferation of large granular lymphocytes in individual patients. In particular, chromosomal abnormalities were found in three of the four patients with CD3‐ LDGL. all of which had a germ‐line configuration of the T cell receptor beta‐chain gene. Thus, the chromosomal abnormalities provide definitive evidence for the clonal origin of the expanded cells in the CD3‐LDGL.
Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans in Fly Ash and Cinders Collected from Several Municipal Incinerators in Japan
Authors: Tadaaki Wakimoto, Ryo Tatsukawa
Journal: Environmental Health Perspectives (1985)

Determination of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in fly ash and cinders collected from nine municipal incinerators in Japan was made. The concentrations of PCDDs and PCDFs in this study were generally in the same range as those in Europe and North America. However, the rather different congener composition compared with those published already were found: higher percentages of lower chlorinated (di- and tri-) dibenzo-p-dioxins and dibenzofurans and no or trace levels of the octachloro compounds, O8CDD and O8CDF. One possible explanation for this difference may be the higher incineration temperature in Japan. The same ranges of concentrations of PCDDs and PCDFs were found in cinders as well as fly ash. The volumes of the cinders are much larger than those of fly ash and therefore the fate and impact of PCDDs and PCDFs in dump sites of these cinders should be studied.
Retinal changes in malignant hypertension.
Authors: E McGregor, C G Isles, J L Jay, A F Lever, G D Murray
Journal: BMJ (1986)

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.
The Hidden Dimension: Psychodynamics in Compulsive Drug Use
Authors: Peter Barglow
Journal: JAMA (1980)

This is a vast book, in its intellectual breadth and its extensive review of pertinent literature. The author has been director of a major medical school alcohol and drug abuse program but is also scholar, physician, philosopher, and psychoanalyst. In describing the intrapsychic experience of the compulsive drug user, Wurmser makes his most important contribution. The author emphasizes and supports with clinical evidence the finding that addicts, except for a few alcoholics and cigarette users, have serious psychopathological conditions that antedate their excessive drug use and that dominate treatment difficulties. The single diagnosis most frequently represented is the "borderline personality organization," extensively described recently by Kohut and Kernberg. In Wurmser's own Methadone Maintenance Program population, 10% of patients were frankly psychotic; 30%, severely paranoid or depressed; 30%, episodically deeply regressed; and only 30% had moderate psychopathological conditions controllable with methadone and the milieu of the treatment facility alone. Through examination
High Human Papillomavirus Oncogene mRNA Expression and Not Viral DNA Load Is Associated with Poor Prognosis in Cervical Cancer Patients
Authors: Marjon A. de Boer, Ekaterina S. Jordanova, Gemma G. Kenter, Alexander A. Peters, Willem E. Corver, J. Baptist Trimbos, Gert Jan Fleuren
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cervical cancer is now known to be caused by infection with an oncogenic type of the human papillomavirus (HPV). However, little is known about the continued role of HPV once cancer has been established. Here, we describe the quantitative relation between HPV DNA copy number and mRNA expression of the viral oncogenes (E6 and E7) and the prognostic value of both measures in cervical cancer patients. Experimental Design: We studied the number of viral DNA copies and the level of HPV E6/E7 mRNA expression in 75 HPV 16–positive or HPV 18–positive International Federation of Gynecology and Obstetrics stage Ib and IIa cervical cancer patients. Measurements were done with quantitative PCR. DNA copy number analysis was done on pure tumor cell samples enriched with flow sorting. mRNA expression data were compensated for the percentage of tumor cells included. Results: The number of viral DNA copies was not predictive of survival in cervical cancer patients. In contrast, high HPV E6/E7 mRNA expression was strongly related to an unfavorable prognosis (P = 0.006). In a multivariate Cox model for overall survival, including all known prognostic variables and stratified for HPV type, the level of E6/E7 mRNA expression was an independent prognostic indicator, second only to lymph node status. No correlation was observed between DNA copy number and the level of HPV E6/E7 mRNA expression, which reflects that not all DNA copies are equally transcriptionally active. Conclusions: Cervical cancer patients with high HPV E6/E7 oncogene mRNA expression have a worse survival independently from established prognostic factors.
ERYTHOXYLON COCA AS A HEART TONIC.
Authors: E. CUTTER
Journal: JAMA (1898)

After the 1871, San Francisco, meeting of theAmerican Medical Association, I went to the Yosemite Valley and ascended the Cap of Liberty, 12,500 feet above sea level. I remember the ascent, which was so steep that I had to pull myself up by the bushes! The diminished atmospheric pressure was such that I could not climb more than forty feet at a time. My pulse ran so high that I could not count it. My heart beat so violently that I felt it would stop if I did not pause, and my whole body was bathed in sweat. As my heart was somewhat enlarged and so weak that its usual beats were forty per minute, I suppose I ran an imminent risk of losing my life, but as a result I had herpes zoster. This California mountain experience helps me to understand how climbers have vertigo on the summit
Proxy and Surrogate Consent in Geriatric Neuropsychiatric Research: Update and Recommendations
Authors: Scott Y.H. Kim, Paul S. Appelbaum, Dilip V. Jeste, Jason T. Olin
Journal: American Journal of Psychiatry (2004)

The ethics of involving decisionally incapable adults in research will continue to grow in importance as more research is conducted to address the problems of decisionally impaired persons, especially elderly persons. The authors provide an updated discussion, critique, and recommendations regarding the need for clear legal and regulatory policy on this issue.The authors summarize and build on discussions of a workshop on proxy and surrogate consent in geriatric neuropsychiatric research sponsored by the Aging Research Consortium of the National Institute of Mental Health. They incorporate the views of various stakeholders present at the workshop as well as review recent federal and state initiatives, recent empirical research and media reports, and various commission reports and relevant regulations.Despite a wave of initiatives in the late 1990s to clarify policy, surrogate consent for research continues to be a murky legal area and incapable subjects in the United States still lack clear regulatory protection. There is evidence that conservative risk management strategies by institutional review boards and their institutions may severely restrict research with decisionally impaired subjects. A passive approach to this problem may no longer be feasible. A recent federal advisory report on human research protections and legislative initiatives in some states could begin to provide a blueprint for future policy making. Interim recommendations for various stakeholders are given.It is imperative that the scientific community, patients and their advocates, and policy makers at all levels establish a constructive dialogue to clarify ethical and legal standards in the area of proxy and surrogate consent for research.
Human reasoning includes a mental logic
Authors: David P. O'Brien
Journal: Behavioral and Brain Sciences (2009)

Abstract Oaksford &amp; Chater (O&amp;C) have rejected logic in favor of probability theory for reasons that are irrelevant to mental-logic theory, because mental-logic theory differs from standard logic in significant ways. Similar to O&amp;C, mental-logic theory rejects the use of the material conditional and deals with the completeness problem by limiting the scope of its procedures to local sets of propositions.
Vasoactive factors in sickle cell disease: In vitro evidence for endothelin‐1‐mediated vasoconstriction
Authors: Sitki Ergul, Chris Y. Brunson, Jim Hutchinson, Amany Tawfik, Abdullah Kutlar, R. Clinton Webb, Adviye Ergul
Journal: American Journal of Hematology (2004)

Abstract While systemic plasma endothelin‐1 (ET‐1) levels are increased during acute crisis in sickle cell disease, the relative levels of potent vasoactive factors that contribute to the regulation of vascular function, such as ET‐1, NO, and cell‐free hemoglobin, during the course of periodic vaso‐occlusive episodes remain unclear. Moreover, whether and to what extent sickling‐induced release of ET‐1 alters vascular tone is not completely understood. To investigate the sequential changes in circulating vasoactive factors, we measured plasma ET‐1, NO metabolites (NOx), and cell‐free hemoglobin (Hb) before (steady‐state), during (crisis), and after a vaso‐occlusive (post‐crisis) episode. Steady‐state ET‐1 levels (fmol/mL) increased from 2.3 ± 0.4 to 11.0 ± 1.4 and 4.2 ± 1.0 during crisis and post‐crisis periods, respectively. There was no significant difference in plasma NOx levels. Cell‐free Hb levels were significantly higher in sickle cell patients in all phases as compared to the control group, and especially during crisis cell‐free Hb levels were elevated by 4‐fold (209,000 ± 31,000 vs. 46,000 ± 5,300 ng/mL in steady‐state). Conditioned medium from human pulmonary artery endothelial cells exposed to sickled erythrocytes prepared by deoxygenation induced contraction of aortic rings, and this effect was blocked by an ET A receptor antagonist. These findings indicate that ET‐1 is the predominant contractile factor released by cultured endothelial cells upon exposure to deoxygenated sickled SS erythrocytes and ET‐1–NO–NO scavenger balance is altered in favor of vasoconstriction during an acute episode in SCD. Am. J. Hematol. 76:245–251, 2004. © 2004 Wiley‐Liss, Inc.
SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism
Authors: Weiwei Tao, Siyu Chen, Guangsen Shi, Jinhu Guo, Ying Xu, Chang Liu
Journal: Hepatology (2011)

Many aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism, are under precise control by the mammalian circadian clock. However, the molecular mechanism for coordinate integration of the circadian clock and various metabolic pathways is poorly understood. Here we show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show abnormalities in the rhythmic expression pattern of clock and metabolic genes and in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs the oscillation of clock genes in serum-shocked HepG2 cells. At the molecular level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation of retinoid-related orphan receptor alpha (RORα). In addition, BAF60a is present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into the active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinated regulation of hepatic circadian clock and energy metabolism in mammals. (Hepatology 2011;)
The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults
Authors: Anastassios G. Pittas, Bess Dawson-Hughes
Journal: Diabetes Care (2007)

We would like to thank Tournis and Mitrakou (1) for their comments on our recent publication (2), and we appreciate the opportunity to respond. We agree that the favorable effects of vitamin D on glycemia may, at least in part, be due to the favorable …
EPIDEMIC CEREBROSPINAL MENINGITIS AT CAMP McCLELLAN
Authors: E. M. MEDLAR
Journal: JAMA (1918)

The preliminary report by Major Herrick 1 on the epidemic of meningitis at Camp Jackson calls attention to the incorrectness of the generally accepted view that epidemic cerebrospinal meningitis is primarily a meningitis. His view, that it is a secondary involvement of the meninges, appears to be the correct conception, and it is my purpose here to emphasize, from observations made at Camp McClellan, the importance of his conclusions.  As far as is known, all meningitis, exclusive of traumatic meningitis and brain abscess, is secondary to hematogenous infection. This is common knowledge with regard to tuberculous, pneumococcic, streptococcic, staphylococcic, influenzal, typhoidal and anthrax meningitis. That meningococcic meningitis should also fall into this class is but a logical deduction because of the fact that blood cultures are often positive early in the disease, while later they are very rarely positive. It is probable that if seen early enough, all cases of
Relationship between body weight and blood pressure and some metabolic parameters in psoriatic patients
Authors: ANDREA PESERICO, G. ZANETTI, S. PADOVAN, PATRIZIA BERTOLI, C.VELLER FORNASA, R. CIPRIANI, G.B. AMBROSIO, S. ZAMBONI, A. PAGNAN
Journal: British Journal of Dermatology (1988)

The relationship between body weight and blood pressure, total serum cholesterol, triglycerides, uric acid and glucose was investigated in 203 psoriatic patients in comparison with 904 healthy controls. In the psoriatic patients, these parameters were clearly related to their body weight. Those psoriatic patients of normal weight exhibited lower mean values of all the parameters compared with overweight psoriatic patients while they did not differ from control subjects of normal weight. Our results suggest that only overweight psoriatic patients exhibit the metabolic abnormalities frequently reported in the literature, while psoriatic patients of normal weight do not differ from the general population in this respect.
Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy
Authors: A. Pivarcsi, F. Meisgen, N. Xu, M. Ståhle, E. Sonkoly
Journal: British Journal of Dermatology (2013)

MicroRNAs (miRNAs) are endogenous, nonprotein-coding, regulatory RNAs with important roles in health and disease. miRNAs are present in the circulation in a stable form and their levels are altered in diseases.To determine whether antitumour necrosis factor (TNF)-α therapy affects serum miRNA levels in patients with psoriasis.Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. miRNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti-TNF-α-regulated miRNAs in patients' sera. The expression of five miRNAs regulated by etanercept was measured by quantitative polymerase chain reaction (qPCR) in sera from patients and controls.Etanercept significantly suppressed a panel of 38 miRNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by qPCR showed that serum levels of miR-106b, miR-26b, miR-142-3p, miR-223 and miR-126 were significantly downregulated by etanercept in responders (Psoriasis Area and Severity Index change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not upregulated in patients with psoriasis compared with healthy controls. The level of four circulating miRNAs was significantly different (increased: miR-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum.The level of circulating miRNAs is altered in psoriasis. Anti-TNF-α therapy has a profound effect on the serum level of miRNAs; however, these are not related to disease severity. Our results suggest that changes in the miRNA level may reflect a previously unknown effect of anti-TNF-α therapy. Our results suggest the involvement of miRNAs in pathways affected by anti-TNF-α therapy and warrant further investigation of serum miRNAs as potential biomarkers for therapy response in psoriasis.