tbuckley/cabot-search huggingface dataset:
Carbon monoxide?mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver
Authors: Mikiji Mori, Makoto Suematsu, Takanori Kyokane, Tsuyoshi Sano, Hidekazu Suzuki, Tokio Yamaguchi, Yuzuru Ishimura, Hiromasa Ishii
Journal: Hepatology (1999)

This study aimed to examine whether acetaminophen (AAP), an anti-inflammatory agent producing hepatocellular damages with its overdose, evokes hepatocellular dysfunction through mechanisms involving carbon monoxide (CO) generated by heme oxygenase (HO). In perfused rat livers, CO and bilirubin were determined in venous perfusate and bile samples as indices of heme degradation. Biliary excretion of transportally injected horseradish peroxidase was also determined to assess paracellular junctional permeability and vesicular transport across hepatocytes. AAP at 20 mmol/L induced a transient choleresis, followed by a reduction of bile output. Under these circumstances, the release of CO and bilirubin IXalpha, terminal products of the HO-mediated heme degradation, became 2. 5-fold greater than the control. The rate of CO production appeared stoichiometric to the degradation rate of microsomal cytochrome P-450. Mechanisms for the AAP-induced cholestasis involved an increase in the junctional permeability that coincided with a reduction of vesicular transport across hepatocytes. Clotrimazole, a cytochrome P-450 inhibitor, or zinc protoporphyrin IX, an HO inhibitor, but not copper protoporphyrin IX, which did not inhibit HO, attenuated these AAP-induced changes. Furthermore, administration of CO at concentrations comparable with those induced by AAP elicited a marked elevation of the paracellular junctional permeability concurrent with a reduction of transcellular vesicular transport, mimicking effects of the AAP administration. Thus, CO serves as a putative regulator of hepatocellular function that is overproduced through acute heme degradation during xenobiotic transformation.
Research Projects in Burkitt's Lymphoma
Authors: John L. Ziegler
Journal: JAMA (1972)

In July 1967, a collaborative research project, the Uganda Cancer Institute, was established at Makerere University, Kampala, with contract support from the National Cancer Institute. As a senior investigator from the NCI, I was sent to Uganda in an advisory capacity to help set up research projects in Burkitt's lymphoma and other cancers. Over the past five years more than 150 patients with Burkitt's lymphoma have been treated according to randomized clinical trials designed to improve the effectiveness of chemotherapy in this disease. These trials showed that 90% of patients with Burkitt's lymphoma had complete remissions following a single intravenous dose of cyclophosphamide, 40 mg/kg of body weight. Remissions were more durable in patients treated with multiple doses, as compared with a single dose, of the drug. Introduction of other agents in the primary treatment of the disease including vincristine sulfate, methotrexate, and cytosine arabinoside also improved remission duration, but
Multi-modal treatment with peptide vaccine, metronomic cyclophosphamide and anti-PD1 monoclonal antibody provides effective control of tumors in multiple models
Authors: Genevieve Weir, Olga Hrytsenko, Marianne Stanford, Neil Berinstein, Robert Liwski, Mohan Karkada, Marc Mansour
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Future cancer immunotherapies will combine multiple treatments to improve immune responses to cancer through synergistic, multi-modal mechanisms. In a Phase I clinical trial, we found that the immune response to a peptide vaccine targeting survivin, DPX-Survivac, by ovarian cancer
Differentiating Early-Onset Persistent Versus Childhood-Limited Conduct Problem Youth
Authors: Edward D. Barker, Barbara Maughan
Journal: American Journal of Psychiatry (2009)

Objective: Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. Method: To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Results: Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Conclusions: Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.
Risk for Cardiovascular Autonomic Neuropathy Is Associated with the HLA-DR3/4 Phenotype in Type I Diabetes Mellitus
Authors: Joshua Barzilay, James H. Warram, Lawrence I. Rand, Michael A. Pfeifer, Andrzej S. Krolewski
Journal: Annals of Internal Medicine (1992)

▪ Objective: To identify risk factors for the development of cardiovascular autonomic neuropathy in patients with juvenile-onset type I diabetes mellitus. ▪ Design: Cross-sectional examination of an inception cohort 15 to 21 years after the onset of diabetes. ▪ Setting: Outpatient diabetes clinic. ▪ Patients: Seventy-nine patients with type I diabetes who experienced onset of disease before 21 years of age and who were followed for 15 to 21 years. ▪ Measurements: Autonomic nerve function was evaluated in all patients using deep breathing and tilt tests. On the basis of these tests, an index of cardiovascular autonomic neuropathy was derived and patients were classified as having intact, mildly impaired, or significantly impaired autonomic function. ▪ Results: The group with significantly impaired function had a higher mean hemoglobin A1 at the time of examination than the group without impairment, yet the groups did not differ regarding glycemie control during the first decade of diabetes. The HLA-DR3/4 phenotype was present in more than 50% of the patients with significant autonomic dysfunction and conferred relative odds of 6.2 (95% Cl, 1.7 to 23.3) for the development of autonomic neuropathy when compared with other HLA-DR phenotypes. Sex, percent ideal body weight, and smoking did not have a statistically significant effect on the development of autonomic neuropathy. ▪ Conclusions: The development of cardiovascular autonomic neuropathy in type I diabetes mellitus is strongly associated with the HLA-DR3/4 phenotype. Thus, genetic predisposition may play an important role in the development of this complication.
ACUTE-PHASE EFFICACY OF ZS-9 IN PATIENTS WITH BASELINE SERUM POTASSIUM LEVELS ABOVE 5.5 MEQ/L: ANALYSIS FROM A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL
Authors: Mohamed El-Shahawy, Henrik S. Rasmussen, Philip T. Lavin, Alex Yang, David K. Packham
Journal: Journal of the American College of Cardiology (2015)
The Natural History of Alcoholism: Causes, Patterns, and Paths to Recovery
Authors: DONALD W. GOODWIN
Journal: American Journal of Psychiatry (1984)

Back to table of contents Previous article Next article ArticlepublicationContent.noAccessThe Natural History of Alcoholism: Causes, Patterns, and Paths to RecoveryDONALD W. GOODWINDONALD W. GOODWINpublicationContent.publishedOnline:1 Apr 2006https://doi.org/10.1176/ajp.141.5.708publicationContent.aboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations share.shareLabelShare onFacebookTwitterLinked InEmail "The Natural History of Alcoholism: Causes, Patterns, and Paths to Recovery." American Journal of Psychiatry, 141(5), pp. 708–709 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Register for access Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). publicationContent.figurespublicationContent.referencespublicationContent.citedBypublicationContent.detailspublicationContent.citedByNone Volume 141Issue 5 May 1984Pages 708-709 Metrics publicationContent.pdfDownload History Published online 1 April 2006 Published in print 1 May 1984
Targeted delivery of liposomal dexamethasone phosphate to the spleen provides a persistent therapeutic effect in rat antigen-induced arthritis
Authors: U Rauchhaus, R W Kinne, D Pohlers, S Wiegand, A Wolfert, M Gajda, R Brauer, S Panzner
Journal: Annals of the Rheumatic Diseases (2009)

Although long-term suppression of experimental arthritis has been reported for liposomal glucocorticoids, direct effects on subsequent flare-up reactions have not been investigated. The glucocorticoid dexamethasone phosphate (DXM-P) was encapsulated in large, non-PEGylated liposomes (DPPC/DPPG/Chol, 50/10/40 mol%, size: 295 (SD 15) nm) and its therapeutic efficacy was compared with free (non-liposomal) drug in rat antigen-induced arthritis (AIA). The specific aim was to assess the therapeutic persistence of an initial acute phase treatment with liposomal DXM-P on the induction of a subsequent flare-up reaction.

Intravenous injection of liposomal DXM-P (1.25 mg/kg body weight) at 6, 24 and 48 h following arthritis induction completely suppressed joint swelling. The tight treatment schedule was chosen based on the rapid kinetics of arthritis development in this model (6 h: half-maximal swelling; 24–48 h peak arthritis). No rebound was seen until day …
Cancer therapy combination: green tea and a phosphodiesterase 5 inhibitor?
Authors: Chung S. Yang, Hong Wang
Journal: Journal of Clinical Investigation (2013)

The major constituent of green tea, (–)-epigallocatechin-3-O-gallate (EGCG), has been shown to have cancer-preventive and therapeutic activities. Numerous molecular targets for EGCG have been proposed, but the mechanisms of its anticancer activities are not clearly understood. In this issue of the JCI, Kumazoe et al. report that EGCG activates 67-kDa laminin receptor (67LR), elevates cGMP levels, and induces cancer cell apoptosis. Furthermore, a phosphodiesterase 5 inhibitor, vardenafil, synergizes with EGCG to induce cancer cell death. This is a provocative observation with important implications for cancer therapy. It also raises several issues for further investigation, such as the mechanism by which EGCG specifically activates 67LR.
Asking the right question
Authors: A. Hamilton
Journal: BMJ (2003)

Ten years ago I was feeling overwhelmed by the plethora of scientific papers at the annual Australasian STD Congress when I noticed a paper to be presented in one of the smaller lecture theatres. It looked as if it might be relevant to my work in a city sexual health clinic: Should the question “Have you been sexually abused?” be asked routinely when taking a sexual health history? 1

Of 407 patients asked this question in September 1992 at the Auckland Sexual Health Centre, 90% had never been asked this before by a health professional, …
A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man.
Authors: J M Wilson, J T Stout, T D Palella, B L Davidson, W N Kelley, C T Caskey
Journal: Journal of Clinical Investigation (1986)

We characterized 24 unrelated patients with a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) in an attempt to better understand the nature and spectrum of mutations that underlie this prototype-inherited disease. Lymphoblast cell lines derived from each patient were analyzed at multiple molecular levels including the structure and function of the residual HPRT enzyme, messenger RNA (mRNA), and gene. Our studies demonstrate the following: (a) at least 16 of the 24 patients represent unique and independent mutations at the HPRT structural gene; (b) the majority of cell lines have normal quantities of mRNA but undetectable quantities of enzyme; (c) 33% of patients retain significant quantities of structurally altered, functionally abnormal, HPRT enzyme variants; and (d) a minority of patients are void of both enzyme and mRNA, possibly representing examples of aberrations in gene expression. Our studies provide direct evidence for marked genetic heterogeneity in this disorder and illustrate the kinds of mutations and mutational consequences that underlie inherited disease in humans.
Abstract 3233: Inhibition of aldose reductase prevents lung cancer cell growth <i>in vitro</i> and <i>in vivo</i>
Authors: Kota V. Ramana, Ravinder Tammali, Sharad S. Singhal, Sanjay Awasthi, Satish K. Srivastava
Journal: Cancer Research (2010)

Abstract Lung cancer is the second most common cancer and the leading cause of cancer death among both men and women. Although, tobacco smoking is the dominant etiologic factor responsible for the vast majority of lung cancers, other factors such as asbestos, pollutants, polycyclic aromatic hydrocarbons, nutritional and dietary factors which can cause pulmonary inflammation can also drive carcinogenesis by altering cellular and molecular targets and pathways that are crucial to normal tissue homeostasis. However, the molecular signaling events specific to the pulmonary inflammation and their effects on pulmonary cells leading to carcinogenesis are poorly understood. Hence, we investigated the role of polyol pathway enzyme aldose reductase (AR), an oxidative stress response protein that catalyzes the reduction of lipid peroxidation -derived lipid aldehydes and their glutathione conjugates, in the mediation of carcinogenic signals leading to lung cancer. We examined the effect of pharmacological and siRNA -mediated inhibition of AR on in vitro human lung carcinoma cell line A549 growth as well as tumor growth in nude mice xenografts. We have also examined the molecular mechanisms by which AR inhibition prevents carcinogenic signaling events that cause lung cancer cell growth. Treatment of A549 cells with AR inhibitors prevented the activation of NF-kB and expression of NF-kB- dependent inflammatory markers such as iNOS and Cox-2. AR inhibition also prevented the proliferation of cultured human lung cancer cells. Further, AR inhibition significantly arrested the tumor growth in nude mice bearing lung adenocarcinoma xenografts. Similar results were observed in AR-siRNA treated nude mice xenografts. Immunohistochemical analysis of nude mice tumor cross sections indicated that AR inhibition prevents activation of iNOS, Cox-2, AR and NF-kB. Our studies thus strongly suggest that AR may be a critical regulator of signaling pathway(s) that cause lung cancer. Hence, disrupting these signals by AR inhibition could be a novel preventive approach in lung cancer progression. 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 3233.
Olympic gold doctor
Authors: Dee Arnold
Journal: British Journal of Sports Medicine (2010)

Stephanie Cook was the winner of the gold medal in the modern pentathlon at the 2000 Sydney Olympics and went on to become European and world champion in 2001. She retired from competition in 2001 to return to medicine as a full-time doctor. Dee Arnold caught up with her.

My first 2 years at Cambridge gave me a chance to be a proper student and get involved. My sister was a cox for the university rowing team, and although I’d never rowed before, I decided to give it a go. Eventually, I rowed as part of the crew that beat Oxford—an unforgettable memory.

I studied social anthropology in my intercalated year, which also looked at how cultures and societies view health. It has given me a wider understanding of patients’ beliefs and expectations about health in our cosmopolitan society.

Eric Liddell, of the Chariots …
Single lung alveolar volume and gas transfer: effect of expansion of the other lung.
Authors: B Johansen, O Bjortuft
Journal: Thorax (1994)

BACKGROUND--Temporary occlusion of one mainstem bronchus permits measurement of single lung function. A previous study suggested that the volume at which one lung is occluded may influence the expansion of the other. The effect of ipsilateral occlusion volume on the contralateral effective alveolar volume (VA, EFF,SL), inspired volume (VI,SL), single breath estimated residual volume (RVSB,SL), carbon monoxide (CO) transfer (TLCO,SL) and transfer coefficient (KCO,SL) has been examined. METHODS--Single breath measurements of CO transfer were made in duplicate in 12 healthy subjects aged 19-44 years, without and during occlusion of one mainstem bronchus by a balloon at RV and at total lung capacity (TLC). RESULTS--Mean VA,EFF,SL, VI,SL, and TLCO,SL were lower during occlusion at RV than during occlusion at TLC (2.84 v 3.26 l; 2.18 v 2.54 l; and 4.70 v 5.51 mmol/kPa/min respectively). RVSB,SL was independent of occlusion volume and KCO,SL not different from the KCO of both lungs (KCO,BL). Single lung values during occlusion at TLC were fairly reproducible and were, except for KCO,SL, approximately half the values for both lungs. During occlusion at RV the second TLCO,SL and KCO,SL were lower than the first. CONCLUSIONS--Occlusion of one lung permits reliable determinations of gas transfer indices of the other, provided the lung is occluded at TLC. Occlusion at RV significantly reduces VA,EFF,SL, and hence TLCO,SL, but does not affect KCO,SL of the other lung.
Parenteral nutrition product is suspected as cause of 18 cases of septicaemia in neonates
Authors: I. Torjesen
Journal: BMJ (2014)

Public Health England and the Medicines and Healthcare Products Regulatory Agency (MHRA) are investigating 18 cases of septicaemia, including one death, that have occurred in neonatal intensive care units at a small number of hospitals in England.

Investigations are ongoing, but the infections are believed to be linked to a batch of parenteral nutrition given to neonates that had become contaminated with Bacillus cereus . The feed was manufactured by ITH Pharma, which has recalled all remaining stocks of that batch, and the MHRA has issued a class 1 drug alert to the recall. The batch of affected feed …
TREATMENT OF ECLAMPSIA
Authors: J. CLIFTON EDGAR
Journal: JAMA (1918)

Convulsive toxemia, except in a small minority of instances, is always preventable. There are even those optimists who state that if certain measures of prevention are carried out, eclamptic convulsions will cease to exist.  Be this as it may, the symptoms of a pregnancy toxemia are readily recognizable. Witness the almost entire absence of convulsive toxemia among the antepartum patients of a maternity hospital and among patients in private practice, who are under conscientious medical observation from early pregnancy, and who faithfully follow the directions of their medical attendant. The exceptional cases that get by, so to speak, are the fulminant cases of hepatic toxemia, with no edema, little change in the composition or output of the urine, and with convulsions following shortly on the onset of the nausea and vomiting, headache or visual disturbances.  The nausea, vomiting, headache, edema, diminished urinary output, constipation, eye symptoms, nervous symptoms, and high
Tranilast Prevents Atrial Remodeling and Development of Atrial Fibrillation in a Canine Model of Atrial Tachycardia and Left Ventricular Dysfunction
Authors: Yosuke Nakatani, Kunihiro Nishida, Masao Sakabe, Naoya Kataoka, Tamotsu Sakamoto, Yoshiaki Yamaguchi, Jotaro Iwamoto, Koichi Mizumaki, Akira Fujiki, Hiroshi Inoue
Journal: Journal of the American College of Cardiology (2012)
FIFTY YEARS IN PSYCHIATRY
Authors: John B. Chapin
Journal: American Journal of Psychiatry (1905)

FRIENDS: It is a trite saying that no one is consulted about the date or the place of birth, nor the number of his days-whether they shall be short, or by a kindly Providence be prolonged.It is another proverbial utterance that it is as much in the natural ordering of things that there shall be limitations and endings of the life of man, or of his activities, as that he shall be brought into being.Four years ago, when an intimation was given out that a desire existed to take some notice of the term of my hospital service, a postponement was asked, if any such serious intention was to be carried out, until the completion of a period of fifty years of duty in a hospital for the insane.If such an event is to be considered creditable and worthy of this commemorative occasion, then it should be remembered in this connection that it could only have been possible-and I would emphasize the fact-through a conservative policy of the boards of managers under whom I have served, whose confidence it has been my privilege to enjoy.In giving a physician a reasonably secure tenure of office, these boards have established a most creditable precedent that is a protest against changes due to the corroding and degenerating influences of medical or State politics, or against changes due to capriciousness, or those schemes that are promoted on the hypothesis that change is necessarily an element of reform or improvement.