tbuckley/cabot-search huggingface dataset:
Intranasal DNA Vaccination Induces Potent Mucosal and Systemic Immune Responses and Cross-protective Immunity Against Influenza Viruses
Authors: Lea Torrieri-Dramard, Bénédicte Lambrecht, Helena Lage Ferreira, Thierry Van den Berg, David Klatzmann, Bertrand Bellier
Journal: Molecular Therapy (2010)

The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following intranasal administration of luciferase-coding DNA. Using PEI formulation, intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or intranasal immunization with naked-DNA. Furthermore, intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of intranasal DNA as an effective vaccination route. The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following intranasal administration of luciferase-coding DNA. Using PEI formulation, intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or intranasal immunization with naked-DNA. Furthermore, intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of intranasal DNA as an effective vaccination route.
Assessment of Domestic Violence at the Scene of Domestic Assaults
Authors: Elizabeth M. Datner
Journal: JAMA (1997)

<h3>To the Editor.</h3> —We applaud Dr Brookoff and colleagues<sup>1</sup>for looking beyond the medical setting to understand the dynamics of domestic disputes. Clinicians who treat victims of domestic violence know that these are episodic events that we only occasionally glimpse. The participants in this study admitted that they had been victims of abuse over time but had not used medical services as a primary means for seeking assistance. To date, much of the research on domestic violence has myopically focused on the clinical arena and has not stressed the potential lethality of these cases. Several sources confirm that many victims of domestic violence eventually succumb to homicide.<sup>2</sup>We have had a similar experience with evaluating victims and their use of the 911 emergency system. In a preliminary observational study, we found that of 29 women (aged 13-73 years) who had been murdered in domestic disputes, 17 (59%)
A conversation with Thomas Starzl
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2012)

Today in the United States, more than 6,000 people a year receive a liver transplant, and since liver transplants have begun, over 200,000 patients have received this therapy. They survive today due to the efforts of a legendary scientist and surgeon: Thomas Starzl (Figure ​(Figure1)1) of the University of Pittsburgh Medical Center. He performed the first successful liver transplant in 1967 and refined the use of immunosuppressive drugs such that patients could tolerate their grafts — some for decades. With Starzl’s efforts over the last 50 years, thousands of patients with end-stage liver disease have been able to live long and active lives. The full interview can be seen on the JCI website, http://www.jci.org/kiosk/cgm.
Regulation of c-Myc Ubiquitination Controls Chronic Myelogenous Leukemia Initiation and Progression
Authors: Linsey Reavie, Shannon M. Buckley, Evangelia Loizou, Shoichiro Takeishi, Beatriz Aranda-Orgilles, Delphine Ndiaye-Lobry, Omar Abdel-Wahab, Sherif Ibrahim, Keiichi I. Nakayama, Iannis Aifantis
Journal: Cancer Cell (2013)
IMPACT OF THE FIGURE OF TWO BALLOONS DURING KISSING BALLOON TECHNIQUE AS A PREDICTOR OF SUBOPTIMAL SIROLIMUS-ELUTING STENT EXPANSION IN LEFT MAIN DISTAL BIFURCATION LESIONS
Authors: Hiroyuki Shibata, Shinichiro Yamada, Takatoshi Hayashi, Yasuyo Taniguchi, Sachiyo Iwata, Katsunori Okajima, Akira Shimane, Tomofumi Takaya, Gaku Kanda, Naoki Miyoshi, Kiminobu Yokoi, Yukio Mizuguchi, Syogo Ohishi, Keiko Yodoi, Takayoshi Toba, Teishi Kajiya
Journal: Journal of the American College of Cardiology (2011)
Randomised controlled trial of atenolol and pindolol in human pregnancy: effects on fetal haemodynamics.
Authors: S. Montan, I. Ingemarsson, K. Marsal, N. O. Sjoberg
Journal: BMJ (1992)

OBJECTIVE--To compare the effects of uteroplacental circulation of two beta adrenoceptor blockers, atenolol (cardioselective) and pindolol (non-selective with intrinsic sympathomimetic activity). DESIGN--Controlled double blind double dummy study. SETTING--Departments of obstetrics and gynaecology in two Swedish university hospitals. SUBJECTS--29 women with pregnancy induced hypertension in the third trimester, 13 randomised to atenolol and 16 to pindolol. MAIN OUTCOME MEASURES--Pulsatility index in fetal aorta, umbilical artery, and maternal arcuate artery. Volumetric blood flow in fetal aorta and umbilical vein. RESULTS--Mean arterial blood pressure decreased by 9.0 (95% confidence interval -13.0 to -5.0) mm Hg in the atenolol group and by 7.8 (-11.4 to -4.2) mm Hg in the pindolol group. During atenolol treatment the pulsatility index increased significantly from 1.82 (SD 0.20) to 2.07 (0.32) in the fetal thoracic descending aorta, from 1.44 (0.28) to 1.79 (0.27) in the abdominal aorta, and from 0.93 (0.17) to 1.05 (0.19) in the umbilical artery; the volumetric blood flow in the umbilical vein decreased from 106 (28.8) to 84 (22.6) ml/min/kg. No such changes were seen after treatment with pindolol. Birth weight was similar in the two groups but placental weight was significantly different (529 (122) g in atenolol group v 653 (136) g in pindolol group; p = 0.03). CONCLUSION--The hypotensive effect was similar with both drugs, but only the beta 1 blocker atenolol had significant effects on fetal haemodynamics, although within normal ranges. The implications of these findings can be only speculative, but negative fetal consequences of beta 1 adrenoceptor blockade cannot be excluded.
Abnormal liver function tests in pregnancy
Authors: I. Walker, L. C. Chappell, C. Williamson
Journal: BMJ (2013)

#### Learning points

A 34 year old South Asian nursery worker presented to her general practitioner at 32 weeks’ gestation in her first pregnancy complaining of increasingly severe itching. There was no relevant medical or family history, and she was not taking regular medication. Physical examination was normal with no evident rash. Her blood pressure was 115/65 mm Hg, and there was no proteinuria. The liver function tests were: total bilirubin 6 μmol/L, alkaline phosphatase 178 IU/L, alanine transaminase 42 IU/L, and albumin 34 g/L.

Alkaline phosphatase normally increases during pregnancy because of production of the placental isoenzyme and, by term, may reach three times the normal adult upper reference value. The value of 178 IU/L is therefore likely to be normal (table 1⇓). Pregnant women with isolated raised alkaline phosphatase in this range do not need any further investigation. Likewise, albumin is often decreased in normal pregnancy (table 1⇓) as a consequence of haemodilution. In contrast, the concentrations of the transaminases (alanine and aspartate) and γ-glutamyltransferase normally decrease during pregnancy, and it is important to compare values to an appropriate reference range (table 1). The alanine transaminase result of 42 IU/L is therefore not normal and, because liver disease in pregnancy can have serious consequences, should be followed up within a week.

View this table:

Table 1 
 Typical reference ranges for …
TCT-147 Platelet Volume Indices Are Associated With Responsiveness To Antiplatelet Therapy In Patients Undergoing Percutaneous Coronary Intervention.
Authors: Yun Gi Kim, Inho Chae, Young-Seok Cho, Dong-Ju Choi, Il-Young Oh, Jung-Won Suh, Chang-Hwan Yoon, Tae-Jin Youn
Journal: Journal of the American College of Cardiology (2013)
Phototesting and dosimetry for photochemotherapy
Authors: K. WOLFFF, F. GSCHNAIT, H. HONIGSMANN, K. KONRAD, J.A. PARRISH, T.B. FITZPATRICK
Journal: British Journal of Dermatology (1977)

Journal Article Phototesting and dosimetry for photochemotherapy Get access K. WOLFFF, K. WOLFFF Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Request for reprints to: Dr Klaus Wolff, Department of Dermatology I, University of Innsburck, Anichstr, 35 A‐6020, Innsbruck, Australia. Search for other works by this author on: Oxford Academic Google Scholar F. GSCHNAIT, F. GSCHNAIT Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Search for other works by this author on: Oxford Academic Google Scholar H. HÖNIGSMANN, H. HÖNIGSMANN Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Search for other works by this author on: Oxford Academic Google Scholar K. KONRAD, K. KONRAD Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Search for other works by this author on: Oxford Academic Google Scholar J.A. PARRISH, J.A. PARRISH Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Search for other works by this author on: Oxford Academic Google Scholar T.B. FITZPATRICK T.B. FITZPATRICK Division of Experimental Dermatology, Department of Dermatology I., University of Vienna, and Department of Dermatology, Harvard Medical School, and the Massachusetts General Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 96, Issue 1, 1 January 1977, Pages 1–10, https://doi.org/10.1111/j.1365-2133.1977.tb05177.x Published: 01 January 1977
Promotion of lung tumors in mice.
Authors: H P Witschi
Journal: Environmental Health Perspectives (1983)

Several elements of two-stage carcinogenesis apply to the development of lung tumors in Strain A or Swiss-Webster mice. At least three agents which have been identified as promoters in skin, urinary bladder and liver will also enhance tumor formation in lung; phorbol, saccharin and butylated hydroxytoluene (BHT). The antioxidant BHT acts in many respects like a typical promoting agent: it is effective if animals are treated after exposure to an initiating agent, but not if they are treated beforehand. Administration of BHT can be delayed up to 5 months after urethan treatment and still enhance tumor formation. BHT enhances lung tumor formation regardless of its route of administration (IP injection, gavage, or ingestion in the diet). The lowest dose of BHT required to produce an effect has not yet been determined. In at least one mouse strain, BHT also enhances tumor formation in animals initiated with 3-methylcholanthrene or dimethylnitrosamine. On the other hand, no evidence is available yet to show that BHT would enhance tumor development in animals treated with subcarcinogenic doses of an initiating compound. Nor has it been possible to produce more tumors with BHT in mouse strains which have a low spontaneous tumor incidence and respond poorly to urethan. The question has not been resolved whether BHT accelerates growth of preformed tumors only or whether it induces the formation of more tumors. Nevertheless, the data collected on the effects of BHT on mouse lung tumor development have broadened the concept of two-stage carcinogenesis and complement the evidence for initiation- promotion available for other epithelial tissues such as liver, colon, stomach, trachea, urinary bladder and mammary gland.
Complications of Intravenous Administration of Heparin in Elderly Women
Authors: Walter V. R. Vieweg
Journal: JAMA (1970)

A review of two years' experience with heparin therapy administered intravenously in a coronary care unit population revealed that elderly women were particularly susceptible to bleeding episodes. Congestive heart failure may have been a contributing factor. Bleeding into the hip and groin occurred with unusual frequency and may have been due, in part, to parenteral administration into the buttocks of medications other than heparin. The first warning of bleeding occurred on an average of 48 hours before overt evidence of bleeding was noted.
Vaginal Spermicides and Gonorrhea
Authors: Hershel Jick
Journal: JAMA (1982)

All positive cultures for<i>Neisseria gonorrhoeae</i>recorded from Dec 20, 1978, through Dec 31, 1980, for women born between 1940 and 1960 were identified among members of Group Health Cooperative of Puget Sound, Seattle, and rates of gonorrhea were calculated for recent oral contraceptive users, recent vaginal spermicide users, and women with surgical sterilization. The risk ratio (RR) estimate, based on the included population, for spermicide users compared with all others was 0.23 (90% confidence interval [CI], 0.10, 0.50). When women with positive cultures for<i>N gonorrhoeae</i>were compared with women with negative cultures, the RR estimate comparing spermicide users with all others was 0.13 (90% CI, 0.05, 0.34). The results are consistent with a protective effect of vaginal spermicides against gonorrhea. (<i>JAMA</i>1982;248:1619-1621)
Panel Proposes National Plan to Screen Newborns for Congenital Heart Disease
Authors: Mike Mitka
Journal: JAMA (2011)

neurological status. • Thestrokeunitshouldhaveatelemetry system monitoring blood pressure, pulse, respiration, and oxygenation. • Neurosurgical services should be available within 2 hours of the time they are deemed clinically necessary. • Primary stroke centers must have the capability to perform computed tomography (CT) scans within 25 minutes of being ordered. Magnetic resonance imaging (MRI) of the brain may be performed in place of CT if the same time frame can be met. Studies show that MRI is more sensitive than CT for detecting some acute strokes, small strokes, and lesions that produce stroke-like symptoms. • Cardiac imaging is recommended because a significant percentage of strokes are caused by blood clots from the heart. • Laboratory work should include tests for HIV and pregnancy, a chest film, an electrocardiogram; it also should include a drug toxicology screening because of the association between illicit drug use and stroke.
Clinical Geriatric Medicine
Authors: Theodore R. Reiff
Journal: JAMA (1983)

This is an important collection of reviews of 17 topics in clinical gerontology, arranged mainly as discussions of organ systems. The authors reside throughout the United States and some are well known in their specialty disciplines with respect to gerontology. The caliber of the chapters is generally good and, in some instances, excellent. The limited number of pages obviously precludes the amount of information and depth that many of the authors might have wished to pursue. The subjects, all related to aging, include the immune system, infectious diseases, nutrition, pharmacology and therapeutics, clinical manifestations of disease, disorders of the CNS, psychogeriatrics, cardiovascular disease, hypertension, the respiratory system, gastrointestinal tract disease, genitourinary disease, renal disease, endocrine disorders, bone and joint disease, and dermatologic aspects. Until recently, geriatric medicine has been a much neglected field in both undergraduate and postgraduate medical education. Most medical schools had not had curricula devoted to gerontology
The Return of Blood to the Heart: Venous Pumps in Health and Disease
Authors: David I. Abramson
Journal: JAMA (1990)

In contrast to the extensive research programs that have been and continue to be carried out in the area of arterial disorders of the limbs, the venous system in these sites has been exposed to only relatively minimal scrutiny and study. Hence, an investigation of mechanisms responsible for return of blood to the heart, as attempted in this monograph, is a welcome addition to our limited knowledge of the field. One of the senior authors is a surgeon, the other a radiologist. There are also a chapter and an appendix by other contributors. The volume is made up of eight chapters and six appendixes. The first two chapters are devoted to the historical background of capillaries and veins and methods of investigating the venous circulation, including videophlebography and Doppler ultrasound. The next three chapters deal with the physiology of the microcirculation (primarily the capillaries), the veins of the foot and
944 PK/PD ASSESSMENT OF A PHASE 1 HEALTHY VOLUNTEER STUDY WITH ANA773, AN ORAL PRODRUG OF A TLR7 AGONIST FOR THE TREATMENT OF HCV
Authors: S. Fletcher, L. Bauman, B. Eam, M. Sergeeva, O. Khatsenko, T. Harding, M. Rahimy, J. Freddo, J. Appleman
Journal: Journal of Hepatology (2009)
Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy
Authors: Everett J. Moding, Katherine D. Castle, Bradford A. Perez, Patrick Oh, Hooney D. Min, Hannah Norris, Yan Ma, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch
Journal: Science Translational Medicine (2015)

Cancer clinics currently use high-dose stereotactic body radiation therapy as a curative treatment for several kinds of cancers. However, the contribution of vascular endothelial cells to tumor response to radiation remains controversial. Using dual recombinase technology, we generated primary sarcomas in mice with targeted genetic mutations specifically in tumor cells or endothelial cells. We selectively mutated the proapoptotic gene Bax or the DNA damage response gene Atm to genetically manipulate the radiosensitivity of endothelial cells in primary soft tissue sarcomas. Bax deletion from endothelial cells did not affect radiation-induced cell death in tumor endothelial cells or sarcoma response to radiation therapy. Although Atm deletion increased endothelial cell death after radiation therapy, deletion of Atm from endothelial cells failed to enhance sarcoma eradication. In contrast, deletion of Atm from tumor cells increased sarcoma eradication by radiation therapy. These results demonstrate that tumor cells, rather than endothelial cells, are critical targets that regulate sarcoma eradication by radiation therapy. Treatment with BEZ235, a small-molecule protein kinase inhibitor, radiosensitized primary sarcomas more than the heart. These results suggest that inhibiting ATM kinase during radiation therapy is a viable strategy for radiosensitization of some tumors.
An explanation for the reported observation that ATP dependent potassium channel openers mimic preconditioning
Authors: J. M Downey
Journal: Cardiovascular Research (1993)

Journal Article An explanation for the reported observation that ATP dependent potassium channel openers mimic preconditioning Get access James M Downey James M Downey Department of Physiology, MSB 3024, University of South Alabama, Mobile, AL 36688, USA: Professor J M Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 9, September 1993, Page 1565, https://doi.org/10.1093/cvr/27.9.1565 Published: 01 September 1993
Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice
Authors: Jean-Philippe Gratton, Michelle I. Lin, Jun Yu, Erik D. Weiss, Zao Li Jiang, Todd A. Fairchild, Yasuko Iwakiri, Roberto Groszmann, Kevin P. Claffey, Yung-Chi Cheng, William C. Sessa
Journal: Cancer Cell (2003)
Program Organization Following Corporate Merger of Community Hospitals
Authors: Ernest C. Shortliffe
Journal: JAMA (1968)

To compress the history of developments leading to the creation of the Wilmington Medical Center and then to comment further upon program development since that creation, and to do all of this briefly presents me with many problems. I have therefore chosen to present only a summary of the history leading to our development. Between the period from 1959 through 1963, in Wilmington among the boards of directors of three equal-sized community general hospitals, there was a preoccupation with rising operating and capital costs and with the deterioration of medical education as measured in terms of the quantity and quality of intern and resident applicants, as well as the quality of ongoing medical education for the members of the three medical staffs. Efforts were made through a mechanism of cooperation, not only to resolve some of these problems but to examine their implications and possible new and somewhat startling methods
Oral Clonidine Loading in Hypertensive Urgencies
Authors: Ron J. Anderson, Gary R. Hart, Charles P. Crumpler, William Gary Reed, Carol A. Matthews
Journal: JAMA (1981)

The response to oral clonidine hydrochloride loading in 36 severely hypertensive patients is presented. Each patient initially received 0.2 mg of clonidine hydrochloride, followed by 0.1 mg each hour until a dose of 0.7 mg had been given, or the diastolic blood pressure (BP) reached a predetermined goal (110 mm Hg or total fall of at least 20 mm Hg). Only two patients (6%) failed to reach this goal. Supine BP in the group fell from 212 +/- 22 (SD)/139 +/- 11 (SD) mm Hg to 151 +/- 21 (SD) mm Hg at six hours. The average dose of clonidine required was 0.45 mg and control was maximized at five hours. The response to oral clonidine loading in the individual patient was not predictive of the eventual dose of clonidine necessary to achieve acceptable BP control at two weeks. Oral clonidine loading is safe and effective in the management of "hypertensive urgencies" and offers several advantages over parenteral antihypertensive agents in this clinical situation.
High Anterior Myocardial Infarction
Authors: MYRON PRINZMETAL, REXFORD KENNAMER, RASHID A. MASSUMI
Journal: Circulation (1957)

Out of a large series of patients with coronary artery disease 6 were selected with high anterior myocardial infarction. These cases are presented in detail and their special electrocardiographic characteristics are described. The difficulty in making the diagnosis of infarction by the usual leads and the need for special leads are pointed out.