tbuckley/cabot-search huggingface dataset:
Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice
Authors: Abhijit De, Xiaoman Zhou Lewis, Sanjiv Sam Gambhir
Journal: Molecular Therapy (2003)

Lentiviral-mediated gene delivery holds significant promise for sustained gene expression within living systems. Vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 1-based lentiviral vectors can be used to introduce transgenes in a broad spectrum of dividing as well as nondividing cells. In the current study, we construct a lentiviral vector carrying two reporter genes separated by an internal ribosomal entry site and utilize that virus in delivering both genes into neuroblastoma cells in cell culture and into cells implanted in living mice. We utilize two reporter genes, a mutant herpes simplex virus type 1 (HSV1) sr39tk as a reporter gene compatible with positron emission tomography (PET) and a bioluminescent optical reporter gene, firefly luciferase (Fluc), to image expression in living mice by an optical charge-coupled device (CCD) camera. By using this lentivirus, neuroblastoma (N2a) cells are stably transfected and a high correlation (R2 = 0.91) between expressions of the two reporter genes in cell culture is established. Imaging of both reporter genes using microPET and optical CCD camera in living mice is feasible, with the optical approach being more sensitive, and a high correlation (R2 = 0.86) between gene expressions is again observed in lentiviral-infected N2a tumor xenografts. Indirect imaging of HSV1-sr39tk suicide gene therapy utilizing Fluc is also feasible and can be detected with increased sensitivity by using the optical CCD. These preliminary results validate the use of lentiviral vectors carrying reporter genes for multimodality imaging of gene expression and should have many applications, including imaging of xenografts, metastasis, and cell trafficking as well as noninvasive monitoring of lentiviral-mediated gene delivery and expression.
A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys.
Authors: M H Fisher, A M Amend, T J Bach, J M Barker, E J Brady, M R Candelore, D Carroll, M A Cascieri, S H Chiu, L Deng, M J Forrest, B Hegarty-Friscino, X M Guan, G J Hom, J E Hutchins, L J Kelly, R J Mathvink, J M Metzger, R R Miller, H O Ok, E R Parmee, R Saperstein, C D Strader, R A Stearns, D E MacIntyre
Journal: Journal of Clinical Investigation (1998)

Activation of beta3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to up-regulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta3 agonists in the treatment of human obesity.
Cardiac Arrhythmias During Electroshock Therapy: Significance, Prevention, and Treatment
Authors: GERALD MCKENNA, RALPH P. ENGLE, HAROLD BROOKS, JAMES DALEN
Journal: American Journal of Psychiatry (1970)

Respiratory acidosis and hypercapnia frequently accompany electroshock therapy (EST) and can be the cause of significant ventricular arrhythmias, which may have lethal sequelae in patients with coronary artery disease. The authors present measures to prevent these arrhythmias by hyperventilation with oxygen and ways to treat them if they occur.
Sexual Dysfunction in Women With Type 1 Diabetes: Long-Term Findings From the DCCT/EDIC Study Cohort
Authors: Ketan K. Dhatariya
Journal: Diabetes Care (2009)

Enzlin et al. (1) outline the high frequency of female sexual dysfunction (FSD) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort. However, their data need further clarification. They say that the prevalence of FSD, at 35%, is moderately high for a population with …
ARE THE MADIT2 CRITERIA FOR ICD IMPLANTATION APPROPRIATE FOR JAPANESE PATIENTS?: INCIDENCE AND PREDICTORS OF APPROPRIATE THERAPY IN 10-YEAR EXPERIENCE
Authors: Yoshimori An, Kenji Ando, Yoshimitsu Soga, Michio Nagashima, Masatsugu Ooe, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2012)
Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism.
Authors: M Brink, J Wellen, P Delafontaine
Journal: Journal of Clinical Investigation (1996)

The renin-angiotensin system regulates normal cardiovascular homeostasis and is activated in certain forms of hypertension and in heart failure. Angiotensin II has multiple physiological effects and we have shown recently that its growth-promoting effects on vascular smooth muscle require autocrine activation of the IGF I receptor. To study the effect of angiotensin II on circulating IGF I, we infused rats with 500 ng/kg/min angiotensin II for up to 14 d. Angiotensin II markedly reduced plasma IGF I levels (56 and 41% decrease at 1 and 2 wk, respectively) and IGF binding protein-3 levels, and increased IGF binding protein-2 levels, a pattern suggestive of dietary restriction. Compared with sham, angiotensin II-infused hypertensive rats lost 18-26% of body weight by 1 wk, and pair-feeding experiments indicated that 74% of this loss was attributable to a reduction in food intake. The vasodilator hydralazine and the AT1 receptor antagonist losartan had comparable effects to reverse angiotensin II-induced hypertension, but only losartan blocked the changes in body weight and in circulating IGF I and its binding proteins produced by angiotensin II. Moreover, in Dahl rats that were hypertensive in response to a high-salt diet, none of these changes occurred. Thus, angiotensin II produces weight loss through a pressor-independent mechanism that includes a marked anorexigenic effect and an additional (likely metabolic) effect. These findings have profound implications for understanding the pathophysiology of conditions, such as congestive heart failure, in which the renin-angiotensin system is activated.
Detection of novel leukocyte differentiation antigens on basophils and mast cells by HLDA8 antibodies
Authors: S. Florian, K. Sonneck, M. Czerny, F. Hennersdorf, A. W. Hauswirth, H.‐J. Bühring, P. Valent
Journal: Allergy (2006)

Background: Basophils (BA) and mast cells (MC) are important effector cells in allergic reactions. Development, growth and effector cell functions are regulated by a network of cytokines, other ligands, and respective cell surface antigens. Methods: We examined the expression of novel CD antigens on human BA, lung MC, the BA cell line KU‐812, and the MC line HMC‐1. Expression of surface antigens was analyzed by monoclonal antibodies (mAb) of the HLDA8 workshop and flow cytometry. Results: Basophils were found to stain positive for CXCR1 (CD181), CCR1 (CD191), CCR2 (CD192), CCR7 (CD197), IL‐18R α (CDw218a), IL‐18R β (CDw218b), TRAIL‐R1 (CD261), TRAIL‐R2 (CD262), TACI (CD267), TLR‐4 (CD284), LAIR1 (CD305), EMR‐2 (CD312), JAM1 (CD321), and JAM2 (CD322). Lung MC were found to react with mAb against EMR‐2 (CD312) and JAM1 (CD321). KU‐812 cells were found to stain positive for CXCR1 (CD181), TRAIL‐R2 (CD262), B7H2 (CD275), TLR‐4 (CD284), JAM1 (CD321), and E‐Cadherin (CD324). HMC‐1 cells were recognized by mAb against TRAIL‐R2 (CD262), B7H2 (CD275), LAIR1 (CD305), EMR‐2 (CD312), JAM1 (CD321), and Siglec‐6 (CDw327). Conclusions: Extensive phenotyping with antibodies against novel CD antigens provides further evidence that BA and MC represent two separate hematopoietic cell lineages with unique phenotypic properties observed in mature cells as well as malignant immature cells. Further studies are required to define the functional role of these CD antigens expressed in BA and MC.
The acute metabolic and hemodynamic responses of the left ventricle to ethanol.
Authors: R J Regan, G Koroxenidis, C B Moschos, H A Oldewurtel, P H Lehan, H K Hellems
Journal: Journal of Clinical Investigation (1966)

Although ethyl alcohol has a long medicinal his- tory (1), its precise effects on the cardiovascular system have not been defined.Acute alcohol in- gestion is known to result in triglyceride accumula- tion in the liver, which appears dependent upon an intact sympathetic nervous system (2).Evidence for stimulation of this system after ethanol ingestion has been advanced (3).Since sustained catecholamine infusion has been associated with lipid accumulation in the myocardium (4, 5), a study of the acute effects of ethanol on myocardial metabolism and function has been undertaken in animals considered nutritionally normal.The quantity given produced blood level concentrations usually associated with moderate intoxication. MethodsMongrel male dogs weighing 19 to 22 kg were anes- thetized 18 hours postprandially with morphine sulfate, 3 mg per kg, and pentobarbital (Nembutal), 12 mg per kg, and studied without opening the chest.After in- sertion of an endotracheal tube, respiration was regulated with a Harvard respiratory pump, facilitating the maintenance of arterial oxygen saturation and pH in the normal range.Catheters were placed in the coronary sinus, pulmonary artery, aorta, and left ventricle for *
THE HUMANE SIDE OF WARFARE.
Authors: N. SENN
Journal: JAMA (1900)

War has always been and always will be a great national calamity. The deliberate, legitimate killing of men on the field of battle has remained as a necessary evil and continues to receive the sanction of the most civilized peoples when it becomes necessary to protect the rights of nations, tribes or individuals, and to diffuse liberty and humanity by a contest of arms. Under the influence of modern civilization the legitimate causes for war are becoming less and less from one century to another, and warfare itself more and more humane. The battlefield itself is rapidly losing its barbaric aspects and is assuming the scene of a dignified, manly contest between the armed forces representing the<i>casus belli</i>. Personal ambition, the spirit of revenge, religious fanaticism, individual and national greed, which so often have provoked war in the past, seldom suffice now in inciting nations to a resort to
Serotonin and Antiserotonins
Authors: ROBERT W. WILKINS, WILLIAM HOLLANDER
Journal: Circulation (1957)

Serotonin, a smooth-muscle constrictor, has been suggested as possibly important in the pathogenesis of arterial hypertension. The benzyl analog of serotonin (BAS) was developed as an antimetabolite of serotonin, and has certain demonstrable antiserotonin effects in man. Orally it has moderate antihypertensive and other clinical effects resembling those of reserpine, which also has a definite antiserotonin action. However, there is question whether the clinical effects of oral BAS or of reserpine in hypertension are due to "antiserotonin" or other pharmacologic actions. BAS is clinically useful in the therapy of some patients with essential hypertension.
Process based functionalism instead of structural functionalism is needed
Authors: Endre E. Kadar, M. T. Turvey
Journal: Behavioral and Brain Sciences (1997)

Latash &amp; Anson's intention to describe only the regularities of motor behavior is compromised by the homunculus paradigm. Although we concur on the need to redefine “normal movements” in atypical populations, we contend that this enterprise requires a process based functionalism. We argue for accommodating movement control and perceptual processes with physical and task constraints in a natural setting.
Sickle Cell Hemoglobin: Molecule to Man
Authors: A. P. Kraus
Journal: JAMA (1974)

The material presented is divided into eight chapters. The first three, authored by Dr. Murayama, discuss the chemical and three-dimensional structure of human hemoglobin, the bioenergetics of sickling, and Dr. Murayama's hypotheses explaining the mechanism of the sickling phenomenon. This material is stated in a clear and concise fashion. After discussing the primary, secondary, tertiary, and quarternary structure of the hemoglobin molecule, Dr. Murayama reviews his published experiments and uses them as a basis for his hypothesis of the sickling phenomenon, including the need for a cofactor. Not everybody agrees with Dr. Murayama's ideas, but they are well presented here. Dr. Nalbandian follows these introductory chapters with a detailed discussion of his ideas on sickle cell disease, starting with intrauterine erythropoeisis, and then discusses the Murayama (dithionate-urea) test, an automated mass screening program for sickle cell disease, and the theoretical and clinical practical use of urea in sickle cell disease.
Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.
Authors: G Birnbaum, L Kotilinek, M Schwartz, M Sternad
Journal: Journal of Clinical Investigation (1984)

Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens.
Licking latency with licorice
Authors: Jeffrey I. Cohen
Journal: Journal of Clinical Investigation (2005)

Numerous viruses cause latent infections in humans, and reactivation often results in pain and suffering. While vaccines for several of these viruses are available or currently being studied in clinical trials, and antiviral therapies have been successful in preventing or treating active infection, therapy to eradicate latent infection has lagged behind. A new study reported in this issue of the JCI shows that treatment of cells latently infected with Kaposi sarcoma–associated herpesvirus (KSHV) with glycyrrhizic acid, a component of licorice, reduces synthesis of a viral latency protein and induces apoptosis of infected cells. This finding suggests a novel way to interrupt latency.
Increased Cell Membrane Permeability in the Pathogenesis of Hereditary Spherocytosis *
Authors: Harry S. Jacob, James H. Jandl, Susan C. Bell, Nancye M. Files
Journal: Journal of Clinical Investigation (1964)

1 Normal human serum albumin was obtained from Massachusetts Public Health Biologic Laboratories as a 25% solution.After dialysis against appropriate buffer the solution was diluted to a final concentration of 5% in buffer.Previous studies (26, 27), especially evidence recently presented (28), indicate that plasma when in- cubated undergoes alterations in its lipid moieties that
The radiological examination of the colon
Authors: C I Bartram
Journal: Gut (1983)

the quality of some of the chapters is quite outstand- ing.The section on ultrasonic puncture techniques will prove particularly useful for those interested in this aspect of ultrasound.The author describes the various methods and applications of the technique in detailed manner that will prove a valuable practical guide for anyone wishing to acquire expertise in this rapidly developing branch of the subject.Overall the book presents a good range of topics, some new, some already established but looked at in a refreshing new light.The book is a 'must' for anyone interested in ultrasound.
Hygeia on the TV Screen
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1972)

From time to time, the editor of this Journal, driven perhaps by zealous commitment to the First Amendment, publishes a polemic summons from the far right or left — Sade,1 for example, denying Americans their right to health care, or Harper2 suggesting that our hero should be Che Guevara. Most readers forgive such deviations. But with the publication of the article "Health Information During a Week of Television" (page 516 of this issue), the editor has gone too far. Not only do the authors of this derogatory tract insinuate that the nation's great television industry slights health, but they . . .
Leukotriene B<sub>4</sub> in atopic dermatitis: increased skin levels and altered sensitivity of peripheral blood T‐cells
Authors: S. Thorsen, K. Fogh, U. Broby‐Johansen, J. Sosndergaard
Journal: Allergy (1990)

Employing a radioimmunoassay, de‐proteinated suction blister fluid from 12 patients with active atopic dermatitis appeared to contain higher levels of the pro‐inflammatory and immunomodulatory mediator leukotriene B 4 (LTB4) than suction blister fluid from 12 non‐atopic individuals. Indirect support for the identity of the mediator was obtained by HPLC of pooled samples. Nylon wool enriched T cells from six patients with atopic dermatitis and six non‐atopic people preincubated with LTB4 (10 −10 M−10 −8 M) expressed no statistically significant suppression in co‐culture with mitogen stimulated autologous mononuclear cells, and there was no difference between atopic and non‐atopic T cells in this respect. In contrast, LTB4 induced a dose‐dependent reduction in the percentage of phenotypic Leu 2a (suppressor) cells leading to an increased helper/suppressor ratio in five atopic patients that was not observed in five non‐atopics. Elevated skin levels of LTB4 may initiate or amplify dermal inflammation, and abnormal T cell response to the mediator may account for the increased helper/suppressor ratio characteristic of patients with atopic dermatitis.
Pulsed Doppler: determination of blood velocity and volume flow in normal and diseased common carotid arteries in man
Authors: D. E FITZGERALD, A. M O'SHAUGHNESSY, V. T KEAVENY
Journal: Cardiovascular Research (1982)

A pulsed Doppler velocimeter with an adjustable range gated time system and a double transducer probe has been used to measure volume blood flow in 50 normal and 50 diseased common carotid arteries. A significant difference in mean volume flow between normal and diseased arteries was found (P less than 0.0001). On-line audio-frequency display of velocity signals were evaluated in each of the arteries together with angiographic description of the diseased arteries. Disturbance of the velocity profile develops before significant changes in volume flow or angiogram occur. Volume flow results and angiogram appearance relate best when the angiogram description is either of minimal disease or severe disease. Determination of dynamic flow conditions from structural appearance of arteries are not consistently dependable.
Assessing the Benefit-Risk for New Drugs
Authors: Eric P. Brass
Journal: Diabetes Care (2013)

The U.S. Food and Drug Administration (FDA) regulates which drugs can be marketed in the U.S. as well as their label requirements. A congressionally authorized advisory committee process allows the FDA to receive input from outside experts on important regulatory decisions (1). Further, the advisory committee process enhances transparency by allowing the public, including health care professionals, to understand the issues being considered. The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) “reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of endocrine and metabolic disorders, and makes appropriate recommendations to the Commissioner of Food and Drugs” (2). Operationally, the FDA’s Division of Metabolism and Endocrinology Products (DMEP) is responsible for the review of most drugs used for indications relevant to endocrinologists and coordinates the EMDAC’s meetings.

In recent years, the EMDAC has been asked to review a number of controversial drugs, particularly those for the treatment of diabetes and obesity. Often the assessment of these drugs requires integration of preclinical and clinical data to formulate a benefit-risk assessment. The assessment of benefit-risk for drugs is increasingly recognized to be a challenging task, and formal tools have been proposed to make this process more effective (3–7). In contrast with the DMEP and other FDA staff, most EMDAC members will have limited experience in these types of integrative, complex evaluations. Further, EMDAC members will spend considerably less time evaluating the available data in comparison with DMEP staff. Thus, it seems important to compare the recommendations made by EMDAC with the subsequent marketing and label decisions to assess concordance between the evaluative approaches used by EMDAC and that of DMEP (DMEP will be used as shorthand for the full FDA’s involvement in regulatory decisions).

At most of the EMDAC …
Clinical metabolism of body water and electrolytes
Authors: Mackenzie Walser
Journal: JAMA (1963)

As the editor notes in his preface, many books on this subject have been published in recent years. The present effort differs from most in being a collection of contributions by several authors, many of whom have reviewed the same material in other articles, or in books of their own. If carefully organized and edited, the result might nevertheless have been worthwhile. Unfortunately, such is not the case. Well over half of the 600 pages are repetitious. Thus, the Starling hypothesis of transcapillary exchange is presented in complete detail not once, but three times. The "Gamblegrams" of normal body fluids appear seven times, with variations, but some consistent errors ( such as indicating the major intracellular anions to be inorganic phosphate and sulfate, thereby overestimating the values for these ions at least twenty-fold). Bland, the author of 5 of the 22 chapters, should have read F. D. Moore's chapter, where it
Bad sanitation and antivaccination
Authors: T. Dalrymple
Journal: BMJ (2012)

Few causes in the 19th century were more popular than that of antivaccination. When vaccination, held by many to be medically wrong, was made compulsory, it called forth widespread opposition and even civil disobedience. The antivaccination literature was vast, and among my small collection of the genre is a peculiar book published in 1892 by John Pickering, fellow of the Royal Geographical Society, called Which? Sanitation and Sanitary Remedies or Vaccination and the Drug Treatment? 

The author starts with an admission that makes him a hostage to fortune: “This book is unsatisfactory to me . . . Book-making is not my forte .” Among other peculiarities is the following lukewarm endorsement from Florence Nightingale: “You do me too much honour. I …