tbuckley/cabot-search huggingface dataset:
CCK receptor antagonism by loxiglumide and gall bladder contractions in response to cholecystokinin, sham feeding and ordinary feeding in man.
Authors: J W Konturek, S J Konturek, A Kurek, J Bogdal, J Oleksy, L Rovati
Journal: Gut (1989)

The postprandial contractions of the gall bladder result from the interaction of neurohormonal factors but their relative contribution is unknown. This study was designed to determine the role of cholecystokinin (CCK) in gall bladder contractions using a highly selective and potent CCK-receptor antagonist, CR-1505 (loxiglumide) in healthy men either infused with exogenous CCK in graded doses (1.56-50 pmol/kg/h) or subjected to modified sham feeding (MSF) and ordinary feeding tests. The gall bladder volume measured by real time ultrasonography showed dose dependent decrease in the gall bladder volume in 10 subjects when CCK8 was infused iv in graded doses reaching about 15% at 1.56 pmol/kg/h and 91% at 50 pmol/kg/h. Close correlation between the decrease in gall bladder volume and the dosage of CCK or the increments in plasma CCK-bioactivity was observed. After pretreatment with loxiglumide, CCK resulted in similar increments in plasma CCK-bioactivity but failed to affect the gall bladder volume at CCK doses up to 6.25 pmol/kg/h and caused only 53% reduction at 50 pmol/kg/h. Modified sham feeding and real feeding reduced the volume of gall bladder by 20% and 70%, respectively and loxiglumide decreased these values to 15% and 30%, respectively. This study provides evidence that loxiglumide is highly potent and selective CCK antagonist and that endogenous CCK plays an important role both in the postprandial contractions of gall bladder.
HEALTH OF SHARECROPPERS
Authors: Joseph M. Krimsky
Journal: JAMA (1941)

<h3>To the Editor:—</h3> The article inThe Journal, July 5, by Dr. J. W. Thompson on the clinical status of a group of Negro sharecroppers provokes discussion. An evaluation of the health of Negro sharecroppers is made on the basis of a sample of 24 subjects on whom a history was taken and a physical examination made. The data gleaned by the author seemed to indicate a dangerous state. Yet he concludes that he doubts that the "Negro sharecroppers are apt to be in a lamentable state of ill health." Finally he stafes that all but 1 were in good general condition and not far below the excellence found in a group of Harvard students—who did not show a single abnormal finding. I recapitulate Dr. Thompson's observations: pyorrhea in 50 per cent, syphilis in 8 per cent, pellagra in 4 per cent, pulmonary signs—not investigated—in 8 per cent, possible heart
Primary Pneumococcal Pericarditis
Authors: David Schlossberg
Journal: JAMA (1975)

PURULENT pericarditis caused by<i>Streptococcus pneumoniae</i>is a rare disease, usually a complication of a primary lung infection with contiguous pleural involvement.<sup>1</sup>To our knowledge, only two cases of primary pneumococcal pericarditis have been reported in the English literature. Recently, we have seen three patients with pneumococcal pericarditis in whom no other site of pneumococcal infection was apparent. One patient was a 56-year-old man, another was a 2-year-old boy, and a third was a 53-year-old woman, whose case we are reporting in detail. <h3>Report of a Case</h3> A 53-year-old woman was admitted on Nov 3, 1974, with a sudden onset of substernal pain radiating to her neck and left arm. She gave a history of angina pectoris that usually was relieved by nitroglycerin, but the current bout of pain was unrelieved by this medication. On physical examination, the blood pressure was 120/70 mm Hg; pulse, 100 beats per minute
Vasoprotection by nitric oxide: mechanisms and therapeutic potential
Authors: M Gewaltig
Journal: Cardiovascular Research (2002)

Endothelial production of nitric oxide (nitrogen monoxide, NO) has become a major research area in vascular biology. Some of the most important effects that NO exerts in the vascular wall are potentially vasoprotective, because these effects maintain important physiological functions such as vasodilation, anticoagulation, leucocyte adhesion, smooth muscle proliferation, and the antioxidative capacity. During the last 2 decades it has become apparent that a variety of diseases are associated with an impairment of endothelium-dependent NO activity. One of the major causes is believed to be an increased production of reactive oxygen species, in particular superoxide, which have been shown to interfere with many steps of the NO–cyclic guanosine monophosphate (cGMP) pathway. This phenomenon has been found in diverse conditions such as atherosclerosis, hypertension, diabetes, hypercholesterolemia, heart failure, and cigarette smoking. The aim of this review is to examine the cellular and molecular mechanisms whereby NO exerts potentially vasoprotective effects and to discuss pharmacologic approaches targeting the NO pathway in view of their potential to improve endothelial function and to reduce the progression of atherosclerotic vascular disease. We conclude that there is compelling evidence for vasoprotective actions of NO which are mediated by cGMP-dependent and cGMP-independent mechanisms. These effects may contribute to the beneficial effects of established drugs such as ACE inhibitors or statins. Unfortunately, clinical data on the effect of long-term treatment with nitrates on the progression of coronary artery disease are lacking. Finally, l-arginine or new activators of the NO pathway may become therapeutic options in the future.
Abstract 3071: Obesity-associated growth factor signaling upregulates aromatase expression and estrogen receptor activity in breast cancer cells
Authors: Laura W. Bowers, Rebecca De Angel, Rajeshwar Tekmal, Andrew Brenner, Stephen Hursting, Linda deGraffenried
Journal: Cancer Research (2012)

Abstract Obesity increases the risk of breast cancer by approximately 50% in postmenopausal women and is also associated with a worse prognosis. Elevated estrogen synthesis by the local mammary epithelia and adipose tissue is thought to be the principal mediator of breast tumorigenesis in this population, which primarily develops estrogen receptor alpha (ERα) positive breast cancer. However, the elevated levels of free insulin-like growth factor 1 (IGF-1) that accompany obesity are also thought to play a role. IGF-1 has significant tumorigenic effects in the breast and also regulates aromatase, the key enzyme in the conversion of androgens to estrogen. Consequently, we hypothesized that obesity increases the risk of postmenopausal breast cancer via growth factor-induced aromatase expression and/or activity in the local mammary tissue. We have previously shown that MMTV-Wnt-1 mammary tumors from obese ovariectomized mice express higher levels of aromatase in comparison to tumors from lean ovariectomized mice. To examine the molecular pathways responsible for this effect, we have utilized an in vitro model of obesity in which ERα positive MCF-7 breast cancer cells were exposed to human sera obtained from postmenopausal women and pooled by BMI category. Our data indicates that exposure to obese (BMI ≤ 30 kg/m2) human serum stimulates greater aromatase expression in comparison to control (BMI: 18.5-24.9 kg/m2). This is coupled with enhanced ERα activity when exogenous androgen is present, indicating that the increased aromatase expression results in greater estrogen production. Obese human sera also activates MCF-7 cells’ Akt pathway to a greater degree than control, while MCF-7 cells expressing a constitutively active Akt demonstrate higher levels of aromatase expression in comparison to MCF-7 cells. This suggests that circulating growth factors in the obese sera, like IGF-1, may induce elevated aromatase expression via the downstream PI3K/Akt pathway. To expand on our findings, we plan to assess whether treatment with PI3K/Akt pathway inhibitors eliminates the difference in MCF-7 cells’ aromatase expression following exposure to obese versus control sera. We will also examine how inhibition of the PI3K/Akt pathway affects ERα activity in sera-exposed MCF-7 cells. Through elucidation of the signaling pathways responsible for obesity's upregulation of local aromatase expression, we ultimately hope to develop rational and effective chemopreventive and chemotherapeutic regimens for the high-risk obese postmenopausal population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3071. doi:1538-7445.AM2012-3071
Tumor Necrosis Factor-α Regulates Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Expression in Vascular Smooth Muscle
Authors: A. Anwar, A.A. Zahid, K.J. Scheidegger, M. Brink, P. Delafontaine
Journal: Circulation (2002)

Background — Inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and interferon γ (IFN-γ) may change coronary plaque integrity by altering vascular smooth muscle cell (VSMC) survival and modifying the extracellular matrix. Insulin-like growth factor-1 (IGF-1) prevents apoptosis, promotes matrix formation, and can decrease TNF-α or IL-1β–induced proteoglycan degradation. Methods and Results — To determine the effects of cytokines on the IGF-1 system, rat aortic VSMCs were exposed to TNF-α (10 to 500 ng/mL), IL-1β (20 pg to 10 ng/mL), IL-6 (100 pg to 15 ng/mL), or IFN-γ (10 to 600 U/mL). IL-1β, IL-6, and IFN-γ did not regulate IGF-1, IGF-1 receptor (R), or IGF binding proteins (IGFBPs). However, TNF-α markedly decreased IGF-1 mRNA (85% reduction at 24 hours) and increased IGFBP-3 mRNA and protein (300% increase at 24 hours). These changes were blocked by actinomycin D, consistent with a transcriptional mechanism. Experiments using TNF binding protein-1 indicated that these effects were not attributable to secretion of an autocrine factor. Anti–IGFBP-3 antibodies increased VSMC DNA synthesis 3-fold. In addition, apoptosis induced by TNF-α, IFN-γ, and Fas ligand was markedly reduced by desamino-(1-3)-IGF-1. Conclusions — TNF-α, a cytokine that is upregulated in atherosclerotic plaques, reduces IGF-1 and increases IGFBP-3 in VSMCs, likely leading to a reduction in bioactive IGF-1. Because IGF-1 is important for growth and survival of VSMCs, its downregulation by TNF-α possibly plays a crucial role in acute and chronic coronary syndromes by decreasing VSMC viability and promoting plaque instability.
A RARE COMPLICATION FOLLOWING APPENDECTOMY
Authors: George Webb
Journal: JAMA (1923)

Mrs. Y., aged 35, Japanese, was admitted to the Pioneer Mill Company Hospital, Feb. 2, 1922, with severe pains in the right lower abdominal quadrant, a temperature of 102, and a pulse ranging from 100 to 110. The diagnosis of acute appendicitis was made (details of the clinical and laboratory examinations are omitted for the sake of brevity), and she was operated on immediately. An enlarged, acutely inflamed and distended appendix was easily delivered and removed. The technic used was the usual one, the stump of the appendix (about 2 mm. in length) being inverted and buried by a purse-string suture. No drains were used, and the convalescence was entirely uneventful. Twelve days later the patient was discharged, feeling well and strong. April 17, 1923 (two years and two months later), the patient was readmitted to the wards of the hospital complaining of continuous dull pain in the lower right
Experts' opinions on the role of liver biopsy in HCV infection: A Delphi survey by the Italian Association of Hospital Gastroenterologists (A.I.G.O.)
Authors: Piero Luigi Almasio, Mauro Niero, Donato Angioli, Antonio Ascione, Sergio Gullini, Giorgio Minoli, Nadia C. Oprandi, Giovan Battista Pinzello, Giorgio Verme, Angelo Andriulli
Journal: Journal of Hepatology (2005)
TUMOUR IN THE ANTRUM: EXTIRPATION OF THE RIGHT SUPERIOR MAXILLARY BONE
Authors: E. Jones
Journal: BMJ (1855)

JANE DAvIES, aged 44 years, a pauper, belonging to the Ruthin Union, North Wales, was sent to the Liverpool Northern Hospital, for the purpose of having the right upper jaw removed.She was admitted early in March of the present year.The patient attributed the origin of the disease to her husband, who, about eighteen months ago, in a momentary fit of passion, pushed his thumb into her mouth, and with the force of his fingers pressed violently against the anterior and posterior walls of the antrum.This violence at the time gave her considerable pain; and
Amniocentesis in Tay-Sachs Disease
Authors: E. James Roberts
Journal: JAMA (1975)

<h3>To the Editor.—</h3> I read with interest Dr. Fred Rosner's letter regarding amniocentesis for Tay-Sachs disease. Since I am not a medical doctor, I am not qualified to respond on the medical aspects of this problem, but as a minister, I am concerned with the arbitrary moral stance taken by Dr. Rosner. I would, therefore, like to raise the following points on this aspect of his letter. I take "traditional Judaism," as used by Dr. Rosner, to be a euphemism for Orthodox Judaism. The inference is that his point of view is definitive for all Jews, including those of the Conservative and Reformed traditions. I would question this presumption! Dr. Rosner seems to separate "ethical and religious considerations, such as the Biblical commandment to procreate" from "medical and genetic factors," as though they were mutually exclusive. Dr. Rosner's real problem is a rigid adherence to<i>one</i>part of the moral
GLYCOSURIA — ITS COMPLICATIONS AND THERAPEUTICS.
Authors: OSCAR C. DE WOLF
Journal: JAMA (1883)

[Read before the Chicago Medical Society, November 19, 1883.] In a former paper1 I reviewed the pathology of glycosuria, designing in this to present a series of cases, but the literature of the complications of the disease has proven so voluminous, that I defer the grouping and detail of such cases as have come within my observation to a future time, confining myself now to an attempt to deduce a few rational Principles of therapeusis from the mass of observations now before the profession. Glycosuria is a secondary complication of many diseases; the treatment of the primary affection cures the glycosuria without affecting it other than indirectly. The secondary nature of the glycosuria is ignored, and it is regarded as amenable to treatment which could affect it, if at all, only indirectly. Glycosuria appears and disappears under certain conditions with equal facility, whether treatment be followed or neglected. Such elements
Color M-mode estimation of the spatial distribution of the diastolic intraventricular pressure gradient with a left ventricular aneurysm
Authors: Junko Watanabe, Michael Jones, Takahiro Shiota, Hiroyuki Tsujino, Neil L. Greenberg, Zoran B. Popovic, Arthur D. Zetts, None Jian Xin Qin, Lisa A. Cardon, Mario J. Garcia, James D. Thomas
Journal: Journal of the American College of Cardiology (2002)
1094. Self-Complementary Vectors Significantly Enhance AAV-Mediated Gene Transfer to Joint Tissues
Authors: Jesse Kay, Elvire Gouze, Kenneth Warrington, Irene Zolotukhin, Rachael Watson, Marsha Bush, Jeetpaul Saran, Jean-Noel Gouze, Douglas McCarty, Paul Robbins, Christopher Evans, Steven Ghivizzani
Journal: Molecular Therapy (2006)

Gene delivery approaches have been proposed as a means to improve treatment of the arthritides. By delivering cDNAs encoding anti-arthritic proteins to the cells in the synovial lining, the gene products may be expressed and secreted locally into the joint space. Vectors based on AAV offer advantages that would favor their use as a vehicles for direct, intra-articular gene transfer; however, reports of the effectiveness of this vector have been widely variable. Much of this inconsistency may be due to limitations in synovial lining/ joint capsular cells to initiate second strand DNA synthesis of the recombinant virus. To address this hypothesis we evaluated self-complementary (sc; double-stranded) AAV serotype 2 vectors for their capacity to deliver and enable expression of exogenous cDNAs in synovial fibroblasts in vitro, and in the joints of rabbits in vivo.
UK academy wants neuroscience research to benefit patients more quickly
Authors: Chibuzo Odigwe
Journal: BMJ (2004)

The Academy of Medical Sciences in the United Kingdom has called for more rapid translation of basic research in neuroscience to better management and patient care for patients with neurological diseases.

In a report published this week, the academy suggests that an opportunity exists to move from current treatments that primarily help patients with neurological conditions suchas Alzheimer's disease, stroke, and cerebral palsy to adapt to their brain impairment to a new era that focuses on helping the brain to achieve a measure of functional recovery. It argued that increased investment in research into diseases of the brain was offering the potential to develop treatments that would reduce the …
Inhibition of poly (ADP-ribose) Synthetase Attenuates Neutrophil Recruitment and Exerts Antiinflammatory Effects
Authors: Csaba Szabó, Lina H.K. Lim, Salvatore Cuzzocrea, Stephen J. Getting, Basilia Zingarelli, Roderick J. Flower, Andrew L. Salzman, Mauro Perretti
Journal: The Journal of Experimental Medicine (1997)

A cytotoxic cycle triggered by DNA single-strand breakage and poly (ADP-ribose) synthetase activation has been shown to contribute to the cellular injury during various forms of oxidant stress in vitro. The aim of this study was to investigate the role of poly (ADP-ribose) synthetase (PARS) in the process of neutrophil recruitment and in development of local and systemic inflammation. In pharmacological studies, PARS was inhibited by 3-aminobenzamide (10–20 mg/kg) in rats and mice. In other sets of studies, inflammatory responses in PARS−/− mice were compared with the responses in corresponding wild-type controls. Inhibition of PARS reduced neutrophil recruitment and reduced the extent of edema in zymosan- and carrageenan-triggered models of local inflammation. Moreover, inhibition of PARS prevented neutrophil recruitment, and reduced organ injury in rodent models of inflammation and multiple organ failure elicited by intraperitoneal injection of zymosan. Inhibition of PARS also reduced the extent of neutrophil emigration across murine mesenteric postcapillary venules. This reduction was due to an increased rate of adherent neutrophil detachment from the endothelium, promoting their reentry into the circulation. Taken together, our results demonstrate that PARS inhibition reduces local and systemic inflammation. Part of the antiinflammatory effects of PARS inhibition is due to reduced neutrophil recruitment, which may be related to maintained endothelial integrity.
Prestin-Driven Cochlear Amplification Is Not Limited by the Outer Hair Cell Membrane Time Constant
Authors: Stuart L. Johnson, Maryline Beurg, Walter Marcotti, Robert Fettiplace
Journal: Neuron (2011)

Outer hair cells (OHCs) provide amplification in the mammalian cochlea using somatic force generation underpinned by voltage-dependent conformational changes of the motor protein prestin. However, prestin must be gated by changes in membrane potential on a cycle-by-cycle basis and the periodic component of the receptor potential may be greatly attenuated by low-pass filtering due to the OHC time constant (τ(m)), questioning the functional relevance of this mechanism. Here, we measured τ(m) from OHCs with a range of characteristic frequencies (CF) and found that, at physiological endolymphatic calcium concentrations, approximately half of the mechanotransducer (MT) channels are opened at rest, depolarizing the membrane potential to near -40 mV. The depolarized resting potential activates a voltage-dependent K+ conductance, thus minimizing τ(m) and expanding the membrane filter so there is little receptor potential attenuation at the cell's CF. These data suggest that minimal τ(m) filtering in vivo ensures optimal activation of prestin.
Response to Kennedy and Farthing
Authors: Mary Dixon-Woods
Journal: Journal of the Royal Society of Medicine (2010)

I am not sure where the ‘serious error’ in my editorial1 lies. Kennedy and Farthing provide some helpful information on responses to, and adoption of, the UKRIO's procedure for investigating research misconduct. However, I suggested that it was not clear how widely used it is, and adoption is not the same as use. I look forward to learning more about how often the procedure has been used, by which organizations, and to what effect.
CD: Dynamic Practical Electrocardiography: A Virtual Clinic and Classroom
Authors: E. Yu
Journal: BMJ (2000)

Galen S Wagner, Robert A Waugh, William T Lawson Jr Lippincott-Williams and Wilkins, £42 ISBN: 0 683 30380 3 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> This CD Rom is a timely teaching resource. It is truly multimedia, with animation, text, and search capabilities. Its content is suitable for both beginners in electrocardiography as well … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
We all need an Annie's Place
Authors: C. Brittain
Journal: BMJ (1996)

Yesterday I sat within earshot of Heathrow Airport in a cold impersonal hotel ready to start one of our many medical meetings. By common consent we all stood in silence as a homage to those who had been touched by the horror at Dunblane three days before. Many of us around the table knew the area well. We had worked, trained, and socialised with many of the professionals who were now trying to bring love and care out of chaos and horror. During the silence my mind went back to the warmth and comfort of Annie's Place. For nearly 17 years it had been my privilege to serve as medical adviser and crew member to our local lifeboat. It was luckily not a busy station, but we did have our share of excitement and disasters. These affected each of the crew in different ways. Like many of our friends in the lifeboat service, however, we also had our secret resource, Annie and Bill. They ran a small pub that sat beside the lifeboat shed and was always known as Annie's Place.

It was a typical harbour pub used by travellers and fishermen over the years. The …
Early aortic valve cusp rupture in relapsing polychondritis.
Authors: D A Marshall, R Jackson, A P Rae, H A Capell
Journal: Annals of the Rheumatic Diseases (1992)

Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation.
Spezielle neurologische Untersuchungsmethoden
Authors: Oscar Sugar
Journal: JAMA (1968)

This is apparently a companion volume to an extensive treatise on general neurology in preparation by Professor Schaltenbrand of Würzburg. He and Bammer describe the techniques for obtaining and studying cerebrospinal fluid. Most useful is a four-page table which compares values of the various physical and chemical components of lumbar spinal fluid and blood serum. There is rather more than usual detail concerning the variety of colloidal reactions used in various countries. Roentgen investigation of the skull (Nadjmi and Schwind) is given much more emphasis than that of the spinal column. Pneumography and angiography are illustrated in detail. The reproduction of the angiograms is not as good as usual, and there is reversal of figures and legends for cisterns of the brain in Fig 47b and c. Myelography is only briefly described, with a picture of a special needle and catheter for removing opaque oil the day after the study