tbuckley/cabot-search huggingface dataset:
125. AAV Vector-Mediated Neonatal Gene Transfer: Efficient Transgene Expression in Muscles after Intraperitoneal Cavity Vector Injection
Authors: Tsuyoshi Ogura, Hiroaki Mizukami, Jun Mimuro, Takashi Okada, Hiromi Hamada, Akihiro Kume, Hiroyuki Yoshikawa, Yoichi Sakata, Keiya Ozawa
Journal: Molecular Therapy (2005)

Neonatal or fetal gene transfer is a useful approach to treat genetic diseases which cause irreversible manifestations in adulthood, and is also advantageous in transducing tissues at relatively low vector doses. Among the routes of administration, intraperitoneal cavity injection is potentially useful for neonates as it is possible to administer larger amount of vector stocks under easier and safer circumstances. In this study, we explored the optimal use of AAV vectors administered into intraperitoneal cavity for neonatal gene therapy in mice. For this purpose, vectors carrying human coagulation factor IX (hFIX) gene under cytomegalovirus (CMV)-derived promoter using AAV1-5 capsids were injected intraperitoneally into immune-competent (C57BL/6) mice within 24 hours after birth. Each neonate mouse received a dose of 1|[times]|1010 genome copy per body and plasma concentrations of hFIX were monitored. As a result, AAV1 vector injection group showed the highest hFIX concentration (195.3|[plusmn]|60.2 ng/ml), followed by AAV5 (11.8|[plusmn]|1.8 ng/ml) and AAV2 (3.7|[plusmn]|6.5 ng/ml) groups. The concentration of hFIX observed after intraperitoneal AAV1 injection was slightly higher than the group with intramuscular injection of AAV1 at the same dose. Dose escalation is feasible for intraperitoneal cavity injection up to 1|[times]|1011 genome copy per body and the result showed a marked increase in hFIX concentration (613.5|[plusmn]|223.5 ng/ml), a level that is considered within fully therapeutic range. The hFIX concentration remained constant for more than 24 weeks. To analyze tissue distribution of expression, AAV1 vectors encoding LacZ or luciferase were administered intraperitoneally and analyzed by X-Gal staining or bioluminescence imaging analysis using IVIS system, respectively. Interestingly, both results showed transgene expression in muscles of trunk and proximal limbs adjacent to the peritoneal tissue in addition to peritoneal epithelium. Analysis of organ specific expression after sacrifice confirmed expression in muscles of thorax, thigh, brachial and iliopsoas region. Muscle mediated expression appear to contribute to high level of transgene expression even the vectors were administered intraperitoneally. These findings support the efficacy of neonatal gene therapy and would guide to design strategies for neonatal gene therapy using AAV vectors.
Mechanism of the Development of Gastric Ulcer after Percutaneous Endoscopic Gastrostomy
Authors: J. Kanie, H. Akatsu, Y. Suzuki, H. Shimokata, A. Iguchi
Journal: Endoscopy (2002)

The present study was carried out in order to elucidate the mechanism of the development of gastric ulcer, one of the serious complications of PEG tube placement.This retrospective study included 92 patients who underwent gastric endoscopy after PEG tube placement. Gastric ulcers detected at gastroscopy were examined in relation to the length of the protrusion from the PEG tubes intragastric bumper and the use of histamine H 2 -receptor antagonists.Gastric ulcers were found in nine of the 92 patients, and in all nine the ulcer was found on the posterior wall of the gastric body, where the tip of the PEG tube was attached. Seven of the 21 patients (33.3 %) who had a PEG tube with a long protrusion from the intragastric bumper developed gastric ulcer. By contrast, only two of the 71 patients (2.8 %) who had a PEG tube with a short protrusion developed gastric ulcer. The use of H 2 -blockers had no significant impact on the development of gastric ulcer.The occurrence of gastric ulcer after PEG placement was attributable to the shape of the PEG tube within the intragastric space, and not to the use of H 2 -blockers, suggesting that appropriate placement of the PEG tube is an important factor in preventing gastric ulcer.
FOUR OPEN SAFETY-PINS IN THE ESOPHAGUS
Authors: Chevalier Jackson
Journal: JAMA (1923)

The problems of the quick and safe peroral, esophagoscopic removal of a safety-pin in the esophagus have been well worked out and established on a sound basis. The case here reported, however, presented heretofore unrecorded difficulties: <h3>REPORT OF CASE</h3> A boy, aged 9 months, was referred to Drs. Cornelius Coakley and W. F. Cunningham, with the history that on admission to the Southampton Hospital for a phimosis operation an open safety-pin had been found in the stools by the nurse. The mother stated that an older child had put a safety-pin in the patient's mouth. Roentgen-ray examination was promptly made for other safety-pins, and four, all open and all of a very large size, were found lodged in the esophagus (Figs. 1 and 2). They had probably been present for nearly two months. Esophagoscopy revealed that the pins were interlocked so that when the point of one was brought into
A STUDY OF THE GENERALIZATION OF VACCINE VIRUS FROM ENHANCED SKIN LESIONS
Authors: Fred W. Stewart, F. Duran-Reynals
Journal: The Journal of Experimental Medicine (1929)

Rabbits bearing very intensive skin lesions resulting from the intracutaneous injection of neurovirus plus testicular extract show typical histological alterations in the gonads, suprarenals, liver, spleen, lung, lymph nodes, and bone marrow. Similar but less wide-spread alterations are found after intravenous injection of neurovirus. Although testicle extract injected intracutaneously with neurovirus has a marked enhancing action upon the activity of the latter, the same mixture injected intravenously yields no sign of any such enhancement. The significance of these observations as regards the question of the ectodermotropism of vaccine virus is discussed, and the doctrine of specific organ affinities is considered.
Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm.
Authors: J P Kemp, R J Dockhorn, W W Busse, E R Bleecker, A Van As
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Physical exercise is a common trigger for bronchial asthma. We evaluated the preventive effect on exercise-induced bronchospasm (EIB) of a single 42 micrograms dose of salmeterol, a uniquely long-acting inhaled bronchodilator, and compared salmeterol with 180 micrograms albuterol in two independent, randomized, double-blind, placebo-controlled studies involving 161 subjects. Three exercise challenges were conducted over 12 h, and bronchoconstriction following the serial challenges was assessed as change in FEV1 compared with predose values. The mean maximal percentage decrease in FEV1 after the three exercise challenges was 5% at 0.5 h, 8% at 5.5 h, and 13% at 11.5 h postdose in the salmeterol group compared with 7, 25, and 27%, respectively, in the albuterol group and 27, 27, and 26%, respectively, in the placebo group (p < 0.001, overall treatment difference). Albuterol provided complete protection against EIB (defined as < 10% decrease in FEV1 compared with predose values) only after the first exercise challenge, but salmeterol continued to provide complete protection in the majority of subjects after each exercise challenge: 80% (44 of 55) at 0.5 h, 70% (37 of 53) at 5.5 h, and 55% (29 of 53) at 11.5 h. Electrocardiographic monitoring revealed no clinically significant changes in any treatment group 15 and 30 min following each exercise challenge. In summary, these data demonstrate that salmeterol is effective against EIB and that a single 42 micrograms dose can prevent EIB for up to 12 h.
Characterization of the Nuclear Import Pathways of Galectin-3
Authors: Susumu Nakahara, Natsuo Oka, Yi Wang, Victor Hogan, Hidenori Inohara, Avraham Raz
Journal: Cancer Research (2006)

Abstract Galectin-3 (Gal-3), a pleiotropic β-galactoside–binding protein, was shown to be involved in several nuclear-dependent functions, including up-regulation of transcriptional factors, RNA processing, and cell cycle regulation. Gal-3 compartmentalization in the nucleus versus the cytoplasm affects, in part, the malignant phenotype of various cancers. However, to date, the mechanism by which Gal-3 translocates into the nucleus remains debatable. Thus, we have constructed and expressed a variety of fusion proteins containing deletion mutants of Gal-3 fused with monomers, dimers, and trimers of enhanced green fluorescent protein and searched for the Gal-3 sequence motifs essential for its nuclear localization in vivo. In addition, a digitonin-permeabilized, cell-free transport in vitro assay was used to directly examine the mechanism of Gal-3 nuclear import. Partial deletions of the COOH-terminal region (114-250) of the human Gal-3 significantly decreases its nuclear translocation, whereas a peptide (1-115) was transported to the nuclei. The in vitro nuclear import assay revealed that there are at least two independent nuclear pathways for shuttling Gal-3 into the nucleus: a passive diffusion and an active transport. This is the first article providing direct evidence for the nuclear import mechanisms of Gal-3 and suggests that Gal-3 nuclear translocation is governed by dual pathways, whereas the cytoplasmic/nuclear distribution may be regulated by multiple processes, including cytoplasmic anchorage, nuclear retention, and or nuclear export. These results may lead to the development of a therapeutic modality aiming at abrogating Gal-3 translocation into the nucleus and thus hampering its activity during cancer progression and metastasis. (Cancer Res 2006; 66(20): 9995-10006)
Power Failure, Liver Failure
Authors: Daniel Francis Schafer, Michael Floyd Sorrell
Journal: New England Journal of Medicine (1997)

The literature on fulminant hepatic failure is studded with exotica. Hepatic failure has been caused by mushrooms, overheated hot tubs, and the infamous unripe ackee fruit that is associated with Jamaican vomiting illness. The report by Mahler and associates in this issue of the Journal 1 is not just the description of yet another cause of hepatic failure. What sets this report apart is the inclusion of experiments that suggest the mechanism of the liver failure.The tragic story began with a physician and his 17-year-old son eating rewarmed pasta. The father became ill, though not seriously. But within four days, . . .
Treadmill protocols for determination of maximum oxygen uptake in runners.
Authors: T R McConnell, B A Clark
Journal: British Journal of Sports Medicine (1988)

Four testing protocols were completed by each of 10 runners using a common speed for protocols 1 and 2 (P1 and P2), each runner's training pace for protocol 3 (P3) and a speed selected manually by the runner for protocol 4 (P4). Stages were increased by 2.5% grade every 2 min for each protocol except for P1, which had 1 min stages. There were no significant differences in maximum oxygen uptake (VO2 max) between protocols (P1, 65.0 +/- 5.6 ml.kg-1 min-1; P2, 64.5 +/- 5.3 ml.kg-1 min-1; P3, 66.2 +/- 3.9 ml.kg-1 min-1; P4, 64.7 +/- 5.8 ml.kg-1 min-1). Treadmill time was significantly less for P1 than for the other protocols. The rate of perceived exertion obtained at maximal exercise during P1 was less than that obtained during the other three protocols. Heart rate was significantly lower (P less than 0.05) at any level of submaximal VO2 during P3 than during the other protocols. We recommend a testing protocol using speeds approximating the runner's training pace and 1 min stages. This may result in lower perception of difficulty and HR throughout the test and shorter testing times.
Effects of a Brief Intervention for Reducing Violence and Alcohol Misuse Among Adolescents
Authors: Maureen A. Walton, Stephen T. Chermack, Jean T. Shope, C. Raymond Bingham, Marc A. Zimmerman, Frederic C. Blow, Rebecca M. Cunningham
Journal: JAMA (2010)

<h3>Context</h3>Emergency department (ED) visits present an opportunity to deliver brief interventions to reduce violence and alcohol misuse among urban adolescents at risk of future injury.<h3>Objective</h3>To determine the efficacy of brief interventions addressing violence and alcohol use among adolescents presenting to an urban ED.<h3>Design, Setting, and Participants</h3>Between September 2006 and September 2009, 3338 patients aged 14 to 18 years presenting to a level I ED in Flint, Michigan, between 12 PM and 11 PM 7 days a week completed a computerized survey (43.5% male; 55.9% African American). Adolescents reporting past-year alcohol use and aggression were enrolled in a randomized controlled trial (SafERteens).<h3>Intervention</h3>All patients underwent a computerized baseline assessment and were randomized to a control group that received a brochure (n = 235) or a 35-minute brief intervention delivered by either a computer (n = 237) or therapist (n = 254) in the ED, with follow-up assessments at 3 and 6 months. Combining motivational interviewing with skills training, the brief intervention for violence and alcohol included review of goals, tailored feedback, decisional balance exercise, role plays, and referrals.<h3>Main Outcome Measures</h3>Self-report measures included peer aggression and violence, violence consequences, alcohol use, binge drinking, and alcohol consequences.<h3>Results</h3>About 25% (n = 829) of screened patients had positive results for both alcohol and violence; 726 were randomized. Compared with controls, participants in the therapist intervention showed self-reported reductions in the occurrence of peer aggression (therapist, −34.3%; control, −16.4%; relative risk [RR], 0.74; 95% confidence interval [CI], 0.61-0.90), experience of peer violence (therapist, −10.4%; control, +4.7%; RR, 0.70; 95% CI, 0.52-0.95), and violence consequences (therapist, −30.4%; control, −13.0%; RR, 0.76; 95% CI, 0.64-0.90) at 3 months. At 6 months, participants in the therapist intervention showed self-reported reductions in alcohol consequences (therapist, −32.2%; control, −17.7%; odds ratio, 0.56; 95% CI, 0.34-0.91) compared with controls; participants in the computer intervention also showed self-reported reductions in alcohol consequences (computer, −29.1%; control, −17.7%; odds ratio, 0.57; 95% CI, 0.34-0.95).<h3>Conclusion</h3>Among adolescents identified in the ED with self-reported alcohol use and aggression, a brief intervention resulted in a decrease in the prevalence of self-reported aggression and alcohol consequences.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00251212
Depression and obesity are major causes of maternal death in Britain
Authors: Madeleine Brettingham
Journal: BMJ (2004)

Depression and obesity are now the major causes of deaths related to pregnancy among women in the United Kingdom, a report published by the Royal College of Obstetricians and Gynaecologists said last week. Although numbers of deaths as a result of direct physiological complications such as thromboembolism have fallen broadly, indirect psychological and lifestyle factors continue to pose a significant risk.

The Confidential Enquiry into Maternal Death assessed 391 deaths over a period of three years, from 2000 to 2002, to arrive at its findings. “There has been a vast reduction in the number of direct obstetric complications, and that shows a great improvement in medical science,” said Richard Congdon, …
Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?
Authors: K.F. Chung
Journal: European Respiratory Journal (2000)

In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro-inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T-cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro-activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.
Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings
Authors: G Hein, C Weiss, G Lehmann, T Niwa, G Stein, S Franke
Journal: Annals of the Rheumatic Diseases (2005)

The process of bone remodelling is disturbed in the development of osteoporosis.To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings.Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N(epsilon)-carboxymethyllysine.Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs.It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.
STUDIES UPON MINUTE HEMOLYTIC STREPTOCOCCI
Authors: Perrin H. Long, Eleanor A. Bliss, Charles F. Walcott
Journal: The Journal of Experimental Medicine (1934)

1. Minute beta hemolytic streptococci were found to occur from one-third to one-half as frequently in normal individuals as do ordinary beta hemolytic streptococci. 2. They were rarely isolated from the rhinopharynges of individuals suffering from chronic disease. 3. In acute respiratory tract infection other than that due to the ordinary beta hemolytic streptococcus the incidence of minute streptococci was slightly higher than in normal individuals. 4. In acute streptococcal infections, scarlet fever and acute tonsillitis, for example, the incidence of minute hemolytic streptococci did not significantly vary from the incidence found in normal human beings. 5. Minute beta hemolytic streptococci were found in the throats of 33 out of 42 patients ill with glomerular nephritis and in 25 out of 59 patients who were suffering from the various manifestations of rheumatic fever. 6. In glomerular nephritis and rheumatic infection the minute beta hemolytic streptococci were isolated from the throats of more patients than were the ordinary beta hemolytic streptococci.
Capillary Permeability to Macromolecules
Authors: KARLMAN WASSERMAN, LEOPOLD LOEB, H. S. MAYERSON, Allen H. Mackenzie, Arthur S. Cummins
Journal: Circulation Research (1955)

Small infusions of dextran fractions having average molecular weights ranging from 10,600 to 412,000 yield plasma to lymph concentration ratios which are directly proportional to molecular weight. The concentration gradient for a specific molecular weight, however, decreases as the volume of infusion is increased. This volume effect, explained in terms of stretching of capillary pores, consequently provides less resistance to the passage of macromolecules through the capillary wall. The significance of these results in terms of the conventional pore theory of capillary permeability is discussed.
Cellular electrophysiology of human myocardial infarction. 1. Abnormalities of cellular activation.
Authors: J F Spear, L N Horowitz, A B Hodess, H MacVaugh, E N Moore
Journal: Circulation (1979)

Ventricular tissues were obtained at the time of operation from 12 patients who underwent aneurysmectomy or mitral valve replacement. The electrophysiologic characteristics of these tissues were determined in a tissue bath using microelectrodes. Normal-appearing action potentials were recorded from surviving Purkinje fibers and ventricular muscle cells within infarcted ventricular tissues. Normal muscle action potential recordings from infarcted tissues were similar to action potentials from noninfarcted papillary muscles, except that the duration of the action potential was significantly longer in the former. In other areas slow response potentials were recorded. These action potentials conducted slowly and were eliminated by verapamil. We observed verapamil-sensitive slow response automaticity, but this did not correlate with ventricular tachycardias, present in three patients. Variable amplitude responses arising from normal resting potentials and characterized by stimulus intensity-dependent changes in action potential amplitude were recorded in tissues from two patients. These potentials had many characteristics similar to the slow response, but were not eliminated by verapamil. We also saw inexcitable cells with both normal and abnormal resting potentials. The heterogeneous electrophysiologic characteristics of these tissues provide a likely substrate for arrhythmias and may be the source of the ectopic ventricular rhythms observed in these patients.
Stimulation of Sympathetic Centers by Histamine
Authors: U. TRENDELENBURG
Journal: Circulation Research (1957)

Contraction of the nictitating membrane of the cat following intravenous injections of histamine persisted after adrenalectomy when cocaine had been injected. Since histamine has no direct effect on the nictitating membrane and since its action on the Superior cervical ganglion is abolished by cocaine, the effect seemed to be due to an action of histamine in the central nervous system. Proof has been obtained that it has such an action. In addition, injections of small doses of histamine into the ventricles of the cat's brain have been found to cause a rise of systemic blood pressure which was of central origin.
The Medical School Admissions Dilemma
Authors: Frederick J. Ramsay
Journal: JAMA (1977)

THERE was a time when admitting a candidate to medical school was a relatively simple and straightforward proposition. The number of acceptable applicants roughly corresponded to the number of available places. Admissions of women and minorities were, for the most part, concentrated in the three schools that "specialized" in educating these students (Woman's Medical College of Pennsylvania, Howard University College of Medicine, and Meharry Medical College School of Medicine). However, in the past two decades medical education has experienced changes of almost cataclysmic proportions—in curricular content, facilities, faculties, and the numbers and kinds of students enrolled. At the same time, the cost of educating physicians has skyrocketed, which in turn has required increased federal support, and that has inevitably been accompanied by increased regulatory restraints and an unprecedented measure of control. Since 1956, the number of places available in the first year of medical school has doubled while the number