tbuckley/cabot-search huggingface dataset:
1110. Selective Chemical Modification on Polyethylenimine and Its Effects on Transfection Efficiency and Cytotoxicity
Authors: Xiang Gao, Dexi Liu
Journal: Molecular Therapy (2005)

Top of pageAbstract
Branched polyethylenimine 25,000 is an efficient cationic polymeric transfection agent that possesses both DNA condensation and endosome lytic functionalities. Its abundant primary, secondary and tertiary amine groups contribute to transfection activity as well as significant toxicity to cells. To better understand to what extend each type of amine group is responsible for transfection and toxicity, selective chemical modification was performed on individual primary, secondary amine groups or both types on PEI by acylation (charge elimination) or reductive amination (transformation to tertiary amines). The resulted PEI derivatives have different amounts of each type of amine groups and varied degrees of charge density. Here we show the synthesis of these derivatives and the characterization in relationship to DNA binding, transfection efficiency, and cytotoxicity. Our initial results suggest that primary amine groups are mainly responsible for high affinity of DNA binding and toxicity, and that selective elimination of a portion of the primary amine groups resulted in polymers with enhanced gene transfection efficiency and significantly reduced toxicity. Secondary amine groups also contributed to a certain degree of toxicity while polymers that contain tertiary amine groups to the entirety are still transfectionally competent. These results add to the existing knowledge about the structural details of PEI25,000 relevant to its biological activities.
Aneuploidy-driven non-heritable genomic variations demonstrate area-specific distribution in the Alzheimer’s disease brain
Authors: Ivan lourov, Svetlana Vorsanova, Thomas Liehr, Yuri Yurov
Journal: Molecular Neurodegeneration (2013)

Background Post-zygotic aneuploidy is the prominent genetic feature of the human brain (1). Genomically mosaic brain results from that the excess of aneuploid neurons due to early developmental disturbances (somatic genome variations), abnormal cell cycle regulation and altered programmed cell death. As the result, aneuploidization of the brain is a likely susceptibility factor (mechanism) for brain disorders including Alzheimer’s disease.
Major histocompatibility complex-linked diabetogenic gene of the nonobese diabetic mouse. Analysis of genomic DNA amplified by the polymerase chain reaction.
Authors: H Ikegami, G S Eisenbarth, M Hattori
Journal: Journal of Clinical Investigation (1990)

Inheritance of insulin-dependent diabetes mellitus (IDDM) is polygenic, and at least one of the genes conferring susceptibility to diabetes is tightly linked to the MHC. Recent studies have suggested that DQB1 of humans and I-A beta of mice are closely associated with susceptibility and resistance to IDDM. For further characterization and localization of the MHC-linked diabetogenic gene, we studied the genomic sequence of the A beta gene of the nonobese diabetic (NOD) mouse, an animal model of IDDM, in comparison with those of its sister strains, nonobese nondiabetic and cataract Shionogi (CTS) mice, and the original strain, outbred Imperial Cancer Research (ICR) mice. Genomic DNAs from these strains were amplified in vitro by the polymerase chain reaction with thermostable Taq polymerase. The amplified sequences were analyzed by restriction endonuclease digestion, hybridization with allele-specific oligonucleotide probes, and direct sequencing. The unique I-A beta sequence of NOD mice was observed in the sister strain, CTS mice, and in one mouse of the original strain, outbred ICR mice. These data together with the results of MAb typing of MHC molecules and restriction mapping of the I-A region suggest that the unique class II MHC of NOD mice is not the result of a recent mutation, but is derived from the original strain. Since class I MHC of CTS mice is different from the MHC of NOD mice at both the K and D loci, CTS mice are a naturally occurring recombinant strain with NOD type class II MHC and non-NOD type class I MHC. Thus, breeding studies in crosses of NOD with CTS mice should provide biological information on whether the unique class II MHC of NOD mice is diabetogenic.
Newspapers' job is to report results for lay readers
Authors: C. Wilson
Journal: BMJ (1996)

EDITOR,—Richard Smith's comments about the Independent show a complete misunderstanding of national newspapers, their audience, and their purpose.1 It is absurd to apply the sort of critical appraisal used for papers published in medical journals to our news coverage.

The Independent addresses an informed, intelligent, lay readership. We provide clear, unbiased coverage that is accessible to all. In reporting the results of research our priority is to take the most interesting and relevant points …
Accuracy and safety of Tc99m-MIBI scintigraphy with high dose dipyridamole test in effort pectoris. A multicenter study
Authors: Oberdan Parodi, Claudio Marcasa, Gianmario Sambuoati, Ruggiró Casucci, Edoardo Verna, Michale Galli, Eugento Inglese, Paolo Merzuilo, Salvatore Pirelli, Gianni Bist, Raffaele Giubbini, Francesco Scopinaro
Journal: Journal of the American College of Cardiology (1990)
Finding the Unreached Patient
Authors: Philip W. Brickner
Journal: JAMA (1973)

Current hospital and medical practice is based on the premise that the sick person seeks out and goes to the source of health care. In requiring the patient to take this initiative, however, we are ignoring those who are unable or unwilling to come to us. The medical community is not reaching the isolated, homebound, aged. A withering of physical capacity forces many old people in urban areas to suffer a hazardous existence alone in single rooms and welfare hotels. Poverty is a common additional disadvantage. Such people, out of contact with the medical care system, are often too disabled, frightened, or bewildered to seek help—nor does medical assistance usually go to them. Occasionally a neighbor may find a failing person and call an emergency ambulance. However, it is too late for effective treatment when a patient comes to an emergency room dying or in an advanced stage of disease.
Infants at Risk for the Acquired Immunodeficiency Syndrome
Authors: Stanley A. Plotkin
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The AIDS Task Force of the American Academy of Pediatrics is distressed by the lack of understanding on the part of some personnel in neonatal intensive care units regarding the natural history of fetuses exposed to the human immunodeficiency virus (HIV) during pregnancy. This is shown in the article by Levin et al.<sup>1</sup>The therapeutic decisions recommended for HIV-seropositive neonates assumed that treatment of those infants was futile. This attitude could have deprived infants at risk for HIV infection of life-prolonging treatment and may have jeopardized care for uninfected infants who were seropositive owing to passive transfer of HIV antibody across the placenta. The true incidence of infection with HIV of seropositive newborns in the United States is approximately 30% and may be considerably less.<sup>2</sup>Treatment has become more available and the mean survival of infected children is increasing.<sup>3</sup>In any case, the diagnosis
The Philadelphia School for Nurses.
Authors: Linn Emerson
Journal: JAMA (1906)

Orange, N. J., May 17, 1906. <h3>To the Editor:</h3> —In a recent<i>Bulletin of the Philadelphia School for Nurses</i>there are given several hundred names of physicians who endorse this school. A paragraph printed at the head of these names reads as follows: "In every instance one or more letters have been received giving specific permission to use the writer's name as reference in connection with this movement." Under Orange, N. J., the names of eleven physicians are given, my own among that number. As I have never endorsed this school I was interested to know how many of the men named had actually done so. I find two of the men named removed from Orange more than two years ago, and I understand one of them is now dead. Another is a graduate of 48 years' standing and has not engaged in practice for more than 35 years. Of
Heart failure falling in women but not in men
Authors: S. Gottlieb
Journal: BMJ (2002)

New cases of heart failure have declined steadily among women over the last 50 years but remain nearly unchanged among men.

The main reason for the difference between the sexes is that men and women tend to develop heart failure for different reasons, according to a new study. The report is based on the 54 year Framingham heart study ( New England Journal of Medicine 2002;347:1397-444).

In the study Dr Daniel Levy of …
ALLERGY TO IRON-DEXTRAN
Authors: OSCAR SWINEFORD
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 January 1967ALLERGY TO IRON-DEXTRANOSCAR SWINEFORD JR., M.D.OSCAR SWINEFORD JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-1-237_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The following comments seem appropriate to "Fatal Anaphylaxis After Intramuscular Iron-Dextran," which appeared in the ANNALS 65: 745, 1966.Kabat, Turino, Tarrow, and Maurer (1) reported that dextran was allergenic in man. Hehre and Sugg (2) showed that dextran formed specific precipitates with types II, XII, and XX antipneumococcal sera. It was shown in this laboratory (3-5) that specific type antipneumococcal rabbit serum sensitized sufficiently to mediate fatal anaphylaxis from 2.0 mg of dextran intravenously. Dextran desensitized sensitive guinea pigs against dextran but did not desensitize against the specific type II pneumococcal polysaccharide. Precipitation of dextran with...References1. RABATTURINOTARROWMAURER EAGMABPH: Studies on the immunochemical basis of allergic reactions to dextran in man. J. Clin. Invest. 36: 1160, 1957. CrossrefMedlineGoogle Scholar2. HEHRESUGG EJJY: Serologically reactive polysaccharides produced through the action of bacterial enzymes. I. Dextran of Leuconostoc mesenteroides from sucrose. J. Exp. Med. 75: 339, 1942. CrossrefMedlineGoogle Scholar3. SWINEFORDHOENEQUELCHSAMSELL ORSD: Purification of antibodies. I. Dextranase purification of antibody precipitated from Type II antipneumoccal rabbit serum by dextran. J. Allerg. 30: 433, 1959. CrossrefMedlineGoogle Scholar4. SWINEFORDQUELCHSAMSELL OSD: Dominant and recessive precipitating and desensitizing haptens. Introductory report. Ann. Allerg. 18: 276, 1960. MedlineGoogle Scholar5. HOENESWINEFORDQUELCH ROS: Desensitization with haptens: role of molecular size in specific precipitation, anaphylaxis, and desensitization with dextran fractions. J. Allerg. 32: 381, 1961. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Allergy Research Laboratory Department of Internal Medicine University of Virginia School of Medicine Charlottesville, Va. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1967Volume 66, Issue 1Page: 237-237KeywordsAllergensAllergy and immunologyAnaphylaxisDextranGuinea pigsPolysaccharidesRabbitsResearch laboratories Issue Published: 1 January 1967 PDF downloadLoading ...
Lung structural remodeling and pulmonary hypertension after myocardial infarction: complete reversal with irbesartan
Authors: J Jasmin
Journal: Cardiovascular Research (2003)

Objectives: The severity of pulmonary hypertension associated with heart failure carries a poor prognosis. The lungs are very sensitive to the constrictive and proliferative effects of angiotensin-II and could represent a preferential target for this peptide. Methods: Rats with large myocardial infarcts or sham surgery received the angiotensin-II receptor antagonist irbesartan (40 mg/kg/day) or vehicle for 2 or 8 weeks (n = 5 to 8 for each group). Hemodynamic and morphometric measurements were obtained followed by immunohistochemistry, immunofluorescence analysis and electron microscopic characterization of lung sections. Results: The infarct groups developed progressive pulmonary hypertension and right ventricular hypertrophy with elevated left ventricular filling pressures (all P<0.01). Despite similar infarct size, filling pressures were lower (P<0.01) while pulmonary hypertension and right ventricular hypertrophy were completely normalized by irbesartan. Isolated lungs pressure–flow relationships were identical at 2 weeks. At 8 weeks it was steepest and shifted upward in the infarct group (P<0.001), and completely normalized by irbesartan. Lung weight doubled after infarct with no evidence of pulmonary edema and was also normalized by irbesartan. Important lungs structural remodeling evidenced by collagen and reticulin deposition, thickening of the alveolar septa and proliferation of cells with ultrastructural characteristics of myofibroblasts (pericytes) were identified after infarct. Conclusions: After large myocardial infarct there is important pulmonary structural remodeling in which myofibroblasts (pericytes) proliferation may play an important role. This initially protective mechanism against high filling pressures could eventually contribute to the development of pulmonary hypertension and right ventricular hypertrophy. Future studies are needed to determine if angiotensin-II directly modulates pulmonary remodeling after myocardial infarct.
Interkingdom Host Jumping Underground: Phylogenetic Analysis of Entomoparasitic Fungi of the Genus Cordyceps
Authors: Naruo Nikoh, Takema Fukatsu
Journal: Molecular Biology and Evolution (2000)

Most members of the ascomycetous genus Cordyceps are endoparasitic fungi of insects and other arthropods, but about 20 of the 300 described species are parasitic to hart's truffles, Elaphomyces spp. In order to understand the evolution of host specificity and the process of interkingdom host jumping in Cordyceps, we investigated the phylogenetic relationships of 22 representatives, including 4 truffle parasites and 18 insect parasites, based on nuclear and mitochondrial rDNA sequences. Five monophyletic groups were identified in both nuclear and mitochondrial phylogenies. In three of the five clades, the members utilized hosts from the same insect group, suggesting that the endoparasite-host connections have been conserved to some extent. On the other hand, it was also shown that major host shifts between distantly related insects must have occurred repeatedly. Notably, phylogenetic analyses strongly suggested that parasites of hart's truffles originated from parasites of cicada nymphs during the evolution of the Cordyceps. The common habitats of cicada nymphs and hart's truffles, deep underground and associated with tree roots, suggest that the interkingdom host jumping from Animalia to Fungi might have been promoted by the overlapping ecological niche of the unrelated hosts. This finding provides an impressive case of a drastic host shift in favor of the host habitat hypothesis.
Working as a ship's doctor
Authors: S. Shafi
Journal: BMJ (1998)

If you enjoy your work as a general practitioner, but dream of world travel on a payroll, becoming a ship's doctor might just be what you're looking for. It is one of the less common career avenues considered by doctors, very little has been written about it, and the doctors that do go out to sea have little or no contact with any particular group of doctors when on dry land. The result is that most doctors know little of the speciality.

In this currently changing political climate of general practice, many of the doctors who would have proceeded onto becoming principals after their training are looking for alternatives and are less willing to commit themselves to any long term practice partnerships.

   ![][1] 

Becoming a doctor at sea for a year or more will enrich your knowledge of the world and its people. This is probably the opposite end of the spectrum to working for a voluntary services organization yet there are some fundamental principles which are similar.

The cruise ship industry is slowly expanding to reach a wider population. The number and size of ships built is increasing every year and increasingly cruises are being marketed to younger people and those with families, not just the wealthy or retired.

General practice training is essential. Basic training during the vocational training scheme should have included an accident and emergency post and experience in an intensive care unit. You should have the Advanced Cardiac Life Support certificate, and, if the ship is serves American passengers, have been on an Advanced Trauma Life Support course for medicolegal reasons.

The ideal ships doctor a broad base of knowledge in as many fields as possible: experience in other specialties such as general medicine, care of the elderly, or psychiatry will be a bonus to you. …

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Calcium influx mechanisms underlying calcium oscillations in rat hepatocytes
Authors: Bertina F. Jones, Rebecca R. Boyles, Sung‐Yong Hwang, Gary S. Bird, James W. Putney
Journal: Hepatology (2008)

The process of capacitative or store-operated Ca2+ entry has been extensively investigated, and recently two major molecular players in this process have been described. Stromal interacting molecule (STIM) 1 acts as a sensor for the level of Ca2+ stored in the endoplasmic reticulum, and Orai proteins constitute pore-forming subunits of the store-operated channels. Store-operated Ca2+ entry is readily demonstrated with protocols that provide extensive Ca2+ store depletion; however, the role of store-operated entry with modest and more physiological cell stimuli is less certain. Recent studies have addressed this question in cell lines; however, the role of store-operated entry during physiological activation of primary cells has not been extensively investigated, and there is little or no information on the roles of STIM and Orai proteins in primary cells. Also, the nature of the Ca2+ influx mechanism with hormone activation of hepatocytes is controversial. Hepatocytes respond to physiological levels of glycogenolytic hormones with well-characterized intracellular Ca2+ oscillations. In the current study, we have used both pharmacological tools and RNA interference (RNAi)-based techniques to investigate the role of store-operated channels in the maintenance of hormone-induced Ca2+ oscillations in rat hepatocytes. Pharmacological inhibitors of store-operated channels blocked thapsigargin-induced Ca2+ entry but only partially reduced the frequency of Ca2+ oscillations. Similarly, RNAi knockdown of STIM1 or Orai1 substantially reduced thapsigargin-induced calcium entry, and more modestly diminished the frequency of vasopressin-induced oscillations. Conclusion: Our findings establish that store-operated Ca2+ entry plays a role in the maintenance of agonist-induced oscillations in primary rat hepatocytes but indicate that other agonist-induced entry mechanisms must be involved to a significant extent. (HEPATOLOGY 2008.)
The coronary pressure-flow determinants left ventricular compliance in dogs.
Authors: C O Olsen, D E Attarian, R N Jones, R C Hill, J D Sink, K L Lee, A S Wechsler
Journal: Circulation Research (1981)

Displacement of the left ventricular diastolic pressure-dimension relationship (change in compliance) has been observed with alterations in coronary perfusion pressure. The relative contribution of coronary (myocardial) blood flow, as compared with the perfusion pressure at which flow occurs, was studied in 10 dogs during diastolic relaxation potassium arrest during cardiopulmonary bypass. The normalized left ventricular pressure-dimension relationships, obtained during passive, gradual filling of the left ventricle (0-20 mm Hg) were shifted progressively to the left as coronary perfusion pressure was increased. Myocardial blood flow was 0.06 ml/mg per min +/- 0.02 ml/mg per min (mean +/- SEM) at a coronary perfusion pressure of 40 mm Hg and increased to 0.38 ml/mg per min +/- 0.11 ml/mg per min as the coronary perfusion pressure was raised to 120 mm Hg. Addition of adenosine significantly increased myocardial blood flow by 109% at a coronary perfusion pressure of 80 and by 147% at a coronary perfusion pressure of 120 mm Hg, but caused no additional significant shifts in the pressure-dimension relationships, compared to the same coronary perfusion pressures without adenosine. Coronary perfusion pressure, and not coronary blood flow, is a more direct determinant of cardiac diastolic properties.
Assessment of an incentivised scheme to provide annual health checks in primary care for adults with intellectual disability: a longitudinal cohort study
Authors: Marta Buszewicz, Catherine Welch, Laura Horsfall, Irwin Nazareth, David Osborn, Angela Hassiotis, Gyles Glover, Umesh Chauhan, Matthew Hoghton, Sally-Ann Cooper, Gwen Moulster, Rosalyn Hithersay, Rachael Hunter, Pauline Heslop, Ken Courtenay, André Strydom
Journal: The Lancet Psychiatry (2014)

People with intellectual disabilities (ID) have many comorbidities but experience inequities in access to health care. National Health Service England uses an opt-in incentive scheme to encourage annual health checks of patients with ID in primary care. We investigated whether the first 3 years of the programme had improved health care of people with ID.We did a longitudinal cohort study that used data from The Health Improvement Network primary care database. We did multivariate logistic regression to assess associations between various characteristics and whether or not practices had opted in to the incentivised scheme.We assessed data for 8692 patients from 222 incentivised practices and those for 918 patients in 48 non-incentivised practices. More blood tests (eg, total cholesterol, odds ratio [OR] 1·88, 95% CI 1·47-2·41, p<0·0001) general health measurements (eg, smoking status, 6·0, 4·10-8·79, p<0·0001), specific health assessments (eg, hearing, 24·0, 11·5-49·9, p<0·0001), and medication reviews (2·23, 1·68-2·97, p<0·0001) were done in incentivised than in non-incentivised practices, and more health action plans (6·15, 1·41-26·9, p=0·0156) and secondary care referrals (1·47, 1·05-2·05, p=0·0256) were made. Identification rates were higher in incentivised practices for thyroid disorder (OR 2·72, 95% CI 1·09-6·81, p=0·0323), gastrointestinal disorders (1·94, 1·03-3·65, p=0·0390), and obesity (2·49, 1·76-3·53, p<0·0001).Targeted annual health checks for people with ID in primary care could reduce health inequities.National Institute for Health Research.
SCRIBE-A Method for Producing Automated Narrative Psychiatric Case Histories
Authors: EUGENE LASKA, D. MORRILL, NATHAN S. KLINE, E. HACKETT, GEORGE M. SIMPSON
Journal: American Journal of Psychiatry (1967)

The computer methods described in the foregoing paragraphs are intended only as brief outline of the programming techniques used by SCRIBE to handle the most common problems in punctuation and editing of the GPPQ narrative output. There are other techniques in the program too technical to describe here; however, complete documentation is available from the authors on request. It is difficult to estimate the considerable savings in man-hours of work and the research potential from such consistent information. Certainly the convenience of immediately available data through the system justifies its existence.