tbuckley/cabot-search huggingface dataset:
100. Inducible and Reversible Transgene Expression in Human Stem Cells Stably Transduced by Novel Lentiviral Vectors
Authors: Betty Y. Zhou, Zhaohui Ye, Peter Gao, Linzhao Cheng
Journal: Molecular Therapy (2006)

It is ideal, and quite often necessary, to have regulated or inducible transgene expression in stem cell-based gene therapies or basic studies, in which stage-specific or lineage-specific gene expression is crucial in analyzing progeny cells after stable gene transfer to the ancestral stem cells. We have previously shown that self-inactivating (SIN) lentiviral vectors confer promoter-specific transgene expression. In this study, we used the tetracycline repressor (tetR) that is fused with the KRAB transcriptional suppression domain (tTS) to specifically suppress transgene expression from stably transduced human cells. The transgene expression is controlled by a regular promoter adjacent to a high affinity-binding site (tetO7) of tTS. After optimizing a lentiviral vector containing a strong ubiquitous promoter such as EF1a and UBC and the location of the tetO7 site in the vector, we achieved better inducible transgene expression than previous lentiviral system containing the |[ldquo]|tet-off|[rdquo]| or |[ldquo]|tet-on|[rdquo]| system. In the new system, the transgene transcription from a regular promoter such as EF1a or UBC is suppressed by the tTS bound to the nearby tetO7 site in the absence of a tet analog doxycycline (Dox). In the presence of Dox, however, the tTS binding is off from the vector DNA and the regular transcription is restored. Thus the new system (dubbed as tet-SUPER) simply adds an extra level of regulation on transgene transcription, regardless which type of promoter is used. We tested the tet-SUPER system in human CD34- positive multipotent hematopoietic progenitor cell line TF1 and human embryonic stem (hES) cell lines H1 and I-6, using a dual-gene vector containing the GFP reporter (titers remain at 10-20 million transducing units per ml). In both human cell systems, we observed a tight regulation (suppression) in the un-induced or |[ldquo]|off|[rdquo]| state when Dox is absent. However, the suppression is reversible even after long-term suppression in the absence of Dox. The specific suppression was abolished and transgene expression was restored at a very low level of Dox (5 ng/ml). The presence of the tet-SUPER system did not alter unique properties of hES cells. In addition, the tet-SUPER lentiviral vector also conferred inducible transgene expression of the human PIG-A gene in a mutated human cell line that is deficient in the PIG-A gene and thus GPI-anchored proteins on cell surface. Together with recent papers published by Dr. Trono and others, we show that it is now possible to achieve inducible and reversible transgene expression in essentially any mammalian cell types.
Points from Letters: Changed Character of Osteomyelitis
Authors: H. R. W. Lunt
Journal: BMJ (1967)

MEDICAsOHRNALIn it you will observe that during a 12- month period in 1962/63, in the County Borough of Wolverhampton, a carefully designed prospective survey of random early discharge from hospital of 1,044 mothers and 1,044 babies, each of whom was followed up objectively for two months after confinement, made these important findings: that mortality was non-existent in mothers and small in babies; that morbidity was low for both; that neither could be attributed to early discharge; and that race, not duration of stay, was the most decisive and highly significant factor in establishment and maintenance of breast feeding.It should be added that the final survey confirmed the results of a pilot survey-to test methodology and recording-of 969 simultaneous mother and baby discharges over the preceding twelve months and that it assisted substantially in presentation earlier this year of a case for the revision of the bed ratio on which planning of hospital maternity resources is based.'-I am, etc.,
Human monocyte Arg-Serpin cDNA. Sequence, chromosomal assignment, and homology to plasminogen activator-inhibitor.
Authors: A C Webb, K L Collins, S E Snyder, S J Alexander, L J Rosenwasser, R L Eddy, T B Shows, P E Auron
Journal: The Journal of Experimental Medicine (1987)

An LPS-stimulated, human monocyte cDNA library was screened for stimulation-specific clones. One clone (pcD-1214) contained a 1.9-kb pair insert that hybridized to a 2,000-nucleotide mRNA expressed by peripheral blood monocytes, the histiocytic lymphoma cell line U937, and umbilical cord endothelial cells. The 415-amino-acid precursor polypeptide predicted from the cDNA (46,596 molecular weight) has a putative 22-residue signal peptide and approximately 35% homology with members of the serine protease inhibitor (Serpin) superfamily. On the basis of amino acid homology and alignment of COOH-terminal residues within the Serpin-reactive center, the clone pcD-1214 was identified as coding for an Arg-Serpin. Southern blot analysis of human-mouse somatic cell hybrid DNA locates the Arg-Serpin gene on human chromosome 18. A perfect match between amino acid residues 347-376 in this Arg-Serpin and the published sequence of a 30-residue, tryptic peptide from the COOH-terminus of a monocyte plasminogen activator-inhibitor (PAI-2), strongly suggests that the Arg-Serpin encoded by pcD-1214 is PAI-2.
Endoscopic Appearance of Serrated Adenomas in the Colon
Authors: E. Jaramillo, S. Tamura, H. Mitomi
Journal: Endoscopy (2005)

The endoscopic features of serrated adenomas are illustrated and clues are described that we hope may help in the recognition of these lesions. The demographic characteristics, clinicopathology, genetics, and molecular features of serrated adenomas are discussed elsewhere [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16].
Nifedipine and conventional therapy for unstable angina pectoris: a randomized, double-blind comparison.
Authors: J E Muller, Z G Turi, D L Pearle, J F Schneider, D H Serfas, J Morrison, P H Stone, R E Rude, B Rosner, B E Sobel
Journal: Circulation (1984)

To characterize the potential of nifedipine in the therapy of unstable angina pectoris we implemented a blinded, randomly assigned, titrated schedule of conventional therapy (propranolol, if not contraindicated, and isosorbide dinitrate) or nifedipine for 14 days in 126 patients hospitalized in a coronary care unit for ischemic chest pain of less than 45 min duration. There were no significant differences between conventionally and nifedipine-treated patients with regard to (1) the time to relief of pain as judged by life table analysis, (2) the decrease in anginal attacks per 24 hr from day 0 to day 2 (-2.5 +/- 0.4 for conventional therapy vs; -2.8 +/- 0.3 for nifedipine), (3) the decrease in the number of nitroglycerin tablets consumed per 24 hr (-2.0 +/- 0.5 for conventional vs -2.1 +/- 0.4 for nifedipine therapy), (4) the percentage of patients requiring morphine on day 1 (13% for conventional vs 21% for nifedipine therapy), or (5) the percentage of patients who developed infarction (14% in both groups). Among the 27 patients who did not respond to initial conventional (n = 13) or nifedipine therapy (n = 14), five in each group became pain free when the opposite therapy (either nifedipine or conventional therapy) was added. In the subgroup of 67 patients who were receiving propranolol before randomization, addition of nifedipine was more effective in controlling pain than was an increase in conventional therapy (p = .026). In the subgroup of 59 patients not receiving prior propranolol, initiation of conventional therapy produced more rapid pain relief than initiation of nifedipine therapy alone (p less than .001), which tended to increase heart rate. Thus, for the study population as a whole therapy with nifedipine alone was equivalent to conventional therapy for unstable angina, although this overall equivalence may result from a combination of superiority of nifedipine therapy in patients previously receiving beta-blocker therapy and superiority of beta-blocker therapy in patients not previously receiving beta-blockers.
A Scientific Relational Database Combined with a Report Generator for Endoscopy in Networks: EndoNet
Authors: M. Sackmann, R. Rosette, T. Busl, G. Sauter, G. Fischer, T. Hengstenberg, M. Weinzierl, J. Holl, M.-C. Jung, U. G. Klueppelberg, G. Paumgartner
Journal: Endoscopy (1998)

The flexibility required in academic endoscopy units is not provided by the available database systems. In a project involving substantial cooperation between endoscopists and computer scientists, we have developed an adaptable database, combined with a report generator embedded in the hospital's intranet.Six workstations in different areas of the hospital were clustered with a UNIX operating system to implement multi-user capability and access control. A relational database was used to design an application appropriate to the specific needs of the endoscopy unit in a teaching hospital engaged in scientific research. Both the terminology used in standardized endoscopy nomenclature and a free text block facility were included. A graphical user interface was developed to assemble pertinent data, generate the reports, and supervise the database.A total of 4936 examinations including 2988 patients were entered consecutively during continuous routine operation of the system. Complete report generation required five minutes (median; range 1-9 minutes). Both structured items and free text were used in all the reports. Querying of the database was possible, concerning matters such as the need for repeated endoscopic therapy in acute gastrointestinal bleeding (4%), the search for Helicobacter pylori in appropriate patients (64%), the rate of accidental pancreatic duct visualization in endoscopic retrograde cholangiography (24%), and links between examinations and active trials (2%). Indicating improved report quality, the number and the diameter of esophageal varices in patients with varices were more frequently reported with the new report system than with previous typed reports (P<0.001). An anonymous questionnaire revealed that the readability of the computer-generated reports was better than that of the previous typewritten reports (P=0.01).This report describes the creation of a database application and a report generator meeting the needs of scientific and routine use, and the successful application of this system in an academic endoscopy unit.
Prevalence and Correlates of Suicidal Behavior Among Soldiers
Authors: Matthew K. Nock, Murray B. Stein, Steven G. Heeringa, Robert J. Ursano, Lisa J. Colpe, Carol S. Fullerton, Irving Hwang, James A. Naifeh, Nancy A. Sampson, Michael Schoenbaum, Alan M. Zaslavsky, Ronald C. Kessler
Journal: JAMA Psychiatry (2014)

The suicide rate among US Army soldiers has increased substantially in recent years.To estimate the lifetime prevalence and sociodemographic, Army career, and psychiatric predictors of suicidal behaviors among nondeployed US Army soldiers.A representative cross-sectional survey of 5428 nondeployed soldiers participating in a group self-administered survey.Lifetime suicidal ideation, suicide plans, and suicide attempts.The lifetime prevalence estimates of suicidal ideation, suicide plans, and suicide attempts are 13.9%, 5.3%, and 2.4%. Most reported cases (47.0%-58.2%) had pre-enlistment onsets. Pre-enlistment onset rates were lower than in a prior national civilian survey (with imputed/simulated age at enlistment), whereas post-enlistment onsets of ideation and plans were higher, and post-enlistment first attempts were equivalent to civilian rates. Most reported onsets of plans and attempts among ideators (58.3%-63.3%) occur within the year of onset of ideation. Post-enlistment attempts are positively related to being a woman (with an odds ratio [OR] of 3.3 [95% CI, 1.5-7.5]), lower rank (OR = 5.8 [95% CI, 1.8-18.1]), and previously deployed (OR = 2.4-3.7) and are negatively related to being unmarried (OR = 0.1-0.8) and assigned to Special Operations Command (OR = 0.0 [95% CI, 0.0-0.0]). Five mental disorders predict post-enlistment first suicide attempts in multivariate analysis: pre-enlistment panic disorder (OR = 0.1 [95% CI, 0.0-0.8]), pre-enlistment posttraumatic stress disorder (OR = 0.1 [95% CI, 0.0-0.7]), post-enlistment depression (OR = 3.8 [95% CI, 1.2-11.6]), and both pre- and post-enlistment intermittent explosive disorder (OR = 3.7-3.8). Four of these 5 ORs (posttraumatic stress disorder is the exception) predict ideation, whereas only post-enlistment intermittent explosive disorder predicts attempts among ideators. The population-attributable risk proportions of lifetime mental disorders predicting post-enlistment suicide attempts are 31.3% for pre-enlistment onset disorders, 41.2% for post-enlistment onset disorders, and 59.9% for all disorders.The fact that approximately one-third of post-enlistment suicide attempts are associated with pre-enlistment mental disorders suggests that pre-enlistment mental disorders might be targets for early screening and intervention. The possibility of higher fatality rates among Army suicide attempts than among civilian suicide attempts highlights the potential importance of means control (ie, restricting access to lethal means [such as firearms]) as a suicide prevention strategy.
Book: Ice Bound: One Woman's Incredible Battle for Survival at the South Pole
Authors: J. A. Rosenfeld
Journal: BMJ (2001)

Jerri Nielsen Ebury Press, £16.99, pp 362 ISBN 0 09 185623 X Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> I ce Bound is the story of a woman's survival during the long, dark, six month winter with 40 other people at the South Pole installation run by the National Science Foundation. As a tale of endurance, courage, patience, and boredom in the pursuit of knowledge, it is worth reading. However, it is also the story of a 47 year old emergency room doctor who goes to serve and to have an adventure but then finds her true self … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Pneumococcal Pneumonia Treated with Aqueous Penicillin at Twelve-Hour Intervals
Authors: Philip A. Tumulty, Gordon Zubrod
Journal: New England Journal of Medicine (1948)

The efficacy of penicillin in the treatment of patients with pneumococcal lobar pneumonia is well established.1 , 2 However, the manner in which it may be employed to yield the best therapeutic results and with the least discomfort to the patient is still debated. It has been considered that to achieve maximum therapeutic response the blood concentration of penicillin must be maintained constantly at a level greater than the penicillin sensitivity of the particular organism.3 Because of this assumption penicillin has generally been administered either in aqueous solution at frequent intervals or in some repository form. On the other hand, it has . . .
Results of Surgical Treatment of Cancer of the Stomach
Authors: N. N. Trapeznikov
Journal: BMJ (1959)

AFRICANS BmT= 857etc.-may be a major factor responsible for the alarming increase of lung cancer in South Africa and Britain, and presumably elsewhere. SummaryAnalysis of the 1947-56 male lung cancer deaths in South Africa by age, country of birth, and place of residence has shown that among those dying aged 45 to 64 (but not among those dying aged 65 and over) British immigrants have had much higher lung cancer mortality rates than Union-born men or immigrants from other countries.Further, among all three categories in South Africa-Union-born men, British male immigrants, and male immigrants from other countries-the lung cancer mortality rates have increased approximately with the level of urbanization and industrialization.Neither the differences between the lung cancer mortality rates of these three groups nor the urban/rural gradient can be attributed to differences in smoking habits.Instead, both would seem to have been due to the exposure of the men concerned to different degrees of atmospheric pollution.The excess lung cancer mortality amnong British immigrants aged 45-64 would seem to have been due to their exposure in Britain to some form of atmospheric pollution to which those emigrating before 1910 had not been subject The urban/rural lung cancer mortality gradient in South Africa would appear to reflect the increasing atmospheric pollution that is encountered in passing from rural areas to areas of increasing industrialization.
Early neutrophil alveolitis after rechallenge in drug induced alveolitis.
Authors: S Salmeron, L Brochard, B Rain, P Herve, F Brenot, G Simonneau, P Duroux
Journal: Thorax (1988)

A patient with drug induced alveolitis due to an antidepressant drug, nomifensine, is described. After an inadvertent rechallenge by the patient sequential bronchoalveolar lavage was carried out. Twenty four hours after the rechallenge the lavage fluid contained a high cell count with neutrophils predominating. Seven days after challenge the cells were predominantly lymphocytes.
Photosensitizing Therapeutic Agents
Authors: Wiley M. Sams
Journal: JAMA (1960)

The antibacterial sulfonamides, the related group of hypoglycemic agents, the group of chlorothiazide diuretics, and the phenothiazine group of central sympathetic suppressants may induce cutaneous reactions when the patient is exposed to sunlight. There are numerous reports that demethylated chlortetracycline may act as a photosensitizing agent, and a few reports that griseofulvin may do so. Photosensitization dermatoses are infrequently associated with serious reactions.
The Radionuclide Detection of Lower Gastrointestinal Bleeding Sites
Authors: MICHAEL WINN, HEIDI S. WEISSMANN, SEYMOUR SPRAYREGEN, LEONARD M. FREEMAN
Journal: Clinical Nuclear Medicine (1983)

A retrospective review of two years' experience with radionuclide screening to detect lower gastrointestinal bleeding sites was conducted at New York's Montefiore Medical Center. Of 82 studies performed in 63 patients, 13 identified active bleeding sites. Only three of eight angiograms obtained in these 13 patients were positive. Thirteen contrast angiograms were performed in the group of 50 patients with negative radionuclide studies of which ten were negative and one was equivocal. The results of this study suggest that the Tc-99m sulfur colloid study for active lower gastrointestinal (GI) bleeding is an effective screening procedure. Positive studies help determine which vessel to catheterize selectively if an angiogram is to be performed. If vascular ectasis is still suspected following a negative radionuclide study, contrast angiography can be more efficaciously performed on a nonemergent basis.
Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome?
Authors: Y Zhou, C H Damsky, S J Fisher
Journal: Journal of Clinical Investigation (1997)

In human pregnancy, placental cytotrophoblasts that invade the uterus downregulate the expression of adhesion receptors that are characteristic of their epithelial origin, and upregulate the expression of adhesion receptors that are expressed by vascular cells. We suggest that this transformation could be critical to endovascular invasion, the process whereby cytotrophoblasts invade the uterine spiral arterioles and line their walls (Zhou et al. J. Clin. Invest. 1997. 99: 2139-2151.). To better understand the in vivo significance of these findings, we tested the hypothesis that in preeclampsia, an important disease of pregnancy in which endovascular invasion is abrogated, cytotrophoblasts fail to adopt a vascular adhesion phenotype. In experiments described here we stained placental bed biopsy specimens from age-matched control pregnancies and from those complicated by preeclampsia with antibodies that recognize adhesion molecules that are normally modulated during this transformation. In preeclampsia, differentiating/invading cytotrophoblasts fail to express properly many of these molecules, including integrin, cadherin, and Ig superfamily members. These results suggest that preeclampsia is associated with failure of cytotrophoblasts to mimic a vascular adhesion phenotype. The functional consequences of this abnormality are unknown, but are likely to affect negatively cytotrophoblast endovascular invasion and uterine arteriole remodeling, thereby compromising blood flow to the maternal-fetal interface.
Crisis in General Practice
Authors: John Lister
Journal: New England Journal of Medicine (1965)

THE present crisis in the general-practitioner service of the National Health Service is another milestone on the rugged road of coexistence between the doctors and the state. It has been developing for many months and has culminated in the rejection by the profession of the Government's offer to give the family doctors a conditional addition of £5,500,000 to the central pool from which they are paid and a call from the British Medical Association for all general practitioners in the National Health Service to be prepared to resign from the service.To understand the present situation, it is necessary to . . .
In Vivo Actions of Peroxisome Proliferator–Activated Receptors
Authors: Roy Eldor, Ralph A. DeFronzo, Muhammad Abdul-Ghani
Journal: Diabetes Care (2013)

Peroxisome proliferator–activated receptors (PPARs) form a family of nuclear hormone receptors involved in energy hemostasis and lipid metabolism (1,2) and include three isotypes encoded by different genes: PPARα (chromosome 22q12–13.1), PPARβ/δ (chromosome 6p21.2–21.1), and PPARγ (chromosome 3p25). PPARα was the first discovered and causes cellular peroxisome proliferation in rodent livers (3), giving this receptor family its name. Upon activation, PPARs interact with retinoid X receptor to create heterodimers, which bind to a specific DNA sequence motif termed peroxisome proliferator response element (4). Peroxisome proliferator response element usually appears in promoter regions and is constructed from repeats of nucleotide sequence AGGTCA separated by a single nucleotide.

PPARα is widely expressed in tissues with high fatty acid catabolic activity: brown fat, heart, liver, kidney, and intestine (5). Upon activation by endogenous fatty acids and their derivatives, PPARα mediates fatty acid catabolism, gluconeogenesis, and ketone body synthesis, mainly in liver (6–9). In rodents, PPARα activation also influences immune modulation (10,11) and amino acid metabolism (12), reduces plasma triglyceride, reduces muscle and liver steatosis, and ameliorates insulin resistance (IR) (13,14). Pharmacologic PPARα activation is achieved by fibrates (7) and results in reduced (30–50%) triglyceride and VLDL levels by increasing lipid uptake, lipoprotein lipase–mediated lipolysis, and β-oxidation (15). This is accompanied by a modest increase in HDL cholesterol (5–20%), secondary to transcriptional induction of apolipoprotein A-I/A-II synthesis in liver (15). In man, the primary effect of PPARα is to reduce plasma triglyceride concentration; effects on plasma free fatty acid (FFA) concentration/FFA oxidation, muscle/liver fat content, and muscle/hepatic insulin sensitivity have not been demonstrated with current PPARα agonists such as fenofibrate (16,17). Fibrates are used to treat severe hypertriglyceridemia and combined hyperlipidemia (18–20). Clinical trials to establish a role for PPARα agonists (fenofibrate, gemfibrozil) …