tbuckley/cabot-search huggingface dataset:
Ischemic Preconditioning
Authors: Reena Sandhu, Roberto J. Diaz, Guo D. Mao, Gregory J. Wilson
Journal: Circulation (1997)

Background We compared ischemic preconditioning (IP) induced with a single cycle of transient ischemia and reperfusion with that induced by multiple cycles in terms of (1) efficacy of protection against myocardial necrosis and (2) susceptibility to pharmacological blockade by inhibition of protein kinase C (PKC) or elevation of cAMP. Methods and Results All rabbits were subjected to 30 minutes of regional ischemia and 90 minutes of reperfusion in vivo. IP was induced with either one or three cycles of 5-minute transient ischemia and 10-minute reperfusion given before the 30-minute ischemia. Drug-treated hearts received a bolus dose of one of the following just before the 30-minute ischemia: (1) the PKC inhibitor chelerythrine (3.8 mg/kg), (2) the PKC inhibitor polymyxin B (10 mg/kg), or (3) the cAMP-increasing agent NKH477 (45 μg/kg). IP induced with either one or three cycles of transient ischemia and reperfusion significantly protected the heart against infarction, although the extent of protection was significantly greater with three-cycle IP. Chelerythrine, polymyxin B, or NKH477 alone did not alter infarct size in control hearts, nor did they increase infarct size in hearts preconditioned with three-cycle IP. In contrast, when IP was induced with only a single cycle, all three of these drugs significantly increased infarct size above that of the untreated one-cycle IP group. However, infarct size in all three of these drug-treated one-cycle IP groups was still significantly lower than that in the corresponding drug-treated controls, indicating a partial block of IP. Conclusions Three-cycle IP provided more effective protection against myocardial necrosis than one-cycle IP and was less susceptible to blockade by inhibitors of PKC or an agent that increases cAMP levels. However, single-cycle IP was only partially blocked by either inhibition of PKC or stimulation of cAMP production. Neither activation of the PKC pathway nor reduced formation of cAMP alone fully accounted for the necrosis protection by IP even when induced with only a single cycle of transient ischemia.
IL-12p70–producing patient DC vaccine elicits Tc1-polarized immunity
Authors: Beatriz M. Carreno, Michelle Becker-Hapak, Alexander Huang, Megan Chan, Amer Alyasiry, Wen-Rong Lie, Rebecca L. Aft, Lynn A. Cornelius, Kathryn M. Trinkaus, Gerald P. Linette
Journal: Journal of Clinical Investigation (2013)

Systemic administration of IL-12p70 has demonstrated clinical activity in cancer patients, but dose-limiting toxicities have hindered its incorporation in vaccine formulations. Here, we report on the immunological and clinical outcomes upon vaccination with CD40L/IFN-γ-matured, IL-12p70-producing DCs.7 HLA-A*0201+ newly diagnosed stage IV melanoma patients were immunized against the gp100 melanoma antigen using autologous peptide-pulsed, CD40L/IFN-γ-matured DCs. PBMCs were taken weekly for immune monitoring by tetramer analysis and functional assays. CT imaging was performed at baseline, week 9, and week 18 for clinical assessment using RECIST.6 of 7 treated patients developed sustained T cell immunity to all 3 melanoma gp100 antigen-derived peptides. 3 of the 6 immunological responders developed confirmed clinical responses (1 complete remission >4 years, 2 partial response). Importantly, DC vaccine-derived IL-12p70 levels positively correlated with time to progression (P = 0.019, log-rank), as did T-cytotoxic 1 (Tc1) immunity, as assessed by IFN-γ/IL-13 and IFN-γ/IL-5 ratios (P = 0.035 and P = 0.030, respectively, log-rank). In contrast, a pathway-specific defect in IL-12p35 transcription was identified upon CD40L/IFN-γ activation in clinical nonresponder patient DCs, and gp100-specific T cells from these patients displayed a Tc2 phenotype. Incorporation of TLR3 and TLR8 agonists into the CD40L/IFN-γ activation protocol corrected the IL-12p70 production defect in DCs derived from clinical nonresponder patients.These findings underscore the essential role of IL-12p70 in the development of therapeutic type 1 antigen-specific CD8+ T cell immunity in humans with cancer.
How to tackle the prescription opioid crisis
Authors: J. Norman, C. Caisley
Journal: BMJ (2011)

Dhalla and colleagues show that we need to face up to a prescription opioid crisis in chronic pain.1 Opioid treatment is, however, well established, and we would have welcomed their views on how individual clinicians should treat this group of patients. We offer simple dos and don’ts based on the actions and behaviours we see every week:
Identification of novel insertion sites in the Ad5 genome That utilize the Ad splicing machinery for therapeutic gene expression
Authors: Fang Jin, Peter J. Kretschmer, Terry W. Hermiston
Journal: Molecular Therapy (2005)

Therapeutic transgene expression from oncolytic viruses represents one approach to increasing the effectiveness of these agents as cancer therapeutics. In the case of the oncolytic adenovirus (Ad), however, the genomic packaging capacity is constrained. To address this, we explored whether a transposon-based system could identify sites in the viral genome where endogenous Ad promoters could drive transgene expression via splicing and still maintain the replication capacity of the virus. Using GFP as a reporter gene and an E3-deleted Ad genome as a target, we tested three splicing signals. RACE analysis confirmed that gene expression from the GFP-expressing Ads occurs via splicing and traced expression to the Ad major late promoter (MLP). Replacement of the GFP transposon by an equivalent splice acceptor–luciferase expression cassette in the same orientation confirmed that substitute transgenes are also expressed via splicing from the MLP. Interestingly, insertion of the substitute transgene in the opposite orientation also resulted in expression that, in some cases, originated from within the ITR region of the viral genome. In summary, splice acceptor sequences can be used to control transgene expression from endogenous Ad promoters and this represents a genomically economical approach to arming oncolytic Ads.
Myths and Mirths — Women in Medicine
Authors: Howard M. Spiro
Journal: New England Journal of Medicine (1975)

OF all the revolutions of the past few years, the one that seems most likely to have the longest life is that in sex, simply because people have a vested or, as appropriately, a "bloused" interest. "Women's lib" in medicine bids fair to be as permanent as any revolution can be. We physicians ought to have accepted the idea that women have as much right to be physicians as men and indeed that they have the same abilities. This now seems so obvious to me that, like any convert, I have been startled to find many of my friends still . . .
The Inevitable Failure of Cost-Containment Strategies
Authors: Frank E. Samuel
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Dr Schwartz<sup>1</sup>keeps reminding us that health care ration cards are inevitably just around the bend because of our insatiable appetite for health care services and technologies that are very expensive and perhaps fundamentally useless. Although much of what Dr Schwartz says is thoughtful, in at least two respects he is wrong. First, he seems impervious to the alleviation of human suffering made by technologies that make but a marginal change in the big picture. He discusses with extraordinary superficiality advances like coronary angioplasty that make a modest, but real percentage of coronary artery bypass surgery actually—as opposed to statistically—unnecessary. He discusses this particular advance as meaningless, apparently because it isn't important enough to change the big picture. No matter that many candidates for bypass surgery need not endure, among other things, having their breastbones cut down the middle by a surgical saw. And if the
Accidental Intra-arterial Injection of Penicillin G
Authors: Harry Schanzer
Journal: JAMA (1979)

WHEN administered by the intraarterial route, many drugs induce lesions in the small arterioles, resulting in thrombosis and ischemic damage to tissues supplied by them.<sup>1-7</sup>Intra-arterial injection of penicillin has been reported to induce damage by this same mechanism.<sup>8-11</sup> This communication refers to two cases of accidental intra-arterial injection of penicillin. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 10-month-old infant was brought to the emergency room of Mt Sinai Hospital, New York, with a two-day history of fever and pain in the right ear. On examination, a purulent right otitis media was found and a mixture of penicillin G benzathine and penicillin G procaine (Bicillin C-R), 1,200,000 units, was administered in the upper third of the external aspect of the left thigh. Immediately after injection, the child became very irritable; four hours later, the mother noticed marked swelling of the left inferior extremity. In the emergency room, the swelling
Abnormal Immune Response to Varicella Vaccine in Subjects with Atopic Dermatitis Compared to Non-atopic controls
Authors: L SCHNEIDER, A WEINBERG, M BOGUNIEWICZ, D ZACCARO, P TAYLOR, I BORRASCOUGHLIN, L HEUGHAN, R SAMUELS, D LEUNG
Journal: Journal of Allergy and Clinical Immunology (2008)
Technetium-99m in the Diagnosis of Thyrotoxicosis
Authors: W. V. Hoff, G. G. Pover, N. M. Eiser
Journal: BMJ (1972)

The thyroid uptake at 20 minutes of intravenously administered Technetium-99<sup>m</sup> (<sup>99m</sup>Tc) was measured in 117 patients with a standard scintillation counter. Patients were divided into three groups on the basis of clinical assessment, four-hour <sup>131</sup>I uptake, triiodothyronine (T-3) resin uptake, and protein-bound iodine measurements. In 31 patients with no evidence of thyroid disease the mean <sup>99m</sup> Tc uptake was 1·8% ±S.D. 1·1%. In 32 patients with thyroid enlargement who were euthyroid the mean uptake was 2·5% ±S.D. 2·2%. In 54 thyrotoxic patients the mean uptake was 17·7% with a range of 4·1 to 44%, all cases having an uptake above the upper limit of normal (4·0%). These results agree closely with reported uptake studies using scanning techniques. In seven patients the extrathyroidal neck activity was measured by using a scanner, and the mean was 6·3% of the extrathyroidal total body radioactivity comparing favourably with an assumed 6% used in our calculations. We have shown that the measurement of the thyroid uptake of <sup>99m</sup>Tc with a scintillation counter is of value, and that it is not necessary to use scanning techniques in the diagnosis of thyrotoxicosis. Advantages of <sup>99m</sup> Tc are minimal radiation, reduction in patient and laboratory time, and low cost.
Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients
Authors: A Alvarez-Larrán, F Cervantes, B Bellosillo, M Giralt, A Juliá, J C Hernández-Boluda, A Bosch, L Hernández-Nieto, V Clapés, C Burgaleta, C Salvador, E Arellano-Rodrigo, D Colomer, C Besses
Journal: Leukemia (2007)
High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.
Authors: J M McCune, R Loftus, D K Schmidt, P Carroll, D Webster, L B Swor-Yim, I R Francis, B H Gross, R M Grant
Journal: Journal of Clinical Investigation (1998)

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults (</= 39 yr) with CD4 counts in the range 300-500 cells/microl and in older subjects (> 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.
PI3K Signaling in the Ventromedial Hypothalamic Nucleus Is Required for Normal Energy Homeostasis
Authors: Yong Xu, Jennifer W. Hill, Makoto Fukuda, Laurent Gautron, Jong-Woo Sohn, Ki-Woo Kim, Charlotte E. Lee, Michelle J. Choi, Danielle A. Lauzon, Harveen Dhillon, Bradford B. Lowell, Jeffrey M. Zigman, Jean J. Zhao, Joel K. Elmquist
Journal: Cell Metabolism (2010)
Dirt and Disease: Polio Before FDR
Authors: Alan R. Hinman
Journal: JAMA (1994)

The author describes this book as a social history of polio, dealing with society's response to poliomyelitis rather than with the impact of the disease on morbidity and mortality. As a case study, it focuses on the 1916 epidemic in New York City. Individual chapters treat the way sanitarians/public health reformers tried to deal with polio, the impact of developing laboratory science on both public and professional perceptions, proposals from the lay public on how to deal with polio, and the ways the emerging discipline of epidemiology tried to decipher the epidemic. Finally, there is a brief summary of polio since Franklin D. Roosevelt, touching on the societal impact of having a president with paralysis due to polio and the development and introduction of inactivated and live attenuated vaccines. There are both good points and drawbacks to the book. It appears to be an expansion of a doctoral thesis and
Airway wall remodeling after cessation of exposure to isocyanates in sensitized asthmatic subjects.
Authors: M Saetta, P Maestrelli, G Turato, C E Mapp, G Milani, F Pivirotto, L M Fabbri, A Di Stefano
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To determine whether the cessation of exposure to isocyanates is associated with structural changes of the airway wall in sensitized subjects, we studied bronchial biopsies from 10 subjects with occupational asthma induced by toluene diisocyanate (TDI). Bronchial challenges with TDI and methacholine were performed and biopsies were taken on two occasions, at diagnosis and 6 to 21 mo after cessation of exposure to TDI. After bronchoscopy, biopsies were formalin-fixed or snap-frozen in liquid nitrogen and then processed for a quantitative histochemical and immunohistochemical analysis. After cessation of exposure, we observed a significant decrease of the sensitivity to TDI (p < 0.05), of the thickness of subepithelial fibrosis (p < 0.007), and of the numbers of subepithelial fibroblasts (p < 0.05), mast cells (p < 0.02), and lymphocytes (p < 0.03) as compared with values at diagnosis. By contrast, the nonspecific bronchial hyperresponsiveness and the numbers of macrophages and eosinophils did not change. In conclusion, in patients with occupational asthma induced by TDI, the cessation of exposure to the sensitizing agent is associated with a reduced thickness of subepithelial fibrosis and with a reduced number of subepithelial fibroblasts, mast cells, and lymphocytes in the bronchial mucosa, suggesting a remodeling of the airway wall with the avoidance of the specific stimulus.
Sensitivity of lymphocytes from vulcanizers to the in vitro induction of sister chromatid exchanges.
Authors: F Degrassi, R De Salvia, M Fiore, R Ricordy, C Tanzarella, R Benigni, F Palitti
Journal: Environmental Health Perspectives (1993)

Spontaneous frequencies of sister chromatid exchanges (SCEs) and SCEs induced in vitro by chemicals with different mechanisms of action such as mitomycin C, 4-nitroquinoline oxide, and 3-aminobenzamide were examined in phytohemagglutinin-stimulated peripheral blood lymphocytes from a group of workers in a rubber plant and a control group, both of which had been analyzed for levels of spontaneous SCEs 2 years earlier. An interindividual variability in the induction of SCEs was found after in vitro treatments with the different mutagens, which did not correlate with occupational exposure. This variability in the sensitivity to the induction of SCEs might be correlated to genetic differences among individuals, which have to be taken into account in environmental monitoring programs.
P491Transcriptional regulatory roles of G-quadruplex DNA in promoters of genes involved in beta-adrenergic signaling pathway
Authors: W Zhou, R Vilar, L Ying, SE Harding
Journal: Cardiovascular Research (2014)

Background: G-quadruplexes (G4s) are four-stranded DNA secondary structures involved in a diverse range of biological processes. We have previously revealed that G4s are important in cardiac function-related genes and pathways. In the beta-adrenergic receptor signaling pathway, which is directly involved in heart failure (HF), conserved G4s have been found in the promoter of ADRB1 and ADCY5. We hypothesize that by targeting these conserved promoter G4s using synthetic G4-binding ligands, we can inhibit downstream gene expression as an alternative genetic approach for the treatment of HF beyond β-blockers. Methods: Promoter fragments of rat Adrb1 and Adcy5 were amplified from rat genomic DNA by PCR, and inserted into the pGL4.10 luciferase vector. Site-directed mutagenesis was used to disrupt G4-forming sequences. Neonatal rat cardiomyocytes (NRCMs) were isolated from ventricles of 1-3-day-old pups, and grown for 16hrs prior to transfection. Transfected NRCMs were incubated with/without 100μM TMPyP4, a general G4-binding ligand, for 48hrs. Promoter activity differences were measured by dual-luciferase assays. Endogenous Adrb1 and Adcy5 mRNA changes in response to TMPyP4 were determined by real-time PCR. All experiments were done in triplicates for 2-3 repeats. Results: When treated with TMPyP4, the downstream luciferase activity decreased by 24.6% in Adrb1 promoter and 34.6% (P=0.001, n=3) in Adcy5 promoter. Endogenous Adrb1 and Adcy5 mRNA levels decreased significantly in response to TMPyP4 (decreased by 57.2%, and 58.5%, P<0.0001, n=3, respectively). The mRNA of housekeeping Gapdh, which does not contain conserved promoter G4, changed little (P=0.7, n=3). In rat Adcy5 promoter, disruption of the 1st(+1154 to +1185bp), 2nd(+601 to +624bp), 4th(-159 to -136bp), or 5th(-383 to -356bp) G4-forming sequence all induced significant transcription inhibition in response to TMPyP4 (activities decreased by 97.9%, 91.3%, 95.6%, and 95.8% respectively). However, when the 3rd (-82 to -35bp) Adcy5 promoter G4 was disrupted, TMPyP4-induced inhibition effect was not observed. Conclusion: When stabilised by the general G4-binding ligand, conserved G4s in promoters of Adrb1 and Adcy5 can be used as targets to inhibit downstream gene transcription and translation as expected. This may provide certain cardiac protective effects in the progress of HF. In the case of Adcy5, only the 3rd G4 acts as a strong repressor, while other G4s act as activators. Thus, the actual structure and function of G4s need to be investigated individually to guide the design of more specific G4-binding ligands with improved inhibition effects.
Bacterial growth in raw and pasteurised human milk.
Authors: S A Roberts, M Severn
Journal: BMJ (1978)

they were analysed separately.Although making a difference in the control group, in the iv heparin group giving sc heparin (eight patients) or not (13 patients) made no difference and therefore the results of these two groups were combined in the table.The results on drip life were analysed by the Student's t test, and the comparisons between rates of spontaneous stoppage and elective removal by x2 with Yates's correction.Both sc and iv heparin prolonged the life of a drip (see table ), there being significant differences between the control group and both the heparin groups, and also between the two heparin groups themselves.In the iv heparin group there was a significant increase in elective removals, with a parallel decrease in spontaneous stoppages as compared with control patients.
Transcutaneous oxygen recovery and toe pulse reappearance time in the assessment of peripheral vascular disease.
Authors: H B Kram, R A White, J Tabrisky, P L Appel, A W Fleming, W C Shoemaker
Journal: Circulation (1985)

The accuracy of measurements of transcutaneous oxygen tension (Ptco2) in the diagnosis of peripheral vascular disease (PVD) may be significantly increased by stressing limb circulation with the use of temporary ischemia. The purpose of this study was to compare the transcutaneous oxygen recovery half-time (TORT) and the toe pulse reappearance time (PRT/2) in a series of patients with symptomatic PVD before and after vascular reconstruction. The TORT was defined as the time required to recover half of the decrease in the limb/chest Ptco2 ratio caused by temporary limb ischemia, and is conceptually comparable to the toe PRT/2, the time required to recover half of the control toe pulse amplitude. Measurement of TORT was found to be more feasible (100% vs 58%) and to have a greater diagnostic yield (100% vs 92%) than that of the toe PRT/2. When measured on the dorsum of the foot, TORT values were found to correlate well with the severity of symptoms of PVD; toe PRT/2 values did not correlate with severity of symptoms. Patients who underwent successful vascular reconstruction had significant improvement in their calf and foot TORT values after surgery (p less than .005 and .0005, respectively); postoperative values were similar to those obtained in normal subjects. Toe PRT/2 values usually improved postoperatively, but in many patients postoperative values overlapped with values that were considered abnormal. There was no overlap of TORT values in normal subjects with those in patients with symptomatic PVD. The measurement of TORT may be clinically useful for screening patients with suspected PVD and for assessing quantitatively the results of conservative and surgical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
SOME FURTHER RESULTS IN TREATING EARS BY MASSAGE METHODS.
Authors: LOUIS J. LAUTENBACH
Journal: JAMA (1898)

During the past year I have persevered with my tympanic massage treatment, and the results but confirm those obtained in the past. The results, so far as the relief of deafness is concerned, continue favorable, the tinnitus, unless attended by severe aural vertigo, usually disappearing also. These results are nearly uniform and can be demonstrated readily. It is a method that if properly applied is painless and harmless, and one that seems borne out by common-sense reasoning. Diseased ear structures occasioning tinnitus and poor hearing are usually of the nature of closed or obstructed Eustachian tubes; diseased and thickened structures within the middle ear, such as anchyloses or hindered articulations, thickened, retracted and adherent membrane, or a nerve which either from disuse or pressure, or both, has become dormant. My massage machines, which are applied to the auditory meatus, occasion a suction action (or in a few cases a pressure