tbuckley/cabot-search huggingface dataset:
Identification of a CD4+ T cell-stimulating antigen of pathogenic bacteria by expression cloning.
Authors: S Sanderson, D J Campbell, N Shastri
Journal: The Journal of Experimental Medicine (1995)

Identifying the immunogenic proteins that elicit pathogen-specific T cell responses is key to rational vaccine design. While several approaches have succeeded in identifying major histocompatibility complex (MHC) class I bound peptides that stimulate CD8+ T cells, these approaches have been difficult to extend to peptides presented by MHC class II molecules that stimulate CD4+ T cells. We describe here a novel strategy for identifying CD4+ T cell-stimulating antigen genes. Using Listeria monocytogenes-specific, lacZ-inducible T cells as single-cell probes, we screened a Listeria monocytogenes genomic library as recombinant Escherichia coli that were fed to macrophages. The antigen gene was isolated from the E. coli clone that, when ingested by the macrophages, allowed generation of the appropriate peptide/MHC class II complex and T cell activation. We show that the antigenic peptide is derived from a previously unknown listeria gene product with characteristics of a membrane-bound protein.
Metformin suppresses high glucose–induced poly(adenosine diphosphate–ribose) polymerase overactivation in aortic endothelial cells
Authors: Meriem Mahrouf-Yorgov, Nicolas Marie, Didier Borderie, Raja Djelidi, Dominique Bonnefont-Rousselot, Alain Legrand, Jean-Louis Beaudeux, Jacqueline Peynet
Journal: Metabolism (2009)
Activation of the Cooh-Terminal Src Kinase (Csk) by Camp-Dependent Protein Kinase Inhibits Signaling through the T Cell Receptor
Authors: Torkel Vang, Knut Martin Torgersen, Vibeke Sundvold, Manju Saxena, Finn Olav Levy, Bjørn S. Skålhegg, Vidar Hansson, Tomas Mustelin, Kjetil Taskén
Journal: The Journal of Experimental Medicine (2001)

In T cells, cAMP-dependent protein kinase (PKA) type I colocalizes with the T cell receptor-CD3 complex (TCR/CD3) and inhibits T cell function via a previously unknown proximal target. Here we examine the mechanism for this PKA-mediated immunomodulation. cAMP treatment of Jurkat and normal T cells reduces Lck-mediated tyrosine phosphorylation of the TCR/CD3 zeta chain after T cell activation, and decreases Lck activity. Phosphorylation of residue Y505 in Lck by COOH-terminal Src kinase (Csk), which negatively regulates Lck, is essential for the inhibitory effect of cAMP on zeta chain phosphorylation. PKA phosphorylates Csk at S364 in vitro and in vivo leading to a two- to fourfold increase in Csk activity that is necessary for cAMP-mediated inhibition of TCR-induced interleukin 2 secretion. Both PKA type I and Csk are targeted to lipid rafts where proximal T cell activation occurs, and phosphorylation of raft-associated Lck by Csk is increased in cells treated with forskolin. We propose a mechanism whereby PKA through activation of Csk intersects signaling by Src kinases and inhibits T cell activation.
Improving the care for patients with acute severe respiratory disease
Authors: M W Elliott
Journal: Thorax (2003)

Services to improve the care of patients with acute severe medical conditions in general, and respiratory disease in particular, need to be improved. This includes access to a non-invasive ventilation service, available 24 hours per day, in all hospitals admitting patients with acute medical conditions.

In the early 1960s the first coronary care units (CCU) were established and are now a “given” in every hospital admitting patients with acute cardiac disease. For patients admitted to hospital with physiological disturbance due to non-acute cardiac medical conditions, the only options are usually either admission to an intensive care unit (ICU) or to a general medical ward. Inevitably, given the differences in staffing and facilities with one nurse looking after one patient with comprehensive physiological monitoring on the ICU compared with perhaps only two or three nurses looking after 30 patients at night with minimal continuous monitoring on a general medical ward, some patients will be admitted to the ICU who could be managed elsewhere. This is economically disadvantageous. Alternatively, patients may be looked after in an area in which proper care is not possible. This is an issue of standards of care and clinical governance. In the UK there are a number of drivers towards improving the acute care for medical patients including two recent reports—one from the Royal College of Physicians of London1 and the other from the NHS Modernisation Agency.2 Patients with respiratory failure constitute a significant proportion of medical admissions and the development of appropriate services for these patients is important from both the clinical governance and the economic perspectives. The provision of appropriate facilities for patients with acute severe respiratory disease is not just an issue in the UK.3

The report by the Royal College of Physicians (RCP) Working Party looked at the interface between …
A manometric assessment of oesophagogastrostomy.
Authors: D W Ward, H R Mathews
Journal: Thorax (1976)

Intraluminal pressures were recorded in 14 patients who had undergone oesophagogastrectomy. Seven of these had a mid-thoracic and seven a high cervical oesophagogastrostomy. The incidence of postoperative reflux complications in each group was noted. No pressure gradient across the anastomosis was detected in any patient but the upper oesophageal sphincter was shown to be retained as a functioning unit in all cases. It is considered that the thoracic anastomosis provides no demonstrable barrier to reflux. In addition, a high cervical oesophagogastrostomy does not adversely affect the upper oesophageal sphincter. The wider application of this latter procedure may be associated with a decreased incidence of postoperative reflux complications.
Mitofusin 2 Joins the Sarcoplasmic Reticulum and Mitochondria at the Hip to Sustain Cardiac Energetics
Authors: Klitos Konstantinidis, W. Jonathan Lederer, Rosario Rizzuto, Richard N. Kitsis
Journal: Circulation Research (2012)

T he divalent cation calcium (Ca 2ϩ ) is best known in cardiomyocytes for its role in excitation-contraction coupling, where it triggers myosin-actin cross-bridge formation.However, Ca 2ϩ regulates myriad fundamental processes in all cells.Among these are the activities of enzymes, channels, pumps, transcription, translation, motility, exocytosis, metabolism, growth, differentiation, and death. 1 Mitochondria are the primary venue for some of these processes, such as metabolism and cell death.This raises a question that appears seemingly straightforward but has proven to be complex and contentious: How does Ca 2ϩ get from its major storage depot, the sarcoplasmic reticulum (SR)/endoplasmic reticulum (ER), to mitochondria?In this issue of Circulation Research, Chen et al 2 address this issue in cardiomyocytes.
Use of electromyography to study leg muscle activity in patients with arthritis and in normal subjects during rising from a chair.
Authors: J S Munton, M I Ellis, V Wright
Journal: Annals of the Rheumatic Diseases (1984)

A previous study indicated the need for patients with arthritis to have an armchair from which it is easy to rise. To determine criteria for such a chair a greater understanding of the rising activity and the objective assessment of chair design is required. The major muscle groups of the leg were monitored by electromyography (EMG) in normal subjects and for patients with arthritis during rising from a chair. The effects on EMG patterns of changes of seat height, foot position, and the use of armrests were studied. This paper outlines the practical difficulties that must be borne in mind when designing an EMG study on arthritic and elderly subjects. The results did not illustrate any differences in the pattern of muscle activity between arthritic and normal subjects, nor did they show any differences caused by changing the variables of chair design.
Distinguishing myelodysplastic syndromes (MDS) from idiopathic cytopenia of undetermined significance (ICUS): HUMARA unravels clonality in a subgroup of patients
Authors: T. Schroeder, L. Ruf, A. Bernhardt, B. Hildebrandt, M. Aivado, C. Aul, N. Gattermann, R. Haas, U. Germing
Journal: Annals of Oncology (2010)
Enucleation of Six Ovarian Dermoids from One Woman, with Conservation of Ovaries
Authors: C. S. Russell
Journal: BMJ (1945)

MEDICAL JOURNEHhigh as a point two inches below the elbow-joint.The limb is elevated for several days in order to minimize tissue oedema.Active exercises are instituted for the fingers after 48 houLrs, togetherwith active exercises at the elbowand shoulder-joints.
Heme Oxygenase-1 Regulates Cardiac Mitochondrial Biogenesis via Nrf2-Mediated Transcriptional Control of Nuclear Respiratory Factor-1
Authors: Claude A. Piantadosi, Martha Sue Carraway, Abdelwahid Babiker, Hagir B. Suliman
Journal: Circulation Research (2008)

Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis program via induction of NF-E2–related factor (Nrf)2 gene expression and nuclear translocation. Nrf2 upregulates the mRNA, protein, and activity for HO-1 as well as mRNA and protein for nuclear respiratory factor (NRF)-1. Mechanistically, in cardiomyocytes, endogenous carbon monoxide (CO) generated by HO-1 overexpression stimulates superoxide dismutase-2 upregulation and mitochondrial H 2 O 2 production, which activates Akt/PKB. Akt deactivates glycogen synthase kinase-3β, which permits Nrf2 nuclear translocation and occupancy of 4 antioxidant response elements (AREs) in the NRF-1 promoter. The ensuing accumulation of nuclear NRF-1 protein leads to gene activation for mitochondrial biogenesis, which opposes apoptosis and necrosis caused by the cardio-toxic anthracycline chemotherapeutic agent, doxorubicin. In cardiac cells, Akt silencing exacerbates doxorubicin-induced apoptosis, and in vivo CO rescues wild-type but not Akt1 −/− mice from doxorubicin cardiomyopathy. These findings consign HO-1/CO signaling through Nrf2 and Akt to the myocardial transcriptional program for mitochondrial biogenesis, provide a rationale for targeted mitochondrial CO therapy, and connect cardiac mitochondrial volume expansion with the inducible network of xenobiotic and antioxidant cellular defenses.
Daytime oxygen delivery predicts its success during nocturnal supplementation in Cheyne-Stokes breathing
Authors: Mihaela Hubatsch
Journal: European Respiratory Journal (2014)

Objective  Based on our results indicating that certain increase in PaCO 2  value (3.31 mmHg) predicts nocturnal O 2  therapeutic efficacy in Cheyne-Stokes breathing (CSB), we looked for a method to determine therapy9s efficiency based on the changes of PaCO 2  level in patients who underwent daytime O 2  supply.   Design/subjects  Prospective intervention study of 16 consecutive patients with hypoxic respiratory failure identified from 55 patients with predominant CSB. The mean age was 73.5 yrs (SD=8.65), two were women.   Methods  Blood gases analyses were performed at admission, after 4 hours of daytime nasal O 2  administration at a range of 1 to 2 l/min to correct hypoxia and finally after overnight polysomnography (PSG) with O 2  supplementation.   Results  Therapy effectiveness is defined as the reduction of apnoea-hypopnea index (AHI) under 5/h. O 2  therapy proved to be effective in 56.25%. There was no statistically significant (p=0.72) increase in the overall PaCO 2  but significant mean difference of 2.22 mmHg was noted in the therapy efficient subgroup.   Conclusion  Certain increase in PaCO 2  level during a 4 hour daytime O 2  supplementation could predict nocturnal O 2  therapeutic efficacy.
Opening characteristics of three-cusp tissue heart valves
Authors: P. D. Swales, M. P. Holden, D. Dowson, M. I. Ionescu
Journal: Thorax (1973)

Since April 1969, frame-mounted three-cusp fascia lata and pericardial valves have been used in over 200 patients for heart valve replacement. Six autologous fascia lata valves have been removed from the mitral position because of regurgitation produced by shrinkage of one or two cusps. To elucidate the cause and mechanism of graft failure the opening characteristics of fascia lata and Silastic valves were studied in a steady state flow rig. In virtually all valves examined the cusps opened in sequence and the order in which the cusps of a particular valve opened was maintained irrespective of its position in the testing apparatus. Under the conditions prevailing in this experiment the sequential opening of the cusps seems to be inherent in the design of the valve. Inequalities in the size and shape of the cusps or in the physical properties of the material accentuated this phenomenon. Fully open valves were geometrically similar and the relationship between pressure gradient, flow rate, and valve diameter has the form: pd<sup>4</sup>=4,600 Q<sup>2</sup>. This formula will apply to all such valves tested in water, irrespective of material or size, provided that they are fully open. The experiment has shown that the pressure gradient across the valve increases rapidly as the diameter of the valve is reduced and that with reduction in valve diameter a decreased flow rate is required for complete valve opening. It is postulated that in patients with postoperative low cardiac output, large grafts in the mitral position may not open fully and consequently the cusp or cusps with little or no mobility may undergo structural changes leading to fibrosis with thickening or atrophy.
LPP Expression During In Vitro Smooth Muscle Differentiation and Stent-Induced Vascular Injury
Authors: I. Gorenne, L. Jin, T. Yoshida, J.M. Sanders, I.J. Sarembock, G.K. Owens, A.P. Somlyo, A.V. Somlyo
Journal: Circulation Research (2006)

Lipoma preferred partner (LPP) has been identified as a protein highly expressed in smooth muscle (SM) tissues. The aim of the present study was to determine mechanisms that regulate LPP expression in an in vitro model of SM cell (SMC) differentiation and in stent-induced pig coronary vessel injury. All trans-retinoic acid treatment of A404 cells induced a strong increase in LPP, as well as SM alpha-actin, SM myosin heavy chain, and smoothelin mRNA levels, in a Rho kinase (ROK)-dependent manner. Adenovirus mediated overexpression of myocardin in A404 cells significantly increased LPP mRNA expression. Interestingly, inactivation of RhoA with C3-exoenzyme or treatment with ROK inhibitors strongly inhibited myocardin mRNA expression in retinoic acid-treated A404 cells or human iliac vein SMCs. LPP silencing with short interfering RNA significantly decreased SMC migration. LPP expression was also markedly decreased in focal adhesion kinase (FAK)-null cells known to have impaired migration but rescued with inducible expression of FAK. LPP expression in FAK-null fibroblasts enhanced cell spreading. In stented pig coronary vessels, LPP was expressed in the neointima of cells lacking smoothelin and showed expression patterns identical to those of SM alpha-actin. In conclusion, LPP appears to be a myocardin-, RhoA/ROK-dependent SMC differentiation marker that plays a role in regulating SMC migration.
THE RELATIVE AFFINITY OF ANTIBODIES SYNTHESIZED IN THE SECONDARY RESPONSE
Authors: Lisa A. Steiner, Herman N. Eisen
Journal: The Journal of Experimental Medicine (1967)

In response to a second injection of rabbits with a dinitrophenylated antigen, given 2 months to 2 yr after the first injection, there was rapid synthesis of large amounts of antibody high in relative affinity for the dinitrophenyl (DNP) determinant. The antibodies formed 3 days after restimulation were already high in affinity. Amounts of antigen too small to elicit detectable antibody production may prime the animal for a partial secondary response characterized by the formation of antibody of intermediate affinity after a second antigenic stimulus. Investigations into the specificity requirements for the secondary response indicated that variation in the carrier protein and in the haptenic determinant could be tolerated. Thus, after immunization with DNP-bovine gamma-globulin, DNP-hemocyanin elicited the vigorous production of high affinity anti-DNP antibodies. However, DNP serum albumin was much less effective: it elicited a secondary response in some animals primed with DNP-bovine gamma-globulin only when the interval between injections was increased from 10 to 28 wk. A secondary response was also evoked when the haptenic determinent of the second immunogen differed slightly from that of the one injected initially (i.e., 2,4,6-trinitrophenyl versus 2,4-dinitrophenyl).
Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma
Authors: Graziella Filippini, Chiara Falcone, Amerigo Boiardi, Giovanni Broggi, Maria G. Bruzzone, Dario Caldiroli, Rita Farina, Mariangela Farinotti, Laura Fariselli, Gaetano Finocchiaro, Sergio Giombini, Bianca Pollo, Mario Savoiardo, Carlo L. Solero, Maria G. Valsecchi
Journal: Neuro-Oncology (2007)

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient's age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence.
Locoregional Radiation Therapy in Patients With High-Risk Breast Cancer Receiving Adjuvant Chemotherapy: 20-Year Results of the British Columbia Randomized Trial
Authors: J. Ragaz, I. A. Olivotto, J. J. Spinelli, N. Phillips, S. M. Jackson, Kenneth. S. Wilson, M. A. Knowling, C. M. L. Coppin, L. Weir, K. Gelmon, N. Le, R. Durand, A. J. Coldman, M. Manji
Journal: JNCI Journal of the National Cancer Institute (2005)

The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up.Survival was analyzed by the Kaplan-Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided.At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk [RR] = 0.36, 95% confidence interval [CI] = 0.18 to 0.71; P = .002), systemic relapse-free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms.For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.
DOES WHOLE-BODY CRYOTHERAPY AFFECT THE RECOVERY PROCESS AFTER HAMSTRING DAMAGING EXERCISE: A CROSSOVER STUDY
Authors: G Markovic, B Fonda, Š Nejc
Journal: British Journal of Sports Medicine (2014)

Background Delayed onset muscle soreness, induced by strenuous exercise, is one of the most common recurrent forms of sports injury and is associated with exercise-induced muscle damage (EIMD). Objective We examined the effects of whole-body cryotherapy (WBC) on biochemical markers, pain, and performance parameters during a 5-day recovery period after a damaging plyometric exercise. We hypothesized that WBC would have beneficial effects on muscle recovery after such an exercise bout. Design Randomized crossover study design. Setting Recreational athletes. Participants 11 recreational male athletes volunteered in this study. Inclusion criteria were that the subjects were familiar with plyometric exercise, but they did not perform this type of exercise for at least 3 months prior to the study, were not injured or receiving any medications in the last 9 months, and were within normal baseline levels for biochemical markers. Interventions Participants completed a bout of damaging exercise for the hamstring muscles on two separate occasions separated by 10 weeks. During the control condition, subjects received no treatment after the damaging exercise. The experimental condition consisted of WBC everyday during the recovery period. WBC included single 3-min daily exposures to low temperatures (–140 to –195 °C) in the cryo-cabin. Main outcome measurements Biochemical markers, perceived pain sensation, squat- and counter movement-jump, maximal and explosive isometric torque production. Results Majority of the observed variables showed statistically significant time effects (P&lt;.05) in control group, which indicates the presence of muscle damage. Significant interaction between the control and WBC condition was evident for the rate of torque development (P&lt;.05). Pain measures substantially differed between the WBC and the control condition after the exercise. Conclusions The results of the present study do not provide conclusive support for the use of WBC as a technique to enhance functional recovery after EIMD.