tbuckley/cabot-search huggingface dataset:
Isotype-specific Selection of High Affinity Memory B Cells in Nasal-associated Lymphoid Tissue
Authors: Michiko Shimoda, Toru Nakamura, Yoshimasa Takahashi, Hideki Asanuma, Shin-ichi Tamura, Takeshi Kurata, Tsuguo Mizuochi, Norihiro Azuma, Choemon Kanno, Toshitada Takemori
Journal: The Journal of Experimental Medicine (2001)

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Cα. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken γ globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG+ B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cγ, operated efficiently in NALT. Both IgG+ and IgA+ GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the VH gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.
Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival.
Authors: L Qin, K D Chavin, J Lin, H Yagita, J S Bromberg
Journal: The Journal of Experimental Medicine (1994)

Indefinite graft survival was obtained with murine cardiac allografts using the combined administration of monoclonal antibodies (mAbs) directed against the receptor ligand pair CD2-CD48. Although each antibody could prolong graft survival when given alone, neither resulted in the indefinite graft survival seen with the combination. Combined mAb administration is associated with inhibition of T cell priming and help and subsequent cytotoxic T lymphocyte generation. This indicates that the interaction between CD2 and its ligand is important for antigen priming and recognition, and combined mAbs may prove to be a useful therapeutic regimen for transplantation.
Antigen-reactive T cells can be activated buy autologous macrophages in the absence of added antigen.
Authors: P B Hausman, D P Stites, J D Stobo
Journal: The Journal of Experimental Medicine (1981)

T cells responsive to macrophages (M phi) in the autologous mixed lymphocyte reaction (AMLR) contain those cells that can be induced to proliferate by soluble antigens. Negative solution (5-bromo-2-deoxyuridine and light) of T cells activated by autologous M phi also removed those cells required for reactivity to Candida albicans and purified protein derivative. Positive selection of T cells responsive to autologous M phi yields a population that is simultaneously enriched in antigen reactivity. Some patients demonstrating cutaneous anergy and diminished in vitro blast transformation in response to soluble antigen also lack T cells responsive to the AMLR to M phi. When considered in conjunction with previously reported data, these findings indicate the AMLR occurring between T cells and M phi in the absence of soluble antigen represents self recognition occurring between antigen-reactive T cells and antigen-presenting M phi.
Left ventricular energetics. Heat loss and temperature distribution of canine myocardium.
Authors: G H ten Velden, G Elzinga, N Westerhof
Journal: Circulation Research (1982)

The sum of total left ventricular heat loss and left ventricular mean total external power was compared with the product of oxygen consumption and its energy equivalent. Myocardial blood flow, measured with 15 +/- 3 micrometers radioactive microspheres, was multiplied by the transcoronary arteriovenous temperature difference and by oxygen content difference to obtain coronary heat loss and oxygen consumption, respectively. Since only part of the heat is carried away by the coronary system a thermodilution technique was used to obtain the ratio between the heat removed by the coronary system and the external heat loss. A correction was made for the endothermic reactions of hemoglobin deoxygenation and carbon dioxide reactions with blood. Left ventricular oxygen consumption corresponded to 2.26 +/- 0.66 W/100 g, and for the sum of total left, ventricular heat loss and external power, 2.09 +/- 0.51 W/100 g was found (n = 14). In a second series, the measured transmyocardial temperature distribution was compared with the calculated temperature distribution, assuming that heat production in the myocardium is uniform and that heat is lost by coronary flow and diffusion. When thoracic and luminal myocardial surface temperatures were about equal, blood flow was found to be about the same in the various layers of the heart, whereas myocardial temperature was found to be highest near the middle of the wall (0.36 +/ 0.07 degrees C warmer than luminal temperature (n = 6). When thoracic surface temperature was increased or decreased (by + 1.56 +/- 0.99 degrees and -1.10 +/- 0.59 degrees C, respectively), consistent changes were seen for the temperature distribution in the myocardium, but not for the local flow (endo/epi ratio: 1.06 +/- 0.29 and 0.96 +/- 0.21, respectively). These data suggest that myocardial blood flow is independent of tissue temperature.
Challenge of Balancing Alcohol Intake
Authors: Michelle D. Holmes
Journal: Journal of Clinical Oncology (2010)

tweenalcoholandmortalityinanobservationalstudyofnearly86,000 women without major disease at the study’s outset. In that study, alcohol intake had a U-shaped association with mortality. The risk of dying as a result of any cause was decreased for women who were moderate drinkers, compared with nondrinkers; the RR for alcohol consumption of 5.0 to 14.9 g/d (0.5 to 1.5 drinks per day) was 0.88 (95% CI, 0.79 to 0.99), and was similar for 15.0 to 29.9 g/d (1.5 to 2 drinksperday),withanRRof0.89(95%CI,0.77to1.02),whereasthe risk of dying as a result of any cause was slightly increased for those drinking 30 g/d (2 drinks per day), with an RR of 1.19 (95% CI, 1.02 to 1.38). Analyzing the data for specific causes of death revealed that,comparedwithnondrinkers,theriskofdyingfrombreastcancer increased over the alcohol-intake ranges of 5.0 to 14.9 g/d (RR, 0.96; CI,0.71to1.32),15.0to29.9g/d(RR,1.37;CI,0.96to1.96),and30 g/d(RR,1.67;CI,1.10to2.53).However,theriskofdyingasaresultof cardiovascular disease was decreased over the entire range: the RRs were0.73(95%CI,0.56to0.95),0.66(95%CI,0.47to0.93),and0.74 (95% CI, 0.51 to 1.08) for the same categories, respectively. 18 In this study of initially healthy women, the U-shaped relationship between total mortality and alcohol intake in this range represents the balance betweentwocompetingforces:moderatealcoholintakeincreasingthe risk of dying as a result of breast cancer, while decreasing the risk of dyingasaresultofcardiovasculardisease.Optimaloverallsurvivalwas observedwiththeintakeof5.0to14.9g/d,or0.5to1.5drinksperday. With early detection and modern treatments, prognoses for US women with early-stage breast cancer are excellent. Overall, 89% will live more than 5 years after their breast cancer diagnosis, including
Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events
Authors: Arthur J. Moss, W. Jackson Hall, David S. Cannom, Helmut Klein, Mary W. Brown, James P. Daubert, N.A. Mark Estes, Elyse Foster, Henry Greenberg, Steven L. Higgins, Marc A. Pfeffer, Scott D. Solomon, David Wilber, Wojciech Zareba
Journal: New England Journal of Medicine (2009)

This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex.During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments.During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups.CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.)
Ultrasound evaluation of focal neuropathies in athletes: a clinically-focused review
Authors: Evan Peck, Jeffrey A Strakowski
Journal: British Journal of Sports Medicine (2015)

Focal neuropathies represent a rare but clinically important and potentially challenging aetiology of pain in athletes. Diagnostic ultrasound is commonly used in the evaluation of nerve entrapments, and has several advantages over other imaging modalities, including high resolution, portability, lack of ionising radiation, low cost, point-of-care access, ease of contralateral comparison and capability of Doppler and dynamic imaging techniques. In this review, we discuss the use of ultrasound for the evaluation of injuries to the brachial plexus including ‘stingers,’ suprascapular nerve, ulnar nerve, radial nerve, common fibular nerve, tibial nerve and interdigital nerves of the foot at selected common sites of entrapment.
Traumatic aorta to pulmonary artery fistula
Authors: R. Zajtchuk, L. Resnekov, K. Ranniger, L. Gonzalez-Lavin
Journal: Thorax (1971)

A case of chronic aortic to pulmonary artery traumatic fistula is presented and the surgical repair is detailed. Closure through the aorta is recommended; this approach provides a dry operative field and avoids the need for dissection of adhesions around the fistulous tract. Fistulae of this type are not common and the pertinent literature is reviewed.
Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial
Authors: Umberto Veronesi, Roberto Orecchia, Patrick Maisonneuve, Giuseppe Viale, Nicole Rotmensz, Claudia Sangalli, Alberto Luini, Paolo Veronesi, Viviana Galimberti, Stefano Zurrida, Maria Cristina Leonardi, Roberta Lazzari, Federica Cattani, Oreste Gentilini, Mattia Intra, Pietro Caldarella, Bettina Ballardini
Journal: The Lancet Oncology (2013)
Neutrophil extracellular traps in bronchial aspirates: a quantitative analysis
Authors: Shigeto Hamaguchi, Tomoya Hirose, Naoya Matsumoto, Yukihiro Akeda, Taro Irisawa, Masafumi Seki, Hideo Hosotsubo, Kouji Yamamoto, Osamu Tasaki, Kazunori Oishi, Takeshi Shimazu, Kazunori Tomono
Journal: European Respiratory Journal (2014)

Neutrophil extracellular traps (NETs) are structures composed of DNA and granular proteins, which rapidly trap and kill pathogens. The formation of NETs has been detected during infection in animal experiments, but their role in humans is unclear. The purposes of this study were to quantitatively evaluate the production of NETs during acute respiratory infection and to study the relationship between the NET length and various inflammatory mediators. We examined bronchial aspirates collected from nine intubated patients in an intensive care unit. Samples were collected at the onset of acute respiratory infection (day 0) and on days 1, 3–5, and 6–8. The NET length was visualised by immunohistochemistry and quantified using computer tracing software. The NET length was measured and compared at each time point. The length differed significantly between time points (p&lt;0.001). NETs were significantly longer on day 1 than on day 0 (p&lt;0.001). Neutrophils released NETs abundantly in response to respiratory infection and regression analysis showed that NET length correlated with six clinical parameters (white blood cells, platelets, lactate, CXC ligand-2, interleukin-8, and procalcitonin) as the explanatory variables. NETs in bronchial aspirates may reflect disease progression of respiratory infections. Quantification of NETs in bronchial aspirates may provide a new indicator of inflammation.
What else is driving ritualized behavior, besides the “Hazard-Precaution system”? Developmental, psychopathological, and ethnological considerations
Authors: Oana Benga, Ileana Benga
Journal: Behavioral and Brain Sciences (2006)

The target article presents arguments for a motivational system dedicated exclusively to the detection of, and reaction to, particular threats to fitness, the so-called “Hazard-Precaution System,” which, according to the authors, drives ritualized behavior. We approach the issue of a motivational system from three perspectives – developmental, psychopathological, and ethnological.
Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial
Authors: Peter Daley, Vijayakumar Jagannathan, K R John, Joy Sarojini, Asha Latha, Reinhold Vieth, Shirly Suzana, Lakshmanan Jeyaseelan, Devasahayam J Christopher, Marek Smieja, Dilip Mathai
Journal: The Lancet Infectious Diseases (2015)
‘Sedentary behaviour counselling’: the next step in lifestyle counselling in primary care; pilot findings from the Rapid Assessment Disuse Index (RADI) study
Authors: Kerem Shuval, Loretta DiPietro, Celette Sugg Skinner, Carolyn E Barlow, Jay Morrow, Robert Goldsteen, Harold W Kohl
Journal: British Journal of Sports Medicine (2012)

Background Accumulating evidence emphasises a relationship between prolonged sitting and increased risk for cardiometabolic disorders and premature death irrespective of the protective effects of physical activity. Primary care physicians have the potential to play a key role in modifying patients’ sedentary behaviour alongside physical activity. Methods A pilot study examining sedentary behaviour and physical activity counselling in a primary care clinic. A total of 157 patients completed a detailed survey related to lifestyle counselling received from their primary care physician. We analysed these responses to describe counselling practices within the 5A framework, and to examine correlates (ie, patients’ demographics, sedentary behaviour and physical activity and clinical variables) related to receiving counselling. Results A total of 10% received general advice to decrease sitting time, in comparison with 53% receiving general physical activity counselling. None, however, received a written plan pertaining to sedentary behaviour whereas 14% received a written physical activity prescription. Only 2% were provided with specific strategies for sedentary behaviour change in comparison with 10% for physical activity change. Multivariable analysis revealed that patients who were obese were more likely to receive counselling to decrease sitting (OR=7.0; 95% CI 1.4 to 35.2). In comparison, higher odds for receiving physical activity counselling were associated with being younger, aged 40–59 years (OR=2.4; 95% CI 1.1 to 5.4); and being a non-smoker (OR=6.1; 95% CI 1.3 to 28.4). Conclusions This study is the first to assess sedentary behaviour counselling practices in primary care and such practices appear to be infrequent. Future research should attempt to establish a ‘knowledge base’ to inform development of sedentary behaviour interventions, which should be followed by testing feasibility, efficacy, and subsequent effectiveness of these programmes in a clinical setting.
Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection
Authors: Afam Okoye, Martin Meier-Schellersheim, Jason M. Brenchley, Shoko I. Hagen, Joshua M. Walker, Mukta Rohankhedkar, Richard Lum, John B. Edgar, Shannon L. Planer, Alfred Legasse, Andrew W. Sylwester, Michael Piatak, Jeffrey D. Lifson, Vernon C. Maino, Donald L. Sodora, Daniel C. Douek, Michael K. Axthelm, Zvi Grossman, Louis J. Picker
Journal: The Journal of Experimental Medicine (2007)

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4+ CCR5+ effector–memory T (TEM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4+ memory T cell proliferation appears to prevent collapse of effector site CD4+ TEM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4+ TEM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4+ TEM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4+ TEM cells from central–memory T (TCM) cell precursors. The instability of effector site CD4+ TEM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5− CD4+ TCM cells. These data suggest that although CD4+ TEM cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4+ TCM cells.
Treatment of Childhood Acute Lymphoblastic Leukemia: Results of Dana-Farber ALL Consortium Protocol 87-01
Authors: Jean Marie LeClerc, Amy L. Billett, Richard D. Gelber, Virginia Dalton, Nancy Tarbell, Jeffrey M. Lipton, Ronald Barr, Luis A. Clavell, Barbara Asselin, Craig Hurwitz, Marshall Schorin, Steven E. Lipshultz, Lieven Declerck, Lewis B. Silverman, Harvey J. Cohen, Stephen E. Sallan
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To improve efficacy and reduce toxic- ity of treatment for children with acute lymphoblas- tic leukemia. PATIENTS AND METHODS: Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated). RESULTS: At a median follow-up of 9.2 years, the 9-year event-free survival (EFS ± SE) was 75% ± 2% for all 369 patients, 77% ± 4% for the 142 SR patients, and 73% ± 3% for the 227 HR/VHR patients (P = .37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% ± 2% for the entire population, 93% ± 2% for SR children, and 79% ± 3% for HR and VHR children (P < .01 comparing SR and HR/VHR). CONCLUSION: A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem.
The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria
Authors: Babs O. Fabriek, Robin van Bruggen, Dong Mei Deng, Antoon J. M. Ligtenberg, Kamran Nazmi, Karin Schornagel, Rianka P. M. Vloet, Christine D. Dijkstra, Timo K. van den Berg
Journal: Blood (2008)
Skin-infiltrating neutrophils following exposure to solar-simulated radiation could play an important role in photoageing of human skin
Authors: F. Rijken, R.C.M. Kiekens, P.L.B. Bruijnzeel
Journal: British Journal of Dermatology (2005)

The pathophysiology of photoageing of the skin has been studied extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and fibroblasts are thought to play a primary role in this process. Although neutrophils are potent producers of a wide array of proteolytic substances and are present in sunburned skin, their contribution to the pathophysiology of photoageing has been described only in murine studies.To determine the role of neutrophils in photoageing of human skin.Healthy white-skinned volunteers were recruited and their sun-protected buttock skin was exposed to solar-simulated radiation (SSR) in dose-response and time-course studies. Punch biopsies were taken and the influx of neutrophils and the expression of neutrophil elastase and MMPs was studied using immunohistochemical techniques and in situ zymography.Neutrophil elastase and MMPs were detected only in skin irradiated with erythemogenic doses (> or = 1 minimal erythema doses) of SSR. Immunohistochemical double staining demonstrated neutrophils to be the major source of MMP-1, MMP-8 and MMP-9. In situ zymography showed elastase, collagenase and gelatinase enzyme activity in those cells.Our study suggests that neutrophils participate in the process of photoageing of human skin as they infiltrate the skin and release enzymatically active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP-9).
Meniscotibial ligament strains: a prospective survey.
Authors: A P Millar
Journal: British Journal of Sports Medicine (1991)

Medial knee pain is an increasingly common presentation in sports medicine practice. A prospective review was undertaken of 72 patients, mean age 48 years, seen in 1986-1987. The physical findings which were most diagnostic were a loss of some degrees of flexion which was painful medially when forced, and tenderness over the posteromedial joint line. Treatment was either injection of local steroid, or physiotherapy, together with emphasis on quadriceps exercise. Five patients failed to respond and were referred for arthroscopy. Nine patients relapsed once but no subsequent episode has occurred. Meniscotibial ligament strain is a common cause of knee pain in middle-aged sports people.