tbuckley/cabot-search huggingface dataset:
Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans
Authors: C.E.M. Griffiths, M. Cumberbatch, S.C. Tucker, R.J. Dearman, S. Andrew, D.R. Headon, I. Kimber
Journal: British Journal of Dermatology (2001)

Background Lactoferrin (LF), an iron-binding protein found in exocrine secretions, is known to possess antibacterial properties. It has recently been proposed that LF may also influence inflammatory reactions. Objectives To characterize in humans the ability of recombinant homologous LF to inhibit the induced migration of epidermal Langerhans cells (LCs) from the skin, a process known to be dependent upon the proinflammatory cytokines tumour necrosis factor (TNF)-α and interleukin 1β and to influence cutaneous inflammatory reactions. Methods We investigated the anti-inflammatory properties of LF in human volunteers. Results Topical exposure to LF 2 h prior to sensitization caused a significant reduction in contact allergen (diphenylcyclopropenone, DPC)-induced LC migration from the epidermis as judged by the altered frequency of cells expressing either HLA-DR or CD1a determinants. That this reduction was secondary to an inhibition of TNF-α production was indicated by the fact that LF failed to influence LC migration induced by intradermal injection of this cytokine. In approximately 50% of those volunteers who displayed local inflammation in response to DPC, LF was found to cause a discernible reduction in the clinical severity of the reaction, associated with reduced infiltration of inflammatory cells. Conclusions These data demonstrate that LF is able to influence cutaneous immune and inflammatory responses, possibly because of an impaired production of local proinflammatory cytokines.
Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.
Authors: Y Shimizu, G A van Seventer, E Ennis, W Newman, K J Horgan, S Shaw
Journal: The Journal of Experimental Medicine (1992)

Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression.
Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome–positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study
Authors: Adrienne de Labarthe, Philippe Rousselot, Françoise Huguet-Rigal, Eric Delabesse, Francis Witz, Sébastien Maury, Delphine Réa, Jean-Michel Cayuela, Marie-Christine Vekemans, Oumedaly Reman, Agnès Buzyn, Arnaud Pigneux, Martine Escoffre, Yves Chalandon, Elizabeth MacIntyre, Véronique Lhéritier, Jean-Paul Vernant, Xavier Thomas, Norbert Ifrah, Hervé Dombret
Journal: Blood (2006)
Estimation of gene frequency and test for Hardy-Weinberg equilibrium in the HLA system.
Authors: M Matsuura, S Eguchi
Journal: Environmental Health Perspectives (1990)

This paper concerns the testing for Hardy-Weinberg equilibrium and the estimation of gene frequency in the human leukocyte antigens (HLA) system. An extensive simulation study for both testing and estimation is given for investigating the performance of the projection method by Eguchi and Matsuura, which has a closed form, and the method is asymptotically equivalent to the maximum likelihood method. We compare our projection test statistic with the likelihood ratio test and the single degree of freedom chi-square test suggested by Nam and Gart. Actual mean square errors of the projection estimator of gene frequency under the Hardy-Weinberg equilibrium are compared with the maximum likelihood estimator and some other estimators recently discussed by Nam.
Continuing Education and Patient Care Research
Authors: John W. Williamson
Journal: JAMA (1967)

The feasibility of developing continuing education programs based on patient care research has been explored through a study of physician response to apparently unexpected abnormalities in three routine screening tests (urinalysis, fasting blood glucose, and hemoglobin). Initial assessment revealed no apparent response of any kind to approximately two thirds of these test abnormalities. A specially designed workshop conference, a full complement of interns, and repeated newsletter reminders failed to improve the quality or quantity of responses. Obscuring abnormal data on the laboratory slip with removable fluorescent tape resulted in significant improvement, more than half of which was maintained six months after use of the tape was discontinued. This study illustrates the complementary relationship between patient care research and continuing education that can be profitably integrated in programs to improve medical care.
Complication after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of rectal lesion
Authors: G. Mezzi, P. Arcidiacono, S. Carrara, M. Freschi, C. Boemo, P. Testoni
Journal: Endoscopy (2007)

A 50-year-old woman was referred to undergo an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of a lesion in the posterior region of the rectum. Informed consent was obtained. EUS, performed with a linear probe (3830UT, Pentax, Hamburg), confirmed a hypoechoic lesion with well-defined margins at 10 cm from the anal sphincter, between the posterior region of the rectum and sacrum (33 mm). Prophylactic antibiotics were administered (ampicillin 2 g; gentamicin 80 mg intravenously [IV]). Conscious sedation was initiated with midazolam, 2 mg IV. EUS-FNA used a 25 G ultrasound needle (Wilson-Cook Medical Inc., USA) ([Figure 1]). No complications were encountered. Cytological examination of the lesion revealed amorphous granular material, numerous squamous cells without atypical features, rare stromal cells, and few normal glandular aggregates; no malignant cells were found ([Figure 2]). Five days following the procedure, the patient complained of pain in the posterior region of the rectum, and experienced fever and spontaneous cutaneous drainage. EUS showed the lesion to be hypoechoic, with anechoic areas and undefined margins, compatible with pelvic abscess or hematic extravasation after EUS-FNA. The patient was hospitalized and underwent clinical revalutation. Magnetic resonance imaging revealed features in the presacral-coccyx region consistent with an abscess surrounded by granular tissue. The patient was discharged in good clinical condition 10 days later.
Incremental Prognostic Significance of Peripheral Endothelial Dysfunction in Patients With Heart Failure With Normal Left Ventricular Ejection Fraction
Authors: Eiichi Akiyama, Seigo Sugiyama, Yasushi Matsuzawa, Masaaki Konishi, Hiroyuki Suzuki, Toshimitsu Nozaki, Keisuke Ohba, Junichi Matsubara, Hirofumi Maeda, Yoko Horibata, Kenji Sakamoto, Koichi Sugamura, Megumi Yamamuro, Hitoshi Sumida, Koichi Kaikita, Satomi Iwashita, Kunihiko Matsui, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2012)
Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation. The role of N-methyl-D-aspartate receptors.
Authors: G W Bong, S Rosengren, G S Firestein
Journal: Journal of Clinical Investigation (1996)

The effect of spinal adenosine receptor ligation on peripheral leukocyte accumulation was studied in two rat models of inflammation. Neutrophil infiltration into dermal inflammatory sites was signficantly reduced by adenosine A1 receptor agonists injected through intrathecal catheters. These effects were reversed by N-methyl-D-aspartate (NMDA), and were mimicked by (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), a glutamate NMDA receptor antagonist. Peripheral adenosine levels, as measured in air pouch exudates, decreased markedly in inflamed pouches but remained near normal after intrathecal treatment with AP-5. Moreover, the antiinflammatory effects of intrathecal A1 receptor agonists and AP-5 were reversed by an adenosine A2 receptor antagonist administered intraperitoneally. Hence, central NMDA receptor activity can regulate neutrophil accumulation in peripheral inflammatory sites by reducing local levels of adenosine, an antiinflammatory autacoid which inhibits neutrophil function through A2 receptor activation. This represents a previously unknown pathway by which the central nervous system influences inflammatory responses.
Tacrolimus dual therapy versus cyclosporin-microemulsion triple therapy in paediatric liver transplant recipients: results of a 12-month comparative study
Authors: Burkhard Rodeck, D. Kelly, P. Jara, R. Reding, O. Bernard, M. Burdelski, M. Becker, B. Gridelli, O. Boillot, J. Manzanares
Journal: Journal of Hepatology (2002)
Abstract 2274: Docosahexaenoic acid-induced cell death may be related to inhibition of mTOR through AMPK activation and PI3K/Akt inhibition in human non-small cell lung cancer cells
Authors: Kyu Lim, Nayeong Kim, Kaipeng Jing, Soyeon Jeong, Soyeon Shin, Hyerim Oh, Eun-Ah Jo, Jun-Young Heo, Ji-Hoon Park, Kang-Sik Seo, Kyoung-Sub Song, Jeongsu Han, Jong-Il Park, Seung-Kiel Park, Gi-Ryang Kweon, Wan-Hee Yoon, Byung-Doo Hwang
Journal: Cancer Research (2012)

Abstract Over 80% of the lung cancer patients have non-small cell lung cancer (NSCLC). Although the anticancer mechanisms of omega-3 polyunsaturated fatty acids (≥3-PUFAs) have been reported in several cancers, it is still unclear in lung cancer. In this study, we have identified a novel anticancer effect of docosahexaenoic acid (DHA), a α3-PUFAs, on NSCLC. DHA induced cytotoxicity and morphology change in A549 and H1299 NSCLC cells and was confirmed that apoptosis and autophagy are responsible for the cytotoxicity induced by DHA. DHA increased AMPK activity and inhibited PI3K/Akt signaling as well as mTOR signaling molecules. Knockdown AMPK using small interfering RNAs specific for AMPK and overexpression Akt significantly enhanced the mTOR activity and attenuated the cell death caused by DHA treatment, indicating that DHA induces NSCLC cell death via the AMPK- and Akt-regulated mTOR inactivation. We also confirmed this effect of α3-PUFAs in vivo using Fat-1 transgenic mice that are capable of producing α3-PUFAs. When mouse lung cancer LLC cells were subcutaneously implanted into Fat-1 mice, the growth of tumor was markedly inhibited with decrease the level of p-Akt as well as increases in TUNEL-positive staining cells and autophagic levels, compared to wild-type mice. Taken together, these data suggest that the apoptosis and autophagy induced by DHA may be related to mTOR inhibition through AMPK activation and PI3K/Akt inhibition in NSCLC. Therefore, utilization of DHA may represent a potential effective therapy for the chemoprevention and treatment of human non-small cell lung cancer. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (2011-0013263 and 2011-0006232)] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2274. doi:1538-7445.AM2012-2274
Association of Occult Metastases in Sentinel Lymph Nodes and Bone Marrow With Survival Among Women With Early-Stage Invasive Breast Cancer
Authors: Armando E. Giuliano, Debra Hawes, Karla V. Ballman, Pat W. Whitworth, Peter W. Blumencranz, Douglas S. Reintgen, Monica Morrow, A. Marilyn Leitch, Kelly K. Hunt, Linda M. McCall, Andrea Abati, Richard Cote
Journal: JAMA (2011)

Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination.To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer.From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study.All 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results.Overall survival (primary end point) and disease-free survival (a secondary end point).Of 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P = .64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P = .64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P = .04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P = .70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P = .15) was statistically significant on multivariable analysis.Among women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival.clinicaltrials.gov Identifier: NCT00003854.
A largely random AAV integration profile after LPLD gene therapy
Authors: Christine Kaeppel, Stuart G Beattie, Raffaele Fronza, Richard van Logtenstein, Florence Salmon, Sabine Schmidt, Stephan Wolf, Ali Nowrouzi, Hanno Glimm, Christof von Kalle, Harald Petry, Daniel Gaudet, Manfred Schmidt
Journal: Nature Medicine (2013)
The Autopsy: Its Decline and a Suggestion for Its Revival
Authors: William C. Roberts
Journal: New England Journal of Medicine (1978)

The hospital autopsy rate in the United States dropped from 41 per cent in 1964 to 22 per cent in 1975. This reduction is attributable to a declining interest for many reasons by clinicians, surgeons, pathologists, families of the deceased and hospital administrators and hospital accreditors. Various advances in medicine and surgery in recent years have not replaced the value of the autopsy; indeed they have increased the potential information to be gained from it. For interest in autopsies to be revived among physicians and surgeons, pathologists must provide more expert information from the autopsy. To provide the type of information sought from autopsies by physicians and surgeons, the training of pathologists must be altered so that there can be more specialization in anatomic pathology and more subspecialization in the various organ systems, as in internal medicine. In addition, the means of communication between anatomic pathologists and clinicians needs altering so that important clinical questions are recognized by pathologists, and the answers sought and promptly, understandably and diplomatically communicated to physicians and surgeons. Moreover, the large body of information obtained in recent years from autopsies alone needs to be better recognized by clinicians so that they may better understand the value of these examinations.
Cytokine production in patients with inflammatory bowel disease.
Authors: M Nakamura, H Saito, J Kasanuki, Y Tamura, S Yoshida
Journal: Gut (1992)

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn9s disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn9s disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn9s disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn9s disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn9s disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn9s disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn9s disease, or both.
Fetal bile salt metabolism. The intestinal absorption of bile salt.
Authors: R Lester, R A Smallwood, J M Little, A S Brown, G J Piasecki, B T Jackson
Journal: Journal of Clinical Investigation (1977)

The intestinal absorption of sodium taurocholate was studied in the near-term fetal and neonatal dog. Absorption rates were measured in vivo in isolated loops of fetal jejunum and ileum. Absorption was also measured in vitro in everted sacs and rings of fetal and neonatal jejunum and ileum. The maximal rates of taurocholate absorption observed after instillation of 1 micronmol taurocholate into closed segments of fetal jejunum and ileum with intact blood supply were not significantly different (P less than 0.2), and equalled 0.282+/-0.026 (mean+/-SEM) and 0.347+/-0.051 micronmol/h per 10-cm segment length jejunum and ileum, respectively. Similarly, the rates of absorption from open segments of jejunum and ileum perfused with 0.4 and 1.0 mM taurocholate were nearly identical (0.232+/-0.040 and 0.255+/-0.039, respectively at 0.4 mM, and 0.470+/-0.065 and 0.431+/-0.013, respectively at 1.0 mm) (P greater than 0.2). At perfusate concentrations of 4.0 mM, moreoever, jejunal absorption exceeded ileal absorption (1.490+/-0.140 and 0.922+/-0.200, respectively (P less than 0.05). As expected, concentration of taurocholate by the mucosa was readily demonstrated in adult ileal, but not in adult jejunal everted rings. In contrast, there were no significant differences in mucosal uptake of taurocholate by fetal jejunal and ileal rings. Fetal ileal mucosal concentrations were not significantly above those in the incubation medium after 1-h exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. Uptake was proportional to incubation medium concentration over the full range of values. This was also true of tissues from 1-wk-old neonates. However, by 2 wk of age, ileal mucosal concentration of taurocholate was evident and adult levels were attained by 5 wk of age. It is concluded that taurocholate is absorbed by the fetal gut and that ileal absorption is no more efficient than jejunal absorption. Although active glucose transport was demonstrable in both jejunum and ileum, it was not possible to demonstrate an ileal mechanism for active transport of taurocholate in the fetus. Active ileal transport was not demonstrable in the newborn until at least 2 wk after birth.
Incidence and Risk Factors for Gout in White Men
Authors: Ronenn Roubenoff
Journal: JAMA (1991)

To identify potentially modifiable risk factors for the development of gout.Longitudinal cohort study (The Johns Hopkins Precursors Study).Of 1337 eligible medical students, 1271 (95%) received a standardized medical examination and questionnaire during medical school. The participants were predominantly male (91%), white (97%), and young (median age, 22 years) at cohort entry.The development of gout.Sixty cases of gout (47 primary and 13 secondary) were identified among 1216 men; none occurred among 121 women (P = .01). The cumulative incidence of all gout was 8.6% among men (95% confidence interval, 5.9% to 11.3%). Body mass index at age 35 years (P = .01), excessive weight gain (greater than 1.88 kg/m2) between cohort entry and age 35 years (P = .007), and development of hypertension (P = .004) were significant risk factors for all gout in univariate analysis. Multivariate Cox proportional hazards models confirmed the association of body mass index at age 35 years (relative risk [RR] = 1.12; P = .02), excessive weight gain (RR = 2.07; P = .02), and hypertension (RR = 3.26; P = .002) as risk factors for all gout. Hypertension, however, was not a significant risk factor for primary gout.Obesity, excessive weight gain in young adulthood, and hypertension are risk factors for the development of gout. Prevention of obesity and hypertension may decrease the incidence of and morbidity from gout; studies of weight reduction in the primary and secondary prevention of gout are indicated.
Prognostic Influence of Elevated Values of Cardiac Troponin I in Patients With Unstable Angina
Authors: Marcello Galvani, Filippo Ottani, Donatella Ferrini, Jack H. Ladenson, Antonio Destro, Daniele Baccos, Franco Rusticali, Allan S. Jaffe
Journal: Circulation (1997)

Elevations of the MB isoform of creatine kinase (CK) and cardiac troponin T seem to confer an adverse prognosis in unstable angina. We examined whether this prognostic influence is also present for cardiac troponin I (cTnI), a new and even more specific marker of myocardial injury.We studied 106 patients with the clinical diagnosis of unstable angina showing chest discomfort at rest within 48 hours of admission, ECG evidence of myocardial ischemia, and normal values of total CK over the initial 16 hours of observation. The primary end point was death or nonfatal myocardial infarction (MI) at 30 days; the secondary end point was the incidence of cardiac events at 1 year. Blood was drawn every 8 hours for 3 days. Thirteen patients were excluded because of increased CK-MB mass concentrations within 16 hours of admission (non-Q-wave MI) and 2 because of inadequate blood sampling. Of the remaining 91 patients, 22 had cTnI elevations on admission (n=7) or after 8 hours (n=15). At 30 days, no deaths (0%) and 4 MIs (5.8%) occurred in the 69 patients with normal cTnI compared with 2 deaths (9.1%) and 4 MIs (18.2%) in the 22 patients with elevated cTnI. The combined incidence of death and nonfatal MI was 5.8% and 27.3%, respectively (P=.02). At 1 year, only 68% of patients with elevated cTnI were free of cardiac events, compared with 90% of those without elevations (P=.01).These data indicate that cTnI is an important prognostic variable in patients with unstable angina. Elevations of cTnI predict an adverse short- and long-term prognosis.