tbuckley/cabot-search huggingface dataset:
INHIBITION OF SPECIFIC CELL-MEDIATED CYTOTOXICITY BY ANTI-T-CELL RECEPTOR ANTIBODY
Authors: Arthur K. Kimura
Journal: The Journal of Experimental Medicine (1974)

The present study describes a method for the production of a specific anti-T-cell receptor antiserum, and characteristics of its ability to block specific cell-mediated cytotoxicity in vitro. Immunization and antiserum adsorption procedures were designed to select for idiotypic differences in the recognition units of C3H lymphocytes immune to two different strains of mouse cells, such that the reactivity of only one population of effector cells is inhibited by this antiserum. Both in vivo and in vitro sensitized effector T cells are subject to this inhibition. That the site of the antiserum blockade is clearly on the effector cell and not on the target cell is demonstrated.
Nasal CPAP and weight loss in hypertensive patients with obstructive sleep apnoea.
Authors: H Rauscher, D Formanek, W Popp, H Zwick
Journal: Thorax (1993)

BACKGROUND--The high prevalence of obstructive sleep apnoea (OSA) in patients with systemic hypertension and of hypertension in patients with OSA suggests a causal link between the two disorders. This study was carried out to determine whether nasal continuous positive airway pressure (CPAP) and weight loss affect daytime hypertension in OSA. METHODS--Sixty hypertensive patients with OSA took part in the study; 33 accepted nasal CPAP and used their machine for 5.7 (0.2) hours per night, and the remaining 27 patients refused nasal CPAP and upper airway surgery so the only therapeutic intervention was a recommendation of weight loss. A significant change in hypertension during follow up was defined as either a change in mean blood pressure of at least 10 mm Hg (or more than 8%) without a change in drug treatment, or a reduction in drug dosage with mean blood pressure within these limits. Weight loss was defined as a body mass index of at least 5% below the baseline value. RESULTS--After 512 (41) days, hypertension had become less severe in seven of 12 patients (58%) treated with weight loss only, in eight of 28 patients (29%) with nasal CPAP only, in two of five patients with nasal CPAP and weight loss, and in one of 15 patients without nasal CPAP or weight loss. Multivariate analysis of variance with the outcome of hypertension at follow up as the dependent variable revealed that only the percentage change in body mass index significantly contributed to the course of hypertension. CONCLUSION--The course of hypertension in OSA is more closely linked to weight loss than to elimination of sleep apnoea by nasal CPAP.
Genetic control of the immune response to collagen. II. Antibody responses produced in fetal liver restored radiation chimeras and thymus reconstituted F1 hybrid nude mice.
Authors: S M Hedrick, J Watson
Journal: The Journal of Experimental Medicine (1979)

The level of antibody produced in response to calf skin collagen in mice is influenced by genes which are closely linked to the I region of the H-2 major histocompatibility complex. This influence is shown to be expressed during lymphoid maturation by testing the antibody responsiveness to collagen in two types of chimeric mice. First, high responder and low responder parental strain mice were lethally irradiated and restored with fetal liver cells from (high X low responder) F1 mice. These F1 leads to parent chimeras exhibited an immune response phenotype characteristic of the irradiated parental strain animals, establishing that H-2 determinants of the host affect antigen responsiveness. Second, (high X low responder) F1 congenitally athymic (nude) mice were restored with fetal thymus transplants from either high or low responder parental strain mice. After a period of maturation these mice were shown to be competent for a T-dependent IgG response to SRBC. The responsiveness to collagen in these mice was characteristic of the parental strain thymus donors, indicating that the expression of H-2 determinants in thymic tissue during lymphoid maturation influences the antibody response phenotype expressed by mice.
B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor
Authors: Nicholas Chiorazzi, Manlio Ferrarini
Journal: Annual Review of Immunology (2003)

B cell chronic lymphocytic leukemia (B-CLL) is an accumulative disease of slowly proliferating CD5(+) B lymphocytes that develops in the aging population. Whereas some patients with B-CLL have an indolent course and die after many years from unrelated causes, others progress very rapidly and succumb within a few years from this currently incurable leukemia. Over the past decade studies of the structure and function of the B cell antigen receptor (BCR) used by these leukemic cells have helped redefine the nature of this disease. In this review we summarize and reinterpret several aspects of these BCR-related studies and how they might relate to the disease. In particular, we address the ability of antigens to select out and drive B cell clones from the normal state to overt leukemic cells by binding to BCRs that are relatively unique and characteristic of B-CLL cells. The differential capacity of some B-CLL cases to continue to transduce signals through the BCR during the leukemic phase and the consequences for the in vivo biology of the leukemic clone is also considered. Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress.
Temporomandibular joint pseudogout: an uncommon site for a familiar condition
Authors: F Goldblatt
Journal: Annals of the Rheumatic Diseases (2004)

It is well recognised that the temporomandibular joint (TMJ) may be affected by rheumatoid or psoriatic arthritides and ankylosing spondylitis. Interestingly, however, calcium pyrophosphate dihydrate (CPPD) crystal deposition is unusual in this site, and authors of several large case series of CPPD disease failed to report any acute attacks affecting this joint.1,2 As far as we are aware, only infrequent reports of CPPD crystal deposition in the TMJ have been published.3–7 We therefore present the following case to highlight a possible differential diagnosis for patients presenting with TMJ pain and/or swelling.

A 57 year old man presented with an acute onset of severe pain and swelling affecting his right TMJ, on a background of chronic right sided TMJ discomfort. There were no associated systemic features. The patient had a past history of hypertension, hypercholesterolaemia, lumbar spine osteoarthritis, fifty (50) pack year smoking …
Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study
Authors: F. Demenais, H. Mohamdi, V. Chaudru, A. M. Goldstein, J. A. Newton Bishop, D. T. Bishop, P. A. Kanetsky, N. K. Hayward, E. Gillanders, D. E. Elder, M. F. Avril, E. Azizi, P. van Belle, W. Bergman, G. Bianchi-Scarrà, B. Bressac-de Paillerets, D. Calista, C. Carrera, J. Hansson, M. Harland, D. Hogg, V. Höiom, E. A. Holland, C. Ingvar, M. T. Landi, J. M. Lang, R. M. Mackie, G. J. Mann, M. E. Ming, C. J. Njauw, H. Olsson, J. Palmer, L. Pastorino, S. Puig, J. Randerson-Moor, M. Stark, H. Tsao, M. A. Tucker, P. van der Velden, X. R. Yang, N. Gruis
Journal: JNCI Journal of the National Cancer Institute (2010)

Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02).Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction
Authors: P Di Sebastiano
Journal: Gut (2003)

Chronic pancreatitis (CP) is an inflammatory, often painful, disease of the exocrine pancreas which leads to exocrine insufficiency. The pathophysiology of pain in CP is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. Here, the different pain hypotheses are discussed and evidence is presented that neuroimmune interactions are significant in the pathogenesis of pain generation and inflammation in CP. A better understanding of the complex cellular and molecular mechanisms of neuroimmune interactions should offer possibilities for innovative therapy and long term disease prevention.
Incidence, Morphology, Angiographic Findings, and Outcomes of Intramural Hematomas After Percutaneous Coronary Interventions
Authors: Akiko Maehara, Gary S. Mintz, Anh B. Bui, Marco T. Castagna, Olga R. Walter, Chrysoula Pappas, Ellen E. Pinnow, Augusto D. Pichard, Lowell F. Satler, Ron Waksman, William O. Suddath, John R. Laird, Kenneth M. Kent, Neil J. Weissman
Journal: Circulation (2002)

Background — Intramural hematomas during percutaneous coronary intervention (PCI) have not been well studied. Methods and Results — We used intravascular ultrasound to determine the incidence, morphology, and clinical features of post-PCI intramural hematomas. In 905 patients with 1025 consecutive native coronary artery, non–in-stent restenosis lesions undergoing PCI, 72 hematomas were detected in 69 arteries in 68 patients. The incidence of intramural hematomas per artery was 6.7% (69 of 1025); 36% (26 of 72) involved the proximal reference artery, 18% (13 of 72) were confined to the lesion, and 46% (33 of 72) involved the distal reference artery. The entry site from the lumen into the hematoma was identified in 86% of hematomas (62 of 72) and had the appearance of a dissection into the media. Conversely, a re-entry site was identifiable in only 8% (6 of 72). The axial extension of the hematoma was distal in 63% and proximal in 37%. In 60% of the hematomas (42 of 72) the angiogram had the appearance of a dissection; in 11% (8 of 72), it appeared to be a new stenosis; and in 29% (22 of 72), no significant abnormality was detected. Non–Q-wave myocardial infarctions occurred in 26% of patients (17 of 65). In 3 patients, the creatine kinase-MB was not measured during the hospital stay. Repeat revascularization occurred in 2 patients in-hospital, 2 additional patients at 1 month, and 8 additional patients at 1 year. There were 3 sudden deaths at 1 year. Conclusions — Intravascular ultrasound identified intramural hematomas after 6.7% of PCIs. The mechanism appeared to be a dissection into the media where blood accumulated because of a lack of re-entry. A third of ultrasound-identified hematomas showed no angiographic abnormalities. There was a high rate of non–Q-wave myocardial infarction, need for repeat revascularization, and sudden death in patients with hematomas.
Interactions Between Amino Acid–Defined Major Histocompatibility Complex Class II Variants and Smoking in Seropositive Rheumatoid Arthritis
Authors: Kwangwoo Kim, Xia Jiang, Jing Cui, Bing Lu, Karen H. Costenbader, Jeffrey A. Sparks, So‐Young Bang, Hye‐Soon Lee, Yukinori Okada, Soumya Raychaudhuri, Lars Alfredsson, Sang‐Cheol Bae, Lars Klareskog, Elizabeth W. Karlson
Journal: Arthritis & Rheumatology (2015)

Objective To define the interaction between cigarette smoking and HLA polymorphisms in seropositive rheumatoid arthritis (RA), in the context of a recently identified amino acid–based HLA model for RA susceptibility. Methods We imputed Immunochip data on HLA amino acids and classical alleles from 3 case–control studies (the Swedish Epidemiological Investigation of Rheumatoid Arthritis [EIRA] study [1,654 cases and 1,934 controls], the Nurses' Health Study [NHS] [229 cases and 360 controls], and the Korean RA Cohort Study [1,390 cases and 735 controls]). We examined the interaction effects of heavy smoking (&gt;10 pack‐years) and the genetic risk score (GRS) of multiple RA‐associated amino acid positions (positions 11, 13, 71, and 74 in HLA–DRβ1, position 9 in HLA–B, and position 9 in HLA–DPβ1), as well as the interaction effects of heavy smoking and the GRS of HLA–DRβ1 4–amino acid haplotypes (assessed via attributable proportion due to interaction [AP] using the additive interaction model). Results Heavy smoking and all investigated HLA amino acid positions and haplotypes were associated with RA susceptibility in the 3 populations. In the interaction analysis, we found a significant deviation from the expected additive joint effect between heavy smoking and the HLA–DRβ1 4–amino acid haplotype (AP 0.416, 0.467, and 0.796, in the EIRA, NHS, and Korean studies, respectively). We further identified the key interacting variants as being located at HLA–DRβ1 amino acid positions 11 and 13 but not at any of the other RA risk–associated amino acid positions. For residues in positions 11 and 13, there were similar patterns between RA risk effects and interaction effects. Conclusion Our findings of significant gene–environment interaction effects indicate that a physical interaction between citrullinated autoantigens produced by smoking and HLA–DR molecules is characterized by the HLA–DRβ1 4–amino acid haplotype, primarily by positions 11 and 13.
An evolving new paradigm: endothelial cells – conditional innate immune cells
Authors: Jietang Mai, Anthony Virtue, Jerry Shen, Hong Wang, Xiao-Feng Yang
Journal: Journal of Hematology & Oncology (2013)

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies.
Pathobiology of pulmonary arterial hypertension and right ventricular failure
Authors: Norbert F. Voelkel, Jose Gomez-Arroyo, Antonio Abbate, Harm J. Bogaard, Mark R. Nicolls
Journal: European Respiratory Journal (2012)

Pulmonary arterial hypertension (PAH) is no longer an orphan disease. There are three different classes of drugs for the treatment of PAH that are currently being used and an increasing number of patients are being treated with a single drug or combination therapy. During the last 25 yrs, new insights into the pathobiology of PAH have been gained. The classical mechanical concepts of pressure, flow, shear stress, right ventricle wall stress and impedance have been complemented with the new concepts of cell injury and repair and interactions of complex multicellular systems. Integrating these concepts will become critical as we design new medical therapies in order to change the prognosis of patients with these fatal diseases. This review intends to summarise recent pathobiological concepts of PAH and right ventricle failure mainly derived from human studies, which reflect the progress made in the understanding of this complex group of pulmonary vascular diseases.
A Mutant Form of the Wilms’ Tumor Suppressor Gene WT1 Observed in Denys-Drash Syndrome Interferes with Glomerular Capillary Development
Authors: Thomas A. Natoli, Jing Liu, Vera Eremina, Karen Hodgens, Cong Li, Yuki Hamano, Peter Mundel, Raghu Kalluri, Jeffrey H. Miner, Susan E. Quaggin, Jordan A. Kreidberg
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The Wilms’ tumor suppressor gene WT1 encodes a zinc finger protein that is required for urogenital development. In the kidney, WT1 is most highly expressed in glomerular epithelial cells or podocytes, which are an essential component of the filtering system. Human subjects heterozygous for point mutations in the WT1 gene develop renal failure because of the formation of scar tissue within glomeruli. The relationship between WT1 expression in podocytes during development and glomerular scarring is not well understood. In this study, transgenic mice that expressed a mutant form of WT1 in podocytes were derived. The capillaries within transgenic glomeruli were dilated, indicating that WT1 might regulate the expression of growth factors that affect capillary development. Platelet endothelial cell adhesion molecule-1 expression was greatly reduced on glomerular endothelial cells of transgenic kidneys. These results suggest that WT1 controls the expression of growth factors that regulate glomerular capillary development and that abnormal capillary development might lead to glomerular disease.
Vitamin C, Collagen, and Cracks in the Plaque
Authors: Peter Libby, Masanori Aikawa
Journal: Circulation (2002)

ost fatal acute myocardial infarctions result from a fracture of the plaque's fibrous cap.We proposed the hypothesis some years ago that the level of collagen in the fibrous cap depends on a dynamic balance of synthesis and degradation. 13][4][5] Given the capital importance of collagen in protecting the plaque from rupture and hence thrombosis, the metabolism of this complex molecule merits consideration in depth.
Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism
Authors: T. Ha, F. Hua, X. Liu, J. Ma, J. R. McMullen, T. Shioi, S. Izumo, J. Kelley, X. Gao, W. Browder, D. L. Williams, R. L. Kao, C. Li
Journal: Cardiovascular Research (2008)

The ability of lipopolysaccharide (LPS) pre-treatment to induce cardioprotection following ischaemia/reperfusion (I/R) has been well documented; however, the mechanisms have not been fully elucidated. LPS is a Toll-like receptor 4 (TLR4) ligand. Recent evidence indicates that there is cross-talk between the TLR and phosphoinositide 3-kinase/Akt (PI3K/Akt) signalling pathways. We hypothesized that activation of PI3K/Akt signalling plays a critical role in LPS-induced cardioprotection.To evaluate this hypothesis, we pre-treated mice with LPS 24 h before the hearts were subjected to ischaemia (45 min) and reperfusion (4 h). We examined activation of the PI3K/Akt/GSK-3beta signalling pathway. The effect of PI3K/Akt inhibition on LPS-induced cardioprotection was also evaluated. LPS pre-treatment significantly reduced infarct size (71.25%) compared with the untreated group (9.3+/-1.58 vs. 32.3+/-2.92%, P<0.01). Cardiac myocyte apoptosis and caspase-3 activity in LPS-pre-treated mice were significantly reduced following I/R. LPS pre-treatment significantly increased the levels of phospho-Akt, phospho-GSK-3beta, and heat shock protein 27 in the myocardium. Pharmacological inhibition of PI3K by LY294002 or genetic modulation employing kinase-defective Akt transgenic mice abolished the cardioprotection induced by LPS.These results indicate that LPS-induced cardioprotection in I/R injury is mediated through a PI3K/Akt-dependent mechanism.
Blaming the Right Fluorescent in Situ Hybridization
Authors: Rahma Warsame, Angela Dispenzieri
Journal: Journal of Clinical Oncology (2015)

Bochtler et al 1 have observed that patients with light chain (AL) amyloidosis with t(11;14) fare worse with bortezomib-based therapy.This observation is difficult to reconcile given both the fact that a majority of patients with AL have t(11;14), and that bortezomib has been observed to be a highly effective therapy in patients with AL. 2 Making sense of these discrepant observations is only possible in larger studies, and we question whether some of the findings by Bochtler et al 1 are artifacts of small sample size.In a series of 396 patients with AL, 175 of whom had the t(11;14) translocation, we found that t(11;14) is a negative risk factor among patients with less than 10% bone marrow plasma cells. 3In response to the publication by Bochtler et al, 1 we performed a reanalysis of our published data and found that 51 patients received bortezomib as first-line therapy.There was a nonsignificant, steeper, early death rate among patients who received bortezomib and had t(11;14) compared with those who either did not receive bortezomib but had t(11;14), or who received bortezomib but did not harbor t(11;14).The early death rate among patients who received bortezomib and had t(11;14) raises the specter of potential increased toxicity rather than reduced efficacy of bortezomib; there was no difference in overall survival.When this data set was subjected to multivariable analysis that included bortezomib as first-line therapy, t(11;14), and the Mayo Clinic 2012 staging system, only the Mayo Clinic staging system was a significant risk factor for death.On repeating the multivariable analysis to include only those patients with t(11;14), treatment with bortezomib had no impact on overall survival. 4s a result of small sample size, neither our analysis nor the analysis by Bochtler et al 1 settle the question of whether patients with AL with the t(11;14) translocation do poorly while receiving bortezomib or if these patients have poor prognoses in general.