tbuckley/cabot-search huggingface dataset:
Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations
Authors: L De Rycke
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera. <b>Objective:</b> To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations. <b>Methods:</b> Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA. <b>Results:</b> In population 1, we defined adapted cut offs corresponding to a specificity of ⩾98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations. <b>Conclusion:</b> A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies.
Is fracture risk increased in patients with coeliac disease?
Authors: J Compston
Journal: Gut (2003)

Concerns about fracture risk in patients with coeliac disease may have been exaggerated

Metabolic bone disease is a well established complication of coeliac disease. Early reports focused mainly on the association with vitamin D deficiency and osteomalacia1 but more recently attention has turned to osteoporosis.2 A number of studies have demonstrated reduced bone mineral density in individuals with coeliac disease, particularly in untreated cases and in those who fail to respond fully to a gluten free diet.3 Furthermore, the need to consider coeliac disease as a pathogenetic factor in individuals presenting with osteoporosis has been emphasised; this particularly applies to those with clinical features of the disease and those who fail to respond to treatment for their osteoporosis.

The clinical significance of the observed reduction in bone mineral density associated with coeliac disease is unclear. While a small proportion of patients undoubtedly develop severe osteoporosis with multiple fragility fractures, the question of whether fracture risk is significantly increased across the clinical spectrum of coeliac disease has only recently been explored. Studies in small numbers of selected patients, drawn from hospital clinics, have suggested that fracture risk is increased4, …
Fireproofing Material Incorrectly Identified
Authors: Leslie A. Barron
Journal: JAMA (1977)

To the Editor.—  An article that was published inThe Journalentitled AspergillusInfections in Cancer Patients purports that the structural steel frame of the Baltimore Cancer Research Center was fireproofed with a cellulosic-based fireproofing material (235:411, 1976). I have made exhaustive inquiries and investigations into this and have determined that the structural frame of this particular edifice was fireproofed with a mineral fiber material and an inorganic binder. Clearly, this is not a cellulosicbased fireproofing material. I think it was rather unfortunate that allegations were made against a material that was not used in this particular hospital.
Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning
Authors: Trung H.M. Pham, Peter Baluk, Ying Xu, Irina Grigorova, Alex J. Bankovich, Rajita Pappu, Shaun R. Coughlin, Donald M. McDonald, Susan R. Schwab, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2009)

Lymphocyte egress from lymph nodes (LNs) is dependent on sphingosine-1-phosphate (S1P), but the cellular source of this S1P is not defined. We generated mice that expressed Cre from the lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1) locus and that showed efficient recombination of loxP-flanked genes in lymphatic endothelium. We report that mice with Lyve-1 CRE-mediated ablation of sphingosine kinase (Sphk) 1 and lacking Sphk2 have a loss of S1P in lymph while maintaining normal plasma S1P. In Lyve-1 Cre+ Sphk-deficient mice, lymphocyte egress from LNs and Peyer's patches is blocked. Treatment with pertussis toxin to overcome Gαi-mediated retention signals restores lymphocyte egress. Furthermore, in the absence of lymphatic Sphks, the initial lymphatic vessels in nonlymphoid tissues show an irregular morphology and a less organized vascular endothelial cadherin distribution at cell–cell junctions. Our data provide evidence that lymphatic endothelial cells are an in vivo source of S1P required for lymphocyte egress from LNs and Peyer's patches, and suggest a role for S1P in lymphatic vessel maturation.
Proteolysis of serum amyloid A and AA amyloid proteins by cysteine proteases: cathepsin B generates AA amyloid proteins and cathepsin L may prevent their formation
Authors: C Rocken
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid proteins are proteolytic fragments obtained from serum amyloid A (SAA). Previous studies have provided evidence that endosomes or lysosomes might be involved in the processing of SAA, and contribute to the pathology of AA amyloidosis. <b>Objective:</b> To investigate the anatomical distribution of cathepsin (Cath) B and CathL in AA amyloidosis and their ability to process SAA and AA amyloid proteins. <b>Methods and results:</b> CathB and CathL were found immunohistochemically in every patient with AA amyloidosis and displayed a spatial relationship with amyloid in all the cases studied. Both degraded SAA and AA amyloid proteins in vitro. With the help of mass spectrometry 27 fragments were identified after incubation of SAA with CathB, nine of which resembled AA amyloid proteins, and seven fragments after incubation with CathL. CathL did not generate AA amyloid-like peptides. When native human AA amyloid proteins were used as a substrate 26 fragments were identified after incubation with CathB and 18 after incubation with CathL. <b>Conclusion:</b> The two most abundant and ubiquitously expressed lysosomal proteases can cleave SAA and AA amyloid proteins. CathB generates nine AA amyloid-like proteins by its carboxypeptidase activity, whereas CathL may prevent the formation of AA amyloid proteins by endoproteolytic activity within the N-terminal region of SAA. This is particularly interesting, because AA amyloidosis is a systemic disease affecting many organs and tissue types, almost all of which express CathB and CathL.
Cholecystokinin antagonists: Pharmacological and therapeutic potential
Authors: Rosario Herranz
Journal: Medicinal Research Reviews (2003)

Abstract Cholecystokinin (CCK) is a regulatory peptide hormone, predominantly found in the gastrointestinal tract, and a neurotransmitter present throughout the nervous system. In the gastrointestinal system CCK regulates motility, pancreatic enzyme secretion, gastric emptying, and gastric acid secretion. In the nervous system CCK is involved in anxiogenesis, satiety, nociception, and memory and learning processes. Moreover, CCK interacts with other neurotransmitters in some areas of the CNS. The biological effects of CCK are mediated by two specific G protein coupled receptor subtypes, termed CCK 1 and CCK 2 . Over the past fifteen years the search of CCK receptor ligands has evolved from the initial CCK structure derived peptides towards peptidomimetic or non‐peptide agonists and antagonists with improved pharmacokinetic profile. This research has provided a broad assortment of potent and selective CCK 1 and CCK 2 antagonists of diverse chemical structure. These antagonists have been discovered through optimization programs of lead compounds which were designed based on the structures of the C‐terminal tetrapeptide, CCK‐4, or the non‐peptide natural compound, asperlicin, or derived from random screening programs. This review covers the main pharmacological and therapeutic aspects of these CCK 1 and CCK 2 antagonist. CCK 1 antagonists might have therapeutic potential for the treatment of pancreatic disorders and as prokinetics for the treatment of gastroesophageal reflux disease, bowel disorders, and gastroparesis. On the other hand, CCK 2 antagonists might have application for the treatment of gastric acid secretion and anxiety disorders. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 5, 559–605, 2003
Neuroendocrine Control of Thymus Physiology*
Authors: Wilson Savino, Mireille Dardenne
Journal: Endocrine Reviews (2000)

The thymus gland is a central lymphoid organ in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected thymocytes to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, formed of epithelial cells, macrophages, dendritic cells, fibroblasts, and extracellular matrix components. Various interactions occurring between microenvironmental cells and differentiating thymocytes are under neuroendocrine control. In this review, we summarize data showing that thymus physiology is pleiotropically influenced by hormones and neuropeptides. These molecules modulate the expression of major histocompatibility complex gene products by microenvironmental cells and the extracellular matrix-mediated interactions, leading to enhanced thymocyte adhesion to thymic epithelial cells. Cytokine production and thymic endocrine function (herein exemplified by thymulin production) are also hormonally controlled, and, interestingly in this latter case, a bidirectional circuitry seems to exist since thymic-derived peptides also modulate hormonal production. In addition to their role in thymic cell proliferation and apoptosis, hormones and neuropeptides also modulate intrathymic T cell differentiation, influencing the generation of the T cell repertoire. Finally, neuroendocrine control of the thymus appears extremely complex, with possible influence of biological circuitry involving the intrathymic production of a variety of hormones and neuropeptides and the expression of their respective receptors by thymic cells.
What evidence could validate the definition of COPD?
Authors: R. de Marco
Journal: Thorax (2008)

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and death in both the developed and developing worlds,1–3 and it is largely underdiagnosed.4

While it is generally accepted that the ratio between forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) or slow vital capacity (SVC) is the most important measure that characterises airflow obstruction,5 6 there is still no consensus on what the best definition of COPD should be.

In an attempt to simplify the diagnosis of COPD, improve the detection of the disease in primary care and standardise methods to measure the prevalence of COPD in different countries, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has defined COPD as a post-bronchodilator FEV1/FVC ratio <0.70.5

As the FEV1/FVC ratio decreases with age, this fixed ratio has been criticised as it may overdiagnose the disease in elderly subjects7 and underdiagnose it in young adults.8 For this reason, the ATS/ERS guidelines on lung function testing9 propose using the lower limit of normality (LLN) instead of a fixed cut-off to define COPD. LLN is the lower fifth percentile of the frequency distribution of the FEV1/FVC ratio in a healthy population of a given sex and age. The guidelines also point out that the SVC could be more accurate than FVC to diagnose airflow obstruction.

A hot debate between the supporters of the two different points of view is currently ongoing, as can …
INTELLECTUAL AND AFFECTIVE CHANGES IN ESSENTIAL HYPERTENSION
Authors: RALPH M. REITAN
Journal: American Journal of Psychiatry (1954)

The Rorschach test was administered to 3 diagnostic groups of patients with neurosis, organic brain-damage, and essential hypertension. The subjects were individually matched with respect to color, sex, age, formal education, and I. Q. Intergroup statistical comparisons were made of the mean values on each of the Rorschach variables. The relative frequencies of Rorschach " signs" of organic cerebral damage in the 3 groups were compared using the chi-square technique. The results indicate that the mean scores of the hypertensive group consistently fall between those of the other 2 groups. The Rorschach " signs" of brain damage occur more frequently in the brain-damage than hypertensive group, but there was no significant difference in this respect between the hypertensives and neurotics. An interpretative review of the protocols in the 3 groups indicates a considerable amount of neurotic symptomatology in each group, but confirms the quantitative results which indicated intellectual impairment due to organic brain damage in some of the patients with essential hypertension.
The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever
Authors: Emily S Jentes, Gilles Poumerol, Mark D Gershman, David R Hill, Johan Lemarchand, Rosamund F Lewis, J Erin Staples, Oyewale Tomori, Annelies Wilder-Smith, Thomas P Monath
Journal: The Lancet Infectious Diseases (2011)
Curcumin inhibits hepatic protein-tyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats
Authors: Jian-Mei Li, Yu-Cheng Li, Ling-Dong Kong, Qing-Hua Hu
Journal: Hepatology (2010)

High consumption of dietary fructose is an important contributory factor in the development of hepatic steatosis in insulin or leptin resistance. We investigated the effects of curcumin on fructose-induced hypertriglyceridemia and liver steatosis and explored its preventive mechanisms in rats. Curcumin reduced serum insulin and leptin levels in fructose-fed rats. This compound could increase phosphorylation of insulin receptor and insulin receptor substrate 1 to enhance Akt and extracellular signal-regulated kinase1/2 (ERK1/2) activation in the liver of fructose-fed rats. Moreover, curcumin increased phosphorylation of hepatic janus-activated kinase-signal transducer 2 and subsequently also stimulated Akt and ERK1/2 activation in this model. Suppression of curcumin on leptin signaling overstimulation in tyrosine1138 phosphorylation of the long form of leptin receptor and signal transducer and activator of transcription 3 resulted in down-regulation of suppressor of cytokine signaling 3 in the liver of fructose-fed rats. Thus, improvement of insulin and leptin signaling transduction and subsequently elevation of peroxisome proliferator-activated receptor α expression by curcumin led to reduction of very-low-density lipoprotein overproduction and triglyceride hypersynthesis. Furthermore, overexpression and hyperactivity of hepatic protein tyrosine phosphatase 1B (PTP1B) associated with defective insulin and leptin signaling were observed in fructose-fed rats. Additionally, curcumin was found to significantly reduce hepatic PTP1B expression and activity in this model. Conclusion: Our data indicate that the mechanisms by which curcumin protects against fructose-induced hypertriglyceridemia and hepatic steatosis are its inhibition on PTP1B and subsequently improvement of insulin and leptin sensitivity in the liver of rats. This PTP1B inhibitory property may be a promising therapeutic strategy for curcumin to treat fructose-induced hepatic steatosis driven by hepatic insulin and leptin resistance. (Hepatology 2010.)
Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment
Authors: F Blasi
Journal: Thorax (2002)

A study was undertaken to evaluate Chlamydia pneumoniae chronic infection, other respiratory infections, and functional impairment in patients with chronic bronchitis (stage 1) and to examine chronic C pneumoniae infection, rate of acute exacerbations of chronic bronchitis, and rate of C pneumoniae eradication following antibiotic treatment (stage 2).In the stage 1 study respiratory specimens from 42 patients with steady state chronic bronchitis were analysed for Gram staining, sputum culture, and C pneumoniae DNA detection by nested touchdown polymerase chain reaction (PCR). On the basis of the results of stage 1, a second population of 141 consecutive patients with steady state mild to moderate chronic bronchitis (FEV(1) >or=50% predicted) was studied. On admission, at regular intervals, and at exacerbation all patients underwent serological testing for C pneumoniae (microimmunofluorescence) and a nested touchdown PCR to detect C pneumoniae DNA was performed on peripheral blood mononuclear cells (PBMCs). Patients were assessed over a 12 month period. Information regarding the previous 12 months was taken from medical records.Chronic colonisation of the sputum with C pneumoniae was significantly associated with lower FEV(1) and greater airway bacterial colonisation. On admission to the stage 2 study, 80 patients were PCR negative and 61 were PCR positive. Over the 2 years a mean (SD) of 1.43 (1.32) acute exacerbations occurred in PCR negative patients and 2.03 (1.21) in PCR positive patients (p<0.01). During the 12 month follow up period 34 PCR positive patients had acute exacerbations and were treated with azithromycin for 6 weeks. Serological evidence of acute C pneumoniae reinfection/reactivation was found in two of the 34 patients. The rate of C pneumoniae DNA clearance from blood following treatment was 29% at follow up.Chronic colonisation with C pneumoniae is associated with a higher rate of exacerbations of chronic bronchitis. Long term treatment is required to obtain clearance of the organism from the blood.
Identification of High Potency Microbial and Self Ligands for a Human Autoreactive Class II–restricted T Cell Clone
Authors: Bernhard Hemmer, Burkhard T. Fleckenstein, Marco Vergelli, Günther Jung, Henry McFarland, Roland Martin, Karl-Heinz Wiesmüller
Journal: The Journal of Experimental Medicine (1997)

CD4+ class II–restricted T cells specific for self antigens are thought to be involved in the pathogenesis of most human autoimmune diseases and molecular mimicry between foreign and self ligands has been implicated as a possible mechanism for their activation. In this report we introduce combinatorial peptide libraries as a powerful tool to identify cross-reactive ligands for these T cells. The antigen recognition of a CD4+ T cell clone (TCC) specific for myelin basic protein peptide (MBP) (86-96) was dissected by the response to a set of 220 11-mer peptide sublibraries. Based on the results obtained with the libraries for each position of the antigen, artificial peptides were found that induced proliferative responses at much lower concentrations than MBP(86-96). In addition stimulatory ligands derived from protein sequences of self and microbial proteins were identified, some of them even more potent agonists than MBP(86-96). These results indicate that: (a) for at least some autoreactive CD4+ T cells antigen recognition is highly degenerate; (b) the autoantigen used to establish the TCC represents only a suboptimal ligand for the TCC; (c) a completely random and unbiased approach such as combinatorial peptide libraries can decrypt the spectrum of stimulatory ligands for a T cell receptor (TCR).
Identification of a high-affinity receptor for native human interleukin 1 beta and interleukin 1 alpha on normal human lung fibroblasts.
Authors: J Chin, P M Cameron, E Rupp, J A Schmidt
Journal: The Journal of Experimental Medicine (1987)

Native human IL-1 beta and IL-1 alpha stimulated prostaglandin E2 secretion by human embryonic lung fibroblasts at half-maximal concentrations of 3 +/- 1.2 pM (+/- SEM) and 10 +/- 2.3 pM, respectively. In contrast to the 20-50-fold lower affinities previously found for IL-1-R on 3T3 cells as well as murine and human lymphoblastoid lines, monoiodo 125I-IL-1 beta bound to normal human fibroblasts with a Kd of 8.4 +/- 4.1 pM in direct binding experiments, and with a Ki of 11.2 +/- 2.8 pM in competitive binding experiments. IL-1 alpha bound to the receptor identified by 125I-IL-1 beta with a Ki of 50 +/- 18 pM. The receptor exhibited homogeneous affinity for IL-1 beta or IL-1 alpha. The receptor did not recognize IL-2, IFN-gamma, tumor necrosis factor alpha, a functionally related monokine, or bovine acidic fibroblast growth factor, a structurally related mediator. Comparison of the biological response curves and binding curves obtained for IL-1 alpha and IL-1 beta showed that they were parallel and that 10-15% occupancy of the estimated 3,000 sites by either species of IL-1 was sufficient to give half-maximal stimulation of prostaglandin E2 secretion. Thus, the amount of apparent signal amplification observed on fibroblasts was considerably lower than the 100-100,000 fold amplification previously reported for lymphoid lines. Crosslinking experiments revealed a major band with a corrected molecular mass of approximately 80 kD and a minor band of approximately 200 kD. Labeling of these bands was blocked by IL-1 beta and IL-1 alpha but not by IL-2, IFN-gamma, or tumor necrosis factor alpha. These results demonstrate that normal human embryonic lung fibroblasts bear IL-1-R of sufficiently high affinity to mediate their biological responsiveness to low picomolar concentrations of IL-1 beta and IL-1 alpha and are consistent with the existence of a single receptor mediating the biological properties of both human IL-1 species.