tbuckley/cabot-search huggingface dataset:
Neuroimmune alterations of ENS functioning
Authors: L Bueno
Journal: Gut (2000)

Only recently has it been considered that numerous interactions between the enteric nervous system and local immunocytes are responsible for adaptive functional changes, including motility and secretion (fig 1). Several neuropeptides such as tachykinins, vasoactive intestinal peptide, somatostatin, and opioids are involved in both intrinsic and extrinsic innervation but can also affect immune reactions directly. They exert a dual role in the regulation of local and peripheral motor and secretory reflexes and affect the release of cytokines and proinflammatory mediators. On the other hand, proinflammatory mediators such as eicosanoids and cytokines may activate intrinsic neurones directly or stimulate extrinsic neurones indirectly, releasing neuropeptides which act on intrinsic neurones, smooth muscle cells, or enterocytes. These acute immediate neuroimmune reactions are often followed by long term changes in the number of receptors at the presynaptic or postsynaptic level as well as phenotypic changes of the effector cells, as evidenced for smooth muscle cells and enteric neurones which can synthetise cytokines.



Figure 1 
Interaction between the central nervous system and the immune system. VIP, vasoactive intestinal peptide; SP, substance P; SOM, somatostatin; G, ganglion; GALT, gut associated lymphoid tissue; MLN, mesenteric lymph node. (From Ottaway.20)



There are at least three major target cells affected by the presence of inflammatory mediators: smooth muscle cells, glial cells, and neurones. Both intrinsic enteric neurones and terminals of extrinsic afferent and efferent nerves are affected …
Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide stimulation is associated with rheumatoid arthritis and with joint damage
Authors: J K de Vries-Bouwstra, Y P M Goekoop-Ruiterman, J Wesoly, H J Hulsmans, A J M de Craen, F C Breedveld, B A C Dijkmans, C F Allaart, T W J Huizinga
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objectives:</b> (1) To assess innate ex vivo production of interleukin 1β (IL1β) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent-onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess the association of ex vivo IL1β and IL1Ra production with progression of joint damage in RA; (3) to determine whether differences in ex vivo IL1β production are explained by distribution of the IL1β single nucleotide polymorphism C-511T. <b>Methods:</b> Levels of IL1β and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide) and distribution of IL1β C-511T were compared in 76 patients with recent-onset RA who had received no disease-modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based on ex vivo IL1β and IL1Ra production were calculated. Association of ex vivo IL1β and IL1Ra production with progression of joint damage (Sharp–van der Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics. <b>Results:</b> Patients with recent-onset RA showed lower ex vivo IL1β and higher ex vivo IL1Ra production than healthy controls (p&lt;0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1β-producers and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with progression of joint damage (p = 0.01). The IL1β C-511T genotype distribution was not significantly different between patients and controls. <b>Conclusions:</b> Patients with recent-onset RA had decreased ex vivo IL1β production and increased ex vivo IL1Ra production compared with controls. Ex vivo IL1Ra production is an independent predictor of progression of joint damage in recent-onset RA.
Reexpression of LSAMP inhibits tumor growth in a preclinical osteosarcoma model
Authors: Tale Barøy, Stine H Kresse, Magne Skårn, Marianne Stabell, Russell Castro, Silje Lauvrak, Antonio Llombart-Bosch, Ola Myklebost, Leonardo A Meza-Zepeda
Journal: Molecular Cancer (2014)

Osteosarcomas are the most common primary malignant tumors of bone, showing complex chromosomal rearrangements with multiple gains and losses. A frequent deletion within the chromosomal region 3q13.31 has been identified by us and others, and is mainly reported to be present in osteosarcomas. The purpose of the study was to further characterize the frequency and the extent of the deletion in an extended panel of osteosarcoma samples, and the expression level of the affected genes within the region. We have identified LSAMP as the target gene for the deletion, and have studied the functional implications of LSAMP- reexpression. LSAMP copy number, expression level and protein level were investigated by quantitative PCR and western blotting in an osteosarcoma panel. The expression of LSAMP was restored in an osteosarcoma cell line, and differences in proliferation rate, tumor formation, gene expression, migration rate, differentiation capabilities, cell cycle distribution and apoptosis were investigated by metabolic dyes, tumor formation in vivo, gene expression profiling, time-lapse photography, differentiation techniques and flow cytometry, respectively. We found reduced copy number of LSAMP in 45/76 osteosarcoma samples, reduced expression level in 25/42 samples and protein expression in 9/42 samples. By restoring the expression of LSAMP in a cell line with a homozygous deletion of the gene, the proliferation rate in vitro was significantly reduced and tumor growth in vivo was significantly delayed. In response to reexpression of LSAMP, mRNA expression profiling revealed consistent upregulation of the genes hairy and enhancer of split 1 (HES1), cancer/testis antigen 2 (CTAG2) and kruppel-like factor 10 (KLF10). The high frequency and the specificity of the deletion indicate that it is important for the development of osteosarcomas. The deletion targets the tumor suppressor LSAMP, and based on the functional evidence, the tumor suppressor function of LSAMP is most likely exerted by reducing the proliferation rate of the tumor cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2 or KLF10. To our knowledge, this study describes novel functions of LSAMP, a first step to understanding the functional role of this specific deletion in osteosarcomas.
The surgical management of discrete and diffuse supravalvar aortic stenosis.
Authors: J F Keane, K E Fellows, C G LaFarge, A S Nadas, W F Bernhard
Journal: Circulation (1976)

Between 1956 and 1976, 18 patients underwent surgery for supravar aortic stenosis at the The Children's Hospital Medical Center, Boston. Discrete obstruction, present in 11, was treated by insertion of a prosthetic gusset placed across the area of narrowing and extending into the noncoronary sinus of Valsalva. There was one operative death. Residual gradients (measured in five patients) ranged from 4-55 mm Hg, one of which was supravalvar in location. Significant aortic regurgitation was not common preoperatively. The diffuse form of supravalvar obstruction, a more difficult surgical problem, was present in seven patients. There were three operative deaths. Complete relief of the pressure gradient was achieved only in one instance by insertion of a left ventricular-aortic bypass shunt diverting the majority of the cardiac output into the descending thoracic aorta. This patient is now asymptomatic 20 months following operation. On the basis of this experience, it is suggested that patients with the diffuse form of supravalvar obstruction, and perhaps even those with a hypoplastic annulus alone, would benefit from a left ventricular-aortic bypass shunt.
Phase III Double-Blind, Placebo-Controlled Study of Thalidomide in Extensive-Disease Small-Cell Lung Cancer After Response to Chemotherapy: An Intergroup Study FNCLCC cleo04–IFCT 00-01
Authors: Jean Louis Pujol, Jean Luc Breton, Radj Gervais, Marie-Laure Tanguy, Elisabeth Quoix, Philippe David, Henri Janicot, Virginie Westeel, Sabine Gameroff, Jean Genève, Dominique Maraninchi
Journal: Journal of Clinical Oncology (2007)

This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer (SCLC).One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4'-epidoxorubicin (PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide (400 mg daily) or placebo.After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo (n = 43) or thalidomide (n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant (minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log-rank test: hazard ratio [HR] = 0.74; 95% CI, 0.49 to 1.12; P = .16). Patients with a performance status (PS) of 1 or 2 who received thalidomide had a significantly longer survival (HR = 0.59; 95% CI, 0.37 to 0.92; P = .02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide (HR = 0.54; 95% CI, 0.36 to 0.87; P = .02), whereas the difference did not reach statistical significance for the whole population (HR = 0.74; 95% CI, 0.49 to 1.12; P = .15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group (33% v 12%, respectively).Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 (exploratory analyses), deserving further studies targeting angiogenesis in this disease.
Oropharyngeal deposition of 3.5 microns particles inhaled through an elongated mouthpiece
Authors: K Svartengren, M Anderson, M Svartengren, K Philipson, P Camner
Journal: European Respiratory Journal (1996)

We previously studied the deposition of inhaled particles in the oropharynx of asthmatic patients, and found that a pharyngeal narrowing during inhalation seems to be one reason for high oropharyngeal deposition. In the present study, we investigated whether by-passing a larger part of the oral cavity by using an elongated mouthpiece would reduce deposition in the oropharynx, and increase deposition in the lungs. Deposition in the oropharynx and in the lungs was estimated in nine patients with obstructive airway diseases. In earlier investigations, three of these patients had repeatedly shown extremely high oropharyngeal deposition (> 70%). In the present study, the patients inhaled 3.5 microns (aerodynamic diameter) radiolabelled Teflon particles at 0.5 L.s-1, with and without an individually adapted elongated mouthpiece. Radioactivity was measured using a profile scanner. On average, oropharyngeal deposition was 27% (range 12-45%) and 30% (range 11-77%) of the total amount of particles deposited in the body, with and without elongated mouthpiece, respectively. There was no significant difference between these values (p > 0.05), nor between the values of lung deposition. However, oropharyngeal deposition was markedly reduced, with a corresponding increase in lung deposition, by the elongated mouthpiece in the one and only patient who still showed extremely high oropharyngeal deposition (> 70%). Our study shows that lengthening of the mouthpiece is not sufficient to reduce average deposition of aerosol particles in the oropharynx in patients with comparatively normal deposition values. This result, however, does not exclude a beneficial effect in patients with extremely high oropharyngeal deposition.
THE EXPERIMENTAL PRODUCTION OF PERIARTERITIS NODOSA IN THE RABBIT WITH A CONSIDERATION OF THE SPECIFIC CAUSAL EXCITANT
Authors: William H. Harris, Andrew V. Friedrichs
Journal: The Journal of Experimental Medicine (1922)

1. Periarteritis nodosa is a specific infectious disease which is transmissible to the rabbit. 2. The lesions induced in rabbits are identical with those occurring in man and consist of exudative and degenerative processes within the walls of the smaller arteries resulting in aneurysmal formations and thromboses. 3. The microorganism inducing the disease is capable of going through a Berkefeld N filter and is therefore to be classed with the group of so called filter passers.
High expression of CD56 (N‐CAM) in a patient with cutaneous CD4‐positive lymphoma
Authors: Masaaki Adachi, Kazuo Maeda, Mutsuhiro Takekawa, Yuji Hinoda, Kohzoh Imai, Sadao Sugiyama, Akira Yachi
Journal: American Journal of Hematology (1994)

Abstract Cutaneous lymphoma is a disease characterized with massive skin infiltration of lymphoid malignant cells. They commonly express some T‐cell markers, such as CD2, CD3, CD4, and CD7, and thus termed as CTCL (cutaneous T cell lymphoma). Here, we present a case with CD56/N‐CAM‐positive cutaneous lymphoma, which appears lymphocytic morphology and expresses CD4, but does not express CD2, CD3, CD8, CD14, CD16, CD57, and CD20. The most malignant cells contained no distinctive azurophilic granules in the cytoplasm. Southern blot analysis revealed that T cell receptor‐β, γ, and immunoglobulin heavy chain genes in the cells were in germ‐line configurations. Electron microscopic examination showed characteristics of lymphoid cells with higher nucleocytoplasmic ratio and lacked structures typical of other cell types (i.e., epithelial cells, neuroendocrine cells, and mesenchymal cells). Thus, the cells are likely to be immature lymphoid cells. Histological analysis revealed the cells infiltrate mainly into the dermis with angiocentric growth pattern. The clinical course was aggressive, with rapid involvement of bone marrow and central nervous system. These striking features of the patient may represent a novel fraction (CD2−, CD4+, and CD56+) of cutaneous lymphoma. © 1994 Wiley‐Liss, Inc.
Defining osteoarthritis of the hand for epidemiological studies: the Chingford Study.
Authors: D Hart, T Spector, P Egger, D Coggon, C Cooper
Journal: Annals of the Rheumatic Diseases (1994)

<h3>Objective</h3> To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. <h3>Design</h3> Cross-sectional observational study. <h3>Setting</h3> The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. <h3>Participants</h3> Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). <h3>Main outcome measures</h3> Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. <h3>Results</h3> 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p&lt;0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p&lt;0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p&lt;0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p&lt;0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p&lt;0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. <h3>Conclusions</h3> Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.
Hypernatremia, Azotemia, and Dehydration Due to High-Protein Tube Feeding
Authors: M. HENRY GAULT
Journal: Annals of Internal Medicine (1968)

Severe dehydration, hypernatremia and hyponatruria, and azotemia in marked excess of creatinemia developed in three patients given high-protein tube feedings. The patients were fully conscious when tube feeding was instituted, and each had a tracheostomy coincidental to treatment of carcinoma of the larynx or oral cavity. In two cases, several features demonstrated that the hypernatremia was due predominantly to dehydration and not to excess salt. In patients who are unconscious or who for other reasons are unable to experience, communicate, or alleviate their thirst this syndrome may develop rapidly when fluid losses are increased, and tube feeding water protein ratios may be higher than those ordinarily well-tolerated. A similar degree of care should be exercised in the regulation of constituents and the monitoring of fluid and electrolyte balance with the use of tube feedings as is done when intravenous therapy is given.
Environmental allergen exposure, sensitisation and asthma: from whole populations to individuals at risk
Authors: A Custovic
Journal: Thorax (2004)

To prevent asthma and allergies we need to design interventions appropriate for individual susceptibilities, taking account of both genes and the environment

Sensitisation to inhalant allergens remains a major risk factor for asthma,1 but the size of the effect is hotly debated.2,3 Several cross sectional studies have suggested a simple dose-response relationship between dust mite allergen exposure and specific sensitisation, both within communities4–7 and between communities exposed to differing levels of mite allergens.8 The threshold concentration of 2 μg Group 1 mite allergen per gram of dust for developing mite sensitisation in children at high risk has been suggested, but a much higher cut off level of 80 μg/g appeared significant in low risk children.4 For other allergens the relationship between exposure and sensitisation is less well defined. Several studies in the US inner city areas reported that children are more likely to become sensitised to cockroach with increasing cockroach allergen exposure,9 and that high exposure to mouse allergen appears to be associated with an increased prevalence of sensitisation to mouse.10 Some studies in older children and adults reported a close relationship between specific allergen sensitisation and current domestic exposure for mite and cockroach, but not cat allergen.5,11 This, together with studies reporting a protective effect of high cat allergen exposure on sensitisation,12,13 raises the question of whether the dose-response relationship between exposure and sensitisation may be different for different allergens. However, there are remarkably few published data on the longitudinal relationship between allergen exposure and the development of specific sensitisation.

Several observational birth cohort studies investigating risk factors for the development of allergen sensitisation and asthma have measured allergen levels in dust samples collected in early life to examine the association between allergen exposure and the …
Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems.
Authors: R Kiessling, G Petranyi, K Kärre, M Jondal, D Tracey, H Wigzell
Journal: The Journal of Experimental Medicine (1976)

Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.
Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial
Authors: J. Hetzel, R. Eberhardt, F.J.F. Herth, C. Petermann, G. Reichle, L. Freitag, I. Dobbertin, K.J. Franke, F. Stanzel, T. Beyer, P. Möller, P. Fritz, G. Ott, P.A. Schnabel, H. Kastendieck, W. Lang, A.T. Morresi-Hauf, M.N. Szyrach, R. Muche, P.L. Shah, A. Babiak, M. Hetzel
Journal: European Respiratory Journal (2011)

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.