tbuckley/cabot-search huggingface dataset:
Isotypic and allotypic specificity of mouse rheumatoid factors.
Authors: J L Van Snick, V Stassin, B de Lestré
Journal: The Journal of Experimental Medicine (1983)

The specificity of polyclonal mouse rheumatoid factors (RF) was analyzed by competition experiments with heat-aggregated mouse IgG subclasses. The RF spontaneously produced by three normal mouse strains (129/Sv, CBA/Ht, and C57Bl/6) and by two strains with autoimmune diseases (MRL/l and NZB) were found to consist of distinct non-cross-reactive antibody subpopulations each specific for one IgG subclass. The sera of the normal strains contained IgG1- and IgG2a-specific RF. The autoimmune strains produced an additional variety of RF that was specific for The autoimmune strains produced an additional variety of RF that was specific for IgG2b. Also, the RF secreted by spleen cells of various normal strains after in vitro polyclonal activation with lipopolysaccharide could be resolved into distinct subpopulations specific for IgG1 or IgG2a. These results were confirmed by the analysis of monoclonal RF derived from BALB/c, C57Bl/6, CBA/Ht, and 129/Sv mice: of 73 hybridomas with RF activity, 71 displayed a strict subclass specificity. The subclass predominantly recognized depended on the origin of the spleen cells used to generate the hybridomas. After polyclonal activation in vitro, a broad spectrum of different specificities was obtained with 16 RF specific for IgG1, 13 for IgG2a, and 4 for IgG2b. In contrast, 27 of 28 monoclonal RF derived from 129/Sv and BALB/c mice without prior polyclonal activation were specific for IgG2a, and of these 75% were allotype specific since they failed to react with IgG2a of the b allotype. These results demonstrate the importance of subclass specificity in the production of RF in vivo. With the exception of the IgG2b-specific clones, all these monoclonal RF reacted preferentially with heat-aggregated or antigen-bound IgG. Among the hybridomas generated by the fusion of in vitro polyclonally activated spleen cells of 4-wk-old mice, the frequency of clones with RF activity was at least 40 times higher than that of clones specific for mouse IgM, human IgG, ovalbumin, and hen lysozyme.
Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer
Authors: K. Azuma, K. Ota, A. Kawahara, S. Hattori, E. Iwama, T. Harada, K. Matsumoto, K. Takayama, S. Takamori, M. Kage, T. Hoshino, Y. Nakanishi, I. Okamoto
Journal: Annals of Oncology (2014)
THE STRUCTURE OF ANTIGEN-ANTIBODY COMPLEXES
Authors: June Almeida, Bernhard Cinader, Allan Howatson
Journal: The Journal of Experimental Medicine (1963)

Negatively stained aggregates of antigen (polyoma or verruca vulgaris virus) and antibody (from rabbit or goat) were examined in the electron microscope. The antibody molecules appeared as cylindrical rods (often, but not always, showing a beaded appearance) with a long axis of 250 to 270 A and a short axis of 35 to 40 A. The combining sites were at the opposite short ends of the antibody molecules separated by the length of 250 to 270 A of the antibody molecule. Aggregates of antigen and antibody showed regions of orderly arrangements and frequently ring structures of five or more linked virus particles. Sometimes a virus particle in the center of these ring structures was linked to the peripheral particles. In extreme antibody excess, cross-linking was only rarely observed and virus particles were surrounded by a dense aura of antibody molecules. The specificity of the two combining sites of most antibody molecules is identical. This was utilized to examine the antigenic relation between the normal (icosahedral) and aberrant forms of polyoma virus.
Platelets Release CXCL4L1, a Nonallelic Variant of the Chemokine Platelet Factor-4/CXCL4 and Potent Inhibitor of Angiogenesis
Authors: Sofie Struyf, Marie D. Burdick, Paul Proost, Jo Van Damme, Robert M. Strieter
Journal: Circulation Research (2004)

Platelet factor-4 (PF-4)/CXCL4 was the first chemokine described to inhibit neovascularization. Here, the product of the nonallelic variant gene of CXCL4, PF-4var1/PF-4alt, designated CXCL4L1, was isolated for the first time from thrombin-stimulated human platelets and purified to homogeneity. Although secreted CXCL4 and CXCL4L1 differ in only three amino acids, CXCL4L1 was more potent in inhibiting chemotaxis of human microvascular endothelial cells toward interleukin-8 (IL-8)/CXCL8 or basic fibroblast growth factor (bFGF). In vivo, CXCL4L1 was also more effective than CXCL4 in inhibiting bFGF-induced angiogenesis in rat corneas. Thus, activated platelets release CXCL4L1, a potent regulator of endothelial cell biology, which affects angiogenesis and vascular diseases.
An Empirical Examination of the Stage Theory of Grief
Authors: Paul K. Maciejewski, Baohui Zhang, Susan D. Block, Holly G. Prigerson
Journal: JAMA (2007)

The stage theory of grief remains a widely accepted model of bereavement adjustment still taught in medical schools, espoused by physicians, and applied in diverse contexts. Nevertheless, the stage theory of grief has previously not been tested empirically.To examine the relative magnitudes and patterns of change over time postloss of 5 grief indicators for consistency with the stage theory of grief.Longitudinal cohort study (Yale Bereavement Study) of 233 bereaved individuals living in Connecticut, with data collected between January 2000 and January 2003.Five rater-administered items assessing disbelief, yearning, anger, depression, and acceptance of the death from 1 to 24 months postloss.Counter to stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most frequently endorsed item and yearning was the dominant negative grief indicator from 1 to 24 months postloss. In models that take into account the rise and fall of psychological responses, once rescaled, disbelief decreased from an initial high at 1 month postloss, yearning peaked at 4 months postloss, anger peaked at 5 months postloss, and depression peaked at 6 months postloss. Acceptance increased throughout the study observation period. The 5 grief indicators achieved their respective maximum values in the sequence (disbelief, yearning, anger, depression, and acceptance) predicted by the stage theory of grief.Identification of the normal stages of grief following a death from natural causes enhances understanding of how the average person cognitively and emotionally processes the loss of a family member. Given that the negative grief indicators all peak within approximately 6 months postloss, those who score high on these indicators beyond 6 months postloss might benefit from further evaluation.
Apparent hip osteoarthritis in a 16 year old girl
Authors: C. Rougerie, O. Pidet, X. Chevalier, B. Larget-Piet, D. Goutallier, P. Claudepierre
Journal: Annals of the Rheumatic Diseases (1997)

JC Thijs, AA van Zwet, W Moolenaar, MJ Wolfhagen, J ten Bokkel Huinink. Triple therapy vs. citnoxicillin plusomeprazole for treatment of Helicobacter pylori infection: a multicenter, prospective, randomized, controlled study of efficacy and side effects. Am J Gastroenterol, 1996 Jan;91:93–7.
Rectal epithelial cell proliferation patterns as predictors of adenomatous colorectal polyp recurrence.
Authors: M Anti, G Marra, F Armelao, A Percesepe, R Ficarelli, G M Ricciuto, A Valenti, G L Rapaccini, I De Vitis, G D'Agostino
Journal: Gut (1993)

To determine whether proliferative patterns in flat rectal mucosal samples can predict the recurrence of adenomatous colorectal polyps, after polypectomy, biopsy specimens from normal looking rectal mucosa were obtained at endoscopy from 55 patients diagnosed for the first time as having adenomatous colorectal polyps. Epithelial cell proliferation was assessed in biopsy specimens through 3H-thymidine autoradiography. After polypectomy, patients were followed for 24 months and underwent complete colonoscopy every 6 months to detect and remove any metachronous lesions. In 40 patients second biopsy specimens were taken during one of the follow up colonoscopies to evaluate the stability of proliferative indices over time. The ratio of labelled (S phase) to total cells (labelling index) for the entire crypt, as well as ratios for each of the five equal compartments into which the crypt had been divided longitudinally, was calculated for each patient. Mean labelling indices for upper crypt compartments 3 and 4 + 5 in the 22 patients in whom polyps recurred were significantly higher (respectively p &lt; 0.05 and p &lt; 0.01) than those of the 33 without recurrence suggesting that an upward shift of the crypt9s replicative compartment is associated with polyp recurrence. Labelling indices remained essentially unchanged in those patients who underwent biopsy twice. Reproducible kinetic parameters such as these might be useful in planning follow up of patients with adenomatous polyps after polypectomy.
The degree of skin involvement identifies distinct lung disease outcomes and survival in systemic sclerosis
Authors: Tricia R Cottrell, Robert A Wise, Fredrick M Wigley, Francesco Boin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To determine whether the pattern of skin involvement can predict clinical features, risk of restrictive lung disease (RLD) and survival in a large scleroderma (SSc) cohort. <h3>Methods</h3> Demographic and clinical data collected over 30 years from 2205 patients with SSc were retrospectively analysed after subdividing subjects into four subtypes based on pattern of skin fibrosis: type 0 (no skin involvement), type 1 (limited to metacarpophalangeal joints), type 2 (distal to elbows/knees) and type 3 (proximal to elbows/knees). Clinical features associated with skin subsets were identified by regression analyses. Kaplan–Meier and Cox proportional hazards models were used to compare time to RLD and survival across subtypes. <h3>Results</h3> The presence and severity of RLD were positively associated with skin subtype (p&lt;0.001). RLD prevalence incrementally ranged from 51.9% in type 0 to 76.7% in type 3 (p&lt;0.001). Type 2 SSc exhibited a distinct phenotype with intermediate risk for RLD relative to type 1 (higher, p&lt;0.001) and type 3 (lower, p&lt;0.001) and a unique autoantibody profile, with a prevalence of anticentromere antibodies lower than type 1 (28.9% vs 44.1%, p=0.001) and of anti-topoisomerase I antibodies similar to type 3 (32.8% vs 28.7%, p=0.38). These autoantibodies were also found to be significant negative (OR=0.33, p&lt;0.001) and positive (OR=1.6, p=0.01) predictors of RLD risk, respectively. Mortality was also intermediate in type 2 patients relative to type 3 (p=0.0003) and type 1 (p=0.066). <h3>Conclusions</h3> These data suggest that the current classification subdividing SSc into limited and diffuse cutaneous subtypes misclassifies an intermediate group of patients exhibiting unique autoantibody profile, disease course and clinical outcomes.
Deficiency of Adipose Differentiation-Related Protein Impairs Foam Cell Formation and Protects Against Atherosclerosis
Authors: Antoni Paul, Benny Hung-Junn Chang, Lan Li, Vijay K. Yechoor, Lawrence Chan
Journal: Circulation Research (2008)

Foam cells are a hallmark of atherosclerosis. However, it is unclear whether foam cell formation per se protects against atherosclerosis or fuels it. In this study, we investigated the role of adipose differentiation-related protein (ADFP), a major lipid droplet protein (LDP), in the regulation of foam cell formation and atherosclerosis. We show that ADFP expression facilitates foam cell formation induced by modified lipoproteins in mouse macrophages in vitro. We show further that Adfp gene inactivation in apolipoprotein E-deficient (ApoE(-/-)) mice reduces the number of lipid droplets in foam cells in atherosclerotic lesions and protects the mice against atherosclerosis. Moreover, transplantation of ADFP-null bone marrow-derived cells effectively attenuated atherosclerosis in ApoE(-/-) mice. Deficiency of ADFP did not cause a detectable compensatory increase in the other PAT domain proteins in macrophages in vitro or in vivo. Mechanistically, ADFP enables the macrophage to maintain its lipid content by hindering lipid efflux. We detected no significant difference in lesion composition or in multiple parameters of inflammation in macrophages or in their phagocytic activity between mice with and without ADFP. In conclusion, Adfp inactivation in ApoE(-/-) background protects against atherosclerosis and appears to be a relatively pure model of impaired foam cell formation.
TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis
Authors: Evelien Zonneveld-Huijssoon, Femke van Wijk, Sarah Roord, Eveline Delemarre, Jenny Meerding, Wilco de Jager, Mark Klein, Eyal Raz, Salvatore Albani, Wietse Kuis, Marianne Boes, Berent J Prakken
Journal: Annals of the Rheumatic Diseases (2012)

Peptide-based immune tolerance induction is considered an attractive treatment option for autoimmune diseases. The authors have developed a novel method that can enhance the induction of protective peptide-specific T-cell responses, using a rat arthritis model. The authors focused on the Toll-like receptor 9 ligand CpG, which was shown to stimulate regulatory T-cell proliferation when added to plasmacytoid dendritic cells (pDC) using in-vitro cultures.
Bone resorption is regulated by cell-autonomous negative feedback loop of Stat5–Dusp axis in the osteoclast
Authors: Jun Hirose, Hironari Masuda, Naoto Tokuyama, Yasunori Omata, Takumi Matsumoto, Tetsuro Yasui, Yuho Kadono, Lothar Hennighausen, Sakae Tanaka
Journal: The Journal of Experimental Medicine (2013)

Signal transducer and activator of transcription 5 (Stat5) is essential for cytokine-regulated processes such as proliferation, differentiation, and survival in hematopoietic cells. To investigate the role of Stat5 in osteoclasts, we generated mice with an osteoclast-specific conditional deletion of Stat5 (Stat5 conditional knockout [cKO] mice) and analyzed their bone phenotype. Stat5 cKO mice exhibited osteoporosis caused by an increased bone-resorbing activity of osteoclasts. The activity of mitogen-activated protein kinases (MAPKs), in particular extracellular signal–related kinase, was increased in Stat5 cKO osteoclasts, whereas the expression of the MAPK phosphatases dual specificity phosphatase 1 (Dusp1) and Dusp2 was significantly decreased. Interleukin-3 (IL-3) stimulated the phosphorylation and nuclear translocation of Stat5 in osteoclasts, and Stat5 expression was up-regulated in response to receptor activator of nuclear factor κB ligand (RANKL). The results suggest that Stat5 negatively regulates the bone-resorbing function of osteoclasts by promoting Dusp1 and Dusp2 expression, and IL-3 promotes Stat5 activation in osteoclasts.
Serum and intestinal secretory IgA in alcoholic cirrhosis of the liver.
Authors: G Pelletier, M J Briantais, C Buffet, J Pillot, J P Etienne
Journal: Gut (1982)

Serum and intestinal secretory IgA (sIgA) were investigated in control subjects and patients with alcoholic cirrhosis of the liver. Intestinal secretions were sampled by intraluminal perfusion with a balloon catheter. Monomeric IgA and sIgA were assayed by reversed radial immunodiffusion and nephelometry after separation by Ultrogel column filtration. High levels of serum sIgA were found only in patients with severe cirrhosis accompanied by jaundice. The intestinal rate of secretion of sIgA measured in these patients was significantly lower than that observed in either controls or the patients with compensated cirrhosis. Such an intestinal sIgA deficiency, which could be explained either by a fall in small intestinal immunocyte synthesis or by a defect in the transenterocyte transport system, could be partially responsible for the high incidence of intestinal infection observed in severe cirrhosis.
Identification of a new cystic fibrosis transmembrane regulator mutation in a severely affected patient
Authors: E. Spitzer, D. Staab, R. Hanke, U. Wahn, R. Grosse
Journal: European Respiratory Journal (2002)

By using a combination of multiplex polymerase chain reaction and allele­specific labelled probes, the oligo­ligation assay is designed to detect known cystic fibrosis transmembrane regulator mutations. This study shows that this assay may also be useful to detect new mutations. The second child of a family of Bosnic origin showed all the symptoms of intestinal and pulmonary manifestations of cystic fibrosis. No signal could be obtained for the allele­specific probe 1898+1G&gt;A. This could be explained by a nearby localized sequence change that prevented polymerase chain reaction primers or oligonucleotide probes from binding to the target sequence. Indeed, sequence analysis revealed a new 1894G&gt;T exchange (Glu587Stop). Both parents and the healthy brother carried this mutation. Thus, the index patient was homozygous for 1894G&gt;T, which was inherited from both parents.
The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma
Authors: E. Andreopoulou, P.J. Ross, M.E.R. O'Brien, H.E.R. Ford, K. Priest, T. Eisen, A. Norton, S. Ashley, I.E. Smith
Journal: Annals of Oncology (2004)
A Congenital Bronchopulmonary Cyst Associated with an Anomalous Artery
Authors: M. Abul-Wafa
Journal: Thorax (1954)

Although bronchogenic cysts of the lungs are not very common, the widespread use of mass miniature radiography and check radiography of the chest is revealing more and more of such con- genital anomalies.It may therefore be of advan- tage for radiographers and chest physicians to bear in mind this possibility in the differential diagnosis and appropriate treatment of such cases.The present case is of interest because there was also a widespread murmur over the chest due to an associated vascular anomaly.CASE HISTORY A 15-year-old boy who left school before Christ- mas, 1952, had a routine mass miniature radiograph taken with his schoolmates, and this revealed a shadow lying anteriorly in the right lung (Figs. 1 and 2).He started to work as an apprentice joiner in anterol in the reinoXh mdloe FIG.1.-Postero-anterior radiograph of the lungs showing a cyst with a fluid level in the right paracardiac area.
<i>TP53</i> Mutation Is Frequently Associated With <i>CTNNB1</i> Mutation or <i>MYCN</i> Amplification and Is Compatible With Long-Term Survival in Medulloblastoma
Authors: Elke Pfaff, Marc Remke, Dominik Sturm, Axel Benner, Hendrik Witt, Till Milde, André O. von Bueren, Andrea Wittmann, Anna Schöttler, Norbert Jorch, Norbert Graf, Andreas E. Kulozik, Olaf Witt, Wolfram Scheurlen, Andreas von Deimling, Stefan Rutkowski, Michael D. Taylor, Uri Tabori, Peter Lichter, Andrey Korshunov, Stefan M. Pfister
Journal: Journal of Clinical Oncology (2010)

Purpose The role of TP53 mutations in the tumorigenesis of sporadic medulloblastoma (MB) and the value of TP53 mutation status as a prognostic marker are not yet definitely elucidated. A recent report identified TP53 mutations in MB as an adverse prognostic marker. Hence, the current study was conducted to validate the prognostic role of TP53 mutation in MB and to understand its contribution to tumorigenesis. Methods A comprehensive genetic analysis of 310 MB samples was performed by screening for TP53 mutations and further relating the TP53 mutation status to p53 immunostaining, cytogenetic aberrations, and clinical variables. Results Mutation analysis of TP53 revealed mutations in 21 (6.8%) of 310 samples. Germline TP53 mutations were found in two patients with a history suggestive of a hereditary cancer syndrome. TP53 mutation status was not associated with unfavorable prognosis (P = .63) and was not linked to 17p allelic loss but was over-represented in the prognostically favorable WNT subgroup of MB as defined by CTNNB1 mutation (seven of 35 TP53-mutated tumors v 14 of 271 TP53 wild-type tumors; P = .005) and in tumors carrying high-level MYCN amplification (seven of 21 TP53-mutated tumors v 14 of 282 TP53 wild-type tumors; P = .001). Conclusion The contradictory results in the recent literature concerning the prognostic value of TP53 mutation might be explained by different frequencies of WNT MBs, different frequencies of patients with Li-Fraumeni syndrome, and different cumulative doses of alkylating drugs applied in these studies.
S4 Short term use of continuous positive airway pressure (CPAP) by obese patients with obstructive sleep apnoea syndrome (OSAS) diagnosed during assessment for bariatric surgery
Authors: S Thomas, HR Gribbin, G Danjoux, R Sathyamurthy
Journal: Thorax (2013)

<h3></h3> Around one in three patients with OSAS is unable to continue with CPAP. The reasons for this are still poorly understood. Patients being assessed for Bariatric Surgery are informed that untreated OSAS can increase peri-operative risk. We investigated whether this information had an effect on CPAP use. Over a six month period we identified 22 obese patients (Mean BMI 49.3) with OSAS discovered during assessment for Bariatric Surgery (OSAS Bar). Over the same period we identified a group of 33 obese patients (Mean BMI 42.1) with OSAS referred through conventional pathways by General Practitioners and Hospital Doctors (OSAS Conv) not under consideration for Bariatric Surgery. OSAS was diagnosed by overnight pulse oximetry, clinical interview and Epworth Sleepiness Score (ESS) using established criteria. <h3>Results</h3> There were more women than men in the OSAS Bar group (41%) than in the OSAS Conv group (18%). Apart from this the 2 groups (OSAS Bar vs OSAS Conv) were well matched prior to CPAP for: Age (Mean 51.2 vs 48.3, p = ns), &gt;4% Oxygen Desaturation Index (Mean 31.9/hour vs 42.3/hour, p = ns) and ESS (Mean 12.8 vs 14.8, p = ns). By 6 weeks after Out-Patient CPAP initiation, 6(27%) of the OSAS Bar group and 7(21%) of the OSAS Conv group had stopped using CPAP. In the patients continuing with CPAP there was no difference between the two groups in hours of CPAP used per night as measured from the CPAP device clock: CPAP Bar (Mean 5, Range 1 8, hours), CPAP Conv (Mean 6, Range 1.5 8.5, hours) or in the ESS on CPAP: CPAP Bar (Mean ESS 6.8), CPAP Conv (Mean ESS 5.8). <h3>Conclusion</h3> This group of obese patients with OSAS under assessment for Bariatric Surgery had similar CPAP use to obese patients with OSAS not considering surgical intervention. Information on peri-operative risk does not appear to be a motivator in overcoming whatever inhibiting factors prevent patients from using CPAP. Pre-operative assessment clinics should be aware that CPAP prescription does not necessarily mean that CPAP is being used.